bluuebunny/crossref_metadata_2025 huggingface dataset:
Thiolated silicone oils as adhesive skin protectants for improved barrier function
Authors: Partenhauser A. , Zupančič O. , Rohrer J. , Bonengel S. , Bernkop‐Schnürch A.
Published: October 2015

Objective

The purpose of this study was the evaluation of thiolated silicone oil as novel skin protectant exhibiting prolonged residence time, enhanced barrier function and reinforced occlusivity.

Methods

Two silicone conjugates were synthesized with mercaptopropionic acid (MPA) and thioglycolic acid (TGA) as thiol ligands. Adhesion, protection against artificial urine and water vapour permeability with both a Payne cup set‐up and transepidermal water loss (TEWL) measurements on porcine skin were assessed.

Results

Silicone thiomers showed pronounced substantivity on skin with 22.1 ± 6.3% and 39.2 ± 6.7% remaining silicone after 8 h for silicone‐TGA and silicone‐MPA, respectively, whereas unmodified silicone oil and dimethicone were no longer detectable. In particular, silicone‐MPA provided a protective shield against artificial urine penetration with less than 25% leakage within 6 h. An up to 2.5‐fold improved water vapour impermeability for silicone‐MPA in comparison with unmodified control was discovered with the Payne cup model. In addition, for silicone‐MPA a reduced TEWL by two‐thirds corresponding to non‐thiolated control was determined for up to 8 h.

Conclusion

Thiolation of silicone oil leads to enhanced skin adhesiveness and barrier function, which is a major advantage compared to commonly used silicones and might thus be a promising treatment modality for various topical applications.
Urinary tract infection‐like symptom is associated with worse bladder cancer outcomes in the Medicare population: Implications for sex disparities
Authors: Richards Kyle A , Ham Sandra , Cohn Joshua A , Steinberg Gary D
Published: October 2015

Objectives

To determine the time to bladder cancer diagnosis from initial infection‐like symptoms and its impact on cancer outcomes.

Methods

Using Surveillance, Epidemiology and End Results‐Medicare, we designed a retrospective cohort study identifying beneficiaries aged ≥66 years diagnosed with bladder cancer from 2007 to 2009. Patients were required to have a hematuria or urinary tract infection claim within 1 year of bladder cancer diagnosis (n = 21 216), and have 2 years of prior Medicare data (n = 18 956) without any precedent hematuria, bladder cancer or urinary tract infection claims (n = 12 195). The number of days to bladder cancer diagnosis was measured, as well as the impact of sex and presenting symptom on time to diagnosis, pathology, and oncological outcomes.

Results

The mean time to bladder cancer diagnosis was 72.2 days in women versus 58.9 days in men (P < 0.001). A logistic regression model identified the greatest predictors of ≥pT2 pathology were both women (odds ratio 2.08, 95% confidence interval 1.70–2.55) and men (odds ratio 1.71, 95% confidence interval 1.49–1.97) presenting with urinary tract infection. Cox proportional hazards analysis identified an increased risk of mortality from bladder cancer and all causes in women presenting with urinary tract infection (hazard ratio 1.37, 95% confidence interval 1.10–1.71, and hazard ratio 1.47, 95% confidence interval 1.28–1.69) compared with women with hematuria.

Conclusions

Women have a longer interval from urinary tract infection to diagnosis of bladder cancer. Urinary tract infection presentation can adversely affect time to diagnosis, pathology and survival. Time to diagnosis seems not to be an independent predictor of bladder cancer outcomes.
Corticosteroids as co‐analgesics with opioids for cancer pain: a survey of Australian and New Zealand palliative care clinicians
Authors: Eastman P. , Le B.
Published: October 2015

Corticosteroids are commonly used as co‐analgesics with opioids for cancer pain; however limited quality data exist supporting their efficacy for this purpose. Further, little is known about individual prescribing practices. The current study surveyed members of the Australian New Zealand Society of Palliative Medicine about their use of corticosteroids as adjuvant analgesics in cancer pain. It confirmed high rates of utilisation and found variability in starting doses and associated decision‐making. Further research is required to determine the efficacy and safety of corticosteroids as co‐analgesics in cancer pain management.
Deming, Data and Observational Studies
Authors: Young S. Stanley , Karr Alan
Published: October 2015

“Any claim coming from an observational study is most likely to be wrong.” Startling, but true. Coffee causes pancreatic cancer. Type A personality causes heart attacks. Trans-fat is a killer. Women who eat breakfast cereal give birth to more boys. All these claims come from observational studies; yet when the studies are carefully examined, the claimed links appear to be incorrect. What is going wrong? Some have suggested that the scientific method is failing, that nature itself is playing tricks on us. But it is our way of studying nature that is broken and that urgently needs mending, say S. Stanley Young and Alan Karr; and they propose a strategy to fix it.
Galton's Millions
Authors: Bottone Michele
Published: October 2015

How much is a million? How can we make sense of a number that big? Francis Galton tried to measure a million in flowers. There are other ways. In homage to the great man, Michele Bottone argues that a million is all around us, and all that is required to visualise it is a bit of ingenuity, patience and imagination.
Hypoglycemia and glycemic variability are associated with mortality in non‐intensive care unit hospitalized infectious disease patients with diabetes mellitus
Authors: Takeishi Soichi , Mori Akihiro , Hachiya Hiroki , Yumura Takayuki , Ito Shun , Shibuya Takashi , Hayashi Shintaro , Fushimi Nobutoshi , Ohashi Noritsugu , Kawai Hiromi
Published: October 2015

Aims/Introduction

We aimed to identify factors – glycemic control, reactive inflammatory biomarkers or vital signs – associated with mortality in diabetic patients admitted to hospital for various infections (non‐intensive care unit).

Materials and Methods

We retrospectively analyzed the cases of 620 diabetic patients admitted to hospital for various infections (non‐intensive care unit) who underwent glucose monitoring >3 times per day. We extracted data regarding reactive inflammatory biomarkers and vital signs recorded on day 1 of hospital stay, and data on bacteremia and hypoglycemia status, glycemic variability (GV; coefficient of variation and standard deviation) and mean glucose concentrations during the entire hospital stay. Univariate and stepwise multivariate logistic regression analyses were carried out to determine the association between these factors and mortality.

Results

The mortality rate was 10.1%. Reactive inflammatory biomarkers, vital signs and bacteremia were not associated with mortality. According to the results of the adjusted analysis, hypoglycemia showed a significant positive association with mortality, increasing death risk by 266% (odds ratio [OR] 2.66, 95% confidence interval [95% CI] 1.22–5.83; P = 0.0006). High coefficient of variation and standard deviation values were significantly associated with increased mortality, increasing death risk by 18% (OR 1.18, 95% CI 1.01–1.38; P = 0.03) and 9% (OR 1.09, 95% CI 1.01–1.18; P = 0.03), respectively. Mean glucose concentrations were also significantly associated with mortality, increasing death risk by 5% (OR 1.05, 95% CI 1.02–1.08; P = 0.0008).

Conclusions

Glycemic indices (especially hypoglycemia and GV), rather than reactive inflammatory biomarkers or vital signs, were associated with mortality in non‐intensive care unit diabetes mellitus patients with infections.
Elevated circulating level of a cytokine, pancreatic‐derived factor, is associated with metabolic syndrome components in a Chinese population
Authors: Cao Xiaopei , Yang Chijiao , Lai Fenghua , Hong Zhenzhen , Lin Huimei , Liu Juan , Li Yanbing
Published: October 2015

Aims/Introduction

Pancreatic‐derived factor (PANDER) is an important factor involved in obesity, glucose intolerance and abnormal lipid metabolism in animals. Nevertheless, the relationship between PANDER and metabolic syndrome (MetS) in humans has not yet been reported.

Materials and Methods

To determinate the relationship between PANDER and MetS components, 212 individuals aged between 40 and 65 years were recruited. Fasting plasma PANDER and other variables were measured. Correlations of plasma PANDER and other variables were carried out. Plasma PANDER level was compared in participants with no metabolic components and those with any metabolic components, as well as in normal glucose tolerance, impaired glucose tolerance and diabetes mellitus participants.

Results

In all the participants, there were 65 participants in the no metabolic components group and 147 participants in the any metabolic components group. Plasma PANDER level was increased with the number of MetS components (P < 0.05) and correlated with metabolic score (r = 0. 529, P < 0.001). In addition, plasma PANDER significantly correlated with fasting plasma glucose (r = 0.187, P = 0.046), 2‐h plasma glucose (r = 0.195, P = 0.035), homeostasis model assessment of β‐cell function (r = −0.191, P = 0.039), triglyceride (r = 0.305, P = 0.001) and high‐density lipoprotein cholesterol (r = −0.333, P < 0.001). Using multivariable logistic regression analysis, circulating PANDER was associated with an increased risk ratio of impaired glucose tolerance or diabetes mellitus (odds ratio 2.22, 95% confidence interval 1.15–4.42, P = 0.018) after adjustment of the other possible confounders.

Conclusions

Circulating level of PANDER in relation to the accumulation in MetS suggested that persons with elevated levels of PANDER were associated with an increased risk of metabolic syndrome.
Bioactive Compounds, Physical and Sensory Properties of Cake Made with Walnut Press‐Cake
Authors: Bakkalbasi Emre , Meral Raciye , Dogan Ismail S.
Published: October 2015

Walnut press‐cake, a rich source of phenolics, is a by‐product of walnut oil processing. In this study, the effects of walnut press‐cake on cake quality, health‐enhancing substances and antioxidant activity were determined. Wheat flour was replaced with walnut press‐cake at 0, 5, 10, 15 and 20% levels. Results show that specific volume, firmness, resilience, cohesiveness, chewiness, crust a, b and crumb L, b values reduced with increasing walnut press‐cake levels. However, polyunsaturated fatty acids, tocopherols, total phenolic content and antioxidant capacity of cakes increased. Antioxidant capacity measured by 2,2‐diphenyl‐1‐picrylhydrazyl and 2,2′‐azino‐bis (3‐ethylbenzothiazoline‐6‐sulfonic acid) assays of cakes prepared with 20% walnut press‐cake were 10.04‐ and 5.56‐fold, respectively, greater than that of the cake without walnut press‐cake. Cakes added with 15% walnut press‐cake to wheat flour had the highest scores in all sensory parameters. Walnut press‐cake can be successfully incorporated into cake formulation to improve sensory properties and antioxidant activity of the cake.

Practical Applications

Interest in walnut oil has increased during the past years due to its high polyunsaturated fatty acid content. Although walnut oil has been used in the food, pharmaceutical and cosmetic industries, there is no information about the use of walnut press‐cake. Walnut press‐cake is a rich source of bioactive compounds, and it is a new by‐product with potential use in the baking industry as a supplement. The results of this study provide guidance for the use of walnut press‐cake in the manufacture of cakes with higher sensory and nutritional quality.
Overcoming uncertainty and barriers to adoption of Blue‐Green Infrastructure for urban flood risk management
Authors: Thorne C.R. , Lawson E.C. , Ozawa C. , Hamlin S.L. , Smith L.A.
Published: October 2015

Blue‐Green Infrastructure (BGI) and Sustainable Drainage Systems (SuDS) are increasingly recognised as vital components of urban flood risk management. However, uncertainty regarding their hydrologic performance and lack of confidence concerning their public acceptability create concerns and challenges that limit their widespread adoption. This paper investigates barriers to implementation of BGI in Portland, Oregon, using the Relevant Dominant Uncertainty (RDU) approach. Two types of RDU are identified: scientific RDUs related to physical processes that affect infrastructure performance and service provision, and socio‐political RDUs that reflect a lack of confidence in socio‐political structures and public preferences for BGI. We find that socio‐political RDUs currently exert the strongest negative influences on BGI decision making in Portland. We conclude that identification and management of both biophysical and socio‐political uncertainties are essential to broadening the implementation of BGI and sustainable urban flood risk management solutions that are practical, scientifically sound, and supported by local stakeholders.
Important factors determining the nanoscale tracking precision of dynamic microtubule ends
Authors: BOHNER G. , GUSTAFSSON N. , CADE N.I. , MAURER S.P. , GRIFFIN L.D. , SURREY T.
Published: October 2015

Tracking dynamic microtubule ends in fluorescence microscopy movies provides insight into the statistical properties of microtubule dynamics and is vital for further analysis that requires knowledge of the trajectories of the microtubule ends. Here we analyse the performance of a previously developed automated microtubule end tracking routine; this has been optimized for comparatively low signal‐to‐noise image sequences that are characteristic of microscopy movies of dynamic microtubules growing in vitro. Sequences of simulated microtubule images were generated assuming a variety of different experimental conditions. The simulated movies were then tracked and the tracking errors were characterized. We found that the growth characteristics of the microtubules within realistic ranges had a negligible effect on the tracking precision. The fluorophore labelling density, the pixel size of the images, and the exposure times were found to be important parameters limiting the tracking precision which could be explained using concepts of single molecule localization microscopy. The signal‐to‐noise ratio was found to be a good single predictor of the tracking precision: typical experimental signal‐to‐noise ratios lead to tracking precisions in the range of tens of nanometres, making the tracking program described here a useful tool for dynamic microtubule end tracking with close to molecular precision.
SAD‐B kinase regulates pre‐synaptic vesicular dynamics at hippocampal Schaffer collateral synapses and affects contextual fear memory
Authors: Watabe Ayako M. , Nagase Masashi , Hagiwara Akari , Hida Yamato , Tsuji Megumi , Ochiai Toshitaka , Kato Fusao , Ohtsuka Toshihisa
Published: October 2015

Synapses of amphids defective (SAD)‐A/B kinases control various steps in neuronal development and differentiation, such as axon specifications and maturation in central and peripheral nervous systems. At mature pre‐synaptic terminals, SAD‐B is associated with synaptic vesicles and the active zone cytomatrix; however, how SAD‐B regulates neurotransmission and synaptic plasticity in vivo remains unclear. Thus, we used SAD‐B knockout (KO) mice to study the function of this pre‐synaptic kinase in the brain. We found that the paired‐pulse ratio was significantly enhanced at Shaffer collateral synapses in the hippocampal CA1 region in SAD‐B KO mice compared with wild‐type littermates. We also found that the frequency of the miniature excitatory post‐synaptic current was decreased in SAD‐B KO mice. Moreover, synaptic depression following prolonged low‐frequency synaptic stimulation was significantly enhanced in SAD‐B KO mice. These results suggest that SAD‐B kinase regulates vesicular release probability at pre‐synaptic terminals and is involved in vesicular trafficking and/or regulation of the readily releasable pool size. Finally, we found that hippocampus‐dependent contextual fear learning was significantly impaired in SAD‐B KO mice. These observations suggest that SAD‐B kinase plays pivotal roles in controlling vesicular release properties and regulating hippocampal function in the mature brain.

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Synapses of amphids defective (SAD)‐A/B kinases control various steps in neuronal development and differentiation, but their roles in mature brains were only partially known. Here, we demonstrated, at mature pre‐synaptic terminals, that SAD‐B regulates vesicular release probability and synaptic plasticity. Moreover, hippocampus‐dependent contextual fear learning was significantly impaired in SAD‐B KO mice, suggesting that SAD‐B kinase plays pivotal roles in controlling vesicular release properties and regulating hippocampal function in the mature brain.
Reduction in Aβ‐induced cell death in the hippocampus of 17β‐estradiol‐treated female rats is associated with an increase in IGF‐I signaling and somatostatinergic tone
Authors: Perianes‐Cachero Aránzazu , Canelles Sandra , Aguado‐Llera David , Frago Laura M. , Toledo‐Lobo María Val , Carrera Iván , Cacabelos Ramón , Chowen Julie A , Argente Jesús , Arilla‐Ferreiro Eduardo , Barrios Vicente
Published: October 2015

Several studies indicate that 17β‐estradiol (E2) protects against amyloid β‐peptide (Aβ)‐induced cell death and activates factors associated with learning and memory, a function involving the hippocampal somatostatinergic system. As alterations in somatostatin have been demonstrated in Alzheimer′s disease, we examined whether E2 prevents changes in the hippocampal somatostatinergic system induced by Aβ25‐35 and cell death, as well as the possible involvement of leptin and insulin‐like growth factor (IGF)‐I signaling. We also measured the levels of Aβ proteases neprilysin and insulin‐degrading‐enzyme. Co‐administration of E2 with Aβ25‐35 reduced both its levels and cell death, in addition to preventing the Aβ‐induced depletion of some somatostatinergic parameters. Activation of leptin and IGF‐I pathways increased after E2 co‐administration, and this correlated with changes in the somatostatinergic system. Changes in some components of this system were inversely related with Aβ levels and cell death. Moreover, neprilysin levels were increased only in Aβ plus E2‐treated rats and E2 prevented the Aβ‐induced insulin‐degrading‐enzyme reduction. Our results suggest that the E2‐induced reduction in cell death is related to lower Aβ levels, probably because of IGF‐I and somatostatin modulation of Aβ proteases.

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We asked how 17β‐estradiol (E2) protects against β‐amyloid (Aβ)‐induced cell death. E2 co‐administration prevents Aβ‐produced depletion of hippocampal somatostatin (SRIF) by an IGF‐I‐mediated mechanism, being related this protective effect with an increase in Aβ proteases. Our results suggest that the E2‐induced reduction in cell death is related to lower Aβ levels, probably because of SRIF modulation of Aβ proteases. CREB, cAMP response element‐binding protein; IGF‐I, insulin‐like growth factor‐I; STAT3, signal transducer and activator of transcription‐3.
Vinorelbine and epirubicin share common features with polysialic acid and modulate neuronal and glial functions
Authors: Loers Gabriele , Saini Vedangana , Mishra Bibhudatta , Gul Sheraz , Chaudhury Sidhartha , Wallqvist Anders , Kaur Gurcharan , Schachner Melitta
Published: October 2015

Polysialic acid (PSA), a large, linear glycan composed of 8 to over 100 α2,8‐linked sialic acid residues, modulates development of the nervous system by enhancing cell migration, axon pathfinding, and synaptic targeting and by regulating differentiation of progenitor cells. PSA also functions in developing and adult immune systems and is a signature of many cancers. In this study we identified vinorelbine, a semi‐synthetic third generation vinca alkaloid, and epirubicin, an anthracycline and 4′‐epimer of doxorubicin, as PSA mimetics. Similar to PSA, vinorelbine and epirubicin bind to the PSA‐specific monoclonal antibody 735 and compete with the bacterial analog of PSA, colominic acid in binding to monoclonal antibody 735. Vinorelbine and epirubicin stimulate neurite outgrowth of cerebellar neurons via the neural cell adhesion molecule, via myristoylated alanine‐rich C kinase substrate, and via fibroblast growth factor receptor, signaling through Erk pathways. Furthermore, the two compounds enhance process formation of Schwann cells and migration of cerebellar neurons in culture, and reduce migration of astrocytes after injury. These novel results show that the structure and function of PSA can be mimicked by the small organic compounds vinorelbine and epirubicin, thus raising the possibility to re‐target drugs used in treatment of cancers to nervous system repair.

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Vinorelbine and epirubicin, identified as PSA mimetics, enhance, like PSA, neuronal migration, neuritogenesis, and formation of Schwann cell processes, and reduce astrocytic migration. Ablating NCAM, inhibiting fibroblast growth factor (FGFR) receptor, or adding the effector domain of myristoylated alanine‐rich C kinase substrate (MARCKS) minimize the vinorelbine and epirubicin effects, indicating that they are true PSA mimetics triggering PSA‐mediated functions.
Effect of Deletion of Ghrelin‐O‐Acyltransferase on the Pulsatile Release of Growth Hormone in Mice
Authors: Xie T. Y. , Ngo S. T. , Veldhuis J. D. , Jeffery P. L. , Chopin L. K. , Tschöp M. , Waters M. J. , Tolle V. , Epelbaum J. , Chen C. , Steyn F. J.
Published: October 2015

Ghrelin, a gut hormone originating from the post‐translational cleavage of preproghrelin, is the endogenous ligand of growth hormone secretagogue receptor 1a (GHS‐R1a). Within the growth hormone (GH) axis, the biological activity of ghrelin requires octanoylation by ghrelin‐O‐acyltransferase (GOAT), conferring selective binding to the GHS‐R1a receptor via acylated ghrelin. Complete loss of preproghrelin‐derived signalling (through deletion of the Ghrl gene) contributes to a decline in peak GH release; however, the selective contribution of endogenous acyl‐ghrelin to pulsatile GH release remains to be established. We assessed the pulsatile release of GH in ad lib. fed male germline goat−/− mice, extending measures to include mRNA for key hypothalamic regulators of GH release, and peripheral factors that are modulated relative to GH release. The amount of GH released was reduced in young goat−/− mice compared to age‐matched wild‐type mice, whereas pulse frequency and irregularity increased. Altered GH release did not coincide with alterations in hypothalamic Ghrh, Srif, Npy or Ghsr mRNA expression, or pituitary GH content, suggesting that loss of Goat does not compromise canonical mechanisms that contribute to pituitary GH production and release. Although loss of Goat resulted in an irregular pattern of GH release (characterised by an increase in the number of GH pulses observed during extended secretory events), this did not contribute to a change in the expression of sexually dimorphic GH‐dependent liver genes. Of interest, circulating levels of insulin‐like growth factor (IGF)‐1 were elevated in goat−/− mice. This rise in circulating levels of IGF‐1 was correlated with an increase in GH pulse frequency, suggesting that sustained or increased IGF‐1 release in goat−/− mice may occur in response to altered GH release patterning. Our observations demonstrate that germline loss of Goat alters GH release and patterning. Although the biological relevance of altered GH secretory patterning remains unclear, we propose that this may contribute to sustained IGF‐1 release and growth in goat−/− mice.
Cultural Competence Among Italian Nurses: A Multicentric Survey
Authors: Cicolini Giancarlo , Della Pelle Carlo , Comparcini Dania , Tomietto Marco , Cerratti Francesca , Schim Stephanie M. , Di Giovanni Pamela , Simonetti Valentina
Published: October 2015

Purpose

To assess Italian nurses’ cultural competence, as they are increasingly called upon to care for people of foreign origins.

Design

A cross‐sectional, multicentric study.

Methods

From September 2013 to May 2014, a survey was carried out among Italian nurses. Cultural competence was assessed by the Cultural Competence Assessment tool, translated and adapted to the Italian context.

Findings

Nurses who completed the survey numbered 1,432; 70.6% were female; 42.6% ranged in age from 41 to 50 years; and 50.0% were bachelor's prepared. More than 50% had participated in some kind of cultural diversity training. Overall, cultural competence was moderate, showing a moderately high level of cultural awareness and sensitivity (mean = 5.41; SD = 0.66) and a moderate level of culturally competent behaviors (mean = 4.33; SD = 1.10).

Conclusions

Although Italian nurses’ cultural competence was acceptable, given the growing diversity of the patient population, nurses should be better prepared to face the changing health requests.

Clinical Relevance

Providing culturally competent care has been associated with improved provider–client communication, higher satisfaction with care, and health status improvement, as full comprehension of health status, adherence to medications and lifestyle recommendations, and appropriate utilization of the health system. Healthcare providers need to be adequately trained to provide culturally competent care. This research provides, for the first time, a report on Italian nurses’ levels of cultural competence, and strengthens the current literature underlining the need for continuous education to enhance cultural competence among nurses.
Expressive Shareholder Democracy: A Multilevel Study of Shareholder Dissent in 15 Western European Countries
Authors: Sauerwald Steve , Van Oosterhout J. (Hans) , Van Essen Marc
Published: October 2015

This study develops an expressive understanding of shareholder dissent. In this view, shareholder dissent is not only about the voting outcomes of proposals put to the vote, but also expresses an evaluation of the firm's corporate governance set‐up. We hypothesize that shareholder dissent expresses an agency theoretical evaluation of corporate governance, but that the degree to which the capitalist system of a country is a coordinated market economy (CME) leads shareholders to evaluate corporate governance more in team production terms. We test our theoretical model using multilevel techniques on a sample of 12,513 proposals voted on in 717 firms listed in 15 Western European countries and find support for our predictions. Our study not only contributes to a better understanding of the corporate governance role of shareholder dissent, but also shows that what shareholders express through dissent differs across national contexts.
Melatonin rescues cardiovascular dysfunction during hypoxic development in the chick embryo
Authors: Itani Nozomi , Skeffington Katie L. , Beck Christian , Niu Youguo , Giussani Dino A.
Published: October 2015

There is a search for rescue therapy against fetal origins of cardiovascular disease in pregnancy complicated by chronic fetal hypoxia, particularly following clinical diagnosis of fetal growth restriction (FGR). Melatonin protects the placenta in adverse pregnancy; however, whether melatonin protects the fetal heart and vasculature in hypoxic pregnancy independent of effects on the placenta is unknown. Whether melatonin can rescue fetal cardiovascular dysfunction when treatment commences following FGR diagnosis is also unknown. We isolated the effects of melatonin on the developing cardiovascular system of the chick embryo during hypoxic incubation. We tested the hypothesis that melatonin directly protects the fetal cardiovascular system in adverse development and that it can rescue dysfunction following FGR diagnosis. Chick embryos were incubated under normoxia or hypoxia (14% O2) from day 1 ± melatonin treatment (1 mg/kg/day) from day 13 of incubation (term ~21 days). Melatonin in hypoxic chick embryos rescued cardiac systolic dysfunction, impaired cardiac contractility and relaxability, increased cardiac sympathetic dominance, and endothelial dysfunction in peripheral circulations. The mechanisms involved included reduced oxidative stress, enhanced antioxidant capacity and restored vascular endothelial growth factor expression, and NO bioavailability. Melatonin treatment of the chick embryo starting at day 13 of incubation, equivalent to ca. 25 wk of gestation in human pregnancy, rescues early origins of cardiovascular dysfunction during hypoxic development. Melatonin may be a suitable antioxidant candidate for translation to human therapy to protect the fetal cardiovascular system in adverse pregnancy.
Heterogeneous ribonucleoprotein R regulates arylalkylamine N‐acetyltransferase synthesis via internal ribosomal entry site‐mediated translation in a circadian manner
Authors: Lee Hwa‐Rim , Kim Tae‐Don , Kim Hyo‐Jin , Jung Youngseob , Lee Dohyun , Lee Kyung‐Ha , Kim Do‐Yeon , Woo Kyung‐Chul , Kim Kyong‐Tai
Published: October 2015

Rhythmic arylalkylamine N‐acetyltransferase (AANAT) synthesis is a prominent circadian‐controlled response that occurs in most mammals. AANAT is the core enzyme in melatonin production; because melatonin participates in many physiological processes, the regulation of AANAT is an important research topic. In this study, we focused on the role of heterogeneous ribonucleoprotein R (hnRNP R) in the translation of AANAT. A novel RNA‐binding protein hnRNP R widely interacted with the 5′ untranslated region (UTR) of AANAT mRNA and contributed to translation through an internal ribosomal entry site (IRES). Fine‐tuning of AANAT protein synthesis occurred in response to knockdown and overexpression of hnRNP R. Nocturnal elevation of AANAT protein was dependent on the rhythmic changes of hnRNP R, whose levels are elevated in the pineal gland during nighttime. Increases in hnRNP R additionally improved AANAT production in rat pinealocytes under norepinephrine (NE) treatment. These results suggest that cap‐independent translation of AANAT mRNA plays a role in the rhythmic synthesis of melatonin through the recruitment of translational machinery to hnRNP R‐bound AANAT mRNA.
Spiegelman Studies Part 1 of 2: Maus
Authors: Smith Philip
Published: October 2015

Art Spiegelman is one of the most‐discussed creators in Comic Book Studies. His Pulitzer‐winning work Maus (1980 and 1991) was, alongside The Dark Knight Returns (1986) and Watchmen (1987), the catalyst to a sea change in the commercial and critical fortunes of the alternative comic book during the mid‐1980s. It has been a landmark text in critical discourses on comics ever since. The purpose of this and its companion paper is to offer a synthesis and reinvestigation of both the existing critical literature on Spiegelman as well as, perhaps most importantly, the lacunae within that literature. The aims of these two papers, then, are two‐fold: firstly, to establish where we have got to and, secondly, to suggest some directions for the future of Spiegelman scholarship. This, the first of the two papers, will be devoted to the richest vein of Spiegelman scholarship, on Maus.
Degarelix Versus Goserelin Plus Bicalutamide in the Short‐Term Relief of Lower Urinary Tract Symptoms in Prostate Cancer Patients: Results of a Pooled Analysis
Authors: MASON Malcolm , RICHAUD Pierre , BOSNYAK Zsolt , MALMBERG Anders , NEIJBER Anders
Published: October 2015

Objective

In patients with prostate cancer (PCa), prostate enlargement may give rise to lower urinary tract symptoms (LUTS); many patients suffer from moderate‐to‐severe symptoms. We compare the efficacy of degarelix and goserelin plus bicalutamide in improving LUTS in PCa patients.

Methods

Data were pooled from three Phase 3, randomized clinical trials of once‐monthly treatment for 12 weeks with degarelix (240/80 mg; n = 289) or goserelin (3.6 mg) plus bicalutamide (50 mg; n = 174) for initial flare protection. LUTS at weeks 4, 8, and 12 were compared to baseline. Clinically relevant LUTS relief was a ≥3‐point International Prostate Symptom Score (IPSS) decrease. Adverse events were assessed throughout the trials.

Results

Patients receiving degarelix had significantly greater decreases in IPSS vs. goserelin at week 12 (adjusted difference: −1.24; 95% CI −2.33 to −0.14, P = 0.03). Clinically relevant LUTS relief with degarelix was especially pronounced in patients with moderate‐to‐severe LUTS (baseline IPSS ≥13) (odds ratio; OR 2.31; 95% CI 1.19–4.47, P = 0.01) and advanced PCa (OR 2.36; 95% CI 1.10–5.04, P = 0.03). A twofold higher OR for early (week 4) LUTS relief was seen with degarelix vs. goserelin (OR 2.03; 95% CI 1.14–3.60, P = 0.02). No difference in total prostate volume or urinary tract infection‐related adverse events (2%) was seen between treatment groups.

Conclusion

An early, significant and clinically more pronounced improvement of LUTS, especially in patients with moderate‐to‐severe LUTS or advanced PCa, was seen with degarelix vs. goserelin plus bicalutamide.
ON THE BIOECONOMICS OF MARINE RESERVES WHEN DISPERSAL EVOLVES
Authors: MOBERG EMILY A. , SHYU ESTHER , HERRERA GUILLERMO E. , LENHART SUZANNE , LOU YUAN , NEUBERT MICHAEL G.
Published: October 2015

Marine reserves are an increasingly used and potentially contentious tool in fisheries management. Depending upon the way that individuals move, no‐take marine reserves can be necessary for maximizing equilibrium rent in some simple mathematical models. The implementation of no‐take marine reserves often generates a redistribution of fishing effort in space. This redistribution of effort, in turn, produces sharp spatial gradients in mortality rates for the targeted stock. Using a two‐patch model, we show that the existence of such gradients is a sufficient condition for the evolution of an evolutionarily stable conditional dispersal strategy. Thus, the dispersal strategy of the fish depends upon the harvesting strategy of the manager and vice versa. We find that an evolutionarily stable optimal harvesting strategy (ESOHS)—one which maximizes equilibrium rent given that fish disperse in an evolutionarily stable manner– ‐ never includes a no‐take marine reserve. This strategy is economically unstable in the short run because a manager can generate more rent by disregarding the possibility of dispersal evolution. Simulations of a stochastic evolutionary process suggest that such a short‐run, myopic strategy performs poorly compared to the ESOHS over the long run, however, as it generates rent that is lower on average and higher in variability.
Three‐dimensional analysis of palatal shape in patients treated with SARME using traditional and geometric morphometrics
Authors: Trefný P. , Krajíček V. , Velemínská J.
Published: October 2015

Structured Abstract

Objectives

To demonstrate the advantages of dense surface models in the evaluation of surgical‐assisted rapid maxillary expansion's effect (SARME) on palatal morphology. Furthermore, we compared the palatal surface before (T1) and after (T2) therapy with controls.

Setting and Sample Population

Surgical‐assisted rapid maxillary expansion's effect group of 15 adult patients (Le Fort I and midpalatal sagittal osteotomy, hyrax screw) and 50 adult individuals. Patients were treated in General Faculty Hospital, Prague.

Materials and Methods

Eighty plaster casts were digitized using a three‐dimensional laser scanner and evaluated using traditional and geometric morphometrics.

Results

An unpaired Student's t‐test on the controls and the SARME T1 group revealed significant differences in all width measurements. Between the controls and the SARME T2 group, significant differences were only related to the interdental angle between the first molars and particularly to the palatal height. The most remarkable differences between the pre‐ and post‐treatment palatal morphology were a widening of the dental arch and buccal shift of the lateral teeth associated with apparent flattening of the alveolar crest.

Conclusions

Dense surface model provided descriptive visualization of the treatment effect and was helpful in the evaluation of palatal shape variability including detection of the most difficult patients. Correction of the dental arch width discrepancy by SARME was successfully achieved. After therapy, palatal shape variability of most of the patients was comparable to the variability of the control group.
Upregulation of Bpifb1 expression in the parotid glands of non‐obese diabetic mice
Authors: Nashida T. , Yoshimura K. , Yoshie S. , Mizuhashi F. , Shimomura‐Kuroki J.
Published: October 2015

Objective

To define the increased mRNA expression of Bpifb1, a member of the bactericidal/permeability‐increasing protein family, in parotid acinar cells from non‐obese diabetic (NOD) mice, an animal model for Sjögren's syndrome.

Materials and methods

Parotid acinar cells were prepared from female NOD (NOD/ShiJcl) mice with or without diabetes, as well as from control (C57BL/6JJcl) mice. Total RNA and homogenate were prepared from the parotid acinar cells. Embryonic cDNA from a Mouse MTC™ Panel I kit was used. The expression of Bpifb1 was determined by cDNA microarray analysis, RT‐PCR, real‐time PCR, northern blotting and in situ hybridization.

Results

The expression of Bpifb1 mRNA was high in parotid acinar cells from diabetic and non‐diabetic NOD mice at 5–50 weeks of age. Acinar cells in the C57BL/6 mice had a low expression of Bpifb1 mRNA at an age >8 weeks, but had a relatively high expression in the foetus and infantile stages.

Conclusions

Bpifb1 mRNA is upregulated in parotid acinar cells in NOD mice, but its expression is not related to the onset of diabetes. These findings suggest that high expression levels of Bpifb1 might predict disease traits before the onset of autoimmunity.
Predicting the occurrence of persistent hotspots in ecosystem variables
Authors: Hammond Matthew P. , Kolasa Jurek
Published: October 2015

Ecological resources and services (e.g. organisms, nutrient cycling) are distributed heterogeneously across landscapes. While spatial variation has been studied extensively, the pattern of hotspots and coolspots persisting over time – called persistent spatial variation (PSV) – has not. Yet this pattern imparts key information to managers about whether resources will be found consistently in certain locations or vary unpredictably. Anticipating whether an ecosystem variable will display PSV is thus a valuable prospect. We tested the ability of attributes of variables (e.g. niche breadth, abundance, temporal scale) to predict the occurrence of PSV. Using a new measure of PSV based on the F‐value of analysis of variance, we were able to 1) decompose the pattern of persistent hotspots into spatial and temporal components – ‘spatial variation’ of site mean values and ‘stability’ of time series at each site – and 2) identify predictors of these patterns in temperate lakes and tropical coastal rock pools. We found PSV to be highly predictable (R2 = up to 0.80) from an estimate of stability taken at a single site, as well as from other factors related to stability. These factors included whether the variable was environmental (stable, slow) or was an aggregate of other variables (stabilized by statistical averaging). Species properties like niche position and abundance were modest predictors because they correlated with PSV components of site occupancy, spatial variation and stability. We conclude that PSV and the distribution of resources in space and time might be predicted from simple temporal indicators (e.g. stability at a single location) when data are scarce.
Cost Burden of Chronic Pain Patients in a Large Integrated Delivery System in the United States
Authors: Park Peter W. , Dryer Richard D. , Hegeman‐Dingle Rozelle , Mardekian Jack , Zlateva Gergana , Wolff Greg G. , Lamerato Lois E.
Published: October 2015

Objectives

To estimate all‐cause healthcare resource utilization and costs among chronic pain patients within an integrated healthcare delivery system in the United States.

Methods

Electronic medical records and health claims data from the Henry Ford Health System were used to determine healthcare resource utilization and costs for patients with 24 chronic pain conditions. Patients were identified by ≥ 2 ICD‐9‐CM codes ≥ 30 days apart from January to December, 2010; the first ICD‐9 code was the index event. Continuous coverage for 12 months pre‐ and postindex was required. All‐cause direct medical costs were determined from billing data.

Results

A total of 12,165 patients were identified for the analysis. After pharmacy, the most used resource was outpatient visits, with a mean of 18.8 (SD 13.2) visits per patient for the postindex period; specialty visits accounted for 59.0% of outpatient visits. Imaging was utilized with a mean of 5.2 (SD 5.5) discrete tests per patient, and opioids were the most commonly prescribed medication (38.7%). Annual direct total costs for all conditions were $386 million ($31,692 per patient; a 40% increase from the pre‐index). Pharmacy costs comprised 14.3% of total costs, and outpatient visits were the primary cost driver.

Conclusions

Chronic pain conditions impose a substantial burden on the healthcare system, with musculoskeletal conditions associated with the highest overall costs. Costs appeared to be primarily related to use of outpatient services. This type of research supports integrated delivery systems as a source for assessing opportunities to improve patient outcomes and lower the costs for chronic pain patients.
Effect of Hyaluronidase Addition to Lidocaine for Trigger Point Injection in Myofascial Pain Syndrome
Authors: Choi Ji Won , Lee Chul Joong , Lee Sangmin M. , Shin Byung Seop , Jun Byunghui , Sim Woo Seog
Published: October 2015

Introduction

This randomized, double‐blind study compared the efficacy of hyaluronidase co‐injection with that of local anesthesia alone on the degree of pain and quality of life in patients with myofascial pain syndrome (MPS).

Methods

Sixty‐one adults, aged 25 to 75 years, with MPS affecting both trapezius muscles were randomly assigned to one of the 2 treatment groups: lidocaine (group L: n = 31) or hyaluronidase (group H: n = 30). All patients received Trigger point injection (TPI). Group L received 3.2 mL 0.5% lidocaine alone. Group H received the same solution of lidocaine mixed with hyaluronidase (600 iu/mL). Patients were followed for 14 days (pre‐ and post‐TPI days 0, 1, 4, 7, and 14) with the verbal numerical rating scale (VNRS), and the primary outcome was VNRS on day 7. Also, we evaluated the neck disability index (NDI) and the short form of brief pain inventory (BPI‐SF) on pre‐ and post‐TPI day 14.

Results

In both groups, VNRS decreased on days 4, 7, and 14 compared to the pre‐TPI. However, in group H, VNRS decreased on day 1 also. There were no significant differences of VNRS between the 2 groups during 14 days. NDI and BPI‐SF scores also significantly decreased after TPI in both groups.

Conclusions

There were no significant differences between groups in terms of VNRS, NDI, or BPI‐SF scores. However, TPI consisting of lidocaine mixed with hyaluronidase worked more effectively than lidocaine alone on post‐TPI day 1. Further, hyaluronidase showed a tendency to reduce TPI‐related soreness.
Genome distribution of differential homoeologue contributions to leaf gene expression in bread wheat
Authors: Harper Andrea L. , Trick Martin , He Zhesi , Clissold Leah , Fellgett Alison , Griffiths Simon , Bancroft Ian
Published: October 2015

Using a combination of de novo transcriptome assembly, a newly developed 9495‐marker transcriptome SNP genetic linkage map and comparative genomics approaches, we developed an ordered set of nonredundant transcripts for each of the subgenomes of hexaploid wheat: A (47 160 unigenes), B (59 663 unigenes) and D (40 588 unigenes). We used these as reference sequences against which to map Illumina mRNA‐Seq reads derived from young leaf tissue. Transcript abundance was quantified for each unigene. Using a three‐way reciprocal BLAST approach, 15 527 triplet sets of homoeologues (one from each genome) were identified. Differential expression (P < 0.05) was identified for 5248 unigenes, with 2906 represented at greater abundance than their two homoeologues and 2342 represented at lower abundance than their two homoeologues. Analysis of gene ontology terms revealed no biases between homoeologues. There was no evidence of genomewide dominance effects, rather the more highly transcribed individual genes were distributed throughout all three genomes. Transcriptome display tile plot, a visualization approach based on CMYK colour space, was developed and used to assess the genome for regions of skewed homoeologue transcript abundance. Extensive striation was revealed, indicative of many small regions of genome dominance (transcripts of homoeologues from one genome more abundant than the others) and many larger regions of genome repression (transcripts of homoeologues from one genome less abundant than the others).
Realism and Constructivism in Kantian Metaethics (2): The Kantian Conception of Rationality and Rationalist Constructivism
Authors: Schafer Karl
Published: October 2015

In the second half of this essay, I discuss the robust conception of rationality that lies at the heart of the Kantian version of Rationalist Constructivism – offering some reasons to prefer this conception to the more minimal accounts of rationality associated with Humean views. I then go on to discuss some of the potential metaethical advantages of the resulting form of constructivism.
Exploring Safe Sleep and SIDS Risk Perception in an African‐American Community: Focused Ethnography
Authors: Zoucha Rick , Walters Cynthia A. , Colbert Alison M. , Carlins Eileen , Smith Eileen
Published: October 2015

Objectives

Explore the cultural influences of safe sleep practices by African‐American caregivers of children under 2 years old. Explore the role of health care professionals in promoting safe sleep.

Design and Sample

A focused ethnography was used to understand the contextual cultural meaning and experiences of safe sleep practices of African‐American caregivers of children under 2 years. Nineteen African‐Americans participated in this study.

Measures

Demographic data were collected and semi‐structured interviews were conducted with individuals and small groups. Saturation of the data occurred after 17 interviews. Data were analyzed using Leininger's four Phases of qualitative data analysis.

Results

(Themes): (1) The informants expressed both accurate and inaccurate knowledge of Sudden Infant Death Syndrome (SIDS) and safe sleep practices influenced by personal experiences, hospital education, family, extended family and television; (2) Sleeping with infants and children was viewed as a cultural caring behavior promoting comfort, closeness and protection for infants, children, parents and caregivers; (3) The informants want and are seeking collaboration with nurses and health care professionals who are viewed as important in promoting accurate information about SIDS and safe sleep practices.

Conclusion

The role of the nurse can impact accurate outcomes about SIDS and safe sleep practices.
How can asymmetric detachment faults generate symmetric Ocean Continent Transitions?
Authors: Gillard Morgane , Manatschal Gianreto , Autin Julia
Published: October 2015

Asymmetry or symmetry of magma‐poor rifted margins refers commonly to the crustal architecture and the occurrence or absence of large‐scale extensional detachment faults. While distal parts of magma‐poor rifted margins are often considered to be asymmetric, the observation of downlapping sedimentary sequences over exhumed mantle domains at conjugate margins suggests a symmetric evolution during mantle exhumation. On the basis of seismic observations along the Iberia–Newfoundland and Australia–Antarctica margins, we propose that their most distal parts show evidence for the development of multiple, out‐of‐sequence asymmetric detachment faults. We present evidence for cyclic delocalization and re‐localization of deformation, resulting in an apparent symmetry of the exhumed mantle domain. The interaction between out‐of‐sequence detachment systems and the successive rise of the asthenosphere may explain the observed transition from fault‐controlled to magma‐controlled strain accommodation and the transition to more symmetric and localized accretion associated with the formation of a stable spreading center.