bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-invasive stroke volume measurement and passive leg raising predict volume responsiveness in medical ICU patients: an observational cohort study
Authors: Thiel Steven W , Kollef Marin H , Isakow Warren
Published: July 2009

Introduction

The assessment of volume responsiveness and the decision to administer a fluid bolus is a common dilemma facing physicians caring for critically ill patients. Static markers of cardiac preload are poor predictors of volume responsiveness, and dynamic markers are often limited by the presence of spontaneous respirations or cardiac arrhythmias. Passive leg raising (PLR) represents an endogenous volume challenge that can be used to predict fluid responsiveness.

Methods

Medical intensive care unit (ICU) patients requiring volume expansion were eligible for enrollment. Non-invasive measurements of stroke volume (SV) were obtained before and during PLR using a transthoracic Doppler ultrasound device prior to volume expansion. Measurements were then repeated following volume challenge to classify patients as either volume responders or non-responders based on their hemodynamic response to volume expansion. The change in SV from baseline during PLR was then compared with the change in SV with volume expansion to determine the ability of PLR in conjunction with SV measurement to predict volume responsiveness.

Results

A total of 102 fluid challenges in 89 patients were evaluated. In 47 of the 102 fluid challenges (46.1%), SV increased by ≥15% after volume infusion (responders). A SV increase induced by PLR of ≥15% predicted volume responsiveness with a sensitivity of 81%, specificity of 93%, positive predictive value of 91% and negative predictive value of 85%.

Conclusions

Non-invasive SV measurement and PLR can predict fluid responsiveness in a broad population of medical ICU patients. Less than 50% of ICU patients given fluid boluses were volume responsive.
Betrayed Promises: Politics and Sexual Revolution in the Films of Márta Mészáros, Miloš Forman, and Dušan Makavejev
Authors: Parvulescu Constantin
Published: July 2009

Eastern Europe has been a terrain on which the twentieth century has challengingly experimented with revolutionary discourse, and cinema has been there to document these experiments. This article focuses on a constellation of Eastern European films from the 1960s and the early 1970s that interrogate sexual practices in “real-existing socialism”: Márta Mészáros's Riddance, Miloš Forman's Loves of a Blonde, and Dušan Makavejev's Love Affair, or The Case of the Missing Switchboard Operator and WR: Mysteries of the Organism. To what extent has the communist revolution also been a sexual revolution? How did it mange to reform (or fail to reform) some of the state's most enduring institutions, marriage and the family? Has the revolution betrayed its promises to radically address the “woman question”? Has it perpetuated bourgeois values? Could the subjects and regimes of Eastern Europe have survived a sexual revolution? What does sexuality tell us about the repressive politics of Eastern European revolutionary governments?
Oceans Apart
Authors: Pollard Ingrid
Published: July 2009

The Atlantic Ocean as physical and psyche space forms the basis of this work. During the last 600 years, stretches from the eastern shores in the Caribbean and the America's and the western shores and England and Europe, have been the sites of important arrivals and departures. Using the juxtapositions of various voices this work examines how the legacy of black families in the Caribbean connects with the stories of European maritime `hero's, such as Frances Drake, Christopher Columbus, Walter Raleigh and James Cook. Images of state sanctioned and educational authorities are placed alongside those preserved in family albums and the throwaway colloquialisms of letters, intimate voices that are often overlooked. Hand tinted silver prints and Xeroxes, & text.11x 24x20inch.
Reconstructing Manhood; or, The Drag of Black Masculinity
Authors: Walcott Rinaldo
Published: July 2009

The attempt to narrate and represent a coherent black masculinity in its singularity is in part what I want to respond to in this essay. But even more, I want to suggest that thinking about a range and variety of black manhoods and masculinities might provide analysts with a set of interesting refigurings of black manhood outside of its current and historical spectacularizations that offer a lens for seeing black manhood differently, and thus thinking about black manhood differently. I am interested in highlighting modes of self-fashioning that allow for a reconstruction of black manhood from the place of incoherence and femininity which might be best exemplified, or at the least typified, in recent representations of and by black trans-cultures, but not exclusive to them.
The Stranger's Work
Authors: Reid-Pharr Robert F.
Published: July 2009

The Stranger's Work reads Hazel Carby's Reconstructing Womanhood into a critical tradition that considers the awkwardness and “outsider” status of Western intellectuals, particularly those who take up the subjects of diaspora and colonization. With special emphasis on C.L.R. James' Mariners, Renegades, and Castaways, Albert Camus' The Stranger, and James Baldwin's “Stranger in the Village” Reid-Pharr argues that Carby's particular genius is her sensitivity to the ways that the works of colonial and diasporic intellectuals must by necessity grapple with their own outsider status. In particular, he suggests that these intellectuals have little choice but to operate within routes established by the very forms of oppression that they attempt to disrupt.
Autobiography Out of Empire
Authors: Lowe Lisa
Published: July 2009

In Reconstructing Womanhood, Hazel Carby showed us that reading lost histories required the deconstruction of liberal institutions and ideologies that had worked to render them illegible. My contribution takes up this dimension of Carby's work as I discuss the place of the autobiographical genre in reckoning with histories of slavery and empire, beginning with The Interesting Narrative of the Life of Olaudah Equiano, or Gustavus Vassa, the African, Written by Himself (1789), and concluding with Carby's own autobiography-in-progress, “Child of Empire: Racializing Subjects in Post World War II Britain.”
The Residue of Memory
Authors: Boddie Terry
Published: July 2009

Artist project.
AIMP2 promotes TNFα-dependent apoptosis via ubiquitin-mediated degradation of TRAF2
Authors: Choi Jin Woo , Kim Dae Gyu , Park Min Chul , Um Jung Yeon , Han Jung Min , Park Sang Gyu , Choi Eung-Chil , Kim Sunghoon
Published: July 2009

AIMP2 (aminoacyl-tRNA synthetase interacting multifunctional protein 2; also known as JTV-1) was first identified as p38 in a macromolecular protein complex that consisted of nine different aminoacyl-tRNA synthetases and two other auxiliary factors. AIMP2 also plays pivotal roles in the regulation of cell proliferation and death. Although AIMP2 was previously shown to augment TNFα-induced cell death, its working mechanism in this signal pathway was not understood. Here, we investigate the functional significance and mode of action of AIMP2 in TNFα signaling. TNFα-induced cell death was compromised in AIMP2-deficient or -suppressed cells and exogenous supplementation of AIMP2 augmented apoptotic sensitivity to TNFα signaling. This activity was confirmed by the AIMP2-dependent increase of IκB and suppression of NFκB. We found binding of AIMP2 to TRAF2, a key player in the TNFα signaling pathway. AIMP2 augmented the association of an E3 ubiquitin ligase, c-IAP1, with TRAF2, causing ubiquitin-dependent degradation of TRAF2. These findings suggest that AIMP2 can mediate the pro-apoptotic activity of TNFα via the downregulation of TRAF2 expression.
Electrochemiluminescence Devices Consisting of ZnO Nanorods Vertically Grown on Substrate
Authors: Tanaka Tomohito , Takishita Hiroshi , Sagawa Takashi , Yoshikawa Susumu , Hayase Shuzi
Published: July 2009

Unique behaviors of electrochemiluminescence from a device consisting of ZnO nanorod (Cell-1) are reported. Cell-1 emitted more intense electrochemiluminescence than cell consisting of two flat electrodes (Cell-2). The onset potential at which the emission starts was 1.5 V for Cell-1, which was lower than 2.5 V for Cell-2. The unique behaviors were explained by asymmetric collision modes of emitting species (RuI and RuIII) in the nanospace among ZnO nanorods and were characteristic to the ZnO nanorod array.
Synthesis of Hollow Nanospheres Consisting of Amphiphilic Block Copolymers
Authors: Matsune Hideki , Sakurai Daisuke , Takenaka Sakae , Kishida Masahiro
Published: July 2009

Hollow polymeric nanospheres with shells consisting of inner hydrophilic and outer hydrophobic polymer chains are prepared by a surface-initiated living radical polymerization of 2-trimethylsilyloxyethyl acrylate and methyl methacrylate from initiator-modified silica nanoparticles; these nanospheres are subsequently prepared by intraparticle cross-linking and by dissolution of silica matrices with HF. The translation behavior of hydrophilic substrates from an aqueous phase to an oil phase through the nanocapsules is investigated.
Stability of Boronic Esters to Hydrolysis: A Comparative Study
Authors: Bernardini Raffaella , Oliva Ambrogio , Paganelli Alessandro , Menta Ernesto , Grugni Mario , Munari Sergio De , Goldoni Luca
Published: July 2009

Boronic esters are key intermediates in the synthesis of biologically active compounds such as thrombin and proteasome inhibitors. However, they have low hydrolytic stability both during synthetic reactions and in biological media. We report the preparation of several boronic esters and a comparative study of their stability to hydrolysis vs. the corresponding pinanediol boronic esters, which are among the most hydrolytically stable. We discovered that the boronic esters derived from (1,1′-bicyclohexyl)-1,1′-diol are the most stable among those examined.
Epoxidized Natural Rubber Bionanocomposite: A Model Case of Bionanocomposite Using Nanofibrous Chitosan and Its Consequent Functional Properties
Authors: Lertwattanaseri Tipparat , Ichikawa Naoya , Mizoguchi Tetuo , Tanaka Yasuyuki , Chirachanchai Suwabun
Published: July 2009

A bionanocomposite of epoxidized natural rubber (ENR) with nanofibrous chitosan is proposed. The bionanocomposite is formed under the reaction between epoxy groups of ENR and amino and hydroxy groups of chitosan as confirmed by qualitative and quantitative FTIR techniques. The nanofibrous chitosan induces stiffness at nanoscale as observed by AFM and tensile strength at microscale to the ENR–chitosan nanocomposite system. The nanocomposite also shows the copper ion absorptivity as investigated by SEM metal ion mapping mode.
Surface Accumulable Coreactant for Bright Electrogenerated Chemiluminescence at Trace Level Concentrations
Authors: Kurita Ryoji , Nakamoto Kohei , Kato Dai , Niwa Osamu
Published: July 2009

We applied trimethylammonioethanethiol as an electrogenerated chemiluminescence coreactant for obtaining bright emission in a low concentration region. This is because trimethylammoniomethanethiol has the bifunctional properties of luminescence acceleration and surface accumulation on a gold electrode surface.
Continuous-Infusion β-Lactam Antibiotics During Continuous Venovenous Hemofiltration for the Treatment of Resistant Gram-Negative Bacteria
Authors: Moriyama Brad , Henning Stacey A , Neuhauser Melinda M , Danner Robert L , Walsh Thomas J
Published: July 2009

Objective:

To describe the rationale, principles, and dosage calculations for continuous-infusion β-lactam antibiotics to treat multidrug-resistant bacteria in patients undergoing continuous venovenous hemofiltration (CVVH).

Data Sources:

A MEDLINE search (1968–November 2008) of the English-language literature was performed using the terms continuous infusion and Pseudomonas or Acinetobacter, hemofiltration or CVVH or hemodiafiltration or CVVHDF or continuous renal replacement therapy or pharmacokinetics; and terms describing different β-lactam antibiotics.

Study Selection and Data Extraction:

In vitro, in vivo, and human studies were evaluated that used continuous-infusion β-lactam antibiotics to treat Pseudomonas aeruginosa and Acinetobacter baumannii infections. Studies were reviewed that described the pharmacokinetics of β-lactam antibiotics during CVVH as well as other modalities of continuous renal replacement therapy.

Data Synthesis:

Continuous infusion of β-lactam antibiotics, maintaining drug concentrations 4–5 times higher than the minimum inhibitory concentration, is a promising approach for managing infections caused by P. aeruginosa and A. baumannii. Safe yet effective continuous infusion therapy is made difficult by the occurrence of acute renal failure and the need for renal replacement therapy. Case series and pharmacokinetic properties indicate that several β-lactam antimicrobials that have been studied for continuous infusion, such as cefepime, ceftazidime, piperacillin, ticarcillin, clavulanic acid, and tazobactam, are significantly cleared by hemofiltralion. Methodology and formulas are provided that allow practitioners to calculate dosage regimens and reach target drug concentrations for continuous β-lactam antibiotic infusions during CVVH based on a literature review, pharmacokinetic principles, and our experience at the National Institutes of Health Clinical Center.

Conclusions:

Continuous infusion of β-lactam antibiotics may be a useful treatment strategy for multidrug-resistant gram-negative infections in the intensive care unit. Well-established pharmacokinetic and pharmacodynamic principles can be used to safely reach and maintain steady-state target concentrations of β-lactam antibiotics in critical illness complicated by acute renal failure requiring CVVH.
An Open-Label Study of Mirtazapine as Treatment for Combat-Related PTSD
Authors: Alderman Christopher P , Condon John T , Gilbert Andrew L
Published: July 2009

Background:

Posttraumatic stress disorder (PTSD) is common among war veterans. Antidepressants are effective in reducing symptoms and associated disability for some patients.

Objective:

To assess the effectiveness of mirtazapine for combat-related PTSD among veterans treated in an Australian hospital.

Methods:

This open-label prospective study assessed the effectiveness of mirtazapine as empirical treatment for combat-related PTSD. The initial dose was 15 mg at night, titrated against response to 15–45 mg. PTSD symptoms were assessed using the Mississippi Scale for Combat-Related Posttraumatic Stress Disorder and the Clinician-Administered PTSD Scale (CAPS). Subjects also completed the Hospital Anxiety and Depression Scale (HADS). Body weight and biochemical assessments, including fasting blood glucose (FBG), total serum cholesterol, and serum triglycerides, were also measured. Baseline measurements were repeated after 12 weeks.

Results:

During the 18-month recruitment phase, 17 subjects were enrolled and 13 completed the protocol. The CAPS measurement decreased from a mean pretreatment score of 87.5 to 64.4 (p = 0.01). In 4 cases, the CAPS score decreased to below the diagnostic cut-point, consistent with a remission of PTSD. The Mississippi scale measurement decreased from a mean pretreatment score of 126.6 to 115.5 (p < 0.01). The mean HADS anxiety score decreased from 15.6 ± 4.2 to 13.5 ± 5.6 (p = 0.016), although the proportion of subjects with scores above the diagnostic cut-point remained high. The mean HADS depression score at baseline was not significantly different from the postintervention score. One subject had a postintervention FBG of 155 mg/dL (consistent with diabetes mellitus), which was increased from the baseline level of 83 mg/dL. All subjects experienced an increase in body weight. One subject had an increase in body weight of 8.75 kg (8.4%) from baseline.

Conclusions:

Although small and with methodological limitations, this study suggests that mirtazapine is an effective treatment for combat-related PTSD. Additional research incorporating an appropriately powered, double-blind, placebo-controlled study design is required.
Medication Adherence and Its Effect on Relapse Among Patients Discharged from a Veterans Affairs Posttraumatic Stress Disorder Treatment Program
Authors: Lockwood Anna , Steinke Douglas T , Botts Sheila R
Published: July 2009

Background:

Clinical outcomes in patients with posttraumatic stress disorder (PTSD) can be affected by several factors, including medication adherence. PTSD is associated with an increased likelihood of missed appointments, medication underuse or abuse, and treatment nonadherence.

Objective:

To evaluate medication adherence and its effect on relapse following discharge of veterans from a PTSD residential rehabilitation program (PRRP).

Methods:

A retrospective evaluation of drug adherence and relapse in the 12 months following discharge of patients from a PRRP was performed. All veterans who were discharged from January 1, 2005, to December 31, 2006, and were receiving antidepressant therapy were included. Adherence to antidepressant therapy was assessed by electronic prescription claims and defined as a medication possession ratio of at least 0.8 in the year following discharge. Relapse was defined as a hospitalization for psychiatric symptomatology. Predictive factors of adherence were also explored.

Results:

Twenty-eight of the 82 (34%) veterans included in our study were adherent to medication during the 12 months following discharge. Seventeen (20.7%) veterans were re hospitalized for psychiatric symptoms, but nonadherence was not significantly associated with relapse (p = 0.91). The total number of drugs that a veteran received was related to adherence; patients who had a higher median number of medications were more adherent (p = 0.014). Age, comorbid substance abuse, combat service, and service connection were not associated with drug adherence.

Conclusions:

The majority of patients who were discharged from a residential PTSD treatment program were nonadherent to antidepressant drug therapy. One in 5 veterans with PTSD was rehospitalized within 1 year; however, medication adherence did not affect this outcome.
Safety and Clinical Outcomes when Utilizing High-Dose (≥8 mg/kg) Daptomycin Therapy
Authors: Moise Pamela A , Hershberger Ellie , Amodio-Groton Maria I , Lamp Kenneth C
Published: July 2009

Background:

Daptomycin is approved for the treatment of skin and skin-structure infections (4 mg/kg) and Staphylococcus aureus bacteremia, including right-sided endocarditis (β mg/kg). In vitro and animal studies have reported increased activity with increased daptomycin doses. There are limited clinical data on use of daptomycin at doses greater than 6 mg/kg.

Objective:

To evaluate the safety and efficacy of higher doses (≥8 mg/kg) of daptomycin when administered for a variety of gram-positive infections.

Methods:

Data were collected retrospectively as part of an ongoing registry (the Cubicin Outcomes Registry and Experience database) for the 2005–2007 program years. For the purpose of this study, the safety and efficacy of daptomycin were evaluated in patients who received doses of 8 m/kg or higher.

Results:

Ninety-four (2.6%) of 3617 patients received daptomycin doses of 6 mg/kg or higher; 18 (19%) of those patients received doses of 10 mg/kg or higher. The most common infections were bacteremia (30/94), skin and skin-structure infections (22/94), and endocarditis (15/94). The most common pathogens were Enterococcus spp. (37/94; 57% vancomycin-resistant) and S. aureus (28/94; 68% methicllin-resistant). Fifty-one percent of the patients were male. 39% were aged 66 years or older, 27% had an initial creatinine clearance less than 30 mL/min, and 17% were on dialysis. The median duration of daptomycin therapy was 15 days (minimum 1, maximum 90). Six (6.4%) of the 94 patients experienced 1 or more adverse events or abnormal laboratory value changes possibly related to daptomycin; in 2 (2.1%) of the 94 patients, daptomycin was discontinued due to treatment-related adverse events. Seventy-four (79%) patients were considered evaluable for efficacy. The overall clinical success rate was 89% (bacteremia, 91 %; skm and skin-structure infections. 88%: endocarditis. 67%)

Conclusions:

Daptomycin was well tolerated and effective at doses of 8 mg/kg or higher in patients with gram-positive infections. Further prospective and comparative studies of daptomycin at doses greater than 6 mg/kg are warranted.
Ordering Off the Menu: Assessing Compliance with a Nonformulary Medication Policy
Authors: Pummer Tara L , Shalaby Karen M , Erush Sarah C
Published: July 2009

Background:

Use of nonformulary medications (NFMs) may create added costs and potential safety issues. Institutional policies can support compliance with formulary systems and address these issues. However, periodic review is needed to assess the effectiveness of NFM policies.

Objective:

To evaluate NFM use at a large university medical center and assess for compliance with the established policy as well as for prescribing errors, procurement procedures, and delivery times.

Methods:

All new medication orders entered as NFM in the computerized order entry system during a 6-week period were evaluated and followed until administration of the first NFM dose. Orders were categorized as NFMs, formulary medications (FMs), or the patient's own medications. Each order was evaluated to determine the prescriber, service and location of the patient, and any prescribing errors. Additional information, such as the indication, location where the medication was obtained, and the delivery time, was obtained through patient chart review and the pharmacist intervention database.

Results:

A total of 237 orders were entered as nonformulary; 72 (30%) were FMs and 165(70%) were NFMs. Of the 165 NFM orders, 71 (43%) were orders for the patient's own medication. Of the remaining 94 NFMs, only 39% met the institution's established policy criteria. Overall, 28% of all orders entered as nonformulary had a prescribing error. Of these, 49% were incorrect dosages and 33% were misspelled orders. Seventy percent of NFMs were obtained from the institution's standard locations. The institution's nonformulary turnaround time was achieved with 96% of NFMs.

Conclusions:

The majority of NFM orders did not meet the institution's established criteria and these orders frequently contained prescribing errors. Routine assessment of NFM use and policy compliance can present opportunities for improvement.
Acquired Fanconi Syndrome After Treatment with Capecitabine, Irinotecan, and Bevacizumab
Authors: Shaikh Aisha , Wiisanen Matthew E , Gunderson Heidi D , Leung Nelson
Published: July 2009

Objective:

To describe a case of acquired Fanconi syndrome after treatment with capecitabine, irinotecan, and bevacizumab.

Case Summary:

A 77-year-old female with metastatic colon cancer presented with vomiting and diarrhea. The patient had been diagnosed with stage IIIC (T3, N2, M0) colon cancer 18 months earlier and was initially treated with FOLFOX6 (regimen of oxaliplatin, fluorouracil, and leucovorin) after her hemicolectomy. She was switched to a capecitabine/oxaliplatin regimen after 4 cycles due to central access problems. She did well until 10 months after her cancer diagnosis, when metastasis was discovered. She was started on reduced doses of capecitabine, irinotecan, and bevacizumab. After her eleventh cycle, she presented to the hospital with the above symptoms. Laboratory test results showed hypokalemia, hypocalcemia, hypophosphatemia, and hypouricemia. The patient had not been started on any new medications other than chemotherapy for over 1 year. The electrolyte derangements were new, since the patient had laboratory values checked every 3 weeks. Despite daily intravenous replacements, the electrolyte abnormalities persisted. Laboratory evaluations demonstrated the presence of euglycemic glucosuria and a high fractional excretion of phosphorus in the setting of hypophosphatemia. Fanconi syndrome was confirmed by demonstration of aminoaciduria.

Discussion:

Fanconi syndrome is a disorder characterized by proximal tubular dysfunction resulting in electrolyte wasting. In the acquired form, medications and multiple myeloma are the most common causes. Based on the Naranjo probability scale, a drug was the probable cause of Fanconi syndrome in our patient. However, because multiple drugs were involved, it was not possible to determine which one was the culprit.

Conclusions:

This is the first case of Fanconi syndrome reported after the administration of capecitabine, irinotecan, and bevacizumab. More studies are needed to confirm this association.
Sex Differences in Inappropriate Drug Use: a Register-Based Study of Over 600,000 Older People
Authors: Johnell Kristina , Weitoft Gunilla Ringbäck , Fastbom Johan
Published: July 2009

Background:

Several studies have observed a higher rate of inappropriate drug use in elderly women than in elderly men, although few have focused explicitly on sex differences. Also, educational level (a measure of socioeconomic status) has been associated with both polypharmacy and inappropriate drug use in the elderly population, which could explain sex differences in inappropriate drug use.

Objective:

To investigate whether sex is associated with inappropriate drug use in a large general population of older people, after adjustment for age, socioeconomic status (ie, educational level), and comorbidity (ie, number of drugs).

Methods:

We conducted an analysis of data on sex, age, dispensed drugs, and education for people aged 75–89 years who were registered in the Swedish Prescribed Drug Register between July and October 2005 (N = 645,429). The main outcome measures were the filling of prescriptions for anticholinergic drugs or long-acting benzodiazepines, concurrent use of 3 or more psychotropic drugs, and potentially serious drug–drug interactions.

Results:

Potentially inappropriate drug use was more common in women (24.6%) than in men (19.3%). More women than men were exposed to all types of inappropriate drug use, except for potentially serious drug–drug interactions. Logistic regression analysis showed that women were more likely to be exposed to potentially inappropriate drug use than were men (OR 1.24; 95% CI 1.23 to 1.26) after adjustment for age, education, and number of drugs (used as a proxy for comorbidity). In particular, female sex was highly associated with Inappropriate psychotropic use (eg, long-acting benzodiazepines: adjusted OR [ORadjusted] 1.45; 95% CI 1.42 to 1.49; >3 psychotropic drugs: QRadjusted 1.50; 95% CI 1.47 to 1.53). In contrast, women had a lower probability of potentially serious drug-drug interactions than did men (ORadjusted 0.81; 95% CI 0.80 to 0.83).

Conclusions:

Inappropriate drug use in the elderly should be monitored separately for women and men. Our results suggest that neither socioeconomic status nor comorbidity seem to explain sex differences in inappropriate drug use. Future research in other large study populations is needed for investigation of other explanations behind these sex differences.
Dapagliflozin for the Treatment of Type 2 Diabetes
Authors: Brooks Amie McCord , Thacker Stacey M
Published: July 2009

Objective:

To review the literature and describe the pharmacology, pharmacokinetics, clinical safety, and efficacy of dapagliflozin, a compound currently in Phase 3 clinical trials.

Data Sources:

A search of the literature was conducted via MEDLINE (1995–March 2009) and ClinicalTrials.gov using the search terms dapagliflozin, SGLT2 inhibitor, sodium-glucose co-transport inhibition, and renal glucose reabsorption inhibition. Bibliographies of identified articles were also used to identify useful references.

Study Selection and Data Extraction:

All English-language reports evaluating dapagliflozin were included in this review, including abstracts and scientific presentations.

Data Synthesis:

Due to the increasing prevalence of type 2 diabetes, suboptimal management of the associated hyperglycemia, morbidity and mortality associated with the disease, and the limitations of currently available therapies, novel therapeutic strategies are needed for its treatment. Dapagliflozin represents the first selective, sodium-glucose cotransporter 2 inhibitor that functions by regulating renal glucose reabsorption. Clinical trial data are limited, but available evidence supports clinically significant reductions in fasting plasma glucose, postprandial plasma glucose, hemoglobin A1c, and body weight with this agent. In addition, dapagliflozin has demonstrated excellent tolerability with safety data demonstrated in both Phase 1 and Phase 2 studies.

Conclusions:

Dapagliflozin represents the first in a new class of drugs that may represent a promising new option in the treatment of type 2 diabetes. Results of ongoing Phase 3 clinical trials are necessary to demonstrate efficacy and safety of this agent across various patient populations and clinical scenarios.
Executive, single party and ministers in Franco's regime during the war years, 193645
Authors: Mir Miguel Jerez
Published: July 2009

After noting some of the unique features of Franco's dictatorship this article analyses the institutional configuration of Franco's first government. It then addresses the relationship between General Franco and the official party, Falange Espaola y de las JONS from its creation in April 1937, and the relationship between it and the government after the creation of the first cabinet in February 1938; the internal composition, the dynamics of the council of ministers and its political priorities during the war years; and the recruitment criteria, socio-biographical profile and political careers of those who became ministers.
Political decision-making in the Portuguese New State (193339): The dictator, the council of ministers and the inner-circle
Authors: Raimundo Filipa , Ferreira Nuno Estvo , de Carvalho Rita Almeida
Published: July 2009

This article seeks to contribute to the study of political centralisation in Portugal under Salazar, focusing on the council of ministers and its decision-making role and exploring the links between the dictator and his ministers (193339). The authors discuss the centralist strategy
of the dictator based on a quantitative and qualitative study of Antnio de Oliveira Salazar's diaries: detailed accounts of his routines, audiences, meetings and even telephone calls. Our conclusions indicate Salazar perceived his cabinet more as a crisis management committee, as meetings
occurred irregularly and the agenda was considerably focused on internal and external crises and major international political events. The article also provides a more accurate notion of the main features of decision-making during the regime's institutionalisation by exploring Salazar's individual
relations with his ministers and inner circle. As Salazarism is often compared to its Iberian counterpart, Francoism, important differences between the two regimes in this domain are noted.
Fusion as the result of sperm–somatic cell interaction
Authors: Mattioli M , Gloria A , Mauro A , Gioia L , Barboni B
Published: July 2009

The research has been designed to investigate whether acrosome-reacted spermatozoa can fuse with somatic cells and to check whether this event may involve the molecular machinery implicated in the sperm–egg fusion. Boar spermatozoa were capacitatedin vitroand then treated with A23187 to induce acrosome reaction and activate their fusogenic potential. Reacted spermatozoa, loaded with the membrane-permeant fluorescent dye calcein AM, were incubated with plated granulosa cells or cells derived from stable cell lines: CRFK, VERO, and ESK4. The fusion between spermatozoa and somatic cells was revealed by the diffusion of the fluorescent dye from the sperm to the cell as membrane fusion and cytoplasmic continuity between the two cells were established. The involvement of integrin α6 and tetraspanin CD9 in the process of fusion was assessed by carrying out the experiment in the presence of antibodies against these molecules. Moreover, the incidence of fusion displayed by the different cell types used was analyzed in relation to their content in the above molecules assessed by western blot and immunostaining. The role of CD9 was additionally investigated by using CD9-negative cells. The data presented demonstrate that boar spermatozoa can fuse with different somatic cell types derived from different species and the process requires the combined presence of both integrin and tetraspanin molecules on the cell plasma membrane.
Discrimination between Bacteroides, Dichelobacter, Fusobacterium, Porphyromonas and Prevotella isolated from caprine footrot by PCR-RFLP — Short communication
Authors: Lacombe-Antoneli Ángela , Píriz Segundo , Quesada Alberto , Vadillo Santiago
Published: July 2009

Footrot is widely considered the most severe and most common foot pathology in small ruminants. This study tested the ability of a molecular typing system based on polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay of the 16S rRNA gene to discriminate between the strict anaerobe genera most commonly isolated from footrot (Bacteroides, Dichelobacter, Fusobacterium, PorphyromonasandPrevotella) in goats in Extremadura (Spain), with a view to facilitating identification for diagnostic purposes and thus providing a useful tool for future epidemiological studies. Although the electrophoretic patterns obtained with the enzymeTru1I were more readily interpreted, and may thus be the best initial option, results may be confirmed by a second enzyme (RsaI). The PCR-RFLP assay of the 16S rRNA gene may therefore prove a useful addition to conventional biochemical identification techniques, providing taxonomic information at genus level.
Effects of melatonin treatment on follicular development and oocyte quality in Chios ewes — Short communication
Authors: Tsiligianni Theodora , Valasi Irene , Cseh Sándor , Vainas Emmanuel , Faigl Vera , Samartzi Fotini , Papanikolaou Thomas , Dovolou Eleni , Amiridis Georgios
Published: July 2009

Follicular development and oocyte quality were assessed by laparoscopic observation and
in vitro
fertilisation, respectively, in melatonin-treated (Group M) and control (Group C) anoestrous Chios ewes (n = 10 in each group). Fourteen days after melatonin insertion, all ewes had laparoscopic evaluation of the follicular population followed by oocyte pick-up (OPU); on day 22 intravaginal progestagen sponges were inserted for 14 days. Two days after sponge removal the follicular population was re-evaluated and a second follicular aspiration was performed. Collected oocytes from the second OPU underwent
in vitro
maturation, fertilisation and culture. The number of large follicles was higher in Group M than in the control ewes during the first OPU and tended to be so (P = 0.06) at the second. Morphologically, oocytes collected from controls were of better quality than those from Group M; however, more oocytes collected from melatonintreated animals fertilised and developed
in vitro
. These results indicate that melatonin is a potent regulator of follicular development and oocyte competence during the anoestrous period of the ewe.
Papillomavirus-associated fibropapillomas of red deer ( Cervus elaphus )
Authors: Erdélyi Károly , Gál János , Sugár László , Ursu Krisztina , Forgách Petra , Szeredi Levente , Steineck Theodora
Published: July 2009

Oval, firm, cutaneous tumours with a rough, hairless, pigmented surface, exhibiting a moderately pronounced papillary structure were detected on the abdominal skin of two young red deer (Cervus elaphus). One animal was shot in Lower Austria in 2004, the other at a deer farm in Hungary in 2007. Histological examination of both samples classified the tumours as fibropapillomas, showing marked proliferation of fibroblasts and connective tissue, accompanied by hyperkeratosis, parakeratosis and acanthosis of the overlaying epidermis, and occasional foci of inflammation. The distribution of cytokeratin and vimentin was characterised in the lesion. The presence of papillomavirus (PV) antigen was demonstrated by immunohistochemistry in both cases. Papillomavirus-specific DNA was successfully amplified by PCR from one sample. The obtained partial nucleotide sequence of the L2 ORF exhibited the highest critical identity values with the homologous regions of Delta-papillomaviruses, especially the Roe deer papillomavirus (93%). Phylogenetic analysis of the partial L2 ORF sequence alignment of 10 papillomaviruses by both neighbour-joining and maximum parsimony method confirmed that the Red deer PV is very closely related to the Western roe deer papillomavirus (CcPV1).
Two-dimensional echocardiographic measurements of the left atrium in dogs with cardiac disease
Authors: Dudás-Györki Zoltán , Bende Boglárka , Hetyey Csaba , Manczur Ferenc , Reiczigel Jenő , Vörös Károly
Published: July 2009

The aim of the present study was to verify the validity of two-dimensional echocardiographic (2DE) measurement technique in dogs with left atrial enlargement. Thirty-one dogs with clinically and echocardiographically proven cardiac diseases were randomly selected. The left atrial right-to-left diameter (
Lar−l
) and the diameter of the left atrium just above the mitral annulus (
Laama
) as well as the ratio of left atrial to aortic diameter (
La/Ao
) were measured by 2DE. The
Lar−l
/
Laama
ratio was independent of body weight (R
2
= 0.0006) and age (R
2
= 0.0012), respectively. A significant linear relationship was found between
Laama
and
La/Ao
(the ratio that expresses the severity of atrial enlargement):
Laama
=
1.2238 La/Ao + 1.1608
(R
2
= 021; P < 0.01). There was also a positive linear relationship between
Lar−l
and
La/Ao
:
Lar−l
=
1.6876 La/Ao + 1.2648
(R
2
= 0.27; P < 0.005). In our dogs with cardiac disease, the
Lar−l
/
Laama
ratio showed no significant relation to the
La/Ao
index (R
2
= 0.028). Thus,
Lar−l
/
Laama
proved to be independent of the severity of atrial enlargement. Based on the strong relationship stated in the equation between
Laama
and
Lar−l
[
Lar−l
/
Laama
=
1.31159
(95% confidence interval)],
Laama
can also be used for the assessment of left atrial size even in dogs with cardiac disease.
M-mode and two-dimensional echocardiographic reference values for three Hungarian dog breeds: Hungarian Vizsla, Mudi and Hungarian Greyhound
Authors: Vörös Károly , Hetyey Csaba , Reiczigel Jenő , Czirok Gábor
Published: July 2009

The aim of the study was to establish normal reference echocardiographic values for three Hungarian dog breeds, and to determine the potential dependence of intracardiac parameters on body weight, age and gender. M-mode and two-dimensional echocardiography were performed on 95 clinically healthy dogs including 45 Hungarian Vizslas, 28 Mudis and 22 Hungarian Greyhounds. Linear intracardiac measurements included interventricular septal thickness (IVS), left ventricular internal diameter (LVID), left ventricular posterior wall thickness (LVPW) both in systole and diastole, as well as left atrial internal diameter (LAD), and aortic diameter (AOD) in early diastole. Fractional shortening (FS), end-diastolic and end-systolic left ventricular volumes (EDV and ESV), as well as LAD:AOD ratio were calculated from the linear parameters. Mean, range and standard deviation of measurements were calculated for each breed. Body weight positively correlated in all three breeds with all left ventricular dimensions, such as IVSd, IVSs, LVIDd, LVIDDs, LVPWdand LVPWsparameters. LA values showed positive correlations to body weight in all three breeds. AOD and LA demonstrated a positive correlation with body weight in Hungarian Vizslas and Mudis, whilst the LAD:AOD ratio was related to body weight only in Mudis. Gender did not correlate with any of the measured echocardiographic parameters in any breeds. In Mudis, a positive correlation was found between the LAD:AOD ratio and age, as well as between the LAD:AOD ratio and E point to septal separation (EPSS).
Effect of citric acid on electrocardiographic parameters of broiler chickens with pulmonary hypertension
Authors: Hassanpour Hossein , Moghaddam Abdol , Zarei Hamed
Published: July 2009

To clarify the effect of orally administered citric acid on the electrocardiographic parameters of pulmonary hypertensive broilers, chicks were reared at high altitude and treated with citric acid for 45 days. Increase of cardiac indices such as right ventricle/total ventricles (RV/TV), RV/body weight and TV/body weight ratio was not observed in the treated groups as compared to the control groups. Decrease of S amplitude in the treated groups (leads II, III, aVF) was only significant (P < 0.05) at 45 days of age (leads II, aVF; 1.5 g/l of citric acid). There were significant reductions of T amplitude at 28 (lead aVR) and 36 days (lead aVL) and significant reductions of R wave at 28 (lead aVL, all doses of citric acid) and 45 days of age (lead aVR, 1 and 1.5 g/l citric acid) in the treated groups. The QRS interval was significantly higher at 28 (leads III and aVF), 36 (leads II, III and aVF, 1 g/l citric acid) and 45 days of age (leads II and aVF) in the treated groups. The QT interval was significantly (P < 0.05) increased at 28 and 45 days of age (lead aVL) and the RR interval also showed an increase at 28 (leads aVR and aVL) and 45 (lead aVL) days of age as compared to the controls. Our data indicate that citric acid modulates the induction of pulmonary hypertension at high altitude and this effect is detectable in the electrocardiographic parameters.
Pathological changes induced by rancid feed in rats and effects on growth and protein utilisation
Authors: Fekete Sándor , Andrásofszky Emese , Glávits Róbert
Published: July 2009

The objective of this trial was to study the effect of rancid feeds on the health status and growth of rats and to determine the pathological changes induced by dietary rancidity. Forty-two weaned male rats (body weight: 69.3 ± 1.0 g) were divided into seven experimental groups (n = 6 each). Rats in the different groups were fed diets containing meat-and-bone meal at an inclusion rate of 19 to 22%, low or high in peroxides and high in organic acids, with or without antioxidant. The diets were isoproteic (10%) and isolipidic (6%). During the 26-day-long trial (5 days for adjustment and 21 days for the main period) the body weight gain and the feed consumption were recorded. At the end of the trial detailed gross and histopathological examinations were performed. Feeding high-peroxide feed mixtures for 21 days significantly (P < 0.05) decreased feed intake and liveweight gain, while high organic acid concentration had only slight negative effects. Antioxidant supplementation alleviated the harmful effects, especially in the high-peroxide group. The ingestion of rancid feed mixtures and the subsequent decreased feed intake caused a decrease of glycogen content in the hepatocytes, accompanied by a slight centrolobular fatty infiltration. Peroxides caused lymphocyte depletion in the spleen, decreased the size of Malpighian bodies and the number of lymphoblasts, and altered the spermatogenesis. The protective effect of the antioxidant mixture seemed to be negligible in this respect.
Harderian gland adenocarcinoma in a Florida Red-bellied Turtle ( Pseudemys Nelsoni ) — Case report
Authors: Gál János , Demeter Zoltán , Palade Elena , Rusvai Miklós , Géczy Csaba
Published: July 2009

The authors describe a case of unilateral adenocarcinoma emerging from the Harderian gland, filling the right orbital cavity of a Florida Red-bellied Turtle (
Pseudemys nelsoni
). The tumour did not produce any metastasis but presented an expansive growth and led to the dislocation and protrusion of the right eyeball. Histopathological analysis revealed the presence of numerous mitotic figures in the cellular population that made up the tumour. The tumour cells completely filled the alveoli of the gland and had a nest-like structure. The authors also emphasise the importance of the differential diagnosis of this rare pathological change in turtles. Epithelial hyperplasia of the Harderian gland’s duct, observed in animals suffering from vitamin A deficiency, can also lead to an enlargement of the eyelid, but in these cases the change usually involves both eyelids symmetrically. This is the first description of a Harderian gland adenocarcinoma in a Florida Red-bellied Turtle.
Late Ordovician geographic patterns of extinction compared with simulations of astrophysical ionizing radiation damage
Authors: Melott Adrian L. , Thomas Brian C.
Published: July 2009

Terrestrial mass extinctions have been attributed to a wide range of causes. Some of them are external to Earth, such as bolide impacts (as widely discussed for the K/T boundary) and radiation events. Among radiation events, there are possible large solar flares, nearby supernovae, gamma-ray bursts (GRBs), and others. These have variable intensity, duration, and probability of occurrence, although some generalizations are possible in understanding their effects (Ejzak et al. 2007). Here we focus on gamma-ray bursts (Thorsett 1995; Scalo and Wheeler 2002), a proposed causal agent for the end-Ordovician extinction. These are the most remote and infrequent of events, but by virtue of their power, a threat approximately competitive with, for example, that of nearby supernovae. A GRB of the most powerful type (Woosley and Bloom 2006) is thought to result from a supernova at the end of stellar evolution for very massive stars with high rotational speed. Much of their energy is channeled into beams, or jets, which include very high energy electromagnetic energy, i.e., gamma-rays and X-rays. It is a testament to the power of these events, far across the observable universe, that they were first detected in the 1969–1970 results from monitoring satellites designed to detect nuclear explosions on Earth's surface. It was not until the 1990s, when the distance to the events became known, that their power became apparent. Several such events occur every day in the observable universe. Other kinds of events are also potentially damaging, such as so-called short bursts and solar flares, but rate information is only now beginning to clarify how much threat is likely from such sources.