bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel and Selective Nociceptin Receptor (NOP) Agonist (1‐(1‐((cis)‐4‐isopropylcyclohexyl)piperidin‐4‐yl)‐1H‐indol‐2‐yl)methanol (AT‐312) Decreases Acquisition of Ethanol‐Induced Conditioned Place Preference in Mice
Authors: Zaveri Nurulain T. , Marquez Paul V. , Meyer Michael E. , Polgar Willma E. , Hamid Abdul , Lutfy Kabirullah
Published: December 2017

Background

Nociceptin/orphanin FQ, the endogenous peptide agonist for the opioid receptor‐like receptor (also known as NOP or the nociceptin receptor), has been shown to block the acquisition and expression of ethanol (EtOH)‐induced conditioned place preference (CPP). Here, we report the characterization of a novel small‐molecule NOP ligand AT‐312 (1‐(1‐((cis)‐4‐isopropylcyclohexyl)piperidin‐4‐yl)‐1H‐indol‐2‐yl)methanol) in receptor binding and GTPγS functional assays in vitro. We then investigated the effect of AT‐312 on the rewarding action of EtOH in mice using the CPP paradigm. Further, using mice lacking the NOP receptor and their wild‐type controls, we also examined the involvement of NOP in the effect of AT‐312. Motivational effects of AT‐312 alone were also assessed in the CPP paradigm.

Methods

Female mice lacking NOP and/or their wild‐type controls received conditioning in the presence or absence of the NOP agonist [AT‐312 (1, 3, and 10 mg/kg) or the control NOP agonist SCH221510 (10 mg/kg)] followed by saline/EtOH for 3 consecutive days (twice daily) and tested for CPP in a drug‐free state on the next day.

Results

Our in vitro data showed that AT‐312 is a high‐affinity, selective NOP full agonist with 17‐fold selectivity over the mu opioid receptor and >200‐fold selectivity over the kappa opioid receptor. The results of our in vivo studies showed that AT‐312 reduced EtOH CPP at the lowest dose (1 mg/kg) tested but completely abolished EtOH CPP at higher doses (3 or 10 mg/kg) compared to their vehicle‐treated control group. AT‐312 (3 mg/kg) did not alter EtOH‐induced CPP in mice lacking NOP, confirming that AT‐312 reduced EtOH CPP through its action at the NOP receptor. AT‐312 (3 mg/kg) did not induce reward or aversion when administered alone, showing that the novel small‐molecule NOP agonist shows efficacy in blocking EtOH‐induced CPP via the NOP receptor.

Conclusions

Together, these data suggest that small‐molecule NOP agonists have the potential to reduce alcohol reward and may be promising as medications to treat alcohol addiction.
The impact of Corynebacterium glucuronolyticum on semen parameters: a prospective pre–post‐treatment study
Authors: Meštrović T. , Bedenić B. , Wilson J. , Ljubin‐Sternak S. , Sviben M. , Neuberg M. , Ribić R. , Kozina G. , Profozić Z.
Published: December 2017

Corynebacterium glucuronolyticum (C. glucuronolyticum) is a rare isolate that is only recently being acknowledged as a potential urogenital pathogen. The bibliographical references on this bacterial species are scarce, and its influence on all semen parameters was hitherto unknown – therefore, the aim of this study was to evaluate its effects on a range of sperm quality parameters. A prospective approach to compare semen parameters before and after treatment was used in this study. C. glucuronolyticum in semen specimens was identified using analytical profile index biotyping system (API Coryne) and additionally confirmed by matrix‐assisted laser desorption/ionization time‐of‐flight mass‐spectrometry (MALDI‐TOF MS), with the determination of antimicrobial susceptibility by Kirby–Bauer method. Semen analysis was performed according to the criteria from the World Health Organization (with the use of Tygerberg method of sperm morphology categorization). Very strict inclusion criteria for participants also included detailed medical history and urological evaluation. From a total of 2169 screened semen specimens, the inclusion rate for participants with C. glucuronolyticum that satisfied all the criteria was 1.01%. Antibiogram‐guided treatment of the infection with ensuing microbiological clearance has shown that the resolution of the infection correlates with statistically significant improvement in the vitality of spermatozoa, but also with a lower number of neck and mid‐piece defects. Parameters such as sperm count, motility and normal morphology were not affected. In addition, susceptibility testing revealed a trend towards ciprofloxacin resistance, which is something that should be considered when selecting an optimal treatment approach. Albeit it is rarely encountered as a monoisolate in significant quantities, C. glucuronolyticum may negatively influence certain sperm parameters; therefore, it has to be taken into account in the microbiological analysis of urogenital samples.
Thyroid hormones alter estrous cyclicity and antioxidative status in the ovaries of rats
Authors: Wei Quanwei , Fedail Jaafar Sulieman , Kong Lingfa , Zheng Kaizhi , Meng Chunhua , Fadlalla Mohamed Babo , Shi Fangxiong
Published: December 2017

To expand our understanding of the roles of thyroid hormones on female reproduction, we induced hypo‐ and hyper‐T rat models to investigate the roles of thyroid hormones on estrous cyclicity, as well as the antioxidative status in the ovaries of rats. In the current study, our data show that hypothyroidism (hypo‐T) and hyperthyroidism (hyper‐T) led to significantly reduced body weights and ovarain weights and delayed vaginal opening day. For hyper‐T, thyroxine (T4), tri‐iodothyronine (T3), progesterone (P4) and follicle‐stimulating hormone (FSH) were significantly increased, while estradiol (E2) and luteinizing hormone (LH) were significantly decreased. For hypo‐T rats, serum levels of total T4 and T3, E2, P4, FSH and LH were significantly increased, while concentrations of E2 and LH were significantly decreased. For ovary morphology, the numbers of secondary and antral follicles were significantly decreased with more atretic antral follicles and less corpora lutea in both hyper‐ and hypo‐T groups. Both hyper‐T and hypo‐T treatment significantly decreased the expressions of thyroid hormone receptor α1 in the ovary. Hypo‐T significantly reduced nitric oxide (NO), total NO synthase (tNOS), inducible NOS and constitutive NOS activities, but hyper‐T increased them. For antioxidative parameters, hypo‐T and hyper‐T treatment significantly increased malondialdehyde (MDA) contents. The activities of both glutathione peroxidase (GSH‐Px) and catalase (CAT) significantly decreased in the hypo‐T group but increased in the hyper‐T group. Total superoxide dismutase (T‐SOD) activity was significantly increased in the hyper‐T group. In summary, thyroid hormones alter estrous cyclicity and antioxidative status in the ovary of the rat may act through the NOS signaling pathway.
Helicobacter pylori induces caudal‐type homeobox protein 2 and cyclooxygenase 2 expression by modulating microRNAs in esophageal epithelial cells
Authors: Teng Guigen , Dai Yun , Chu Yunxiang , Li Jing , Zhang Hongchen , Wu Ting , Shuai Xiaowei , Wang Weihong
Published: December 2017

Dysregulation of microRNAs (miRNAs) has been linked to virulence factors of Helicobacter pylori. The role of H. pylori in esophageal disease has not been clearly defined. We previously reported that H. pylori esophageal colonization promotes the incidence of Barrett's esophagus and esophageal adenocarcinoma in vivo. Here, we studied the direct effects of H. pylori on the transformation of esophageal epithelial cells, with particular focus on whether H. pylori exerts its effects by modulating miRNAs and their downstream target genes. The normal human esophageal cell line HET‐1A was chronically exposed to H. pylori extract and/or acidified deoxycholic acid for up to 36 weeks. The miRNA profiles of the esophageal epithelial cells associated with H. pylori infection were determined by microarray analysis. We found that chronic H. pylori exposure promoted acidified deoxycholic acid‐induced morphological changes in HET‐1A cells, along with aberrant overexpression of intestinal metaplasia markers and tumorigenic factors, including caudal‐type homeobox protein 2 (CDX2), mucin 2, and cyclooxygenase 2 (COX2). Helicobacter pylori modified the miRNA profiles of esophageal epithelial cells, particularly aberrant silencing of miR‐212‐3p and miR‐361‐3p. Moreover, in biopsies from Barrett's esophagus patients, esophageal H. pylori colonization was associated with a significant decrease in miR‐212‐3p and miR‐361‐3p expression. Furthermore, we identified COX2 as a target of miR‐212‐3p, and CDX2 as a target of miR‐361‐3p. Helicobacter pylori infection of esophageal epithelial cells was associated with miRNA‐mediated upregulation of oncoprotein CDX2 and COX2. Our observations provide new evidence about the molecular mechanisms underlying the association between H. pylori infection and esophageal carcinogenesis.
MEGA‐EVENTS AND TOURISM: THE CASE OF BRAZIL
Authors: Baumann Robert , Matheson Victor
Published: December 2017

Mega‐sporting events such as the Fédération Internationale de Football Association (FIFA) World Cup are expensive affairs. Host countries often justify the spending required to stage these events by predicting that mega‐events will draw large numbers of tourists. This paper analyzes monthly foreign tourist arrivals into Brazil between 2003 and 2015 and finds that the 2014 FIFA World Cup increased foreign tourism by roughly 1 million visitors. This number far exceeded expectations, but we show that roughly a quarter of this increase in foreign tourism was caused by the fortuitous advancement of Argentina's national team, and potential hosts should not count on the event to consistently produce out‐sized tourism figures. We conclude that on‐field results can greatly influence FIFA World Cup tourism. (JEL L83, F14)
I Will Pay Tomorrow, or Maybe the Day After. Credit Card Repayment, Present Biased and Procrastination
Authors: Barboza Gustavo
Published: December 2017

Procrastinating the repayment in full on a month‐to‐month balance in credit card debt is a problem affecting a large segment of the population. This paper studies the role that present‐biased preferences and impatience play in the repayment behaviour of consumers. Evidence from a field study using a sample of 380 college students provides empirical support to the hypothesis that individuals with present‐biased preferences tend to adopt a strategic procrastination repayment behaviour that is not optimal to accomplish repayment in full. More specifically, individuals suffering from self control issues and using credit cards to bridge unexpected shortage of income are more likely to fail to repay credit cards in full in the period after the purchase was completed, therefore, carrying over a month‐to‐month balance. In addition, people with a simple present‐biased revealed effect are also more likely to fall behind on credit card repayment, vis‐à‐vis those that have a higher marginal propensity to save. By the same token, we find that individuals consistently behave inconsistently, that is evidence from our sample indicates the predominance of dynamically inconsistent preferences, in opposition to the prescriptions of the neoclassical theory. In this regard, the naïve type of individuals with present‐bias preferences consume beyond their income capabilities and are much more likely to carry over credit card debt into the next period, vis‐à‐vis individuals that are more sophisticated.
Sexual Identity and Relationship Quality in Australia and the United Kingdom
Authors: Perales Francisco , Baxter Janeen
Published: December 2017

Objective

To investigate the quality of intimate relationships of bisexual, gay, lesbian, and heterosexual individuals in Australia and the United Kingdom.

Background

There is a shortage of research on the relationship quality of nonheterosexual individuals, and the majority of the available evidence comes from the United States. We add to existing knowledge by considering bisexual individuals; examining mixed‐orientation couples; and using recent, large, and nationally representative cross‐national data.

Method

Data from 25,348 individuals in the United Kingdom (Understanding Society study) and 9,206 individuals in Australia (Household, Income and Labour Dynamics in Australia Survey) were used to estimate regression models predicting relationship quality while adjusting for confounds.

Results

Relationship quality in same‐sex couples was as high as in heterosexual couples in the United Kingdom, and higher in Australia. The lowest relationship quality in both countries was reported by bisexual individuals.

Conclusion

Our results provide robust evidence to combat deep‐rooted and erroneous social perceptions of same‐sex relationships being conflictual, unhappy, and dysfunctional.

Implications

Our findings support policies that seek to legalize same‐sex marriage and parenting rights. They also highlight the need to give further attention to bisexual individuals as a distinct group because their outcomes are comparatively poor.
Rubicon: LC3‐associated phagocytosis and beyond
Authors: Wong Sing‐Wai , Sil Payel , Martinez Jennifer
Published: December 2017

Rubicon (Rubcn) was initially identified as a component of the Class III PI3K complex and a negative regulator of canonical autophagy and endosomal trafficking. However, Rubicon has attracted the most notoriety because of its critical role in LC3‐associated phagocytosis (LAP), a form of noncanonical autophagy that utilizes some components of the autophagy machinery to process extracellular cargo. Additionally, Rubicon has been identified as a key modulator of the inflammatory response and viral replication. In this review, we discuss the known functions of Rubicon in LAP and other signaling pathways and examine the disease pathologies associated with Rubicon dysfunction in animal models and humans.
Fast Food Data: Where User‐Generated Content Works and Where It Does Not
Authors: Folch David C. , Spielman Seth E. , Manduca Robert
Published: December 2017

As big urban data usage expands in the social sciences, there remain real concerns about fidelity to on the ground conditions. In this paper, we examine the correspondence between Phoenix metro area restaurants identified by a social media source (yelp.com) and those from an administrative source (Maricopa Association of Governments [MAG]). We find that they capture largely disjoint subsets of Phoenix restaurants, with only about one‐third of restaurants in each data set present in the other. Point pattern analyses indicate that the Yelp data is significantly clustered relative to the MAG data. Specifically, restaurants in Yelp are concentrated in certain parts of metro Phoenix, most notably the downtowns of Phoenix, Scottsdale, and Tempe. Further analysis indicates that areas with more Yelp than MAG restaurants tend to have more college‐educated workers and workers employed in the Arts, Entertainment, and Recreation sector. Our comparison highlights the strengths and weaknesses of each data source: Yelp data is far more detailed and comprehensive in certain locations, while MAG data is more consistent across the entire region due to its systematic construction. When combined, administrative and user generated databases seem to provide a more holistic and comprehensive picture of the world than either would provide by itself.
Once frail, always frail? Frailty transitions in home care users with intellectual and developmental disabilities
Authors: Martin Lynn , McKenzie Katherine , Ouellette‐Kuntz Hélène
Published: December 2017

Aim

Frailty is understood as a dynamic non‐linear process, and used to indicate age‐related decline. Recent work has shown that adults with intellectual and developmental disabilities experience higher rates of frailty at much earlier ages than the general population. The present study describes transitions in frailty status (i.e. non‐frail, pre‐frail, frail) over 1 year, and explores the association between baseline frailty status and worsening/death over time.

Methods

Results are based on secondary analysis of 2893 individuals with intellectual and developmental disabilities receiving community‐based home care services in Ontario (Canada). Frailty status is based on a validated 42‐item frailty index (FI); where FI ≤0.21 indicates non‐frail, 0.21 < FI ≤ 0.3 indicates pre‐frail and FI >0.30 indicates frail. Baseline characteristics of frailty groups at baseline were compared using the χ2‐test/analysis of variance. Relative risk of worsening/dying was calculated using a modified Poisson regression model.

Results

Initially, 67.0% of participants were non‐frail, 16.2% were pre‐frail and 16.8% were frail. Of those non‐frail at baseline, 84.3% remained non‐frail, 11.8% worsened and 3.9% died. Among those initially pre‐frail, 37.0% remained stable, 35.3% improved, 18.2% worsened and 9.6% died. Although similar proportions of frail individuals improved (37.4%) or remained stable (36.8%), 25.9% had died. After controlling for other factors, being pre‐frail at baseline was associated with an increase in the risk of worsening or death (RR 1.24, 95% CI 1.04–1.49).

Conclusions

While many experience worsening of frailty status, stability and improvement are viable goals of care. Future research should examine the rate at which non‐frail, pre‐frail and frail individuals accumulate deficits, as well as the impact of home care services on frailty. Geriatr Gerontol Int 2018; 18: 547–553.
Analysis of sensitive skin barrier function: basic indicators and sebum composition
Authors: Fan L. , Jia Y. , Cui L. , Li X. , He C.
Published: December 2017

Objectives

Sensitive skin (SS) is a condition characterised by high reactivity, low tolerance, and susceptibility to allergies of the skin. Owing to changes in the environment and marketing strategies, as well as the increasing public awareness about skin care, attention to skin condition is gradually increasing. The aim of this study is to explore the differences in the skin barrier of SS and normal skin (NS).

Methods

A questionnaire survey was conducted and basic indicators of the skin barrier were analysed. It was found that sebum secretion in the SS group was lower than that in the NS group, suggesting that the development of SS might be associated with sebum secretion and its specific components. Next, an ultra performance liquid chromatography‐quadruple time‐of‐flight mass spectrometer was used to identify facial sebum components in female volunteers.

Results

The results showed that the sebum of female volunteers with SS had high levels of ceramides, glycerophosphoethanolamines, and diacylglycerols, and low levels of glucosylceramides, glycerophosphoserines, glycerophosphocholines, and triacylglycerols.

Conclusion

Analysis of lipid functions suggested that the main reason for SS development in women might be a barrier dysfunction caused by excessive apoptosis and lack of water. Therefore, anti‐allergy additives in cosmetic products that could inhibit apoptosis of keratinocytes and methods to maintain the stability of water molecules in the skin should be further studied.
Restraining the Court: Assessing Accounts of Congressional Attempts to Limit Supreme Court Authority
Authors: Mark Alyx , Zilis Michael A.
Published: December 2017

We propose a multilevel account of legislative Court curbing in order to assess existing explanations as to why such proposals come about. We argue that although Court curbing is commonly seen as the result of institutional conflict between Congress and the Supreme Court, it is best understood as a product of three interrelated factors: the individual motivations on the part of lawmakers, the partisan context in which they operate, and institutional disagreements between Court and legislature. We find evidence that micro‐level factors offer an important insight into Court curbing that institution‐focused explanations alone cannot.
Cortical thickness, resting state heart rate, and heart rate variability in female adolescents
Authors: Koenig Julian , Parzer Peter , Reichl Corinna , Ando Ayaka , Thayer Julian F. , Brunner Romuald , Kaess Michael
Published: December 2017

Resting state heart rate variability (HRV) is a psychophysiological marker that has gained increasing research interest, in particular in developmental neuroscience. HRV has been shown to be associated with mental and physical health, beyond simple measures of heart rate (HR) and shows inter‐ and intraindividual variance across aging. Recently, three studies reported on a positive correlation between resting state HRV and cortical thickness in selected regions of interest (ROIs) in adult samples. Structural thickness, HRV, and HR change during the sensitive period of adolescence. Previously, no study has addressed the structural concomitants of resting HR and HRV in adolescents. Cortical thickness (3‐T MRI), HR, and HRV were recorded in 20 healthy, female adolescents (mean age: 15.92 years; SD = 1.06; range: 14–17). In line with existing research in adults, cortical thickness in a number of ROIs was associated with resting state HRV but not HR. The comparison of regression analyses using the Bayes factor revealed evidence for a correlation between HRV and cortical thickness of the bilateral rostral anterior cingulate cortex. However, unlike in adults, greater cortical thickness was associated with reduced HRV in female adolescents. Analyses on HR showed no superior model fit. Results suggest that greater HRV might be beneficial for cortical development during adolescence (cortical thinning). On the other hand, cortical development might determine changes in autonomic nervous system function in adolescents. Future studies are needed to replicate these findings in larger samples including boys and to test these hypotheses in longitudinal designs.
Curb Your Embodiment
Authors: Pecher Diane
Published: December 2017

To explain how abstract concepts are grounded in sensory‐motor experiences, several theories have been proposed. I will discuss two of these proposals, Conceptual Metaphor Theory and Situated Cognition, and argue why they do not fully explain grounding. A central idea in Conceptual Metaphor Theory is that image schemas ground abstract concepts in concrete experiences. Image schemas might themselves be abstractions, however, and therefore do not solve the grounding problem. Moreover, image schemas are too simple to explain the full richness of abstract concepts. Situated cognition might provide such richness. Research in our laboratory, however, has shown that even for concrete concepts, sensory‐motor grounding is task dependent. Therefore, it is questionable whether abstract concepts can be significantly grounded in sensory‐motor processing.
Potential of autologous adipose‐derived stem cells to regenerate atrophied muscle in a rat model
Authors: Park Ji‐Ung , Kwon Sung‐Tack
Published: December 2017

Muscle atrophy results in severe functional impairment and is a significant clinical problem. We examined and characterized the therapeutic effects of autologous adipose‐derived stem cells (ADSCs) using an in vivo muscle atrophy rat model. To identify the effect of injected ADSCs into muscle, we developed the following two models of muscle atrophy in rats: induction of denervation by sciatic nerve defects; and nerve repair after severing the sciatic nerve. The inguinal fat pads were harvested from each rat and autologous ADSCs were cultured and ADSCs were injected in the right hind limbs as the experimental group, while normal saline was injected in the left hind limbs, which served as the control group. After 2 weeks, gross examination and histologic analyses were performed. Additionally, to investigate the survival of ADSCs in muscle tissues, we traced the injected ADSCs. The fate of injected ADSCs into muscle was investigated using a green fluorescent protein (GFP) tagging method with lentivirus transfection. The muscle weight and cross‐sectional area of muscle were greater and proliferation of connective tissue was less prominent in the ADSC‐injected group. Alpha‐bungarotoxin binding in the neuromuscular junction was significantly increased, and neoangiogenesis was higher in the ADSCs‐injected group. green fluorescent protein‐labeled ADSCs survived in the gastrocnemius muscle after 2 weeks. These findings could give a support in finding the role of autologous ADSCs as new therapeutic modality for regeneration of atrophied muscle.
Impact of male partner involvement on modern contraceptive use among married or partnered women in developing countries: a protocol for systematic review
Authors: Gebrie Serebe Abay , Abraha Yosef Gebreyohannes , Garoma Desalegn Ararso , Deribe Fasil Mengistu , Tefera Mamuye Hadis , Morankar Sudhakar
Published: December 2017

Review question/objective:

: The objective of this systematic review is to explore the impact of male partner involvement on modern contraceptive use among married or partnered women of reproductive age in developing countries. Specifically, does male partner involvement:

i) Increase the rate of modern contraceptive use?

ii) Reduce unwanted pregnancies and unsafe abortions?
Experiences of healthcare middle managers in developing capacity and capability to manage complexity: a systematic review protocol
Authors: Hartviksen Trude Anita , Aspfors Jessica , Uhrenfeldt Lisbeth
Published: December 2017

Review question/objective:

: The objective of this review is to explore the experiences of healthcare middle managers in developing capacity and capability to manage in a leadership role characterized by high complexity.
Educational interventions that address handover skills of healthcare professionals: a scoping review protocol
Authors: Bøje Rikke Buus , Ludvigsen Mette Spliid
Published: December 2017

Objectives:

The objective of this scoping review is to identify, organize and present existing literature on training interventions on handovers for healthcare professionals to highlight the existing gaps in evidence to inform future research in this field. More specifically the objectives are to:

i) Identify and present the underpinning theories, teaching methods and content that have been used in training interventions on handovers.

ii) Identify and present the evaluation tools used to measure the outcome of training interventions on handovers and to present the level of outcomes.
Registered nurse experiences of nursing professional identity: a qualitative systematic review protocol
Authors: Ferrell Christina , Christian Robin , Rachel Marcia
Published: December 2017

Review question/objective:

The objective of this review is to identify, appraise and synthesize the best available evidence related to registered nurses’ experiences of nursing professional identity in nursing care settings.
Effectiveness of decision aids on smoking cessation in adult patients: a systematic review protocol
Authors: Moyo Fernea , Archibald Ella , Slyer Jason T.
Published: December 2017

Review question:

The objective of this review is to determine the effectiveness of the use of decision aids in a shared decision-making encounter between any healthcare provider and adult patients who smoke, compared to standard education on smoking cessation, in any healthcare setting.

Specifically, the review questions are: What is the effectiveness of the use of decision aids in a shared decision-making encounter in any healthcare setting between the healthcare provider and adult patients who smoke compared to standard education, based on the patient's:

Smoking cessation rates and number of cessation attempts?

Knowledge of smoking cessation methods?

Smoking cessation decisional quality?
Kv4.2 channel activity controls intrinsic firing dynamics of arcuate kisspeptin neurons
Authors: Mendonça Philipe R. F. , Kyle Victoria , Yeo Shel‐Hwa , Colledge William H. , Robinson Hugh P. C.
Published: December 2017

Key points

Neurons in the hypothalamus of the brain which secrete the peptide kisspeptin are important regulators of reproduction, and normal reproductive development.

Electrical activity, in the form of action potentials, or spikes, leads to secretion of peptides and neurotransmitters, influencing the activity of downstream neurons; in kisspeptin neurons, this activity is highly irregular, but the mechanism of this is not known.

In this study, we show that irregularity depends on the presence of a particular type of potassium ion channel in the membrane, which opens transiently in response to electrical excitation.

The results contribute to understanding how kisspeptin neurons generate and time their membrane potential spikes, and how reliable this process is.

Improved understanding of the activity of kisspeptin neurons, and how it shapes their secretion of peptides, is expected to lead to better treatment for reproductive dysfunction and disorders of reproductive development.

Kisspeptin neurons in the hypothalamus are critically involved in reproductive function, via their effect on GnRH neuron activity and consequent gonadotropin release. Kisspeptin neurons show an intrinsic irregularity of firing, but the mechanism of this remains unclear. To address this, we carried out targeted whole‐cell patch‐clamp recordings of kisspeptin neurons in the arcuate nucleus (Kiss1Arc), in brain slices isolated from adult male Kiss‐Cre:tdTomato mice. Cells fired irregularly in response to constant current stimuli, with a wide range of spike time variability, and prominent subthreshold voltage fluctuations. In voltage clamp, both a persistent sodium (NaP) current and a fast transient (A‐type) potassium current were apparent, activating at potentials just below the threshold for spiking. These currents have also previously been described in irregular‐spiking cortical interneurons, in which the A‐type current, mediated by Kv4 channels, interacts with NaP current to generate complex dynamics of the membrane potential, and irregular firing. In Kiss1Arc neurons, A‐type current was blocked by phrixotoxin, a specific blocker of Kv4.2/4.3 channels, and consistent expression of Kv4.2 transcripts was detected by single‐cell RT‐PCR. In addition, firing irregularity was correlated to the density of A‐type current in the membrane. Using conductance injection, we demonstrated that adding Kv4‐like potassium conductance (gKv4) to a cell produces a striking increase in firing irregularity, and excitability is reduced, while subtracting gKv4 has the opposite effects. Thus, we propose that Kv4 interacting dynamically with NaP is a key determinant of the irregular firing behaviour of Kiss1Arc neurons, shaping their physiological function in gonadotropin release.
Modeling the Flow of Non-Newtonian Fluids Through Sharp
Orifices
Authors: Rituraj  , Vacca Andrea
Published: December 2017

This paper proposes a novel orifice flow model for non-Newtonian fluids. The orifice model is developed for sharp orifices with small apertures (orifice to pipe diameter ratio: 0.04 ≤ β ≤ 0.16) for which predictive models are not present in the literature. The orifice flow experiment is conducted with three different orifices and three different fluids. From the experimental data, a correlation is developed that relates Euler number to Reynolds number and orifice diameter ratio. It also accounts for elastic effects of the fluid on orifice flow by including Weissenberg number in the model. The developed model predicts the experimental data within reasonable accuracy.
Analysis of Aerothermal Characteristics of Surface Microstructures
Authors: Kapsis M. , He L.
Published: December 2017

Recent advances in manufacturing technologies, such as additive manufacturing (AM), have raised the potential of choosing surface finish pattern as a design parameter. Hence, understanding and prediction of aerothermal effects of machined microstructures (machined roughness) would be of great interest. So far, however, roughness has been largely considered as a stochastic attribute and empirically modeled. A relevant question is: if and how would shape of the machined roughness elements matter at such fine scales? In this paper, a systematic computational study has been carried out on the aerothermal impact of some discrete microstructures. Two shapes of configurations are considered: hemispherical and rectangular elements for a Reynolds number range typical for such structures (Re < 5000). Several validation cases are studied as well as the turbulence modeling and grid sensitivities are examined to ensure the consistency of the results. Furthermore, large eddy simulation (LES) analyses are performed to contrast the behavior in a well-established turbulent to a transitional flow regime. The results reveal a distinctive common flow pattern change (from an “open separation” to a “reattached separation”) associated with a drastic change of drag correlation from a low to a high loss regime. The results indicate a clear dependence of drag and heat transfer characteristics on the element pattern and orientation relative to the flow. The distinctive performance correlations with Reynolds number can be affected considerably by the element shape, for both a transitional and a turbulent flow regime. The results also consistently illustrate that conventional empirical stochastic roughness parameters would be unable to predict these trends.
Patterned Microstructure Array Fabrication by Using a Novel Standing Surface Acoustic Wave Device
Authors: Wang Yancheng , Xue Dai , Mei Deqing
Published: December 2017

This paper develops a novel standing surface acoustic wave (SAW) device with three pairs of interdigital transducers (IDTs) to fabricate the patterned microstructure arrays with the assistance of ultraviolet (UV) polymerization. The working principle, structural design, and fabrication of the SAW device are presented. Then, experimental setup was conducted to investigate the fabrication process and method of the patterned microstructure arrays on a thin photosensitive polymer surface. By adjusting the working wavelength and input voltage and selecting the pairs of IDTs, several types of patterned microstructure arrays, such as linear and latticed undulate with different surface morphologies, could be fabricated. For the application of the microstructure arrays, L929 mouse fibroblasts are cultured on the surface with linear undulate microstructure arrays. Preliminary results showed that the cells aligned well with the direction of the patterned surface and the array can enhance the cell culturing. Therefore, using the developed SAW device with the assistance of UV polymerization is an effective method to fabricate the patterned microstructure arrays, which may have great potential in the applications of biomedical and/or microelectronic fields.
Intracerebroventricular delivery of hematopoietic progenitors results in rapid and robust engraftment of microglia-like cells
Authors: Capotondo Alessia , Milazzo Rita , Garcia-Manteiga Jose M. , Cavalca Eleonora , Montepeloso Annita , Garrison Brian S. , Peviani Marco , Rossi Derrick J. , Biffi Alessandra
Published: December 2017

We report a novel method to generate morphologically, antigenically and transcriptionally dependable microglia-like cells in vivo.
Global patterns of dust and bedrock nutrient supply to montane ecosystems
Authors: Arvin Lindsay J. , Riebe Clifford S. , Aciego Sarah M. , Blakowski Molly A.
Published: December 2017

Dust may serve as a vital nutrient source for many montane ecosystems despite substantial nutrient supply from bedrock.
Spatiotemporal gene expression trajectories reveal developmental hierarchies of the human cortex
Authors: Nowakowski Tomasz J. , Bhaduri Aparna , Pollen Alex A. , Alvarado Beatriz , Mostajo-Radji Mohammed A. , Di Lullo Elizabeth , Haeussler Maximilian , Sandoval-Espinosa Carmen , Liu Siyuan John , Velmeshev Dmitry , Ounadjela Johain Ryad , Shuga Joe , Wang Xiaohui , Lim Daniel A. , West Jay A. , Leyrat Anne A. , Kent W. James , Kriegstein Arnold R.
Published: December 2017

Building a brain

The human brain is built in an inside-out manner as a series of layers. Although progenitor cells spin off new neurons in a seemingly organized fashion, the devil is in the details. Nowakowski
et al.
analyzed the transcriptomes of single cells from the developing brain to elucidate the hidden complexity of brain construction. For each cell, its position within the brain matters, as well as what type of neuron is being made at what point during overall development. These individual expression patterns result in organized diversity in the brain's cortex.

Science
, this issue p.
1318
Metabolic markers as cancer clues
Authors: Mayers Jared R.
Published: December 2017

Changes in branched-chain amino acids may be first sign of certain cancers
Harassment in science is real
Authors: Bell Robin E. , Koenig Lora S.
Published: December 2017

As the rallying cry against sexual harassment and bullying in many fields, including academia, continues to grow, more and more victims are coming forward with their stories, reflecting how this damaging culture has been the norm across sectors for decades. Studies of women in academia report that more than half have experienced harassment. This behavior has remained obscured for many reasons: fear, resignation, and acceptance. The scientific community must recognize the difficult conversations that have started and embrace this watershed moment as an opportunity for rapid and essential cultural change.
Choroidal neovascular membrane in paediatric patients: clinical characteristics and outcomes
Authors: Padhi Tapas Ranjan , Anderson Bradley J , Abbey Ashkan M , Yonekawa Yoshihiro , Stem Maxwell , Alam Danish , Modi Rohit Ramesh , Savla Laxmi Prabhavathi , Trese Michael T , Capone Antonio , Drenser Kimberly A , Besirli Cagri G
Published: December 2017

Purpose

To analyse the clinical characteristics and treatment outcomes of choroidal neovascular membranes (CNVM) in paediatric subjects at three paediatric retina referral centres.

Methods

Medical charts of patients aged 18 years or less with a diagnosis of CNVM were retrospectively reviewed. The demographic profile, laterality, presenting complaint, corrected vision, underlying pathology, fundus, fundus fluorescein angiogram and optical coherence tomogram (OCT) were analysed. CNVM type, frequency, treatment indications, recurrences and final visual acuity were noted.

Results

There were a total of 35 subjects (43 eyes) with a mean age of 11.2 years. The CNVMs were mostly type 2 (90.0%), classic (90.9%), subfoveal (59.09%) and active (84.1%). Best vitelliform macular dystrophy was found to be the most common association (32.5%). Intravitreal injection of an anti-vascular endothelial growth factor (VEGF) agent was the initial therapy of choice in all. Eyes with CNVMs responsive to anti-VEGF alone required a mean of 2.11 injections. Patients with recurrent disease (21.21%) had an average of 1.14 episodes per eye. While 50% of recurrent CNVMs stabilised with repeat anti-VEGF treatment, the remaining patients required photodynamic therapy, laser or surgery.

Conclusion

Paediatric CNVMs in this series differed from those in the adult population with regard to aetiology, OCT and angiographic characteristics, treatment response and rate of recurrence.
Successfully implementing and embedding guidelines to improve the nutrition and growth of preterm infants in neonatal intensive care: a prospective interventional study
Authors: Johnson Mark J , Leaf Alison A , Pearson Freya , Clark Howard W , Dimitrov Borislav D , Pope Catherine , May Carl R
Published: December 2017

Objectives

We aimed to improve the nutritional care of preterm infants by developing a complex (multifaceted) intervention intended to translate current evidence into practice. We used the sociological framework of Normalization Process Theory (NPT), to guide implementation in order to embed the new practices into routine care.

Design

A prospective interventional study with a before and after methodology.

Participants

Infants <30 weeks gestation or <1500 g at birth.

Setting

Tertiary neonatal intensive care unit.

Interventions

The intervention was introduced in phases: phase A (control period, January–August 2011); phase B (partial implementation; improved parenteral and enteral nutrition solutions, nutrition team, education, August–December 2011); phase C (full implementation; guidelines, screening tool, ‘nurse champions’, January–December 2012); phase D (postimplementation; January–June 2013). Bimonthly audits and staff NPT questionnaires were used to measure guideline compliance and ‘normalisation’, respectively. NPT Scores were used to guide implementation in real time. Data on nutrient intakes and growth were collected continuously.

Results

There were 52, 36, 75 and 35 infants in phases A, B, C and D, respectively. Mean guideline compliance exceeded 75% throughout the intervention period, peaking at 85%. Guideline compliance and NPT scores both increased over time, (r=0.92 and 0.15, p<0.03 for both), with a significant linear association between the two (r=0.21, p<0.01). There were significant improvements in daily protein intake and weight gain between birth and discharge in phases B and Ccompared with phase A (p<0.01 for all), which were sustained into phase D.

Conclusions

NPT and audit results suggest that the intervention was rapidly incorporated into practice, with high guideline compliance and accompanying improvements in protein intake and weight gain. NPT appears to offer an effective way of implementing new practices such that they lead to sustained changes in care. Complex interventions based on current evidence can improve both practice and clinical outcomes.
‘At-risk’ individuals’ responses to direct to consumer advertising of prescription drugs: a nationally representative cross-sectional study
Authors: Khalil Zadeh Neda , Robertson Kirsten , Green James A
Published: December 2017

Objectives

The factors determining individuals’ self-reported behavioural responses to direct to consumer advertising of prescription drugs were explored with an emphasis on ‘at-risk’ individuals’ responses.

Design

Nationally representative cross-sectional survey.

Setting

Community living adults in New Zealand.

Participants

2057 adults (51% women).

Primary outcome measures

Self-reported behavioural responses to drug advertising (asking a physician for a prescription, asking a physician for more information about an illness, searching the internet for more information regarding an illness and asking a pharmacist for more information about a drug).

Methods

Multivariate logistic regressions determined whether participants’ self-reported behavioural responses to drug advertising were predicted by attitudes towards advertising and drug advertising, judgements about safety and effectiveness of advertised drugs, self-reported health status, materialism, online search behaviour as well as demographic variables.

Results

Identifying as Indian and to a less extent Chinese, Māori and ‘other’ ethnicities were the strongest predictors of one or more self-reported responses (ORs 1.76–5.00, Ps<0.05). Poorer self-reported health status (ORs 0.90–0.94, all Ps<0.05), favourable attitude towards drug advertising (ORs 1.34–1.61, all Ps<0.001) and searching for medical information online (ORs 1.32–2.35, all Ps<0.01) predicted all self-reported behavioural outcomes. Older age (ORs 1.01–1.02, Ps<0.01), less education (OR 0.89, P<0.01), lower income (ORs 0.89–0.91, Ps<0.05) and higher materialism (ORs 1.02–1.03, Ps<0.01) also predicted one or more self-reported responses.

Conclusions

Taken together, the findings suggest individuals, especially those who are ‘at-risk’ (ie, with poorer self-reported health status, older, less educated, lower income and ethnic minorities), may be more vulnerable to drug advertising and may make uninformed decisions accordingly. The outcomes raise significant concerns relating to the ethicality of drug advertising and suggest a need for stricter guidelines to ensure that drug advertisements provided by pharmaceutical companies are ethical.
Atrial fibrillation in patients with severe mental disorders and the risk of stroke, fatal thromboembolic events and bleeding: a nationwide cohort study
Authors: Søgaard Mette , Skjøth Flemming , Kjældgaard Jette Nordstrøm , Larsen Torben Bjerregaard , Hjortshøj Søren Pihlkjær , Riahi Sam
Published: December 2017

Objectives

Outcomes of atrial fibrillation (AF) in patients with severe mental disorders are largely unknown. We compared rates of stroke, fatal thromboembolic events and bleeding in patients with AF with and without mental disorders.

Design

Nationwide registry-based cohort study.

Setting

Denmark (population 5.6 million), 2000–2015.

Participants

Patients with AF with schizophrenia (n=534), severe depression (n=400) or bipolar disease (n=569) matched 1:5 on age, sex and calendar time to patients with AF without mental disorders.

Exposure

Inpatient or hospital-based outpatient diagnosis of schizophrenia, severe depression or bipolar disease.

Primary and secondary outcome measures

HRs for stroke, fatal thromboembolic events and major bleeding comparing patients with and without mental disorders estimated by Cox regression with sequential adjustment for risk factors for stroke and bleeding, comorbidity and initiation of oral anticoagulant therapy (OAT).

Results

Compared with matched comparisons, crude 5-year HRs of ischaemic stroke were 1.37 (95% CI 0.88 to 2.14) for schizophrenia, 1.36 (95% CI 0.89 to 2.08) for depression and 1.04 (95% CI 0.69 to 1.56) for bipolar disease. After adjusting for risk factors, comorbidity and OAT, these HRs declined towards the null. Crude HRs of fatal thromboembolic events were 3.16 (95% CI 1.78 to 5.61) for schizophrenia, 1.31 (95% CI 0.67 to 2.56) for depression and 1.53 (95% CI 0.93 to 2.53) for bipolar disease. Rates of major bleeding were increased in patients with schizophrenia (crude HR 1.37, 95% CI 0.99 to 1.90) and severe depression (HR 1.25, 95% CI 0.87 to 1.78) but not bipolar disease (HR 0.82, 95% CI 0.58 to 1.15).

Conclusion

Patients with AF with schizophrenia or severe depression experienced increased rates of stroke and major bleeding compared with matched comparisons. This increase was largely explained by differences in the prevalence of risk factors for stroke and bleeding, comorbidity and initiation of OAT during follow-up. Patients with AF with schizophrenia further experienced higher mortality following thromboembolic events than matched comparisons without mental disorders.
The association between the use of biomedical services and the holistic use of traditional East Asian medicine: a national survey of outpatients in South Korea
Authors: Shim Jae-Mahn , Lee Yun-Suk
Published: December 2017

Objectives

The holistic use of a system of complementary and alternative medicine (CAM) is potentially linked to its treatment outcomes. This paper examines how the use of biomedicine is associated with the holistic use of CAM, focusing on traditional East Asian medicine (EM) that is uniquely integrated in the medical system in South Korea.

Design/Settings

A representative national sample of EM outpatients in South Korea.

Participants

3861 survey respondents.

Methods

By using the 2011 Korean National Survey of EM patients, ordered logistic regression models specify the relationship between EM outpatients’ use of biomedicine and their holistic use of EM modalities.

Results

Among EM outpatients who used at least one EM modality in the past 3 months, people who used two (33.3%) or three (29.4%) modalities together are the two highest proportions, followed by users of four (18.1%), five (7.2%), six (2.1%) and seven (0.6%) modalities. The odds for EM users to use EM holistically are 17% greater among EM users who used biomedicine as well, compared with EM users who did not use biomedicine.

Conclusions

The healthcare community should recognise that CAM use likely becomes holistic as people use biomedicine concomitantly, when the practice rights over a CAM system are comprehensively and exclusively entitled to a group of CAM professionals who are independent from practitioners of biomedicine.