bluuebunny/crossref_metadata_2025 huggingface dataset:
Mixed solvent system as binder for the production of silicified microcrystalline cellulose‐based pellets
Authors: Ting Grace Loong , Chan Yen Yee , Chaw Cheng Shu
Published: May 2019

Silicified microcrystalline cellulose pellets with hydroxypropyl methylcellullose (HPMC) as modifier were prepared using a mixed solvent as liquid binder. Pellets were produced using extrusion‐spheronization with a mixed solvent consisting of water and isopropanol as liquid binder. The key spheronization aid was Prosolv® SMCC 90. Low viscosity grade HPMC was incorporated aiming to modify release of indometacin. Physical characteristics including breaking load, apparent density and flow properties, particle size distribution and shape were determined. Drug loaded pellets were also tested for dissolution profiles. By adjusting liquid binder property, at isopropanol to water ratio of 3.5 to 6.5, pellets of desirable size and shape with reasonable yields were obtained. Pellets exhibited good flow property and they were mechanically strong. Pellet with higher HPMC content displayed a faster drug dissolution profile. This was because low viscosity grade HPMC was not enough to create strong gel. Instead hydration of HPMC molecules increased matrix's hydrophilicity and weakened the structure of pellet faster. The release of indometacin was partly based on the erosion of hydrated matrix. The presence of HPMC in the pellets would require a mixed solvent to produce desirable shape. Incorporation of HPMC had modified drug release from the pellets without further coating. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47924.
Tandem IBX‐Promoted Primary Alcohol Oxidation/Opening of Intermediate β,γ‐Diolcarbonate Aldehydes to (E)‐γ‐Hydroxy‐α,β‐enals
Authors: Kumari Anupama , Gholap Sachin P. , Fernandes Rodney A.
Published: May 2019

A tandem IBX‐promoted oxidation of primary alcohol to aldehyde and opening of intermediate β,γ‐diolcarbonate aldehyde to (E)‐γ‐hydroxy‐α,β‐enal has been developed. Remarkably, the carbonate opening delivered exclusively (E)‐olefin and no over‐oxidation of γ‐hydroxy was observed. The method developed has been extended to complete the stereoselective total synthesis of both (S)‐ and (R)‐coriolides and d‐xylo‐ and d‐arabino‐C‐20 guggultetrols.
Assembly of Functionalized 4‐Alkynylisoxazoles by Palladium‐Catalyzed Three‐Component Cascade Cyclization/Alkynylation
Authors: Li Jianxiao , Huang Ruikang , Li Can , Lin Shao , Wu Wanqing , Jiang Huanfeng
Published: May 2019

A novel N‐heterocyclic carbene (NHC)‐palladium‐catalyzed three‐component cascade cyclization/alkynylation for the synthesis of structurally diverse 4‐alkynylisoxazoles was efficiently developed in ionic liquids. The operational simplicity, without additives, no additional ligands, and 0.5 mol % catalyst loading under air are some of the attractive features of this present protocol.
Characterization of intact glycopeptides reveals the impact of culture media on site‐specific glycosylation of EPO‐Fc fusion protein generated by CHO‐GS cells
Authors: Wang Qiong , Yang Ganglong , Wang Tiexin , Yang Weiming , Betenbaugh Michael J. , Zhang Hui
Published: May 2019

With the increasing demand to provide more detailed quality attributes, more sophisticated glycan analysis tools are highly desirable for biopharmaceutical manufacturing. Here, we performed an intact glycopeptide analysis method to simultaneously analyze the site‐specific N‐ and O‐glycan profiles of the recombinant erythropoietin Fc (EPO‐Fc) protein secreted from a Chinese hamster ovary glutamine synthetase stable cell line and compared the effects of two commercial culture media, EX‐CELL (EX) and immediate advantage (IA) media, on the glycosylation profile of the target protein. EPO‐Fc, containing the Fc region of immunoglobulin G1 (IgG1) fused to EPO, was harvested at Day 5 and 8 of a batch cell culture process followed by purification and N‐ and O‐glycopeptide profiling. A mixed anion exchange chromatographic column was implemented to capture and enrich N‐linked glycopeptides. Using intact glycopeptide characterization, the EPO‐Fc was observed to maintain their individual EPO and Fc N‐glycan characteristics in which the EPO region presented bi‐, tri‐, and tetra‐branched N‐glycan structures, while the Fc N‐glycan displayed mostly biantennary glycans. EPO‐Fc protein generated in EX medium produced more complex tetra‐antennary N‐glycans at each of the three EPO N‐sites while IA medium resulted in a greater fraction of bi‐ and tri‐antennary N‐glycans at these same sites. Interestingly, the sialylation content decreased from sites 1–4 in both media while the fucosylation progressively increased with a maximum at the final IgG Fc site. Moreover, we observed that low amounts of Neu5Gc were detected and the content increased at the later sampling time in both EX and IA media. For O‐glycopeptides, both media produced predominantly three structures, N1F1F0SOG0, N1H1F0S1G0, and N1H1F0S2G0, with lesser amounts of other structures. This intact glycopeptide method can decipher site‐specific glycosylation profile and provide a more detailed characterization of N‐ and O‐glycans present for enhanced understanding of the key product quality attributes such as media on recombinant proteins of biotechnology interest.
Rational surface engineering of an arginine deiminase (an antitumor enzyme) for increased PEGylation efficiency
Authors: Cheng Feng , Yang Jianhua , Schwaneberg Ulrich , Zhu Leilei
Published: May 2019

Arginine deiminase (ADI) is a therapeutic protein for cancer therapy of arginine‐auxotrophic tumors. However, its application as anticancer drug is hampered by its poor stability under physiological conditions in the bloodstream. Commonly, random PEGylation is being used for increasing the stability of ADI and in turn the improved half‐life. However, the traditional random PEGylation usually leads to poor PEGylation efficiency due to the limited number of Lys on the protein surface. To boost the PEGylation efficiency and enhance the stability of ADI further, surface engineering of PpADI (an ADI from Pseudomonas plecoglossicida) to increase the suitable PEGylation sites was carried out. A new in silico approach for increasing the PEGylation sites was developed. The validation of this approach was performed on previously identified PpADI variant M31 to increase potential PEGylation sites. Four Arg residues on the surface of PpADI M31 were selected through three criteria and subsequently substituted to Lys, aiming for providing primary amines for PEGylation. Two out of the four substitutions (R299K and R382K) enhanced the stability of PEGylated PpADI in human serum. The average numbers of PEGylation sites were increased from ~12 (tetrameric PpADI M31, starting point) to ~20 (tetrameric PpADI M36, final variant). Importantly, the PEGylated PpADI M36 after PEGylation exhibited significantly improved Tm values (M31: 40°C; M36: 40°C; polyethylene glycol [PEG]‐M31: 54°C; PEG‐M36: 64°C) and half‐life in human serum (M31: 1.9 days; M36: 2.0 days; PEG‐M31: 3.2 days; PEG‐M36: 4.8 days). These proved that surface engineering is an effective approach to increase the PEGylation efficiency which therefore enhances the stability of therapeutic enzymes. Furthermore, the PEGylated PpADI M36 represents a highly attractive candidate for the treatment of arginine‐auxotrophic tumors.
New insights into developing antibiofouling surfaces for industrial photobioreactors
Authors: Zeriouh Ouassim , Marco‐Rocamora Arturo , Reinoso‐Moreno José Vicente , López‐Rosales Lorenzo , García‐Camacho Francisco , Molina‐Grima Emilio
Published: May 2019

The biofouling formation of the marine microalga Nannochloropsis gaditana on nontoxic surfaces was quantified on rigid materials, both coated (with fouling release coatings and nanoparticle coatings) and noncoated, to cover a wide range of surface properties from strongly hydrophobic to markedly hydrophilic under conditions similar to those prevailing in outdoor massive cultures of marine microalgae. The effect of seawater on surfaces that presented the best antibiofouling properties was also evaluated. The adhesion intensity on the different surfaces was compared with the predictions of the biocompatibility theories developed by Baier and Vogler using water adhesion tension (τ0) as the quantitative parameter of surface wettability. For the most hydrophobic surfaces, τ0 ≤ 0, the microalgae adhesion density increased linearly with τ0, following the Baier's theory trend. However, for the rest of the surfaces, τ0 ≥ 0, a tendency toward minimum adhesion was observed for amphiphilic surfaces with a τ0 = 36 mJ/m2, a value close to that which minimizes cell adhesion according to Vogler's theory. The understanding and combination of the two biocompatibility theories could help to design universal antibiofouling surfaces that minimize the van der Waals forces and prevent foulant adsorption by using a thin layer of hydration.
Effect of protein cryoconcentration and processing conditions on kinetics of dimer formation for a monoclonal antibody: A case study on bioprocessing
Authors: Mehta Shyam B. , Subramanian Srishty , D'Mello Rowena , Brisbane Charlene , Roy Shouvik
Published: May 2019

Monoclonal antibodies (mAbs) may be prone to self‐association leading to formation of dimers, trimers, or other high molecular weight species during bio‐processing. In order to implement appropriate manufacturing control strategies during bio‐processing, it is important to understand various real life bio‐processing conditions where such self‐associations may manifest. One such case study is presented here of increase in dimer content for an mAb during scale‐up bio‐processing and the approach taken to understand the under‐lying mechanism. In this example, a therapeutic mAb demonstrated a consistently higher dimer values (~0.5% higher) in the drug product (DP) during release when compared to the same value measured in the corresponding drug substance (DS) lot. This observation was interesting since the DS was supplied frozen, and the DS and DP share the same formulation composition and therefore investigation of this dimer change was the scope of the characterization study. Variable path length spectroscopy and size exclusion chromatography was used for protein quantification and to monitor %dimer respectively during characterization of fill‐finish unit operations. At the start of DP manufacturing process, immediately after thaw of bulk DS, a protein concentration gradient was observed and the concentration ranged from 90 mg/mL (top of container) to 210 mg/mL (bottom of container). The dimerization kinetics in the same DS container was dependent on concentration with higher concentrations demonstrating higher rates of dimerization. After the bulk DS was mixed for further processing, %dimer in purified bulk DS was quantitated to be approximately 1.4% which is identical to levels observed during scale‐up manufacturing of DP. After each unit operation, the in‐process samples tested for %dimer showed a gradual increase in dimer as a function of time over the next 7 days accumulating to 1.8% dimer at the end of DP manufacturing process. Samples subjected to static incubation at 2–8°C and room temperature (RT; 15–25°C) showed a gradual increase in dimer over the same time frame; however, the rate of increase in dimer at RT was higher compared to samples stored at 2–8°C. The results from this demonstrate two important key findings: self‐association kinetics of mAbs could be exacerbated by protein cryoconcentration and temperature conditions during bioprocessing. Since these two parameters are commonly encountered during manufacturing, the proposed mitigation strategy is to ensure homogeneity of the bulk DP during processing. The temperature dependent self‐association kinetics of mAb could be mitigated by processing at lower temperature (e.g., 2–8°C) and by storing the finished DP at lower temperature after manufacturing. The results from this study also highlight the criticality of setting slightly wider specifications for DP compared to DS following ICH Q6B guidelines.
Establishment of epithelial and fibroblast cell cultures and cell lines from primary renal cancer nephrectomies
Authors: Yap Ning Yi , Ong Teng Aik , Morais Christudas , Pailoor Jayalakshmi , Gobe Glenda C. , Rajandram Retnagowri
Published: May 2019

Renal cell carcinoma (RCC) is one of the most lethal urogenital cancers and effective treatment of metastatic RCC remains an elusive target. Cell lines enable the in vitro investigation of molecular and genetic changes leading to renal carcinogenesis and are important for evaluating cellular drug response or toxicity. This study details a fast and easy protocol of establishing epithelial and fibroblast cell cultures or cell lines concurrently from renal cancer nephrectomy tissue. The protocol involves mechanical disaggregation, collagenase digestion and cell sieving for establishing epithelial cells while fibroblast cells were grown from explants. This protocol has been modified from previous published reports with additional antibiotics and washing steps added to eliminate microbial contamination from the surgical source. Cell characterisation was carried out using immunofluorescence and quantitative polymerase chain reaction. Eleven stable epithelial renal tumour cell lines of various subtypes, including rare subtypes, were established with a spontaneous immortalisation rate of 21.6% using this protocol. Eight fibroblast cell cultures grew successfully but did not achieve spontaneous immortalisation. Cells of epithelial origin expressed higher expressions of epithelial markers such as pan‐cytokeratin, cytokeratin 8 and E‐cadherin whereas fibroblast cells expressed high α‐smooth muscle actin. Further mutational analysis is needed to evaluate the genetic or molecular characteristics of the cell lines.
X‐ray fused with MRI guidance of pre‐selected transcatheter congenital heart disease interventions
Authors: Grant Elena K. , Kanter Joshua P. , Olivieri Laura J. , Cross Russell R. , Campbell‐Washburn Adrienne , Faranesh Anthony Z. , Cronin Ileen , Hamann Karin S. , O'Byrne Michael L. , Slack Michael C. , Lederman Robert J. , Ratnayaka Kanishka
Published: May 2019

Objectives

To determine whether X‐ray fused with MRI (XFM) is beneficial for select transcatheter congenital heart disease interventions.

Background

Complex transcatheter interventions often require three‐dimensional (3D) soft tissue imaging guidance. Fusion imaging with live X‐ray fluoroscopy can potentially improve and simplify procedures.

Methods

Patients referred for select congenital heart disease interventions were prospectively enrolled. Cardiac MRI data was overlaid on live fluoroscopy for procedural guidance. Likert scale operator assessments of value were recorded. Fluoroscopy time, radiation exposure, contrast dose, and procedure time were compared to matched cases from our institutional experience.

Results

Forty‐six patients were enrolled. Pre‐catheterization, same day cardiac MRI findings indicated intervention should be deferred in nine patients. XFM‐guided cardiac catheterization was performed in 37 (median age 8.7 years [0.5–63 years]; median weight 28 kg [5.6–110 kg]) with the following prespecified indications: pulmonary artery (PA) stenosis (n = 13), aortic coarctation (n = 12), conduit stenosis/insufficiency (n = 9), and ventricular septal defect (n = 3). Diagnostic catheterization showed intervention was not indicated in 12 additional cases. XFM‐guided intervention was performed in the remaining 25. Fluoroscopy time was shorter for XFM‐guided intervention cases compared to matched controls. There was no significant difference in radiation dose area product, contrast volume, or procedure time. Operator Likert scores indicated XFM provided useful soft tissue guidance in all cases and was never misleading.

Conclusions

XFM provides operators with meaningful three‐dimensional soft tissue data and reduces fluoroscopy time in select congenital heart disease interventions.
Multiple Covalent Triazine Frameworks with Strong Polysulfide Chemisorption for Enhanced Lithium‐Sulfur Batteries
Authors: Wang De‐Gao , Tan Lei , Wang Huan , Song Min , Wang Jiexi , Kuang Gui‐Chao
Published: May 2019

Endowed with high theoretical energy density, low cost, and environmental friendliness, lithium‐sulfur batteries have a promising future in energy storage. The volume expansion of the sulfur cathode, shuttle effects, and the insulating nature of polysulfide result in poor cycling stability and limit practical applications of lithium‐sulfur batteries. In this work, these matters are relieved by physically and chemically restricting sulfur species in highly fluorinated sulfur‐rich multiple covalent triazine frameworks synthesized through nucleophilic aromatic substitution reaction chemistry. It exhibits a specific capacity of 681 mAh g−1 and capacity retention of 62.6 % after 400 cycles, indicating a 0.09 % degradation per cycle. The superiority in cycle performance is attributed to the homogeneous distribution of sulfur, covalent bonding of sulfur, and affinity for polysulfide of triazine rings.
Layered Crystalline and Amorphous Platinum Disulfide (PtS2): Contrasting Electrochemistry
Authors: Wang Yong , Szokolova Katerina , Nasir Muhammad Zafir Mohamad , Sofer Zdenek , Pumera Martin
Published: May 2019

Group 6 transition metal dichalcogenides (TMDs), such as MoS2 and WS2 have been extensively studied for various applications while few studies have delved into other TMDs such as platinum dichalcogenides. In this work, layered crystalline and amorphous platinum disulfide (PtS2) were synthesized, characterised and their fundamental electrochemical properties were investigated. Both materials exhibited inherent oxidation and reduction reactions which would limit their operating potential window for sensing applications. Amorphous phase materials are considered to be promising electrocatalysts due to the porous, and nanostructured morphology with high concentration of unsaturated active sites. The electrocatalytic performances towards oxygen reduction (ORR) and hydrogen evolution reactions (HER) of crystalline and amorphous PtS2 were analysed. Amorphous PtS2 was found to exhibit superior electrocatalytic performances towards ORR and HER as compared to crystalline PtS2. For HER, amorphous and crystalline PtS2 have overpotential values of 0.30 V and 0.70 V (vs. RHE) at current density of 10 mA cm−2, respectively. The influence of electrochemical reduction pre‐treatment on their catalytic behaviours was also investigated. Electrochemical reduction pre‐treatment on both crystalline and amorphous PtS2 removed the oxidized sulfate groups and increased the proportion of Pt0 oxidation state which exposed more catalytic sites. As such, these materials were activated and displayed improved ORR and HER performances. Electrochemically reduced amorphous PtS2 outperformed the untreated counterparts and exhibited the best HER performance with overpotential of 0.17 V (vs. RHE) at current density of −10 mA cm−2. These findings provide insights into the electrochemical properties of noble metal PtS2 in both crystalline and amorphous states which can be activated by electrochemical reduction pre‐treatment.
Chiral Symmetry Breaking of Spiropyrans and Spirooxazines by Dynamic Enantioselective Crystallization
Authors: Ishikawa Hiroki , Uemura Naohiro , Saito Rei , Yoshida Yasushi , Mino Takashi , Kasashima Yoshio , Sakamoto Masami
Published: May 2019

Dynamic enantioselective crystallization enabled the chiral symmetry breaking of two spiropyrans and one spirooxazine. The three spiro compounds afforded racemic conglomerate crystals, and easily racemized in alcoholic solution without irradiation. Optically pure enantiomorphic crystals were obtained by vapor‐diffusion crystallization or attrition‐enhanced deracemization (Viedma ripening). Their absolute configurations were determined by single‐crystal X‐ray analysis and each enantiomorphic crystal was correlated with its solid‐state circular dichroism (CD) spectrum.
Pd‐Catalyzed Synthesis of Vinyl Arenes from Aryl Halides and Acrylic Acid
Authors: Gao Yang , Ou Yang , Gooßen Lukas J.
Published: May 2019

Acrylic acid is presented as an inexpensive, non‐volatile vinylating agent in a palladium‐catalyzed decarboxylative vinylation of aryl halides. The reaction proceeds through a Heck reaction of acrylic acid, immediately followed by protodecarboxylation of the cinnamic acid intermediate. The use of the carboxylate group as a deciduous directing group ensures high selectivity for monoarylated products. The vinylation process is generally applicable to diversely substituted substrates. Its utility is shown by the synthesis of drug‐like molecules and the gram‐scale preparation of key intermediates in drug synthesis.
Uranyl‐Bound Tetra‐Dentate Non‐Innocent Ligands: Prediction of Structure and Redox Behaviour Using Density Functional Theory
Authors: Arumugam Krishnamoorthy , Burton Neil A.
Published: May 2019

Computational methods have been applied to understand the reduction potentials of [UO2‐salmnt‐L] complexes (L=pyridine, DMSO, DMF and TPPO), and their redox behavior is compared with previous experiments in dichloromethane solution. Since the experimental results were inconclusive regarding the influence of the uranyl‐bound tetra‐dentate ‘salmnt’ ligand, here we will show that salmnt acts as a redox‐active ligand and exhibits non‐innocent behavior to interfere with the otherwise expected one‐electron metal (U) reduction. We have employed two approaches to determine the uranyl (VI/V) reduction potentials, using a direct study of one‐electron reduction processes and an estimation of the overall reduction using isodesmic reactions. Hybrid density functional theory (DFT) methods were combined with the Conductor‐like Polarizable Continuum Model (CPCM) to account for solvation effects. The computationally predicted one‐electron reduction potentials for the range of [UO2‐salmnt‐L] complexes are in excellent agreement with shoulder peaks (∼1.4 eV) observed in the cyclic voltammetry experiments and clearly correlate with ligand reduction. Highly conjugated pi‐bonds stabilize the ligand based delocalized orbital relative to the localized U f‐orbitals, and as a consequence, the ligand traps the incoming electron. A second reduction step results in metal U(VI) to U(V) reduction, in good agreement with the experimentally assigned uranyl (VI/V) reduction potentials.
Decreased heart rate variability as a predictor for diabetes—A prospective study of the Brazilian longitudinal study of adult health
Authors: Hoshi Rosangela A. , Santos Itamar S. , Dantas Eduardo M. , Andreão Rodrigo V. , Schmidt Maria Inês , Duncan Bruce B. , Mill José G. , Lotufo Paulo A. , Bensenor Isabela
Published: May 2019

Aim

To investigate whether heart rate variability (HRV) is a predictor for the incidence of diabetes in a 4‐year follow‐up.

Materials and methods

The HRV of 9192 participants free of diabetes was analysed in time and frequency domains and stratified based on the reference values presented in the literature. The participants were then allocated to one of three groups, according to age‐specific value distributions for each HRV domain: lower than the 25th percentile, between the 25th and 75th percentiles, and higher than the 75th percentile. The association between HRV and diabetes incidence at 4‐year follow‐up was analysed using Poisson regression models with robust estimator.

Results

Six hundred thirty‐four participants (6.90%) developed diabetes within 4 years and five out of six HRV analysed indices showed increased relative risk of developing diabetes associated with low HRV: SDNN (RR = 1.29; 95% CI, 1.09‐1.52; .003), pNN50 (RR = 1.33; 95% CI, 1.11‐1.58; .001), RMSSD (RR = 1.29; 95% CI, 1.09‐1.53; .004), LF (RR = 1.25; 95% CI, 1.05‐1.48; .012), and HF (RR = 1.39; 95% CI, 1.16‐1.63; .001).

Conclusions

This study suggests that both overall variability and changes in parasympathetic modulation precede the incidence of diabetes. For four HRV indices below the 25th percentile, the risk for incident diabetes was 68% higher than for those participants who presented none. We concluded that HRV is an independent risk predictor of diabetes in a 4‐year period.
An Entry to Double Phosphanyl‐Bridged Dinuclear Rhodium(II) Complexes
Authors: Böttcher Hans‐Christian , Graf Marion , Mayer Peter , Scheer Manfred
Published: May 2019

The reaction of [RhCp(coe)2] (1, coe = cis‐cyclooctene) with one equivalent of the secondary phosphines PR2H in refluxing toluene afforded in situ the new complexes [RhCp(coe)(PR2H)] (R = Ph, 2a; R = o‐tolyl, 2b; R = tBu, 2c) in good yields. Further thermolysis of 2a and 2b, respectively, in refluxing xylene resulted in the formation of the dinuclear doubly phosphanyl‐bridged rhodium(II) species [{RhCp(µ‐PR2)}2] (3a and 3b). This thermolytic approach does not work in the case of 2c since the tBu substituents increase the electron density on the rhodium center and impede, therefore, the loss of the olefinic ligand presumably caused by a stronger back donation effect. On the way from 2a to 3a the intermediate rhodium(III) complex [{RhCp(µ‐PPh2)(H)2}2] (4a) was isolated. All new compounds were fully characterized by spectroscopic methods as well as by X‐ray crystallography in the case of 3a, 3b and 4a confirming their molecular structures in the crystal. The compound [{RhCp(µ‐PPh2)}2] did not react with dihydrogen at ambient conditions and not even in refluxing toluene affording the complex 4a by oxidative addition as originally assumed.
A feasibility study comparing a web‐based intervention to a workshop intervention for caregivers of adults with eating disorders
Authors: Dimitropoulos Gina , Landers Ashley , Freeman Victoria , Novick Jason , Schmidt Ulrike , Olmsted Marion
Published: May 2019

Objective

To assess for the validity of a future trial, the current feasibility study aimed to compare the feasibility and efficacy of a web‐ and workshop‐based education intervention for caregivers of adults with eating disorders.

Methods

Psychoeducation was provided to caregivers, who were randomly assigned to a web or workshop condition. Independent samples t tests were conducted to analyse the between‐group effect sizes for intervention condition with regard to change over time. A random selection of participants from each intervention provided qualitative feedback about their experiences.

Results

Overall, participants reported positive experiences in both education interventions. From baseline to the end of intervention, small between‐group effect sizes were observed for changes in caregiver accommodation, problem‐solving abilities, the quality of psychological health, and the quality of social relationships, favouring the web‐based intervention, and changes in expressed emotion in the family context, caregiver burden, perceived stress, and the quality of the environment, supporting the workshop intervention.

Conclusions

There was a difference in initial feasibility of the web intervention. A future large‐scale trial of these interventions is supported by the results of this feasibility study.
Gastrointestinal alterations in anorexia nervosa — A systematic review
Authors: Schalla Martha A. , Stengel Andreas
Published: May 2019

Objective

Anorexia nervosa (AN) is an eating disorder characterized by body schema disruptions, underweight (>15% reduction of the ideal body weight or a body mass index <17.5 kg/m2), self‐induced weight reduction, and endocrine impairments. The three latter features greatly impact on most physiological functions including the cardiovascular, skeletal, reproductive, and the gastrointestinal system, which results in an increased mortality rate in affected individuals. Especially, gastrointestinal alterations are described as particularly bothersome by patients.

Methods

To address the need for a better understanding of the interplay between AN and the gastrointestinal (GI) tract, a systematic data search in the databases Medline, Embase, and PsycINFO was conducted.

Results

Over 1,235 studies were identified, out of these, 107 appropriate articles were selected and discussed in the present review.

Conclusion

AN has large impact on GI alterations and symptoms; conversely, GI symptoms may also affect the manifestation and course of AN as discussed in the present review. Despite increasing data, several gaps in knowledge exist especially on the pathophysiology underlying the changes described.
Multimodal [18F]FDG PET/CT Is a Direct Readout for Inflammatory Bone Repair: A Longitudinal Study in TNFα Transgenic Mice
Authors: Hayer Silvia , Zeilinger Markus , Weiss Volker , Dumanic Monika , Seibt Markus , Niederreiter Birgit , Shvets Tetyana , Pichler Florian , Wadsak Wolfgang , Podesser Bruno K , Helbich Thomas H , Hacker Marcus , Smolen Josef S , Redlich Kurt , Mitterhauser Markus
Published: May 2019

In rheumatoid arthritis (RA), chronic joint inflammation leading to bone and cartilage damage is the major cause of functional impairment. Whereas reduction of synovitis and blockade of joint damage can be successfully achieved by disease modifying antirheumatic therapies, bone repair upon therapeutic interventions has only been rarely reported. The aim of this study was to use fluorodeoxyglucose ([18F]FDG) and [18F]fluoride µPET/CT imaging to monitor systemic inflammatory and destructive bone remodeling processes as well as potential bone repair in an established mouse model of chronic inflammatory, erosive polyarthritis. Therefore, human tumor necrosis factor transgenic (hTNFtg) mice were treated with infliximab, an anti-TNF antibody, for 4 weeks. Before and after treatment period, mice received either [18F]FDG, for detecting inflammatory processes, or [18F]fluoride, for monitoring bone remodeling processes, for PET scans followed by CT scans. Standardized uptake values (SUVmean) were analyzed in various joints and histopathological signs of arthritis, joint damage, and repair were assessed. Longitudinal PET/CT scans revealed a significant decrease in [18F]FDG SUVs in affected joints demonstrating complete remission of inflammatory processes due to TNF blockade. In contrast, [18F]fluoride SUVs could not discriminate between different severities of bone damage in hTNFtg mice. Repeated in vivo CT images proved a structural reversal of preexisting bone erosions after anti-TNF therapy. Accordingly, histological analysis showed complete resolution of synovial inflammation and healing of bone at sites of former bone erosion. We conclude that in vivo multimodal [18F]FDG µPET/CT imaging allows to quantify and monitor inflammation-mediated bone damage and reveals not only reversal of synovitis but also bone repair upon TNF blockade in experimental arthritis. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.
The clinical significance of neutrophil gelatinase‐associated lipocalin in ischemic stroke patients with acute kidney injury
Authors: Xiao Wei , Chen Wei , Hu Hanning , Huang Xiaomei , Luo Yi
Published: May 2019

Background

Acute kidney injury (AKI) has become a common complication of acute ischemic stroke (AIS) and may have a significant impact on the clinical outcomes. Neutrophil gelatinase‐associated lipocalin (NGAL), an acute phase protein, has been identified as a novel biomarker for acute kidney impairment. Here, we studied the early expression of NGAL in AIS patients with AKI and its clinic value in predicting and diagnosis of AKI after stroke.

Methods

A total of 205 subjects diagnosed as first‐ever AIS were recruited in this study, including 40 AIS with AKI and 165 AIS without AKI defined using the KDIGO guidelines. The serum and urine levels of NGAL were measured with ELISA. To evaluate the clinic value of NGAL, we also detected creatinine, urea nitrogen and cystatin C and microalbumin (mALB) in serum or urine using chemiluminescence or immunoturbidimetry method, and then the receiver operating characteristic (ROC) curve and correlation was analyzed. The severity of AIS patients was evaluated based on the National Institutes of Health Stroke Scale (NIHSS) score.

Results

The serum and urine NGAL levels were significantly increased in AIS patients with AKI, and line regression analysis indicated that there was a positive correlation between the serum NGAL and creatinine level in AIS patients accompanied AKI. Additionally, the concentration of serum NGAL in AIS patients with AKI increased with the severity of stroke.

Conclusion

The increased serum NGAL may be used as a valuable complementary marker for the diagnoses and prediction of AKI in the early stage of AIS patients.
Mitochonic acid‐5 attenuates TNF‐α‐mediated neuronal inflammation via activating Parkin‐related mitophagy and augmenting the AMPK–Sirt3 pathways
Authors: Huang Dezhi , Liu Min , Jiang Yugang
Published: May 2019

Mitochondrial dysfunction has been found to be associated with neuronal inflammation; however, no effective drug is available to attenuate neuroinflammation via sustaining mitochondrial function. In the current study, experiments were performed to understand the beneficial effects of mitochonic acid 5 (MA‐5) on tumor necrosis factor‐α (TNF‐α)‐mediated neuronal injury and mitochondrial damage. Our data illustrated that MA‐5 pretreatment reduced inflammation response induced by TNF‐α in CATH.a cells. Molecular investigations demonstrated that MA‐5 pretreatment repressed oxidative stress, inhibited endoplasmic reticulum stress, sustained cellular energy metabolism, and blocked cell apoptosis induced by TNF‐α stress. Further, we found that MA‐5 treatment elevated the expression of Sirtuin 3 (Sirt3) and this effect was dependent on the activation of AMP‐activated protein kinase (AMPK) pathway. Blockade of AMPK abolished the promotive action of MA‐5 on Sirt3 and thus mediated mitochondrial damage and cell death. Besides, we also found that MA‐5 treatment augmented Parkin‐related mitophagy and increased mitophagy promoted CATH.a cells survival via improving mitochondrial function. Knockdown of Parkin abolished the beneficial action of MA‐5 on mitochondrial homeostasis and CATH.a cell survival. Altogether, our results confirm that MA‐5 is an effective drug to attenuate neuroinflammation via sustaining mitochondrial damage and promoting CATH.a cell survival. The protective action of MA‐5 on neuronal damage is associated with Parkin‐related mitophagy and the activation of AMPK–Sirt3 pathways.
In situ needle deflection technique using a steerable introducer for site‐selective radiofrequency transseptal puncture
Authors: Itoh Taihei , Kimura Masaomi , Ishida Yuji , Tomita Hirofumi
Published: May 2019

Transseptal puncture (TP) is a prerequisite for gaining access to the left atrium. Selection of a puncture site in the fossa ovalis can impact on catheter ablation of left atrial arrhythmias. However, TP sometimes requires a needle shape modification in vitro, which can make it difficult to accomplish site‐selective TP. This report illustrated a novel needle deflection technique in vivo using a steerable introducer. This in situ needle deflection technique is useful in excluding the needle shape modification in vitro and achieving fine adjustment of the needle curve in vivo, thus contributing to site‐selective radiofrequency TP and reducing procedure time.
Oropharyngeal Administration of Mother's Milk Prior to Gavage Feeding in Preterm Infants: A Pilot Randomized Control Trial
Authors: Abd‐Elgawad Mahmoud , Eldegla Heba , Khashaba Mohammed , Nasef Nehad
Published: May 2019

Background

Oropharyngeal administration of mother's colostrum in early days has an immunoprotective effect in preterm infants.

Objectives

Our aim was to study the effect of oropharyngeal administration of mother's milk (OPAMM) on decreasing the incidence of nosocomial sepsis.

Methods

In a pilot prospective randomized study on preterm (<32 weeks gestation and 1500 g weight) infants, we compared OPAMM practice (applying 0.2 mL of mother's colostrum or milk prior to gavage feeding until full oral feeding is reached) with regular gavage feeding. The primary outcome was incidence of culture‐proven nosocomial sepsis. Secondary outcomes included bacterial colonization of the gastrointestinal tract, feeding intolerance, time to reach full feeding, incidence of necrotizing enterocolitis, ventilator‐associated pneumonia, duration of respiratory support, incidence of bronchopulmonary dysplasia (BPD), length of hospital stay, and neonatal mortality.

Results

The outcomes of 200 neonates (100 in each group) were analyzed. OPAMM practice did not significantly reduce the incidence of culture proven nosocomial sepsis (8% vs 13%, P = 0.35). Infants in the OPAMM group had a significantly lower growth of Klebsiella species in the oropharyngeal pouch, borderline lower incidence of ventilator‐associated pneumonia, shorter duration of oxygen therapy, less episodes of feeding intolerance, reached full feeding earlier, and had a shorter length of hospital stay. OPAMM practice did not affect the incidence of necrotizing enterocolitis, BPD, or neonatal mortality.

Conclusion

OPAMM prior to gavage feeding does not reduce the incidence of nosocomial sepsis but had beneficial effects on early achievement of feeding, and early hospital discharge in preterm very low‐birth‐weight infants.
Fermentation of pseudocereals quinoa, canihua, and amaranth to improve mineral accessibility through degradation of phytate
Authors: Castro‐Alba Vanesa , Lazarte Claudia E , Perez‐Rea Daysi , Carlsson Nils‐Gunnar , Almgren Annette , Bergenståhl Björn , Granfeldt Yvonne
Published: May 2019

BACKGROUND

Pseudocereals are nutrient‐rich grains with high mineral content but also phytate content. Phytate is a mineral absorption inhibitor. The study's aim was to evaluate phytate degradation during spontaneous fermentation and during Lactobacillus plantarum 299v® fermentation of quinoa, canihua, and amaranth grains and flours. It also aimed to evaluate the accessibility of iron, zinc, and calcium and to estimate their bioavailability before and after the fermentation of flours with starter culture. Lactic acid, pH, phytate, and mineral content were analyzed during fermentation.

RESULTS

Higher phytate degradation was found during the fermentation of flours (64–93%) than during that of grains (12–51%). Results suggest that phytate degradation was mainly due to endogenous phytase activity in different pseudocereals rather than the phytase produced by added microorganisms. The addition of Lactobacillus plantarum 299v® resulted in a higher level of lactic acid (76.8–82.4 g kg−1 DM) during fermentation, and a relatively quicker reduction in pH to 4 than in spontaneous fermentation. Mineral accessibility was increased (1.7–4.6‐fold) and phytate : mineral molar ratios were reduced (1.5–4.2‐fold) in agreement with phytate degradation (1.8–4.2‐fold) in fermented flours. The reduced molar ratios were still above the threshold value for the improved estimated mineral bioavailability of mainly iron.

CONCLUSION

Fermentation proved to be effective for degrading phytate in pseudocereal flours, but less so in grains. Fermentation with Lactobacillus plantarum 299v® improved mineral accessibility and estimated bioavailability in flours. © 2019 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Facial nerve venous malformation: A radiologic and histopathologic review of 11 cases
Authors: Guerin Julie B. , Takahashi Edwin A. , Lane John I. , Hoxworth Joseph M. , Weindling Steven M. , Blessing Melissa M. , Jentoft Mark E. , Carlson Matthew L. , Neff Brian A. , Wood Christopher P.
Published: May 2019

Objective

The purpose of this article was to provide a combined pathologic and radiologic review of previous pathologically diagnosed facial nerve “hemangiomas” to confirm that these lesions are most characteristic of venous malformations rather than neoplasms.

Study Design

Retrospective radiologic, clinical, and histopathologic review of all patients with a previous pathologically diagnosed facial nerve hemangioma of the temporal bone who underwent computed tomography or magnetic resonance imaging (MRI) were included. A consensus radiologic review for characteristic features and pathologic analysis was performed.

Materials and Methods

A panel of 4 neuroradiologists retrospectively analyzed CT and MRI exams for 11 facial nerve hemangiomas and provided a consensus agreement on the characteristic imaging features. Concurrently, two neuropathologists reevaluated archived tissue specimens from these lesions and applied additional immunohistochemical and histochemical stains including D240, CD31, smooth muscle actin (SMA), Verhoeff Van Gieson (VVG) and glucose transporter 1 (GLUT1).

Results

Lesions were composed of dilated vascular spaces with a simple, CD31‐positive endothelial lining and a smooth muscle component. All lesions were negative for markers found in arterial and lymphatic malformations and infantile hemangiomas. They had characteristic radiologic features previously ascribed to facial nerve hemangiomas. Namely, these lesions are typically T1 isointense or hypointense and T2 hyperintense relative to cerebral cortex and heterogeneously enhance on MRI. Bony canal expansion and erosion, intralesional calcification, and intracranial extension are common.

Conclusions

On the basis of this radiologic and pathologic review, these lesions are best characterized as venous malformations.

Level of Evidence

4
Intraoperative Versus Extended Antibiotic Prophylaxis in Liver Transplant Surgery: A Randomized Controlled Pilot Trial
Authors: Berry Puja S. , Rosenberger Laura H. , Guidry Christopher A. , Agarwal Avinash , Pelletier Shawn , Sawyer Robert G.
Published: May 2019

The appropriate duration of surgical antibiotic prophylaxis in orthotopic liver transplantation (OLT) in the presence of significant iatrogenic immunosuppression is unclear. We hypothesized that 72 hours of perioperative antibiotic prophylaxis would decrease rates of surgical site infection (SSI) in OLT patients when compared with intraoperative antibiotic prophylaxis alone. OLT recipients were randomized to receive either intraoperative antibiotics only (short antibiotics [SAs]) or 72 hours of perioperative antibiotics (extended antibiotics [EAs]). A total of 102 patients were randomized: 51 to the EA group and 51 to the SA group. Rates of SSI and nosocomial infection (NI) in the SA group were 19% and 17%, respectively, compared with 27% (SSI; P = 0.36) and 22% (NI; P = 0.47) in the EA group, although these differences were not statistically significant. Intensive care unit (ICU) length of stay (LOS), hospital LOS, 30‐day mortality, and time to infection were also similar between the 2 groups. Patients developing infections had longer ICU LOS and hospital LOS and a higher association with reoperation, endoscopic retrograde cholangiopancreatography, and 30‐day readmission. In conclusion, extending perioperative antibiotics to 72 hours from intraoperative dosing alone in OLT patients does not appear to decrease the incidence of SSI or NI. The results from this pilot trial with 60% power suggest that it is acceptable for OLT recipients to receive intraoperative antibiotic prophylaxis alone.
Regulatory mechanisms mediated by peroxisome proliferator‐activated receptor‐β/δ in skin cancer
Authors: Peters Jeffrey M. , Kim Dae J. , Bility Moses T. , Borland Michael G. , Zhu Bokai , Gonzalez Frank J.
Published: May 2019

Considerable progress has been made during the past 20 years towards elucidating the role of peroxisome proliferator‐activated receptor‐β/δ (PPARβ/δ) in skin cancer. In 1999, the original notion that PPARβ/δ was involved with epithelial cell function was postulated based on a correlation between PPARβ/δ expression and the induction of messenger RNAs encoding proteins that mediate terminal differentiation in keratinocytes. Subsequent studies definitively revealed that PPARβ/δ could induce terminal differentiation and inhibit proliferation of keratinocytes. Molecular mechanisms have since been discovered to explain how this nuclear receptor can be targeted for preventing and treating skin cancer. This includes the regulation of terminal differentiation, mitotic signaling, endoplasmic reticulum stress, and cellular senescence. Interestingly, the effects of activating PPARβ/δ can preferentially target keratinocytes with genetic mutations associated with skin cancer. This review provides the history and current understanding of how PPARβ/δ can be targeted for both nonmelanoma skin cancer and melanoma and postulates how future approaches that modulate PPARβ/δ signaling may be developed for the prevention and treatment of these diseases.
In‐situ Grown SnO2 Nanospheres on Reduced GO Nanosheets as Advanced Anodes for Lithium‐ion Batteries
Authors: Wang Zhen , Chen Lei , Feng Jingjie , Liu Shenghong , Wang Yang , Fan Qinghua , Zhao Yanming
Published: May 2019

Nanostructured tin dioxide (SnO2) has emerged as a promising anode material for lithium‐ion batteries (LIBs) due to its high theoretical capacity (1494 mA h g−1) and excellent stability. Unfortunately, the rapid capacity fading and poor electrical conductivity of bulk SnO2 material restrict its practical application. Here, SnO2 nanospheres/reduced graphene oxide nanosheets (SRG) are fabricated through in‐situ growth of carbon‐coated SnO2 using template‐based approach. The nanosheet structure with the external layer of about several nanometers thickness can not only accommodate the volume change of Sn lattice during cycling but also enhance the electrical conductivity effectively. Benefited from such design, the SRG composites could deliver an initial discharge capacity of 1212.3 mA h g−1 at 0.1 A g−1, outstanding cycling performance of 1335.6 mA h g−1 after 500 cycles at 1 A g−1, and superior rate capability of 502.1 mA h g−1 at 5 A g−1 after 10 cycles. Finally, it is believed that this method could provide a versatile and effective process to prepare other metal‐oxide/reduced graphene oxide (rGO) 2D nanocomposites.
Surface molecular imprinting of nylon fibers for chiral recognition of d‐phenyllactic acid
Authors: Bukhari Abeer Abdulaziz H , Monier Mohammed , Elsayed Nadia H
Published: May 2019

In the current work, synthetic polyamide nylon fibers were modified via the strategy of surface molecular imprinting to develop enantio‐selective adsorbent fabrics for chiral recognition of d‐phenyllactic acid (d‐PhLA). The nylon fibers were first modified by grafting of polyacrylamide and then the incorporated amide groups were converted into functional amino groups via treatment with NaOCl (Hofmann degradation). The amino‐functionalized nylon fibers (Ny‐NH2) were interacted with the targeted d‐PhLA enantiomer before crosslinking the amino‐containing grafted chains with glutaraldehyde crosslinker followed by leashing the template d‐PhLA out of the formed surface polymeric matrix by lowering the pH to 1 to finally produce the desired enantio‐selective adsorbent fibers DP‐Ny. Different instrumental methods such as elemental analysis, Fourier transform infrared spectroscopy, XRD and TGA were employed to examine all the synthetic procedures. SEM was also utilized to observe the morphological appearances of both native and modified nylon fibers. Moreover, the optimum extraction of d‐PhLA was found to occur at pH 7. Isotherm studies of the prepared DP‐Ny fibers obeyed the common Langmuir linear equation with qm values 130 ± 2 and 75 ± 1 mg g−1 in the case of d‐PhLA and l‐PhLA, respectively. Furthermore, the enantiomeric resolution of (±)‐PhLA racemate was successfully carried out by a column technique with enantiomeric excess reaching approximately 78%. © 2019 Society of Chemical Industry