bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased angiogenesis and VEGF expression correlates with disease severity in prurigo patients
Authors: Krull C. , Schoepke N. , Ohanyan T. , Brachaczek M. , Maurer M. , Lange‐Asschenfeldt B. , Metz M.
Published: October 2015

Background

Vascular endothelial growth factor‐A (VEGF‐A) is known as the major skin angiogenesis factor and can be produced by various resident skin cells including keratinocytes.

Objectives

To identify and characterize the role of VEGF‐A in the pathogenesis of prurigo.

Methods

Expression of VEGF, VEGFR2, CD‐31, and D2‐40 was analyzed in the skin of eleven prurigo patients and seven healthy controls by immunohistochemistry.

Results

VEGF immunoreactivity (IR) was markedly increased in the epidermis, dermis and subcutis of prurigo patients, whereas expression of the main receptor for VEGF‐A in the skin, VEGFR2, was comparable to that of healthy controls. The increased VEGF expression in the skin was associated with a marked increase in the number (12.8 ± 2.1 vs 5.6 ± 0.5, P < 0.05) but not in the size of blood vessels, as assessed by staining of the endothelial cell marker CD31. This increase in small blood vessels correlated closely with increases in the epidermal thickness in prurigo lesions. The number of lymphatic vessels as assessed by D2‐40 staining was found to be similar in prurigo patients and healthy controls.

Conclusions

Based on these findings, we speculate that the observed profound vascular remodelling in prurigo might contribute to the pathogenesis of prurigo and the corresponding clinical symptoms and that targeting of VEGF may present a novel therapeutic strategy in the treatment of prurigo patients.
Alternative Medications for Medications in the Use of High‐Risk Medications in the Elderly and Potentially Harmful Drug–Disease Interactions in the Elderly Quality Measures
Authors: Hanlon Joseph T. , Semla Todd P. , Schmader Kenneth E.
Published: October 2015

The National Committee for Quality Assurance (NCQA) and the Pharmacy Quality Alliance (PQA) use the American Geriatrics Society (AGS) Beers Criteria to designate the quality measure Use of High‐Risk Medications in the Elderly (HRM). The Centers for Medicare and Medicaid Services (CMS) use the HRM measure to monitor and evaluate the quality of care provided to Medicare beneficiaries. NCQA additionally uses the AGS Beers Criteria to designate the quality measure Potentially Harmful Drug–Disease Interactions in the Elderly. Medications included in these measures may be harmful to elderly adults and negatively affect a healthcare plan's quality ratings. Prescribers, pharmacists, patients, and healthcare plans may benefit from evidence‐based alternative medication treatments to avoid these problems. Therefore the goal of this work was to develop a list of alternative medications to those included in the two measures. The authors conducted a comprehensive literature review from 2000 to 2015 and a search of their personal files. From the evidence, they prepared a list of drug‐therapy alternatives with supporting references. A reference list of nonpharmacological approaches was also provided when appropriate. NCQA, PQA, the 2015 AGS Beers Criteria panel, and the Executive Committee of the AGS reviewed the drug therapy alternatives and nonpharmacological approaches. Recommendations by these groups were incorporated into the final list of alternatives. The final product of drug‐therapy alternatives to medications included in the two quality measures and some nonpharmacological resources will be useful to health professionals, consumers, payers, and health systems that care for older adults.
Individual scoring and mapping of hard and soft tissues of the anterior hard palate for orthodontic miniscrew insertion
Authors: Poorsattar‐Bejeh Mir Arash , Haghanifar Sina , Poorsattar‐Bejeh Mir Morvarid , Rahmati‐Kamel Manoucher
Published: October 2015

Aim

The aim of the present study was to introduce a scoring system to select optimal sites to insert a miniscrew in a hard palate.

Methods

The present study consisted of 37 adult patients (21 females and 16 males) aged between 20 and 50 years, with a mean age of 34.81 (±9.52) years. Hard and soft tissues of the anterior hard palate were assessed using cone‐beam computed tomography. The scoring system was as follows: mucosal thickness: 0–2 mm (2 points), 2–4 mm (1 point), and 4–6 mm (0 points); total bone vertical height: ≥5 mm (1 point) and <5 mm (0 points); and palatal cortical thickness: ≥1 mm (1 point) and <1 mm (0 points).

Results

Significant variability was found between the individuals. Total vertical bone height decreased posteriorly and laterally. Mucosal thickness decreased posteriorly, but increased laterally. Palatal cortical thicknesses were higher than the nasal cortical thicknesses. The most balanced sites (highest point) were the midpalatal suture, followed by paramedian points located 3 mm lateral to the midline and 4 mm posterior to the incisive canal.

Conclusions

Considering that both hard and soft tissue parameters are crucial to obtain the best possible success rates, careful investigation is recommended prior to clinical decisions being made.
Nursing Science: Claiming the Future
Authors: Grady Patricia A. , Gough Lisa Lucio
Published: October 2015

Purpose

The National Institute of Nursing Research (NINR) is dedicated to improving health and health care through the funding of nursing science and research training. With a focus on guiding the nation's nursing science research agenda and improving quality of life, the NINR is ideally positioned to meet current healthcare challenges and anticipate future challenges and priorities. In this article, coinciding with the NINR's 30th anniversary, examples of NINR‐supported research are described, along with its training activities designed to develop a strong cadre of 21st century nurse scientists. In addition, we discuss priorities and future directions for advancing cutting‐edge nursing science to “claim the future” and improve the health of the nation over the next 30 years and beyond.

Clinical Relevance

The evidence base developed by nurse scientists informs clinical practice, promotes health, and improves the lives of individuals across the lifespan. NINR‐supported research has had a profound impact on health over the past 30 years and is ideally positioned to continue to address the most important health challenges now and in the coming decades.
Salivary metabolomics in the diagnosis of oral cancer and periodontal diseases
Authors: Mikkonen J. J. W. , Singh S. P. , Herrala M. , Lappalainen R. , Myllymaa S. , Kullaa A. M.
Published: October 2015

Metabolomics is a systemic study of metabolites, which are small molecules generated by the process of metabolism. The metabolic profile of saliva can provide an early outlook of the changes associated with a wide range of diseases, including oral cancer and periodontal diseases. It is possible to measure levels of disease‐specific metabolites using different methods as presented in this study. However, many challenges exist including incomplete understanding of the complicated metabolic pathways of different oral diseases. The review concludes with the discussion on future perspectives of salivary metabolomics from a clinician point of view. Salivary metabolomics may afford a new research avenue to identify local and systemic disorders but also to aid in the design and modification of therapies. A MEDLINE search using keywords “salivary metabolomics” returned 23 results in total, of which seven were omitted for being reviews or letters to the editor. The rest of the articles were used for preparation of the review, 13 of these were published in the last 5 years.
Uncoupling the Impact of Fracture Properties and Composition on Sensory Perception of Emulsion‐Filled Gels
Authors: Devezeaux de Lavergne Marine , Strijbosch Veerle M.G. , Van den Broek Annemiek W.M. , Van de Velde Fred , Stieger Markus
Published: October 2015

The aim of the study is to investigate the effect of fracture properties and composition of emulsion‐filled gels on dynamic texture perception. Twelve emulsion‐filled gels varying in fracture stress (High/Low) and strain (High/Low) were prepared from three binary gel mixtures. Mechanical properties, syneresis, friction properties, microstructure, melting behavior, oral breakdown and texture perception of the gels were determined. Gels varying in composition but exhibiting similar fracture properties were obtained. Serum release, melting in mouth and friction varied between gels differing in composition. Fracture properties and melting of gels impacted oral breakdown. Fracture properties impacted perception of texture attributes at first bite and during chew down. Melting and syneresis impacted chew down perception of gels. We conclude that fracture stress mainly impacted texture perception at first bite, whereas fracture strain impacted perception of chew down texture attributes with high fracture strain gels being perceived creamy. The composition of gels impacted properties such as melting and serum release, which accounted for high variations in perception of moistness and creaminess between samples.

Practical Applications

Fracture properties of food are known to impact the perception of first bite texture attributes. Moreover, they are known to control breakdown of food during oral processing. However, little is known about the impact of fracture properties on perception of chew down texture attributes. The current study highlights the impact of fracture properties on chew down texture perception. It identifies other gel properties depending on gels composition that account for variation in perception between gels. The use of emulsion‐filled gels enabled the investigation of sensory attributes related to fat perception. Such knowledge can be used for food reformulation, for instance formulation of low fat soft solid foods. This study indicates which mechanical properties should be controlled to obtain a desired texture profile of soft solid foods.
A Distributional Analysis of Public–Private Wage Differential in India
Authors: Azam Mehtabul , Prakash Nishith
Published: October 2015

In this paper, we examine public–private wage differential among men in India across the entire wage distribution. We find that the raw wage gap between public and private sector is positive across the entire wage distribution in both urban and rural areas. A quantile regression‐based decomposition reveals that that the public sector workers enjoy a positive wage premium across the entire wage distribution in both urban and rural areas, although the magnitude of wage premium is smaller at the top quantiles.
Overexplicit Referent Tracking in L2 English: Strategy, Avoidance, or Myth?
Authors: Ryan Jonathon
Published: October 2015

The tendency of intermediate and advanced second language speakers to underuse pronouns and zero anaphora has been characterized as a developmental stage of overexplicitness, yet little consideration has been given to whether learners create sufficient contexts for their use. This study analyzed references across eight degrees of accessibility, revealing that this did not account for infrequent pronoun use by Chinese learners of English. Further analysis revealed that participants were seldom overexplicit when referring to highly accessible individuals, particularly those that represented continued topics, but were significantly more likely than native speakers to use lexical noun phrases elsewhere, particularly for main characters. This is discussed in relation to a possible role of overexplicitness as a clarity‐based communication strategy.
Acquisition of Second Language Grammar Under Incidental Learning Conditions: The Role of Frequency and Working Memory
Authors: Denhovska Nadiia , Serratrice Ludovica , Payne John
Published: October 2015

Although frequency is recognized as an important factor in second language (L2) acquisition, it has remained relatively underinvestigated in terms of its impact on the acquisition of grammatical knowledge under incidental learning conditions. This article reports the results of an experiment where 100 novice adult learners were exposed to a complex noun–adjective agreement pattern in Russian under four incidental learning conditions in which type and token frequencies of the stimuli were manipulated. The results show that accuracy was greater in the low type/low token condition and that low token frequency played a more significant role than low type frequency, supporting a “starting small” approach for productive knowledge acquisition. Working memory was differentially involved in production of acquired knowledge in different conditions and not engaged when learning was facilitated by frequency.
Cutaneous Mucinosis of Infancy: A Rare Congenital Case with Coexisting Progressive, Eruptive, and Spontaneously Involuting Lesions
Authors: Mir‐Bonafé José M. , Vicente‐Villa Asunción , Suñol Mariona , Soria Xavier , González‐Enseñat María Antonia
Published: October 2015

Cutaneous mucinosis in infancy is rare. We report an infant with multiple congenital papules distributed over the trunk, neck, and extremities. These papules were mainly dispersed, but they also coalesced into plaques. Histopathologic findings showed features of cutaneous mucinosis of infancy (CMI). Over 2 years of follow‐up, we observed that the preexisting lesions on the lower back and left trunk progressively increased in size, and a few new scattered papules continued to appear, mainly on the trunk; several lesions spontaneously resolved with no further complications. CMI is considered to be a persistent cutaneous disorder, even though spontaneously regressing cases have rarely been reported. This case demonstrates the broad clinical spectrum of CMI, with progressive, eruptive, and spontaneously involuting lesions all present in the same patient. This condition should be considered in the differential diagnosis of congenital or infantile‐onset papules and plaques, especially those yellowish in color.
Febrile Ulceronecrotic Mucha–Habermann Disease: Two Cases with Excellent Response to Methotrexate
Authors: Griffith‐Bauer Kelly , Leitenberger Sabra L. , Krol Alfons
Published: October 2015

Febrile ulceronecrotic Mucha–Habermann disease (FUMHD), a severe form of pityriasis lichenoides et varioliformis acuta (PLEVA), featuring large, ulcerative, necrotic skin plaques, high fever, and other systemic symptoms, is a rare disorder of unknown etiology. No randomized controlled trials have established treatment guidelines and multiple modalities are often employed, making it difficult to assess the efficacy of any single agent. We report two cases of this condition in which treatment with methotrexate plus antibiotic treatment for superinfection led to rapid improvement.
Onychoheterotopia Due to a Traumatically Transplanted Nail in a Child
Authors: Greywal Tanya , Maroñas‐Jiménez Lidia , Friedlander Sheila Fallon
Published: October 2015

Onychoheterotopia is a rare condition characterized by ectopic nail tissue growth. It is a digital mass that is commonly misdiagnosed. We describe a 6‐year‐old girl who presented with onychoheterotopia after trauma to the digit. Her onychoheterotopia was incorrectly diagnosed as a common wart. It is important to include onychoheterotopia in the differential diagnosis of digital masses, especially in the setting of previous traumatic injury.
Administration of Oral Itraconazole Capsule with Whole Milk Shows Enhanced Efficacy As Supported by Scanning Electron Microscopy in a Child with Tinea Capitis Due to Microsporum canis
Authors: Chen Shuang , Ran Yuping , Dai Yalin , Lama Jebina , Hu Wenying , Zhang Chaoliang
Published: October 2015

Although diagnosis and treatment of tinea capitis in children are not difficult, treatment failures are still somewhat common. We report a case of pediatric tinea capitis cured using oral itraconazole administered with whole milk, after prior treatment failure when oral itraconazole was administered with water. This apparent enhanced efficacy in one individual was demonstrated using scanning electron microscopy.
Venue Effects: How State Policy Source Influences Policy Support
Authors: Gash Alison , Murakami Michael H.
Published: October 2015

Does receiving information about a policy's source shape individual support for the policy? Is the public more supportive of policies issued by courts, legislatures, or citizens voting on a ballot initiative? Using a survey experiment, we find strong evidence that learning about a policy's source can affect support for the policy. Specifically, we find that state‐level policy sources influence both the degree and direction of influence on policy support. In general, when informed about a policy's source, survey participants are least likely to support the policy when it is judicially determined and instead prefer the policy when it is produced either through the legislature or by the voters. However, upon learning of the policy's source, self‐identified partisans and Independents differ significantly in their support for the policy.

Related Articles

Grossmann, Matt. 2014. “.” Politics & Policy 42 (): 881‐904. http://onlinelibrary.wiley.com/doi/10.1111/polp.12102/abstract

Ertas, Nevbahar. 2015. “.” Politics & Policy 43 (): 426‐451. http://onlinelibrary.wiley.com/doi/10.1111/polp.12120/abstract

Rugeley, Cynthia R., and
John David Gerlach. 2012. “.” Politics & Policy 40 (): 444‐470. http://onlinelibrary.wiley.com/doi/10.1111/j.1747-1346.2012.00352.x/abstract

Related Media

Fox, Joe, and
James Nubile. (2012) “Question 1: The Battle for Same Sex Marriage in America.” http://www.q1-themovie.com/

Klink, Jack. 2013. “Rise above the Mark.” https://riseabovethemark.com/
Expression of mRNA Encoding the LH Receptor (LHR) and LHR Binding Protein in Granulosa Cells from Nelore (Bos indicus) Heifers Around Follicle Deviation
Authors: Ereno RL , Loureiro B , Castilho ACS , Machado MF , Pegorer MF , Satrapa RA , Nogueira MFG , Buratini J , Barros CM
Published: October 2015

Contents

The time at which follicles acquire LHR in bovine granulosa cells is the subject of some controversy among researchers. The main objective of the present study was to assess the mRNA expression of LHR and LRBP (mRNA protein binding), a post‐transcriptional suppressor of LHR mRNA expression, in granulosa cells from the two largest follicles around the expected time of follicle deviation in Nelore heifers. First, the interval between ovulation and follicle deviation in 20 Nelore heifers was determined (2.3 ± 0.2 days after ovulation). Ovulation was hormonally synchronized, and then, heifers were slaughtered on days 2, 2.5 and 3 after ovulation (before, during and after, respectively, the expected time of follicle deviation), and granulosa cells from the two largest follicles were collected. The mRNA abundance of an LHR fragment common to all isoforms (total LHR) and LRBP was assessed by real‐time RT‐PCR, and LHR alternative transcripts were assessed by semiquantitative RT‐PCR followed by electrophoresis. LHR mRNA expression was not detected before the expected time of deviation. Total LHR mRNA abundance was greater in the largest follicle and increased from day 2.5 to 3. In contrast, LRBP mRNA was detected starting on day 2 and was more expressed in the second largest follicle on days 2.5 and 3. The present data suggest that the expression of LHR mRNA in bovine granulosa cells is established after follicle deviation and that the lower abundance of LRBP mRNA after the expected time of deviation may contribute to greater expression of LHR in the bovine dominant follicle.
Oestrogen and Progesterone Receptors and COX‐2 Expression in Endometrial Biopsy Samples During Maternal Recognition of Pregnancy in Llamas (Lama glama)
Authors: Bianchi CP , Meikle A , Benavente MA , Álvarez MA , Trasorras VL , Miragaya MH , Rodríguez E , Aba MA
Published: October 2015

Contents

Endometrial expression of oestrogen receptor‐α (ERα), progesterone receptor (PR) and cyclooxigenase‐2 (COX‐2) was evaluated in non‐pregnant and pregnant llamas during the period when luteolysis/maternal recognition of pregnancy is expected to occur. Females (n = 28) were divided into two groups: non‐pregnant llamas were induced to ovulate with a Buserelin injection, and endometrial biopsies were obtained on day 8 (n = 5) or 12 (n = 5) post‐induction of ovulation. Animals of the pregnant group (n = 18) were mated with a fertile male. Pregnancy was confirmed by the visualization of the embryo collected by transcervical flushing in 5 of 9 animals on day 8 post‐mating and by progesterone profile on day 12 post‐mating in 4 of 9 animals, when endometrial biopsies were obtained. An immunohistochemical technique was used to evaluate receptors population and COX‐2 expression. Pregnant llamas showed a higher percentage of positive cells and stronger intensity for ERα than for non‐pregnant llamas in stroma on day 8 and in the luminal epithelium on day 12 post‐induction of ovulation, while a deep decrease in endometrial PR population was reported in pregnant llamas on that day in luminal and glandular epithelia and stroma. In the luminal epithelium, COX‐2 expression was lower in pregnant than in non‐pregnant animals. Briefly, the increase of ERα in pregnant llamas gives further support to the hypothesis that oestrogens are involved in the mechanism of maternal recognition of pregnancy. Endometrial PR decrease in pregnant llamas might be a necessary event to allow the expression of proteins involved in conceptus attachment, a mechanism widely accepted in other species. Moreover, embryo seems to attenuate maternal PGF2α secretion during early pregnancy by decreasing the endometrial expression of COX‐2 in the luminal epithelium of pregnant llamas.
Dysfunctional state institutions, trust, and governance in areas of limited statehood
Authors: Börzel Tanja A. , Risse Thomas
Published: October 2015

Areas of limited statehood where the state is absent or dysfunctional are rarely ungoverned or ungovernable spaces. The provision of rules and regulations, as well as of public goods and services – governance – does not necessarily depend on the existence of functioning state institutions. How can this be explained? To begin with, we identify functional equivalents to state institutions that fail to govern hierarchically. Moreover, we focus on informal institutions based on trust that are endogenous to areas of limited statehood. Personalized trust among community members enables actors to overcome collective action problems and enhances the legitimacy of governance actors. The main challenge in areas of limited statehood, which are often characterized by social heterogeneity and deep social and cultural cleavages (particularly in post‐conflict societies) is to move to generalized trust beyond the local level and to “imagined communities among strangers,” despite dysfunctional state institutions. We propose two mechanisms: First, the more group‐based identities are constructed in inclusive ways and the more group identities are cross‐cutting and overlapping, the more they lead to and maintain generalized trust. Second, experiences with fair and impartial institutions and governance practices – irrespective of whether state or non‐state – also lead to generalized trust beyond the local level and allow for the upscaling of governance.
The Roles of Innovators and Labor in a Schumpeterian Factor Endowments Based Model of Intra‐industry Trade
Authors: Sedgley Norman H. , Tan Kerry M.
Published: October 2015

This paper builds a model of Schumpeterian innovation and trade that emphasizes endowments of innovators and labor as a key factor in determining the pattern of trade. The model suggests a strong complementarity between intra‐industry and inter‐industry trade. The pattern of inter‐industry vs intra‐industry trade is analyzed using the Grubel–Lloyd index. The theoretical model predicts that the prominence of intra‐industry trade is a nonlinear function of the ratio of the proportion of world knowledge domestically generated to the domestic share of the world labor supply. Strong empirical evidence for this key result is presented and implications are discussed.
Market Structure and the Environmental Implications of Trade Liberalization: Russia's Accession to the World Trade Organization
Authors: Böhringer Christoph , Rutherford Thomas F. , Tarr David G. , Turdyeva Natalia
Published: October 2015

We investigate the environmental impacts of Russia's World Trade Organization (WTO) accession with a computable general equilibrium model incorporating imperfectly competitive firms, foreign direct investment and endogenous productivity. WTO accession increases CO2 emissions through technique (−), composition (+) and scale (+) effects. We consider three complementary policies to limit CO2 emissions: cap and trade, emission intensity standards and energy efficiency standards. With imperfectly competitive firms, gains from WTO accession result with any of these policies. If we assume perfectly competitive market structures, the negative environmental impacts of WTO accession are smaller and no net gains arise when environmental regulation involves energy intensity or efficiency standards.
Driven to sanity: An ethnographic critique of the senses in automobilities
Authors: Dawson Andrew
Published: October 2015

This article reviews critically approaches to embodiment and the senses in contemporary automobilities research, highlighting particularly their critical representation of sensory disengagement in driving. In contrast, through passenger‐seat ethnography conducted in Bosnia and Herzegovina, the article explores the roles of sensory engagement in driving in ameliorating post‐socialist and post‐war unease concerning namely identification, mistrust, insecurity and estrangement. Globally cars are the largest single item of consumer expenditure after housing, and the consequences of this are manifold and devastating. In this context it becomes pressingly important to understand why people drive as much as they do and, as part of this, how driving makes us feel. In order to achieve this automobilities research must, I argue, stand back from its disposition of critique and develop a more thoroughgoing ethnography of driving. Anthropology is beginning to provide this, albeit sparsely and belatedly. This article represents a contribution.
Comparison of Short‐Term Postoperative Analgesia by Epidural, Femoral Nerve Block, or Combination Femoral and Sciatic Nerve Block in Dogs Undergoing Tibial Plateau Leveling Osteotomy
Authors: McCally Ryan E. , Bukoski Alex , Branson Keith R. , Fox Derek B. , Cook James L.
Published: October 2015

Objective

To compare early postoperative analgesia in dogs undergoing unilateral tibial plateau leveling osteotomy (TPLO) that received bupivacaine via preoperative femoral nerve block (FNB), combination femoral‐sciatic nerve block (F+SNB), or lumbosacral epidural (EPI).

Study Design

Randomized, blinded, prospective clinical trial.

Animals

Forty‐five client‐owned dogs undergoing unilateral TPLO.

Methods

Dogs undergoing unilateral TPLO were enrolled and randomly allocated to 1 of 3 treatments: FNB, F+SNB, or EPI. Assessments were completed by an observer blinded to treatment at 0, 1, 2, 4, 6, and 8 hours after extubation using the Glasgow Composite Pain Score‐Short Form (GCPS‐SF). Dogs with a total score ≥6 or ≥3 in any category were given a rescue analgesic. Outcome measures analyzed for differences across treatments were the GCPS‐SF at each time point, time to first rescue analgesic, and total number of rescue analgesic doses per dog.

Results

The GCPS‐SF score at extubation was significantly higher for FNB (median 3) compared to F+SNB (median 2). A significantly higher proportion of dogs receiving FNB (4/14) than F+SNB (0/17) required rescue analgesic at extubation. There was no significant difference in the proportion of dogs requiring rescue at extubation between FNB and EPI (2/14) or between F+SNB and EPI. There was no significant difference in the median time to first rescue between FNB (0 hours) and F+SNB (2 hours) or between F+SNB and EPI (1.5 hours).

Conclusion

In dogs undergoing unilateral TPLO, bupivacaine administered via FNB, alone or in combination with sciatic nerve block, can provide short‐term postoperative analgesia not different to that with administration via lumbosacral epidural.
Regulation of B‐type natriuretic peptide synthesis by insulin in obesity in male mice
Authors: Zhang Haihua , Thoonen Robrecht , Yao Vincent , Buys Emmanuel S. , Popovich John , Su Yan Ru , Wang Thomas J. , Scherrer‐Crosbie Marielle
Published: October 2015

New Findings

What is the central question of this study?

The plasma concentration of brain natriuretic peptide (BNP) is decreased in obesity, a finding that may be deleterious from a cardiovascular, renal and metabolic standpoint. The present study used a mouse model of high‐fructose, high‐fat (HFHF) diet and isolated cardiomyocytes to investigate the mechanisms involved in this decrease.

What is the main finding and its importance?

The gene expression level of BNP is decreased in the left ventricle of mice fed a HFHF diet for 4 weeks and in cardiomyocytes exposed to prolonged high doses of insulin. A decrease in BNP synthesis may contribute to the decreased BNP plasma concentrations observed in obesity and insulin resistance.

Human studies suggest that insulin resistance and obesity are associated with a decrease in B‐type natriuretic peptide (BNP) plasma concentrations. The objective of the study was to gain insights into the mechanisms involved in the association between insulin resistance and decreased BNP plasma concentrations. Mice fed a high‐fat, high‐fructose (HFHF) diet for 4 weeks developed mild obesity and systemic insulin resistance. Elevated plasma concentrations of insulin, glucose and triglycerides were noted. The HFHF diet was also associated with myocardial insulin resistance, characterized by an impaired response of the phosphoinositide 3‐kinase–AKT (PI3K–AKT) pathway to insulin in the left ventricle. Myocardial BNP expression and protein were decreased in HFHF‐fed mice compared with control animals. Exposure of cardiomyocytes to 100 nm insulin activated PI3K–AKT signalling (15 min) and induced a 1.9 ± 0.3‐fold increase in BNP gene expression (6 h). Prolonged exposure of cardiomyocytes to a high insulin concentration (100 nm) for 48 h induced insulin resistance, characterized by an impaired response of the PI3K–AKT signalling pathway and a decreased response of the BNP gene expression to insulin. The decreased response in BNP gene expression was reproduced by treating cardiomyocytes for 7 h with a PI3‐kinase inhibitor (wortmannin). In conclusion, HFHF diet in vivo, prolonged exposure to an elevated concentration of insulin or inhibition of the PI3K–AKT pathway in vitro all decrease BNP mRNA levels; this decrease may in turn contribute to the decreased BNP peptide concentrations in plasma observed in insulin‐resistant individuals.
Bosch etching for the creation of a 3D nanoelectroporation system for high throughput gene delivery
Authors: Bertani Paul , Lu Wu , Chang Lingqian , Gallego-Perez Daniel , James Lee Ly , Chiang Chiling , Muthusamy Natarajan
Published: October 2015

In order to create a high-throughput electroporation based cell transfection system, it is required that each cell has localized delivery and minimal membrane damage to ensure optimal transfection and longevity post-biomolecule delivery. To meet these requirements, a three-dimensional (3D) nanochannel device was fabricated on a Si platform due its ease of etching, wide industrial availability, and mechanical stability. The device is designed to shoot desired biomolecules into a seated array of target cells to achieve the high-throughput of bulk electroporation, but with greatly reduced cell mortality. To accomplish this, a wafer-scale Bosch etching process was optimized to etch a 3D array of channels consisting of larger microchannels feeding into smaller nanochannels that cells are ultimately seated on for transfection. The microchannel array consists of 50 μm wells spaced 50 μm apart, which are etched from the “back side.” The wafer is then flipped over to etch the smaller 650 nm channels on the “front side.” In the creation of the 3D silicon device, other feature sizes were explored, and their Bosch etching was characterized for comparison. The results show that when etching samples with the same feature sizes, but different densities, there was no relation between feature density and etch rate for our recipe. However, when etching features, or more specifically, circular channels of different sizes (650 nm–150 μm), the results show a positive correlation with etch rate (1.10–4.06 μm/min). Standard deviations indicate very uniform etching with an average value of 0.1 μm/min across all etches. After optimization, the 3D Si device was tested to ensure successful cell seating and transfection via electroporation, using fluorescence as the tool of evaluation. Fluorescent imaging (postelectroporation) indicates a transfection efficiency of approximately 70% with a cell viability of roughly 90%.
Incorporation of Ca, P, and Si on bioactive coatings produced by plasma electrolytic oxidation: The role of electrolyte concentration and treatment duration
Authors: Marques Isabella da Silva Vieira , da Cruz Nilson Cristino , Landers Richard , Yuan Judy Chia-Chun , Mesquita Marcelo Ferraz , Sukotjo Cortino , Mathew Mathew T. , Barão Valentim Adelino Ricardo
Published: October 2015

The objectives of the present study were to produce bioactive coatings in solutions containing Ca, P, and Si by plasma electrolytic oxidation (PEO) on commercially pure titanium, to investigate the influence of different electrolytes concentration and treatment duration on the produced anodic films and to evaluate biocompatibility properties. The anodic films were characterized using scanning electron microscopy, energy-dispersive spectroscopy, atomic force microscopy, and x-ray diffraction and x-ray photoelectron spectroscopies. The surface energy and roughness were also evaluated. PEO process parameters influenced the crystalline structure formation and surface topography of the anodic films. Higher Ca content produced larger porous (volcanolike appearance) and thicker oxide layers when compared to the lower content. Treatment duration did not produce any topography difference. The treatment modified the surface chemistry, producing an enriched oxide layer with bioactive elements in the form of phosphate compounds, which may be responsible for mimicking bone surface. In addition, a rough surface with increased surface energy was generated. Optimal spreading and proliferation of human mesenchymal stem cells was achieved by PEO treatment, demonstrating excellent biocompatibility of the surface. The main finding is that the biofunctionalization with higher Ca/P on Ti-surface can improve surface features, potentially considered as a candidate for dental implants.
Jet pumps for thermoacoustic applications: Design guidelines based on a numerical parameter study
Authors: Oosterhuis Joris P. , Bühler Simon , Wilcox Douglas , van der Meer Theo H.
Published: October 2015

The oscillatory flow through tapered cylindrical tube sections (jet pumps) is characterized by a numerical parameter study. The shape of a jet pump results in asymmetric hydrodynamic end effects which cause a time-averaged pressure drop to occur under oscillatory flow conditions. Hence, jet pumps are used as streaming suppressors in closed-loop thermoacoustic devices. A two-dimensional axisymmetric computational fluid dynamics model is used to calculate the performance of a large number of conical jet pump geometries in terms of time-averaged pressure drop and acoustic power dissipation. The investigated geometrical parameters include the jet pump length, taper angle, waist diameter, and waist curvature. In correspondence with previous work, four flow regimes are observed which characterize the jet pump performance and dimensionless parameters are introduced to scale the performance of the various jet pump geometries. The simulation results are compared to an existing quasi-steady theory and it is shown that this theory is only applicable in a small operation region. Based on the scaling parameters, an optimum operation region is defined and design guidelines are proposed which can be directly used for future jet pump design.
Prehistoric Eurasians streamed into Africa, genome shows
Authors: Gibbons Ann
Published: October 2015

First genome of an ancient African suggests widespread mixing with farmers from the Middle East.
Feeling the chill
Authors: Cho Adrian
Published: October 2015

The bizarre properties of liquid helium transfixed generations of physicists. But its spell is fading.
Don’t get lost in translation: How smart design and technology are enabling bench-to-bedside in translational research
Authors: Levine Bruce , Ramsborg Chris , Cooper Laurence J. N.
Published: October 2015

In recent years, cell-based therapies such as immunotherapy have shown very interesting and promising results, most notably in the fields of oncology and tissue regeneration. As researchers in these and other related fields continue to solve increasingly difficult scientific problems, they need to prepare for the next step: moving their treatment out of the research lab and into a larger-scale manufacturing environment. This step presents an entirely new set of critical challenges, including workflow management, resource planning, and ensuring the most efficient use of precious patient samples. In this webinar you'll hear from leading professionals who are experienced in both scaling-up (generating more cells per batch) and scaling-out (generating more batches) the production of their “living drugs” in the most effective way possible. The reliability of this process has real-world impacts on patient well-being and survival.

View the Webinar
Hidden order in spin-liquid Gd
3
Ga
5
O
12
Authors: Paddison Joseph A. M. , Jacobsen Henrik , Petrenko Oleg A. , Fernández-Díaz Maria Teresa , Deen Pascale P. , Goodwin Andrew L.
Published: October 2015

Elucidating order within disorder

In some materials, the geometry of the crystal lattice gets in the way of magnetic ordering. Their spins, although magnetically interacting, remain seemingly disordered and form a so-called spin liquid. Paddison
et al.
propose a different model for the spin-liquid compound Gd
3
Ga
5
O
12
. Neutron diffraction measurements and numerical techniques revealed that even though individual spins in this material were disordered, they formed 10-spin loops that were correlated with one another. The nature of this “hidden order” was such that it escaped direct detection by conventional techniques

Science
, this issue p.
179
Deposition, exhumation, and paleoclimate of an ancient lake deposit, Gale crater, Mars
Authors: Grotzinger J. P. , Gupta S. , Malin M. C. , Rubin D. M. , Schieber J. , Siebach K. , Sumner D. Y. , Stack K. M. , Vasavada A. R. , Arvidson R. E. , Calef F. , Edgar L. , Fischer W. F. , Grant J. A. , Griffes J. , Kah L. C. , Lamb M. P. , Lewis K. W. , Mangold N. , Minitti M. E. , Palucis M. , Rice M. , Williams R. M. E. , Yingst R. A. , Blake D. , Blaney D. , Conrad P. , Crisp J. , Dietrich W. E. , Dromart G. , Edgett K. S. , Ewing R. C. , Gellert R. , Hurowitz J. A. , Kocurek G. , Mahaffy P. , McBride M. J. , McLennan S. M. , Mischna M. , Ming D. , Milliken R. , Newsom H. , Oehler D. , Parker T. J. , Vaniman D. , Wiens R. C. , Wilson S. A.
Published: October 2015

Ancient lake system at Gale crater

Since 2012, the Curiosity rover has been diligently studying rocky outcrops on Mars, looking for clues about past water, climate, and habitability. Grotzinger
et al.
describe the analysis of a huge section of sedimentary rocks near Gale crater, where Mount Sharp now stands (see the Perspective by Chan). The features within these sediments are reminiscent of delta, stream, and lake deposits on Earth. Although individual lakes were probably transient, it is likely that there was enough water to fill in low-lying depressions such as impact craters for up to 10,000 years. Wind-driven erosion removed many of these deposits, creating Mount Sharp.

Science
, this issue p.
10.1126/science.aac7575
, see also p.
167
From transient infection to chronic disease
Authors: Nathan Carl
Published: October 2015

Can some infections “scar” the immune system?
A chance to get science right
Authors: Turk James L.
Published: October 2015

The upcoming Canadian election later this month will provide a welcome opportunity to reboot the federal government's controversial approach to science policy and research. The current Conservative government has been undermining science for the past 9 years, damaging the institutions that make scientific advancement possible and trying to ensure that political and ideological priorities dominate scientific work.
Norovirus Antigen Detection with a Combination of Monoclonal and Single-Chain Antibodies
Authors: Kou Baijun , Huang Wanzhi , Neill Frederick H. , Palzkill Timothy , Estes Mary K. , Atmar Robert L.
Published: October 2015

The performance of a norovirus antigen detection assay was assessed using monoclonal antibody NV23 and single-chain antibody HJT-R3-A9 to identify both virus-like particles and virus-containing fecal samples. The detection of 25 different norovirus genotypes as recombinant virus-like particles or in clinical samples was dependent on virus or antigen concentration.
Tropheryma whipplei, a Potential Commensal Detected in Individuals Undergoing Routine Colonoscopy
Authors: Grasman M. E. , Pettersson A. M. , Catsburg A. , Koek A. G. , van Bodegraven A. A. , Savelkoul P. H. M.
Published: October 2015

Mucosal biopsy samples from individuals not suspected of having Whipple's disease were tested for the presence of
Tropheryma whipplei
. A sensitive and specific real-time PCR assay targeting a sequence present seven times in the
T. whipplei
genome was used.
T. whipplei
DNA was detected in 2.0 and 3.8% of the patients undergoing gastroduodenoscopy and colonoscopy, respectively, who were tested.
Distinct Escape Pathway by Hepatitis C Virus Genotype 1a from a Dominant CD8
+
T Cell Response by Selection of Altered Epitope Processing
Authors: Walker Andreas , Skibbe Kathrin , Steinmann Eike , Pfaender Stephanie , Kuntzen Thomas , Megger Dominik A. , Groten Svenja , Sitek Barbara , Lauer Georg M. , Kim Arthur Y. , Pietschmann Thomas , Allen Todd M. , Timm Joerg
Published: October 2015

Antiviral CD8
+
T cells are a key component of the adaptive immune response against HCV, but their impact on viral control is influenced by preexisting viral variants in important target epitopes and the development of viral escape mutations. Immunodominant epitopes highly conserved across genotypes therefore are attractive for T cell based prophylactic vaccines. Here, we characterized the CD8
+
T cell response against the highly conserved HLA-B*51-restricted epitope IPFYGKAI
1373–1380
located in the helicase domain of NS3 in people who inject drugs (PWID) exposed predominantly to HCV genotypes 1a and 3a. Despite this epitope being conserved in both genotypes, the corresponding CD8
+
T cell response was detected only in PWID infected with genotype 3a and HCV-RNA negative PWID, but not in PWID infected with genotype 1a. In genotype 3a, the detection of strong CD8
+
T cell responses was associated with epitope variants in the autologous virus consistent with immune escape. Analysis of viral sequences from multiple cohorts confirmed HLA-B*51-associated escape mutations inside the epitope in genotype 3a, but not in genotype 1a. Here, a distinct substitution in the N-terminal flanking region located 5 residues upstream of the epitope (S1368P;
P
= 0.00002) was selected in HLA-B*51-positive individuals. Functional assays revealed that the S1368P substitution impaired recognition of target cells presenting the endogenously processed epitope. The results highlight that, despite an epitope being highly conserved between two genotypes, there are major differences in the selected viral escape pathways and the corresponding T cell responses.

IMPORTANCE
HCV is able to evolutionary adapt to CD8
+
T cell immune pressure in multiple ways. Beyond selection of mutations inside targeted epitopes, this study demonstrates that HCV inhibits epitope processing by modification of the epitope flanking region under T cell immune pressure. Selection of a substitution five amino acids upstream of the epitope underlines that efficient antigen presentation strongly depends on its larger sequence context and that blocking of the multistep process of antigen processing by mutation is exploited also by HCV. The pathways to mutational escape of HCV are to some extent predictable but are distinct in different genotypes. Importantly, the selected escape pathway of HCV may have consequences for the destiny of antigen-specific CD8
+
T cells.
The ownership and clinical use of smartphones by doctors and nurses in the UK: a multicentre survey study
Authors: Mobasheri Mohammad H , King Dominic , Johnston Maximilian , Gautama Sanjay , Purkayastha Sanjay , Darzi Ara
Published: October 2015

Background

Much interest has arisen around the use of smartphones, tablet devices and related apps in the healthcare context. It has been suggested that increasing numbers of healthcare professionals are using these technologies in the workplace. We have performed an up-to-date UK-based, multicentre, cross-sectional survey study exploring the ownership rates and uses of these technologies among doctors and nurses, specifically focusing on the clinical environment.

Methods

After initial piloting, all doctors (n=2107) and nurses (n=4069) at 5 hospital sites were invited to complete a 36-item (nurses) or 38-item (doctors) survey. Exploratory descriptive statistics were calculated and the χ2test was used to compare differences in categorical data between groups. Statistical significance was taken at a level of p<0.05.

Results

98.9% of doctors and 95.1% of nurses owned a smartphone, while 73.5% and 64.7% owned a tablet device, respectively. Also, 92.6% of the doctors and 53.2% of nurses found their smartphone to be ‘very useful’ or ‘useful’ in helping them to perform their clinical duties, while 89.6% of doctors and 67.1% of nurses owning medical apps were using these as part of their clinical practice. Doctors and nurses were using short-message-script messaging (64.7% and 13.8%, respectively), app-based messaging (33.1% and 5.7%), and picture messaging (46.0% and 7.4%) (p=0.0001 for all modalities) to send patient-related clinical information to their colleagues. Therefore, 71.6% of doctors and 37.2% of nurses wanted a secure means of sending such information.

Conclusions

Compared to earlier studies, we have demonstrated much higher smartphone ownership among doctors and nurses, who perceive these devices to be useful when performing their clinical duties. Large numbers of staff are sending patient related clinical information using smartphone messaging modalities. Care must be taken by doctors and nurses to ensure that no identifiable patient data is transmitted in this way, and healthcare organisations must develop strategies and policies to support the safe and secure use of these technologies by front-line staff.