bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Solid Dispersion of Quercetin Shows Enhanced Nrf2 Activation and Protective Effects against Oxidative Injury in a Mouse Model of Dry Age-Related Macular Degeneration
Authors: Shao Yan , Yu Haitao , Yang Yan , Li Min , Hang Li , Xu Xinrong 
Published: November 2019

Age-related macular degeneration (AMD) represents a major reason for blindness in the elderly population. Oxidative stress is a predominant factor in the pathology of AMD. We previously evaluated the effects of phospholipid complex of quercetin (Q-PC) on oxidative injury in ARPE-19 cells, but the underlying mechanisms are not fully understood. Herein, the solid dispersion of quercetin-PC (Q-SD) was prepared with solubility being 235.54 μg/mL in water and 2.3×104 μg/mL in chloroform, which were significantly higher than that of quercetin (QT) and Q-PC. Q-SD also exhibited a considerably higher dissolution rate than QT and Q-PC. Additionally, Q-SD had Cmax of 4.143 μg/mL and AUC of 12.015 μg·h/mL in rats, suggesting better bioavailability than QT and Q-PC. Then, a mouse model of dry AMD (Nrf2 wild-type (WT) and Nrf2 knockout (KO)) was established for evaluating the effects of Q-SD in vivo. Q-SD more potently reduced retinal pigment epithelium sediments and Bruch’s membrane thickness than QT and Q-PC at 200 mg/kg in Nrf2 WT mice and did not work in Nrf2 KO mice at the same dosage. Additionally, Q-SD significantly decreased ROS and MDA contents and restored SOD, GSH-PX, and CAT activities of serum and retinal tissues in Nrf2 WT mice, but not in Nrf2 KO mice. Furthermore, Q-SD more potently increased Nrf2 mRNA expression and stimulated its nuclear translocation in retinal tissues of Nrf2 WT mice. Q-SD significantly increased the expression of Nrf2 target genes HO-1, HQO-1, and GCL of retinal tissues in Nrf2 WT mice, not in Nrf2 KO mice. Altogether, Q-SD had improved physicochemical and pharmacokinetic properties compared to QT and Q-PC and exhibited more potent protective effects on retina oxidative injury in vivo. These effects were associated with activation of Nrf2 signaling and upregulation of antioxidant enzymes.
Dietary Supplementation of the Antioxidant Curcumin Halts Systemic LPS-Induced Neuroinflammation-Associated Neurodegeneration and Memory/Synaptic Impairment via the JNK/NF-κB/Akt Signaling Pathway in Adult Rats
Authors: Khan Muhammad Sohail , Muhammad Tahir , Ikram Muhammad , Kim Myeong Ok 
Published: November 2019

Curcumin is a natural polyphenolic compound widely known to have antioxidant, anti-inflammatory, and antiapoptotic properties. In the present study, we explored the neuroprotective effect of curcumin against lipopolysaccharide- (LPS-) induced reactive oxygen species- (ROS-) mediated neuroinflammation, neurodegeneration, and memory deficits in the adult rat hippocampus via regulation of the JNK/NF-κB/Akt signaling pathway. Adult rats were treated intraperitoneally with LPS at a dose of 250 μg/kg for 7 days and curcumin at a dose of 300 mg/kg for 14 days. After 14 days, the rats were sacrificed, and western blotting and ROS and lipid peroxidation assays were performed. For immunohistochemistry and confocal microscopy, the rats were perfused transcardially with 4% paraformaldehyde. In order to verify the JNK-dependent neuroprotective effect of curcumin and to confirm the in vivo results, HT-22 neuronal and BV2 microglial cells were exposed to LPS at a dose of 1 μg/ml, curcumin 100 μg/ml, and SP600125 (a specific JNK inhibitor) 20 μM. Our immunohistochemical, immunofluorescence, and biochemical results revealed that curcumin inhibited LPS-induced oxidative stress by reducing malondialdehyde and 2,7-dichlorofluorescein levels and ameliorating neuroinflammation and neuronal cell death via regulation of the JNK/NF-κB/Akt signaling pathway both in vivo (adult rat hippocampus) and in vitro (HT-22/BV2 cell lines). Moreover, curcumin markedly improved LPS-induced memory impairment in the Morris water maze and Y-maze tasks. Taken together, our results suggest that curcumin may be a potential preventive and therapeutic candidate for LPS-induced ROS-mediated neurotoxicity and memory deficits in an adult rat model.
miRNA-Mediated Suppression of a Cardioprotective Cardiokine as a Novel Mechanism Exacerbating Post-MI Remodeling by Sleep Breathing Disorders
Authors: Du Yunhui , Wang Xiao , Li Linyi , Hao Wenjing , Zhang Huina , Li Yu , Qin Yanwen , Nie Shaoping , Christopher Theodore A. , Lopez Bernard L. , Lau Wayne Bond , Wang Yajing , Ma Xin-Liang , Wei Yongxiang 
Published: November 2019

Rationale:
Obstructive sleep apnea-hypopnea syndrome, a sleep breathing disorder in which chronic intermittent hypoxia (CIH) is the primary pathology, is associated with multiple cardiovascular diseases. However, whether and how CIH may affect cardiac remodeling following myocardial infarction (MI) remains unknown.

Objective:
To determine whether CIH exposure at different periods of MI may exacerbate post-MI heart failure and to identify the mechanisms underlying CIH-exacerbated post-MI remodeling.

Methods and Results:

Adult male mice were subjected to MI (4 weeks) with and without CIH (4 or 8 weeks). CIH before MI (CIH+MI) had no significant effect on post-MI remodeling. However, double CIH exposure (CIH+MI+CIH) or CIH only during the MI period (MI+CIH) significantly exacerbated pathological remodeling and reduced survival rate. Mechanistically, CIH activated TGF-β (tumor growth factor-β)/Smad (homologs of both the Drosophila protein MAD and the C. elegans protein SMA) signaling and enhanced cardiac epithelial to mesenchymal transition, markedly increasing post-MI cardiac fibrosis. Transcriptome analysis revealed that, among 15 genes significantly downregulated (MI+CIH versus MI),
Ctrp9
(a novel cardioprotective cardiokine) was one of the most significantly inhibited genes. Real-time polymerase chain reaction/Western analysis confirmed that cardiomyocyte CTRP9 expression was significantly reduced in MI+CIH mice. RNA-sequencing, real-time polymerase chain reaction, and dual-luciferase reporter assays identified that microRNA-214-3p is a novel
Ctrp9
targeting miRNA. Its upregulation is responsible for
Ctrp9
gene suppression in MI+CIH. Finally, AAV9 (adeno-associated virus 9)-mediated cardiac-specific CTRP9 overexpression or rCTRP9 (recombinated CTRP9) administration inhibited TGF-β/Smad and Wnt/β-catenin pathways, attenuated interstitial fibrosis, improved cardiac function, and enhanced survival rate in MI+CIH animals.

Conclusions:
This study provides the first evidence that MI+CIH upregulates miR-214-3p, suppresses cardiac CTRP9 (C1q tumor necrosis factor-related protein-9) expression, and exacerbates cardiac remodeling, suggesting that CTRP9 may be a novel therapeutic target against pathological remodeling in MI patients with obstructive sleep apnea-hypopnea syndrome.
Prevalence and Clinical Correlates of Poststroke Behavioral Dysexecutive Syndrome
Authors: Tang Wai Kwong , Lau Chieh Grace , Liang Yan , Wang Lisha , Mok Vincent , Soo Oi Yan Yannie , Leung Wai Hong Thomas , Ungvari Gabor S. , Uchiyama Shinichiro , Kim Jong S. 
Published: November 2019

Background

Behavioral dysexecutive syndrome (
BDES
) is a common phenomenon following stroke. To date, research has focused mainly on individual behavioral symptoms rather than a more comprehensive characterization of goal‐directed behavior in stroke survivors. This cross‐sectional study evaluated the prevalence and clinical correlates of
BDES
in Hong Kong stroke survivors.

Methods and Results

A total of 369 stroke survivors were recruited from a regional hospital at 3 months after their index stroke. Patients’ demographic and clinical characteristics were extracted from a comprehensive stroke database.
BDES
was measured with the Chinese version of the Dysexecutive Questionnaire. Four neurocognitive batteries assessed domains of cognitive executive functions. The prevalence of
BDES
3 months poststroke was 18.7%. At that time point, the Hospital Anxiety Depression Scale and Mini‐Mental State Examination scores and the presence of depression were significant predictors of
BDES
in a multivariate logistic regression analysis. These parameters remained significant predictors of the Dysexecutive Questionnaire score in a linear stepwise regression analysis and together accounted for 28.5% of the variance. Current depression was predictive of the Dysexecutive Questionnaire score in patients with
BDES
, with a variance of 9.7%. Furthermore, compared with the non‐
BDES
group, patients with
BDES
exhibited poor performance‐based executive function in the Chinese version of the Frontal Assessment Battery and color trails, arrow, and category fluency tests.

Conclusions

Symptoms of anxiety, current depression, and global cognitive function may be independent predictors of the presence and severity of
BDES
3 months poststroke. Stroke survivors with
BDES
exhibit poor executive functioning, including goal maintenance and semantic memory.
Subpial Hemorrhage of the Neonate
Authors: Cain Donald W. , Dingman Andra L. , Armstrong Jennifer , Stence Nicholas V. , Jensen Alexandria M. , Mirsky David M. 
Published: November 2019

Background and Purpose—
Subpial hemorrhage of the neonate is a rare stroke subtype reported in few case series. Birth trauma and coagulopathy are commonly proposed etiologies. We evaluated our subpial hemorrhage of the neonate patient cohort to expand current understanding

Methods—
Cases of subpial hemorrhage of the neonate were identified by keyword searches of the institutional database. The medical records and magnetic resonance imagings were reviewed.

Results—
Seventeen cases were identified. Assisted delivery occurred in 12% of cases, and acute coagulation abnormalities occurred in 77%. Subpial hemorrhage of the neonate was located in the temporal lobe in 82%, with cytotoxic edema and medullary vein congestion and thrombosis subjacent to the hemorrhages in 100% and 76% of cases, respectively. Neurological disability was present in 44% of survivors. Three patients had chronic coagulation abnormalities.

Conclusions—
In our cohort, clinical findings supporting a potential relationship with birth trauma were infrequent. The imaging findings suggest a nonarterial, deep venous pattern of hemorrhagic ischemia.
Stagnating National Declines in Stroke Mortality Mask Widespread County-Level Increases, 2010–2016
Authors: Hall Eric W. , Vaughan Adam S. , Ritchey Matthew D. , Schieb Linda , Casper Michele 
Published: November 2019

Background and Purpose—
Recent national and state-level trends show a stalling or reversal of previously declining stroke death rates. These national trends may mask local geographic variation and changes in stroke mortality. We assessed county-level trends in stroke mortality among adults aged 35 to 64 and ≥65 years.

Methods—
We used data from National Vital Statistics Systems and a Bayesian multivariate space-time conditional autoregressive model to estimate age-standardized annual stroke death rates for 2010 through 2016 among middle-aged adults (35–64 years) and older adults (≥65 years) in US counties. We used log-linear regression models to estimate average annual and total percent change in stroke mortality during the period.

Results—
Nationally, the annual percent change in stroke mortality from 2010 to 2016 was −0.7% (95% CI, −4.2% to 3.0%) among middle-aged adults and −3.5% (95% CI, −10.7% to 4.3%) among older adults, resulting in 2016 rates of 15.0 per 100 000 and 259.8 per 100 000, respectively. Increasing county-level stroke mortality was more prevalent among middle-aged adults (56.6% of counties) compared with among older adults (26.1% of counties). About half (48.3%) of middle-aged adults, representing 60.2 million individuals, lived in counties in which stroke mortality increased.

Conclusions—
County-level increases in stroke mortality clarify previously reported national and state-level trends, particularly among middle-aged adults. Roughly 3×as many counties experienced increases in stroke death rates for middle-aged adults compared with older adults. This highlights a need to address stroke prevention and treatment for middle-aged adults while continuing efforts to reduce stroke mortality among the more highly burdened older adults. Efforts to reverse these troubling local trends will likely require joint public health and clinical efforts to develop innovative and integrated approaches for stroke prevention and care, with a focus on community-level characteristics that support stroke-free living for all.
Hounsfield Unit Value of Interpeduncular Cistern Hematomas Can Predict Symptomatic Vasospasm
Authors: Ishihara Hideyuki , Oka Fumiaki , Kawano Reo , Shinoyama Mizuya , Nishimoto Takuma , Kudomi Shohei , Suzuki Michiyasu 
Published: November 2019

Background and Purpose—
Symptomatic vasospasm is an important factor that affects the outcomes of aneurysmal subarachnoid hemorrhage. Subarachnoid blood volume can predict symptomatic vasospasm, and we postulated that the blood clot density would also be an important factor involved in such events. The present study aimed to determine the relationship between the incidence of symptomatic vasospasm and the Hounsfield unit (HU) value of the interpeduncular cistern that reflects the density of hematomas.

Methods—
Data from 323 patients admitted and treated at a single center between 2008 and 2017 within 24 hours of subarachnoid hemorrhage onset were retrospectively analyzed. Initial HU values of the interpeduncular cistern were measured using CT, then correlations with the incidence of symptomatic vasospasm and HU values as well as other variables were assessed.

Results—

Symptomatic vasospasm developed in 54 (16.7%) of the 323 patients. The incidence of symptomatic vasospasm was low (1.8%, 2/166) for HU <50, but this incidence increased greatly when the HU value exceeded 50 (23.7%, 22/93 for HU >50 to ≤60, and 45.3%, 29/64 for HU >60). The odds ratio for symptomatic vasospasm was 2.0 (95% CI, 1.6–2.4) per 5 HU increase. Symptomatic vasospasm correlated significantly with intraventricular hemorrhage (
P
=0.05) and with intracerebral hematoma (
P
=0.046) but even more significantly with the HU value of the interpeduncular cistern (
P
<0.0001).

Conclusions—
The HU value of the interpeduncular cistern on initial CT is an accurate and reliable predictor of symptomatic vasospasm.
Exemplarity and Its Discontents: Hellenistic Jewish Wisdom Texts and Greco-Roman Didactic Poetry
Authors: Najman Hindy , Reinhardt Tobias 
Published: November 2019

AbstractThis article sets up a dialogue between two bodies of ancient texts, i.e. Jewish wisdom literature and Greco-Roman didactic of the Hellenistic period, with an awareness of the scholarly and interpretive communities that have studied, taught and transformed these bodies of texts from antiquity until the present. The article does not claim direct influence or cross-pollination across intellectual, religious or social communities in the Hellenistic period. Instead, the article suggests four discrete frameworks for thinking about comparative antiquity: creation, the law, the sage and literary form. The comparative model proposed here intends to create the conditions for noticing parallels and kindred concepts. However, the article resists the temptation to repeat earlier scholarly arguments for dependency or priority of influence. Instead, the essay demonstrates remarkable alignments, suggestively similar developments, and synergies. Perhaps, the ideal first reader for this article is none other than Philo of Alexandria.
The Impacts of Horizontal Resolution on the Seasonally Dependent Biases of the Northeastern Pacific ITCZ in Coupled Climate Models
Authors: Song Fengfei , Zhang Guang J. 
Published: November 2019

ABSTRACTThe double-ITCZ bias has puzzled the climate modeling community for more than two decades. Here we show that, over the northeastern Pacific Ocean, precipitation and sea surface temperature (SST) biases are seasonally dependent in the NCAR CESM1 and 37 CMIP5 models, with positive biases during boreal summer–autumn and negative biases during boreal winter–spring, although the easterly wind bias persists year round. This seasonally dependent bias is found to be caused by the model’s failure to reproduce the climatological seasonal wind reversal of the North American monsoon. During winter–spring, the observed easterly wind dominates, so the simulated stronger wind speed enhances surface evaporation and lowers SST. It is opposite when the observed wind turns to westerly during summer–autumn. An easterly wind bias, mainly evident in the lower troposphere, also occurs in the atmospheric model when the observed SST is prescribed, suggesting that it is of atmospheric origin. When the atmospheric model resolution is doubled in the CESM1, both SST and precipitation are improved in association with the reduced easterly wind bias. During boreal spring, when the double-ITCZ bias is most significant, the northern and southern ITCZ can be improved by 29.0% and 18.8%, respectively, by increasing the horizontal resolution in the CESM1. When dividing the 37 CMIP5 models into two groups on the basis of their horizontal resolutions, it is found that both the seasonally dependent biases over the northeastern Pacific and year-round biases over the southeastern Pacific are reduced substantially in the higher-resolution models, with improvement of ~30% in both regions during boreal spring. Close relationships between wind and precipitation biases over the northeastern and southeastern Pacific are also found among CMIP5 models.
Use of adaptable solutions to achieve near-zero energy buildings through a combined thermal and comfort performance approach
Authors: Ochoa Carlos , Massey Beth 
Published: November 2019

The existing residential building stock in many industrialized countries is large but extremely energy inefficient, despite the existence of energy directives that apply mostly to new construction. Prefabricated building refurbishment for energy upgrading is a viable option for the existing building stock, but solutions need to adapt to each case and usage in order to respond to specific requirements. The “RECO2ST” project (Horizon 2020) is used as example of a forecast methodology that can help achieve nearly zero energy refurbishments, through selection of innovative modular elements for the opaque and transparent areas of the building envelope, covering diverse energy reduction strategies while improving thermal comfort and indoor air quality. This integrated approach is not usual in the field. The Technical Note studies a series of facade and active window technologies that supply climate strategies such as insulation, heat recovery and ventilation. The methodology is demonstrated for three sample cases using a typical refurbishment scenario. It is evaluated through energy simulation and analysis of improvements in thermal comfort and indoor air quality indicators. Practical application: The methodology helps to reduce guesswork for actions to be taken in order to refurbish and upgrade the existing housing stock to comply with current energy directives. It takes into account at the same time energy performance and user comfort, as expressed through indoor air quality.
Effect of blood viscosity on the performance of virtually wall-less venous cannulas
Authors: Abdel-Sayed Saad , Abdel-Sayed Philippe , Berdaj Denis , Ferrari Enrico , Halbe Maximilian , von Segesser Ludwig Karl , Maisano Francesco 
Published: November 2019

Aim: This study was designed to quantify the influence of blood as test medium compared to water in cannula bench performance assessment. Methods: An in vitro circuit was set-up with silicone tubing between two reservoirs. The test medium was pumped from the lower reservoir by centrifugal pump to the upper reservoir. The test-cannula was inserted in a silicone tube connected between the lower reservoir and the centrifugal pump. Flow rate and pump inlet-pressure were measured for wall-less versus thin-wall cannula using a centrifugal pump in a dynamic bench-test for an afterload of 40-60 mmHg using two media: blood 10 g/dL and 5.6 g/dL and water 0 g/dL. Results: The wall-less cannula showed significantly higher flows rates as compared to the thin-wall cannula (control), with both hemoglobin concentrations and water. Indeed, for a target volume of 200-250 mL of blood (Hg 10 g/dL) in the upper reservoir, the cannula outlet pressure (P) was −14 ± 14 mmHg versus −18 ± 11 mmHg for the wall-less and control respectively; the cannula outlet flow rate (Q) was 3.91 ± 0.41 versus 3.67 ± 0.45 L/min, respectively. At the same target volume but with a Hg of 5.7 g/dL, P was −16 ± 12 mmHg versus −19 ± 12 mmHg and Q was 4 ± 0.1 versus 4 ± 0.4 L/min for the wall-less cannula and control respectively. Likewise, P and Q values with water were −1 mmHg versus −0.67 ± 0.58 mmHg and 4.17 ± 0.45 L/min versus 4.08 ± 0.47 L/min for the wall-less and control respectively. Conclusion: Walls-less cannula showed 5.6% less pump inlet-pressure differences calculated between blood and water, as compared to that of thin-wall cannula (−21 times). Flow differences were 6% and 10% for the walls-less and thin-wall cannula respectively. We conclude that testing the cannula performance with water is a good scenario and can overestimate the flow by a 10%. However, superiority for wall-less is preserved with both water and blood.
Effects of an adenosine A2A agonist on the rewarding associative properties of nicotine and neural plasticity in a rodent model of schizophrenia
Authors: Gill Wesley Drew , Shelton Heath W , Burgess Katherine C , Brown Russell W 
Published: November 2019

Background: Adenosine A2a receptors form a mutually inhibitory heteromeric complex with dopamine D2 receptors such that each receptor exhibits lower sensitivity to its agonist after the opposing receptor agonist is bound. This study analyzed the effects of CGS 21680, an adenosine A2A agonist, on nicotine conditioned place preference (CPP) in adolescence using a rodent model of schizophrenia (SZ). Methods: Rats were treated from postnatal day (P) 1 to P21 with saline or the dopamine D2/D3 agonist quinpirole (NQ treatment) and raised to P41. After an initial preference test, rats were conditioned with saline or nicotine (0.6 mg/kg base) from P43 to P51. CGS 21680 (0.03 or 0.09 mg/kg) was given 15 minutes before nicotine was administered. The post-conditioning test was administered on P52. On P53, the nucleus accumbens (NAcc) was analyzed for brain-derived neurotrophic factor (BDNF) and glial cell-lined neurotrophic factor (GDNF). Results: Results revealed that NQ treatment enhanced nicotine CPP, and both doses of CGS 21680 alleviated this enhancement. Nicotine also resulted in a CPP in controls, which was alleviated by both doses of CGS 21680. BDNF closely followed the behavioral results: CGS 21680 alleviated the enhancement in NAcc BDNF in NQ-treated animals, and eliminated the increase in NAcc BDNF produced by nicotine in controls. NQ-treated animals conditioned to nicotine resulted in an increase of NAcc GDNF, but this was eliminated by CGS 21680. Both BDNF and GDNF correlated with CPP performance. Conclusions: Results revealed that an adenosine A2A agonist decreased the rewarding aspects of nicotine and its accompanying neural plasticity changes in a model of SZ.