bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of K+ Currents in Type I Vestibular Hair Cells by Gentamicin and Neomycin
Authors: Mann Scott E. , Johnson Matthew , Meredith Frances L. , Rennie Katherine J.
Published: September 2013

Significant ototoxicity limits the use of aminoglycoside (AG) antibiotics. Several mechanisms may contribute to the death of both auditory and vestibular hair cells. In this study the effects of gentamicin and neomycin on K+ currents in mature and early postnatal type I vestibular hair cells (HCI) were tested directly. The whole-cell patch clamp technique was used to assess the effects of AG and KCNQ channel modulators on K+ currents (IK) in HCI acutely isolated from gerbil semicircular canals. Extracellular neomycin (1 mM) rapidly reduced peak outward IK by 16 ± 4% (n = 9) in mature HCI (postnatal days, P, 25-66). Gentamicin (5 mM) reduced outward IK by 16 ± 3% (n = 8). A similar reduction in outward current was seen in immature HCI (P5-9) that lacked the low-voltage-activated component of IK observed in mature cells. Intracellular application of gentamicin and neomycin also reduced IK in mature HCI. Modulators of KCNQ channels were used to probe KCNQ channel involvement. The selective KCNQ antagonist XE991 did not reduce IK and the neomycin-induced reduction in IK was not reversed by the KCNQ agonist flupirtine. Application of intracellular poly-D-lysine to sequester PIP2 did not reduce IK. Application of the K+ channel blocker 4-aminopyridine (4-AP) strongly reduced IK, and extracellular AG in the presence of 4-AP gave no further inhibition of IK. In summary, AG significantly reduce the 4-AP-sensitive IK in early postnatal and mature HCI. K+ current inhibition differs from that seen in outer hair cells, since it does not appear to involve PIP2 sequestration or KCNQ channels.
Epigenetics, Probiotic Metabolites and Colon Cancer Prevention: An Overview of Progress, Opportunities and Challenges
Authors: Kumar Manoj , Hemalatha R. , Kumar Rajesh , Nagpal Ravinder , Devraj J.P. , Verma Vinod , Behare Pradip , Mal G. , Singh B.
Published: September 2013

Colorectal cancer (CRC) is a common epithelial neoplasia across the globe, with about 1.2 million newly diagnosed cases and over 600,000 mortalities annually. The underlying causes are numerous including dietary ingredients, environmental factors and gut metabolome that affect colon cellular gene regulation and post-translational modifications of the proteome. Collectively, these alterations initiate epigenetic modifications leading to the inception of various metabolic diseases and malignancies. Epigenetics is at the core of modern medicine since it deals with complex processes that turn the expression of certain genes on and off, and it elucidates the mechanisms and connections between genotypes and the environment during various stages of life. However, the majority of the vertical molecular mechanisms with reference to epigenomics, epigenetic and metabolic ailments are still unidentified and need further research. This article summarizes the burgeoning role of probiotic metabolites and some prominent therapeutic dietary ingredients in the management of CRC.
Protein degradation systems in platelets
Authors: Kraemer Bjoern F. , Lindemann Stephan , Weyrich Andrew S.
Published: September 2013

Protein synthesis and degradation are essential processes that allow cells to survive and adapt to their surrounding milieu. In nucleated cells, the degradation and/or cleavage of proteins is required to eliminate aberrant proteins. Cells also degrade proteins as a mechanism for cell signalling and complex cellular functions. Although the last decade has convincingly shown that platelets synthesise proteins, the roles of protein degradation in these anucleate cytoplasts are less clear. Here we review what is known about protein degradation in platelets placing particular emphasis on the proteasome and the cysteine protease calpain.
Local Balance and Variability of Atmospheric Heat Budget over Oceans: Observation and Reanalysis-Based Estimates
Authors: Wong Sun , L’Ecuyer Tristan S. , Olson William S. , Jiang Xianan , Fetzer Eric J.
Published: September 2013

The authors quantify systematic differences between modern observation- and reanalysis-based estimates of atmospheric heating rates and identify dominant variability modes over tropical oceans. Convergence of heat fluxes between the top of the atmosphere and the surface are calculated over the oceans using satellite-based radiative and sensible heat fluxes and latent heating from precipitation estimates. The convergence is then compared with column-integrated atmospheric heating based on Tropical Rainfall Measuring Mission data as well as the heating calculated using temperatures from the Atmospheric Infrared Sounder and wind fields from the Modern-Era Retrospective Analysis for Research and Applications (MERRA). Corresponding calculations using MERRA and the European Centre for Medium-Range Weather Forecasts Interim Re-Analysis heating rates and heat fluxes are also performed. The geographical patterns of atmospheric heating rates show heating regimes over the intertropical convergence zone and summertime monsoons and cooling regimes over subsidence areas in the subtropical oceans. Compared to observation-based datasets, the reanalyses have larger atmospheric heating rates in heating regimes and smaller cooling rates in cooling regimes. For the averaged heating rates over the oceans in 40°S–40°N, the observation-based datasets have net atmospheric cooling rates (from −15 to −22 W m−2) compared to the reanalyses net warming rates (5.0–5.2 W m−2). This discrepancy implies different pictures of atmospheric heat transport. Wavelet spectra of atmospheric heating rates show distinct maxima of variability in annual, semiannual, and/or intraseasonal time scales. In regimes where deep convection frequently occurs, variability is mainly driven by latent heating. In the subtropical subsidence areas, variability in radiative heating is comparable to that in latent heating.
A Comparison of Precipitation Occurrence from the NCEP Stage IV QPE Product and the CloudSat Cloud Profiling Radar
Authors: Smalley Mark , L'Ecuyer Tristan , Lebsock Matthew , Haynes John
Published: September 2013

Because of its extensive quality control procedures and uniform space–time grid, the NCEP Stage IV merged Weather Surveillance Radar-1988 Doppler (WSR-88D) radar and surface rain gauge dataset is often considered to be the best long-term gridded dataset of precipitation observations covering the contiguous United States. Stage IV accumulations are employed in a variety of applications, and while the WSR-88D systems are well suited for observing heavy rain events that are likely to affect flooding, limitations in surface radar and gauge measurements can result in missed precipitation, especially near topography and in the western United States. This paper compares hourly Stage IV observations of precipitation occurrence to collocated observations from the 94-GHz CloudSat Cloud Profiling Radar, which provides excellent sensitivity to light and frozen precipitation. Statistics from 4 yr of comparisons show that the CloudSat observes precipitation considerably more frequently than the Stage IV dataset, especially in northern states where frozen precipitation is prevalent in the cold season. The skill of Stage IV for precipitation detection is found to decline rapidly when the near-surface air temperature falls below 0°C. As a result, agreement between Stage IV and CloudSat tends to be best in the southeast, where radar coverage is good and moderate-to-heavy liquid precipitation dominates. Stage IV and CloudSat precipitation detection characteristics are documented for each of the individual river forecast centers that contribute to the Stage IV dataset to provide guidance regarding potential sampling biases that may impact hydrologic applications.
Improving the Representation of Low Clouds and Drizzle in the ECMWF Model Based on ARM Observations from the Azores
Authors: Ahlgrimm Maike , Forbes Richard
Published: September 2013

In this study, the representation of marine boundary layer clouds is investigated in the ECMWF model using observations from the Atmospheric Radiation Measurement (ARM) mobile facility deployment to Graciosa Island in the North Atlantic. Systematic errors in the occurrence of clouds, liquid water path, precipitation, and surface radiation are assessed in the operational model for a 19-month-long period. Boundary layer clouds were the most frequently observed cloud type but were underestimated by 10% in the model. Systematic but partially compensating surface radiation errors exist and can be linked to opposing cloud cover and liquid water path errors in broken (shallow cumulus) and overcast (stratocumulus) low-cloud regimes, consistent with previously reported results from the continental ARM Southern Great Plains (SGP) site. Occurrence of precipitation is overestimated by a factor of 1.5 at cloud base and by a factor of 2 at the surface, suggesting deficiencies in both the warm-rain formation and subcloud evaporation parameterizations. A single-column version of the ECMWF model is used to test combined changes to the parameterizations of boundary layer, autoconversion/accretion, and rain evaporation processes at Graciosa. Low-cloud occurrence, liquid water path, radiation biases, and precipitation occurrence are all significantly improved when compared to the ARM observations. Initial results from the modified parameterizations in the full model show improvement in the global top-of-the-atmosphere shortwave radiation, suggesting the reduced errors in the comparison at Graciosa are more widely applicable to boundary layer cloud around the globe.
miR-202 expression concentration and its clinical significance in the serum of multiple myeloma patients
Authors: Yu Jiajia , Qiu Xiaojun , Shen Xianjuan , Shi Wei , Wu Xinhua , Gu Guohao , Zhu Baoli , Ju Shaoqing
Published: September 2013

Objectives

To explore microRNA-202 (miR-202) expression in serum of patients with multiple myeloma (MM), and investigate correlations between serum miR-202 expression and the development and prognosis of MM.

Design and methods

RNA was extracted from serum by QIAGEN miRNeasy Mini kit. Reverse transcription was performed with specific stem-loop primers. SYBR Green I QF-PCR was applied to detect the relative expression of miR-202 in 40 MM patients and 30 healthy controls. The linearity, specificity and reproducibility were evaluated. In addition, correlations between the relative expression of serum miR-202 and the concentrations of lactic acid dehydrogenase (LDH), β2M, λ light chain and κ light chain were assessed.

Results

The relative expression of miR-202 in MM patients 1.503 (0.161–9.831) was significantly higher than that in healthy controls 1.000 (0.105–3.046) ( P < 0.01) and was significantly correlated with serum β2M and κ light chain concentrations ( r = 0.366, P = 0.0305; r = 0.358, P = 0.0348).

Conclusions

The relative expression of serum miR-202 in MM patients was significantly higher than that in healthy controls, and therefore it may prove to be useful in the auxiliary diagnosis of MM.
Per Edith Farnsworth (1903–1977)
Authors: Delia Giorgio
Published: September 2013

Delineati i tratti essenziali della vita (non poco avventurosa) di Edith Farnsworth, se ne ripercorrono gli ultimi anni fiorentini quando, sulla scia di Contini, la studiosa profonde le sue migliori energie a tradurre alcuni degli autori più originali dell’Otto-Novecento letterario italiano. Si dà conto di quanto pubblicato (le traduzioni di Quasimodo, Montale e Pierro) e, attraverso ricerche d’archivio, si rintracciano i progetti e i propositi rimasti inediti o incompiuti.
Strategic voting and non-voting in Spanish elections
Authors: García-Viñuela Enrique , Artés Joaquín , Jurado Ignacio
Published: September 2013

The literature on strategic voting has provided evidence that some electors support large parties at the voting booth to avoid wasting their vote on a preferred but uncompetitive smaller party. In this paper we argue that district conditions also elicit reactions from abstainers and other party voters. We find that, when ballot gains and losses from different types of responses to the constituency conditions are taken into account, large parties still benefit moderately from strategic behaviour, while small parties obtain substantial net ballot losses. This result stems from a model that allows for abstention in the choice set of voters, and uses counterfactual simulation to estimate the incidence of district conditions in the Spanish general elections of 2000 and 2008.
War on Instagram: Framing conflict photojournalism with mobile photography apps
Authors: Alper Meryl
Published: September 2013

This paper examines recent acclaim for professional embedded photojournalists who visually document the experience of US soldiers in Afghanistan using the popular mobile photo application Hipstamatic. These photos have stirred controversy among fellow journalists and cultural critics regarding the use of photo filters in Hipstamatic and similar app Instagram, their contribution to the de-professionalization of photojournalism, and the depiction of war as stylishly vintage. The debates about Hipstamatic and Instagram in war photography open up a whole series of enduring questions about distinctions between photography and illustration, photography and photojournalism, professional and amateur, and reporting and editorializing. In consideration of the shifting nature of digital photography, photojournalism, and specifically war photojournalism, I argue that this discourse about the use of mobile apps overlooks another important ethical issue: the implications of non-soldiers mimicking the imagined hand of the modern smartphone-equipped US soldier, particularly in light of soldiers’ own complex media-making practices.
Fatigue crack growth monitoring using high-frequency guided waves
Authors: Masserey Bernard , Fromme Paul
Published: September 2013

A common problem in aircraft maintenance is the development of fatigue cracks at fastener holes due to stress concentration. High-frequency guided ultrasonic waves allow for the structural health monitoring of critical areas of a structure and can be measured with high accuracy using a noncontact laser interferometer. The use of a specific type of high-frequency guided ultrasonic wave that has good sensitivity for the detection of small defects, excited using a standard Rayleigh wedge transducer and propagating along the structure, has been investigated. Fatigue crack growth at the side of a fastener hole in a tensile, aluminum specimen was induced by cyclic loading of the structure. The crack length was monitored optically and showed good correlation with fracture mechanics calculations of the expected growth rate. The changes in the guided wave signal due to the fatigue damage were monitored using a noncontact laser interferometer and quantified. The measurements show a good sensitivity for the early detection of fatigue damage and for the monitoring of fatigue crack growth at a fastener hole. The propagation and scattering of the high-frequency guided ultrasonic wave has been simulated numerically using a three-dimensional finite difference code. Good agreement was found between the measured and predicted changes of the ultrasonic signal for the increasing fatigue crack area, allowing in principle for the approximate sizing of the defect.
Plasma gelsolin levels are decreased and correlate with fibrosis in IgA nephropathy
Authors: Han Changsong , Zhang Lei , Zhu Xiaoling , Tang Jing , Jin Xiaoming
Published: September 2013

IgA nephropathy (IgAN) is an immune complex glomerulonephritis that is characterized by recurrent hematuria as the main clinical manifestation. In this study, we used the IgAN mouse model which was previously established to investigate the possible mechanism by which IgAN fibrosis correlates with decreased plasma gelsolin (pGSN) levels. We investigated the levels of pGSN, transforming growth factor β1 (TGFβ1), and oxidative stress markers including superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and malondialdehyde (MDA) in the serum and renal tissues of different groups. The between-group differences and correlations in the results for the IgAN group were analyzed with statistical methods. The pathological and urinalysis results obtained from the IgAN mouse model showed that this model conforms to the basic lesion characteristics observed in human IgAN. The serum pGSN levels and SOD, CAT, GSH levels in renal tissues were decreased in the IgAN group ( P < 0.01), and pGSN, TGFβ1, MDA levels in renal tissues of the IgAN group were increased which compared with those in the other groups ( P < 0.01). The correlation analysis for serum pGSN levels in the IgAN group showed a significant correlation with different test results ( P < 0.01). The possible mechanism by which IgAN fibrosis correlates with decreased pGSN levels involves the regulation of TGFβ1 and oxidative stress.
Documentary noir in the city of fear: Feminicide, impunity and grassroots communication in Ciudad Juarez
Authors: Jeffries Fiona
Published: September 2013

The emergence of a systematic campaign of horrific violence directed at women and girls in the Mexican border city of Ciudad Juarez has become a focus of intense media and activist attention over the last two decades. While the mainstream media devoted much attention to ravaged bodies and sensational theories, state officials reacted to the crimes with a victim-blaming narrative that, activists have argued, provided a lethal accelerant to the violence. This paper explores the role of documentary film in the investigation and politicization of the murders and disappearances of women in Juarez. Along with activists and journalists, critical documentary filmmakers have been among the primary investigators of the crimes. In this paper, I argue that these grassroots media practices have been instrumental in opening spaces of communication that have been enclosed by pervasive fear and systemic insecurity. I pay specific attention to the ways in which Lourdes Portillo’s 2001 documentary Señorita Extraviada interrogates the crimes politically. Through its critical, engaged approach to the aesthetics and politics of evidence, I argue, the film poses a counter-narrative to the neoliberal state’s discourse of responsibilization and individualization in a context of systemic insecurity.
MyD88 mediates the decision to die by apoptosis or necroptosis after UV irradiation
Authors: Harberts Erin , Fishelevich Rita , Liu Juan , Atamas Sergei P , Gaspari Anthony A
Published: September 2013

UV irradiation-induced cellular damage is classically associated with apoptosis and is known to result in systemic immunosuppression. How the decision to undergo apoptosis is made following UV is not fully understood. We hypothesize that a central mediator of TLR signaling, MyD88, determines cell fate after UV exposure. Survival after UV of immortalized bone marrow-derived macrophages (BMDM) and ex vivo peritoneal macrophages (PM) from MyD88 germline-deficient mice (MyD88-/-) was significantly higher than wild type (WT) PM. UV-induced apoptosis (DNA laddering) in PM and epidermis of MyD88-/- animals versus WT was decreased. In MyD88-/- PM, decreased cleavage of caspase 3, as well as pro-necroptotic protein, RIP1, and a significant increase in transcription and release of pro-inflammatory TNF-α, suggest that necroptosis, rather than apoptosis, has been initiated. In vivo studies confirm this hypothesis after UV, showing low apoptosis by TUNEL and inflammation in MyD88-/- skin sections. Considering that MyD88 participates in many TLR pathways, BMDM from TLR2-/-, TLR4-/- and WT mice were compared for evidence of UV-induced apoptosis. Only TLR4-/- BMDM and PM had a similar phenotype to MyD88-/-, suggesting that the TLR4–MyD88 axis importantly contributes to cell fate decision. Our study describes a new cellular consequence of MyD88 signaling after UV, and may provide rationale for therapies to mitigate UV-induced immunosuppression.
Citalopram-Related SIADH
Authors: Ertel Ginger J , Nesbit Todd W
Published: September 2013

Objective:

To report a case of syndrome of inappropriate antidiuretic hormone (SIADH) after the initiation of citalopram and trazodone therapy.

Case Summary:

A 75-year-old white woman developed SIADH after the initiation of citalopram and trazodone therapy.

Discussion:

Selective serotonin-reuptake inhibitors (SSRIs) and trazodone have been associated with hyponatremia in the literature. There are numerous reports of SSRIs, primarily fluoxetine, associated with SIADH. There are 8 case reports of SIADH reported with citalopram in the literature, which were identified through a MEDLINE search that included all languages and bibliographic review of those cases. The number of citalopram cases may not be associated with a reduced incidence but with the infrequency of citalopram use compared with the widespread use of fluoxetine. The mechanism of action of citalopram is enhancement of serotoninergic neurotransmission, which is similar to other serotonin (5-HT) reuptake inhibitors. To date, there are only 2 reports of trazodone associated with hyponatremia in the literature, both as a result of an overdose.

Conclusions:

SIADH has been reported with several SSRIs, but to a lesser degree with citalopram, which may be attributed to the lower number of patients using it compared with other SSRIs. Increased awareness and monitoring of SIADH is important, especially in older patients who may be at an increased risk of SIADH.
Public Attitude toward Drug Technical Package Inserts in Saudi Arabia
Authors: Bawazir Saleh A , Abou-Auda Hisham S , Gubara Othman A , Al-Khamis Khalil I , Al-Yamani Mohammed JMS
Published: September 2013

Objective:

To examine public opinion in Saudi Arabia regarding the technical drug package insert (PI) as a source of information and to assess the need for potential changes to the existing format in favor of a more patient-oriented package insert (PPI).

Design:

A cross-sectional survey was conducted from March through May 1998 by means of a self-administered questionnaire.

Setting:

Eighty-four community pharmacies in Riyadh.

Participants:

Two thousand twenty-nine customers entering community pharmacies in Riyadh were enrolled in this survey.

Results:

Results of the survey showed that 88% of the respondents read the PI. The motives for reading the PI included the desire to know more about the medication (48.7%), to adhere to the prescription (21.7%), and to decide whether to take the medication (13.1%). From the list of information contained therein, respondents listed indications (47.1%) and adverse drug effects (46.6%) as the principal sections of interest. Respondents overwhelmingly endorsed the PI as a complementary source of drug information to the verbal instructions of the physician and the pharmacist. However, readers did criticize its detail, legibility, and poor graphic illustration. Respondents indicated their desire to see a concise PPI introduced, one that highlights only the most common adverse effects of a drug. It should be written in simple Arabic and include, whenever possible, illustrations to enhance comprehension.

Conclusions:

The PI does not have the power to overrule the physician's or pharmacist's instructions. Since some patients may cease taking their medicines if they feel threatened by the adverse effects mentioned in the PI, precautionary statements should be prominently placed in the PI to explain the purpose of mentioning such information and what proper action should be taken by the patient.
Training Pharmacy Technicians in Community Pharmacy about Technical Aspects of Blood Glucose Meters
Authors: Hilaire Michelle L , Powers Mary F , Kitz Michael J
Published: September 2013

Objective:

To develop a structured training module for community pharmacy technicians to enhance on-the-job training, with a focus on the technical aspects associated with blood glucose meters.

Methods:

A 3-hour live training session was offered about the technical features of blood glucose meters. A 54-page manual was developed and provided to enhance the training sessions and for later use as a reference. Participation was voluntary and participants answered a 10-item pre-training survey and a 15-item post-training survey. The surveys contained questions about the knowledge and beliefs the technicians had about blood glucose meters.

Results:

Thirty-nine pharmacy technicians from 21 pharmacies participated in the training. Seventy-three percent of the participants expressed that they were very interested in taking an advanced role as a pharmacy technician. Sixty-four percent of the participants strongly agreed that the content of the program added to their knowledge about blood glucose meters. Fifty-two percent of the participants have been employed for >3 years by their employer.

Conclusions:

Community pharmacists today are striving to integrate patient care with the goods and services traditionally associated with pharmacy. Pharmacy technicians are recognized as an important resource in helping pharmacists provide better patient care. The structured training module described in this article is designed to supplement on-the-job training. Formal training through accredited training programs may be required in the future. Structured technician training modules may provide a means for transition from predominantly on-the-job training to formal training.
Assessing Adherence to an Intravenous Pantoprazole Guideline
Authors: MacLaren Robert , Obritsch Marilee D , Sherman Deborah S , Jung Rose , Fish Douglas N
Published: September 2013

Background:

Despite minimal efficacy data, some institutions frequently use intravenous proton-pump inhibitors (PPIs), such as pantoprazole, for prevention of stress-related mucosal disease (SRMD) bleeding, or the treatment of nonvariceal upper gastrointestinal bleed (GIB). Due to the increased expense of intravenous pantoprazole compared with enteral PPIs, a guideline was implemented to reduce inappropriate use and provide dosing recommendations for SRMD and GIB.

Objective:

To comparatively assess the adherence rates before and after implementation of an institution-specific usage guideline for intravenous pantoprazole.

Methods:

A retrospective chart audit of consecutive patients receiving intravenous pantoprazole for 2 month periods before and after a guideline was implemented over a 2 month education period. The guideline restricted pantoprazole use to bleeding prevention of SRMD in patients unable to tolerate histamine2-receptor antagonists and to receive enteral administration of PPIs (80 mg/day or 40 mg twice daily) or patients with severe GIB (80 mg, then 8 mg/h). Outcomes assessed were the percentage of patients deemed appropriate to receive intravenous pantoprazole and compliance with dosing recommendations.

Results:

Overall, pantoprazole was appropriately chosen in 20 (42.6%) patients with SRMD and 34 (79.1%) of patients with GIB (p < 0.0001). Pantoprazole was appropriately chosen in 16 (55.2%) patients before and 24 (64.9%) patients after implementation of the guideline. The dosage regimen for SRMD was appropriate in 3 (21.4%) before-group patients and 10 (58.9%) after-group patients (p = 0.007). The dosage regimen for GIB was appropriate in 4 (26.7%) patients before and 6 (30%) patients after adoption of the guideline. Length of stay in the intensive care unit was shorter for the after group for both SRMD and GIB, and the mortality rate was lower in the after group for SRMD only, but these outcomes were likely unrelated to implementation of the guideline.

Conclusions:

An intravenous pantoprazole guideline did not change appropriate patient selection and improved prescribing practices for SRMD only.
Barriers to Implementing a Pharmacist-Run Immunization Service, as Perceived by Pharmacists, in a Community Pharmacy Chain
Authors: Capurso Kevin A , Powers Mary F
Published: September 2013

Background:

Thousands of people die each year from vaccine-preventable diseases. Pharmacists can be a valuable resource in aiding the success of immunizations.

Objective:

To determine the barriers to implementing a program utilizing pharmacists as immunizers, as perceived by pharmacists, in a supermarket pharmacy chain.

Methods:

A 15 question survey regarding the perceived barriers to implementing a pharmacist-run immunization program was distributed to 60 pharmacists in a supermarket chain in northwestern Ohio. The responses were tabulated using a 5 point Likert scale. The data were analyzed utilizing the Statistical Package for Social Sciences.

Results:

Of the 60 pharmacists who received the survey, 43 completed the questionnaire (response rate 72.0%). A majority of the pharmacists surveyed believed that patient privacy was an issue in administering adult immunizations in a community pharmacy. The majority of pharmacists were concerned about the risk of adverse reactions to the vaccines and the need for a quick response to control these reactions. Twenty-five pharmacists believed that the prescription volume at their pharmacy limited them from having time to immunize. Twenty-one pharmacists cited cost as the main determining factor in a pharmacy immunization program.

Conclusions:

Many barriers to implementing a pharmacist-run immunization program exist. The future success of such an immunization program rests on overcoming the perceived barriers in a formal and timely manner.
Assessment of Pharmacy Technicians' Salary, Benefits, and Responsibilities in North Dakota
Authors: Scott David M , Halvorson Diane
Published: September 2013

Background:

While the number of pharmacist workforce studies being published is growing, few studies report accurate information concerning the wages, benefits, and responsibilities of pharmacy technicians.

Objective:

To evaluate the wages, benefits, and responsibilities of pharmacy technicians in North Dakota.

Methods:

A mail survey for pharmacy technicians was modified based on the Wage and Benefit Survey for pharmacists used in the Upper Midwest Pharmacists Workforce Study. A list of responsibilities was added to this survey to represent technicians' responsibilities in North Dakota. A survey packet then was mailed to the 456 pharmacy technicians registered in North Dakota. A follow-up postcard and a second survey were mailed to nonrespondents at 4 and 8 weeks, respectively.

Results:

Overall, 256 (56.1%) completed surveys were available for analysis. Pharmacy technicians reported that they worked in a primary employment setting (n = 228) an average of 36.8 hours per week and received an average of 2.3 weeks of vacation. The average hourly rate was $12.34 ($7.00–25.48) and the gross 2004 salary (excluding benefits) was $21,627 ($880–41,600). Hospitals had the highest average hourly pay rate ($12.40), followed by independent ($12.35) and chain ($12.01) pharmacies. Grandfathered technicians (those registered in 1994 when the registration requirement was passed in North Dakota) received the highest average hourly pay rate at $13.11, followed by 1 year, 2 year, and Pharmacist-Assisted Technician Self-Instructional Modules (PATSIM) graduates. The hourly rate for grandfathered pharmacy technicians who have since become certified ($13.30) was highest. Differences between certified and noncertified groups were $0.10 more for 1 year graduates and $0.20 for PATSIM graduates; the difference between grandfathered technicians and 2 year graduates was $0.30. Commonly reported benefits included paid vacation (80%), health insurance for the employee (67%), sick leave (56%), and tax-sheltered plans (54%). Other benefits received were discounts on purchases (61%) and discounts on prescription drugs (54%). Among the most frequently cited distributive functions that technicians perform in their work setting included retrieving products from stock, followed by working with inventory, checking in and putting away medications, filling routine stock supplies, and affixing prescription labels to containers.

Conclusions:

Pharmacy technician wages, benefits, and responsibilities in North Dakota are reflective of levels of training, experience, and certification status. While similar assessments have been conducted on pharmacists in other states, there is a need for similar data on pharmacy technicians.
Impact of Over-the-Counter Medication Misuse and Adverse Drug Events on HIV Patients' Health-Related Quality of Life
Authors: Sansgiry Sujit S , Ajuoga Elizabeth , Ngo Caroline , Yeh Rosa F
Published: September 2013

Background:

Over-the-counter (OTC) medication use has increased among HIV-infected patients. Inappropriate use of OTC drugs may increase the risk of potential adverse drug events (ADEs), thus decreasing health-related quality of life (HRQL).

Objective:

To examine the effect of OTC medication misuse and associated ADEs on HRQL of HIV-infected patients.

Methods:

A cross-sectional field study with HIV-infected patients from an HIV clinic in Houston, Texas, was conducted from April 1, 2005, to June 30, 2005. A validated questionnaire (including questions on OTC medications used; ADEs experienced; and HRQL, Short Form-12, version 2 scale) was administered using self-administered and personal interview techniques. Cronbach's α was estimated to evaluate internal consistency for HRQL scores and χ2 and t-test analyses were performed to evaluate the effect of OTC misuse on ADEs and on HRQL.

Results:

Of the 215 respondents, 80 (37.2%) misused OTC medications. Thirty-six participants (16.7%) experienced ADEs due to OTC use or misuse. ADE incidence was significantly higher in patients misusing OTCs. Significantly lower HRQL scores for the physical component summary score domains were observed in patients reporting ADEs versus those who did not.

Conclusions:

HIV-infected patients had lower HRQL scores when they experienced an OTC-associated ADE. Patients misusing OTC medications had a higher incidence of associated ADEs. Interventions by healthcare providers and patients aimed at reducing misuse and ADEs due to OTC medications would improve care and the quality of life for HIV-infected patients.
Use of Low-Molecular-Weight Heparin for the Treatment of Venous Thromboembolism in Patients with Cancer: A Review of the Literature
Authors: Pitlick Jamie M , Crannage Andrew J , Murphy Julie A
Published: September 2013

Objective:

To evaluate the literature on use of low-molecular-weight heparin (LMWH) for the treatment of venous thromboembolism (VTE) in patients with cancer for the first 3–6 months of anticoagulant therapy.

Data Sources:

A preliminary literature search of PubMed (1966–May 2009) was performed, using the MeSH database when possible, with the terms venous thromboembolism, venous thrombosis, pulmonary embolism, neoplasm, vitamin K antagonist, and low-molecular-weight heparin. Bibliographies of all articles retrieved were also reviewed.

Study Selection and Data Extraction:

All studies published in English with data describing the safety and/or efficacy of LMWH in subjects with cancer for the first 3–6 months of anticoagulant therapy for VTE were included.

Data Synthesis:

Five studies that met the above criteria were identified. When compared with vitamin K antagonists, LMWH therapy decreased recurrent VTE in subjects with cancer. Many of these studies had important limitations, including open-label design, relatively short duration, ineffective LMWH dosing, and small sample size.

Conclusions:

The studies analyzed support the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines' recommendation for the use of LMWH for the first 3–6 months of anticoagulant therapy for VTE in patients with cancer. Specifically, in clinical trials, tinzaparin and dalteparin have demonstrated increased efficacy compared with vitamin K antagonists.

ACPE Universal Program Number:

407-000-09-055-H01-P (Pharmacists)
From Bench to Bedside: Understanding the Science behind the Pharmacologic Management of MDMA- and other Sympathomimetic-Mediated Hyperthermia
Authors: Banks Matthew L , Sprague Jon E
Published: September 2013

Objective:

To evaluate the scientific rationale and efficacy of pharmacologic and nonpharmacologic treatments for sympathomimetic-induced hyperthermia and related sequelae.

Data Sources:

Literature was accessed through MEDLINE (1940-September 2010) using the terms MDMA [3,4-methylenedioxymethamphetamine], methamphetamine, toxicity, and hyperthermia. In addition, reference citations from identified publications were reviewed.

Study Selection and Data Extraction:

All articles written in English identified from data sources were evaluated.

Data Synthesis:

The treatment of sympathomimetic-induced hyperthermia is a challenging problem for health-care professionals. The lack of clinical trials further complicates the development of evidence-based treatment algorithms. Preclinical studies have mostly been with the sympathomimetic MDMA and have demonstrated a reversal of MDMA-induced hyperthermia with a mixed serotonin 5-HT1A agonist/5-HT2A antagonist or mixed α1- and β1,2,3-adrenergic receptor antagonists.

Conclusions:

Because of the nature by which patients are exposed to these agents, therapeutic interventions for sympathomimetic-mediated hyperthermia still lack evidence from clinical trials with human subjects. Pharmacologic treatments that should be avoided are antipyretics and the ryanodine receptor antagonist dantrolene. Promising future therapies may involve mixed 5-HT1A agonist/5-HT2A antagonists such as the atypical antipsychotic olanzapine, or mixed α1- and β1,2,3-adrenergic receptor antagonists such as carvedilol, as current preclinical research suggests.
Hypertension Secondary to Ingestion of Licorice Root Tea
Authors: Eid Tony Joseph , Morris Amanda A , Shah Sachin A
Published: September 2013

Objective:

To report a case of hypertension secondary to ingestion of licorice root tea.

Case Summary:

A 46-year-old African American female with newly diagnosed stage 1 hypertension presented with a blood pressure measurement of 144/81 mm Hg and a reduced plasma potassium level of 3.2 mEq/L. The patient attempted lifestyle modifications prior to initiating an antihypertensive agent, but at a follow-up appointment, her blood pressure remained elevated. A current laboratory panel revealed a depressed morning plasma aldosterone concentration (PAC) of 5 ng/dL and low morning plasma renin activity (PRA) of 0.13 ng/mL/h. Later it was revealed that the patient regularly (1–2 cups/day) consumed “Yogi Calming” tea, a blend of herbs, including licorice root. The patient was advised to discontinue consumption of the herbal tea, and at a subsequent appointment, her blood pressure was 128/73 mm Hg and her laboratory panel had improved, including serum potassium concentration of 4.1 mEq/L, PAC of 6 ng/dL, and PRA of 0.19 ng/mL/h.

Discussion:

Excessive consumption of licorice has been well documented to cause pseudohyperaldosteronism, characterized by hypertension, hypokalemia, and suppressed plasma renin and aldosterone levels. Glycyrrhizin, the active ingredient in licorice, inhibits 11β-hydroxysteroid dehydrogenase type 2, an oxidase responsible for the conversion and inactivation of cortisol to cortisone. Chronic ingestion of licorice-containing foods has been demonstrated to cause pseudohyperaldosteronism. These include soft candies, lozenges, and dietary supplements, but licorice-containing teas have been infrequently described. Based on the Naranjo probability score, our patient's hypertension appears to have been a probable licorice-induced reaction secondary to a licorice-containing tea.

Conclusions:

Herbal and dietary supplements are frequently consumed by patients without full knowledge of the contents of the products or the impact on their health. In clinical practice, when hypertension is accompanied by hypokalemia and reduced PRA and PAC, licorice consumption should be investigated and causal hypertension ruled out.
Eptifibatide-Induced Thrombocytopenia and Subsequent Thrombosis
Authors: Giuliano Christopher , Edwin Stephanie B , Kador Hani , Mooney Marjorie
Published: September 2013

Objective:

To report a case of thrombocytopenia and thrombosis associated with the administration of eptifibatide.

Case Summary:

We describe the case of a 63-year-old male who developed thrombocytopenia and thrombosis associated with eptifibatide administration. Eptifibatide (2 μg/kg/min, following a 180-μg/kg bolus) was administered on hospital day 5, with a baseline platelet count of 302 × 103/μL. Ten hours after eptifibatide initiation in the catheterization laboratory, the patient experienced new-onset hypotension, shortness of breath, and tachycardia. Computed tomography angiography revealed bilateral, multilobar, pulmonary emboli. Platelet count decreased to 94 × 103/μL. Eptifibatide was discontinued and lepirudin 16.5 mg/h was administered because of high suspicion of heparin-induced thrombocytopenia (HIT). The platelet count returned to 127 × 103/μL on day 7. Heparin-induced platelet aggregation assay and antiplatelet factor 4 antibodies were negative. Eptifibatide-dependent platelet-reactive antibodies were detected in the patient's serum. The patient's platelet count continued to rise until day 16, when the patient was discharged on enoxaparin and warfarin.

Discussion:

Eptifibatide-associated thrombocytopenia has been described in several case reports, but concomitant thrombosis has been reported in only 2 cases. The Naranjo probability scale suggested a probable association between eptifibatide administration and the development of thrombosis and thrombocytopenia. Our patient also developed positive eptifibatide antibodies and had a negative HIT workup. These factors, in addition to the patient's clinical presentation, suggested that eptifibatide was the most likely cause of thrombocytopenia and thrombosis.

Conclusions:

Despite the low incidence of thrombocytopenia and subsequent thrombosis with eptifibatide administration, it is imperative that patients receiving this drug have careful monitoring of their platelet count. If patients develop a profound thrombocytopenia in the setting of eptifibatide administration, we recommend evaluation for venous thromboembolism until further information is available about this adverse drug reaction.
Effects of Omeprazole on Vitamin and Mineral Absorption and Metabolism
Authors: Humphrey Melissa L , Barkhordari Nooshin , Kaakeh Yaman
Published: September 2013

Objective:

To examine the literature surrounding the effects of omeprazole on oral iron absorption and discuss the long-term use of omeprazole and its effect on vitamins C and B12, calcium, and magnesium absorption.

Data Sources:

The PubMed and MEDLINE databases were searched for reports published in English between January 1968 and August 2012, using the terms absorption, ascorbic acid, proton pump inhibitor, omeprazole, magnesium, calcium, ferrous sulfate, iron, and drug interactions.

Study Selection and Data Extraction:

Studies and reports published in English were selected for review. In some cases, reference citations from selected review articles were evaluated as well.

Data Synthesis:

Several micronutrients require an acidic environment for optimal absorption. Iron, vitamin C, and vitamin B12 absorption are dependent on the intestine's acidic environment. Several studies and case reports describe associations of omeprazole with altered calcium, magnesium, and vitamin B12 absorption. To date, there have been no prospective trials evaluating the effect of proton pump inhibitors (PPIs) on iron absorption.

Conclusions:

Existing data support the conclusion that the acid-suppressing effect of omeprazole can have important clinical implications for vitamin and mineral therapy. Clinicians should be cognizant of this issue in practice. Further studies exploring the relationship of PPIs and iron deficiency are warranted, especially in high-risk populations such as the elderly.
Numerical study of electrode geometry effects on resistance spot welding
Authors: Wei P S , Wu T H
Published: September 2013

This work numerically investigates the geometrical effects of the electrode containing a coolant hole on transport variables during resistance spot welding. The model accounts for transient magneto-fluid mechanics, heat and species transport, bulk resistance in workpiece, and film and constriction resistances at contact interfaces. The computed results show that electrode cooling due to the coolant hole influences transport processes during not only freezing and cooling periods but also heating and melting periods. Electrode cooling can be interpreted by thermal resistance, depending on the shapes of the electrode and coolant hole within the growing thermal diffusion layer. Major factors affecting electrode cooling are different in distinct time stages. In most cases, enhanced electrode cooling due to the coolant hole decreases the electrode temperature and nugget growth rate. A decrease in the electrode face radius strongly increases nugget growth rate and workpiece temperature and decreases electrode temperature, whereas its effect on cooling rate is insignificant. The optimum design and sensitivity analysis of the electrode shapes subject to required cooling rate, nugget growth rate and welding time are revealed.
On and off-target effects of telomere uncapping G-quadruplex selective ligands based on pentacyclic acridinium salts
Authors: Iachettini Sara , Stevens Malcolm FG , Frigerio Mark , Hummersone Marc G , Hutchinson Ian , Garner Thomas P , Searle Mark S , Wilson David W , Munde Manoj , Nanjunda Rupesh , D’Angelo Carmen , Zizza Pasquale , Rizzo Angela , Cingolani Chiara , De Cicco Federica , Porru Manuela , D’Incalci Maurizio , Leonetti Carlo , Biroccio Annamaria , Salvati Erica
Published: September 2013

Quadruplexes DNA are present in telomeric DNA as well as in several cancer-related gene promoters and hence affect gene expression and subsequent biological processes. The conformations of G4 provide selective recognition sites for small molecules and thus these structures have become important drug-design targets for cancer treatment.

The DNA G-quadruplex binding pentacyclic acridinium salt RHPS4 (1) has many pharmacological attributes of an ideal telomere-targeting agent but has undesirable off-target liabilities. Notably a cardiovascular effect was evident in a guinea pig model, manifested by a marked and sustained increase in QTcB interval. In accordance with this, significant interaction with the human recombinant β2 adrenergic receptor, and M1, M2 and M3 muscarinic receptors was observed, together with a high inhibition of the hERG tail current tested in a patch clamp assay.

Two related pentacyclic structures, the acetylamines (2) and (3), both show a modest interaction with β2 adrenergic receptor, and do not significatively inhibit the hERG tail current while demonstrating potent telomere on-target properties comparing closely with 1. Of the two isomers, the 2-acetyl-aminopentacycle (2) more closely mimics the overall biological profile of 1 and this information will be used to guide further synthetic efforts to identify novel variants of this chemotype, to maximize on-target and minimize off-target activities.

Consequently, the improvement of toxicological profile of these compounds could therefore lead to the obtainment of suitable molecules for clinical development offering new pharmacological strategies in cancer treatment.