bluuebunny/crossref_metadata_2025 huggingface dataset:
Solubilization kinetics determines the pulsatory dynamics of lipid vesicles exposed to surfactant
Authors: Chabanon Morgan , Rangamani Padmini
Published: February 2018

We establish a biophysical model for the dynamics of lipid vesicles exposed to surfactants. The solubilization of the lipid membrane due to the insertion of surfactant molecules induces a reduction of membrane surface area at almost constant vesicle volume. This results in a rate-dependent increase of membrane tension and leads to the opening of a micron-sized pore. We show that solubilization kinetics due to surfactants can determine the regimes of pore dynamics: either the pores open and reseal within a second (short-lived pore), or the pore stays open up to a few minutes (long-lived pore). First, we validate our model with previously published experimental measurements of pore dynamics. Then, we investigate how the solubilization kinetics and membrane properties affect the dynamics of the pore and construct a phase diagram for short and long-lived pores. Finally, we examine the dynamics of sequential pore openings and show that cyclic short-lived pores occur at a period inversely proportional to the solubilization rate. By deriving a theoretical expression for the cycle period, we provide an analytic tool to measure the solubilization rate of lipid vesicles by surfactants. Our findings shed light on some fundamental biophysical mechanisms that allow simple cell-like structures to sustain their integrity against environmental stresses, and have the potential to aid the design of vesicle-based drug delivery systems.
Cholesterol depletion by MβCD enhances membrane tension, its heterogeneity and affects cellular integrity
Authors: Biswas Arikta , Kashyap Purba , Datta Sanchari , Sengupta Titas , Sinha Bidisha
Published: February 2018

Cholesterol depletion in cells by MβCD remodels the plasma membrane’s mechanics and its interactions with the underlying cytoskeleton. Decoupling the two effects and studying various alterations to the membrane’s mechanical parameters is important for understanding cholesterol’s role in cellular response to stress. By mapping membrane height fluctuations in single cells, we report that MβCD treatment reduces temporal fluctuations and flattens out the membrane – but does not supress activity-driven fluctuations. We find that membrane tension increase contributes most to the altered fluctuations, among the multiple mechanical parameters computed. Maps also reveal an enhanced long-range heterogeneity within single cells, both in amplitude of fluctuations and membrane tension on cholesterol depletion. To check if this alters the tenacity of membrane to mechanical stress we use hypo-osmotic shock. We find that on MβCD treatment, cells are more prone to rupture than control cells, and this is not hindered by actomyosin perturbations. We report increased rupture sizes on cholesterol depletion and argue that, together, this indicates decreased lysis and line tension. Therefore, we show that cholesterol depletion directly affects cell membranes not only by enhancing membrane-cytoskeleton interactions, but also by increasing membrane tension while reducing lysis tension – hence making cells prone to rupture.
Tunable molecular tension sensors reveal extension-based control of vinculin loading
Authors: LaCroix Andrew S. , Lynch Andrew D. , Berginski Matthew E. , Hoffman Brenton D.
Published: February 2018

Molecular tension sensors have contributed to a growing understanding of mechanobiology. However, the limited dynamic range and inability to specify the mechanical sensitivity of these sensors has hindered their widespread use in diverse contexts. Here, we systematically examine the components of tension sensors that can be altered to improve their functionality. Guided by the development of a first principles model describing the mechanical behavior of these sensors, we create a collection of sensors that exhibit predictable sensitivities and significantly improved performancein cellulo.Utilized in the context of vinculin mechanobiology, a trio of these new biosensors with distinct force- and extension- sensitivities reveal that an extension-based control paradigm regulates vinculin loading. To enable the rational design of molecular tension sensors appropriate for diverse applications, we predict the mechanical behavior, in terms of force and extension, of additional 1020 distinct designs.
Demystifying continuous participation in game applications at social networking sites
Authors: Wu Yi , Cui Tingru , Liu Na , Deng Yimeng , Guo Junpeng
Published: February 2018

Purpose

Drawn from the social playfulness literature and the elaboration likelihood model, the purpose of this paper is to propose and test a research model to examine users’ continuous participation in SNS game applications.

Design/methodology/approach

A field survey with 133 subjects was conducted to test the research model.

Findings

Two identified design features, symbolic physicality and inherent sociability, are found to influence users’ perceived curiosity and perceived enjoyment toward playing SNS game applications. Perceived enjoyment is significantly associated with perceived curiosity and predicts users’ continuous participation of SNS game applications. The authors also observed a gender difference of social playfulness design on perceived curiosity.

Research limitations/implications

Use intention was used as a proxy for actual use behavior, since objective data on continuance behavior was not available. Additionally, the contributions of this study may be constrained by one single sample.

Practical implications

The findings of the study suggest practical guidelines for designing game applications in SNS through socialization design and symbolic physicality. Further, based on the findings of gender differences, a personalization game design strategy is provided.

Originality/value

The study contributes to the post-adoption IS literature and sheds light on the interesting area of social media participation. Additionally, this study enriches the online gaming research by demonstrating gender differences.
The role of a knowledge leader in a changing organizational environment. A conceptual framework drawn by an analysis of four large companies
Authors: Bertoldi Bernardo , Giachino Chiara , Rossotto Camillo , Bitbol-Saba Nathalie
Published: February 2018

Purpose

The purpose of this paper is to investigate the role of knowledge leader readiness within large companies operating in a changing environment.

Design/methodology/approach

A conceptual framework emerged from an analysis of four large companies and a review of the knowledge management literature. Secondary research was conducted to compare the four large companies against the proposed framework.

Findings

The conceptual model is a support to understand an organizations’ reaction to external changes and the role of the knowledge leader’s readiness in managing these changes and adjusting the knowledge management accordingly. From the analysis, it emerged that a knowledge leader’s readiness plays a relevant role in a changing organizational environment owing to his ability to acquire, handle and diffuse knowledge within the company.

Practical implications

The study emphasizes the significance of internal knowledge in managing changes. Practitioners could use this framework as a conceptual guide for their daily challenges and to recruit future leaders.

Originality/value

This study aims to contribute to the knowledge management literature by providing a practical model for organizations facing a changing environment. The originality of the model is the design of different managerial profiles that combine the leaders’ disposition to knowledge and their ability to drive change.
Foraging responses of sheep to plant spatial micro‐patterns can cause diverse associational effects of focal plant at individual and population levels
Authors: Huang Yue , Wang Ling , Wang Deli , Zeng De‐Hui , Li Yexing , Liu Jun , Wang Yue
Published: February 2018

Multiple‐scale foraging decisions by large herbivores can cause associational effects of focal plant individuals neighboured with different species. Spatial micro‐patterns between the focal plant and its neighbouring species within patches can affect herbivore foraging selectivity at within‐ and between‐patch scales, which may consequently lead to associational plant effects occurring at both plant individual and population levels. However, these associational effects have not been explored together in the plant–herbivore interaction studies.

We aim to evaluate how plant spatial micro‐pattern within different quality patches mediate herbivore foraging selectivity, thereby affecting the associational effects of focal plant individuals and population.

Using sheep as the model herbivore and a medium preferred species as the focal plant, we conducted a manipulative experiment by allowing sheep grazing freely among three different quality patches, each of which consisted of preferred, unpreferred and focal plant species with different abundances forming spatially aggregated or dispersed micro‐patterns.

Results showed that, compared with the aggregated plant micro‐pattern, dispersed plant micro‐patterns within different quality patches increased sheep within‐patch selectivity, and caused diverse associational effects of focal plant individuals. Focal plant individuals experienced neighbour contrast defence (i.e. got protection in the high quality patch) and associational defence (i.e. got protection in the low quality patch), respectively, when plants distributed dispersedly in the low and high quality patch. Focal plant individuals simultaneously experienced associational susceptibility (i.e. got damage in the high quality patch) and neighbour contrast susceptibility (i.e. got damage in the low quality patch) when plants distributed dispersedly in the medium quality patch. Furthermore, dispersed plant micro‐patterns reduced sheep foraging selectivity between patches, and led to a lower consumption of focal plant population compared with the aggregated plant micro‐pattern.

Herbivores adopt different within‐ and between‐patch foraging decisions to maintain a high intake of the preferred species in response to various plant micro‐patterns, and consequently cause diverse associational effects of both focal plant individuals and population. These associational effects have important implications for understanding the species coexistence and plant community assembly in the grazing ecosystems.
TNF‐α level affects etanercept clearance: TNF‐α concentration as a new correction factor of allometric scaling to predict individual etanercept clearances in patients with ankylosing spondylitis
Authors: Deng Yuwei , Hu Li , Qiang Wei , Cheng Zeneng , Wang Lei , Wang Xiaoxia
Published: February 2018

Etanercept (ETN) is a widely used anti‐tumour necrosis factor‐α (TNF‐α) agent, which relieves the symptoms of ankylosing spondylitis (AS) by binding to TNF‐α to inhibit its inflammation effects. In this study, the effect of TNF‐α level on ETN clearance (CL) was investigated, and the TNF‐α concentration was initially set as a correction factor for allometric scaling to improve the predictions of individual ETN CLs. Individual ETN CLs and TNF‐α concentrations in healthy volunteers and patients with AS were determined by performing ETN pharmacokinetic studies in the two cohorts. Accordingly, individual ETN CLs in both healthy volunteers and patients with AS were predicted from data of two animal species using different methods, including simple allometric scaling, scaling with a correction factor of maximum life span potential or brain weight, and scaling with a correction factor of the TNF‐α concentration. The accuracies of such predictions were evaluated by the percentage errors. Consequently, increased TNF‐α concentration was shown to improve ETN CL, by comparing both ETN CLs and TNF‐α concentrations between healthy volunteers and patients with AS. More importantly, better predictions of individual ETN CLs were achieved in patients with AS using allometric scaling with TNF‐α concentration as the correction factor. In conclusion, in vivo levels of TNF‐α can affect ETN CL, and allometric scaling corrected with the TNF‐α concentration can be used to estimate the individual CLs of anti‐TNF‐α monoclonal antibodies based on preclinical data.
Social learning in nest‐building birds watching live‐streaming video demonstrators
Authors: GUILLETTE Lauren M. , HEALY Susan D.
Published: February 2018

Determining the role that social learning plays in construction behaviors, such as nest building or tool manufacture, could be improved if more experimental control could be gained over the exact public information that is provided by the demonstrator, to the observing individual. Using video playback allows the experimenter to choose what information is provided but will only be useful in determining the role of social learning if observers attend to, and learn from, videos in a manner that is similar to live demonstration. The goal of the current experiment was to test whether live‐streamed video presentations of nest building by zebra finches Taeniopygia guttata would lead observers to copy the material choice demonstrated to them. Here, males that had not previously built a nest were given an initial preference test between materials of 2 colors. Those observers then watched live‐stream footage of a familiar demonstrator building a nest with material of the color that the observer did not prefer. After this experience, observers were given the chance to build a nest with materials of the 2 colors. Although two‐thirds of the observer males preferred material of the demonstrated color after viewing the demonstrator build a nest with material of that color more than they had previously, their preference for the demonstrated material was not as strong as that of observers that had viewed live demonstrator builders in a previous experiment. Our results suggest researchers should proceed with caution before using video demonstration in tests of social learning.
HPV‐testing versus HPV‐cytology co‐testing to predict the outcome after conization
Authors: Bruhn Lærke Valsøe , Andersen Sisse Josephine , Hariri Jalil
Published: February 2018

Introduction

The purpose of this study was to determine the feasibility of human Papillomavirus (HPV) testing alone as a prognostic tool to predict recurrent disease within a three‐year follow‐up period after treatment for cervical intraepithelial neoplasia (CIN)2+.

Material and methods

Retrospectively, 128 women with histologically verified CIN2+ who had a conization performed at Southern Jutland Hospital in Denmark between 1 January 2013 and 31 December 2013 were included. Histology, cytology and HPV test results were obtained for a three‐year follow‐up period.

Results

4.7% (6/128) of the cases developed recurrent disease during follow‐up. Of the cases without free margins, recurrent dysplasia was detected normal in 10.4% (5/48), whereas in the group with free margins it was 1.3% (1/80). The post‐conization HPV test was negative in 67.2% (86/128) and Pap smear normal in 93.7% (120/128). Combining resection margins, cytology and HPV had sensitivity for prediction of recurrent dysplasia of 100%. Specificity was 45.8%, positive predictive value (PPV) 8.5% and negative predictive value (NPV) 100%. Using HPV test alone as a predictor of recurrent dysplasia gave a sensitivity of 83.3%, specificity 69.7%, PPV 11.9% and NPV 98.8%. Combining resection margin and HPV test had a sensitivity of 100%, specificity 45.9%, PPV 8.3% and NPV 100%.

Conclusion

HPV test at six months control post‐conization gave an NPV of 98.8% and can be used as a solitary test to identify women at risk for recurrent disease three years after treatment for precursor lesions. Using both resection margin and HPV test had a sensitivity of 100% and NPV 100%. Adding cytology did not increase the predictive value.
Comparison of self‐reported and directly measured weight and height among women of reproductive age: a systematic review and meta‐analysis
Authors: Seijo Mariana , Minckas Nicole , Cormick Gabriela , Comandé Daniel , Ciapponi Agustín , BelizÁn José M.
Published: February 2018

Introduction

The use of self‐report as a strategy for collecting data on women's weight and height is widespread in both clinical practice and epidemiological studies. This study aimed to compare self‐reported and directly measured weight and height among women of reproductive age.

Material and methods

In July 2015 we searched MEDLINE, EMBASE, COCHRANE, CINHAL, LILACS and gray literature. We included women of reproductive age (12–49 years old) independently of their weight or height at the time of the study. Women with any condition that implies regular tracking of their weight (for example, eating disorder) were excluded. Two reviewers independently selected, extracted and assessed the risk of bias of the studies. We used REVMAN 5.3 to perform the meta‐analysis. Heterogeneity was assessed using the I2 statistic.

Results

Following eligibility assessment, 21 studies of 18 749 women met the inclusion criteria. The results of the meta‐analysis showed an underestimation of weight by −0.94 kg (95% CI −1.17 to −0.71 kg; p < 0.0001; I2 = 0%) in the overall sample and an overestimation of height by 0.36 cm (95% CI 0.20–0.51; p < 0.0001; I2 = 35%) based on self‐reported vs. directly measured values.

Conclusion

This review shows that self‐reported weight and height of women of reproductive age differs slightly from direct measures. We consider that the magnitude at which self‐reported data over‐ or underestimates the real value, is negligible regarding clinical and research use.
Feasibility and Safety of a Cemented PEEK‐on‐PE Knee Replacement in a Goat Model: A Preliminary Study
Authors: Du Zhe , Zhu Zhonglin , Yue Bing , Li Zhanchun , Wang You
Published: February 2018

Polyether‐ether‐ketone (PEEK) is a potential alternative to metal alloys for use in the orthopedic implants; however, an in vivo study in an appropriate animal model is essential and has not yet been initiated. The aim of the present study was to gather some preliminary evidence regarding the performance and safety of a cemented PEEK‐based knee replacement device in a goat model. Fifteen adult goats were randomly divided into two groups; the control group (n = 5), which received a sham operation, and the experimental group (n = 10), which received a total knee arthroplasty with a PEEK‐based knee replacement device. The animals were sacrificed at 12 (control n = 5; experimental n = 5) or 24 weeks (experimental n = 5). Blood parameter measurements and radiographs of the knee joints were obtained. The synovium and main organs were removed and histologically assessed. The knee joints with the prosthesis were analyzed via micro‐computed tomography and laser confocal microscopy. There was no occurrence of implant fracture or prosthesis sinking during the 24 weeks of radiological observations, except for one case of prosthesis dislocation at 4 weeks. There was a 6% decrease in femoral bone density (BD) at 12 weeks, but no further decrease by 24 weeks. No changes in BD were observed in the tibial ends. The bulk implant was biocompatible in terms of histological analysis of the local synovium and organs. There were no optical scratches on the surface of the retrieved components; the femoral component surface was rougher, while the tibial insert was smoother after 24 weeks. The novel PEEK‐based knee replacement device in a goat model was feasible and safe; however, prior to use in humans, further studies concerning PEEK high load‐bearing implant designs should be carried out to expand on our results.
Variable Contribution of TMEM16A to Tone in Murine Arterial Vasculature
Authors: Jensen Anders Bisgaard , Joergensen Henrik Black , Dam Vibeke Secher , Kamaev Dmitrii , Boedtkjer Donna , Füchtbauer Ernst‐Martin , Aalkjaer Christian , Matchkov Vladimir V.
Published: February 2018

TMEM16A is essential for Ca2+‐activated Cl− conductance in vascular smooth muscle. The importance of TMEM16A for agonist‐induced vascular constriction and blood pressure control is, however, under debate. Previous studies suggested that TMEM16A might have a complex cellular function beyond being essential for the Ca2+‐activated Cl− conductance, for example modulation of Ca2+ channel expression. Mice with constitutive, smooth muscle‐specific expression of siRNA directed against Tmem16a (transgenic mice, TG) were generated. Isometric constrictions of isolated aorta, mesenteric, femoral and tail arteries from TG mice were compared with wild‐types. Protein expression was analysed by Western blots. Blood pressure and heart rate were studied telemetrically. Significant TMEM16A down‐regulation was seen in aorta and tail arteries, while no changes were detected in mesenteric and femoral arteries. Contractile responses of mesenteric and femoral arteries from TG and wild‐type mice were not different. Aorta from TG mice showed reduced agonist‐induced constriction, while their responses to elevated K+ were unchanged. Tail arteries from TG mice also constricted less to adrenergic stimulation than wild‐types. Surprisingly, tail arteries from TG mice constricted less to elevated K+ too and were more sensitive to nifedipine‐induced relaxation. Consistently, TMEM16A down‐regulation in tail arteries was associated with reduction in CACNA1C protein (i.e. vascular L‐type Ca2+ channel) expression. No differences in blood pressure and heart rate between the groups were seen. This study suggests a complex contribution of TMEM16A in vascular function. We suggest that TMEM16A modulates arterial contractility, at least in part, indirectly via regulation of CACNA1C expression.
Reversal of Hartmann's procedure: a single‐centre experience of 533 consecutive cases
Authors: Royo‐Aznar A. , Moro‐Valdezate D. , Martín‐Arévalo J. , Pla‐Martí V. , García‐Botello S. , Espín‐Basany E. , Espí‐Macías A.
Published: February 2018

Aim

Hartmann's procedure (HP) is common. However, restoration of intestinal continuity is not so frequent. The aim of this study was to determine predictive factors which might influence outcomes following the reversal of HP.

Method

All consecutive patients who underwent elective and emergency HP in a single institution between January 1999 and December 2014 were included. Data concerning patient, disease and treatment features were collected. Univariate and multivariate binary logistic regression models were used to determine prognostic factors.

Results

A total of 533 consecutive patients underwent HP over the 16‐year period. Factors that were associated with a higher probability of reversal were age (< 69 years), American Society of Anesthesiologists (ASA) grade (I or II), indication for HP (likelihood of anastomotic leakage) and length of rectal stump reaching or exceeding the sacral promontory. A reduced probability of intestinal reconstruction was associated with anal incontinence, Stage IV cancer, postoperative transfusion or elective surgery.

Conclusion

Age, ASA grade, the indication for HP, the length of rectal stump, anal incontinence, tumour stage, postoperative transfusion and elective surgery determine the probability of reversal.
Efficacy and safety of trans‐bronchial cryo in comparison with forceps biopsy in lung allograft recipients: Analysis of 402 procedures
Authors: Gershman Evgeni , Ridman Elena , Fridel Ludmila , Shtraichman Osnat , Pertzov Barak , Rosengarten Dror , Rahman Nader Abdel , Shitenberg Dorit , Kramer Mordechai R.
Published: February 2018

Background

Trans‐bronchial forceps biopsy (TBFB) is the gold standard to establish the presence of allograft rejection or infection after lung transplantation. We aimed to analyze the diagnostic yield and safety of trans‐bronchial cryobiopsy (TBCB) in lung allografts.

Methods

Retrospective analysis of 402 TBB procedures in 362 lung recipients was performed between 2011 and 2016. Half of the cases (201) were performed by TBCB and the other half by TBFB. One hundred random slides of TBB specimens from lung allografts were reviewed for artifacts, bleeding, and histological evidence.

Results

Both TBB groups were comparable in age, gender distribution, and time following transplantation. Acute rejection was diagnosed in 21.9% of the TBCB group vs 14.9% in the TBFB group (P = .09) and only 2 cases (1%) of nondiagnostic tissue in TBCB group and 4 cases (2%) in TBFB group (P = .685). Complications of pneumothorax and bleeding occurred in 9 (4.5%) vs 8 (4%) and 5 (2.5%) vs 4 (2%) in TBCB vs TBFB groups, respectively. The TBCB specimens were larger than TBFB (average 16.6 vs 6.6 mm2; P < .001). Crush and bleeding artifacts were seen in 11 (22%) and 23 (46%) of TBFB, respectively, yet none in TBCB group (P < .001).

Conclusion

Trans‐bronchial cryobiopsy is safe and effective for diagnosis of lung allograft rejection.
Dobutamine stress echocardiography, myocardial perfusion scintigraphy, invasive coronary angiography, and post‐liver transplantation events: Systematic review and meta‐analysis
Authors: Soldera Jonathan , Camazzola Fábio , Rodríguez Santiago , Brandão Ajacio
Published: February 2018

The impact of coronary artery disease on the clinical course of patients enrolled for liver transplantation (LT) has changed over the years as these patients become older and sicker. The purpose of this systematic review and meta‐analysis was to investigate the value of dobutamine stress echocardiography (DSE), myocardial perfusion scintigraphy (MPS), and invasive coronary angiography (ICA) in predicting cardiac events post‐LT in cirrhotic patients. A literature search was conducted using Scopus, Web of Science, EMBASE, MEDLINE (via PubMed), BIREME (regional medical library of the Pan American Health Organization), LILACS (Latin American and Caribbean Health Sciences Literature), Cochrane Library for Systematic Reviews, and OpenGrey Repository (www.opengrey.eu) electronic databases. A total of 322 records were retrieved for DSE, 90 for MPS, and 149 for ICA. In the final analysis, 11 records for DSE, 7 for MPS, and 8 for ICA were included. The relative risk and confidence interval for major adverse cardiac events were 30.2 (2.8‐325.4) for DSE, 2.6 (1.09‐6.1) for MPS, and 2.1 (1.0‐2.3) for ICA, while the relative risk and confidence interval for all‐cause mortality was 4.7 for DSE (1.8‐12.0), 2.7 (1.25‐5.9) for MPS, and 1.5 (0.89‐3.2) for ICA. In conclusion, this meta‐analysis found that DSE, MPS, and ICA do not satisfactorily predict increased risk of perioperative MACE or all‐cause mortality among cirrhotic patients listed for LT, among small and heterogenous studies.
Molecular testing practices and perceptions among dermatopathologists
Authors: Torre Kristin , Jhorar Preeti , Wu Rong , Pfeifer John , Elaba Zendee , Murphy Michael
Published: February 2018

Background

We evaluated how dermatopathologists are employing molecular testing in the setting of neoplastic skin diseases, and assessed their opinions of the broader role and utility of molecular technologies in clinical practice.

Methods

A 15‐question online survey was sent to Fellows of the American Society of Dermatopathology in April 2017.

Results

One hundred and thirty‐six dermatopathologists completed the survey (response rate = 16%). A majority (94%) of respondents reported experience with one or more molecular testing strategies. Sixty‐two percent of dermatopathologists order 12 or more molecular tests per year, while 5% of respondents order 2 or fewer assays per year. More frequent utilization of molecular testing is associated with relevant instruction during residency training (P = .009), primary board certification in pathology (P = .008), academic medical center affiliation (P = <.0001), higher volume clinical practice (P = .0004), presence of on‐site clinical molecular pathology/cytogenetics laboratory (P = .007), and greater physician confidence incorporating test results into histopathological assessments (P = <.0001).

Conclusions

Wider adoption of molecular testing in dermatopathology may be limited by factors such as physician training, test costs/insurance coverage, logistical issues and lack of evidence‐based clinical practice guidelines. Dermatopathologists have concerns regarding clinical validity/utility and inappropriate/overuse of some molecular tests. The importance of longitudinal education in molecular technologies and their applications for trainee and practicing physicians is highlighted.
Use of non‐vitamin K oral anticoagulants in people with atrial fibrillation and diabetes mellitus
Authors: Itzhaki Ben Zadok O. , Eisen A.
Published: February 2018

Aims

To examine the efficacy and safety of non‐vitamin K oral anticoagulants in people with both atrial fibrillation and diabetes mellitus.

Methods

We reviewed efficacy and safety data from the warfarin‐controlled phaseIIInon‐vitamin K oral anticoagulants trials (ARISTOTLE,RE‐LY,ROCKET‐AF,ENGAGE AF‐TIMI48) and theirpost hocanalyses with regard to diabetes status. We also reviewed the updated literature regarding this population.

Results

At baseline 20–40% of the participants in the phaseIIInon‐vitamin K oral anticoagulants trials had diabetes mellitus at baseline. This population, in comparison with those without diabetes, was more likely to have other comorbidities, such as hypertension and coronary artery disease; thus, their cardiovascular risk was higher. Participants with diabetes had higher rates of stroke and systemic embolism than participants without diabetes. This risk was decreased using non‐vitamin K oral anticoagulants, with no significant interaction by diabetic status or the specific drug used. Overall, compared with warfarin, non‐vitamin K oral anticoagulants were safe and reduced the incidence of major bleeding in people with atrial fibrillation and diabetes, although the results varied with the different non‐vitamin K oral anticoagulants.

Conclusions

The efficacy and safety of non‐vitamin K oral anticoagulants compared with warfarin generally extend to participants with diabetes mellitus, although dedicated randomized trials or real‐world data are lacking.
Concomitant lipomatous hypertrophy and left atrial mass: Distinguishing benign from malignant
Authors: Kleiman Amanda M. , Harding Lindsay M. , Bechtel Allison J.
Published: February 2018

Masses in and near the interatrial septum may be either benign or malignant. The most common mass near the interatrial septum is lipomatous atrial septal hypertrophy (LASH). LASH can be present in patients with intracardiac malignancies, myxomas, lipomas, or other cardiac masses. It is important to recognize the transesophageal echocardiography (TEE) characteristics of these pathologies to arrive at an accurate diagnosis with an appropriate plan for intraoperative resection. At the authors’ institution, patients have been referred for surgery due to a finding of significant LASH masquerading as a left atrial myxoma. In challenging cases, TEE offers a thorough evaluation of the interatrial septum to delineate between multiple intracardiac masses.
Neonatal adoptive transfer of lymphocytes rescues social behaviour during adolescence in immune‐deficient mice
Authors: Clark Sarah M. , Vaughn Chloe N. , Soroka Jennifer A. , Li Xin , Tonelli Leonardo H.
Published: February 2018

Accumulating evidence has shown that lymphocytes modulate behaviour and cognition by direct interactions with the central nervous system. Studies have shown that reconstitution by adoptive transfer of lymphocytes from wild type into immune‐deficient mice restores a number of neurobehavioural deficits observed in these models. Moreover, it has been shown that these effects are mostly mediated by T lymphocytes. Studies of adoptive transfer thus far have employed adult mice, but whether lymphocytes may also modulate behaviour during development remains unknown. In this study, neonate lymphocyte‐deficient Rag2−/− mice were reconstituted within 48 hours after birth with lymphoid cells from transgenic donors expressing green fluorescent protein, allowing for their identification in various tissues in recipient mice while retaining all functional aspects. Adolescent Rag2−/− and reconstituted Rag2−/− along with C57BL/6J wild‐type mice underwent a series of behavioural tests, including open field, social interaction and sucrose preference tests. At 12 weeks, they were evaluated in the Morris water maze (MWM). Reconstituted mice showed changes in almost all aspects of behaviour that were assessed, with a remarkable complete rescue of impaired social behaviour displayed by adolescent Rag2−/− mice. Consistent with previous reports in adult mice, neonatal reconstitution in Rag2−/− mice restored spatial memory in the MWM. The presence of donor lymphocytes in the brain of neonatally reconstituted Rag2−/− mice was confirmed at various developmental points. These findings provide evidence that lymphocytes colonize the brain during post‐natal development and modulate behaviour across the lifespan supporting a role for adaptive immunity during brain maturation.
Reduced low‐frequency power and phase locking reflect restoration in the auditory continuity illusion
Authors: Kaiser Mathis , Senkowski Daniel , Roa Romero Yadira , Riecke Lars , Keil Julian
Published: February 2018

Interruptions in auditory input can be perceptually restored if they coincide with a masking sound, resulting in a continuity illusion. Previous studies have shown that this continuity illusion is associated with reduced low‐frequency neural oscillations in the auditory cortex. However, the precise contribution of oscillatory amplitude changes and phase alignment to auditory restoration remains unclear. Using electroencephalography, we investigated induced power changes and phase locking in response to 3 Hz amplitude‐modulated tones during the interval of an interrupting noise. We experimentally manipulated both the physical continuity of the tone (continuous vs. interrupted) and the masking potential of the noise (notched vs. full). We observed an attenuation of 3 Hz power during continuity illusions in comparison with both continuous tones and veridically perceived interrupted tones. This illusion‐related suppression of low‐frequency oscillations likely reflects a blurring of auditory object boundaries that supports continuity perception. We further observed increased 3 Hz phase locking during fully masked continuous tones compared with the other conditions. This low‐frequency phase alignment may reflect the neural registration of the interrupting noise as a newly appearing object, whereas during continuity illusions, a spectral portion of this noise is delegated to filling the interruption. Taken together, our findings suggest that the suppression of slow cortical oscillations in both the power and phase domains supports perceptual restoration of interruptions in auditory input.
Sestrin2 facilitates glutamine‐dependent transcription of PGC‐1α and survival of liver cancer cells under glucose limitation
Authors: Kumar Ashish , Giri Sagnik , Shaha Chandrima
Published: February 2018

Differential utilization of metabolites and metabolic plasticity can confer adaptation to cancer cells under metabolic stress. Glutamine is one of the vital and versatile nutrients that cancer cells consume avidly for their proliferation, and therefore mechanisms related to glutamine metabolism have been identified as targets. Recently, sestrin2 (SESN2), a stress‐inducible protein, has been reported to regulate survival in glutamine‐depleted cancer cells; based on this, we explored if SESN2 could regulate glutamine metabolism during glucose starvation. This report highlights the role of SESN2 in the regulation of glutamine‐dependent activation of the mitochondrial biogenesis marker peroxisome proliferator‐activated receptor γ coactivator 1α (PGC‐1α) under glucose scarcity in liver cancer cells (HepG2). We demonstrate that down‐regulation of SESN2 induces a decrease in the levels of intracellular glutamine and PGC‐1α under glucose deprivation, concomitant with a decline in cell survival, but no effect was observed on the invasive or migration potential of the cells. Under similar metabolic conditions, SESN2 forms a complex with c‐Jun N‐terminal kinase (JNK) and forkhead box protein O1 (FOXO1). Absence of SESN2 or inhibition of JNK reduces nuclear translocation of FOXO1, consequently causing transcriptional inhibition of PGC‐1α. Notably, our observations demonstrate a reduction in cell viability under high glutamine and low glucose conditions during SESN2 down‐regulation that could be rescued on JNK inhibition. To recover from acetaminophen‐induced mitochondrial damage, SESN2 was crucial for glutamine‐mediated activation of PGC‐1α in HepG2 cells. Collectively, we demonstrate a novel role of SESN2 in mediating activation of PGC‐1α by modulating glutamine metabolism that facilitates cancer cell survival under glucose‐limited metabolic conditions.
The world language teacher shortage: Taking a new direction
Authors: Swanson Pete , Mason Shannon
Published: February 2018

Since the end of World War II, international leaders have made calls addressing the world language teacher shortage. For almost 70 years, such rhetoric has been advanced, yet world language teacher shortages remain in many countries such as Australia, Canada, Ireland, New Zealand, the United Kingdom, and the United States. In this article, the authors discuss the past and current state of affairs of the shortage before advancing ideas for language teacher recruitment and retention to which a variety of stakeholders (e.g., parents, administrators, language teacher associations) can contribute immediately in order to address the world language teacher shortage in earnest.
P2O5‐Fe2O3‐CaO‐SiO2 ferromagnetic glass‐ceramics for hyperthermia
Authors: Ji PengTian , Wang YongYa , Zhang MoRan , Li Bin , Zhang GuiXiang
Published: February 2018

Ferromagnetic glass‐ceramics are an important kind of thermoseed material for hyperthermia treatments. In order to investigate the applications of glass‐ceramics in magnetic hyperthermia, P2O5‐Fe2O3‐CaO‐SiO2 (PFCS) glass‐ceramics with different compositions were prepared by the sol‐gel method. The crystal phase, magnetic properties, induction heating ability, and cytotoxicity of the as‐prepared glass‐ceramics were investigated. The results show that all the samples exhibit low cytotoxicity and good induction heating ability. Moreover, it was found that the phosphorus content affected the crystal phase component of the sample, and thus influenced the induction heating ability. Results of the magnetic hyperthermia experiments showed that the PFCS glass‐ceramic samples induced significant cell death of the LoVo cancer cells. The highest cell death rate for sample B2P7 was more than 95%, which suggests good application prospects in the field of hyperthermia therapy.
Calcicolous plants colonize limed mires after long‐distance dispersal
Authors: Lönnell Niklas , Hylander Kristoffer
Published: February 2018

Aim

Dispersal range is a key factor for understanding species' persistence in dynamic landscapes. However, dispersal, especially over long distances, is inherently difficult to study. Making use of a unique system of anthropogenically disturbed, geographically isolated mires, we assessed dispersal ranges for a group of plants restricted to wet calcareous conditions via empirical studies of colonization patterns. We hypothesized that more species would have colonized the less isolated mires and that colonization frequencies would be related to traits influencing propagule pressure.

Location

Sweden.

Taxon

Calcicolous vascular plants and bryophytes.

Methods

The study system consisted of 52 acidic mires that had acquired a high pH through active liming by the Swedish government during the past two decades. These conditions killed off mat‐forming peat mosses, rendering the mires open to colonization by other species. In each mire, we recorded the presence of rich fen plant species typically found in high pH wet soils throughout the country. We used citizen science‐collected records of occurrences of obligate‐rich fen species surrounding each mire to examine the likely dispersal distances that were involved in creating the colonization patterns.

Results

A lower proportion of vascular plants than bryophytes from their respective species pools colonized the limed mires (27% vs. 67%, p = .001). The number of colonized rich fen species per site was 0–6 for vascular plants and 10–31 for bryophytes, and was positively related to potential diaspore sources >20 km from the mires (p = .026 and p = .012, respectively). The proportion of colonized mires was positively related to the species' regional frequency, but not with their diaspores' terminal velocity.

Main conclusions

Many bryophyte species can effectively disperse over long distances (tens of kilometres) and variation among species in total diaspore production seems to be an important regulator of colonization across landscapes, for both vascular plants and bryophytes, in communities that are open to colonization.
Difference in normal limit values of nerve conduction parameters between Westerners and Japanese people might need to be considered when diagnosing diabetic polyneuropathy using a Point‐of‐Care Sural Nerve Conduction Device (NC‐stat®/DPNCheck™)
Authors: Hirayasu Kazuhiro , Sasaki Hideyuki , Kishimoto Shohei , Kurisu Seigo , Noda Koji , Ogawa Kenichi , Tanaka Hiroto , Sakakibara Yumiko , Matsuno Shohei , Furuta Hiroto , Arita Mikio , Naka Keigo , Nanjo Kishio
Published: February 2018

Aim/Introduction

Studies on a novel point‐of‐care device for nerve conduction study called DPNCheck have been limited to Westerners. We aimed to clarify Japanese normal limits of nerve action potential amplitude (Amp) and conduction velocity by DPNCheck (investigation I), and the validity of DPNCheck to identify diabetic symmetric sensorimotor polyneuropathy (DSPN; investigation II).

Materials and Methods

For investigation I, 463 non‐neuropathic Japanese participants underwent DPNCheck examinations. Regression formulas calculating the normal limits of Amp and conduction velocity (Japanese regression formulas [JRF]) were determined by quantile regression and then compared with regression formulas of individuals from the USA (USRF). For investigation II, in 92 Japanese diabetes patients, ‘probable DSPN’ was diagnosed and nerve conduction abnormalities (NCA1: one or more abnormalities, and NCA2: two abnormalities in Amp and conduction velocity) were determined. Validity of NCAs to identify ‘probable DSPN’ was evaluated by determining sensitivity, specificity, reproducibility (kappa‐coefficient) and the area under the curve of receiver operating characteristic curves.

Results

For investigation I, JRF was different from USRF, and normal limits by JRF were higher than that of USRF. The prevalence of Amp abnormality calculated by JRF was significantly higher than that of USRF. For investigation II, the sensitivity, specificity and reproducibility of NCA1 and NCA2 judged from JRF were 85%, 86% and 0.57, and 43%, 100% and 0.56, respectively. These values of JRF were higher than those of USRF. The area under the curve of JRF (0.89) was larger than USRF (0.82).

Conclusions

A significant difference in the normal limits of nerve conduction parameters by DPNCheck between Japanese and USA individuals was suggested. Validity to identify DSPN of NCAs might improve by changing the judgment criteria from USRF to JRF.
Transportability of non‐target arthropod field data for the use in environmental risk assessment of genetically modified maize in Northern Mexico
Authors: Corrales Madrid J. L. , Martínez Carrillo J. L. , Osuna Martínez M. B. , Durán Pompa H. A. , Alonso Escobedo J. , Javier Quiñones F. , Garzón Tiznado J. A. , Castro Espinoza L. , Zavala García F. , Espinoza Banda A. , González García J. , Jiang C. , Brown C. R. , de la F. Martínez J. M. , Heredia Díaz O. , Whitsel J. E. , Asiimwe P. , Baltazar B. M. , Ahmad A.
Published: February 2018

In country, non‐target arthropod (NTA) field evaluations are required to comply with the regulatory process for cultivation of genetically modified (GM) maize in Mexico. Two sets of field trials, Experimental Phase and Pilot Phase, were conducted to identify any potential harm of insect‐protected and glyphosate‐tolerant maize (MON‐89Ø34‐3 × MON‐88Ø17‐3 and MON‐89Ø34‐3 × MON‐ØØ6Ø3‐6) and glyphosate‐tolerant maize (MON‐ØØ6Ø3‐6) to local NTAs compared to conventional maize. NTA abundance data were collected at 32 sites, providing high geographic and environmental diversity within maize production areas from four ecological regions (ecoregions) in northern Mexico. The most abundant herbivorous taxa collected included field crickets, corn flea beetles, rootworm beetles, cornsilk flies, aphids, leafhoppers, plant bugs and thrips while the most abundant beneficial taxa captured were soil mites, spiders, predatory ground beetles, rove beetles, springtails (Collembola), predatory earwigs, ladybird beetles, syrphid flies, tachinid flies, minute pirate bugs, parasitic wasps and lacewings. Across the taxa analysed, no statistically significant differences in abundance were detected between GM maize and the conventional maize control for 69 of the 74 comparisons (93.2%) indicating that the single or stacked insect‐protected and herbicide‐tolerant GM traits generally exert no marked adverse effects on the arthropod populations compared with conventional maize. The distribution of taxa observed in this study provides evidence that irrespective of variations in overall biodiversity of a given ecoregion, important herbivore, predatory and parasitic arthropod taxa within the commercial maize agroecosystem are highly similar indicating that relevant data generated in one ecoregion can be transportable for the risk assessment of the same or similar GM crop in another ecoregion.
Melatonin‐mediated inhibition of Cav3.2 T‐type Ca2+ channels induces sensory neuronal hypoexcitability through the novel protein kinase C‐eta isoform
Authors: Zhang Yuan , Ji Heyi , Wang Jiangong , Sun Yufang , Qian Zhiyuan , Jiang Xinghong , Snutch Terrance P. , Sun Yangang , Tao Jin
Published: February 2018

Recent studies implicate melatonin in the antinociceptive activity of sensory neurons. However, the underlying mechanisms are still largely unknown. Here, we identify a critical role of melatonin in functionally regulating Cav3.2 T‐type Ca2+ channels (T‐type channel) in trigeminal ganglion (TG) neurons. Melatonin inhibited T‐type channels in small TG neurons via the melatonin receptor 2 (MT2 receptor) and a pertussis toxin‐sensitive G‐protein pathway. Immunoprecipitation analyses revealed that the intracellular subunit of the MT2 receptor coprecipitated with Gαo. Both shRNA‐mediated knockdown of Gαo and intracellular application of QEHA peptide abolished the inhibitory effects of melatonin. Protein kinase C (PKC) antagonists abolished the melatonin‐induced T‐type channel response, whereas inhibition of conventional PKC isoforms elicited no effect. Furthermore, application of melatonin increased membrane abundance of PKC‐eta (PKCη) while antagonism of PKCη or shRNA targeting PKCη prevented the melatonin‐mediated effects. In a heterologous expression system, activation of MT2 receptor strongly inhibited Cav3.2 T‐type channel currents but had no effect on Cav3.1 and Cav3.3 current amplitudes. The selective Cav3.2 response was PKCη dependent and was accompanied by a negative shift in the steady‐state inactivation curve. Furthermore, melatonin decreased the action potential firing rate of small TG neurons and attenuated the mechanical hypersensitivity in a mouse model of complete Freund's adjuvant‐induced inflammatory pain. These actions were inhibited by T‐type channel blockade. Together, our results demonstrated that melatonin inhibits Cav3.2 T‐type channel activity through the MT2 receptor coupled to novel Gβγ‐mediated PKCη signaling, subsequently decreasing the membrane excitability of TG neurons and pain hypersensitivity in mice.