bluuebunny/crossref_metadata_2025_split huggingface dataset:
Head Office Commitment to Quality-Related Event Reporting in Community Pharmacy
Authors: Scobie Andrea C. , Boyle Todd A. , MacKinnon Neil J. , Mahaffey Thomas 
Published: May 2012

Background: This research explores how perceptions of head office commitment to quality-related event (QRE) reporting differ between pharmacy staff type and between pharmacies with high and low QRE reporting and learning performance. QREs include known, alleged or suspected medication errors that reach the patient as well as medication errors that are intercepted prior to dispensing. Methods: A survey questionnaire was mailed in the spring of 2010 to 427 pharmacy managers, pharmacists and pharmacy technicians in Nova Scotia. Nonparametric statistics were used to determine differences based on pharmacy staff type and pharmacy performance. Content analysis was used to analyze the responses to open-ended survey questions. Results: A total of 210 surveys were returned, for a response rate of 49.2%. However, the current study used only the subgroup of pharmacy staff who self-reported working at a chain pharmacy, for a total of 124 usable questionnaires. The results showed that community pharmacies viewed head office commitment to QRE reporting as an area to improve. In general, high-performing pharmacies ranked head office commitment higher than low-performing pharmacies. Discussion: One possible reason why high-performing pharmacies ranked the variables higher may be that increased levels of head office support for QRE processes have led these pharmacies to adopt and commit to QRE processes and thus increase their performance. Conclusion: Demonstrated commitment to QRE reporting, ongoing encouragement and targeted messages to staff could be important steps for head office to increase QRE reporting and learning in community pharmacies.
Analysis of Initial Injury Radiographs of Occult Femoral Neck Fractures in Elderly Patients: A Pilot Study
Authors: Chiang Chao-Ching , Wu Hung-Ta , Lin Chien-Fu Jeff , Tzeng Yun-Hsuan , Huang Ching-Kuei , Chen Wei-Ming , Liu Chien-Lin 
Published: May 2012

Diagnosis of occult hip fractures by initial radiographs remains challenging in the emergency department. Previously, the gold standard for accurate diagnosis of occult hip fractures was magnetic resonance imaging. This study used initial radiographs obtained in the emergency department to evaluate specific signs and measurements as diagnostic references for occult femoral neck fractures in elderly patients.
Initial negative radiographs were reviewed for 2 groups of patients: a group with occult femoral neck fractures (n=16) and a group without fractures (n=32). Reviews of initial radiographs and all imaging studies were performed by a senior orthopedist (C-C.C.) and a radiologist (H-T.W.). Diagnostic signs included lateral, medial, anterior, and posterior signs; measurements included elevation of the fat pad and external rotation of the femur. The prevalence of occult femoral neck fracture was 3.3%. Initial radiographs of occult femoral neck fractures were not routinely negative; 14 (87.5%) of 16 patients with fractures had at least 1 radiographic sign. Using the positive lateral or posterior sign as the diagnostic reference, the sensitivity was 0.875 and the specificity was 0.906. When elevation of the fat pad was ⩾1.5 mm, the sensitivity was 0.867 and the specificity was 0.857 for the diagnosis of occult femoral neck fracture.
The lateral and posterior signs and elevation of the fat pad ⩾1.5 mm on initial radiographs are recommended as diagnostic references for occult femoral neck fracture. These references are clearly defined and may offer important information for all clinicians and radiologists in the emergency department.
Fly Fishing–related Lesser Tuberosity Avulsion in an Adolescent
Authors: Teixeira Rafael P. , Johnson Alan R. , Higgins Brendan T. , Carrino John A. , McFarland Edward G. 
Published: May 2012

Stress lesions of the shoulder in athletic and active adolescents are most commonly associated with overhead sports. One of the most uncommon stress lesions of the shoulder in adolescents is an avulsion of the lesser tuberosity of the proximal humerus. To our knowledge, only 2 other cases of lesser tuberosity avulsions from repetitive motion have been reported, both of which were secondary to baseball pitching.
This article describes a case of an isolated partial avulsion of the lesser tuberosity of the humerus in an adolescent as a result of repetitive stress from fly fishing. The patient had no symptoms in his shoulder until after casting for approximately 10 hours a day for 3 days. He presented with anterior shoulder pain that worsened with abduction and external rotation. On examination, he had tenderness over the lesser tuberosity and pain with subscapularis muscle testing, such as the lift-off test. He had a negative apprehension sign but no signs of a superior labrum tear. Conventional radiography with an axillary view confirmed the diagnosis. He recovered with rest and gradual return to activities. Two years after injury, the patient had no limitations functionally, and his shoulder examination was normal.
This case highlights the importance of being aware that (1) this lesion can occur in activities other than baseball, (2) characteristic physical findings exist with this lesion, (3) obtaining an axillary radiograph can confirm diagnosis, and (4) these avulsions can be treated successfully with nonoperative interventions.
Factors Associated With Strabismus in Spina Bifida Myelomeningocele
Authors: Anderson Heather A. , Stuebing Karla K. , Buncic Ray , Mazow Malcolm , Fletcher Jack M. 
Published: May 2012

Purpose:
Higher prevalence of strabismus in individuals with spina bifida myelomeningocele (SBM) has previously been attributed to hydrocephalus; however, SBM is associated with many other complications. This study investigates the relation between strabismus and other factors in SBM.

Methods:
Children aged 3 to 18 years with SBM (n = 112) received an eye examination including assessment of ocular alignment by cover or Hirschberg test. Gestational age, respiratory distress at birth, birth weight, maternal age at birth, number of shunt revisions, and spinal lesion level were also obtained. The relation between these factors and strabismus was analyzed.

Results:

Forty-two participants had strabismus. Maternal age (
P
= .4) and respiratory distress (
P
= .6) were not significantly related to strabismus. Lower birth weight was suggestive of a relation with strabismus (logistic regression,
P
= .05) and younger gestational age was related to strabismus (logistic regression,
P
= .01). Participants who had at least one shunt revision were more likely to have strabismus (Fisher’s exact test,
P
= .038). Spinal lesion level was significantly related to strabismus with increased likelihood of strabismus for spinal lesions closer to the brain (Wald chi-square, 1,100 = 4.29,
P
= .038).

Conclusion:
These findings indicate that several factors are associated with strabismus in SBM. Some of these factors (lower birth weight and younger gestational age) are associated with strabismus in the general population, whereas the association of strabismus and level of spinal lesion may be unique to SBM and may be related to the more severe brain dysmorphology associated with upper level spinal lesions.
Comparison of Preoperative and Postoperative Anterior Segment Measurements With Pentacam
®
in Strabismus Surgery
Authors: Jung Jae Ho , Choi Hee Young 
Published: May 2012

Purpose:
This study was intended to evaluate the effect of horizontal muscle surgery on anterior segment measurements in patients with strabismus.

Methods:
Forty-two eyes of 28 patients with exotropia undergoing recession or recession combined with resection procedure were included. Consecutive cases were imaged using a Pentacam (Oculus, Inc., Berlin, Germany) immediately prior to surgery and 1 and 3 months after surgery. The refractive power of the anterior surface of the cornea on the horizontal and vertical axis, the thinnest corneal thickness, anterior chamber depth, anterior chamber volume, and cornea volume were analyzed. The clinical characteristics of patients, visual acuity, astigmatism, and size of the deviations before and after surgery were reviewed.

Results:
Muscle recession and recession plus resection surgery were performed in 28 and 14 eyes, respectively. Overall, no significant changes were noted when comparing preoperative and postoperative data. Patients were divided into two groups, recession or recession plus resection, and only anterior chamber depth was found to be significantly reduced in the recession group 1 month postoperatively. Three months postoperatively, the reduced anterior chamber depth in the recession group returned to the preoperative value.

Conclusion:
In this series, the recession procedure in patients with strabismus induced an anterior chamber depth change during the early postoperative period. However, the anterior chamber depth returned to its preoperative state by 3 months after surgery. These findings indicate that extraocular muscle surgery could induce reversible changes to the anterior segment of the eye.
Foldable Iris-fixated Phakic Intraocular Lens vs Femtosecond Laser–assisted LASIK for Myopia Between −6.00 and −9.00 Diopters
Authors: Albarrán-Diego César , Muñoz Gonzalo , Ferrer-Blasco Teresa , García-Lázaro Santiago , Belda-Salmerón Lurdes 
Published: May 2012

PURPOSE:
To compare visual, refractive, and clinical outcomes of foldable iris-fixated phakic intraocular lens (PIOL) implantation versus femtosecond laser–assisted LASIK for myopia between −6.00 and −9.00 diopters (D).

METHODS:
Forty-six myopic patients were randomized to undergo bilateral Artiflex (Ophtec BV) PIOL implantation or bilateral femtosecond laser–assisted conventional LASIK with the VISX S2 (Abbott Medical Optics). Refraction, uncorrected (UDVA) and corrected (CDVA) distance visual acuity, contrast sensitivity, corneal endothelial cell count, rate of retreatment, and complications were compared.

RESULTS:

Twelve months after surgery, no statistically significant differences were noted in spherical equivalent refraction (
P
=.19) or UDVA (
P
=.28), whereas CDVA was better in the PIOL group (
P
<.001). Spherical equivalent refraction was within ±0.50 D in 42 (91.3%) LASIK eyes and 41 (89.1%) PIOL eyes (
P
>.99). The percentage of eyes gaining lines of CDVA was significantly higher in the PIOL group (50.0% vs 8.7%;
P
<.001). Contrast sensitivity was better for PIOL eyes at 1.5 cycles per degree (cpd) (
P
=.03) and 6 cpd (
P
=.008). The LASIK eyes showed a mean endothelial cell count increase of 3.7%±2.8%, whereas PIOL eyes showed a mean decrease of 9.1%±2.0% (
P
<.001). The rate of retreatment was similar (
P
=.37), and no serious complications occurred in either group.

CONCLUSIONS:
The Artiflex PIOL provided better CDVA and contrast sensitivity at high spatial frequencies than femtosecond laser–assisted conventional LASIK, suggesting that PIOL implantation is a reasonable option for myopia between −6.00 and −9.00 D.
Differential Regulation of the Let-7 Family of MicroRNAs in CD4+ T Cells Alters IL-10 Expression
Authors: Swaminathan Sanjay , Suzuki Kazuo , Seddiki Nabila , Kaplan Warren , Cowley Mark J. , Hood Chantelle L. , Clancy Jennifer L. , Murray Daniel D. , Méndez Catalina , Gelgor Linda , Anderson Ben , Roth Norman , Cooper David A. , Kelleher Anthony D. 
Published: May 2012

AbstractMicroRNAs (miRNAs) are ∼22-nt small RNAs that are important regulators of mRNA turnover and translation. Recent studies have shown the importance of the miRNA pathway in HIV-1 infection, particularly in maintaining latency. Our initial in vitro studies demonstrated that HIV-1–infected HUT78 cells expressed significantly higher IL-10 levels compared with uninfected cultures. IL-10 plays an important role in the dysregulated cytotoxic T cell response to HIV-1, and in silico algorithms suggested that let-7 miRNAs target IL10 mRNA. In a time course experiment, we demonstrated that let-7 miRNAs fall rapidly following HIV-1 infection in HUT78 cells with concomitant rises in IL-10. To show a direct link between let-7 and IL-10, forced overexpression of let-7 miRNAs resulted in significantly reduced IL-10 levels, whereas inhibition of the function of these miRNAs increased IL-10. To demonstrate the relevance of these results, we focused our attention on CD4+ T cells from uninfected healthy controls, chronic HIV-1–infected patients, and long-term nonprogressors. We characterized miRNA changes in CD4+ T cells from these three groups and demonstrated that let-7 miRNAs were highly expressed in CD4+ T cells from healthy controls and let-7 miRNAs were significantly decreased in chronic HIV-1 infected compared with both healthy controls and long-term nonprogressors. We describe a novel mechanism whereby IL-10 levels can be potentially modulated by changes to let-7 miRNAs. In HIV-1 infection, the decrease in let-7 miRNAs may result in an increase in IL-10 from CD4+ T cells and provide the virus with an important survival advantage by manipulating the host immune response.
Protein Kinase C-θ Promotes Th17 Differentiation via Upregulation of Stat3
Authors: Kwon Myung-Ja , Ma Jian , Ding Yan , Wang Ruiqing , Sun Zuoming 
Published: May 2012

Abstract
Although protein kinase C-θ (PKC-θ)-deficient mice are resistant to the induction of Th17-dependent experimental autoimmune encephalomyelitis, the function of PKC-θ in Th17 differentiation remains unknown. In this article, we show that purified, naive CD4 PKC-θ−/− T cells were defective in Th17 differentiation, whereas Th1 and Th2 differentiation appeared normal. Activation of PKC-θ with PMA promoted Th17 differentiation in wild type (WT) but not PKC-θ−/− T cells. Furthermore, PKC-θ−/− T cells had notably lower levels of Stat3, a transcription factor required for Th17 differentiation, and PMA markedly stimulated the expression of Stat3 in WT but not PKC-θ−/− T cells. In contrast, activation of Stat4 and Stat6, which are critical for Th1 and Th2 differentiation, was normal in PKC-θ−/− T cells. Forced expression of Stat3 significantly increased Th17 differentiation in PKC-θ−/− T cells, suggesting that reduced Stat3 levels were responsible for impaired Th17 differentiation, and that Stat3 lies downstream of PKC-θ. Constitutively active PKC-θ, or WT PKC-θ activated by either PMA or TCR cross-linking, stimulated expression of a luciferase reporter gene driven by the Stat3 promoter. PKC-θ–mediated activation of the Stat3 promoter was inhibited by dominant-negative AP-1 and IκB kinase-β, but stimulated by WT AP-1 and IκB kinase-β, suggesting that PKC-θ stimulates Stat3 transcription via the AP-1 and NF-κB pathways. Lastly, conditions favoring Th17 differentiation induced the highest activation level of PKC-θ. Altogether, the data indicate that PKC-θ integrates the signals from TCR signaling and Th17 priming cytokines to upregulate Stat3 via NF-κB and AP-1, resulting in the stimulation of Th17 differentiation.
Aminopeptidase Substrate Preference Affects HIV Epitope Presentation and Predicts Immune Escape Patterns in HIV-Infected Individuals
Authors: Zhang Shao Chong , Martin Eric , Shimada Mariko , Godfrey Sasha Blue , Fricke Jennifer , Locastro Shirley , Lai Nicole Y. , Liebesny Paul , Carlson Jonathan M. , Brumme Chanson J. , Ogbechie Oluwatobi Awele , Chen Huabiao , Walker Bruce D. , Brumme Zabrina L. , Kavanagh Daniel G. , Le Gall Sylvie 
Published: May 2012

Abstract
Viruses evade immune detection partly through immune-associated mutations. Analyses of HIV sequences derived from infected individuals have identified numerous examples of HLA-associated mutations within or adjacent to T cell epitopes, but the potential impact of most mutations on epitope production and presentation remains unclear. The multistep breakdown of proteins into epitopes includes trimming of N-extended peptides into epitopes by aminopeptidases before loading onto MHC class I molecules. Definition of sequence signatures that modulate epitope production would lead to a better understanding of factors driving viral evolution and immune escape at the population level. In this study, we identified cytosolic aminopeptidases cleavage preferences in primary cells and its impact on HIV Ag degradation into epitopes in primary human cell extracts by mass spectrometry and on epitope presentation to CTL. We observed a hierarchy of preferred amino acid cleavage by cytosolic aminopeptidases. We demonstrated that flanking mutations producing more or less cleavable motifs can increase or decrease epitope production and presentation by up to 14-fold. We found that the efficiency of epitope production correlates with cleavability of flanking residues. These in vitro findings were supported by in vivo population-level analyses of clinically derived viral sequences from 1134 antiretroviral-naive HIV-infected individuals: HLA-associated mutations immune pressures drove the selection of residues that are less cleavable by aminopeptidases predominantly at N-flanking sites, leading to reduced epitope production and immune recognition. These results underscore an important and widespread role of Ag processing mutations in HIV immune escape and identify molecular mechanisms underlying impaired epitope presentation.
Spontaneous hemorrhagic Descemet membrane detachment causing pupillary block
Authors: Eide Macpherson James F. , Slettedal Jon Klokk , Drolsum Liv , Thilesen Trond 
Published: May 2012

Purpose To present a unique case of a 65-year-old man using warfarin who presented with acute unilateral loss of vision due to hemorrhagic Descemet membrane detachment (DMD) with pupillary block and elevated intraocular pressure and its subsequent treatment and challenges. Methods Case report. Results Clinical examination showed a visual acuity of finger counting, central DMD with near contact to the iris and premembrane hemorrhage, an intraocular pressure (IOP) of 19 mmHg, and normal pupillary reaction. An International Normalized Ratio (INR) of 4.9 was treated with dose reduction and vitamin K. Twelve hours later the patient re-presented with an acute increase in pain and an IOP of 78 mmHg with pupillary block and iris bombé. YAG-laser membranotomy, anterior chamber paracentesis, and maximal topical and systemic therapy were unsuccessful in reducing the IOP. Surgical management, including irrigation and aspiration of blood, led to a normalization of the IOP. Descemet stripping automated endothelial keratoplasty (DSAEK) resulted in a visual acuity of 0.3. Deep stromal/pre-Descemet membrane neovascularization was found bilaterally, suspicious for a previous interstitial keratitis. Conclusions The previously unreported complication of pupillary block following a pre-Descemet membrane hemorrhage was treated successfully for the first reported time, in a 2-step DSAEK. This indicates that DSAEK could be considered as a treatment option for DMD, especially in traumatic circumstances.
In VitroandIn VivoModels of Drug Metabolism
Authors: Sinz Michael A. 
Published: May 2012

AbstractUnderstanding the metabolism of newly developed drugs is paramount because of the central role metabolism plays in unraveling the possible toxicity or developability of new drug candidates. Therefore it is always important to understand the full set of metabolic reactions and enzymes involved in the metabolism of a compound in both preclinical models as well as in humans to avoid unnecessary complications or failures in drug development. Drug metabolismin vivooccurs everywhere within the body to differing extents, however metabolism occurs predominately in those organs involved in elimination and those to which the drug is first exposed.In vitro, there are multiple reagents that can be employed to evaluate metabolism or drug–drug interaction potential, such as microsomes, hepatocytes, and numerous subcellular fractions. The following text describes variousin vitroandin vivomodels often employed throughout drug discovery and development, as well as the purpose each model system serves to provide valuable information to elucidate the metabolic disposition of new drug molecules.
Metabonomics in Understanding Drug Metabolism and Toxicology
Authors: Wen Bo 
Published: May 2012

AbstractMost xenobiotics, including drugs, are transformed in animals and humans to a variety of metabolites. Although many of these metabolites are physiologically inactive, some are active either therapeutically or toxicologically. Metabolic activation leading to formation of chemically reactive metabolites is a long‐standing issue inasmuch as some, but not all, reactive intermediates play a role as mediators of drug‐induced toxicities, which represent a significant attritional hurdle in drug development. The safety assessment profile/decision‐making guide requires a comprehensive understanding of the molecular mechanisms of drug‐induced toxicities, which still remains as an enormous challenge. Metabonomics, the comprehensive analysis of small molecules in a biofluid, can reveal biologically relevant perturbations that result from xenobiotic exposure. This review discusses the current progress in the application of metabonomics in bridging the relationships between drug metabolism, drug/metabolite–protein interactions, and their toxicological consequences and how these variables possibly provide a deeper insight into mechanistic aspects of drug‐induced toxicities.
Conjugation, Transport, and Elimination of Drugs in Humans
Authors: Savage Ronald E. 
Published: May 2012

AbstractThis article reviews the conjugation, transport, and elimination of drugs in humans. Drug‐conjugating enzymes discussed include UGTs, SULTs, GSTs, MTs, and NATs. In addition, the excretion of drugs in humans and the role of transport proteins and their relationship to drugs and their conjugated metabolites as well as the role of NRs governing the expression of DMEs and NRs are presented. Finally, factors that impact the conjugation, transport, and elimination of drugs are summarized including drug–drug interactions, dietary phytochemicals and herbal supplements, and intrinsic factors such as genetics, gender, and age.
Role of PhaseIMetabolism in Drug Activation and Clinical Treatment Outcomes
Authors: Testa Bernard , Pannatier André 
Published: May 2012

AbstractDrug metabolism plays a major role in modulating the activity and clinical outcomes of medicines. The chapter focuses on the formation of active metabolites by considering drugs having no active metabolite (e.g. soft drugs), drugs producing active metabolites, and prodrugs whose activity is due solely to an active metabolite. Drug–drug interactions are also exemplified using protease inhibitors.