bluuebunny/crossref_metadata_2025_split huggingface dataset:
Function of ankle ligaments for subtalar and talocrural joint stability during an inversion movement – an in vitro study
Authors: Li Lu , Gollhofer Albert , Lohrer Heinz , Dorn‐Lange Nadja , Bonsignore Guiseppe , Gehring Dominic 
Published: March 2019

AbstractBackgroundThe lateral ankle ligament complex consisting of the anterior talofibular ligament (ATFL), the calcaneofibular ligament (CFL) and the posterior talofibular ligament (PTFL) is known to provide stability against ankle joint inversion. As injuries of the ankle joint have been reported at a wide range of plantarflexion/dorsiflexion angles, the aim of the present study was to evaluate the stabilizing function of these ligaments depending on the sagittal plane positioning of the ankle joint.MethodsEight fresh‐frozen specimens were tested on a custom‐built ankle deflection tester allowing the application of inversion torques in various plantarflexion/dorsiflexion positions. A motion capture system recorded kinematic data from the talus, calcaneus and fibula with bone‐pin markers during inversion movements at 10° of dorsiflexion, at neutral position and at plantarflexion 10°. ATFL, CFL and PTFL were separately but sequentially sectioned in order to assess the contribution of the individual ligament with regard to ankle joint stability.ResultsJoint‐ and position‐specific modulations could be observed when the ligaments were cut. Cutting the ATFL did not lead to any observable alterations in ankle inversion angle at a given torque. But subsequently cutting the CFL increased the inversion angle of the talocrural joint in the 10° plantarflexed position, and significantly increased the inversion angle of the subtalar joint in the 10° dorsiflexed position. Sectioning of the PTFL led to minor increases of inversion angles in both joints.ConclusionsThe CFL is the primary ligamentous stabilizer of the ankle joint against a forced inversion. Its functioning depends greatly on the plantar−/dorsiflexion position of the ankle joint complex, as it provides the stability of the talocrural joint primarily during plantarflexion and the stability of the subtalar joint primarily during dorsiflexion.
The gut microbiome and response to immune checkpoint inhibitors: preclinical and clinical strategies
Authors: Gong Jun , Chehrazi‐Raffle Alexander , Placencio‐Hickok Veronica , Guan Michelle , Hendifar Andrew , Salgia Ravi 
Published: March 2019

AbstractThere is growing interest in identifying predictive biomarkers for inhibitors of programmed cell death protein 1 receptor (PD‐1), programmed death ligand 1 (PD‐L1), and cytotoxic T‐lymphocyte associated protein 4 (CTLA‐4). Given the links between the stool microbiota, anticancer immunosurveillance, and general health, the composition of the gut microbiome has recently undergone investigation as a biomarker for immunotherapy. In this review, we highlight published results from preclinical and clinical studies to date supporting a relationship between the gut microbiome and antitumor efficacy of immune checkpoint inhibitors. Despite the promising and hypothesis‐generating findings that have been produced in this arena to date, there remain some inconsistencies amongst present data that may need to be resolved to contribute to further development. Among these, a better understanding of the immunomodulatory function of the microbiome, standardization in sampling, sequencing techniques, and data analysis, and ensuring uniformity across various aspects of study design are warranted in conducting future prospective studies seeking to validate the gut microbiome as a potential biomarker of response to checkpoint blockade.
Contemporary decongestant practices of Canadian otolaryngologists for endoscopic sinus surgery
Authors: Reid Jonathan W. , Rotenberg Brian W. , Sowerby Leigh J 
Published: March 2019

Background Cocaine has traditionally been the topical decongestant most frequently used for visualization of the surgical field in Endoscopic Sinus Surgery (ESS). Alternatives include xylometazoline, oxymetazoline, and epinephrine. The understanding of the safety profile of each agent is changing, as are the practices of Otolaryngologists-Head & Neck Surgeons. The objective of this study is to determine decongestant use practices in ESS across Canada, which has not previously been studied. Methods A cross-sectional survey design using a 24-item electronic questionnaire was distributed to actively practicing members of the Canadian Society of Otolaryngology-Head and Neck Surgery via email. A French translated version of the survey was also available. Questions explored the respondents’ demographics and decongestion practices for ESS. Results Ninety-six surveys from otolaryngologists practicing in Canada were completed (19% response rate). The average time in practice was 16.5 years (range 1–50 years, SD 12.0 years). Twenty-six (27%) of respondents use some form of cocaine solution for topical decongestion in ESS. Over a total of over 1500 combined practice-years, eight respondents (8%) personally experienced an adverse event that could be attributed to cocaine, including two mortalities. One cardiac even was directly attributable to the patients’ use of recreational cocaine in the immediate pre-operative period. Conclusion The popularity of cocaine for topical decongestion in ESS in present-day Canada is less than in surveys from other countries. However, there are few reported adverse events with long-term consequences that are attributable to intraoperative cocaine. Considering the beneficial effects of cocaine for visualization and pain control, this change in practice warrants further investigation.
How to evoke consumer approach intention toward VR stores? Sequential mediation through telepresence and experiential value
Authors: Jang Ju Yeun , Hur Hee Jin , Choo Ho Jung 
Published: March 2019

AbstractThis study explores the roles of vividness and interactivity—two technological dimensions of virtual reality mediums—for consumers’ approach intention toward immersive virtual reality stores. In addition to telepresence, a well-established variable in explaining the effectiveness of virtual mediums, this study proposes experiential value as the second mediator that can lead to successful consumer experiences in commercial virtual environments. We recruited 101 volunteers who were willing to experience a virtual reality store with head-mounted displays. The results show that participants who perceive higher vividness and interactivity of an immersive virtual reality store tend to show stronger approach intentions, and that such positive influences are serially mediated by perceived telepresence and experiential shopping value. In multiple-step mediation analysis, the perceived experiential shopping value is found to be the key determinant in evoking consumers’ approach intention. The study concludes that virtual reality stores should be built in a way that provides experiential value by utilizing strong telepresence to achieve positive consumers’ approach intention. Suggestions for further research and practical applications are also discussed.
Burden of health behaviours and socioeconomic position on health care expenditure in Ontario
Authors: Manuel Douglas G. , Bennett Carol , Perez Richard , Wilton Andrew S. , Rohit Dass Adrian , Laporte Audrey , Henry David A. 
Published: March 2019

Background: Smoking, unhealthy alcohol consumption, poor diet and physical inactivity are leading risk factors for morbidity and mortality, and contribute substantially to overall healthcare costs. The availability of health surveys linked to health care provides population-based estimates of direct healthcare costs. We estimated health behaviour and socioeconomic-attribute healthcare costs, and how these have changed during a period when government policies have aimed to reduce their burden. Methods: The Ontario samples of the Canadian Community Health Surveys (conducted in 2003, 2005, and 2007-2008) were linked at the individual level to all records of health care use of publicly funded healthcare. Generalized linear models were estimated with a negative binomial distribution to ascertain the relationship of health behaviours and socioeconomic risk factors on health care costs. The multivariable cost model was then applied to unlinked, cross-sectional CCHS samples for each year from 2004 to 2013 to examine the evolution of health behaviour and socioeconomic-attributable direct health care expenditures over a 10-year period. Results: We included 80,749 respondents, aged 25 years and older, and 312,952 person-years of follow-up. The cost model was applied to 200,324 respondents aged 25 years and older (CCHS 2004 to 2013). During the 10-year period from 2004 to 2013, smoking, unhealthy alcohol consumption, poor diet and physical inactivity attributed to 22% of Ontario’s direct health care costs. Ontarians in the most disadvantaged socioeconomic position contributed to 15% of the province’s direct health care costs. Taken together, health behaviours and socioeconomic position were associated with 34% ($134 billion) of direct health care costs (2004 to 2013). Over this time period, we estimated a 1.9% reduction in health care expenditure ($5.0 billion) attributable to improvements in some health behaviours, most importantly reduced rates of smoking. Conclusions: Health behaviours and socioeconomic position cause a large direct health care system cost burden.
Comparing the Pemberton osteotomy and modified San Diego acetabuloplasty in developmental dysplasia of the hip
Authors: Badrinath R. , Bomar J. D. , Wenger D. R. , Mubarak S. J. , Upasani V. V. 
Published: March 2019

Purpose Patients with developmental dysplasia of the hip (DDH) may require a pelvic osteotomy to treat acetabular dysplasia. The Pemberton osteotomy and modified San Diego acetabuloplasty are two options available when surgically treating DDH. The purpose of this study was to compare outcomes following the Pemberton and modified San Diego when treating patients with acetabular dysplasia in typical DDH. Methods We included 45 hips in the modified San Diego group and 38 hips in the Pemberton group. Hips with less than two years follow-up and patients with a neuromuscular diagnosis were excluded. Clinical outcomes were rated using the modified McKay criteria with radiographic outcomes graded using the Severin score. Avascular necrosis (AVN) was assessed using the Kalamchi and MacEwen criteria. Results Mean follow-up was 4.9 years (2.1 to 11.2). Both procedures produced similar decreases in the acetabular index (modified San Diego: 17.0° versus Pemberton: 15.2°; p = 0.846). Most hips had good/excellent results using the modified McKay criteria (modified San Diego: 78%, Pemberton: 94%; p = 0.055). Most hips were rated as good/excellent on the Severin scale (modified San Diego: 100%, Pemberton: 97%, p = 0.485). The proportion of hips with AVN grade 2 or higher were similar between groups (modified San Diego: 0%, Pemberton: 3%; p = 0.458). Conclusion The modified San Diego acetabuloplasty is a safe and effective alternative to treat acetabular dysplasia in patients with typical DDH. By maintaining an intact medial cortex, acetabular reshaping can be customized to address each patient's specific acetabular deficiency Level of evidence Level III retrospective comparison
The Longitudinal Association Between Passive Social Networking Site Usage and Depressive Symptoms: The Mediating Role of Envy and Moderating Role of Life Satisfaction
Authors: Wang Hai-Zhen , Yang Ting-Ting , Gaskin James , Wang Jin-Liang 
Published: March 2019

Introduction: The relationship between Social Networking Site (SNS) usage and depressive symptoms is a growing concern among mental health researchers and practitioners. The purpose of this study was to better understand the mechanism and context under which SNS use affects depressive symptoms.Method: We did this by examining envy as a mediator of the relationship between passive SNS usage and depression over time, with life satisfaction as a moderator of this mediation effect. The sample included 266 college students, who completed the surveys in two waves.Results: The results showed that envy fully mediated the association between passive SNS usage and depression. This indirect relationship was moderated by level of life satisfaction. Specifically, and unexpectedly, among individuals with higher levels of life satisfaction, more frequent passive SNS use was related to increased envy, which, in turn, was associated with increased depressive symptoms. However, this indirect relationship was non-significant for those with lower levels of life satisfaction.Discussion: Thus, the potential of passive SNS use to increase depressive symptoms through envy among individuals with high life satisfaction should be considered when mental health practitioners design interventions.
Cannabinoids Stimulate the TRP Channel-Dependent Release of Both Serotonin and Dopamine to Modulate Behavior inC. elegans
Authors: Oakes Mitchell , Law Wen Jing , Komuniecki Richard 
Published: March 2019

Cannabis sativaalters sensory perception and exhibits potential medicinal benefits. In mammals, cannabinoids activate two canonical receptors, CB1/CB2, as well additional receptors/ion channels whose overall contributions to cannabinoid signaling have yet to be fully assessed. InCaenorhabditis elegans, the endogenous cannabinoid receptor agonist, 2-arachidonoylglycerol (2-AG) activates a CB1ortholog, NPR-19, to modulate behavior (Oakes et al., 2017). In addition, 2-AG stimulates the NPR-19 independent release of both serotonin (5-HT) and dopamine (DA) from subsets of monoaminergic neurons to modulate locomotory behaviors through a complex monoaminergic signaling pathway involving multiple serotonin and dopamine receptors. 2-AG also inhibits locomotion in remodeled monoamine receptor mutant animals designed to measure the acute release of either 5-HT or DA, confirming the direct effects of 2-AG on monoamine release. 2-AG-dependent locomotory inhibition requires the expression of transient receptor potential vanilloid 1 (TRPV1) and TRPN-like channels in the serotonergic or dopaminergic neurons, respectively, and the acute pharmacological inhibition of the TRPV1-like channel abolishes both 2-AG-dependent 5-HT release and locomotory inhibition, suggesting the 2-AG may activate the channel directly. This study highlights the advantages of identifying and assessing both CB1/CB2-dependent and independent cannabinoid signaling pathways in a genetically tractable, mammalian predictive model, where cannabinoid signaling at the molecular/neuronal levels can be correlated directly with changes in behavior.SIGNIFICANCE STATEMENTThis study is focused on assessing CB1/CB2-independent cannabinoid signaling in a genetically tractable, whole-animal model where cannabinoid signaling at the molecular/neuronal levels can be correlated with behavioral change.Caenorhabditis eleganscontains a cannabinoid signaling system mediated by a canonical cannabinoid receptor, NPR-19, with orthology to human CB1/CB2(Oakes et al., 2017). The present study has characterized an NPR-19-independent signaling pathway that involves the cannabinoid-dependent release of both serotonin and dopamine and the expression of distinct TRP-like channels on the monoaminergic neurons. Our work should be of interest to those studying the complexities of CB1/CB2-independent cannabinoid signaling, the role of TRP channels in the modulation of monoaminergic signaling, and the cannabinoid-dependent modulation of behavior.
Pituitary Adenylate Cyclase-Activating Polypeptide Modulates Dendritic Spine Maturation and Morphogenesis via MicroRNA-132 Upregulation
Authors: Hayata-Takano Atsuko , Kamo Toshihiko , Kijima Harui , Seiriki Kaoru , Ogata Katsuya , Ago Yukio , Nakazawa Takanobu , Shintani Yusuke , Higashino Kosuke , Nagayasu Kazuki , Shintani Norihito , Kasai Atsushi , Waschek James A. , Hashimoto Hitoshi 
Published: March 2019

Alterations in pituitary adenylate cyclase-activating polypeptide (PACAP), a multifunctional neuropeptide, and its receptors have been identified as risk factors for certain psychiatric disorders, including schizophrenia. Increasing evidence from human genetic and animal model studies suggest an association between various psychiatric disorders and altered dendritic spine morphology. In the present study, we investigated the role of exogenous and endogenous PACAP in spine formation and maturation. PACAP modified the density and morphology of PSD-95-positive spines in primary cultured hippocampal neurons. Notably, PACAP increased the levels of microRNA (miR)-132 and decreased expression of corresponding miR-132 target genes and protein expression of p250GAP, a miR-132 effector known to be involved in spine morphology regulation. In corroboration, PSD-95-positive spines were reduced in PACAP-deficient (PACAP−/−) mice versus WT mice. Golgi staining of hippocampal CA1 neurons revealed a reduced spine densities and atypical morphologies in the malePACAP−/−mice. Furthermore, viral miR-132 overexpression reversed the reduction in hippocampal spinal density in the malePACAP−/−mice. These results indicate that PACAP signaling plays a critical role in spine morphogenesis possibly via miR-132. We suggest that dysfunction of PACAP signaling may contribute to the pathogenesis of neuropsychiatric disorders, at least partly through its effects on spine formation.SIGNIFICANCE STATEMENTPituitary adenylate cyclase-activating polypeptide (PACAP) signaling dysfunction and dendritic spine morphology alterations have recently been suggested as important pathophysiological mechanisms underlying several psychiatric and neurological disorders. In this study, we investigated whether PACAP regulates dendritic spine morphogenesis. In a combination of pharmacological and viral gain- and loss-of-function approachesin vitroandin vivoexperiments, we found PACAP to increase the size and density of dendritic spines via miR-132 upregulation. Together, our data suggest that a dysfunction of PACAP signaling may contribute to the pathogenesis of neuropsychiatric disorders, at least partly through abnormal spine formation.
Endothelial Adora2a Activation Promotes Blood–Brain Barrier Breakdown and Cognitive Impairment in Mice with Diet-Induced Insulin Resistance
Authors: Yamamoto Masaki , Guo De-Huang , Hernandez Caterina M. , Stranahan Alexis M. 
Published: March 2019

Obesity and insulin resistance elicit blood–brain barrier (BBB) breakdown in humans and animal models, but the relative contributions of the two pathologies remain poorly understood. These studies initially addressed the temporal progression of cerebrovascular dysfunction relative to dietary obesity or diet-induced insulin resistance in male mice. Obesity increased BBB permeability to the low molecular weight fluorophore sodium fluorescein (NaFl), whereas diet-induced insulin resistance increased permeability to both NaFl and Evans blue, which forms a high molecular weight complex with serum albumin. Serial section transmission electron microscopy analysis of hippocampal capillaries revealed that diabetes promotes involution of tight junctions, fenestration of endothelial cells, and pericyte regression. Chronic activation of adenosine receptor 2a (Adora2a) erodes tight junctions between endothelial cells of the cerebral vasculature in other models of chronic neuropathology, and we observed that acute Adora2a antagonism normalized BBB permeability in wild-type mice with diet-induced insulin resistance. Experiments in mice with inducible deletion of Adora2a in endothelial cells revealed protection against BBB breakdown with diet-induced insulin resistance, despite comparable metabolic dysfunction relative to nontransgenic littermates. Protection against BBB breakdown was associated with decreased vascular inflammation, recovery of hippocampal synaptic plasticity, and restoration of hippocampus-dependent memory. These findings indicate that Adora2a-mediated signaling in vascular endothelial cells disrupts the BBB in dietary obesity, and implicate cerebrovascular dysfunction as the underlying mechanism for deficits in synaptic plasticity and cognition with obesity and insulin resistance.SIGNIFICANCE STATEMENTThe blood–brain barrier (BBB) restricts the entry of circulating factors into the brain, but obesity promotes BBB breakdown in humans and animal models. We used transgenic mice with resistance to BBB breakdown to investigate the role of neurovascular dysfunction in high-fat diet (HFD)-induced cognitive impairment. Transgenic mice with inducible ablation of Adora2a in endothelial cells were protected against BBB breakdown on HFD, despite comparable metabolic impairments relative to normal mice. Transgenic mice were also resistant to HFD-induced cognitive dysfunction and were protected against deficits in hippocampal synaptic plasticity. These findings indicate that Adora2a-mediated signaling in endothelial cells mediates obesity-induced BBB breakdown, and implicate cerebrovascular dysfunction as the mechanism for deficits in synaptic plasticity and cognition with obesity and diabetes.
Neural Maps of Interaural Time Difference in the American Alligator: A Stable Feature in Modern Archosaurs
Authors: Kettler Lutz , Carr Catherine E. 
Published: March 2019

Detection of interaural time differences (ITDs) is crucial for sound localization in most vertebrates. The current view is that optimal computational strategies of ITD detection depend mainly on head size and available frequencies, although evolutionary history should also be taken into consideration. In archosaurs, which include birds and crocodiles, the brainstem nucleus laminaris (NL) developed into the critical structure for ITD detection. In birds, ITDs are mapped in an orderly array or place code, whereas in the mammalian medial superior olive, the analog of NL, maps are not found. As yet, in crocodilians, topographical representations have not been identified. However, nontopographic representations of ITD cannot be excluded due to different anatomical and ethological features of birds and crocodiles. Therefore, we measured ITD-dependent responses in the NL of anesthetized American alligators of either sex and identified the location of the recording sites by lesions made after recording. The measured extracellular field potentials, or neurophonics, were strongly ITD tuned, and their preferred ITDs correlated with the position in NL. As in birds, delay lines, which compensate for external time differences, formed maps of ITD. The broad distributions of best ITDs within narrow frequency bands were not consistent with an optimal coding model. We conclude that the available acoustic cues and the architecture of the acoustic system in early archosaurs led to a stable and similar organization in today's birds and crocodiles, although physical features, such as internally coupled ears, head size, or shape, and audible frequency range, vary among the two groups.SIGNIFICANCE STATEMENTInteraural time difference (ITD) is an important cue for sound localization, and the optimal strategies for encoding ITD in neuronal populations are the subject of ongoing debate. We show that alligators form maps of ITD very similar to birds, suggesting that their common archosaur ancestor reached a stable coding solution different from mammals. Mammals and diapsids evolved tympanic hearing independently, and local optima can be reached in evolution that are not considered by global optimal coding models. Thus, the presence of ITD maps in the brainstem may reflect a local optimum in evolutionary development. Our results underline the importance of comparative animal studies and show that optimal models must be viewed in the light of evolutionary processes.