bluuebunny/crossref_metadata_2025_split huggingface dataset:
A clinical knowledge measurement tool to assess the ability of community pharmacists to detect drug-related problems
Authors: Williams Mackenzi , Peterson Gregory M , Tenni Peter C , Bindoff Ivan K 
Published: February 2012

AbstractIntroductionDrug-related problems (DRPs) are associated with significant morbidity and mortality, with most DRPs thought to be preventable. Community pharmacists can detect and either prevent or resolve many of these DRPs. A survey-based clinical knowledge measurement tool was designed and validated to estimate a community pharmacist's clinical knowledge and ability to detect and appropriately resolve DRPs.MethodsNine clinical cases with seven multiple-choice statements (63 statements in total) were constructed, based on scenarios that were found to occur frequently in Australian community pharmacies. The statements aimed to assess a pharmacist's ability to identify, gather relevant information about and make appropriate recommendations to resolve, a DRP. The survey was pilot tested with 18 academics at three Australian pharmacy schools, resulting in the removal of 23 statements. The survey was then administered to undergraduate pharmacy students (28 fourth-year, 41 third-year and 42 first-year students) and to 433 Australian community pharmacists who were participating in an intervention documentation trial. The pharmacists' resultant survey scores were correlated against their actual rate of documenting clinical interventions.ResultsThe tool had relatively good internal consistency. Significant differences were seen between the three groups of students (P &lt; 0.01). Community pharmacists with additional clinical qualifications had a significantly higher score than other participating pharmacists (P &lt; 0.01). A moderate, but significant, correlation was seen between the pharmacists' survey score and their clinical intervention rate in practice during the trial (P &lt; 0.01).ConclusionThe clinical knowledge measurement tool appeared to estimate a pharmacist's ability to detect and resolve DRPs within the community pharmacy environment.
The voltage dependence of Ih in human myelinated axons
Authors: Howells James , Trevillion Louise , Bostock Hugh , Burke David 
Published: February 2012

Key points
Pacemaking in cardiac and neuronal cells is primarily controlled by the interaction between different voltage gated ion channels, and in particular the hyperpolarization‐activated cyclic‐nucleotide gated (HCN) family of channels.
HCN channels are activated by membrane hyperpolarization and play a key role in the determination of resting membrane potential.
We provide evidence suggesting that differences in (i) the modulation and expression of HCN channels, (ii) the expression of slow K+ channels; and (iii) the resultant changes in resting membrane potential are the major determinants of the functional differences between human motor and sensory axons.
Contrary to current wisdom, this study supports the view that the greater persistent Na+ current observed in sensory axons is not due to greater expression of persistent Na+ channels but instead to the relatively depolarized membrane potential driving greater resting activation.
Exploiting the Anti-HIV-1 Activity of Acyclovir: Suppression of Primary and Drug-Resistant HIV Isolates and Potentiation of the Activity by Ribavirin
Authors: Vanpouille Christophe , Lisco Andrea , Introini Andrea , Grivel Jean-Charles , Munawwar Arshi , Merbah Melanie , Schinazi Raymond F. , Derudas Marco , McGuigan Christopher , Balzarini Jan , Margolis Leonid 
Published: February 2012

ABSTRACT

Multiple clinical trials have demonstrated that herpes simplex virus 2 (HSV-2) suppressive therapy using acyclovir (ACV) or valacyclovir in HIV-1/HSV-2-infected persons increased the patient's survival and decreased the HIV-1 load. It has been shown that the incorporation of ACV-monophosphate into the nascent DNA chain instead of dGMP results in the termination of viral DNA elongation and directly inhibits laboratory strains of HIV-1. We evaluated here the anti-HIV activity of ACV against primary HIV-1 isolates of different clades and coreceptor specificity and against viral isolates resistant to currently used drugs, including zidovudine, lamivudine, nevirapine, a combination of nucleoside reverse transcriptase inhibitors (NRTIs), a fusion inhibitor, and two protease inhibitors. We found that, at clinically relevant concentrations, ACV inhibits the replication of these isolates in human tissues infected
ex vivo
. Moreover, addition of ribavirin, an antiviral capable of depleting the pool of intracellular dGTP, potentiated the ACV-mediated HIV-1 suppression. These data warrant further clinical investigations of the benefits of using inexpensive and safe ACV alone or in combination with other drugs against HIV-1, especially to complement or delay highly active antiretroviral therapy (HAART) initiation in low-resource settings.
Efflux Pumps of Mycobacterium tuberculosis Play a Significant Role in Antituberculosis Activity of Potential Drug Candidates
Authors: Balganesh Meenakshi , Dinesh Neela , Sharma Sreevalli , Kuruppath Sanjana , Nair Anju V. , Sharma Umender 
Published: February 2012

ABSTRACT

Active efflux of drugs mediated by efflux pumps that confer drug resistance is one of the mechanisms developed by bacteria to counter the adverse effects of antibiotics and chemicals. To understand these efflux mechanisms in
Mycobacterium tuberculosis
, we generated knockout (KO) mutants of four efflux pumps of the pathogen belonging to different classes. We measured the MICs and kill values of two different compound classes on the wild type (WT) and the efflux pump (EP) KO mutants in the presence and absence of the efflux inhibitors verapamil and
l
-phenylalanyl-
l
-arginyl-β-naphthylamide (PAβN). Among the pumps studied, the efflux pumps belonging to the ABC (ATP-binding cassette) class, encoded by
Rv1218c
, and the SMR (small multidrug resistance) class, encoded by
Rv3065
, appear to play important roles in mediating the efflux of different chemical classes and antibiotics. Efflux pumps encoded by
Rv0849
and
Rv1258c
also mediate the efflux of these compounds, but to a lesser extent. Increased killing is observed in WT
M. tuberculosis
cells by these compounds in the presence of either verapamil or PAβN. The efflux pump KO mutants were more susceptible to these compounds in the presence of efflux inhibitors. We have shown that these four efflux pumps of
M. tuberculosis
play a vital role in mediating efflux of different chemical scaffolds. Inhibitors of one or several of these efflux pumps could have a significant impact in the treatment of tuberculosis. The identification and characterization of
Rv0849
, a new efflux pump belonging to the MFS (major facilitator superfamily) class, are reported.
Factors shaping gene flow in red deer (Cervus elaphus) in seminatural landscapes of central Europe
Authors: Niedziałkowska M. , Fontaine M.C. , Jędrzejewska B. 
Published: February 2012

We studied gene flow and connectivity between three subpopulations and nine groups of red deer ( Cervus elaphus L., 1758) occurring in forests in northeastern Poland and western Belarus. The red deer in this region mostly originated from translocated individuals that were introduced primarily in the 19th and 20th centuries. The genetic structure of the population has been identified during the previous study. Using 14 microsatellite loci, we detected 14 first-generation migrants between the three subpopulations and 21 among the nine groups of deer. The number of effective migrants (Nm) was estimated to be 2.5 individuals/generation between the subpopulations and 6.2 individuals/generation between the groups. About 80% of first-generation migrants moved less than 150 km. The gene flow of hinds and stags was similar. A least cost path (LCP) analysis was performed using different habitat types: deciduous and mixed forests, coniferous forests, wetlands, meadows, arable lands, scarce settlements, dense settlements, and waters. No significant barriers to dispersal were detected, but individual dispersal was restricted in space by the significant isolation by distance. The best model, explaining the genetic distance (FST/1 – FST) between the forests, suggested that LCP corridor length limited gene flow and high forest cover within LCP corridors increased gene flow among the forests.
Ionic regulation and shell mineralization in the bivalveAnodonta cygnea(swan mussel) following heavy-metal exposure
Authors: Lopes-Lima Manuel , Freitas Susana , Pereira Liliana , Gouveia Eugenia , Hinzmann Mariana , Checa Antonio , Machado Jorge 
Published: February 2012

Freshwater mussels are one of the most imperiled faunistic groups in the world and environmental exposure to toxic heavy metals, which result in deregulation of calcium absorption and deposition in the laboratory, may be a contributing factor in their decline. To address potential effects of heavy-metal exposure on calcium transport and metabolism in freshwater bivalves, adult Anodonta cygnea (L., 1758) were exposed to a sublethal concentration (1.0 × 10−6 mol/L) of essential (Zn2+and Cu2+) or nonessential (Pb2+and Cr3+) metal for 30 days in the laboratory. Inorganic composition of extrapallial, haemolymph, heart, and pericardium fluids, and kidney tissue, as well as shell morphology by scanning electron microscopy, were compared in treated and untreated mussels. Calcium levels in fluids varied after exposure to any of the metals investigated, although the magnitude and threshold of effect were metal- and compartment-specific. Ca2+levels increased robustly in all fluids following exposure to Zn2+, Cu2+, or Cr3+, whereas levels decreased significantly in heart fluid alone following Pb2+exposure (p < 0.05). In constrast to exposure to the other metals, Cu2+revealed an interesting reverse-accumulation pattern, decreasing in the fluids but not in the kidney, where it clearly accumulates for excretion. In addition, whereas essential Cu2+and Zn2+are closely regulated, the nonessential metals Pb2+and Cr3+increase to very high levels. Drastic alterations in shell morphology, specifically the structure of border and inner pallial regions of the nacreous layer, were observed after Cu2+or Cr3+exposure. Collectively, data suggest that prolonged exposure to a sublethal concentration of these heavy metals can adversely affect compartmental calcium availability and shell composition in A. cygnea.
Beach and demersal spawning in capelin (Mallotus villosus) on the northeast Newfoundland coast: egg developmental rates and mortality
Authors: Penton P.M. , Davoren G.K. , Montevecchi W.A. , Andrews D.W. 
Published: February 2012

Timing of spawning and site selection in fish are important fitness-related traits that ultimately influence reproductive success. Capelin ( Mallotus villosus (Müller, 1776)), a key forage fish in the north Atlantic, spawn eggs that adhere to sediments on beaches and in demersal (deep-water) habitats throughout their geographic range, resulting in divergent thermal regimes for the incubating eggs. We compare the timing and duration of spawning of capelin and its influence on the developmental and survival rates of eggs between a beach and a demersal spawning site on the northeast Newfoundland coast in 2004 and 2005. Spawning events at the beach were at least 10 days earlier and shorter (2–3 days) relative to the demersal site (8–12 days). Hourly and mean daily incubation temperatures at the beach were higher and more variable relative to the demersal site, resulting in two distinct developmental strategies: low to high mortality and rapid development (beach) versus low mortality and slow development (demersal). Higher egg mortality at beach sites was explained by higher and more variable temperatures and potentially limited oxygen replenishment relative to demersal sites. The divergent biology of beach and demersally spawned eggs suggest that each will respond differently to environmental change and, thus, require different approaches for successful management.
History of Diabetes and Risk of Head and Neck Cancer: A Pooled Analysis from the International Head and Neck Cancer Epidemiology Consortium
Authors: Stott-Miller Marni , Chen Chu , Chuang Shu-Chun , Lee Yuan-Chin Amy , Boccia Stefania , Brenner Hermann , Cadoni Gabriela , Dal Maso Luigino , La Vecchia Carlo , Lazarus Philip , Levi Fabio , Matsuo Keitaro , Morgenstern Hal , Müller Heiko , Muscat Joshua , Olshan Andrew F. , Purdue Mark P. , Serraino Diego , Vaughan Thomas L. , Zhang Zuo-Feng , Boffetta Paolo , Hashibe Mia , Schwartz Stephen M. 
Published: February 2012

Abstract
Background: A history of diabetes is associated with an increased risk of several types of cancers. Whether diabetes is a risk factor for head and neck cancer (HNC) has received little attention.
Methods: We pooled data from 12 case–control studies including 6,448 cases and 13,747 controls, and estimated OR and 95% CI for the associations between diabetes and HNC, adjusted for age, education level, sex, race/ethnicity, study center, cigarette smoking, alcohol use, and body mass index.
Results: We observed a weak association between diabetes and the incidence of HNC overall (OR, 1.09; 95% CI: 0.95–1.24). However, we observed a modest association among never smokers (OR, 1.59; 95% CI: 1.22–2.07), and no association among ever smokers (OR, 0.96; 95% CI: 0.83–1.11); likelihood ratio test for interaction P = 0.001.
Conclusion: A history of diabetes was weakly associated with HNC overall, but we observed evidence of effect modification by smoking status, with a positive association among those who never smoked cigarettes.
Impact: This study suggests that glucose metabolism abnormalities may be a HNC risk factor in subgroups of the population. Prospective studies incorporating biomarkers are needed to improve our understanding of the relationship between diabetes and HNC risk, possibly providing new strategies in the prevention of HNC. Cancer Epidemiol Biomarkers Prev; 21(2); 294–304. ©2011 AACR.
Soy Isoflavone Supplementation for Breast Cancer Risk Reduction: A Randomized Phase II Trial
Authors: Khan Seema A. , Chatterton Robert T. , Michel Nancy , Bryk Michelle , Lee Oukseub , Ivancic David , Heinz Richard , Zalles Carola M. , Helenowski Irene B. , Jovanovic Borko D. , Franke Adrian A. , Bosland Maarten C. , Wang Jun , Hansen Nora M. , Bethke Kevin P. , Dew Alexander , Coomes Margerie , Bergan Raymond C. 
Published: February 2012

AbstractSoy isoflavone consumption may protect against breast cancer development. We conducted a phase IIB trial of soy isoflavone supplementation to examine its effect on breast epithelial proliferation and other biomarkers in the healthy high-risk breast. One hundred and twenty-six consented women underwent a random fine-needle aspiration (rFNA); those with 4,000 or more epithelial cells were randomized to a double-blind 6-month intervention of mixed soy isoflavones (PTIG-2535) or placebo, followed by repeat rFNA. Cells were examined for Ki-67 labeling index and atypia. Expression of 28 genes related to proliferation, apoptosis, and estrogenic effect was measured using quantitative reverse transcriptase PCR. Hormone and protein levels were measured in nipple aspirate fluid (NAF). All statistical tests were two-sided. Ninety-eight women were evaluable for Ki-67 labeling index. In 49 treated women, the median Ki-67 labeling index was 1.18 at entry and 1.12 post intervention, whereas in 49 placebo subjects, it was 0.97 and 0.92 (P for between-group change: 0.32). Menopausal stratification yielded similar results between groups, but within premenopausal soy-treated women, Ki-67 labeling index increased from 1.71 to 2.18 (P = 0.04). We saw no treatment effect on cytologic atypia or NAF parameters. There were significant increases in the expression of 14 of 28 genes within the soy, but not the control group, without significant between-group differences. Plasma genistein values showed excellent compliance. A 6-month intervention of mixed soy isoflavones in healthy, high-risk adult Western women did not reduce breast epithelial proliferation, suggesting a lack of efficacy for breast cancer prevention and a possible adverse effect in premenopausal women. Cancer Prev Res; 5(2); 309–19. ©2012 AACR.
A Review of Cancer in U.S. Hispanic Populations
Authors: Haile Robert W. , John Esther M. , Levine A. Joan , Cortessis Victoria K. , Unger Jennifer B. , Gonzales Melissa , Ziv Elad , Thompson Patricia , Spruijt-Metz Donna , Tucker Katherine L. , Bernstein Jonine L. , Rohan Thomas E. , Ho Gloria Y.F. , Bondy Melissa L. , Martinez Maria Elena , Cook Linda , Stern Mariana C. , Correa Marcia Cruz , Wright Jonelle , Schwartz Seth J. , Baezconde-Garbanati Lourdes , Blinder Victoria , Miranda Patricia , Hayes Richard , Friedman-Jiménez George , Monroe Kristine R. , Haiman Christopher A. , Henderson Brian E. , Thomas Duncan C. , Boffetta Paolo 
Published: February 2012

AbstractThere are compelling reasons to conduct studies of cancer in Hispanics, the fastest growing major demographic group in the United States (from 15% to 30% of the U.S. population by 2050). The genetically admixed Hispanic population coupled with secular trends in environmental exposures and lifestyle/behavioral practices that are associated with immigration and acculturation offer opportunities for elucidating the effects of genetics, environment, and lifestyle on cancer risk and identifying novel risk factors. For example, traditional breast cancer risk factors explain less of the breast cancer risk in Hispanics than in non-Hispanic whites (NHW), and there is a substantially greater proportion of never-smokers with lung cancer in Hispanics than in NHW. Hispanics have higher incidence rates for cancers of the cervix, stomach, liver, and gall bladder than NHW. With respect to these cancers, there are intriguing patterns that warrant study (e.g., depending on country of origin, the five-fold difference in gastric cancer rates for Hispanic men but not Hispanic women). Also, despite a substantially higher incidence rate and increasing secular trend for liver cancer in Hispanics, there have been no studies of Hispanics reported to date. We review the literature and discuss study design options and features that should be considered in future studies. Cancer Prev Res; 5(2); 150–63. ©2012 AACR.
New Directions in Reducing Stress Effects on Cancer
Authors: Melhem-Bertrandt Amal , Sood Anil K. 
Published: February 2012

Abstract
A growing body of evidence is now connecting neuroendocrine mediators of the stress response to cancer biology. Al-Wadei and colleagues report a study in this issue of the journal (beginning on page 189) that provides a new piece of this evidence, adding the inhibitory neurotransmitter γ-aminobutyric acid to this intricate pathway. Their mouse model study supports the hypothesis that stress mediators contribute to lung cancer progression and that known inhibitors of the stress pathway might block such effects, thus adding to the impetus for studying cancer prevention strategies targeting the stress pathway. Cancer Prev Res; 5(2); 147–9. ©2012 AACR.
The Types of Neurological Deficits Might Not Justify Withholding Treatment in Patients With Low Total National Institutes of Health Stroke Scale Scores
Authors: Leira Enrique C. , Ludwig Bryan R. , Gurol M. Edip , Torner James C. , Adams Harold P. 
Published: February 2012

Background and Purpose—
There is controversy regarding the threshold for treating patients with mild strokes. Physicians often withhold acute treatment in these patients if they perceive the symptoms are not going to be disabling. We tested the appropriateness of this practice by analyzing the relationship between specific neurological deficits in the National Institutes of Health Stroke Scale (NIHSS) score and long-term outcome among patients with a low total NIHSS score.

Methods—
We performed a secondary analysis on those patients enrolled in the Trial of ORG 10172 in Acute Stroke Treatment that presented within 4.5 hours of symptom onset and had a baseline NIHSS score ≤6 (n=194). We performed multivariate logistic regression analyses using very favorable outcome at 3 months as the outcome variable and each of the individual items of the baseline NIHSS examination and syndromic combinations of NIHSS scores as predictors. The analyses were adjusted for potential confounders with and without adjusting for total NIHSS score.

Results—
Baseline total NIHSS scores were inversely associated with very favorable outcome at 3 months. No individual NIHSS item, or syndromic combination of NIHSS scores, was independently associated with very favorable outcome in a consistent manner after accounting for confounders and collinearity.

Conclusions—
The types of neurological deficits in the baseline NIHSS are not independent predictors of long-term prognosis for patients with mild stroke. These exploratory findings argue against the practice of withholding reperfusion treatment in patients with mild stroke when the types of baseline NIHSS deficits are perceived to be nondisabling.
A Structured Reading Algorithm Improves Telemetric Detection of Atrial Fibrillation After Acute Ischemic Stroke
Authors: Kallmünzer Bernd , Breuer Lorenz , Hering Christiane , Raaz-Schrauder Dorette , Kollmar Rainer , Huttner Hagen B. , Schwab Stefan , Köhrmann Martin 
Published: February 2012

Background and Purpose—
Anticoagulation is a highly effective secondary prevention in patients with cardioembolic stroke and atrial fibrillation/flutter (AF). However, the condition remains underdiagnosed, because paroxysmal AF may be missed by diagnostic tests in the acute phase. In this study, the sensitivity of AF detection was assessed for serial electrocardiographic recordings and continuous stroke unit telemetric monitoring with or without a structured algorithm to analyze telemetric data (SEA-AF).

Methods—
Three hundred forty-six consecutive patients with acute ischemic stroke were prospectively included and subjected to standard telemetric monitoring. In addition, telemetric data were separately analyzed following SEA-AF, consisting of a structured evaluation of episodes with high risk for AF and a chronological beat-to-beat screening of the full registration. Serial electrocardiograms were conducted in 24-hour intervals.

Results—
Median effective telemetry monitoring time was 75.5 hours (interquartile range 64–86 hours). Overall, AF was diagnosed in 119 of 346 patients (34.4%). The structured reading algorithm was the most sensitive method to detected AF. Conventional telemetry and serial electrocardiographic assessments were less effective. However, only 35% of patients with previously documented paroxysmal AF and negative baseline electrocardiogram demonstrated AF episodes during monitoring.

Conclusions—
Continuous stroke unit telemetry using SEA-AF shows a significantly higher detection rate for AF compared with daily electrocardiographic assessments and standard telemetry without structured reading. The low overall probability to detect paroxysmal AF with either method during the first days after stroke demonstrates the urgent need for complementary diagnostic strategies such as long-term monitoring and frequent follow-up assessments.

Clinical Trial Registration—

URL:
www.clinicaltrials.gov
. Unique identifier: NCT01177748.
Reading ἔγραψα in 2 Corinthians 2:9 as an Epistolary Aorist
Authors: Stegman Thomas D. 
Published: February 2012

Abstract
This article offers a re-reading of ἔγραψα in 2 Cor 2:9. It argues that this verb should be interpreted as an epistolary aorist—thereby indicating a reason for why Paul is presently writing—rather than as a preterit aorist, referring to the “tearful letter.” Reading ἔγραψα as an epistolary aorist in 2:9 resolves tensions with the preceding context produced by the typical interpretation. It also results in a fully coherent reading of 2:5-11, where Paul exhorts the Corinthians to receive back the offender. This study supplements K.L. McKay’s treatment of the epistolary aorist in Novum Testamentum.