bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enzymatic properties and substrate specificity of a bacterial phosphatidylcholine synthase
Authors: Aktas Meriyem , Köster Stefan , Kizilirmak Sarah , Casanova Javier C. , Betz Heidi , Fritz Christiane , Moser Roman , Yildiz Özkan , Narberhaus Franz 
Published: June 2014

Phosphatidylcholine (PC) is a rare membrane lipid in bacteria, but is crucial for virulence of the plant pathogen Agrobacterium tumefaciens and various other pathogens. Agrobacterium tumefaciens uses two independent PC biosynthesis pathways. One is dependent on the integral membrane protein PC synthase (Pcs), which catalyzes the conversion of cytidine diphosphate–diacylglycerol (CDP–DAG) and choline to PC, thereby releasing a cytidine monophosphate (CMP). Here, we show that Pcs consists of eight transmembrane segments with its N‐ and C‐termini located in the cytoplasm. A cytoplasmic loop between the second and third membrane helix contains the majority of the conserved amino acids of a CDP‐alcohol phosphotransferase motif (DGX2ARX12GX3DX3D). Using point mutagenesis, we provide evidence for a crucial role of this motif in choline binding and enzyme activity. To study the catalytic features of the enzyme, we established a purification protocol for recombinant Pcs. The enzyme forms stable oligomers and exhibits broad substrate specificity towards choline derivatives. The presence of CDP–DAG and manganese is a prerequisite for cooperative binding of choline. PC formation by Pcs is reversible and proceeds via two successive reactions. In a first choline‐ and manganese‐independent reaction, CDP–DAG is hydrolyzed releasing a CMP molecule. The resulting phosphatidyl intermediate reacts with choline in a second manganese‐dependent step to form PC.Structured digital abstract

Pcs and Pcs bind by molecular sieving (1, 2, 3)
Evaluating pharmacist prescribing for minor ailments
Authors: Mansell Kerry , Bootsman Nicole , Kuntz Arlene , Taylor Jeff 
Published: June 2014

Abstract

Objectives
Saskatchewan is the second Canadian province to allow pharmacists to prescribe medications for minor ailments and the only province that remunerates for this activity. The aim of this project was to determine whether patients prescribed such treatment by a pharmacist symptomatically improve within a set time frame.

Methods
Pharmacists were asked to hand a study-invitation card to anyone for whom they prescribed a medication for a minor ailment during the 1-year study period. Consenting participants contacted the study researchers directly and were subsequently instructed to complete an online questionnaire at the appropriate follow-up time.

Key findings
Ninety pharmacies in Saskatchewan participated, accruing 125 participants. Cold sores were the most common minor ailment (34.4%), followed by insect bites (20%) and seasonal allergies (19.2%). Trust in pharmacists and convenience were the most common reasons for choosing a pharmacist over a physician, and 27.2% would have chosen a physician or emergency department if the minor ailment service were not available. The condition significantly/completely improved in 80.8%; only 4% experienced bothersome side effects. Satisfaction with the pharmacist and service was strong; only 5.6% felt a physician would have been more thorough.

Conclusions
Participants were very satisfied with their symptomatic improvement and with the service in general, albeit for a small number of conditions. Participants reported getting better, and side effects were not a concern. These results are encouraging for pharmacists; however, a comparison of physician care with pharmacist care and unsupported self-care is required to truly know the benefit of pharmacist prescribing.
Efficacy of traditional and alternative sunitinib treatment schedules in Japanese patients with metastatic renal cell carcinoma
Authors: Ohzeki Takayuki , Fukasawa Satoshi , Komaru Atsushi , Namekawa Takeshi , Sato Yosuke , Takagi Kimiaki , Kobayashi Masayuki , Uemura Hirotsugu , Ichikawa Tomohiko , Ueda Takeshi 
Published: June 2014

AbstractWe report the adverse events and efficacy of traditional (4 weeks on 2 weeks off) and alternative sunitinib treatment schedules for Japanese patients with metastatic renal cell carcinoma. We retrospectively investigated 54 patients who received sunitinib for metastatic renal cell carcinoma between May 2006 and June 2012: 32 received a traditional treatment schedule and 22 received an alternative schedule. According to the Memorial Sloan‐Kettering Cancer Center risk classification, five patients had favorable prognoses, 42 had intermediate prognoses and seven had poor prognoses. The mean observation periods were 16.3 and 20 months for the traditional and alternative schedule groups, respectively. Adverse events were significantly less common in the alternative schedule group, including most high‐grade events. In the traditional and alternative schedule groups, median times to failure were 4.1 and 11.6 months (P = 0.040), median progression‐free survival times were 4.1 and 11.3 months (P = 0.031), and median overall survival times were 12.0 and 32.1 months (P = 0.018), respectively. Each of these measures was better in the group of patients who received an alternative treatment schedule, suggesting that individualized changes to the sunitinib administration schedule can be effective.
Are testicular mast cells involved in the regulation of germ cells in man?
Authors: Windschüttl S. , Nettersheim D. , Schlatt S. , Huber A. , Welter H. , Schwarzer J. U. , Köhn F. M. , Schorle H. , Mayerhofer A. 
Published: June 2014

SummaryProtease activated receptor‐2 (PAR‐2) is the receptor for the prototype mast cell product tryptase. PAR‐2 expression by cells of the human germinal epithelium was reported, but the exact cellular sites of testicular expression remained unknown. That became of interest, because mast cells, expressing tryptase, were found in the walls of seminiferous tubules of patients suffering from sub‐ and infertility. This location suggested that mast cells via tryptase might be able to influence PAR‐2‐expressing cells in the germinal epithelium. To explore these points, we used testicular paraffin‐embedded sections for immunohistochemistry. PAR‐2‐positive cells were mostly basally located cells of the seminiferous epithelium, namely spermatogonia. Some stained for the receptor for GDNF (GFRalpha‐1), and possibly represent spermatogonial stem cells (SSCs). As true human SSCs could not be examined, we turned to TCam‐2 seminoma cells, expressing PAR‐2 and stem cell markers, including GFRalpha‐1. TCam‐2 cells robustly responded to stimulation with a specific PAR‐2 agonist (SLIGKV) by increased intracellular Ca2+ levels. Recombinant tryptase and trypsin, but not a control peptide (VKGILS) evoked this response, implying functional PAR‐2. Video imaging and caspase 3/7 assays showed that SLIGKV and tryptase prevented spontaneous apoptosis and increased proliferation of TCam‐2 cells. The expression of the marker of pluripotency OCT3/4 was unchanged upon activation of PAR‐2, suggesting that the stem cell‐like character is not changed. Furthermore, human germ cell cancers were examined. A subset of seminoma and carcinoma in situ samples expressed PAR‐2, indicating that yet unknown subgroups exist. Collectively, the descriptive data obtained in human testicular sections, in germ cell cancers and the functional results in TCam‐2 cells imply a trophic role of mast cell‐derived tryptase for human germ cells. This may be relevant for subtypes of human germ cell cancers, and possibly SSCs. It also raises the possibility that PAR‐2 agonists might be useful for the in vitro propagation of human SSCs.
Expression of testicular androgen receptor in non‐obstructive azoospermia and its change after hormonal therapy
Authors: Kato Y. , Shiraishi K. , Matsuyama H. 
Published: June 2014

SummarySeveral trials aimed at improving the sperm retrieval from men with non‐obstructive azoospermia (NOA) by optimizing intratesticular testosterone (ITT) have reported partial responses, however, an appropriate level of ITT has not been identified. In this study, we examined the expression of the testicular androgen receptor (AR) in NOA and investigated its correlation with clinical and pathological parameters. Expression of the testicular AR was investigated in 52 men with NOA and 22 men with obstructive azoospermia (OA). Twenty‐two patients for whom sperm retrieval failed during microdissection testicular sperm extraction (micro‐TESE) were enrolled in hormonal therapy using hCG with or without recombinant human follicle stimulating hormone (rhFSH) prior to a second micro‐TESE. Sertoli cells were identified by vimentin immunostaining, and positivity in Sertoli cells was used as the AR index. AR immunostaining was robust in the nuclei of Sertoli cells [Sertoli cell androgen receptor (SCAR)] in both OA and NOA. The mean AR index in NOA was significantly higher than that in OA (p < 0.05). In NOA patients, there was no correlation between the AR index and the clinical parameters, whereas the AR index of early maturation arrest (MA) was significantly lower than that of Sertoli cell only, late MA and hypospermatogenesis (p < 0.05). A significant increase in the AR index after salvage hormonal therapy was shown, particularly when using rhFSH. The AR index in patients from whom spermatozoa could be retrieved at the second micro‐TESE increased significantly after hormonal therapy. In human testes, the expression of AR is dominant in Sertoli cells, and the expression of SCAR is upregulated by FSH. Germ cell maturation, especially during spermatogonia to spermatocyte stage, has been shown to be SCAR‐dependent. Taken together, the results indicate that SCAR elevation is closely associated with sperm retrieval after hormonal therapy and that FSH‐based hormonal therapy is potentially effective in NOA men with MA.
Association between fluid balance and survival in critically ill patients
Authors: Lee J. , de Louw E. , Niemi M. , Nelson R. , Mark R. G. , Celi L. A. , Mukamal K. J. , Danziger J. 
Published: June 2014

AbstractObjectiveAlthough the consequences of chronic fluid retention are well known, those of iatrogenic fluid retention that occurs during critical illness have not been fully determined. Therefore, we investigated the association between fluid balance and survival in a cohort of almost 16 000 individuals who survived an intensive care unit (ICU) stay in a large, urban, tertiary medical centre.DesignLongitudinal analysis of fluid balance at ICU discharge and 90‐day post‐ICU survival.MeasurementsAssociations between fluid balance during the ICU stay, determined from the electronic bedside record, and survival were tested using Cox proportional hazard models adjusted for severity of critical illness.ResultsThere were 1827 deaths in the first 90 days after ICU discharge. Compared with the lowest quartile of discharge fluid balance [median (interquartile range) −1.5 (−3.1, −0.7) L], the highest quartile [7.6 (5.7, 10.8) L] was associated with a 35% [95% confidence interval (CI) 1.13–1.61)] higher adjusted risk of death. Fluid balance was not associated with outcome amongst individuals without congestive heart failure or renal dysfunction. Amongst patients with either comorbidity, however, fluid balance was strongly associated with outcome, with the highest quartile having a 55% (95% CI 1.24–1.95) higher adjusted risk of death than the lowest quartile. Isotonic fluid balance, defined as the difference between intravenous isotonic fluid administration and urine output, was similarly associated with 90‐day outcomes.ConclusionPositive fluid balance at the time of ICU discharge is associated with increased risk of death, after adjusting for markers of illness severity and chronic medical conditions, particularly in patients with underlying heart or kidney disease. Restoration of euvolaemia prior to discharge may improve survival after acute illness.
Mindfulness as a cognitive–emotional segmentation strategy: An intervention promoting work–life balance
Authors: Michel Alexandra , Bosch Christine , Rexroth Miriam 
Published: June 2014

Employees struggling with work‐related cognitions, emotions, and associated energy levels during non‐work time can find their private roles impaired and work–life balance derogated. To reduce unwanted psychological preoccupation with work concerns, boundary theory suggests employees find their ideal way to integrate or segment both life domains. In this study, the authors design and evaluate an intervention teaching mindfulness as a cognitive–emotional segmentation strategy to promote work–life balance. They use a randomized waitlist control group design to evaluate effects of a 3‐week online self‐training intervention, with 246 employees participating at pre‐ and post‐test, and 191 participating at a 2‐week follow‐up. As expected, experimental group participants, compared with control group participants, experienced significantly less strain‐based work–family conflict and significantly more psychological detachment and satisfaction with work–life balance.Practitioner points

Mindfulness, a cognitive–emotional segmentation strategy, enables employees to balance between work and private life.

Voluntary organizational health and work–life balance programmes should include low‐cost but effective brief mindfulness interventions.
Transcriptional profiles of SHH pathway genes in keratocystic odontogenic tumor and ameloblastoma
Authors: Gurgel Clarissa Araújo Silva , Buim Marcilei Eliza Cavichiolli , Carvalho Kátia Cândido , Sales Caroline Brandi Schlaepfer , Reis Mitermayer Galvão , de Souza Renata Oliveira , de Faro Valverde Ludmila , de Azevedo Roberto Almeida , dos Santos Jean Nunes , Soares Fernando Augusto , Ramos Eduardo Antônio Gonçalves 
Published: June 2014

BackgroundSonic hedgehog (SHH) pathway activation has been identified as a key factor in the development of many types of tumors, including odontogenic tumors. Our study examined the expression of genes in the SHH pathway to characterize their roles in the pathogenesis of keratocystic odontogenic tumors (KOT) and ameloblastomas (AB).MethodsWe quantified the expression of SHH, SMO, PTCH1, SUFU, GLI1, CCND1, and BCL2 genes by qPCR in a total of 23 KOT, 11 AB, and three non‐neoplastic oral mucosa (NNM). We also measured the expression of proteins related to this pathway (CCND1 and BCL2) by immunohistochemistry.ResultsWe observed overexpression of SMO, PTCH1, GLI1, and CCND1 genes in both KOT (23/23) and AB (11/11). However, we did not detect expression of the SHH gene in 21/23 KOT and 10/11 AB tumors. Low levels of the SUFU gene were expressed in KOT (P = 0.0199) and AB (P = 0.0127) relative to the NNM. Recurrent KOT exhibited high levels of SMO (P = 0.035), PTCH1 (P = 0.048), CCND1 (P = 0.048), and BCL2 (P = 0.045) transcripts. Using immunolabeling of CCND1, we observed no statistical difference between primary and recurrent KOT (P = 0.8815), sporadic and NBCCS‐KOT (P = 0.7688), and unicystic and solid AB (P = 0.7521).ConclusionsOverexpression of upstream (PTCH1 and SMO) and downstream (GLI1, CCND1 and BCL2) genes in the SHH pathway leads to the constitutive activation of this pathway in KOT and AB and may suggest a mechanism for the development of these types of tumors.
Metallothionein, a marker of antiapoptosis, is associated with clinical forms of oral lichen planus
Authors: Allon Irit , Ofir Merav , Vered Hanna , Hirshberg Abraham 
Published: June 2014

ObjectivesTo investigate the expression of anti‐ and proapoptosis markers, metallothionein (MT), and caspase‐2, in the epithelial and inflammatory cells of oral lichen planus (OLP) patients, and to investigate the association with clinical parameters.Materials and MethodsIncluded were biopsies of 70 OLP patients. The clinical data were collected from patients' charts. The expression of MT and caspase‐2 was immunomorphometrically analyzed in the epithelial and inflammatory cells, and the results were correlated with the clinical presentation.ResultsThe epithelial and inflammatory cells expressed MT (10.2 ± 5.75 and 0.68 ± 0.86) and caspase‐2 (1.54 ± 2.6 and 0.98 ± 1.15) which show a trend toward an inverse expression. The expression of MT in the epithelium was significantly higher in patients presenting with keratotic lichen planus than in patients with the atrophic and erosive forms (P = 0.0008). In the inflammatory cells, the expression of MT was inversely correlated with increasing age (R = 0.34, P = 0.0069).ConclusionsThe pattern of expression of MT and caspase‐2 in OLP suggests an extensive antiapoptotic response in the keratotic form of the disease. Symptomatic patients may benefit from therapy targeted to apoptosis in the future.
Systemic toxic effects during early phases of topical 4‐NQO‐induced oral carcinogenesis in rats
Authors: Barcessat Ana Rita Ribeiro , Huang Isaac , Rabelo Gustavo Davi , Rosin Flávia Cristina Perillo , Ferreira Luciana Gonçalves Valente , de Cerqueira Luz João Gualberto , Corrêa Luciana 
Published: June 2014

BackgroundMost studies have demonstrated 4‐NQO toxicity to oral epithelium during oral carcinogenesis induction, but systemic toxicity has been poorly addressed. The aim of this study was to describe the systemic effect of 4‐NQO topical application during early phases of oral cancer induction.MethodsA 4‐NQO propylene glycol ointment was topically applied on the rat tongue three times a week for 16 weeks. Local and systemic 4‐NQO toxicity was evaluated by body weight gain, hematology, and serum chemistry analyses, histopathology, and proliferating cell nuclear antigen (PCNA) immunohistochemistry.ResultsSignificant reduction in body weight gain and in white blood cell count as well as significant increase in serum ALT and AST was observed after 16 weeks of 4‐NQO topical application. Focal hepatic lobular necrosis, renal tubular degeneration, and decreased cellularity in the splenic white pulp were also detected.Conclusions4‐NQO topical application on the tongue of rats for 16 weeks seems to have caused hepatic, renal, and splenic toxicity. Potential systemic toxicity should be considered to monitor for variables that could interfere in topical oral carcinogenesis experiments.
Relational motivation and well‐being: A cross‐cultural comparison
Authors: Yi Lyna , Gore Jonathan S. , Kanagawa Chie 
Published: June 2014

AbstractCulture plays a crucial role in motivation. Personally autonomous reasons (PARs) for goals reflect the needs, desires, and commitment for oneself, whereas relationally autonomous reasons (RARs) for goals reflect the needs within close relationships. It was hypothesized thatPARs are the better predictor of well‐being forAmericans, whileRARs are the better predictor of well‐being for Japanese. One‐hundred and seventyAmerican and 219Japanese university students completed well‐being questionnaires and rated seven goals on several attributes. The results confirmed thatRARs were a better predictor of well‐being forJapanese than forAmericans, butPARs predicted well‐being for both groups. Implications for theories of goal motivation are discussed.
Obstructive Uropathy and Vesicovaginal Fistula Secondary to a Retained Sex Toy in the Vagina
Authors: Donaldson James Fergus , Tait Campbell , Rad Marcel , Walker Shonagh , Lam Thomas B.L. , Abdel-Fattah Mohammed , Swami Satchi Kuchibhotla 
Published: June 2014

Abstract

Introduction
Vaginal foreign bodies (FBs) are a rare cause of vesicovaginal, rectovaginal, or urethrovaginal fistulae.

Aim
The aim of this study was to describe a rare case of vesicovaginal fistula (VVF) and obstructive uropathy and to review the literature.

Methods
A case is presented. A comprehensive review of the literature was performed (1948–2013).

Results
A 38-year-old woman presenting with sepsis, obstructive uropathy, and severe emaciation was found to have a sex toy retained in her vagina for 10 years. This had caused a VVF and bilateral hydroureteronephrosis. Bilateral nephrostomies were inserted and she underwent cystoscopy and examination under anesthesia (EUA) with retrieval of FB. A left ureteric stricture was demonstrated. Transabdominal VVF repair with omental flap and left ureteric re-implantation was performed. The VVF recurred, which was successfully re-repaired transvaginally. Seventy-six full text articles were reviewed. There were no previously published cases of VVF following vaginal sex toy insertion. There are four cases of obstructive uropathy secondary to a vaginal FB in the literature: three pessaries and one plastic cap. There are 44 cases of VVF secondary to FB: 22 plastic caps (typically from aerosol bottles, inserted for masturbation or contraception) and 5 pessaries. At least nine were in girls aged ≤18 years. Average presentation is 15 months (range 2 months to 35 years) after FB insertion. Most cases were managed with surgical repair; predominantly transvaginal.

Conclusions
This case describes an extremely rare but potentially life-threatening case of obstructive uropathy caused by a chronically retained sex toy, and adds to the list of potentially rare causes of a VVF and obstructive uropathy. We advocate urinary diversion, staged removal of FB, upper urinary tract imaging, and EUA with VVF repair and/or ureteric reimplantation if required. Transvaginal is the preferred access for FB-associated VVF repair without concomitant ureteric reimplantation.
Revisiting 26Al‐26Mg systematics of plagioclase in H4 chondrites
Authors: Telus M. , Huss G. R. , Nagashima K. , Ogliore R. C. 
Published: June 2014

AbstractZinner and Göpel (, ) found clear evidence for the former presence of 26Al in the H4 chondrites Ste. Marguerite and Forest Vale. They assumed that the 26Al‐26Mg systematics of these chondrites date “metamorphic cooling of the H4 parent body.” Plagioclase in these chondrites can have very high Al/Mg ratios and low Mg concentrations, making these ion probe analyses susceptible to ratio bias, which is inversely proportional to the number of counts of the denominator isotope (Ogliore et al. ). Zinner and Göpel () used the mean of the ratios to calculate the isotope ratios, which exacerbates this problem. We analyzed the Al/Mg ratios and Mg isotopic compositions of plagioclase grains in thin sections of Ste. Marguerite, Forest Vale, Beaver Creek, and Sena to evaluate the possible influence of ratio bias on the published initial 26Al/27Al ratios for these meteorites. We calculated the isotope ratios using total counts, a less biased method of calculating isotope ratios. The results from our analyses are consistent with those from Zinner and Göpel (), indicating that ratio bias does not significantly affect 26Al‐26Mg results for plagioclase in these chondrites. Ste. Marguerite has a clear isochron with an initial 26Al/27Al ratio indicating that it cooled to below 450 °C 5.2 ± 0.2 Myr after CAIs. The isochrons for Forest Vale and Beaver Creek also show clear evidence that 26Al was alive when they cooled, but the initial 26Al/27Al ratios are not well constrained. Sena does not show evidence that 26Al was alive when it cooled to below the Al‐Mg closure temperature. Given that metallographic cooling rates for Ste. Marguerite, Forest Vale, and Beaver Creek are atypical (>5000 °C/Myr at 500 °C) compared with most H4s, including Sena, which have cooling rates of 10–50 °C/Myr at 500 °C (Scott et al. ), we conclude that the Al‐Mg systematics for Ste. Marguerite, Forest Vale, and Beaver Creek are the result of impact excavation of these chondrites and cooling at the surface of the parent body, instead of undisturbed cooling at depth in the H chondrite parent body, like many have assumed.