bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a Population Pharmacokinetic Model To Describe Azithromycin Whole-Blood and Plasma Concentrations over Time in Healthy Subjects
Authors: Pene Dumitrescu T. , Anic-Milic T. , Oreskovic K. , Padovan J. , Brouwer K. L. R. , Zuo P. , Schmith V. D. 
Published: April 2013

ABSTRACT

Azithromycin (AZI), a broad-spectrum antibiotic, accumulates in polymorphonuclear cells and peripheral blood mononuclear cells. The distribution of AZI in proinflammatory cells may be important to the anti-inflammatory properties. Previous studies have described plasma AZI pharmacokinetics. The objective of this study was to describe the pharmacokinetics of AZI in whole blood (concentration in whole blood [

C
b

]) and plasma (concentration in plasma [

C
p

]) of healthy subjects. In this study, 12 subjects received AZI (500 mg once a day for 3 days). AZI

C
b

and

C
p

were quantified in serial samples collected up to 3 weeks after the last dose and analyzed using noncompartmental and compartmental methods. After the last dose,

C
b

was greater than

C
p

. Importantly,

C
b

, but not

C
p

, was quantifiable in all but one subject at 3 weeks. The blood area under the curve during a 24-h dosing interval (AUC
24
) was ∼2-fold greater than the plasma AUC
24
, but simulations suggested that

C
b

was not at steady state by day 3. Upon exploration of numerous models, an empirical 3-compartment model adequately described

C
p

and

C
b

, but

C
p

was somewhat underestimated. Intercompartmental clearance (CL; likely representing cells) was lower than apparent oral CL (18 versus 118 liters/h). Plasma, peripheral, and cell compartmental volumes were 439 liters, 2,980 liters, and 3,084 liters, respectively. Interindividual variability in CL was low (26.2%), while the volume of distribution variability was high (107%). This is the first report to describe AZI

C
b

in healthy subjects, the distribution parameters between

C
p

and

C
b

, and AZI retention in blood for up to 3 weeks following 3 daily doses. The model can be used to predict

C
b

from

C
p

for AZI under various dosing regimens. (This study has been registered at ClinicalTrials.gov under registration no. NCT01026064.)
Regulation of Rab5 Function during Phagocytosis of Live Pseudomonas aeruginosa in Macrophages
Authors: Mustafi Sushmita , Rivero Nathalie , Olson Joan C. , Stahl Philip D. , Barbieri M. Alejandro 
Published: April 2013

ABSTRACT

Pseudomonas aeruginosa
, a Gram-negative opportunistic human pathogen, is a frequent cause of severe hospital-acquired infections. Effectors produced by the type III secretion system disrupt mammalian cell membrane trafficking and signaling and are integral to the establishment of
P. aeruginosa
infection. One of these effectors, ExoS, ADP-ribosylates several host cell proteins, including Ras and Rab GTPases. In this study, we demonstrated that Rab5 plays a critical role during early stages of
P. aeruginosa
invasion of J774-Eclone macrophages. We showed that live, but not heat-inactivated,
P. aeruginosa
inhibited phagocytosis and that this occurred in conjunction with downregulation of Rab5 activity. Inactivation of Rab5 was dependent on ExoS ADP-ribosyltransferase activity, and in J744-Eclone cells, ExoS ADP-ribosyltransferase activity caused a more severe inhibition of phagocytosis than ExoS Rho GTPase activity. Furthermore, we found that expression of Rin1, a Rab5 guanine exchange factor, but not Rabex5 and Rap6, partially reversed the inactivation of Rab5 during invasion of live
P. aeruginosa
. These studies provide evidence that live
P. aeruginosa
cells are able to influence their rate of phagocytosis in macrophages by directly regulating activation of Rab5.
Anaesthesia management for acute appendicitis in cases with Sjögren's syndrome accompanying autoimmune hepatitis
Authors: Demirel Ismail , Ozer Ayse Belin , Bayar Mustafa K , Erhan Omer L 
Published: April 2013

Characterised by lymphocytic infiltration of exocrine glands, Sjögren's syndrome (SS) is a chronic autoimmune disease. Symptoms belonging to the involved systems may occur owing to the fact that it affects multiple systems. While rheumatoid arthritis is observed concomitantly, its co-occurrence with autoimmune hepatitis is astonishingly common. Through this case report, we intended to review issues that should be attended to while administering anaesthesia to a patient with SS accompanying autoimmune hepatitis. In the light of literature, we aimed to discuss anaesthesia management to the patient with SS and issues stemming from the clinical features of SS. In SS, the expected issues are liver problems related autoimmune hepatitis and respiratory problems related pulmonary fibrosis.A careful preoperative evaluation, a comprehensive preparation against difficulty in intubation, a selective anaesthesia management in terms of autoimmune hepatitis and close monitoring of postoperative respiration may prevent or decrease possible complications.
Polyglandular autoimmune syndrome disguised as mental illness
Authors: Wei Randy , Chang Allen , Rockoff Aaron 
Published: April 2013

Our case acts to highlight the numerous presentations of polyglandular autoimmune syndromes. A 62-year-old Taiwanese woman with a history of schizophrenia presented to our emergency department with a brain tumour causing her headaches. She was admitted due to severe anaemia, and after further investigation, the patient was discovered to have pernicious anaemia and autoimmune thyroiditis—consistent with the diagnosis of polyglandular autoimmune syndrome IIIb. Her underlying primary psychiatric diagnosis was then questioned. The diagnosis of her endocrinopathies were likely delayed for many years due to the psychiatric disorder which may have been due to her long-standing autoimmune hypothyroidism and/or vitamin B12deficiency. Initial treatment brought about major behavioural improvement, and encourages physicians to investigate secondary causes of psychosis and other coexisting autoimmune diseases when a patient presents with one endocrinopathy.
Gender Differences in Correlates of Colorectal Cancer Screening Among Black Medicare Beneficiaries in Baltimore
Authors: Martinez Kathryn A. , Pollack Craig E. , Phelan Darcy F. , Markakis Diane , Bone Lee , Shapiro Gary , Wenzel Jennifer , Howerton Mollie , Johnson Lawrence , Garza Mary A. , Ford Jean G. 
Published: April 2013

Abstract
Background: Previous research has shown colorectal cancer (CRC) screening disparities by gender. Little research has focused primarily on gender differences among older Black individuals, and reasons for existing gender differences remain poorly understood.
Methods: We used baseline data from the Cancer Prevention and Treatment Demonstration Screening Trial. Participants were recruited from November 2006 to March 2010. In-person interviews were used to assess self-reported CRC screening behavior. Up-to-date CRC screening was defined as self-reported colonoscopy or sigmoidoscopy in the past 10 years or fecal occult blood testing in the past year. We used multivariable logistic regression to examine the association between gender and self-reported screening, adjusting for covariates. The final model was stratified by gender to examine factors differentially associated with screening outcomes for males and females.
Results: The final sample consisted of 1,552 female and 586 male Black Medicare beneficiaries in Baltimore, Maryland. Males were significantly less likely than females to report being up-to-date with screening (77.5% vs. 81.6%, P = 0.030), and this difference was significant in the fully adjusted model (OR: 0.72; 95% confidence interval, 0.52–0.99). The association between having a usual source of care and receipt of cancer screening was stronger among males compared with females.
Conclusions: Although observed differences in CRC screening were small, several factors suggest that gender-specific approaches may be used to promote screening adherence among Black Medicare beneficiaries.
Impact: Given disproportionate CRC mortality between White and Black Medicare beneficiaries, gender-specific interventions aimed at increasing CRC screening may be warranted among older Black patients. Cancer Epidemiol Biomarkers Prev; 22(6); 1037–42. ©2013 AACR.
The co-occurrence of common mental and physical disorders within Australian families: A national population-based study
Authors: Saha Sukanta , Stedman Terry J , Scott James G , McGrath John J 
Published: April 2013

Objective: Because comorbidity between mental and physical disorders is commonly found in patients, it would be expected that this pattern would also be reflected at the family level. During a recent population-based survey of common mental disorders, respondents were asked about the presence of selected mental and physical disorders in their relatives. The aim of this research was to describe the within-family co-occurrence of selected common physical and mental disorders in a population-based sample. Methods: Subjects were drawn from the Australian National Survey of Mental Health and Wellbeing 2007. A modified version of the World Mental Health Survey Initiative of the Composite International Diagnostic Interview (WMH-CIDI 3.0, henceforth CIDI) was used to identify lifetime-ever common psychiatric disorders (anxiety disorders, depression, drug or alcohol disorders). The respondents were asked if any of their relatives had one of a list of psychiatric (anxiety, bipolar disorder, depression, drug or alcohol problem, schizophrenia) or general physical disorders (cancer, heart problems, intellectual disability, memory problems). We examined the relationship between the variables of interest using logistic regression, adjusting for potential confounding factors. Results: Compared to otherwise-well respondents, those who had a CIDI diagnosis of major depressive disorders, anxiety disorders, or drug or alcohol abuse/dependence were significantly more likely to have first-degree relatives with (a) the same diagnosis as the respondent, (b) other mental disorders not identified in the respondent, and (c) a broad range of general physical conditions. Conclusions: Individuals with common mental disorders report greater familial co-occurrence for a range of mental and physical disorders. When eliciting family histories, clinicians should remain mindful that both mental and physical disorders can co-occur within families.
Oltre la tradizione del romanzo storico ad argomento risorgimentale: La riscrittura di donna e nazione ne Il sorriso dell’ignoto marinaio di Vincenzo Consolo
Authors: Bouchard Norma 
Published: April 2013

Fin dalla sua pubblicazione presso la casa editrice Einaudi nel 1976, Il sorriso dell’ignoto marinaio di Vincenzo Consolo è stato oggetto di una pressoché costante attenzione da parte della comunità critica internazionale, che ha rilevato l’importanza rivestita dal testo all’interno della tradizione del romanzo storico in Italia. Dopo una breve discussione della relazione fra genere e nazione nel canone di romanzi ad argomento risorgimentale (per esempio in Ultime lettere di Jacopo Ortis di Ugo Foscolo, I Viceré di Federico De Roberto, I vecchi e i giovani di Luigi Pirandello e Il Gattopardo di Giuseppe Tomasi di Lampedusa) e della genealogia discorsiva che li sottende, il saggio esamina il personaggio di Catena Carnevale, soggetto simbolico fondamentale nel Sorriso letto nel contesto del revisionismo storico di stampo femminista (i.e. Pieroni Bortolotti, Annarita Buttafuoco, Simonetta Soldani, Michela DeGiorgio, et al.) la cui origine risale proprio agli anni della pubblicazione del romanzo.
Evolution of MHC class I genes in the endangered loggerhead sea turtle (Caretta caretta) revealed by 454 amplicon sequencing
Authors: Stiebens Victor A , Merino Sonia E , Chain Frédéric J J , Eizaguirre Christophe 
Published: April 2013

Abstract

Background
In evolutionary and conservation biology, parasitism is often highlighted as a major selective pressure. To fight against parasites and pathogens, genetic diversity of the immune genes of the major histocompatibility complex (MHC) are particularly important. However, the extensive degree of polymorphism observed in these genes makes it difficult to conduct thorough population screenings.

Methods
We utilized a genotyping protocol that uses 454 amplicon sequencing to characterize the MHC class I in the endangered loggerhead sea turtle (Caretta caretta) and to investigate their evolution at multiple relevant levels of organization.

Results
MHC class I genes revealed signatures of trans-species polymorphism across several reptile species. In the studied loggerhead turtle individuals, it results in the maintenance of two ancient allelic lineages. We also found that individuals carrying an intermediate number of MHC class I alleles are larger than those with either a low or high number of alleles.

Conclusions
Multiple modes of evolution seem to maintain MHC diversity in the loggerhead turtles, with relatively high polymorphism for an endangered species.
Prepackaged central line kits reduce procedural mistakes during central line insertion: a randomized controlled prospective trial
Authors: Fenik Yelena , Celebi Nora , Wagner Robert , Nikendei Christoph , Lund Frederike , Zipfel Stephan , Riessen Reimer , Weyrich Peter 
Published: April 2013

Abstract

Background
Central line catheter insertion is a complex procedure with a high cognitive load for novices. Providing a prepackaged all-inclusive kit is a simple measure that may reduce the cognitive load. We assessed whether the use of prepackaged all-inclusive central line insertion kits reduces procedural mistakes during central line catheter insertion by novices.

Methods
Thirty final year medical students and recently qualified physicians were randomized into two equal groups. One group used a prepackaged all-inclusive kit and the other used a standard kit containing only the central vein catheter and all other separately packaged components provided in a materials cart. The procedure was videotaped and analyzed by two blinded raters using a checklist. Both groups performed central line catheter insertion on a manikin, assisted by nursing students.

Results
The prepackaged kit group outperformed the standard kit group in four of the five quality indicators: procedure duration (26:26 ± 3:50 min vs. 31:27 ± 5:57 min, p = .01); major technical mistakes (3.1 ± 1.4 vs. 4.8 ± 2.6, p = .03); minor technical mistakes (5.2 ± 1.7 vs. 8.0 ± 3.2, p = .01); and correct steps (83 ± 5% vs. 75 ± 11%, p = .02). The difference for breaches of aseptic technique (1.2 ± 0.8 vs. 3.0 ± 3.6, p = .06) was not statistically significant.

Conclusions
Prepackaged all-inclusive kits for novices improved the procedure quality and saved staff time resources in a controlled simulation environment. Future studies are needed to address whether central line kits also improve patient safety in hospital settings.
Averaging of the 3D non-autonomous Benjamin-Bona-Mahony equation with singularly oscillating forces
Authors: Zhao Mingxia , Yang Xinguang , Zhang Lingrui 
Published: April 2013

Abstract
For

ε
∈
(
0
,
1
)

, we investigate the convergence of corresponding uniform attractors of the 3D non-autonomous Benjamin-Bona-Mahony equation with singularly oscillating force contrast with the averaged Benjamin-Bona-Mahony equation (corresponding to the limiting case

ε
=
0

). Under suitable assumptions on the external force, we shall obtain the uniform boundedness and convergence of the related uniform attractors as

ε
→

0
+

.

MSC:35B40, 35Q99, 80A22.
Automatic segmentation of male pelvic anatomy on computed tomography images: a comparison with multiple observers in the context of a multicentre clinical trial
Authors: Geraghty John P , Grogan Garry , Ebert Martin A 
Published: April 2013

Abstract

Background
This study investigates the variation in segmentation of several pelvic anatomical structures on computed tomography (CT) between multiple observers and a commercial automatic segmentation method, in the context of quality assurance and evaluation during a multicentre clinical trial.

Methods
CT scans of two prostate cancer patients (‘benchmarking cases’), one high risk (HR) and one intermediate risk (IR), were sent to multiple radiotherapy centres for segmentation of prostate, rectum and bladder structures according to the TROG 03.04 “RADAR” trial protocol definitions. The same structures were automatically segmented using iPlan software for the same two patients, allowing structures defined by automatic segmentation to be quantitatively compared with those defined by multiple observers. A sample of twenty trial patient datasets were also used to automatically generate anatomical structures for quantitative comparison with structures defined by individual observers for the same datasets.

Results
There was considerable agreement amongst all observers and automatic segmentation of the benchmarking cases for bladder (mean spatial variations < 0.4 cm across the majority of image slices). Although there was some variation in interpretation of the superior-inferior (cranio-caudal) extent of rectum, human-observer contours were typically within a mean 0.6 cm of automatically-defined contours. Prostate structures were more consistent for the HR case than the IR case with all human observers segmenting a prostate with considerably more volume (mean +113.3%) than that automatically segmented. Similar results were seen across the twenty sample datasets, with disagreement between iPlan and observers dominant at the prostatic apex and superior part of the rectum, which is consistent with observations made during quality assurance reviews during the trial.

Conclusions
This study has demonstrated quantitative analysis for comparison of multi-observer segmentation studies. For automatic segmentation algorithms based on image-registration as in iPlan, it is apparent that agreement between observer and automatic segmentation will be a function of patient-specific image characteristics, particularly for anatomy with poor contrast definition. For this reason, it is suggested that automatic registration based on transformation of a single reference dataset adds a significant systematic bias to the resulting volumes and their use in the context of a multicentre trial should be carefully considered.
Obesity and statins are both independent predictors of enhanced coronary arteriolar dilation in patients undergoing heart surgery
Authors: Cassuto James , Feher Attila , Lan Ling , Patel Vijay S , Kamath Vinayak , Anthony Daniel C , Bagi Zsolt 
Published: April 2013

Abstract

Background
A paradoxical inverse relationship between body mass index, morbidity and mortality in patients with ischemic heart disease has been noted; but the underlying mechanisms remain unclear. Given that coronary resistance arteries are the primary regulators of myocardial blood flow, we examined the effects of obesity and medication on dilator function in coronary microvessels.

Methods
Bradykinin-induced coronary dilation was assessed by videomicroscopy in ex vivo coronary arterioles obtained from 64 consecutive patients undergoing heart surgery. Multi-variable linear regression and logistic regression were used to investigate the effects of obesity (BMI ≥ 30 kg/M2) and the influences of medications on vessel responses.

Results
In isolated, pressurized (80 mmHg) coronary arterioles of obese and non-obese patient the active (73±4 vs. 79±13 μm) and passive (111 ± 5.5 vs. 118 ± 5.0 μm) diameters were similar. Bradykinin elicited substantial dilation in coronary arterioles, with a similar magnitude in obese and non-obese patients (to 10-8 M: 55 ± 5% vs. 46 ± 5%, P = 0.20), but with significantly enhanced sensitivity in obesity (EC50: 8.2x10-9 M vs. 1.9x10-8 M, respectively, P = 0.03). When adjusted for other risk factors and medications, obesity and statins were determined to be the only positive predictors of enhanced dilation, as assessed with multiple regression analysis. Moreover, obese patients with or without statin exhibited significantly increased coronary dilation to bradykinin, when compared to non-obese patients without statin therapy.

Conclusions
Obesity and statin therapy are independently associated with an enhanced dilator function of coronary arterioles in patients undergoing heart surgery, which may offer a potential mechanism for the better cardiovascular outcome described earlier as the obesity paradox.
Safety, pharmacokinetics and pharmacodynamics of remogliflozin etabonate, a novel SGLT2 inhibitor, and metformin when co-administered in subjects with type 2 diabetes mellitus
Authors: Hussey Elizabeth K , Kapur Anita , O’Connor-Semmes Robin , Tao Wenli , Rafferty Bryan , Polli Joseph W , James Charles D , Dobbins Robert L 
Published: April 2013

Abstract

Background
The sodium-dependent glucose co-transporter-2 (SGLT2) is expressed in absorptive epithelia of the renal tubules. Remogliflozin etabonate (RE) is the prodrug of remogliflozin, the active entity that inhibits SGLT2. An inhibitor of this pathway would enhance urinary glucose excretion (UGE), and potentially improve plasma glucose concentrations in diabetic patients. RE is intended for use for the treatment of type 2 diabetes mellitus (T2DM) as monotherapy and in combination with existing therapies. Metformin, a dimethylbiguanide, is an effective oral antihyperglycemic agent widely used for the treatment of T2DM.

Methods
This was a randomized, open-label, repeat-dose, two-sequence, cross-over study in 13 subjects with T2DM. Subjects were randomized to one of two treatment sequences in which they received either metformin alone, RE alone, or both over three, 3-day treatment periods separated by two non-treatment intervals of variable duration. On the evening before each treatment period, subjects were admitted and confined to the clinical site for the duration of the 3-day treatment period. Pharmacokinetic, pharmacodynamic (urine glucose and fasting plasma glucose), and safety (adverse events, vital signs, ECG, clinical laboratory parameters including lactic acid) assessments were performed at check-in and throughout the treatment periods. Pharmacokinetic sampling occurred on Day 3 of each treatment period.

Results
This study demonstrated the lack of effect of RE on steady state metformin pharmacokinetics. Metformin did not affect the AUC of RE, remogliflozin, or its active metabolite, GSK279782, although Cmax values were slightly lower for remogliflozin and its metabolite after co-administration with metformin compared with administration of RE alone. Metformin did not alter the pharmacodynamic effects (UGE) of RE. Concomitant administration of metformin and RE was well tolerated with minimal hypoglycemia, no serious adverse events, and no increase in lactic acid.

Conclusions
Coadministration of metformin and RE was well tolerated in this study. The results support continued development of RE as a treatment for T2DM.

Trial registration
ClinicalTrials.gov, NCT00376038