bluuebunny/crossref_metadata_2025_split huggingface dataset:
Docosahexaenoic acid (DHA) prevents corticosterone‐induced changes in astrocyte morphology and function
Authors: Champeil‐Potokar Gaëlle , Hennebelle Marie , Latour Alizée , Vancassel Sylvie , Denis Isabelle 
Published: December 2015

AbstractThe many functions of astrocytes, such as glutamate recycling and morphological plasticity, enable them to stabilize synapses environment and protect neurons. Little is known about how they adapt to glucocorticoid‐induced stress, and even less about the influence of dietary factors. We previously showed that omega‐3 polyunsaturated fatty acids (ω3PUFA), dietary fats which alleviate stress responses, influence the way astroglia regulate glutamatergic synapses. We have explored the role of docosahexaenoic acid (DHA), the main ω3PUFA, in the astroglial responses to corticosterone, the main stress hormone in rodents to determine whether ω3PUFA help astrocytes resist stress. Cultured rat astrocytes were enriched in DHA or arachidonic acid (AA, the main ω6PUFA) and given 100 nM corticosterone for several days. Corticosterone stimulated astrocyte glutamate recycling by increasing glutamate uptake and glutamine synthetase (GS), and altered the astrocyte cytoskeleton. DHA‐enriched astrocytes no longer responded to the action of corticosterone on glutamate uptake, had decreased GS, and the cytoskeletal effect of corticosterone was delayed, while AA‐enriched cells were unaffected. The DHA‐dependent anti‐corticosterone effect was related to fewer glucocorticoid receptors, while corticosterone increased DHA incorporation into astrocyte membranes. Thus, DHA helps astrocytes resist the influence of corticosterone, so perhaps promoting a sustainable response by the stressed brain.imageWe show that corticosterone increases the glutamate recycling capacity of rat cortical astrocytes in culture, and alters their morphology, which may be detrimental in the long term. Increasing the membrane incorporation of docosahexaenoic acid (DHA), the main omega‐3 in brain, reduces the amount of glucocorticoid receptors (GR) and prevents the effects of corticosterone. This may help the astrocytes maintain a functional phenotype in chronic stress situations.
Effects of cold temperatures on the excitability of rat trigeminal ganglion neurons that are not for cold sensing
Authors: Kanda Hirosato , Gu Jianguo G. 
Published: December 2015

AbstractAside from a small population of primary afferent neurons for sensing cold, which generate sensations of innocuous and noxious cold, it is generally believed that cold temperatures suppress the excitability of primary afferent neurons not responsible for cold sensing. These not‐for‐cold‐sensing neurons include the majority of non‐nociceptive and nociceptive afferent neurons. In this study we have found that the not‐for‐cold‐sensing neurons of rat trigeminal ganglia (TG) change their excitability in several ways at cooling temperatures. In nearly 70% of not‐for‐cold‐sensing TG neurons, a cooling temperature of 15°C increases their membrane excitability. We regard these neurons as cold‐active neurons. For the remaining 30% of not‐for‐cold‐sensing TG neurons, the cooling temperature of 15°C either has no effect (cold‐ineffective neurons) or suppress their membrane excitability (cold‐suppressive neurons). For cold‐active neurons, the cold temperature of 15°C increases their excitability as is evidenced by increases in action potential (AP) firing numbers and/or the reduction in AP rheobase when these neurons are depolarized electrically. The cold temperature of 15°C significantly inhibits M‐currents and increases membrane input resistance of cold‐active neurons. Retigabine, an M‐current activator, abolishes the effect of cold temperatures on AP firing, but not the effect of cold temperature on AP rheobase levels. The inhibition of M‐currents and the increases of membrane input resistance are likely two mechanisms by which cooling temperatures increase the excitability of not‐for‐cold‐sensing TG neurons.This article is part of the special article series “Pain”.
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Exosomal cellular prion protein drives fibrillization of amyloid beta and counteracts amyloid beta‐mediated neurotoxicity
Authors: Falker Clemens , Hartmann Alexander , Guett Inga , Dohler Frank , Altmeppen Hermann , Betzel Christian , Schubert Robin , Thurm Dana , Wegwitz Florian , Joshi Pooja , Verderio Claudia , Krasemann Susanne , Glatzel Markus 
Published: December 2015

AbstractAlzheimer's disease is a common neurodegenerative, progressive, and fatal disorder. Generation and deposition of amyloid beta (Aβ) peptides associate with its pathogenesis and small soluble Aβ oligomers show the most pronounced neurotoxic effects and correlate with disease initiation and progression. Recent findings showed that Aβ oligomers bind to the cellular prion protein (PrPC) eliciting neurotoxic effects. The role of exosomes, small extracellular vesicles of endosomal origin, in Alzheimer's disease is only poorly understood. Besides serving as disease biomarkers they may promote Aβ plaque formation, decrease Aβ‐mediated synaptotoxicity, and enhance Aβ clearance. Here, we explore how exosomal PrPC connects to protective functions attributed to exosomes in Alzheimer's disease. To achieve this, we generated a mouse neuroblastoma PrPC knockout cell line using transcription activator‐like effector nucleases. Using these, as well as SH‐SY5Y human neuroblastoma cells, we show that PrPC is highly enriched on exosomes and that exosomes bind amyloid beta via PrPC. Exosomes showed highest binding affinity for dimeric, pentameric, and oligomeric Aβ species. Thioflavin T assays revealed that exosomal PrPC accelerates fibrillization of amyloid beta, thereby reducing neurotoxic effects imparted by oligomeric Aβ. Our study provides further evidence for a protective role of exosomes in Aβ‐mediated neurodegeneration and highlights the importance of exosomal PrPC in molecular mechanisms of Alzheimer's disease.
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We show that the prion protein (PrPC) on exosomes captures neurotoxic species of amyloid beta (Aβ) promoting its fibrillization. Our study provides evidence for a protective role of exosomes in Alzheimer`s disease and suggests that, depending on its membrane topology, PrPC holds a dual function: when expressed at the neuronal surface it acts as receptor for Aβ leading to neurotoxic signaling, whereas it detoxifies Aβ when present on exosomes. This provides further support for key roles of PrPC in Alzheimer's disease.
Read the Editorial Highlight for this article on page 9.Cover Image for this issue: doi: 10.1111/jnc.13312.
Spatial variation in osteon population density at the human femoral midshaft: histomorphometric adaptations to habitual load environment
Authors: Gocha Timothy P. , Agnew Amanda M. 
Published: December 2015

AbstractIntracortical remodeling, and the osteons it produces, is one aspect of the bone microstructure that is influenced by and, in turn, can influence its mechanical properties. Previous research examining the spatial distribution of intracortical remodeling density across the femoral midshaft has been limited to either considering only small regions of the cortex or, when looking at the entirety of the cortex, considering only a single individual. This study examined the spatial distribution of all remodeling events (intact osteons, fragmentary osteons, and resorptive bays) across the entirety of the femoral midshaft in a sample of 30 modern cadaveric donors. The sample consisted of 15 males and 15 females, aged 21–97 years at time of death. Using geographic information systems software, the femoral cortex was subdivided radially into thirds and circumferentially into octants, and the spatial location of all remodeling events was marked. Density maps and calculation of osteon population density in cortical regions of interest revealed that remodeling density is typically highest in the periosteal third of the bone, particularly in the lateral and anterolateral regions of the cortex. Due to modeling drift, this area of the midshaft femur has some of the youngest primary tissue, which consequently reveals that the lateral and anterolateral regions of the femoral midshaft have higher remodeling rates than elsewhere in the cortex. This is likely the result of tension/shear forces and/or greater strain magnitudes acting upon the anterolateral femur, which results in a greater amount of microdamage in need of repair than is seen in the medial and posterior regions of the femoral midshaft, which are more subject to compressive forces and/or lesser strain magnitudes.
Arginase inhibition improves endothelial function in patients with familial hypercholesterolaemia irrespective of their cholesterol levels
Authors: Kovamees O. , Shemyakin A. , Eriksson M. , Angelin B. , Pernow J. 
Published: December 2015

AbstractBackgroundElevated LDL cholesterol is an important risk factor for atherosclerosis. Endothelial dysfunction, an early event in the development of atherosclerosis, is characterized by a reduction in nitric oxide (NO) bioavailability. Arginase has emerged as a key regulator of endothelial function through competition with NO synthase for the common substrate l‐arginine. Arginase in endothelial cells is activated by oxidized LDL. The study aim was to investigate the importance of arginase for endothelial dysfunction in patients with familial hypercholesterolaemia (FH).Methods and resultsEndothelial function was evaluated in 12 patients with heterozygous FH and 12 age‐matched healthy normocholesterolaemic subjects using forearm venous occlusion plethysmography. The evaluations in FH patients occurred when they were on lipid‐lowering therapy and 4 weeks after withdrawal of treatment. Endothelium‐dependent vasodilatation (EDV) was assessed by intrabrachial artery infusion of serotonin, and endothelium‐independent dilatation was assessed by infusion of nitroprusside before and after 120 min administration of the arginase inhibitor N ω‐hydroxy‐nor‐l‐arginine (nor‐NOHA; 0.1 mg min−1). In FH patients LDL cholesterol increased from 4.3 ± 0.9 mmol L−1 at baseline to 7.6 ± 1.9 mmol L−1 at follow‐up (P < 0.001). Arginase inhibition enhanced EDV in FH patients by a similar degree independent of lipid‐lowering therapy. The improvement in EDV by arginase inhibition was significantly greater in FH patients than in the control group.ConclusionArginase inhibition results in greater improvement in endothelial function in patients with FH compared to healthy controls irrespective of their cholesterol levels. Arginase may be a promising therapeutic target for improving endothelial function in patients with hypercholesterolaemia.
Gender Differences in Time Perception During Olfactory Stimulation
Authors: Giovannelli F. , Giganti F. , Saviozzi A. , Rebai M. , Marzi T. , Righi S. , Tramacere L. , Borgheresi A. , Cincotta M. , Viggiano M.P. 
Published: December 2015

AbstractIn this study, we conducted two experiments to evaluate the effect of different types of odors on a time reproduction task, comparing performances of males to those of females. In the first experiment, subjects had to estimate short (510, 600, 690 ms) and long (1700, 2000, 2300 ms) interval durations under three odor conditions: positive, negative and neutral. A gender specific effect of olfactory stimulation on time estimation was found only for short durations. Namely, females were less accurate (overestimated) in reproducing short time intervals during the unpleasant odor presentation. This effect was confirmed and strengthened in the second experiment in which the intensity of the negative odor was enhanced. The present findings suggest that the neural network underlying time estimation is more “sensitive” to context manipulations in females than in men.Practical ApplicationsThe first important point is that there might be relevant gender differences in the processing of time (time estimation) that are mediated by olfactory stimulation. This new evidence might have important implications and applications in health issues and especially in workplace safety, for example in jobs or contexts in which fast processing and rapid decisions or choices are required. Therefore, the knowledge that females are more influenced by unpleasant odors than males during time estimation should be seriously considered in situations in which time plays a crucial role such as during rapid decision‐making, where automatic processes should be efficiently activated. Overall, the higher sensitivity to specific olfactory stimulation observed in women probably reflects individual differences in a complex process such as time processing.
Correlates of past year dental health visits: findings from the Indiana black men's health study
Authors: Stapleton Shauna , Finlayson Tracy L. , Ohmit Anita , Hunte Haslyn E. R. 
Published: December 2015

AbstractObjectivesTo examine the role of social support and additional predisposing, enabling and need factors that may be associated with past year dental visits among adult Black men.MethodsData came from a 2011 study of 1,444 Black men from 12 Indiana counties. Based on Andersen's Behavioral Model of Health Service Utilization, we conducted multivariable logistic regression analyses examining predisposing (age, sex, marital status, education), enabling (income, employment, health insurance, place of sick care, social support) and need factors (self‐reported smoking status, health status, mental health days, and fruit and vegetable consumption).ResultsOverall, 42% of African American males sought dental care in the past year. Several predisposing (being married, having a college degree), enabling (being unemployed, having higher income, having health insurance and reporting high levels of social support) and need (increased fruit consumption) factors were found to be positively associated (P < 0.05) with past year dental care utilization in the fully adjusted model. Vegetable consumption was not significantly associated with past year dental use.ConclusionAdult black men in this sample underutilized dental services. Results suggest several factors that can be used to target Black men to increase utilization rates. In particular, social support may be a promising factor that should be explored in further studies.
Melatonin reverses flow shear stress‐induced injury in bone marrow mesenchymal stem cells via activation of AMP‐activated protein kinase signaling
Authors: Yang Yang , Fan Chongxi , Deng Chao , Zhao Lin , Hu Wei , Di Shouyin , Ma Zhiqiang , Zhang Yu , Qin Zhigang , Jin Zhenxiao , Yan Xiaolong , Jiang Shuai , Sun Yang , Yi Wei 
Published: December 2015

AbstractTissue‐engineered heart valves (TEHVs) are a promising treatment for valvular heart disease, although their application is limited by high flow shear stress (FSS). Melatonin has a wide range of physiological functions and is currently under clinical investigation for expanded applications; moreover, extensive protective effects on the cardiovascular system have been reported. In this study, we investigated the protection conferred by melatonin supplementation against FSS‐induced injury in bone marrow mesenchymal stem cells (BMSCs) and elucidated the potential mechanism in this process. Melatonin markedly reduced BMSC apoptotic death in a concentration‐dependent manner while increasing the levels of transforming growth factor β (TGF‐β), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), platelet‐derived growth factor (PDGF) and B‐cell lymphoma 2 (Bcl2), and decreasing those of Bcl‐2‐associated X protein (Bax), p53 upregulated modulator of apoptosis (PUMA), and caspase 3. Notably, melatonin exerted its protective effects by upregulating the phosphorylation of adenosine monophosphate‐activated protein kinase (AMPK), which promotes acetyl‐CoA carboxylase (ACC) phosphorylation. Further molecular experiments revealed that luzindole, a nonselective antagonist of melatonin receptors, blocked the anti‐FSS injury (anti‐FSSI) effects of melatonin. Inhibition of AMPK by Compound C also counteracted the protective effects of melatonin, suggesting that melatonin reverses FSSI in BMSCs through the AMPK‐dependent pathway. Overall, our findings indicate that melatonin contributes to the amelioration of FSS‐induced BMSC injury by activating melatonin receptors and AMPK/ACC signaling. Our findings may provide a basis for the design of more effective strategies that promote the use of TEHCs in patients.
Inducing tolerability of adverse events increases sorafenib exposure and optimizes patient's outcome in advanced hepatocellular carcinoma
Authors: Ponziani Francesca Romana , Bhoori Sherrie , Germini Alessandro , Bongini Marco , Flores Maria , Sposito Carlo , Facciorusso Antonio , Gasbarrini Antonio , Mazzaferro Vincenzo 
Published: December 2015

AbstractBackground & AimsVarious grades of adverse events are associated with sorafenib and have recently been considered as a surrogate of response in patients with advanced hepatocellular carcinoma. The aim of this prospective study was to measure the efficacy of a sorafenib dose reduction regimen, adjusted on patient's tolerability, and aimed at increasing the exposure to the drug.MethodsA total of 73/140 patients with advanced hepatocellular carcinoma receiving sorafenib developed relevant adverse events (grade ≥2) and were managed with a tolerable‐adverse‐event‐protocol consisting of a drug stepwise dose reduction adjusted on patient's tolerability. The remaining 67 patients with toxicity grade 0–1 (minor adverse event group) were managed conventionally with just symptomatic treatment.ResultsMedian follow‐up was 7 months. By adopting the tolerable‐adverse‐event‐protocol, 48% of patients meant to transiently or definitively interrupt the drug were kept on treatment. Macrovascular invasion with/out extra‐hepatic spread (HR = 1.9, 95% CI: 1.3–2.8; P = 0.001) and sorafenib exposure <2 months (HR = 4, 95% CI: 2.5–6.4; P < 0.0001) were independently related to a worse survival. Overall disease control rate, time to progression and survival were: 63.5%, 6 and 9.1 months respectively. The tolerable‐adverse‐event‐protocol group experienced a more favourable outcome with respect to the minor adverse event group as for disease control rate (78% vs. 48%: P < 0.0001), time to progression (9.5 vs. 3 months; HR = 0.3, 95% CI: 0.2–0.5, P < 0.0001) and survival (12.5 vs. 5.7 months; HR = 0.4, 95% CI: 0.3–0.6; P < 0.0001).ConclusionsIn patients with advanced hepatocellular carcinoma, sorafenib dose adjustments based on inducing tolerability of relevant adverse events prolong drug exposure and maximize survival.
Anti‐Müllerian Hormone in the Domestic Dog during the Anestrus to Oestrous Transition
Authors: Nagashima JB , Hansen BS , Songsasen N , Travis AJ , Place NJ 
Published: December 2015

ContentsThe reproductive cycle of the domestic dog features a long period of relative ovarian inactivity or anestrus. The mechanism of anestrous termination/oestrous resumption is not yet fully understood, which presents a challenge to the development of oestrous induction protocols. In this study, we assess the possibility that anti‐Müllerian hormone (AMH) might play a role in this transition by characterizing its patterns of expression in the circulation during the transition from anestrus to oestrous and in all stages of ovarian follicular growth. Serum samples from five beagles (2.0–4.5 years) were collected three times per week at least 30 days prior to the onset of oestrous and assessed for AMH concentrations. Serum AMH concentration increased significantly during the transition from anestrus to proestrus and then declined back to the anestrous baseline beginning on day −4 before the luteinizing hormone surge, which was determined by changes in serum progesterone concentrations. Cortical sections of ovaries from females undergoing routine ovariohysterectomy (aged 8 months–5 years, n = 4) were evaluated for AMH by immunohistochemistry. Pre‐antral and small antral follicles were most strongly immunoreactive for AMH. These data suggest that the increase in the number of antral follicles is associated with the rise in serum AMH as the anestrous period comes to an end. The rise in AMH might be useful in predicting the onset of oestrus and therefore assist with the optimization of oestrous induction protocols and possibly other assisted reproductive technologies.
Apatite Composition of Representative Magnetite‐series and Ilmenite‐series Granitoids in Japan
Authors: Ishihara Shunso , Moriyama Takeru 
Published: December 2015

AbstractApatites of representative magnetite‐series and ilmenite‐series granitoids were studied in the Japanese Islands. Concentrations of the volatile components F, Cl and SO3 are differently distributed in apatites of these granitoid series. Apatites are always fluoroapatite. They have weakly higher F content in the ilmenite series than in the magnetite series. In contrast, Cl and SO3, are significantly concentrated in apatites of the magnetite series compared to the ilmenite series. These characteristics reflect the original concentrations of these components in the host granitic magmas. A high fO2 seems most important for the S‐concentration as sulfate in apatite of the magnetite series. REE and Y are only erratically high in the studied apatites.
Patients' experiences of communication and involvement in decision‐making about atrial fibrillation treatment in consultations with nurses and physicians
Authors: Siouta Eleni , Hellström Muhli Ulla , Hedberg Berith , Broström Anders , Fossum Bjöörn , Karlgren Klas 
Published: December 2015

BackgroundInsights in consultations across patient interactions with physicians and nurses are of vital importance for strengthening the patients' involvement in the treatment decision‐making process. The experience of involvement and communication in decision‐making from the patients' perspective has been sparsely explored.ObjectiveTo examine how patients describe involvement in and communication about decision‐making regarding treatment in consultations with nurses and physicians.MethodTwenty‐two patients with atrial fibrillation (AF), aged 37–90 years, were interviewed directly after their consultations with nurses and physicians in outpatient AF clinics in six Swedish hospitals.ResultsIn consultations with nurses, the patients felt involved when obtaining clarifications about AF as a disease and its treatment and when preparing for and building up confidence in decision‐making. In consultations with physicians, the patients felt involved when they could cooperate in decision‐making, when acquiring knowledge, and when they felt that they were being understood. One shared category was found in consultations with both nurses and physicians, and the patients felt involved when they had a sense of trust and felt secure during and between consultations.ConclusionsPatients with AF stated that they would need to acquire knowledge and build up confidence and ability in order to be effectively involved in the decision‐making about treatment. Despite not being actively involved in decision‐making, patients felt involved through experiencing supportive and confirming communication.Practice implicationsAttention must be given to the relationship with the patient to create the conditions for patient involvement in the consultation. This can be achieved through supportive communication attempting to create a feeling of clarity and building confidence. This will support involvement in decision‐making concerning AF treatment and feelings of being understood and of trust in physicians and/or nurses.