Detección de una recidiva muscular solitaria de un cáncer pulmonar no microcítico mediante PET/TC con 18F-FDG

Publication date: Available online 19 May 2018
Source:Revista Española de Medicina Nuclear e Imagen Molecular
Author(s): R. Wang, C. Chen, C. Fan, M. Su




https://ift.tt/2IuPE6s

Generation of rat-mouse chimeras by introducing single cells of rat inner cell masses into mouse blastocysts

Publication date: Available online 18 May 2018
Source:Journal of Genetics and Genomics
Author(s): Tianda Li, Leyun Wang, Xinxin Zhang, Liyuan Jiang, Yufei Li, Junjie Mao, Tongtong Cui, Wei Li, Liu Wang, Qi Zhou




https://ift.tt/2KEL9H7

Classifying medical relations in clinical text via convolutional neural networks

Publication date: Available online 18 May 2018
Source:Artificial Intelligence in Medicine
Author(s): Bin He, Yi Guan, Rui Dai
Deep learning research on relation classification has achieved solid performance in the general domain. This study proposes a convolutional neural network (CNN) architecture with a multi-pooling operation for medical relation classification on clinical records and explores a loss function with a category-level constraint matrix. Experiments using the 2010 i2b2/VA relation corpus demonstrate these models, which do not depend on any external features, outperform previous single-model methods and our best model is competitive with the existing ensemble-based method.



https://ift.tt/2KCzeJE

Therapeutic vaccines and immune checkpoints inhibition options for gynecological cancers

Publication date: Available online 18 May 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Chiara Di Tucci, Michele Carlo Schiavi, Pierangelo Faiano, Ottavia D'Oria, Giovanni Prata, Valentina Sciuga, Andrea Giannini, Innocenza Palaia, Ludovico Muzii, Pierluigi Benedetti Panici
Treatments for gynecological cancer include surgery, chemotherapy, and radiation. However, overall survival is not improved, and novel approaches are needed. Immunotherapy has been proven efficacious in various types of cancers and multiple approaches have been recently developed. Since numerous gynecological cancers are associated to human papilloma virus (HPV) infections, therapeutic vaccines, targeting HPV epitopes, have been developed. The advancing understanding of the immune system, regulatory pathways and tumor microenvironment have produced a major interest in immune checkpoint blockade, Indeed, immune checkpoint molecules are important clinical targets in a wide variety of tumors, including gynecological.In this review, we will describe the immunotherapeutic targets and modalities available and review the most recent immunotherapeutic clinical trials in the context of gynecological cancers. The synergic results obtained from the combination of HPV therapeutic vaccines with radiotherapy, chemotherapy, or immune checkpoint inhibitors, may underlie the potential for a novel therapeutic scenario for these tumors.



https://ift.tt/2x3lS7F

5-Lipoxygenase: its involvement in gastrointestinal malignancies

Publication date: Available online 18 May 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Neha Merchant, Lakkakula Venkata Kameswara Subrahmanya Bhaskar, Saimila Momin, Peela Sujatha, Aramati B.M. Reddy, Ganji Purnachandra Nagaraju
Lipoxygenases (LOXs) are dioxygenases that catalyze the peroxidation of linoleic acid (LA) or arachidonic acid (AA), in the presence of molecular oxygen. The existence of inflammatory component in the tumor microenvironment intimately links the LOXs to gastrointestinal (GI) cancer progression. Amongst the six-different human LOX-isoforms, 5-LOX is the most vital enzyme for leukotriene (LT) biosynthesis, which is the main inflammation intermediaries. As recent investigations have shown the association of 5-LOX with tumor metastasis, there has also been significant progress in discovering the function of 5-LOX pathway in GI cancer. Studies on GI cancer cells using the pharmacological drugs targeting 5-LOX pathway have shown antiproliferative and proapoptotic effects. Pharmacogenetic discoveries in other diseases have revealed strong heritable basis for the leukotriene pathway, which helps in exploring the mechanistic source of genetic alteration within the leukotriene pathway and offer insights into GI cancer pathogenesis and future prospects for treatment and prevention. This review recapitulates the current research status of 5-LOX activity in GI malignancies.



https://ift.tt/2IUUfCs

Editorial Board

Publication date: May 2018
Source:Cancer Treatment Reviews, Volume 66





https://ift.tt/2Iv6amF

Acidic domain of WRNp is critical for autophagy and up-regulates age associated proteins

Publication date: Available online 18 May 2018
Source:DNA Repair
Author(s): Jyotirindra Maity, Biswadip Das, Vilhelm A. Bohr, Parimal Karmakar
Impaired autophagy may be associated with normal and pathological aging. Here we explore a link between autophagy and domain function of Werner protein (WRNp). Werner (WRN) mutant cell lines AG11395, AG05229 and normal aged fibroblast AG13129 display a deficient response to tunicamycin mediated endoplasmic reticulum (ER) stress induced autophagy compared to clinically unaffected GM00637 and normal young fibroblast GM03440. Cellular endoplasmic reticulum (ER) stress mediated autophagy in WS and normal aged cells is restored after transfection with wild type full length WRN, but deletion of the acidic domain from wild type WRN fails to restore autophagy. The acidic domain of WRNp was shown to regulate its transcriptional activity, and here, we show that it affects the transcription of certain proteins involved in autophagy and aging. Furthermore, siRNA mediated silencing of WRN in normal fibroblast WI-38 resulted in decrease of age related proteins Lamin A/C and Mre11.



https://ift.tt/2rUN3eN

Formation and Transformation of Calcium Phosphate Phases under Biologically Relevant Conditions: Experiments and Modelling.

Publication date: Available online 18 May 2018
Source:Acta Biomaterialia
Author(s): Agnese Carino, Christian Ludwig, Antonio Cervellino, Elisabeth Müller, Andrea Testino
The experimental data on calcium phosphates formation were collected in dilute solution at constant pH (7.40) and temperature (37.0 °C) at different levels of ionic strength (IS). The evolution of the solid phase formation is described in detail using a thermodynamic-kinetic model. The thermodynamic model takes into account all relevant chemical species as well as Posner's clusters; the kinetic model, based on the discretized population balance approach, accounts for the solid formation from solution. The experimental data are consistent with an initial formation of dicalcium phosphate dihydrate (DCPD, brushite), which dominates the nucleation rate, and its rapid transformation into octacalcium phosphate (OCP) or hydroxyapatite (HA), which dominates the growth rate. Depending on the experimental conditions and, including the influence of the IS level, OCP may be further transformed into apatite. The classical nucleation theory is able to describe the experimental results very well and the solid phase growth is limited by the diffusion of Ca²⁺ ions. The precipitation pathway described by a complete thermodynamic-kinetic model is expected to contribute to the understating of the in vivo osteogenesis.Statement of significanceThe formation mechanism of calcium phosphates under biomimetic conditions is unraveled. The formation pathway is mathematically described based on a thermodynamic-kinetic model in which (i) the nucleation stages (primary and secondary) are dominated by the formation of dicalcium phosphate dihydrate (DCPD) and (ii) the fast growth stage is limited by the diffusion of Ca2+ ions under the driving force of octacalcium phosphate (OCP), or hydroxyapatite (HA), solubility. The obtained solid phase seems correlated to the activity coefficient of phosphate ions, thus to the ionic strength and local phosphate speciation. The model, being able to highlight the details of the precipitation pathway, is expected to contribute to the understanding of the apatitic phase formation in the biomineralization-biodemineralization processes under in-vivo conditions.

Graphical abstract

https://ift.tt/2IwF6DT

Therapeutic antibody directed osteogenic differentiation of Induced pluripotent stem cells derived MSCs

Publication date: Available online 18 May 2018
Source:Acta Biomaterialia
Author(s): Qingqing Wu, Bo Yang, Cong Cao, Kevin Hu, Ping Wang, Yi Man
Induced pluripotent stem cells (iPSCs) are regarded as a new cell source for regenerative medicine. Recent advances in tissue engineering have brought to light the therapeutic application of induced pluripotent stem cells (iPSCs) in bone defect repair. However, a safe and efficient way to differentiate iPSCs into osteogenic lineage remains to be a major challenge. Here we describe an approach using anti-BMP2 antibodies (Abs) to mediate osteogenic differentiation of iPSC-derived mesenchymal stromal cells (iMSCs). We first proved that 3G7 (an anti-BMP2 Ab) not only bound to BMP2, but also allowed the bound BMP2 to engage the BMP2 receptors on iMSCs. Subcutaneous implantation sites loaded with iMSCs+3G7 group showed significant bone formation and vascularization in mice while those sites with exogenous BMP2 exhibited dystrophic calcification and significantly lower vascularization. Our In vitro study demonstrated that the anti-BMP2 Ab/BMP2 immune complex were capable of dictating the acquisition of osteogenic phenotype of iMSCs and subsequent mineralization. The study provided the first evidence of antibody-mediated differentiation of iMSCs and osseous regeneration in vivo. This novel strategy takes full advantage of the endogenous bioactive molecules for osseous regeneration and its potential therapeutic application is promising.Statement of SignificanceInduced pluripotent stem cells (iPSCs) and its derived cells hold significant promise for the treatment of bone defects. In present study, we carried out the concept of antibody-mediated bone regeneration into the iPSC research for the first time. We demonstrated that anti-BMP2 Ab/BMP2 immune complex was capable of promoting osteogenic differentiation of iPSC-derived MSCs (iMSCs), likely through the classical BMP2/Smad1/Runx2 pathway. Subcutaneous co-delivery of iMSCs and anti-BMP2 Abs resulted in significant bone formation and vascularization. These findings suggested antibody mediated osteogenic differentiation may be a favorable approach for iPSC-based bone tissue engineering.

Graphical abstract

https://ift.tt/2IRc6Kk

Assessing the external benefits of contaminated soil remediation in Korea: a choice experiment study

Abstract

Korean government has made and will continue to make a considerable investment in contaminated soil remediation to rectify the problems that arise from soil pollution. Quantitative information on the benefits of contaminated soil remediation is widely demanded by the public as well as the government. This article aims to assess the external benefits of contaminated soil remediation. A survey of 1000 randomly selected households was undertaken in Korea. The results show that the marginal willingness to pay values for a 1% decrease in human health hazard, a 1% improvement in biodiversity restoration, and 1000 new job creation by contaminated soil remediation are estimated to be KRW 204 (USD 0.17), 593 (0.50), and 238 (0.20) per household per year. The findings can provide policy-makers with useful information for both evaluating and planning the contaminated soil remediation.

https://ift.tt/2wSbTBP

Clinical applications of gut microbiota in cancer biology

Publication date: Available online 18 May 2018
Source:Seminars in Cancer Biology
Author(s): Sunny H. Wong, Thomas N.Y. Kwong, Chun-Ying Wu, Jun Yu
The involvement of microorganisms in cancer has been increasing recognized. Collectively, microorganisms have been estimated to account for ~20% of all cancers worldwide. Recent advances in metagenomics and bioinformatics have provided new insights on the microbial ecology in different tumors, pinpointing the roles of microorganisms in cancer formation, development and response to treatments. Furthermore, studies have emphasized the importance of host-microbial and inter-microbial interactions in the cancer microbiota. These studies have not only revolutionized our understanding of cancer biology, but also opened up new opportunities for cancer prevention, diagnosis, prognostication and treatment. This review article aims to summarize the microbiota in various cancers and their treatments, and explore clinical applications for such relevance.



https://ift.tt/2rQ1bWK

Molecular subtyping of colorectal cancer: Recent progress, new challenges and emerging opportunities

Publication date: Available online 18 May 2018
Source:Seminars in Cancer Biology
Author(s): Wei Wang, Raju Kandimalla, Hao Huang, Lina Zhu, Ying Li, Feng Gao, Ajay Goel, Xin Wang
Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Similar to many other malignancies, CRC is a heterogeneous disease, making it a clinical challenge for optimization of treatment modalities in reducing the morbidity and mortality associated with this disease. A more precise understanding of the biological properties that distinguish patients with colorectal tumors, especially in terms of their clinical features, is a key requirement towards a more robust, targeted-drug design, and implementation of individualized therapies. In the recent decades, extensive studies have reported distinct CRC subtypes, with a mutation-centered view of tumor heterogeneity. However, more recently, the paradigm has shifted towards transcriptome-based classifications, represented by six independent CRC taxonomies. In 2015, the colorectal cancer subtyping consortium reported the identification of four consensus molecular subtypes (CMSs), providing thus far the most robust classification system for CRC. In this review, we summarize the historical timeline of CRC classification approaches; discuss their salient features and potential limitations that may require further refinement in near future. In other words, in spite of the recent encouraging progress, several major challenges prevent translation of molecular knowledge gleaned from CMSs into the clinic. Herein, we summarize some of these potential challenges and discuss exciting new opportunities currently emerging in related fields. We believe, close collaborations between basic researchers, bioinformaticians and clinicians are imperative for addressing these challenges, and eventually paving the path for CRC subtyping into routine clinical practice as we usher into the era of personalized medicine.



https://ift.tt/2k8AUzE

Integrating Physical and Molecular Insights on Immune Cell Migration

Publication date: Available online 17 May 2018
Source:Trends in Immunology
Author(s): Hélène D. Moreau, Matthieu Piel, Raphaël Voituriez, Ana-Maria Lennon-Duménil
The function of most immune cells depends on their ability to migrate through complex microenvironments, either randomly to patrol for the presence of antigens or directionally to reach their next site of action. The actin cytoskeleton and its partners are key conductors of immune cell migration as they control the intrinsic migratory properties of leukocytes as well as their capacity to respond to cues present in their environment. In this review we focus on the latest discoveries regarding the role of the actomyosin cytoskeleton in optimizing immune cell migration in complex environments, with a special focus on recent insights provided by physical modeling.



https://ift.tt/2IVxs9D

The Supraclavicular Artery Perforator Flap: A Comparative Study of Imaging Techniques Used in Preoperative Mapping

J reconstr Microsurg
DOI: 10.1055/s-0038-1639577

Background The supraclavicular artery flap is an excellent flap for head and neck reconstruction. The aim of this study is to assess imaging techniques to define the precise vascular boundaries of this flap. Methods Six imaging techniques were used for supraclavicular artery mapping in 65 cases; handheld Doppler, triplex ultrasound, computed tomography angiography, magnetic resonance angiography, digital subtraction angiography, and indocyanine green angiography. We checked the site of the perforators, the course of a supraclavicular artery, and anatomical mapping of the supraclavicular artery. Results Handheld Doppler identified perforators' sites in 80% of the cases but showed no results for the course of the vessel. Triplex ultrasound identified the site of perforators in 52.9%, and partial mapping of the course of a supraclavicular artery in 64.7% of the cases. Computerized tomography angiography showed the site of perforators in 60%, and the course of supraclavicular artery completely in 45%, and partially in an additional 30%of the cases examined. Magnetic resonance angiography showed negative results for all parameters. Digital subtraction angiography showed the partial course of a supraclavicular artery in 62.5%, but showed no perforators. Indocyanine green angiography showed the site of perforators in 60% and a partial course of supraclavicular artery distal to perforators in 60%.Anatomical mapping of the vessel was possible with computerized tomography angiogram completely in 45%, and partially in 30%, and was also possible with indocyanine green angiography partially in 60%. Conclusion Computerized tomography angiography showed best results in the mapping of the supraclavicular artery, but with an inability to define the perforator perfusion territories, and also with risks of irradiation, while indocyanine green angiography is a good alternative as it could precisely map the superficial course of the artery and angiosomes, with no radiation exposure.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Classification and Microvascular Flap Selection for Anterior Cranial Fossa Reconstruction

J reconstr Microsurg
DOI: 10.1055/s-0038-1649520

Background Microvascular reconstruction of the anterior cranial fossa (ACF) creates difficult challenges. Reconstructive goals and flap selection vary based on the defect location within the ACF. This study evaluates the feasibility and reliability of free tissue transfer for salvage reconstruction of low, middle, and high ACF defects. Methods A retrospective review was performed. Reconstructions were anatomically classified as low (anterior skull base), middle (frontal bar/sinus), and high (frontal bone/soft tissue). Subjects were evaluated based on pathologic indication and goal, type of flap used, and complications observed. Results Eleven flaps in 10 subjects were identified and anatomic sites included: low (n = 5), middle (n = 3), and high (n = 3). Eight of 11 reconstructions utilized osteocutaneous flaps including the osteocutaneous radial forearm free flap (OCRFFF) (n = 7) and fibula (n = 1). Other reconstructions included a split calvarial graft wrapped within a temporoparietal fascia free flap (n = 1), latissimus myocutaneous flap (n = 1), and rectus abdominis myofascial flap (n = 1). All 11 flaps were successful without microvascular compromise. No complications were observed in the high and middle ACF defect groups. Two of five flaps in the low defect group using OCRFFF flaps failed to achieve surgical goals despite demonstrating healthy flaps upon re-exploration. Complications included persistent cerebrospinal fluid leak (n = 1) and pneumocephalus (n = 1), requiring flap repositioning in one subject and a second microvascular flap in the second subject to achieve surgical goals. Conclusion In our experience, osteocutaneous flaps (especially the OCRFFF) are preferred for complete autologous reconstruction of high and middle ACF defects. Low skull base defects are more difficult to reconstruct, and consideration of free muscle flaps (no bone) should be weighed as an option in this anatomic area.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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From Auto- to Allotransplantation: Immunomodulatory Protocol for Hand and Arm Transplantation

J reconstr Microsurg
DOI: 10.1055/s-0038-1651524

Aim To achieve a favorable risk–benefit balance for hand transplantation, an immunomodulatory protocol was developed in the laboratory and translated to clinical application. Methods Following donor bone marrow infusion into transplant recipients, hand and arm allografts have been maintained on low-dose tacrolimus monotherapy. Results Good-to-excellent functional recovery has been achieved in patients compliant with medication and therapy, thus restoring autonomous and productive lives. Conclusion The risk-benefit balance can be tilted in favor of the hand transplant recipients by using an immunomodulatory protocol with minimum immunosuppression.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

https://ift.tt/2KEzkRl

Ability of blue laser imaging with magnifying endoscopy for the diagnosis of gastric intestinal metaplasia

Abstract

We aimed to determine the utility of blue laser imaging (BLI) with magnifying endoscopy (BLI-ME) for the prediction and diagnosis of gastric intestinal metaplasia (GIM). Participants, aged between 40 and 75 years, undergoing gastroscopy from January to April 2017 were included in this study. The ability of BLI-ME and white light endoscopy (WLE) to detect GIM was assessed by comparing the endoscopic findings with the histological findings. The correlation between the grades of light blue crest (LBC) appearance and histology grade of GIM was calculated. We included 100 participants in this study. GIM was diagnosed in 27 participants; 20 participants were detected by both BLI and WLE, four by BLI only, and three exclusively by random biopsies. The values of sensitivity, specificity, positive predictive values, and negative predictive values for detecting GIM were 34.9, 38.9, 25.4, and 57.1%, respectively, for WLE and 88.9, 96.7, 94.1, and 93.3%, respectively, for BLI-ME. The diagnostic accuracy for GIM was 43% for WLE and 94.0% for BLI-ME. A good correlation between the grades of LBC and the grades of GIM on histology was observed (P < 0.01). BLI-ME achieved a good diagnostic efficiency for detection of GIM. LBC seen on BLI-ME is a typical indicator of GIM.

https://ift.tt/2rWx4Nc

Underlying Neural Alpha Frequency Patterns Associated with Intra-hemispheric Inhibition During an Interhemispheric Transfer Task

Publication date: Available online 18 May 2018
Source:Biological Psychology
Author(s): Stephanie L. Simon-Dack, Brian Kraus, Zachary Walter, Shelby Smith, Chelsea Cadle
Interhemispheric transfer measured via differences in right- or left-handed motoric responses to lateralized visual stimuli, known as the crossed-uncrossed difference (CUD), is one way of identifying patterns of processing that are vital for understanding the transfer of neural signals. Examination of interhemispheric transfer by means of the CUD is not entirely explained by simple measures of response time. Multiple processes contribute to wide variability observed in CUD reaction times. Prior research has suggested that intra-hemispheric inhibitory processes may be involved in regulation of speed of transfer. Our study examined electroencephalography recordings and time-locked alpha frequency activity while 18 participants responded to lateralized targets during performance of the Poffenberger Paradigm. Our results suggest that there are alpha frequency differences at fronto-central lateral electrodes based on target, hand-of-response, and receiving hemisphere. These findings suggest that early motoric inhibitory mechanisms may help explain the wide range of variability typically seen with the CUD.



https://ift.tt/2LbGT2Z

Trainability of hemodynamic parameters: A near-infrared spectroscopy based neurofeedback study

Publication date: Available online 18 May 2018
Source:Biological Psychology
Author(s): Silvia Erika Kober, Vanessa Hinterleitner, Günther Bauernfeind, Christa Neuper, Guilherme Wood
We investigated the trainability of the hemodynamic response as assessed with near-infrared spectroscopy (NIRS) during one neurofeedback (NF) session. Forty-eight participants were randomly assigned to four different groups that tried to either increase or decrease oxygenated (oxy-Hb) or deoxygenated hemoglobin (deoxy-Hb) over the inferior frontal gyrus during imagery of swallowing movements. Deoxy-Hb could be successfully up-regulated while oxy-Hb could be successfully down-regulated during NF. Participants were not able to down-regulate deoxy-Hb or to up-regulate oxy-Hb. These results show that the natural course of oxy- and deoxy-Hb during movement imagery can be reinforced by providing real-time feedback of the corresponding NIRS parameter since deoxy-Hb generally increases and oxy-Hb decreases during imagery of swallowing. Furthermore, signal-to-noise ratio of deoxy-Hb but not of oxy-Hb improved during training. Our results provide new insights into the trainability of the hemodynamic response as assessed with NIRS and have an impact on the application of NIRS-based real-time feedback.



https://ift.tt/2Gw9Lzl

Electroencephalographic and cardiovascular markers of vulnerability within families of suicidal adolescents: A pilot study

Publication date: Available online 18 May 2018
Source:Biological Psychology
Author(s): Erin A. Kaufman, Sheila E. Crowell, James Coleman, Megan E. Puzia, Douglas D. Gray, David L. Strayer
Suicide, self-injury, and predisposing vulnerabilities aggregate in families. Those at greatest risk often show deficits in two biologically-mediated domains: behavioral control and emotion regulation. This pilot study explored electroencephalographic and cardiovascular indices of self-regulation among typical and suicidal adolescents (n = 30/group) and biological family members (mothers, fathers, and siblings). We measured event-related potentials during a flanker task designed to evoke impulsive responding and respiratory sinus arrhythmia (RSA) at rest and during social rejection. Multilevel models indicate control families' RSA was unaffected by social rejection (slope = 0.136, p = .097, d = 0.09), whereas clinical families demonstrated RSA withdrawal (slope = −0.191, p = .036, d = −0.13). Clinical families displayed weaker positive voltage (Pe) deflections following behavioral errors relative to controls (coefficient = −2.723, p = .017, d = −0.45), indicating risk for compromised cognitive control. Thus, families with suicidal adolescents showed autonomic and central nervous system differences in biological markers associated with suicide risk.



https://ift.tt/2IRsqLa

Irisin levels increase after treatment in patients with newly diagnosed Hashimoto thyroiditis

Abstract

Purpose

Irisin is a newly identified myokine secreted by skeletal muscle and has significant effects on body metabolism. Thyroidal functional state has a profound influence on the metabolism of human body. Therefore, the aim of this study was to investigate the possible changes in serum irisin concentrations before and after treatment in hypothyroid subjects.

Methods

The study included 26 patients with overt hypothyroidism due to Hashimoto thyroiditis and 19 healthy subjects. Baseline serum thyroid function tests and presence of thyroid autoantibodies and levels of creatine kinase (CK) and irisin were measured in both groups. All measurements in the hypothyroid group were repeated after euthyroidism was achieved.

Results

Serum irisin levels were significantly lower in the hypothyroid groups than the control group (p < 0.001). Negative correlation between irisin and thyroid stimulating hormone and CK levels (r = − 0.623, p < 0.001 and r = − 0.389, p = 0.008, respectively) and a positive correlation between irisin and free thyroxine (fT4) levels (r = 0.570, p < 0.001) was found. Serum CK levels decreased significantly after treatment (p < 0.001). Serum irisin levels significantly increased (from 57.4 to 99.8 U/L, p < 0.001) when the hypothyroid patients were treated to achieve euthyroidism.

Conclusions

To the best of our knowledge, this is the first study providing insight that low serum irisin levels significantly increased following treatment to euthyroid state in overt hypothyroid patients with Hashimoto thyroiditis. Larger scale studies are needed to confirm these results and to ensure irisin as a possible biomarker of Hashimoto's thyroiditis.

https://ift.tt/2LfQjKu

Modelling correlated data: Multilevel models and generalized estimating equations and their use with data from research in developmental disabilities

Publication date: Available online 18 May 2018
Source:Research in Developmental Disabilities
Author(s): Dimitrios Vagenas, Vasiliki Totsika
BackgroundThe use of Multilevel Models (MLM) and Generalized Estimating Equations (GEE) for analysing clustered data in the field of intellectual and developmental disability (IDD) research is still limited.MethodWe present some important features of MLMs and GEEs: main function, assumptions, model specification and estimators, sample size and power. We provide an overview of the ways MLMs and GEEs have been used in IDD research.ResultsWhile MLMs and GEEs are both appropriate for longitudinal and/or clustered data, they differ in the assumptions they impose on the data, and the inferences made. Estimators in MLMs require appropriate model specification, while GEEs are more resilient to misspecification at the expense of model complexity. Studies on sample size seem to suggest that Level 1 coefficients are robust to small samples/clusters, with any higher-level coefficients less so. MLMs have been used more frequently than GEEs in IDD research, especially for fitting developmental trajectories.ConclusionsClustered data from research in the IDD field can be analysed flexibly using MLMs and GEEs. These models would be more widely used if journals required the inclusion of technical specification detail, simulation studies examined power for IDD study characteristics, and researchers developed core skills during basic studies.



https://ift.tt/2IN3Hrg

Placenta-derived mesenchymal stromal cells and their exosomes exert therapeutic effects in Duchenne muscular dystrophy

Publication date: August 2018
Source:Biomaterials, Volume 174
Author(s): Ariel Bier, Peter Berenstein, Noam Kronfeld, Daria Morgoulis, Amotz Ziv-Av, Hodaya Goldstein, Gila Kazimirsky, Simona Cazacu, Rinat Meir, Rachela Popovtzer, Amir Dori, Chaya Brodie
Duchenne muscular dystrophy (DMD) is a degenerative lethal, X-linked disease of skeletal and cardiac muscles caused by mutations in the dystrophin gene. Cell therapy using different cell types, including mesenchymal stromal cells (MSCs), has been considered as a potential approach for the treatment of DMD. MSCs can be obtained from autologous sources such as bone marrow and adipose tissues or from allogeneic placenta and umbilical cord. The safety and therapeutic impact of these cells has been demonstrated in pre-clinical and clinical studies and their functions are attributed to paracrine effects that are mediated by secreted cytokines and extracellular vesicles. Here, we studied the therapeutic effects of placenta-derived MSCs (PL-MSCs) and their secreted exosomes using mouse and human myoblasts from healthy controls, Duchenne patients and mdx mice. Treatment of myoblasts with conditioned medium or exosomes secreted by PL-MSCs increased the differentiation of these cells and decreased the expression of fibrogenic genes in DMD patient myoblasts. In addition, these treatments also increased the expression of utrophin in these cells. Using a quantitative miR-29c reporter, we demonstrated that the PL-MSC effects were partly mediated by the transfer of exosomal miR-29c. Intramuscular transplantation of PL-MSCs in mdx mice resulted in decreased creatine kinase levels. PL-MSCs significantly decreased the expression of TGF-β and the level of fibrosis in the diaphragm and cardiac muscles, inhibited inflammation and increased utrophin expression. In vivo imaging analyses using MSCs labeled with gold nanoparticles or fluorescent dyes demonstrated localization of the cells in the muscle tissues up to 3 weeks post treatment. Altogether, these results demonstrate that PL-MSCs and their secreted exosomes have important clinical applications in cell therapy of DMD partly via the targeted delivery of exosomal miR-29c.



https://ift.tt/2KxOibq

Small Whitish Painful Agminated Papules on Fingers: Answer

No abstract available

https://ift.tt/2IsFUh0

Spectrum of Hybrid Cysts and Their Clinical Significance

Abstract: A hybrid cyst is a cutaneous cyst combining different types of keratinization of those seen in the folliculo-sebaceous-apocrine unit. Previous reports found that it may be occasionally associated with Gardner syndrome. This study aimed to clarify the pathologic findings and clinical significance of hybrid cyst based on case series observations. We retrospectively reviewed patients who fulfilled the pathological criteria of hybrid cyst from 2001 to 2015. The patient profiles, clinical presentations, pathological findings, and associated diseases were analyzed by reviewing the medical records and slides. A total of 71 hybrid cysts were confirmed over the study period. There were 12 pathologic variants. The most frequent variant was combined infundibular cyst and tricholemmal cyst (22 in 71 cases, 30%), followed by infundibular cyst and pilomatricoma (14 in 71 cases, 19%). There was no significant association between sex, age, or site and the pathological type of hybrid cyst. Neither extra-intestinal manifestation nor a family history of Gardner syndrome was found in any case. Hybrid cysts could contain a variety of combinations of components from the folliculo-sebaceous-apocrine unit. No clinical significance was found between demographics and the type of hybrid cyst. No association with Gardner syndrome was identified in this case series.

https://ift.tt/2wV83Ih

Utility of Immunohistochemistry in Distinguishing Primary Adnexal Carcinoma From Metastatic Breast Carcinoma to Skin and Squamous Cell Carcinoma

Abstract: The distinction between primary adnexal carcinoma (PAC) from metastatic breast carcinoma (BrCa) to skin and squamous cell carcinoma (SCC), particularly those with ductal differentiation (SCCDD), can be quite challenging, despite adequate history. The aim of the study was to determine the utility of an immunohistochemistry (IHC) panel to differentiate these entities and apply them to ambiguous tumors. Twenty-seven PAC, 7 metastatic BrCa, 28 SCC, and 16 ambiguous cases (SCCDD vs. PAC, n = 13 and metastatic BrCa vs. PAC, n = 3) were analyzed using CD23, PAX5, D2-40, P63, and CD117 immunohistochemistry. A total of 9 (33%) PAC were CD117 positive, whereas all metastatic BrCa and SCC were negative (P = 0.0002). D2-40 was expressed in 16 (59%) PAC and 16 (57%) SCC cases, but none of the metastatic BrCa cases (P = 0.0041). Of the 13 ambiguous tumors with a differential diagnosis of SCCDD versus PAC, all were positive for P63, 10 were positive for D2-40, and 1 was positive for CD117. Of the 3 ambiguous tumors with a differential diagnosis of PAC versus metastatic BrCA, 2 were positive for CD117, whereas none showed reactivity for D2-40 or P63. All cases were negative for CD23 and PAX5. Our study indicates that CD117 reactivity favors a PAC with a sensitivity and specificity of 33% and 100%, respectively. D2-40 and P63 expression highlighted both PAC and SCC and seems to be useful in excluding metastatic BrCa with a sensitivity and specificity of 58% and 100%, and 98% and 100%, respectively. Despite previous reports, CD23 and PAX5 do not seem to be useful.

https://ift.tt/2rSFExD

Holocrine Poroma: A Distinctive Adnexal Tumor

Abstract: There are 36 cases of complex poroid tumors with folliculosebaceous and apocrine differentiation reported in the literature. The authors evaluated 111 poroid tumors including 63 typical eccrine poromas and 48 poroid tumors with folliculosebaceous elements. Folliculosebaceous poroid tumors (FSPT) had basaloid and squamous cells (100%), ducts with steatocystoma-like cuticles and holocrine secretions (89.6%), infundibular follicular structures (66.7%), and entrapped sebocytes (56.3%). No definite apocrine decapitation secretions in FSPT were found. Immunohistochemistry was strongly positive for CK903 and focally positive for CAM5.2, epithelial membrane antigen, and carcinoembryonic antigen. No loss of MLH-1, MSH-2, or MSH-6 mismatch repair proteins was found. FSPT had distinctive features that differentiate them from eccrine poromas including the frequent head and neck locations (62.5% vs. 20.6%, P

https://ift.tt/2wRT41D

A Not-So-Benign Papular Eruption: Challenge

No abstract available

https://ift.tt/2ItDaQD

Relationship Between Pityriasis Lichenoides and Mycosis Fungoides: A Clinicopathological, Immunohistochemical, and Molecular Study

Background: Several cases of pityriasis lichenoides (PL) have been reported to evolve into mycosis fungoides (MF). Objective: To elucidate clues to this progression. Methods: Fifty-eight patients with PL between 2000 and 2013 (follow-up: 3–16 years, average: 8.3). Results: A total of 3 (5.2%) of the 58 patients with PL developed MF after 3–11 years of prolonged clinical course. Papules and small plaques characterized PLs, and patches and larger plaques subsequent MFs. A total of 35 of 41 (85%) followed up non-MF associated patients with PL reported lasting complete remissions. Histopathologically, apoptotic keratinocytes disappeared mostly or completely in subsequent MFs. The presence of epidermotropism, folliculotropism, and epidermal lymphocytic nuclear atypia in PLs was not predictive of MF. CD8+ cells were the dominant intraepidermal lymphocytes in the 3 PLs but remained so in only 1 subsequent MF. CD7+ lymphocytes decreased substantially in 2 MFs, and lymphocytic nuclear atypia increased markedly in 1. T-cell receptor gene rearrangement studies demonstrated clonal populations in 1 of 2 studied PLs and in all 3 subsequent MFs. Conclusions: A few PLs may evolve into MF. Prolonged clinical course, appearance of patches and larger plaques, markedly increased lymphocytic nuclear atypia, marked diminution of apoptotic keratinocytes and CD7+ and CD8+ lymphocytes, and clonal T-cell receptor gene rearrangement may serve as clues.

https://ift.tt/2wZMDKa

A Not-So-Benign Papular Eruption: Answer

No abstract available

https://ift.tt/2IuSA79

Measuring Scholastic Production by Dermatopathologists Using the H-Index: A Cross-Sectional Study

Abstract: Academic advancement in dermatopathology requires evidence of scientific production. The H-index is a useful bibliometric for measuring scientific production because it weights both volume and impact of an individual's scholastic production. The H-index distribution among academic dermatopathologists is unknown. In this cross-sectional study of 299 dermatopathologists with academic appointments in North America, H-index, publication counts, and citation counts were retrieved from Thomas Reuters Web of Science. Analytic statistics were performed to identify best predictors of academic rank and cutoff points between academic ranks. The H-index was a superior predictor of overall academic rank than publication or citation counts. The median H-index for assistant, associate, and full professors was 4, 6, and 11, respectively. H-index cutoff scores of 8 and 10 favored associate and full professor rank, respectively. These data provide benchmarks for dermatopathologists to gauge their scientific productivity against that of their peers. Although advancement decisions will depend on a careful examination of the scope and impact of a candidate's work, assistant professors of dermatopathology with H-index scores of >7 and associate professors of dermatopathology with H-index scores of >9 may wish to consider application for promotion.

https://ift.tt/2GwyF1C

Melanoma Manifesting as Tumoral Melanosis; Now You See It, Now You Don't

No abstract available

https://ift.tt/2rRngFk

Recurrent Cutaneous Angiosarcoma of the Scalp With Aberrant Expression of S100: A Case Report

Abstract: Angiosarcoma (AS) is a malignant mesenchymal neoplasm of endothelial origin with a predominantly lymphatic immunophenotype, which accounts for less than 1% of all sarcomas. Cutaneous AS of the scalp is associated with high rates of local recurrence and a poor prognosis. Histologically, poorly differentiated AS often comprises solid epithelioid cells, although rare variants involving spindle cells have been reported; diagnosis requires immunohistochemical analysis using vascular cell markers. We report on a cutaneous spindle-cell AS of the scalp in a female patient; key features included spontaneous regression after biopsy, local recurrence 2 years later, and aberrant nuclear staining for S100 protein in an area of the tumor not expressing CD34 or D2-40. Tumor cells exhibited positivity for vascular markers CD31, CD34, D2-40, ERG and FLI-1 and were negative for myoid markers (αSMA and desmin), epithelial (EMA and cytokeratin AE1/AE3) and melanocyte markers (HMB45 and melan-A). Cutaneous spindle-cell AS of the scalp is a rare variant with a poor prognosis. Diagnosis of spindle-cell AS was confirmed by immunohistochemical analysis using CD31, CD34, ERG, FLI-1, podoplanin (D2-40), and claudin-5. Although a number of authors have noted aberrant expression of cytokeratins, CD30, CD117 and neuroendocrine markers (synaptophysin and chromogranin A) in AS, intense positive nuclear staining for S100 protein in neoplastic cells has not hitherto been observed. This article reports on a spindle-cell AS of the scalp notable for aberrant expression of S100, spontaneous regression and recurrence 2 years later at the same site and displaying identical histological and immunohistochemical features.

https://ift.tt/2wQnQrL

Small Whitish Painful Agminated Papules on Fingers: Challenge

No abstract available

https://ift.tt/2rTrKLv

Eruptive Keratoacanthoma-Like Discoid Lupus Erythematosus

Abstract: Hypertrophic discoid lupus erythematosus can resemble keratoacanthoma histomorphologically. We describe a unique case of eruptive keratoacanthomatous scaly papules in a 56-year-old woman with discoid lupus erythematosus. We review the literature and conclude by discussing important histologic features and useful immunostains to consider when attempting to discern the underlying identity and pathogenicity of such lesions.

https://ift.tt/2GtWwPr

Primary Cutaneous Spindle Cell Squamous Carcinoma Expressing Smooth Muscle Actin: Diagnostic Pitfalls

Abstract: Alpha smooth muscle actin (SMA) belongs to the actin proteins. It is a known immunohistochemical marker for tumors of mesenchymal origin. There have been reports of expression of SMA in certain epithelial malignancies in the head and neck and genital regions. In this study, the authors report a primary cutaneous spindle cell squamous carcinoma expressing SMA. Both high- and low-molecular-weight keratins and p63 were positive, and S100 protein, SOX10, MART-1/Melan-A, and muscle-specific actin stains were negative. This case highlights that an epithelial tumor could express a mesenchymal marker, thereby making the diagnosis problematic.

https://ift.tt/2rRZMQ9

Myoepithelial-Rich and Infiltrative Giant Vascular Eccrine Spiradenoma: A Unique Presentation of a Rare Adnexal Tumor

Abstract: A rare variant of the eccrine spiradenoma, the giant vascular eccrine spiradenoma, has been characterized as a large circumscribed and sometimes hemorrhagic solitary tumor occurring in adults older than 50 years. Histopathologically, the lesion is comprised of distinct cell populations and cystic hemorrhagic glandular spaces. We present a 68-year-old Bengali man with a giant vascular eccrine spiradenoma and describe immunohistochemical features of this tumor. In addition, we highlight unique aspects of this case, including a rich myoepithelial component and focal pseudocapsular infiltration.

https://ift.tt/2GwwR8W

Painful Pustules on Hands and Feet With Acute Hepatitis: Answer

No abstract available

https://ift.tt/2IsXVMi

Cutis Laxa Acquisita After Urticarial Vasculitis in SLE Patients

Abstract: Cutis laxa is a rare connective tissue disease involving damage to dermal elastic fibers creating a clinical appearance of loose, sagging skin. The condition can be either acquired or genetic. Autoimmune diseases, neoplasms, infections, and medications have been proposed as the cause of, or in association with, the acquired form. In nearly 50% of cases, erythematous plaques present before the onset of cutis laxa. Separately, urticarial vasculitis and systemic lupus erythematosus have been linked to cutis laxa acquisita. Our case is the first in the literature documenting a coexistence of cutis laxa acquisita, hypocomplementemic urticarial vasculitis, and systemic lupus erythematosus.

https://ift.tt/2GuXHhu

Subcutaneous Histiocytoid Sweet Syndrome in a Patient With Relapsed Acute Myeloblastic Leukemia

No abstract available

https://ift.tt/2IuS7Sr

Mixed Lichenoid and Follicular T- and B-Cell Lymphoid Reaction to Red Tattoos With Monoclonal T Cells

Abstract: Pseudolymphomatous reactions have been described to occur in tattoos. Most cases have exhibited T-cell predominance and polyclonal T-cell receptor gene rearrangements. One case with monoclonal IgH gene rearrangements progressed into B-cell lymphoma. Lichenoid infiltrates are commonly described but lymphoid follicles much less frequently. We report a case with mixed lichenoid and follicular T- and B-cell reaction to red tattoos. The histopathology and the immunohistochemical studies were constant with a mixed T- and B-cell pseudolymphoma, the IgH gene rearrangement study was polyclonal, but the T-cell receptor gene rearrangement study was monoclonal. The patient who responded to intralesional corticosteroid injections remains under close scrutiny.

https://ift.tt/2LbTC5q

Spitz Nevus Intermingling With Hemangioma, Angiomatoid Spitz Nevus, Angiotropism, and Vascular Co-option Viewed With Differing Availability Heuristics

No abstract available

https://ift.tt/2Iw1E7v

Late-Stage Erythema Elevatum Diutinum Mimicking a Fibroblastic Tumor: A Potential Pitfall

Abstract: Erythema elevatum diutinum (EED) is a rare dermatosis with evolving histopathological features that vary according to the age of the lesions, with a variable fibrosis and a fascicled proliferation of spindle cells in late phases. The authors present an otherwise healthy 57-year-old woman with multiple indurated nodules on the inner aspect of both feet. Skin biopsy showed storiform interlacing bundles of spindled cells with plump nuclei and some areas with neutrophils and leukocytoclasia. CD34 and S100 were negative. This case is noteworthy clinically due to its location and its histopathological presentation that comprises a wide differential diagnosis, including inflammatory pseudotumor, dermatofibrosarcoma protuberans, superficial nodular fasciitis, hyalinized leiomyoma, sclerosing spindle cell perineuroma, and sclerotic fibroma. The authors have reviewed the main histopathological and immunohistochemical features that help in the differential diagnosis of this rare variant of EED. A careful search for leukocytoclasia and neutrophilic vasculitis is mandatory to establish the right diagnosis of nodular or late-stage EED and avoid the pitfall of considering this a neoplastic process.

https://ift.tt/2LbT7IA

A quality assurance device for measuring afterloader performance and transit dose for nasobiliary high-dose-rate brachytherapy

Publication date: Available online 17 May 2018
Source:Brachytherapy
Author(s): Christopher L. Deufel, John P. Mullins, Mark J. Zakhary
PurposeNasobiliary high-dose-rate (HDR) brachytherapy has emerged as an effective tool to boost the radiation dose for patients with unresectable perihilar cholangiocarcinoma. This work describes a quality assurance (QA) tool for measuring the HDR afterloader's performance, including the transit dose, when the source wire travels through a tortuous nasobiliary catheter path.Methods and MaterialsThe nasobiliary QA device was designed to mimic the anatomical path of a nasobiliary catheter, including the nasal, stomach, duodenum, and bile duct loops. Two of these loops, the duodenum and bile duct loops, have adjustable radii of curvature, resulting in the ability to maximize stress on the source wire in transit. The device was used to measure the performance over time for the HDR afterloader and the differences between intraluminal catheter lots. An upper limit on the transit dose was also measured using radiochromic film and compared with a simple theoretical model.ResultsThe QA device was capable of detecting performance variations among nasobiliary catheter lots and following radioactive source replacement. The transit dose from a nasobiliary treatment increased by up to one order of magnitude when the source wire encountered higher than normal friction. Three distinct travel speeds of the source wire were observed: 5.2, 17.4, and 54.7 cm/s. The maximum transit dose was 0.3 Gy at a radial distance of 5 mm from a 40.3 kU ¹⁹²Ir source.ConclusionsThe source wire encounters substantially greater friction when it navigates through the nasobiliary brachytherapy catheter. A QA tool that mimics the nasal, stomach, duodenum, and bile duct loops may be used to evaluate transit dose and the afterloader's performance over time.



https://ift.tt/2rTvjBe

The pyrophosphohydrolase RppH is involved in the control of RsmA/CsrA expression in Azotobacter vinelandii and Escherichia coli

Publication date: Available online 18 May 2018
Source:Microbiological Research
Author(s): Leidy Patricia Bedoya-Pérez, Luis Felipe Muriel-Millán, Soledad Moreno, Elva Quiroz-Rocha, Nancy Rivera-Gómez, Guadalupe Espín
In bacteria, the 5′-end-dependent RNA degradation is triggered by the RNA pyrophosphohydrolase RppH converting tri/diphosphate to monophosphate transcripts. This study shows that in the soil bacterium Azotobacter vinelandii, inactivation of rppH gene negatively affected the production of bioplastic poly-β-hydroxybutyrate (PHB) by reducing the expression at the translational level of PhbR, the specific transcriptional activator of the phbBAC biosynthetic operon. The effect of RppH on the translation of phbR seemed to be exerted through the translational repressor RsmA, as the inactivation of rsmA in the rppH mutant restored the phbR expression. Interestingly, in Escherichia coli inactivation of rppH also affected the expression of CsrA, the RsmA homolog. The level of the csrA transcript was higher and more stable in the E. coli rppH mutant than in the wild type strain. Additionally, and in contrast to the csrA mutants that are known to have a defective swimming phenotype, the E. coli rppH mutant showed a hyper-swimming phenotype that was suppressed by a csrA mutation, and the AvRppH restored to wild type level the swimming phenotype to the E. coli rppH mutant. We propose that in both A. vinelandii and E. coli, RppH activity plays a role in the expression of the translational repressor protein RsmA/CsrA.



https://ift.tt/2GuzHeN

Kein Nachweis einer reduzierten Spättoxizität durch Dosisreduktion im elektiven Lymphknotenbereich in der primären Radiochemotherapie von Kopf-Hals-Tumoren

https://ift.tt/2rV3iZd

The confounding effect of background odors on olfactory sensitivity testing

Publication date: Available online 18 May 2018
Source:Journal of Neuroscience Methods
Author(s): A. Oleszkiewicz, L. Rambacher, K.L. Whitcroft, T. Hummel
BackgroundHuman olfactory sensitivity is known to vary significantly across subjects. Furthermore, environmental factors such as background noise and odor are known to affect target odor threshold scores but have not yet been fully delineated. We aimed to determine whether congruent and non-congruent background odor impaired target odor threshold scores.New methodWe performed odor threshold testing in 103 normosmic adults, using phenylethylalcohol (PEA) or linalool as target odors, under three conditions: (a) congruent target and background odors (e.g., PEA in the test and PEA in the background), (b) non-congruent target and background odors (e.g. PEA in the test and Linalool in the background) and (c) no background odor. Background odor was applied to the investigator's glove and testing was performed in an otherwise odorless room.ResultsWe found that congruent background odors significantly impaired target odor threshold scores. Non-congruent background odors also impaired target odor threshold, but significantly more so with PEA as background odor and linalool as target. The best threshold scores were obtained with no background odor. Comparison with Existing Method(s)At present, many testing environments may be contaminated with ambient background odors. We have shown that this may negatively affect odor threshold scores, particularly where background and target odors are congruent.ConclusionsWe suggest that investigators performing odor threshold testing do so in well ventilated, odor free environments.



https://ift.tt/2GxLCrY

Evaluating resective surgery targets in epilepsy patients: A comparison of quantitative EEG methods

Publication date: Available online 18 May 2018
Source:Journal of Neuroscience Methods
Author(s): Michael Müller, Kaspar Schindler, Marc Goodfellow, Claudio Pollo, Christian Rummel, Andreas Steimer
BackgroundQuantitative analysis of intracranial EEG is a promising tool to assist clinicians in the planning of resective brain surgery in patients suffering from pharmacoresistant epilepsies. Quantifying the accuracy of such tools, however, is nontrivial as a ground truth to verify predictions about hypothetical resections is missing.New methodAs one possibility to address this, we use customized hypotheses tests to examine the agreement of the methods on a common set of patients. One method uses machine learning techniques to enable the predictive modeling of EEG time series. The other estimates nonlinear interrelation between EEG channels. Both methods were independently shown to distinguish patients with excellent post-surgical outcome (Engel class I) from those without improvement (Engel class IV) when assessing the electrodes associated with the tissue that was actually resected during brain surgery. Using the AND and OR conjunction of both methods we evaluate the performance gain that can be expected when combining them.ResultsBoth methods' assessments correlate strongly positively with the similarity between a hypothetical resection and the corresponding actual resection in class I patients. Moreover, the Spearman rank correlation between the methods' patient rankings is significantly positive.Comparison with existing method(s)To our best knowledge, this is the first study comparing surgery target assessments from fundamentally differing techniques.ConclusionsAlthough conceptually completely independent, there is a relation between the predictions obtained from both methods. Their broad consensus supports their application in clinical practice to provide physicians additional information in the process of presurgical evaluation.



https://ift.tt/2Iq9L9I

Semi-automated quantification and neuroanatomical mapping of heterogeneous cell populations

Publication date: Available online 18 May 2018
Source:Journal of Neuroscience Methods
Author(s): Oscar A. Mendez, Colin J. Potter, Michael Valdez, Thomas Bello, Theodore P. Trouard, Anita A. Koshy
BackgroundOur group studies the interactions between cells of the brain and the neurotropic parasite Toxoplasma gondii. Using an in vivo system that allows us to permanently mark and identify brain cells injected with Toxoplasma protein, we have identified that Toxoplasma-injected neurons (TINs) are heterogeneously distributed throughout the brain. Unfortunately, standard methods to quantify and map heterogeneous cell populations onto a reference brain atlas are time consuming and prone to user bias.New methodWe developed a novel MATLAB-based semi-automated quantification and mapping program to allow the rapid and consistent mapping of heterogeneously distributed cells on to the Allen Institute Mouse Brain Atlas. The system uses two-threshold background subtraction to identify and quantify cells of interest.ResultsWe demonstrate that we reliably quantify and neuroanatomically localize TINs with low intra- or inter-observer variability. In a follow up experiment, we show that specific regions of the mouse brain are enriched with TINs.Comparison with existing methodsThe procedure we use takes advantage of simple immunohistochemistry labeling techniques, use of a standard microscope with a motorized stage, and low cost computing that can be readily obtained at a research institute. To our knowledge there is no other program that uses such readily available techniques and equipment for mapping heterogeneous populations of cells across the whole mouse brain.ConclusionThe quantification method described here allows reliable visualization, quantification, and mapping of heterogeneous cell populations in immunolabeled sections across whole mouse brains.



https://ift.tt/2Gv0c3v

Estrogen receptor positive breast tumors resist chemotherapy by the overexpression of P53 in Cancer Stem Cells

Publication date: Available online 17 May 2018
Source:Journal of the Egyptian National Cancer Institute
Author(s): Fatma Ashour, Mohammed H. Awwad, Hayam E.L. Sharawy, Mohamed Kamal
Background and ObjectivesBreast cancer (BC) is classified according to estrogen receptor (ER) status into ER⁺ and ER⁻ tumors. ER⁺ tumors have a worse response to chemotherapy compared to ER⁻ tumors. BCL-2, TP53, BAX and NF-ΚB are involved in drug resistance in the ER⁺ tumors. Recently it was shown that Cancer Stem Cells (CSCs) play an important role in drug resistance. In this study we tested the hypothesis that CSCs of the ER⁺ tumors resist drug through the overexpression of BCL-2, TP53, BAX and NF-ΚB.MethodsCSCs were isolated by anoikis resistance assay from MCF7 (ER⁺) and MDA-MB-231 (ER⁻) cell lines. Isolated CSCs were treated with doxorubicin (DOX) and the mRNA expression levels of BCL-2, TP53, BAX and NFKB were investigated by quantitative real time PCR (qPCR) with and without treatment.ResultsBCL-2, BAX and NF-ΚB showed decreased expression in MCF7 bulk cancer cells after DOX treatment whereas only BCL-2 and BAX showed decreased expression in MDA-MB-231 bulk cancer cells. Interestingly TP53 was the only gene showed a considerable increase in its expression in CSCs of the ER⁺ MCF7 cell line compared to bulk cancer cells. Moreover, TP53 was the only gene showing exceptionally higher level of expression in MCF7-CSCs compared to MDA-MB-231-CSCs.ConclusionOur results suggest that CSCs in the ER⁺ cells escape the effect of DOX treatment by the elevation of p53 expression.



https://ift.tt/2Izd9eq

Expression of truncated HER2 and its prognostic value in HER2-positive breast cancer patients

Publication date: Available online 17 May 2018
Source:Journal of the Egyptian National Cancer Institute
Author(s): Alaa Mohamed Maria, Mohamed El-Shebiney, Ayman Mohamed El-Saka, Yomna Zamzam
PurposeThe purpose of this work was to assess the truncated form of human epidermal growth factor receptor 2 (HER2) such as p95-HER2 expression in HER2-positive breast cancer (BC) patients who developed metastatic disease after adjuvant treatment with a trastuzumab-containing regimen.Patients and methodsThirty-two histologically diagnosed HER2-positive BC patients who developed distant failure after treatment with trastuzumab-based chemotherapy (CT) regimen as an adjuvant therapy were included in the study. Immunohistochemistry (IHC) method was used to analyze p95-HER2 expression in the formalin-fixed, paraffin-embedded (FFPE) blocks of the enrolled patients.Resultsp95-HER2 was positive in 34.4% of the patients. The median overall survival (OS) was 22.5 and 35 months for p95-HER2 positive and negative patients, respectively (p = 0.036) and the median time to metastases was 14 and 21 months, respectively (p = 0.006). There was a statistically significant association between positive p95-HER2 expression and negative hormonal receptors expression (p = 0.004), high Ki-67 expression (p < 0.001) and development of visceral metastasis (p = 0.034).ConclusionExpression of p95-HER2 in HER2-positive BC patients is significantly associated with negative hormonal receptors expression, high Ki-67 expression, presence of visceral metastases and worse overall survival. A larger study is required to confirm its association with different prognostic factors and its effect on survival.



https://ift.tt/2L7OVK9

Endometrial carcinoma in a single horn of a bicornuate uterus: A case report

Publication date: Available online 17 May 2018
Source:Journal of the Egyptian National Cancer Institute
Author(s): Khaled Gaballa, Carla Cicero, Valerio Gallotta, Gianfranco Zannoni, Giovanni Scambia
We discuss the diagnosis and the management of endometrial carcinoma in a single horn of bicornuate uterus in a 64-year-old woman as a case report. The case underwent laparoscopic radical hysterectomy and bilateral iliac lymphadenectomy.The gross examination of the uterus revealed a bicornuate uterus with a greater horn of 12 × 9 × 8 cm and a smaller horn of 10 × 3 cm. The cavity of the greater horn showed a neoplastic growth of 10 cm with infiltration of about 1,8 cm of the myometrium from whole thickness of 1.9 cm. while the other horn was free of tumor tissue.The microscopic examination of the uterus revealed G2 endometrioid adenocarcinoma of the endometrium of the greater horn with infiltration of more than 50% of the myometrium.In the presence of bicornuate uterus, a bilateral endometrial biopsy should be performed in order to reduce the risk of delayed or missed diagnosis.The management of a case of bicornuate unicollis uterus with endometrial carcinoma in only one horn is the same as patients with endometrial cancer in single uterus and depends mainly on stage and histological grade of the tumor.The possibility of existence of a separate uterine cavity should always be considered when endometrial cancer is clinically suspected but pathology fails to confirm the diagnosis. This points out the importance of a careful physical examination and radiographic evaluation in such cases.



https://ift.tt/2KCqZNE

A synthetic mitochondrial-based vector for therapeutic purposes

Publication date: Available online 18 May 2018
Source:Medical Hypotheses
Author(s): Michael Renteln
Delivery of large DNA constructs is necessary for combinatorial, anti-aging gene therapy. However, this is hindered by the lack of a non-inflammatory vector with sufficient packaging space and the ability to effectively spread through tissue. It is possible that a mitochondrion, altered to be able to secrete therapeutic proteins, could serve as an ideal gene delivery vector in this regard (for post-mitotic cells at least). Initial transfection of mitochondria with a therapeutic gene vector could be undertaken by MITO-Porter, i.e., a dual-layered fusogenic liposomal-based delivery system. Then, once a protein export pathway from the mitochondrial matrix to the cytoplasm is achieved via Sec translocon installation in the inner membrane (IM), three other components would be necessary for vector maintenance. First of all, fusion with other mitochondria must be prevented through mitofusin-cleaving protease expression on the outer membrane (OM). Second of all, mitophagy must be evaded via the expression of deubiquitylases (DUBs) on the OM. Third of all, free radical damage to the membrane over time could be prevented by shutting down electron transport chain (ETC) activity via destruction of the endogenous mitochondrial DNA (mtDNA) inside the vector – and expression of an ATP import channel to harvest sufficient energy from the host cell. The most crucial part of this plan would be to achieve Sec translocon installation in the IM. The hypothesis of this article is that Sec translocon installation into the IM may be achieved using one of a few molecular methods described herein. It is possible that it could simply occur through gene expression from a mitochondrial matrix-localized gene construct and spontaneous (or Oxa1-assisted) insertion into the mitochondrial IM. Alternatively, it could be incorporated into the MITO-Porter IM prior to fusion with patient-derived mitochondria. Lastly, it may be sent to the mitochondrial IM via the TIM/TOM complex, although hydrophobic membrane proteins may fold prematurely in the cytoplasm before reaching the mitochondrial TIM/TOM complex. Regardless, SecYEG, when present in the IM to a small degree initially, should suffice to install more copies of itself from a mitochondrial matrix-localized gene vector. After proteins (with a C-terminal tag and autotransporter domain) have been sent to the intermembrane space from the matrix in unfolded form, the endogenous SAM complex would suffice to export them to the OM, where the relevant (passenger) domain may be cleaved off by an orthogonal protease and released into the cytoplasm.



https://ift.tt/2Gw5JXt

Prevalence of temporomandibular disorders in patients with Hashimoto thyroiditis

Abstract

Objectives

Autoimmune thyroid disease (AITD), also known as Hashimoto thyroiditis (HT), is a degenerative inflammatory disease with high prevalence among women and has been associated with fibromyalgia and widespread chronic pain. The goal was to determine the frequency of temporomandibular disorders (TMD) in patients with HT.

Methods

In all, 119 women (age 19–60 years) were divided into a study (52 women diagnosed with HT) and a control (67 healthy individuals, of which 15 were excluded) group. Serum concentrations of thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), anti-thyroglobulin (Tg) and anti-thyroid peroxidase (TPO) antibody levels were measured. The temporomandibular jaw and muscles were examined using the German Society of Functional Diagnostics and Therapy guidelines. The Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) was used to assess TMD. Standardized questionnaires, incorporating epidemiological criteria, state and treatment of the thyroid disease, Helkimo Index (HI), and Fonseca Anamnestic Index (FAI), were filled out by all patients.

Results

The two groups did not differ in terms of demographic parameters or mandibular jaw mobility. Significantly higher levels of anti-TPO and anti-Tg were attested in all subjects of the HT group. Markedly elevated prevalence of TMD was found in the HT group. Muscle pain and stiffness were found in 45 (86.5%) subjects of the HT group (p < 0.001), of whom 33 (63.4%) also had disc displacement with reposition (p < 0.001). Whereas 50% of the control group showed no TMD symptoms, all subjects in the HT group had symptoms.

Conclusions

A significantly elevated prevalence of TMD was found in patients with HT. Thus, patients with TMD who do not respond to therapy should be referred for thyroid diagnostic workup.

https://ift.tt/2Kzr5G2

Association of anterior and posterior occlusal planes with different Angle and skeletal classes in permanent dentitions

Abstract

Objectives

Malocclusions affect about two-thirds of the population and orthodontic treatment is justified in 65% of these. However, the associations between anterior and posterior occlusal plane (AOP, POP) inclinations and Angle classification are lacking.

Patients and methods

In a retrospective study, lateral cephalometric radiograph tracings of 230 previously untreated Caucasians, aged 13 to 49 years, yielded inclines of the bisector occlusal plane, AOP, and POP. All inclinations were referenced to the Sella-Nasion line and the Frankfort horizontal and were assigned to the Angle classification as well as skeletal groups (retrognathic, neutral, prognathic). Quantile regressions were calculated.

Results

In the skeletal groups the angles between Sella-Nasion line and both AOP and POP were significantly different between the groups (p < 0.01), showing steep inclines in skeletal class II and flat inclines in skeletal class III. The angles Frankfort horizontal-to-POP and Frankfort horizontal-to-AOP showed the same trends but only the latter differed significantly between the groups (p = 0.02). Among the Angle groups, AOP inclinations did not differ significantly for both reference planes whereas POP inclinations were significantly different (p = 0.01 to Frankfort horizontal, p = 0.02 to Sella-Nasion). Angle class I patients showed the flattest POP.

Conclusion

Occlusal plane inclines, measured to Sella-Nasion, were more consistent than those referenced to Frankfort horizontal. Sella-Nasion related anterior and posterior occlusal plane inclinations were steep in skeletal class II and flat in skeletal class III patients over all quantiles. Using the Angle classification, anterior and posterior occlusal plane inclinations did not follow this principle.

https://ift.tt/2IxcDxN

Prevalence of temporomandibular disorders in patients with Hashimoto thyroiditis

Abstract

Objectives

Autoimmune thyroid disease (AITD), also known as Hashimoto thyroiditis (HT), is a degenerative inflammatory disease with high prevalence among women and has been associated with fibromyalgia and widespread chronic pain. The goal was to determine the frequency of temporomandibular disorders (TMD) in patients with HT.

Methods

In all, 119 women (age 19–60 years) were divided into a study (52 women diagnosed with HT) and a control (67 healthy individuals, of which 15 were excluded) group. Serum concentrations of thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), anti-thyroglobulin (Tg) and anti-thyroid peroxidase (TPO) antibody levels were measured. The temporomandibular jaw and muscles were examined using the German Society of Functional Diagnostics and Therapy guidelines. The Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) was used to assess TMD. Standardized questionnaires, incorporating epidemiological criteria, state and treatment of the thyroid disease, Helkimo Index (HI), and Fonseca Anamnestic Index (FAI), were filled out by all patients.

Results

The two groups did not differ in terms of demographic parameters or mandibular jaw mobility. Significantly higher levels of anti-TPO and anti-Tg were attested in all subjects of the HT group. Markedly elevated prevalence of TMD was found in the HT group. Muscle pain and stiffness were found in 45 (86.5%) subjects of the HT group (p < 0.001), of whom 33 (63.4%) also had disc displacement with reposition (p < 0.001). Whereas 50% of the control group showed no TMD symptoms, all subjects in the HT group had symptoms.

Conclusions

A significantly elevated prevalence of TMD was found in patients with HT. Thus, patients with TMD who do not respond to therapy should be referred for thyroid diagnostic workup.

https://ift.tt/2Kzr5G2

Use patterns and frequency of hand hygiene in healthcare facilities: Analysis of electronic surveillance data

Publication date: Available online 18 May 2018
Source:American Journal of Infection Control
Author(s): Jessica Albright, Bruce White, Daniel Pedersen, Pete Carlson, Lisa Yost, Cheryl Littau
BackgroundHealthcare workers perform hand hygiene much more frequently than workers in other fields. As a result, healthcare workers have a higher exposure to topical antiseptic products.MethodsFive tertiary care facilities were equipped with an electronic hand hygiene compliance monitoring system. Alcohol-based handrub (ABHR) and handwash use was recorded on a worker-specific basis for 6 months. Total hand hygiene product use and total hours worked were calculated for each worker to determine use frequency.ResultsA detailed, descriptive analysis of hand hygiene practices was performed. All facilities demonstrated high hand hygiene compliance rates (>85%). ABHR use was more frequent (9.1 uses/hour, 95^th percentile) than handwashing (2.1 uses/hour, 95^th percentile). This study identified a relationship between hand hygiene frequency and job function. Nursing and nonclinical support staff demonstrated higher usage rates than other healthcare workers. For these workers with high hand hygiene frequency, 95^th percentile usage rates for ABHR use and handwashing were 9.6 and 2.2 uses/hour, respectively.ConclusionsThis extensive dataset, monitoring nearly 4000 healthcare workers and more than 6 million data points, provides a detailed description of current hand hygiene practices of hospital staff. ABHR was used more frequently than handwashing. Job function was found to affect hand hygiene frequency, with nonclinical staff and nursing staff demonstrating elevated rates of hand hygiene.



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Lack of improvement in antimicrobial prescribing after a diagnosis of Clostridium difficile and impact on recurrence

Publication date: Available online 18 May 2018
Source:American Journal of Infection Control
Author(s): Richard L. Watson, Christopher J. Graber
BackgroundAntimicrobial use is one of the largest modifiable risk factors for development of Clostridium difficile infection (CDI). We sought to determine if a recent diagnosis of CDI affected the appropriateness of subsequent antimicrobial prescribing.MethodsThis study is a retrospective electronic chart review of the Greater Los Angeles Veterans Administration. Medication administration records were reviewed for all patients with new CDI from 2015-2016 to determine the appropriateness (drug choice, duration, and dosage) of all non-CDI antimicrobials prescribed within 90 days pre- and post-initial CDI (iCDI) positive testing.ResultsOf the 210 patients diagnosed with new-onset iCDI, 140 met inclusion criteria. Of antimicrobial courses prescribed, 40.6% of pre-iCDI were inappropriate compared with 43.1% of post-iCDI, demonstrating no difference in prescribing habits (P = .717). Thirty-three patients developed recurrent CDI (rCDI). After adjustment for other known risk factors, inappropriate antimicrobial use was associated with a significant increased risk of recurrence compared with appropriate use alone (odds ratio [OR], 6.19; 95% confidence interval [CI], 1.45-26.42). Antimicrobial use in general was associated with increased recurrence compared with no antimicrobial use post-iCDI (OR, 2.6; 95% CI, 1.16-5.84); however, after adjustment, it was no longer significant (OR, 2.13; 95% CI, 0.90-5.04).ConclusionsThe appropriateness of antimicrobial prescribing was not affected by the diagnosis of recent CDI. Inappropriate antimicrobial use after iCDI was associated with higher risk of rCDI.



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Prevalence of infections and antimicrobial prescribing in Australian aged care facilities: Evaluation of modifiable and nonmodifiable determinants

Publication date: Available online 18 May 2018
Source:American Journal of Infection Control
Author(s): Bennett Noleen, Nabeel Imam, Rodney James, Caroline Chen, Ann Bull, Karin Thursky, Kirsty Buising, Leon Worth
BackgroundInfections in aged care residents are associated with poor outcomes, and inappropriate antimicrobial prescribing contributes to adverse events, such as the emergence of antimicrobial resistance. The objective of this study was to identify resident- and facility-level factors associated with infection and antimicrobial prescribing in Australian aged care residents.MethodsUsing data captured by a national point-prevalence survey (the Aged Care National Antimicrobial Prescribing Survey), risk and protective factors were determined by multivariate Poisson regression.ResultsIn 2017, 292 facilities were surveyed. Infection prevalence was 2.9% (95% confidence interval [CI], 2.6%-3.2%), and antimicrobial use prevalence was 8.9% (95% CI, 8.4%-9.4%). Resident-level factors associated with infection prevalence included urinary catheterization and hospital admission within the last 30 days; facility-level factors included state and multipurpose service provision. Resident-level factors associated with antimicrobial prescribing included infection signs and symptoms; facility-level factors included state, nonmetropolitan locality, and not-for-profit status. Availability of guidelines for urinary tract infection (UTI) management was associated with reduced antimicrobial prescribing.ConclusionsLooking ahead, reports should be peer grouped by significant facility-level factors. Priority should be given to implementing UTI management guidelines and prevention of infection in residents with indwelling urinary catheters. Enhanced monitoring and prevention strategies are required for residents recently admitted to hospital.



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Enacting high reliability principles while caring for people with Ebola Virus Disease

Publication date: Available online 18 May 2018
Source:American Journal of Infection Control
Author(s): Bonnie Mowinski Jennings, Katherine A. Yeager, Nancye R. Feistritzer, Mary M. Gullatte, Kristy K. Martyn
BackgroundFear surrounds Ebola Virus Disease (EVD) because it is highly infectious. Yet members of the Serious Communicable Diseases Unit (SCDU) at Emory University Hospital (EUH) had to overcome that fear when caring for patients with EVD.PurposeThe analysis reported here illustrates how the members of EUH's SCDU tacitly enacted high reliability (HR) principles while caring for patients with EVD.MethodsA qualitative study was conducted to describe the experience of members of the EUH SCDU who worked with EVD patients in 2014. We completed 17 semi-structured interviews involving registered nurses, physicians, and support personnel (eg, laboratory technicians). Interview recordings were transcribed and analyzed using conventional content analysis. Exploring HR principles was not among the questions guiding this exploration, but the participants repeatedly described concepts related to HR.ResultsThe goal of the SCDU team was to save patients' lives while protecting their own lives. Rigorous training and meeting high standards were required to make the team. The fear surrounding EVD set in motion the enactment of HR principles. HR principles served to alleviate failures or breakdowns in infection prevention and control, thus keeping patients and staff safe.ConclusionsThese findings illustrate that it is possible to move HR principles from theory to practice in high-risk situations. HR principles were essential to safety and to infection prevention and control.



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Hand hygiene adherence in relation to influenza season during 6 consecutive years

Publication date: Available online 18 May 2018
Source:American Journal of Infection Control
Author(s): Rosamaria Fulchini, Philipp Kohler, Christian R. Kahlert, Werner C. Albrich, Rolf Kuhn, Matthias Hoffmann, Matthias Schlegel
Hand hygiene (HH) is the single most important measure in reducing the burden of healthcare-acquired infections. Based on 12,740 HH opportunities observed during 6 consecutive years at our tertiary care center, HH adherence among healthcare workers (HCWs) was significantly better during influenza season compared to non-influenza periods, after controlling for important covariables (odds ratio = 1.17, 95% confidence interval 1.05-1.30). This finding suggests that HH awareness is increased during influenza periods, which could have implications for HCW education.



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Do WiFi-based hand hygiene dispenser systems increase hand hygiene compliance?

Publication date: Available online 18 May 2018
Source:American Journal of Infection Control
Author(s): Simone Scheithauer, Johannes Bickenbach, Hans Heisel, Patrick Fehling, Gernot Marx, Sebastian Lemmen
Innovative methods to ensure better compliance in hand hygiene are urgently needed. The aim of this study was to determine if WiFi-based hand hygiene dispenser-driven self-assessment systems (Wireless Fidelity, WiFi-dispenser) can support the work of infection control teams. Our results suggest that the continuous monitoring of dispenser usage can be a valuable addition to infection prevention and control programs, when used in a bundle in combination with conventional hand hygiene training.



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How to better monitor and clean irregular surfaces in operating rooms: Insights gained by using both ATP luminescence and RODAC assays

Publication date: Available online 18 May 2018
Source:American Journal of Infection Control
Author(s): Olivia Ellis, Hilary Godwin, Maren David, Dan J. Morse, Romney Humphries, Daniel Z. Uslan
BackgroundA major limitation to developing evidence-based approaches to infection prevention is the paucity of real-time, quantitative methods for monitoring the cleanliness of environmental surfaces in clinical settings. One solution that has been proposed is adenosine triphosphate (ATP) bioluminescence assays, but this method does not provide information about the source of the ATP.Materials/MethodsTo address this gap, we conducted a study in which ATP bioluminescence was coupled with traditional RODAC sampling and matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry to assess which organisms were viable and present. Using this mixed assessment approach, we evaluated cleaning of 5 different types of high-touch surfaces (overhead lights, door handles, anesthesia keyboards, mattresses, and side tables) in operating rooms.ResultsWhether surfaces tested cleaner after turnaround than they did before turnaround depended on the surface type. Before and after cleaning, flat, covered surfaces (mattresses and side tables) were more likely to pass as "clean" by ATP assay than uncovered, irregularly shaped surfaces (overhead lights, door handles, and anesthesia keyboards). Irregularly shaped surfaces were more likely to pass by RODAC assay than by ATP assay after cleaning.ConclusionOur results suggest that irregularly shaped surfaces in operating rooms may require enhanced covering, cleaning, and monitoring protocols compared to more regularly shaped surfaces.



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Effect of methicillin-resistant Staphylococcus aureus in Japan

Publication date: Available online 18 May 2018
Source:American Journal of Infection Control
Author(s): Hironori Uematsu, Kazuto Yamashita, Seiko Mizuno, Susumu Kunisawa, Keigo Shibayama, Yuichi Imanaka
BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) is the most common antimicrobial-resistant organism identified in Japanese health care facilities. This study analyzed the clinical and economic burdens attributable to methicillin resistance in S aureus in Japanese hospitals.MethodsWe retrospectively investigated data from 14,905 inpatients of 57 hospitals combined with data from nosocomial infection surveillance and administrative claim databases. The participants were inpatients with admission from April 1, 2014, to discharge on March 31, 2016. The outcomes were evaluated according to length of stay, hospital charges, and in-hospital mortality. We compared the disease burden of MRSA infections with methicillin-susceptible S aureus (MSSA) infections based on patients' characteristics and onset periods.ResultsWe categorized 7,188 and 7,717 patients into MRSA and MSSA groups, respectively. The adjusted effects of the MRSA group were 1.03-fold (95% confidence interval [CI] 1.01-1.05) and 1.04-fold (95% CI, 1.01-1.06), respectively, with an odds ratio of 1.14 (95% CI, 1.02-1.27).ConclusionsThe results of this study found that patient severity and onset delays were positively associated with both MRSA and burden and that the effect of methicillin resistance remained significant after adjustment.



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Evaluation of adenosine triphosphate test for cleaning assessment of gastroscopes and the effect on workload in a busy endoscopy center

Publication date: Available online 18 May 2018
Source:American Journal of Infection Control
Author(s): Cristiane Schmitt, Amanda Luiz Pires Maciel, Icaro Boszczowski, Thaís Pereira da Silva, Eliane Aparecida Job Neves, Giulio Fabio Rossini, Camila Rizek, Silvia Figueiredo Costa, Rogério Ferreira Lourenço, Michelle J. Alfa
ObjectiveUsing adenosine triphosphate (ATP) tests to assess manual cleaning of gastroscopes and to determine the associated workload in a busy endoscopy unit.MethodsPatient-used gastroscopes were sampled before and after cleaning to assess ATP levels, bioburden, and protein. Samples were collected by flushing 20 mL of sterile water through the biopsy port to the distal end. Time spent for reprocessing and performing the ATP test was recorded.ResultsTwenty-four samples were collected from 10 gastroscopes. After manual cleaning, 14/24 (58.3%) samples had no microbial growth (mean, 21 colony-forming units/cm²), and in 22/24 (91.7%) samples the protein was undetectable (mean, 0.04 µg/cm²). ATP test was above the cutoff (200 relative light units [RLU]) in 17/24 (70.8%) samples (mean, 498 RLU). After the second cleaning, 11/17 (64.7%) gastroscopes still failed the ATP test (mean, 321.2 RLU). The mean time spent to perform manual cleaning and ATP tests was 16 and 8 minutes, respectively. Hence, each test increased the length of time for cleaning plus testing cleanliness by 50%.ConclusionFurther studies regarding the optimal cutoff for ATP tests are needed. ATP tests for cleaning monitoring are easy to perform and provide immediate feedback to the team. However, the increased workload needs to be considered.



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Exploring the why and how questions associated with adoption of evidence-based practices to reduce health care-associated infections

Publication date: Available online 18 May 2018
Source:American Journal of Infection Control
Author(s): Joan N. Hebden




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Vaccines and the risk of acute disseminated encephalomyelitis

Publication date: Available online 18 May 2018
Source:Vaccine
Author(s): Yong Chen, Fubao Ma, Yuanling Xu, Xuhua Chu, Jinlin Zhang
BackgroundIt is important to examine the risk of Acute disseminated encephalomyelitis (ADEM) after vaccination.MethodsWe conducted a nested case–control study between January 2011 and December 2015. Four controls per case were matched for age, gender, address. An independent expert committee validated the diagnoses of cases and controls. Data on vaccinations were obtained from computerized vaccination records. The analyses were conducted with the use of conditional logistic regression.ResultsThe analyses include 272 cases of ADEM and 1096 controls. No increase in the risk of ADEM was observed for vaccination against hepatitis B, influenza, polio(live), diphtheria, pertuss(acellular), tetanusis, measles, mumps, rubella, Japanese Encephalitis, meningitis, hepatitis A, varicella and rabies vaccines. Vaccine was associated with a statistically significant increase in risk in the 31–60-day exposure interval (OR, 4.04 [95% CI, 1.07–12.69]), but not the 0–30 and 61–180-day interval. There was no association between vaccine received and the recurrence of ADEM.ConclusionsFindings from the present study do not demonstrate an association of vaccines with an increased risk of ADEM and its recurrence among either paediatric (≤18 years) or adult (>18 years) individuals within the 180 days after vaccinations. The finding in children in the 31–60 day risk interval is likely coincidental and was not confirmed in separate self-control analyses.



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A viral-vectored RSV vaccine induces long-lived humoral immunity in cotton rats

Publication date: Available online 18 May 2018
Source:Vaccine
Author(s): Jessica L. Grieves, Zhiwei Yin, Adolfo Garcia-Sastre, Ignacio Mena, Mark E. Peeples, Heidi P. Risman, Hannah Federman, Marvin J. Sandoval, Russell K. Durbin, Joan E. Durbin
Human respiratory syncytial virus (RSV) is the leading cause of lower airway disease in infants worldwide and repeatedly infects immunocompetent individuals throughout life. Severe lower airway RSV infection during infancy can be life-threatening, but is also associated with important sequelae including development of asthma and recurrent wheezing in later childhood. The basis for the inadequate, short-lived adaptive immune response to RSV infection is poorly understood, but it is widely recognized that RSV actively antagonizes Type I interferon (IFN) production. In addition to the induction of the anti-viral state, IFN production during viral infection is critical for downstream development of robust, long-lived immunity. Based on the hypothesis that a vaccine that induced robust IFN production would be protective, we previously constructed a Newcastle disease virus-vectored vaccine that expresses the F glycoprotein of RSV (NDV-F) and demonstrated that vaccinated mice had reduced lung viral loads and an enhanced IFN-γ response after RSV challenge. Here we show that vaccination also protected cotton rats from RSV challenge and induced long-lived neutralizing antibody production, even in RSV immune animals. Finally, pulmonary eosinophilia induced by RSV infection of unvaccinated cotton rats was prevented by vaccination. Overall, these data demonstrate enhanced protective immunity to RSV F when this protein is presented in the context of an abortive NDV infection.



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Knowledge gaps persist and hinder progress in eliminating mumps

Publication date: Available online 18 May 2018
Source:Vaccine
Author(s): R. Ramanathan, E.A. Voigt, R.B. Kennedy, G.A. Poland
Mumps, a common childhood disease in the pre-vaccine era that causes swelling of the parotid salivary glands, can lead to orchitis, viral meningitis, and sensorineural deafness. While the incidence of disease decreased dramatically after the vaccine was added to standard vaccination schedules, the disease has made a substantial resurgence in recent years. As a result, it becomes critical to examine the factors involved in recurring outbreaks. Although low and incomplete vaccination coverage may be a key reason, it does not fully explain the issue due to the high rate of occurrence in populations with high vaccination coverage rates. Multiple studies suggest that waning immunity and secondary vaccine failure play a large role, the effects of which were previously masked by subclinical boosting. Significant knowledge gaps persist around the exact role and mechanism of waning immunity and demonstrate the need for more research in this area, as well as a reevaluation of mumps vaccine policy.



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Challenges of cold chain quality for routine EPI in south-west Burkina-Faso: An assessment using automated temperature recording devices

Publication date: Available online 18 May 2018
Source:Vaccine
Author(s): C. Sow, C. Sanou, C. Medah, M. Schlumberger, F. Mireux, I. Ouédraogo, S.M. Ouédraogo, E. Betsem
BackgroundAbnormal temperatures are a major issue for vaccines within the Expanded Program of Immunization in tropical climates. Prolonged exposure to temperatures outside the standard +2 °C/+8 °C range can impact vaccine potency.MethodsThe current study used automatic temperature recording devices (Testostore 171-1©) to monitor cold chain in remote areas of Western Burkina Faso. A series of 25 randomly selected health centers representing 33% of the existing 176 EPI facilities in Western Burkina Faso were prospectively assessed for eight months in 2015. Automatic measurements were compared to routine temperature loggers and vaccine vial monitors (VVM).ResultsThe median age for all refrigerators was 9 years with 10/25 (42%) older than 10 years. Adverse temperatures were recorded in 20/24 (83%) refrigerators and ranged from −18.5 °C to +34.2 °C with 12,958/128,905 (10%) abnormal hourly records below +2 °C and 7357/128,905 (5.7%) above +8 °C. Time of day significantly affected the rate of temperature excursions, with higher rates from 00 am to 06 am (p < 0.001) for low temperatures and 10–12 am (p < 0.001) and 13–16 pm (p < 0.001) for high temperatures. Abnormal temperatures lasted from 1 h to 24 h below +2 °C and 13–24 h above +8 °C. Standard manual registers reported only 182/2761 (7%) inadequate temperatures and VVM color change detected only 133/2465 (5%) disruptions. Reliability of the refrigerators ranged from 48% to 98.7% with a median of 70%. Risk factors for excursions were old age of the refrigerators, the months of April and May, hours of high activity during the day, and health staff-associated factors such as inappropriate actions or insufficient knowledge.ConclusionImportant cold chain reliability issues reported in the current study in Western Burkina Faso raise concern about vaccine potency. In the absence of systematic renewal of the cold chain infrastructure or improved staff training and monitoring, antibody response assessment is recommended to study levels of effective immunization coverage.



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Epidemiology of acute diarrhea caused by rotavirus in sentinel surveillance sites of Vietnam, 2012–2015

Publication date: Available online 18 May 2018
Source:Vaccine
Author(s): Dang Thi Thanh Huyen, Duong Thi Hong, Nguyen Thanh Trung, Tran Thi Nguyen Hoa, Nguyen Kieu Oanh, Ho Vinh Thang, Nguyen Thi Thanh Thao, Do Manh Hung, Makiko Iijima, Kimberley Fox, Varja Grabovac, James Heffelfinger, Nyambat Batmunkh, Dang Duc Anh
A prospective, multicentre study was conducted in four sentinel surveillance hospitals to assess the trend and epidemiology of acute diarrhea caused by Rotavirus in Vietnam. During the period 2012–2015, a total 8,889 children under 5 years of age were enrolled in the surveillance, and 8689 stool samples were collected. Of these cases, Rotavirus was most common pathogen 46.7% (4054 cases); in which 26.6% (1117) rotavirus-positive stool samples were evaluated to identify genotypes. The proportion of rotavirus positive specimens decreased annually from 54.7% in 2012 to 36.6% in 2015. Rotavirus was detected year-round, but most rotavirus gastroenteritis cases (77.1%) occurred between December and May, corresponding to the rotavirus seasonality. It is found that the peaks varied by regions. Rotavirus positivities varied between the youngest and oldest age, but children 6–11 months old (38.8%) and 12–23 months old (38.4%) counted for most cases. A significant higher number of diarrhea within 24 hours (8.3 times, 95%CI: 8.1–8.4 times) and higher proportion of severe dehydration (12.9%) in Rotavirus positive group than that in Rotavirus negative group (7.7 times, 95%CI: 7.6–7.9 times; and 9.7%, respectively). A downtrend of prevalence of G1P[8] was observed from 82% in 2013 to 15% in 2015. However, G2P[4] was found in 5% of samples in 2012, 9% in 2013, 36% in 2014, and 28% in 2015. Rotavirus infection is the most important cause of acute diarrhea among hospitalized children in Vietnam, and a rotavirus vaccination program for children may significantly reduce this disease.



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Overexpression of ABCB4 contributes to acquired doxorubicin resistance in breast cancer cells in vitro

Abstract

Purpose

Doxorubicin is one of the most active agents in the first-line therapy for metastatic breast cancer, but its utility is partially limited by the frequent emergence of doxorubicin resistance. In this study, we aimed to investigate the role of ATP-binding cassette sub-family B, member 4 (ABCB4) in acquired doxorubicin resistance in breast cancer cells, as well as its potential mechanism.

Methods

In doxorubicin-sensitive and -resistant breast cancer cell lines MCF-7 and MDA-MB-231, the expression levels of ABCB4 were detected using real-time quantitative PCR and Western blot analysis, the DNA methylation and histone acetylation status of ABCB4 gene were investigated by bisulfite-sequencing PCR (BSP) and chromatin immunoprecipitation (ChIP) assays, and the doxorubicin sensitivity and intracellular doxorubicin accumulation were observed using cell cytotoxicity assay and flow cytometry. In Madin–Darby Canine Kidney (MDCKII) cells, In vitro transport assay was used to assess the ABCB4-mediated transport of doxorubicin.

Results

ABCB4 was overexpressed in doxorubicin-resistant breast cancer cells compared to their doxorubicin-sensitive counterparts, which was associated with reduced DNA methylation as well as increased histone acetylation at the ABCB4 promoter. ABCB4 could actively pump doxorubicin out of the cells, and knockdown of ABCB4 increased doxorubicin sensitivity and intracellular accumulation in doxorubicin-resistant breast cancer cells.

Conclusions

Our results indicate that ABCB4 is overexpressed in breast cancer cells with acquired doxorubicin resistance, which could be attributed, at least partially, to the epigenetic modifications of ABCB4 gene. ABCB4 mediates the efflux transport of doxorubicin, and contributes to the acquired resistance of doxorubicin in breast cancer cells.

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