Input: The aggregation behavior of cationic 5, 5', 6, 6'-tetrachloro-1, 1', 3, 3'-tetraethylbenzimidacarbocyanine with chloride (TTBC-Cl) or iodide counterions (TTBC-I) in aqueous solution is investigated by absorption, linear dichroism, and fluorescence spectroscopies, as well as cryogenic transmission electron microscopy (cryo-TEM) and atomic force microscopy (AFM).

5, 5', 6, 6'-tetrachloro-1, 1', 3, 3'-tetraethylbenzimidacarbocyanine

chloride

TTBC-Cl

iodide

TTBC-I


Input: TTBC-Cl is found to form J-aggregates with a classical Davydov-split absorption band (type I spectrum) even under different preparation conditions.

TTBC-Cl


Input: These aggregates remain stable for months.


Input: Unlike the chloride salt, the iodide salt TTBC-I forms two different types of J-aggregates depending on the pH of the aqueous solution.

chloride

iodide

TTBC-I


Input: The TTBC-I aggregates prepared in pure water (pH = 6) are characterized by a single redshifted absorption band (type III spectrum), whereas those prepared in alkaline solution at pH = 13 show a typical Davydov-split (type I) absorption band.

TTBC-I


Input: Despite differences in counterions, preparation method, stability, and spectroscopic behavior, cryo-TEM reveals an identical tubular architecture for all these J-aggregates.


Input: Among the new structure models discussed here is a cylindrical brickwork layer of dye molecules for single-banded J-aggregates (type III).


Input: For Davydov-split aggregates (type I), a molecular herringbone-like pattern is proposed instead.


Input: Moreover, absorption spectra have revealed an additional single redshifted absorption band (type II spectrum) that is assigned to a surface aggregate and is induced by a specific interaction of the dye cation with the negatively charged cuvette wall.


Input: AFM measurements of analogous preparations on negatively charged mica surfaces have supported this interpretation and revealed the formation of monolayered sheet structures.


Input: Synthesis of indolyl-3-acetonitrile derivatives and their inhibitory effects on nitric oxide and PGE2 productions in LPS-induced RAW 264. 7 cells.

nitric oxide


Input: Arvelexin is one of major constituents of Brassica rapa that exerts anti-inflammatory activities.

Arvelexin


Input: Several indolyl-3-acetonitrile derivatives were synthesized as arvelexin analogs and evaluated for their abilities to inhibit NO and PGE2 productions in LPS-induced RAW 264. 7 cells.

arvelexin

NO


Input: Of the indolyl-3-acetonitriles synthesized, compound 2k, which possesses a hydroxyl group at C-7 position of the indole ring and an N-methyl substituent, more potently inhibited NO and PGE2 productions and was less cytotoxic than arvelexin on macrophage cells.

hydroxyl

indole

N-methyl

NO

arvelexin


Input: Discovery of a synthetic Aminopeptidase N inhibitor LB-4b as a potential anticancer agent.


Input: APN inhibitors have been considered as potential anticancer agents for years.


Input: LB-4b is the first synthetic APN inhibitor to be evaluated for both of its anti-invasion and anti-angiogenesis effects.


Input: As a potent synthetic APN inhibitor (IC50 = 850nM, versus bestatin of 8. 1 mu M), LB-4b was determined to have more significant block effects to cancer cell invasion and angiogenesis than bestatin.

bestatin

bestatin


Input: Besides, it is able to be easily synthesized with a high total yield, while the reported synthetic methods of bestatin are much more complex.

bestatin


Input: Atropa acuminata Royle Ex Lindl. blunts production of pro-inflammatory mediators eicosanoids., leukotrienes, cytokines in vitro and in vivo models of acute inflammatory responses.

eicosanoids

leukotrienes


Input: ETHNOPHARMACOLOGICAL RELEVANCE: Atropa acuminata Royle Ex Lindl. has been widely used in folk medicine for several inflammatory disorders such as arthritis, asthma, conjunctivitis, encephalitis, pancreatitis, peritonitis, acute infections and neuroinflammatory disorders.


Input: AIM OF THE STUDY: Our aim was to evaluate Atropa acuminata for its anti-inflammatory properties and to delineate its possible mechanism of action on the modulation of the inflammatory mediators.


Input: MATERIALS AND METHODS: We investigated the inhibitory action of ethanolic extract of Atropa acuminata (AAEE) on production of NO, TNF-alpha and IL-1 beta in lipopolysaccharide (LPS)-stimulated RAW264. 7 cells and also assayed it for COX 1/2 and 5-LOX inhibitory activities.

NO


Input: Next AAEE was tested in acute inflammatory animal models., carragenean induced rat paw edema, carragenean induce pleurisy in rats and vascular permeability in mice and the effects on NO, PGE2 and LTB4 production in the pleural fluid and paw exudates were evaluated.

NO


Input: In addition the effects on leukocyte migration and exudation and vascular permeability were also observed.


Input: RESULTS: Our findings summarized novel anti-inflammatory mechanisms for Atropa acuminata based on dual in vitro cyclooxygenase 1/2/and 5-Lipoxygenase inhibitory activities and also significant downregulation of nitric oxide (NO) and pro-inflammatory cytokin (TNF-alpha and Il-1 beta) release in LPS-stimulated RAW 246. 7 macrophage cell line.

nitric oxide

NO


Input: In acute inflammatory models in vivo (carragenean induced edema, carragenean induced pleurisy in rats and vascular permeability in mice), AAEE exhibited an extensive diverse mechanism for anti-inflammatory properties.


Input: This was indicated on the basis of dose dependent suppression of multi targeted inflammatory mediators., NO, TNF-alpha and IL-1 beta, eicosanoids., PGE2 and leukotrienes., LTB4 along with significantly decreased leucocyte migration, exudation and decreased vascular permeability.

NO

eicosanoids

leukotrienes


Input: These effects were more potent and prolonged than traditional NSAIDS, thereby indicating fewer side effects.


Input: AAEE was found to be safe for long term administration, as confirmed by the results of acute toxicity studies and MTT assay.

MTT


Input: The complex mode of action of the herbs was attributed possibly due to the high polyphenolic, flavanol and flavonoid content present in the extracts as observed by means of quantitative screening for phytochemicals.

polyphenolic

flavanol

flavonoid


Input: CONCLUSION: Our study provides scientific evidence to support the traditional anti-inflammatory uses of Atropa acuminata and is probably due to inhibitory effects on multiple inflammatory mediators which indicates a promising potential for the development of a strong anti-inflammatory agent from this plant.


Input: Reversal of Morphine Analgesic Tolerance by Ethanol in the Mouse.

Morphine

Ethanol


Input: The chronic use of opioids in humans, accompanied by the development of tolerance, is a dangerous phenomenon in its own right.


Input: However chronic opioid use is often made more dangerous by the co-consumption of other substances.


Input: It has been observed that the blood level of opioids in postmortem analyses of addicts, who consumed ethanol along with the opioid, was much less than that observed in individuals that died from opioids alone.

ethanol


Input: This relationship between ethanol and opioids led us to investigate the hypothesis that ethanol alters tolerance to opioids.

ethanol

ethanol


Input: In the present study, we report that ethanol significantly and dose-dependently reduced the antinociceptive tolerance produced by morphine and the cross tolerance between DAMGO and morphine in the mouse tail-flick test.

ethanol

morphine

DAMGO

morphine


Input: The reversal of morphine tolerance was partially blocked by both the GABAA receptor blocker bicuculline and by the GABAB receptor blocker phaclofen and the administration of both inhibitors completely reversed the effects of ethanol on morphine tolerance.

morphine

bicuculline

phaclofen

ethanol

morphine


Input: Diazepam, like ethanol, decreased morphine tolerance.

Diazepam

ethanol

morphine


Input: However, this inhibition was reversed by the GABAA antagonist bicuculline but not by the GABAB antagonist phaclofen.

bicuculline

phaclofen


Input: These findings have important implications for individuals who abuse opioids and ethanol as well as suggest a mechanism to reduce the amount of opioid needed in chronic pain treatment.

ethanol


Input: Physiological costs and carry-over effects of avian interspecific brood parasitism influence reproductive tradeoffs.


Input: Although models of co-evolution between brood parasites and their hosts primarily focus upon the cost to hosts in the current reproductive bout, the impact of brood parasitism may carry over to future reproductive attempts by altering resource allocation.


Input: Glucocorticoid stress hormones help mediate resource allocation to reproduction, yet they have rarely been examined in brood parasitic systems.


Input: Here we determined if shifts in parental care and corticosterone had carry-over effects on future reproductive effort in the rufous-and-white wren (Thryophilus rufalbus), a host of the Central American striped cuckoo (Tapera naevia).

corticosterone


Input: We found that parasitized parents had significantly higher stress-induced, but not baseline, corticosterone than natural parents during the fledgling stage, which was associated with changes in parental care.

corticosterone


Input: The high investment in current reproduction while parasitized may be due to the value of fledged chicks in tropical systems.


Input: This maladaptive response by parasitized parents was associated with delayed re-nesting and a reduced likelihood of nesting in the subsequent breeding season.


Input: Although a reduction in future reproductive effort can result from a combination of factors, this work suggests that fitness costs of brood parasitism are mediated by changes in corticosterone and parental care behavior that carry over into subsequent breeding seasons.

corticosterone


Input: The short course in toxinology: Training the trainers.


Input: Clinical toxinology is the medical discipline dealing with the diagnosis, treatment and prevention of toxin diseases caused by exposure to venomous animals and poisonous animals, plants and mushrooms.


Input: Currently there is no national or international organisation accrediting or training doctors in this discipline.


Input: A few courses covering some aspects of clinical toxinology exist, either with limited curricula, or with only a minor clinical focus, or with a very regional, non-global focus.


Input: The only comprehensive clinical toxinology course is the one provided in Adelaide, Australia, running regularly since 1997.


Input: Hundreds of doctors from many nations have attended the course since 1997.


Input: This course covers venomous animals, poisonous animals, plants and mushrooms, from a full global perspective, with an international faculty and an exit exam.


Input: Though lasting only one week, extensive pre-reading material is mandated.


Input: The current Course Handbook is about 500 pages.


Input: Emphasis is on clinically relevant information and is focused on the needs of doctors treating cases.


Input: While it is expected that attendees will have, or acquire, direct experience managing cases of toxin disease and will use the knowledge and skills gained in the course in direct patient care, they may also act as resource people in their home region/nation to promote increased skills in clinical toxinology amongst the wider medical workforce.


Input: This course may form the nucleus from which IST can develop a global accredited training scheme in clinical toxinology.


Input: Such a scheme will require input from diverse global regions and will be far more comprehensive and over a much longer time than the current Short Course, though likely will incorporate the Short Course in some way, or a derivative of it.


Input: Two novel saponins of 20, 26-epoxy derivatives of pseudojujubogenin from the seeds of Hovenia trichocarpa.

saponins

20, 26-epoxy

pseudojujubogenin


Input: Two new saponins of 20, 26-epoxy derivatives of pseudojujubogenin, hoduloside XI (1) and hoduloside XII (2) were isolated from the seeds of Hovenia trichocarpa.

saponins

20, 26-epoxy

pseudojujubogenin

hoduloside XI

hoduloside XII


Input: The structures of the new compounds were established by extensive NMR experiments and chemical methods.


Input: Hoduloside XI was confirmed to be 3-O-{beta-d-glucopyranosyl (1 --> 3)-[beta-d-xylopyranosyl (1 --> 2)]-alpha-l-arabinopyranosyl}-20, 26-epoxypseudojujubogenin.

Hoduloside XI

3-O-{beta-d-glucopyranosyl (1 --> 3)-[beta-d-xylopyranosyl (1 --> 2)]-alpha-l-arabinopyranosyl}-20, 26-epoxypseudojujubogenin


Input: Hoduloside XII was identified as 3-O-{beta-d-xylopyranose (1 --> 2) glucopyranosyl (1 --> 3) [rhamnopyranose (1 --> 2)] beta-d-glucopyranosyl}-20, 26-epoxypseudojujubogenin.

Hoduloside XII

3-O-{beta-d-xylopyranose (1 --> 2) glucopyranosyl (1 --> 3) [rhamnopyranose (1 --> 2)] beta-d-glucopyranosyl}-20, 26-epoxypseudojujubogenin


Input: The in vitro cytotoxic activity of compounds 1 and 2 was assayed.


Input: They displayed inhibitive activities against human cancer cell lines HL60 and K562.


Input: Antinociceptive effect and gastroprotective mechanisms of 3, 5-diprenyl-4-hydroxyacetophenone from Ageratina pichinchensis.

3, 5-diprenyl-4-hydroxyacetophenone


Input: The present study aimed to evaluate the antinociceptive activity (in inflammatory and neuropathic pain models) and gastroprotective effect of the 3, 5-diprenyl-4-hydroxyacetophenone (HYDP), isolated from Ageratina pichinchensis.

3, 5-diprenyl-4-hydroxyacetophenone

HYDP


Input: The gastroprotective activity of this plant was previously reported by our workgroup, finding encesanescin to be one active compound.

encesanescin


Input: The present results show that HYDP reduced nociception in a dose-dependent manner in carrageenan and L5/L6 spinal nerve ligation, with efficacies of 72. 6 and 57. 1%, respectively, at doses of 100 and 562mg/kg.

HYDP


Input: HYDP also showed gastroprotective activity in the model of ethanol-induced gastric lesion, with a 75. 59% maximum inhibition of ulcers at a dose of 100mg/kg.

HYDP

ethanol


Input: This gastroprotective effect was attenuated by N (G)-nitro-l-arginine methyl ester, indomethacin and N-ethylmaleimide, indicating that NO, prostaglandins and sulfhydryl groups are involved in the mechanisms of action.

N (G)-nitro-l-arginine methyl ester

indomethacin

N-ethylmaleimide

NO

prostaglandins

sulfhydryl


Input: This is the first evidence, to our knowledge, of the antinociceptive and gastroprotective activities of HYDP.

HYDP


Input: The effect of sodium selenite on lead induced cognitive dysfunction.

sodium selenite


Input: The effect of lead (Pb) on spatial memory and hippocampal long-term potentiation (LTP) as a key risk factor has been widely recognized and the oxidative damage has been proposed as a possible mechanism of lead neurotoxicity.

Pb


Input: Selenium (Se) is a nutritionally essential trace element with known antioxidant potential.

Selenium

Se


Input: In this study we investigated the effect and the underlying mechanisms of Se supplementary on Pb induced cognition and synaptic plasticity impairment.

Se

Pb


Input: Lactating Sprague-Dawley rats (SD rats) were randomly divided to four groups: 0ppm lead acetate (Pb); 0ppm Pb and 0. 2ppm sodium selenite (Se); 100ppm Pb; 100ppm Pb and 0. 2ppm Se.

lead acetate

Pb

Pb

sodium selenite

Se

Pb

Pb

Se


Input: Lactating rats were treated with or without Pb and/or Se throughout lactation until weaning.

Pb

Se


Input: The levels of hippocampal LTP, the spatial memory, the apoptosis of hippocampal neurons, the levels of lactate dehydrogenase (LDH) release, and the serum level of superoxide dismutase (SOD) and malondialdehyde (MDA) were assayed.

lactate

superoxide

malondialdehyde

MDA


Input: It had been observed that in Pb group the spatial memory, the induce level of LTP, the serum SOD level decreased, the LDH release level, the neurons apoptosis level, the serum MDA level increased, while in the Se supplements groups, the spatial memory, the induce level of LTP increased significantly.

Pb

MDA

Se


Input: Compared with the Pb group, Se supplements shown down regulated the level of LDH, the neurons apoptosis and the serum MDA, and up regulated the level of serum SOD.

Pb

Se

MDA


Input: We could draw the conclusion that Se supplements could alleviate toxic effect of lead on hippocampal LTP and spatial memory.

Se


Input: The treated with selenium around 0. 2ppm may protect against spatial memory dysfunction induced by lead exposure.

selenium


Input: A critical examination of best dose analysis for determining cognitive-enhancing potential of drugs: studies with rhesus monkeys and computer simulations.


Input: RATIONALE: Best dose analysis involves identifying the dose associated with the greatest improvement in performance for each subject and comparing performances associated with these individually determined best doses to control performances.


Input: OBJECTIVES: The current experiments were conducted to examine whether significant best dose effects might result from the selective analysis of data rather than an actual drug effect.


Input: METHODS: Experiment 1 examined the effects of nicotine and methylphenidate on delayed matching-to-sample (DMTS) and self-ordered spatial search (SOSS) performances in rhesus monkeys (DMTS: n = 7; SOSS: n = 6) to determine the validity and reliability of best dose effects.

nicotine

methylphenidate


Input: Experiment 2 used Monte Carlo computer simulations to estimate the likelihood of obtaining a significant outcome when the best dose method was applied to randomly generated data sets for which no difference existed.


Input: RESULTS: Significant effects were obtained when the best dose analysis was applied to performances from nondrug sessions, and best dose performances were not significantly different from the best nondrug performances.


Input: The doses identified as best doses from two nicotine dose-response curve determinations were unrelated, and the improvement associated with the best dose observed during the first dose-response curve determination was not reliable when the dose was administered repeatedly.

nicotine


Input: Finally, there was a high likelihood of obtaining a statistically significant difference when no real difference existed.


Input: CONCLUSIONS: Best dose analysis for the identification of potential therapeutic agents should be replaced by single-subject designs.


Input: Exposure of Bacillus subtilis to mercury induces accumulation of shorter tRNA Cys species.

mercury

Cys


Input: RNA processing is an essential pathway in the regulation of genetic expression in the cell.


Input: In this work, Bacillus subtilis was used to understand the effects of mercury on the mechanism of tRNA metabolism.

mercury


Input: The CVAAS (cold vapor atomic absorption spectroscopy) method revealed that from the addition of HgCl2 (0. 75 mu g ml (-1)) during the bacterial exponential phase, ca.


Input: 48% of the added mercury was taken up by the cells.

mercury


Input: This led to an immediate reduction in the rate of cell division.


Input: During this response, we observed accumulation of species shorter than mature tRNA (Cys) over a 10 h period.

Cys


Input: We did not observe this accumulation for another five tRNAs analyzed.


Input: tRNA processing is largely dependent on RNase R and PNPase in B. subtilis.


Input: Thus, when the exonuclease PNPase was absent, we found that the shorter tRNA (Cys) species increased and mature tRNA (Cys) decreased after mercury addition, but this proportion changed during the time analyzed.

Cys

Cys

mercury


Input: However, in the absence of RNase R and PNPase the accumulation of the shorter tRNA (Cys) was more pronounced and the mature form was not recovered.

Cys


Input: In the single rnr mutant strain the shorter tRNA (Cys) was not observed.

Cys


Input: All together, we provide in vivo evidence that PNPase and RNase R are indispensable in controlling tRNA (Cys) quality in the presence of mercury.

Cys

mercury


Input: Insights into the adsorption and energy transfer of Ag clusters on the AgCl (100) surface.

Ag

AgCl


Input: It is fundamental to uncover the real adsorption properties of Ag clusters on an AgCl surface and the energy transfer mechanisms at the interface to understand the highly active photocatalytic performance and the stability of the plasmonic photocatalyst Ag @AgCl.

Ag

AgCl

Ag

AgCl


Input: Based on density functional theory calculations we provide valuable insights into the binding nature of Ag clusters on AgCl surface, where the binding between Ag atoms in the cluster and on the surface plays a decisive role in determining the most stable adsorption configurations.

Ag

AgCl

Ag


Input: Our results demonstrate that there is energy transfer from the plasmonic metals to substrate.


Input: The hot holes excited by the decay of surface plasmon resonance on the metals can diffuse into the Cl ions in the outermost two layers of the surface producing highly oxidative Cl atoms.

Cl

Cl


Input: The dipole-dipole interaction between the plasmonic metal clusters and substrate Cl ions can also generate electron-hole pairs in the surface layers.

Cl


Input: It is deduced that the positively charged nature of adsorbed clusters acting as electron trapping centers and reduction sites plays a crucial role in keeping the stability of the Ag @AgCl system during the photocatalytic process.

Ag

AgCl


Input: Finally, the validity of the cluster adsorption model for energy transfer is verified with respect to the nucleation and aggregation process of Ag atoms on the AgCl surface and a detailed description of the formation and evolution of Ag nanoparticles on an AgCl surface is provided.

Ag

AgCl

Ag

AgCl


Input: The present study may be helpful for understanding and designing this novel plasmonic photocatalyst and can be useful for investigating other relevant photocatalysts as well.


Input: Diagnostic performance of (99m) Tc-MIBI scan in predicting the malignancy of thyroid nodules: a meta-analysis.

(99m) Tc-MIBI


Input: Several studies have investigated the diagnostic performance of (99m) Tc-MIBI scan in the evaluation of thyroid nodules suspicious for malignancy with conflicting results.

(99m) Tc-MIBI


Input: The aim of our study is to meta-analyze published data on this topic.


Input: A comprehensive literature search of studies published through December 2012 regarding the diagnostic performance of (99m) Tc-MIBI scan in the evaluation of thyroid nodules suspicious for malignancy was carried out.

(99m) Tc-MIBI


Input: Pooled sensitivity and specificity of (99m) Tc-MIBI scan on a per lesion-based analysis and the area under the ROC curve were calculated.

(99m) Tc-MIBI


Input: Pathological reports of thyroid nodules were considered as reference standard.


Input: Twenty-one studies were included in the meta-analysis.


Input: Pooled sensitivity and specificity of (99m) Tc-MIBI scan in detecting malignant thyroid nodules were 85. 1% [95% confidence interval (95% CI): 81. 1-88. 5%] and 45. 7% (95% CI: 42. 7-48. 7%), respectively, on a per lesion-based analysis, irrespective of eventual results of previous technetium pertechnetate ((99m) TcO4) or iodine-123 ((123) I) scan.

(99m) Tc-MIBI

technetium pertechnetate

(99m) TcO4

(123) I


Input: The area under the ROC curve was 0. 78.


Input: A sub-analysis restricted to data on hypofunctioning nodules on (99m) TcO4 or (123) I scans was performed: pooled sensitivity and specificity of (99m) Tc-MIBI scan in these nodules were 82. 1% (95% CI: 77. 2-86. 3%) and 62. 8% (95% CI: 58. 9-66. 7%), respectively, on a per lesion-based analysis.

(99m) TcO4

(123) I

(99m) Tc-MIBI


Input: The area under the ROC curve was 0. 81.


Input: (99m) Tc-MIBI scan is a sensitive diagnostic tool in predicting the malignancy of thyroid nodules.

(99m) Tc-MIBI


Input: Therefore, this imaging method could be helpful in patients with thyroid nodules in which malignancy is suspected on the basis of conventional diagnostic techniques.


Input: Higher specificity can be reached when hypofunctioning thyroid nodules are considered.


Input: Synthesis, antimicrobial evaluation and molecular modelling of novel sulfonamides carrying a biologically active quinazoline nucleus.

sulfonamides

quinazoline


Input: A novel series of quinazolines 5-10, triazoloquinazolines 11-17 and triazinoquinazoline 19 bearing a biologically active sulfonamide moiety were synthesized, utilizing methyl 2-isothiocyanato benzoate 2.

quinazolines

triazoloquinazolines

triazinoquinazoline

sulfonamide

methyl 2-isothiocyanato benzoate


Input: Some of the newly synthesized compounds revealed promising bacterial growth inhibition, compared with the ampicillin, as the reference drug.

ampicillin


Input: A LigandScout approach-generated pharmacophore model for the Staph aureus bacteria growth inhibition was done.


Input: The degree of fitting of the test set compounds (3, 4, 6, 8, 11, 17) to the generated hypothetical model revealed a qualitative measure of the more or less microbial inhibition of Staphylococcus aureus.


Input: Compounds (7, 8, 10, 12, 15, 17 and 22), which revealed significant activity, are able to effectively satisfy the proposed pharmacophore geometry, using the energy accessible conformers (E conf < 20 kcal/mol).


Input: Agreement Between ICU Clinicians and Electrophysiology Cardiologists on the Decision to Initiate a QTc-interval Prolonging Medication in Critically Ill Patients with Potential Risk Factors for Torsade de Pointes: A Comparative, Case-Based Evaluation.


Input: STUDY OBJECTIVES: To measure concordance between different intensive care unit (ICU) clinicians and a consensus group of electrophysiology (EP) cardiologists for use of a common rate-corrected QT interval (QTc)-prolonging medication in cases containing different potential risk factor (s) for torsade de pointes (TdP).


Input: DESIGN: Prospective case-based evaluation.


Input: SETTING: Academic medical center with 320 beds.


Input: SUBJECTS: Medical house staff (MDs) and ICU nurses (RNs) from one center and select critical care pharmacists (PHs).


Input: INTERVENTION: Completion of a survey containing 10 hypothetical ICU cases in which patients had agitated delirium for which a psychiatrist recommended intravenous haloperidol 5 mg every 6 hours.

haloperidol


Input: Each case contained different potential risk factor (s) for TdP in specific combinations.


Input: A group of five EP cardiologists agreed that haloperidol use was safe in five cases and not safe in five cases.

haloperidol


Input: MEASUREMENTS AND MAIN RESULTS: For each case, participants were asked to document whether they would administer haloperidol, to provide a rationale for their decision, and to state their level of confidence in that decision.

haloperidol


Input: Most clinicians (92 of 115 [80%]) invited to participate completed the cases.


Input: Among the five cases where EP cardiologists agreed that haloperidol was not safe, 29% of respondents felt that haloperidol was safe.

haloperidol

haloperidol


Input: Conversely, in the five cases where EP cardiologists felt haloperidol was safe, 21% of respondents believed that it was not safe.

haloperidol


Input: Overall respondent-EP cardiologist agreement for haloperidol use across the 10 cases was moderate (kappa = 0. 51).

haloperidol


Input: MDs and PHs were in agreement with the EP cardiologists more than RNs (p = 0. 03).


Input: Interprofessional variability existed for the TdP risk factors each best identified.


Input: Clinician confidence correlated with EP cardiologist concordance for MDs (p = 0. 002) and PHs (p = 0. 0002), but not for RNs (p = 0. 69).


Input: CONCLUSION: When evaluating use of a QTc interval-prolonging medication, ICU clinicians often fail to identify the TdP risk factors that EP cardiologists feel should prevent its use.


Input: Clinician-EP cardiologist concordance varies by the specific risk factor (s) for TdP and the ICU professional conducting the assessment.


Input: High-Purity Prostate Circulating Tumor Cell Isolation by a Polymer Nanofiber-Embedded Microchip for Whole Exome Sequencing.


Input: Handpick single cancer cells: A modified NanoVelcro Chip is coupled with ArcturusXT laser capture microdissection (LCM) technology to enable the detection and isolation of single circulating tumor cells (CTCs) from patients with prostate cancer (PC).


Input: This new approach paves the way for conducting next-generation sequencing (NGS) on single CTCs.


Input: Rapid Improvement of Diabetes After Gastric Bypass Surgery: Is It the Diet or Surgery?


Input: OBJECTIVEImprovements in diabetes after Roux-en-Y gastric bypass (RYGB) often occur days after surgery.


Input: Surgically induced hormonal changes and the restrictive postoperative diet are proposed mechanisms.


Input: We evaluated the contribution of caloric restriction versus surgically induced changes to glucose homeostasis in the immediate postoperative period. RESEARCH DESIGN AND METHODSPatients with type 2 diabetes planning to undergo RYGB participated in a prospective two-period study (each period involved a 10-day inpatient stay and periods were separated by a minimum of 6 weeks of wash-out) in which patients served as their own controls.

glucose


Input: The presurgery period consisted of diet alone.


Input: The postsurgery period was matched in all aspects (daily matched diet) and included RYGB surgery.


Input: Glucose measurements were performed every 4 h throughout the study.

Glucose


Input: A mixed meal challenge test was performed before and after each period. RESULTSTen patients completed the study and had the following characteristics: age, 53. 2 years (95% CI, 48. 0-58. 4); BMI, 51. 2 kg/m (2) (46. 1-56. 4); diabetes duration, 7. 4 years (4. 8-10. 0); and HbA1c, 8. 52% (7. 08-9. 96).


Input: Patients lost 7. 3 kg (8. 1-6. 5) during the presurgery period versus 4. 0 kg (6. 2-1. 7) during the postsurgery period (P = 0. 01 between periods).


Input: Daily glycemia in the presurgery period was significantly lower (1, 293. 58 mg/dL * day [1, 096. 83-1, 490. 33) vs. 1, 478. 80 mg/dL * day [1, 277. 47-1, 680. 13]) compared with the postsurgery period (P = 0. 02 between periods).


Input: The improvements in the fasting and maximum poststimulation glucose and 6-h glucose area under the curve (primary outcome) were similar during both periods. CONCLUSIONSGlucose homeostasis improved in response to a reduced caloric diet, with a greater effect observed in the absence of surgery as compared with after RYGB.

glucose

glucose

CONCLUSIONSGlucose


Input: These findings suggest that reduced calorie ingestion can explain the marked improvement in diabetes control observed after RYGB.


Input: Structural basis for activation of ZAP-70 by phosphorylation of the SH2-kinase linker.


Input: Serial activation of the tyrosine kinases Lck and ZAP-70 initiates signaling downstream of the T-cell receptor.

tyrosine


Input: We had previously reported the structure of an autoinhibited ZAP-70 variant in which two regulatory tyrosine residues (315 and 319) in the SH2-kinase linker were replaced by phenylalanine.

tyrosine

phenylalanine


Input: We now present the crystal structure of ZAP-70 in which Tyr 315 and Tyr 319 are not mutated, leading to the recognition of a five-residue sequence register error in the SH2-kinase linker of the original crystallographic model.

Tyr

Tyr


Input: The revised model identifies distinct roles for these two tyrosines.

tyrosines


Input: As seen in a recently reported structure of the related tyrosine kinase Syk, Tyr 315 of ZAP-70 is part of a hydrophobic interface between the regulatory apparatus and the kinase domain, and the integrity of this interface would be lost upon engagement of doubly-phosphorylated peptides by the SH2 domains.

tyrosine

Tyr


Input: Tyr 319 is not necessarily dislodged by SH2 engagement, which activates ZAP-70 by only ~ 5-fold in vitro.

Tyr


Input: In contrast, phosphorylation by Lck activates ZAP-70 by ~ 100-fold.


Input: This difference is due to the ability of Tyr 319 to suppress ZAP-70 activity even when the SH2 domains are dislodged from the kinase domain, providing stringent control of ZAP-70 activity downstream of Lck.

Tyr


Input: Laser welding of ruptured intestinal tissue using plasmonic polypeptide nanocomposite solders.


Input: Approximately 1. 5 million people suffer from colorectal cancer and inflammatory bowel disease in the United States.


Input: Occurrence of leakage following standard surgical anastomosis in intestinal and colorectal surgery is common and can cause infection leading to life-threatening consequences.


Input: In this report, we demonstrate that plasmonic nanocomposites, generated from elastin-like polypeptides (ELPs) cross-linked with gold nanorods, can be used to weld ruptured intestinal tissue upon exposure to near-infrared (NIR) laser irradiation.


Input: Mechanical properties of these nanocomposites can be modulated based on the concentration of gold nanorods embedded within the ELP matrix.


Input: We employed photostable, NIR-absorbing cellularized and noncellularized GNR-ELP nanocomposites for ex vivo laser welding of ruptured porcine small intestines.


Input: Laser welding using the nanocomposites significantly enhanced the tensile strength, leakage pressure, and bursting pressure of ruptured intestinal tissue.


Input: This, in turn, provided a liquid-tight seal against leakage of luminal liquid from the intestine and resulting bacterial infection.


Input: This study demonstrates the utility of laser tissue welding using plasmonic polypeptide nanocomposites and indicates the translational potential of these materials in intestinal and colorectal repair.


Input: Bioinspired Water-Enhanced Mechanical Gradient Nanocomposite Films That Mimic the Architecture and Properties of the Squid Beak.


Input: Inspired by the water-enhanced mechanical gradient character of the squid beak, we herein report a nanocomposite that mimics both the architecture and properties of this interesting natural material.


Input: Similar to the squid beak, we have developed nanocomposites where the degree of cross-linking is controlled along the length of the film.


Input: In this study, we utilized tunicate cellulose nanocrystals as the nanofiller that are functionalized with allyl moieties.

allyl


Input: Using photoinduced thiol-ene chemistry, we have been able to cross-link the CNC nanofiller.

thiol


Input: In the dry state where strong CNC interactions can occur, only a small mechanical contrast is observed between the cross-linked and uncross-linked samples.


Input: However, when the films are exposed to water, which " switches off " the noncovalent CNC interactions, a significant mechanical contrast is observed between the same films.


Input: For example, at 20 wt% CNC (in the dry film), an increase in wet modulus from 60 to 300 MPa (~ 500% increase) is observed after photoirradiation.


Input: Furthermore, we show that the wet modulus can be controlled by altering the UV exposure time which allows access to mechanical gradient films.


Input: Multitarget Global Sensitivity Analysis of n-Butanol Combustion.

n-Butanol


Input: A model for the combustion of butanol is studied using a recently developed theoretical method for the systematic improvement of the kinetic mechanism.

butanol


Input: The butanol mechanism includes 1446 reactions, and we demonstrate that it is straightforward and computationally feasible to implement a full global sensitivity analysis incorporating all the reactions.

butanol


Input: In addition, we extend our previous analysis of ignition-delay targets to include species targets.


Input: The combination of species and ignition targets leads to multitarget global sensitivity analysis, which allows for a more complete mechanism validation procedure than we previously implemented.


Input: The inclusion of species sensitivity analysis allows for a direct comparison between reaction pathway analysis and global sensitivity analysis.


Input: Design, Synthesis, Biological Evaluation, and Docking Studies of (S)-Phenylalanine Derivatives with a 2-Cyanopyrrolidine Moiety as Potent Dipeptidyl Peptidase 4 Inhibitors.

(S)-Phenylalanine


Input: A novel series of (S)-phenylalanine derivatives with a 2-cyanopyrrolidine moiety were designed and synthesized through a rational drug design strategy.

(S)-phenylalanine


Input: Biological evaluation revealed that most tested compounds were potent dipeptidyl peptidase 4 (DPP-4) inhibitors, among them, the cyclopropyl-substituted phenylalanine derivative 11h displayed the most potent DPP-4 inhibitory activity with an IC50 value of 0. 247 mu M.

cyclopropyl-substituted phenylalanine


Input: In addition, molecular docking analysis of the representative compounds 11h, 11k, and 15a were performed, which not only revealed the impact of binding modes on DPP-4 inhibitory activity, but also provided additional methodological values for design and optimization.


Input: (c) 2013 John Wiley & Sons A/S.


Input: HISTONE DEACETYLASE INHIBITION AFFECTS SODIUM IODIDE SYMPORTER (NIS) EXPRESSION AND INDUCES (1) (3) (1) I CYTOTOXICITY IN ANAPLASTIC THYROID CANCER CELLS.

SODIUM IODIDE

(1) (3) (1) I


Input: Background: Anaplastic thyroid cancers (ATC) represent only 1-2% of all thyroid tumors, but they account for up to 50% of the mortality.


Input: Treatment of differentiated thyroid carcinomas is well standardized and the use of radioiodine represents an essential step; in contrast, there is no standardized therapeutic approach for anaplastic tumors and their prognosis is poor.

radioiodine


Input: The resistance of anaplastic thyroid cancer to radioiodine treatment is principally due to the absence of expression of the sodium iodide symporter (NIS), mainly due to epigenetic silencing.

radioiodine

sodium iodide


Input: The acetylation status of histones is involved in the epigenetic control of gene expression and is usually disrupted in advanced thyroid cancer.


Input: Histone deacetylase inhibitors have been demonstrated as potent anticancer drugs with several different effects on cell viability and differentiation.


Input: Methods: Stabilized anaplastic thyroid cancer cell lines (BHT-101 and CAL-62) and primary cultures from patients who underwent thyroidectomy for anaplastic thyroid cancer were treated with the histone deacetylase inhibitor LBH589.


Input: After treatment, we evaluated the expression and function of NIS.


Input: Gene expression was evaluated by real-time PCR (RT-PCR); NIS promoter activity was determined with a luciferase reporter assay; and protein expression was assessed through immunofluorescence.


Input: We tested the protein function by 125I uptake and efflux experiments; finally the cytotoxic effect of 131I was determined with a clonogenic assay.


Input: Results: Our results demonstrate that treatment with LBH589 leads to NIS RNA expression as shown by RT-PCR and luciferase assay, and to protein expression as determined by immunofluorescence in vitro and by immunohistochemistry in xenograft tumors.


Input: Moreover, 125I uptake and efflux experiments show the correct protein function and iodine retention, that translate into cytotoxicity effects, as demonstrated by a clonogenic assay with 131I.

iodine


Input: Conclusions: This study supplies a new potential strategy for the treatment of ATC by modifying gene expression with the aim of inducing responsiveness towards radioiodine therapy.

radioiodine


Input: Adhesion and Nanomechanics of Pili from the Probiotic Lactobacillus rhamnosus GG.


Input: Knowledge of the mechanisms by which bacterial pili adhere to host cells and withstand external forces is critical to our understanding of their functional roles and offers exciting avenues in biomedicine for controlling the adhesion of bacterial pathogens and probiotics.


Input: While much progress has been made in the nanoscale characterization of pili from Gram-negative bacteria, the adhesive and mechanical properties of Gram-positive bacterial pili remain largely unknown.


Input: Here, we use single-molecule atomic force microscopy to unravel the binding mechanism of pili from the probiotic Gram-positive bacterium Lactobacillus rhamnosus GG (LGG).


Input: First, we show that SpaC, the key adhesion protein of the LGG pilus, is a multifunctional adhesin with broad specificity.


Input: SpaC forms homophilic trans-interactions engaged in bacterial aggregation and specifically binds mucin and collagen, two major extracellular components of host epithelial layers.


Input: Homophilic and heterophilic interactions display similar binding strengths and dissociation rates.


Input: Next, pulling experiments on living bacteria demonstrate that LGG pili exhibit two unique mechanical responses, that is, zipper-like adhesion involving multiple SpaC molecules distributed along the pilus length and nanospring properties enabling pili to resist high force.


Input: These mechanical properties may represent a generic mechanism among Gram-positive bacterial pili for strengthening adhesion and withstanding shear stresses in the natural environment.


Input: The single-molecule experiments presented here may help us to design molecules capable of promoting or inhibiting bacterial-host interactions.


Input: Using whole mount in situ hybridization to examine thyroid hormone deiodinase expression in embryonic and larval zebrafish: A tool for examining OH-BDE toxicity to early life stages.

thyroid hormone

OH-BDE


Input: Polybrominated diphenyl ethers (PBDEs) and their oxidative metabolites (hydroxylated PBDEs; OH-BDEs) are known endocrine disrupting contaminants that have been shown to disrupt thyroid hormone regulation both in mammals and in fish.

Polybrominated diphenyl ethers

PBDEs

hydroxylated PBDEs

OH-BDEs

thyroid hormone


Input: The purpose of this study was to determine the precise organ and tissue locations that express genes critical to thyroid hormone regulation in developing zebrafish (Danio rerio), and to determine the effects of an OH-BDE on their expression.

thyroid hormone

OH-BDE


Input: While RT-PCR can provide quantitative data on gene expression, it lacks spatial sensitivity to examine localized gene expression; and, isolation of organs from zebrafish embryos is technically difficult, if not impossible.


Input: For this reason, the present study used whole mount in situ hybridization to simultaneously localize and quantify gene expression in vivo.


Input: While PBDEs and OH-BDEs have been shown to inhibit the activity and expression of deiodionases, a family of enzymes that regulate thyroid hormone concentrations intracellularly, it is unclear whether or not they can affect regional expression of the different isoforms during early development.

PBDEs

OH-BDEs

thyroid hormone


Input: In this study we investigated deiodinase 1 (Dio1), deiodinase 2 (Dio2), and deiodinase 3 (Dio3) mRNA expression at the following life stages (2, 8, and 1k-cells; 50%-epiboly, 6 and 18-somites, 22, 24, 48, 72 hpf and/or 10 dpf) in zebrafish and found life stage specific expression of these genes that were highly localized.


Input: To demonstrate the use of this technique for investigating potential endocrine disrupting effects, zebrafish embryos were exposed to 1, 10 and 100nM 6-OH-BDE-47.


Input: Significant increases in mean intensity of Dio1 and Dio3 expression in the periventricular zone of brain and pronephric duct, respectively (quantified by measuring intensity of coloration using ImageJ analysis software) were observed, suggesting localized response at the HPT axis with the possibility of impacting neurodevelopment.


Input: Our results demonstrate effects of OH-BDEs on thyroid regulating gene expression and provide more insight into potential sites of injury during early life stages.

OH-BDEs


Input: Transport Function and Transcriptional Regulation of a Liver-Enriched Human Organic Anion Transporting Polypeptide 2B1 Transcriptional Start Site Variant.


Input: Human Organic Anion Transporting Polypeptide 2B1 (OATP2B1) is a membrane transporter that facilitates the cellular uptake of a number of endogenous compounds and drugs.


Input: OATP2B1 is widely expressed in tissues including the small intestine, liver, kidney, placenta, heart, skeletal muscle and platelets.


Input: Recently, it has been shown that differential promoter usage in tissues results in expression of five OATP2B1 transcriptional start site variants which utilize distinct first exons but share common subsequent exons.


Input: These variants are expected to encode either a full length (OATP2B1-FL) or shortened protein lacking 22 N-terminus amino acids (OATP2B-Short).

N

amino acids


Input: Little is known regarding the transport activity and regulation of OATP2B1 variants with N-terminus truncation.

N


Input: Here, using absolute quantitative polymerase chain reaction we find the full length variant is the major form expressed in duodenum but the short variant predominates in liver.


Input: Using a transient heterologous cell expression system, we find that the transport activities of the short OATP2B1 variant towards substrates estrone sulfate and rosuvastatin are similar to the well-characterized full length variant.

estrone sulfate

rosuvastatin


Input: Transcriptional activity screening of the liver enriched OATP2B1 variant promoter identified hepatocyte nuclear factor 4 alpha (HNF4 alpha) as a novel transacting factor.


Input: With a combination of in silico screening, promoter mutation in cell-based reporter assays, siRNA knockdown and chromatin immunoprecipitation studies, we identified a functional HNF4 alpha binding site close to the transcription start site (-17 to-4 bp).


Input: We conclude that the major OATP2B1 protein form in liver is transport competent and its hepatic expression is regulated by HNF4 alpha.


Input: Genome-wide association study in a Chinese population identifies a susceptibility locus for type 2 diabetes at 7q32 near PAX4.


Input: AIMS/HYPOTHESIS: Most genetic variants identified for type 2 diabetes have been discovered in European populations.


Input: We performed genome-wide association studies (GWAS) in a Chinese population with the aim of identifying novel variants for type 2 diabetes in Asians.


Input: METHODS: We performed a meta-analysis of three GWAS comprising 684 patients with type 2 diabetes and 955 controls of Southern Han Chinese descent.


Input: We followed up the top signals in two independent Southern Han Chinese cohorts (totalling 10, 383 cases and 6, 974 controls), and performed in silico replication in multiple populations.


Input: RESULTS: We identified CDKN2A/B and four novel type 2 diabetes association signals with p < 1 x 10 (-5) from the meta-analysis.


Input: Thirteen variants within these four loci were followed up in two independent Chinese cohorts, and rs10229583 at 7q32 was found to be associated with type 2 diabetes in a combined analysis of 11, 067 cases and 7, 929 controls (p meta = 2. 6 x 10 (-8); OR [95% CI] 1. 18 [1. 11, 1. 25]).


Input: In silico replication revealed consistent associations across multiethnic groups, including five East Asian populations (p meta = 2. 3 x 10 (-10)) and a population of European descent (p = 8. 6 x 10 (-3)).


Input: The rs10229583 risk variant was associated with elevated fasting plasma glucose, impaired beta cell function in controls, and an earlier age at diagnosis for the cases.

glucose


Input: The novel variant lies within an islet-selective cluster of open regulatory elements.


Input: There was significant heterogeneity of effect between Han Chinese and individuals of European descent, Malaysians and Indians.


Input: CONCLUSIONS/INTERPRETATION: Our study identifies rs10229583 near PAX4 as a novel locus for type 2 diabetes in Chinese and other populations and provides new insights into the pathogenesis of type 2 diabetes.


Input: Disrupting the scaffold to improve focal adhesion kinase-targeted cancer therapeutics.


Input: Focal adhesion kinase (FAK) is emerging as a promising cancer target because it is highly expressed at both the transcriptional and translational level in cancer and is involved in many aspects of tumor growth, invasion, and metastasis.


Input: Existing FAK-based therapeutics focus on inhibiting the kinase' s catalytic function and not the large scaffold it creates that includes many oncogenic receptor tyrosine kinases and tumor suppressor proteins.

tyrosine


Input: Targeting the FAK scaffold is a feasible and promising approach for developing highly specific therapeutics that disrupt FAK signaling pathways in cancer.


Input: ERP evidence suggests executive dysfunction in ecstasy polydrug users.

ecstasy


Input: BACKGROUND: Deficits in executive functions such as access to semantic/long-term memory have been shown in ecstasy users in previous research.

ecstasy


Input: Equally, there have been many reports of equivocal findings in this area.


Input: The current study sought to further investigate behavioural and electro-physiological measures of this executive function in ecstasy users.

ecstasy


Input: METHOD: Twenty ecstasy-polydrug users, 20 non-ecstasy-polydrug users and 20 drug-na i ve controls were recruited.

ecstasy

ecstasy


Input: Participants completed background questionnaires about their drug use, sleep quality, fluid intelligence and mood state.


Input: Each individual also completed a semantic retrieval task whilst 64 channel Electroencephalography (EEG) measures were recorded.


Input: RESULTS: Analysis of Variance (ANOVA) revealed no between-group differences in behavioural performance on the task.


Input: Mixed ANOVA on event-related potential (ERP) components P2, N2 and P3 revealed significant between-group differences in the N2 component.


Input: Subsequent exploratory univariate ANOVAs on the N2 component revealed marginally significant between-group differences, generally showing greater negativity at occipito-parietal electrodes in ecstasy users compared to drug-na i ve controls.

ecstasy


Input: Despite absence of behavioural differences, differences in N2 magnitude are evidence of abnormal executive functioning in ecstasy-polydrug users.

ecstasy


Input: In vitro read-through of phenylalanine hydroxylase (PAH) nonsense mutations using aminoglycosides: a potential therapy for phenylketonuria.

phenylalanine

aminoglycosides


Input: Phenylketonuria (PKU, OMIM 261600) is an autosomal recessive inborn error of phenylalanine metabolism, predominantly caused by mutations in the phenylalanine hydroxylase (PAH) gene.

phenylalanine

phenylalanine


Input: Approximately 10% of patients carry a nonsense mutation, which results in an inactive or unstable truncated protein.


Input: In some genetic disorders, including cystic fibrosis and Duchenne muscular dystrophy, restoration of full-length protein has been achieved by aminoglycoside antibiotics, such as gentamicin and G-418 (Geneticin).

aminoglycoside

gentamicin

Geneticin


Input: More recently, nonsense read-through has been induced at greater rates using a non-aminoglycoside drug, PTC124 (Ataluren), which has the advantage of being non-toxic in contrast to the antibiotics.

aminoglycoside

Ataluren


Input: The efficacy of read-through induced by three compounds, aminoglycosides G418 and gentamicin, and PTC124 were evaluated for four nonsense mutations of PAH in an in vitro expression system in two mammalian cell lines (COS-7 and HEK293).

aminoglycosides G418

gentamicin


Input: The production of full-length PAH was investigated using western blotting and the functionality confirmed by enzyme activity.


Input: Gentamicin and G-418 induced read-through of nonsense PAH mutations in HEK293 cells.

Gentamicin


Input: The read-through product partially restored enzymatic activity, which was significantly less than that of wild-type, but comparable to a missense mutation of PAH associated with less severe forms of PKU.


Input: Treatment with PTC124 up to 100 mu M did not result in full-length PAH polypeptide.


Input: Nonsense read-through drugs are a potential form of treatment for PKU, although the high dosage of aminoglycosides used is not appropriate in a clinical setting.

aminoglycosides


Input: In vitro studies with new non-toxic read-through agents as well as in vivo studies would also be essential to determine the extent of read-through required to restore normal phenylalanine levels.

phenylalanine


Input: Implication of circulating omentin-1 level on the arterial stiffening in type 2 diabetes mellitus.


Input: Omentin-1 is an adipokine implicated in diabetes, inflammation, and cardiovascular disease.


Input: However, no prospective studies have examined the impact of circulating omentin-1 levels on arterial stiffening in patients with type 2 diabetes mellitus.


Input: For the purpose of this study, we recruited 120 patients with type 2 diabetes mellitus and measured serum omentin-1, adiponectin, and high-sensitivity C-reactive protein levels as well as other cardiovascular risk factors.


Input: Arterial stiffness was assessed by brachial ankle pulse wave velocity (baPWV).


Input: An increase in the level of circulating omentin-1 over a period of 1 year was positively correlated with changes in levels of HbA1c and serum adiponectin as well as baPWV.


Input: Subjects with higher baseline serum omentin-1 levels tended to have a reduced arterial stiffness after 1 year (P for linear trend = 0. 03).


Input: In the group with increased baPWV after 1 year, the magnitude of increase of circulating omentin-1 levels was significantly higher than in the group with a lower baPWV after 1 year (134. 3 [16. 6, 277. 1] ng/mL vs. 15. 9 [-67. 6, 145. 7] ng/mL, P < 0. 01).


Input: Multiple stepwise logistic regression analysis revealed that an increase in systolic blood pressure and an increase in serum omentin-1 level were independently correlated with arterial stiffening, even after adjusting for other cardiovascular risk factors and medication history.


Input: Baseline serum omentin-1 levels can predict arterial stiffness changes occurring within a year.


Input: Furthermore, changes in serum omentin-1 levels after a year can function as independent markers of arterial stiffening in patients with type 2 diabetes mellitus.


Input: High-Grade Prostatic Intraepithelial Neoplasia (HGPIN) and topographical distribution in 1, 374 prostatectomy specimens: Existence of HGPIN near prostate cancer.


Input: PURPOSE: High-grade prostatic intraepithelial neoplasia (HGPIN) is believed to be a precursor of prostate cancer (PCa).


Input: This study evaluated whether HGPIN was located close to PCa in whole radical prostatectomy specimens (RPSs).


Input: MATERIALS AND METHODS: We evaluated 1, 374 prostate specimens from 1999 to 2010 using a cMDX-based map model of the prostate.


Input: The distribution of 10, 439 PCa foci was analyzed and visualized on a heat map.


Input: The color gradient of the heat map was reduced to six colors representing the frequency classification of the relative frequency of PCa using an image posterization effect.


Input: We defined 22 regions in the prostate according to the frequency of PCa occurrence.


Input: Seven hundred ninety RPSs containing 6, 374 PCa foci and 4, 502 HGPIN foci were evaluated.


Input: The topographical association between PCa and HGPIN in the RPSs was analyzed by estimating the frequencies of PCa and HGPIN in 22 regions.


Input: A logistic regression analysis was performed to assess the odds ratios of HGPIN for the presence of PCa in 22 regions.


Input: RESULTS: Fifty-eight percent of PCa specimens included HGPIN and had significantly more favorable Gleason scores, lower PSA levels and smaller relative tumor volumes than isolated PCa specimens.


Input: HGPIN (68%) and PCa (69%) were predominantly localized to the apical half of the prostate.


Input: HGPIN was mainly concentrated in the peripheral zone medial to regions with high PCa frequencies.


Input: Upon logistic regression analysis, HGPIN was a significant predictor of PCa co-existence in 11 regions.


Input: CONCLUSIONS: HGPIN was located adjacent to PCa in whole RPSs.


Input: PCa concomitant with HGPIN had more favorable pathologic features than isolated PCa.


Input: Prostate (c) 2013 Wiley Periodicals, Inc.


Input: The Joubert Syndrome Associated Missense Mutation (V443D) in the Abelson-helper Integration Site 1 (AHI1) Protein Alters Its Localization and Protein-Protein Interactions.


Input: Mutations in AHI1 cause Joubert syndrome (JBTS), a neurodevelopmental ciliopathy, characterized by midbrain-hindbrain malformations and motor/cognitive deficits.


Input: Here, we show that primary cilia (PC) formation is decreased in fibroblasts from individuals with JBTS and AHI1 mutations.


Input: Most missense mutations in AHI1, causing JBTS, occur in known protein domains, however, a common V443D mutation in AHI1 is found in a region with no known protein motifs.


Input: We show that cells transfected with AHI1-V443D, or a new JBTS-causing mutation, AHI1-R351L, have aberrant localization of AHI1 at the basal bodies of PC and at cell-cell junctions, likely through decreased binding of mutant AHI1 to NPHP1 (another JBTS-causing protein).


Input: The AHI1-V443D mutation causes decreased AHI1 stability, since there is a 50% reduction in AHI1-V443D protein levels compared to wildtype AHI1.


Input: Huntingtin-associated protein-1 (Hap1) is a regulatory protein that binds Ahi1, and Hap1 knockout mice have been reported to have JBTS-like phenotypes, suggesting a role for Hap1 in ciliogenesis.


Input: Fibroblasts and neurons with Hap1 deficiency form PC with normal growth factor-induced ciliary signaling, indicating that the Hap1 JBTS-phenotype is likely not through effects at PC.


Input: These results also suggest that the binding of Ahi1 and Hap1 may not be critical for ciliary function.


Input: However, we show that HAP1 has decreased binding to AHI1-V443D indicating that this altered binding could be responsible for the JBTS-like phenotype through an unknown pathway.


Input: Thus, these JBTS-associated missense mutations alter their subcellular distribution and protein interactions, compromising functions of AHI1 in cell polarity and cilium-mediated signaling, thereby contributing to JBTS.


Input: Bioimaging real-time PXR-dependent mdr1a gene regulation in mdr1a. fLUC reporter mice.


Input: The MDR1 gene encodes P-glycoprotein, a transmembrane drug efflux transporter that confers multidrug resistance in cancer cells and affects drug pharmacokinetics by virtue of its expression in the liver, kidney, and colon.


Input: Nuclear receptors SXR and CAR are possible master regulators of xenobiotic-inducible MDR1 expression in drug processing organs, but the mechanism of MDR1 regulation has yet to be directly demonstrated in vivo.


Input: Moreover, it has previously been impossible to determine the sustained or cumulative effect of repeated doses of xenobiotics on in vivo MDR1 expression.


Input: We previously reported a mouse model containing firefly luciferase (fLUC) knocked into the mdr1a genomic locus, allowing non-invasive bioimaging of intestinal mdr1a gene expression in live animals.


Input: In the current study, we crossed mdr1a. fLUC mice into the pxr knockout (pxr (-/-)) genetic background and injected mice with pregnenolone-16 alpha-carbonitrile (PCN), a strong PXR ligand, and two therapeutically relevant taxanes, paclitaxel and docetaxel.

pregnenolone-16 alpha-carbonitrile

PCN

taxanes

paclitaxel

docetaxel


Input: All three agents induced mdr1a. fLUC expression (bioluminescence), but only PCN and docetaxel appeared to act primarily via PXR.

PCN

docetaxel


Input: Luminescence returned to baseline by 24-48 hrs after drug injection and was re-inducible over two additional rounds of drug dosing in pxr (+/+) mice.


Input: TCPOBOP, a CAR ligand, modestly induced mdr1a. fLUC in pxr (+/+) and pxr (-/-) strains, consistent with CAR' s minor role in mdr1a regulation.

TCPOBOP


Input: Collectively, these results demonstrate that the mdr1a. fLUC bioimaging model can capture changes in mdr1 gene expression under conditions of repeated xenobiotic treatment in vivo and that it can be used to probe the mechanism of gene regulation in response to different xenobiotic agents.


Input: SpecDis: quantifying the comparison of calculated and experimental electronic circular dichroism spectra.


Input: This article outlines theory and practice of the comparison of calculated and experimental electronic circular dichroism (ECD) curves to determine the absolute configuration of chiral molecules.


Input: The focus is on the evaluation of excited-state calculations giving hints at the identification of the correct bandwidth and the application of the so-called " UV shift " as a correction factor.


Input: A similarity factor is introduced, which helps to quantify the degree of matching of curves.


Input: In addition, a few common errors are described that can be made during the measurements of ECD and UV spectra-and advice is given of how to avoid these mistakes.


Input: All equations mentioned in the article are implemented in our SpecDis software, which has been developed to rapidly compare calculated ECD and UV curves with experimental ones, and to produce graphics in publication quality.


Input: O-heterocyclic embeurekols from Embellisia eureka, an endophyte of Cladanthus arabicus.

O-heterocyclic embeurekols


Input: Three new polyketides ((-)-1, (+)-1, and 2) were isolated from the EtOAc extract of the fungus Embellisia eureka, an endophyte of the Moroccan plant Cladanthus arabicus (Asteraceae).

EtOAc


Input: The structures of these new compounds were determined on the basis of one-and two-dimensional NMR spectroscopy as well as by high-resolution mass spectrometry.


Input: The absolute configurations of (-)-1, (+)-1, and 2 were determined by TDDFT ECD calculations of solution conformers, online HPLC-ECD analysis, and the modified Mosher method.


Input: Increased activin bioavailability enhances hepatic insulin sensitivity while inducing hepatic steatosis in male mice.


Input: The development of insulin resistance is tightly linked to fatty liver disease and is considered a major health concern worldwide, although their mechanistic relationship remains controversial.


Input: Activin has emerging roles in nutrient homeostasis but its metabolic effects on hepatocytes remain unknown.


Input: In this study, we investigated the effects of increased endogenous activin bioactivity on hepatic nutrient homeostasis by creating mice with inactivating mutations that deplete the circulating activin antagonists, follistatin like-3 (FSTL3) or the follistatin 315 isoform (FST315; FST288-only mice).


Input: We investigated liver histology and lipid content, hepatic insulin sensitivity, and metabolic gene expression including the HepG2 cell and primary hepatocyte response to activin treatment.


Input: Both FSTL3KO and FST288-only mice had extensive hepatic steatosis and elevated hepatic triglyceride (TG) content.

triglyceride


Input: Unexpectedly, insulin signaling, as assessed by phospho-AKT, was enhanced in both mouse models.


Input: Pretreatment of HepG2 cells with activin A increased their response to subsequent insulin challenge.


Input: Gene expression analysis suggests that increased lipid uptake, enhanced de novo lipid synthesis, decreased lipolysis and/or enhanced glucose uptake contribute to increased hepatic TG content in these models.

glucose


Input: However, activin treatment recapitulated only some of these gene changes suggesting that increased activin bioactivity may be only partially responsible for this phenotype.


Input: Nevertheless, our results indicate that activin enhances hepatocyte insulin response which ultimately leads to hepatic steatosis despite the increased insulin sensitivity.


Input: Thus, regulation of activin bioactivity is critical for maintaining normal liver lipid homeostasis and response to insulin while activin agonists may be useful for increasing liver insulin sensitivity.


Input: Calculation of Electron Transfer Rates Using Mixed Quantum Classical Approaches: Nonadiabatic Limit and Beyond.


Input: We investigate the applicability of the Ehrenfest and surface hopping methods to calculate electron transfer rates using the spin-boson model with different parameters.


Input: Rate constants are obtained from short time dynamics performed in both the diabatic and adiabatic basis sets.


Input: Numerical results and theoretical analysis show that these two methods can be reasonably accurate in the nonadiabatic limit, by staying close to an approximate Fermi' s golden rule.


Input: Beyond the nonadiabatic limit, the calculated mixed quantum classical rates are compared with numerical exact results, and similar accuracy was found as in the nonadiabatic limit.


Input: The relation between the current finding and recent studies using the surface hopping method based on long time dynamics is also discussed.


Input: It is found that the short time dynamics could be more accurate in calculating rate constants using the mixed quantum classical methods.


Input: Effect of surface charge density on the affinity of oxide nanoparticles for the vapor-water interface.

oxide


Input: Using in-situ X-ray photoelectron spectroscopy at the vapor-water interface, the affinity of nanometer-sized silica colloids to adsorb at the interface is shown to depend on colloid surface charge density.

silica


Input: In aqueous suspensions at pH 10 corrected Debye-H u ckel theory for surface complexation calculations predict that smaller silica colloids have increased negative surface charge density that originates from enhanced screening of deprotonated silanol groups (= Si-O (-)) by counterions in the condensed ion layer.

silica

silanol

= Si-O (-)


Input: The increased negative surface charge density results in an electrostatic repulsion from the vapor-water interface that is seen to a lesser extent for larger particles that have a reduced charge density in the XPS measurements.


Input: We compare the results and interpretation of the in-situ XPS and corrected Debye-H u ckel theory for surface complexation calculations with traditional surface tension measurements.


Input: Our results show that controlling the surface charge density of colloid particles can regulate their adsorption to the interface between two dielectrics.


Input: Two-dimensional penning ionization electron spectroscopy of open-shell metallocenes: outer valence ionic States of vanadocene and nickelocene.

metallocenes

vanadocene

nickelocene


Input: In order to investigate outer valence ionic states of open-shell metallocenes, we have applied two-dimensional collision-energy/electron-energy-resolved Penning ionization electron spectroscopy (2D-PIES) upon collision with metastable He * (2 (3) S) excited atoms as well as a high level ab initio molecular orbital calculation (the partial third-order quasiparticle theory of the electron propagator (P3)) to ionization from neutral ground states of vanadocene ((4) A2g) and nickelocene ((3) A2g).

metallocenes

He

vanadocene

nickelocene


Input: Assignments of observed Penning ionization electron/He I ultraviolet photoelectron spectra were consistent with the P3 calculation results for ionization of alpha and beta spin electrons except for electron correlation bands observed by PIES.

He


Input: Negative collision energy dependence of partial Penning ionization cross-sections (CEDPICS) indicate attractive interaction with He * (2 (3) S) around the molecule.

He


Input: Results by model potential calculation utilizing Li (2 (2) S) instead of He * (2 (3) S) for interaction between He * (2 (3) S) and open-shell metallocenes do not explain the strong negative CEDPICS of the bands observed in PIES.

Li

He

He

metallocenes


Input: Antifreeze (Glyco) protein Mimetic Behavior of Poly (vinyl alcohol): Detailed Structure Ice Recrystallization Inhibition Activity Study.

Poly (vinyl alcohol)


Input: This manuscript reports a detailed study on the ability of poly (vinyl alcohol) to act as a biomimetic surrogate for antifreeze (glyco) proteins, with a focus on the specific property of ice-recrystallization inhibition (IRI).

poly (vinyl alcohol)


Input: Despite over 40 years of study, the underlying mechanisms that govern the action of biological antifreezes are still poorly understood, which is in part due to their limited availability and challenging synthesis.


Input: Poly (vinyl alcohol) (PVA) has been shown to display remarkable ice recrystallization inhibition activity despite its major structural differences to native antifreeze proteins.

Poly (vinyl alcohol)

PVA


Input: Here, controlled radical polymerization is used to synthesize well-defined PVA, which has enabled us to obtain the first quantitative structure-activity relationships, to probe the role of molecular weight and comonomers on IRI activity.

PVA


Input: Crucially, it was found that IRI activity is " switched on " when the polymer chain length increases from 10 and 20 repeat units.


Input: Substitution of the polymer side chains with hydrophilic or hydrophobic units was found to diminish activity.


Input: Hydrophobic modifications to the backbone were slightly more tolerated than side chain modifications, which implies an unbroken sequence of hydroxyl units is necessary for activity.

hydroxyl


Input: These results highlight that, although hydrophobic domains are key components of IRI activity, the random inclusion of addition hydrophobic units does not guarantee an increase in activity and that the actual polymer conformation is important.


Input: Skin Sensitization of Epoxyaldehydes: Importance of Conjugation.

Epoxyaldehydes


Input: Structure-activity relationship (SAR) models are important tools for predicting the skin sensitization potential of new compounds without animal testing.


Input: In compounds possessing a structural alert (aldehyde) and an activation alert (double bond), it is important to consider bioactivation/autoxidation (e. g., epoxidation).

aldehyde


Input: In the present study, we have explored a series of aldehydes with regard to contact allergy.

aldehydes


Input: The chemical reactivity of these 6 aldehydes toward a model hexapeptide was investigated, and their skin sensitization potencies were evaluated using the local lymph node assay (LLNA).

aldehydes


Input: Overall, we observed a similar trend for the in vitro reactivity and the in vivo sensitization potency for the structural analogues in this study.


Input: The highly reactive conjugated aldehydes (alpha, beta-unsaturated aldehydes and 2, 3-epoxyaldehydes) are sensitizing moieties, while nonconjugated aldehydes and nonterminal aliphatic epoxides show low reactivity and low sensitization potency.

aldehydes

alpha, beta-unsaturated aldehydes

2, 3-epoxyaldehydes

aldehydes

epoxides


Input: Our data show the importance of not only double bond conjugation to aldehyde but also epoxide-aldehyde conjugation.

aldehyde

epoxide

aldehyde


Input: The observations indicate that the formation of nonconjugated epoxides by bioactivation or autoxidation is not sufficient to significantly increase the sensitization potency of weakly sensitizing parent compounds.

epoxides


Input: Monomeric PcrA helicase processively unwinds plasmid lengths of DNA in the presence of the initiator protein RepD.


Input: The helicase PcrA unwinds DNA during asymmetric replication of plasmids, acting with an initiator protein, in our case RepD.


Input: Detailed kinetics of PcrA activity were measured using bulk solution and a single-molecule imaging technique to investigate the oligomeric state of the active helicase complex, its processivity and the mechanism of unwinding.


Input: By tethering either DNA or PcrA to a microscope coverslip surface, unwinding of both linear and natural circular plasmid DNA by PcrA/RepD was followed in real-time using total internal reflection fluorescence microscopy.


Input: Visualization was achieved using a fluorescent single-stranded DNA-binding protein.


Input: The single-molecule data show that PcrA, in combination with RepD, can unwind plasmid lengths of DNA in a single run, and that PcrA is active as a monomer.


Input: Although the average rate of unwinding was similar in single-molecule and bulk solution assays, the single-molecule experiments revealed a wide distribution of unwinding speeds by different molecules.


Input: The average rate of unwinding was several-fold slower than the PcrA translocation rate on single-stranded DNA, suggesting that DNA unwinding may proceed via a partially passive mechanism.


Input: However, the fastest dsDNA unwinding rates measured in the single-molecule unwinding assays approached the PcrA translocation speed measured on ssDNA.


Input: Mechanisms of the anti-proliferative and anti-inflammatory effects of the herbal fixed combination STW 5 (Iberogast ((R))) on colon adenocarcinoma (HT29) cells in vitro.


Input: INTRODUCTION: Several conventional pharmaceuticals like non-steroidal anti-inflammatory drugs (NSAIDS) or selective cyclooxygenase-2 (COX-2) inhibitors have been demonstrated to exert anti-proliferative effects and to induce apoptosis in a variety of cell lines, e. g. colon, stomach, or prostate cancer cells.


Input: STW 5 (Iberogast ((R))), a combination of nine plant extracts, is widely used in the treatment of gastrointestinal disorders, including functional dyspepsia and irritable bowel syndrome for which the involvement of an inflammatory etiology is discussed.


Input: To investigate the possible anti-proliferative effects, STW 5 and its components have been tested by using the colon-carcinoma cell line HT-29.


Input: The analyses have been performed in comparison to acetylsalicylic acid (ASA) and diclofenac (Diclo), which are well-known to reduce colon carcinoma risk.

acetylsalicylic acid

ASA

diclofenac

Diclo


Input: RESULTS: STW 5 showed significant anti-proliferative and pro-apoptotic effects on HT-29 cancer cells, similar to NSAIDs under test.


Input: However, using the LDH assay, STW 5 revealed significantly lower cytotoxicity than Diclo at same concentrations.

Diclo


Input: In contrast to NSAIDs, STW 5 induced COX-1/COX-2, caspase-3 and Bax mRNA expressions in HT-29 and blocked LPS mediated translocation of the NF-kappa B p65 from the cytoplasm into the nucleus in PMA-differentiated THP-1 macrophages.

PMA


Input: These effects might be relevant, e. g. for prevention of undesirable side effects like gastric erosions.


Input: CONCLUSION: Our data suggest that the pro-apoptotic effect of STW 5 on HT-29 cells is involving multiple targets and is possibly due to an activation of the caspase cascade via mitochondrial destabilization.


Input: Active concentrations of STW 5 are, in relation to therapeutic doses, comparable to those of ASA and Diclo, suggesting a similar favorable effect on colon carcinoma risk.

ASA

Diclo


Input: Cajaninstilbene acid (CSA) exerts cytoprotective effects against oxidative stress through the Nrf2-dependent antioxidant pathway.

Cajaninstilbene acid

CSA


Input: Cajaninstilbene acid (CSA), an active compound separated from pigeon pea leaves, possesses the highly efficient antioxidant activities.

Cajaninstilbene acid

CSA


Input: Transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) is an important regulator of cellular oxidative stress.


Input: This study examined the role of Nrf2 in CSA-mediated antioxidant effects on human hepatocarcinoma (HepG2) cell line.

CSA


Input: The generation of reactive oxygen species (ROS) upon H2O2 and CSA treatment was lower than that of H2O2 alone.

oxygen

CSA


Input: CSA activated Nrf2 as evaluated by Western blotting.

CSA


Input: A luciferase reporter assay also demonstrated that CSA-activated signaling resulted in the increased transcriptional activity of Nrf2 through binding to the antioxidant response element (ARE) enhancer sequence.

CSA


Input: Our study indicated that treatment of HepG2 cells with CSA induces Nrf2-dependent ARE activity and gene expression of heme oxygenase-1 (HO-1), NAD (P) H quinone oxidoreductase 1 (NQO1), and glutamate-cysteine ligase modifier subunits by activation of PI3K/AKT, ERK and JNK signaling pathways.

CSA

heme

NAD (P) H quinone

glutamate

cysteine


Input: Inhibition of Nrf2 by siRNA reduced CSA-induced upregulation of these Nrf2-related enzymes.

CSA


Input: These results suggest that the Nrf2/ARE pathway plays an important role in the regulation of CSA-mediated antioxidant effects in HepG2 cells.

CSA


Input: Enantiocomplementary access to carba-analogs of C-nucleoside derivatives by recombinant Baeyer-Villiger monooxygenases.

C-nucleoside


Input: A novel and stereoselective synthetic route towards carba-C-nucleosides was investigated applying an enantiodivergent biooxidation strategy by two different Baeyer-Villiger monooxygenases.

carba-C-nucleosides


Input: Within only three chemo-enzymatic steps it was possible to introduce four chiral centers starting from commercially available non-chiral starting material.


Input: Use of asenapine in clinical practice for the management of bipolar mania.

asenapine


Input: Bipolar disorder is a chronic mental illness associated with high levels of somatic morbidity, comorbidity and mortality.


Input: Treatment guidelines for bipolar mania generally recommend initiating first-line therapy with a second-generation antipsychotic or mood stabiliser, either alone or in combination.


Input: Asenapine is a second-generation antipsychotic with a unique receptor binding profile, licensed for the treatment of manic episodes in adults with bipolar I disorder.

Asenapine


Input: ' Real-world' data are needed to complement evidence from clinical trials, in order to provide clinicians with pragmatic information regarding the likely risks and benefits of using a new agent in clinical practice.


Input: Evidence from real-world case reports demonstrates that-as in clinical trials-asenapine is effective in treating mania and mixed episodes associated with bipolar I disorder, whether used as monotherapy or in combination with a mood stabiliser.

asenapine


Input: It has a rapid onset of antimanic effect and an early improvement is associated with treatment outcome.


Input: Asenapine also shows promise in controlling depressive symptoms and clinically challenging mixed states.

Asenapine


Input: Asenapine has a favourable tolerability profile, compared with other first-line agents, having a minimal impact on weight and metabolic parameters.

Asenapine


Input: Asenapine should be considered a first-line treatment option for adults with bipolar I disorder.

Asenapine


Input: Force nanoscopy of cell mechanics and cell adhesion.


Input: Cells are constantly exposed to mechanical stimuli in their environment and have several evolved mechanisms to sense and respond to these cues.


Input: It is becoming increasingly recognized that many cell types, from bacteria to mammalian cells, possess a diverse set of proteins to translate mechanical cues into biochemical signalling and to mediate cell surface interactions such as cell adhesion.


Input: Moreover, the mechanical properties of cells are involved in regulating cell function as well as serving as indicators of disease states.


Input: Importantly, the recent development of biophysical tools and nanoscale methods has facilitated a deeper understanding of the role that physical forces play in modulating cell mechanics and cell adhesion.


Input: Here, we discuss how atomic force microscopy (AFM) has recently been used to investigate cell mechanics and cell adhesion at the single-cell and single-molecule levels.


Input: This knowledge is critical to our understanding of the molecular mechanisms that govern mechanosensing, mechanotransduction, and mechanoresponse in living cells.


Input: While pushing living cells with the AFM tip provides a means to quantify their mechanical properties and examine their response to nanoscale forces, pulling single surface proteins with a functionalized tip allows one to understand their role in sensing and adhesion.


Input: The combination of these nanoscale techniques with modern molecular biology approaches, genetic engineering and optical microscopies provides a powerful platform for understanding the sophisticated functions of the cell surface machinery, and its role in the onset and progression of complex diseases.


Input: Geographical differences in the prevalence of chronic polypharmacy in older people: eleven years of the EPIFARM-Elderly Project.


Input: PURPOSE: To compare the geographical differences in the prevalence of chronic polypharmacy in community-dwelling older people over 11 years.


Input: METHODS: This study analyzed nearly two million patients aged 65-94 years recorded in the Drug Administrative Database of the Lombardy Region (Northern Italy) from 2000 to 2010.


Input: Chronic polypharmacy was defined as taking five or more drugs in 1 month for at least 6 months (consecutive or not) in a year.


Input: RESULTS: There was a significant spatial autocorrelation that increased at the municipality level from 2000 (Moran' s I Index = 0. 26, z score = 16. 91, p < 0. 0001) to 2010 (Moran' s I Index = 0. 36, z score = 23. 78, p < 0. 0001).


Input: Clusters of high (Z (G) > 1. 96) and low (Z (G) <-1. 96) prevalence rates of chronic polypharmacy were found and were not influenced by age.


Input: Chronic polypharmacy weakly correlated with hospital admission (2000: rho = 0. 08, p = 0. 0032; 2005: rho = 0. 11, p < 0. 0001; 2010: rho = 0. 18, p < 0. 0001), but not with mortality.


Input: CONCLUSIONS: There were geographical differences in the prevalence of older people with chronic polypharmacy that were only partly explained by health indicators.


Input: Targeted activities on prescription practice to ensure that the prescribing of chronic polypharmacy is appropriate are required.


Input: The effects of gender difference on monocrotaline-induced pulmonary hypertension in rats.

monocrotaline


Input: The present study aimed to compare the effect of gender difference on hemodynamic consequences in the development of monocrotaline (MCT)-induced pulmonary hypertension in rat.

monocrotaline

MCT


Input: The effect of antioxidant enzyme systems on the development of pulmonary hypertension mediated by the phytotoxin MCT and the effect of gender on these antioxidant systems were also investigated.

MCT


Input: For this purpose, the right ventricular pressures (RVPs) and right ventricular/heart weight (HW) ratios were compared between groups and the glutathione (GSH) level and superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST) activities were determined in lung and liver tissue samples of rats.

glutathione

GSH

superoxide

glutathione

S


Input: RVP and right ventricular/HW ratios significantly increased in the MCT group compared to the control group.

MCT


Input: In the MCT group, RVP was significantly higher in males than females.

MCT


Input: MCT-induced pulmonary hypertension resulted in decreased GSH level, decreased GST and SOD activities and increased CAT activity in lung and liver tissues of both male and female rats.

MCT

GSH


Input: In addition, the lung and liver GSH level and GST and SOD levels were higher in female control rats compared to male control rats.

GSH


Input: The results of the present study, that antioxidant enzyme activities were different between the groups, highlight the possible role of oxidative stress in the pathogenesis of MCT-induced pulmonary hypertension in rats.

MCT


Input: Moreover, the lower antioxidant defense capacity of male rats than female rats may be considered as a cause of more aggressive course of MCT-induced pulmonary hypertension in males compared to females.

MCT


Input: Injection of ropivacaine into the subarachnoid changes the ultrastructure and proteome of the rat spinal cord.

ropivacaine


Input: Abstract 1.


Input: In the present study, we investigated the impact of 1. 0% ropivacaine on the ultrastructure and proteome of the rat spinal cord.

ropivacaine


Input: Rats received three injections (90-min intervals, 0. 2 mL/kg) of 0. 9% NaCl, 0. 5% ropivacaine or 1. 0% ropivacaine via an implanted intrathecal catheter.

NaCl

ropivacaine

ropivacaine


Input: Transmission electron microscopy was performed to exam the ultrastructure of the spinal cord.


Input: Two-dimensional electrophoresis followed by mass spectrometry identification were carried out to investigate the proteome.


Input: In the rats administered 1. 0% ropivacaine, deformed organelles, detached myelinated nerve fiber layer, and incomplete inner and outer shaft membranes were observed in the spinal cord and posterior root shrunken nuclei.

ropivacaine


Input: Furthermore, in the rat spinal cord 1. 0% ropivacaine induced the down-regulation of voltage-dependent anion channel 2 (VDAC2) and mitochondrial pyruvate dehydrogenase subunit alpha (ODPA), the upregulation of myelin basic protein (MBP), the disappearance of myelin transcription factor 1 (MYT1) and the appearance of heat shock protein 25 (HSP25).

ropivacaine

pyruvate


Input: Little change was observed in the 0. 5% ropivacaine or control groups.

ropivacaine


Input: Our results suggest that 1. 0% ropivacaine treatment led to neurotoxicity, as shown by ultrastructural and proteomic changes in the rat spinal cord.

ropivacaine


Input: Specific proteins were identified that are implicated in 1. 0% ropivacaine-induced neurotoxicity.

ropivacaine


Input: Temperature Dependence and Energetics of Single Ions at the Aqueous Liquid-Vapor Interface.


Input: We investigate temperature-dependence of free energetics with two single halide anions, I-and Cl-, crossing the aqueous liquid-vapor interface through molecular dynamics simulations.

halide

I

Cl


Input: The result shows that I-has a modest surface stability of 0. 5 kcal/mol at 300 K and the stability decreases as the temperature increases, indicating the surface adsorption process for the anion is entropically disfavored.

I


Input: In contrast, Cl-shows no such surface state at all temperatures.

Cl


Input: Decomposition of free energetics reveals that water-water interactions provide a favorable enthalpic contribution, while the desolvation of ion induces an increase in free energy.


Input: Calculations of surface fluctuations demonstrate that I-generates significantly greater interfacial fluctuations compared to Cl-.

I

Cl


Input: The fluctuation is attributed to the malleability of the solvation shells, which allows for more long-ranged perturbations and solvent density redistribution induced by I-as the anion approaches the liquid-vapor interface.

I


Input: The increase in temperature of the solvent enhances the inherent thermally-excited fluctuations and consequently reduces the relative contribution from anion to surface fluctuations, which is consistent with the decrease in surface-stability of I-.

I


Input: Our results indicate a strong correlation with induced interfacial fluctuations and anion surface stability; moreover, resulting temperature dependent behavior of induced fluctuations suggests the possibility of a critical level of induced fluctuations associated with surface stability.


Input: Molecular Mechanism of the Inhibition of EGCG on the Alzheimer A beta 1-42 Dimer.

EGCG


Input: Growing evidence supports that amyloid beta (A beta) oligomers are the major causative agents leading to neural cell death in Alzheimer' s disease.


Input: The polyphenol (-)-epigallocatechin gallate (EGCG) was recently reported to inhibit A beta fibrillization and redirect A beta aggregation into unstructured, off-pathway oligomers.

polyphenol (-)-epigallocatechin gallate

EGCG


Input: Given the experimental challenge to characterize the structures of A beta/EGCG complexes, we performed extensive atomistic replica exchange molecular dynamics simulations of A beta 1-42 dimer in the present and absence of EGCG in explicit solvent.

EGCG

EGCG


Input: Our equilibrium A beta dimeric structures free of EGCG are consistent with the collision cross section from ion-mobility mass spectrometry and the secondary structure composition from circular dichroism experiment.

EGCG


Input: In the presence of EGCG, the A beta structures are characterized by increased inter-center-of-mass distances, reduced interchain and intrachain contacts, reduced beta-sheet content, and increased coil and alpha-helix contents.

EGCG


Input: Analysis of the free energy surfaces reveals that the A beta dimer with EGCG adopts new conformations, affecting therefore its propensity to adopt fibril-prone states.

EGCG


Input: Overall, this study provides, for the first time, insights on the equilibrium structures of A beta 1-42 dimer in explicit aqueous solution and an atomic picture of the EGCG-mediated conformational change on A beta dimer.

EGCG


Input: Lipopolysaccharide Interactions of C-Terminal Peptides from Human Thrombin.

C


Input: Interactions with bacterial lipopolysaccharide (LPS), both in aqueous solution and in lipid membranes, were investigated for a series of amphiphilic peptides derived from the C-terminal region of human thrombin, using ellipsometry, dual polarization interferometry, fluorescence spectroscopy, circular dichroism (CD), dynamic light scattering, and z-potential measurements.

C


Input: The ability of these peptides to block endotoxic effects caused by LPS, monitored through NO production in macrophages, was compared to peptide binding to LPS and its endotoxic component lipid A, and to size, charge, and secondary structure of peptide/LPS complexes.

NO


Input: While the antiendotoxic peptide GKY25 (GKYGFYTHVFRLKKWIQKVIDQFGE) displayed significant binding to both LPS and lipid A, so did two control peptides with either selected D-amino acid substitutions or with maintained composition but scrambled sequence, both displaying strongly attenuated antiendotoxic effects.

D-amino acid


Input: Hence, the extent of LPS or lipid A binding is not the sole discriminant for the antiendotoxic effect of these peptides.


Input: In contrast, helix formation in peptide/LPS complexes correlates to the antiendotoxic effect of these peptides and is potentially linked to this functionality.


Input: Preferential binding to LPS over lipid membrane was furthermore demonstrated for these peptides and preferential binding to the lipid A moiety within LPS inferred.


Input: Structural Changes in Cytochrome c Oxidase Induced by Binding of Sodium and Calcium Ions: An ATR-FTIR Study.

Sodium

Calcium


Input: Attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy was used to investigate the binding of Na (+) and Ca (2 +) cations to bovine cytochrome c oxidase in its fully oxidized and partially reduced, cyanide-ligated (a (2 +) a3 (3 +)-CN) (mixed valence) forms.

Na (+)

Ca (2 +)

cyanide

CN


Input: These ions induced distinctly different IR binding spectra, indicating that the induced structural changes are different.


Input: Despite this, their binding spectra were mutually exclusive, confirming their known competitive binding behavior.


Input: Dissociation constants for Na (+) and Ca (2 +) with the oxidized enzyme were 1. 2 mM and 11 mu M, respectively and Na (+) binding appeared to involve cooperative binding of two Na (+).

Na (+)

Ca (2 +)

Na (+)

Na (+)


Input: Ca (2 +) binding induced a large IR spectrum, with prominent amide I/II polypeptide changes, bandshifts assigned to carboxylate and an arginine, and a number of bandshifts of heme a.

Ca (2 +)

amide

carboxylate

arginine

heme a


Input: The Na (+)-induced binding spectrum showed much weaker amide I/II and heme a changes but had similar shifts assignable to carboxylate and arginine residues.

Na (+)

amide

heme a

carboxylate

arginine


Input: Yeast CcO also displayed a calcium-induced IR and UV/visible binding spectra, though of lower intensities.

calcium


Input: This was attributed to the difficulty in fully depleting Ca (2 +) from its binding site, as has been found with bacterial CcOs.

Ca (2 +)


Input: The implications of Ca (2 +)/Na (+) ion binding are discussed in terms of structure and possible modulation of core catalytic function.

Ca (2 +)

Na (+)


Input: NMDA receptor-dependent function and plasticity in inhibitory circuits.

NMDA


Input: NMDA receptors have been known to play a central role in long-term potentiation at glutamatergic synapses in principal cells for thirty years.

NMDA


Input: In contrast, their roles in the development and activity-dependent plasticity of synapses in inhibitory circuits have only recently begun to be understood.


Input: Progress has, to a great extent, been hampered by the extensive diversity of GABAergic cell types in the CNS.


Input: However, anatomical, immunohistochemical and electrophysiological methods have allowed distinct types to be identified, with the result that consistent patterns of synaptic plasticity have begun to emerge.


Input: This review summarizes recent evidence on the role of NMDA receptors in the development and plasticity of GABAergic synapses on principal cells and of glutamatergic synapses on identified interneurons.

NMDA


Input: A major challenge is to understand how NMDA receptors affect the routing of information in healthy inhibitory circuits, and how changes in NMDA receptor function may contribute to altered circuit function in disorders such as schizophrenia.

NMDA

NMDA


Input: This article is part of a Special Issue entitled " Glutamate receptor-dependent synaptic plasticity ".

Glutamate


Input: Nanocarrier systems for oral drug delivery: Do we really need them?


Input: In particular since the last two decades there is constantly increasing interest in nanocarrier systems.


Input: They are utilized in order to overcome the major challenges being associated with this route of administration-namely poor solubility (I), poor permeability (II) and poor GI-stability (III).


Input: In order to improve drug solubility nanonization of the API, the use of solid lipid nanoparticles and porous adsorbent particles have shown great potential.


Input: Nanocrystals and selfnanoemulsifying drug delivery systems (SNEDDS) resulted already in numerous marketed drug products.


Input: Moreover, proof-of-principle studies for nanocarrier systems providing enhanced oral drug uptake are available.


Input: By providing a comparatively more intimate contact with the absorption membrane, a prolonged GI-residence time and/or exhibiting permeation enhancing properties, oral absorption can be strongly improved.


Input: Likely because of safety considerations and because of insufficiently high bioavailability improvements (< 5-fold), however, a commercial interest in these systems is limited.


Input: Poor GI-stability can be overcome by incorporating the drug in nanocarrier systems providing a protective effect towards an enzymatic attack in the GI-tract.


Input: Furthermore, as nanocarrier systems can at least to some extent diffuse into the mucus gel layer releasing their payload there, a presystemic metabolism of the drug on the way between the delivery system and the absorption membrane can be excluded.


Input: Future trends are mainly focusing on carrier systems capable of not just improving solubility but providing also controlled drug release as well as on nanocarrier systems capable of efficiently permeating the mucus gel layer without destroying it.


Input: Amino acids as co-amorphous stabilizers for poorly water soluble drugs-Part 1: Preparation, stability and dissolution enhancement.

Amino acids


Input: Poor aqueous solubility of an active pharmaceutical ingredient (API) is one of the most pressing problems in pharmaceutical research and development because up to 90% of new API candidates under development are poorly water soluble.


Input: These drugs usually have a low and variable oral bioavailability, and therefore an unsatisfactory therapeutic effect.


Input: One of the most promising approaches to increase dissolution rate and solubility of these drugs is the conversion of a crystalline form of the drug into its respective amorphous form, usually by incorporation into hydrophilic polymers, forming glass solutions.


Input: However, this strategy only led to a small number of marketed products usually because of inadequate physical stability of the drug (crystallization).


Input: In this study, we investigated a fundamentally different approach to stabilize the amorphous form of drugs, namely the use of amino acids as small molecular weight excipients that form specific molecular interactions with the drug resulting in co-amorphous forms.

amino acids


Input: The two poorly water soluble drugs carbamazepine and indomethacin were combined with amino acids from the binding sites of the biological receptors of these drugs.

carbamazepine

indomethacin

amino acids


Input: Mixtures of drug and the amino acids arginine, phenylalanine, tryptophan and tyrosine were prepared by vibrational ball milling.

amino acids arginine

phenylalanine

tryptophan

tyrosine


Input: Solid-state characterization with X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) revealed that the various blends could be prepared as homogeneous, single phase co-amorphous formulations indicated by the appearance of an amorphous halo in the XRPD diffractograms and a single glass transition temperature (Tg) in the DSC measurements.


Input: In addition, the Tgs of the co-amorphous mixtures were significantly increased over those of the individual drugs.


Input: The drugs remained chemically stable during the milling process and the co-amorphous formulations were generally physically stable over at least 6months at 40 degrees C under dry conditions.


Input: The dissolution rate of all co-amorphous drug-amino acid mixtures was significantly increased over that of the respective crystalline and amorphous pure drugs.

amino acid


Input: Amino acids thus appear as promising excipients to solve challenges connected with the stability and dissolution of amorphous drugs.

Amino acids


Input: Dysfunctions of the translational machinery in digestive glands of mussels exposed to mercury ions.

mercury


Input: Mercury is an element naturally occurring in the biosphere, but is also released into the environment by human activities, such as mining, smelting, and industrial discharge.

Mercury


Input: Mercury is a biologically harmful element and any exposure of living organisms mainly due to contamination, can cause severe or even lethal side effects.

Mercury


Input: In every form detected, elemental, inorganic, or organic, mercury exhibits toxicity associated with induced oxidative stress.

mercury