bluuebunny/crossref_metadata_2025 huggingface dataset:
Time trends in absolute and relative socioeconomic inequalities in leisure time physical inactivity in northern Sweden
Authors: Szilcz Máté , Mosquera Paola A. , Sebastián Miguel San , Gustafsson Per E.
Published: July 2017

Aims: The aim was to investigate the time trends in educational, occupational, and income-related inequalities in leisure time physical inactivity in 2006, 2010, and 2014 in northern Swedish women and men. Methods: This study was based on data obtained from the repeated cross-sectional Health on Equal Terms survey of 2006, 2010, and 2014. The analytical sample consisted of 20,667 (2006), 31,787 (2010), and 21,613 (2014) individuals, aged 16–84. Logistic regressions were used to model the probability of physical inactivity given a set of explanatory variables. Slope index of inequality (SII) and relative index of inequality (RII) were used as summary measures of the social gradient in physical inactivity. The linear trend in inequalities and difference between gender and years were estimated by interaction analyses. Results: The year 2010 displayed the highest physical inactivity inequalities for all socioeconomic position indicators, but educational and occupational inequalities decreased in 2014. However, significant positive linear trends were found in absolute and relative income inequalities. Moreover, women had significantly higher RII of education in physical inactivity in 2014 and significantly higher SII and RII of income in physical inactivity in 2010, than did men in the same years. Conclusions:The recent reduction in educational and occupational inequalities following the high inequalities around the time of the great recession in 2010 suggests that the current policies might be fairly effective. However, to eventually alleviate inequities in physical inactivity, the focus of the researchers and policymakers should be directed toward the widening trends of income inequalities in physical inactivity.
Factors influencing trends in trauma-associated orbital cavity reconstruction procedures and time delay: New Zealand national data 2000–2014
Authors: Samaranayaka Chamil , Samaranayaka Ari , Barson Dave , De Silva RK
Published: July 2017

Aim

Surgical reconstructions of orbital fractures due to trauma are increasing worldwide. This study identifies characteristics of patients facing such procedures, possible causes for increasing trends, and factors associated with the duration from trauma to surgical procedures.

Methods

Trauma-related orbital reconstruction procedures in New Zealand over a 15-year period were identified from Ministry of Health hospital discharge data. Age-standardised rates for each year and age-specific rates for each gender were calculated using age, sex and year-specific population data from New Zealand population censuses. The contribution of these procedures to total trauma-related maxillofacial procedures was assessed. Descriptive statistics were used to identify demographic, trauma-related, and procedure-related characteristics associated with higher frequency and increasing trends. Characteristics independently associated with time delay from trauma to surgery were identified by multivariable Cox regression modelling.

Results

Orbital procedures are most common among males and the young to middle aged, and trends in frequency and rates of procedures are sharply increasing outnumbering other types of trauma-related maxillofacial procedures, with interpersonal violence being a major contributor to this increase. Younger age and higher number of injuries are associated with less time delay from injury to procedure while Asian ethnicity, motor vehicle accidents, non-maxillofacial primary diagnoses, and higher number of medical comorbidities are associated with longer delay.

Conclusion

The first three findings are consistent with international literature, and could be considered by policy makers when deriving preventive measures. The findings related to time delay are new and could contribute information towards forming clinical guidelines if similar patterns were identified elsewhere.
Maturity of hospital information systems: Most important influencing factors
Authors: Vidal Carvalho João , Rocha Álvaro , Abreu António
Published: July 2017

Maturity models facilitate organizational management, including information systems management, with hospital organizations no exception. This article puts forth a study carried out with a group of experts in the field of hospital information systems management with a view to identifying the main influencing factors to be included in an encompassing maturity model for hospital information systems management. This study is based on the results of a literature review, which identified maturity models in the health field and relevant influencing factors. The development of this model is justified to the extent that the available maturity models for the hospital information systems management field reveal multiple limitations, including lack of detail, absence of tools to determine their maturity and lack of characterization for stages of maturity structured by different influencing factors.
Prediction of the wheel profile wear using railroad vehicle dynamics simulation: Comparison of simulation and test results
Authors: Feldmeier Christofer , Li Huaxia , Yamazaki Yosuke , Kato Takanori , Fujimoto Takahiro , Kondo Osamu , Sugiyama Hiroyuki
Published: July 2017

Wear is a fundamental problem in the railroad vehicle design and performance evaluation. Slight changes in the profile shape result in significant impact on the contact geometry characteristics of wheel and rail, thereby altering the dynamic performance as well as derailment safety of railroad vehicles. In this study, a wear simulation capability integrated with multibody railroad vehicle dynamics simulation algorithms is developed considering multipoint contact exhibited between wheel and rail profiles in the wear evolution and validated against experimentally measured profiles obtained by the two-roller and scaled wheel wear tests. It was shown that worn profile shape as well as the magnitude of the weight loss agreed well between the simulation and test results in the two-roller test. Using wear test of a scaled wheel, it was found that the flange contact falls into severe wear regime, while the tread contact is in mild wear regime in the two-roller wear test data. However, a severe flange contact led to much higher wear rate than that obtained using the two-roller test for the same material and the same wear index, while the wear rate for the tread contact adhered to that of the two-roller test in the mild wear regime. This is attributed to the fact that contact condition of the severe flange contact scenario is greatly different from the two-roller contact condition due to the high contact pressure and slippage occurring in the small thin contact patch, leading to a vastly different wear rate per contact area. It is demonstrated that utilizing the flange wear rate leads to good agreement with the measured profile shape, while the two-roller wear rate leads to a significant underestimate of the flange wear due to significantly lower wear rate in severe wear regime.
Jocks versus jockettes: An analysis of the visual portrayal of male and female cover models on sports magazines
Authors: Wasike Ben
Published: July 2017

There are known gender-based disparities in sports news coverage. However, few have examined how these disparities manifest in sports news visuals such as sports magazine covers. Therefore, this study examined pertinent dynamics among all covers published to date for both Sports Illustrated and ESPN The Magazine. The study examined sexualization, camera angle, and nonverbal communication cues and their interplay with gender. Women appearing on the covers were likelier than men to be portrayed in a sexualized manner, in terms of skin exposure and suggestive poses. Men were likelier to be portrayed in active poses, and the cover lines emphasized gender over athletic achievement for women. The results also indicate that women were more likely to be portrayed smiling, as well as being portrayed in more positive camera angle shots. The author discusses the ramifications of gendered portrayal regarding sports magazines.
Legislative amendments and informal politics in the European Union: A text reuse approach
Authors: Cross James P , Hermansson Henrik
Published: July 2017

The ability to amend legislative proposals introduced by the Commission is central to legislative process in the European Union. Despite this, very few attempts have been made to capture and explain such amendments. This study addresses this gap in the literature by considering the changes between the Commission’s proposals and the final legislative outcome passed by the European Union. It does so by implementing minimum edit distance algorithms to measure changes between legislative proposals and outcomes. The findings suggest that legislative amendments are determined by the formal and informal institutional structures in which negotiations take place and characteristics of the proposal itself. Our conclusions contribute to the ongoing debate on the nature and distribution of legislative powers in the European Union.
Automatic generation of battle maps from replay data
Authors: Wallner Guenter
Published: July 2017

With the advent of online gaming, access to in-game data has become increasingly important for players as it provides great opportunities for them to reflect and improve upon their gameplay or to compare their performance with others. Some of the currently most popular games focus on strategy and tactics, requiring players to skillfully position and maneuver units in order to achieve victory in battle. However, current visualizations for retrospective analysis of battles and that are targeted toward players are mainly limited to heatmaps and hence are not well suited for conveying the flow of battle. By contrast, military planners and historians alike have long used maps to provide a concise visual overview of troop movements. In this article, we are proposing an algorithm for automatically creating such battle maps from tracked in-game data. Several parameters allow to adjust the level-of-detail in the resulting maps. To demonstrate the practicality of our approach for post hoc analysis, we apply it to actual gameplay data obtained from a massively multiplayer online game and collected preliminary feedback among players of the game through an online survey.
Hayek’s neo-Roman liberalism
Authors: Irving Sean
Published: July 2017

This article argues that Hayek employed a neo-Roman concept of liberty. It will show that Hayek’s definition of liberty conforms to that provided by Philip Pettit and Quentin Skinner, respectively the chief theorist and leading historian of the neo-Roman concept. It will go on to demonstrate how the genealogy of liberty Hayek provides is also the same as that offered by Pettit and Skinner. This is important, as the neo-Roman concept is not regarded, either by Hayek or by neo-republicans led by Pettit, as a product of political theory. Instead it is viewed as underpinning a historical tradition. Hayek’s self-conscious association with this tradition reinforces the article’s prior claim that Hayek’s conceptual writing on liberty is neo-Roman. Finally, the article considers how the neo-Roman nature of Hayek’s work complicates the historical narrative and political claims the neo-republicans make for the neo-Roman concept. It concludes that it is open to use by another, very different, political tradition: free market liberalism.
Sensitivity analysis of traffic efficiency in restricted channel influenced by the variance of ship speed
Authors: Wang Hongbo , Liu Jingxian , Liu Kezhong , Zhang Jinfen , Wang Zhan
Published: July 2017

Enhancing the traffic efficiency of restricted channels is one of the most important objectives for maritime transportation, especially in busy waterways and ports. In many cases, the variance of ship speed would impede the traffic efficiency in restricted channels where overtaking between ships is not allowed. The ship behaviors in restricted channels are studied in this article. Two indicators are applied to evaluate traffic efficiency, which are the percentage of ships that reduce speed and the increase of navigating time in the channel due to speed reduction. Screening method is introduced to make sensitivity analysis considering five factors, which are the mean value of ship speed, variance of ship speed, channel length, safety distance and arriving rate. The results indicate that the mean value of ship speed is most sensitive to traffic efficiency, followed by the variance of ship speed and arriving rate. The safety distance is the least sensitive to channel efficiency. Quadratic equation models and response surface method are further used to make interaction analysis between the factors. High degree of interactions among the mean value, variance of ship speed, arriving rate and channel length are identified. These findings are valuable for the guidance of making effective measurements to make full use of channel resource to promote its efficiency.
A Confucian perspective of self-cultivation in learning: Its implications for self-directed learning
Authors: Tan Charlene
Published: July 2017

This article explores a Confucian perspective of self-cultivation in learning and its implications for self-directed learning. Focussing on two key Confucian texts, Xueji (Record of Learning) and Xunzi, this essay expounds the purpose, content, process and essence of self-cultivation in learning. From a Confucian viewpoint, self-cultivation is aimed at morally transforming the learners so that they can realise the Way ( dao). The learning process involves being committed to studying, improving oneself by observing rituals and living ethically, and being guided by one’s teacher. Throughout the learning process, both the independence and inter-dependence of the self are emphasised. The article further discusses two major implications from a Confucian interpretation of self-cultivation in learning for self-directed learning. What is recommended is a model of self-directed learning that is underpinned by a shared moral vision of the good and underscores the collective resources and wisdom to promote individual and group learning.
Breathlessness services as a new model of support for patients with respiratory disease
Authors: Bausewein Claudia , Schunk Michaela , Schumacher Philipp , Dittmer Julika , Bolzani Anna , Booth Sara
Published: July 2017

The complexity of breathlessness in advanced disease requires a diversity of measures ideally tailored to the individual patient needs. ‘Breathlessness services’ have been systematically developed and tested to provide specific interventions and support for patients and their carers. The aim of this article is (1) to identify and describe components of breathlessness services and (2) to describe the clinical model of one specific service in more detail. This article is based on a systematic review evaluating randomized controlled trials (RCTs) and quasi-RCTs which examine the effectiveness of services aiming to improve breathlessness of patients with advanced disease. The Munich Breathlessness Service (MBS) is described in detail as an example of a recently set-up specialist service. Five service models were identified which were tested in six RCTs. Services varied regarding structure and composition with face-to-face meetings, some with additional telephone contacts. Service duration was median 6 weeks (range 2–12 weeks). Involved professions were nurses, various therapists and, in two models, also physicians. The breathing–thinking–functioning model was targeted by various service components. The MBS is run by a multi-professional team mainly with physicians and physiotherapists. Patients are seen weekly over 5–6 weeks with an individualized management plan. Breathlessness services are a new model for patients with advanced disease integrating symptom management and early access to palliative care.
Oral prednisolone for 4 days does not increase exercise tolerance in men with COPD
Authors: Karlsson SL , Backer V , Godtfredsen Nina Skavlan
Published: July 2017

One of the primary objectives in management of chronic obstructive pulmonary disease (COPD) is preventing decrease in lung function and reducing the annual number of acute exacerbations of COPD (AECOPD). An oral course of systemic corticosteroids is a commonly used treatment in AECOPD. We hypothesize that this treatment also increases exercise performance and decreases muscle fatigue. In a randomized double-blinded, parallel, placebo-controlled trial, we investigated 14 men (8 on prednisolone 37.5 mg vs. 6 on placebo) with severe and very severe COPD. For 5 consecutive days, the patients performed a submaximal endurance test measuring time to exhaustion (TTE, primary endpoint), spirometry, maximal inspiratory and expiratory pressure and maximal isometric contraction of the quadriceps femoris muscle (maximum voluntary contraction (MVC)). At visits 2, 3 and 4, a fatigue protocol was carried out after 40 minutes of cycling at 40% of maximal effort. No differences between groups were found for TTE, lung function or maximal inspiratory or expiratory pressure, however, patients on prednisolone showed significant increased MVC: median 5.15 [3.35; 9.15] against placebo: −2 [−5.57; 3.95] ( p = 0.03). This finding indicates an impact of corticosteroids on muscle groups being exposed to submaximal endurance.
Investigating Cognitive Effort and Response Quality of Question Formats in Web Surveys Using Paradata
Authors: Höhne Jan Karem , Schlosser Stephan , Krebs Dagmar
Published: July 2017

Measuring attitudes and opinions employing agree/disagree (A/D) questions is a common method in social research because it appears to be possible to measure different constructs with identical response scales. However, theoretical considerations suggest that A/D questions require a considerable cognitive processing. Item-specific (IS) questions, in contrast, offer content-related response categories, implying less cognitive processing. To investigate the respective cognitive effort and response quality associated with A/D and IS questions, we conducted a web-based experiment with 1,005 students. Cognitive effort was assessed by response times and answer changes. Response quality, in contrast, was assessed by different indicators such as dropouts. According to our results, single IS questions require higher cognitive effort than single A/D questions in terms of response times. Moreover, our findings show substantial differences in processing single and grid questions.
Correlation Between Natural Killer Cell Activity and Systemic Inflammatory Markers for Heterogeneous Cancer Patients Treated With Wheel Balance Cancer Therapy
Authors: Kang Hwi-Joong , Bae Kyeore , Kim Jee-Hye , Cho Chong-Kwan , Yoo Hwa-Seung
Published: July 2017

Background and Objective: Natural killer (NK) cells are known to have an effect on the prevention of tumorigenesis for the initial cancer, as well as the metastatic cancer. For the past several years, the relationship between cancer and inflammation has been actively studied in preclinical and clinical settings, but there are no reports on alterations in and correlation for NK cell activity (NKA) and systemic inflammatory markers. Accordingly, this study aimed to measure correlation between NKA and the levels of other systemic inflammatory markers in patients with gastric, breast, and pancreatic cancer who received Wheel Balance Cancer Therapy (WBCT). Methods: Forty-two electronic charts of patients with gastric, breast, and pancreatic cancer treated with WBCT from February 1, 2015 to September 30, 2015, were reviewed retrospectively. These charts were statistically analyzed, looking for alterations of and correlation for NKA and the expressions of systemic inflammatory markers. Results: Patients with a NKA of under 300 pg/mL at admission showed significantly higher erythrocyte sedimentation rate (ESR) and neutrophil-to-lymphocyte ratio (NLR) values and decreasing NLR values due to WBCT than patients with an NKA greater than 300 pg/mL. As a result of the correlation analysis between NKA and the levels of the systemic inflammatory markers, NKA showed significant negative correlation with NLR, ESR, and fibrinogen values. Conclusions: Negative correlation was identified between NKA and NLR, NKA and ESR, and NKA and fibrinogen in patients with heterogeneous cancer patients.
Changes in R-R and Q-T Intervals Following Cardiac Vagotomy in Neonatal Swine
Authors: Khan Muhammad S. , Zhao Ning , Sica Anthony L. , Gootman Norman , Gootman Phyllis M.
Published: July 2017

Asymmetric innervation of the myocardium, especially a predominance of sympathetic innervation, may establish conditions whereby electrical instability could result. Using a swine animal model, we studied the effect of right cardiac vagal denervation on the variability of R-R and Q-T intervals. Newborn pigs were assigned randomly to two groups: sham-operated controls (C), or denervation of the right cardiac vagus nerve (RCVX). EKGs were recorded weekly until the two groups exhibited significant heart rate differences. Analysis of the EKG included measurements of R-R and Q-T intervals and corrected Q-T intervals (QTc). Poincaré plots were used to display age-related differences in R-R and Q-T intervals. For RCVX animals, decreased QTc and R-R intervals were noted at 6 and 7 weeks after denervation, respectively. Unexpectedly, one RCVX animal exhibited marked sudden pauses in sinus rhythm. These data indicated that reduced vagal cardiac modulation during development might alter cardiac electrical stability in conscious swine.
Metabolism of Chylomicron Cholesterol is Delayed by Estrogen. An In Vivo Study in the Rat
Authors: Bravo Elena , Cantafora Alfredo , Avella Michael , Botham Kathleen M.
Published: July 2017

In order to test the effects of estrogen on the clearance of cholesterol of dietary origin from the blood and its elimination from the body via the bile in an in vivo animal model, the fate of radioactivity from intravenously injected [3H]cholesterol-labeled chylomicrons was investigated in the rat. The labeled lipoproteins were administered intrajugularly to male rats previously given 17α ethinyl estradiol or the vehicle only, and the removal of the radioactivity from the blood and its uptake by the liver and secretion into bile was determined. Experiments were carried out in animals with or without prior drainage (20 hr) of the pool of bile acids in the enterohepatic circulation, to take account of the different demands of the liver for cholesterol in the two conditions. In rats without biliary drainage, estrogen treatment decreased the rate of removal of radioactivity from the blood by about 30% and the recovery of cholesterol in the liver by about 50% in the first 30 min after injection of the labeled chylomicrons. After biliary drainage, however, the recovery of label in the liver after 90 min was similar in estrogen-treated and control animals, although its secretion into bile was markedly reduced in the estrogen-treated group (total biliary secretion in 90 min was 26% of the value found in control rats). In addition, the apolipoprotein E (aopE) content of the serum total lipoproteins was markedly reduced by estrogen. These results provide direct evidence indicating that estrogen retards the elimination of dietary cholesterol from the body via the bile in the rat, and this is likely to be mainly due to a reduced level of apoE in chylomicrons. In view of this, we suggest that the hypothesis that estrogen increases the hepatic uptake of chylomicron cholesterol, and its excretion in the bile during contraceptive and hormone replacement therapy should be reexamined.
Changes in Ryanodine Receptor-Mediated Calcium Release During Skeletal Muscle Differentiation. II. Resolution of a Caffeine-Ryanodine Paradox
Authors: Wingertzahn Mark A. , Ochs Raymond S.
Published: July 2017

Our previous study demonstrated a disparity of action between two established pharmacological modulators of the same calcium (Ca2+) release channel, the ryanodine receptor (RyR). Specifically, we observed that caffeine sensitivity was elicited at earlier stages of development than that of ryanodine. In the present study, we offer a hypothesis to resolve this paradox. We provide evidence that ryanodine acts as a pure uncompetitive inhibitor of Ca2+ transport, with respect to Ca2+ itself. This explains why little ryanodine inhibition was observed at low Ca2+ concentrations, while maximal ryanodine inhibition was observed at saturating Ca2+ concentrations. In order to exclude the possibility of nonspecific ryanodine actions as an alternative explanation, we established the phenomenon of capacitative calcium entry (CCE) for L6 cells. Since it is known that CCE is inversely correlated with [Ca2+] of the ER/SR lumen, the extent of CCE is therefore an indirect measure of Ca2+ concentration within the SR. We also demonstrated the functional pathway for Ca2+ entry. Employing pharmacological inhibitors, we found that a T-type plasma membrane channel was predominant in the myoblasts, while an L-type channel was predominant in the adult myotubes. Our data using these inhibitors made nonspecific ryanodine actions an unlikely explanation of the disparity in action between ryanodine and caffeine. Moreover, we found no evidence that inositol trisphosphate, a proposed regulator of CCE for other cells, could influence CCE in L6 cells. We conclude that the disparity between caffeine and ryanodine can be explained by Ca2+ dependence of ryanodine action. This study may also offer an explanation of other studies showing unclear actions of ryanodine binding and action.
Effect of Estradiol and FBS on PRL Cells, GH Cells, and PRL/GH Cells in Primary Cultures of Pituitary Cells from Prenatal Rats
Authors: Yamamuro Yutaka , Aoki Tomohiro , Sensui Naoto
Published: July 2017

The effects of estradiol (E2) treatment on prolactin (PRL) cells, GH cells, and PRL/GH cells in immature pituitary cells were determined using primary cultures from prenatal rats and immunocytochemistry with fluorescent antibodies. Anterior pituitaries obtained from fetuses on day 22 of pregnancy were monodispersed and cultured in chemically defined medium or medium containing 10% fetal bovine serum (FBS). After preincubation for 24 hr, E2 (final concentrations were 0 M, 10-8 M, 10-7 M, and 10-6 M) was added into each medium. After 72 hr of incubation, cells were subjected to Immunocytochemistry. E2 stimulated the increase of PRL cells in a dose-dependent manner, and the PRL cell percentage cultured with FBS in all groups was significantly higher than that cultured in chemically-defined medium. PRL/GH cells also responded to E2 in the same manner as PRL cells. E2 was not effective in proliferating GH cells, and GH cell percentage significantly decreased with the addition of FBS into the medium. These results suggest that E2 is dose-dependently capable of increasing immature PRL cells and/or PRL/GH cells in vitro. Moreover, there is a factor(s) in FBS that regulates the increase of these cells.
The Role of Inducible-Nitric Oxide in Cocaine-Induced Kindling
Authors: Park Kwan-Kyun , Reuben Jayne S. , Soliman Karam F. A.
Published: July 2017

Experimentally naive male Sprague Dawley rats (weighing 85–110 g) were used to examine the role of inducible nitric oxide synthase (iNOS) in cocaine-induced kindling. Repeated administration of cocaine (45 mg/kg, ip) to Sprague Dawley male rats for 7 consecutive days produced a progressive increase in the Convulsive responsiveness and death. Pretreatment with iNOS inhibitors, L-N6-(1-iminoethyl)lysine (NIL; 10 mg/kg, ip) and (–)-ePigalloocatechin gallate (EGCG; 10 mg/kg, ip) 30 min before cocaine (45 mg/kg, ip) administration for 7 days attenuated the development of cocaine kindling and blocked cocaine-induced death. Results of NMDA receptor binding assay in the hippocampus showed a significant increase in the affinity without changes in the density in animals treated with cocaine, but there were no changes in these parameters in the cortex. Pretreatment with NIL or EGCG prior to cocaine administration abolished the cocaine-induced effect in the NMDA receptor affinity in the hippocampus. These results suggest that iNOS induction followed by an increase of NMDA receptor affinity in the hippocampus after repeated exposure to cocaine may participate in the process of the development of cocaine kindling.
Redox-Dependent Modulation of Lipid Synthesis Induced by Oleic Acid in the Human Intestinal Epithelial Cell Line Caco-2
Authors: Rivabene Roberto , Napolitano Mariarosaria , Cantafora Alfredo , Bravo Elena
Published: July 2017

The absorption, remodeling, and delivery of dietary lipids by intestinal cells are part of a complex multi-step process, the dynamics of which is influenced by the lipid composition of the diet and the physiological state of enterocytes. Emerging data indicate that, among the parameters known to modulate the cell functionality, the internal oxidative balance plays a pivotal role. In this study, we analyzed the effects of varying redox equilibria on the way in which the intestinal Caco-2 cell line utilize an otogenous lipid source such as oleic acid. Firstly, we manipulated the intracellular levels of soluble thiols (glutathione), and the amount of cell-associated products of lipid peroxidation, commonly regarded as two critical parameters characterizing the redox profile of the cells. Two different perturbants having opposite effects on the cell's redox profile were used: the pro-oxidizing agent CuSO4 (2.5 and 10 µM) and the antioxidant and thiol supplier N-acetylcysteine (NAC, 2.5 and 5 mM). The influence of these mild but critical manipulations on the incorporation of oleate (50 and 500 µM) into cholesterol, triacylglycerol, end phospholipid was then evaluated. We found that the emerging pro-oxidant condition induced by CuSO4 pre-exposure was associated with a significant up-regulation of phospholipid synthesis, while minor modifications were detected in that of triacylgiycerols. Conversely, when a more reducing state was induced by NAC pre-treatment, there was a significant down-regulation of triacylglycerol synthesis, with minor modifications in that of phospholipids. In addition, the incorporation of oleic acid in the cholesteryl ester fraction appeared to be unmodified under all the redox conditions reported. On the whole, these results indicate that the pre-existing internal redox potential of the enterocytes is a critical factor that is able to differentially modulate lipid synthesis at the Intestinal level. Thus, the adoption of a strategy designed to control/buffer the antioxidant capacity of the gastrointestinal tract could have important consequences for the modulation of lipid balance in the body.
Identification and Role of Thiols in Toxoplasma gondii Egress
Authors: Stommel Elijah W. , Cho Eunsung , Steide Jean Alex , Seguin Rosanne , Barchowsky Aaron , Schwartzman Joseph D. , Kasper Lloyd H.
Published: July 2017

The nucleoside triphosphate hydrolase of Toxoplasma gondii is a potent apyrase that is secreted into the parasitophorous vacuole where it appears to be essentially Inactive in an oxidized form. Recent evidence shows that nucleoside triphosphate hydrolase can be activated by dithiothreitol in vivo. On reduction of the enzyme, there is a rapid depletion of host cell ATP. Previous results also demonstrate a dithiothreitol induced egress of parasites from the host cell with a concurrent Ca2+ flux, postulated to be a consequence of the release of ATP-dependent Ca2+ stores within the tubulovesicular network of the parasitophorous vacuole. Reduction of the nucleoside triphosphate hydrolase appears crucial for Its activation; however, the exact mechanism of reduction/activation has not been determined. Using a variety of techniques, we show here that glutathione promoters activate a Ca2+ flux and decrease ATP levels in Infected human fibroblasts. We further show the in vitro activation of nucleoside triphosphate hydrolase by endogenous reducing agents, one of which we postulate might be secreted into the PV by T. gondii. Our findings suggest that the reduction of the parasite nucleoside triphosphate hydrolase, and ultimately parasite egress, is under the control of the parasites themselves.
Coumestrol Antagonizes Neuroendocrine Actions of Estrogen via the Estrogen Receptor α
Authors: Jacob Dena A. , Temple Jennifer L. , Patisaul Heather B. , Young Larry J. , Rissman Emilie F.
Published: July 2017

The phytoestrogen coumestrol has estrogenic actions on peripheral reproductive tissues. Yet in the brain this compound has both estrogenic and anti-estrogenic effects. We used estrogen receptor α knockout mice (ERαKO) to determine whether coumestrol has estrogenic actions in mice and also if these effects are mediated by the classic ERα. Female wild-type (WT) and ERαKO mice were ovariectomized and treated with estradiol (E2), dietary coumestrol, both, or neither compound. Ten days later the animals were sacrificed, blood was collected, and brain tissues were perfused. Fixed brains were sectioned and immunocytochemistry was employed to quantify progesterone receptors (PR) in the medial preoptic (POA) and ventromedial nucleus of the hypothalamus (VMN). Plasma was assayed for luteinizing hormone (LH). Estrogen treatment induced PR immunoreactivity in both regions in brains of WT females. In ERαKO mice, lower levels of PR were induced. The stimulatory effects of E2 on PR were attenuated in the POA by cotreatment with coumestrol, and the same trend was noted in the VMN. WT ovariectomized females treated with E2 had low levels of LH, while LH was high in untreated females and even higher in ovariectomized females treated with coumestrol. ERαKO females in all treatment groups had high levels of LH. Taken together, the results show that coumestrol has anti-estrogenic actions in the brain and pituitary and that ERα mediates these effects.
The Immune Response to Ocular Herpes Simplex Virus Type 1 Infection
Authors: Carr Daniel J.J. , Härle Peter , Gebhardt Bryan M.
Published: July 2017

Herpes simplex virus type 1 (HSV-1) is a prevalent microbial pathogen infecting 60% to 90% of the adult world population. The co-evolution of the virus with humans is due, in part, to adaptations that the virus has evolved to aid it in escaping immune surveillance, including the establishment of a latent infection in its human host. A latent infection allows the virus to remain in the host without inducing tissue pathology or eliciting an immune response. During the acute infection or reactivation of latent virus, the immune response is significant, which can ultimately result in corneal blindness or fatal sporadic encephalitis. In fact, HSV-1 is one of the leading causes of infectious corneal blindness in the world as a result of chronic episodes of viral reactivation leading to stromal keratitis and scarring. Significant inroads have been made in identifying key immune mediators that control ocular HSV-1 infection and potentially viral reactivation. Likewise, viral mechanisms associated with immune evasion have also been identified and will be discussed. Lastly, novel therapeutic strategies that are currently under development show promise and will be included in this review. Most investigators have taken full advantage of the murine host as a viable working in vivo model of HSV-1 due to the sensitivity and susceptibility to viral infection, ease of manipulation, and a multitude of developed probes to study changes at the cellular and molecular levels. Therefore, comments in this review will primarily be restricted to those observations pertaining to the mouse model and the assumption (however great) that similar events occur in the human condition.
Plasma Drug Levels Compared with DNA Incorporation of 3′-azido-3′-Deoxythymidine (AZT) in Adult Cynomolgus (Macaca fascicularis) Monkeys
Authors: Olivero Ofelia A. , Reddy Madhavi K. , Pietras Sara M. , Poirier Miriam C.
Published: July 2017

Zidovudine (3′-azido-3′-deoxythymidine, AZT), widely used for the therapy of the Human Immunodeficiency Virus-1 (HIV-1), is a nucleoside analog of thymidine that becomes phosphorylated and incorporated into nuclear and mitochondrial DNA. Levels of AZT incorporation into DNA of humans, monkeys, and mice are highly variable and suggest interindividual variability in phosphorylation pathways. In addition, studies in rhesus monkeys (1) have shown a lack of correlation between levels of unbound AZT in plasma and tissue AZT-DNA. However, the correlation between plasma AZT and tissue AZT-DNA has not been previously examined in the same primate. Here we examine the relationship between AZT-DNA incorporation in leukocytes and multiple organs, and levels of the drug circulating in plasma of adult female cynomolgus (Macaca fascicularis) monkeys. Three monkeys were dosed with 40.0 mg of AZT/day for 30 days by naso-gastric intubation. The average daily dose of 9.9 mg of AZT/kg/body wt was similar to the ~8.6 mg of AZT/kg/body wt (600 mg/day) given to adult HIV-1-infected patients. In all three monkeys, at the time of sampling, values for AZT concentrations in plasma were similar and values for AZT incorporation into leukocyte DNA (86.1, 100.0, and 114.1 molecules of AZT/106 nucleotides) were also similar. AZT-DNA incorporation was detected in liver, uterus, spleen, and kidney from the three AZT-exposed animals, with values for positive samples ranging from 5.8 to 97.4 molecules of AZT/106 nucleotides. In brain cortex and lung DNA from AZT-exposed animals, AZT incorporation was undetectable. The data suggest that organ-specific differences in AZT uptake and/or metabolism may contribute to AZT phosphorylation and subsequent drug incorporation into DNA. In addition, AZT-DNA levels in monkey organs were similar to or lower than values observed in peripheral leukocytes of adult AIDS patients.
Genomic Growth Hormone Gene Polymorphisms in Native Chinese Chickens
Authors: Ip Stephen C.Y. , Zhang Xiquan , Leung Frederick C.
Published: July 2017

Chicken growth hormone (cGH), a polypeptide hormone synthesized in and secreted by the pituitary gland, is involved in a wide variety of physiological functions such as growth, body composition, egg production, aging, and reproduction. Chicken growth hormone polymorphisms have been reported to be associated with certain phenotypes. Our objective is to investigate the GH gene polymorphism in selected strains of native Chinese chickens. Yellow Wai Chow GH gene was characterized by sequencing and was found to have one silent substitution, 31 insertions, and other substitutions spread among the introns. In addition, a novel Mspl site has been identified and characterized in the first intron. Allele frequencies of the intron 1 polymorphism were characterized among 28 populations of native Chinese chickens. Thus, polymorphism of the cGH gene may be useful in phylogenetic analysis, as well as in the design of breeding programs.
Immunocytochemical Localization of Aquaporin-1 in Bovine Corneal Endothelial Cells and Keratocytes
Authors: Wen Quan , Diecke Friedrich P.J. , Iserovich Pavel , Kuang Kunyan , Sparrow Janet , Fischbarg Jorge
Published: July 2017

For immunocytochemistry, cultured bovine corneal endothelial cells (CBCEC) and bovine corneal cryosections were utilized. Preparations were fixed, permeabilized, and incubated with primary rabbit anti-rat aquaporin 1 (AQP1) antibody followed by rhodamine-conjugated secondary antibody, and were counter-stained with Sytox nuclear acid stain. Confocal microscopy of CBCEC in the x, y, and z planes showed rhodamine fluorescence, indicating the presence of AQP1 antibody localized to the apical and basolateral domains of the plasma membrane, but not to the membranes of intracellular compartments or other subcellular locations. Preabsorption with control antigenic peptide yielded no positive staining. Similar results were obtained using freshly dissected bovine corneas; in addition, these images showed AQP1 distributed to the plasma membranes of keratocytes. No AQP1 staining was seen in corneal epithelium, and no staining was observed in CBCEC layers exposed to AQP3, AQP4, and AQP5 antibodies.
Omega-3 Polyunsaturated Fatty Acids and Skeletal Health1
Authors: Watkins Bruce A. , Li Yong , Lippman Hugh E. , Seifert Mark F.
Published: July 2017

This minireview on skeletal biology describes the actions of prostaglandins and cytokines involved in the local regulation of bone metabolism, it documents the role of lipids in bone biology, and it presents relationships between fatty acids and other factors that impact skeletal metabolism. The data presented herein show consistent and reproducible beneficial effects of omega-3 (n-3) fatty acids on bone metabolism and bone/joint diseases. Polyunsaturated fatty acids modulate eicosanoid biosynthesis in numerous tissues and cell types, alter signal transduction, and influence gene expression. These effects have not been explored in the skeletal system. Future research on n-3 fatty acids in bone biology should focus on the following two aspects. First, the further elucidation of how n-3 fatty acids alter biochemical and molecular processes involved in bone modeling and bone cell differentiation, and second, the evaluation of the potential pharmaceutical applications of these nutraceutical fatty acids in maintaining bone mineral status and controlling inflammatory bone/joint diseases.
Selected Features of Nonendocrine Pancreatic Cancer
Authors: Anderson Ken M. , Harris Jules E.
Published: July 2017

We survey some interesting features of gene expression in non-endocrine pancreatic cancer, the response to some less widely known agents as they impact on pancreatic cell proliferation and programmed death, and several developing approaches to therapy. The proliferative and cellular suicide responses of Panc-1 cells to the free radical spin trap, NTBN, and to the 5-lipoxygenease inhibitor, MK 886, the latter assessed with CLONTECH Atlas Human cDNA Array 1, are reviewed. Difficulties in identifying those factors whose suppression or augmentation could result in inhibition of malignantly transformed cell properties are considered.
Na+ Effects on Mitochondrial Respiration and Oxidative Phosphorylation in Diabetic Hearts
Authors: Babsky Andriy , Doliba Nicolai , Doliba Nataliya , Savchenko Andrey , Wehrli Suzanne , Osbakken Mary
Published: July 2017

Intracellular Na+ is approximately two times higher in diabetic cardiomyocytes than in control. We hypothesized that the increase in Na+1 activates the mitochondrial membrane Na+/Ca2+ exchanger, which leads to loss of intramitochondrial Ca2+, with a subsequent alteration (generally depression) in bioenergetic function. To further evaluate this hypothesis, mitochondria were isolated from hearts of control and streptozotocin-induced (4 weeks) diabetic rats. Respiratory function and ATP synthesis were studied using routine polarography and 31P-NMR methods, respectively. While addition of Na+ (1–10 mM) decreased State 3 respiration and rate of oxidative phosphorylation in both diabetic and control mitochondria, the decreases were significantly greater for diabetic than for control. The Na+ effect was reversed by providing different levels of extramitochondrial Ca2+ (larger Ca2+ levels were needed to reverse the Na+ depressant effect in diabetes mellitus than in control) and by inhibiting the Na+/Ca2+exchanger function with diltiazem (a specific blocker of Na+/Ca2+ exchange that prevents Ca2+ from leaving the mitochondrial matrix). On the other hand, the Na+ depressant effect was enhanced by Ruthenium Red (RR, a blocker of mitochondrial Ca2+ uptake, which decreases intramitochondrial Ca2+). The RR effect on Na+ depression of mitochondrial bioenergetic function was larger in diabetic than control. These findings suggest that intramitochondrial Ca2+ levels could be lower in diabetic than control and that the Na+ depressant effect has some relation to lowered intramitochondrial Ca2+. Conjoint experiments with 31P-NMR in isolated superfused mitochondria embedded in agarose beads showed that Na+ (3–30 mM) led to significantly decreased ATP levels in diabetic rats, but produced smaller changes in control. These data support our hypothesis that in diabetic cardiomyocytes, increased Na+ leads to abnormalities of oxidative processes and subsequent decrease in ATP levels, and that these changes are related to Na+ induced depletion of intramitochondrial Ca2+.
Black Tea Extract, Thearubigin Fraction, Counteracts the Effect of Tetanus Toxin in Mice
Authors: Satoh Eiki , Ishii Toshiaki , Shimizu Yoshio , Sawamura Sin-ichi , Nishimura Masakazu
Published: July 2017

The aim of this study was to find an inactivating substance for tetanus toxin in natural foodstuff. Tetanus toxin (4 μg/ml) abolished indirect twitches in in vitro mouse phrenic nervediaphragm preparations within 2.5 hr. Hot water infusion of black tea mixed with tetanus toxin blocked the inhibitory effect of the toxin. Mixing the toxin with thearubigin fraction extracted from black tea infusion produced an identical result. Furthermore, thearubigin fraction mixed with the toxin protected against the in vivo paralytic effect of the toxin. Thearubigin fraction had no protective effect on other toxins, such as tetrodotoxin and saxitoxin. The specific binding of [125I]tetanus toxin to rat cerebrocortical synaptosomes was inhibited by mixing iodinated toxin with thearubigin fraction. These results imply that thearubigin fraction counteracts the effect of tetanus toxin by binding with toxin, and also suggest that this fraction may be able to apply for prophylaxis of tetanus.
Partial Restoration of Lutropin Activity by an Intersubunit Disulfide Bond: Implications for Structure/Function Studies
Authors: Einstein Monica , Lin Win , Macdonald Gordon J. , Moyle William R.
Published: July 2017

Gonadal function is controlled by lutropins and follitropins, heterodimeric cystine knot proteins that have nearly identical α-subunits. These heterodimeric proteins are stabilized by a portion of the hormone-specific β-subunit termed the “seatbelt” that is wrapped around α-subunit loop 2 (α2). Here we show that replacing human chorionic gonadotropin (hCG) α2 residue Lys51 with cysteine or alanine nearly abolished its lutropin activity, an observation that implies that αLys51 has a key role in hormone activity. The activity of the heterodimer containing αK51C, but not that containing αK51 A, was increased substantially when β-subunit seatbelt residue pAsp99 was converted to cysteine. As had been reported by others, heterodimers containing αK51C and βD99C were crosslinked by a disulfide. The finding that an intersubunit disulfide restored some of the activity lost by replacing αLys51 suggests that this residue is not crucial for receptor binding or signaling and also that hCG and related hormones may be particularly sensitive to mutations that alter interactions between their subunits. We propose the unique structures of hCG and related family members may permit some subunit movement in the heterodimer, making it difficult to deduce key residues involved in receptor contacts simply by correlating the activities of hormone analogs with their amino acid sequences.