bluuebunny/crossref_metadata_2025 huggingface dataset:
Insulin—From its Discovery to the Industrial Synthesis of Modern Insulin Analogues
Authors: Moroder Luis , Musiol Hans‐Jürgen
Published: May 2017

After the discovery of insulin as a drug for diabetes, the pharmaceutical companies were faced with the challenge to meet the demand for insulin with the highest possible degree of purity in the required quantities from animal sources. The observation of an immune reaction of patients to insulin from animal pancreatic extracts made the availability of human insulin of highest priority. Only the enzyme‐catalyzed semisynthesis at the C‐terminus of the insulin B‐chain led to a commercial process, but it depended on porcine insulin and was aggravated by supply concerns. The advent of rDNA technology allowed the commercial preparation of human insulin by biosynthesis in virtually unlimited quantities. An increased chemical diversity was only envisaged through chemical synthesis, which was simplified by advances in solid‐phase peptide synthesis and chemical ligation. Single‐chain insulin precursors are now being synthesized that should enable fast screening of insulin analogues for improved biophysical, biological, and thus promising new therapeutic properties, as well as for the industrial manufacture of insulin analogues not accessible by biosynthesis.
Performance study of modified calcium magnesium acetate (MCMA) in the process of high temperature CO2 capture and the application of spent MCMA for sequential SO2 removal
Authors: Sun Xiaoru , Fang Dongdong , Zhang Lihui , Duan Feng , Sun Yunlan
Published: May 2017

The modified calcium magnesium acetate (MCMA) has the similar characteristics and properties to those of CMA and a lower production cost. In this study, the effect of temperature on the performance of MCMA in the cyclic calcination/carbonation reaction (CCCR) process was investigated. The pore structure characteristics of the spent MCMA particles were also studied. A tubular furnace reactor was used to study the sulfation reaction characteristics and kinetic characteristics of the spent MCMA after CCCR. The microstructure and the constituent elements of the spent MCMA after sulfation reaction were analyzed by the scanning electron microscopy (SEM) and the energy dispersive X‐ray spectrometry (EDS). The adsorption characteristics of MCMA were found similar to the analytically pure CMA in the CCCR process. The carbonation conversion of MCMA decreases significantly first and then varies little with increasing the cycle numbers. The sulfation process of all spent MCMA can be divided into two distinct stages including the chemical reaction‐controlled stage and the product layer diffusion‐controlled stage. The shrinking unreacted core model is appropriate to analyze the sulfation kinetic characteristics of the spent MCMA in the sulfation process. The sulfation conversions of the spent MCMA decrease gradually with increasing the cycle numbers of CCCR, while the MCMA‐30 (the modified CMA cycled 30 times in the CCCR process) still shows a sulfation conversion of 35.48%, indicating that the spent MCMA can be used as an ideal desulfurizer before the fresh sorbent serving as a CO2 carrier in the CCCR process. © 2017 Curtin University of Technology and John Wiley & Sons, Ltd.
Three‐Component Aminoalkylations Yielding Dihydronaphthoxazine‐Based Sirtuin Inhibitors: Scaffold Modification and Exploration of Space for Polar Side‐Chains
Authors: Vojacek Steffen , Beese Katja , Alhalabi Zayan , Swyter Sören , Bodtke Anja , Schulzke Carola , Jung Manfred , Sippl Wolfgang , Link Andreas
Published: May 2017

Nonpolar derivatives of heterocyclic aromatic screening hits like the non‐selective sirtuin inhibitor splitomicin tend to be poorly soluble in biological fluids. Unlike sp3‐rich natural products, flat aromatic compounds are prone to stacking and often difficult to optimize into leads with activity in cellular systems. The aim of this work was to identify anchor points for the introduction of sp3‐rich fragments with polar functional groups into the newly discovered active (IC50 = 5 μM) but nonpolar scaffold 1,2‐dihydro‐3H‐naphth[1,2‐e][1,3]oxazine‐3‐thione by a molecular modeling approach. Docking studies were conducted with structural data from crystallized human SIRT2 enzyme. Subsequent evaluation of the in silico hypotheses through synthesis and biological evaluation of the designed structures was accomplished with the aim to discover new SIRT2 inhibitors with improved aqueous solubility. Derivatives of 8‐bromo‐1,2‐dihydro‐3H‐naphth[1,2‐e][1,3]oxazine‐3‐thione N‐alkylated with a hydrophilic morpholino‐alkyl chain at the thiocarbamate group intended for binding in the acetyl‐lysine pocket of the enzyme appeared to be promising. Both the sulfur of the thiocarbamate and the bromo substituent were assumed to result in favorable hydrophobic interactions and the basic morpholino‐nitrogen was predicted to build a hydrogen bond with the backbone Ile196. While the brominated scaffold showed moderately improved activity (IC50 = 1.8 μM), none of the new compounds displayed submicromolar activity. Synthesis and characterization of the new compounds are reported and the possible reasons for the outcome are discussed.
Association of MicroRNA‐618 Expression With Altered Frequency and Activation of Plasmacytoid Dendritic Cells in Patients With Systemic Sclerosis
Authors: Rossato Marzia , Affandi Alsya J. , Thordardottir Soley , Wichers Catharina G. K. , Cossu Marta , Broen Jasper C. A. , Moret Frederique M. , Bossini‐Castillo Lara , Chouri Eleni , van Bon Lenny , Wolters Femke , Marut Wioleta , van der Kroef Maarten , Silva‐Cardoso Sandra , Bekker Cornelis P. J. , Dolstra Harry , van Laar Jacob M. , Martin Javier , van Roon Joel A. G. , Reedquist Kris A. , Beretta Lorenzo , Radstake Timothy R. D. J.
Published: May 2017

Objective

Plasmacytoid dendritic cells (PDCs) are a critical source of type I interferons (IFNs) that can contribute to the onset and maintenance of autoimmunity. Molecular mechanisms leading to PDC dysregulation and a persistent type I IFN signature are largely unexplored, especially in patients with systemic sclerosis (SSc), a disease in which PDCs infiltrate fibrotic skin lesions and produce higher levels of IFNα than those in healthy controls. This study was undertaken to investigate potential microRNA (miRNA)–mediated epigenetic mechanisms underlying PDC dysregulation and type I IFN production in SSc.

Methods

We performed miRNA expression profiling and validation in highly purified PDCs obtained from the peripheral blood of 3 independent cohorts of healthy controls and SSc patients. Possible functions of miRNA‐618 (miR‐618) on PDC biology were identified by overexpression in healthy PDCs.

Results

Expression of miR‐618 was up‐regulated in PDCs from SSc patients, including those with early disease who did not present with skin fibrosis. IFN regulatory factor 8, a crucial transcription factor for PDC development and activation, was identified as a target of miR‐618. Overexpression of miR‐618 reduced the development of PDCs from CD34+ cells in vitro and enhanced their ability to secrete IFNα, mimicking the PDC phenotype observed in SSc patients.

Conclusion

Up‐regulation of miR‐618 suppresses the development of PDCs and increases their ability to secrete IFNα, potentially contributing to the type I IFN signature observed in SSc patients. Considering the importance of PDCs in the pathogenesis of SSc and other diseases characterized by a type I IFN signature, miR‐618 potentially represents an important epigenetic target to regulate immune system homeostasis in these conditions.
A Seventh‐Degree Cubature Kalman Filter
Authors: Meng Dong , Miao Lingjuan , Shao Haijun , Shen Jun
Published: May 2017

The fifth‐degree cubature Kalman filter (CKF) has been proved to be a kind of algorithm that has higher precision than the third‐degree CKF and unscented Kalman filter (UKF). In order to further improve the performance of CKF, the seventh‐degree CKF is proposed in this paper by expanding the spherical‐radial rule, and a new kind of deterministic sampling method is derived based on the seventh‐degree cubature rule. Through the comparison in target tracking simulation, the seventh‐degree CKF methods are shown to be able to enhance filtering precision compared to the fifth‐degree CKF, the third‐degree CKF and the UKF filter.
Lebesgue‐p NORM Convergence OF Fractional‐Order PID‐Type Iterative Learning Control for Linear Systems
Authors: Li Lei
Published: May 2017

This paper discusses first‐ and second‐order fractional‐order PID‐type iterative learning control strategies for a class of Caputo‐type fractional‐order linear time‐invariant system. First, the additivity of the fractional‐order derivative operators is exploited by the property of Laplace transform of the convolution integral, whilst the absolute convergence of the Mittag‐Leffler function on the infinite time interval is induced and some properties of the state transmit function of the fractional‐order system are achieved via the Gamma and Bata function characteristics. Second, by using the above properties and the generalized Young inequality of the convolution integral, the monotone convergence of the developed first‐order learning strategy is analyzed and the monotone convergence of the second‐order learning scheme is derived after finite iterations, when the tracking errors are assessed in the form of the Lebesgue‐p norm. The resultant convergences exhibit that not only the fractional‐order system input and output matrices and the fractional‐order derivative learning gain, but also the system state matrix and the proportional learning gain, and fractional‐order integral learning gain dominate the convergence. Numerical simulations illustrate the validity and the effectiveness of the results.
Evaluation of piggyBac‐mediated CHO pools to enable material generation to support GLP toxicology studies
Authors: Rajendra Yashas , Balasubramanian Sowmya , McCracken Neil A. , Norris Dawn L. , Lian Zhirui , Schmitt Matthew G. , Frye Christopher C. , Barnard Gavin C.
Published: May 2017

Generating purified protein for GLP toxicology studies (GLP‐Tox) represents an important and often rate limiting step in the biopharmaceutical drug development process. Toxicity testing requires large amounts of therapeutic protein (>100 g), typically produced in a single 500–2,500 L bioreactor, using the final CHO clonally derived cell line (CDCL). One approach currently used to save time is to manufacture GLP‐Tox material using pools of high‐producing CHO CDCLs instead of waiting for the final CDCL. Recently, we reported CHO pools producing mAb titers >7 g/L using piggyBac‐mediated gene integration (PB CHO pools). In this study, we wanted to leverage high titer PB CHO pools to produce GLP‐Tox material. A detailed product quality attribute (PQA) assessment was conducted comparing PB CHO pools to pooled Top4 CDCLs. Four mAbs were evaluated. First, we found that PB CHO pools expressed all four mAbs at high titers (2.8–4.4 g/L in shake flasks). Second, all four PB CHO pools were aged to 55 generations (Gen). All four PB CHO Pools were found to be suitable over 55 Gen. Finally, we performed bioreactor scale‐up. PB CHO pool titers (3.7–4.8 g/L) were similar or higher than the pooled Top 4 CDCLs in 5 L bioreactors (2.4–4.1 g/L). The PQAs of protein derived from PB CHO pools were very similar to pooled Top 4 CHO CDCLs according to multiple orthogonal techniques including peptide mapping analysis. Taken together, these results demonstrate the technical feasibility of using PB CHO pools to manufacture protein for GLP‐Tox. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1436–1448, 2017
Increased production of yersiniabactin and an anthranilate analog through media optimization
Authors: Moscatello Nicholas , Qi Ruiquan , Ahmadi Mahmoud Kamal , Pfeifer Blaine A.
Published: May 2017

Yersiniabactin (Ybt) is a mixed nonribosomal peptide‐polyketide natural product that binds a wide range of metals with the potential to impact processes requiring metal retrieval and removal. In this work, we substantially improved upon the heterologous production of Ybt and an associated anthranilate analog through systematic screening and optimization of culture medium components. Specifically, a Plackett‐Burman design‐of‐experiments methodology was used to screen 22 components and to determine those contributing most to siderophore production. L‐cysteine, L‐serine, glucose, and casamino acids significantly contributed to the production of both compounds. Using this approach together with metabolic engineering of the base biosynthetic process, Ybt and the anthranilate analog titers were increased to 867 ± 121 mg/L and 16.6 ± 0.3 mg/L, respectively, an increase of ∼38 and ∼79‐fold relative to production in M9 medium. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1193–1200, 2017
Prognostic impact of the cumulative dose and dose intensity of everolimus in patients with pancreatic neuroendocrine tumors
Authors: Berardi Rossana , Torniai Mariangela , Pusceddu Sara , Spada Francesca , Ibrahim Toni , Brizzi Maria Pia , Antonuzzo Lorenzo , Ferolla Piero , Panzuto Francesco , Silvestris Nicola , Partelli Stefano , Ferretti Benedetta , Freddari Federica , Gucciardino Calogero , Testa Enrica , Concas Laura , Murgioni Sabina , Bongiovanni Alberto , Zichi Clizia , Riva Nada , Rinzivillo Maria , Brunetti Oronzo , Giustini Lucio , Di Costanzo Francesco , Delle Fave Gianfranco , Fazio Nicola , De Braud Filippo , Falconi Massimo , Cascinu Stefano
Published: May 2017

The aim of this work is to assess if cumulative dose (CD) and dose intensity (DI) of everolimus may affect survival of advanced pancreatic neuroendocrine tumors (PNETs) patients. One hundred and sixteen patients (62 males and 54 females, median age 55 years) with advanced PNETs were treated with everolimus for ≥3 months. According to a Receiver operating characteristics (ROC) analysis, patients were stratified into two groups, with CD ≤ 3000 mg (Group A; n = 68) and CD > 3000 mg (Group B; n = 48). The response rate and toxicity were comparable in the two groups. However, patients in group A experienced more dose modifications than patients in group B. Median OS was 24 months in Group A while in Group B it was not reached (HR: 26.9; 95% CI: 11.0–76.7; P < 0.0001). Patients who maintained a DI higher than 9 mg/day experienced a significantly longer OS and experienced a trend to higher response rate. Overall, our study results showed that both CD and DI of everolimus play a prognostic role for patients with advanced PNETs treated with everolimus. This should prompt efforts to continue everolimus administration in responsive patients up to at least 3000 mg despite delays or temporary interruptions.
Cerebral white matter lesion burden is associated with the degree of aortic valve calcification and predicts peri‐procedural cerebrovascular events in patients undergoing transcatheter aortic valve implantation (TAVI)
Authors: Doerner Jonas , Kupczyk Patrick A. , Wilsing Marius , Luetkens Julian A. , Storm Klaus , Fimmers Rolf , Hickethier Tilman , Eichhorn Lars , Naehle Claas P. , Schild Hans H. , Werner Nikos , Nickenig Georg , Ghanem Alexander
Published: May 2017

Objectives

To investigate the impact of aortic valve calcification and brain morphology on acute peri‐procedural cerebrovascular events (CVEs) in patients undergoing transcatheter aortic valve implantation (TAVI).

Background

Aortic valve calcification and stenosis can be assessed with echocardiography. Cerebral magnetic resonance imaging (MRI) depicts and quantifies morphological signs of hypoperfusion and vascular embolism, which is of special interest in patients with severe aortic stenosis. Furthermore, subjects who undergo TAVI are prone to suffer of clinically silent peri‐procedural CVEs.

Methods

A total of 119 patients referred to TAVI were investigated for aortic valve calcification using trans‐esophageal echocardiography. Cerebral MRI prior to and immediate after implantation was performed in all patients using a dedicated scan protocol. Prior to TAVI, brain morphology was characterized. Post TAVI, brains were investigated for the onset of acute peri‐procedural CVEs using diffusion weighted imaging (DWI).

Results

Seventy‐eight patients (65.5%) revealed acute peri‐procedural CVEs on MRI after TAVI with a favor of the left hemisphere (57.5%). The degree of valve calcification was associated with peri‐procedural CVEs. Patients with a high WML burden had an increased risk for CVEs ((OR) 2.36 (95% CI: 1.09–5.15; P = 0.037)), especially when distributed periventricular ((OR: 3.27; 95% CI: 1.47–7.26; P = 0.0038)).

Conclusion

In patients undergoing TAVI, the degree of aortic valve calcification and periventricular WML burden were correlated with acute peri‐procedural CVEs. Future studies are needed to evaluate their independent value for the long‐term clinical outcome.
Correlation of Sol–Gel Alumina‐Supported Cobalt Catalyst Processing to Cobalt Speciation, Ethanol Steam Reforming Activity, and Stability
Authors: Passos Aline R. , Martins Leandro , Pulcinelli Sandra H. , Santilli Celso V. , Briois Valérie
Published: May 2017

The effect of sol–gel alumina characteristics on the supported Co catalyst properties was investigated at the different steps of catalyst preparation. Porous alumina with variable surface reactivity were prepared from the sol–gel transition and the spinodal decomposition induced by polymers. The hydrophobicity of polymer or the calcination temperature controls the amount of the hydroxyl groups. The dried catalysts are composed of cobalt alumina hydrotalcite‐like compounds up to 64 %. After calcination, higher proportions of CoAl2O4 are observed in the alumina presenting a greater content of hydroxyl and hydrotalcite. The Co speciation during activation investigated by Quick X‐ray absorption spectroscopy evidences that both Co3O4 and CoAl2O4 are first fully reduced to CoO and then partially transformed into point‐like Co0 nucleus. The catalysts were highly active in the ethanol steam reforming reaction; however, coke deposition leads to deactivation. This deleterious effect was minimized for catalysts operating with a CoO/Co0 ratio close to 1:3.
Secondary‐Rim γ‐Cyclodextrin Functionalization to Conjugate with C60: Improved Efficacy as a Photosensitizer
Authors: Zhu Xiaolei , Quaranta Annamaria , Bensasson René V. , Sollogoub Matthieu , Zhang Yongmin
Published: May 2017

DIBAL‐H‐mediated demethylation provides a novel method to access secondary‐rim functionalized γ‐cyclodextrin. 2A,3B‐Dihydroxyl‐per‐O‐methylated‐γ‐cyclodextrin has been obtained, whose conjugation with C60 allows access to the most water‐soluble C60 conjugate described so far. The water solubility of 0.12 m (550 mg mL−1) is 150 times higher than that of the native γ‐CD/C60 complex. Its singlet oxygen (1O2) quantum yield is 0.39, an increase of one to two orders of magnitude compared to that of α(β)CD–C60 conjugates.
Simulation of nonlinear transient elastography: finite element model for the propagation of shear waves in homogeneous soft tissues
Authors: Ye W. , Bel‐Brunon A. , Catheline S. , Combescure A. , Rochette M.
Published: May 2017

In this study, visco‐hyperelastic Landau's model, which is widely used in acoustical physic field, is introduced into a finite element formulation. It is designed to model the nonlinear behaviour of finite amplitude shear waves in soft solids, typically, in biological tissues. This law is used in finite element models based on elastography, experiments reported in Jacob et al, the simulations results show a good agreement with the experimental study: It is observed in both that a plane shear wave generates only odd harmonics and a nonplane wave generates both odd and even harmonics in the spectral domain. In the second part, a parametric study is performed to analyse the influence of different factors on the generation of odd harmonics of plane wave. A quantitative relation is fitted between the odd harmonic amplitudes and the non‐linear elastic parameter of Landau's model, which provides a practical guideline to identify the non‐linearity of homogeneous tissues using elastography experiment.
Redox‐Enabled, pH‐Disabled Pyrazoline–Ferrocene INHIBIT Logic Gates
Authors: Scerri Glenn J. , Cini Miriam , Schembri Jonathan S. , da Costa Paola F. , Johnson Alex D. , Magri David C.
Published: May 2017

Pyrazoline‐ferrocene conjugates with an “electron‐donor–spacer–fluorophore–receptor” format are demonstrated as redox‐fluorescent two‐input INHIBIT logic gates.
Cannabis Smoking and Cardiovascular Health: It's Complicated
Authors: Piano MR
Published: May 2017

Many states have legalized cannabis use for treatment of certain medical conditions or have legalized cannabis for recreational use. Consequently, cannabis use prevalence has escalated, giving rise to concerns about potential health effects. Cannabis smoking remains the most prevalent route of administration and is associated with inhalation of chemical toxicants. The aim of this article is to summarize the effects of cannabis smoking on the vasculature and occurrence of cardiovascular (CV) events such as myocardial infarction (MI) and stroke.
Fluorophore Release from a Polymethinic Photoremovable Protecting Group Through a Nonlinear Optical Process
Authors: Rodríguez‐Romero Jesús , Guarin Cesar A. , Arroyo‐Pieck Andres , Gutiérrez‐Arzaluz Luis , López‐Arteaga Rafael , Cortés‐Guzmán Fernando , Navarro Pedro , Peon Jorge
Published: May 2017

Triggering the release of chemical species through the use of light is crucial for modern microscopy applications, such as single‐molecule localization and, in general, in the regulation of molecular effectors. Herein, we demonstrate a nonlinear‐optical scheme for the control of photorelease. Our system consists of a two‐photon‐absorbing photoremovable protecting group (PPG) bonded to a second chromophore which undergoes photo‐induced detachment and activation upon excitation with λ=850 nm femtosecond pulses. The two‐photon PPG section consists of a cyanine‐type dye, and the releasable section is a highly fluorescent derivatized anthracene chromophore bonded to the cyanine through a photolabile etheric‐meso‐carbon bond. This method allows for the release of a fluorophore following a spatially localized two‐photon excitation event. Both the excitation energy and the long lifetime of the upper excited states of the PPG chromophore are thought to be involved in the release process.
A cross‐sectional scanning capacitance microscopy characterization of GaAs based solar cell structures
Authors: Szyszka Adam , Dawidowski Wojciech , Stafiniak Andrzej , Prażmowska Joanna , Ściana Beata , Tłaczała Marek
Published: May 2017

Scanning Capacitance Microscopy was applied in investigation of individual components of tandem solar cell. The InGaAs tunnel junction, GaAs top subcell and GaAsN bottom subcell devices were grown by atmospheric pressure metalorganic vapour phase epitaxy. It was shown that accuracy of p‐n junction position determination by SCM method depends on doping concentration of layers in structure and measurement parameters.
Synthesis, Structural Characterization and Catalytic Activities of Sulfur‐Functionalized NHC–Copper(I) Complexes
Authors: Szadkowska Anna , Zaorska Ewelina , Staszko Sebastian , Pawłowski Robert , Trzybiński Damian , Woźniak Krzysztof
Published: May 2017

The synthesis of a family of N‐heterocyclic carbene–copper complexes bearing a sulfur moiety by using different copper(I) halides through convenient procedures is reported. The solid‐state structures of the presented copper compounds were elucidated based on X‐ray crystallographic analysis. The obtained complexes were examined in various catalytic transformations including 1,3‐dipolar cycloaddition of alkynes and azides, A3 coupling reaction, and β‐hydroboration.
A century of victimhood: Antecedents and current impacts of perceived suffering in World War I across Europe
Authors: Bouchat Pierre , Licata Laurent , Rosoux Valérie , Allesch Christian , Ammerer Heinrich , Bovina Inna , Bruckmüller Susanne , Cabecinhas Rosa , Chryssochoou Xenia , Cohrs J. Christopher , Csertő István , Delouvée Sylvain , Durante Federica , Ernst‐Vintila Andreea , Flassbeck Christine , Hilton Denis , Kesteloot Chantal , Kislioglu Resit , Krenn Alice , Macovei Irina , Mari Silvia , Petrovic Nebojša , Pólya Tibor , Sá Alberto , Sakki Inari , Turjacanin Vladimir , van Ypersele Laurence , Volpato Chiara , Bilewicz Michal , Klein Olivier
Published: May 2017

The present study addresses antecedents and consequences of collective victimhood in the context of World War I (WWI) across 15 European nations (N = 2423 social science students). Using multilevel analysis, we find evidence that collective victimhood is still present a hundred years after the onset of the war and can be predicted by WWI‐related objective indicators of victimization at national and family levels. This suggests that collective victimhood is partly grounded in the actual experience of WWI. In addition, we show that sense of collective victimhood positively predicts acknowledgment of the suffering inflicted by one's nation on other countries during WWI. This is consistent with a social representation of WWI as involving a vast massacre in which nations were both victim and perpetrator. Finally, we find that objective indicators of victimization predict pacifism in divergent ways, with an indicator at the national level associated with more pacifist attitudes and an indicator at the family level being associated with less pacifist attitudes. This finding suggests that war‐torn societies may have developed social representations favouring peaceful coexistence whereas, at the family level, victimization may still foster retaliatory tendencies.
Current practice and challenges in night‐time care for people with dementia living in care homes: a qualitative study
Authors: Nunez Kayleigh Marie , Khan Zunera , Testad Ingelin , Lawrence Vanessa , Creese Byron , Corbett Anne
Published: May 2017

Objective

To explore the current practices and challenges in night‐time care for people with dementia living in care homes in the UK.

Methods

Focus group discussions (FGD) were held with care staff and family carers from five care homes in South London. To supplement the FGD data, an online survey was circulated to family carers (n = 16), and informal interviews were conducted with night‐time care staff and nurses (n = 19). The questions for the online survey were designed to specifically explore the themes that emerged from the FGD.

Results

Thematic analysis revealed eight key themes in the management of sleep disturbance in people with dementia living in care homes: current night‐time care practices, dissonance in perceived causes of sleep disturbances, inconsistencies in treatment options, insufficient staffing levels, working relationships between shifts, nurse burden and responsibility, communication as a critical challenge, connecting with residents and one overarching theme of balance.

Conclusions

The findings of this study highlight the need for an evidence‐based sleep disturbance management programme designed for use in care homes and informed by stakeholders. The key themes identified represent the major barriers to good quality care and areas which future programmes will need to address to improve the quality of night‐time care in care homes. There are clearly opportunities for future examination of non‐pharmacological night‐time care management programmes for use in the population. Copyright © 2017 John Wiley & Sons, Ltd.
Effect of ceramic calcium–phosphorus ratio on chondrocyte‐mediated biosynthesis and mineralization
Authors: Boushell Margaret K. , Khanarian Nora T. , LeGeros Raquel Z. , Lu Helen H.
Published: May 2017

The osteochondral interface functions as a structural barrier between cartilage and bone, maintaining tissue integrity postinjury and during homeostasis. Regeneration of this calcified cartilage region is thus essential for integrative cartilage healing, and hydrogel‐ceramic composite scaffolds have been explored for calcified cartilage formation. The objective of this study is to test the hypothesis that Ca/P ratio of the ceramic phase of the composite scaffold regulates chondrocyte biosynthesis and mineralization potential. Specifically, the response of deep zone chondrocytes to two bioactive ceramics with different calcium–phosphorus ratios (1.35 ± 0.01 and 1.41 ± 0.02) was evaluated in agarose hydrogel scaffolds over two weeksin vitro. It was observed that the ceramic with higher calcium–phosphorus ratio enhanced chondrocyte proliferation, glycosaminoglycan production, and induced an early onset of alkaline phosphorus activity, while the ceramic with lower calcium–phosphorus ratio performed similarly to the ceramic‐free control. These results underscore the importance of ceramic bioactivity in directing chondrocyte response, and demonstrate that Ca/P ratio is a key parameter to be considered in osteochondral scaffold design. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2694–2702, 2017.
Revisiting the concept of inflammatory cell‐induced corrosion
Authors: Yuan Nathaniel , Park Sang‐Hyun , Luck James V. , Campbell Patricia A.
Published: May 2017

A peculiar type of surface pitting damage to revised joint replacement implant metal surfaces has been attributed to cellular activity and termed “inflammatory cell‐induced‐corrosion.” We visually examined 1859 explanted metal implants to document the presence and extent of these features. The data was used to examine correlations between these features and the implant material, and modularity as well as clinical variables. The features were observed in approximately 77% of modular and 30% of monobloc hip implants in a variety of metals, as well as to some degree in various other implants. To test the possibility that these features were an artefact of electrocautery damage during revision surgery, a cleaned, flat, polished, CoCr disk was exposed to a variety of electrocautery interactions. This led to the production of pits and markings comparable to the published damage and to the damage found on the explants we examined. It is concluded that electrocautery damage rather than cellular activity is the cause of these features. Although rarely reported, this damage may be associated with femoral neck fracture. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1148–1155, 2018.
Flare‐Up After Maxillofacial Surgery in a Patient With Fibrodysplasia Ossificans Progressiva: An [18F]‐NaF PET/CT Study and a Systematic Review
Authors: Eekhoff E Marelise W , Netelenbos J Coen , de Graaf Pim , Hoebink Max , Bravenboer Nathalie , Micha Dimitra , Pals Gerard , de Vries Teun J , Lammertsma Adriaan A , Raijmakers Pieter GHM , van Es Robert JJ
Published: May 2017

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder leading to progressive heterotopic ossifications (HO) of muscles, tendons, and ligaments, which can be induced by trauma or by surgery. Despite strong medical advice to the contrary, an FOP patient insisted on surgery to alleviate her complete trismus, which caused an unbearable impact on her quality of life (QOL). The entire trismus history of this FOP patient is presented. [18F]‐NaF position emission tomography/computed tomography (PET/CT) scans were introduced as an imaging method for heterotopic bone formation activity. To place our findings into context, a systematic review on jaw surgery in FOP was performed. After falling down the stairs, a 9‐year‐old patient developed mobility impairment of her left‐sided jaw. During the following 13 years bone scintigraphy showed persistent activity of the disease leading to progressive left‐sided zygomatico‐mandibular fusion by HO, resulting in complete trismus. Within 1 month after HO removal on the left side and a matching right coronoidectomy, [18F]‐NaF PET/CT demonstrated a substantial flare‐up activity followed by new HO in both masseter and temporalis muscles. Despite recurrent HO and trismus her QOL increased due to a stable increased interincisal opening of 5.5 mm. Although systematic review reveals a 100% risk of HO recurrence after jaw surgery, information on improved QOL is scarce. In conclusion, surgery in FOP may be beneficial for QOL despite new HO formation. Assessment of disease activity using [18F]‐NaF PET/CT is possible before HO is evident on CT and may serve as a new and quantitative marker of the disease. © 2017 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.
Metacarpal Growth During Adolescence in a Longitudinal South African Cohort
Authors: Magan Ansuyah , Nyati Lukhanyo H , Micklesfield Lisa K , Norris Shane A , Pettifor John M
Published: May 2017

To monitor the drift of the periosteal and endocortical surfaces during metacarpal growth longitudinally, radiogrammetry was carried out on hand-wrist X-rays of 572 children from the Birth to Twenty Bone Health Cohort annually from ages 9 to 21 years. This is the largest collection of longitudinal X-rays in African children. The second metacarpal bone length, bone width, and medullary width were measured using digital vernier calipers on a total of 4730 X-rays. Superimposition by Translation and Rotation (SITAR) was used to obtain age at peak metacarpal length velocity (PLV). Bone width and medullary width were modeled using SITAR against both chronological age and age from PLV. In black and white females, tempo and velocity of metacarpal length growth was synchronized. Black males, however, attained PLV 7 months later than white males (p < 0.0001). Compared to white males, black males had a longer second metacarpal (p < 0.05), and greater bone width size (p < 0.02), tempo (p < 0.0009), and velocity (p < 0.0001). Medullary width growth velocity in black participants peaked 2 years prior to attainment of PLV and exceeded that of their white peers (p < 0.0001) in whom it peaked 6 to 12 months post-PLV attainment. Black adolescents therefore had wider bones with relatively thinner cortices and wider medullary cavities than their white peers. Ethnic and sex differences also occurred in the timing of medullary width contraction that accompanied expansion in bone width and cortical thickness. In black males, medullary width contraction commenced approximately 3 years later than in black females, whereas in white males this occurred a year later than in white females. The ethnic and sex differences in bone acquisition reported in this study may differentially affect bone mass in later life. © 2017 American Society for Bone and Mineral Research.
Destabilization of Human Insulin Fibrils by Peptides of Fruit Bromelain Derived From Ananas comosus (Pineapple)
Authors: Das Sromona , Bhattacharyya Debasish
Published: May 2017

Deposition of insulin aggregates in human body leads to dysfunctioning of several organs. Effectiveness of fruit bromelain from pineapple in prevention of insulin aggregate was investigated. Proteolyses of bromelain was done as par human digestive system and the pool of small peptides was separated from larger peptides and proteins. Under conditions of growth of insulin aggregates from its monomers, this pool of peptides restricted the reaction upto formation of oligomers of limited size. These peptides also destabilized preformed insulin aggregates to oligomers. These processes were followed fluorimetrically using Thioflavin T and 1‐ANS, size‐exclusion HPLC, dynamic light scattering, atomic force microscopy, and transmission electron microscopy. Sequences of insulin (A and B chains) and bromelain were aligned using Clustal W software to predict most probable sites of interactions. Synthetic tripeptides corresponding to the hydrophobic interactive sites of bromelain showed disaggregation of insulin suggesting specificity of interactions. The peptides GG and AAA serving as negative controls showed no potency in destabilization of aggregates. Disaggregation potency of the peptides was also observed when insulin was deposited on HepG2 liver cells where no formation of toxic oligomers occurred. Amyloidogenic des‐octapeptide (B23‐B30 of insulin) incapable of cell signaling showed cytotoxicity similar to insulin. This toxicity could be neutralized by bromelain derived peptides. FT‐IR and far‐UV circular dichroism analysis indicated that disaggregated insulin had structure distinctly different from that of its hexameric (native) or monomeric states. Based on the stoichiometry of interaction and irreversibility of disaggregation, the mechanism/s of the peptides and insulin interactions has been proposed. J. Cell. Biochem. 118: 4881–4896, 2017. © 2017 Wiley Periodicals, Inc.
Protein Z and Endothelin‐1 genetic polymorphisms in pediatric Egyptian sickle cell disease patients
Authors: Khorshied Mervat M. , Mohamed Nohair S. , Hamza Rania S. , Ali Rasha M. , El‐Ghamrawy Mona K.
Published: May 2017

Background

Sickle cell disease (SCD) is a monogenic disease associated with multisystem morbidity. Vasculopathy caused by delicate imbalance between coagulation and endothelial systems plays a pivotal role in disease course. As Protein Z and Endothelin‐1 genetic polymorphisms may increase the thrombotic risk, the aim of the current work was to verify the possible impact of Protein Z (PROZ G79A) and Endothelin‐1 (EDN1 G5665T) polymorphisms on the clinic‐laboratory features of the SCD in a cohort of Egyptian pediatric patients.

Methods

Genotyping of Protein Z G79A and Endothelin‐1 G5665T was carried out by polymerase chain reaction‐restricted fragment length polymorphism (PCR‐RFLP) assay for 100 SCD patients and 100 controls.

Results

Protein ‐Z G79A polymorphism was not associated with vascular complications in the studied SCD patients. Endothelin‐1 G5665T polymorphism was associated with pulmonary dysfunction (pulmonary artery hypertension and acute chest syndrome) and severe vaso‐occlusive crises (VOC).

Conclusion

Endothelin‐1 G5665T polymorphism could be considered as a molecular predictor for pulmonary dysfunction and severe VOC in SCD. Further researches with larger cohorts are recommended to understand the pathophysiology of SCD and to explain the inter‐patients’ variability of disease severity.
The performance of MALBAC and MDA methods in the identification of concurrent mutations and aneuploidy screening to diagnose beta‐thalassaemia disorders at the single‐ and multiple‐cell levels
Authors: Liu WeiQiang , Zhang HuiMin , Hu Dan , Lu SiJia , Sun XiaoFang
Published: May 2017

Aim

To select an optimal whole‐genome amplification (WGA) method to improve the efficiency of the preimplantation genetic diagnosis and screening (PGD/PGS) of beta‐thalassaemia disorders.

Methods

Fifty‐seven fibroblast samples with defined beta‐thalassaemia variations and forty‐eight single‐blastomere samples were amplified from single‐, two‐, and five‐cell samples by multiple annealing and looping‐based amplification cycles (MALBAC) and the multiple displacement amplification (MDA) method. Low‐depth, high‐throughput sequencing was performed to evaluate and compare the coefficiencies of the chromosomal copy number variation (CNV) detection rate and the allele dropout (ADO) rate between these two methods.

Results

At the single‐cell level, the success rates of the CNV detection in the fibroblast samples were 100% in the MALBAC group and 91.67% in the MDA group; the coefficient of variation in the CNV detection in the MALBAC group was significantly superior to that in the MDA group (0.15 vs 0.37). The total ADO rate in the HBB allele detection was 4.55% in the MALBAC group, which was significantly lower than the 22.5% rate observed in the MDA group. However, when five or more cells were used as the starting template, the ADO rate significantly decreased, and these two methods did not differ significantly.

Conclusions

For the genetic diagnosis of HBB gene variation at the single‐cell level, MALBAC is a more suitable method due to its higher level of uniformity and specificity. When five or more cells are used as the starting template, both methods exhibit similar efficiency, increased accuracy, and a similar success rate in PGD/PGS.
Microtubules regulate brush border formation
Authors: Tonucci Facundo M. , Ferretti Anabela , Almada Evangelina , Cribb Pamela , Vena Rodrigo , Hidalgo Florencia , Favre Cristián , Tyska Matt J. , Kaverina Irina , Larocca Maria C.
Published: May 2017

Most epithelial cells contain apical membrane structures associated to bundles of actin filaments, which constitute the brush border. Whereas microtubule participation in the maintenance of the brush border identity has been characterized, their contribution to de novo microvilli organization remained elusive. Hereby, using a cell model of individual enterocyte polarization, we found that nocodazole induced microtubule depolymerization prevented the de novo brush border formation. Microtubule participation in brush border actin organization was confirmed in polarized kidney tubule MDCK cells. We also found that centrosome, but not Golgi derived microtubules, were essential for the initial stages of brush border development. During this process, microtubule plus ends acquired an early asymmetric orientation toward the apical membrane, which clearly differs from their predominant basal orientation in mature epithelia. In addition, overexpression of the microtubule plus ends associated protein CLIP170, which regulate actin nucleation in different cell contexts, facilitated brush border formation. In combination, the present results support the participation of centrosomal microtubule plus ends in the activation of the polarized actin organization associated to brush border formation, unveiling a novel mechanism of microtubule regulation of epithelial polarity.
Spray congealing as innovative technique for enzyme encapsulation
Authors: Engelmann Claudia , Kragl Udo
Published: May 2017

BACKGROUND

Spray congealing is investigated as a new innovative immobilization technique for biocatalysts. The immobilization is realized by atomization of a mixture of a melted carrier and the enzyme, which is re‐solidifyed due to temperature decrease. This method needs neither organic solvents, nor difficult downstream processing after preparation. For the encapsulation of different matrices, long chain alcohols and glyceryl derivatives, with melting points below 86 °C and environmentally friendly properties, are chosen and tested for their suitability for enzyme encapsulation.

RESULTS

The immobilization of a laccase (EC 1.10.3.2, Novozym 51003, from Myceliophthora thermophila) was investigated and the produced microparticles were characterized. The obtained particles showed a mean particle size around 40 μm and a spherical surface with different structures depending on the used matrix. Spray congealing with the laccase reached yields of 80% and residual activities up to 56%. Furthermore, four consecutive reactions were realized with cetyl alcohol as carrier and an activity of 20% was retained.

CONCLUSION

Cetyl alcohol was found to be the most appropriate carrier for the immobilization of the investigated laccase, due to easy handling and high yields. In comparison with the other tested carriers, the best retained activities were obtained and recycling of the biocatalyst was realized. © 2017 Society of Chemical Industry
Cytokine response in crimean‐congo hemorrhagic fever virus infection
Authors: Ergönül Önder , Şeref Ceren , Eren Şebnem , Çelikbaş Aysel , Baykam Nurcan , Dokuzoğuz Başak , Gönen Mehmet , Can Füsun
Published: May 2017

We described the predictive role of cytokines in fatality of Crimean Congo Hemorrhagic Fever Virus (CCHFV) infection by using daily clinical sera samples. Consequent serum samples of the selected patients in different severity groups and healthy controls were examined by using human cytokine 17‐plex assay. We included 12 (23%) mild, 30 (58%) moderate, 10 (19%) severe patients, and 10 healthy volunteers. The mean age of the patients was 52 (sd 15), 52% were female. Forty‐six patients (88%) received ribavirin. During disease course, the median levels of IL‐6, IL‐8, IL‐10, IL‐10/12, IFN‐γ, MCP‐1, and MIP‐1b were found to be significantly higher among CCHF patients than the healthy controls. Within the first 5 days after onset of disease, among the fatal cases, the median levels of IL‐6 and IL‐8 were found to be significantly higher than the survived ones (Fig. 3), and MCP‐1 was elevated among fatal cases, but statistical significance was not detected. In receiver operating characteristic (ROC) analysis, IL‐8 (92%), IL‐6 (92%), MCP‐1 (79%) were found to be the most significant cytokines in predicting the fatality rates in the early period of the disease (5 days). IL‐6 and IL‐8 can predict the poor outcome, within the first 5 days of disease course. Elevated IL‐6 and IL‐8 levels within first 5 days could be used as prognostic markers.
Field identification of minerals at burning coal dumps using miniature Raman spectrometers
Authors: F. Košek , A. Culka , J. Jehlička
Published: May 2017

Earthy, finely crystalline, weathering, and condensation products sometimes occur at the surface and subsurface of waste dumps or burning coal dumps which remain after coal mining. Surface crusts at the burning dumps of bituminous coal at Heřmanice (Silesia, Czech Republic) were investigated using a lightweight portable Raman spectrometer. The compact instrument, with 785‐nm diode excitation, allowed for the recording of good quality Raman spectra, and for the identification of a series of more‐or‐less complex sulfates (mascagnite, letovicite, sabieite, pyracmonite) as well as common sal ammoniac and sulfur. The great complexity of the mineral associations is demonstrated in aggregates of efremovite, godovikovite, boussingaultite, and sabieite. In this case, the handheld instrumentation does not allow for ideal detection and discrimination of finely crystalline minerals in complex mixtures. Copyright © 2017 John Wiley & Sons, Ltd.
Sensitive ‘on the fiber’ detection of synthetic organic dyes by laser photoinduced plasmonic Ag nanoparticles
Authors: Bonacini Irene , Gallazzi Francesca , Espina Alba , Cañamares Maria Vega , Prati Silvia , Mazzeo Rocco , Sanchez‐Cortes Santiago
Published: May 2017

The photoreduction of aqueous Ag+ to silver nanoparticles (AgNPs) on a substrate was studied aiming at the application of surface‐enhanced Raman scattering (SERS) technique to the sensitive analysis of organic colorants directly on artworks. In particular, the presence of the synthetic dyes methyl violet (BV1) and fuchsine (BV14), in both standard and historical wool fibers, was analyzed. Scanning electron microscopy was employed to study the morphology and distribution of the NPs obtained on the fiber. We have carried out an investigation of the influence of several factors on the morphology of NPs: excitation wavelength, substrate, laser power and laser irradiation time. The resulting materials were analyzed at different laser wavelengths in order to evaluate the application range of the probe laser after the NPs formation. SERS spectra of the BV1 and BV14 dyes on the fiber were obtained and compared with those obtained in suspended conventional AgNPs, in order to deduce the possible influence of the wool substrate on the Raman spectra. SERS spectra were analyzed considering the possible resonance Raman processes. Bands attributed to the protein substrate were also identified. The main goal of this work was to assess and optimize a general method of analysis of organic dyes on natural fibers based on the direct preparation of AgNPs by laser SERS technique. Copyright © 2017 John Wiley & Sons, Ltd.