bluuebunny/crossref_metadata_2025 huggingface dataset:
Randomized clinical trial of open versus laparoscopic left lateral hepatic sectionectomy within an enhanced recovery after surgery programme (ORANGE II study)
Authors: Wong-Lun-Hing E M , van Dam R M , van Breukelen G J P , Tanis P J , Ratti F , van Hillegersberg R , Slooter G D , de Wilt J H W , Liem M S L , de Boer M T , Klaase J M , Neumann U P , Aldrighetti L A , Dejong C H C , Terkivatan T , Verhoef C , Porte R J , Haverman J W , Busch O R , Boermeester M A , Besselink M G , Molenaar I Q , Borel Rinkes I H M , Bosscha K , van der Vorst J R , de Waard J W D , Gerhards M F , Patijn G A , Schmeding M , Primrose J N , Abu Hilal M , Dagher I , Laurent A , Topal B , Edwin B , Lassen K , van Duyn E B , Ambergen A W , Olde Damink S W , Bemelmans M H
Published: January 2017

Background

Laparoscopic left lateral sectionectomy (LLLS) has been associated with shorter hospital stay and reduced overall morbidity compared with open left lateral sectionectomy (OLLS). Strong evidence has not, however, been provided.

Methods

In this multicentre double-blind RCT, patients (aged 18–80 years with a BMI of 18–35 kg/m2 and ASA fitness grade of III or below) requiring left lateral sectionectomy (LLS) were assigned randomly to OLLS or LLLS within an enhanced recovery after surgery (ERAS) programme. All randomized patients, ward physicians and nurses were blinded to the procedure undertaken. A parallel prospective registry (open non-randomized (ONR) versus laparoscopic non-randomized (LNR)) was used to monitor patients who were not enrolled for randomization because of doctor or patient preference. The primary endpoint was time to functional recovery. Secondary endpoints were length of hospital stay (LOS), readmission rate, overall morbidity, composite endpoint of liver surgery-specific morbidity, mortality, and reasons for delay in discharge after functional recovery.

Results

Between January 2010 and July 2014, patients were recruited at ten centres. Of these, 24 patients were randomized at eight centres, and 67 patients from eight centres were included in the prospective registry. Owing to slow accrual, the trial was stopped on the advice of an independent Data and Safety Monitoring Board in the Netherlands. No significant difference in median (i.q.r.) time to functional recovery was observed between laparoscopic and open surgery in the randomized or non-randomized groups: 3 (3–5) days for OLLSversus 3 (3–3) days for LLLS; and 3 (3–3) days for ONRversus 3 (3–4) days for LNR. There were no significant differences with regard to LOS, morbidity, reoperation, readmission and mortality rates.

Conclusion

This RCT comparing open and laparoscopic LLS in an ERAS setting was not able to reach a conclusion on time to functional recovery, because it was stopped prematurely owing to slow accrual. Registration number: NCT00874224 (https://www.clinicaltrials.gov).
A UPLC–MS/MS method for analysis of vancomycin in human cerebrospinal fluid and comparison with the chemiluminescence immunoassay
Authors: Mei Shenghui , Wang Jiaqing , Zhu Leting , Chen Ruiling , Li Xingang , Chen Kai , Chen Guangqiang , Zhou Jianxin , Wang Qiang , Zhao Zhigang
Published: January 2017

Vancomycin (VCM) is clinically used in treating patients with postoperative intracranial infections. The cerebrospinal fluid (CSF) concentration of VCM varies greatly among patients. To guide the dosage regimens, monitoring of VCM in CSF is needed. However a method for analysis of VCM in human CSF is lacking. An ultraperformance liquid chromatography tandem mass spectrometry (UPLC–MS/MS) was developed and validated for analysis of VCM in human CSF, and the agreement of UPLC–MS/MS and chemiluminescence immunoassay (CLIA) in the analysis of CSF VCM was evaluated. The ion transitions were m/z 725.5 > 144.1 for VCM and m/z 455.2 > 308.2 for methotrexate (internal standard). The agreement between UPLC–MS/MS and CLIA was evaluated by Bland–Altman plot in 179 samples. The calibration range of the UPLC–MS/MS method was 1–400 mg/L. The inaccuracy and imprecision were −0.69–10.80% and <4.95%. The internal standard normalized recovery and matrix factor were 86.14–99.31 and 85.84–92.07%, respectively. The measurements of CLIA and UPLC–MS/MS were strongly correlated (r > 0.98). The 95% limit of agreement of the ratio of CLIA to UPLC‐MS/MS was 61.66–107.40%. Further studies are warranted to confirm the results.
Linear and Cyclic Depsipeptidomimetics with β‐Lactam Cores: A Class of New αvβ3 Integrin Receptor Inhibitors
Authors: Zabala‐Uncilla Nerea , Miranda José I. , Laso Antonio , Fernández Xavier , Ganboa Jose I. , Palomo Claudio
Published: January 2017

The αvβ3 integrin receptor plays an important role in tumor metastasis and tumor‐induced angiogenesis. The inhibition of this receptor with diverse ligands, antibodies, or cyclic peptides is a promising research field for the treatment of a variety of tumors. The replacement of Phe‐(Me)Val dipeptide by a β‐lactam ring in Cilengitide has led to new products that show higher inhibitory activity than the parent cyclopeptide. In particular, substitution of a peptide bond β‐lactam‐NH‐Asp linkage by a β‐lactam‐O‐Asp ester linkage increases the activity of the new cyclodepsipeptide. In the same way it has been found that open‐chain compounds of the form Asp‐β‐lactam‐Arg can interact with the receptor and inhibit its activity moderately. The integrin inhibitory activity of the synthesized compounds has been established by using the CGH array, a method that appears to be a more reliable trial than the classical adhesion test.
Long‐term follow‐up of arrhythmogenic right ventricular cardiomyopathy patients with an implantable cardioverter‐defibrillator for prevention of sudden cardiac death
Authors: Yin Kang , Ding Ligang , Li Yuqiu , Hua Wei
Published: January 2017

Background

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare inherited cardiomyopathy with a high burden of ventricular arrhythmia, which is an important cause of sudden cardiac death (SCD). Implantable cardioverter‐defibrillator (ICD) is believed to be the most reliable management against SCD.

Hypothesis

Ventricular arrhythmia does not necessarily confer a poor prognosis in ARVC patients with an ICD.

Methods

A total of 39 ARVC patients (34 male) implanted with an ICD at our electrophysiology center and followed up continuously were included in this study. The mean age at diagnosis was 42.1 ± 14.8 years.

Results

Thirty‐three patients (84.6%) had suffered ventricular arrhythmia with hemodynamic compromise before ICD implantation. During a median follow‐up of 48.6 months (interquartile range, 32.3–73.3), 3 patients (7.7%) died, 1 of sudden death, 1 of heart failure, and 1 of cerebral infarction. Twenty‐eight patients (71.8%) experienced 540 appropriate ICD interventions. The first appropriate ICD intervention occurred more than 2 years after initial ICD implantation in 5 patients (12.8%). Twelve patients (30.8%) suffered from electrical storm. The event‐free period was significantly shorter in patients who did not have broad precordial T wave inversion ≥V1–V3 (hazard ratio = 0.39, 95% confidence interval: 0.16‐0.96). No significant difference was shown in antiarrhythmic drugs and radiofrequency catheter ablation before ICD implantation between patients with and without appropriate ICD therapies (P > 0.05).

Conclusions

Recurrence of sustained ventricular tachycardia/ventricular fibrillation is frequent in high‐risk patients with ARVC. The prognosis is favorable for ARVC patients treated with an ICD for prevention of SCD.
Hydro‐Chemical Conditions of Shaping the Water Quality of Shallow Łęczna‐Włodawa Lakes (Eastern Poland)
Authors: Ferencz Beata , Toporowska Magdalena , Dawidek Jarosław , Sobolewski Wojciech
Published: January 2017

Although water quality has been the main concern of ecologists over the last decades, a deterioration of both the quality and quantity of water has been observed worldwide. Understanding the dominant processes shaping eutrophication processes is crucial to sustainable water management in lake catchments. The aim of the study was to determine the importance of elements of lake‐catchment system structures in the processes of shaping lake water quality. The values of loads delivered to the lake basins from their catchments as well as nutrient output were calculated on the basis of stream discharge and nutrient concentration. A range of hydro‐chemical influences of each stream was presented by means of a range of a radius. A model of nutrient transport (prepared in GIS software) was used in the catchment of a lake without tributaries. Additionally, phytoplankton abundance and water quality indices were calculated. The results showed a clear pattern for the following lakes, Syczyńskie > Pniówno > Chuteckie > Tarnowskie, in terms of nutrient load as well as water quality. The hydro‐chemical influence of lake tributaries was determined by runoff processes, which reflected catchment geology, relief, and flushing time. The Q index showed a good ecological status for lakes Chuteckie and Tarnowskie, moderate for Lake Pniówno, and poor for Lake Syczyńskie.
Factors predicting prostate cancer upgrading on magnetic resonance imaging–targeted biopsy in an active surveillance population
Authors: Lai Win Shun , Gordetsky Jennifer B. , Thomas John V. , Nix Jeffrey W. , Rais‐Bahrami Soroush
Published: January 2017

BACKGROUND

The objective of this study was to create a nomogram model integrating clinical and multiparametric magnetic resonance imaging (MP‐MRI)–based variables to predict prostate cancer upgrading in a population of active surveillance (AS) patients.

METHODS

Prostate cancer patients on AS who underwent MP‐MRI with magnetic resonance imaging (MRI)/ultrasound (US) fusion–guided biopsy were identified. Clinical and imaging variables, including the prostate‐specific antigen density (PSAD), number of lesions, total lesion volume, total lesion density, Prostate Imaging Reporting and Data System magnetic resonance imaging suspicion score (MRI‐SS), and duration between prereferral systematic and MRI/US fusion–guided biopsy sessions, were assessed. Logistic regression modeling was used to assess upgrading on MRI/US fusion–guided biopsy. A predictive model for upgrading was calculated with the significant factors identified.

RESULTS

Seventy‐six patients were analyzed with a mean age of 62.5 years and a median prostate‐specific antigen (PSA) level of 5.1 ng/mL. The average duration between prereferral and MRI/US biopsies was 21 months. Twenty patients (26.32%) were upgraded. The PSAD, duration between prereferral and MRI/US biopsies, MRI‐SS, and MRI total lesion density were significantly associated with upgrading. A logistic regression model using these factors to predict upgrading on confirmatory MRI/US fusion biopsy had an area under the curve (AUC) of 0.84, whereas the AUC was 0.69 with PSA alone. On the basis of this model, a nomogram was generated, and using a probability cutoff of 22% as an indication of upgrading, it produced sensitivity, specificity, positive predictive, and negative predictive values of 80%, 81.25%, 57.1%, and 92.86%, respectively.

CONCLUSIONS

The integration of MRI findings with clinical parameters can add value to a model predicting upgrading from a Gleason score of 3 + 3 = 6 in men on AS. This can potentially be used as a noninvasive approach to confirm AS patients with low‐risk disease for whom biopsy may be deferred. Cancer 2017;123:1941–1948. © 2017 American Cancer Society.
A qualitative investigation in the role of the baby in recovery from postpartum psychosis
Authors: Plunkett Charlene , Peters Sarah , Wieck Angelika , Wittkowski Anja
Published: January 2017

Psychosis after childbirth is a rare but severe type of mental health difficulty experienced by perinatal women. Research has explored mothers' experiences of onset and recovery from psychosis after childbirth. This study explored the role of the baby in 12 mothers' experiences of recovery. A thematic analysis of the data identified three core themes that described the role of the baby in the mothers' recovery from psychosis after childbirth. Findings revealed that the baby was central to recovery, experienced by mothers as both helpful and unhelpful. The baby interacted with the mother, increasing self‐efficacy, and reducing emotional distress. Findings also showed that the baby could act as a barrier to recovery by increasing the women's emotional distress and hindering access to help and self‐care. The findings of the study add to the existing evidence based on recovery from psychosis after childbirth. The research and clinical implications of these findings are discussed with reference to the existing literature.

Key Practitioner Message

The baby has an important role in recovery from psychosis after childbirth.

The baby can be perceived by mothers to both hinder and help their recovery.

Interacting with the baby can be helpful for the mothers' recovery by improving their self‐efficacy and reducing emotional distress.

Specialist interventions offered by a mother and baby unit can provide practical support that facilitates mother–baby interactions, which helps move women forward in the recovery process.
Quantitative tumor heterogeneity assessment on a nuclear population basis
Authors: Wessel Lindberg Anne‐Sofie , Conradsen Knut , Larsen Rasmus , Friis Lippert Michael , Røge Rasmus , Vyberg Mogens
Published: January 2017

Immunohistochemistry Ki‐67 stain is widely used for visualizing cell proliferation. The common method for scoring the proliferation is to manually select and score a hot spot. This method is time‐consuming and will often not give reproducible results due to subjective selection of the hotspots and subjective scoring. An automatic hotspot detection and proliferative index scoring would be time‐saving, make the determination of the Ki‐67 score easier and minimize the uncertainty of the score by introducing a more objective and standardized score.

Tissue Micro Array cores stained for Ki‐67 and their neighbor slide stained for Pan Cytokeratin were aligned and Ki‐67 positive and negative nuclei were identified inside tumor regions. A heatmap was calculated based on these and illustrates the distribution of the heterogenous response of Ki‐67 positive nuclei in the tumor tissue. An automatic hot spot detection was developed and the Ki‐67 score was calculated. All scores were compared with scores provided by a pathologist using linear regression models.

No significant difference was found between the Ki‐67 scores guided by the developed heatmap and the scores provided by a pathologist. For comparison, scores were also calculated at a random place outside the hot spot and these scores were found to be significantly different from the pathologist scores.

A heatmap visualizing the heterogeneity in tumor tissue expressed by Ki‐67 was developed and used for an automatic identification of hot spots in which a Ki‐67 score was calculated. The Ki‐67 scores did not differ significantly from scores provided by a pathologist. © 2017 International Society for Advancement of Cytometry
Structural insights into anticancer activity of D‐ring modified estrone derivatives using their lipophilicity in estimation of SAR and molecular docking studies
Authors: Trifunović Jovana , Borčić Vladan , Vukmirović Saša , Mikov Momir
Published: January 2017

Many forms of breast carcinoma are hormone‐dependent and therefore development of novel aromatase inhibitors is of particular interest. Since brain metastases are frequent in patients with advanced breast carcinoma, one of the goals of modern drug development is the discovery of drugs with specific pharmacokinetic profile. High performance thin layer chromatography (HPTLC) is often used to determine lipophilicity of the molecules based on their retention constant. As a predictive analysis, multiple linear regression method was performed to connect pharmacokinetic‐dependent parameters with independent physicochemical properties such are: RM0, TPSA and Mw of fourteen D‐ring modified oestrone derivatives. Additionally, docking studies were performed. Conducted correlation analysis indicates excellent dependence between experimental RM parameter values and calculated values of pharmacokinetic parameters. Results show sufficient intestinal absorption of all the investigated molecules as well as moderate volumes of distribution and strong affinity for binding to plasma proteins. Crossing blood–brain barrier is predicted to be successful for 11 compounds. The created quantitative structure activity relationship model represents an excellent predictive tool and enables determination of pharmacokinetic properties of examined compounds. Docking analysis defined molecules I3 and II3 to be the best candidates; however, compound II3 violates the Lipinski rule. It has been concluded that molecules with hydroxyl group at C‐3 more effectively pass through blood–brain barrier while structures with benzyloxy groups have stronger interactions with CYP1A19. Molecules II2, II4, II6, and II7 are regarded as most suitable candidates for further investigation considering their good pharmacokinetic and docking characteristics. Copyright © 2017 John Wiley & Sons, Ltd.
Two‐step adaptive management for choosing between two management actions
Authors: Moore Alana L. , Walker Leila , Runge Michael C. , McDonald‐Madden Eve , McCarthy Michael A.
Published: January 2017

Adaptive management is widely advocated to improve environmental management. Derivations of optimal strategies for adaptive management, however, tend to be case specific and time consuming. In contrast, managers might seek relatively simple guidance, such as insight into when a new potential management action should be considered, and how much effort should be expended on trialing such an action. We constructed a two‐time‐step scenario where a manager is choosing between two possible management actions. The manager has a total budget that can be split between a learning phase and an implementation phase. We use this scenario to investigate when and how much a manager should invest in learning about the management actions available. The optimal investment in learning can be understood intuitively by accounting for the expected value of sample information, the benefits that accrue during learning, the direct costs of learning, and the opportunity costs of learning. We find that the optimal proportion of the budget to spend on learning is characterized by several critical thresholds that mark a jump from spending a large proportion of the budget on learning to spending nothing. For example, as sampling variance increases, it is optimal to spend a larger proportion of the budget on learning, up to a point: if the sampling variance passes a critical threshold, it is no longer beneficial to invest in learning. Similar thresholds are observed as a function of the total budget and the difference in the expected performance of the two actions. We illustrate how this model can be applied using a case study of choosing between alternative rearing diets for hihi, an endangered New Zealand passerine. Although the model presented is a simplified scenario, we believe it is relevant to many management situations. Managers often have relatively short time horizons for management, and might be reluctant to consider further investment in learning and monitoring beyond collecting data from a single time period.
Immunosuppressive treatment in fulminant myocarditis and gene expression pattern associated with, but no histological confirmation of giant cell myocarditis
Authors: Fruhwald Friedrich , Lassner Dirk , Fruhwald Sonja , Gross Ulrich M. , Dapunt Otto , Schultheiss Heinz‐Peter
Published: January 2017

A healthy woman with acute onset of pulmonary oedema and severely depressed left ventricular function underwent endomyocardial biopsy under the clinical suspicion of fulminant myocarditis. While awaiting the results of biopsy, the situation deteriorated to Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) and extracorporeal membrane oxygenation was implanted. Finally, immunohistochemistry in biopsy specimen corresponded to fulminant lymphocytic myocarditis, although active myocarditis was excluded. Furthermore, gene expression profiling identified giant cell myocarditis although multinuclear cells were absent. This prompted the start of immunosuppression with cortisone and cyclosporine. The patient fully recovered.
The Allyl Cyanate/Isocyanate Rearrangement: An Efficient Tool for the Stereocontrolled Formation of Allylic C–N Bonds
Authors: Nocquet Pierre‐Antoine , Henrion Sylvain , Macé Aurélie , Carboni Bertrand , Villalgordo Jose Manuel , Carreaux François
Published: January 2017

[3,3]‐Sigmatropic rearrangements represent powerful methods in the toolbox of synthetic organic chemists for the stereoselective construction of carbon–carbon as well as carbon–heteroatom bonds. Thus, the allyl cyanate/isocyanate rearrangement, although still underused for the preparation of allylamine derivatives, offers clear advantages over other similar methods. It usually occurs at or below ambient temperature with no need to use any metal catalyst, in a stereospecific way, and with a complete transfer of chirality. Moreover, combined with the high reactivity of the resulting isocyanates towards nucleophiles, this rearrangement gives access to various classes of compounds with wide structural and functional diversity. This microreview provides an overview of synthetic applications of this rearrangement since its discovery, with particular emphasis on its utility for the synthesis of complex nitrogen‐containing molecules such as natural products.
The Role of Learning in Health Technology Assessments: An Empirical Assessment of Endovascular Aneurysm Repairs in German Hospitals
Authors: Varabyova Yauheniya , Blankart Carl Rudolf , Schreyögg Jonas
Published: January 2017

Changes in performance due to learning may dynamically influence the results of a technology evaluation through the change in effectiveness and costs. In this study, we estimate the effect of learning using the example of two minimally invasive treatments of abdominal aortic aneurysms: endovascular aneurysm repair (EVAR) and fenestrated EVAR (fEVAR). The analysis is based on the administrative data of over 40,000 patients admitted with unruptured abdominal aortic aneurysm to more than 500 different hospitals over the years 2006 to 2013. We examine two patient outcomes, namely, in‐hospital mortality and length of stay using hierarchical regression models with random effects at the hospital level. The estimated models control for patient and hospital characteristics and take learning interdependency between EVAR and fEVAR into account. In case of EVAR, we observe a significant decrease both in the in‐hospital mortality and length of stay with experience accumulated at the hospital level; however, the learning curve for fEVAR in both outcomes is effectively flat. To foster the consideration of learning in health technology assessments of medical devices, a general framework for estimating learning effects is derived from the analysis. © 2017 The Authors. Health Economics published by John Wiley & Sons, Ltd.
Comparison of protocols measuring diffusion and partition coefficients in the stratum corneum
Authors: Rothe H. , Obringer C. , Manwaring J. , Avci C. , Wargniez W. , Eilstein J. , Hewitt N. , Cubberley R. , Duplan H. , Lange D. , Jacques‐Jamin C. , Klaric M. , Schepky A. , Grégoire S.
Published: January 2017

Partition (K) and diffusion (D) coefficients are important to measure for the modelling of skin penetration of chemicals through the stratum corneum (SC). We compared the feasibility of three protocols for the testing of 50 chemicals in our main studies, using three cosmetics‐relevant model chemicals with a wide range of logP values. Protocol 1: SC concentration‐depth profile using tape‐stripping (measures KSC/v and DSC/HSC2, where HSC is the SC thickness); Protocol 2A: incubation of isolated SC with chemical (direct measurement of KSC/v only) and Protocol 2B: diffusion through isolated SC mounted on a Franz cell (measures KSC/v and DSC/HSC2, and is based on Fick's laws). KSC/v values for caffeine and resorcinol using Protocol 1 and 2B were within 30% of each other, values using Protocol 2A were ~two‐fold higher, and all values were within 10‐fold of each other. Only indirect determination of KSC/v by Protocol 2B was different from the direct measurement of KSC/v by Protocol 2A and Protocol 1 for 7‐EC. The variability of KSC/v for all three chemicals using Protocol 2B was higher compared to Protocol 1 and 2A. DSC/HSC2 values for the three chemicals were of the same order of magnitude using all three protocols. Additionally, using Protocol 1, there was very little difference between parameters measured in pig and human SC. In conclusion, KSC/v, and DSC values were comparable using different methods. Pig skin might be a good surrogate for human skin for the three chemicals tested. Copyright © 2017 The Authors Journal of Applied Toxicology published by John Wiley & Sons Ltd.
Micropatterning of reagent‐free, high energy crosslinked gelatin hydrogels for bioapplications
Authors: Heyart Benedikt , Weidt Astrid , Wisotzki Emilia I. , Zink Mareike , Mayr Stefan G.
Published: January 2017

Hydrogels are crosslinked polymeric gels of great interest in the field of tissue engineering, particularly as biocompatible cell or drug carriers. Reagent‐free electron irradiated gelatin is simple to manufacture, inexpensive and biocompatible. Here, the potential to micropattern gelatin hydrogel surfaces during electron irradiation crosslinking was demonstrated as a promising microfabrication technique to produce thermally stable structures on highly relevant length scales for bioapplications. In the present work, grooves of 3.75 to 170 µm width and several hundred nanometers depth were transferred onto gelatin hydrogels during electron irradiation and characterized by 3D confocal microscopy after exposure to ambient and physiological conditions. The survival and influence of these microstructures on cellular growth was further characterized using NIH 3T3 fibroblasts. Topographical modifications produced surface structures on which the cultured fibroblasts attached and responded by adapting their morphologies. This developed technique allows for simple and effective structuring of gelatin and opens up new possibilities for irradiation crosslinked hydrogels in biomedical applications in which cell attachment and contact guidance are favored. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 320–330, 2018.
“IT'S LIKE A SHOULDER TO LEAN ON”: SOCIAL SUPPORT PROVIDED BY AN INNER‐CITY WORKFORCE DEVELOPMENT PROGRAM
Authors: Powell Terrinieka W. , Jo Meghan , Martin Christopher , Philip Winston , Astone Nan M.
Published: January 2017

The goal of this study was to examine the types of social support provided by STRIVE, an inner‐city‐based workforce development program. Life history interviews were conducted with 20 African American graduates (aged 18–24 years) of the workforce development program. Nearly half of the sample was male (45%). Over half of the sample was employed at the time of the interview (65%). Participants described receiving extensive informational and emotional support from the workforce development program. After participating in the workforce development program, respondents described themselves as being less stressed and more self‐confident. Participants described using the skills gained and support offered to gain employment, enroll in educational programs, and interact more effectively with others. Thus, workforce development programs may be a viable option to address employment needs and provide meaningful support to vulnerable young people during their transition into adulthood.
High glucose alters the secretome of mechanically stimulated osteocyte‐like cells affecting osteoclast precursor recruitment and differentiation
Authors: Maycas Marta , Portolés María Teresa , Matesanz María Concepción , Buendía Irene , Linares Javier , Feito María José , Arcos Daniel , Vallet‐Regí María , Plotkin Lilian I. , Esbrit Pedro , Gortázar Arancha R.
Published: January 2017

Diabetes mellitus (DM) induces bone deterioration, while mechanical stimulation promotes osteocyte‐driven bone formation. We aimed to evaluate the interaction of acute exposure (24 h) to high glucose (HG) with both the pro‐survival effect conferred to osteocytic MLO‐Y4 cells and osteoblastic MC3T3‐E1 cells by mechanical stimulation and the interaction of these cells with osteoclast precursor RAW264.7 cells. We found that 24 h of HG (25 mM) pre‐exposure prevented both cell survival and ERK and β‐catenin nuclear translocation upon mechanical stimulation by fluid flow (FF) (10 min) in both MLO‐Y4 and MC3T3‐E1 cells. However, migration of RAW 264.7 cells was inhibited by MLO‐Y4 cell‐conditioned medium (CM), but not by MC3T3‐E1 cell‐CM, with HG or FF. This inhibitory effect was associated with consistent changes in VEGF, RANTES, MIP‐1α, MIP‐1β MCP‐1, and GM‐CSF in MLO‐Y4 cell‐CM. RAW264.7 proliferation was inhibited by MLO‐Y4 CM under static or HG conditions, but it increased by FF‐CM with or without HG. In addition, both FF and HG abrogated the capacity of RAW 264.7 cells to differentiate into osteoclasts, but in a different manner. Thus, HG‐CM in static condition allowed formation of osteoclast‐like cells, which were unable to resorb hydroxyapatite. In contrast, FF‐CM prevented osteoclastogenesis even in HG condition. Moreover, HG did not affect basal RANKL or IL‐6 secretion or their inhibition induced by FF in MLO‐Y4 cells. In conclusion, this in vitro study demonstrates that HG exerts disparate effects on osteocyte mechanotransduction, and provides a novel mechanism by which DM disturbs skeletal metabolism through altered osteocyte‐osteoclast communication.
Temperature‐Induced Phase Transition Characterization of Responsive Polymer Brushes Grafted onto Nanoparticles
Authors: Schweizerhof Sjören , Demco Dan Eugen , Mourran Ahmed , Keul Helmut , Fechete Radu , Möller Martin
Published: January 2017

Temperature‐induced phase transition parameters of responsive free polymer and brushes onto nanoparticles are measured using high‐resolution magic‐angle sample spinning (HRMAS) NMR spectroscopy. To this purpose, a two‐state statistical model of temperature dependence of thermodynamic observables is developed and applied to obtain parameters which characterize the process of temperature‐induced phase transition of stimuli‐sensitive polymers. In this investigation the thermodynamic observable is the integral intensity of the 1H HRMAS NMR spectrum peaks and the derived thermodynamic parameters are transition temperature and transition entropy. This approach is applied to investigate the dependence of temperature‐induced coil‐to‐globule transition of poly(N‐isopropylacrylamide), (PNIPAm), asymmetric end functionalized with benzyl and thiol groups (Bn–PNIPAm–SH) on molecular weight in the range 3600–30 000 g mol–1 in aqueous solutions. The characteristics of the phase transition represented by transition temperature, and transition entropy are compared to that of Bn–PNIPAm–SH brushes onto gold nanorods in the same range of molecular weight. The method used for measuring the characteristics of phase transition is based on transverse magnetization relaxation (T2) spin‐echo enhance editing of the integral intensities of the 1H HRMAS NMR spectra. This NMR observable reflects changes in transverse relaxation times as an indicative of the polymer chains conformations and dynamics reached in the process of temperature‐induced phase transition.

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PAX3–FOXO1 is essential for tumour initiation and maintenance but not recurrence in a human myoblast model of rhabdomyosarcoma
Authors: Pandey Puspa R , Chatterjee Bishwanath , Olanich Mary E , Khan Javed , Miettinen Markku M , Hewitt Stephen M , Barr Frederic G
Published: January 2017

The PAX3–FOXO1 fusion gene is generated by a 2;13 chromosomal translocation and is a characteristic feature of an aggressive subset of rhabdomyosarcoma (RMS). To dissect the mechanism of oncogene action during RMS tumourigenesis and progression, doxycycline‐inducible PAX3–FOXO1 and constitutive MYCN expression constructs were introduced into immortalized human myoblasts. Although myoblasts expressing PAX3–FOXO1 or MYCN alone were not transformed in focus formation assays, combined PAX3–FOXO1 and MYCN expression resulted in transformation. Following intramuscular injection into immunodeficient mice, myoblasts expressing PAX3–FOXO1 and MYCN formed rapidly growing RMS tumours, whereas myoblasts expressing only PAX3–FOXO1 formed tumours after a longer latency period. Doxycycline withdrawal in myoblasts expressing inducible PAX3–FOXO1 and constitutive MYCN following tumour formation in vivo or focus formation in vitro resulted in tumour regression or smaller foci associated with myogenic differentiation and cell death. Following regression, most tumours recurred in the absence of doxycycline. Analysis of recurrent tumours revealed a subset without PAX3–FOXO1 expression, and cell lines derived from these recurrent tumours showed transformation in the absence of doxycycline. The doxycycline‐independent oncogenicity in these recurrent tumour‐derived lines persisted even after PAX3–FOXO1 was inactivated with a CRISPR/Cas9 editing strategy. Whereas cell lines derived from primary tumours were dependent on PAX3–FOXO1 and differentiated following doxycycline withdrawal, recurrent tumour‐derived cells without PAX3–FOXO1 expression did not differentiate under these conditions. These findings indicate that PAX3–FOXO1 collaborates with MYCN during early RMS tumourigenesis to dysregulate proliferation and inhibit myogenic differentiation and cell death. Although most cells in the primary tumours are dependent on PAX3–FOXO1, recurrent tumours can develop by a PAX3–FOXO1‐independent mechanism, in which rare cells are postulated to acquire secondary transforming events that were activated or selected by initial PAX3–FOXO1 expression. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.
Synthesis of ubiquitylated histone H3 using a thiirane linker for chemical ligation
Authors: Kawakami Toru , Mishima Yuichi , Hojo Hironobu , Suetake Isao
Published: January 2017

Post‐translational modifications of histone proteins, which form nucleosome cores, play an important role in gene regulation. Ubiquitin modification is one such modification. We previously reported on the use of a thiirane linker to introduce a 1,2‐aminothiol moiety at a cysteine residue for native chemical ligation with peptide thioesters, which permitted isopeptide mimetics to be produced. In this report, we describe the preparation of the ubiquitylated full length histone H3 at the 18 position and the construction of tetranucleosomes with recombinant histones H2A, H2B, H4, and DNA, which are slightly more stable than those that are prepared without ubiquitin modification. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.
On optimal predefined‐time stabilization
Authors: Jiménez‐Rodríguez E. , Sánchez‐Torres J. D. , Loukianov A. G.
Published: January 2017

This paper addresses the problem of optimal predefined‐time stability. Predefined‐time stable systems are a class of fixed‐time stable dynamical systems for which the minimum bound of the settling‐time function can be defined a priori as an explicit parameter of the system. Sufficient conditions for a controller to solve the optimal predefined‐time stabilization problem for a given nonlinear system are provided. These conditions involve a Lyapunov function that satisfies a certain differential inequality for guaranteeing predefined‐time stability. It also satisfies the steady‐state Hamilton–Jacobi–Bellman equation for ensuring optimality. Furthermore, for nonlinear affine systems and a certain class of performance index, a family of optimal predefined‐time stabilizing controllers is derived. This class of controllers is applied to optimize the sliding manifold reaching phase in predefined time, considering both the unperturbed and perturbed cases. For the perturbed case, the idea of integral sliding mode control is jointly used to ensure robustness. Finally, as a study case, the predefined‐time optimization of the sliding manifold reaching phase in a pendulum system is performed using the developed methods, and numerical simulations are carried out to show their behavior. Copyright © 2017 John Wiley & Sons, Ltd.
Mesenchymal Stem Cell-Derived Extracellular Vesicles as Mediators of Anti-Inflammatory Effects: Endorsement of Macrophage Polarization
Authors: Lo Sicco Claudia , Reverberi Daniele , Balbi Carolina , Ulivi Valentina , Principi Elisa , Pascucci Luisa , Becherini Pamela , Bosco Maria Carla , Varesio Luigi , Franzin Chiara , Pozzobon Michela , Cancedda Ranieri , Tasso Roberta
Published: January 2017

Mesenchymal Stem Cells (MSCs) are effective therapeutic agents enhancing the repair of injured tissues mostly through their paracrine activity. Increasing evidences show that besides the secretion of soluble molecules, the release of extracellular vesicles (EVs) represents an alternative mechanism adopted by MSCs. Since macrophages are essential contributors toward the resolution of inflammation, which has emerged as a finely orchestrated process, the aim of the present study was to carry out a detailed characterization of EVs released by human adipose derived-MSCs to investigate their involvement as modulators of MSC anti-inflammatory effects inducing macrophage polarization. The EV-isolation method was based on repeated ultracentrifugations of the medium conditioned by MSC exposed to normoxic or hypoxic conditions (EVNormo and EVHypo). Both types of EVs were efficiently internalized by responding bone marrow-derived macrophages, eliciting their switch from a M1 to a M2 phenotype. In vivo, following cardiotoxin-induced skeletal muscle damage, EVNormo and EVHypo interacted with macrophages recruited during the initial inflammatory response. In injured and EV-treated muscles, a downregulation of IL6 and the early marker of innate and classical activation Nos2 were concurrent to a significant upregulation of Arg1 and Ym1, late markers of alternative activation, as well as an increased percentage of infiltrating CD206pos cells. These effects, accompanied by an accelerated expression of the myogenic markers Pax7, MyoD, and eMyhc, were even greater following EVHypo administration. Collectively, these data indicate that MSC-EVs possess effective anti-inflammatory properties, making them potential therapeutic agents more handy and safe than MSCs.
Making Sense of Learner Performance on Tests of Productive Vocabulary Knowledge
Authors: Fitzpatrick Tess , Clenton Jon
Published: January 2017

This article offers a solution to a significant problem for teachers and researchers of language learning that confounds their interpretations and expectations of test data: The apparent simplicity of tests of vocabulary knowledge masks the complexity of the constructs they claim to measure. The authors first scrutinise task elements in two widely cited productive vocabulary measures, Lex30 (Meara & Fitzpatrick, 2000) and the Lexical Frequency Profile (LFP; Laufer & Nation, 1995), to gain a more precise understanding of the relationship between test performance and learner knowledge. Next, in three empirical studies (N = 80, 80, 100) they compare second language learners’ performance on Lex30, as the static point of reference, with LFP and with two new tests designed to investigate specific elements of the vocabulary test tasks. Correlation analyses indicate systematic differences in the tests’ capacity to capture information about the quality of learners’ word knowledge and the size of their vocabulary resource. Using the findings from this empirical work, the authors formulate a model of vocabulary capture onto which test tasks can be mapped. They demonstrate how capturing key elements of the relationship between test scores and lexical competence can guide teachers and researchers in applying and interpreting vocabulary tests.
Controllable Generation of a Submillimeter Single Bubble in Molten Metal Using a Low-Pressure Macrosized Cavity
Authors: Konovalenko Alexander , Sköld Per , Kudinov Pavel , Bechta Sevostian , Grishchenko Dmitry
Published: January 2017

We develop a method for generation of a single gas bubble in a pool of molten metal. The method can be useful for applications and research studies where a controllable generation of a single submillimeter bubble in opaque hot liquid is required. The method resolves difficulties with bubble detachment from the orifice, wettability issues, capillary channel and orifice surfaces degradation due to contact with corrosive hot liquid, etc. The macrosized, 5- to 50-mm3 cavity is drilled in the solid part of the pool. Flushing the cavity with gas, vacuuming it to low pressure, as well as sealing and consequent remelting cause cavity implosion due to a few orders in magnitude pressure difference between the cavity and the molten pool. We experimentally demonstrate a controllable production of single bubbles ranging from a few milliliters down to submillimeter size. The uncertainties in size and bubble release timing are estimated and compared with experimental observations for bubbles ranging within 0.16 to 4 mm in equivalent-volume sphere diameter. Our results are obtained in heavy liquid metals such as Wood’s and Lead-Bismuth eutectics at 353 K to 423 K (80 °C to 150 °C).
Gastric vascular and motor responses to anaphylactic hypotension in anesthetized rats, in comparison to those with hemorrhagic or vasodilator-induced hypotension
Authors: Kuda Yuhichi , Shibamoto Toshishige , Zhang Tao , Yang Wei , Tanida Mamoru , Kurata Yasutaka
Published: January 2017

Anaphylactic shock is life-threatening, but pathophysiology of the stomach lesion remains unclear. We determined gastric hemodynamics and gastric functions during anaphylactic hypotension, as compared to hypotension induced by hemorrhage or sodium nitroprusside (SNP) in anesthetized and ovalbumin-sensitized Sprague–Dawley rats. Systemic arterial pressure, portal venous pressure, and gastric arterial blood flow were measured, and gastric vascular resistance (GVR) was determined. Separately, the intragastric pressure (IGP) and gastric effluent, as a measure of gastric flux, were continuously measured. During anaphylaxis, GVR decreased only transiently at 0.5 min, followed by an increase. IGP increased markedly, while gastric flux decreased. During hemorrhage, GVR and IGP increased, while gastric flux did not change. When SNP was injected, both GVR and IGP decreased and gastric flux increased only just after injection. In conclusion, gastric vasodilatation occurs only transiently after antigen injection, and gastric motility increases, but gastric emptying deceases during anaphylactic hypotension in anesthetized rats.
Clinical Issues‐February 2017
Authors: Ogg Mary J. , Wood Amber
Published: January 2017

This Month

Implementing surgical smoke evacuation practices

Key words: surgical smoke, compliance, health effects, smoke evacuators.

Surgical smoke evacuation policies and procedures

Key words: surgical smoke, smoke evacuation, policy, procedure.

Measuring compliance with surgical smoke evacuation practices

Key words: surgical smoke, smoke evacuation, compliance.

Patient safety and hand hygiene

Key words: hand hygiene, hand wash, hand rub, patient safety, point of use.
Urine Culture Testing in Community Nursing Homes: Gateway to Antibiotic Overprescribing
Authors: Sloane Philip D. , Kistler Christine E. , Reed David , Weber David J. , Ward Kimberly , Zimmerman Sheryl
Published: January 2017

OBJECTIVE

To describe current practice around urine testing and identify factors leading to overtreatment of asymptomatic bacteriuria in community nursing homes (NHs)

DESIGN

Observational study of a stratified random sample of NH patients who had urine cultures ordered in NHs within a 1-month study period

SETTING

31 NHs in North Carolina

PARTICIPANTS

254 NH residents who had a urine culture ordered within the 1-month study period

METHODS

We conducted an NH record audit of clinical and laboratory information during the 2 days before and 7 days after a urine culture was ordered. We compared these results with the urine antibiogram from the 31 NHs.

RESULTS

Empirical treatment was started in 30% of cases. When cultures were reported, previously untreated cases received antibiotics 89% of the time for colony counts of ≥100,000 CFU/mL and in 35% of cases with colony counts of 10,000–99,000 CFU/mL. Due to the high rate of prescribing when culture results returned, 74% of these patients ultimately received a full course of antibiotics. Treated and untreated patients did not significantly differ in temperature, frequency of urinary signs and symptoms, or presence of Loeb criteria for antibiotic initiation. Factors most commonly associated with urine culture ordering were acute mental status changes (32%); change in the urine color, odor, or sediment (17%); and dysuria (15%).

CONCLUSIONS

Urine cultures play a significant role in antibiotic overprescribing. Antibiotic stewardship efforts in NHs should include reduction in culture ordering for factors not associated with infection-related morbidity as well as more scrutiny of patient condition when results become available.

Infect Control Hosp Epidemiol2017;38:524–531
Interhospital Comparison of Surgical Site Infection Rates in Orthopedic Surgery
Authors: Skufca Jozica , Ollgren Jukka , Virtanen Mikko J. , Huotari Kaisa , Lyytikäinen Outi
Published: January 2017

OBJECTIVE

To investigate whether comparison by deep or adjusted deep surgical site infection (SSI) rates in orthopedic surgeries are a better basis for feedback to Finnish hospitals than overall SSI rates

DESIGN

Retrospective cohort study

SETTING

Hospitals conducting surveillance of hip arthroplasties (HPROs) and knee arthroplasties (KPROs) in the Finnish Hospital Infection Program

METHODS

We analyzed surveillance data for 73,227 HPROs and 56,860 KPROs performed in 18 hospitals during 1999–2014. For each hospital, the overall, deep, and adjusted deep SSI rates with 95% confidence intervals (CIs) were calculated, and the hospital ranks were simulated in the Bayesian framework. Adjustments were performed using relevant patient and hospital characteristics. The correlation between the median expected hospital ranks in overall versus deep SSI rates and deep vs adjusted deep SSI rates were assessed using Spearman’s correlation coefficient ρ.

RESULTS

For HPRO, the overall SSI rates ranged from 0.92 to 6.83, the deep SSI rates ranged from 0.34 to 1.86, and the adjusted deep hospital-specific SSI rates ranged from 0.37 to 1.85. For KPRO, the overall SSI rates ranged from 0.71 to 5.03, the deep SSI rates ranged from 0.42 to 1.60, and the adjusted deep hospital-specific SSI rates ranged from 0.56 to 1.55. For both procedures, the 95% CIs of the rates between hospitals largely overlapped; only single outliers were detected. Hospital rank did not correlate between overall and deep SSI rates (HPRO, ρ=0.03; KPRO, ρ=0.40), but a correlation was observed in hospital rank for deep and adjusted deep SSI rates (HPRO, ρ=0.85; KPRO, ρ=0.94).

CONCLUSION

Deep SSI rates may be a better tool for interhospital comparisons than overall SSI rates. Although the adjustment could lead to fairer hospital ranking, it is not always necessary for feedback.

Infect Control Hosp Epidemiol 2017;38:423–429
Classical shipwreck excavation at Tektaş Burnu, Turkey
Authors: Gibbins David
Published: January 2017

In 1999 the Institute of Nautical Archaeology (INA) began the excavation of a 5th-century BC shipwreck off Tektaş Burnu, a rocky headland on the west coast of Turkey between the Greek islands of Chios and Samos. The site was discovered in 1996 during INA’s annual survey, which has pinpointed more than 100 ancient wrecks off southwest Turkey. Since 1960 teams under Gcorge Bass have excavated wrecks ranging in date from Bronze Age to medieval, but the high classical period of Greece remained unrepresented. Interest in the Tektas wreck was spurred by its likely date, in the third quarter of the 5th century BC; it is the only wrecked merchantman to be securely dated to these years, and is therefore shedding unique light on seafaring and trade at the height of classical Athens.