bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analytical quantification, intoxication case series, and pharmacological mechanism of action for N‐ethylnorpentylone (N‐ethylpentylone or ephylone)
Authors: Costa Jose Luiz , Cunha Kelly Francisco , Lanaro Rafael , Cunha Ricardo Leal , Walther Donna , Baumann Michael H. 
Published: September 2018

AbstractSynthetic cathinones continue to proliferate in clandestine drug markets worldwide. N‐ethylnorpentylone (also known as N‐ethylpentylone or ephylone) is a popular emergent cathinone, yet little information is available about its toxicology and pharmacology. Here we characterize the analytical quantification, clinical presentation, and pharmacological mechanism of action for N‐ethylnorpentylone. Liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS) was used to quantify N‐ethylnorpentylone in blood obtained from human cases. Clinical features exhibited by the intoxicated individuals are described. The activity of N‐ethylnorpentylone at plasma membrane transporters for dopamine (DAT), norepinephrine (NET) and 5‐HT (SERT) was assessed using in vitro assays measuring uptake inhibition and evoked release of [3H] neurotransmitters in rat brain synaptosomes. Our LC–MS/MS method assayed N‐ethylnorpentylone concentrations with limits of detection and quantification of 1 and 5 ng/mL, respectively. Quantitation was linear from 5 to 500 ng/mL, and the method displayed specificity and reproducibility. Circulating concentrations of N‐ethylnorpentylone ranged from 7 to 170 ng/mL in clinical cases, and the associated symptoms included palpitations, tachycardia, agitation, hallucinations, coma and death. N‐Ethylnorpentylone was a potent inhibitor at DAT (IC50 = 37 nM), NET (IC50 = 105 nM) and SERT (IC50 = 383 nM) but displayed no transporter releasing activity. We present a validated method for quantifying N‐ethylnorpentylone in human case work. The drug is a psychomotor stimulant capable of inducing serious cardiovascular and neurological side‐effects which can be fatal. In vitro findings indicate that N‐ethylnorpentylone exerts its effects by potent blockade of DAT and NET, thereby elevating extracellular levels of dopamine and norepinephrine in the brain and periphery.
Developmental processes regulate craniofacial variation in disease and evolution
Authors: Merkuri Fjodor , Fish Jennifer L. 
Published: September 2018

SummaryVariation in development mediates phenotypic differences observed in evolution and disease. Although the mechanisms underlying phenotypic variation are still largely unknown, recent research suggests that variation in developmental processes may play a key role. Developmental processes mediate genotype–phenotype relationships and consequently play an important role regulating phenotypes. In this review, we provide an example of how shared and interacting developmental processes may explain convergence of phenotypes in spliceosomopathies and ribosomopathies. These data also suggest a shared pathway to disease treatment. We then discuss three major mechanisms that contribute to variation in developmental processes: genetic background (gene–gene interactions), gene–environment interactions, and developmental stochasticity. Finally, we comment on evolutionary alterations to developmental processes, and the evolution of disease buffering mechanisms.
Direct and cascading effects of landscape structure on tropical forest and non‐forest frugivorous birds
Authors: Morante‐Filho José Carlos , Arroyo‐Rodríguez Víctor , Pessoa Michaele de Souza , Cazetta Eliana , Faria Deborah 
Published: September 2018

AbstractGlobal biodiversity is increasingly threatened by land‐use change, but the direct and indirect drivers of species diversity in human‐modified tropical landscapes are poorly known. Forest‐dependent species are expected to be particularly sensitive to changes in landscape composition (e.g., forest loss) and configuration (e.g., increase of forest edges), both directly and indirectly through cascading landscape effects on local patterns of forest structure and resource availability. In contrast, non‐forest‐dependent species are probably more strongly related to landscape changes than to local forest patterns, as these species are able to use resources not only from the forest, but also from other landscape elements over larger spatial scales. We tested these hypotheses using structural equation modeling. In particular, we sampled 20 landscapes (115 ha each) from the Brazilian Atlantic rainforest to assess the effect of landscape‐scale forest cover and amount of forest edges on the diversity of frugivorous birds, both directly and indirectly through the effect that these landscape variables may have on vegetation complexity and fruit biomass. We separately assessed the response of forest‐dependent and non‐forest‐dependent frugivores to infer potential mechanisms underlying bird assemblages in fragmented landscapes. The diversity of forest‐dependent birds mainly decreased with the simplification of vegetation complexity in more deforested landscapes, but increased with increasing fruit biomass in more forested landscapes (indirect effects). Both patterns were significant, thus supporting a strong bottom‐up control, i.e., local habitat simplification and resource scarcity in highly deforested landscapes limits the maintenance of forest‐dependent birds. Conversely, but as expected, non‐forest‐dependent birds were more strongly and directly related to landscape‐scale patterns. In particular, landscapes with higher forest edge amount showed higher bird species diversity, probably because the increasing length of ecotones and interspersion/juxtaposition of different habitat types in landscapes with more forest edges can increase resource availability and foraging efficiency of non‐forest‐dependent birds. As the seed dispersal services offered by forest‐dependent species cannot be ecologically compensated for by the proliferation of non‐forest‐dependent species, preventing forest loss is imperative to maintain forest‐dependent birds and forest regeneration in this vanishing biodiversity hotspot.
Assessing the long-term effect of exposure to dispersant-treated oil on fish health using hypoxia tolerance and temperature susceptibility as ecologically relevant biomarkers
Authors: Mauduit Florian , Farrell Anthony P. , Domenici Paolo , Lacroix Camille , Le Floch Stéphane , Lemaire Philippe , Nicolas-Kopec Annabelle , Whittington Mark , Le Bayon Nicolas , Zambonino-Infante José-Luis , Claireaux Guy 
Published: September 2018

Abstract

The ecological and economic importance of fish act as a brake on the development of chemical dispersants as operational instruments following oil spills. Although a valuable and consistent body of knowledge exists, its use in spill response is limited. The objective of the present study was to increase current knowledge base to facilitate the translation of published data into information of operational value. Thus we investigated the dose–response relationship between dispersant-treated oil exposure and ecologically relevant consequences by combining laboratory and field experiments. Effects were examined over almost a year using juveniles of the slowly growing, commercially important European sea bass (Dicentrarchus labrax). A reliable interpretation of biomarker responses requires a complete knowledge of the factors likely to affect them. Interpopulational variability is of particular importance in environmental impact assessment because biomarker responses from a population collected in an impacted area are classically compared with those collected in a clean site. Our study revealed no effect of the exposure to dispersant-treated oil on fish hypoxia tolerance and temperature susceptibility at 1 and 11 mo post exposure. Similarly, no effect of the exposure was observed on the ability of the fish to cope with environmental contingencies in the field, regardless of the dose tested. Thus we feel confident to suggest that a 48-h exposure to chemically treated oil does not affect the ability of sea bass to cope with mild environmental contingencies. Finally, investigation of interpopulation variability revealed large differences in both hypoxia tolerance and temperature susceptibility among the 2 populations tested, suggesting that this variability may blur the interpretation of population comparisons as classically practiced in impact assessment. Environ Toxicol Chem 2019;38:210–221. © 2018 SETAC
Supporting Scientific Advice through a Boundary Organization
Authors: Kennedy Eric B. 
Published: September 2018

AbstractThe complex socio‐environmental issues faced by society – including climate change, resource management, and fostering resiliency in landscapes that intermix human and natural features – are difficult challenges that demand contextually appropriate evidence‐based interventions. Institutional arrangements for providing scientific advice range from individual science advisors to large scientific committees or advisory councils, with a great deal of variation in their formal and informal structures. Regardless of the structuring of advisors, however, these arrangements face a common challenge: being required to speak to a wide range of issues in a time‐sensitive manner, each of which has extensive stakeholder communities, deep disciplinary knowledge, and many complicating attributes. It is argued that creating a formally associated, supporting boundary organization that is tasked with supporting the advisory functions can help to resolve this challenge and improve the overall quality of advice offered. Using a case study – the California Ocean Science Trust and its advice on coastal and ocean management issues – it is argued that boundary organizations can help science advisors maintain links with disparate stakeholder communities, adjudicate between competing forms of expertise, help to provide nuance in grappling with the tensions between science and politics, and support an “honest broker” advising function.
Inhibition of hematopoietic cell kinase dysregulates microglial function and accelerates early stage Alzheimer's disease‐like neuropathology
Authors: Lim Siok Lam , Tran Diana Nguyen , Zumkehr Joannee , Chen Christine , Ghiaar Sagar , Kieu Zanett , Villanueva Emmanuel , Gallup Victoria , Rodriguez‐Ortiz Carlos J. , Kitazawa Masashi 
Published: September 2018

AbstractEmerging evidence have posited that dysregulated microglia impair clearance and containment of amyloid‐β (Aβ) species in the brain, resulting in aberrant buildup of Aβ and onset of Alzheimer's disease (AD). Hematopoietic cell kinase (Hck) is one of the key regulators of phagocytosis among the Src family tyrosine kinases (SFKs) in myeloid cells, and its expression is found to be significantly altered in AD brains. However, the role of Hck signaling in AD pathogenesis is unknown. We employed pharmacological inhibition and genetic ablation of Hck in BV2 microglial cells and J20 mouse model of AD, respectively, to evaluate the impact of Hck deficiency on Aβ‐stimulated microglial phagocytosis, Aβ clearance, and resultant AD‐like neuropathology. Our in vitro data reveal that pharmacological inhibition of SFKs/Hck in BV2 cells and genetic ablation of their downstream kinase, spleen tyrosine kinase (Syk), in primary microglia significantly attenuate Aβ oligomers‐stimulated microglial phagocytosis. Whereas in Hck‐deficient J20 mice, we observed exacerbated Aβ plaque burden, reduced microglial coverage, containment, and phagocytosis of Aβ plaques, and induced iNOS expression in plaque‐associated microglial clusters. These multifactorial changes in microglial activities led to attenuated PSD95 levels in hippocampal DG and CA3 regions, but did not alter the postsynaptic dendritic spine morphology at the CA1 region nor cognitive function of the mice. Hck inhibition thus accelerates early stage AD‐like neuropathology by dysregulating microglial function and inducing neuroinflammation. Our data implicate that Hck pathway plays a prominent role in regulating microglial neuroprotective function during the early stage of AD development.
Syncytial isopotentiality: A system‐wide electrical feature of astrocytic networks in the brain
Authors: Kiyoshi Conrad M. , Du Yixing , Zhong Shiying , Wang Wei , Taylor Anne T. , Xiong Bangyan , Ma Baofeng , Terman David , Zhou Min 
Published: September 2018

AbstractSyncytial isopotentiality, resulting from a strong electrical coupling, emerges as a physiological mechanism that coordinates individual astrocytes to function as a highly efficient system in brain homeostasis. However, whether syncytial isopotentiality occurs selectively to certain brain regions or is universal to astrocytic networks remains unknown. Here, we have explored the correlation of syncytial isopotentiality with different astrocyte subtypes in various brain regions. Using a nonphysiological K+‐free/Na+ electrode solution to depolarize a recorded astrocyte in situ, the existence of syncytial isopotentiality can be revealed: the recorded astrocyte's membrane potential remains at a quasi‐physiological level due to strong electrical coupling with neighboring astrocytes. Syncytial isopotentiality appears in Layer I of the motor, sensory, and visual cortical regions, where astrocytes are organized with comparable cell densities, interastrocytic distances, and the quantity of directly coupled neighbors. Second, though astrocytes vary in their cytoarchitecture in association with neuronal circuits from Layers I–VI, the established syncytial isopotentiality remains comparable among different layers in the visual cortex. Third, neurons and astrocytes are uniquely organized as barrels in Layer IV somatosensory cortex; interestingly, astrocytes both inside and outside of the barrels do electrically communicate with each other and also share syncytial isopotentiality. Fourth, syncytial isopotentiality appears in radial‐shaped Bergmann glia and velate astrocytes in the cerebellar cortex. Fifth, although fibrous astrocytes in white matter exhibit a distinct morphology, their network syncytial isopotentiality is comparable with protoplasmic astrocytes. Altogether, syncytial isopotentiality appears as a system‐wide electrical feature of astrocytic networks in the brain.
Decreased BOLD fluctuations in lateral temporal cortices of premature born adults
Authors: Shang Jing , Bäuml Josef G. , Koutsouleris Nikolaos , Daamen Marcel , Baumann Nicole , Zimmer Claus , Bartmann Peter , Boecker Henning , Wolke Dieter , Sorg Christian 
Published: September 2018

AbstractLasting volume reductions in subcortical and temporal‐insular cortices after premature birth suggest altered ongoing activity in these areas. We hypothesized altered fluctuations in ongoing neural excitability and activity, as measured by slowly fluctuating blood oxygenation of resting‐state functional MRI (rs‐fMRI), in premature born adults, with altered fluctuations being linked with underlying brain volume reductions. To investigate this hypothesis, 94 very preterm/very low birth weight (VP/VLBW) and 92 full‐term born young adults underwent structural and rs‐fMRI data acquisition with voxel‐based morphometry and amplitude of low‐frequency fluctuations (ALFF) as main outcome measure. In VP/VLBW adults, ALFF was reduced in lateral temporal cortices, and this reduction was positively associated with lower birth weight. Regions of reduced ALFF overlapped with reduced brain volume. On the one hand, ALFF reduction remained after controlling for volume loss, supporting the functional nature of ALFF reductions. On the other hand, ALFF decreases were positively associated with underlying brain volume loss, indicating a relation between structural and functional changes. Furthermore, within the VP/VLBW group, reduced ALFF was associated with reduced IQ, indicating the behavioral relevance of ALFF decreases in temporal cortices. These results demonstrate long‐term impact of premature birth on ongoing BOLD fluctuations in lateral temporal cortices, which are linked with brain volume reductions. Data suggest permanently reduced fluctuations in ongoing neural excitability and activity in structurally altered lateral temporal cortices after premature birth.
The impact of health transformation plan on hospitalization rates in Iran: An interrupted time series
Authors: Piroozi Bakhtiar , Rashidian Arash , Takian Amirhossein , Amerzadeh Mohammad , Sakha Minoo Alipouri , Faraji Obeidollah , Moradi Ghobad 
Published: September 2018

SummaryObjectiveThe study aims to assess the impact of health transformation plan (HTP) as a major health system reform on hospitalization rate in Iran. Health transformation plan adopted different measures to increase the coverage of basic health insurance, increase the quality of outpatient visit care, improve and expand the family physician program, expand health services to suburban areas, reduce out‐of‐pocket (OOP) payments for inpatient services, and update tariffs to more realistic ones.MethodsWe selected Kurdistan province, a province that was not a patient referral hub, for the collection of monthly hospitalization data over a period of 50 months. Interrupted time series (ITS) analysis was carried out, and segmented regression analysis was employed to assess the abrupt (or short‐term) and gradual (or long‐term) effects of HTP on hospitalization rate.ResultsAlthough before the intervention, there was no significant increase or decline in hospitalization rate in the Kurdistan province, after the implementation of HTP, a significant increase in the intercept and slope of hospitalization rate was observed (P < 0.001).ConclusionHealth transformation plan has improved the utilization of hospitalization care services in a province that historically had been suffering from underutilized hospital services.
Use of Lean techniques in health care in Spain to improve involvement and satisfaction of workers
Authors: Damián Sanz Marina , Yagüe‐Fabra José A. , Gracia Matilla Rosa 
Published: September 2018

SummaryThe purpose of this study was to improve the organization of work, reduce physical effort, and obtain greater satisfaction of workers in the Pre‐analytical Area of the Clinical Biochemistry Service at the Miguel Servet University Hospital of Zaragoza, in Spain, by applying Lean techniques. Such techniques were applied in two steps to obtain a final situation where the reduction of the space occupied, the required physical effort, and the work time is clear. The satisfaction of the workers was analyzed during the whole process by means of surveys, concluding that the sum of all the improvements managed to increase the satisfaction of the professionals. One key aspect to get these results was to use always the information and opinions of the staff making them feel the protagonists of the process. For that, it was essential the role of the agent of change that fundamentally sought the involvement of professionals in the improvement processes. Another key point was the careful application of Lean techniques always little by little, by applying small changes that became habits and achieved permanent results. In conclusion, in this work, a methodology to improve involvement and satisfaction of workers in health care has been presented and validated.
Does level of minority presence and hospital reimbursement policy influence hospital referral region health rankings in the United States
Authors: Hamadi Hanadi , Apatu Emma , Loh Chung‐Ping Albert , Farah Hyett , Walker Kirk , Spaulding Aaron 
Published: September 2018

SummaryThe shift from a fee‐for‐service payment to a value‐based payment scheme, sparked by the Patient Protection and Affordable Care Act, introduced pay‐for‐performance programs such Hospital Value Based Purchasing. Previous inquiry has not considered how local community factors may affect hospital system performance. This study investigated the association between local health performance and minority population in a hospital referral region (HRR). The primary objective was to ascertain whether community diversity levels are significantly associated to local health performance guided by the ecological model. Secondary data analysis collected from the 2016 American Hospital Association, Area Health Resource File, Commonwealth Fund Scorecard on Local Health System Performance, and the Dartmouth Atlas HRR dataset was used. Our primary findings show that the more diverse a HRR is, the more likely it is to be associated with lower ranking for access and affordability prevention and treatment avoidable hospital use and cost as well as healthy lives. Total performance score was significantly related to a better health ranking on prevention and treatment, hospital use, and cost, as well as healthy lives. This research supports the assertion that communities, particularly minorities in those communities, affect local health care performance in a variety of ways.
Risk of stillbirth among Zambian women with a prior cesarean delivery
Authors: Castillo Marcela C. , Vwalika Bellington , Stoner Marie C.D. , Chi Benjamin H. , Stringer Jeffrey S.A. , Kasaro Margaret , Kumwenda Andrew , Stringer Elizabeth M. 
Published: September 2018

AbstractObjectiveCesarean delivery (CD) may be associated with stillbirth in future pregnancies. We investigated prior CD as a risk factor for stillbirth in Lusaka, Zambia.MethodsWe conducted a retrospective cohort analysis of women with only one prior pregnancy who delivered between February 1, 2006, and May 31, 2013. We analysed data from the Zambia Electronic Perinatal System. Maternal and infant characteristics were analyzed for association with stillbirth using Pearson's χ2 test or the Wilcoxon rank‐sum test. We calculated risk ratios for the relationship between stillbirth (antepartum vs intrapartum) and prior CD, with a log Poisson model to adjust for confounding.ResultsOf 57 320 women in our cohort, 1933 (3.4%) reported a prior CD. There were 1012 (1.8%) stillbirths in the no prior CD group and 81 (4.2%) in the prior CD group (P<0.001). In multivariate models adjusting for stillbirth risk factors, prior CD was associated with antepartum (adjusted risk ratio 1.56, 95% confidence interval 1.08–2.24) and intrapartum (adjusted risk ratio 3.26, 95% confidence interval 2.40–4.42) stillbirth compared with no prior CD. The difference between groups was most apparent at 36–37 weeks’ gestation (log‐rank P<0.001).ConclusionPrior CD was associated with increased risk of stillbirth. Improved monitoring during labor and safe methods for induction are urgently needed in low‐resource settings.
Orexin A Suppresses Oxidized LDL Induced Endothelial Cell Inflammation via MAPK p38 and NF‐κB Signaling Pathway
Authors: Zhang Haiyang , Liang Bin , Li Tao , Zhou Yi , Shang Deya , Du Zhongjun 
Published: September 2018

AbstractOrexin A is a multifaceted peptide produced in hypothalamus. We examined the effect of orexin A on vascular endothelial cells. Our study showed that orexin A had a profound inhibitory effect against endothelial inflammation by oxidized low‐density lipoprotein (ox‐LDL) in endothelial cells. Orexin A partially suppressed ox‐LDL‐induced monocytes THP‐1 cells attachment to endothelial cells by limiting expression of vascular molecules including VCAM‐1, ICAM‐1, and E‐selectin. Mechanistically, orexin A ameliorated endothelial dysfunction by reducing MAP kinase p38 and NF‐κB activation via its receptor‐OX1R. Orexin A suppressed phosphorylation of MAP kinase p38 and the NF‐κB cascade kinases IKKα and IκBα, and prevented the shuttle of p65 protein into nuclear. Additionally, we reported that OX1R was expressed in HUVECs. Silence of OX1R completely abolished the inhibitory function of orexin in attachment of THP‐1 cells. Collectively, our data suggest that orexin A ameliorated endothelial dysfunction under inflammatory stimuli. © 2018 IUBMB Life, 70(10):961–968, 2018