bluuebunny/crossref_metadata_2025 huggingface dataset:
Participation of protein kinases and phosphatases in the progesterone‐induced acrosome reaction and calcium influx in human spermatozoa
Authors: Barón L. , Fara K. , Zapata‐Carmona H. , Zuñiga L. , Kong M. , Signorelli J. , Díaz E. S. , Morales P.
Published: October 2016

In human spermatozoa, protein kinases have a role in the acrosome reaction (AR) induced by a variety of stimuli. However, there is disagreement or a lack of information regarding the role of protein kinases and phosphatases in the progesterone (P)‐induced increase in intracellular calcium concentration ([Ca2+]i). In addition, there are no studies regarding the role of Ser/Thr and Tyr phosphatases and there are contradictory results regarding the role of Tyr kinases in the P‐induced acrosome reaction. Here, we performed a simultaneous evaluation of the involvement of protein kinases and phosphatases in the P‐induced acrosome reaction and in the P‐induced calcium influx. Motile spermatozoa were capacitated for 18 h and different aliquots were allocated to treated or control groups and then evaluated for their ability to undergo the acrosome reaction and to increase [Ca2+]i in response to P. The acrosome reaction was evaluated using Pisum sativum agglutinin (PSA)‐FITC, and [Ca2+]i was evaluated using fura 2AM. At all of the concentrations tested, PKA inhibitors significantly reduced the percentage of the P‐induced acrosome reaction (p < 0.001). However, only the highest concentrations of PKA inhibitors reduced the P‐induced calcium influx; lower concentrations of PKA inhibitors did not affect it. Similar results were apparent for PKC inhibitors and for tyrosine kinase inhibitors. None of the Ser/Thr phosphatase inhibitors affected the P‐induced acrosome reaction or the P‐induced calcium influx, except for the PP2B inhibitors that significantly reduced the P‐induced acrosome reaction without affecting calcium influx. Finally, the protein tyrosine phosphatase inhibitors significantly blocked the P‐induced acrosome reaction and reduced the amplitude of the P‐induced calcium transient (p < 0.001) as well as the amplitude of the plateau phase (p < 0.01). The data suggest that protein kinases and possibly PP2B have a role on the acrosome reaction at some point downstream of calcium entry and that Tyr phosphatases have a role on the acrosome reaction upstream of calcium entry.
Velamentous or marginal cord insertion and the risk of spontaneous preterm birth, prelabor rupture of the membranes, and anomalous cord length, a population‐based study
Authors: Ebbing Cathrine , Johnsen Synnøve L. , Albrechtsen Susanne , Sunde Ingvild D. , Vekseth Christina , Rasmussen Svein
Published: October 2016

Introduction

Anomalous cord insertion is associated with increased risk of adverse maternal and perinatal outcome. Our aim was to study whether anomalous cord insertion is associated with prelabor rupture of membranes (PROM), preterm PROM (pPROM), long or short umbilical cord, and time trend of spontaneous preterm birth (SPTB) and anomalous cord insertion.

Material and methods

A population‐based register study using data from the Medical Birth Register of Norway including all singleton births (gestational age >16 weeks and <45 weeks) during 1999–2013 (n = 860 465) to calculate odds ratios (ORs) for PROM, pPROM, SPTB, and cord length (>95th or <5th centile) according to the cord insertion site by logistic regression with adjustment for possible confounders. We also assessed time trends of SPTB and anomalous cord insertion.

Results

Velamentous insertion of the cord was associated with an increased risk of PROM (OR 1.6, 95% CI 1.5–1.7), pPROM (OR 2.7, 95% CI 2.4–3.0), SPTB (OR 2.0, 95% CI 1.9–2.2), and a short cord (OR 1.7, 95% CI 1.5–1.8). Marginal insertion was to a lesser extent associated with these complications. Occurrences of SPTB and anomalous insertion declined. The decline in SPTB persisted after including an interaction term between anomalous insertion and time.

Conclusions

Velamentous and, to a lesser extent, marginal cord insertions were associated with increased risk of PROM, pPROM, SPTB, and short cord. This suggests a common pathogenesis behind altered function of the membranes, cord, and placenta. The decline in SPTB could not be explained by the reduction in the occurrence of anomalous cord insertion.
‘At least in person there would have been a cup of tea’: interviewing via Skype
Authors: Adams‐Hutcheson Gail , Longhurst Robyn
Published: October 2016

Fieldwork is being stretched in new directions across time and space. In this article we examine the kinds of emotional and affective encounters constructed in online interviews. We draw on Lefebvre's notion of rhythm and Ash's concept of ‘affective atmospheres’ to help identify moments of disjuncture in research interviews. These moments of disjuncture can be prompted by researchers and participants not being able to share a range of senses (touch, smell and taste) during Skype interviews. The technology does not sink into the background but instead can, for some, prompt an uncomfortable ‘affective atmosphere’. Finally, we argue that bodies, performance, digital interfaces, movement, senses, emotion and affect need to grappled with methodologically as increasing numbers of researchers turn to online interviewing.
In vitro evaluation of apoptotic effect of bis(acetylacetonato‐k2O,O′)(1,10‐phenanthroline‐k2 N,N′)Zn(II) complex
Authors: Trejo‐Solis Cristina , Alvarez‐Lemus Mayra A. , Jiménez‐Farfán Dolores , Anaya‐Rubio Isabel , López‐González Rosendo , Palencia Guadalupe , Frías‐Márquez Dora M. , González‐García Gerardo , Rubio‐Osornio Carmen , Calvillo‐Velasco Minerva , Márquez‐Chablé Guadalupe
Published: October 2016

Phenanthroline derivatives have been reported as potential bioactive compounds because of their ability to interact with DNA. To evaluate the antiproliferative effect of bis(acetylacetonate‐k2 O,O)(1,10‐phenanthroline‐k2 N,N)Zn(II) or Zn(acac)2(phen) complex, the compound was obtained in a simple manner and further characterized to determine crystal structure, thermal behavior, morphology, and spectroscopic properties. The structure of the complex was confirmed by X‐ray single structure as well as by 1H and 13C nuclear magnetic resonance (NMR) in dmso‐d6 (dimethyl sulfoxide) solution and in the solid state by 13C CP/MAS. Although preparation of this compound has been described previously, there are no reports on its biological activity; here, we assessed its antiproliferative effect on fibroblasts, A253, FaDu, Cal‐27, RH‐30, RD, U‐373, C6, A‐549, MDA‐MB‐231, and MCF‐7 cancer cell lines at different doses (50–100 and 150 μg/ml). The cell viability was determined by MTT assay and high activity was observed for the most of the cell lines, and TUNEL results showed the induction of apoptosis.
The rs2274911 polymorphism in GPRC6A gene is associated with insulin resistance in normal weight and obese subjects
Authors: Di Nisio Andrea , Rocca Maria Santa , Fadini Gian Paolo , De Toni Luca , Marcuzzo Giorgio , Marescotti Maria Cristina , Sanna Marta , Plebani Mario , Vettor Roberto , Avogaro Angelo , Foresta Carlo
Published: October 2016

Objective

Identification of the novel endocrine role of osteocalcin (OC) and its receptor GPRC6A has given rise to a new branch of research in OC/GPRC6A axis related to glucose metabolism. GPRC6A‐ and OC‐deficient mice share features of the metabolic syndrome, in addition to male infertility. Recently, the polymorphism rs2274911 in GPRC6A was shown to be associated with testicular impairment. We aimed to investigate the role of rs2274911 polymorphism in glucose and lipid metabolism in a cohort of normal weight and obese subjects

Design, Patients, Settings

A total of 392 male and females, including 218 obese patients and 174 age‐matched normal weight controls, were retrospectively selected.

Results

The distribution of rs2274911 alleles and genotypes did not differ either between normal weight and obese subjects or sexes (all P > 0·05). Age‐ and OC‐adjusted multivariate analysis revealed that, in the normal weight group, fasting insulin and HOMA‐IR increased in GA (P = 0·016 and P = 0·025) and AA genotypes (P = 0·033 and P = 0·040) compared with GG homozygotes. In the obese group, AA homozygotes had increased fasting glucose (P = 0·041 vs GG). Triglycerides, fasting insulin and HOMA‐IR increased in both GA (P = 0·020, P < 0·001 and P = 0·001) and AA genotype (P = 0·021, P = 0·013 and P = 0·013).

Conclusion

In a cohort of normal weight and obese subjects, we found that the nonrare polymorphism rs2274911 in the GPRC6A gene was associated with insulin resistance features, independently of the metabolic phenotype and OC levels.
New York University School of Medicine Drug Development Educational Program: 2‐Year Benchmark
Authors: Plaksin J , Cymerman RM , Caso Caso R , Galeano C , Ramasamy R , Gold‐von Simson G
Published: October 2016

Drug development (DD) is a multidisciplinary process that spans the translational continuum, yet remains an understudied entity in medical schools and biomedical science institutes. In response to a growing interest and unmet need, we implemented a DD course series that details identification of viable molecular targets, clinical trial design, intellectual property, and marketing. Enrollment is open to faculty, postdoctoral trainees, and MD, PhD, and MS students. After 2 years, 37 students and 23 students completed the fall and spring courses, respectively. Pre/post‐surveys demonstrated gained knowledge across course topics, with mean survey scores increased by 66% (p < 0.001) after each course. Lectures for each course were consistently rated highly, with a mean course rating of 4.1/5. Through this program, trainees will have a more innovative approach toward identification of therapeutic targets and modalities. Furthermore, they will learn to integrate technology and biomedical informatics to find creative solutions in the DD process.
Implicit and explicit false belief development in preschool children
Authors: Grosse Wiesmann Charlotte , Friederici Angela D. , Singer Tania , Steinbeis Nikolaus
Published: October 2016

The ability to represent the mental states of other agents is referred to as Theory of Mind (ToM). A developmental breakthrough in ToM consists of understanding that others can have false beliefs about the world. Recently, infants younger than 2 years of age have been shown to pass novel implicit false belief tasks. However, the processes underlying these tasks and their relation to later‐developing explicit false belief understanding, as well as to other cognitive abilities, are not yet understood. Here, we study a battery of implicit and explicit false belief tasks in 3‐ and 4‐year‐old children, relating their performance to linguistic abilities and executive functions. The present data show a significant developmental change from failing explicit false belief tasks at 3 years of age to passing them at the age of 4, while both age groups pass implicit false belief tasks. This differential developmental trajectory is reflected by the finding that explicit and implicit false belief tasks do not correlate. Further, we demonstrate that explicit false belief tasks correlate with syntactic and executive functions, whereas implicit false belief tasks do not. The study thus indicates that the processes underlying implicit false belief tasks are different from later‐developing explicit false belief understanding. Moreover, our results speak for a critical role of syntactic and executive functions for passing standard explicit false belief tasks in contrast to implicit tasks.
Assessment of the family environment in pediatric neurodisability: a state‐of‐the‐art review
Authors: Ketelaar Marjolijn , Bogossian Aline , Saini Michael , Visser‐Meily Anne , Lach Lucyna
Published: October 2016

The importance of the family environment for the development of children with neurodisabilities is undisputed. The objective of this study is to describe how family environment has been measured in research on families of children with neurodisabilities, in order to support researchers and clinicians to select appropriate methods for use. A three‐step approach was used and 13 measures of family environment were identified within 77 studies. Five measures were used most commonly across a majority of studies (n=50). The measures varied considerably in terms of theoretical background, content, subscales, and populations for which they were developed and validated. These measures were used with considerable variability between studies and with a limited range of research respondents, most typically the child's mother. Challenges, opportunities, and suggestions on how to improve the application of family environment measures in research are discussed.
Dispersal differences of a pest and a protected Cerambyx species (Coleoptera: Cerambycidae) in oak open woodlands: a mark–recapture comparative study
Authors: TORRES‐VILA LUIS M. , MENDIOLA‐DIAZ FRANCISCO J. , SÁNCHEZ‐GONZÁLEZ ÁLVARO
Published: October 2016

1. Cerambyx welensii (Cw) and Cerambyx cerdo (Cc) are two large saproxylic beetles living on Quercus trees in the Western Palearctic whose current pest and legal status differs markedly. Cw is an emerging pest involved in oak decline while Cc is an internationally protected species.

2. Acquiring knowledge of the ecology, demography and behaviour of Cw and Cc in forests harbouring mixed populations is a demanding task to optimise their management or protection. Here, we report the results of a mark–recapture study on the flight behaviour and dispersal potential of both species in holm oak open woodlands.

3. Average flights, dispersal rates and diffusion models were remarkably similar in Cw and Cc, reflecting a low‐dispersal tendency and sedentary behaviour. However, a subset of adults in both species exhibited a huge propensity to disperse and flew more than 1 km. An aggregated distribution of dispersal distances suggested that a behavioural polymorphism might underlie the flight pattern.

4. Adults moved preferentially in those spatial directions with neighbouring trees, while prevailing winds did not significantly affect dispersal patterns. The main interspecific differences were as follows: (i) Cc performed longer crosswind flights than Cw on windy days; (ii) Cc tended to fly farther than Cw at low temperatures; and (iii) adult feeding improved dispersal but only in small Cw females. Moon phase did not affect flight activity.

5. The results are discussed in an effort to interpret how these ecological and behavioural differences might shape the life history of both congeneric species when they live in sympatry in dehesa woodlands.
Iron oxides and rare earth elements in the clay fractions of a soil chronosequence in southern Spain
Authors: Martín‐García J. M. , Sánchez‐Marañón M. , Calero J. , Aranda V. , Delgado G. , Delgado R.
Published: October 2016

Mineralogical (XRD), crystallochemical (DXRD), geochemical (ICP‐ms and ICP‐AES) and spectroscopic colour (DRS) properties of the clay fractions confirmed that five soils (a Fluvisol, two Calcisols and two Luvisols) on fluvial terraces in southern Spain form a genuine chronosequence that extends back to 600 ka. Analyses showed that goethite was more abundant than haematite. Both iron (hydr)oxide contents and Al substitution in goethite (mole %) increased with soil age. The Fe in the (hydr)oxides came from the transformation of illites to smectite + mixed‐layer phyllosilicates. Rare earth element contents correlated with a mafic alteration index and with soil age. Soil colours reflected variation in the proportions of calcite and iron (hydr)oxides, and became redder with age. Most soil properties were fitted by logarithmic chronofunctions that approach asymptotes at 70–100 ka.

Highlights

A chronosequence is confirmed from the soil of fluvial terraces in southern Spain.

Goethite exceeds haematite throughout and increases with soil age.

Rare earth elements correlate with a mafic alteration index and soil age.

Most soil attributes show logarithmic chronofunctions with asymptotes at 70–100 ka.
Understanding and monitoring the consequences of human impacts on intraspecific variation
Authors: Mimura Makiko , Yahara Tetsukazu , Faith Daniel P. , Vázquez‐Domínguez Ella , Colautti Robert I. , Araki Hitoshi , Javadi Firouzeh , Núñez‐Farfán Juan , Mori Akira S. , Zhou Shiliang , Hollingsworth Peter M. , Neaves Linda E. , Fukano Yuya , Smith Gideon F. , Sato Yo‐Ichiro , Tachida Hidenori , Hendry Andrew P.
Published: October 2016

Intraspecific variation is a major component of biodiversity, yet it has received relatively little attention from governmental and nongovernmental organizations, especially with regard to conservation plans and the management of wild species. This omission is ill‐advised because phenotypic and genetic variations within and among populations can have dramatic effects on ecological and evolutionary processes, including responses to environmental change, the maintenance of species diversity, and ecological stability and resilience. At the same time, environmental changes associated with many human activities, such as land use and climate change, have dramatic and often negative impacts on intraspecific variation. We argue for the need for local, regional, and global programs to monitor intraspecific genetic variation. We suggest that such monitoring should include two main strategies: (i) intensive monitoring of multiple types of genetic variation in selected species and (ii) broad‐brush modeling for representative species for predicting changes in variation as a function of changes in population size and range extent. Overall, we call for collaborative efforts to initiate the urgently needed monitoring of intraspecific variation.
Theorising Interdisciplinary Public Sector Accounting Research
Authors: Jacobs Kerry
Published: October 2016

Asbtract

While the volume of interdisciplinary public sector accounting research has expanded, there has been a call to deepen the theorisation. This paper explores the theorisation of the most highly cited interdisciplinary public sector accounting as a tool to understand better what constitutes the dominant or doxic theoretical approaches. Accountability, New Public Management (NPM) and Habermasian theorisation were the three most significant and dominant approaches which could be seen as examples of what Llewellyn (2003) classifies as grand theory (Habermas) and conceptual innovation (accountability and NPM). Much of the accountability work presents the notion of a clash between different forms of accountability, particularly associated with managerialist NPM characteristics. Despite Llewellyn's (2003) criticism of grand theoretical approaches, there are many examples of Habermasian elements being combined with other theoretical approaches to assist exploration of both micro practices and the broader social and societal impact of public sector changes. As such, there is an endorsement of theoretical approaches which address both the micro behaviour and the macro impact of accounting practices in the context of the public sector.
Not What It Said on the Tin? Reflections on Three Decades of UK Public Management Reform
Authors: Hood Christopher , Dixon Ruth
Published: October 2016

Despite decades of research, we still need more long‐term evidence of the effects of New Public Management (NPM) and accompanying changes in government over a generation. Looking at UK experience, a key case in NPM and digital‐age developments, this paper evaluates administrative data to show what happened to indicators of fairness and consistency and of prudent management through limitation of running costs in public administration over three decades. The analysis shows that running costs rose substantially in real terms (contrary to the cost‐cutting stereotype of NPM), while indicators of first‐stage formal challenges to government suggest increased dissatisfaction with fairness and consistency in administration.
New Public Management: The Story Continues
Authors: Hyndman Noel , Lapsley Irvine
Published: October 2016

New Public Management (NPM) has aroused significant interest amongst academe, policy makers and practitioners, since its first articulation in the seminal articles by Hood (1991 and 1995). However, in the 21stcentury, a body of opinion has developed which asserts that the NPM ispassé. This paper seeks to determine the contemporary status of NPM in the context of the UK, one of the early adopters of NPM. Close inspection of UK Government policy underlines the importance of NPM ideas in the New Labour Governmentmodernisationpolicy (1997‐2010). Furthermore, the policy actions of the 2010–2015 UK Coalition Government reveal that the global financial crisis intensified the drive for NPM in the UK's public sector. This discussion reveals no evidence in support of the demise of NPM.
Phosphatidic acid induces decidualization by stimulating Akt‐PP2A binding in human endometrial stromal cells
Authors: Lee So Young , Lee Yun Young , Choi Joong Sub , Yoon Mee‐Sup , Han Joong‐Soo
Published: October 2016

Decidualization of human endometrial stromal cells (hESCs) is crucial for successful uterine implantation and maintaining pregnancy. We previously reported that phospholipase D1 (PLD1) is required for cAMP‐induced decidualization of hESCs. However, the mechanism by which phosphatidic acid (PA), the product of PLD1 action, might regulate decidualization is not known. We confirmed that PA induced decidualization of hESCs by observing morphological changes and measuring increased levels of decidualization markers such as IGFBP1 and prolactin transcripts (P < 0.05). Treatment with PA reduced phosphorylation of Akt and consequently that of FoxO1, which led to the increased IGFBP1 and prolactin mRNA levels (P < 0.05). Conversely, PLD1 knockdown rescued Akt phosphorylation. Binding of PP2A and Akt increased in response to cAMP or PA, suggesting that their binding is directly responsible for the inactivation of Akt during decidualization. Consistent with this observation, treatment with okadaic acid, a PP2A inhibitor, also inhibited cAMP‐induced decidualization by blocking Akt dephosphorylation.
Structural basis for endotoxin neutralization by the eosinophil cationic protein
Authors: Pulido David , Garcia‐Mayoral Maria Flor , Moussaoui Mohammed , Velázquez Diego , Torrent Marc , Bruix Marta , Boix Ester
Published: October 2016

Acute infection by Gram‐negative pathogens can induce an exacerbated immune response that leads to lethal septic shock syndrome. Bacterial lipopolysaccharide (LPS) is a major pathogen‐associated molecular pattern molecule that can initiate massive and lethal immune system stimulation. Therefore, the development of new and effective LPS‐neutralizing agents is a top priority. The eosinophil cationic protein (ECP) is an antimicrobial protein secreted in response to infection, with a remarkable affinity for LPS. In the present study, we demonstrate that ECP is able to neutralize bacterial LPS and inhibit tumor necrosis factor‐α production in human macrophages. We also characterized ECP neutralizing activity using progressively truncated LPS mutants, and conclude that the polysaccharide moiety and lipid A portions are required for LPS‐mediated neutralization. In addition, we mapped the structural determinants required for the ECP–LPS interaction by nuclear magnetic resonance. Our results show that ECP is able to neutralize LPS and therefore opens a new route for developing novel therapeutic agents based on the ECP structural scaffolding.
Corporate Governance, Product Market Competition, and the Wealth Effect of R&D Spending Changes
Authors: Liao Tsai‐Ling , Lin Wen‐Chun
Published: October 2016

This article examines whether corporate governance and product market competition interact to affect the profitability of corporate research and development (R&D) investments. Firms announcing R&D spending changes experience positive and significant wealth effects, and these effects are mainly driven by good‐governance firms. Investors appear to view announcements of R&D spending changes undertaken by firms with stronger shareholder rights as evidence of value creation. Moreover, the favorable wealth effects are stronger for good‐governance firms in noncompetitive industries than in competitive industries, supporting the argument that good governance substitutes for product market competition.
Field‐grown transgenic switchgrass (Panicum virgatum L.) with altered lignin does not affect soil chemistry, microbiology, and carbon storage potential
Authors: DeBruyn Jennifer M. , Bevard David A. , Essington Michael E. , McKnight Julie Y. , Schaeffer Sean M. , Baxter Holly L. , Mazarei Mitra , Mann David G. J. , Dixon Richard A. , Chen Fang , Zhuo Chunliu , Wang Zeng‐Yu , Stewart Charles Neal
Published: October 2016

Cell wall recalcitrance poses a major challenge on cellulosic biofuel production from feedstocks such as switchgrass (Panicum virgatum L.). As lignin is a known contributor of recalcitrance, transgenic switchgrass plants with altered lignin have been produced by downregulation of caffeic acid O‐methyltransferase (COMT). Field trials of COMT‐downregulated plants previously demonstrated improved ethanol conversion with no adverse agronomic effects. However, the rhizosphere impacts of altering lignin in plants are unknown. We hypothesized that changing plant lignin composition may affect residue degradation in soils, ultimately altering soil processes. The objective of this study was to evaluate effects of two independent lines of COMT‐downregulated switchgrass plants on soils in terms of chemistry, microbiology, and carbon cycling when grown in the field. Over the first two years of establishment, we observed no significant differences between transgenic and control plants in terms of soil pH or the total concentrations of 19 elements. An analysis of soil bacterial communities via high‐throughput 16S rRNA gene amplicon sequencing revealed no effects of transgenic plants on bacterial diversity, richness, or community composition. We also did not observe a change in the capacity for soil carbon storage: There was no significant effect on soil respiration or soil organic matter. After five years of establishment, δ13C of plant roots, leaves, and soils was measured and an isotopic mixing model used to estimate that 11.2 to 14.5% of soil carbon originated from switchgrass. Switchgrass‐contributed carbon was not significantly different between transgenic and control plants. Overall, our results indicate that over the short term (two and five years), lignin modification in switchgrass through manipulation of COMT expression does not have an adverse effect on soils in terms of total elemental composition, bacterial community structure and diversity, and capacity for carbon storage.
ERK activation in endothelial cells is a novel marker during neovasculogenesis
Authors: Nagasawa‐Masuda Ayumi , Terai Kenta
Published: October 2016

Vasculogenesis is essential during early development to construct networks transporting oxygen, blood and nutrients. Tip and stalk cells are specialized endothelial cells involved in novel vessel formation because of their behavior such as sprouting as a leading cell and following tip cell. However, the spatiotemporal details determining the emergence of these cells are unknown. Here, we first show that the ERK activity in endothelial cells represents the precursor of tip and stalk cells for vasculogenesis in zebrafish. We identified that tip and stalk cells for intersegmental vessel (ISV) formation were already specialized in the dorsal aorta (DA) before sprouting. Furthermore, similar specialization was observed in tip cells during parachordal vessel (PAV) formation in lymphangiogenesis. We also identified that the ERK activity was required for specialized cells to emerge from existing blood vessels. Our data show that the ERK activity is a novel marker for determining the emergence of cells in both angiogenesis and lymphangiogenesis.
Increased lipogenesis in spite of upregulated hepatic 5'AMP‐activated protein kinase in human non‐alcoholic fatty liver
Authors: von Loeffelholz Christian , Döcke Stephanie , Lock Johan F. , Lieske Stefanie , Horn Paul , Kriebel Jennifer , Wahl Simone , Singmann Paula , de las Heras Gala Tonia , Grallert Harald , Raschzok Nathaniel , Sauer Igor M. , Heller Regine , Jahreis Gerhard , Claus Ralf A. , Bauer Michael , Stockmann Martin , Birkenfeld Andreas L. , Pfeiffer Andreas F.H.
Published: October 2016

Aims

Molecular adaptations in human non‐alcoholic fatty liver disease (NAFLD) are incompletely understood. This study investigated the main gene categories related to hepatic de novo lipogenesis and lipid oxidation capacity.

Methods

Liver specimens of 48 subjects were histologically classified according to steatosis severity. In‐depth analyses were undertaken using real‐time polymerase chain reaction, immunoblotting, and immunohistochemistry. Lipid profiles were analyzed by gas chromatography/flame ionization detection, and effects of key fatty acids were studied in primary human hepatocytes.

Results

Real‐time polymerase chain reaction, immunoblotting, and immunohistochemistry indicated 5'AMP‐activated protein kinase (AMPK) to be increased with steatosis score ≥ 2 (all P < 0.05), including various markers of de novo lipogenesis and lipid degradation (all P < 0.05). Regarding endoplasmic reticulum stress, X‐Box binding protein‐1 (XBP1) was upregulated in steatosis score ≥ 2 (P = 0.029) and correlated with plasma palmitate (r = 0.34; P = 0.035). Palmitate incubation of primary human hepatocytes increased XBP1 and downstream stearoyl CoA desaturase‐1 mRNA expression (both P < 0.05). Moreover, plasma and liver tissue exposed a NAFLD‐related lipid profile with reduced polyunsaturated/saturated fatty acid ratio, increased palmitate and palmitoleate, and elevated lipogenesis and desaturation indices with steatosis score ≥ 2 (all P < 0.05).

Conclusion

In humans with advanced fatty liver disease, hepatic AMPK protein is upregulated, potentially in a compensatory manner. Moreover, pathways of lipid synthesis and degradation are co‐activated in subjects with advanced steatosis. Palmitate may drive lipogenesis by activating XBP1‐mediated endoplasmic reticulum stress and represent a target for future dietary or pharmacological intervention.
Evaluation of root maturation after revitalization in immature permanent teeth with nonvital pulps by cone beam computed tomography and conventional radiographs
Authors: Linsuwanont P. , Sinpitaksakul P. , Lertsakchai T.
Published: October 2016

Aim

To investigate the response of immature permanent teeth with nonvital pulps after revitalization procedures using cone beam computed tomography imaging and conventional radiograph.

Methodology

Clinical records of patients who had undergone revitalization between 1997 and 2014 were collected. Seventeen patients attended the follow‐up examination. Clinical examination and radiographic examination by means of CBCT imaging and conventional radiographs were conducted to evaluate treatment outcomes, especially the dimensional changes of the root and the pattern of root maturation. Statistical analysis was conducted using Fisher's exact test and Monte Carlo test to investigate the effect of potential outcome predictors.

Results

For the follow‐up period as far as 96 months, thirteen teeth (76%) were classified as a ‘success’. Conventional radiographs showed various degrees of dimensional changes in the immature roots ranging from 0% to 73% changes. The mean percentage changes of root length and root wall thickness were 14.38 ± 20.92% and 13.82 ± 11.17%, respectively. CBCT images illustrated various patterns of root maturation including incomplete root development with wide‐open apices and fully formed roots with various apical shapes. Root canal contents varied radiographically from empty canals to many degrees of unpredictable patterning of radiopaque deposits.

Conclusion

Revitalization in immature teeth with nonvital pulps resulted in unpredictable responses in terms of continued root development. Various types of root maturation and root canal contents were observed radiographically, which were different from typical root development.
A new method for the assessment of the surface topography of NiTi rotary instruments
Authors: Ferreira F. , Barbosa I. , Scelza P. , Russano D. , Neff J. , Montagnana M. , Zaccaro Scelza M.
Published: October 2016

Aim

To describe a new method for the assessment of nanoscale alterations in the surface topography of nickel–titanium endodontic instruments using a high‐resolution optical method and to verify the accuracy of the technique.

Methodology

Noncontact three‐dimensional optical profilometry was used to evaluate defects on a size 25, .08 taper reciprocating instrument (WaveOne®), which was subjected to a cyclic fatigue test in a simulated root canal in a clear resin block. For the investigation, an original procedure was established for the analysis of similar areas located 3 mm from the tip of the instrument before and after canal preparation to enable the repeatability and reproducibility of the measurements with precision. All observations and analysis were taken in areas measuring 210 × 210 μm provided by the software of the equipment.

Results

The three‐dimensional high‐resolution image analysis showed clear alterations in the surface topography of the examined cutting blade and flute of the instrument, before and after use, with the presence of surface irregularities such as deformations, debris, grooves, cracks, steps and microcavities.

Conclusions

Optical profilometry provided accurate qualitative nanoscale evaluation of similar surfaces before and after the fatigue test. The stability and repeatability of the technique enables a more comprehensive understanding of the effects of wear on the surface of endodontic instruments.
Climate change and the epidemiology of selected tick‐borne and mosquito‐borne diseases: update from the International Society of Dermatology Climate Change Task Force
Authors: Andersen Louise K. , Davis Mark D. P.
Published: October 2016

Climate change refers to variation in the climate of a specific region or globally over time. A change has been reported in the epidemiology of tick‐ and mosquito‐borne diseases in recent decades. Investigators have postulated that this effect may be associated with climate change. We reviewed the English‐language literature describing changes in the epidemiology of specific tick‐ and mosquito‐borne diseases, including the tick‐borne diseases of Lyme disease, tularemia, Crimean‐Congo hemorrhagic fever, Mediterranean spotted fever, and Rocky Mountain spotted fever and the mosquito‐borne diseases of dengue, malaria, West Nile virus infection, Ross River virus disease, and Barmah Forest virus disease. We postulate that the changing epidemiology of tick‐ and mosquito‐borne diseases is related to climate change.
Prescribing antibiotics in diabetic foot infection: what is the role of initial microscopy and culture of tissue samples?*
Authors: Chisman Robin , Lowry Danielle , Saeed Mujahid A , Tiwari Alok , David Miruna D
Published: October 2016

The aim of this study was to evaluate the role of microscopy, Gram stain and the culture of tissue samples in the antibiotic treatment of patients with diabetic foot infection. A retrospective review of patients with a diabetic foot infection was undertaken. Data analysed included the severity of infection, antibiotic prescribing patterns, microscopy and culture results. A total of 71 patients were included, from whom 114 tissue samples were collected. Gram stain results were in agreement with final culture results in 45·8% (n = 54) of samples. Overall sensitivity and specificity of the Gram stains were low (74·5% and 69·8%, respectively), although the specificity for Gram‐negative rods was high (98·5%). The presence or absence of ‘pus cells’ on microscopy was a poor predictor of culture results. Empirical prescribing of antibiotics was in accordance with local policy in 31·1% of patients, improving to 86·8 % following culture results. Microscopy, a skilled laboratory procedure, was generally a poor predictor of tissue culture results. However, the presence of Gram‐negative rods was suggestive of isolation in the culture of such organisms and could allow the early broadening of antibiotic treatment. Despite initial poor compliance of empirical antibiotic treatment regimens, prescribing was adjusted in light of culture results, suggesting these were important for clinicians.
The anti‐ageing hormone klotho induces Nrf2‐mediated antioxidant defences in human aortic smooth muscle cells
Authors: Maltese Giuseppe , Psefteli Paraskevi‐Maria , Rizzo Benedetta , Srivastava Salil , Gnudi Luigi , Mann Giovanni E. , Siow Richard C.M.
Published: October 2016

Vascular ageing in conditions such as atherosclerosis, diabetes and chronic kidney disease, is associated with the activation of the renin angiotensin system (RAS) and diminished expression of antioxidant defences mediated by the transcription factor nuclear factor erythroid 2‐related factor 2 (Nrf2). The anti‐ageing hormone klotho promotes longevity and protects against cardiovascular and renal diseases. Klotho has been shown to activate Nrf2 and attenuate oxidative damage in neuronal cells, however, the mechanisms by which it protects against vascular smooth muscle cell VSMC dysfunction elicited by Angiotensin II (AngII) remain to be elucidated. AngII contributes to vascular ageing and atherogenesis by enhancing VSMC oxidative stress, senescence and apoptosis. This study demonstrates that soluble klotho (1 nM, 24 hrs) significantly induces expression of Nrf2 and the antioxidant enzymes haeme oxygenase (HO‐1) and peroxiredoxin‐1 (Prx‐1) and enhances glutathione levels in human aortic smooth muscle cells (HASMC). Silencing of Nrf2 attenuated the induction of HO‐1 and Prx‐1 expression by soluble klotho. Furthermore, soluble klotho protected against AngII‐mediated HASMC apoptosis and senescence via activation of Nrf2. Thus, our findings highlight a novel Nrf2‐mediated mechanism underlying the protective actions of soluble klotho in HAMSC. Targeting klotho may thus represent a therapeutic strategy against VSMC dysfunction and cardiovascular ageing.
Clinical and dermoscopic clues to differentiate pigmented nail bands: an International Dermoscopy Society study
Authors: Benati E. , Ribero S. , Longo C. , Piana S. , Puig S. , Carrera C. , Cicero F. , Kittler H. , Deinlein T. , Zalaudek I. , Stolz W. , Scope A. , Pellacani G. , Moscarella E. , Piraccini B.M. , Starace M. , Argenziano G.
Published: October 2016

Background

Longitudinal melanonychia might be difficult to differentiate and the use of dermoscopy can be useful for the preoperative evaluation and management decision.

Objectives

The aim of our study was to investigate clinical and dermoscopic criteria of acquired longitudinal melanonychia in adults to identify the best predictors of melanoma using a multivariate analysis and to explore eventual new dermoscopic criteria for nail melanoma diagnosis.

Methods

In this retrospective observational study, 82 histopathologically diagnosed, acquired nail pigmented bands were collected and examined. All variables were included in the analysis and examined as possible predictors of nail melanoma. Both univariate and multivariable analyses have been performed.

Results

Among 82 cases, 25 were diagnosed as nail melanoma and 57 as benign lesions (including 32 melanocytic nevi and 25 benign melanocytic hyperplasia). Melanoma cases were significantly associated with a width of the pigmented band higher than 2/3 of the nail plate, grey and black colours, irregularly pigmented lines, Hutchinson and micro‐Hutchinson signs, and nail dystrophy. Granular pigmentation, a newly defined dermoscopic criterion, was found in 40% of melanomas and only in 3.51% of benign lesions.

Conclusions

Dermoscopic examination of longitudinal melanonychia provides useful information that could help clinicians to improve melanoma recognition.
Diaminodiphenylmethane Sensitization in north‐eastern Italy from 1996 to 2012
Authors: Zuliani F. , Prodi A. , Fortina A.B. , Corradin M.T. , Bovenzi M. , Filon F. Larese
Published: October 2016

Background

4,4′‐Diaminodiphenylmethane (DDM) is an aromatic amine used as a hardener, insulator and anticorrosive. Exposure implies risk of being sensitized and developing contact dermatitis.

Objective

The aim of this study was to determine the occurrence of contact sensitization to DDM among patients with contact dermatitis and the role of occupational exposure.

Patients and Methods

From 1996 to 2012, 24 056 consecutive patients with suspected allergic contact dermatitis were patch tested in north‐eastern Italy. Individual characteristics were collected through a standardized questionnaire in eight departments of dermatology and occupational medicine.

Results

The overall prevalence of DDM sensitization was 2.5% (n = 599) with a decreasing trend in considered years. Trieste area had the higher prevalence of sensitization (3.2%). Mechanics and chemical industry workers had a significant higher risk of being sensitized to DDM.

Conclusion

DDM sensitization is decreasing in years and is associated with some occupational exposures.
Comparing performance of 30‐day readmission risk classifiers among hospitalized primary care patients
Authors: Garrison Gregory M. , Robelia Paul M. , Pecina Jennifer L. , Dawson Nancy L.
Published: October 2016

Rationale, aims and objectives

Hospital readmission within 30 days of discharge occurs in almost 20% of US Medicare patients and may be a marker of poor quality inpatient care, ineffective hospital to home transitions, or disease severity. Within a patient centered medical home, care transition interventions may only be practical from cost and staffing perspectives if targeted at patients with the greatest risk of readmission. Various scoring algorithms attempt to predict patients at risk for 30‐day readmission, but head‐to‐head comparison of performance is lacking. Compare published scoring algorithms which use generally available electronic medical record data on the same set of hospitalized primary care patients.

Methods

The LACE index, the LACE+ index, the HOSPITAL score, and the readmission risk score were computed on a consecutive cohort of 26,278 hospital admissions. Classifier performance was assessed by plotting receiver operating characteristic curves comparing the computed score with the actual outcome of death or readmission within 30 days. Statistical significance of differences in performance was assessed using bootstrapping techniques.

Results

Correct readmission classification on this cohort was moderate with the following c‐statistics: Readmission risk score 0.666; LACE 0.680; LACE+ 0.662; and HOSPITAL 0.675. There was no statistically significant difference in performance between classifiers.

Conclusions

Logistic regression based classifiers yield only moderate performance when utilized to predict 30‐day readmissions. The task is difficult due to the variety of underlying causes for readmission, nonlinearity, and the arbitrary time period of concern. More sophisticated classification techniques may be necessary to increase performance and allow patient centered medical homes to effectively focus efforts to reduce readmissions.
Better Global Assessment of Worker Inequality: Comment on “The Employment Footprints of Nations”
Authors: Reyes Rachel C. , Lenzen Manfred , Murray Joy
Published: October 2016

This commentary responds to the previously published Journal of Industrial Ecology article “The Employment Footprints of Nations: Uncovering Master‐Servant Relationships” by Alsamawi and colleagues. Their article uses extended input‐output analysis to calculate employment and income footprints and, consequently, quantifies and provides an analysis of the average wages embodied in consumption of countries in comparison with the wages received by domestic workers. In effect, Alsamawi and colleagues show the extent of inequality in labor income, especially between developed and developing economies, traced throughout the global supply chains, but ignore the price differentials existing between countries in their discussion of the welfare implications of global trade on workers. This commentary contends the appropriateness of adjusting nominal compensation of workers to purchasing power parity (PPP) when undertaking global comparisons that pertain to well‐being and recalculates the employment footprints and income footprints of nations with PPP adjustment. The price adjustment in this work is intended to show a more accurate depiction of the disparity among workers of different nations when their labor incomes are deflated by the index price of consumption goods in their country. Using observations covering 189 countries and 14,839 sectors for the period 1990–2011, the results of the adjustment reveal that the ratio of domestic wages to foreign wages paid in support of a country's consumption (footprint wages) tends to be underestimated for labor‐exporting countries (developing economies with relatively cheaper consumption goods) and overestimated for labor‐importing countries (developed economies with more expensive consumption goods), thus demonstrating, generally, relatively less income inequality than previously exposed.
Widespread brain transcriptome alterations underlie the neuroprotective actions of dietary saffron
Authors: Skladnev Nicholas V. , Ganeshan Varshika , Kim Ji Yeon , Burton Thomas J. , Mitrofanis John , Stone Jonathan , Johnstone Daniel M.
Published: October 2016

Dietary saffron has shown promise as a neuroprotective intervention in clinical trials of retinal degeneration and dementia and in animal models of multiple CNS disorders, including Parkinson's disease. This therapeutic potential makes it important to define the relationship between dose and protection and the mechanisms involved. To explore these two issues, mice were pre‐conditioned by providing an aqueous extract of saffron (0.01% w/v) as their drinking water for 2, 5 or 10 days before administration of the parkinsonian neurotoxin MPTP (50 mg/kg). Five days of saffron pre‐conditioning provided the greatest benefit against MPTP‐induced neuropathology, significantly mitigating both loss of functional dopaminergic cells in the substantia nigra pars compacta (p < 0.01) and abnormal neuronal activity in the caudate‐putamen complex (p < 0.0001). RNA microarray analysis of the brain transcriptome of mice pre‐conditioned with saffron for 5 days revealed differential expression of 424 genes. Bioinformatics analysis identified enrichment of molecular pathways (e.g. adherens junction, TNFR1 and Fas signaling) and expression changes in candidate genes (Cyr61, Gpx8, Ndufs4, and Nos1ap) with known neuroprotective actions. The apparent biphasic nature of the dose–response relationship between saffron and measures of neuroprotection, together with the stress‐inducible nature of many of the up‐regulated genes and pathways, lend credence to the idea that saffron, like various other phytochemicals, is a hormetic stimulus, with functions beyond its strong antioxidant capacity. These findings provide impetus for a more comprehensive evaluation of saffron as a neuroprotective intervention.

image