bluuebunny/crossref_metadata_2025 huggingface dataset:
Monocyte MicroRNA Expression in Active Systemic Juvenile Idiopathic Arthritis Implicates MicroRNA‐125a‐5p in Polarized Monocyte Phenotypes
Authors: Schulert Grant S. , Fall Ndate , Harley John B. , Shen Nan , Lovell Daniel J. , Thornton Sherry , Grom Alexei A.
Published: March 2016

Objective

Systemic juvenile idiopathic arthritis (JIA) is an inflammatory disease of childhood in which cells of the monomyelocytoid lineage are thought to be key effector cells. Monocytes from patients with systemic JIA have a distinct phenotype, with features of both M1 and M2 alternative activation. MicroRNAs are critical regulators of monocyte polarization and function, but cellular microRNAs in systemic JIA have not been examined systematically.

Methods

MicroRNA TaqMan arrays were used to determine the expression profiles of monocytes from children with systemic JIA. Expression of microRNA‐125a‐5p (miR‐125a‐5p) and its contribution to monocyte polarization were examined using in vitro–polarized THP‐1 cells and primary human monocytes.

Results

A total of 110 microRNAs were found to be differentially expressed in monocytes from patients with active systemic JIA, including molecules implicated in rheumatoid arthritis pathogenesis, cytokine production, and monocyte polarization. MicroRNA‐125a‐5p was identified as being highly up‐regulated in monocytes from children with active systemic JIA, as compared to those from children with clinically inactive JIA or those with active polyarticular JIA, and correlated with systemic features of the disease. In vitro, monocyte miR125a‐5p expression was increased after polarization under M2b or M2c conditions. Inhibition of miR‐125a‐5p showed that this microRNA contributed to full polarization of M2b regulatory macrophages. In contrast, miR‐125a‐5p overexpression enhanced M2b polarization and altered other polarized populations, including increasing the production of M2 markers. Indeed, in vitro overexpression of this microRNA altered the macrophage phenotype toward that observed in systemic JIA.

Conclusion

Children with active systemic JIA have profound alterations in the expression of microRNAs that are implicated in monocyte function and polarization. One of these microRNAs, miR‐125a‐5p, is also a regulator of immunoregulatory M2b macrophages.
Consensus-based training and assessment model for general surgery
Authors: Szasz P , Louridas M , de Montbrun S , Harris K A , Grantcharov T P
Published: March 2016

Background

Surgical education is becoming competency-based with the implementation of in-training milestones. Training guidelines should reflect these changes and determine the specific procedures for such milestone assessments. This study aimed to develop a consensus view regarding operative procedures and tasks considered appropriate for junior and senior trainees, and the procedures that can be used as technical milestone assessments for trainee progression in general surgery.

Methods

A Delphi process was followed where questionnaires were distributed to all 17 Canadian general surgery programme directors. Items were ranked on a 5-point Likert scale, with consensus defined as Cronbach's α of at least 0·70. Items rated 4 or above on the 5-point Likert scale by 80 per cent of the programme directors were included in the models.

Results

Two Delphi rounds were completed, with 14 programme directors taking part in round one and 11 in round two. The overall consensus was high (Cronbach's α = 0·98). The training model included 101 unique procedures and tasks, 24 specific to junior trainees, 68 specific to senior trainees, and nine appropriate to all. The assessment model included four procedures.

Conclusion

A system of operative procedures and tasks for junior- and senior-level trainees has been developed along with an assessment model for trainee progression. These can be used as milestones in competency-based assessments.
Pharmacokinetic comparison of five tanshinones in normal and arthritic rats after oral administration of Huo Luo Xiao Ling Dan or its single herb extract by UPLC‐MS/MS
Authors: Ma Wen , Peng Yan , Wang Weihui , Bian Qiaoxia , Wang Nannan , Lee David Y.‐W. , Dai Ronghua
Published: March 2016

A fast, sensitive and reliable ultra performance liquid chromatography–tandem mass spectrometry (UPLC‐MS/MS) method has been developed and validated for simultaneous quantitation and pharmacokinetic study of five tanshinones (tanshinone I, tanshinone IIA, tanshinone IIB, dihydrotanshinone I, cryptotanshinone), the bio‐active ingredients of Huo Luo Xiao Ling Dan (HLXLD) in rat plasma. After liquid–liquid extraction, chromatographic separation was accomplished on a Shim‐pack XR‐ODS column (75 × 3.0 mm, 2.2 µm particles) and eluted with a mobile phase consisting of acetonitrile–0.05% formic acid aqueous solution (80:20, v/v) at a flow rate of 0.4 mL/min, and the total run time was 7.0 min. The detection was performed on a triple quadrupole tandem mass spectrometry equipped with an electrospray ionization source in positive ionization and multiple reaction monitoring mode. The lower limits of quantification were 0.050–0.400 ng/mL for all the analytes. Linearity, precision and accuracy, the mean extraction recoveries and matrix effects all satisfied criteria for acceptance. This validated method was successfully applied to a comparative pharmacokinetic study of five bio‐active components in rat plasma after oral administration of HLXLD or Salvia miltiorrhiza extract in normal and arthritic rats. The results showed that there were different pharmacokinetic characteristics among different groups. Copyright © 2016 John Wiley & Sons, Ltd.
Anatomy of the long head of biceps femoris: An ultrasound study
Authors: Tosovic D. , Muirhead J.C. , Brown J.M.M. , Woodley S.J.
Published: March 2016

Hamstring strains, particularly involving the long head of biceps femoris (BFlh) at the proximal musculotendinous junction (MTJ), are commonly experienced by athletes. With the use of diagnostic ultrasound increasing, an in‐depth knowledge of normal ultrasonographic anatomy is fundamental to better understanding hamstring strain. The aim of this study was to describe the architecture of BFlh, using ultrasonography, in young men and cadaver specimens. BFlh morphology was examined in 19 healthy male participants (mean age 21.6 years) using ultrasound. Muscle, tendon and MTJ lengths were recorded and architectural parameters assessed at four standardised points along the muscle. Measurement accuracy was validated by ultrasound and dissection of BFlh in six male cadaver lower limbs (mean age 76 years). Intra‐rater reliability of architectural parameters was examined for repeat scans, image analysis and dissection measurements. Distally the BFlh muscle had significantly (P < 0.05) shorter fascicles and larger pennation angles than proximal sites. Agreement between ultrasound and dissection (cadaver study) was excellent for all architectural parameters, except pennation angle (PA), and MTJ length. All other measures demonstrated good‐excellent repeatability. BFlh is not uniform in architecture when imaged using ultrasound. It is likely that its distal‐most segment is better suited for force production in comparison to the more proximal segments, which show excursive potential, traits which possibly contribute to the high rate of injury at the proximal MTJ. The data presented in this study provide specific knowledge of the normal ultrasonographic anatomy of BFlh, which should be of assistance in analysing BFlh injury via imaging. Clin. Anat. 29:738–745, 2016. © 2016 Wiley Periodicals, Inc.
Frankincense Revisited, Part I: Comparative Analysis of Volatiles in Commercially Relevant Boswellia Species
Authors: Niebler Johannes , Buettner Andrea
Published: March 2016

The genus Boswellia comprises many species which are famous for their production of frankincense, a fragrant gum resin. In the published literature, manifold studies on the volatiles and semivolatiles in individual samples of these gum resins exist, yet very few studies have investigated multiple samples. Contradictory results with regard to the volatile composition exist in literature. In this first part of the study, a large sample set (n = 46) of mostly commercially obtained gum resins and essential oils was investigated by solid‐phase microextraction gas chromatography/mass spectrometry. A total of 216 compounds were identified or tentatively identified from the four commercially relevant species, namely B. sacra, B. serrata, B. papyrifera, and B. frereana, and the statistical evaluation of the resulting chemical profiles allowed a clear distinction between the species by their volatile profile. With only few exceptions, the designated species was found to be in accordance with the composition reported in reliable literature sources and detected in botanically identified samples. Chemotaxonomic marker substances were suggested to facilitate the differentiation of commercial gum resins or essential oils based on their volatile profile.
First implantable hemodynamic monitoring device placement in single ventricle fontan anatomy
Authors: Bradley Elisa A. , Berman Darren , Daniels Curt J.
Published: March 2016

The Fontan anatomy leads to elevated central venous pressure along with chronic venous congestion and low cardiac output; this is felt to be responsible for deterioration of exercise tolerance and functional capacity over time. Real‐time hemodynamic evaluation of the Fontan anatomy has not been evaluated until now. Here, we report the technical aspects of the first two adult Fontan patients to undergo placement of an invasive hemodynamic monitor (IHM). We validate IHM readings with invasive pulmonary artery catheter derived hemodynamics in the Fontan and show successful home transmission of pulmonary artery hemodynamic tracings. This technology has the capacity to change current understanding of Fontan hemodynamics and treatment in patients with complex single‐ventricle anatomy. © 2016 Wiley Periodicals, Inc.
Centrifugal pump performance when handling highly non‐Newtonian clays and tailings slurries
Authors: Furlan John , Visintainer Robert , Sellgren Anders
Published: March 2016

Recent loop testing performed at the GIW Hydraulic Lab[1,2] has provided pump performance data for two highly non‐Newtonian slurries with significantly different characteristics: a high clay content slurry with minimal coarse solids; and a typical, low clay content, two‐component tailings slurry. The importance of air removal in the sump and pipe loop was demonstrated using a simple, yet novel de‐aeration system. In addition to the measurement of performance losses, determination of the upper limit of “pumpability” for these slurries relative to their concentration and associated yield stress was investigated. However, once the slurry was de‐aerated, no limits could be found, other than those dictated by suction side losses (NPSHA) or excessive pipeline friction gradients, indicating that the only true limit in practice is one of system economics, i.e. pump operating and capital cost.

Experimentally measured pump head and efficiency were compared against corresponding predictions from two different models: the Walker and Goulas technique[3] and the Graham et al. technique,[4] with special focus given to the dependence of the losses on pump rotary speed.
A spatiotemporal characterization method for the dynamic cytoskeleton
Authors: Alhussein Ghada , Shanti Aya , Farhat Ilyas A. H. , Timraz Sara B. H. , Alwahab Noaf S. A. , Pearson Yanthe E. , Martin Matthew N. , Christoforou Nicolas , Teo Jeremy C. M.
Published: March 2016

The significant gap between quantitative and qualitative understanding of cytoskeletal function is a pressing problem; microscopy and labeling techniques have improved qualitative investigations of localized cytoskeleton behavior, whereas quantitative analyses of whole cell cytoskeleton networks remain challenging. Here we present a method that accurately quantifies cytoskeleton dynamics. Our approach digitally subdivides cytoskeleton images using interrogation windows, within which box‐counting is used to infer a fractal dimension (Df) to characterize spatial arrangement, and gray value intensity (GVI) to determine actin density. A partitioning algorithm further obtains cytoskeleton characteristics from the perinuclear, cytosolic, and periphery cellular regions. We validated our measurement approach on Cytochalasin‐treated cells using transgenically modified dermal fibroblast cells expressing fluorescent actin cytoskeletons. This method differentiates between normal and chemically disrupted actin networks, and quantifies rates of cytoskeletal degradation. Furthermore, GVI distributions were found to be inversely proportional to Df, having several biophysical implications for cytoskeleton formation/degradation. We additionally demonstrated detection sensitivity of differences in Df and GVI for cells seeded on substrates with varying degrees of stiffness, and coated with different attachment proteins. This general approach can be further implemented to gain insights on dynamic growth, disruption, and structure of the cytoskeleton (and other complex biological morphology) due to biological, chemical, or physical stimuli. © 2016 The Authors. Cytoskeleton Published by Wiley Periodicals, Inc.
Global Well‐Posedness of Incompressible Elastodynamics in Two Dimensions
Authors: Lei Zhen
Published: March 2016

We prove that for sufficiently small initial displacements in some weighted Sobolev space, the Cauchy problem of the systems of incompressible isotropic Hookean elastodynamics in two space dimensions admits a uniqueness global classical solution. © 2016 Wiley Periodicals, Inc.
Association between high serum carcinoembryonic antigen and clinical state of male anorexia nervosa: A case report
Authors: Ochi Shinichiro , Shimizu Hideaki , Ueno Shu‐ichi
Published: March 2016

Anorexia nervosa (AN) is a complex psychiatric disorder, which is not yet fully understood. Several studies reported that AN was associated with disruption of cytokine network. Carcinoembryonic antigen (CEA) is a glycoprotein related to its network, used as a tumor marker of adenocarcinoma, and suggested to stimulate monocytes and macrophages to release proinflammatory cytokines. Here, we report a 41‐year‐old male suffering from AN who was suspected of having a malignant tumor due to markedly elevated serum CEA levels. However, on further examinations, he was discovered to have no malignant tumors, and, interestingly, his CEA levels actually decreased as his clinical state of AN improved. Furthermore, it was found that his CEA levels were elevated proportionally to his clinical state of AN and that his body mass index was significantly correlated with serum CEA levels. Therefore, it is suggested that inflammatory responses may be associated with the clinical state of AN. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:428–431).
Effects of mesopotamian marsh (iraq) desiccation on the cultural knowledge and livelihood of marsh arab women
Authors: Al‐mudaffar fawzi Nadia , Goodwin Kelly P. , Mahdi Bayan A. , Stevens Michelle L.
Published: March 2016

In this study, we evaluate ecological and cultural resiliency in response to desertification of the Mesopotamian Marshes of Southern Iraq. Our research illustrates that the desiccation of the marshes has caused a drastic change in how Marsh Arab women interact with their environment; specifically, in comparison to the predesiccation period, women’s roles are increasingly limited to domestic rather than marsh‐dependent activities. With the exception of raising water buffalo and limited horticulture activities, most families today have little opportunity to utilize women’s ability to generate income by applying their traditional ecological knowledge and skills. Furthermore, these women are no longer transmitting their marsh‐specific knowledge and skills to the next generation, and these valuable and ancient cultural memories are being lost. Upstream dam construction, drought, and regional climate change is depriving Marsh Arab communities of marsh ecosystem services such as potable water, water buffalo forage, fish yields, and reed production. In marsh areas, where enough water remains to sustain ecosystem services (such as in Chibayish and the Iraq Marshlands National Park), cultural knowledge has been retained and passed on to the next generations. We recommend that programs be implemented to preserve these traditional skills, to develop a market for handicrafts to support women and their families, and to support cultural knowledge. Otherwise, with the passing of the older generation, these remnants of ancient Sumerian knowledge systems and traditional ways of life will soon be forgotten.
Retain low‐income, first‐generation students by making good habits mandatory
Authors: Hope Joan
Published: March 2016

Mars Hill University in North Carolina was created to provide educational opportunities for students who otherwise wouldn't have them. That was in 1856, and the institution has undergone a few name changes since then.
Close correlation of copy number aberrations detected by next‐generation sequencing with results from routine cytogenetics in acute myeloid leukemia
Authors: Vosberg Sebastian , Herold Tobias , Hartmann Luise , Neumann Martin , Opatz Sabrina , Metzeler Klaus H. , Schneider Stephanie , Graf Alexander , Krebs Stefan , Blum Helmut , Baldus Claudia D. , Hiddemann Wolfgang , Spiekermann Karsten , Bohlander Stefan K. , Mansmann Ulrich , Greif Philipp A.
Published: March 2016

High throughput sequencing approaches, including the analysis of exomes or gene panels, are widely used and established to detect tumor‐specific sequence variants such as point mutations or small insertions/deletions. Beyond single nucleotide resolution, sequencing data also contain information on changes in sequence coverage between samples and thus allow the detection of somatic copy number alterations (CNAs) representing gain or loss of genomic material in tumor cells arising from aneuploidy, amplifications, or deletions. To test the feasibility of CNA detection in sequencing data we analyzed the exomes of 25 paired leukemia/remission samples from acute myeloid leukemia (AML) patients with well‐defined chromosomal aberrations, detected by conventional chromosomal analysis and/or molecular cytogenetics assays. Thereby, we were able to confirm chromosomal aberrations including trisomies, monosomies, and partial chromosomal deletions in 20 out of 25 samples. Comparison of CNA detection using exome, custom gene panel, and SNP array analysis showed equivalent results in five patients with variable clone size. Gene panel analysis of AML samples without matched germline control samples resulted in confirmation of cytogenetic findings in 18 out of 22 cases. In all cases with discordant findings, small clone size (<33%) was limiting for CNA detection. We detected CNAs consistent with cytogenetics in 83% of AML samples including highly correlated clone size estimation (R = 0.85), while six out of 65 cytogenetically normal AML samples exhibited CNAs apparently missed by routine cytogenetics. Overall, our results show that high throughput targeted sequencing data can be reliably used to detect copy number changes in the dominant AML clone. © 2016 Wiley Periodicals, Inc.
Numerical investigation of the influence of the driving frequency during pile installation of tubular piles
Authors: Heins Evelyn , Hamann Thorben , Grabe Jürgen , Hannot Stephan
Published: March 2016

Numerical investigation of the influence of the driving frequency during pile installation of tubular piles: Offshore and nearshore structures are predominantly founded by the use of open‐ended profiles. The installation of open‐ended profiles into the subsoil is usually done using the impact pile driving technique. To make the installation process more efficient, especially when considering the penetration velocity of the pile and the noise level, a new pile driving method was developed by IHC IQIP, formerly known as IHC Hydrohammer B.V. The influence of the standard driving method in comparison to the new driving technique is investigated in this contribution. This is done using the Finite Element Method (FEM) including a two‐phase model for fully saturated soil.

Numerische Untersuchung zum Einfluss der Schlagfrequenz beim Einbringen von Rohrpfählen. Für die Gründung von Offshore‐ und Nearshore‐Anlagen werden vorwiegend offene Profile verwendet. Die Einbringung der offenen Profile in den anstehenden Boden erfolgt meist schlagend. Um den Pfahlinstallationsprozess insbesondere hinsichtlich Einbringgeschwindigkeit und Schallemission effizienter zu gestalten, wurde von IHC IQIP, früher bekannt als IHC Hydrohammer B.V., eine neue Schnellschlagramme entwickelt. In diesem Beitrag soll der Einfluss der Standardramme im Vergleich zur Schnellschlagramme untersucht werden. Dies geschieht mithilfe der Finite‐Elemente‐Methode (FEM) unter Berücksichtigung eines Zweiphasenmodells für den wassergesättigten Boden.

Dieser Artikel wurde aus technischen Problemen doppelt veröffentlicht 10.1002/gete.201600014.
Spatio‐temporal characteristics of metabotropic glutamate receptor 5 traffic at or near the plasma membrane in astrocytes
Authors: Lee William , Parpura Vladimir
Published: March 2016

Astrocytes can sense extracellular glutamate and respond to it by elevating their intracellular Ca2+ levels via the activation of G‐protein coupled receptors, such as metabotropic glutamate receptor 5 (mGluR5), which, during early postnatal development, is the primary receptor responsible for glutamatergic signaling in astrocytes. However, the detailed spatio‐temporal characteristics of mGluR5 traffic at or near the plasma membrane of astrocytes are not well understood. To address this issue, we expressed recombinant fluorescent protein chimera of mGluR5 and used total internal reflection fluorescence microscopy on rat visual cortical astrocytes in culture. We used astrocytes lacking major processes, otherwise posing as a diffusion barrier, to infer into the general dynamics of this receptor. We found that plasmalemmal mGluR5 clusters in distinct areas, the size, and initial spatio‐temporal level of occupancy of which dictated mGluR5 trafficking characteristics upon glutamate stimulation. These findings will be valuable in the interpretation of point‐to‐point information transfer and volume transmission between astrocytes and neurons, as well as that of paracrine signaling within astrocytic networks. GLIA 2016;64:1050–1065
General and specialized brain correlates for analogical reasoning: A meta‐analysis of functional imaging studies
Authors: Hobeika Lucie , Diard‐Detoeuf Capucine , Garcin Béatrice , Levy Richard , Volle Emmanuelle
Published: March 2016

Reasoning by analogy allows us to link distinct domains of knowledge and to transfer solutions from one domain to another. Analogical reasoning has been studied using various tasks that have generally required the consideration of the relationships between objects and their integration to infer an analogy schema. However, these tasks varied in terms of the level and the nature of the relationships to consider (e.g., semantic, visuospatial). The aim of this study was to identify the cerebral network involved in analogical reasoning and its specialization based on the domains of information and task specificity. We conducted a coordinate‐based meta‐analysis of 27 experiments that used analogical reasoning tasks. The left rostrolateral prefrontal cortex was one of the regions most consistently activated across the studies. A comparison between semantic and visuospatial analogy tasks showed both domain‐oriented regions in the inferior and middle frontal gyri and a domain‐general region, the left rostrolateral prefrontal cortex, which was specialized for analogy tasks. A comparison of visuospatial analogy to matrix problem tasks revealed that these two relational reasoning tasks engage, at least in part, distinct right and left cerebral networks, particularly separate areas within the left rostrolateral prefrontal cortex. These findings highlight several cognitive and cerebral differences between relational reasoning tasks that can allow us to make predictions about the respective roles of distinct brain regions or networks. These results also provide new, testable anatomical hypotheses about reasoning disorders that are induced by brain damage. Hum Brain Mapp 37:1953–1969, 2016. © 2016 Wiley Periodicals, Inc.
Cerebral infarction after intraarterial and intravenous chemoradiotherapy for head and neck cancer: A retrospective analysis using a Japanese inpatient database
Authors: Suzuki Sayaka , Yasunaga Hideo , Matsui Hiroki , Fushimi Kiyohide , Saito Yuki , Yamasoba Tatsuya
Published: March 2016

Background

The occurrence of cerebral infarction after intraarterial chemoradiotherapy (CRT) remains uncertain.

Methods

We conducted a retrospective cohort study using the Diagnosis Procedure Combination (DPC) database from 2010 to 2013. We performed a 1:4 propensity score‐matched analysis between patients undergoing intraarterial or intravenous CRT, and determined the association between cerebral infarction and intraarterial CRT.

Results

Among patients with head and neck cancer receiving platinum‐based chemotherapy and concurrent radiotherapy, we identified 776 patients with intraarterial CRT and 7157 with intravenous CRT. The occurrence of cerebral infarction was significantly higher in the intraarterial CRT group than in the intravenous CRT group: 1.4% (11 of 775) versus 0.4% (12 of 3100; p = .002). There was no significant difference in mucosal toxicity or febrile neutropenia.

Conclusion

About 10% of patients received intraarterial CRT. Intraarterial CRT was associated with a higher incidence of cerebral infarction than was intravenous CRT. This result is useful when considering the procedure‐related risks and the potential benefits of intraarterial CRT. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1354–1358, 2016
Primary surgery for advanced‐stage laryngeal cancer: A stage and subsite‐specific survival analysis
Authors: Harris Brianna N. , Bhuskute Aditi A. , Rao Shyam , Farwell D. Gregory , Bewley Arnaud F.
Published: March 2016

Background

Treatment recommendations for advanced‐stage laryngeal squamous cell carcinoma (SCC) have evolved significantly over the last 2 decades.

Methods

We retrospectively analyzed patients in the Surveillance, Epidemiology, and End Results (SEER) database with advanced‐stage laryngeal SCC treated between 2004 and 2012.

Results

A total of 6797 patients were identified in the SEER database who met inclusion criteria, with 2051 patients undergoing primary surgery and 4746 patients undergoing primary radiotherapy (RT) or chemoradiotherapy (CRT). Disease‐specific survival (DSS) and overall survival (OS) were significantly better for patients treated with primary surgery when compared using Kaplan–Meier curves and a Cox multivariate regression. When survival analysis was repeated for patients stratified by T classification, N classification, and subsite, OS and DSS benefits from primary surgery were observed for patients with T3 and T4a tumors, N0 neck disease, or supraglottic primaries.

Conclusion

Patients with advanced‐stage laryngeal SCC with T3 and T4a tumors, N0 neck disease, or supraglottic primaries have the greatest chance of survival when treated with primary surgery. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1380–1386, 2016
Assessing the therapeutic potential of lab‐made hepatocytes
Authors: Rezvani Milad , Grimm Andrew A. , Willenbring Holger
Published: March 2016

Hepatocyte transplantation has potential as a bridge or even alternative to whole‐organ liver transplantation. Because donor livers are scarce, realizing this potential requires the development of alternative cell sources. To be therapeutically effective, surrogate hepatocytes must replicate the complex function and ability to proliferate of primary human hepatocytes. Ideally, they are also autologous to eliminate the need for immune suppression, which can have severe side effects and may not be sufficient to prevent rejection long term. In the past decade, several methods have been developed to generate hepatocytes from other readily and safely accessible somatic cells. These lab‐made hepatocytes show promise in animal models of liver diseases, supporting the feasibility of autologous liver cell therapies. Here, we review recent preclinical studies exemplifying different types of lab‐made hepatocytes that can potentially be used in autologous liver cell therapies. To define the therapeutic efficacy of current lab‐made hepatocytes, we compare them to primary human hepatocytes, focusing on engraftment efficiency and posttransplant proliferation and function. In addition to summarizing published results, we discuss animal models and assays effective in assessing therapeutic efficacy. This analysis underscores the therapeutic potential of current lab‐made hepatocytes, but also highlights deficiencies and uncertainties that need to be addressed in future studies aimed at developing liver cell therapies with lab‐made hepatocytes. (Hepatology 2016;64:287–294)
Evidence that the adenosine triphosphate‐binding cassette G5/G8‐independent pathway plays a determinant role in cholesterol gallstone formation in mice
Authors: Wang Helen H. , Li Xiaodan , Patel Shailendra B. , Wang David Q.‐H.
Published: March 2016

The adenosine triphosphate‐binding cassette (ABC) sterol transporter, Abcg5/g8, is Lith9 in mice, and two gallstone‐associated variants in ABCG5/G8 have been identified in humans. Although ABCG5/G8 plays a critical role in determining hepatic sterol secretion, cholesterol is still secreted to bile in sitosterolemic patients with a defect in either ABCG5 or ABCG8 and in either Abcg5/g8 double‐ or single‐knockout mice. We hypothesize that in the defect of ABCG5/G8, an ABCG5/G8‐independent pathway is essential for regulating hepatic secretion of biliary sterols, which is independent of the lithogenic mechanism of the ABCG5/G8 pathway. To elucidate the effect of the ABCG5/G8‐independent pathway on cholelithogenesis, we investigated the biliary and gallstone characteristics in male wild‐type (WT), ABCG5(‐/‐)/G8(‐/‐), and ABCG8 (‐/‐) mice fed a lithogenic diet or varying amounts of cholesterol, treated with a liver X receptor (LXR) agonist, or injected intravenously with [3H]sitostanol‐ and [14C]cholesterol‐labeled high‐density lipoprotein (HDL). We found that ABCG5(‐/‐)/G8(‐/‐) and ABCG8 (‐/‐) mice displayed the same biliary and gallstone phenotypes. Although both groups of knockout mice showed a significant reduction in hepatic cholesterol output compared to WT mice, they still formed gallstones. The LXR agonist significantly increased biliary cholesterol secretion and gallstones in WT, but not ABCG5(‐/‐)/G8(‐/‐) or ABCG8 (‐/‐), mice. The 6‐hour recovery of [14C]cholesterol in hepatic bile was significantly lower in both groups of knockout mice than in WT mice and [3H]sitostanol was detected in WT, but not ABCG5(‐/‐)/G8(‐/‐) or ABCG8 (‐/‐), mice. Conclusions: The ABCG5/G8‐independent pathway plays an important role in regulating biliary cholesterol secretion, the transport of HDL‐derived cholesterol from plasma to bile, and gallstone formation, which works independently of the ABCG5/G8 pathway. Further studies are needed to observe whether this pathway is also operational in humans. (Hepatology 2016;64:853‐864)
Use of thermo‐coagulation as an alternative treatment modality in a ‘screen‐and‐treat’ programme of cervical screening in rural Malawi
Authors: Campbell Christine , Kafwafwa Savel , Brown Hilary , Walker Graeme , Madetsa Belito , Deeny Miriam , Kabota Beatrice , Morton David , Ter Haar Reynier , Grant Liz , Cubie Heather A.
Published: March 2016

The incidence of cervical cancer in Malawi is the highest in the world and projected to increase in the absence of interventions. Although government policy supports screening using visual inspection with acetic acid (VIA), screening provision is limited due to lack of infrastructure, trained personnel, and the cost and availability of gas for cryotherapy. Recently, thermo‐coagulation has been acknowledged as a safe and acceptable procedure suitable for low‐resource settings. We introduced thermo‐coagulation for treatment of VIA‐positive lesions as an alternative to cryotherapy within a cervical screening service based on VIA, coupled with appropriate, sustainable pathways of care for women with high‐grade lesions and cancers. Detailed planning was undertaken for VIA clinics, and approvals were obtained from the Ministry of Health, Regional and Village Chiefs. Educational resources were developed. Thermo‐coagulators were introduced into hospital and health centre settings, with theoretical and practical training in safe use and maintenance of equipment. A total of 7,088 previously unscreened women attended VIA clinics between October 2013 and March 2015. Screening clinics were held daily in the hospital and weekly in the health centres. Overall, VIA positivity was 6.1%. Almost 90% received same day treatment in the hospital setting, and 3‐ to 6‐month cure rates of more than 90% are observed. Thermo‐coagulation proved feasible and acceptable in this setting. Effective implementation requires comprehensive training and provider support, ongoing competency assessment, quality assurance and improvement audit. Thermo‐coagulation offers an effective alternative to cryotherapy and encouraged VIA screening of many more women.
Regulatory and effector functions of gamma–delta (γδ) T cells and their therapeutic potential in adoptive cellular therapy for cancer
Authors: Paul Sourav , Lal Girdhari
Published: March 2016

γδ T cells are an important innate immune component of the tumor microenvironment and are known to affect the immune response in a wide variety of tumors. Unlike αβ T cells, γδ T cells are capable of spontaneous secretion of IL‐17A and IFN‐γ without undergoing clonal expansion. Although γδ T cells do not require self‐MHC‐restricted priming, they can distinguish “foreign” or transformed cells from healthy self‐cells by using activating and inhibitory killer Ig‐like receptors. γδ T cells were used in several clinical trials to treat cancer patient due to their MHC‐unrestricted cytotoxicity, ability to distinguish transformed cells from normal cells, the capacity to secrete inflammatory cytokines and also their ability to enhance the generation of antigen‐specific CD8+ and CD4+ T cell response. In this review, we discuss the effector and regulatory function of γδ T cells in the tumor microenvironment with special emphasis on the potential for their use in adoptive cellular immunotherapy.
Effect of binder‐free graphene–cetyltrimethylammonium bromide anode on the performance of microbial fuel cells
Authors: Xue Lixian , Yang Na , Ren Yueping , Li Xiufen , Shi Yugang , Hua Zhaozhe , Wang Xinhua
Published: March 2016

BACKGROUND

Graphene has been widely used as an anode modification material to enhance the performance of microbial fuel cells (MFCs). The hydrophobicity of graphene and the insulation of the binders used in the electrode preparation were two adverse factors for performance enhancement of the graphene (G) anodes. In this work, binder‐free graphene–cetyltrimethylammonium bromide (CTAB) anodes (G‐CTAB‐2.5, G‐CTAB‐5 and G‐CTAB‐10) prepared with low loadings of CTAB treated graphene were fabricated through a simple strategy and their performance tested in single‐chamber MFCs.

RESULTS

The biofilms on the positively charged and hydrophilic G‐CTAB anodes had higher electrocatalytic activity and more diverse microbial populations than those on the G anode. The G‐CTAB‐5 anode showed the best performance, and the maximum output power density (Pmax) of the MFC was 731.3 mW m−2 which was 3.7 times higher than that of the MFC with the G anode.

CONCLUSION

The results showed that the G‐CTAB anode with very low graphene loading exhibited excellent performance. This work provides new prospects for the development of better graphene anodes to further enhance the performance of MFCs. © 2016 Society of Chemical Industry
Enactment of a Sustainable Vision in the Dual Context of the Tropical Biosphere and the Developing World: A Case Study of Belize Natural Energy
Authors: Kosempel Paul , Olson Linda G.
Published: March 2016

Nowhere is economic, cultural, and environmental sustainability more critical than in a country like Belize, where the developing world merges with the tropical biosphere. Through a single‐organization case study design, the authors provide insight into Belize's only oil‐producing company, specifically examining its sustainability practices and its enactment of an organizational vision centered on sustainability. Our global economy relies heavily on fossil fuels; such reliance requires us to understand the sustainability efforts of these companies. Determining how sustainability is enacted in these organizations forms the basis for how these practices can be replicated. Data collection included multiple interviews with employees throughout the organization, ethnographic observation, and document analysis. The results yielded an understanding of how sustainability practices are enacted in organizational communication.
Development and morphological variation of the axial and appendicular skeleton in hylidae (Lissamphibia, Anura)
Authors: Soliz Mónica , Ponssa María Laura
Published: March 2016

The axial and appendicular skeleton, the associated musculature and tendons form a functional system related to specific modes of locomotion in anurans. Many transformations in the structures linked with the locomotor function of the adult occur during larval stages and metamorphosis. In this study, we present the larval ontogeny and adult morphology of the axial and appendicular skeletons of 14 species of frogs in the family Hylidae with different locomotor modes and habitat uses. Among Hylidae, a diversity of shapes, locomotory types occurs (e.g., walker, swimmer, jumper, hopper) and different habitat types occupied (shrubby, terrestrial, aquatic, arboreal). Many elements complete differentiation at the end of metamorphosis; others, such as sesamoids, still show an incomplete development at that stage. Sixty seven characters were scored and optimized in an available phylogeny. Nine characters of developmental timing and adult osteology are optimized as synapomorphies of specific groups. Some characters appear to be related to the locomotor type (e.g., the sacro‐urostyle region configuration is highly linked with the jumping mode; nonexpanded diapophyses would related to aquatic habitat use). Nevertheless, the functional interpretations are quite particular to this family. Monophyletic clades are also groups with shared locomotory modes or habitat uses. Hence, the hypothesis of common ancestry or adaptation can be evaluated, taking into account the analysis level of the phylogenetic context, so that, when a character is inherited via common ancestry, it necessarily means that functional constraints could also be inherited. Here, we outline the basis for further work on: postmetamorphic development as a fundamental period for the complete differentiation of structures related to a full locomotor functionality; the biomechanical performance in relationship to the variation in ligaments and sesamoids; the importance of analyzing these topics within the frame of heterochrony. J. Morphol. 277:786–813, 2016. © 2016 Wiley Periodicals, Inc.
Evaluation of magnetic matrix solid‐phase dispersion for the determination of polychlorinated biphenyls in water samples by gas chromatography with electron capture detection
Authors: Diao Chun‐peng , Yu Xiaoting , Li Cong , Yang Xiao , Sun Aling , Liu Renmin
Published: March 2016

A vortex‐assisted magnetic matrix solid‐phase dispersion method was proposed for the determination of polychlorinated biphenyls in different matrix water samples by gas chromatography with electron capture detection. Magnetic bamboo charcoal (MBC) was synthesized for the adsorption of polychlorinated biphenyls in water samples. Complete separation of the liquid phase and the solid magnetic bamboo charcoal was easily achieved by using a permanent magnet. Under the optimized conditions, good linearity in the range of 0.006–5.0 μg/L was obtained with regression coefficients (r) higher than 0.9986. Based on a signal‐to‐noise ratio of 3, limits of detection were found to be 0.001–0.003 μg/L. Relative standard deviations ranged from 2.92 to 6.56%. Relative recoveries were 96.6–111.2% for the spiked wastewater sample and 90.7–104.7% for the spiked lake water sample. All results showed that the proposed method was simple, sensitive, and reliable for the determination of polychlorinated biphenyls in water samples.
Preparation of a K+‐imprinted polymer for the selective recognition of K+ in food samples
Authors: Hashemi Beshare , Shamsipur Mojtaba , Seyedzadeh Zahra
Published: March 2016

An analytical method is reported for the preparation of K+‐imprinted nanoparticles using cryptand 222 as the complexing agent, methacrylic acid as the functional monomer, ethylene glycol dimethacrylate as the crosslinker and 2,2′‐azobisisobutyronitrile as the radical initiator. The prepared particles have a diameter of 200–250 nm. The maximum adsorption capacity of potassium ion‐imprinted polymer particles was 120 μmol/g. The optimum pH for quantitative extraction was 9.0. The nature of the eluent, eluent concentration, adsorption and desorption times, weight of the polymer material, aqueous phase, and desorption volumes were also studied. The relative selectivity coefficients of K+/Li+, K+/Na+, K+/Rb+ and K+/Cs+ were 48.10, 4.80, 29.70, and 43.4, respectively. The relative standard deviation and limit of detection of the method were obtained 1.61% and 4.62 ng/L, respectively. Finally, the method was applied for the determination of potassium ions from different samples using flame photometry.
Ceftolozane/Tazobactam Pharmacokinetics in a Critically Ill Adult Receiving Continuous Renal Replacement Therapy
Authors: Bremmer Derek N. , Nicolau David P. , Burcham Pam , Chunduri Anil , Shidham Ganesh , Bauer Karri A.
Published: March 2016

Limited data are available on ceftolozane/tazobactam dosing in patients receiving continuous renal replacement therapy (CRRT). Thus we performed a pharmacokinetic analysis of intravenous ceftolozane/tazobactam in a critically ill patient receiving CRRT at our medical center. A 47‐year‐old critically ill man with multidrug‐resistant Pseudomonas aeruginosa pneumonia, bacteremia, and osteomyelitis was receiving ceftolozane/tazobactam 3 g (ceftolozane 2 g/tazobactam 1 g) every 8 hours while receiving continuous venovenous hemodiafiltration (CVVHDF). After the fifth dose of ceftolozane/tazobactam, plasma samples were obtained at 1‐, 2‐, 4‐, 6‐, and 8‐hour time points. Two additional post‐hemodialysis filter plasma samples were obtained to assess CVVHDF clearance. The maximum and minimum plasma concentrations for ceftolozane were 163.9 μg/ml and 79.4 μg/ml, respectively. The area under the plasma concentration–time curve from 0–8 hours (AUC0–8) was 689 μg hour/ml; the plasma half‐life was 13.3 hours. The ceftolozane CVVHDF clearance and total clearance were 2.4 L/hour and 2.9 L/hour, respectively. Compared with a patient with normal renal function, this patient receiving CVVHDF had decreased ceftolozane clearance. A ceftolozane/tazobactam dosage of 1.5 g every 8 hours should adequately achieve a desired drug concentration above the minimum inhibitory concentration of 8 μg/ml for the treatment of pneumonia. Additional pharmacokinetic data are needed to confirm our results and for alternative forms of CRRT.
Chemotherapy following radium‐223 dichloride treatment in ALSYMPCA
Authors: Sartor Oliver , Hoskin Peter , Coleman Robert E. , Nilsson Sten , Vogelzang Nicholas J. , Petrenciuc Oana , Staudacher Karin , Thuresson Marcus , Parker Christopher
Published: March 2016

BACKGROUND

Radium‐223 prolongs overall survival in patients with castration‐resistant prostate cancer (CRPC) and symptomatic bone metastases, regardless of prior docetaxel. Whether or not chemotherapy can be safely administered following radium‐223 treatment is of clinical importance. An exploratory analysis of prospectively collected data, from the ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) patient subgroup who received chemotherapy after radium‐223 or placebo treatment, was conducted to evaluate the safety and efficacy of chemotherapy following radium‐223.

METHODS

In ALSYMPCA, CRPC patients with symptomatic bone metastases and no visceral metastases were randomized 2:1 to receive six injections of radium‐223 (50 kBq/kg IV) or placebo plus best standard of care, stratified by prior docetaxel, baseline alkaline phosphatase, and current bisphosphonate use. In this exploratory analysis, chemotherapy agents administered following study treatment were identified; timing and duration were calculated. Hematologic safety was reviewed, and overall survival analyzed.

RESULTS

Overall, 142 radium‐223 and 64 placebo patients received subsequent chemotherapy; most common were docetaxel (70% radium‐223, 72% placebo) and mitoxantrone (16% radium‐223, 20% placebo). The majority of patients (61% radium‐223, 58% placebo) had received prior docetaxel. Radium‐223 patients started subsequent chemotherapy later than placebo patients; chemotherapy duration was similar between groups. In radium‐223 and placebo patients receiving subsequent chemotherapy, median hematologic values (hemoglobin, neutrophils, and platelets) remained nearly constant up to 18 months following start of chemotherapy, regardless of prior docetaxel treatment. A low percentage of patients in both groups had grades 3–4 hematologic values (<10%). Platelet count decline, from last measurement before chemotherapy, was numerically greater in radium‐223 versus placebo patients. Median overall survivals from start of chemotherapy were 16.0 and 15.8 months following radium‐223 and placebo, respectively.

CONCLUSIONS

Chemotherapy following radium‐223, regardless of prior docetaxel, is feasible and appears to be well tolerated in patients with CRPC and symptomatic bone metastases. Prostate 76:905–916, 2016. © 2016 The Authors. The Prostate published by Wiley Periodicals, Inc.
Surgical Non‐governmental Organizations: Global Surgery’s Unknown Nonprofit Sector
Authors: Ng‐Kamstra Joshua S. , Riesel Johanna N. , Arya Sumedha , Weston Brad , Kreutzer Tino , Meara John G. , Shrime Mark G.
Published: March 2016

Background

Charitable organizations may play a significant role in the delivery of surgical care in low‐ and middle‐income countries (LMICs). However, in order to quantify their collective contribution, to account for the care they provide in national surgical plans, and to maximize coordination between organizations, a comprehensive database of these groups is required. We aimed to create such a database using web‐available data.

Methods

We searched for organizations that meet the United Nations Rule of Law definition of non‐governmental organizations and provide surgery in LMICs. We termed these surgical non‐governmental organizations (s‐NGOs). We screened multiple sources including a listing of disaster relief organizations, medical volunteerism databases, charity commissions, and the results of a literature search. We performed a secondary review of each eligible organization’s website to verify inclusion criteria and extracted data.

Results

We found 403 s‐NGOs providing surgery in all 139 LMICs, with most (61 %) incorporating surgery into a broader spectrum of health services. Over 80 % of s‐NGOs had an office in the USA, the UK, Canada, India, or Australia, and they most commonly provided surgery in India (87 s‐NGOs), Haiti (71), Kenya (60), and Ethiopia (55). The most common specialties provided were general surgery (184), obstetrics and gynecology (140), and plastic surgery (116).

Conclusions

This new catalog includes the largest number of s‐NGOs to date, but this is likely to be incomplete. This list will be made publicly available to promote collaboration between s‐NGOs, national health systems, and global health policymakers.