bluuebunny/crossref_metadata_2025 huggingface dataset:
Paracrine Secretion of Transforming Growth Factor β by Ductal Cells Promotes Acinar-to-Ductal Metaplasia in Cultured Human Exocrine Pancreas Tissues
Authors: Akanuma Naoki , Liu Jun , Liou Geou-Yarh , Yin Xue , Bejar Kaitlyn R. , Liu Chengyang , Sun Lu-Zhe , Storz Peter , Wang Pei
Published: September 2017

Objective

We aimed to evaluate the contribution of acinar-to-ductal metaplasia (ADM) to the accumulation of cells with a ductal phenotype in cultured human exocrine pancreatic tissues and reveal the underlying mechanism.

Methods

We sorted and cultured viable cell populations in human exocrine pancreatic tissues with a flow cytometry–based lineage tracing method to evaluate possible mechanisms of ADM. Cell surface markers, gene expression pattern, and sphere formation assay were used to examine ADM.

Results

A large proportion of acinar cells gained CD133 expression during the 2-dimensional culture and showed down-regulation of acinar markers and up-regulation of ductal markers, assuming an ADM phenotype. In a serum-free culture condition, ADM induction was mainly dependent on transforming growth factor β (TGF-β) secreted from cultured ductal cells. Human acinar cells when cultured alone for a week in a serum-free condition do not undergo ADM. However, serum may contain other factors besides TGF-β to induce ADM in human acinar cells. In addition, we found that TGF-β cannot induce ADM of murine acinar cells.

Conclusions

Ductal cells are the major source of TGF-β that induces ADM in cultured human exocrine pancreatic tissues. This culture system might be a useful model to investigate the mechanism of ADM in human cells.
Initial Features of Hepatic Metastases From Pancreatic Cancer
Authors: Katada Tomohiro , Hashidate Hideki , Yokoyama Naoyuki , Sudo Natsuru , Mitsuma Koko , Otani Tetsuya
Published: September 2017

Objective

The pathophysiology of primary-stage hepatic metastases from gastrointestinal cancers may provide clues to their formation. We investigated initial features of hepatic metastases from pancreatic cancer by examining the histologies of radiographically occult hepatic micrometastases.

Methods

We examined 133 consecutive pancreatic cancer patients with no evident hepatic metastases on preoperative imaging. An indocyanine green near-infrared camera system was used to detect hepatic metastases during surgery; preoperatively acquired images of patients were then retrospectively reviewed.

Results

Hepatic micrometastases were histologically confirmed in 20 patients (15%). Immunohistochemically, the metastatic cells were with higher positivity of carcinoembryonic antigen (100%), p53 overexpression (40%), and Ki-67 labeling index (38%, median). All the micrometastases were portal thromboemboli in the intrahepatic portal triad that invaded extravenous structures, causing desmoplasis, local biliary obstruction, and indocyanine green–contained bile stasis A review of preoperative dynamic computed tomography or magnetic resonance images revealed focal circular alterations presenting as arterioportal shunts in 50% of the patient with micrometastases and 11% of those without (P < 0.01).

Conclusions

Hepatic metastasis from pancreatic cancer involves portal vein thrombosis that alters local circulation and bile stasis at the portal triad; this is detectable by presurgical radiological examination or intraoperative fluorescent imaging.
Sudden Death in an Adult Due to Nontraumatic Diaphragmatic Hernia
Authors: Kato Hideaki , Aoki Yasuhiro , Ohtaki Jun , Nakamura Yoshimi , Gaballah Mohammed Hassan , Fukuta Mamiko , Kobayashi Katsumasa
Published: September 2017

Sudden death due to diaphragmatic hernia in an adult is exceptionally rare. A 43-year-old man was found dead by his cohabiting mother, lying supine on the floor in his house. He had complained of epigastric discomfort for 1 month, and respiratory symptoms occurred 1 day before his death. He had no history of trauma. Postmortem computed tomography scan revealed the enlarged fluid-filled stomach herniated into the left pleural cavity, compressing the left lung with a mediastinal shift to the right. At autopsy, the left pleural cavity was occupied by herniated abdominal contents with mediastinal shift. The herniation of the stomach, the whole spleen, a portion of the colon, and omentum into the left pleural cavity had occurred through a smooth oval 9 × 5-cm defect in the posterolateral part of the light diaphragm. The stomach was markedly distended and contained 1600 mL of yellowish brown liquid with food residue. Ischemic changes of the herniated organs were not observed. Death was attributed to respiratory failure from abdominal viscera herniation into the left pleural cavity.
Induction of DISE in ovarian cancer cellsin vivo
Authors: Murmann Andrea E. , McMahon Kaylin M. , Haluck-Kangas Ashley , Ravindran Nandini , Patel Monal , Law Calvin , Brockway Sonia , Wei Jian-Jun , Thaxton C. Shad , Peter Marcus E.
Published: September 2017

The death receptor CD95/Fas can be activated by immune cells to kill cancer cells. shRNAs and siRNAs derived from CD95 or CD95 ligand (CD95L) are highly toxic to most cancer cells. We recently found that these sh/siRNAs kill cancer cells in the absence of the target by targeting the 3’UTRs of critical survival genes through canonical RNAi. We have named this unique form of off-target effect DISE (for death induced by survival gene elimination). DISE preferentially kills transformed cells and cancer stem cells. We demonstrate that DISE induction occurs in cancer cellsin vivoafter introducing a lentiviral CD95L derived shRNA (shL3) into HeyA8 ovarian cancer cells grown as i.p. xenografts in mice, when compared to a scrambled shRNA. To demonstrate the possibility of therapeutically inducing DISE, we coupled siRNAs to templated lipoprotein nano particles (TLP).In vitro,TLPs loaded with a CD95L derived siRNA (siL3) selectively silenced a biosensor comprised of Venus and CD95L ORF and killed ovarian cancer cells.In vivo,two siRNA-TLPs (siL2-TLP and siL3-TLP) reduced tumor growth similarly as observed for cells expressing the shL3 vector. These data suggest that it is possible to kill ovarian cancer cellsin vivovia DISE induction using siRNA-TLPs.
Propofol induces a metabolic switch to glycolysis and cell death in a mitochondrial electron transport chain-dependent manner
Authors: Sumi Chisato , Okamoto Akihisa , Tanaka Hiromasa , Nishi Kenichiro , Kusunoki Munenori , Shoji Tomohiro , Uba Takeo , Matsuo Yoshiyuki , Adachi Takehiko , Hayashi Jun-Ichi , Takenaga Keizo , Hirota Kiichi
Published: September 2017

The intravenous anesthetic propofol (2,6-diisopropylphenol) has been used for the induction and maintenance of anesthesia in operating rooms and for sedation in intensive care units. Although there is no widely accepted definition of propofol infusion syndrome (PRIS), PRIS is defined as the development of metabolic acidosis, rhabdomyolysis, hyperkalemia, hepatomegaly, renal failure, arrhythmia, and progressive cardiac failure. In vitro evidence suggests that PRIS is related to the impaired mitochondrial function. There are indications that preexisting mitochondrial disorders predispose to PRIS. However, the precise molecular mechanisms, including mitochondrial defects and a metabolic conversion by propofol, are largely unknown as yet. To elucidate the underlying cellular and molecular mechanisms of PRIS, we investigated the effects of propofol on the cellular metabolic mode and cell death. We demonstrated that clinically relevant concentrations of propofol, used within a clinically relevant exposure time, suppressed the mitochondrial function, caused the generation of reactive oxygen species, and induced a metabolic switch, from oxidative phosphorylation to glycolysis, by targeting complexes I and III of mitochondria. The data also indicated that a predisposition to mitochondrial dysfunction, caused by a genetic mutation or pharmacological suppression of the electron transport chain by biguanides such as metformin and phenformin, promoted the cell death and caspase activation induced by propofol.
Extinction models of robustness for weighted ecological networks
Authors: Bane Miranda S. , Pocock Michael J. O. , James Richard
Published: September 2017

Analysis of ecological networks is a valuable approach to understanding the vulnerability of systems to environmental change. The tolerance of ecological networks to co-extinctions, resulting from sequences of primary extinctions, is a widely-used tool for modelling network ‘robustness’. Previously, these ‘extinction models’ have been developed for and applied mostly to binary networks and recently used to predict cascades of co-extinctions in plant-pollinator networks. There is a need for robustness models that can make the most of the weighted data available and most importantly there is a need to understand how the structure of a network affects its robustness.

Here, we developed a framework of extinction models for bipartite ecological networks (specifically plant-pollinator networks). In previous models co-extinctions occurred when nodes lost all their links, but by relaxing this rule (according to a set threshold) our models can be applied to binary and weighted networks, and can permit structurally correlated extinctions, i.e. the potential for avalanches of extinctions. We tested how the average and the range of robustness values is impacted by network structure and the impact of structurally-correlated extinctions sampling non-uniformly from the distribution of random extinction sequences.

We found that the way that structurally-correlated extinctions are modelled impacts the results; our two ecologically-plausible models produce opposing effects which shows the importance of understanding the model. We found that when applying the models to networks with weighted interactions, the effects are amplified and the variation in robustness increases. Variation in robustness is a key feature of these extinction models and is driven by the structural heterogeneity (i.e. the skewness of the degree distribution) of nodes (specifically, plant nodes) in the network.

Our new framework of models enables us to calculate robustness with weighted, as well as binary, bipartite networks, and to make direct comparisons between models and between networks. This allows us to differentiate effects of the model and of the data (network structure) which is vital for those making ecological inferences from robustness models. The models can be applied to mutualistic and antagonistic networks, and can be extended to food webs.
Replication Timing Networks: a novel class of gene regulatory networks
Authors: Rivera-Mulia Juan Carlos , Kim Sebo , Gabr Haitham , Chakraborty Abhijit , Ay Ferhat , Kahveci Tamer , Gilbert David M.
Published: September 2017

DNA replication occurs in a defined temporal order known as the replication-timing (RT) program and is regulated during development, coordinated with 3D genome organization and transcriptional activity. However, transcription and RT are not sufficiently coordinated to predict each other, suggesting an indirect relationship. Here, we exploit genome-wide RT profiles from 15 human cell types and intermediate differentiation stages derived from human embryonic stem cells to construct different types of RT regulatory networks. First, we constructed networks based on the coordinated RT changes during cell fate commitment to create highly complex RT networks composed of thousands of interactions that form specific functional sub-network communities. We also constructed directional regulatory networks based on the order of RT changes within cell lineages and identified master regulators of differentiation pathways. Finally, we explored relationships between RT networks and transcriptional regulatory networks (TRNs), by combining them into more complex circuitries of composite and bipartite networks, revealing noveltransinteractions between transcription factors and downstream RT changes that were validated with ChIP-seq data. Our findings suggest a regulatory link between the establishment of cell type specific TRNs and RT control during lineage specification.
Common framework for “virtual lesion” and state-dependent TMS: the facilitatory/suppressive range model of online TMS effects on behavior
Authors: Silvanto Juha , Cattaneo Zaira
Published: September 2017

The behavioral effects of Transcranial Magnetic Stimulation (TMS) are often nonlinear; factors such as stimulation intensity and brain state can modulate the impact of TMS on observable behavior in qualitatively different manner. Here we propose a theoretical framework to account for these effects. In this model, there are distinct intensity ranges for facilitatory and suppressive effects of TMS: low intensities facilitate neural activity and behavior whereas high intensities induce suppression. The key feature of the model is that these ranges are shifted by changes in neural excitability: consequently, a TMS intensity, which normally induces suppression, can have a facilitatory effect if the stimulated neurons are being inhibited. For example, adaptation reduces excitability of adapted neurons; the outcome is that TMS intensities which inhibit non-adapted neurons induce a facilitation on adapted neural representations, leading to reversal of adaptation effects. In conventional virtual lesion paradigms, similar effects occur because neurons not tuned to the target stimulus are inhibited. The resulting reduction in excitability can turn high intensity inhibitory TMS to low intensity facilitatory TMS for these neurons (whereas neurons tuned to the target stimulus are inhibited), leading to a reduction in signal-to-noise ratio. Thus differential excitability levels of neural populations contributing to behavior, combined with nonlinear neural effects, can explain how TMS modulates behavior.
Master’s thesis research in social marketing (1971-2015)
Authors: Truong V. Dao , Dietrich Timo
Published: September 2017

Purpose

Limited attention has been given to the study of social marketing at the graduate level. Such a study not only reveals research interests and trends, but also provides insights into the level of academic evolution or maturity of the social marketing field. This paper aims to examine social marketing as the subject of master’s theses.

Design/methodology/approach

A search strategy found 266 social marketing-focused master’s theses completed from 1971 to 2015. These theses were analysed by host countries, institutions, disciplinary contexts and degree programmes for which they were submitted.

Findings

Only four theses were submitted from 1971-1980 and eight completed in 1981-1990. The number of theses increased to 35 in 1991-2000, 118 between 2001 and 2010 and 101 in the past five years (2011-2015). The USA was the leading producer of social marketing master’s theses, followed by Canada, Sweden, China, South Africa, the UK and Kenya. A majority of theses were housed in the disciplines of business, health and communication, and none of them was submitted for a Master of Social Marketing degree.

Originality/value

This is the first study that investigates master’s theses with an exclusive focus on social marketing. Implications for the evolution, learning and teaching of social marketing are provided.
Lasioglossins LLIII affect the morphogenesis of Candida albicans and reduces the duration of experimental vaginal candidiasis in mice
Authors: Vrablikova Alena , Czernekova Lydie , Cahlikova Romana , Novy Zbynek , Petrik Milos , Imran Saima , Novak Zdenek , Krupka Michal , Cerovsky Vaclav , Turanek Jaroslav , Raska Milan
Published: September 2017

Lasioglossins are a group of peptides with identified antimicrobial activity. The inhibitory effects of two synthetic lasioglossin derivatives, LLIII and D‐isomeric variant LLIII‐D, on morphological changes in Candida albicans in vitro and the effect of local administration of LLIII during experimental murine candidiasis were investigated. C. albicans blastoconidia were grown in the presence of lasioglossin LLIII or LLIII‐D at concentrations of 11.5 μM and 21 μM, respectively, for 1, 2 and 3 days and their viability determined by flow cytometry using eosin Y staining. Morphological changes were examined by light and fluorescent microscopy. The Candida‐inhibitory effect of daily intravaginal administration of 0.7 or 1.4 μg of LLIII was assessed in mice with experimentally‐induced vaginal candidiasis. LLIII and LLIII‐D lasioglossins exhibited candidacidal activity in vitro (>76% after 24 hr and >84% after 48 hr of incubation). After 72 hr incubation of Candida with low concentration of lasioglossins, an increase in viability was detected, probably due to a Candida antimicrobial peptides evasion strategy. Furthermore, lasioglossins inhibited temperature‐induced morphotype changes toward hyphae and pseudohyphae with sporadic occurrence of atypical cells with two or enlarged nuclei, suggesting interference with mitosis or cytokinesis. Local application of LLIII reduced the duration of experimental candidiasis with no evidence of adverse effects. Lasioglossin LLIII is a promising candidate for development as an antimicrobial drug for treating the vaginal candidiasis.
Cellulose production is coupled to sensing of the pyrimidine biosynthetic pathway via c‐di‐GMP production by the DgcQ protein of Escherichia coli
Authors: Rossi Elio , Motta Sara , Aliverti Alessandro , Cossu Federica , Gourlay Louise , Mauri Pierluigi , Landini Paolo
Published: September 2017

Production of cellulose, a stress response‐mediated process in enterobacteria, is modulated in Escherichia coli by the activity of the two pyrimidine nucleotide biosynthetic pathways, namely, the de novo biosynthetic pathway and the salvage pathway, which relies on the environmental availability of pyrimidine nitrogenous bases. We had previously reported that prevalence of the salvage over the de novo pathway triggers cellulose production via synthesis of the second messenger c‐di‐GMP by the DgcQ (YedQ) diguanylate cyclase. In this work, we show that DgcQ enzymatic activity is enhanced by UTP, whilst being inhibited by N‐carbamoyl‐aspartate, an intermediate of the de novo pathway. Thus, direct allosteric control by these ligands allows full DgcQ activity exclusively in cells actively synthesizing pyrimidine nucleotides via the salvage pathway. Inhibition of DgcQ activity by N‐carbamoyl‐aspartate appears to be favoured by protein‐protein interaction between DgcQ and PyrB, a subunit of aspartate transcarbamylase, which synthesizes N‐carbamoyl‐aspartate. Our results suggest that availability of pyrimidine bases might be sensed, somehow paradoxically, as an environmental stress by E. coli. We hypothesize that this link might have evolved since stress events, leading to extensive DNA/RNA degradation or lysis of neighbouring cells, can result in increased pyrimidine concentrations and activation of the salvage pathway.
Application of Visible/Near‐Infrared Spectroscopy in the Prediction of Azodicarbonamide in Wheat Flour
Authors: Che Wenkai , Sun Laijun , Zhang Qian , Zhang Dan , Ye Dandan , Tan Wenyi , Wang Lekai , Dai Changjun
Published: September 2017

Azodicarbonamide is wildly used in flour industry as a flour gluten fortifier in many countries, but it was proved by some researches to be dangerous or unhealthy for people and not suitable to be added in flour. Applying a rapid, convenient, and noninvasive technique in food analytical procedure for the safety inspection has become an urgent need. This paper used Vis/NIR reflectance spectroscopy analysis technology, which is based on the physical property analysis to predict the concentration of azodicarbonamide in flour. Spectral data in range from 400 to 2498 nm were obtained by scanning 101 samples which were prepared using the stepwise dilution method. Furthermore, the combination of leave‐one‐out cross‐validation and Mahalanobis distance method was used to eliminate abnormal spectral data, and correlation coefficient method was used to choose characteristic wavebands. Partial least squares, back propagation neural network, and radial basis function were used to establish prediction model separately. By comparing the prediction results between 3 models, the radial basis function model has the best prediction results whose correlation coefficients (R), root mean square error of prediction (RMSEP), and ratio of performance to deviation (RPD) reached 0.99996, 0.5467, and 116.5858, respectively.

Practical Application

Azodicarbonamide has been banned or limited in many countries. This paper proposes a method to predict azodicarbonamide concentrate in wheat flour, which will be used for a rapid, convenient, and noninvasive detection device.
Is microbial terroir related to geographic distance between vineyards?
Authors: Miura Toshiko , Sánchez Roland , Castañeda Luis E. , Godoy Karina , Barbosa Olga
Published: September 2017

While there are substantial studies suggesting that characteristics of wine are related to regional microbial community composition (microbial terroir), there has been little discussion about what factors affect variation in regional microbial community composition. In this study, we compared the microbial community composition of leaves and berries of a grape variety (Carmenere) from six different Chilean vineyards within 35 km of each other. In order to determine relationships between spatial proximity and microbial compositional dissimilarity, we sequenced amplicons of the internal transcribed spacer (ITS) region for fungi and 16S rRNA gene for bacteria. Results showed that both the fungal and the bacterial community compositions of the studied vineyards differed, but this difference was much clearer in fungi than in bacteria. In addition, while bacterial community dissimilarity was not correlated with geographic distance, the leaf and berry fungal community dissimilarities between locations increased with geographic distance. This indicates that spatial processes play an important role in structuring the biogeographic pattern of grape‐associated fungal communities at local scales, which might in turn contribute to the local identity of wine.
High‐level resistance of Melissococcus plutonius clonal complex 3 strains to antimicrobial activity of royal jelly
Authors: Takamatsu Daisuke , Osawa Aya , Nakamura Keiko , Yoshiyama Mikio , Okura Masatoshi
Published: September 2017

Melissococcus plutonius is the causative agent of European foulbrood of honey bee larvae. Among its three genetically distinct groups (CC3, CC12 and CC13), CC3 strains have been suggested to be more virulent at the colony level. Honey bee larvae are fed royal or worker jellies by adult bees, and these jellies exhibit antimicrobial activity. Since M. plutonius orally infects larvae via brood food, we herein investigated the resistance of M. plutonius to the antimicrobial activity of royal jelly (RJ). The results obtained revealed that M. plutonius strains were more resistant to RJ and its component, 10‐hydroxy‐2‐decenoic acid, than the other species tested. Moreover, among the M. plutonius strains examined, CC3 strains exhibited the strongest resistance to antimicrobial activity; they temporarily proliferated and survived for a long period in 50% RJ‐containing broth. However, resistance was not observed when freshly cultured bacteria were used, it was only detected after a preculture on agar media for five or more days, suggesting that, under certain conditions, CC3 strains change their physiological state to that which is advantageous for survival in brood food. This high‐level RJ resistance of CC3 strains may contribute to their virulence in the field.
How Much Voice for Borrowers? Restricted Feedback and Recursivity in Microfinance
Authors: Mader Philip
Published: September 2017

This paper studies the governance of microfinance and asks about its recursivity: whether the system is responsive to changes prompted by feedback from borrowers or not. It draws on Hirschmann's heuristic of exit and voice and the idea of participation in development, to examine three channels of feedback from borrowers to rule‐makers and ask to what extent they have facilitated or restricted recursivity in microfinance. The standardisation of microfinance along a financial template is shown to have created very open flows of financial information, useful for monitoring clients' exit, but not granting them voice. The more recent creation of systems for social performance management and pursuing ‘responsible' microfinance, however, has not resulted in similarly robust information flows, because, despite intentions to capture client satisfaction and feedback, these channels are severely restricted. They offer borrowers little chance to practically exercise voice and convey feedback which affects the rules. Recursivity studies, it is suggested, might integrate participation and exit/voice frameworks to explore the prospects of feedback from grassroots rule‐subjects and better understand the factors that can restrict it. For microfinance, it is suggested that government regulation and clients' collective action could be necessary where the sector's governance system shows itself to be unresponsive.
Introduction to the Special Section: Policy Instruments for Innovation, Investment and Global Trade
Authors: Klasen Andreas
Published: September 2017

This Special Section on policy instruments for innovation, investment and global trade presents several approaches how to foster economic growth. It deals with well‐known instruments such as guarantees and loans for trade finance as well as export credits. It also sheds light on how foreign direct investment strategies can be tremendously successful, and how governments can learn from effective policy approaches. It shows how financial instruments for investors can be used to manage and minimise risks. And, last but not least, it has a look at the government toolbox for innovation as well as the ingredients for an ecosystem combining different policy instruments.
Case report of apatinib mesylate treatment in rare advanced tracheal adenoid cystic carcinoma
Authors: Wang Hongmei
Published: September 2017

A 57‐year‐old man was admitted to our department 10 years ago, diagnosed with tracheal adenoid cystic carcinoma. After discontinuing chemotherapy and radiotherapy, the disease recurred in December 2016. Apatinib mesylate (500 mg/day) was administered and computed tomography revealed that his symptoms were significantly relieved. Treatment with apatinib mesylate represents a novel method of treatment for tracheal adenoid cystic carcinoma.
Light therapy: is it safe for the eyes?
Authors: Brouwer A. , Nguyen H.‐T. , Snoek F. J. , van Raalte D. H. , Beekman A. T. F. , Moll A. C. , Bremmer M. A.
Published: September 2017

Objective

Light therapy has become an increasingly popular treatment for depression and a range of other neuropsychiatric conditions. Yet, concerns have been raised about the ocular safety of light therapy.

Method

We conducted the first systematic review into the ocular safety of light therapy. A PubMed search on January 4, 2017, identified 6708 articles, of which 161 were full‐text reviewed. In total, 43 articles reporting on ocular complaints and ocular examinations were included in the analyses.

Results

Ocular complaints, including ocular discomfort and vision problems, were reported in about 0% to 45% of the participants of studies involving light therapy. Based on individual studies, no evident relationship between the occurrence of complaints and light therapy dose was found. There was no evidence for ocular damage due to light therapy, with the exception of one case report that documented the development of a maculopathy in a person treated with the photosensitizing antidepressant clomipramine.

Conclusion

Results suggest that light therapy is safe for the eyes in physically healthy, unmedicated persons. The ocular safety of light therapy in persons with preexisting ocular abnormalities or increased photosensitivity warrants further study. However, theoretical considerations do not substantiate stringent ocular safety‐related contraindications for light therapy.
Behavioural Addiction Open Definition 2.0—using the Open Science Framework for collaborative and transparent theoretical development
Authors: Billieux Joël , van Rooij Antonius J. , Heeren Alexandre , Schimmenti Adriano , Maurage Pierre , Edman Johan , Blaszczynski Alexander , Khazaal Yasser , Kardefelt‐Winther Daniel
Published: September 2017

Commentary to: How can we conceptualize behavioural addiction without pathologizing common behaviours?
Effects of epidural volume extension by saline injection on the efficacy and safety of intrathecal local anaesthetics: systematic review with meta‐analysis, meta‐regression and trial sequential analysis
Authors: Heesen M. , Weibel S. , Klimek M. , Rossaint R. , Arends L. R. , Kranke P.
Published: September 2017

Epidural volume extension, a modification of combined spinal–epidural anaesthesia, involves the epidural injection of saline in order to increase the spread of drugs given intrathecally. Results from individual studies have so far been contradictory and we aimed to gather the available evidence for this technique. We performed a systematic literature search for randomised, controlled trials comparing epidural volume extension after spinal injection with a control group without epidural injection in patients undergoing surgery. Conventional meta‐analyses, trial sequential analyses and meta‐regression were performed, with the Grading of Recommendations on Assessment, Development and Evaluation (GRADE) approach used to express reliability of outcome estimates. We included 15 studies with 1177 participants. Meta‐analyses for the primary outcomes, such as maximum sensory height (6 studies, 274 participants, mean difference (MD) (95%CI) −0.59 (−1.24 to 0.07) dermatomes, low‐quality evidence) and hypotension (10 studies, 683 participants, risk ratio (95%CI) 0.84 (0.66–1.07), low‐quality evidence), did not differ significantly between the two treatment arms, but trial sequential analysis suggested insufficient evidence to be certain of these findings. Meta‐regression suggested a volume‐dependent effect, with higher volumes causing a higher spread of intrathecal drugs and a higher incidence of hypotension. A sub‐group analysis indicated a pronounced effect on motor block recovery time when a lower anaesthetic dose plus epidural volume extension was compared with a higher anaesthetic dose without epidural volume extension, the MD (95%CI) being −66.75 (−76.0 to −57.5) min, with trial sequential analysis suggesting the evidence was sufficient to draw this conclusion. In trials using the same anaesthetic mixture in the epidural volume extension and the control groups, motor block recovery time did not differ between groups, with a MD (95%CI) of −1.06 (−5.48 to 3.36) min, although trial sequential analysis suggested insufficient evidence. In summary, there is not enough evidence to draw definite conclusions on the effect of epidural volume extension. The quality of the current evidence is low for both efficacy (maximum sensory height) and safety (hypotension). However, there may be a significantly shorter motor block recovery time when different anaesthetic mixtures are used in epidural volume extension and control groups; this warrants further investigation.
External evaluation of population pharmacokinetic models for ciclosporin in adult renal transplant recipients
Authors: Mao Jun‐Jun , Jiao Zheng , Yun Hwi‐Yeol , Zhao Chen‐Yan , Chen Han‐Chao , Qiu Xiao‐Yan , Zhong Ming‐Kang
Published: September 2017

Aims

Several population pharmacokinetic (popPK) models for ciclosporin (CsA) in adult renal transplant recipients have been constructed to optimize the therapeutic regimen of CsA. However, little is known about their predictabilities when extrapolated to different clinical centres. Therefore, this study aimed to externally evaluate the predictive ability of CsA popPK models and determine the potential influencing factors.

Methods

A literature search was conducted and the predictive performance was determined for each selected model using an independent data set of 62 patients (471 predose and 500 2‐h postdose concentrations) from our hospital. Prediction‐based diagnostics and simulation‐based normalized prediction distribution error were used to evaluate model predictability. The influence of prior information was assessed using Bayesian forecasting. Additionally, potential factors influencing model predictability were investigated.

Results

Seventeen models extracted from 17 published popPK studies were assessed. Prediction‐based diagnostics showed that ethnicity potentially influenced model transferability. Simulation‐based normalized prediction distribution error analyses indicated misspecification in most of the models, especially regarding variance. Bayesian forecasting demonstrated that the predictive performance of the models substantially improved with 2–3 prior observations. The predictability of nonlinear Michaelis–Menten models was superior to that of linear compartmental models when evaluating the impact of structural models, indicating the underlying nonlinear kinetics of CsA. Structural model, ethnicity, covariates and prior observations potentially affected model predictability.

Conclusions

Structural model is the predominant factor influencing model predictability. Incorporation of nonlinear kinetics in CsA popPK modelling should be considered. Moreover, Bayesian forecasting substantially improved model predictability.
Partners of nulliparous women with severe fear of childbirth: A longitudinal study of psychological well‐being
Authors: Ryding Elsa Lena , Read Sanna , Rouhe Hanna , Halmesmäki Erja , Salmela‐Aro Katariina , Toivanen Riikka , Tokola Maiju , Saisto Terhi
Published: September 2017

Background

Little is known about the psychological status of partners of women with severe fear of childbirth (FOC). In this longitudinal study from Helsinki University Central Hospital, we investigated FOC, depression, and posttraumatic stress in the partners of women with severe FOC, and possible effects of group psychoeducation and mode of birth.Methods: During pregnancy, 250 partners of nulliparous women with severe FOC participated, 93 in the intervention group and 157 in the control group. At 3 months postpartum, 52 partners in the intervention group and 93 in the control group participated. Both the partners and the childbearing women filled in the Wijma Delivery Expectancy/Experience Questionnaire and the Edinburgh Postnatal Depression Scale mid‐pregnancy as well as 3 months postpartum, when they also filled in the Traumatic Event Scale.

Results

Partners of women with severe FOC reported less antenatal and postnatal FOC and fewer depressive symptoms than the childbearing women. No partner reached the threshold of severe FOC. No partner reported a possible posttraumatic stress disorder. Group psychoeducation with relaxation was not associated with better or worse psychological well‐being of the partners. An emergency cesarean delivery was associated with a more fearful delivery experience in the partners.

Conclusion

Partners of nulliparous women with severe FOC neither seem to suffer from severe FOC nor reported posttraumatic stress symptoms after childbirth. They reported better psychological well‐being than the mothers both during pregnancy and after delivery. An unexpected cesarean may be a negative experience even for partners of childbearing women.
The sleeping patterns of Head Start children and the influence on developmental outcomes
Authors: Schlieber M. , Han J.
Published: September 2017

Background

Sleep has a significant influence on children's development. The objective of this study was to investigate Head Start children's sleeping patterns and the impact on cognitive and behavioural outcomes.

Methods

Using the 2009 cohort of the Head Start Family and Child Experiences Survey (N = 2,868), information on sleeping patterns was assessed through parent interviews. Cognitive outcomes were assessed using direct assessments (Peabody Picture Vocabulary Test‐IV, the Expressive One‐Word Picture Vocabulary Test, and Subtests of the Woodcock–Johnson III) in addition to teacher report. Behavioural outcomes were assessed through parent and teacher reports. A multiple regression analysis was performed for each outcome variable.

Results

Descriptive findings showed that 89% of children had a regular bedtime at least 4 days per week and that the average amount of sleep per night was 10.41 hr. White mothers were more likely than other racial groups to adhere to a consistent bedtime, and maternal employment predicted less hour of sleep per night. Multiple regression analyses revealed that disrupted sleep had a negative influence on cognitive outcomes, especially in areas of mathematical problem solving, receptive language, teacher‐reported literacy behaviours, and approaches to learning. Disrupted sleep was associated with the risk of misbehaviour by increasing teacher and parent ratings on aggressive behaviours, hyperactivity, and withdrawing in addition to decreased scores on overall social skills. Having an inconsistent bedtime negatively predicted expressive vocabulary and teacher‐reported literacy behaviours.

Conclusions

The findings of this study support the influential role of sleep on children's development. Sleeping through the night and having a consistent bedtime were found to be predictive of many areas of cognitive and behavioural development. Head Start staff can provide the supports to increase parental knowledge on appropriate child sleep practices.
IL‐33 and IgE stimulate mast cell production of IL‐2 and regulatory T cell expansion in allergic dermatitis
Authors: Salamon P. , Shefler I. , Moshkovits I. , Munitz A. , Horwitz Klotzman D. , Mekori Y. A. , Hershko A. Y.
Published: September 2017

Background

We have previously shown that mast cells (MCs) suppress chronic allergic dermatitis in mice. The underlying mechanism involves MC‐derived IL‐2, which supports regulatory T cell (Treg) response at the site of inflammation. However, it is not clear what are the factors that drive MCs to produce IL‐2.

Objective

To understand the mechanisms that lead to IL‐2 production from MCs in chronic allergic dermatitis.

Methods

Isolated murine bone marrow‐derived MCs (BMMCs) were incubated with various stimulators, and IL‐2 production was assessed by RT‐PCR and ELISA. The response of signalling pathways was evaluated by MAPK inhibitors and Western blot analysis. The effect of MC‐IL‐2 on Tregs was studied by incubation of splenic T cells with conditioned media obtained from activated BMMCs. Dermatitis was elicited by repeated exposures of mouse ears to oxazolone. MCs in mouse and human skin samples were evaluated by immunostaining.

Results

BMMCs released IL‐2 in response to IL‐33, and IL‐2 production was further enhanced by concomitant FcεRI activation. The effect of IL‐33 was mediated by activation of the MAPK family members. IL‐2 in conditioned media from IL‐33 and IgE‐stimulated BMMCs led to considerable expansion of Tregs in vitro. IL‐33 levels were elevated in oxazolone‐challenged ears along with increased numbers of IL‐2‐expressing MCs. Human skin with chronic inflammation also contained IL‐2‐expressing MCs that colocalized with IL‐33 staining in the dermis.

Conclusions

IL‐33, in collaboration with IgE, is critical for MC‐IL‐2 production in allergic skin disease, thus leading to Treg stimulation and suppression of allergic dermatitis.
Network meta‐analysis of lorcaserin and oral hypoglycaemics for patients with type 2 diabetes mellitus and obesity
Authors: Neff L. M. , Broder M. S. , Beenhouwer D. , Chang E. , Papoyan E. , Wang Z. W.
Published: September 2017

In addition to weight loss, randomized controlled trials have shown improvement in glycaemic control in patients taking lorcaserin. The aim of this study aim was to compare adding lorcaserin or other glucose lowering medications to metformin on weight and glycaemic control. A systematic review and network meta‐analysis of randomized controlled trials were conducted. Included studies (published 1990–2014) were of lorcaserin or glucose lowering medications in type 2 diabetic patients compared to placebo or different active treatments. Studies had to report ≥1 key outcome (change in weight or HbA1c, % HbA1c <7, hypoglycaemia). Direct meta‐analysis was performed using DerSimonian and Laird random effects models, and network meta‐analysis with Bayesian Markov‐chain Monte Carlo random effects models; 6552 articles were screened and 41 included. Lorcaserin reduced weight significantly more than thiazolidinediones, glinides, sulphonylureas and dipeptidyl peptidase‐4 inhibitors, some of which may have led to weight gain. There were no significant differences in weight change between lorcaserin and alpha‐glucoside inhibitors, glucagon‐like peptide‐1 agonists and sodium/glucose cotransporter 2 inhibitors. Network meta‐analysis showed lorcaserin was non‐inferior to all other agents on HbA1c reduction and % achieving HbA1c of <7%. The risk of hypoglycaemia was not significantly different among studied agents except that sulphonylureas were associated with higher risk of hypoglycaemia than lorcaserin. Although additional studies are needed, this analysis suggests in a population of patients with a body mas index of ≥27 who do not achieve glycaemic control on a single agent, lorcaserin may be added as an alternative to an add‐on glucose lowering medication.
funrar: An R package to characterize functional rarity
Authors: Grenié Matthias , Denelle Pierre , Tucker Caroline M. , Munoz François , Violle Cyrille
Published: September 2017

Emphasis has been put in recent ecological research on investigating phylogenetic, functional and taxonomic facets of biological diversity. While a flourishing number of indices have been proposed for assessing functional diversity, surprisingly few options are available to characterize functional rarity. Functional rarity can play a key role in community and ecosystem dynamics. We introduce here the funrar R package to quantify functional rarity based on species trait differences and species frequencies at local and regional scales. Because of the increasing availability of big datasets in macroecology and biogeography, we optimized funrar to work with large datasets of thousands of species and sites. We illustrate the use of the package to investigate the functional rarity of North and Central American mammals.
Identification and measurement of dystonia in cerebral palsy
Authors: Supiot Frédéric
Published: September 2017

This commentary is on the original article by Rice et al. on pages 1249–1255.
Carpal tunnel syndrome in mucopolysaccharidosis I: a registry‐based cohort study
Authors: Viskochil David , Muenzer Joseph , Guffon Nathalie , Garin Christophe , Munoz‐Rojas M Veronica , Moy Kristin A , Hutchinson Douglas T
Published: September 2017

Aim

To characterize carpal tunnel syndrome (CTS) in patients with mucopolysaccharidosis I (MPS I).

Method

Data were included for patients with MPS I who had either nerve conduction examination that included a diagnosis of CTS or who had CTS release surgery. Although this represented a subset of patients with CTS in the MPS I Registry, the criteria were considered the most objective for data analysis.

Results

As of March 2016, 994 patients were categorized with either severe (Hurler syndrome) or attenuated (Hurler–Scheie or Scheie syndromes) MPS I. Among these, 291 had a CTS diagnosis based on abnormal nerve conduction (n=54) or release surgery (n=237). Median ages (minimum, maximum) at first CTS diagnosis were 5 years 2 months (10mo, 16y 2mo) and 9y 11mo (1y 8mo, 44y 1mo) for patients with severe and attenuated MPS I respectively. Most patients had their first CTS diagnosis after MPS I diagnosis (94%) and treatment (hematopoietic stem cell transplant and/or enzyme replacement therapy) (74%). For 11% of patients with attenuated disease, CTS diagnosis preceded MPS I diagnosis by a mean of 7 years 6 months.

Interpretation

CTS is a rare complication in pediatric patients and should alert medical care providers to the potential diagnosis of MPS I. Significant delays exist between diagnosis of CTS and MPS I for patients with attenuated disease.

What this paper adds

There are significant delays in diagnosing carpal tunnel syndrome (CTS) in patients with mucopolysaccharidosis I (MPS I).

Enzyme replacement therapy or hematopoietic stem cell transplant do not prevent the development of CTS.

Testing for CTS in patients with MPS I is recommended to prevent irreparable damage.

CTS in pediatric patients should alert physicians to potential diagnosis of MPS I.
Social dimensions of land rights reform in Liberia: Some unresolved issues and policy dilemmas
Authors: Brown David
Published: September 2017

This article is concerned with coherence in public policy in highly differentiated societies. It explores the challenges faced when seeking to develop policy in ways which both respond to progressive thinking and protect the interests of the poor. Land policy in Liberia illustrates the theme, specifically the 2013 ‘Land Rights Policy.’ The article shows how pressures for reform of customary governance and gender relations may undermine the institutions of local land management, and threaten the ability of the rural poor to defend their interests. This is of particular concern at the present time, given the appetite of external capital for land acquisition in Liberia, and the close alliances which it is forging with the Liberian elite.
Do patients benefit from orthognathic surgery? A systematic review on the effects of elective orthognathic surgery on psychosocial functioning and patient satisfaction
Authors: Broers Dyonne L. M. , van der Heijden Geert J. M. G. , Rozema Frederik R. , de Jongh Ad
Published: September 2017

The main purpose of this systematic review was to determine the current state of evidence regarding patient satisfaction with, and the impact of, orthognathic surgery on psychosocial functioning of patients 17 yr of age and older. A secondary aim was to determine whether individuals with psychiatric disorders and mental health conditions are more likely to be dissatisfied with the treatment outcome than those without. We systematically searched PubMed, PsycInfo, and Embase for relevant studies (up to 6 June 2016). After selection of articles we determined the Directness of Evidence (DoE) and Risk of Bias (RoB). We identified 3,948 studies (1,053 studies in Pubmed, 2,023 in Embase, and 872 in PsycInfo). Of these, 87 remained after screening of title and abstract, while after full‐text screening only nine remained for DoE and RoB assessment. All nine studies had a high RoB and a low or moderate DoE. The quality of the methods of studies, published to date, on the effects of orthognathic surgery on patient satisfaction or the psychosocial impact carry a high RoB. Therefore, these do not allow inferences on the effects of orthognathic surgery on patient satisfaction or their psychosocial functioning.