bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of Genomic Damage in Peripheral Lymphocytes from Occupationally Exposed Anesthetists: Assessment of the Effects of Age, Sex, and GSTT1 Gene Polymorphism
Authors: Santovito Alfredo , Cervella Piero , Delpero Massimiliano 
Published: February 2015

ABSTRACTOccupational exposure to anaesthetic gases is one of the major hazards to healthcare personnel. We evaluated the cytogenetic effects of chronic exposure to low concentrations of anaesthetic gases in operating theatres. The study included 21 anesthetists and 21 control subjects who matched in age and gender. Chromosome aberrations (CAs) and sister chromatid exchanges (SCEs) assays were performed. All subjects were also genotyped for glutathione S‐transferase T1 (GSTT1) gene polymorphisms. Significant differences were found between exposed and controls in terms of SCEs frequency (P = 0.001) and replication index value (P = 0.005), but not in terms of CAs (P = 0.201) and aberrant cells (P = 0.227) frequencies. Regression analyses indicated that age and the years of employment did not influence the level of chromosomal damage in both groups. Finally, among anesthetists, GSTT1 null individuals showed a significant higher frequency of SCE with respect to GSTT1‐positive subjects.
Physico‐chemical properties and hypoglycaemic activity of fermented milks prepared with Anemarrhena asphodeloides water extracts
Authors: Zhang Rong , Yang Liu , Ji Jing , Li Bei‐bei , Li Lan , Ye Ming 
Published: February 2015

AbstractBACKGROUNDIn this research, water extract solutions of Anemarrhena asphodeloides (AA) rhizomes were added to reconstituted milk at 5%, 10% and 15% (v/v) to prepare AA fermented milk (AAFM5, AAFM10 and AAFM15). The AAFM10 was selected for investigation of hypoglycaemic activity.RESULTSCompared with the control fermented milk, titratable acidity values and water‐holding capacities of AA fermented milk were increased to different extents, but syneresis values were reduced. The viable counts of Streptococcus thermophilus, Lactobacillus bulgaricus and Bifidobacterium adolescentis were significantly increased, respectively. The blood sugar level of streptozotocin diabetic mice taking AAFM10 was reduced by 14.4%, and the food intake was decreased. The contents of malondialdehyde, blood urea nitrogen, serum creatinine, triglycerides, total cholesterol, and low‐density lipoprotein cholesterol were reduced by different degrees, and insulin and total superoxide dismutase were significantly increased.CONCLUSIONAAFM10 had a significant hypoglycaemic effect and improvement in the complications (such as kidney disease and hyperlipemia) in the mouse model of diabetes. © 2015 Society of Chemical Industry
Sensory characterization during repeated ingestion of small‐molecular‐weight phenolic acids
Authors: Duizer Lisa M , Langfried Allison 
Published: February 2015

AbstractBACKGROUNDCharacterization of the sensory properties of small‐molecular‐weight phenolic acids such as ferulic and vanillic acids has been limited. The objectives of this study were to characterize the sensory perceptions of these acids and the effects of their repeated consumption on sourness, bitterness and astringency. This knowledge will further the understanding of the impact of these acids on the sensory characteristics of foods in which they are typically consumed.RESULTSTwo time–intensity sensory evaluation experiments were conducted with nine trained panelists: a single‐sip study and a sequential‐sip study. Concentrations of phenolic acids typically found in whole grain bread were tested. For both experiments, vanillic acid was perceived to be significantly more sour than ferulic acid, and ferulic acid was perceived to be significantly more bitter than vanillic acid. Maximum sourness, bitterness and astringency intensities significantly increased with increasing molarity for both acids. During sequential sipping, astringency and bitterness intensity increased with each sip. Sourness, however, increased to sip 3 but did not significantly increase after that point.CONCLUSIONThis research demonstrates that even small quantities of phenolic acids can be perceived as increasingly bitter and astringent with repeated exposures. © 2015 Society of Chemical Industry
1064 nm long‐pulsed Nd:YAG laser treatment of basal cell carcinoma
Authors: Ortiz Arisa E. , Anderson R. Rox , Avram Mathew M. 
Published: February 2015

Background and ObjectiveStandard surgical and destructive treatments for basal cell carcinoma (BCC) can result in significant morbidity and scarring, stimulating the investigation of alternative non‐surgical options. The objective of this study was to determine the safety, clinical, and histological efficacy of pulsed, high‐fluence 1064 nm Nd:YAG laser therapy for the treatment of BCC on the trunk and extremities.Study Design/Materials and MethodsThis was a prospective, non‐randomized, open‐label clinical trial. Ten subjects with a biopsy‐proven BCC less than 1.5 cm in diameter on the trunk or extremities received one treatment with a 10 milliseconds pulsed 1064 nm Nd:YAG laser. Standard excision was performed 1 month after laser treatment to confirm histologic clearance.ResultsThe laser treatment was quick and well tolerated. There was complete histologic clearance after one treatment in 92% of the BCC tumors, overall. At higher fluences, there was 100% histologic clearance after one treatment. No significant adverse events were seen, including scarring.ConclusionsThe 1064 nm long‐pulsed Nd:YAG laser may offer a safe alternative for treating BCC off the face. A larger study is highly warranted to confirm these preliminary results. Lasers Surg. Med. 47:106–110, 2015. © 2015 Wiley Periodicals, Inc.
Low‐fluence 585 nm Q‐switched Nd:YAG laser: A novel laser treatment for post‐acne erythema
Authors: Panchaprateep Ratchathorn , Munavalli Girish 
Published: February 2015

BackgroundPersistent post‐acne erythema is one of the most common aesthetic sequelae to arise after active acne resolves. The treatment remains challenging due to lack of effective laser modalities.ObjectivesTo evaluate the safety and efficacy of a low‐fluence 585 nm Q‐switched Nd:YAG laser for the treatment of post‐acne erythema.Materials & MethodsTwenty‐five patients with post‐acne erythema were treated with a low‐fluence Q‐switched Nd:YAG laser using the 585 nm Gold Toning™ handpiece (5 mm spot size, 5–10 ns, 0.30–0.55 J/cm2, 2–4 passes) for three sessions at 2‐week intervals. Erythema lesion (macules) count, inflammatory acne (papules, pustules) count, erythema index, degree of post‐acne erythema and overall improvement in post‐acne erythema and acne scar were assessed at baseline, every 2 weeks and 6 weeks after the last treatment. Subjective degrees of satisfaction were also evaluated. Adverse events were recorded and pain was scored using a visual analog scale (VAS).ResultsAt 6 weeks after 3 sessions of laser treatment, all patients demonstrated clinical improvement. Erythema lesion counts decreased by 20.1% (versus baseline) after the first treatment (P = 0.004), by 32.7% after the second treatment, by 46.5% at 2 weeks after the third treatment and by 58.7% at the 6‐week follow‐up (allP < 0.001). Significant improvements were also noted in erythema indices (22.29 ± 2.4 to 17.51 ± 1.8) and mean post‐acne erythema scores after the first treatment (bothP < 0.001). The mean scores of independent physician assessments were 4.04 ± 0.9 in term of the improvement of post‐acne erythema and 3.44 ± 0.9 in the improvement of scaring. In addition, we could observe a significant decrease in inflammatory acne lesion counts after two laser treatments with a decrease in mean lesion counts by 67% at the 6‐week follow‐up. Treatment was well‐tolerated and adverse effects were limited to transient erythema and edema at treatment sites.ConclusionsLow‐fluence 585 nm Q‐switched Nd:YAG laser treatment is safe and effective for the treatment of post‐acne erythema with minimal discomfort and quantifiable improvement in the appearance of early acne scarring and inflammatory acne. Lasers Surg. Med. 47:148–155, 2015. © 2015 Wiley Periodicals, Inc.
Concentration, working speed and memory: Cognitive problems in young childhood cancer survivors and their siblings
Authors: Wengenroth L. , Rueegg C. S. , Michel G. , Gianinazzi M. E. , Essig S. , von der Weid N. X. , Grotzer M. , Kuehni Claudia E. ,   for the Swiss Paediatric Oncology Group SPOG
Published: February 2015

BackgroundCognitive problems can have a negative effect on a person's education, but little is known about cognitive problems in young childhood cancer survivors (survivors). This study compared cognitive problems between survivors and their siblings, determined if cognitive problems decreased during recent treatment periods and identified characteristics associated with the presence of a cognitive problem in survivors.MethodsAs part of the Swiss Childhood Cancer Survivor Study, a questionnaire was sent to all survivors, aged 8–20 years, registered in the Swiss Childhood Cancer Registry, diagnosed at age <16 years, who had survived ≥5 years. Parent‐reported (aged 8–15 years) and self‐reported (aged 16–20 years) cognitive problems (concentration, working speed, memory) were compared between survivors and siblings. Multivariable logistic regression was used to identify characteristics associated with cognitive problems in survivors.ResultsData from 840 survivors and 247 siblings were analyzed. More often than their siblings, survivors reported problems with concentration (12% vs. 6%; P = 0.020), slow working speed (20% vs. 8%; P = 0.001) or memory (33% vs. 15%; P < 0.001). Survivors from all treatment periods were more likely to report a cognitive problem than were siblings. Survivors of CNS tumors (OR = 2.82 compared to leukemia survivors, P < 0.001) and those who had received cranial irradiation (OR = 2.10, P = 0.010) were most severely affected.ConclusionChildhood cancer survivors, even those treated recently (2001–2005), remain at risk to develop cognitive problems, suggesting a need to improve therapies. Survivors with cognitive problems should be given the opportunity to enter special education programs. Pediatr Blood Cancer 2015;62:875–882. © 2015 Wiley Periodicals, Inc.
Does the average drug exposure in pregnant women affect pregnancy outcome? A comparison of two approaches to estimate the baseline risks of adverse pregnancy outcome
Authors: Wacker Evelin , Navarro Ana , Meister Reinhard , Padberg Stephanie , Weber‐Schoendorfer Corinna , Schaefer Christof 
Published: February 2015

AbstractPurposeThe results of observational cohort studies on drug effects on pregnancy outcome may depend among others on suitable comparison cohorts. The aim of this investigation was to compare two distinct definitions of maternal exposure status for comparison cohorts.MethodsWe performed an observational cohort study of prospectively ascertained pregnant women who spontaneously contacted the Teratology Information Service (TIS) Berlin for drug risk consultation. The only exclusion criteria were exposures to established teratogens and/or fetotoxicants. Pregnancy outcomes of 3250 women with this “average drug exposure” were compared with 546 non‐exposed or insignificantly exposed pregnancies.ResultsNeither the rate of major birth defects (3.0%; aOR 1.62; 95% CI 0.8–3.3) nor the risk of spontaneous abortion (16.0%; aHR 1.20; 95% CI 0.8–1.7) was significantly increased after average drug exposure, whereas the rate of electively terminated pregnancies was higher (11.1%; aHR 2.05; 95% CI 1.2–3.4). There were no differences in the risk of preterm birth (9.9%; aOR 1.38; 95% CI 0.9–2.0) and infants' birth weight (p = 0.60).ConclusionsThis study does not provide evidence for an increased risk of adverse pregnancy outcome after average drug exposure during pregnancy. Therefore, comparison cohorts with average drug exposure are appropriate for studies on potential teratogens or fetotoxicants based on observational data collected by TIS. Copyright © 2015 John Wiley & Sons, Ltd.
Homo‐double helix formation of an optically active conjugated polymer bearing carboxy groups and amplification of the helicity upon complexation with achiral and chiral amines
Authors: Makiguchi Wataru , Kobayashi Shinzo , Furukawa Keisuke , Iida Hiroki , Furusho Yoshio , Yashima Eiji 
Published: February 2015

ABSTRACTAn optically active, m‐terphenyl‐based π‐conjugated polymer bearing carboxy groups was synthesized by the copolymerization of the diethynyl monomer bearing a carboxy group with (S,S)‐2,5‐bis(2‐methylbutoxy)‐1,4‐dibromobenzene using Sonogashira reaction. The copolymer showed a weak circular dichroism (CD) in the main‐chain chromophore region due to a homo‐double helix formation with an excess helical handedness biased by the chiral alkoxy substituents through self‐association. However, upon complexation with achiral amines, such as piperidine, the CD intensity of the polymer significantly increased resulting in the formation of a greater excess one‐handed homo‐double helix via hydrogen‐bonded inclusion complexation with the achiral amines between each strand, leading to the amplification of the helicity. A preferred‐handed homo‐double helix was also induced in the polymer in the presence of nonracemic amines. The effect of the achiral and chiral amines on the homo‐double helix formation was investigated by comparing the CD spectra of the polymer to those of its model dimer. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 990–999
Aromatic cluster mutations produce focal modulations of β‐sheet structure
Authors: Biancalana Matthew , Makabe Koki , Yan Shude , Koide Shohei 
Published: February 2015

AbstractSite‐directed mutagenesis is a powerful tool for altering the structure and function of proteins in a focused manner. Here, we examined how a model β‐sheet protein could be tuned by mutation of numerous surface‐exposed residues to aromatic amino acids. We designed these aromatic side chain “clusters” at highly solvent‐exposed positions in the flat, single‐layer β‐sheet of Borrelia outer surface protein A (OspA). This unusual β‐sheet scaffold allows us to interrogate the effects of these mutations in the context of well‐defined structure but in the absence of the strong scaffolding effects of globular protein architecture. We anticipated that the introduction of a cluster of aromatic amino acid residues on the β‐sheet surface would result in large conformational changes and/or stabilization and thereby provide new means of controlling the properties of β‐sheets. Surprisingly, X‐ray crystal structures revealed that the introduction of aromatic clusters produced only subtle conformational changes in the OspA β‐sheet. Additionally, despite burying a large degree of hydrophobic surface area, the aromatic cluster mutants were slightly less stable than the wild‐type scaffold. These results thereby demonstrate that the introduction of aromatic cluster mutations can serve as a means for subtly modulating β‐sheet conformation in protein design.
Target validation and structure–activity analysis of a series of novel PCNA inhibitors
Authors: Dillehay Kelsey L. , Seibel William L. , Zhao Daoli , Lu Shan , Dong Zhongyun 
Published: February 2015

AbstractProliferating cell nuclear antigen (PCNA) plays an essential role in DNA replication and repair. Tumor cells express high levels of PCNA, identifying it as a potentially ideal target for cancer therapy. Previously, we identified nine compounds termed PCNA inhibitors (PCNA‐Is) that bind directly to PCNA, stabilize PCNA trimer structure, reduce chromatin‐associated PCNA, and selectively inhibit tumor cell growth. Of these compounds, PCNA‐I1 was most potent. The purpose of this study is to further establish targeting of PCNA by PCNA‐I1 and to identify PCNA‐I1 analogs with superior potencies. We found that PCNA‐I1 does not affect the level of chromatin‐associated PCNA harboring point mutations at the predicted binding site of PCNA‐I1. Forty‐six PCNA‐I1 analogs with structures of 1‐hydrazonomethyl‐2‐hydroxy (scaffold A), 2‐hydrazonomethyl‐1‐hydroxy (scaffold B), 2‐hydrazonomethyl‐3‐hydroxy (scaffold C), and 4‐pyridyl hydrazine (scaffold D) were analyzed for their effects on cell growth in four tumor cell lines and PCNA trimer stabilization. Compounds in scaffold group A and group B showed the highest trimer stabilization and the most potent cell growth inhibitory activities with a significant potency advantage observed in the Z isomers of scaffold A. The absence of trimer stabilization and growth inhibitory effects in compounds of scaffold group D confirms the essentiality of the hydroxynaphthyl substructure. Compounds structure–activity relationship (SAR)‐6 and SAR‐24 were analyzed for their effects on and found to reduce chromatin‐associated PCNA in tumor cells. This study led to the identification of SAR‐24, a compound with superior potencies and potentially improved solubility, which will be used for future development of PCNA‐targeting cancer therapies.
Long‐lasting oral analgesic effects of N‐protected aminophosphinic dual ENKephalinase inhibitors (DENKIs) in peripherally controlled pain
Authors: Bonnard Elisabeth , Poras Hervé , Nadal Xavier , Maldonado Rafael , Fournié‐Zaluski Marie‐Claude , Roques Bernard P. 
Published: February 2015

AbstractThe peripheral endogenous opioid system is critically involved in neuropathic and inflammatory pain generation as suggested by the modulation of opioid receptors expression and enkephalins (ENKs) release observed in these painful conditions. Accordingly, an innovative approach in the treatment of these nocifensive events is to increase and maintain high local concentrations of extracellular pain‐evoked ENKs, by preventing their physiological enzymatic inactivation by two Zn metallopeptidases, the neutral endopeptidase (NEP, neprilysin, EC 3.4.24.11) and the neutral aminopeptidase (APN, EC 3.4.11.2). With this aim, new orally active dual ENKephalinase inhibitors (DENKIs) were designed as soluble prodrugs by introducing a N‐terminal cleavable carbamate in the previously described aminophosphinic inhibitors. This induces long‐lasting antinociceptive responses after oral administration, in various rodent models of inflammatory and neuropathic pain. These responses are mediated through stimulation of peripheral opioid receptors by DENKIs‐protected ENKs as demonstrated by naloxone methiodide reversion. In all tested models, the most efficient prodrug 2a (PL265) was active, at least during 150–180 min, after single oral administration of 25–50 mg/kg in mice and of 100–200 mg/kg in rats. In models of neuropathic pain, both hyperalgesia and allodynia were markedly reduced. Interestingly, combination of inactive doses of 2a (PL265) and of the anti‐epileptic drug gabapentin had synergistic effect on neuropathic pain. Pharmacokinetic studies of 2a (PL265) in rats show that the active drug is the only generated metabolite produced. These encouraging results have made 2a (PL265) a suitable candidate for clinical development.
Preclinical evaluation of the antipsychotic potential of the mGlu2‐positive allosteric modulator JNJ‐40411813
Authors: Lavreysen Hilde , Langlois Xavier , Donck Luc Ver , Nuñez José María Cid , Pype Stefan , Lütjens Robert , Megens Anton 
Published: February 2015

AbstractJNJ‐40411813/ADX71149 (1‐butyl‐3‐chloro‐4‐(4‐phenylpiperidin‐1‐yl) pyridin‐2(1H)‐one) is a positive allosteric modulator (PAM) of the mGlu2 receptor, which also displays 5‐Hydroxytryptamine (5HT2A) antagonism after administration in rodents due to a rodent‐specific metabolite. JNJ‐40411813 was compared with the orthosteric mGlu2/3 agonist LY404039 (4‐amino‐2‐thiabicyclo [3.1.0] hexane‐4,6‐dicarboxylic acid 2,2‐dioxide), the selective mGlu2 PAM JNJ‐42153605 (3‐(cyclopropylmethyl)‐7‐(4‐phenylpiperidin‐1‐yl)‐8‐(trifluoromethyl)[1,2,4]triazolo[4,3‐a]pyridine) and the 5HT2A antagonist ritanserin in rodent models for antipsychotic activity and potential side effects, attempting to differentiate between the various compounds and mechanisms of action. In mice, JNJ‐40411813, JNJ‐42153605, and LY404039 inhibited spontaneous locomotion and phencyclidine‐ and scopolamine‐induced but not d‐amphetamine‐induced hyperlocomotion; the 5HT2A antagonist ritanserin inhibited only spontaneous locomotion and phencyclidine‐induced hyperlocomotion. As measured by 2‐deoxyglucose uptake, all compounds reversed memantine‐induced brain activation in mice. The two mGlu2 PAMs and LY404039, but not ritanserin, inhibited conditioned avoidance behavior in rats. Like ritanserin, the mGlu2 ligands antagonized 2,5‐dimethoxy‐4‐methylamphetamine‐induced head twitches in rats. LY404039 but not the mGlu2 PAMs impaired rotarod performance in rats and increased the acoustic startle response in mice. Our results show that although 5HT2A antagonism has effect in some models, mGlu2 receptor activation is sufficient for activity in several animal models of antipsychotic activity. The mGlu2 PAMs mimicked the in vivo pharmacodynamic effects observed with LY404039 except for effects on the rotarod and acoustic startle, suggesting that they produce a primary activity profile similar to that of the mGlu2/3 receptor agonist while they can be differentiated based on their secondary activity profile. The results are discussed in light of clinical data available for some of these molecules, in particular JNJ‐40411813.
A floatable formulation and laboratory bioassay of Pandora delphacis (Entomophthoromycota: Entomophthorales) for the control of rice pest Nilaparvata lugens Stål (Hemiptera: Delphacidae)
Authors: Zhou Xiang , Su Xiu , Liu Hongbo 
Published: February 2015

AbstractBACKGROUNDThe brown planthopper (BPH), Nilaparvata lugens (Staparvata luera: Delphacidae), is a serious rice pest that easily develops resistance to chemical insecticides and resistant rice varieties. This study evaluated the infectivity of the BPH fungal pathogen, Pandora delphacis, and developed a novel formulation as an alternative means of BPH control.RESULTSIn a multiconidial concentration bioassay, P. delphacis‐infected BPH cadavers were observed on day 4, but most occurred between days 5 and 8. BPH mortality depended on the inoculated conidial concentration. The cumulative mortality of adult BPHs reached 81.7% at 192 conidia mm−2 in 8 days. Inoculation with 40.9 conidia mm−2 was sufficient to induce 50% BPH death, based on analysis of a time‐concentration‐mortality model. A floatable P. delphacis‐based formulation was made for use in paddy fields; mycelium‐containing pellets mimicking mycosed cadavers could produce 7–15.7 × 104 infectious conidia pellet−1 at 11–28 °C. In the laboratory bioassay, three floating pellets in a BPH‐rearing jar caused 75.5% BPH mortality within 8 days, similar to the mortality level caused by direct conidial inoculation.CONCLUSIONP. delphacis is a potential biocontrol agent of BPHs for further research, and the novel floatable formulation holds promise as a method for BPH control. © 2015 Society of Chemical Industry