bluuebunny/crossref_metadata_2025 huggingface dataset:
Does cannabis use moderate smoking cessation outcomes in treatment‐seeking tobacco smokers? Analysis from a large multi‐center trial
Authors: Rabin Rachel A. , Ashare Rebecca L. , Schnoll Robert A. , Cinciripini Paul M. , Hawk Larry W. , Lerman Caryn , Tyndale Rachel F. , George Tony P.
Published: May 2016

Background and Objective

Tobacco and cannabis are frequently used in combination and cannabis co‐use may lead to poor tobacco cessation outcomes. Therefore, it is important to explore if cannabis co‐use is associated with a reduced likelihood of achieving successful tobacco abstinence among treatment‐seeking tobacco smokers. The present study examined whether current cannabis use moderated tobacco cessation outcomes after 12 weeks of pharmacological treatment (varenicline vs. nicotine patch vs. placebo) with adjunctive behavioral counseling.

Methods

Treatment‐seeking tobacco smokers (N = 1,246) were enrolled in an intent‐to‐treat study, of which 220 were current cannabis users. Individuals were randomly assigned to 12 weeks of placebo (placebo pill plus placebo patch), nicotine patch (active patch plus placebo pill), or varenicline (active pill plus placebo patch), plus behavioral counseling. The primary endpoint was biochemically verified 7‐day point prevalence abstinence at the end of treatment.

Results

Controlling for rate of nicotine metabolism, treatment arm, age, sex, alcohol, and level of nicotine dependence, cannabis users were as successful at achieving biochemically verified 7‐day point prevalence abstinence compared to tobacco‐only smokers.

Conclusions and Scientific Significance

Findings suggest that cannabis use does not hinder the ability to quit tobacco smoking. Future tobacco cessation studies should employ prospective, longitudinal designs investigating cannabis co‐use over time and at different severity levels. (Am J Addict 2016;25:291–296)
Specific allergen immunotherapy for the treatment of atopic eczema: a Cochrane systematic review
Authors: Tam H. H. , Calderon M. A. , Manikam L. , Nankervis H. , Núñez I. G. , Williams H. C. , Durham S. R. , Boyle R. J.
Published: May 2016

Background

Specific allergen immunotherapy (SIT) is an effective allergy treatment, but it is unclear whether SIT is effective for atopic eczema (AE). We undertook a systematic review to assess SIT efficacy and safety for treating AE.

Methods

We searched databases, ongoing clinical trials registers, and conference proceedings up to July 2015. Randomized controlled trials (RCTs) of SIT using standardized allergen extracts, compared with placebo/control, for treating AE in patients with allergic sensitization were eligible.

Results

We identified 12 eligible trials with 733 participants. Interventions included subcutaneous (six trials), sublingual (four trials), oral or intradermal SIT in children/adults allergic to house dust mite (10 trials), grass pollen or other inhalants. Risk of bias was moderate, with high loss to follow‐up and nonblinding as the main concerns. For our primary outcomes, three studies (208 participants) reported no significant difference – patient‐reported global disease severity improvement RR 0.75 (95% CI 0.45, 1.26); and eczema symptoms mean difference −0.74 on a 20‐point scale (95% CI −1.98, 0.50). Two studies (85 participants) reported a significant difference – SIT improved global disease severity RR 2.85 (95% CI 1.02, 7.96); and itch mean difference −4.20 on a 10‐point scale (95% CI −3.69, −4.71). Meta‐analysis was limited due to extreme statistical heterogeneity. For some secondary outcomes, meta‐analyses showed benefits for SIT, for example investigator‐rated improvement in eczema severity RR 1.48 (95% CI 1.16, 1.88; six trials, 262 participants). We found no evidence of adverse effects. The overall quality of evidence was low.

Conclusion

We found no consistent evidence that SIT is effective for treating AE, but due to the low quality of evidence further research is needed to establish whether SIT has a role in AE treatment.
Cardiac Index Declines During Long‐Term Left Ventricular Device Support
Authors: Kalathiya Rohan J. , Houston Brian A. , Chaisson Jordan M. , Grimm Joshua C. , Stevens Gerin R. , Sciortino Christopher M. , Shah Ashish S. , Whitman Glenn J. R. , Russell Stuart D. , Tedford Ryan J.
Published: May 2016

To investigate longitudinal trends in valvular and ventricular function with long‐term left ventricular assist device (LVAD) therapy, we analyzed hemodynamic and echocardiographic data of patients with at least 2 years of continuous LVAD support. All 130 patients who underwent HeartMate II implantation at our institution between 2005 and 2012 were reviewed. Twenty patients had hemodynamic and echocardiographic evaluations in both the early (0–6 months) and late (2–3 years) postoperative period. Patients on inotropic therapy or temporary mechanical support were excluded. The average times of early and late hemodynamic evaluations were 59 ± 41 days and 889 ± 160 days, respectively. Cardiac index (CI) declined by an average of 0.4 L/min/m2 (P = 0.04) with concomitant increase in pulmonary capillary wedge pressure (PCWP; P = 0.02). The right atrial pressure to PCWP (RAP:PCWP) ratio decreased during LVAD support suggesting improvement in right ventricular function. While there was an increase in degree of aortic insufficiency (AI) at the late follow‐up period (P = 0.008), dichotomization by median decline in CI (−0.4 L/min/m2) indicated no difference in prevalence of AI among the groups. CI declined in patients with HeartMate II after 2 years of continuous support. An increase in preload and afterload was observed in those with the greatest decline in CI.
4 Experiencing Social Change: Life during the Mimbres Classic Transformation
Authors: Hegmon Michelle , Nelson Margaret C. , Schollmeyer Karen Gust
Published: May 2016

What was it like to live during a time of social transformation? To live during the culture changes and depopulation at the end of the Classic Mimbres period, ca. 1130 C.E.? As part of the Archaeology of the Human Experience we address these questions with an evidence‐based account of what people did and how the changes affected their lives. Where possible and reasonable, we make people the subjects of our sentences. This approach leads to the conclusions that most changes—such as the end of a land tenure system—affected different people in different ways. The approach also raises questions about what happened to the artists when their artistic tradition ended.
8 Who Benefits? Structural Change and Lived Experience in the Late Prehispanic Andes
Authors: Costin Cathy Lynne
Published: May 2016

In this chapter, I identify changes in the division of labor by age, gender, and class, evaluate the intensity of household production, and analyze shifting patterns of consumption to address how the Inka conquest of the Yanamarca Valley differentially affected women and men, children and adults, elites and commoners in Late pre‐Hispanic Peru. Ethnohistoric and archaeological data indicate that the workload increased generally for all conquered peoples, while reordered systems of reward and recognition differentially affected distinct sectors of the population, altering social relations and gender ideology during this period of political and economic change.
9 Social Inequality and Access to Services in Premodern Cities
Authors: Dennehy Timothy J. , Stanley Benjamin W. , Smith Michael E.
Published: May 2016

We use spatial analytical methods to illuminate one aspect of the urban experience: equity of access to facilities that provide material, religious, and assembly services. We compare three cities known from archaeology (Teotihuacan, Tikal, and Empuries) and three historical cities (Bhaktapur, Chester, and Lamu). Some neighborhoods had better access to service facilities than others, pointing to ancient patterns of spatial inequality. Data on house size suggest that status also impacted service access. Greater travel time to service facilities negatively impacts the well‐being of urban residents in two ways: it reduces access to key services, and it takes time away from other activities. Our methods for identifying these spatial patterns of inequality open a new window on the implications of social inequality for the premodern urban experience.
Neutrophil maturation rate determines the effects of dipeptidyl peptidase 1 inhibition on neutrophil serine protease activity
Authors: Gardiner P , Wikell C , Clifton S , Shearer J , Benjamin A , Peters S A
Published: May 2016

Background and Purpose

Neutrophil serine proteases (NSPs) are activated by dipeptidyl peptidase 1 (DPP1) during neutrophil maturation. The effects of neutrophil turnover rate on NSP activity following DPP1 inhibition was studied in a rat pharmacokinetic/pharmacodynamic model.

Experimental Approach

Rats were treated with a DPP1 inhibitor twice daily for up to 14 days; NSP activity was measured in onset or recovery studies, and an indirect response model was fitted to the data to estimate the turnover rate of the response.

Key Results

Maximum NSP inhibition was achieved after 8 days of treatment and a reduction of around 75% NSP activity was achieved at 75% in vitro DPP1 inhibition. Both the rate of inhibition and recovery of NSP activity were consistent with a neutrophil turnover rate of between 4–6 days. Using human neutrophil turnover rate, it is predicted that maximum NSP inhibition following DPP1 inhibition takes around 20 days in human.

Conclusions and Implications

Following inhibition of DPP1 in the rat, the NSP activity was determined by the amount of DPP1 inhibition and the turnover of neutrophils and is thus supportive of the role of neutrophil maturation in the activation of NSPs. Clinical trials to monitor the effect of a DPP1 inhibitor on NSPs should take into account the delay in maximal response on the one hand as well as the potential delay in a return to baseline NSP levels following cessation of treatment.
Environmental justice in the environmental non‐governmental organization landscape of Toronto (Canada)
Authors: Teelucksingh Cheryl , Poland Blake , Buse Chris , Hasdell Rebecca
Published: May 2016

Key Messages

Energy policy in Toronto needs to be sensitive to residents' different social and economic positions.

The study's findings highlight the extent to which ENGOs are adopting environmental justice in Toronto.

In Toronto's neoliberal context, ENGOs have a bridging role between the state and communities.
Imitation, Collaboration, and Their Interaction Among Western and Indigenous Australian Preschool Children
Authors: Nielsen Mark , Mushin Ilana , Tomaselli Keyan , Whiten Andrew
Published: May 2016

This study explored how overimitation and collaboration interact in 3‐ to 6‐year‐old children in Westernized (N = 48 in Experiment 1; N = 26 in Experiment 2) and Indigenous Australian communities (N = 26 in Experiment 2). Whether working in pairs or on their own rates of overimitation did not differ. However, when the causal functions of modeled actions were unclear, the Indigenous Australian children collaborated at enhanced rates compared to the Western children. When the causal role of witnessed actions was identifiable, collaboration rates were correlated with production of causally unnecessary actions, but in the Indigenous Australian children only. This study highlights how children employ imitation and collaboration when acquiring new skills and how the latter can be influenced by task structure and cultural background.
Maternal total T4 during the first half of pregnancy: physiologic aspects and the risk of adverse outcomes in comparison with free T4
Authors: Korevaar Tim I. M. , Chaker Layal , Medici Marco , de Rijke Yolanda B. , Jaddoe Vincent W. V. , Steegers Eric A. P. , Tiemeier Henning , Visser Theo J. , Peeters Robin P.
Published: May 2016

Aim

We aimed to investigate TT4 physiological aspects and associations with clinical end‐points.

Background

Total T4 (TT4) has been suggested as a marker for maternal thyroid function during pregnancy because as compared to FT4 (i) TT4 measurement is not affected by binding protein interference, (ii) TT4 is considered to be more stable from the second trimester onwards, and (iii) TT4 better reflects changes in the hypothalamic–pituitary–thyroid axis. However, this is based on data from small studies, and, more importantly, it is unknown whether TT4 is associated with adverse pregnancy or child outcomes.

Methods

We selected 5647 mother–child pairs from a large population‐based prospective cohort with data on maternal TSH, FT4 and TT4 during early pregnancy (median 13·2 weeks, 95% range 9·8–17·6). We used multivariable (non)linear and logistic regression models to study the association of maternal TT4 with pre‐eclampsia, premature delivery, birthweight and offspring IQ and compare the results with previously obtained results for FT4.

Results

The change of mean TT4 levels was 27·5% compared to 20·2% for FT4. There was a log‐linear association of TT4 and FT4 with TSH, but the explained variability of TSH was much lower for TT4 than for FT4 (R‐squared TT4: 2·5% vs 8·0% for FT4). In contrast to FT4, there was no independent association of maternal TT4 with pre‐eclampsia, premature delivery, birthweight or offspring IQ.

Conclusion

Maternal TT4 levels are highly variable in the first half of pregnancy and are poorly related to maternal TSH. This study shows that maternal TT4 levels are either not associated, or not better associated as compared to FT4, with adverse pregnancy or child outcomes. This suggests that the maternal TT4 is inferior to FT4 in the assessment of maternal thyroid function during the first half of pregnancy.
Prediction of outcome by lymph node ratio in patients with parotid gland cancer
Authors: Meyer M.F. , Kreppel M. , Meinrath J. , Grünewald I. , Stenner M. , Drebber U. , Quaas A. , Odenthal M. , Semrau R. , Huebbers C.U. , Zöller J. , Huettenbrink K‐B. , Buettner R. , Beutner D.
Published: May 2016

Objective

Lymph node ratio (LNR) has been shown to be an independent predictor of recurrence risk and survival in different entities of carcinoma.

Methods

In this retrospective chart review, 128 patients with parotid gland cancer (PGC) subsequently treated by primary surgery were included. About 64% (n = 82) of these patients were additionally treated with adjuvant radiotherapy. Five‐year overall survival rates were determined by subgroups based on LNR value.

Results

Lymph node ratio was found to be significantly associated with overall survival rate (P < 0.001). Using univariate analyses, pathological tumour‐node‐metastasis (TNM)‐stage, UICC‐stage grouping and extracapsular spread were found to be significant predictors of overall survival (P < 0.001). However, with a multivariate analyses, LNR remained the only independent predictor of overall survival (P = 0.043).

Conclusions

After surgery for PGC, evaluation of the neck using LNR was found to reliably stratify the overall survival rate.
Changes in bird‐migration patterns associated with human‐induced mortality
Authors: Palacín Carlos , Alonso Juan C. , Martín Carlos A. , Alonso Javier A.
Published: May 2016

Many bird populations have recently changed their migratory behavior in response to alterations of the environment. We collected data over 16 years on male Great Bustards (Otis tarda), a species showing a partial migratory pattern (sedentary and migratory birds coexisting in the same breeding groups). We conducted population counts and radio tracked 180 individuals to examine differences in survival rates between migratory and sedentary individuals and evaluate possible effects of these differences on the migratory pattern of the population. Overall, 65% of individuals migrated and 35% did not. The average distance between breeding and postbreeding areas of migrant individuals was 89.9 km, and the longest average movement of sedentary males was 3.8 km. Breeding group and migration distance had no effect on survival. However, mortality of migrants was 2.4 to 3.5 times higher than mortality of sedentary birds. For marked males, collision with power lines was the main cause of death from unnatural causes (37.6% of all deaths), and migratory birds died in collisions with power lines more frequently than sedentary birds (21.3% vs 6.3%). The percentage of sedentary individuals increased from 17% in 1997 to 45% in 2012. These results were consistent with data collected from radio‐tracked individuals: The proportion of migratory individuals decreased from 86% in 1997–1999 to 44% in 2006–2010. The observed decrease in the migratory tendency was not related to climatic changes (temperatures did not change over the study period) or improvements in habitat quality (dry cereal farmland area decreased in the main study area). Our findings suggest that human‐induced mortality during migration may be an important factor shaping the migration patterns of species inhabiting humanized landscapes.
Are Children with Siblings Really More Vulnerable Than Only Children in Health, Cognition and Non‐cognitive Outcomes? Evidence from a Multi‐province Dataset in China
Authors: Zhou Hua , Mo Di , Luo Renfu , Yue Ai , Rozelle Scott
Published: May 2016

The general goal of the present study is to analyze whether children with siblings lag behind their only‐child counterparts in terms of health and nutrition, cognition and educational performance, and non‐cognitive outcomes. We draw on a dataset containing 25 871 observations constructed from three school‐level surveys spanning four provinces in China. The analysis compares children with siblings and only children aged 9 to 14 years old in terms of eight different health, cognitive and non‐cognitive indicators. We find that with the exception of the anemia rate, health outcomes of children with siblings are statistically indistinguishable from those of only children. In terms of cognition, children with siblings performed better than only children. Moreover, outcomes of children with siblings are statistically indistinguishable from those of only children in terms of the non‐cognitive outcomes provided by measures of anxiety. According to our results, the same general findings are true regardless of whether the difference between children with and without siblings is disaggregated by gender.
Educational Expectations and Dropout Behavior among Junior High Students in Rural China
Authors: Chang Fang , Min Wenbin , Shi Yaojiang , Kenny Kaleigh , Loyalka Prashant
Published: May 2016

The high level of dropout from junior high school is one of the most serious challenges facing the human capital development of the next generation of workers in China's rural areas. The goal of this paper is to assess to what extent the educational expectations of students are correlated with dropout behavior at the junior high school level in China. Using panel data, this research finds that the cumulative dropout rate is high among grade 7 and 8 students within our sample (as high as 19.5 percent, which implies a 3‐year dropout rate of around 25 percent). Importantly, we find that this high rate of dropout is significantly correlated with students' educational expectations. Specifically, students who reported their expected level of education is “less than high school” or “less than college” are five times and four times more likely to drop out during junior high school than their peers, respectively.
What makes some fisheries references highly cited?
Authors: Branch Trevor A , Linnell Allison E
Published: May 2016

We identify the 199 most‐cited fisheries references up to July 2014, topped by Nelson's Fishes of the World. Few book chapters, databases or reports were included, but review articles and field guides were over‐represented. Publishing in Science, Nature or Proceedings of the National Academy of Sciences USA is associated with a 34‐fold increase in the probability of an article being highly cited, but many highly cited references were also published in journals with impact factors under eight. Proportional contributions to references, taking into account number of authors, author order and other key factors, revealed Bill Ricker and John Roland Brett as the greatest individual contributors, and the US, Canada and the UK as greatest country contributors, with Canada significantly over‐represented. Female representation on the list was historically low before increasing to 21% in the 1990s, and reflected gender changes in the field of fisheries. When compared to >2000 control papers published in the same journal and year, highly cited fisheries papers were significantly longer (20.4 vs. 9.8 pages) and had more authors (5.8 vs. 4.3), references (118 vs. 51), tables and total illustrations; these differences were greater when high‐profile general journals were excluded, but lower when calculated on a per‐page basis. References with more than six authors jumped from 0 to 27% in 2000, coinciding with a rapid uptake of email among fisheries scientists. Overall, we find no shortcut to publishing highly cited references: they require substantial time, effort and knowledge invested in new hypotheses, textbooks, field guides, new discoveries, broad meta‐analyses, new methods and reviews.
Structural domains within the HIV‐1 mRNA and the ribosomal protein S25 influence cap‐independent translation initiation
Authors: Carvajal Felipe , Vallejos Maricarmen , Walters Beth , Contreras Nataly , Hertz Marla I. , Olivares Eduardo , Cáceres Carlos J. , Pino Karla , Letelier Alejandro , Thompson Sunnie R. , López‐Lastra Marcelo
Published: May 2016

The 5′ leader of the HIV‐1 genomic RNA is a multifunctional region that folds into secondary/tertiary structures that regulate multiple processes during viral replication including translation initiation. In this work, we examine the internal ribosome entry site (IRES) located in the 5′ leader that drives translation initiation of the viral Gag protein under conditions that hinder cap‐dependent translation initiation. We show that activity of the HIV‐1 IRES relies on ribosomal protein S25 (eS25). Additionally, a mechanistic and mutational analysis revealed that the HIV‐1 IRES is modular in nature and that once the 40S ribosomal subunit is recruited to the IRES, translation initiates without the need of ribosome scanning. These findings elucidate a mechanism of initiation by the HIV‐1 IRES whereby a number of highly structured sites present within the HIV‐1 5′ leader leads to the recruitment of the 40S subunit directly at the site of initiation of protein synthesis.
Spatially explicit estimates of N2O emissions from croplands suggest climate mitigation opportunities from improved fertilizer management
Authors: Gerber James S. , Carlson Kimberly M. , Makowski David , Mueller Nathaniel D. , Garcia de Cortazar‐Atauri Iñaki , Havlík Petr , Herrero Mario , Launay Marie , O'Connell Christine S. , Smith Pete , West Paul C.
Published: May 2016

With increasing nitrogen (N) application to croplands required to support growing food demand, mitigating N2O emissions from agricultural soils is a global challenge. National greenhouse gas emissions accounting typically estimates N2O emissions at the country scale by aggregating all crops, under the assumption that N2O emissions are linearly related to N application. However, field studies and meta‐analyses indicate a nonlinear relationship, in which N2O emissions are relatively greater at higher N application rates. Here, we apply a super‐linear emissions response model to crop‐specific, spatially explicit synthetic N fertilizer and manure N inputs to provide subnational accounting of global N2O emissions from croplands. We estimate 0.66 Tg of N2O‐N direct global emissions circa 2000, with 50% of emissions concentrated in 13% of harvested area. Compared to estimates from the IPCC Tier 1 linear model, our updated N2O emissions range from 20% to 40% lower throughout sub‐Saharan Africa and Eastern Europe, to >120% greater in some Western European countries. At low N application rates, the weak nonlinear response of N2O emissions suggests that relatively large increases in N fertilizer application would generate relatively small increases in N2O emissions. As aggregated fertilizer data generate underestimation bias in nonlinear models, high‐resolution N application data are critical to support accurate N2O emissions estimates.
Shape selection in Landsat time series: a tool for monitoring forest dynamics
Authors: Moisen Gretchen G. , Meyer Mary C. , Schroeder Todd A. , Liao Xiyue , Schleeweis Karen G. , Freeman Elizabeth A. , Toney Chris
Published: May 2016

We present a new methodology for fitting nonparametric shape‐restricted regression splines to time series of Landsat imagery for the purpose of modeling, mapping, and monitoring annual forest disturbance dynamics over nearly three decades. For each pixel and spectral band or index of choice in temporal Landsat data, our method delivers a smoothed rendition of the trajectory constrained to behave in an ecologically sensible manner, reflecting one of seven possible ‘shapes’. It also provides parameters summarizing the patterns of each change including year of onset, duration, magnitude, and pre‐ and postchange rates of growth or recovery. Through a case study featuring fire, harvest, and bark beetle outbreak, we illustrate how resultant fitted values and parameters can be fed into empirical models to map disturbance causal agent and tree canopy cover changes coincident with disturbance events through time. We provide our code in the r package ShapeSelectForest on the Comprehensive R Archival Network and describe our computational approaches for running the method over large geographic areas. We also discuss how this methodology is currently being used for forest disturbance and attribute mapping across the conterminous United States.
Relevance of environmental impact categories for perennial biomass production
Authors: Wagner Moritz , Lewandowski Iris
Published: May 2016

The decarbonization of the economy will require large quantities of biomass for energy and biomaterials. This biomass should be produced in sufficient quantities and in a sustainable way. Perennial crops in particular are often cited in this context as having low environmental impacts. One example of such crops is miscanthus, a tall perennial rhizomatous C4 grass with high yield potential. There are many studies which have assessed the global warming potential (GWP) of miscanthus cultivation. This is an important impact category which can be used to quantify the environmental benefit of perennial crops. However, the GWP only describes one impact of many. Therefore, the hypothesis of this study was that a holistic assessment also needs to include other impact categories. A life cycle assessment (LCA) with a normalization step was conducted for perennial crops to identify relevant impact categories. This assessed the environmental impact of both miscanthus and willow cultivation and the subsequent combustion for heat production in eighteen categories using a system expansion approach. This approach enables the inclusion of fossil reference system hot spots and thus the evaluation of the net benefits and impacts of perennial crops. The normalized results clearly show the benefits of the substitution of fossil fuels by miscanthus or willow biomass in several impact categories (e.g. for miscanthus: climate change −303.47 kg CO2 eq./MWhth; terrestrial acidification: −0.22 kg SO2 eq./MWhth). Negative impacts however occur, for example, in the impact categories marine ecotoxicity and human toxicity (e.g. for miscanthus: +1.20 kg 1.4‐DB eq./MWhth and +68.00 kg 1.4‐DB eq./MWhth, respectively). The results of this study clearly demonstrate the necessity of including more impact categories than the GWP in order to be able to assess the net benefits and impacts of the cultivation and utilization of perennial plants holistically.
The Spending Multiplier in the Medium Run
Authors: Strulik Holger , Trimborn Timo
Published: May 2016

Most of the discussion about fiscal stimulus focuses on the multiplier of government spending on impact. In this paper we shift the focus to the multiplier at the end, i.e., to the period in which a deficit spending program terminates. We show that recent time-series analyses and neoclassical as well new Keynesian business cycle models predict that the multiplier turns negative before spending expires. This means that aggregate output at the time of expiry of fiscal stimulus is lower than it could be without deficit spending. Here, we show why this phenomenon is a general outcome of mainstream business cycle theory and explain the underlying mechanism. Using phase diagram analysis, we prove that the aggregate capital stock at the time of expiry of fiscal stimulus is lower than it would be without a deficit spending program. This fact explains why aggregate output is below its laissez faire level as well.
Identification and molecular docking studies for novel inverse agonists of SREB, super conserved receptor expressed in brain
Authors: Yanai Toshihiro , Kurosawa Aya , Nikaido Yoshiaki , Nakajima Nozomi , Saito Tamio , Osada Hiroyuki , Konno Ayumu , Hirai Hirokazu , Takeda Shigeki
Published: May 2016

The identification of novel synthetic ligands for G protein‐coupled receptors (GPCRs) is important not only for understanding human physiology, but also for the development of novel drugs, especially for orphan GPCRs for which endogenous ligands are unknown. One of the orphan GPCR subfamilies, Super conserved Receptor Expressed in Brain (SREB), consists of GPR27, GPR85 and GPR173 and is expressed in the central nervous system. We report herein the identification of inverse agonists for the SREB family without their agonists. We carried out an in vitro screening of 5472 chemical compounds from the RIKEN NPDepo chemical library. The binding of [35S]GTPγS to the GPR173–Gsα fusion protein expressed in Sf9 cells was measured and resulted in the identification of 8 novel GPR173 inverse agonists. The most potent compound showed an IC50 of approximately 8 μm. The identified compounds were also antagonists for other SREB members, GPR27 and GPR85. These results indicated that the SREB family could couple Gs‐type G proteins, and SREB–Gsα fusion proteins showed significant constitutive activities. Moreover, a molecular model of GPR173 was constructed using the screening results. The combination of computational and biological methods will provide a unique approach to ligand identification for orphan GPCRs and brain research.
Systemic inflammation and liver damage in HIV/hepatitis C virus coinfection
Authors: Shmagel KV , Saidakova EV , Shmagel NG , Korolevskaya LB , Chereshnev VA , Robinson J , Grivel J‐C , Douek DC , Margolis L , Anthony DD , Lederman MM
Published: May 2016

Objectives

Chronic hepatitis C virus (HCV) and HIV viral infections are characterized by systemic inflammation. Yet the relative levels, drivers and correlates of inflammation in these settings are not well defined.

Methods

Seventy‐nine HIV‐infected patients who had been receiving antiretroviral therapy (ART) for more than 2 years and who had suppressed plasma HIV levels (< 50 HIV‐1 RNA copies/mL) were included in the study. Two patient groups, HCV‐positive/HIV‐positive and HCV‐negative/HIV‐positive, and a control group comprised of healthy volunteers (n = 20) were examined. Markers of systemic inflammation [interleukin (IL)‐6, interferon gamma‐induced protein (IP)‐10, soluble tumour necrosis factor receptor‐I (sTNF‐RI) and sTNF‐RII], monocyte/macrophage activation [soluble CD163 (sCD163), soluble CD14 and neopterin], intestinal epithelial barrier loss [intestinal fatty acid binding protein (I‐FABP) and lipopolysaccharide (LPS)] and coagulation (d‐dimers) were analysed. CD4 naïve T cells and CD4 recent thymic emigrants (RTEs) were enumerated.

Results

Plasma levels of IP‐10, neopterin and sCD163 were higher in HCV/HIV coinfection than in HIV monoinfection and were positively correlated with indices of hepatic damage [aspartate aminotransferase (AST), alanine aminotransferase (ALT) and the AST to platelet ratio index (APRI)]. Levels of I‐FABP were comparably increased in HIV monoinfection and HIV/HCV coinfection but LPS concentrations were highest in HCV/HIV coinfection, suggesting impaired hepatic clearance of LPS. Plasma HCV levels were not related to any inflammatory indices except sCD163. In coinfected subjects, a previously recognized relationship of CD4 naïve T‐cell and RTE counts to hepatocellular injury was defined more mechanistically by an inverse relationship to sCD163.

Conclusions

Hepatocellular injury in HCV/HIV coinfection is linked to elevated levels of certain inflammatory cytokines and an apparent failure to clear systemically translocated microbial products. A related decrease in CD4 naïve T cells and RTEs also merits further exploration.
Pharmacokinetics of once‐daily darunavir/ritonavir in HIV‐1–infected pregnant women
Authors: Crauwels HM , Kakuda TN , Ryan B , Zorrilla C , Osiyemi OO , Yasin S , Brown K , Verboven P , Hillewaert V , Baugh B
Published: May 2016

Objectives

HIV antiretroviral therapy during pregnancy is recommended to reduce the risk of mother‐to‐child transmission and for maternal care. Physiological changes during pregnancy can affect pharmacokinetics. The impact of pregnancy was evaluated for once‐daily (qd) darunavir/ritonavir.

Methods

HIV‐1–infected pregnant women on an antiretroviral regimen that includes darunavir were enrolled in the study and further treated with darunavir/ritonavir 800/100 mg qd. Plasma concentrations were assessed over 24 h during the second and third trimesters and postpartum using a validated high‐performance liquid chromatography tandem mass spectrometry assay for total darunavir and ritonavir, and using 14C‐darunavir–fortified plasma for unbound darunavir. Pharmacokinetic parameters were derived using noncompartmental analysis. Safety and antiviral response were assessed at all visits.

Results

Data were available for 16 women. The area under the plasma concentration–time curve from 0 to 24 h (AUC24h) for total darunavir was 34–35% lower during pregnancy vs. postpartum. Unbound darunavir AUC24h was 20–24% lower during pregnancy vs. postpartum. The minimum plasma concentration of total and unbound darunavir was 32–50% and 13–38% lower, respectively, during pregnancy vs. postpartum. The antiviral response (< 50 HIV‐1 RNA copies/mL) was 59% at baseline and increased to 87–100% during the trial; the CD4 count increased over time. One serious adverse event (gestational diabetes) was judged as possibly related to study medication. All 16 infants born to women remaining in the study at delivery were HIV‐1 negative (two were premature).

Conclusions

Total darunavir exposure decreased during pregnancy, but the decrease was less for unbound (active) darunavir. These changes are not considered clinically relevant. Darunavir/ritonavir 800/100 mg qd may therefore be a treatment option for HIV‐1–infected pregnant women.
Simple and practical screening approach to identify HIV‐infected individuals with depression or at risk of developing depression
Authors: Rodkjaer L , Gabel C , Laursen T , Slot M , Leutscher P , Christensen N , Holmskov J , Sodemann M
Published: May 2016

Objectives

Studies have shown that depression and other mental illnesses are under‐diagnosed among HIV‐infected individuals. The aim of this study was to evaluate the use of mental health history and questionnaire‐based screening instruments to identify HIV‐infected individuals at risk of depression.

Methods

The Beck Depression Inventory II (BDI‐II) was used to assess the prevalence and severity of depressive symptoms among HIV‐infected individuals attending two out‐patient clinics in Denmark. HIV‐infected individuals with a BDI‐II score ≥ 20 were offered a clinical evaluation by a consultant psychiatrist. The BDI‐II score was compared to the outcome of mental health history review, and to results obtained using the European AIDS Clinical Society (EACS) two‐item depression screening tool.

Results

A total of 501 HIV‐infected individuals were included in the study. Symptoms of moderate/major depression (BDI‐II score ≥ 20) were observed in 111 patients (22%); 65 of these patients consulted a psychiatrist, of whom 71% were diagnosed with a co‐existing disorder. The BDI‐II score was compared to the outcome of a mental health history review, and to results obtained using the European AIDS Clinical Society (EACS) two‐item depression screening tool. The two questions showed a sensitivity and specificity of 95% and 68%, respectively, for diagnosis of current depression or risk of depression. A previous psychiatric history and substance abuse were independently associated with an increased risk of depression.

Conclusions

We suggest that the mental health of HIV‐infected individuals should be reviewed and a “risk‐flag” three‐step approach should be used (1) to screen routinely with the two verbal questions suggested by the EACS, (2) to identify whether there is a risk of depression and then screen with the BDI‐II, and (3) to identify whether there is still a risk and then perform a full evaluation and obtain an accurate psychiatric diagnosis by a psychiatrist.
In vitro sensitivity of different activated partial thromboplastin time reagents to mild clotting factor deficiencies
Authors: Toulon P. , Eloit Y. , Smahi M. , Sigaud C. , Jambou D. , Fischer F. , Appert‐Flory A.
Published: May 2016

Introduction

Activated partial thromboplastin time (aPTT) is a routine clotting assay that is widely used to globally screen for coagulation abnormalities. It is commonly admitted that a prolonged test result, may trigger the need for specific assays to be performed, particularly factor measurement. However, the sensitivity of aPTT reagents to deficiencies of clotting factors varies.

Methods

We evaluated, according to the recommendation of the CLSI H47‐A2 guideline, the responsiveness to single factor levels of five aPTT reagents by using factor‐deficient plasmas spiked with a calibration plasma to produce individual factor activities ranging from <1 to ~100 Unit (U)/dL. Test results were expressed as the sample‐to‐control ratio, the latter was defined as the clotting time obtained in the calibration plasma containing ~100 U/dL factor activity. The factor activity producing a prolongation of aPTT above the upper limit of its specific normal range (in ratio) was assigned as the factor responsiveness in U/dL to that reagent.

Results

Responsiveness ranged from 34 to 47 U/dL to FVIII:C, from 18 to 57 U/dL to FIX, from 38 to 52 U/dL to FXI, from 29 to 50 U/dL to FXII, from 40 and 59 U/dL to FV, from 7.5 to 49 U/dL to FX, and from 9.1 to 10.5 U/dL to FII.

Conclusions

These results suggest that the sensitivity of the tested aPTT reagents to single factor deficiency is highly variable. Moreover, for one given aPTT reagent, its sensitivity was very different depending on the deficient factor. This must be considered when analyzing clinical materials.
Cross‐sectional and longitudinal validation of a 13‐item fatigue scale among Japanese postpartum mothers
Authors: Tsuchiya Miyako , Mori Emi , Sakajo Akiko , Iwata Hiroko , Maehara Kunie , Tamakoshi Koji
Published: May 2016

This study examined the psychometric properties of a 13‐item fatigue scale for postpartum mothers. Japanese mothers (n = 2026) from a cohort study completed questionnaires (e.g. fatigue scale, Japanese version of the Edinburgh Postnatal Depression Scale, demographics) during their hospital stay after childbirth (baseline) and at 1, 2, 4 and 6 months postpartum. Initial factor analysis of baseline data revealed that the fatigue scale had three factors or subscales (physical, emotional and cognitive). Within‐group analysis across each measurement time revealed the same three‐factor structure with acceptable fit. Between‐group analysis also showed longitudinal factorial invariance across time. The fatigue subscales had acceptable divergent and convergent validities with the depression scale. The subscale scores differed significantly based on participant background. The Japanese Fatigue Scale is a concise and informative tool for assessing aspects of fatigue in clinical settings and in the community.
Risk factors, cross‐cultural stressors and postpartum depression among immigrant Chinese women in Japan
Authors: Jin Qiongai , Mori Emi , Sakajo Akiko
Published: May 2016

The purpose of this mixed‐method design study was to examine factors contributing to depression among immigrant Chinese women (primipara and multipara) (n = 22) delivering a child for the first time in Japan. Data were obtained just after hospital discharge by using the Edinburgh Postnatal Depression Scale (EPDS), the Social Support Scale, a new scale to measure cross‐cultural stressors in the postpartum setting and a visual analogue scale for stress and a demographic survey. The average EPDS score was 9.0 (SD ± 3.7) at 1–3 weeks postpartum; yet, more than half of the subjects (n = 12; 54.5%) were high risk for depression (EPDS ≥ 10). Low household income and primiparous status were associated with depression scores. New mothers with depression also reported more general stress and more cross‐cultural stress in the postpartum setting, although social support appeared to mediate cross‐cultural stressors. Semi‐structured interviews were held with two immigrant women at high risk for depression; these new mothers described additional stress because they could not follow Zuoyuezi, an important postpartum Chinese tradition, in the Japanese hospital. These findings suggest that immigrant Chinese women are at higher risk for postpartum depression when they give birth for the first time in Japan.
Cultural characteristics of nursing practice in Japan
Authors: Tsujimura Mayuko , Ishigaki Kazuko , Yamamoto‐Mitani Noriko , Fujita Junko , Katakura Naoko , Ogata Yasuko , Mochizuki Yuki , Okamoto Yuko , Shinohara Yuko
Published: May 2016

The population of Japan has become multi‐cultural, and there is more demand for culturally competent nursing care. The purpose of this study was to explore cultural characteristics of nursing practice in Japan focusing on behaviour. We interviewed 25 professionals with experience in or knowledge of nursing practice both in Japan and either the United States, the United Kingdom, Sweden, Thailand or South Korea. Qualitative content analysis has yielded three themes for cultural characteristics of nursing practice in Japan: practice expectations, communication and relationships with patients. Practice expectations for nurses in Japan involved various aspects; nurses conducted a wide range of basic nursing tasks, including bed baths and toileting. They often relied on non‐verbal communication to deliver thoughtfulness and perceptiveness. They typically show deference to doctors and colleagues, emphasizing building and maintaining harmony with them. This emphasis on a multifaceted, non‐verbal, and harmonious approach seemed characteristic of practice among Japanese nurses.
Bisphenol A is associated with insulin resistance and modulates adiponectin and resistin gene expression in obese children
Authors: Menale Ciro , Grandone Anna , Nicolucci Carla , Cirillo Grazia , Crispi Stefania , Di Sessa Anna , Marzuillo Pierluigi , Rossi Sergio , Mita Damiano Gustavo , Perrone Laura , Diano Nadia , Miraglia Del Giudice Emanuele
Published: May 2016

Background

Bisphenol A (BPA) exposure has been associated with increased incidence of diabetes and obesity in adults.

Objectives

To evaluate whether an association between BPA urinary levels and insulin resistance as well as adiponectin and resistin production and serum concentrations may occur in obese children.

Methods

Clinical and biochemical features of 141 obese children were collected. Serum resistin and adiponectin were evaluated. Insulin resistance and urinary BPA levels were assessed. Moreover, the effect of BPA on adiponectin and resistin gene expression in adipocytes from eight normal weight prepubertal children was investigated by quantitative real‐time RT‐PCR (qPCR).

Results

Direct association between BPA and homeostasis model assessment (r = 0.23; p: 0.0069) and a strong inverse association between BPA and adiponectin have been found (r = −0.48; p < 0.0001). In adipocytes, resistin expression was detected only after BPA treatment, while adiponectin expression resulted down‐regulated after BPA exposure (p < 0.05 at both 10 and 100 nM BPA concentrations).

Conclusions

We suggest the involvement of BPA in the development of insulin resistance in childhood obesity highlighting that urinary BPA levels are directly associated with insulin resistance regardless of BMI. This association may be explained, at least partly, by the findings that BPA affects resistin and adiponectin production in adipose tissue cultures.
Risk factors of systemic inflammation response syndrome after endoscopic combined intrarenal surgery in the modified Valdivia position
Authors: Tabei Tadashi , Ito Hiroki , Usui Kimitsugu , Kuroda Shinnosuke , Kawahara Takashi , Terao Hideyuki , Fujikawa Atsushi , Makiyama Kazuhide , Yao Masahiro , Matsuzaki Junichi
Published: May 2016

Objective

To identify risk factors of developing systemic inflammation response syndrome after endoscopic combined intrarenal surgery in the modified Valdivia position for renal stone treatment.

Methods

We retrospectively analyzed 370 consecutive patients who underwent endoscopic combined intrarenal surgery procedures in the modified Valdivia position to treat renal stones. Antibiotic therapy based on preoperative urine cultures was administered to all patients from induction of anesthesia until at least postoperative day 3. Postoperative systemic inflammation response syndrome was diagnosed if the patient met two or more systemic inflammation response syndrome criteria. A multivariate logistic regression model with backward selection was used to evaluate the relationships between the incidence of systemic inflammation response syndrome after endoscopic combined intrarenal surgery and other clinical factors.

Results

Of the 370 patients, 61 patients (16.5%) were diagnosed with systemic inflammation response syndrome after endoscopic combined intrarenal surgery. Significant differences were found between the non‐systemic inflammation response syndrome and systemic inflammation response syndrome groups with regard to female sex (29.8% vs 44.3%, P = 0.027), history of febrile urinary tract infection (16.5% vs 32.8%, P = 0.015) and number of involved calyces (2.68 vs 4.1, P < 0.001). Multivariate analysis found three independent predictors of postoperative systemic inflammation response syndrome: the number of involved calyces (P = 0.017), stone surface area (P = 0.021) and history of febrile urinary tract infection (P = 0.005).

Conclusions

The number of involved calyces larger than four, stone surface area >500 mm2 and a history of febrile urinary tract infection independently predicted the development of systemic inflammation response syndrome after endoscopic combined intrarenal surgery. This is the first study to identify the independent predictors of systemic inflammation response syndrome after endoscopic combined intrarenal surgery in the modified Valdivia position.
Presidential Approval and Public Security in Mexico's War on Crime
Authors: Romero Vidal , Magaloni Beatriz , Díaz-Cayeros Alberto
Published: May 2016

To fight criminal organizations effectively, governments require support from significant segments of society. Citizen support provides important leverage for executives, allowing them to continue their policies. Yet winning citizens' hearts and minds is not easy. Public security is a deeply complex issue. Responsibility is shared among different levels of government; information is highly mediated by mass media and individual acquaintances; and security has a strong effect on peoples' emotions, since it threatens to affect their most valuable assets—life and property. How do citizens translate their assessments of public security into presidential approval? To answer this question, this study develops explicit theoretical insights into the conditions under which different dimensions of public security affect presidential approval. The arguments are tested using Mexico as a case study.