bluuebunny/crossref_metadata_2025 huggingface dataset:
Facile synthesis of high specific activity 4‐[1‐14C]butyl‐1,2‐diphenylpyrazolidine‐3,5‐dione (phenylbutazone) using nucleophilic substitution
Authors: Singh Anuradha , Hakk Heldur , Lupton Sara J.
Published: December 2017

Metabolism, environmental fate, and low concentration food residue studies would be facilitated by the use of radiolabeled test articles that can be readily quantified within complex matrices. However, radiochemical approaches for such studies require high specific activities to allow analytical detection of correspondingly low masses of test article. The synthesis of high specific activity (>50 μCi/μmol) [14C]‐radiolabeled phenylbutazone presents a challenge using existing methodology, mainly due to the low solvent volumes required and vigorous refluxing needed to close the pyrazolidinedione ring. Herein, we report on the significant modification of an existing method that allows the synthesis of low masses of high specific activity (>50 μCi/μmol) [14C]‐phenylbutazone under mild conditions with simple purification and high yield. The closure of the pyrazolidinedione ring of 1,2‐diphenyl‐3,5‐pyrazolidinedione was accomplished as a first step with unlabeled 1,2‐diphenylhydrazine and diethyl malonate in 32% yield under gram‐scale conditions, which avoided the challenges of low solvent use and vigorous refluxing. Low mass of high specific activity n‐[1‐14C]‐butyl bromide was then added via a nucleophilic substitution reaction as a final step. Yields ranged from 65% to 92% during multiple synthetic attempts with unlabeled butyl bromide and were greatly influenced by reaction stoichiometry and the selection of base.
Simultaneous enantioselective determination of six pesticides in aqueous environmental samples by chiral liquid chromatography with tandem mass spectrometry
Authors: Zhao Pengfei , Lei Shuo , Xing Mingming , Xiong Shihang , Guo Xingjie
Published: December 2017

A robust and sensitive method was developed for the enantiomeric analysis of six chiral pesticides (including metalaxyl, epoxiconazole, myclobutanil, hexaconazole, napropamide, and isocarbophos) in aquatic environmental samples. The optimized chromatographic conditions for the quantification of all the 12 enantiomers were performed with Chiralcel OD‐RH column using mobile phase consisting of 0.1% aqueous formic acid and acetonitrile operated under reversed‐phase conditions and then analyzed using liquid chromatography with tandem mass spectrometry. Twelve enantiomers were detected in multiple reaction monitoring mode. Solid‐phase extraction and dispersive liquid–liquid microextraction were employed in this study. Response surface methodology was applied to assist in the dispersive liquid–liquid microextraction optimization. Under the optimum conditions, recoveries of pesticides enantiomers varied from 83.0 to 103.2% at two spiked levels with relative standard deviation less than 11.5%. The concentration factors were up to 1000 times. Method detection and quantification limits varied from 0.11 to 0.48 ng/L and from 0.46 to 1.49 ng/L, respectively. Finally, this method was used to determination of the enantiomers composition of the six pesticides in environmental aqueous matrices, which will help better understand the behavior of individual enantiomer and make accurate risk assessment to ecosystems.
Observational Study Using Ultrasound to Assess Midline Labor Epidural Analgesia Placement and Analgesic Efficacy
Authors: Weiniger Carolyn F. , Cobb Benjamin , Wang Rachel R. , Carvalho Brendan
Published: December 2017

Objectives

Labor epidural analgesia failure may relate to nonmidline placement of epidural catheters. We hypothesized that greater deviations of the epidural catheter insertion point from the ultrasound (US)‐determined midline would be associated with less effective labor analgesia.

Methods

A prospective ethically approved cohort study was conducted. Fifty‐two healthy average‐sized women receiving labor epidural analgesia, inserted by the landmark technique, were approached after delivery. Immediately after removing the epidural catheter, we determined the epidural space midline using US and compared it to the epidural catheter insertion point and to the patient‐identified midline (assessed by a pinprick in 1‐mm increments). Correlations between the US midline‐to‐catheter insertion point distance and additional epidural local anesthetic requirements (primary outcome), pain verbal numeric rating scale scores (0–10) 1 hour after epidural insertion, and maternal satisfaction with analgesia were determined. The differences in distances were assessed by a Bland‐Altman analysis.

Results

There were no significant correlations between the US midline‐to‐epidural catheter insertion point distance and additional epidural local anesthetic requirements (R2 = 0.138; P = .33), pain verbal numeric rating scale scores 1 hour after the epidural (R2 = 0.121; P = .40) or maternal satisfaction (R2 = 0.085; P = .57). The Bland‐Altman analysis revealed that the mean ± SD US midline‐to‐epidural catheter insertion point distance and patient‐identified midline distances were 0.38 ± 0.31 and 0.35 ± 0.46 cm, respectively.

Conclusions

In our laboring population, the hypothesis that nonmidline epidural insertion is associated with less‐effective labor analgesia was not confirmed in this study cohort. We found minimal differences in distances between the US midline to epidural catheter insertion point and US midline to patient‐identified midline.
Time‐resolved monitoring of enzyme activity with ultrafast Hyper‐CEST spectroscopy
Authors: Döpfert Jörg , Schnurr Matthias , Kunth Martin , Rose Honor May , Hennig Andreas , Schröder Leif
Published: December 2017

We propose a method to dynamically monitor the progress of an enzymatic reaction using NMR of hyperpolarized 129Xe in a host–guest system. It is based on a displacement assay originally designed for fluorescence experiments that exploits the competitive binding of the enzymatic product on the one hand and a reporter dye on the other hand to a supramolecular host. Recently, this assay has been successfully transferred to NMR, using xenon as a reporter, cucurbit[6]uril as supramolecular host, and chemical exchange saturation transfer with hyperpolarized Xe (Hyper‐CEST) as detection technique. Its advantage is that the enzyme acts on the unmodified substrate and that only the product is detected through immediate inclusion into the host. We here apply a method that drastically accelerates the acquisition of Hyper‐CEST spectra in vitro using magnetic field gradients. This allows monitoring the dynamic progress of the conversion of lysine to cadaverine with a temporal resolution of ~30 s. Moreover, the method only requires to sample the very early onset of the reaction (<0.5% of substrate conversion where the host itself is required only at μM concentrations) at comparatively low reaction rates, thus saving enzyme material and reducing NMR acquisition time. The obtained value for the specific activity agrees well with previously published results from fluorescence assays. We furthermore outline how the Hyper‐CEST results correlate with xenon T2 measurements performed during the enzymatic reaction. This suggests that ultrafast Hyper‐CEST spectroscopy can be used for dynamically monitoring enzymatic activity with NMR.
Practical aspects of real‐time pure shift HSQC experiments
Authors: Kiraly Peter , Nilsson Mathias , Morris Gareth A.
Published: December 2017

Pure shift NMR spectroscopy has become an efficient tool for improving resolution in proton NMR spectra by removing the effect of homonuclear couplings. The introduction of real‐time acquisition methods has allowed the main drawback of pure shift NMR, the long experiment times needed, to be circumvented. Real‐time methods use periodic application of J‐refocusing pulse sequence elements, acquiring a single free induction decay, in contrast to previous methods that construct a pure shift interferogram by concatenating excerpts from multiple free induction decays. In the important heteronuclear single‐quantum correlation experiment, implementing real‐time pure shift data acquisition typically leads to the simultaneous improvement of both resolution and sensitivity. The current limitations of and problems with real‐time pure shift acquisition methods are discussed here in the context of heteronuclear single‐quantum correlation experiments. We aim to provide a detailed account of the technical challenges, together with a practical guide to exploiting the full potential of such methods.
Crosslinked anion exchange membranes with connected cations
Authors: Zhang Wenxu , Liu Ye , Liu Xiaohui , Horan James L. , Jin Ying , Ren Xiaoming , Ertem S. Piril , Seifert Soenke , Liberatore Matthew W. , Herring Andrew M. , Coughlin Edward Bryan
Published: December 2017

The selective transport of ions has crucial importance in biological systems as well as modern‐day energy devices, such as batteries and fuel cells, and water purification membranes. Control over ion movement can be exerted by ligation, ion channel dimensions, solvation, and electrostatic interactions. Polyelectrolyte hydrogels can provide aligned pathways for counter ion transport but lack mechanical integrity, while polyelectrolyte membranes typically suffer from the absence of an ion transport channel network. To develop polymer membranes for improved ion transport, we present the design of a novel material that combines the advantages of aligned pathways found in polyelectrolyte hydrogel and mechanical robustness in conventional membranes. The ionic species were organized via controlled copolymerization of a quaternizable monomer. Additionally, dimensional stability was then incorporated through a cast/crosslinking method to lock in the network of connected cationic groups. This strategy resulted in dramatically enhanced ion transport, as characterized by ionic conductivities (>80 mS/cm for Cl–, and ∼200 mS/cm for OH–). © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 618–625
Factors driving public tolerance levels and information‐seeking behaviour concerning insects in the household environment
Authors: Schoelitsz Bruce , Poortvliet P Marijn , Takken Willem
Published: December 2017

BACKGROUND

The public's negative attitudes towards household insects drive tolerance for these insects and their control. Tolerance levels are important in integrated pest management (IPM), as are pest knowledge and information. The risk information seeking and processing (RISP) model describes the relationships between personal factors and information‐seeking behaviour. We combined IPM and RISP to determine important relationships between factors driving insect tolerance levels and information‐seeking behaviour through an online survey and tested whether this model is valid and generally applicable.

RESULTS

Relationships between variables from both IPM and RISP models were tested for seven insect species. Tolerance levels were measured with two factors: willingness to pay for pest control and whether insects are tolerated. Willingness to pay for control was positively affected by age, experience, risk perception, insect characteristics, and negative emotions and affected behavioural intention, by influencing information sufficiency and information‐seeking behaviour. Tolerability was influenced by perception of insect characteristics and determines whether control measures are taken.

CONCLUSION

It was possible to combine the RISP and IPM models. Relevant driving factors were a person's age, experience, risk perception, negative affective responses, tolerance levels, relevant channel beliefs about online forums, information sufficiency and information‐seeking behaviour. There was, however, variation in important factors between different insects. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Finding all‐nonmetal transition‐metal‐like superatom and its magnetic building block
Authors: Jiang Hui‐Hui , He Hui‐Min , Li Ying , Wu Di , Liu Jia‐Yuan , Yang Hui , Sun Wei‐Ming , Zhong Rong-Lin , Zhou Zhong-Jun , Hou Jian‐Hua , Wang Jia‐Jun , Li Zhi‐Ru
Published: December 2017

In novel superatom chemistry, it is very attractive that all‐metal clusters can mimic the behaviors of nonmetal atoms and simple nonmetal molecules. Wizardly all‐metal halogen‐like superatom Al13 with 2P5 sub shell (corresponding to the 3p5 of chlorine) is the most typical example. In contrast, how to mimic the behaviors of magnetic transition‐metal atom using all‐nonmetal cluster is an intriguing challenge for superatom chemistry. In response to this based on human intuition, using quantum chemistry methods and extending jellium model from metal cluster to all‐nonmetal cluster, we have found out that all‐nonmetal octahedral B6 cluster with characteristic jellium electron configuration 1S21P62S21D8 in the triplet ground state can mimic the behaviors of transition‐metal Ni atom with electron configuration 3s23p64s23d8 in electronic configuration, physics and chemistry. Interestingly, the characteristic order of 1S1P2S1D for the B6 nonmetal cluster with short B‐B lengths is different from that of the traditional jellium model—1S1P1D2S for metal clusters with long M‐M lengths, which exhibits a novel size effect of nonmetal cluster on jellium orbital ordering. Based on the jellium electron configuration, the B6 with the spin moment value of 2μB is a new all‐nonmetal transition‐metal nickel‐like superatom exhibiting a new kind of all‐nonmetal magnetic superatom. Finding the application of the all‐nonmetal magnetic superatom, we encapsulate the magnetic superatom B6 inside fully hydrogenated fullerene forming a clathrate B6@C60H60 with the spin moment value of 2μB. As the C60H60 cage as a polymerization unit can conserve the spin moment of endohedral B6, the clathrate B6@C60H60 is a new all‐nonmetal magnetic superatom building block. Naturally, magnetic superatom structures of the B6 and B6@C60H60 may be metastable.
Exploring the catalytic efficiency of X‐doped (X=B, N, P) graphene in oxygen reduction reaction: Influence of solvent and border effects
Authors: Aguilar‐Galindo Fernando , Ocón Pilar , Poyato José Manuel L.
Published: December 2017

X doped graphene surfaces, where X is a heteroatom, are interesting for electrocatalytic applications in fuel cell because active sites are generated on the surface. In this work, a new large size surface is proposed to allow several heteroatoms to be located in positions far from the edge of the graphene sheet. Dispersion terms were introduced in the calculations which are crucial in adsorption processes. Natural charges are analyzed to determine the most active sites. A four‐electron transfer mechanism is assumed. The energies calculated for each step of the mechanism reveal that the P‐doped or the B‐doped surface are the ones that favors the oxygen reduction reaction the most, depending on the media.
Acute progression of aspergillosis in a patient with lung cancer receiving nivolumab
Authors: Uchida Naohiro , Fujita Kohei , Nakatani Koichi , Mio Tadashi
Published: December 2017

A 65‐year‐old man with chronic progressive pulmonary aspergillosis (CPPA) was admitted for the treatment of lung adenocarcinoma while receiving an immune checkpoint inhibitor, nivolumab. The tumour responded well to the therapy, but the cavity of CPPA became large in contrast to the tumour after 20 courses of therapy. He was diagnosed as having exacerbation of CPPA and successfully and concurrently treated with an antifungal agent and nivolumab. Since there was absence of obvious immunosuppression and the presence of a drastic effect on tumour remission during nivolumab therapy, this phenomenon suggested that the trigger of CPPA progression was dependent not on immunosuppression but on a hyperreaction to microorganisms, which was similar to the immune reconstitution inflammatory syndrome caused by nivolumab. This was a thought‐provoking case in which the immune checkpoint inhibitor had a paradoxical effect for the tumour and infection.
Cost-effectiveness of WHO-Recommended Algorithms for TB Case Finding at Ethiopian HIV Clinics
Authors: Adelman Max W , McFarland Deborah A , Tsegaye Mulugeta , Aseffa Abraham , Kempker Russell R , Blumberg Henry M
Published: December 2017

Background

The World Health Organization (WHO) recommends active tuberculosis (TB) case finding and a rapid molecular diagnostic test (Xpert MTB/RIF) to detect TB among people living with HIV (PLHIV) in high-burden settings. Information on the cost-effectiveness of these recommended strategies is crucial for their implementation.

Methods

We conducted a model-based cost-effectiveness analysis comparing 2 algorithms for TB screening and diagnosis at Ethiopian HIV clinics: (1) WHO-recommended symptom screen combined with Xpert for PLHIV with a positive symptom screen and (2) current recommended practice algorithm (CRPA; based on symptom screening, smear microscopy, and clinical TB diagnosis). Our primary outcome was US$ per disability-adjusted life-year (DALY) averted. Secondary outcomes were additional true-positive diagnoses, and false-negative and false-positive diagnoses averted.

Results

Compared with CRPA, combining a WHO-recommended symptom screen with Xpert was highly cost-effective (incremental cost of $5 per DALY averted). Among a cohort of 15 000 PLHIV with a TB prevalence of 6% (900 TB cases), this algorithm detected 8 more true-positive cases than CRPA, and averted 2045 false-positive and 8 false-negative diagnoses compared with CRPA. The WHO-recommended algorithm was marginally costlier ($240 000) than CRPA ($239 000). In sensitivity analysis, the symptom screen/Xpert algorithm was dominated at low Xpert sensitivity (66%).

Conclusions

In this model-based analysis, combining a WHO-recommended symptom screen with Xpert for TB diagnosis among PLHIV was highly cost-effective ($5 per DALY averted) and more sensitive than CRPA in a high-burden, resource-limited setting.
Virtual Simulated Care Coordination Rounds for Nursing Students
Authors: Badowski Donna M.
Published: December 2017

Implementation of the Affordable Care Act has nursing education reflecting on paradigm shifts in order to prepare nursing students for the evolving health care environment. The traditional focus of nursing education on nursing care in acute care settings does not provide learning experiences in care coordination and transitional care management skills. Virtual simulated care coordination rounds, using the National League for Nursing Advancing Care Excellence resources, offer nursing students an innovative experience in care coordination and transition care management.
Advanced Nursing Education
Authors: McGhie-Anderson Rose Lavine
Published: December 2017

AIM

The purpose of this study was to gain an understanding of the social processes associated with the decision of diploma and associate degree nurses to advance academically.

BACKGROUND

Advanced nursing education needs to be pursued along the continuum of the nursing career path. This education process is indispensable to the role of nurses as educator, manager, nurse leader, and researcher who will effect policy changes, assume leadership roles as revolutionary thinkers, and implement paradigmatic shifts.

METHOD

Data were collected from two groups of participants using face-to-face, semistructured interviews. Group 1 consisted of diploma and associate degree nurses; Group 2 consisted of baccalaureate, masters, and doctoral degree nurses who have progressed academically.

RESULTS

Emerging from the thick, rich data were core categories of rewarding, motivating, and supporting as critical factors that influence professional advancement.

CONCLUSION

This qualitative study elucidated that professional advancement was the social process that grounds. The emergent theory was the theory of professional advancement.
Foreign Body Reaction Mimicking Sarcoma
Authors: Segreto Francesco , Marangi Giovanni Francesco , Delle Femmine Pietro Francesco , Greco Federico , Persichetti Paolo
Published: December 2017

Foreign body reaction can sometimes mimic the features of sarcoma. A 42-year-old patient was referred to our department for a rapidly growing subcutaneous mass in the posteromedial aspect of the lower leg. Ultrasonography and magnetic resonance imaging were highly suggestive for soft tissue sarcoma. The patient underwent surgical resection. The histho-pathologic diagnosis found that the supposed sarcoma was an inflammatory pseudo-tumor, also referred to as “gossypiboms”. Surgeons must be aware that, in some cases, the imaging cannot reliably distinguish between sarcoma and foreign body reaction.
Biodynamic Excisional Skin Tension Lines for Excisional Surgery of the Lower Limb and the Technique of Using Parallel Relaxing Incisions to Further Reduce Wound Tension
Authors: Paul Sharad P.
Published: December 2017

Background:

Closing of defects of the lower limb after skin cancer excision poses a challenge in lower limb skin. Although the concept of relaxed skin tension lines has been established as ideal on the face, on the lower limb there remains confusion between Langer’s lines and wrinkle lines, and this study was done with the task of identifying and mapping biodynamic excisional skin tension (BEST) lines on the lower limb.

Methods:

Following studies on BEST lines elsewhere on the body, the author investigated BEST lines on the lower limb. Using a specially designed tensiometer, inherent skin tension (pretension) and wound-closing tension were studied along with the force needed to bring the wound edges together after excision of a lesion in 23 cases with defects ranging from 1.5 to 4.5 cm in diameter. Skin tension measurements of skin lines (relaxed skin tension lines (RSTL) versus BEST) and vertical closure (BEST) versus vertical closure with a parallel relaxing incision were undertaken and followed by statistical analyses utilizing the paired t test and the unpaired Student’s t tests.

Results:

BEST lines run in the vertical direction on the lower limb, that is, closure in a vertical direction resulted in a statistically significant reduction in closing tension when compared with other directions. Using a parallel relaxing incision can offer further reduction in tension, if needed.

Conclusion:

BEST lines of the lower limb are discussed, and a new technique of using parallel relaxing incisions to achieve closure of larger defects is also presented as an alternative to cutaneous flaps or grafts in the lower limb.
Changes in Sunken Eyes Combined with Blepharoptosis after Levator Resection
Authors: Mawatari Yuki , Fukushima Mikiko , Kawaji Takahiro
Published: December 2017

Background:

This study aims to report the changes in sunken eyes combined with blepharoptosis after levator resection.

Methods:

Analysis involved 60 eyes from 32 patients with sunken eyes combined with blepharoptosis. Advancement of the levator aponeurosis and the Müller’s muscle complex (levator resection) was performed in these patients. Area of upper eyelid sulcus (AES) was defined as the area of the upper eyelid shadow. The digital images were converted to black and white using image-processing software (Adobe Photoshop), and the AES was calculated using ImageJ software. In addition, margin reflex distance, eyebrow height (EBH), and AES were measured before and 3 months after surgery to assess the changes in the eyelids.

Results:

Preoperative AES was significantly correlated to age (P < 0.0001; r = 0.8062). Sunken eyes were remarkably improved after levator resection in all patients. Mean margin reflex distance significantly increased, whereas mean EBH and mean AES significantly decreased at 3 months after surgery (P < 0.0001). The AES change was significantly correlated to the EBH change (P < 0.0001; r = 0.5184).

Conclusions:

The principal aim of levator resection is to improve upper eyelid height and visual fields; however, this technique can alter the location of the eyebrow and upper orbital fat. The effects fill the hollowness of the upper eyelid and can remarkably improve sunken eyes.
Childhood Infections and Subsequent School Achievement Among 598,553 Danish Children
Authors: Köhler-Forsberg Ole , Sørensen Holger J. , Nordentoft Merete , McGrath John J. , Benros Michael E. , Petersen Liselotte
Published: December 2017

Background:

Hospitalizations for infections have been associated with subsequent decreased cognitive ability, but it is uncertain if childhood infections influence subsequent scholastic achievement (SA). We aimed to estimate the association between infections during childhood and SA.

Methods:

Nationwide prospective cohort study including 598,553 children born in Denmark between 1987 and 1997 and their parents. Exposures were hospitalization for infections and treatment with anti-infective agents. Outcomes were completion of ninth grade and ninth grade test scores. Data were analyzed with logistic and linear regression analysis techniques and adjusted for any mental disorder, birthweight, Apgar score, malformations at birth, chronic somatic diseases, first-born child, parental educational level and parental mental disorders.

Results:

Hospitalization with infections was linked to lower completion of ninth grade with an odds ratio of 0.82 (95% confidence interval: 0.79–0.85) compared with children without prior hospitalizations for infections. Dose–response relationships were observed with respect to number of hospital contacts for infections and a shorter time since last hospitalization (all P < 0.001). Among those who completed the ninth grade test score, we found a dose–response and time–since relationship between number of prior severe infections and subsequent lower grade scores (P < 0.001). Treatment of nonsevere infections with anti-infective agents did not predict lower completion of ninth grade but was associated with lower grade scores (P < 0.001).

Conclusions:

Infections, particularly those requiring hospitalizations, were associated with subsequent affected cognitive ability as indicated by lower SA. These findings might also be explained by missed school days or socioeconomic factors associated with the susceptibility of acquiring infections.
Characterization of CD127− CD25++ Treg from human colostrum
Authors: Cérbulo‐Vázquez Arturo , Hernández‐Peláez Graciela , Arriaga‐Pizano Lourdes A. , Bautista‐Pérez Paulina , Romero‐Venado Jannett , Flores‐González Julio C. , Figueroa‐Damian Ricardo , Soriano‐Becerril Diana , Mancilla‐Herrera Ismael
Published: December 2017

Problem

Breastfeeding's influence on the tolerance to environmental antigens is essential for short‐ and long‐term homeostasis for children. Colostrum is rich in leucocytes, but it is unknown whether regulatory T cells (Treg) account for part of this cell population.

Method of study

Frequencies of CD127− CD25++ Treg and levels of immunoregulatory‐associated cell markers were determined in colostrum and were compared with autologous blood cells. In addition, we evaluated whether the birth conditions can affect these features.

Results

Higher frequencies of CD127 −CD25++ Treg cells expressing Foxp3 and CD45RO were observed in the colostrum. The cells’ CD25, CD152, CD279, and TGF‐β expression levels were greater than those in autologous blood cells. In addition, the CD279 and TGF‐β expressions of colostrum CD127− CD25++ Treg cells were influenced by gestational age and delivery mode.

Conclusion

The higher proportion of these cells with a function‐associated phenotype may reflect certain tolerogenic effects of breastmilk on newborns and infants, contributing to immune system homeostasis.
Australian veterinarians – global challenges
Authors: Schipp M
Published: December 2017

This paper discusses the wide range of roles that Government veterinarians play both in Australia and globally. The paper was presented as a plenary session at the National Australian Veterinary Association Annual Conference.
Teeth of extant Polypteridae and Amiidae have plicidentine organization
Authors: Germain Damien , Meunier François J.
Published: December 2017

The study of teeth of the lower jaws of Amia calva and Polypterus senegalus, with non ‐destructive X‐ray tomography, has revealed that there are dentine folds in the tooth pulp cavity in both species. These folds are simple and present only in the base of the pulp cavity where they strengthen the fixation of teeth on the jaw. So the teeth of these two basal actinopterygian taxa have a simplexodont type of plicidentine like the extinct †Cheirolepis and various extant teleostean predators, whereas the extant Lepisosteids, the sister group of Amiidae, have polyplocodont plicidentine. The phylogenetic/adaptive significance of this simplexodont plicidentine is discussed.
Oral health behaviours of parents and young children in a practice‐based caries prevention trial in Northern Ireland
Authors: O'Malley Lucy , Worthington Helen V. , Donaldson Michael , O'Neil Ciaran , Birch Stephen , Noble Solveig , Killough Seamus , Murphy Lynn , Greer Margaret , Brodison Julie , Verghis Rejina , Tickle Martin
Published: December 2017

Objectives

The NICPIP trial evaluated the costs and effects of a caries prevention intervention delivered to 2‐ to 3‐year‐old children attending dental practices in Northern Ireland. This supplementary study explored the oral health behaviours of children and their parents to help understand the reasons for the trial's findings.

Methods

A mixed methods study that included a questionnaire completed by all parents (n = 1058) at the time they brought their child for the NICPIP final clinical assessment. The questionnaire collected data on frequency of toothbrushing and sugar consumption. Questionnaire data were analysed by trial group and caries status. Parents of trial participants (n = 42) were invited to take part in telephone interviews. Parents were purposively sampled according to trial group and whether or not their child developed caries. The interviews explored how and why oral health behaviours happened. Interview data were audio‐recorded, transcribed verbatim and analysed thematically.

Results

The questionnaire data indicated that toothbrushing and between‐meal sugar snacking were common in the majority of children. The children of parents who automatically reminded their child to brush their teeth were more likely to remain caries‐free (Odds Ratio 1.24; 95% CI 1.08, 1.41; P = .002). Frequency of sweet drink consumption was associated with the child developing caries (Odds Ratio 0.88; 95% CI 0.79, 0.98; P = .021). The interview data showed that parents had positive attitudes towards brushing both in terms of perceived importance and expected outcomes. Attitudes towards sugar snacking were more complex, with parents reporting difficulties in controlling this behaviour. Sugar was described as being something that was “ever present” in children's lives.

Conclusions

Toothbrushing was widely adopted from a young age, but between‐meal sugar consumption was highly prevalent. The results suggest that effective family‐level and population‐level interventions are needed to reduce sugar consumption if substantial improvements in caries prevention are to be achieved.
No augmentation of indoleamine 2,3-dioxygenase (IDO) activity through belatacept treatment in liver transplant recipients
Authors: Bigenzahn S , Juergens B , Mahr B , Pratschke J , Koenigsrainer A , Becker T , Fuchs D , Brandacher G , Kainz A , Muehlbacher F , Wekerle T
Published: December 2017

Belatacept is a second-generation cytotoxic T lymphocyte antigen (CTLA)-4 immunoglobulin (Ig) fusion protein approved for immunosuppression in renal transplant recipients. It was designed intentionally to interrupt co-stimulation via CD28 by binding to its ligands B7·1 and B7·2. Experimental evidence suggests a potential additional mechanism for CTLA-4 Ig compounds through binding to B7 molecules expressed on antigen-presenting cells (APCs) and up-regulation of indoleamine 2,3-dioxygenase (IDO), an immunomodulating enzyme that catalyzes the degradation of tryptophan to kynurenine and that down-regulates T cell immunity. So far it remains unknown whether belatacept up-regulates IDO in transplant recipients. We therefore investigated whether belatacept therapy enhances IDO activity in liver transplant recipients enrolled in a multi-centre, investigator-initiated substudy of the Phase II trial of belatacept in liver transplantation (IM103-045). Tryptophan and kynurenine serum levels were measured during the first 6 weeks post-transplant in liver transplant patients randomized to receive either belatacept or tacrolimus-based immunosuppression. There was no significant difference in IDO activity, as indicated by the kynurenine/tryptophan ratio, between belatacept and tacrolimus-treated patients in per-protocol and in intent-to-treat analyses. Moreover, no evidence was found that belatacept affects IDO in human dendritic cells (DC) in vitro. These data provide evidence that belatacept is not associated with detectable IDO induction in the clinical transplant setting compared to tacrolimus-treated patients.
Long‐term effects on glycaemic control and β‐cell preservation of early intensive treatment in patients with newly diagnosed type 2 diabetes: A multicentre randomized trial
Authors: Chon Suk , Rhee Sang Youl , Ahn Kyu Jeung , Baik Sei Hyun , Park Yongsoo , Nam Moon Suk , Lee Kwan Woo , Yoo Soon Jib , Koh Gwanpyo , Lee Dae Ho , Kim Young Seol , Woo Jeong‐Taek ,   KIIT study investigators
Published: December 2017

Aim

To determine the effects of early intensive glycaemic control with intensive insulin treatment (IIT) or initial combined oral antidiabetic drug (COAD) therapy on long‐term glycaemic control and the preservation of β‐cell function in people with type 2 diabetes mellitus (T2DM).

Methods

Newly diagnosed drug‐naïve patients with T2DM from 8 outpatient diabetes centres were randomized to receive either IIT (n = 50; glargine/glulisine) or COAD (n = 47; glimepiride/metformin) as intensive treatment until the termination criteria to ensure euglycaemia were met. After intensive treatment, the patients completed a follow‐up period with either lifestyle modification (LSM) alone or rescue therapy to maintain target glycated haemoglobin levels of <7% (53 mmol/mol) up to week 104. The primary outcomes were analysed after excluding participants who were anti‐glutamic acid decarboxylase autoantibody‐positive.

Results

Both intensive treatment methods were effective for short‐term glycaemic control, but improvements in the disposition index (DI) were significantly greater in the IIT group than in the COAD group (P = .021). During the follow‐up period after intensive treatment, the two groups significantly differed in rescue method regarding the maintenance of comparable levels of glycaemic control (P = .010) and more participants who received IIT exhibited well‐controlled glycaemia with LSM alone. Additionally, the IIT group maintained a higher DI than the COAD group during the follow‐up period. Cox regression analysis showed that the IIT method was associated with a 52.5% lower risk of failing to maintain drug‐free glycaemic remission compared with the COAD method (P = .015).

Conclusions

The findings indicate that outpatient clinic‐based IIT to ensure euglycaemia in newly diagnosed patients with T2DM might be an effective initial therapeutic option for improvements in β‐cell function and glycaemic control over the long term, without serious adverse events.
Clinical usefulness of prognostic biomarkers in optic neuritis
Authors: Tejeda‐Velarde A. , Costa‐Frossard L. , Sainz de la Maza S. , Carrasco Á. , Espiño M. , Picón C. , Toboso I. , Walo P. E. , Lourido D. , Muriel A. , Álvarez‐Cermeño J. C. , Villar L. M.
Published: December 2017

Background and purpose

Different biological and radiological biomarkers predict clinical conversion to multiple sclerosis (MS) after a clinically isolated syndrome (CIS). The aim was to explore their role in predicting the outcome of patients with optic neuritis (ON), a CIS considered to have a benign prognosis.

Methods

Sixty‐eight consecutive ON patients were followed prospectively. Magnetic resonance imaging (MRI) and cerebrospinal fluid studies including oligoclonal immunoglobulin G (IgG) bands (OCGBs), lipid‐specific oligoclonal IgM bands (LS‐OCMBs) and neurofilament light chain quantification were performed at disease onset. Conversion to clinically definite MS (CDMS) was monitored.

Results

The mean time of follow‐up of our series was 46.4 months. Twenty‐five patients (36.7%) developed CDMS during follow‐up. Neurofilament light chain levels did not predict clinical conversion. By contrast, an abnormal MRI increased the risk of CDMS [hazard ratio (HR) 12.5, P = 0.013]. The clearest association was found in patients with more than three T2 lesions. OCGBs also predicted the onset of CDMS (HR 21.3, P = 0.003) and LS‐OCMBs were associated with a shorter time to CDMS (HR = 116.6, P < 0.001).

Conclusions

Magnetic resonance imaging and OCGBs predicted conversion to CDMS after an ON episode. In addition, LS‐OCMBs identified the ON patients more likely to develop MS early. These results, applicable to the everyday clinical setting, may be of interest for therapeutic decisions.
Visualizing nuclear‐localized RNA using transient expression system in plants
Authors: Kinoshita Natsuko , Arenas‐Huertero Catalina , Chua Nam‐Hai
Published: December 2017

By modifying the existing cytosolic RNA visualization tool pioneered by Schönberger, Hammes, and Dresselhaus (2012), we developed a method to visualize nuclear‐localized RNA. Our method uses (i) an RNA component that consists of an RNA of interest that is fused to a bacteriophage‐derived MS2 sequence; and (ii) GFP fused to MS2 coat protein (MSCP), which binds specifically to MS2 as is also the case in the method for cytosolic RNA visualization. The nuclear localization sequence (NLS) at the C‐terminal of MSCP‐GFP tethers the probe to the nucleus. To reduce background signals in the nucleus, we replaced the NLS with a nuclear export sequence (NES) that anchors the MSCP‐GFP probe in the cytosol. Our nuclear RNA visualization method differs from previous methods in two aspects: (i) We used an NES to reduce nuclear background signal so that the MSCP‐GFP probe localizes in the cytosol by default; (ii) We added mCherry as a visual marker in the RNA component to increase its efficient usage in a transient system.
Contribution of neuraminidase 3 to the differentiation of induced regulatory T cells
Authors: Kaminuma Osamu , Katoh Shigeki , Miyagi Taeko , Watanabe Nobumasa , Kitamura Noriko , Nishimura Tomoe , Saeki Mayumi , Mori Akio , Hiroi Takachika
Published: December 2017

Neuraminidase family enzymes that hydrolyze the terminal sialic acid linkage in biomolecules are involved in various immune responses. We previously showed that Th1 and Th2 cells differentially express several neuraminidases. Herein, the expression of neuraminidases in induced regulatory T (iTreg) cells was investigated in comparison with that in other T‐cell subsets. Contrary to the tendency toward higher neuraminidase 1 mRNA expression in in vitro‐differentiated Th2 cells, compared to Th1, Th17 and iTreg cells, we observed significantly higher expression of neuraminidase 3 (Neu3) in iTreg cells. Furthermore, the expression of Neu3 in FoxP3+CD62L− spleen cells was higher than that in FoxP3+CD62L+ and FoxP3− cells. Lentiviral expression of Neu3 in naïve CD4+ T cells during the stimulation culture led to upregulation of FoxP3 expression. On the basis of these findings, we conclude that Neu3 contributes to the differentiation of iTreg cells by upregulation of FoxP3.
Obsessive, compulsive, and conscientious? The relationship between OCPD and personality traits
Authors: Mike Anissa , King Hannah , Oltmanns Thomas F. , Jackson Joshua J.
Published: December 2017

Objective

Obsessive‐compulsive personality disorder (OCPD) is defined as being overly controlling, rigid, orderly, and perfectionistic. At a definitional level, OCPD would appear to be highly related to the trait of Conscientiousness. The current study attempts to disentangle this relationship by examining the relationship at a facet level using multiple forms of OCPD assessment and using multiple reports of OCPD and personality. In addition, the relationship between OCPD and each Big Five trait was examined.

Method

The study relied on a sample of 1,630 adults who completed self‐reports of personality and OCPD. Informants and interviewers also completed reports on the targets. Bifactor models were constructed in order to disentangle variance attributable to each facet and its general factors.

Results

Across four sets of analyses, individuals who scored higher on OCPD tended to be more orderly and achievement striving, and more set in their ways, but less generally conscientious. OCPD was also related to select facets under each Big Five trait. Notably, findings indicated that OCPD has a strong interpersonal component and that OCPD tendencies may interfere with one's relationships with others.

Conclusions

Findings suggest that OCPD's relationship with personality can be more precisely explained through its relationships with specific tendencies rather than general, higher‐order traits.
Angiotensin‐converting enzyme‐inhibitor therapy in adolescents with type 1 diabetes in a regional cohort: Auckland, New Zealand from 2006 to 2016
Authors: Hornung Rosalie J , Reed Peter W , Mouat Fran , Jefferies Craig , Gunn Alistair J , Hofman Paul L
Published: December 2017

Aim

To review indications and use of angiotensin‐converting enzyme‐inhibitor (ACEI) therapy for the treatment of persistent microalbuminuria (MA) and/or hypertension (HTN) in adolescents with type 1 diabetes mellitus (T1DM).

Methods

Retrospective chart review of adolescent patients with T1DM seen within the paediatric diabetes service in Auckland, New Zealand, from 2006 to 2016. MA, HTN, patient demographic characteristics and ACEI prescribing and monitoring indices were examined.

Results

Five hundred adolescents with T1DM were included. There were 26 patients (5%) with MA and/or HTN. MA alone was present in 16, HTN alone in 3 and both HTN and MA in 7. The 5‐year MA/HTN‐free rate was 98%, and the 10‐year MA/HTN‐free rate was 93%. Longer disease duration and earlier diagnosis were predictors of MA/HTN. There was no significant difference in standard clinical indices between study patients and others. ACEI was prescribed for 17 of 26 patients for either HTN or MA. Within 6 weeks of ACEI commencement, less than half of the subjects had repeat serum creatinine and MA screens and no record of repeat blood pressure measurement. Despite this, all patients had 3‐monthly reviews within outpatient clinics where adjustments of ACEI doses were made.

Conclusion

In our regional adolescent population with T1DM, there were low rates of both MA and/or HTN. In those who required treatment with ACEI, clinical monitoring post‐commencement of therapy was inconsistent. Local consensus guidelines for the management of persistent MA in children and adolescents with diabetes mellitus were developed in response to this study.
The presence of multiple NS5A RASs is associated with the outcome of sofosbuvir and ledipasvir therapy in NS5A inhibitor‐naïve patients with chronic HCV genotype 1b infection in a real‐world cohort
Authors: Kozuka R. , Hai H. , Motoyama H. , Hagihara A. , Fujii H. , Uchida‐Kobayashi S. , Morikawa H. , Enomoto M. , Murakami Y. , Kawada N. , Tamori A.
Published: December 2017

It is unclear whether multiple nonstructural (NS) 5A resistance‐associated substitutions (RASs) correlate with the outcome of sofosbuvir (SOF) and ledipasvir (LDV) therapy. We investigated the effects of multiple NS5A RASs in NS5A inhibitor‐naïve patients with chronic hepatitis C virus genotype 1b infection treated with SOF/LDV. In 313 patients treated with SOF/LDV, we assessed the effects of multiple NS5A RASs on the sustained virological response (SVR). RASs at L28, R30, L31, Q54, P58, Q62, A92, and Y93 in the NS5A region were examined by direct sequencing. The prevalence of RASs was as follows: 2.6% at L28, 8.7% at R30, 6.1% at L31, 48.7% at Q54, 9.9% at P58, 9.9% at Q62, 5.1% at A92, 13.8% at Y93, and 19.2% at L31 or Y93. A total of 133 patients had no RASs. SVR was achieved in 98.7% of the patients. SVR rates significantly differed between patients with and without the L31 or Y93 RAS (93.0% [53/57] vs 100% [250/250], P = .0011). In addition, among patients with the L31 or Y93 RAS, 29.8%, 45.6% and 24.6% had one, two and three or more NS5A RASs, respectively. The SVR rate was significantly lower in patients with the L31 or Y93 RAS with more than three NS5A RASs compared to those with fewer than three NS5A RASs (71.4% [10/14] vs 100% [43/43], P = .0025). Although the prevalence of multiple NS5A RASs at baseline was low in NS5A inhibitor‐naïve patients, the presence of multiple NS5A RASs was associated with the effectiveness of SOF/LDV therapy.
Landscape attributes governing local transmission of an endemic zoonosis: Rabies virus in domestic dogs
Authors: Brunker Kirstyn , Lemey Philippe , Marston Denise A. , Fooks Anthony R. , Lugelo Ahmed , Ngeleja Chanasa , Hampson Katie , Biek Roman
Published: December 2017

Landscape heterogeneity plays an important role in disease spread and persistence, but quantifying landscape influences and their scale dependence is challenging. Studies have focused on how environmental features or global transport networks influence pathogen invasion and spread, but their influence on local transmission dynamics that underpin the persistence of endemic diseases remains unexplored. Bayesian phylogeographic frameworks that incorporate spatial heterogeneities are promising tools for analysing linked epidemiological, environmental and genetic data. Here, we extend these methodological approaches to decipher the relative contribution and scale‐dependent effects of landscape influences on the transmission of endemic rabies virus in Serengeti district, Tanzania (area ~4,900 km2). Utilizing detailed epidemiological data and 152 complete viral genomes collected between 2004 and 2013, we show that the localized presence of dogs but not their density is the most important determinant of diffusion, implying that culling will be ineffective for rabies control. Rivers and roads acted as barriers and facilitators to viral spread, respectively, and vaccination impeded diffusion despite variable annual coverage. Notably, we found that landscape effects were scale‐dependent: rivers were barriers and roads facilitators on larger scales, whereas the distribution of dogs was important for rabies dispersal across multiple scales. This nuanced understanding of the spatial processes that underpin rabies transmission can be exploited for targeted control at the scale where it will have the greatest impact. Moreover, this research demonstrates how current phylogeographic frameworks can be adapted to improve our understanding of endemic disease dynamics at different spatial scales.
Induction of the Spx regulon by cell wall stress reveals novel regulatory mechanisms in Bacillus subtilis
Authors: Rojas‐Tapias Daniel F. , Helmann John D.
Published: December 2017

The transcription factor Spx is the master regulator of the disulfide stress response in Bacillus subtilis. Intriguingly, the activation of Spx by diamide relies entirely on posttranslational regulatory events in spite of the complex transcriptional control of the spx gene. Here, we show that cell wall stress, but not membrane stress, also results in induction of the Spx regulon. Remarkably, two major differences were found regarding the mechanism of induction of Spx under cell wall stress in comparison to disulfide stress. First, transcriptional induction of the spx gene from a σM‐dependent promoter is required for accumulation of Spx in response to cell wall stress. Second, activation of the Spx regulon during cell wall stress is not accompanied by oxidation of the Spx disulfide switch. Finally, we demonstrate that cells lacking Spx have increased sensitivity toward antibiotics inhibiting both early and late steps in peptidoglycan synthesis, suggesting that the Spx regulon plays an important adaptive role in the cell wall stress response. This study expands the functional role of the Spx regulon and reveals novel regulatory mechanisms that result in induction of Spx in B. subtilis.