bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of liposomal and 2-hydroxypropyl-β-cyclodextrin–lidocaine on cell viability and inflammatory response in human keratinocytes and gingival fibroblasts
Authors: Ferreira Luiz Eduardo Nunes , Muniz Bruno Vilela , dos Santos Cleiton Pita , Volpato Maria Cristina , de Paula Eneida , Groppo Francisco Carlos
Published: April 2016

Objectives

The aim of this study was to observe the effect multilamellar liposomes (MLV) and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) in the in-vitro effects of lidocaine in cell viability, pro-inflammatory cytokines and prostaglandin E2 release of both human keratinocytes (HaCaT) and gingival fibroblasts (HGF) cells.

Methods

HaCaT and HGF cells were exposed to lidocaine 100–1 μm in plain, MLV and HP-β-CD formulations for 6 h or 24 h. The formulation effects in cell viability were measured by XTT assay and by fluorescent labelling. Cytokines (IL-8, IL-6 and TNF-α) and PGE2 release were quantified by ELISA.

Key findings

MLV and HP-β-CD formulations did not affect the HaCaT viability, which was significantly decreased by plain lidocaine after 24 h of exposure. Both drug carriers increased all cytokines released by HGF after 24-h exposure, and none of the carriers was able to reduce the PGE2 release induced by lidocaine.

Conclusion

The effect of drug carrier in the lidocaine effects was dependent on the cell type, concentration and time of exposure. MLV and HP-β-CD showed benefits in improving cell viability; however, both of them showed a tendency to increase cytokine release when compared to the plain solution.
Long noncoding RNA H19 mediates melatonin inhibition of premature senescence of c‐kit+ cardiac progenitor cells by promoting miR‐675
Authors: Cai Benzhi , Ma Wenya , Bi Chongwei , Yang Fan , Zhang Lai , Han Zhenbo , Huang Qi , Ding Fengzhi , Li Yuan , Yan Gege , Pan Zhenwei , Yang Baofeng , Lu Yanjie
Published: April 2016

Melatonin, a hormone secreted by the pineal gland, possesses multiple biological activities such as antitumor, antioxidant, and anti‐ischemia. C‐kit+ cardiac progenitor cells (CPCs) have emerged as a promising tool for the treatment of heart diseases. However, the senescence of CPCs due to pathological stimuli leads to the decline of CPCs' functions and regenerative potential. This study was conducted to demonstrate whether melatonin antagonizes the senescence of CPCs in response to oxidative stress. Here, we found that the melatonin treatment markedly inhibited the senescent characteristics of CPCs after exposed to sublethal concentration of H2O2, including the increase in senescence‐associated β‐galactosidase (SA‐β‐gal)‐positive CPCs, senescence‐associated heterochromatin loci (SAHF), secretory IL‐6 level, and the upregulation of p53 and p21 proteins. Senescence‐associated proliferation reduction was also attenuated by melatonin in CPCs. Luzindole, the melatonin membrane receptor blocker, may block the melatonin‐mediated suppression of premature senescence in CPCs. Interestingly, we found that long noncoding RNA H19 and its derived miR‐675 were downregulated by H2O2 in CPCs, but melatonin treatment could counter this alteration. Furthermore, knockdown of H19 or miR‐675 blocked antisenescence actions of melatonin on H2O2‐treated CPCs. It was further verified that H19‐derived miR‐675 targeted at the 3′UTR of USP10, which resulted in the downregulation of p53 and p21 proteins. In summary, melatonin antagonized premature senescence of CPCs via H19/miR‐675/USP10 pathway, which provides new insights into pharmacological actions and potential applications of melatonin on the senescence of CPCs.
The Glory of God is a Human Being Fully Alive: Predictors of Positive Versus Negative Mental Health Among Clergy
Authors: Proeschold‐Bell Rae Jean , Eisenberg Ashley , Adams Christopher , Smith Bruce , Legrand Sara , Wilk Amber
Published: April 2016

Clergy fulfill vital societal functions as meaning makers and community builders. Partly because of their important roles, clergy frequently encounter stressful situations. Further, studies suggest that clergy experience high rates of depression. Despite this, few studies have examined protective factors for clergy that may increase their positive mental health. We invited all United Methodist clergy in North Carolina to participate in a survey. Of church‐serving clergy, 85 percent responded (n = 1,476). Hierarchical multiple regression was used to assess the predictors of three positive and four negative mental health outcomes. The three sets of predictors were: demographics, which explained 2–10 percent of the variances; variables typically related to mental health (social support, social isolation, and financial stress), which explained 14–41 percent of the variances; and clergy‐specific variables, which explained 14–20 percent of the variances, indicating the importance of measuring occupation‐specific variables. Some variables (e.g., congregation demands) significantly related to both positive and negative mental health, whereas others (e.g., positive congregations, congregation support) significantly related primarily to positive mental health. In addition to their intervention implications, these findings support separate consideration for negative versus positive mental health.
Single Nucleotide Polymorphisms in the Leptin‐a Gene and Associations with Growth Traits in the Golden Pompano, Trachinotus blochii
Authors: Wu Changsong , Wu Guangcan , Zhang Guoqing , Wang Qian , Luo Jian , Chen Guohua
Published: April 2016

Leptin is a multifunctional protein involved in processes such as body weight (BWT) regulation, food intake, and appetite regulation. In this study, we isolated and cloned the full‐length leptin‐a gene from the golden pompano, Trachinotus blochii. A search for polymorphisms, as well as association analyses between these polymorphisms and 10 growth traits were performed. A total of 10 polymorphisms, consisting of five single nucleotide polymorphisms (SNPs) in intron 1 (C203T, G252A, C380G, G383C, and G587A), one mutation in exon 2 (T775A), one mutation in exon 3 (G1239A), and three SNPs in the 3′‐untranslated region (G1424A, T1653A, and A1654T) were identified and genotyped in 150 individuals. The C203T and C380G polymorphisms, as well as the G1424A and T1653A polymorphisms, showed complete linkage. Association analyses revealed that the T775A polymorphism was significantly associated with BWT, body height (BWH), body length, and overall length (OL), and genotype TT had negative effects on growth traits. Additionally, the SNP G1239A was significantly associated with BWT, BWH, OL, and head length, with the GA genotype showing positive effects on growth traits. The results indicate that polymorphisms in the leptin‐a gene loci can be used as a selection criterion to improve growth traits in golden pompano.
Effect of Stocking Density on Growth, Physiological Responses, and Body Composition of Juvenile Blunt Snout Bream, Megalobrama amblycephala
Authors: Qi Chenglong , Xie Congxin , Tang Rong , Qin Xiao , Wang Deyi , Li Dapeng
Published: April 2016

The impact of stocking density on growth performance, physiological indicators, and body composition of juvenile blunt snout bream in recirculating aquaculture system was investigated in this study. Juvenile blunt snout bream were raised at stocking densities of 75, 150, 225, 300, and 450 fish/m3 for 12 wk with three replicate tanks at each density. All treatment tanks were supplied with water from the same recirculating system to ensure uniformity of water quality across groups. This study has shown that higher stocking densities had a negative effect on individual growth performance. Final body mass, specific growth rate (SGR), and weight gain decreased significantly as stocking density increased. Individual body mass as well as body length were more uniform in fish stocked at densities of 75 and 150 fish/m3 than in other groups. Stocking densities of 225 and 300 fish/m3 resulted in significant increases in serum total protein, triglyceride, lactate, and cholesterol levels, whereas blood glucose concentrations decreased significantly. In addition, decreased body lipid content and increased body moisture content were observed at stocking densities of 300 and 450 fish/m3. Overall, a density of 150 fish/m3 resulted in higher SGR and more uniform size among juvenile blunt snout bream.
Optimal Recovery from Disruptions in Water Distribution Networks
Authors: Nayak Munir A. , Turnquist Mark A.
Published: April 2016

An optimization model is developed to guide recovery of a disrupted water distribution system. The model minimizes the total cost of recovery, including the disruption cost of unmet demand during the repair process and the repair cost itself. The optimization schedules repair tasks under precedence and resource constraints and contains an embedded flow problem that optimizes the distribution of water in each time period, given the state of the network. A simulated annealing algorithm is developed for scheduling the tasks, with the embedded flow problem solved using a generalized reduced gradient method. Experiments with a test water distribution system confirm the effectiveness of the model and provide insight regarding the effects of limited resources available for recovery and of the usefulness of having multiple modes for execution of specific tasks.
BcIqg1, a fungal IQGAP homolog, interacts with NADPH oxidase, MAP kinase and calcium signaling proteins and regulates virulence and development in Botrytis cinerea
Authors: Marschall Robert , Tudzynski Paul
Published: April 2016

NADPH oxidases (Nox) produce reactive oxygen species (ROS) in multicellular eukaryotic organisms. They trigger defense reactions (‘oxidative burst’) – in phagocytes and plant cells –, and are involved in a broad range of differentiation processes. Fungal Nox‐complexes play a central role in vegetative, sexual and pathogenic processes. In contrast to mammalian systems, knowledge is limited about composition, localisation and connection to major signaling cascades in fungi. Here, we characterize a fungal homolog of the RasGAP scaffold protein IQGAP, which links several major signaling processes, including Nox in mammalian cell lines. We show that BcIqg1 interacts directly with a cytosolic, regulatory component (BcRac) and a membrane‐associated subunit (BcNoxD) of a Nox‐complex in the pathogen Botrytis cinerea. Thus, this protein may be a scaffold that mediates interaction of the catalytic subunits with the regulator BcNoxR. The protein interacts with modules of the MAP kinase‐ and calcium‐dependent signaling pathways. Functional analysis of BcIqg1 substantiated its involvement in different signaling pathways. It mediates the Ca2+‐triggered nuclear translocation of − BcCRZ1 and the MAP kinase BcBmp1. BcIqg1 is involved in resistance against oxidative and membrane stress and is required for several developmental processes including formation of sclerotia, conidial anastomosis tubes and infection cushions as well as for virulence.
Characterization of Botrytis–plant interactions using PathTrack©—an automated system for dynamic analysis of disease development
Authors: Eizner Elad , Ronen Mordechi , Gur Yonatan , Gavish Assaf , Zhu Wenjun , Sharon Amir
Published: April 2016

The measurement of disease development is integral in studies on plant–microbe interactions. To address the need for a dynamic and quantitative disease evaluation, we developed PathTrack©, and used it to analyse the interaction of plants with Botrytis cinerea. PathTrack© is composed of an infection chamber, a photography unit and software that produces video files and numerical values of disease progression. We identified a previously unrecognized infection stage and determined numerical parameters of pathogenic development. Using these parameters, we identified differences in disease dynamics between seemingly similar B. cinerea pathogenicity mutants, and revealed new details on plant susceptibility to the fungus. We showed that the difference between the lesion expansion rate on leaves and colony spreading rate on artificial medium reflects the levels of the plant immune system, suggesting that this parameter can be used to quantify plant defence. Our results shed new light and reveal new details of the interaction between the model necrotrophic pathogen B. cinerea and plants. The concept that we present is universal and may be applied to facilitate the study of various types of plant–pathogen association.
Tinea capitis outbreak among paediatric refugee population, an evolving healthcare challenge
Authors: Mashiah Jacob , Kutz Ana , Ben Ami Ronen , Savion Mihal , Goldberg Ilan , Gan Or Tamar , Zidan Omri , Sprecher Eli , Harel Avikam
Published: April 2016

Outbreaks of tinea capitis (TC) represent a major medical and economic burden. Population migrations have become a phenomenon of increasing relevance for medical conditions management. Given the recent massive arrival of immigrants, we sought to determine epidemiologic trends for TC among paediatric populations at the Tel Aviv Medical Center. We conducted a retrospective study of all TC cases diagnosed between 2010 and 2014 in a paediatric dermatology unit of a tertiary medical centre, serving as a referral centre for the paediatric refugee population from the great Tel Aviv area. Epidemiologic, clinical and treatment data including effectiveness and safety were reviewed. In all, 145 children met the inclusion criteria. Trend analyses showed increases in TC rates over the study period. Incidence rates were higher in boys than in girls. Children of African origin had the highest TC incidence rates as compared with other ethnic groups. Trichophyton violaceum and Microsporum audouinii were the predominant causative organisms. Treatment with griseofulvin was satisfactory in all cases. There was a significant increase in TC incidence rates in the Tel Aviv area over the study period. TV and MA were the predominant organisms. These trends may be a result of poor living conditions and crowded school premises.
Performance of MALDI‐TOF MS platforms for fungal identification
Authors: Cassagne Carole , Normand Anne‐Cécile , L'Ollivier Coralie , Ranque Stéphane , Piarroux Renaud
Published: April 2016

Matrix‐assisted laser desorption/ionisation mass spectrometry (MALDI‐TOF MS) is increasingly used by clinical microbiology laboratories to cope with the need for rapid, cost‐effective and accurate identification of microorganisms. Several research teams have recently succeed in identifying moulds using MALDI‐TOF MS, which was first adapted to bacteria, then to yeast identification. Since 2004, different commercial firms have released several ready‐to‐use MALDI‐TOF MS platforms. This review describes the similarities and differences between the commercially available systems. In two parts, we first describe and compare the preprocessing and identification steps between the platforms and then compare the identification efficacy of yeast, moulds and dermatophytes species.
Molecular epidemiology and in vitro antifungal susceptibility testing of 108 clinical Cryptococcus neoformans sensu lato and Cryptococcus gattii sensu lato isolates from Denmark
Authors: Hagen Ferry , Hare Jensen Rasmus , Meis Jacques F. , Arendrup Maiken Cavling
Published: April 2016

Cryptococcosis is mainly caused by members of the Cryptococcus gattii/Cryptococcus neoformans species complexes. Here, we report the molecular characterisation and in vitro antifungal susceptibility of Danish clinical cryptococcal isolates. Species, genotype, serotype and mating type were determined by amplified fragment length polymorphism (AFLP) fingerprinting and qPCR. EUCAST E.Def 7.2 MICs were determined for amphotericin B, flucytosine, fluconazole, voriconazole and isavuconazole. Most isolates were C. neoformans (serotype A; n = 66) and belonged to genotype AFLP1/VNI (n = 61) or AFLP1B/VNII (n = 5) followed by Cryptococcus deneoformans (serotype D; genotype AFLP2, n = 20), C. neoformans × C. deneoformans hybrids (serotype AD; genotype AFLP3, n = 13) and Cryptococcus curvatus (n = 2). Six isolates were C. gattii sensu lato, and one isolate was a C. deneoformans × C. gattii hybrid (genotype AFLP8). All isolates were amphotericin B susceptible. Flucytosine susceptibility was uniform MIC50 of 4–8 mg l−1 except for C. curvatus (MICs >32 mg l−1). Cryptococcus gattii sensu lato isolates were somewhat less susceptible to the azoles. MICs of fluconazole (>32 mg l−1), voriconazole (≥0.5 mg l−1) and isavuconazole (0.06 and 0.25 mg l−1 respectively) were elevated compared to the wild‐type population for 1/19 C. deneoformans and 1/2 C. curvatus isolates. Flucytosine MIC was elevated for 1/61 C. neoformans (>32 mg l−1). Antifungal susceptibility revealed species‐specific differential susceptibility, but suggested acquired resistance was an infrequent phenomenon.
A cluster of Geotrichum clavatum (Saprochaete clavata) infection in haematological patients: a first Italian report and review of literature
Authors: Del Principe Maria Ilaria , Sarmati Loredana , Cefalo Mariagiovanna , Fontana Carla , De Santis Giovanna , Buccisano Francesco , Maurillo Luca , De Bellis Eleonora , Postorino Massimiliano , Sconocchia Giuseppe , Del Poeta Giovanni , Sanguinetti Maurizio , Amadori Sergio , Pagano Livio , Venditti Adriano
Published: April 2016

Invasive fungal infections, usually Aspergillus and Candida, represent a major cause of morbidity and mortality in patients with malignant haematological diseases, but in the last years rare fungal infections have more frequently been reported. Here, we report the clinical history of three patients affected with haematological malignancies who developed an infection caused by Geotrichum (G.) clavatum. Two out of three patients were affected by acute myeloid leukaemia (AML), and one by mantle cell lymphoma (MCL). All patients received cytarabine‐based chemotherapeutic regimens and developed G. clavatum infection within 3 weeks from therapy initiation. In all cases, G. clavatum was isolated from central venous catheter and peripheral blood cultures. In vitro susceptibility test confirmed an intrinsic resistance to echinocandins and, in all cases, visceral localisations (spleen, liver and lung) were documented by total body computed tomography (CT) scan. A prolonged antifungal therapy with high doses liposomal amphotericin‐B was necessary to obtain fever resolution. Only the patient with MCL died while the other two AML recovered, and one of them after received an allogeneic stem cell transplantation. We consecutively reviewed all published cases of infection caused by G. clavatum. Our experience and literature review indicate that G. clavatum can cause invasive infection in haematological patients, mainly in those with acute leukaemia.
More Than Just “Blowing off Steam”: The Roles of Anger and Advocacy in Promoting Positive Outcomes at Work
Authors: Stickney Lisa T. , Geddes Deanna
Published: April 2016

Employee anger can be suppressed or quieted so that angry individuals only vent frustrations to supportive colleagues, rather than approach those responsible or in an organizational position to help remedy the problematic situation. The Dual Threshold Model (Geddes & Callister,) argues that although these “muted anger” venting episodes may increase unfavorable organizational outcomes, they also may prompt participants or observers of these displays to engage in advocacy or surrogacy on behalf of an angry colleague. The research reported here empirically tests this proposition and reports that advocating on behalf of one's angry colleague can enhance individual relationships at work as well as organizational functioning. Findings also show that observer felt anger intensity is a primary motivator for prompting anger advocacy and, surprisingly, advocacy is less likely on behalf of close colleagues.
The lichen genusUmbilicariain Ecuador
Authors: Hestmark Geir
Published: April 2016

Nine species of the saxicolous lichen genusUmbilicariafrom Ecuador are reported and a key is provided:U. africana, U. aprina, U. cinereorufescens, U. decussata, U. dendrophora, U. haplocarpa, U. leprosa, U. nylanderianaandU. vellea. The species diversity of this genus on the equatorial high mountains of South America is low compared to North America and Eurasia, but similar to that found on high African peaks close to the equator. The species mostly belong to a high‐alpine element with worldwide distribution. Two species belong to an Andean endemic element, vizU. haplocarpaandU. leprosa. The low diversity and low percentage of endemism may reflect the fairly recent uplift of the Andes and the comparatively small geographic extent of the alpine Andean biota. The dense rainforests of Ecuador leave few suitable open rock habitats for the establishment of these light‐craving lichens below the tree‐line (4000–4200 m a.s.l.), and thus their equatorial habitat is almost exclusively restricted to the alpine zone between the tree‐line and the snow‐line (4700–4800 m a.s.l.). The equatorial species mainly reproduce asexually by thalloconidia, and the adaptive significance of this type of reproduction in high altitude habitats is discussed.
Prevalence, characteristics, and treatment outcomes of reflux hypersensitivity detected on pH‐impedance monitoring
Authors: Patel A. , Sayuk G. S. , Gyawali C. P.
Published: April 2016

Background

Positive symptom association probability (SAP) with physiologic esophageal acid exposure time (AET) on pH‐impedance monitoring defines reflux hypersensitivity (RH), a correlate of acid sensitivity on pH monitoring. We evaluated prevalence, clinical characteristics, and symptomatic outcomes of RH in a prospective observational cohort with reflux symptoms undergoing pH‐impedance monitoring.

Methods

Reflux hypersensitivity was diagnosed when SAP was positive with pH‐ and/or impedance‐detected reflux events with physiologic AET. Symptom burden was assessed using dominant symptom intensity (DSI, product of symptom severity and frequency on 5‐point Likert scales) and global symptom severity (GSS, global esophageal symptoms on 100‐mm visual analog scales) by questionnaire, both at baseline and on prospective follow‐up. Clinical characteristics and predictors of symptomatic improvement were assessed with univariate and multivariate analyses.

Key Results

Seventy‐seven patients (29%) met criteria for RH, of which 53 patients (53.7 ± 1.8 years, 66% F) were contacted after 3.3 ± 0.2 years for follow‐up. Reflux hypersensitivity was detected on pH‐impedance testing both on and off antisecretory therapy; pH alone missed 51% of RH. About 57% reported ≥50% GSS improvement. Sixteen patients undergoing antireflux surgery (ARS) reported better symptom improvement compared to 37 patients treated medically (GSS change: p = 0.005; DSI change: p = 0.04). Hiatus hernia (p = 0.03) and surgical management (p ≤ 0.04) predicted symptom improvement on univariate analysis, while acid sensitivity was a negative predictor for outcome on both univariate (p = 0.02) and multivariate analyses (p ≤ 0.04).

Conclusions & Inferences

Reflux hypersensitivity is a mechanism for persistent reflux symptoms in almost one‐third of patients undergoing pH‐impedance testing. While acid sensitivity predicts suboptimal symptom improvement, antireflux therapy may improve RH in select settings.
Management of beta‐thalassemia–associated osteoporosis
Authors: Giusti Andrea , Pinto Valeria , Forni Gian Luca , Pilotto Alberto
Published: April 2016

Beta‐Thalassemia–associated osteoporosis is a multifactorial and complex condition. Different acquired and genetic factors are involved in its pathogenesis. These factors produce an imbalance in bone remodeling by inhibiting osteoblast activity and increasing osteoclast function, leading to bone loss and increased fracture risk. The management of patients presenting with thalassemia‐associated osteoporosis should consist of the implementation of general measures and the prescription of a specific pharmacological agent, with the aim of reducing fracture risk and preventing disability and deterioration of quality of life. General measures include control of anemia, adequate chelation therapy, healthy nutrition and lifestyle, regular exercise, adequate management of comorbid conditions, hormone replacement therapy in patients with hypogonadism, and vitamin D supplementation/therapy. Among the pharmacological agents currently available for the management of osteoporosis in postmenopausal women and men, bisphosphonates have been shown to improve bone mineral density, to reduce bone turnover, and to decrease bone/back pain in patients with thalassemia‐associated osteoporosis, with a good profile of safety and tolerability. On the other hand, there are limited experiences with other pharmacological agents (e.g., denosumab or teriparatide). The complexity of this condition presents diagnostic and therapeutic challenges and underscores the importance of a comprehensive and multidisciplinary approach.
Competition between encrusters on marine hard substrates and its fossil record
Authors: Taylor Paul D.
Published: April 2016

Many animals and plants that colonize hard surfaces in the sea are sessile and either bore into, or cement themselves permanently to the substrate surface. Because they retain their life positions after fossilization, these sclerobionts offer scope for studying biotic interactions in the fossil record. Encrusting sclerobionts compete actively for living space, with dominant competitors overgrowing the edges of subordinates. In addition to such marginal overgrowths, spatial competition may also occur through fouling in which larvae recruit directly onto the living surfaces of established sclerobionts. Spatial competition has been studied extensively in modern marine communities but there has been little research on competition between encrusters in ancient communities. This reflects poor knowledge of the taxonomy of the sclerobionts involved, as well as problems in distinguishing between overgrowth in vivo and post‐mortem. Nevertheless, if carefully interpreted, the fossil record of sclerobionts can provide an as yet largely unexploited resource for studying the long‐term ecological and evolutionary dynamics of competition.
Outcomes following implementation of a pediatric procedural sedation guide for referral to general anesthesia for magnetic resonance imaging studies
Authors: Grunwell Jocelyn R. , Marupudi Neelima K. , Gupta Rohan V. , Travers Curtis D. , McCracken Courtney E. , Williamson Julie L. , Stockwell Jana A. , Fortenberry James D. , Couloures Kevin , Cravero Joseph , Kamat Pradip P.
Published: April 2016

Background/Aims

Guidelines for referral of children to general anesthesia (GA) to completeMRIstudies are lacking. We devised a pediatric procedural sedation guide to determine whether a pediatric procedural sedation guide would decrease serious adverse events and decrease failed sedations requiring rescheduling withGA.

Methods

We constructed a consensus‐based sedation guide by combining a retrospective review of reasons for referral of children toGA(n= 221) with published risk factors associated with the inability to complete theMRIstudy with sedation. An interrupted time series analysis of 11 530 local sedation records from the Pediatric Sedation Research Consortium between July 2008 and March 2013, adjusted for case‐mix differences in the pre‐ and postsedation guide cohorts, evaluated whether a sedation guide resulted in decreased severe adverse events (SAE) and failed sedation rates.

Results

A significant increase in referrals toGAfollowing implementation of a sedation guide occurred (P< 0.001), and fewer children with anASA‐PSclass ≥IIIwere sedated using procedural sedation (P< 0.001). There was no decrease in SAE (P= 0.874) or in SAE plus airway obstruction with concurrent hypoxia (P= 0.435). There was no change in the percentage of failed sedations (P= 0.169).

Conclusions

More studies are needed to determine the impact of a sedation guide on pediatric procedural sedation services.
FK506 positively regulates the migratory potential of melanocyte‐derived cells by enhancing syndecan‐2 expression
Authors: Jung Hyejung , Oh Eok‐Soo
Published: April 2016

Although topical tacrolimus (FK506) is known to promote repigmentation by increasing the pigmentation and migration of melanocytes, the mechanism through which FK506 regulates cell migration remains unclear. Here, we report that FK506 treatment enhanced cell spreading on laminin‐332 and increased migration in both melanocytes and melanoma cells. Interestingly, FK506 also increased the expression of syndecan‐2, a transmembrane heparan sulfate proteoglycan through c‐jun terminal kinase activation. Moreover, siRNA‐mediated reduction of syndecan‐2 expression decreased FK506‐mediated cell spreading and migration in melanoma cells and decreased focal adhesion kinase phosphorylation in both melanocytes and melanoma cells. Consistent with these effects on syndecan‐2 expression, FK506 enhanced the membrane and melanosome localizations of PKCβII, a regulator of tyrosinase activity. This suggests that FK506 may play a dual regulatory role by affecting both melanogenesis and migration in melanocyte‐derived cells. Interestingly, however, FK506 failed to show any synergistic effect on the migration of UVB‐treated melanocyte‐derived cells. Taken together, these data indicate that FK506 regulates cell migration by enhancing syndecan‐2 expression, further suggesting that syndecan‐2 could be a potential target for the treatment of patients with vitiligo.
Hospital volume and mortality due to preterm patent ductus arteriosus
Authors: Michihata Nobuaki , Matsui Hiroki , Fushimi Kiyohide , Yasunaga Hideo
Published: April 2016

Background

Preterm patent ductus arteriosus (PDA) requires neonatal intensive care. The relationship between hospital volume and mortality of PDA remains poorly understood.

Methods

This was a retrospective observational study, using a national inpatient database in Japan. We identified patients who were diagnosed with PDA; exclusion criteria were as follows: (i) other cardiac complications; (ii) mild PDA treated without oral/i.v. indomethacin, surgery, or catheter intervention; (iii) age >1 year at admission; (iv) gestational age ≥32 weeks; (v) death within 3 days of admission; and (vi) transferal to other hospitals. Information was collected using the Japanese Diagnosis Procedure Combination database from July 2010 to March 2013. Hospital volume was defined as the average annual number of neonates with gestational age <32 weeks at each hospital. The outcome measure was in‐hospital mortality.

Results

A total of 2437 eligible patients treated at 199 hospitals were included. Low, medium, and high volume were defined as average annual number of preterm infants <34, 34–65, and >65, respectively. There were no significant differences in in‐hospital mortality according to hospital volume. In‐hospital mortality was identical in patients who received indomethacin alone, surgical or catheter intervention, or both after adjustment for patient background.

Conclusions

There was no significant relationship between hospital volume and in‐hospital mortality due to preterm PDA. Centralization of patients with this condition may not be necessary.
Increased temperature causes protein limitation by reducing the efficiency of nitrogen digestion in the ectothermic herbivore Spodoptera exigua
Authors: Lemoine Nathan P. , Shantz Andrew A.
Published: April 2016

For insect herbivores, rising temperatures lead to exponentially higher metabolic rates. As a result, basic nutritional demands for protein and carbohydrates can be altered at high temperatures. It is hypothesized that temperature‐driven increases in metabolic nitrogen turnover will exacerbate protein limitation by increasing metabolic nitrogen demand. To test this hypothesis, the present study examines whether metabolic nitrogen turnover at higher temperatures causes protein limitation of a generalist herbivore, the beet armyworm Spodoptera exigua Hübner (Lepidoptera : Noctuidae). Third‐instar S. exigua larvae were reared at 25 and 30 °C on three artificial diets of varying protein : carbohydrate ratios (23 : 26, 17 : 26 and 6 : 26 %P : %C, respectively) and their growth rates, metabolic nitrogen demand and consumption rates were measured. Warming was found to lead to temperature‐induced protein limitation of the S. exigua larvae by increasing metabolic nitrogen demand at the same time as reducing nitrogen digestion efficiency. Because climate change is increasing atmospheric temperatures rapidly worldwide, it is suggested that a better understanding of how temperature change can influence metabolic demands will provide key information for predicting herbivore growth rates and foraging strategies in the future.
Testing small molecule analogues of the Acanthocheilonema viteae immunomodulator ES‐62 against clinically relevant allergens
Authors: Janicova L. , Rzepecka J. , Rodgers D. T. , Doonan J. , Bell K. S. , Lumb F. E. , Suckling C. J. , Harnett M. M. , Harnett W.
Published: April 2016

ES‐62 is a glycoprotein secreted by the filarial nematode Acanthocheilonema viteae that protects against ovalbumin (OVA)‐induced airway hyper‐responsiveness in mice by virtue of covalently attached anti‐inflammatory phosphorylcholine (PC) residues. We have recently generated a library of small molecule analogues (SMAs) of ES‐62 based around its active PC moiety as a starting point in novel drug development for asthma and identified two compounds – termed 11a and 12b – that mirror ES‐62's protective effects. In this study, we have moved away from OVA, a model allergen, to test the SMAs against two clinically relevant allergens – house dust mite (HDM) and cockroach allergen (CR) extract. We show that both SMAs offer some protection against development of lung allergic responses to CR, in particular reducing eosinophil infiltration, whereas only SMA 12b is effective in protecting against eosinophil‐dependent HDM‐induced allergy. These data therefore suggest that helminth molecule‐induced protection against model allergens may not necessarily translate to clinically relevant allergens. Nevertheless, in this study, we have managed to demonstrate that it is possible to produce synthetic drug‐like molecules based on a parasitic worm product that show therapeutic potential with respect to asthma resulting from known triggers in humans.
High Dimensional Semiparametric Latent Graphical Model for Mixed Data
Authors: Fan Jianqing , Liu Han , Ning Yang , Zou Hui
Published: April 2016

We propose a semiparametric latent Gaussian copula model for modelling mixed multivariate data, which contain a combination of both continuous and binary variables. The model assumes that the observed binary variables are obtained by dichotomizing latent variables that satisfy the Gaussian copula distribution. The goal is to infer the conditional independence relationship between the latent random variables, based on the observed mixed data. Our work has two main contributions: we propose a unified rank-based approach to estimate the correlation matrix of latent variables; we establish the concentration inequality of the proposed rank-based estimator. Consequently, our methods achieve the same rates of convergence for precision matrix estimation and graph recovery, as if the latent variables were observed. The methods proposed are numerically assessed through extensive simulation studies, and real data analysis.
A Stochastic Graphene Growth Kinetics Model
Authors: Sosina Sobambo , Dasgupta Tirthankar , Huang Qiang
Published: April 2016

Graphene is an emerging nanomaterial for a wide variety of novel applications. Controlled synthesis of high quality graphene sheets requires analytical understanding of graphene growth kinetics. Graphene growth via chemical vapour deposition starts with randomly nucleated islands that gradually develop into complex shapes, grow in size and eventually connect together to form a graphene sheet. Models proposed for this stochastic process do not, in general, permit assessment of uncertainty. We develop a stochastic framework for the growth process and propose Bayesian inferential models, which account for the data collection mechanism and allow for uncertainty analyses, for learning about the kinetics from experimental data. Furthermore, we link the growth kinetics with controllable experimental factors, thus providing a framework for statistical design and analysis of future experiments.
Vancomycin‐induced thrombocytopenia: a rare adverse effect in a patient ­submitted to bone graft in the jaw
Authors: Danieletto Carolina Ferrairo , Ferreira Gustavo Zanna , Farah Gustavo Jacobucci , Cuman Roberto Kenji Nakamura
Published: April 2016

Introduction

Thrombocytopenia is the reduction in the number of blood ­platelets, which may be caused by ­several different conditions such as sepsis, disseminated intravascular ­clotting, and large blood losses. Additionally, in rare situations, thrombocytopenia may also be induced by the use of medicaments. One of these drugs is the vancomycin, a glycopeptide presently used against ­serious infections involving Gram‐positive bacteria such as the methicillin‐resistant Staphylococcus aureus and penicillin‐resistant Streptococcus.

Objective

The objective of this study is to report on a case of serious vancomycin‐induced thrombocytopenia in a patient infected with methicillin‐resistant S. aureus after mandibular reconstruction with autogenous bone graft, and to draw attention to the importance of this clinically rare adverse effect.

Conclusion

Vancomycin‐induced thrombocytopenia is a rare condition, which is also a significant disorder that demands attention and the rapid identification and replacement of the antimicrobial agent.
We Use Dialysate Potassium Levels That Are Too Low in Hemodialysis
Authors: Tucker Bryan , Moledina Dennis G.
Published: April 2016

Sudden cardiac death accounts for a quarter of all deaths in hemodialysis patients. While this group is at high risk for cardiovascular events, there are certain modifiable factors that have been associated with higher risk of sudden cardiac death. These include short dialysis time, high ultrafiltration rate, and dialysate with a low potassium or calcium concentration. While it is impossible to discern the relative contribution of each of these factors, our review focuses on the role of dialysate potassium concentration in sudden cardiac death. Retrospective studies have identified low potassium dialysate (<2–3 mEq/l) as a risk factor for sudden cardiac death, particularly in patients with predialysis serum potassium concentrations <5 mEq/l. However, patients with predialysis hyperkalemia (≥5.5 mEq/l) may be an exception since a significant association of low potassium dialysate with sudden cardiac death was not observed in this subgroup. Dialysis prescribers must employ alternatives to low dialysate potassium concentrations to achieve potassium control such as increasing dialysis time and frequency, dietary restriction of potassium, prevention and treatment of constipation, discontinuation of medications contributing to hyperkalemia and traditional (or newer, better tolerated) potassium binding resins. Finally, one must also address other factors associated with sudden cardiac death such as short dialysis time, high ultrafiltration rate, and low calcium concentration dialysate.
Membrane‐based Therapeutic Plasma Exchange: A New Frontier for Nephrologists
Authors: Gashti Casey N.
Published: April 2016

Therapeutic plasma exchange has long been utilized to manage a variety of immune‐mediated diseases. The underlying principle is the removal of a circulating pathogenic substance from the plasma and substitution with a replacement fluid. Different methodologies of plasma separation include the use of centrifuge, which relies on the variation in the specific gravity of blood components, and membrane‐based separation, which relies on particle size. With advancements in technology and clinical insight into disease pathophysiology, membrane technology has become more biocompatible, safer, and more adaptable to conventional hemodialysis and hemofiltration machines. As such, nephrologists, who are familiar with management of extracorporeal blood purification systems, are increasingly involved with membrane‐based plasma separation. This review aims to highlight the technical aspects of membrane‐based separation, review the prescription for therapy, and draw comparisons with the centrifuge‐based technique when applicable.
Uncommon Ground: The Role of Different Place Attachments in Explaining Community Renewable Energy Projects
Authors: van Veelen Bregje , Haggett Claire
Published: April 2016

For rural communities, energy projects can provide a host of benefits, and yet also be a source of significant conflict. Place attachment has become an increasingly popular concept for understanding local responses to large scale renewable energy installations. However, there has been significantly less attention paid to how place attachment influences local responses to community‐led developments. This study contributes to the body of research on place attachment by examining its role in shaping opinions on two locally initiated projects. Interviews were conducted with residents in two rural communities in the Scottish Highlands, where community organisations are developing renewable energy projects. The findings show that place attachment was an important motivator for the development of these projects, but that different types of place attachment also formed a key source of disagreement. Finally, the implications of these findings for rural communities engaging in community‐led development initiatives will be discussed.
Expression of classical HLA class I molecules: regulation and clinical impacts
Authors: René C. , Lozano C. , Eliaou J.‐F.
Published: April 2016

Human leukocyte antigen (HLA) class I genes are ubiquitously expressed, but in a tissue specific‐manner. Their expression is primarily regulated at the transcriptional level and can be modulated both positively and negatively by different stimuli. Advances in sequencing technologies led to the identification of new regulatory variants located in the untranslated regions (UTRs), which could influence the expression. After a brief description of the mechanisms underlying the transcriptional regulation of HLA class I genes expression, we will review how the expression levels of HLA class I genes could affect biological and pathological processes. Then, we will discuss on the differential expression of HLA class I genes according to the locus, allele and UTR polymorphisms and its clinical impact. This interesting field of study led to a new dimension of HLA typing, going beyond a qualitative aspect.
Impact of HLA in cord blood transplantation outcomes
Authors: Ruggeri A. , Paviglianiti A. , Gluckman E. , Rocha V.
Published: April 2016

Umbilical cord blood (UCB) emerged in the last 20 years as a valid alternative source of hematopoietic stem cell (HSC) in allogeneic transplantation setting, mainly in the absence of a fully human leucocyte antigen (HLA)‐matched sibling. The probability of finding a matched unrelated donor through the registries varies from 20 to 70%, depending on the ethnicity of the patients. Therefore, patients in need may benefit of an HLA‐mismatched hematopoietic stem cell transplantation from haploidentical donors or from UCB. One of the advantages of using UCB is the lower incidence of acute graft‐versus‐host‐disease and allowance of greater HLA mismatch. Conversely, the low number of HSCs and lymphocytes and specific immunological features of T cells are associated with delayed engraftment and immune reconstitution and consequently, increased opportunistic infections. Nevertheless, retrospective studies showed similar results comparing UCB with other stem cell sources, both in pediatric and adult setting. The ability to use partially HLA‐matched UCB units allows expanding the donor pool. Many UCB banks have strategies to increase their inventory including UCB grafts that have rare haplotypes. HLA and cell dose are very important factors associated with outcomes after umbilical cord blood transplantation (UCBT) that interact with each other. Increasing cell dose counterbalances the number of HLA disparities. Understanding those interactions, the role of HLA mismatches and other immunogenic factors, are important to allow clinicians to choose the best cord blood graft for patients. This review will describe the role of HLA in UCBT setting.
Creating a chimeric clathrin heavy chain that functions independently of yeast clathrin light chain
Authors: Boettner Douglas R. , Segarra Verónica A. , Moorthy Balaji T. , de León Nagore , Creagh John , Collette John R. , Malhotra Arun , Lemmon Sandra K.
Published: April 2016

Clathrin facilitates vesicle formation during endocytosis and sorting in the trans‐Golgi network (TGN)/endosomal system. Unlike in mammals, yeast clathrin function requires both the clathrin heavy (CHC) and clathrin light (CLC) chain, since Chc1 does not form stable trimers without Clc1. To further delineate clathrin subunit functions, we constructed a chimeric CHC protein (Chc‐YR) , which fused the N‐terminus of yeast CHC (1–1312) to the rat CHC residues 1318–1675, including the CHC trimerization region. The novel CHC‐YR allele encoded a stable protein that fractionated as a trimer. CHC‐YR also complemented chc1Δ slow growth and clathrin TGN/endosomal sorting defects. In strains depleted for Clc1 (either clc1Δ or chc1Δ clc1Δ), CHC‐YR, but not CHC1, suppressed TGN/endosomal sorting and growth phenotypes. Chc‐YR‐GFP (green fluorescent protein) localized to the TGN and cortical patches on the plasma membrane, like Chc1 and Clc1. However, Clc1‐GFP was primarily cytoplasmic in chc1Δ cells harboring pCHC‐YR, indicating that Chc‐YR does not bind yeast CLC. Still, some partial phenotypes persisted in cells with Chc‐YR, which are likely due either to loss of CLC recruitment or chimeric HC lattice instability. Ultimately, these studies have created a tool to examine non‐trimerization roles for the clathrin LC.
Single‐unit transfusions in the obstetric setting: a qualitative study
Authors: Mayson Eleni , Shand Antonia W. , Ford Jane B.
Published: April 2016

BACKGROUND

The rate of obstetric blood transfusion is increasing, and there is hospital variation in its use. Recent Australian guidelines recommend a restrictive transfusion strategy in maternity patients who are not actively bleeding and advocate single‐unit red blood cell (RBC) transfusions followed by clinical reassessment to determine the need for further transfusion.

STUDY DESIGN AND METHODS

The aim of this study was to identify factors influencing single RBC unit use when initiating transfusion in a postpartum woman with noncritical bleeding. A qualitative research study using semistructured interviews was conducted. Nine maternity hospitals were chosen to cover a range of clinical settings and obstetric transfusion rates in Australia. Interviews were conducted with the key decision makers in obstetric blood transfusion. Interviews were transcribed and coded, and themes were developed.

RESULTS

One hundred twenty‐five interviews were conducted, including 61 doctors' interviews among obstetric (n = 42) and hematology (n = 19) staff. Most doctors (54%) interviewed would initiate transfusion with 2 RBC units; and, of those who started with single‐unit transfusions, most (63%) had practiced obstetrics for less than 5 years. Clinician and external factors influenced decision making. Important clinician factors included perceived utility or clinical need and education/experience. External factors included influence of colleagues, clinical context, availability of RBC units, and regulation mechanisms.

CONCLUSION

The decision to use single‐unit RBC transfusion varied between and within hospitals. Efforts to reduce exposure to blood in the obstetric setting via the number of units transfused may need to target perceptions regarding the utility of single units and lack of experience with this approach.