bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute metabolic and cardiovascular effects of mirabegron in healthy individuals
Authors: Loh Rebecca K. C. , Formosa Melissa F. , La Gerche Andre , Reutens Anne T. , Kingwell Bronwyn A. , Carey Andrew L.
Published: September 2018

Aims

To quantify acute energy expenditure, supraclavicular skin temperature and cardiovascular responses to four doses of the β3‐adrenoceptor agonist, mirabegron.

Materials and methods

A total of 17 individuals (11 men, six women) participated in this ascending‐dose study, receiving single 50‐, 100‐, 150‐ and 200‐mg doses of mirabegron on four separate days with 3 to 14 days wash‐out between each dose. All variables were measured each visit from baseline to 180 minutes post mirabegron treatment. To determine brown adipose tissue (BAT) thermogenic efficacy at each dose, energy expenditure and supraclavicular skin temperature were compared from baseline to 180 minutes post mirabegron treatment. To examine safety, changes in cardiovascular variables at 100, 150 and 200 mg were compared with the standard clinical dose of 50 mg.

Results

Energy expenditure significantly increased after the 100‐ (35.6 ± 5.4 kJ/h) and 200‐mg (35.6 ± 13.1 kJ/h) doses (P ≤ 0.05), and trended towards an increase after 150 mg (24.1 ± 13.6 kJ/h). Supraclavicular skin temperature increased after 50‐ (0.22 ± 0.1°C), 100‐ (0.30 ± 0.1°C) and 150‐mg mirabegron doses (0.29 ± 0.1°C; P ≤ 0.05). The change in systolic blood pressure was greater after 150‐ (7.1 ± 1.3 mm Hg) and 200‐mg doses (9.3 ± 1.9 mm Hg) than after the 50‐mg dose (2.2 ± 1.3 mm Hg; P ≤ 0.05). The change in heart rate was greater after 200 mg (9.0 ± 2.2 bpm) compared with 50 mg (2.9 ± 1.4 bpm; P ≤ 0.05).

Conclusions

A 100‐mg dose of mirabegron increases energy expenditure and supraclavicular skin temperature in a β3‐adrenoceptor‐specific manner, without the off‐target elevations in blood pressure or heart rate observed at higher doses.
Intranasal oxytocin fails to acutely improve glucose metabolism in obese men
Authors: Brede Swantje , Fehr Sebastian , Dalla‐Man Chiara , Cobelli Claudio , Lehnert Hendrik , Hallschmid Manfred , Klement Johanna
Published: September 2018

The hypothalamic neuropeptide oxytocin not only modulates psychosocial function, but also contributes to metabolic regulation. We have recently shown that intranasal oxytocin acutely improves beta‐cell responsivity and glucose tolerance in normal‐weight men. In the present experiment, we investigated the acute glucoregulatory impact of oxytocin in obese men with impaired insulin sensitivity. Fifteen obese healthy men with an average body mass index of 35 kg/m2 and an average body fat content of 33% received a single intranasal dose (24 IU) of oxytocin before undergoing an oral glucose tolerance test. Results were analysed according to the oral minimal model and compared with our findings in normal‐weight participants. In contrast to the results in normal‐weight subjects, oxytocin did not blunt postprandial glucose and insulin excursions in obese men, and moreover failed to enhance beta‐cell responsivity and glucose tolerance. These results indicate that pronounced obesity may be associated with a certain degree of resistance to the glucoregulatory impact of exogenous oxytocin, and underlines the need for further investigations into the potential of oxytocin to improve glucose homeostasis in the clinical context.
The association of basal insulin treatment versus standard care with outcomes in anti‐GAD positive and negative subjects: A post‐hoc analysis of the ORIGIN trial
Authors: Birkeland Kåre I. , Grill Valdemar , Wium Cecilie , McQueen Matthew J. , Lopez‐Jaramillo Patricio , Lee Shun Fu , Gerstein Hertzel C.
Published: September 2018

We compared cardiovascular and other outcomes in patients with dysglycaemia with or without anti‐glutamic acid dehydrogenase (GAD) antibodies participating in the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial. Of the 12 537 participants, 8162 had anti‐GAD measured at baseline and 267 were anti‐GAD positive. The effects of insulin glargine versus standard care and of n‐3 fatty acids supplements versus placebo were compared by testing the interaction of the treatment effects and anti‐GAD status. The effect of glargine on development of new diabetes was assessed in participants without previous diabetes at baseline. The overall incidence of outcomes did not differ between anti‐GAD positive and anti‐GAD negative subjects. The incidence of the composite of cardiovascular death, non‐fatal myocardial infarction, or non‐fatal stroke did not differ between anti‐GAD positive participants randomized to insulin glargine or to standard care, with a hazard ratio (HR) (95% confidence interval [CI]) of 0.80 (0.44‐1.44) or in anti‐GAD negative participants with a HR of 1.07 (0.96‐1.20) (P for interaction = 0.20).
Short chain fatty acids stimulate insulin secretion and reduce apoptosis in mouse and human islets in vitro: Role of free fatty acid receptor 2
Authors: Pingitore Attilio , Gonzalez‐Abuin Noemi , Ruz‐Maldonado Inmaculada , Huang Guo C. , Frost Gary , Persaud Shanta J.
Published: September 2018

Aims

To evaluate the role of free fatty acid receptor 2 (FFAR2)/G‐protein coupled receptor 43 in mediating the effects of the short chain fatty acids (SCFAs) sodium acetate (SA) and sodium propionate (SP) on islet function in vitro, and to identify the intracellular signalling pathways used in SCFA‐induced potentiation of glucose‐induced insulin secretion.

Materials and methods

Islets of Langerhans were isolated from wild‐type and FFAR2−/− mice and from human donors without diabetes. The effects of SA and SP on dynamic insulin secretion from perifused islets were quantified by radioimmunoassay, signalling downstream of SCFAs was profiled by single‐cell calcium microfluorimetry, and measurement of cAMP was performed using a fluorescence assay. Islet apoptosis was induced by exposure to cytokines or sodium palmitate, and the effects of SA and SP in regulating islet apoptosis were assessed by quantification of caspase 3/7 activities.

Results

Deletion of FFAR2 did not affect islet morphology or insulin content. SA and SP reversibly potentiated insulin secretion from mouse islets in a FFAR2‐dependent manner. SCFA‐induced potentiation of insulin secretion was coupled to Gq activation of phospholipase C and protein kinase C, with no evidence of Gi‐mediated signalling. SA and SP protected human and mouse islets from apoptosis, and these pro‐survival properties were dependent on islet expression of FFAR2.

Conclusion

Our results indicate that FFAR2 directly mediates both the stimulatory effects of SA and SP on insulin secretion and their protection against islet apoptosis. We have also shown that SCFA coupling in islets occurs via Gq‐coupled intracellular signalling.
The role of surgery in refractory epilepsy secondary to polymicrogyria in the pediatric population
Authors: Jalloh Ibrahim , Cho Newton , Nga Vincent D.W. , Whitney Robyn , Jain Puneet , Al‐Mehmadi Sameer , Yau Ivanna , Okura Hidehiro , Widjaja Elysa , Otsubo Hiroshi , Ochi Ayako , Donner Elizabeth , McCoy Blathnaid , Drake James , Go Cristina , Rutka James T.
Published: September 2018

Objective

Polymicrogyria (PMG) is a common malformation of cortical development. Many patients with PMG will have medically refractory epilepsy but the role of epilepsy surgery is unclear. The objective of this study was to assess the efficacy of surgical resection/disconnection in achieving seizure control in pediatric patients with PMG.

Methods

A retrospective review of children undergoing epilepsy surgery for PMG between 2002 and 2017 at The Hospital for Sick Children in Toronto, Canada, was performed.

Results

A total of 12 children aged 6 months to 17.8 years (median 8.8 years) underwent resective surgery (7 children) or functional hemispherectomy (5 children). Gross total resection or complete disconnection of PMG was carried out in 7 of 12 children. Follow‐up duration was between 1 and 9 years (median 2.1 years). Nine children remained seizure‐free at last follow‐up. Complete resection or disconnection of PMG led to seizure freedom in 6 of 7 patients (86%), whereas subtotal resection produced seizure freedom in 3 of 5 patients (60%).

Significance

We present one of the largest surgical series of pediatric PMG patients. Seizure outcomes were best with complete resection/disconnection of PMG. However, tailored resections based on electroclinical and neuroradiologic data can produce good outcomes and remain an appropriate strategy for patients with extensive PMG.
Quiet violence: Savannah Sparrows respond to playback‐simulated rivals using low‐amplitude songs as aggressive signals
Authors: Moran Ines G. , Doucet Stéphanie M. , Newman Amy E. M. , Ryan Norris D. , Mennill Daniel J.
Published: September 2018

When animals compete over resources such as breeding territories, they often use signals to communicate their aggressive intentions. By studying which signals are associated with aggressive interactions, we gain a deeper appreciation of animal behaviour. We studied aggressive signalling in male Savannah Sparrows, Passerculus sandwichensis, focusing on signals that precede physical attack against territorial intruders. We simulated intruders using song playback and taxidermic models, and we determined which behaviours were associated with physical attack. Previous studies that have used this approach suggest that many species produce songs of dramatically lower amplitude, or “soft songs,” as signals of aggressive intention. Savannah Sparrows, however, are not known to produce soft songs, and therefore, they provided an interesting system for testing signals that predict attack. Of 93 playback subjects, 23 males attacked the simulated intruder and 70 did not. To our surprise, Savannah Sparrows produced soft songs, and the number of soft songs was a significant predictor of attack on the simulated intruder. Birds also showed a nonsignificant tendency to produce more “chip” calls prior to attack on the simulated intruder, whereas three other measured behaviours (aggressive calls, wing waving and passes over the model) did not predict attack. Our study contributes to the growing body of research on aggressive territorial signals and reveals that soft song is an even more widespread signal of aggression in songbirds than previously recognized.
Innovation as part of a wider behavioural syndrome in the guppy: The effect of sex and body size
Authors: Anderson Berdal Monica , Rosenqvist Gunilla , Wright Jonathan
Published: September 2018

Recent work on animal personalities has shown that individuals within populations often differ consistently in various types of behaviour and that many of these behaviours correlate among individuals to form behavioural syndromes. Individuals of certain species have also been shown to differ in their rate of behavioural innovation in arriving at novel solutions to new and existing problems (e.g., mazes, novel foods). Here, we investigate whether behaviours traditionally studied in personality research are correlated with individual rates of innovation as part of a wider behavioural syndrome. Guppies (Poecilia reticulata) of both sexes from three different wild population sources were assessed: (a) exploration of an open area; (b) speed through a three‐dimensional maze; (c) investigation of a novel object; and (d) attraction to a novel food. The covariance structure (syndrome structure) was examined using structural equation modelling. The best model separated behaviours relating to activity in all contexts from rates of exploration/investigation and innovation. Innovative behaviour (utilizing new food and moving through a novel area) in these fish therefore forms part of the same syndrome as the traditional shy‐bold continuum (exploration of an open area and investigation of a novel object) found in many animal personality studies. There were no clear differences in innovation or syndrome structure between the sexes, or between the three different populations. However, body size was implicated as part of the behavioural syndrome structure, and because body size is highly correlated with age in guppies, this suggests that individual behavioural differences in personality/innovation in guppies may largely be driven by developmental state.
Perception of olfactory aposematic signals by jumping spiders
Authors: Raška Jan , Štys Pavel , Exnerová Alice
Published: September 2018

Studies of aposematism are mostly focused on visual aspects of warning signalization and based on experiments with avian predators. This study presents results of experiments with an arthropod predator, a jumping spider Evarcha arcuata (Araneae: Salticidae) and olfactory (i.e., noncontact chemical) aposematic signals. Spiders were presented with chemically protected firebug Pyrrhocoris apterus (Heteroptera: Pyrrhocoridae). After acquiring the negative experience with the bugs, the spiders were offered a choice between the firebug olfactory signal and a scentless control. Spiders actively avoided the firebug signal, showing that they are able to recognize an unprofitable prey by means of olfactory chemoreception. The results show that olfactory signals alone may function as effective means of aposematic signalization to spiders.
The assessment of fishery status depends on fish habitats
Authors: Brown Christopher J. , Broadley Andrew , Adame Maria F. , Branch Trevor A. , Turschwell Mischa P. , Connolly Rod M.
Published: September 2018

At the crux of the debate over the global sustainability of fisheries is what society must do to prevent over‐exploitation and aid recovery of fisheries that have historically been over‐exploited. The focus of debates has been on controlling fishing pressure, and assessments have not considered that stock production may be affected by changes in fish habitat. Fish habitats are being modified by climate change, built infrastructure, destructive fishing practices and pollution. We conceptualize how the classification of stock status can be biased by habitat change. Habitat loss and degradation can result in either overly optimistic or overly conservative assessment of stock status. The classification of stock status depends on how habitat affects fish demography and what reference points management uses to assess status. Nearly half of the 418 stocks in a global stock assessment database use seagrass, mangroves, coral reefs and macroalgae habitats that have well‐documented trends. There is also considerable circumstantial evidence that habitat change has contributed to over‐exploitation or enhanced production of data‐poor fisheries, like inland and subsistence fisheries. Globally many habitats are in decline, so the role of habitat should be considered when assessing the global status of fisheries. New methods and global databases of habitat trends and use of habitats by fishery species are required to properly attribute causes of decline in fisheries and are likely to raise the profile of habitat protection as an important complementary aim for fisheries management.
Leptin attenuates oxidative stress and neuronal apoptosis in hyperglycemic condition
Authors: Kaeidi Ayat , Hajializadeh Zahra , Jahandari Farank , Fatemi Iman
Published: September 2018

One of the main pathological mechanisms of neurotoxicity in diabetic situation is oxidative stress promoted by hyperglycemia. It has been shown that leptin has neuroprotective effects and may provide neuronal survival signals. This study was designed to reveal the possible neuroprotective effects of leptin in hyperglycemic conditions. Pheochromocytoma (PC12) cell viability was assessed via the MTT test. Cellular reactive oxygen species (ROS) generation was determined by DCFH‐DA analysis. The malondialdehyde (MDA) and glutathione (GSH) levels were measured in high‐glucose‐treated PC12 cells with and without leptin cotreatment. Western blotting was performed to measure apoptosis markers (Cleaved caspase‐3 and Bax/Bcl2 ratio). Elevation of glucose levels (100 mmol/L) consecutively increased intracellular ROS and MDA level, and apoptosis in PC12 cells after 24 h leptin administration (12 and 24 nmol/L) decreased the high‐glucose‐induced cell toxicity, caspase‐3 activation, and Bax/Bcl‐2 ratio. Also, cotreatment with leptin (12 and 24 nmol/L) significantly reduced oxidative damage to PC12 cells in high‐glucose condition, as reflected by the diminution in MDA and ROS levels and the increase in GSH content. Our finding demonstrates that leptin has protective effects against hyperglycemia‐induced neural damage. This could be related to the attenuation of oxidative stress and neural apoptosis.
Tacrolimus diffusion across the peripheral mononuclear blood cell membrane: impact of drug transporters
Authors: Tron Camille , Allard Marie , Petitcollin Antoine , Ferrand‐Sorre Marie‐José , Verdier Marie‐Clémence , Querzerho‐Raguideau Julie , Blanchet Benoit , Le Priol Jérôme , Roussel Mickael , Deugnier Yves , Bellissant Eric , Lemaitre Florian
Published: September 2018

Measuring tacrolimus (TAC) concentration in peripheral blood mononuclear cells (PBMCs) could better reflect the drug effect on its target (calcineurin (CaN) in lymphocytes) than whole blood concentrations. Mechanisms influencing TAC diffusion into PBMC are not well characterized. This work aimed at describing, ex vivo, TAC diffusion kinetics into PBMC and investigating the contribution of membrane transporters to regulate TAC intracellular concentration as well as the impact on CaN activity. PBMCs were incubated with TAC for 5 min to 4 h and under several experimental conditions: 37 °C (physiological conditions), 4 °C (inhibition of influx and efflux active transport), 37 °C + transporter inhibitors (verapamil, carvedilol, and probenecid and bromosulfophthalein, respectively, inhibitors of P‐gp, OAT, and OATP). TAC concentration and CaN activity were measured in PBMC using liquid chromatography coupled with mass spectrometry. TAC intra‐PBMC concentration was maximal after 1 h of incubation. Mean TAC PMBC concentrations were significantly lower in samples incubated at 4 °C compared to the 37 °C groups. Addition of verapamil slightly increased TAC accumulation in PBMC while other inhibitors had no effect. A significant correlation was found between TAC intra‐PBMC concentration and the level of inhibition of CaN. Using an ex vivo cellular model, these results suggest that P‐gp is involved in the drug efflux from PBMC while influx active transporters likely to regulate TAC intra‐PBMC disposition remain to be identified. TAC concentration in PBMC is correlated with its pharmacodynamic effect. Then, TAC intra‐PBMC concentration appears to be a promising biomarker to refine TAC therapeutic drug monitoring.
Care parading as service: Negotiating recognition and equality in user‐controlled personal assistance
Authors: Neumann Cecilie Basberg , Gundersen Tonje
Published: September 2018

This article addresses aspects of the relationship between disabled people and their personal assistants within the user‐controlled personal assistance programme in Norway (BPA — brukerstyrt personlig assistanse). Within this programme, a disabled person and her/his personal assistant (PA) form a working relationship in which the disabled person functions as a supervisor for her/his PA. The purpose of the programme is to enable the supervisor to live as independently as possible, equal to any other member of society. In a study conducted about the work relationship between physically disabled persons and their PAs, we found that many supervisors wanted service, not care, from their PAs. Furthermore, the supervisors’ image of the ideal PA was one who was invisible. In this article, we wish to address the tensions between supervisors’ hard‐won rights to personal assistance in order to live independent lives and the gendered work‐related implications of positioning PAs as invisible service workers within this work relationship.
Epidemiology of Helicobacter pylori infection
Authors: Sjomina Olga , Pavlova Jelizaveta , Niv Yaron , Leja Marcis
Published: September 2018

This review provides the most recent data concerning the epidemiology of Helicobacter pylori infection. Overall, the trend of declining prevalence of H. pylori infection is continuing, with major evidence available from studies in Europe. However, in some parts of the world, for example, in some countries in the Middle East, the prevalence has remained relatively stable. A number of systematic reviews and meta‐analyses have been published during the past year indicating the lowest prevalence rates of the infection in Oceania (24.4%), the highest in Africa (79.1%), and the global annual recurrence rate of H. pylori (4.3%). The recurrence rates were found to be directly related to the human development index and prevalence of infection. Several studies have addressed the correlation between H. pylori infection and sociodemographic conditions, source of drinking water and dietary factors. A hypothesis on the role of insects and yeasts in transmitting H. pylori has been suggested and addressed. Helicobacter sp. have been found in flow flies in Brazil. So far there is no evidence available that H. pylori may survive and persist on the outer body of the fly.
Diagnosis of Helicobacter pylori infection
Authors: Skrebinska Sabine , Mégraud Francis , Bessède Emilie
Published: September 2018

The progress this year in Helicobacter pylori diagnosis concerned essentially endoscopy and molecular techniques. New endoscopy techniques such as blue laser imaging and magnifying narrow band imaging allow the visualization of mucosal aspects representing H. pylori infection, intestinal metaplasia, and even ambiguous early gastric cancer. Several real‐time PCRs have also been used either to quantify H. pylori or to detect mutations associated with clarithromycin resistance in gastric biopsies or applied on gastric juice, stool specimens, or the oral cavity. The presence of H. pylori in free‐living amebae purified from wastewater and drinking water was also determined by PCR and sequencing, as well as culture from a few wastewater samples. Among the noninvasive methods, the urea breath test was used in different conditions, including with a new test meal, which is claimed to avoid the proton‐pump inhibitor washout period before testing. Several articles concerning antibody detection and stool antigen test were also published.
Pathogenesis of Helicobacter pylori infection
Authors: Waskito Langgeng Agung , Salama Nina R. , Yamaoka Yoshio
Published: September 2018

In this review, we highlight progress in the last year in characterizing known virulence factors like flagella and the Cag type IV secretion system with sophisticated structural and biochemical approaches to yield new insight on the assembly and functions of these critical virulence determinants. Several aspects of Helicobacter pylori physiology were newly explored this year and evaluated for their functions during stomach colonization, including a fascinating role for the essential protease HtrA in allowing access of H. pylori to the basolateral side of the gastric epithelium through cleavage of the tight junction protein E‐cadherin to facilitate CagA delivery. Molecular biology tools standard in model bacteria, including regulated gene expression during animal infection and fluorescent reporter gene fusions, were newly applied to H. pylori to explore functions for urease beyond initial colonization and establish high salt consumption as a mediator of gene expression changes. New sequencing technologies enabled validation of long postulated roles for DNA methylation in regulating H. pylori gene expression. On the cell biology side, elegant work using lineage tracing in the murine model and organoid primary cell culture systems has provided new insights into how H. pylori manipulates gastric tissue functions, locally and at a distance, to promote its survival in the stomach and induce pathologic changes. Finally, new work has bolstered the case for genomic variation as an important mechanism to generate phenotypic diversity during changing environmental conditions in the context of diet manipulation in animal infection models and during human experimental infection after vaccination.
Helicobacter: Inflammation, immunology, and vaccines
Authors: Blosse Alice , Lehours Philippe , Wilson Keith T. , Gobert Alain P.
Published: September 2018

Helicobacter pylori infection induces a chronic gastric inflammation which can lead to gastric ulcers and cancer. The mucosal immune response to H. pylori is first initiated by the activation of gastric epithelial cells that respond to numerous bacterial factors, such as the cytotoxin‐associated gene A or the lipopolysaccharide intermediate heptose‐1,7‐bisphosphate. The response of these cells is orchestrated by different receptors including the intracellular nucleotide‐binding oligomerization domain‐containing protein 1 or the extracellular epidermal growth factor receptor. This nonspecific response leads to recruitment and activation of various myeloid (macrophages and dendritic cells) and T cells (T helper‐17 and mucosal‐associated invariant T cells), which magnify and maintain inflammation. In this review, we summarize the major advances made in the past year regarding the induction, the regulation, and the role of the innate and adaptive immune responses to H. pylori infection. We also recapitulate efforts that have been made to develop efficient vaccine strategies.
Treatment of Helicobacter pylori infection in 2018
Authors: O'Morain Neil R. , Dore Maria P. , O'Connor Anthony J. P. , Gisbert Javier P. , O'Morain Colm A.
Published: September 2018

Treatment options for the eradication of Helicobacter pylori continue to evolve. There have been many guidelines for H. pylori treatment published, which may lead to some confusion. However, most are in agreement with the most recent iteration of the Maastricht treatment guidelines. Triple therapy is still the most frequently used treatment, especially in areas of low clarithromycin resistance. Its best results are achieved when taken for a minimum of 10 days and with high‐dose acid suppression. Quadruple therapy is gaining in popularity particularly in areas with increasing resistance to standard triple therapy. Whether three antibiotics, or bismuth and two antibiotics are used, excellent eradication rates are achieved, albeit with increased side effects. Levofloxacin second‐line therapy is widely used; however bismuth, when available, is an increasingly successful option. Sequential therapy is challenging in terms of compliance and is no longer recommended. This past year witnessed a notable increase in the number of studies based on antimicrobial susceptibility testing and tailored eradication therapy, reflecting the role of culture‐guided treatment, which may well represent the future of H. pylori treatment and prevent the inappropriate use of antibiotics.
Phase relations in silicon and germanium nitrides up to 98 GPa and 2400°C
Authors: Nishiyama Norimasa , Langer Julia , Sakai Takeshi , Kojima Yohei , Holzheid Astrid , Gaida Nico A. , Kulik Eleonora , Hirao Naohisa , Kawaguchi Saori I. , Irifune Tetsuo , Ohishi Yasuo
Published: September 2018

Phase relations in silicon and germanium nitrides (Si3N4 and Ge3N4) were investigated using a Kawai‐type multianvil apparatus and a laser‐heated diamond anvil cell combined with a synchrotron radiation. The pressure‐induced phase transition from the β to γ (cubic spinel‐type structure) phase was observed in both compositions. We observed the coexistence of the β and γ phases in Si3N4 at 12.4 GPa and 1800°C, while the appearance of single phase γ‐Ge3N4 was observed at pressures above 10 GPa. Our observations under higher pressures revealed that γ‐Si3N4 and γ‐Ge3N4 have wide stability fields and no postspinel transition was observed up to 98 GPa and 2400°C in both compositions. Using the room‐temperature compression curves of these materials, the bulk moduli (K0) and their pressure derivatives (K′0) were determined: K0 = 317 (16) GPa and K′0 = 6.0 (8) for γ‐Si3N4; K0 = 254 (13) GPa and K′0 = 6.0 (7) for γ‐Ge3N4.
Leadless multisite pacing: A feasibility study using wireless power transfer based on Langendorff rodent heart models
Authors: Lyu Hongming , John Mathews , Burkland David , Greet Brian , Xi Yutao , Sampaio Luiz C. , Taylor Doris A. , Babakhani Aydin , Razavi Mehdi
Published: September 2018

Introduction

Fifteen to thirty percent of patients with impaired cardiac function have ventricular dyssynchrony and warrant cardiac resynchronization therapy (CRT). While leadless pacemakers eliminate lead‐related complications, their current form factor is limited to single‐chamber pacing. In this study, we demonstrate the feasibility of multisite, simultaneous pacing using miniaturized pacing nodes powered through wireless power transfer (WPT).

Methods

A wireless energy transfer system was developed based on resonant coupling at approximately 200 MHz to power multiple pacing nodes. The pacing node comprises circuitry to efficiently convert the harvested energy to output stimuli. To validate the use of these pacing nodes, ex vivo studies were carried out on Langendorff rodent heart models (n = 4). To mimic biventricular pacing, two beating Langendorff rodent heart models, kept 10 cm apart, were paced using two distinct pacing nodes, each attached on the ventricular epicardial surface of a given heart.

Results

All ex vivo Langendorff heart models were successfully paced with a simple coil antenna at 2 to 3 cm from the pacing node. The coil was operated at 198 MHz and 0.3 W. Subsequently, simultaneous pacing of two Langendorff heart models 30 cm apart using an output power of 5 W was reliably demonstrated.

Conclusion

WPT provides a feasible option for multisite, wireless cardiac pacing. While the current system remains limited in design, it offers support and a conceptual framework for future iterations and eventual clinical utility.
Clinical preferences and trends of anti‐vascular endothelial growth factor treatments for diabetic macular edema in Japan
Authors: Sugimoto Masahiko , Tsukitome Hideyuki , Okamoto Fumiki , Oshika Tetsuro , Ueda Tetsuo , Niki Masanori , Mitamura Yoshinori , Ishikawa Hiroto , Gomi Fumi , Kitano Shigehiko , Noma Hidetaka , Shimura Masahiko , Sonoda Shozo , Sawada Osamu , Ohji Masahito , Harimoto Kozo , Takeuchi Masaru , Takamura Yoshihiro , Kondo Mineo , Sakamoto Taiji
Published: September 2018

Aims/Introduction

To determine the current clinical preferences of anti‐vascular endothelial growth factor (VEGF) treatment protocols for diabetic macular edema (DME) in Japan.

Materials and Methods

This was a descriptive cross‐sectional study. Answers to a questionnaire consisting of 16 questions were obtained from 176 of 278 (63.3%) surveyed ophthalmologists.

Results

The results showed that 81.2% preferred intravitreal injections of anti‐VEGF antibodies as the first‐line therapy. The most important indicators for beginning anti‐VEGF therapy were: the best‐corrected visual acuity in 44.3% and the retinal thickness in 30.7%. In the loading phase, 53.4% preferred a single injection, and in the maintenance phase, 75.0% preferred the pro re nata regimen. Financial limitation (85.8%) was reported as the most important difficulty in the treatment. For combination therapy with anti‐VEGF treatment, panretinal photocoagulation, focal photocoagulations and a sub‐Tenon steroid injection were preferred. The contraindications for anti‐VEGF therapy were: prior cerebral infarction (72.7%). Regarding the use of both approved anti‐VEGF agents in Japan, ranibizumab and aflibercept, 39.8% doctors used them appropriately.

Conclusions

Our results present the current clinical preferences of anti‐VEGF treatment for DME in Japan. The best‐corrected visual acuity and the retinal thickness are important indicators to institute this therapy. The majority of the ophthalmologists use anti‐VEGF treatment as first‐line therapy and prefer the 1 + pro re nata regimen.
Toxoplasma gondii, Neospora caninum and Encephalitozoon cuniculi in Animals from Captivity (Zoo and Circus Animals)
Authors: Marková Jiřina , Machačová Tereza , Bártová Eva , Sedlák Kamil , Budíková Marie , Silvestre Pasquale , Laricchiuta Paolo , Russo Marco , Veneziano Vincenzo
Published: September 2018

Problems with parasitic infections are common in zoological gardens and circuses. In some animals it can lead to several disorders such as systemic disease, reproductive disorders (abortions and neonatal mortality), and even to death if severe illness is untreated. Thus, the aim of this study was to evaluate the prevalence of three common parasites in 74 animals from three zoos, and four circuses in Southern Italy. Antibodies to Toxoplasma gondii, Neospora caninum, and Encephalitozoon cuniculi were detected in 51%, 12%, and 20% of animals, respectively. Co‐infections of T. gondii and N. caninum were reported in seven animals (9%) and co‐infection of T. gondii and E. cuniculi in one animal. T. gondii, N. caninum and E. cuniculi seroprevalence differed in type of diet (P ≤ 0.0001; P ≤ 0.037 and P ≤ 0.004, respectively). T. gondii and E. cuniculi seroprevalence also differed in animal families (P ≤ 0.0001) and according to type of housing (P ≤ 0.003), respectively. Statistical differences were not found in other characteristics (gender, age, country of birth, origin, and contact with cats or dogs). This is the first serological study focusing on protozoan and microsporidian parasites in zoo and circus animals from Southern Italy and the first detection of antibodies to E. cuniculi in camels in Europe.
Description of a new Pimelodella (Siluriformes: Heptapteridae) species with a discussion on the upper pectoral girdle homology of Siluriformes
Authors: Slobodian Veronica , Pastana Murilo N. L.
Published: September 2018

A new species of Pimelodella is described from several right‐bank tributaries of the Rio Madeira basin in Amazonas and Rondônia states, Brazil. The new species differs from all congeners by the supraoccipital process not reaching the anterior nuchal plate, 43–45 total vertebrae, maxillary barbels reaching between adpressed anal‐fin terminus and caudal‐fin origin, epiphyseal branch of supraorbital laterosensory canal emerging as two distantly‐positioned pores and a conspicuous black mark at distal third of dorsal fin, between dorsal‐fin spine and third branched ray. A detailed description of the cephalic laterosensory system of the new species is provided and contrasted with other Siluriformes and Ostariophysi. A discussion regarding homology of the catfish upper pectoral girdle bones is offered in light of modifications of the postotic and supratemporal lateral‐line canals. Based on the placement of the pterotic branch of the postotic canal, it is concluded that the extrascapula is fused to the pterotic in Siluriformes. Results presented herein offer an example of how lateral‐line morphology can be used as a compelling source of evidence to help determine homology of cranial and upper pectoral girdle bones.
Regulating nociceptive transmission by VGluT2‐expressing spinal dorsal horn neurons
Authors: Wang Li , Chen Shao‐Rui , Ma Huijie , Chen Hong , Hittelman Walter N. , Pan Hui‐Lin
Published: September 2018

Vesicular glutamate transporter‐2 (VGluT2) mediates the uptake of glutamate into synaptic vesicles in neurons. Spinal cord dorsal horn interneurons are highly heterogeneous and molecularly diverse. The functional significance of VGluT2‐expressing dorsal horn neurons in physiological and pathological pain conditions has not been explicitly demonstrated. Designer receptors exclusively activated by designer drugs (DREADDs) are a powerful chemogenetic tool to reversibly control neuronal excitability and behavior. Here, we used transgenic mice with Cre recombinase expression driven by the VGluT2 promoter, combined with the chemogenetic approach, to determine the contribution of VGluT2‐expressing dorsal horn neurons to nociceptive regulation. Adeno‐associated viral vectors expressing double‐floxed Cre‐dependent Gαq‐coupled human M3 muscarinic receptor DREADD (hM3D)‐mCherry or Gαi‐coupled κ‐opioid receptor DREADD (KORD)‐IRES‐mCitrine were microinjected into the superficial spinal dorsal horn of VGluT2‐Cre mice. Immunofluorescence labeling showed that VGluT2 was predominantly expressed in lamina II excitatory interneurons. Activation of excitatory hM3D in VGluT2‐expressing neurons with clozapine N‐oxide caused a profound increase in neuronal firing and synaptic glutamate release. Conversely, activation of inhibitory KORD in VGluT2‐expressing neurons with salvinorin B markedly inhibited neuronal activity and synaptic glutamate release. In addition, chemogenetic stimulation of VGluT2‐expressing neurons increased mechanical and thermal sensitivities in naive mice, whereas chemogenetic silencing of VGluT2‐expressing neurons reversed pain hypersensitivity induced by tissue inflammation and peripheral nerve injury. These findings indicate that VGluT2‐expressing excitatory neurons play a crucial role in mediating nociceptive transmission in the spinal dorsal horn. Targeting glutamatergic dorsal horn neurons with inhibitory DREADDs may be a new strategy for treating inflammatory pain and neuropathic pain.

image
Combination chemical peels are more effective than single chemical peel in treatment of mild‐to‐moderate acne vulgaris: A split face comparative clinical trial
Authors: Nofal Eman , Nofal Ahmad , Gharib Khalid , Nasr Mohammad , Abdelshafy Ahmed , Elsaid Eman
Published: September 2018

Background

Successful management of acne involves choosing proper medication. Chemical peeling is a well‐known option in treatment of acne vulgaris.

Objective

To evaluate and compare the clinical efficacy and safety of combination chemical peels vs single peel in treatment of mild‐to‐moderate acne.

Methods

The study included 45 patients with mild‐to‐moderate acne divided into three equal groups. Group A underwent combination sequential peels with modified Jessner's solution (MJ) followed by trichloro acetic acid (TCA20%) on the right (Rt) side of the face vs TCA 30% on the left (Lt) side. Group B was treated by combination peels of salicylic (20%) mandelic (10%) (SM) mixture on the Rt half vs salicylic acid 30% on the Lt half. Group C underwent combination sequential peeling of MJ and TCA on the Rt side vs SM combination peels on the Lt side. All patients received six sessions with 2‐week intervals and followed up for 3 months after the last session. Side effects were reported.

Results

Both sides of the face showed significant improvement of acne lesions but improvement was significantly higher and earlier in sides treated by combination peels. Side effects were minimal.

Conclusion

In conclusion, combination peels achieved a higher and earlier therapeutic response with a reasonable cost that is maintained for a relatively long periods than single peel. Combination sequential peels gave the best results.
Evaluation of the delivery of long‐term at‐home nursing care: An example of good practice
Authors: Stojak Zofia , Jamiolkowski Jacek , Marcinowicz Ludmila
Published: September 2018

Aims and objectives

To evaluate the influence of long‐term at‐home nursing care (LTHNC) on patient functional status. The specific aims were as follows: (1) to analyse the influence of LTHNC on patient functional status in terms of activities of daily living; (2) to evaluate the risk of pressure sores and pressure sore prevention in patients receiving LTHNC.

Background

LTHNC is a form of care for chronically ill persons staying at home who do not need hospitalisation, but due to their health problems they require regular nursing care that can be provided at home.

Design

A retrospective descriptive study.

Methods

A document research method was used. We collected data from the medical records of 1,058 patients receiving LTHNC at the Non‐Public Health Care Centre OMNI‐MED in Bialystok (Poland) for the years 2005–2012.

Results

Detailed analysis of scores on the Barthel Activities of Daily Living Index revealed significant improvement in patient functional status as a result of LTHNC. In patients aged 65–80, the Barthel score increased by 8.83 points, and in patients aged 64 years and younger, the score increased by 6.58 points (p < 0.001). In the oldest patients (>80 years), functional status improved the least, gaining a mean of 4.97 points on the Barthel scale. Overall, the demonstrated improvement of patient functional status and reduced risk of pressure sore development provide evidence that LTHNC is an effective form of care for elderly and chronically ill persons staying at home.

Conclusion

The findings of our study represent a positive example of the way good nursing care can benefit patients while promoting the autonomous nature of nursing.

Relevance to clinical practice

The results add to our understanding of the functioning of LTHNC by providing relevant scientific evidence which may contribute to the development of community nursing.
Effects of a Collaborative Board Game on Bullying Intervention: A Group‐Randomized Controlled Trial
Authors: Nieh Hsi‐Ping , Wu Wen‐Chi
Published: September 2018

BACKGROUND

We examined the effects of the Galaxy Rescuers game, a collaborative board game on schoolchildren's bullying intervention.

METHODS

We conducted a group‐randomized controlled trial. We recruited 328 fifth graders at an elementary school in northern Taiwan. The study took place in fall 2015 over a 7‐week period. We used the generalized estimation equation (GEE) to evaluate the intervention effects on students' scores on the outcome measures.

RESULTS

At posttest, the change in bullying knowledge was statistically significant for the game‐only group and the game‐with‐debriefing group. Students in the game‐with‐debriefing group also showed an increase in empathy and a decrease in bullying attitude. At the follow‐up test, knowledge increase remained significant for both the game‐only group and the game‐with‐debriefing group. Game satisfaction survey indicated that 66.8% of the players said that the game was enjoyable.

CONCLUSIONS

The Galaxy Rescuers game is effective in changing players' bullying knowledge, attitude, and empathy. This game is an entertaining tool for promoting awareness of bullying and encouraging defending atmosphere among children.
Active Commuting to School, Physical Activity, and Behavior Problems Among Third‐Grade Children
Authors: Mann Mana , Silver Ellen J. , Stein Ruth E. K.
Published: September 2018

BACKGROUND

We examined factors associated with active commuting to school and the relationships of active commuting and physical activity to child‐ and teacher‐reported internalizing and externalizing behavior problems in a sample of third graders.

METHODS

The study sample consisted of 13,166 third graders enrolled in the Early Childhood Longitudinal Study Kindergarten Class of 1998‐1999. “Active” commuters were children who walked to school and “passive” commuters were those who took the bus or were driven. Linear analyses evaluated differences in behavior problems by school commute, physical activity, and sports team participation after adjusting for sociodemographic, regional, and neighborhood factors.

RESULTS

Overall, 11% of children actively commuted. Type of commute differed by sociodemographics, region, urbanicity, school type, and neighborhood safety. Active commuters had less general physical activity participation and sports team participation. Commuting type and general physical activity were not associated with behavior problems, but sports team participation was associated with fewer child‐reported internalizing and externalizing behaviors as well as fewer teacher‐reported internalizing behaviors.

CONCLUSIONS

Our findings demonstrate the ongoing need for creating and maintaining physical activity programs (such as sports teams) among school‐aged children to optimize children's overall health and well‐being.
The impact of food intake on the luminal environment and performance of oral drug products with a view to in vitro and in silico simulations: a PEARRL review
Authors: Pentafragka Christina , Symillides Mira , McAllister Mark , Dressman Jennifer , Vertzoni Maria , Reppas Christos
Published: September 2018

Objectives

Using the type of meal and dosing conditions suggested by regulatory agencies as a basis, this review has two specific objectives: first, to summarize our understanding on the impact of food intake on luminal environment and drug product performance and second, to summarize the usefulness and limitations of available in vitro and in silico methodologies for the evaluation of drug product performance after food intake.

Key findings

Characterization of the luminal environment and studies evaluating product performance in the lumen, under conditions suggested by regulatory agencies for simulating the fed state, are limited. Various in vitro methodologies have been proposed for evaluating drug product performance in the fed state, but systematic validation is lacking. Physiologically based pharmacokinetic (PBPK) modelling approaches require the use of in vitro biorelevant data and, to date, have been used primarily for investigating the mechanisms via which an already observed food effect is mediated.

Better understanding of the impact of changes induced by the meal administration conditions suggested by regulatory agencies on the luminal fate of the drug product is needed. Relevant information will be useful for optimizing the in vitro test methods and increasing the usefulness of PBPK modelling methodologies.
New perspectives on pre‐Restoration Irish book history
Authors: Empey Mark
Published: September 2018

Early modern Irish book history has been reinvigorated in the last couple of decades; thanks largely to pioneering studies by Raymond Gillespie and Toby Barnard. Examining the impact of the book through the lens of social and cultural change has vastly improved our knowledge of 17th‐century Ireland. Indeed, the genre continues to expand. By focusing on the historian and antiquarian, Sir James Ware (1594–1666), this essay looks at potentially new ways book history can be analyzed. Three key aspects are investigated. First, it assesses Ware's scholarly achievements and suggests that his 11 publications were in some ways reflective of the evolving social dynamics in Stuart Ireland. Second, it analyzes his library and explores the reading habits of individuals who contacted Ware to borrow manuscripts and printed works. The items he loaned to both Catholics and Protestants are revealing, especially given the restrictive nature of institutional and private libraries. Third, it examines Ware's diverse network that crisscrossed ethnic, confessional, and political lines. In so doing, this essay challenges preconceived ideas that the various groupings in Ireland were diametrically opposed to supporting any kind of common endeavor.