bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting Successful Aging at One Hundred Years of Age
Authors: Araújo Lia , Ribeiro Oscar , Teixeira Laetitia , Paúl Constança 
Published: September 2015

Objective: The present study is based upon a multidimensional model of successful aging. It aims to identify subgroups of centenarians sharing communalities in successful aging profiles, and determine the role of sociodemographic factors and psychological, social, and economic resources on successful aging. Methods: A total of 80 centenarians were face-to-face interviewed. A cluster analysis was performed to identify distinct groups of successful aging, and logistic regression models were performed considering the cluster membership as dependent covariate. Results: Two distinct clusters were grouped, with 40 centenarians in each, one of them presenting better results in all domains. Male sex and better income adequacy were the best predictors of successful aging. Conclusion: Results help to identity different patterns of successful aging and provide greater clarity regarding its correlates, increasing current understanding of its modifiable aspects.
Searching for Cedar
Authors: Willson Thomas J. , Shams Alexandra , Lospinoso Joshua , Weitzel Erik , McMains Kevin 
Published: September 2015

ObjectiveTo assess the effect of a single aeroallergen on Internet search activity in 3 distinct geographic regions over time.Study DesignA retrospective time series analysis.SettingTertiary academic medical center.MethodsMountain Cedar pollen counts spanning the periods from 2011 to 2014 were collected for San Antonio, Dallas–Ft Worth, and Houston metro regions (Texas). Google search data for the corresponding period and regions were also obtained for the search terms pollen and mountain cedar. Data were analyzed through time series plots and autoregressive integrated moving average.ResultsSeasonal maximum pollen counts were greatest in San Antonio, ranging from 5413 to 9982 grains per cubic centimeter. In San Antonio, there was a strong, positive, and statistically significant effect of mountain cedar pollen count on search activity for both pollen (P =. 001) and mountain cedar (P <. 001) when evaluated by autoregressive integrated moving average.ConclusionsEnvironmental levels of a single allergen—mountain cedar pollen—show a geographic and temporal relationship between Internet searches and mountain cedar pollen, based on Google Trends. These data are useful to understand patients’ perceptions of the health risk presented by mountain cedar pollen. In turn, this information affords practitioners the opportunity to offer targeted patient education in a geographically unique region, as well as adjust surveillance of related pathologies.
Past climate change on Sky Islands drives novelty in a core developmental gene network and its phenotype
Authors: Favé Marie-Julie , Johnson Robert A. , Cover Stefan , Handschuh Stephan , Metscher Brian D. , Müller Gerd B. , Gopalan Shyamalika , Abouheif Ehab 
Published: September 2015

AbstractBackgroundA fundamental and enduring problem in evolutionary biology is to understand how populations differentiate in the wild, yet little is known about what role organismal development plays in this process. Organismal development integrates environmental inputs with the action of gene regulatory networks to generate the phenotype. Core developmental gene networks have been highly conserved for millions of years across all animals, and therefore, organismal development may bias variation available for selection to work on. Biased variation may facilitate repeatable phenotypic responses when exposed to similar environmental inputs and ecological changes. To gain a more complete understanding of population differentiation in the wild, we integrated evolutionary developmental biology with population genetics, morphology, paleoecology and ecology. This integration was made possible by studying how populations of the ant speciesMonomorium emersonirespond to climatic and ecological changes across five ‘Sky Islands’ in Arizona, which are mountain ranges separated by vast ‘seas’ of desert. Sky Islands represent a replicated natural experiment allowing us to determine how repeatable is the response ofM. emersonipopulations to climate and ecological changes at the phenotypic, developmental, and gene network levels.ResultsWe show that a core developmental gene network and its phenotype has kept pace with ecological and climate change on each Sky Island over the last ∼90,000 years before present (BP). This response has produced two types of evolutionary change within an ant species: one type is unpredictable and contingent on the pattern of isolation of Sky lsland populations by climate warming, resulting in slight changes in gene expression, organ growth, and morphology. The other type is predictable and deterministic, resulting in the repeated evolution of a novel wingless queen phenotype and its underlying gene network in response to habitat changes induced by climate warming.ConclusionOur findings reveal dynamics of developmental gene network evolution in wild populations. This holds important implications: (1) for understanding how phenotypic novelty is generated in the wild; (2) for providing a possible bridge between micro- and macroevolution; and (3) for understanding how development mediates the response of organisms to past, and potentially, future climate change.
Microvascular reactivity and clinical outcomes in cardiac surgery
Authors: Kim Tae Kyong , Cho Youn Joung , Min Jeong Jin , Murkin John M. , Bahk Jae-Hyon , Hong Deok Man , Jeon Yunseok 
Published: September 2015

Abstract
Introduction
Microvascular reactivity is decreased in patients with septic shock; this is associated with worse clinical outcomes. The objectives of the present study were to investigate microvascular reactivity in cardiac surgery patients and to assess any association with clinical outcomes.

Methods
We retrospectively analyzed a prospectively collected registry. In total, 254 consecutive adult patients undergoing cardiac and thoracic aortic surgeries from January 2013 through May 2014 were analyzed. We performed a vascular occlusion test (VOT) by using near-infrared spectroscopy to measure microvascular reactivity. VOT was performed three times per patient: prior to the induction of anesthesia, at the end of surgery, and on postoperative day 1. The primary endpoint was a composite of major adverse complications, including death, myocardial infarction, acute kidney injury, acute respiratory distress syndrome, and persistent cardiogenic shock.

Results
VOT recovery slope decreased during the surgery. VOT recovery slope on postoperative day 1 was significantly lower in patients with composite complications than those without (3.1 ± 1.6 versus 4.0 ± 1.5 %/s, P = 0.001), although conventional hemodynamic values, such as cardiac output and blood pressure, did not differ between the groups. On multivariable regression and linear analyses, low VOT recovery slope on postoperative day 1 was associated with increases of composite complications (odds ratio 0.742; 95 % confidence interval (CI) 0.584 to 0.943; P = 0.015) and hospital length of stay (regression coefficient (B) −1.276; 95 % CI −2.440 to −0.112; P = 0.032).

Conclusion
Microvascular reactivity largely recovered on postoperative day 1 in the patients without composite complications, but this restoration was attenuated in patients with composite complications.

Trial registration
ClinicalTrials.gov NCT01713192. Registered 22 October 2012.
Best proximity point theorems for α-nonexpansive mappings in Banach spaces
Authors: Kong Dezhou , Liu Lishan , Wu Yonghong 
Published: September 2015

AbstractIn this paper, we discuss sufficient and necessary conditions for the existence of best proximity points for non-self-α-nonexpansive mappings in Banach spaces. We obtain convergence results under some assumptions, and we prove the existence of common best proximity points for a family of non-self-α-nonexpansive mappings.
Development of an itraconazole-loaded gelatin microcapsule with enhanced oral bioavailability: physicochemical characterization and in-vivo evaluation
Authors: Li Dong Xun , Park Young-Joon , Oh Dong Hoon , Joe Kwan Hyung , Lee Jung Hoon , Yeo Woo Hyun , Yong Chul Soon , Choi Han-Gon 
Published: September 2015

Abstract

Objectives
The aim of this study was to develop a novel itraconazole-loaded gelatin microcapsule without ethanol with enhanced oral bioavailability.

Methods
Various gelatin microcapsules were prepared using a spray-drying technique. Their physicochemical properties, dissolution, characteristics and pharmacokinetics in rats were evaluated and compared with those of a commercial product.

Key findings
The gelatin microcapsule at a weight ratio for itraconazole/gelatin/citric acid of 1 : 3 : 0.3 was spherical in shape with a smooth surface and inner hole, and gave a maximum drug solubility of about 700 μg/ml. The gelatin microcapsule dramatically increased the initial dissolution rate of itraconazole compared with a commercial product in simulated gastric fluids (pH 1.2). Moreover, at the same dose as the commercial product, it gave significantly higher initial plasma concentrations, Cmax and AUC of itraconazole in rats than did the commercial product, indicating that providing the drug in the gelatin microcapsule caused enhanced absorption in rats. At half dose, it gave similar AUC, Cmax and Tmax values to the commercial product, suggesting that it was bioequivalent to the commercial product in rats.

Conclusions
The itraconazole-loaded gelatin microcapsule without ethanol developed using a spray-drying technique at half the dose of the commercial product can deliver itraconazole in a pattern that allows fast absorption in the initial phase, making it bioequivalent to the commercial product.
Pretreatment with the ciclosporin derivative NIM811 reduces delayed neuronal death in the hippocampus after transient forebrain ischaemia
Authors: Hokari Masaaki , Kuroda Satoshi , Iwasaki Yoshinobu 
Published: September 2015

Abstract

Objectives
There have been several previous studies showing that ciclosporin, a ligand for cyclophilin D (CypD), reduces mitochondrial permeability transition (mPT) and ameliorates delayed neuronal death. NIM811 is a non-immunosuppressive ciclosporin derivative that also inhibits mPT, but has significantly less cytotoxicity than ciclosporin. Actually, in animal experiments, several investigators have reported that NIM811 ameliorates central nervous system disorders, such as traumatic brain injury, transient focal cerebral ischaemia and spinal cord injury. Therefore, we evaluated whether the ciclosporin derivative, NIM811 reduces mPT and ameliorates delayed neuronal death in the hippocampal CA1 sectors in mice when subjected to transient forebrain ischaemia.

Methods
Male C57BL/6 mice were treated with 50 mg/kg ciclosporin, 10, 50 or 100 mg/kg NIM811 or phosphate-buffered saline. At 30 min post-injection, all mice were subjected to 20 min bilateral common carotid artery occlusion (BCCAO). To estimate delayed neuronal death, the sections were prepared for HE staining and terminal deoxynucleotidyl transferase-mediated dUTP end-labelling (TUNEL) staining at 72 h after 20 min BCCAO. Furthermore, using 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolocarbocyanine iodide (JC-1) staining technique, we evaluated whether NIM811 (1, 10, 100 or 1000 μm) inhibited mPT in the neurons exposed to 100 μm glutamate.

Results
Both delayed neuronal injury and apoptosis in the hippocampal CA1 sectors were significantly ameliorated at 72 h after transient forebrain ischaemia in the mice treated with 100 mg/kg NIM811 or 50 mg/kg ciclosporin. The treatments with 100 μm and 1000 μm NIM811 significantly inhibited the reduction of mitochondrial membrane potential in the neurons exposed to 100 μm glutamate.

Conclusions
These findings strongly suggest that NIM811 inhibits mPT and ameliorates delayed neuronal death in mice subjected to transient forebrain ischaemia.
Imidazole inhibits B16 melanoma cell migration via degradation of β-catenin
Authors: Jeong Yun-Mi , Li Hailan , Kim Su Yeon , Yun Hye-Young , Baek Kwang Jin , Kwon Nyoun Soo , Kim Dong-Seok 
Published: September 2015

Abstract

Objectives
In the present study, we determined whether or not imidazole affects B16 murine melanoma cell migration to prevent melanoma metastasis.

Methods
To determine the effects of imidazole on melanoma cell migration, B16 cells were treated with imidazole at various concentrations, and the migration was measured using a scratch migration assay.

Key findings
Imidazole did not exhibit cytotoxic effects on B16 cells at a concentration below 100 μm. The anti-migratory activity of imidazole was determined by the scratch migration assay. Our results showed that imidazole significantly inhibits B16 cell migration. It is known that the Wnt/β-catenin signalling pathway regulates the progression of melanocytic tumours and determines the prognosis in cutaneous melanomas. Western blot analysis demonstrated that imidazole increases phosphorylation of β-catenin and subsequent degradation of β-catenin. Moreover, inhibition of melanoma cell migration by imidazole was restored by MG132, a proteasome inhibitor, via inhibition of β-catenin degradation.

Conclusions
Imidazole inhibits B16 cell migration through β-catenin degradation, suggesting that imidazole is a potential candidate for the treatment of metastatic melanoma.
Cardioprotective effect of matrine on isoproterenol-induced cardiotoxicity in rats
Authors: Li Xiaobing , Zhou Ru , Zheng Ping , Yan Lin , Wu Yang , Xiao Xu , Dai Guidong 
Published: September 2015

Abstract

Objectives
This study was designed to explore the effect and mechanism of matrine, an active component of Chinese traditional medicine, on isoproterenol-induced acute cardiotoxicity in rats.

Methods
Acute myocardial injury was induced in rats by daily subcutaneous injection of isoproterenol (85 mg/kg) for two days. Haemodynamic and biochemical parameters were measured and histopathological examination was performed.

Key findings
Chronic oral administration of matrine (50, 100 or 200 mg/kg per day for 10 days) significantly reduced the release of lactic dehydrogenase, glutamic oxaloacetic transaminase and creatine kinase after isoproterenol-induced myocardial ischaemic injury, improved the left ventricular (LV) dysfunction, including increased LV systolic pressure (LVSP), maximum rate of developed LV pressure (LV dP/dtmax) and minimum rate of developed LV pressure (LV dP/dtmin), increased the activity of superoxide dismutase, catalase and glutathione peroxidase, and also decreased the content of the lipid peroxidation product malondialdehyde in plasma and myocardial tissues in rats. Acute oral administration of matrine at a dose of 100 or 200 mg/kg for two days also had a cardioprotective effect on this rat model. The protective role of matrine on isoproterenol-induced myocardial damage was further confirmed by histopathological examination. There were no significant changes in heart rate and blood pressure in all experimental groups.

Conclusions
Our results suggest that matrine has a significant cardioprotection against isoproterenol-induced cardiotoxicity through its antioxidant property.
Nasal absorption and local tissue reaction of insulin nanocomplexes of trimethyl chitosan derivatives in rats
Authors: Jintapattanakit Anchalee , Peungvicha Penchom , Sailasuta Achariya , Kissel Thomas , Junyaprasert Varaporn Buraphacheep 
Published: September 2015

Abstract

Objectives
The objective of this work was to explore the potential and safety of trimethyl chitosan (TMC) and PEGylated TMC for improved absorption of insulin after nasal administration.

Methods
The nasal absorption of insulin nanocomplexes of TMC or PEGylated TMC was evaluated in anaesthetized rats. Concomitantly, the histopathological effects of these nanocomplexes on rat nasal mucosa were studied using a perfusion fixation technique.

Key findings
All insulin nanocomplexes containing TMC or PEGylated TMC showed a 34–47% reduction in the blood glucose concentration, when the insulin absorption through the rat nasal mucosa was measured indirectly. In addition, the relative pharmacodynamic bioavailability (Fdyn) of the formulations was found to be dependent upon the charge ratio of insulin and polymer, regardless of polymer structure. The Fdyn apparently decreased with increasing charge ratio of insulin : polymer. Although acute alterations in nasal morphology by the formulations were affected by the charge ratio of insulin and polymer, the formulation of insulin/PEGylated TMC nanocomplexes was shown to be less toxic to the nasal epithelial membrane than insulin/TMC nanocomplexes.

Conclusions
PEGylated TMC nanocomplexes were a suitable absorption enhancer for nasal delivery of insulin.
Inhibition of human liver microsomal CYP by nateglinide
Authors: Takanohashi Toshiyuki , Kubo Satoru , Nakayama Akira , Mihara Ryuichi , Hayashi Masahiro 
Published: September 2015

Abstract

Objectives
Nateglinide is metabolized by CYP2C9 and CYP3A4, therefore drug–drug interactions through cytochrome P450 (CYP) inhibition may occur. In this study, we examined the inhibitory effects of nateglinide and its major metabolite N-[trans-4-(1-hydroxy-1-methylethyl)-cyclohexanecarbonyl]-d-phenylalanine (M1) on various CYP isoforms in human liver microsomes.

Methods
We used typical substrates (7-ethoxyresorufin for CYP1A1/2, tolbutamide for CYP2C9, S-mephenytoin for CYP2C19, bufuralol for CYP2D6, chlorzoxazone for CYP2E1 and midazolam for CYP3A4) in the evaluation of the inhibitory effects, and examined the possibility of mechanism-based inhibition (MBI) by evaluating the influence of pre-incubation in the inhibition.

Key findings
The results showed that nateglinide inhibited CYP2C9 and CYP2C19 with an IC50app (apparent value of the 50% inhibitory concentration) of 125 μmol/l and 946 μmol/l, respectively, while M1 did not inhibit any of the CYP isoforms. The inhibition constant (Ki) value of the inhibitory effect of nateglinide on CYP2C9 and the 1 + Iin,max,u/Ki value were estimated (where Iin,max,u= the maximum unbound concentration of nateglinide). The 1 + Iin,max,u/Ki value was 1.02 (close to 1), suggesting a low risk of drug–drug interactions. The influence of pre-incubation on the inhibition by nateglinide of CYP3A4, CYP2C9 and CYP2C19 was examined. The results revealed that the inhibition of CYP by nateglinide was not influenced by pre-incubation, and that the possibility of MBI is very low.

Conclusions
The possibility of drug–drug interactions involving nateglinide that might be attributable to CYP inhibition is low.
Acute withdrawal induced by adenosine A1-receptor activation in isolated guinea-pig ileum: role of opioid receptors and effect of cholecystokinin
Authors: Marini Pietro , Romanelli Luca , Valeri Daniela , Tucci Paolo , Valeri Pacifico , Palmery Maura 
Published: September 2015

Abstract

Objectives
In isolated guinea-pig ileum, the μ-opioid acute withdrawal response is under control of several neuronal systems, including the κ-opioid and the A1-adenosine systems, which are involved in the μ-withdrawal response inhibitory control. After μ-opioid system stimulation, indirect activation of both κ-opioid and A1-adenosine systems is prevented by the peptide cholecystokinin-8 (CCk-8). Guinea-pig ileum exposed to A1-adenosine agonist (CPA), shows a withdrawal contracture precipitated by the A1-adenosine antagonist (CPT). We investigated this response.

Methods
We investigated the involvement of the opioid system in the A1-adenosine acute withdrawal response in guinea-pig ileum, the potential induced cross-dependence between the A1 and the opioid system and also the interaction between the CCk-8 and A1 systems.

Key findings
We found that in the guinea-pig ileum preparation exposed to CPA, μ- and κ-opioid antagonists increased the withdrawal response to CPT. Tissues exposed to CPA showed a contractile response to the opioid receptor antagonist naloxone only after complete removal of the A1-agonist. In the presence of CPA, the response to CCk-8 was inhibited while a significant increase in CPT response intensity was observed.

Conclusions
In guinea-pig ileum, stimulation of the A1 system indirectly activates both μ- and κ-opioid systems; this indirect activation is significantly, albeit not completely, antagonised by CCk-8. Cross dependence between A1 and opioid systems was also observed.
Influence of penetration enhancers on topical delivery of 5-aminolevulinic acid from bioadhesive patches
Authors: Morrow Desmond I J , McCarron Paul A , Woolfson A David , Juzenas Petras , Juzeniene Asta , Iani Vladimir , Moan Johan , Donnelly Ryan F 
Published: September 2015

Abstract

Objectives
The inclusion of chemical penetration enhancers in a novel patch-based system for the delivery of 5-aminolevulinic acid (ALA) was examined in vitro and in vivo. Poor penetration of ALA has been implicated as the primary factor for low response rates achieved with topical ALA-based photodynamic therapy of thicker neoplastic lesions, such as nodular basal cell carcinomas.

Methods
Several chemical permeation enhancers (dimethylsulfoxide, Labrafac CC, Labrafac PG and Labrafil M1944CS) were incorporated into bioadhesive patches tailored to deliver 19 mg ALA/cm2.

Key findings
In-vitro depth penetration studies into excised porcine skin showed that high concentrations of ALA (&gt;9 μmol/cm3) could be delivered to a depth of 1.875 mm. However, inclusion of permeation enhancers did not significantly increase ALA delivery, relative to the control (P &gt; 0.05). In-vivo studies were in strong agreement with in-vitro results, with formulations containing chemical enhancers showing no improvement in delivery compared with the control.

Conclusions
The patches designed in this work are suited to defineable ALA delivery without the need to immobilise patients for up to 6 h, as is common with the cream-under-occlusion approach. Overall, permeation enhancers were not found to markedly enhance the topical delivery of ALA. However, chemical penetration enhancers may have a greater effect on the delivery of more lipophilic ALA prodrugs, which are thought to primarily permeate the stratum corneum via the intercellular pathway.
Effect of lipopeptides and iontophoresis on aciclovir skin delivery
Authors: Nicoli Sara , Eeman Marc , Deleu Magali , Bresciani Eleonora , Padula Cristina , Santi Patrizia 
Published: September 2015

Abstract

Objectives
Lipopeptides are compounds derived from microorganisms that exhibit pronounced surface and emulsifying activity. The ability of lipopeptides to interact with stratum corneum lipids makes them candidates as transdermal penetration enhancers. We have investigated the potential of two lipopeptides, fengycin and surfactin, to act as enhancers for the transdermal penetration and skin accumulation of aciclovir.

Methods
To investigate a possible synergistic effect, surfactin and fengycin were associated with anodal iontophoresis. Permeation experiments were performed using vertical diffusion cells and pig ear skin as barrier. Differential scanning calorimetry was used to study the interaction between fengycin and stratum corneum lipids.

Key findings
The results obtained indicated that surfactin and fengycin were not suitable to enhance aciclovir flux across the skin, not even when associated with iontophoresis. Aciclovir flux was slightly decreased in passive conditions and unchanged (fengycin) or decreased (surfactin) in anodal iontophoretic conditions. When applied in passive conditions, fengycin and surfactin increased aciclovir concentration in the epidermis by a factor of 2.

Conclusions
Surfactin and fengycin did not enhance aciclovir transport across the skin (not even when associated with iontophoresis) although they increased aciclovir concentration in the epidermis by a factor of 2.