bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein binding characteristics and pharmacokinetics of ceftriaxone in intensive care unit patients
Authors: Schleibinger Michael , Steinbach Cathérine L. , Töpper Christoph , Kratzer Alexander , Liebchen Uwe , Kees Frieder , Salzberger Bernd , Kees Martin G. 
Published: March 2015

AimsThe aim of the present study was to assess the pharmacokinetics of total and unbound ceftriaxone in intensive care unit (ICU) patients and its protein binding characteristics.MethodsTwenty patients (m/f 15/5, age 25–86 years, body weight 60–121 kg, APACHE II 7–40, estimated glomerular filtration rate 19–157 ml min–1, albumin 11.7–30.1 g l–1, total bilirubin <0.1–36.1 mg dl–1) treated with intravenous ceftriaxone were recruited from two ICUs. Timed plasma samples were obtained using an opportunistic study protocol. Ceftriaxone concentrations were determined by high‐performance liquid chromatography; unbound concentrations were determined after ultrafiltration using a new method which maintains physiological pH and temperature. The pharmacokinetics was described by a one‐compartment model, the protein‐binding characteristics by Michaelis–Menten kinetics.ResultsFor total drug, the volume of distribution was 20.2 l (median; interquartile range 15.6–24.5 l), the half‐life 14.5 h (10.0–25.5 h) and the clearance 0.96 l h–1 (0.55–1.28 l h–1). The clearance of unbound drug was 1.91 l h–1 (1.46–6.20 l h–1) and linearly correlated with estimated glomerular filtration rate (slope 0.85, y‐intercept 0.24 l h–1, r2 = 0.70). The unbound fraction was higher in ICU patients (33.0%; 20.2–44.5%) than reported in healthy volunteers, particularly when renal impairment or severe hyperbilirubinaemia was present. In all patients, unbound concentrations during treatment with ceftriaxone 2 g once daily remained above the EUCAST susceptibility breakpoint (≤1 mg l–1) throughout the whole dosing interval.ConclusionsProtein binding of ceftriaxone is reduced and variable in ICU patients due to hypoalbuminaemia, but also to altered binding characteristics. Despite these changes, the pharmacokinetics of unbound ceftriaxone is governed by renal function. For patients with normal or reduced renal function, standard doses are sufficient.
Agreement between questionnaire report of allergy‐related outcomes in school‐age children and objective measures of atopy: the Saskatchewan rural health study
Authors: Chu L. , Rennie D. , Cockcroft D. , Pahwa P. , Dosman J. , Hagel L. , Karunanayake C. , Lawson J. 
Published: March 2015

SummaryBackground and ObjectivesIn population‐based studies, questionnaires remain the most efficient tool to assess the presence of allergy and atopic conditions, but the quality of the information obtained needs to be validated. We sought to evaluate the agreement and predictive values of a questionnaire to assess atopy in rural children, an understudied population with regard to atopy and allergic disease.MethodsA total of 480 schoolchildren (grades 1–8) from rural Saskatchewan completed a questionnaire report of allergy and atopic outcomes and participated in skin prick testing (SPT). SPT for 6 common allergens (local grasses, wheat dust, cat dander, house dust mite mixed, Alternaria, and Cladosporium) was completed. Subjects with at least one positive SPT (≥ 3 mm) compared to the negative control were considered to be atopic. We considered per cent concordance, Kappa, sensitivity, specificity, and the positive predictive value and negative predictive value (NPV, PPV) of reported allergies or allergic conditions in comparison with SPT as the gold standard.ResultsWe found that 25.0% of children reported a history of any allergy and 19.4% were atopic based on SPT. The agreement between questionnaire report of allergic triggers and atopy measured by SPT was high (83.0–89.5%). The agreement between atopy and report of allergic conditions ranged from 67.1% to 79.6%. Individual allergic conditions demonstrated high specificity but low sensitivity. The questionnaire report of any allergy had a low PPV in detecting atopy (47.3%) and high NPV (86.3%). The PPV of reported allergic conditions was low (24.8–43.9%), but the NPV was again high (82.0–82.9%).ConclusionsWe found that the standardized questionnaire report of allergy and atopic conditions was shown not to efficiently and reliably predict atopy. However, given the good specificity and the NPV, the questionnaire may be an efficient tool for epidemiological studies that involve the differential inclusion of subjects without atopy.
Mechanisms of immunological tolerance in central nervous system inflammatory demyelination
Authors: Mari Elisabeth R. , Moore Jason N. , Zhang Guang‐Xian , Rostami Abdolmohamad 
Published: March 2015

AbstractMultiple sclerosis is a complex autoimmune disease of the central nervous system that results in a disruption of the balance between pro‐inflammatory and anti‐inflammatory signals in the immune system. Given that central nervous system inflammation can be suppressed by various immunological tolerance mechanisms, immune tolerance has become a focus of research in the attempt to induce long‐lasting immune suppression of pathogenic T cells. Mechanisms underlying this tolerance induction include generation of regulatory T cell populations, anergy and the induction of tolerogenic antigen‐presenting cells. The intravenous administration of encephalitogenic peptides has been shown to suppress experimental autoimmune encephalomyelitis and induce tolerance by promoting the generation of regulatory T cells and inducing apoptosis of pathogenic T cells. Safe and effective methods of inducing long‐lasting immune tolerance are essential for the treatment of multiple sclerosis. By exploring tolerogenic mechanisms, new strategies can be devised to strengthen the regulatory, anti‐inflammatory cell populations thereby weakening the pathogenic, pro‐inflammatory cell responses.
Structural and Qualitative Bone Remodeling Around Repetitive Loaded Implants in Rabbits
Authors: Kuroshima Shinichiro , Yasutake Munenori , Tsuiki Kotaro , Nakano Takayoshi , Sawase Takashi 
Published: March 2015

AbstractBackgroundBone mechanical function is regulated by bone quality and bone mineral density (BMD) that reflect bone strength. The preferential alignment of biological apatite (BAp) c‐axis/collagen fibers and osteocytes is a determinant factor of bone quality. However, the effect of mechanical loading on bone quality around dental implants is unclear.PurposeThe aim of this study was to clarify the effects of mechanical loading on osseointegration, bone volume BMD, and bone quality around dental implants.Materials and MethodsTwenty anodized Ti‐6Al‐4V alloy implants (KYOCERA Co., Kyoto, Japan) were placed in the proximal tibial metaphysis of 10 rabbits. Twelve weeks after surgery, mechanical loading was applied along the long axis of the implant (50 N, 3 Hz, 1,800 cycles, 2 days/week) for 8 weeks. Osseointegration, bone volume, BMD, and bone quality were evaluated using light microscopy, microcomputed tomography, polarized light microscopy, and microbeam X‐ray diffractometer.ResultsMechanical loading increased osseointegration, bone volume, and BMD. Bone quality around dental implant was altered with increased osteocyte numbers and the preferential alignment direction and degree of BAp c‐axis/collagen fibers.ConclusionsThese findings suggest that mechanical loading effectively induces bone anabolic responses around dental implants. Altered bone quality may upregulate bone strength, contributing to long‐term implant stability.
Validation of the English translation of the low anterior resection syndrome score
Authors: Juul T. , Battersby N. J. , Christensen P. , Janjua A. Z. , Branagan G. , Laurberg S. , Emmertsen K. J. , Moran B. ,   the UK LARS Study Group
Published: March 2015

AbstractAimMany patients having anterior resection for rectal cancer suffer from severe long‐term bowel dysfunction, known as low anterior resection syndrome (LARS). The LARS score was developed in Denmark, and Swedish, Spanish and German versions have been validated. The aim of this study was to validate the English translation of the LARS score in British rectal cancer patients.MethodRectal cancer patients who underwent an anterior resection in 12 UK centres received the LARS score questionnaire, the EORTC QLQ‐C30 and a single ad hoc quality of life question. A subgroup of patients received the LARS score questionnaire twice.ResultsThe response rate was 80% and 451 patients were included in the analyses. A strong association between LARS score and quality of life (convergent validity) was found (P < 0.01), discriminative validity was good (P < 0.02) and the test–retest reliability was high (intraclass correlation coefficient 0.83).ConclusionThe English translation of the LARS score has shown good psychometric properties comparable with recently published results from an international multicentre study. Thus, the English translation of the LARS score can be considered a valid and reliable tool for measuring LARS.
Small carcinomas involving less than one‐quarter of the rectal circumference: local excision is still associated with a high risk of nodal positivity
Authors: Ferko A. , Orhalmi J. , Dusek T. , Chobola M. , Hovorkova E. , Hadzi Nikolov D. , Dolejs J. 
Published: March 2015

AbstractAimA study was carried out to determine the relationship between mesorectal lymph nodal involvement and T stage in a group of patients with a rectal cancer involving less than one‐quarter of the rectal circumference, such as might be selected for local excision.MethodThe data of patients having rectal resection between 2010 and 2014 were prospectively entered in a rectal carcinoma registry. A model for describing tumours involving less than one quadrant of the rectal circumference was created to facilitate the evaluation process.ResultsIn all, 304 patients were included in the study. In 68 (22.4%) a small tumour (< 1 quadrant involved) was found. Of these, 26.5% had positive mesorectal lymph nodes (N+). In lesions of Stage ypT0 cancer 12.5% patients were node positive, in Stage Tis and T1 tumours there was no case of node positivity, but in Stage T2 and Stage T3 cancers the incidence of node positivity was 27.5% and 64%.ConclusionThe study demonstrated that, even for small tumours involving only one rectal quadrant, the risk of lymph nodal involvement was about 25%. Had the patients undergone local excision the treatment would have been incomplete.
Family Firm Governance and Financial Policy Choices in Newly Public Firms
Authors: Jain Bharat A. , Shao Yingying 
Published: March 2015

AbstractManuscript TypeEmpiricalResearch Question/IssueUsing agency theory and socioemotional wealth perspective as the theoretical framework, we evaluate the extent to which financing choices subsequent to going public and their economic consequences differ for family firms relative to non‐family firms.Research Findings/InsightsOur results suggest that family firms maintain higher post‐IPO leverage and longer debt maturity structure relative to non‐family firms. Further, family firms raise less external capital subsequent to going public relative to non‐family firms. The reluctance of family firms to raise post‐IPO capital, however, results in higher investment sensitivity to internal cash flows and consequently inefficient investment. In addition, family firm financing choices differentially influence various facets of post‐IPO performance.Theoretical/Academic ImplicationsThis study suggests that agency conflicts among firm stakeholders as well as socioemotional wealth considerations are important determinants of family firm financing behavior subsequent to going public. Further, ownership structure is an important determinant of the extent IPO firms capitalize on the opportunity to raise capital subsequent to going public to finance investments.Practitioner/Policy ImplicationsOur results offer insights to entrepreneurs, managers, venture capitalists, and other capital market participants with regard to the link between firm ownership structure and the economic benefits of going public
Nedd4 E3 ubiquitin ligase promotes cell proliferation and autophagy
Authors: Li Yuyin , Zhang Li , Zhou Jie , Luo Shenheng , Huang Rui , Zhao Changcai , Diao Aipo 
Published: March 2015

AbstractObjectivesNedd4 (neural precursor cell expressed developmentally down‐regulated protein 4) is a member of the HECT E3 ubiquitin ligases, and is elevated in prostate, bladder and colorectal cancers, and promotes colonic cell population expansion. Up to now, molecular mechanisms of how Nedd4 functions, have not been well understood.Materials and methodsIn this study, shRNA was used to reduce expression of Nedd4 in the human prostate carcinoma cell line DU145. To analyse effects of Nedd4 on cell proliferation, MTT and colony formation assays were performed. DAPI staining and FACS analysis were used to investigate outcomes of Nedd4 activity, on apoptosis. Results of Nedd4 expression on lysosomal membrane permeabilization and autophagy were further investigated using acridine orange (AO) staining, immunofluorescence and western blot analysis.ResultsWe found that in HeLa cells, expression of Nedd4 promoted cell proliferation, whereas its knockdown inhibited colony formation and induced apoptosis in DU145 cells. Furthermore, down‐regulation of Nedd4 in DU145 cells promoted lysosomal membrane permeabilization. We also found that down‐regulation of Nedd4 inhibited autophagy in both DU145 and A549 cells. Investigation into mechanisms involved revealed that knockdown of endogenous Nedd4 expression notably increased activated mTOR (p‐mTOR) levels, which suggests that mTOR signalling was involved in the Nedd4‐mediated autophagy.ConclusionsOur results indicate that expression of Nedd4 promoted cell proliferation and colony formation but prevented apoptosis. Moreover, Nedd4 promoted autophagy and was associated with the mTOR signalling pathway.
United Network for Organ Sharing regional variations in appeal denial rates with non‐standard Model for End‐Stage Liver Disease/Pediatric End‐Stage Liver Disease exceptions: support for a national review board
Authors: Gish Robert G. , Wong Robert J. , Honerkamp‐Smith Gordon , Xu Ronghui , Osorio Robert W. 
Published: March 2015

AbstractAlthough it has been generally recognized that there are inconsistencies among Regional Review Boards in the assignment of points for model for end‐stage liver disease (MELD)/pediatric end‐stage liver disease (PELD) exception patients with resulting considerable variation in appeal denial rates, data to actually prove this have been limited. We reviewed 6533 MELD/PELD exception applications submitted between 2005 and 2008, calculated the variation in approval/denial rates, and followed these cases through mid‐2013 to assess the effects on patient outcomes. We found highly significant regional variations in denial rates for appeals by exception patients and in transplantation rates. The odds of transplant for patients whose appeals are approved is 2.45 times that of patients not approved; that this effect does not vary by region suggests that the variation in transplant rates is driven, at least in part, by the variation in appeal denial rates. Health deterioration or death accounts for more than two‐thirds of wait list removals among patients removed for reasons other than transplant. Our findings add to the weight of evidence that a national review board that uses current clinical expertise, peer review literature, and data to consistently assign priority could reduce regional inequities and move toward equitable allocation of organs and compliance with the United States Department of Health & Human Services Final Rule.
Cytopathologists can reliably perform ultrasound‐guided thyroid fine needle aspiration: a 1‐year audit on 3715 consecutive cases
Authors: Bellevicine C. , Vigliar E. , Malapelle U. , Pisapia P. , Conzo G. , Biondi B. , Vetrani A. , Troncone G. 
Published: March 2015

ObjectiveIn our Pathology Department, fine needle aspiration (FNA) of palpable thyroid nodules is performed by cytopathologists who ensure correct sample management and rapid on‐site evaluation (ROSE). Conversely, ultrasound (US)‐guided FNAs have traditionally been carried out by endocrinologists and radiologists in outside clinics, where the presence of a cytopathologist is not always feasible. To overcome this limitation, cytopathologists have started to perform US‐guided FNAs themselves. This study retrospectively evaluates 1 year of this novel practice.MethodsA total of 2225 US‐guided FNAs were performed in our clinic by cytopathologists, whereas 1490 aspirates were taken by a group of non‐cytopathologists. Among these, 756 FNAs were taken by a single experienced endocrinologist. The distribution of the Bethesda classification categories was evaluated in each of these groups.ResultsFNAs performed by cytopathologists were more often diagnostic and better prepared than those taken by non‐cytopathologists, including those taken by the experienced endocrinologist (P < 0.01). The latter operator yielded a higher rate of suspicious and malignant FNAs, reflecting a more appropriate clinical triage of worrisome nodules.ConclusionAlthough the endocrinologist's evaluation is crucial to select clinically relevant thyroid nodules, cytopathologists can reliably perform US guidance in addition to their traditional expertise in sampling, specimen preparation and ROSE.
The role of socio‐economic status and perinatal factors in racial disparities in the risk of cerebral palsy
Authors: Durkin Maureen S , Maenner Matthew J , Benedict Ruth E , Van Naarden Braun Kim , Christensen Deborah , Kirby Russell S , Wingate Martha , Yeargin‐Allsopp Marshalyn 
Published: March 2015

AimTo determine whether racial disparities in cerebral palsy (CP) risk among US children persist after controlling for socio‐economic status (SES) (here indicated by maternal education) and perinatal risk factors.MethodA population‐based birth cohort study was conducted using the Autism and Developmental Disabilities Monitoring Network surveillance and birth data for 8‐year‐old children residing in multi‐county areas in Alabama, Georgia, Missouri, and Wisconsin between 2002 and 2008. The birth cohort comparison group included 458 027 children and the case group included 1570 children with CP, 1202 with available birth records. χ2 tests were performed to evaluate associations and logistic regression was used to calculate relative risks (RR) and adjusted odds ratios (OR) with 95% confidence intervals (CI).ResultsThe risk of spastic CP was more than 50% higher for black versus white children (RR 1.52, 95% CI 1.33–1.73), and this greater risk persisted after adjustment for SES (OR 1.35, 95% CI 1.18–1.55), but not after further adjustment for preterm birth and size for gestational age. The protective effect of maternal education remained after adjustment for race/ethnicity and perinatal factors.InterpretationMaternal education appears to independently affect CP risk but does not fully explain existing racial disparities in CP prevalence in the US.
Feeding behaviour of a virus‐vector leafhopper on host and non‐host plants characterised by electrical penetration graphs
Authors: Tholt Gergely , Samu Ferenc , Kiss Balázs 
Published: March 2015

AbstractMany sap‐feeders are vectors of plant diseases, acquiring and inoculating pathogens at various stages of the feeding process. In oligophagous species, certain aspects of probing behaviour on hosts and non‐hosts may have implications for the range of both pathogens and plants that can be inoculated. We addressed the question of which probing phases (including ingestion) occur on non‐host plants in the case of the common leafhopper Psammotettix alienus (Dahlbom) (Hemiptera: Cicadellidae). This species is a pest on cereals, a vector of the Wheat dwarf virus, and possible carrier of other pathogens. It is regarded as oligophagous on grasses, but has been reported also on other plant families. In a combined electrical penetration graph (EPG) video observation study, we aimed to give a description of the waveforms during the probing process. EPG recordings were made on a suitable host, barley, Hordeum vulgare L. (Poaceae), and on two non‐host plants, the sedge Carex tomentosa L. (Cyperaceae) and the ragweed Ambrosia artemisiifolia L. (Asteraceae). We demonstrated that P. alienus probes on plants other than Poaceae, including dicotyledons. Univariate and multivariate analyses of general probing variables revealed that total and maximal probe durations were shorter and probing progress less advanced on non‐host plants. Waveforms of the pathway phase were stereotypical and statistically not different between the host and non‐host plants. On sedge, the waveform signifying insertion through the plant epidermis was shortened but much more frequent, indicating penetration difficulties and retrials. Most importantly, waveforms indicating phloem ingestion were not present on either of the non‐host plants. Non‐host probing events terminating during the pathway phase suggested that rejection occurred when the stylets were in the mesophyllum. Overall, the EPG signals reflected the unsuitability of A. artemisiifolia and C. tomentosa compared to barley, but the occurrence of probing and the demonstrated level of probing progress imply that pathogen transmission cannot be excluded in the case of many non‐host plants and non‐specific pathogens.
Enhancing resistance in Pinus radiata seedlings to terminal crook (Colletotrichum acutatum) using methyl jasmonate and ultraviolet‐C radiation
Authors: Reglinski T. , Taylor J. T. , Ah Chee A. , Spiers M. 
Published: March 2015

SummaryColletotrichum acutatum is a fungal pathogen that causes terminal crook disease in radiata pine (Pinus radiata) seedlings in New Zealand forest nurseries. Symptoms of infection include malformation or death of the growing tip and a stiffening and thickening of the stem. Although the disease can be managed effectively using fungicides, the New Zealand forest industry is interested in alternative control options such as induced resistance. The aim of this study was to evaluate spray application of chitosan (1.4 g/l) or 2.25 mm methyl jasmonate (MeJA) and irradiation with UV‐C (2.16 kJ/m2) for their potential to induce resistance to terminal crook. The treatments were applied to 4‐month‐old seedlings at 1 week before pathogen inoculation. By the end of the experimental period (42 days after inoculation), there was 80% disease incidence in the controls, with 48% of seedlings exhibiting severe terminal crook symptoms. The most effective treatment (p < 0.05) was MeJA with 16% disease incidence and none with severe symptoms. UV‐C also significantly (p < 0.05) reduced infection with 52% incidence and 20% of seedlings exhibiting severe symptoms. Chitosan did not reduce disease incidence (72%) compared with the control (80%) but did significantly reduce (p < 0.05) disease severity with 28% exhibiting severe symptoms. MeJA was the only treatment that significantly (p < 0.05) reduced the detrimental effects of infection on seedling apical growth and stem diameter. To our knowledge, this is the first report demonstrating the potential for MeJA and UV‐C to control terminal crook in radiata pine.