bluuebunny/crossref_metadata_2025 huggingface dataset:
Niclosamide inhibits vascular smooth muscle cell proliferation and migration and attenuates neointimal hyperplasia in injured rat carotid arteries
Authors: Xiao Xiao‐Lin , Hu Nan , Zhang Xin‐Zi , Jiang Man , Chen Chang , Ma Rui , Ma Zhen‐Gang , Gao Jin‐Lai , Xuan Xiu‐Chen , Sun Zhi‐Jie , Dong De‐Li
Published: February 2018

Background and Purpose

The anti‐helminthic drug niclosamide regulates multiple cellular signals including STAT3, AMP‐activated protein kinase (AMPK), Akt, Wnt/β‐catenin and mitochondrial uncoupling which are involved in neointimal hyperplasia. Here we have examined the effects of niclosamide on vascular smooth muscle cell proliferation, migration and neointimal hyperplasia and assessed the potential mechanisms.

Experimental Approach

Cell migration was measured by using wound‐induced migration assay and Boyden chamber assay. Protein levels were measured by using Western blot technique. Neointimal hyperplasia in vivo was induced in rats by balloon injury to the carotid artery.

Key Results

Niclosamide treatment inhibited serum‐induced (15% FBS) and PDGF‐BB‐induced proliferation and migration of vascular smooth muscle cells (A10 cells). Niclosamide showed no cytotoxicity at anti‐proliferative concentrations, but induced cell apoptosis at higher concentrations. Niclosamide treatment inhibited serum‐induced (15% FBS) and PDGF‐BB‐induced STAT3 activation (increased protein levels of p‐STAT3 at Tyr705) but activated AMPK, in A10 cells. Niclosamide exerted no significant effects on β‐catenin expression and the activities of ERK1/2 and Akt in A10 cells. Injection (i.p.) of soluble pegylated niclosamide (PEG5000‐niclosamide) (equivalent to niclosamide 25 mg·kg−1) attenuated neointimal hyperplasia following balloon‐injury in rat carotid arteries in vivo.

Conclusions and Implications

Niclosamide inhibited vascular smooth muscle cell proliferation and migration and attenuated neointimal hyperplasia in balloon‐injured rat carotid arteries through a mechanism involving inhibition of STAT3.
Defining the ionic mechanisms of optogenetic control of vascular tone by channelrhodopsin‐2
Authors: Rorsman Nils J G , Ta Chau M , Garnett Hannah , Swietach Pawel , Tammaro Paolo
Published: February 2018

Background and Purpose

Optogenetic control of electromechanical coupling in vascular smooth muscle cells (VSMCs) is emerging as a powerful research tool with potential applications in drug discovery and therapeutics. However, the precise ionic mechanisms involved in this control remain unclear.

Experimental Approach

Cell imaging, patch‐clamp electrophysiology and muscle tension recordings were used to define these mechanisms over a wide range of light stimulations.

Key Results

Transgenic mice expressing a channelrhodopsin‐2 variant [ChR2(H134R)] selectively in VSMCs were generated. Isolated VSMCs obtained from these mice demonstrated blue light‐induced depolarizing whole‐cell currents. Fine control of artery tone was attained by varying the intensity of the light stimulus. This arterial response was sufficient to overcome the endogenous, melanopsin‐mediated, light‐evoked, arterial relaxation observed in the presence of contractile agonists. Ca2+ entry through voltage‐gated Ca2+ channels, and opening of plasmalemmal depolarizing channels (TMEM16A and TRPM) and intracellular IP3 receptors were involved in the ChR2(H134R)‐dependent arterial response to blue light at intensities lower than ~0.1 mW·mm−2. Light stimuli of greater intensity evoked a significant Ca2+ influx directly through ChR2(H134R) and produced marked intracellular alkalinization of VSMCs.

Conclusions and Implications

We identified the range of light intensity allowing optical control of arterial tone, primarily by means of endogenous channels and without substantial alteration to intracellular pH. Within this range, mice expressing ChR2(H134R) in VSMCs are a powerful experimental model for achieving accurate and tuneable optical voltage‐clamp of VSMCs and finely graded control of arterial tone, offering new approaches to the discovery of vasorelaxant drugs.
Antinociceptive effects of novel histamine H3 and H4 receptor antagonists and their influence on morphine analgesia of neuropathic pain in the mouse
Authors: Popiolek‐Barczyk Katarzyna , Łażewska Dorota , Latacz Gniewomir , Olejarz Agnieszka , Makuch Wioletta , Stark Holger , Kieć‐Kononowicz Katarzyna , Mika Joanna
Published: February 2018

Background and Purpose

The histaminergic system is a promising target for the development of new analgesics, as histamine H3 and H4 receptors are expressed in regions concerned with nociceptive transmission. Here we have determined the analgesic effects of new H3 and H4 receptor antagonists in naive and neuropathic mice.

Experimental Approach

We used chronic constriction injury (CCI) to the sciatic nerve in mice to model neuropathy. Effects of a new H3 receptor antagonist, E‐162(1‐(5‐(naphthalen‐1‐yloxy)pentyl)piperidine) and H4 receptor antagonist, TR‐7(4‐(4‐chlorophenyl)‐6‐(4‐methylpiperazin‐1‐yl)‐1,3,5‐triazin‐2‐amine) were assessed on mechanical (von Frey) and thermal (cold plate, tail flick) stimuli in mice with and without CCI (7 days after injury). Effects of these antagonists on morphine analgesia were also evaluated, along with the possible participation of H1 receptors in their effects. We analysed the compounds in binding and functional cAMP assays at the H3 and H4 receptors and determined metabolic stability.

Key Results

E‐162 and TR‐7 attenuated nociceptive responses and profound morphine analgesia in males with CCI. These antagonists showed analgesia in naive mice (tail flick test) and produced prolonged analgesia in neuropathic females. E‐162‐induced analgesia was reversed by pyrilamine, an H1 receptor antagonist. E‐162 bound potently to H3 receptors (Ki = 55 nM) and inhibited cAMP accumulation (IC50 = 165 nM). TR‐7 showed lower affinity for H4 receptors (Ki = 203 nM) and IC50 of 512 nM.

Conclusions and Implications

We describe a therapeutic use for new H3 (E‐162) and H4 receptor (TR‐7) antagonists in neuropathy. Targeting H3 and H4 receptors enhanced morphine analgesia, consistent with multimodal pain therapy.
Impact of a hurricane on the herpetofaunal assemblages of a successional chronosequence in a tropical dry forest
Authors: Suazo‐Ortuño Ireri , Urbina‐Cardona José Nicolás , Lara‐Uribe Nancy , Marroquín‐Páramo Jorge , Soto‐Sandoval Yunuen , Rangel‐Orozco Jorge , Lopez‐Toledo Leonel , Benítez‐Malvido Julieta , Alvarado‐Díaz Javier
Published: February 2018

Land‐use change is the main cause of deforestation and degradation of tropical forest in Mexico. Frequently, these lands are abandoned leading to a mosaic of natural vegetation in secondary succession. Further degradation of the natural vegetation in these lands could be exacerbated by stochastic catastrophic events such as hurricanes. Information on the impact of human disturbance parallel to natural disturbance has not yet been evaluated for faunal assemblages in tropical dry forests. To evaluate the response of herpetofaunal assemblages to the interaction of human and natural disturbances, we used information of pre‐ and post‐hurricane herpetofaunal assemblages inhabiting different successional stages (pasture, early forest, young forest, intermediate forest, and old growth forest) of dry forest. Herpetofaunal assemblages were surveyed in all successional stages two years before and two years after the hurricane Jova that hit the Pacific Coast of Mexico on October 2011. We registered 4093 individuals of 61 species. Overall, there were only slight effects of successional stage, hurricane Jova or the interaction between them on abundance, observed species richness and diversity of the herpetofauna. However, we found marked changes in estimated richness and composition of frogs, lizards, and snakes among successional stages in response to hurricane Jova. Modifications in vegetation structure as result of hurricane pass promoted particular changes in each successional stage and taxonomic group (anurans, lizards, and snakes). Secondary forests at different stages of succession may attenuate the negative effects of an intense, short‐duration, and low‐frequency natural disturbance such as hurricane Jova on successional herpetofaunal trajectories and species turnover.
Using Meta‐analytic Structural Equation Modeling to Study Developmental Change in Relations Between Language and Literacy
Authors: Quinn Jamie M. , Wagner Richard K.
Published: February 2018

The purpose of this review was to introduce readers of Child Development to the meta‐analytic structural equation modeling (MASEM) technique. Provided are a background to the MASEM approach, a discussion of its utility in the study of child development, and an application of this technique in the study of reading comprehension (RC) development. MASEM uses a two‐stage approach: first, it provides a composite correlation matrix across included variables, and second, it fits hypothesized a priori models. The provided MASEM application used a large sample (N = 1,205,581) of students (ages 3.5–46.225) from 155 studies to investigate the factor structure and relations among components of RC. The practical implications of using this technique to study development are discussed.
“Nothing goes as planned”: Practitioners reflect on matching children and foster families
Authors: Zeijlmans Kirti , López Mónica , Grietens Hans , Knorth Erik J.
Published: February 2018

Matching children with foster carers is an important step in every nonkinship family foster care placement. Although guidelines for matching are provided in several studies, the case‐specific context of the decision can influence the practitioners' ability to adhere to these guidelines. Therefore, this study answers the following question: “How does the case‐specific context influence the practitioners' decision‐making process regarding matching in family foster care?” Using a qualitative design, 20 semistructured interviews were conducted with practitioners matching children with foster families. Three themes emerged representing different layers of practitioners' everyday decision‐making: matching as planned, matching being tailored, and matching being compromised. The results show that exceptions are part of practitioners' daily work, either due to the belief that it might benefit those involved or because of obstacles presented during the decision‐making process. When the decision is compromised, matching practitioners lower their standards, while at the same time safeguarding the quality of the match. This proves that matching in practice is more than choosing a family, and guidelines are needed to determine what “good‐enough” matching should entail.
The long non‐coding RNA SPRY4‐IT1: An emerging player in tumorigenesis and osteosarcoma
Authors: Li Zheng , Shen Jianxiong , Chan Matthew T. V. , Wu William Ka Kei
Published: February 2018

Accumulating evidence from genome‐wide analysis and functional studies has begun to unveil the important role of long non‐coding RNAs (lncRNAs) in cancer development. The lncRNA SPRY4‐IT1 is derived from an intron of SPRY4 gene and was originally reported to be upregulated in melanoma in which it functioned as an oncogene. Since this discovery, an increasing number of studies have investigated the expression and function of SPRY4‐IT1 in human cancers. Aberrant expression of SPRY4‐IT1 has now been documented in different cancer types, including osteosarcoma, breast, renal, oesophageal and prostate cancers. However, its deregulation and function in lung and gastric cancers remain controversial. Pertinent to clinical practice, SPRY4‐IT1 expression has been shown to predict survival of cancer patients. In this review, we summarize recent evidence concerning SPRY4‐IT1 deregulation and the associated mechanisms in human cancers. We also discuss the potential clinical utilization of this lncRNA as a diagnostic and prognostic biomarker for cancer patients.
The BRAF activated non‐coding RNA: A pivotal long non‐coding RNA in human malignancies
Authors: Liu Xiu‐Fen , Hao Ji‐Long , Xie Tian , Pant Om Prakash , Lu Cheng‐Bo , Lu Cheng‐Wei , Zhou Dan‐Dan
Published: February 2018

Long non‐coding RNAs (lncRNAs) participate in the complex network of cancer and play an important role in tumourigenesis and progression. BRAF activated non‐coding RNA (BANCR), a 4‐exon transcript of 693‐bp, was first discovered as an oncogenic long non‐coding RNA in BRAFV600E melanomas cells in 2012 and was related to melanoma cell migration. Besides melanoma, increasing evidence has explored the potential role of BANCR in the development and progression of multiple other human malignancies, such as retinoblastoma, lung cancer, gastric cancer etc. since its discovery. The expression pattern of BANCR varies in different types of cancers, either as a tumour suppressor or as an accelerator. Functional BANCR may serve as a promising biomarker for cancer diagnosis as well as prognosis evaluation. BANCR‐targeted intervention may also become a valuable novel therapeutic tool against human malignancies. This review summarized the advanced research progresses concerning the expression and role of BANCR in different human malignancies.
Coroglaucigenin induces senescence and autophagy in colorectal cancer cells
Authors: Huang Yong‐Hao , Lei Jing , Yi Guo‐Hui , Huang Feng‐Ying , Li Yue‐Nan , Wang Cai‐Chun , Sun Yan , Dai Hao‐Fu , Tan Guang‐Hong
Published: February 2018

Objectives

Coroglaucigenin (CGN), a natural product isolated from Calotropis gigantean by our research group, has been identified as a potential anti‐cancer agent. However, the molecular mechanisms involved remain poorly understood.

Materials and methods

Cell viability and cell proliferation were detected by MTT and BrdU assays. Flow cytometry, SA‐β‐gal assay, western blotting and immunofluorescence were performed to determine CGN‐induced apoptosis, senescence and autophagy. Western blotting, siRNA transfection and coimmunoprecipitation were carried out to investigate the mechanisms of CGN‐induced senescence and autophagy. The anti‐tumour activities of combination therapy with CGN and chloroquine were observed in mice tumour models.

Results

We demonstrated that CGN inhibits the proliferation of colorectal cancer cells both in vitro and in vivo. We showed that the inhibition of cell proliferation by CGN is independent of apoptosis, but is associated with cell‐cycle arrest and senescence in colorectal cancer cells. Notably, CGN induces protective autophagy that attenuates CGN‐mediated cell proliferation. Functional studies revealed that CGN disrupts the association of Hsp90 with both CDK4 and Akt, leading to CDK4 degradation and Akt dephosphorylation, eventually resulting in senescence and autophagy, respectively. Combination therapy with CGN and chloroquine resulted in enhanced anti‐tumour effects in vivo.

Conclusions

Our results demonstrate that CGN induces senescence and autophagy in colorectal cancer cells and indicate that combining it with an autophagy inhibitor may be a novel strategy suitable for CGN‐mediated anti‐cancer therapy.
Trends in liver transplantation for hepatitis C in a country with reduced access to direct‐acting antiviral agents
Authors: Dirchwolf Melisa , Marciano Sebastián , Giunta Diego H. , Posadas‐Martínez Maria L. , Biggins Scott W. , Ruf Andrés E.
Published: February 2018

Background

Hepatitis C virus (HCV)‐related cirrhosis is a leading indication for liver transplantation (LT) worldwide. Access to effective HCV treatment is inequitable globally. We aimed to analyze whether the introduction of effective HCV treatment caused an impact in LT trends in a middle‐income country.

Methods

Cross‐sectional analysis of all adult patients who were listed/received a LT in Argentina for HCV, alcohol‐related liver disease (ALD), or autoimmune hepatitis/primary biliary cirrhosis (AIH/PBC) from 2007 to 2017. Joinpoint regression analysis was used to identify changes in the cumulative incidence rates in waiting list (WL) registration, WL mortality, and LT.

Results

Liver transplantation WL for HCV increased significantly between 2007 and 2014, with an annual percentage change (APC) +7.8%, P = .01, followed by a downward slope from 2014 to 2017 with an APC −9.8%, P = .1. There were no significant changes in WL mortality. LT trends remained stable. LT for HCV without MELD exception points for HCC decreased (APC −6.6%, P = .01), whereas LT for HCV with HCC exception points increased (APC +11.1, P = .01) during the study period.

Conclusion

Waiting list and LT for HCV without HCC decreased, whereas LT for HCV and HCC increased; this may be related to selective antiviral treatment access for patients with advanced fibrosis.
Colliding, colonizing or combining? Four cases illustrating the unique challenges presented by melanoma arising in conjunction with basal cell carcinoma
Authors: Dinehart Matthew , Abate Mallory S. , Jennings Thomas , Kaley Jennifer R. , Shalin Sara C.
Published: February 2018

Biphasic lesions comprised of melanocytic and epithelial components are rare entities believed to arise either as a collision of 2 histologically distinct lesions in the same anatomic location or as a singular progenitor tumor differentiating along 2 differing lineages. Regardless of mechanism of origin, these tumors present unique challenges in pathologic interpretation and in determining appropriate measurements, which assigns subsequent prognosis to the patient. We present 4 tumors of melanoma co‐existing with basal cell carcinoma (BCC) and discuss relevant literature regarding these biphasic entities. Patients consisted of 3 males and 1 female, ranging in age from 62 to 93, with lesions located on the shoulder, frontal scalp, forearm and nose. Three of 4 lesions showed melanoma cells limited to BCC tumor lobules, without evidence of direct dermal invasion by melanoma cells, raising the question of whether or not these tumors should be classified as in situ or invasive melanoma. These cases highlight the complexity that such lesions pose to dermatopathologists, in terms of their uncertain origin and variable microscopic appearance. In the absence of data regarding outcomes for these tumors (given their rarity), it is important to utilize a case‐by‐case approach, with careful clinical correlation and appropriate use of ancillary techniques.
Temporal and external validation of a prediction model for adverse outcomes among inpatients with diabetes
Authors: Adderley N. J. , Mallett S. , Marshall T. , Ghosh S. , Rayman G. , Bellary S. , Coleman J. , Akiboye F. , Toulis K. A. , Nirantharakumar K.
Published: February 2018

Aim

To temporally and externally validate our previously developed prediction model, which used data from University Hospitals Birmingham to identify inpatients with diabetes at high risk of adverse outcome (mortality or excessive length of stay), in order to demonstrate its applicability to other hospital populations within the UK.

Methods

Temporal validation was performed using data from University Hospitals Birmingham and external validation was performed using data from both the Heart of England NHS Foundation Trust and Ipswich Hospital. All adult inpatients with diabetes were included. Variables included in the model were age, gender, ethnicity, admission type, intensive therapy unit admission, insulin therapy, albumin, sodium, potassium, haemoglobin, C‐reactive protein, estimated GFR and neutrophil count. Adverse outcome was defined as excessive length of stay or death.

Results

Model discrimination in the temporal and external validation datasets was good. In temporal validation using data from University Hospitals Birmingham, the area under the curve was 0.797 (95% CI 0.785–0.810), sensitivity was 70% (95% CI 67–72) and specificity was 75% (95% CI 74–76). In external validation using data from Heart of England NHS Foundation Trust, the area under the curve was 0.758 (95% CI 0.747–0.768), sensitivity was 73% (95% CI 71‐74) and specificity was 66% (95% CI 65–67). In external validation using data from Ipswich, the area under the curve was 0.736 (95% CI 0.711–0.761), sensitivity was 63% (95% CI 59–68) and specificity was 69% (95% CI 67–72). These results were similar to those for the internally validated model derived from University Hospitals Birmingham.

Conclusions

The prediction model to identify patients with diabetes at high risk of developing an adverse event while in hospital performed well in temporal and external validation. The externally validated prediction model is a novel tool that can be used to improve care pathways for inpatients with diabetes. Further research to assess clinical utility is needed.
Effects of resveratrol supplementation on liver fat content in overweight and insulin‐resistant subjects: A randomized, double‐blind, placebo‐controlled clinical trial
Authors: Kantartzis Konstantinos , Fritsche Louise , Bombrich Maria , Machann Jürgen , Schick Fritz , Staiger Harald , Kunz Iris , Schoop Rotraut , Lehn‐Stefan Angela , Heni Martin , Peter Andreas , Fritsche Andreas , Häring Hans‐Ulrich , Stefan Norbert
Published: February 2018

We performed the largest randomized, placebo‐controlled clinical trial to date (N = 112, 12‐week intervention) to investigate the effects and safety of resveratrol supplementation on liver fat content and cardiometabolic risk parameters in overweight and obese and insulin‐resistant subjects. At baseline the variability in liver fat content was very large, ranging from 0.09% to 37.55% (median, 7.12%; interquartile range, 3.85%‐12.94%). Mean (SD) liver fat content was 9.22 (6.85) % in the placebo group and 9.91 (7.76) % in the resveratrol group. During the study liver fat content decreased in the placebo group (−0.7%) but not in the resveratrol group (−0.03%) (differences between groups: P = .018 for the intention‐to‐treat [ITT] population; N = 54, resveratrol, N = 54, placebo and P = .0077 for the per protocol [PP] population). No effects of resveratrol supplementation on cardiometabolic risk parameters were observed. Resveratrol supplementation was well tolerated and safe.

In conclusion, these data suggest that resveratrol supplementation is safe and that it does not considerably impact liver fat content or cardiometabolic risk parameters in humans.
Screening test for direct oral anticoagulants with the dilute Russell viper venom time
Authors: Pratt Jackie , Crispin Philip
Published: February 2018

Objectives

To evaluate the dilute Russell viper venom time (DRVVT) for the detection of direct‐acting oral anticoagulants (DOACs) and to investigate the effect of DOACS on coagulation assays.

Methods

Patients with DOACs and controls had plasma levels determined by an anti‐Xa assay and dilute thrombin clotting time (TCT). Levels were correlated with the DRVVT as well as TCT, prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, protein C, protein S and antithrombin levels. The utility of the DRVVT for detecting clinically significant levels of DOACs was evaluated.

Results

There were 44 samples from patients taking dabigatran, 83 with rivaroxaban, 18 with apixaban and 55 controls. The PT and APTT failed to detect clinically significant doses of anticoagulants adequately. The TCT was increased in patients taking dabigatran and normal in controls and patients on FXa inhibitors. There was a linear correlation with all DOAC levels and the DRVVT, with moderate precision, but it showed high sensitivity (95%) and specificity (90%) for clinically significant DOAC levels.

Conclusion

The DRVVT detects clinically significant levels of DOACs and, in conjunction with the TCT, may be used as a screen for the presence and type of DOAC.
Sense and the identity conception of truth
Authors: Methven Steven J.
Published: February 2018

The identity conception of truth holds that a thinkable is true just in case it is a fact. As such, it sets itself against correspondence theories of truth, while respecting the substantive role played by truth in respect of enquiry. In this article, I motivate and develop that view, and, in so doing, promote a particular conception of sense. This allows me to defend the view from two substantial criticisms. First, that the identity conception of truth is incoherent in respect of its treatment of objects in the realm of reference, and, second, that it is committed to a view of the world in which ordinary objects have no place.
Intra‐operative evaluation of prophylactic hysterectomy and salpingo‐oophorectomy specimens in hereditary gynaecological cancer syndromes
Authors: Wong Serena , Ratner Elena , Buza Natalia
Published: February 2018

Aims

Prophylactic total hysterectomy (TH) and bilateral salpingo‐oophorectomy (BSO) have become routine procedures in women at genetic risk for gynaecological malignancies. Intra‐operative pathology diagnosis of an occult malignancy provides the opportunity for immediate surgical staging and helps to avoid a second surgery. However, no standard guidelines exist for optimal intra‐operative evaluation (IOE) of these specimens. We performed a retrospective analysis of prophylactic TH and BSO cases to assess the presence of gross findings, frozen and permanent section sampling practices, frozen section diagnoses and diagnostic discrepancies.

Methods and results

All prophylactic TH and BSO cases between 1990 and 2017 were retrieved from our departmental archives. A total of 413 cases were included in the study: 27 with Lynch syndrome (LS), 222 with germline BRCA 1 or 2 mutations and 164 cases with strong family or personal history (non‐Lynch/non‐BRCA). Only fewer than half of all cases (159 of 413; 38.5%) were sent for IOE, 15 of 27 (56%) LS cases, 93 of 222 (42%) BRCA cases and 51 of 164 (31%) non‐Lynch/non‐BRCA cases. A total of 19 patients (4.6% of patients combining all three groups) had a final diagnosis of malignancy or premalignancy on permanent sections. Of these 19 cases, eight had a corresponding gross lesion (42%) and could have been diagnosed on frozen section; however, only one of them underwent IOE.

Conclusions

Our results highlight the potential benefits and challenges of IOE in this setting and may provide a basis for future practice recommendations.
Choosing the right sigmoid growth function using the unified‐models approach
Authors: Vrána Jakub , Remeš Vladimír , Matysioková Beata , Tjørve Kathleen M. C. , Tjørve Even
Published: February 2018

Growth of the young is an important part of the life history in birds. However, modelling methods have paid little attention to the choice of regression model used to describe its pattern. The aim of this study was to evaluate whether a single sigmoid model with an upper asymptote could describe avian growth adequately. We compared unified versions of five growth models of the Richards family (the four‐parameter U‐Richards and the three‐parameter U‐logistic, U‐Gompertz, U‐Bertalanffy and U4‐models) for three traits (body mass, tarsus‐length and wing‐length) for 50 passerine species, including species with varied morphologies and life histories. The U‐family models exhibit a unified set of parameters for all models. The four‐parameter U‐Richards model proved a good choice for fitting growth curves to various traits – its extrad‐parameter allows for a flexible placement of the inflection point. Which of the three‐parameter U‐models was the best performing varied greatly between species and between traits, as each three‐parameter model had a different fixed relative inflection value (fraction of the upper asymptote), implying a different growth pattern. Fixing the asymptotes to averages for adult trait value generally shifted the model preference towards one with lower relative inflection values. Our results illustrate an overlooked difficulty in the analysis of organismal growth, namely, that a single traditional three‐parameter model does not suit all growth data. This is mostly due to differences in inflection placement. Moreover, some biometric traits require more attention when estimating growth rates and other growth‐curve characteristics. We recommend fitting either several three‐parameter models from the U‐family, where the parameters are comparable between models, or only the U‐Richards model.
Endodontic applications of 3D printing
Authors: Anderson J. , Wealleans J. , Ray J.
Published: February 2018

Computer‐aided design (CAD) and computer‐aided manufacturing (CAM) technologies can leverage cone beam computed tomography data for production of objects used in surgical and nonsurgical endodontics and in educational settings. The aim of this article was to review all current applications of 3D printing in endodontics and to speculate upon future directions for research and clinical use within the specialty. A literature search of PubMed, Ovid and Scopus was conducted using the following terms: stereolithography, 3D printing, computer aided rapid prototyping, surgical guide, guided endodontic surgery, guided endodontic access, additive manufacturing, rapid prototyping, autotransplantation rapid prototyping, CAD, CAM. Inclusion criteria were articles in the English language documenting endodontic applications of 3D printing. Fifty‐one articles met inclusion criteria and were utilized. The endodontic literature on 3D printing is generally limited to case reports and pre‐clinical studies. Documented solutions to endodontic challenges include: guided access with pulp canal obliteration, applications in autotransplantation, pre‐surgical planning and educational modelling and accurate location of osteotomy perforation sites. Acquisition of technical expertise and equipment within endodontic practices present formidable obstacles to widespread deployment within the endodontic specialty. As knowledge advances, endodontic postgraduate programmes should consider implementing 3D printing into their curriculums. Future research directions should include clinical outcomes assessments of treatments employing 3D printed objects.
EXPERIMENTAL AND SELF‐REPORTED MEASURES OF RISK TAKING AND DIGIT RATIO (2D:4D): EVIDENCE FROM A LARGE, SYSTEMATIC STUDY
Authors: Brañas‐Garza Pablo , Galizzi Matteo M. , Nieboer Jeroen
Published: February 2018

We systematically investigate the links between the digit ratio (2D:4D)—a biomarker for prenatal testosterone exposure—and two measures of individual risk taking: (i) risk preferences (RP) over lotteries with real monetary incentives and (ii) self‐reported risk attitude (RA). We find that both the right‐hand and the left‐hand digit ratio are significantly associated with RP: Subjects with lower digit ratios tend to choose riskier lotteries. Neither digit ratio, however, is associated with self‐reported RA.
BORDER EFFECTS WITHOUT BORDERS: WHAT DIVIDES JAPAN'S INTERNAL TRADE?
Authors: Wrona Jens
Published: February 2018

This article identifies a “border” effect in the absence of a border. The finding that trade between east and west Japan is 23.1% to 51.3% lower than trade within both country parts is established despite the absence of an obvious east–west division due to historical borders, cultural differences, or past civil wars. Postwar agglomeration processes, reflected by the contemporaneous structure of Japan's business and social networks, instead of cultural differences, induced by long‐lasting historical shocks, are identified as an explanation for the east–west bias in intra‐Japanese trade.
How Can Three Questions on Modernity Be Answered? The World‐System Theory and Japanese Experiences
Authors: Yamada Nobuyuki
Published: February 2018

This article addresses three questions on modernity. Can “the premodern” and “the modern” be differentiated in the historical process? If they can, what is the relationship between “the premodern” and “the modern”? And what will become of these relationships in the future? This article attempts to answer these questions by criticizing the world‐system theory and considering some of the experiences of the modernization process in Japan. The world‐system theory has tried to relativize social theories from advanced societies in the global perspective. However, the world‐system, born during the long 16th century, was defined from the start as modern and capitalist. Therefore, logically this theory cannot adequately grasp the modernization process. To overcome this challenge, this article first accepts the differentiation between “the premodern” and “the modern” and defines modern society as one in which “the modern” is not exclusive but dominant. Second, this article turns to some of the Japanese experiences of “modernization”, particularly in industrial relations. This article asserts that a Japanese‐style society tends to keep “the premodern” over a longer term and to replace “modern” relations with “the premodern” ones in management. The author defined this process as informalization. Third, this article stresses that since the late 1990s with globalization, informalization is no longer derived from original “premodern” relations, which are nowadays reproduced by capital. An example of this is the “black company.” This article notes, finally, that capitalism is likely to reproduce premodern forms for its duration.
Present and future needs for nurses
Authors: Daniel Kathryn M. , Smith Christina Y.
Published: February 2018

This review outlines the major contributors of the present and future needs for nursing in the United States as well as how the situation impacts the vision and goals of the National Institute for Nursing Research (NINR). This is a review and is based on current published literature. There is a relative nursing shortage even though the production of new nurses has been greatly increased since 2010. This is due to the delayed retirement of many baby boomer nurses, and millennials who are more likely to choose nursing as a profession than previous cohorts. However, the numbers and geographic distribution of baby boomer nurses will not be matched by millennials in the pipeline. At the same time, the need for nurses in the healthcare workforce is increasing due to expanded roles and sites for care. Compounding this, only a very small percentage of the whole of nurses choose to be involved in research. In order for nurses to be involved in making contributions to address the vision and goals of NINR, the continued aggressive growth and development of the nursing workforce is needed.
Pain amplification—A perspective on the how, why, when, and where of central sensitization
Authors: Woolf Clifford J.
Published: February 2018

Pain is an essential physiological defense against danger, be it external, from the environment, or internal, arising from within the body. The initiation of this acute defensive pain is driven by activation in the periphery of the terminals of high threshold nociceptor sensory neurons by intense or irritant noxious stimuli and comprises both the distinct unpleasant sensation of pain and protective motor responses. Clinical pain, is though, very different from the immediate detection of and reaction to noxious stimuli, it includes ongoing pain and development of pain hypersensitivity in the presence of tissue damage, after nerve injury and in some cases, in the absence of any peripheral pathology. In all these situations, a prominent feature and sometimes prime driver of the pain, is an altered modulation of pain processing within the central nervous system, an amplification consequent on increased excitability and/or reduced inhibition in specific neural networks, which constitute the phenomenon of central sensitization. Recognition of the importance of central sensitization for the maintenance and manifestation of clinical pain states has led to an appreciation that such pain typically is an expression of an altered/disease state of nociceptive circuits in the central nervous system, one triggered but not necessarily sustained by peripheral injury, rather than only a symptom of some ongoing peripheral pathology, and treatment needs to be targeted accordingly.
Use of oral immunosuppressive drugs in the treatment of atopic dermatitis in the Netherlands
Authors: Garritsen F.M. , van den Heuvel J.M. , Bruijnzeel‐Koomen C.A.F.M. , Maitland‐van der Zee A.H. , van den Broek M.P.H. , de Bruin‐Weller M.S.
Published: February 2018

Background

Although atopic dermatitis (AD) is a very common skin disease, data on the percentage of patients with really difficult‐to‐treat AD are scarce. From socio‐economic perspective, it is important to have more insight into these numbers, as new very effective, but expensive, treatment options will be available in the near future for difficult‐to‐treat AD. Estimating the number of patients with AD using oral immunosuppressive drugs can give an impression of the percentage of difficult‐to‐treat patients in the total AD population.

Objective

To give an overview of the use of oral immunosuppressive drugs in patients with AD in the Netherlands.

Methods

Prescription data of oral immunosuppressive drugs in the Netherlands were extracted from a pharmaceutical database (NControl) containing data of 557 million prescriptions and 7.2 million patients. An algorithm, based on the WHO Anatomical Therapeutic Chemical (ATC) codes, was used to identify patients with AD. The prescription of oral immunosuppressive drugs in patients with AD between 1 January 2012 and 1 January 2017 was evaluated.

Results

Based on the algorithm, 65 943 patients with AD were selected. 943 patients with AD (1.4%) used cyclosporine A, methotrexate, azathioprine or mycophenolic acid. Methotrexate was most commonly used, followed by azathioprine and cyclosporine A. A switch in medication was rarely seen. In the evaluation period, a decrease in the prescription of cyclosporine A was seen, together with an increase in the prescription of methotrexate. In 31% of the patients who stopped treatment, the discontinuation took place within the first months of treatment.

Conclusion

In this study population, 1.4% of the patients with AD used oral immunosuppressive drugs for their eczema in a 5‐year period. Methotrexate was the most commonly used systemic drug in the Netherlands for the treatment of AD.
Structure versus time in the evolutionary diversification of avian carotenoid metabolic networks
Authors: Morrison Erin S. , Badyaev Alexander V.
Published: February 2018

Historical associations of genes and proteins are thought to delineate pathways available to subsequent evolution; however, the effects of past functional involvements on contemporary evolution are rarely quantified. Here, we examined the extent to which the structure of a carotenoid enzymatic network persists in avian evolution. Specifically, we tested whether the evolution of carotenoid networks was most concordant with phylogenetically structured expansion from core reactions of common ancestors or with subsampling of biochemical pathway modules from an ancestral network. We compared structural and historical associations in 467 carotenoid networks of extant and ancestral species and uncovered the overwhelming effect of pre‐existing metabolic network structure on carotenoid diversification over the last 50 million years of avian evolution. Over evolutionary time, birds repeatedly subsampled and recombined conserved biochemical modules, which likely maintained the overall structure of the carotenoid metabolic network during avian evolution. These findings explain the recurrent convergence of evolutionary distant species in carotenoid metabolism and weak phylogenetic signal in avian carotenoid evolution. Remarkable retention of an ancient metabolic structure throughout extensive and prolonged ecological diversification in avian carotenoid metabolism illustrates a fundamental requirement of organismal evolution – historical continuity of a deterministic network that links past and present functional associations of its components.
Egg‐laying environment modulates offspring responses to predation risk in an amphibian
Authors: Tóth Zoltán , Hettyey Attila
Published: February 2018

Predator‐induced plasticity has been in the focus of evolutionary ecological research in the last decades, but the consequences of temporal variation in the presence of cues predicting offspring environment have remained controversial. This is partly due to the fact that the role of early environmental effects has scarcely been scrutinized in this context while also controlling for potential maternal effects. In this study, we investigated how past environmental conditions, that is different combinations of risky or safe adult (prenatal) and oviposition (early post‐natal) environments, affected offspring's plastic responses in hatching time and locomotor activity to predation risk during development in the smooth newt (Lissotriton vulgaris). We found that females did not adjust their reproductive investment to the perceived level of risk in the adult environment, and this prenatal environment had generally negligible effect on offspring phenotype. However, when predator cues were absent during oviposition, larvae raised in the presence of predator cues delayed their hatching and exhibited a decreased activity compared to control larvae developing without predator cues, which responses are advantageous when predators pose a threat to hatched larvae. In the presence of predator cues during oviposition, the difference in hatching time persisted, but the difference in general locomotor activity disappeared between risk‐exposed and control larvae. Our findings provide clear experimental evidence that fine‐scale temporal variation in a predictive cue during and after egg‐laying interactively affects offspring phenotype, and highlight the importance of the early post‐natal environment, which may exert a substantial influence on progeny's phenotype also under natural conditions.
Critical appraisal of nonrandomized studies—A review of recommended and commonly used tools
Authors: Quigley Joan M. , Thompson Juliette C. , Halfpenny Nicholas J. , Scott David A.
Published: February 2018

Rationale, aims, and objectives

When randomized controlled trial data are limited or unavailable, or to supplement randomized controlled trial evidence, health technology assessment (HTA) agencies may rely on systematic reviews of nonrandomized studies (NRSs) for evidence of the effectiveness of health care interventions. NRS designs may introduce considerable bias into systematic reviews, and several methodologies by which to evaluate this risk of bias are available. This study aimed to identify tools commonly used to assess bias in NRS and determine those recommended by HTA bodies.

Methods

Appraisal tools used in NRS were identified through a targeted search of systematic reviews (January 2013‐March 2017; MEDLINE and EMBASE [OVID SP]). Recommendations for the critical appraisal of NRS by expert review groups and HTA bodies were reviewed.

Results

From the 686 studies included in the narrative synthesis, 48 critical appraisal tools were identified. Commonly used tools included the Newcastle‐Ottawa Scale, the methodological index for NRS, and bespoke appraisal tools. Neither the Cochrane Handbook nor the Centre for Reviews and Dissemination recommends a particular instrument for the assessment of risk of bias in NRS, although Cochrane has recently developed their own NRS critical appraisal tool. Among HTA bodies, only the Canadian Agency for Drugs and Technologies in Health recommends use of a specific critical appraisal tool—SIGN 50 (for cohort or case‐control studies). Several criteria including reporting, external validity, confounding, and power were examined.

Conclusion

There is no consensus between HTA groups on the preferred appraisal tool. Reviewers should select from a suite of tools on the basis of the design of studies included in their review.
Prostate cancer screening: Beliefs and practices of the Brazilian physicians with different specialties
Authors: da Rocha Araujo Fernando Antonio Glasner , Barroso Ubirajara de Oliveira
Published: February 2018

Rationale, aims, and objectives

Prostate cancer (PC) presents with a high prevalence, but a low mortality. The evaluation of the risk‐benefit ratio of current screening methods has led to conflicting results, which are reflected in some contradictory recommendations proposed by scientific and governmental entities. In this context of uncertainty, our objective is to verify the practices and beliefs of Brazilian physicians of different specialties regarding screening for PC.

Methods

A cross‐sectional study was conducted through a self‐administered questionnaire survey during the main events of the target specialties (general practitioner, geriatrics, and urology) during the year 2016. We evaluated the practices on 6 main points of conduct in PC screening: previous discussion to informed decision, exams indicated, age of onset with and without additional risk factors, repeat interval, and age when screening is suspended. Responses were analysed with descriptive statistics and correlation, using the Statistical Package for the Social Sciences program (IBM SPSS Statistics version 20, 2010).

Results

The screening recommendation for PC differs significantly among specialists in association with previous discussion of benefits/harm (P = 0.026), exams used (P < 0.001), age of beginning screening with and without additional risk (P < 0.001), and age of suspension of the screening program (P < 0.001).

Conclusions

Our findings indicate that there is a significant difference of conduct between doctors in different specialties. To the best of the author's knowledge, this is the first study that directly compares the practices of these different specialists in relation to the main points involved in screening for PC.
General nutrition knowledge among carers at group homes for people with intellectual disability
Authors: Hamzaid N. H. , Flood V. M. , Prvan T. , O'Connor H. T.
Published: February 2018

Background

Good nutrition knowledge among carers of people with intellectual disability (ID) living in group homes is essential as they have a primary role in food provision for residents. Research on the nutrition knowledge of carers is limited.

Method

This cross‐sectional study assessed the level of general nutrition knowledge in a convenience sample of Australian carers (C) of people with ID and compared this to the general Australian community (CM). Nutrition knowledge was evaluated using the validated General Nutrition Knowledge Questionnaire. Total knowledge score as well as performance on instrument sub‐sections (dietary guidelines, nutrient sources, healthy food choices and diet disease relationships) were assessed (expressed as %). Knowledge scores were adjusted for known confounders (age, sex, education level, BMI, living arrangement and English spoken at home) using generalised linear modelling.

Results

A total of 589 participants were recruited (C: n = 40; CM: n = 549). Age (C: 40.8 ± 12.1 year; CM: 37.8 ± 13.3 years; P = 0.145), sex distribution (C: 62.5%; CM: 67.2% female; P = 0.602) and English spoken at home (C: 82.5%; CM: 89.6%; P = 0.183) were similar between groups, but BMI (C: 28.5 ± 5.7 kgm−2; CM: 25.3 kgm−2; P = 0.002) was significantly lower and tertiary education (C: 52.5%; CM: 85.1%; P < 0.0005) significantly higher for CM. Total knowledge score (C: 56.6 ± 12.6%; CM: 67.2 ± 12.6%; P < 0.0005) and performance on all instrument sub‐sections (P ≤ 0.004) were significantly lower for carers. This remained after confounder adjustment except for the knowledge of dietary guidelines sub‐section (P = 0.116).

Conclusion

Limited carer nutrition knowledge may compromise their ability to plan and adapt meals to support a healthy and appropriate diet for people with ID in group homes.