bluuebunny/crossref_metadata_2025 huggingface dataset:
Sildenafil reduces neuroinflammation in cerebellum, restores GABAergic tone, and improves motor in‐coordination in rats with hepatic encephalopathy
Authors: Agusti Ana , Hernández‐Rabaza Vicente , Balzano Tiziano , Taoro‐Gonzalez Lucas , Ibañez‐Grau Andrea , Cabrera‐Pastor Andrea , Fustero Santos , Llansola Marta , Montoliu Carmina , Felipo Vicente
Published: March 2017

Aims

Patients with liver disease may develop hepatic encephalopathy (HE), with cognitive impairment and motor in‐coordination. Rats with HE due to portacaval shunts (PCS) show motor in‐coordination. We hypothesized that in PCS rats: (i) Motor in‐coordination would be due to enhanced GABAergic tone in cerebellum; (ii) increased GABAergic tone would be due to neuroinflammation; (iii) increasing cGMP would reduce neuroinflammation and GABAergic tone and restore motor coordination. To assess these hypotheses, we assessed if (i) treatment with sildenafil reduces neuroinflammation; (ii) reduced neuroinflammation is associated with reduced GABAergic tone and restored motor coordination.

Methods

Rats were treated with sildenafil to increase cGMP. Microglia and astrocytes activation were analyzed by immunohistochemistry, extracellular GABA by microdialysis, and motor coordination in the beam walking.

Results

PCS rats show neuroinflammation in cerebellum, with microglia and astrocytes activation, increased IL‐1b and TNF‐a and reduced YM‐1 and IL‐4. Membrane expression of the GABA transporter GAT1 is reduced, while GAT3 is increased. Extracellular GABA and motor in‐coordination are increased. Sildenafil treatment eliminates neuroinflammation, microglia and astrocytes activation; changes in membrane expression of GABA transporters; and restores motor coordination.

Conclusions

This study supports an interplay between cGMP‐neuroinflammation and GABAergic neurotransmission in impairing motor coordination in PCS rats.
Lacosamide in status epilepticus: Systematic review of current evidence
Authors: Strzelczyk Adam , Zöllner Johann Philipp , Willems Laurent M. , Jost Julie , Paule Esther , Schubert‐Bast Susanne , Rosenow Felix , Bauer Sebastian
Published: March 2017

Objective

The intravenous formulation of lacosamide (LCM) and its good overall tolerability and safety favor the use in status epilepticus (SE). The aim of this systematic review was to identify and evaluate studies reporting on the use of LCM in SE.

Methods

We performed a systematic literature search of electronic databases using a combined search strategy from 2008 until October 2016. Using a standardized assessment form, information on the study design, methodologic framework, data sources, efficacy, and adverse events attributed to LCM were extracted from each publication and systematically reported.

Results

In total, 522 SE episodes (51.7% female) in 486 adults and 36 children and adolescents were evaluated with an overall LCM efficacy of 57%. Efficacy was comparable between use in nonconvulsive (57%; 82/145) and generalized‐convulsive (61%; 30/49; p = 0.68) SE, whereas overall success rate was better in focal motor SE (92%; 34/39, p = 0.013; p < 0.001). The efficacy with later positioning of LCM decreased from 100% to 20%. The main adverse events during treatment of SE are dizziness, abnormal vision, diplopia, and ataxia. Overall, lacosamide is well tolerated and has no clinically relevant drug–drug interactions.

Significance

The available data regarding the use of LCM in SE are promising, with a success rate of 57%. The strength of LCM is the lack of interaction potential and the option for intravenous use in emergency situations requiring rapid uptitration.
Neuronal inhibition and seizure suppression by acetoacetate and its analog, 2‐phenylbutyrate
Authors: Kadowaki Atsushi , Sada Nagisa , Juge Narinobu , Wakasa Ayaka , Moriyama Yoshinori , Inoue Tsuyoshi
Published: March 2017

Objective

The ketogenic diet is clinically used to treat drug‐resistant epilepsy. The diet treatment markedly increases ketone bodies (acetoacetate and β‐hydroxybutyrate), which work as energy metabolites in the brain. Here, we investigated effects of acetoacetate on voltage‐dependent Ca2+ channels (VDCCs) in pyramidal cells of the hippocampus. We further explored an acetoacetate analog that inhibited VDCCs in pyramidal cells, reduced excitatory postsynaptic currents (EPSCs), and suppressed seizures in vivo.

Methods

The effects of acetoacetate and its analogs on VDCCs and EPSCs were evaluated using patch‐clamp recordings from CA1 pyramidal cells of mouse hippocampal slices. The in vivo effects of these reagents were also evaluated using a chronic seizure model induced by intrahippocampal injection of kainate.

Results

Acetoacetate inhibited VDCCs in pyramidal cells of hippocampal slices, and reduced EPSCs in slices exhibiting epileptiform activity. More potent EPSC inhibitors were then explored by modifying the chemical structure of acetoacetate, and 2‐phenylbutyrate was identified as an acetoacetate analog that inhibited VDCCs and EPSCs more potently. Although acetoacetate is known to inhibit vesicular glutamate transporters (VGLUTs), 2‐phenylbutyrate did not inhibit VGLUTs, showing that 2‐phenylbutyrate is an acetoacetate analog that preferably inhibits VDCCs. In addition, 2‐phenylbutyrate markedly reduced EPSCs in slices exhibiting epileptiform activity, and suppressed hippocampal seizures in vivo in a mouse model of epilepsy. The in vivo antiseizure effects of 2‐phenylbutyrate were more potent than those of acetoacetate. Finally, intraperitoneal 2‐phenylbutyrate was delivered to the brain, and its brain concentration reached the level enough to reduce EPSCs.

Significance

These results demonstrate that 2‐phenylbutyrate is an acetoacetate analog that inhibits VDCCs and EPSCs in pyramidal cells, suppresses hippocampal seizures in vivo, and has brain penetration ability. Thus 2‐phenylbutyrate provides a useful chemical structure as a lead compound to develop new antiseizure drugs originating from ketone bodies.
Cognitive network reorganization following surgical control of seizures in Lennox‐Gastaut syndrome
Authors: Warren Aaron E. L. , Harvey A. Simon , Abbott David F. , Vogrin Simon J. , Bailey Catherine , Davidson Andrew , Jackson Graeme D. , Archer John S.
Published: March 2017

We previously observed that adults with Lennox‐Gastaut syndrome (LGS) show abnormal functional connectivity among cognitive networks, suggesting that this may contribute to impaired cognition. Herein we report network reorganization following seizure remission in a child with LGS who underwent functional magnetic resonance imaging (fMRI) before and after resection of a cortical dysplasia. Concurrent electroencephalography (EEG) was acquired during presurgical fMRI. Presurgical and postsurgical functional connectivity were compared using (1) graph theoretical analyses of small‐world network organization and node‐wise strength; and (2) seed‐based analyses of connectivity within and between five functional networks. To explore the specificity of these postsurgical network changes, connectivity was further compared to nine children with LGS who did not undergo surgery. The presurgical EEG‐fMRI revealed diffuse activation of association cortex during interictal discharges. Following surgery and seizure control, functional connectivity showed increased small‐world organization, stronger connectivity in subcortical structures, and greater within‐network integration/between‐network segregation. These changes suggest network improvement, and diverged sharply from the comparison group of nonoperated children. Following surgery, this child with LGS achieved seizure control and showed extensive reorganization of networks that underpin cognition. This case illustrates that the epileptic process of LGS can directly contribute to abnormal network organization, and that this network disruption may be reversible.
Trehalose activates autophagy and decreases proteasome inhibitor‐induced endoplasmic reticulum stress and oxidative stress‐mediated cytotoxicity in hepatocytes
Authors: Honma Yuichi , Sato‐Morita Miyuki , Katsuki Yuka , Mihara Hitomi , Baba Ryoko , Harada Masaru
Published: March 2017

Aim

Endoplasmic reticulum stress is associated with the pathophysiology of various liver diseases. Endoplasmic reticulum stress mediates the accumulation of abnormal proteins and leads to oxidative stress, cytoplasmic inclusion body formation, and apoptosis in hepatocytes. Autophagy is a bulk degradation pathway for long‐lived cytoplasmic proteins or damaged organelles and is also a major degradation pathway for many aggregate‐prone and disease‐causing proteins. We previously reported that rapamycin, a mammalian target of rapamycin inhibitor, activated autophagy and decreased proteasome inhibitor‐mediated ubiquitinated protein accumulation, cytoplasmic inclusion body formation, and apoptosis in hepatocytes. Trehalose is a non‐reducing disaccharide that has been shown to activate autophagy. It has been reported to decrease aggregate‐prone proteins and ameliorate cytotoxicity in neurodegenerative disease models. However, the effects of trehalose in hepatocytes are unclear.

Methods

We show here that trehalose activated autophagy and reduced endoplasmic reticulum stress, cytoplasmic inclusion body formation, and apoptosis in proteasome inhibitor‐treated liver‐derived cultured cells.

Conclusion

To our knowledge, this is the first report showing that trehalose activates autophagy and has cytoprotective effects in hepatocytes. Our findings suggest that trehalose can become a therapeutic agent for endoplasmic reticulum stress‐related liver diseases.
Influence of microstructure properties and layer thickness on strength and permeance of ceramic membranes
Authors: Guan Kang , Liu Yang , Zhu Weiya , Chu Yanhui , Peng Cheng , Lv Ming , Sun Qian , Rao Pinggen , Wu Jianqing
Published: March 2017

We numerically predict the microstructure properties of ceramic membranes and the coupling effects of microstructure properties and layer thickness on the strength and permeance of ceramic membranes. It is found that particle size is the most important factor, followed by thickness and finally by microstructure parameters. The general design principle for strength and permeance are and respectively, with σ, h, and K the strength, thickness and permeability, while the subscript s and t represent the support and sintered layer, respectively.
Validation of noninvasive methods to predict the presence of gastroesophageal varices in a cohort of patients with compensated advanced chronic liver disease
Authors: Llop Elba , Lopez Marta , de la Revilla Juan , Fernandez Natalia , Trapero Maria , Hernandez Marta , Fernández‐Carrillo Carlos , Pons Fernando , Martinez Jose Luis , Calleja Jose Luis
Published: March 2017

Background and Aim

The aim was to validate noninvasive methods to predict the presence of gastroesophageal varices (GEV) in patients with suspected compensated advanced chronic liver disease.

Methods

We retrospectively reviewed clinical and radiological data collected prospectively between September 2013 and September 2015. We reviewed 442 consecutive patients with suspected compensated advanced chronic liver disease measured by transient elastography (TE) and a gastroscopy. We evaluated platelets, spleen diameter, TE, liver stiffness × spleen size/platelets (LSPS), variceal risk index (VRI), Baveno VI strategy, and Augustin algorithm.

Results

One hundred sixty‐one out of 442 patients were included. Patients with GEV were compared with patients without GEV and showed statistically significant differences in platelet count (117 SD 51 vs 149 SD 62; P = 0.02), spleen diameter (13.0 SD 1.9 vs 11.5 SD 2; P = 0.003), and TE (28 SD 15 vs 19 SD 10; P = 0.001). Single methods (platelet count and TE) diagnosed correctly 51% and 71.4% of patients. Combined methods (LSPS, VRI, Baveno VI, and Augustin algorithm) diagnosed correctly 78%, 83.6%, 45.3%, and 57.1% of patients. Patients with GEV misdiagnosed: platelets 5/161 (3.1%), TE 6/161 (3.7%), LSPS 16/159 (10%), VRI 18/159 (11.3%), Baveno VI 3/161 (1.8%), and Augustin algorithm 6/161 (3.7%). Rate of unnecessary gastroscopies: platelets 46%, TE 25%, LSPS 13%, VRI 6%, Baveno VI 53%, and Augustin algorithm 39.1%.

Conclusions

A significant number of patients were classified correctly using TE, LSPS, and VRI; however, LSPS and VRI had unacceptable rates of misdiagnoses. TE is the best noninvasive single method and the Baveno VI strategy the best combined method.
Albumin‐Bilirubin grade predicts prognosis of HCC patients with sorafenib use
Authors: Kuo Yuan‐Hung , Wang Jing‐Houng , Hung Chao‐Hung , Rau Kun‐Ming , Wu I‐Pei , Chen Chien‐Hung , Kee Kwong‐Ming , Hu Tsung‐Hui , Lu Sheng‐Nan
Published: March 2017

Background and Aim

The Albumin‐Bilirubin (ALBI) grade is a new index to assess objectively liver function and prognosis in patients with hepatocellular carcinoma (HCC). This study aimed to elucidate the application of ALBI grade in baseline and sorafenib‐end in advanced HCC patients who received sorafenib.

Methods

A total of 415 consecutive advanced HCC patients in Child–Pugh A received sorafenib in our hospital. Sorafenib was terminated when radiologic tumor progression or clinical liver function deterioration (LD) occurred in the reassessment bimonthly. Patients who failed with sorafenib monotherapy were retrospectively analyzed.

Results

A total of 260 (62.6%) patients were enrolled, including 98 (37.7%) ALBI grade I and 162 (62.3%) grade II in baseline. More patients in ALBI grade II stopped sorafenib because of LD than in grade I (33.3% vs 14.3%, P < 0.001). Those who in baseline ALBI grade I had a superior overall survival than in grade II (8.5 months vs 4.4 months, P = 0.003). Cox regression analysis confirmed that baseline ALBI grade II (P < 0.001) and ALBI grade increase during treatment (P < 0.001) strongly contributed to the mortality of HCC patients who received sorafenib. After sorafenib failure, those with post‐sorafenib treatment had a better post‐sorafenib survival than those without (9.3 vs 1.6 months, P < 0.001). Logistic regression analysis indicated that sorafenib‐end ALBI grade and LD occurrence were the only two predictors of post‐sorafenib treatment after sorafenib failure.

Conclusions

In clinical practice, we firstly demonstrated that not only ALBI grade in baseline but also ALBI grade change during treatment could predict the prognosis of advanced HCC patients who received sorafenib.
The Role of the Facilitator in Couple Relationship Education
Authors: Ketring Scott A. , Bradford Angela B. , Davis Stephanie Y. , Adler‐Baeder Francesca , McGill Julianne , Smith Thomas A.
Published: March 2017

While much of the Couple Relationship Education (CRE) research has focused on participant factors, unexpectedly little research has considered how characteristics of those providing the programming shape its efficacy. The current study draws upon a diverse sample of 225 couples who received CRE from community educators to examine how facilitation alliance is related to relationship outcomes for men and women and whether having a facilitator with similar demographic characteristics is related to the alliance. Results suggest that the facilitation alliance is related to some—though not all—postprogram outcomes and these effects were uniform across gender and relationship status (married vs. unmarried). Having a facilitator of the same gender was associated with a stronger alliance. Implications are discussed.
Action‐semantic and syntactic deficits in subjects at risk for Huntington's disease
Authors: García Adolfo M. , Bocanegra Yamile , Herrera Eduar , Pino Mariana , Muñoz Edinson , Sedeño Lucas , Ibáñez Agustín
Published: March 2017

Frontostriatal networks play critical roles in grounding action semantics and syntactic skills. Indeed, their atrophy distinctively disrupts both domains, as observed in patients with Huntington's disease (HD) and Parkinson's disease, even during early disease stages. However, frontostriatal degeneration in these conditions may begin up to 15 years before the onset of clinical symptoms, opening avenues for pre‐clinical detection via sensitive tasks. Such a mission is particularly critical in HD, given that patients’ children have 50% chances of inheriting the disease. Against this background, we assessed whether deficits in the above‐mentioned domains emerge in subjects at risk to develop HD. We administered tasks tapping action semantics, object semantics, and two forms of syntactic processing to 18 patients with HD, 19 asymptomatic first‐degree relatives, and sociodemographically matched controls for each group. The patients evinced significant deficits in all tasks, but only those in the two target domains were independent of overall cognitive state. More crucially, relative to controls, the asymptomatic relatives were selectively impaired in action semantics and in the more complex syntactic task, with both patterns emerging irrespective of the subjects’ overall cognitive state. Our findings highlight the relevance of these dysfunctions as potential prodromal biomarkers of HD. Moreover, they offer theoretical insights into the differential contributions of frontostriatal hubs to both domains while paving the way for innovations in diagnostic procedures.
Factors Influencing Resident Choice of Prosthodontic Residency Program
Authors: Wojnarwsky Pandora Keala Lee , Wang Yan , Shah Kumar , Koka Sreenivas
Published: March 2017

Purpose

The decision by prosthodontic residency program directors to employ the Match process highlights the need to understand applicant priorities that influence their choice of which programs to rank highly. The purpose of this study is to determine the factors that were most important to residents when choosing from among nonmilitary based prosthodontics dental residency programs in the United States.

Materials and Methods

Following completion of a pilot study, all currently enrolled prosthodontic residents at nonmilitary residency programs were invited to participate via the internet. The study consisted of a survey instrument asking residents to rank 26 possible factors that might impact an applicant's choice of residency program. In addition, the instrument collected other possible influencing variables including gender and debt load. Mean rank scores were compared to determine the most and least important factors. Kruskal‐Wallis test was used to compare specific factors between the possible influencing variables.

Results

Two hundred and thirty residents completed the survey instrument, representing a 54.1% response rate of possible participants. With regard to factors influencing program choice, reputation of the residency program was the factor ranked the highest by participants, followed in descending order by the program director's personality, curriculum content, access to use of the latest digital technology, and opportunities for dental implant placement. Quality of schools for children, community outreach opportunities, and the ability to moonlight were ranked as the least important factors. Male and female residents ranked factors such as tuition/stipend, curriculum content, and community outreach opportunities significantly differently. Depending on debt load, residents ranked the factors tuition/stipend, ability to moonlight, curriculum content, and safety of the area where the program is differently.

Conclusions

Current prosthodontic residents valued the reputation of the program as the most important factor when applying to residency. Participant gender and debt load influence the factors chosen by residents as more or less important. These data will assist prosthodontic educators position their programs in the best possible light to attract applicants to their programs.
Fire frequency filters species by bark traits in a savanna–forest mosaic
Authors: Charles‐Dominique Tristan , Midgley Guy F. , Bond William J.
Published: March 2017

Aims

Savanna and forest biomes co‐occur across many subtropical landscapes in Africa, and can be differentiated by their fire regime: fires are more frequent in savannas compared to forests. Bark thickness is a key trait of savanna trees, promoting their survival in this context. The rate of bark production (increment·yr−1) should therefore be critical for determining how quickly a developing sapling would be protected or bark could regenerate between two fires. Despite this, the rate of bark production has seldom been measured in studies of fire‐tolerant vs fire‐intolerant species.

Location

Hluhluwe‐iMfolozi Game reserve, South Africa.

Methods

We examined the distribution of woody species in a South African park over 253 sites, stratified by biome. We described the bark traits of the 63 most abundant species and related them to the fire frequencies of the sites where they occur.

Results

Bark growth rate was a good predictor of woody plant persistence in fire‐prone savanna ecosystems. A key exception was root‐suckering species, which have their structure physically protected underground and can thus survive frequent fires while producing little bark.

Conclusion

Species of different forest types and savanna have different bark characteristics, highlighting the important role played by fire in shaping biome distribution.
No other species can replace them: evidence for the key role of dominants in an alpine Festuca varia grassland
Authors: Elumeeva Tatiana G. , Onipchenko Vladimir G. , Werger Marinus J.A.
Published: March 2017

Questions

Festuca varia grasslands occupy extensive areas in the alpine belt of the Caucasus. In the Teberda Reserve the dominant, narrow‐leaved grasses Festuca varia and Nardus stricta contribute up to 56% and 22%, respectively, to the total biomass of the community. How does community composition and structure change after removal of the dominant, and is any species able to replace dominants in abundance and function?

Location

Teberda State Biosphere Reserve, northwestern Caucasus, Russia.

Methods

We experimentally removed F. varia and N. stricta (as single dominants and both together). After 20 yr of treatment we compared the expected increase in species richness per plot, above‐ground phytomass, community biomass‐weighted mean SLA and leaf DMC, as well as the inter‐annual dynamics of functional groups and the most abundant species.

Results

Dominant removal led to a decrease in litter after removal of F. varia and of both dominants, and a decrease in total phytomass after removal of both dominants. Biomass of dominants did not respond to the treatments, however N. stricta increased shoot number after F. varia removal. Non‐dominant narrow‐leaved grasses increased in all the treatments, both in biomass and shoot number. Community biomass‐weighted SLA increased in all the treatments, and leaf DMC decreased.

Conclusions

Dominants play a key role in alpine F. varia grasslands and determine the functional structure and composition of the community. Species from other functional groups and, remarkably, species from the same group, are not able to completely replace them. Traits of F. varia, as the main dominant, control community‐weighted leaf traits and litter accumulation.
Interviewers’ approaches to questioning vulnerable child witnesses: The influences of developmental level versus intellectual disability status
Authors: Brown Deirdre , Lewis Charlie , Stephens Emma , Lamb Michael
Published: March 2017

Purpose

Children with intellectual disabilities (CWIDs) are vulnerable to victimization, but we know little about how to interview them about possible maltreatment. We examined whether interviewers used proportionally more direct and option‐posing, and fewer open questions, with CWID than with typically developing (TD) children or with less mature children regardless of disability, taking into account the contribution of the amount of information conveyed by the child.

Method

One hundred and twelve children (4–12 years) participated in a staged event and were interviewed 1 week later using the NICHD Investigative Interview Protocol. We examined the proportions of different interview prompts posed to CWID of either mild (CWID‐Mild) or moderate (CWID‐Moderate) severity compared with typically developing children matched for chronological (CA) and mental (MA) age.

Results

Even when controlling for the amount that the child said, the overall number and relative proportions of each question type posed to each group varied. Interviewers asked more cued invitations and fewer direct questions of CA‐matched children than younger TD participants or both CWID groups. Option‐posing questions comprised a larger proportion of the interviews with both ID groups than with CA matches. The few suggestive questions were posed more to CWID‐Moderate.

Conclusions

Although research has shown that CWID and young TD children can provide reliable information in response to very open prompting, interviewers tend not to ask such questions. Interviewing strategy was influenced by both developmental level and intellectual disability status, in conjunction with children's individual contributions to the interview, emphasizing the importance of interviewers’ understanding the capacities and vulnerabilities of the children they interview from both a developmental and cognitive perspective.
Non‐selective beta‐blockers are not associated with increased mortality in cirrhotic patients with ascites
Authors: Onali Simona , Kalafateli Maria , Majumdar Avik , Westbrook Rachel , O'Beirne James , Leandro Gioacchino , Patch David , Tsochatzis Emmanuel A.
Published: March 2017

Background & Aims

Controversy exists on the impact of non‐selective beta‐blockers (NSBBs) on survival in patients with ascites. We assessed whether NSBB treatment affects survival in a cohort of 316 consecutive patients with ascites undergoing evaluation for liver transplantation.

Methods

Consecutive patients with cirrhosis and ascites assessed for liver transplantation between 2011 and 2014 were retrospectively evaluated. Competing risk Cox regression analysis in the whole population and in propensity score matched patients were performed to identify predictors of survival.

Results

Three hundred and sixteen patients were evaluated: males 229 (73%), mean age 54 years, median follow‐up: 7 months. Refractory ascites was diagnosed in 124 (39%) patients. Patients receiving NSBBs (n=128, 40.5%) had a higher frequency of previous spontaneous bacterial peritonitis (27% vs 17%, P=.025), lower frequency of refractory ascites (32% vs 44%, P=.03) but similar MELD and UKELD scores. Overall 80 (25%) patients died: 20 (16%) in the NSBB group vs. 60 (32%) in the non‐NSBB group (P=.002). In multivariate competing risk Cox regression analysis, NSBB use was associated with reduced mortality (HR=0.55, 95% CI=0.33‐0.94) along with prophylactic antibiotic use (HR=0.33, 95% CI=0.14‐0.74), MELD score (HR=1.10, 95% CI=1.06‐1.14) and sodium levels (HR=0.94, 95% CI: 0.89‐0.98). No impact on survival was found when considering only patients with refractory ascites (NSBB use: HR=0.43, 95% CI=0.20‐1.11).

Conclusions

Patients with ascites on NSBBs did not have impaired survival compared to those not receiving NSSBs and interestingly this observation was also confirmed in the subgroup with refractory ascites. Our results suggest that NSBBs are not detrimental, but instead seem safe even in more advanced stages of cirrhosis in patients on a transplant waiting list.
Prophylactic Atropine Administration Prevents Vasovagal Response Induced by Cryoballoon Ablation in Patients with Atrial Fibrillation
Authors: SUN LIPING , DONG JIAN‐ZENG , DU XIN , BAI RONG , LI SONGNAN , SALIM MOHAMED , MA CHANG‐SHENG
Published: March 2017

Background

Cryoballoon (CB) ablation of pulmonary vein ostia often induces a vagal response. This prospective study was designed to assess the effectiveness of prophylactic intravenous administration of atropine on hemodynamic impairment induced by CB ablation in patients with atrial fibrillation.

Methods

Twenty‐five patients with paroxysmal atrial fibrillation undergoing CB ablation were prospectively enrolled and assigned to one of two groups. First 12 patients (trial group) were administered 1 mg of atropine before deflation of the CB, while the following 13 patients (control group) were given atropine only after the onset of the hemodynamic variation (decrease in heart rate and/or blood pressure). Treatment was considered effective when the hemodynamic variations were restored.

Results

In the trial group, three patients with transient hypotension did not require supportive care throughout the procedures, and one patient with hypotension required supportive care. In the control group, hypotension, bradycardia, and mixed bradycardia with hypotension requiring supportive care occurred in six, three, and three patients, respectively. Overall, the rate of marked vagal responses was significantly lower when prophylactic atropine was administrated (4/12 patients vs 12/13 patients, respectively; P < 0.01).

Conclusions

Atropine is significantly effective in the prevention of all types of vasovagal responses induced by CB ablation in patients with atrial fibrillation.
Premature Trigger of ERI in Medtronic EnRhythm Devices
Authors: MIDDELDORP MELISSA E. , MAHAJAN RAJIV , ELLIOTT ADRIAN D. , PATHAK RAJEEV K. , TWOMEY DARRAGH , WILSON LAUREN , STOLCMAN SIMON , MUNAWAR DIAN A. , KUMAR SHARATH , LAU DENNIS H. , SANDERS PRASHANTHAN
Published: March 2017

Background

Medical technology has made significant advances over the last few decades with smaller and more dynamic pacemakers. However, technical failures leading to premature replacement is a cause of concern. We present a series of Medtronic EnRhythm devices that reached premature elective replacement indicator (ERI).

Methods

The database of Centre of Heart Rhythm Disorders was searched for EnRhythm device implantation from 2006 to 2011. Battery depletion <8.5 years was considered premature considering the projected average longevity to be 8.5–10.5 years. An unexpected premature ERI was defined when it was reached within 3 months of last normal check. Device follow‐up was conducted every 3 months after advisory.

Results

A total of 88 EnRhythm pacemakers were implanted. Over a median follow‐up of 6.2 years (range: 0.3–9.2), 39 (44.3%) EnRhythm devices reached premature ERI. In 11 (28%), ERI was not recognized and patients were being investigated for other causes of unsteadiness or dyspnea prior to device check. Notably, three (7%) patients had premature ERI < 3.5 years. Ten (25.6%) had sudden and unexpected premature ERI. While asynchronous pacing was observed, there were no cases of absence of pacing.

Conclusions

The rate of premature ERI for EnRhythm devices was 44.3%, significantly higher than reported by the manufacturer. Of concern, a sizeable proportion occurred unexpectedly, warranting more frequent reviews and empirical replacement in some patients. With the experience of the EnRhythm, appropriate monitoring strategies are recommended for future advisories.
Cremation of Leadless Pacemaker
Authors: CHEUNG LILY , CHAN GARY C.P. , CHAN JOSEPH Y.S. , LAU CHU‐PAK
Published: March 2017

Cremation of implanted cardiac electronic devices can be associated with explosion from rapid gas formation causing potential hazard to the crematoria staffs and facilities. We present four patients who had undergone cremation with a leadless pacemaker (MicraTM, Medtronic Inc., Minneapolis, MN, USA) left inside their bodies. There was neither reported explosion nor damage to the cremation chamber during the cremation process. In this small series, cremation of MicraTM is not associated with noticeable explosion.
An Innovation in Pacemaker Lead Implantation via Persistent Left Superior Vena Cava: The “3D Alpha Curve” Stylet
Authors: BEIG JAHANGIR RASHID , DAR MOHD. IQBAL , TRAMBOO NISAR A. , HAFEEZ IMRAN , LONE AJAZ A. , RATHER HILAL A.
Published: March 2017

Persistent left superior vena cava (PLSVC) draining into coronary sinus is typically detected incidentally during transcatheter interventions using left subclavian venous approach. In our experience, we have encountered this anomaly on a few occasions and in all these cases we successfully implanted leads in the right ventricle (RV) by shaping the stylet into a “U‐shaped” or “pigtail‐shaped” curve. Herein, we report a case of an adult male who underwent successful dual‐chamber pacemaker implantation via PLSVC through left axillary venous approach. In this case, we were unable to deliver the lead into RV using aforementioned stylets. As an innovation, we used a “three‐dimensional alpha curve”‐shaped stylet that facilitated an easy entry of pacing lead into the RV.
Anterior rectus sheath blocks in children with abdominal wall pain due to anterior cutaneous nerve entrapment syndrome: a prospective case series of 85 children
Authors: Siawash Murid , Mol Frederique , Tjon‐A‐Ten Walther , Perquin Christel , van Eerten Percy , van Heurn Ernst , Roumen Rudi , Scheltinga Marc
Published: March 2017

Background

Chronic abdominal pain in children may be caused by the anterior cutaneous nerve entrapment syndrome. Local nerve blocks are recommended as an initial treatment in adults. Evidence on effectiveness and safety of such a treatment in children is lacking.

Aim

Our aim was to study outcome and adverse events of anterior rectus sheath blocks in childhood anterior cutaneous nerve entrapment syndrome.

Methods

Patients <18 years of age receiving anterior rectus sheath blocks were prospectively followed. Injections were administered using a free‐hand technique in the outpatient department.

Results

A total of 85 children were included (median age 15 years, range 8–17, 76% female). Eighty‐three children reported immediate pain relief following a single lidocaine block and 13 achieved long‐term success. Another 19 children was successfully treated with additional blocks combined with steroids. A total 38% success ratio was attained after a median 17‐month follow‐up (range, 4–39). Pain intensity and diagnostic delay were not associated with a beneficial outcome. However, young age predicted success. An infrequently occurring adverse event was temporarily increased pain some 6 h post injection.

Conclusion

Anterior rectus sheath blocks using local anesthetics and steroids are safe and long‐term successful in more than one‐third of children suffering from abdominal pain due to anterior cutaneous nerve entrapment syndrome.
Training program for Japanese medical personnel to combat child maltreatment
Authors: Tanoue Koji , Senda Masayoshi , An Byongmun , Tasaki Midori , Taguchi Megumi , Kobashi Kosuke , Oana Shinji , Mizoguchi Fumitake , Shiraishi Yuko , Yamada Fujiko , Okuyama Makiko , Ichikawa Kotaro
Published: March 2017

Background

In 2014, we created a training program for personnel in medical institutions in Japan to combat child maltreatment. The aim of the present study was to document the effectiveness of this program.

Methods

Participants completed a questionnaire before and after the training lecture. The questionnaire designed for the training program included demographic questions such years of practice and area of specialty (i.e. physician, nurse, social worker, public health nurse, technician, and others), as well as experience of suspected child maltreatment cases and training in dealing with such cases. The questionnaire included 15 statements designed to ascertain practical knowledge and attitudes relevant to addressing child maltreatment. Baseline score measured before the lecture was compared with that obtained after the lecture.

Results

A total of 760 participants completed the survey, including 227 physicians, 223 nurses, 38 technologists, 27 social workers, 11 public health nurses, and 174 with other occupations, and 60 participants who left their occupation as blank. There was a significant difference between the baseline score of participants with versus without experience in suspected child maltreatment or training to deal with child maltreatment (F = 16.3; P < 0.001). After the lecture, the average score rose above the baseline (11.18 vs 10.57). The rate of correct answers for nine questionnaire items increased significantly.

Conclusions

Professionals from a range of fields need clinical skills and judgement to decide if a child's injuries are due to maltreatment. The combination of increased clinical experience along with a high‐quality didactic lecture, appears to be the most effective method of raising awareness and enhancing skills.
Endometrial biopsy in Bos indicus beef heifers
Authors: Ramirez‐Garzon O , Satake N , Lyons RE , Hill J , Holland MK , McGowan M
Published: March 2017

Contents

An endometrial biopsy allows for a comprehensive assessment of the uterine environment of a breeding female. Although routine in mares, devices used for endometrial biopsies are impracticable in heifers due to the size and structure of the cervix. This report describes the use of a human bronchoscopy biopsy device (Karl Storz® 10366L) for collection of endometrial biopsies in Bos indicus beef heifers. The Storz® device is smaller and thinner and enabled the collection of an endometrial biopsy in 86% of heifers (n = 44/51). The biopsied tissue was of good quality and suitable for transcriptomic assessment of the endometrium, with total RNA yield and RNA integrity number (RIN) averaging 1.3 μg (range 0.4–5.3 μg) and 7.4 (range 5.7–8.4), respectively.
Structural Strain in Science: Organizational Context, Career Stage, Discipline, and Role Composition
Authors: Johnson David R. , Vaidyanathan Brandon , Howard Ecklund Elaine
Published: March 2017

This article examines the relationship between structural strain (the imbalance between actual and preferred conditions of work) and anomie in science (the absence of opportunities to achieve recognition). Using data from a nationally representative survey of physicists and biologists in the United Kingdom (N = 1,604), we test competing hypotheses about the occupational factors that produce structural strain. We find that structural strain is influenced by organizational context and career stage, but not in the manner existing theory suggests. We elaborate existing theoretical frameworks by showing that role composition mediates the effects of organizational context and career stage.
Sepsis after renal transplantation: Clinical, immunological, and microbiological risk factors
Authors: Schachtner Thomas , Stein Maik , Reinke Petra
Published: March 2017

Background

As immunosuppressive therapy and allograft survival have improved, the increased incidence of sepsis has become a major hurdle of disease‐free survival after renal transplantation.

Methods

We identified 112 of 957 kidney transplant recipients (KTRs) with sepsis. In all, 31 KTRs developed severe sepsis or septic shock, and 30 KTRs died from sepsis. KTRs without sepsis were used for comparison. CMV‐specific and alloreactive T cells were measured using an interferon‐γ Elispot assay. The extent of immunosuppression was quantified by lymphocyte subpopulations.

Results

Five‐year patient survival was 70.3% with sepsis compared to 88.2% without (P<.001). Five‐year estimated glomerular filtration rate was lower in KTRs developing sepsis (P<.001). Upon multivariate analysis, diabetes, lymphocyte‐depleting induction, donor age, CMV replication, and acute rejection increased the risk of sepsis (P<.05). Age, diabetes, underweight/obesity, and pneumonia as site of infection were predictive factors of mortality (P<.05). Early‐onset sepsis was associated with decreased CD3+ and CD4+ T cells pre‐transplantation (P<.05). Impaired CMV‐specific cellular immunity pre‐transplantation was associated with CMV replication and early‐onset sepsis (P<.05). High frequencies of alloreactive T cells were associated with acute rejection, lymphocyte‐depleting rejection treatment, and early‐onset sepsis (P<.05).

Conclusion

KTRs developing sepsis show inferior patient survival and allograft function. Identified risk factors and differences in lymphocyte counts, CMV‐specific immunity, and alloreactivity may prove useful to identify KTRs at increased risk.
Red blood cell transfusions can induce proinflammatory cytokines in preterm infants
Authors: Dani Carlo , Poggi Chiara , Gozzini Elena , Leonardi Valentina , Sereni Alice , Abbate Rosanna , Gori Anna Maria
Published: March 2017

BACKGROUND

The risk of developing red blood cell (RBC) transfusion–associated necrotizing enterocolitis (TANEC) in preterm infants has recently been emphasized. Our aim was to assess changes in cytokine serum levels after RBC transfusions in a cohort of very preterm infants to evaluate their possible proinflammatory effect.

STUDY DESIGN AND METHODS

We carried out a prospective observational study. One transfusion event was studied in infants less than 32 weeks' gestation and more than 7 days old (n = 20) admitted to a tertiary neonatal intensive care unit. Interleukin (IL)−1β, IL‐6, IL‐8, tumor necrosis factor‐α, interferon‐γ (IFN‐γ), IL‐17, monocyte chemoattractant protein‐1 (MCP‐1), interferon‐γ–induced protein 10 (IP‐10), intracellular adhesion molecule‐1 (ICAM‐1), and vascular cell adhesion molecule serum levels were measured in enrolled patients within 120 minutes before (T0) the RBC transfusion and then within 120 minutes (T1), 12 ± 3 hours (T2), 24 ± 6 hours (T3), and 48 ± 6 hours (T4) after the end of RBC transfusion.

RESULTS

Infants received 19.8 ± 3.0 mL of RBCs at the mean age of 50 ± 18 days. Their hematocrit level increased from 24.1 ± 1.2% to 39.4 ± 2.9%. IL‐1β, IL‐8, IFN‐γ, IL‐17, MCP‐1, IP‐10, and ICAM‐1 increased significantly after RBC transfusions.

CONCLUSION

Proinflammatory cytokines are increased after RBC transfusion. These findings may contribute to explaining the pathogenesis of TANEC and suggest the opportunity of adopting wise transfusion guidelines that would help to avoid detrimental risks of transfusion‐related immunomodulation and of undertransfusion.
Mother Tongue Teaching at School Comparison of French and Turkish Models
Authors: Bozavlı Ebubekir
Published: March 2017

Like speaking, two other important aspects of language are reading and writing. Speaking is acquired unconsciously in public while other two skills are learned at school and contribute to life-long speaking skills. The present research is to analyze mother tongue teaching at school and compare two different models, one in France, a developed European country and the other in Turkey, a developing and still a candidate country to European Union. The research has been conducted by using document analysis and interview method. Mother tongue teaching textbooks are the samples of the study, those used as of primary school in Turkey and those used as of kindergarten in France. During interview, discussion-like interview has been conducted. Interview was conducted face-to-face with Turkish teachers in Turkey while it was through a questionnaire online that French teachers were interviewed. The data obtained were interpreted by descriptive method. In both countries, rather than similarities, differences were found in mother tongue teaching at schools. These differences result from both education systems and classroom activities. French teachers are more positive about mother tongue teaching activities in classroom compared to Turkish teachers and think more universally. Turkish teachers complain more about lack of physical equipment at this level.
When size matters: transient receptor potential vanilloid 4 channel as a volume‐sensor rather than an osmo‐sensor
Authors: Toft‐Bertelsen Trine L. , Križaj David , MacAulay Nanna
Published: March 2017

Key points

Mammalian cells are frequently exposed to stressors causing volume changes.

The transient receptor potential vanilloid 4 (TRPV4) channel translates osmotic stress into ion flux.

The molecular mechanism coupling osmolarity to TRPV4 activation remains elusive.

TRPV4 responds to isosmolar cell swelling and osmolarity translated via different aquaporins.

TRPV4 functions as a volume‐sensing ion channel irrespective of the origin of the cell swelling.

Transient receptor potential channel 4 of the vanilloid subfamily (TRPV4) is activated by a diverse range of molecular cues, such as heat, lipid metabolites and synthetic agonists, in addition to hyposmotic challenges. As a non‐selective cation channel permeable to Ca2+, it transduces physical stress in the form of osmotic cell swelling into intracellular Ca2+‐dependent signalling events. Its contribution to cell volume regulation might include interactions with aquaporin (AQP) water channel isoforms, although the proposed requirement for a TRPV4–AQP4 macromolecular complex remains to be resolved. To characterize the elusive mechanics of TRPV4 volume‐sensing, we expressed the channel in Xenopus laevis oocytes together with AQP4. Co‐expression with AQP4 facilitated the cell swelling induced by osmotic challenges and thereby activated TRPV4‐mediated transmembrane currents. Similar TRPV4 activation was induced by co‐expression of a cognate channel, AQP1. The level of osmotically‐induced TRPV4 activation, although proportional to the degree of cell swelling, was dependent on the rate of volume changes. Importantly, isosmotic cell swelling obtained by parallel activation of the co‐expressed water‐translocating Na+/K+/2Cl− cotransporter promoted TRPV4 activation despite the absence of the substantial osmotic gradients frequently employed for activation. Upon simultaneous application of an osmotic gradient and the selective TRPV4 agonist GSK1016790A, enhanced TRPV4 activation was observed only with subsaturating stimuli, indicating that the agonist promotes channel opening similar to that of volume‐dependent activation. We propose that, contrary to the established paradigm, TRPV4 is activated by increased cell volume irrespective of the molecular mechanism underlying cell swelling. Thus, the channel functions as a volume‐sensor, rather than as an osmo‐sensor.
From time-resolved atomic-scale imaging of individual donors to their cooperative dynamics
Authors: Kloth Philipp , Wenderoth Martin
Published: March 2017

Pulsed optical excitation in combination with scanning tunnel microscopy resolves charge dynamics at the gallium arsenide surface.
Pure climb creep mechanism drives flow in Earth’s lower mantle
Authors: Boioli Francesca , Carrez Philippe , Cordier Patrick , Devincre Benoit , Gouriet Karine , Hirel Pierre , Kraych Antoine , Ritterbex Sebastian
Published: March 2017

Climb creep provides an efficient deformation mechanism for bridgmanite under lower mantle conditions.
A highly stretchable, transparent, and conductive polymer
Authors: Wang Yue , Zhu Chenxin , Pfattner Raphael , Yan Hongping , Jin Lihua , Chen Shucheng , Molina-Lopez Francisco , Lissel Franziska , Liu Jia , Rabiah Noelle I. , Chen Zheng , Chung Jong Won , Linder Christian , Toney Michael F. , Murmann Boris , Bao Zhenan
Published: March 2017

A polymer is described that is conductive and stretchable, which can lead to electronics that can conform to the human body.
Aflatoxin-free transgenic maize using host-induced gene silencing
Authors: Thakare Dhiraj , Zhang Jianwei , Wing Rod A. , Cotty Peter J. , Schmidt Monica A.
Published: March 2017

Suppression of an
Aspergillus
biosynthetic enzyme effectively alleviates aflatoxin production in transgenic maize kernels.
PPAR-γ promotes type 2 immune responses in allergy and nematode infection
Authors: Chen Ting , Tibbitt Christopher A. , Feng Xiaogang , Stark Julian M. , Rohrbeck Leona , Rausch Lisa , Sedimbi Saikiran K. , Karlsson Mikael C. I. , Lambrecht Bart N. , Karlsson Hedestam Gunilla B. , Hendriks Rudi W. , Chambers Benedict J. , Nylén Susanne , Coquet Jonathan M.
Published: March 2017

PPAR-γ is critical for T
H
2 cell–mediated allergic inflammation and immunity to worm infection.
Natural killer cell–mediated inflammation resolution is disabled in severe asthma
Authors: Duvall Melody G. , Barnig Cindy , Cernadas Manuela , Ricklefs Isabell , Krishnamoorthy Nandini , Grossman Nicole L. , Bhakta Nirav R. , Fahy John V. , Bleecker Eugene R. , Castro Mario , Erzurum Serpil C. , Gaston Benjamin M. , Jarjour Nizar N. , Mauger David T. , Wenzel Sally E. , Comhair Suzy A. , Coverstone Andrea M. , Fajt Merritt L. , Hastie Annette T. , Johansson Mats W. , Peters Michael C. , Phillips Brenda R. , Israel Elliot , Levy Bruce D. ,   National Heart, Lung, and Blood Institute’s Severe Asthma Research Program-3 Investigators
Published: March 2017

Severe asthma is characterized by decreased NK cell cytotoxicity, and corticosteroids further disable NK cell function.