bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular characterization of M2 and M3 muscarinic receptor expression in bladder from women with refractory idiopathic detrusor overactivity
Authors: Mansfield Kylie J. , Liu Lu , Moore Kate H. , Vaux Kenneth J. , Millard Richard J. , Burcher Elizabeth
Published: April 2007

In a study from Sydney, authors present data on the expression of M2 and M3 receptors in human detrusor and bladder mucosa, comparing patients with idiopathic detrusor overactivity with controls. It was found that M3 muscarinic receptor RNA expression was reduced in mucosa from patients with detrusor overactivity, leading to a proposal that mucosal M3 receptors might have an important role in the aetiology of this condition.

OBJECTIVE

To examine the expression of muscarinic M2 and M3 receptors in human bladder detrusor and mucosa, from controls and patients with idiopathic detrusor overactivity (IDO), as antimuscarinic agents are the primary pharmacological treatment for IDO.

PATIENTS AND METHODS

Biopsies from the bladder body were collected at cystoscopy from 20 women with urodynamically confirmed refractory IDO (age range 25–86 years); biopsies were also collected from 30 asymptomatic female controls (age range 32–87 years). Samples were collected into RNA extraction medium and dissected into mucosa (urothelium plus lamina propria) and detrusor. RNA was extracted and the expression of M2 and M3 receptor mRNA determined by quantitative competitive reverse transcription‐polymerase chain reaction. Results were normalized to β‐actin expression in the same sample.

RESULTS

Expression of M3 receptor mRNA, in mucosa of IDO patients (median 0.057 pg M3/100 ng total RNA; interquartile range 0.03–0.13, 12 samples), was four times (P = 0.039, Mann–Whitney) lower than from the control (median 0.22 pg M3/100 ng total RNA; 0.13–0.51, 11 samples). The expression of muscarinic M3 receptor mRNA was higher (14–35 times) in detrusor (control median 3.17; 26 samples) than in mucosa and did not change in IDO (median 2.03; 14 samples). M2 expression was not significantly different with region or with IDO.

CONCLUSIONS

These data show that M3 muscarinic receptor mRNA expression was significantly less in mucosa from IDO patients than from age‐matched controls. The role of mucosal M3 receptors is unknown at present and elucidation of this role might provide a greater understanding of the aetiology of IDO.
Antiviral activity of low‐dose alovudine in antiretroviral‐experienced patients: results from a 4‐week randomized, double‐blind, placebo‐controlled dose‐ranging trial*
Authors: Ghosn J , Quinson A‐M , Sabo ND , Cotte L , Piketty C , Dorléacq N , Bravo M‐L , Mayers D , Harmenberg J , Mårdh G , Valdez H , Katlama C
Published: April 2007

Background

Alovudine inhibits replication of highly nucleoside reverse transcriptase inhibitor (NRTI)‐resistant HIV strains in vitro. However, dose‐dependent safety concerns resulted in its initial development being halted. Recently, a 4‐week course of alovudine 7.5 mg/day added to a stavudine‐free failing regimen yielded a significant decrease in viral load by −1.88 log10 HIV‐1 RNA copies/mL. The magnitude of the reduction in viral load suggested that lower doses might still be effective while offering adequate safety during long‐term use.

Objective

To determine whether lower dosages of alovudine still provide significant antiviral activity in patients with broad NRTI resistance.

Methods

A randomized, double‐blind, placebo‐controlled trial investigating three doses of alovudine (0.5, 1 and 2 mg) or placebo added for 4 weeks to a failing regimen in patients with evidence of NRTI‐resistant HIV strains [≥2 thymidine‐associated mutations (TAMs)]. The primary endpoint was the mean viral load reduction between baseline and week 4.

Results
Seventy‐two patients were enrolled in the study: 21, 13, 18 and 20 in the placebo and 0.5, 1 and 2 mg arms, respectively. Baseline median CD4 count and viral load were 298 cells/μL (range 44–692 cells/μL) and 3.9 log10 copies/mL (range 2.5–5.2 log10 copies/mL), respectively. Baseline viral isolates harboured a median of four TAMs. Alovudine was added to a median four‐drug failing regimen. At week 4, compared with placebo, mean viral load changes were −0.42 log10 [95% confidence interval (CI) −0.67 to −0.18] and −0.30 log10 (−0.55 to −0.06) in the 2 and 1 mg arms, respectively. There was no significant change in CD4 cell count. Alovudine was well tolerated.

Conclusion:

A 4‐week course of alovudine 2 mg/day provided a modest but significant viral load reduction in patients harbouring viruses with a median of four TAMs.
Long‐term evolution of CD4 count in patients with a plasma HIV RNA persistently <500 copies/mL during treatment with antiretroviral drugs
Authors: Le Moing V , Thiébaut R , Chêne G , Sobel A , Massip P , Collin F , Meyohas MC , Al Kaïed F , Leport C , Raffi F ,   the ANRS CO8 (APROCO/COPILOTE) Study Group
Published: April 2007

Background

The increase in CD4 count may reach a plateau after some duration of virological response to highly active antiretroviral therapy (HAART).

Methods

A total of 1281 HIV‐infected patients initiating HAART were enrolled in the AntiPROtease (APROCO) cohort. We investigated determinants of increase in CD4 count using longitudinal mixed models in patients who maintained a plasma HIV RNA <500 HIV‐1 RNA copies/mL.

Results

A total of 870 patients had a virological response at month 4. The median follow‐up time was 57 months. Mean estimated increases in CD4 count in patients with persistent virological response were 29.9 cells/μL/month before month 4, 6.4 cells/μL/month between months 4 and 36, and 0.7 cells/μL/month (not significantly different from 0) after month 36. Three factors were associated with a significantly positive CD4 count slope after month 36: male gender (+0.9), no history of antiretroviral therapy at baseline (+1.7) and baseline CD4 count <100 cells/μL (+2.6). In patients who maintained a virological response after 5 years of HAART, a CD4 count >500 cells/μL was achieved in 83% of those with a baseline CD4 count ≥200 cells/μL and in 45% of those with a baseline CD4 count <200 cells/μL.

Conclusion

The increase in CD4 count reaches a plateau after 3 years of virological response. Even if patients initiating HAART with low CD4 counts still show a CD4 count increase after 3 years, it remains insufficient to overcome immune deficiency in all patients.
Combination antiretroviral therapy without a nucleoside reverse transcriptase inhibitor: experience from 334 patients in three cohorts
Authors: Calmy A , Petoumenos K , Lewden C , Law M , Bocquentin F , Hesse K , Cooper D , Carr A , Bonnet F ,   for the Aquitaine Cohort, Australian HIV Observational Database and St Vincent's Hospital Cohort study groups
Published: April 2007

Background

Toxicity and resistance may limit the use of HIV nucleoside reverse transcriptase inhibitors (NRTIs). We assessed the safety and activity of regimens that did not include an NRTI.

Method and patients
We analysed NRTI‐sparing regimens using pooled data from three cohorts in Australia and France where HIV RNA viral load, CD4 lymphocyte count and metabolic parameters are assessed prospectively. The inclusion criterion was the commencement of any antiretroviral combination excluding NRTIs.

Results

A total of 334 (3.9%) of 8477 patients were included in the present study for a median follow‐up time of 105 weeks. Therapeutic combinations were one nonnucleoside reverse transcriptase inhibitor (NNRTI) plus one protease inhibitor (PI) (58%), two PIs (26%), one PI (16%), and one NNRTI plus two PIs (8%). At baseline, the median CD4 lymphocyte count was 264 cells/μL (interquartile range 164–446 cells/μL) and 25% of patients had plasma HIV RNA below 500 HIV‐1 RNA copies/mL. In intent‐to‐treat analysis, 64% of patients had HIV RNA <500 copies/mL at 6 months and 68% at 24 months. The mean CD4 lymphocyte count increase was 60 cells/μL (95% confidence interval 41–76 cells/μL) at 6 months and 111 cells/μL (95% confidence interval 82–140 cells/μL) at 24 months. Prognostic factors for having HIV RNA <500 copies/mL at 6 months included independently having undetectable HIV RNA at baseline and being naïve for NNRTIs. The proportion of patients with triglycerides >2.3 mmol/L increased from 32% to 63% at 6 months and to 62% at 24 months (P‐trend=0.002), and those with total cholesterol >6.2 mmol/L increased from 18% to 38% at 6 months and to 44% at 24 months (P‐trend <0.001), with an increased risk for patients treated with NNRTI+PIs. Forty‐one per cent of patients discontinued their NRTI‐sparing regimen.

Conclusion

In these antiretroviral‐experienced patients, NRTI‐sparing therapy appeared to have satisfactory virological and immunological efficacy. However, hyperlipidaemia was frequent and requires monitoring of cardiovascular risk factors.
Improved virological response to highly active antiretroviral therapy in HIV‐1‐infected patients carrying the CCR5 Δ32 deletion
Authors: Laurichesse JJ , Persoz A , Theodorou I , Rouzioux C , Delfraissy JF , Meyer L
Published: April 2007

Background

Patients heterozygous for the C‐C chemokine receptor 5 (CCR5) Δ32 deletion spontaneously progress less rapidly to AIDS and death than do wild‐type patients. We investigated whether the CCR5 Δ32 deletion has an impact on immunological, virological and clinical responses to highly active antiretroviral therapy (HAART) in HIV‐1‐infected patients.

Patients and methods

We included in the study 565 HIV‐1‐infected patients from the French HIV‐1 infected cohort with documented date of serconversion (SEROCO)/haemophiliacs HIV‐1 infected (HEMOCO) cohorts, who started HAART after 1996. We investigated virological responses to HAART at 6 months (defined as a plasma HIV‐1 RNA measurement below the threshold of detection or a 2 log HIV‐1 RNA decrease) and at 12 months (defined as a plasma HIV‐1 RNA measurement below the threshold of detection) and clinical response to HAART by Kaplan–Meier survival curves, with AIDS and death as outcomes.

Results

The Δ32 heterozygous patients (n=83; 15%) had a better virological response to HAART than wild‐type patients (73 vs 53% at 6 months, P=0.01; and 60 vs 44% at 12 months, P=0.01). This better virological response was still observed after adjustment for antiretroviral status (whether or not patients were naïve to antiretroviral therapy), year of HAART initiation, number of new antiretroviral drugs and baseline viral load. There was no statistical difference between heterozygous patients and wild‐type patients in terms of survival and AIDS‐free survival.

Conclusions

CCR5 Δ32 heterozygous patients were more likely to have a virological response to HAART than wild‐type patients at 6 and 12 months. However, this virological response did not produce better immunological and clinical responses. The long‐term impact of the Δ32 deletion on survival in HIV‐1‐infected treated patients should be investigated in a meta‐analysis.
Concomitant use of gastric acid‐reducing agents is frequent among HIV‐1‐infected patients receiving protease inhibitor‐based highly active antiretroviral therapy*
Authors: Van Lunzen J , Liess H , Arastéh K , Walli R , Daut B , Schürmann D
Published: April 2007

Objective

The aim of the study was to assess the frequency of the concurrent use of gastric acid‐reducing agents among HIV‐1‐infected patients treated with highly active antiretroviral therapy (HAART) combinations.

Methods

An anonymous, semistructured, self‐administered questionnaire was consecutively distributed among HIV‐1‐infected patients at routine visits to specialized HIV clinics. The questionnaire contained 17 items asking specifically for information on current antiretroviral treatments and the use of gastric acid‐reducing agents as well as demographic data.

Results

A total of 424 patients in 12 centres participated in the study: 85% were male, 88% were of German nationality, 82% were >35 years of age and 201 (47.4%) were receiving a protease inhibitor (PI)‐containing HAART regimen. Of these, 74 (37%) had received an acid‐reducing drug within the previous 6 months and 43 (58%) were currently still on it. Two‐thirds of patients (64.9%) were treated with proton‐pump inhibitors (pantoprazole, omeprazole or esomeprazole) and 56% of patients on PI‐containing regimens had been taking these drugs for longer than 2 months and up to a maximum of 3 years. The majority of patients (77%) had received the prescription for the acid‐reducing drugs from their HIV specialist and the remaining patients had received over the counter (OTC) medication or prescriptions from other medical personnel.

Conclusions

A substantial subset of patients treated with HAART combinations, including those on PI‐containing regimens, were using concomitant acid‐reducing drugs, most often proton‐pump inhibitors. As negative drug–drug interactions between some of the (boosted) PIs and gastric acid‐reducing agents have recently been reported, HIV physicians should take this into account when prescribing PI‐containing HAART combinations in order to avoid an additional risk of treatment failure.
Relative antiviral efficacy of ritonavir‐boosted darunavir and ritonavir‐boosted tipranavir vs. control protease inhibitor in the POWER and RESIST trials
Authors: Hill A , Moyle G
Published: April 2007

Objective

To compare the relative antiviral efficacy of TMC114 with low‐dose ritonavir (TMC114/r) and tipranavir with low‐dose ritonavir (TPV/r) vs. control protease inhibitor (CPI) in treatment‐experienced patients, using data from the POWER 1/2 and RESIST 1/2 trials. These trials recruited antiretroviral‐experienced patients with HIV RNA > 1000 HIV‐1 RNA copies/mL and at least one primary PI mutation, and used optimized nucleoside reverse transcriptase inhibitors with or without enfuvirtide, plus investigator‐selected CPI in the control arms.

Methods

For the POWER trials, data from the 600/100 mg twice a day (bid) dose and CPI arms (n=201) were included, while all data from the RESIST trials (TPV/r 500/200 mg bid and CPI; n=1159) were included. The difference in week 24 efficacy (intent to treat) for the new PI vs. CPI was compared between the trials.

Results

Overall baseline characteristics were well matched across the trials. At week 24, 72% of TMC114/r patients achieved a ≥1 log10 copies/mL reduction in HIV RNA compared with 40% of TPV/r patients (for CPI patients, this percentage was 21 and 18%, respectively, in the POWER and RESIST trials). The treatment benefit of TMC114/r over CPI in the POWER trials was greater (outside the 95% confidence intervals) than the benefit of TPV/r over CPI in the RESIST trials, for the 24‐week HIV RNA endpoints of 1 log10 copies/mL reduction, <400 copies/mL and <50 copies/mL, and also for the mean rise in CD4 count. In sensitivity analysis, this difference in efficacy was strongest for those who did not also use enfuvirtide.

Conclusions

Given the caveats of this type of analysis (for example, possible differences in trial conduct, and undetected differences in baseline resistance profiles), the efficacy benefits of TMC114/r vs. CPI in the POWER trials appear to be greater than the benefits of TPV/r vs. CPI in the RESIST trials, for patients who did not also use enfuvirtide.
Hybrid finite element–finite volume discretization of complex geologic structures and a new simulation workflow demonstrated on fractured rocks
Authors: PALUSZNY A. , MATTHÄI S. K. , HOHMEYER M.
Published: April 2007

The generation of computational meshes of complex geological objects is a challenge: their shape needs to be retained, resolution has to adapt to local detail, and variations of material properties in the objects have to be represented. Also mesh refinement and adaptation must be sufficient to resolve variations in the computed variable(s). Here, we present an unstructured hybrid finite element, node‐centred finite‐volume discretization suitable for solving fluid flow, reactive transport, and mechanical partial differential equations on a complex geometry with inhomogeneous material domains. We show that resulting meshes accurately capture free‐form material interfaces as defined by non‐uniform rational B‐spline curves and surfaces. The mesh discretization error is analysed for the elliptic pressure equation and an error metric is introduced to guide mesh refinement. Finite elements and finite volumes are represented in parametric space and integrations are conducted numerically. Subsequently, integral properties are mapped to physical space using Jacobian transformations. This method even retains its validity when the mesh is deformed. The resulting generic formulation is demonstrated for a transport calculation performed on a complex discrete fracture model.
Predicting occurrence of wolf territories in Scandinavia
Authors: Karlsson J. , Brøseth H. , Sand H. , Andrén H.
Published: April 2007

We used logistic regression to compare a set of habitat features inside known Scandinavian wolf Canis lupus territories with the same habitat features in areas outside known territories, but still close enough to be available for wolf colonization. In addition, we analysed changes in habitat variables over time within wolf territories. Wolf territories had lower densities of roads, built‐up areas and open land than areas outside wolf territories, but there was no difference in the density of the wolves' main prey, elk Alces alces. The logistic regression model classified 79% of Scandinavia outside the reindeer husbandry area as suitable wolf habitat, that is with a probability of wolf occurrence >0.5. The proportion of built‐up areas within the wolf territory decreased as the ‘borders’ of the wolf territory changed over time. Our model had a reasonably high predictive power, with correct classification in 90% (18 of 20) of the observed wolf territories in the study area. Polygons, randomly distributed outside the observed wolf territories, were correctly classified as not being occupied by wolves in 85% of the cases (17 of 20). This allows a more effective use of resources to, for example, prevent wolf depredation on livestock and dogs.
Cell number and cellular composition in vermiform larvae of dicyemid mesozoans
Authors: Furuya H. , Hochberg F. G. , Tsuneki K.
Published: April 2007

Cell numbers and cellular composition were examined in vermiform larvae of 44 species of dicyemid mesozoans phylum Dicyemida belonging to six genera: Conocyema, Dicyema, Dicyemennea, Dicyemodeca, Microcyema and Pseudicyema. In addition, the literature on vermiform larvae of another 59 species was reviewed. Vermiform larvae typically have a constant number of peripheral cells that are species specific. Interspecific variations in the total number of peripheral cells range from 10 to 39. The most frequent number is either 22 or 23. Differences in the total number of peripheral cells are mostly due to differences in the number of trunk peripheral cells, such as parapolar cells, diapolar cells and uropolar cells. The body length of vermiform larvae is positively correlated with the number of trunk peripheral cells. Interspecific variations in the total number of trunk peripheral cells range from 2 to 31. The most frequent number is 14. In species with 14 trunk peripheral cells, individual variations of cell numbers were minimal. In species with more trunk peripheral cells, some individual variations appeared. Increase and decrease of trunk cell number might cause diversity of dicyemids, which is possibly related to speciation in these simple multicellular animals.
Behavioural examination of the infrared sensitivity of ball pythons
Authors: Ebert J. , Müller S. , Westhoff G.
Published: April 2007

The ability to detect infrared (IR) radiation is a characteristic trait in boids and pitvipers. These snakes possess highly sensitive IR receptors, which enable them to perceive IR sources and assess their direction and distance independently of visual cues. Electrophysiological studies have been conducted to determine IR detection thresholds in boids and pitvipers. This, however, is the first behavioural study that focuses on the detection threshold of a boid snake to IR stimuli. Blindfolded ball pythons Python regius were exposed to a moving IR stimulus of constant size and temperature at various distances (10–100 cm). Distinct behavioural changes during stimulus presentation (S‐form posture, freeze and fix, follow and fix) allowed quantification of the behavioural responses. The threshold to elicit behavioural responses was used to assess the IR detection threshold. The results revealed that P. regius can detect a moving IR stimulus resembling a mouse in temperature and size up to a distance of 30 cm, which corresponds to an irradiance contrast of 38.83 × 10−6 W cm−2. This irradiance contrast detection threshold value is about one‐third lower (reveals a 1.5 times higher sensitivity) than the results from earlier electrophysiological studies.
Specificity of regional brain activity in anxiety types during emotion processing
Authors: Engels Anna S. , Heller Wendy , Mohanty Aprajita , Herrington John D. , Banich Marie T. , Webb Andrew G. , Miller Gregory A.
Published: April 2007

The present study tested the hypothesis that anxious apprehension involves more left‐ than right‐hemisphere activity and that anxious arousal is associated with the opposite pattern. Behavioral and fMRI responses to threat stimuli in an emotional Stroop task were examined in nonpatient groups reporting anxious apprehension, anxious arousal, or neither. Reaction times were longer for negative than for neutral words. As predicted, brain activation distinguished anxious groups in a left inferior frontal region associated with speech production and in a right‐hemisphere inferior temporal area. Addressing a second hypothesis about left‐frontal involvement in emotion, distinct left frontal regions were associated with anxious apprehension versus processing of positive information. Results support the proposed distinction between the two types of anxiety and resolve an inconsistency about the role of left‐frontal activation in emotion and psychopathology.
Erythropoietic Protoporphyria (Erythrohepatic Protoporphyria)
Authors: Susan C. Kelly , Stephen M. Purcell , Thomas D. Griffin
Published: April 2007

Abstract:  An 8‐year‐old Caucasian girl had recurrent swelling, itching, burning, and painful sensations in her face and hands since 12 months of age. This reaction occurred after sunlight exposure and to a lesser extent with heat and wind. On physical examination the patient demonstrated mild focal thickening of the skin of the nose and upper lip and dorsa of the hands and toes. Laboratory studies were notable for a high free erythrocyte protoporphyrin level, which is diagnostic for erythropoietic protoporphyria (Erythropoietic Protoporphyria Research and Educational Fund. Available at http://www.brighamandwomens.org/eppref/patient/eppinfo.aspx.). Erythropoietic protoporphyria is a rare genetic disorder of porphyrin metabolism caused by impaired activity of ferrochelatase. The mainstay of therapy is photosensitivity reduction through the use of reflectant sunscreens and beta‐carotene administration.
Familial Uncombable Hair Syndrome: Ultrastructural Hair Study and Response to Biotin
Authors: Boccaletti V. , Zendri E. , Giordano G. , Gnetti L. , De Panfilis G.
Published: April 2007

Abstract:  We report a family affected to the fourth generation by uncombable hair syndrome. This syndrome is characterized by unruly, dry, blond hair with a tangled appearance. The family pedigree strongly supports the hypothesis of autosomal dominant inheritance; some members of the family had, apart from uncombable hair, minor signs of atopy and ectodermal dysplasia, such as abnormalities of the nails. The diagnosis was confirmed by means of extensive scanning electron microscopy. A trial with oral biotin 5 mg/day was started on two young patients with excellent results as regards the hair appearance, although scanning electron microscopy did not show structural changes in the hair. After a 2‐year‐period of follow‐up, hair normality was maintained without biotin, while nail fragility still required biotin supplementation for control.
Prostanoids induce egr1 gene expression in cementoblastic OCCM cells
Authors: Pham L. , Bezouglaia O. , Camargo P. M. , Nervina J. M. , Tetradis S.
Published: April 2007

Background and Objective:  Prostanoids that activate protein kinase C signaling are potent anabolic stimulators of cementoblastic OCCM cells. Using cDNA subtractive hybridization, we identified early growth response gene‐1 (egr1) as a prostanoid‐induced gene. Egr1, a zinc‐finger transcription factor expressed during tooth development, regulates cell growth and differentiation. We hypothesize that Egr1 may mediate part of the prostanoid‐induced anabolic effect in cementoblasts. Our objective was to characterize prostanoid‐induced egr1 gene expression in OCCM cells.

Material and Methods:  Total RNA and proteins were assayed by northern blot and western immunoblot assays.

Results:  Prostaglandin E2‐, prostaglandin F2α‐ and fluprostenol‐induced egr1 mRNA levels peaked at 0.5 h and returned to baseline by 4 h. Prostaglandin F2α and fluprostenol more potently induced egr1 compared with prostaglandin E2. The phorbol ester, phorbol 12‐myristate 13‐acetate, which activates protein kinase C signaling, induced egr1 mRNA levels 66‐fold over the control, whereas forskolin (a cAMP‐protein kinase A activator) and ionomycin (a calcium activator) had no effect. Protein kinase C inhibition significantly inhibited prostaglandin E2‐, prostaglandin F2α‐ and fluprostenol‐induced egr1 mRNA levels. Finally, prostanoids maximally induced Egr1 protein at 1 h.

Conclusion:  egr1 is a primary response gene induced by prostaglandin E2, prostaglandin F2α and fluprostenol in OCCM cells through protein kinase C signaling, suggesting that Egr1 may be a key mediator of anabolic responses in cementoblasts. Cementum is vital for periodontal organ maintenance and regeneration. Periodontal ligament fibers (Sharpey's fibers) insert into bone and cementum, thereby supporting the tooth in the alveolus (1). If the periodontal organ is lost, its regeneration requires cementoblast differentiation in order to form new cementum for periodontal ligament fiber insertion. Early attempts to regenerate cementum have proven difficult and rarely generate sufficient tissue (2). A better understanding of the molecular and cellular regulators that promote cementoblast differentiation is critical for developing targeted periodontal regeneration.
Improved Quality of Nursing Documentation: Results of a Nursing Diagnoses, Interventions, and Outcomes Implementation Study
Authors: Müller‐Staub Maria , Needham Ian , Odenbreit Matthias , Ann Lavin Mary , Van Achterberg Theo
Published: April 2007

PURPOSE.  To evaluate the impact of the quality of nursing diagnoses, interventions, and outcomes in an acute care hospital following the implementation of an educational program.

METHOD.  In a pretest–posttest experimental design study, nurses from 12 wards of a Swiss hospital received an educational intervention—an introductory class and consecutive classes, using a case discussion method—to implement nursing diagnoses, interventions, and outcomes. Two sets of 36 randomly selected nursing records were evaluated before and after implementation. The quality of documented nursing diagnoses, interventions, and nursing‐sensitive patient outcomes was assessed by 29 Likert‐type items with a 0–4 scale instrument, called Quality of Nursing Diagnoses, Interventions, and Outcomes (Q‐DIO) and tested using t‐tests.

FINDINGS.  Significant enhancements in the quality of documented nursing diagnoses, interventions, and outcomes were found following the implementation of a planned educational program.

CONCLUSIONS.  The implementation of NANDA, NIC, and NOC (NNN) nursing diagnoses, interventions, and outcomes led to higher quality of nursing diagnosis documentation, etiology‐specific nursing interventions, and nursing‐sensitive patient outcomes.

IMPLICATIONS FOR NURSING PRACTICE.  Educational measures support nurses to improve documentation of diagnoses, interventions, and outcomes. The Q‐DIO is a useful audit tool.
Patterns of Nursing Intervention Use Across 6 Days of Acute Care Hospitalization for Three Older Patient Populations
Authors: Shever Leah L. , Titler Marita , Dochterman Joanne , Fei Qiang , Picone Debra M.
Published: April 2007

PURPOSE.  The purpose was to (a) identify frequently used nursing interventions, and (b) describe patterns of interventions used for each of the three patient groups.

METHODS.  This secondary data analysis used data from an academic medical center where the Nursing Interventions Classification (NIC) was used to electronically document nursing care. Descriptive statistics describe the types, frequencies, and patterns of NIC interventions delivered to three older acute care populations.

FINDINGS.  Four NIC treatments were frequently used in all patient groups. There were also NIC treatments and patterns of treatments that were unique to each group.

CONCLUSIONS AND IMPLICATIONS.  Using standardized nursing language in electronic medical records (EMRs) enables data extraction and analysis.

Data extracted from EMRs provides nurse administrators with a tool to guide decisions regarding nurse staffing, education, evaluation, and resource allocation.
A new surgical method for the control of the epiphora in dogs: modified parotid duct transposition
Authors: Scotti S. , Klein A. , Vanore M. , Hidalgo A. , Fayolle P. , Moissonnier P.
Published: April 2007

A five‐year‐old, female, spayed beagle with a history of unilateral epiphora of several months’ duration as a result of inadequacy of the lacrimal drainage system was treated successfully with a new surgical method of parotid duct transposition. Data from complete preoperative ophthalmological examination, surgical technique, postoperative treatment, contrast radiography and histological examination were recorded. Absence of complications and complete patency of the stoma at 30 days after surgery confirmed the validity of this new technique. The use of an anatomic duct may be advantageous compared with the current techniques of conjunctivorhinostomy, conjuntivobuccostomy and conjunctival maxillary sinusostomy for the treatment of epiphora in the dogs caused by inadequacy of the lacrimal drainage system.
Aortic endocarditis associated with a perforated septal membranous aneurysm in a boxer dog
Authors: Quintavalla C. , Mavropoulou A. , Buratti E
Published: April 2007

Perimembranous ventricular septal defect is a common congenital heart disease in the dog. It can partially or completely close with age by development of a membranous ventricular septal aneurysm. Aortic endocarditis is a reported complication of ventricular septal defect and membranous ventricular septal aneurysm in human beings. This report describes a case of aortic endocarditis associated with a membranous ventricular septal aneurysm perforated by a small ventricular septal defect in a boxer dog.
Modeling Full-Scale Monolithic Catalytic Converters: Challenges and Possible Solutions
Authors: Mazumder Sandip
Published: April 2007

Modeling full-scale monolithic catalytic converters using state-of-the-art computational fluid dynamics algorithms and techniques encounters a classical multiscale problem: the channels within the monolith have length scales that are ∼1–2 mm, while the converter itself has a length scale that is ∼5–10 cm. This necessitates very fine grids to resolve all the length scales, resulting in few million computational cells. When complex heterogeneous chemistry is included, the computational problem becomes all but intractable unless massively parallel computation is employed. Two approaches to address this difficulty are reviewed, and their effectiveness demonstrated for the computation of full-scale catalytic converters with complex chemistry. The first approach is one where only the larger scales are resolved by a grid, while the physics at the smallest scale (channel scale) are modeled using subgrid scale models whose development entails detailed flux balances at the “imaginary” fluid–solid interfaces within each computational cell. The second approach makes use of the in situ adaptive tabulation algorithm, after significant reformulation of the underlying mathematics, to accelerate computation of the surface reaction boundary conditions. Preliminary results shown here for a catalytic combustion application involving 19 species and 24 reactions indicate that both methods have the potential of improving computational efficiency by several orders of magnitude.
Modeling of Fluid Dynamics and Heat Transfer Induced by Dielectric Barrier Plasma Actuator
Authors: Jayaraman Balaji , Thakur Siddharth , Shyy Wei
Published: April 2007

Glow discharge at atmospheric pressure using a dielectric barrier discharge can induce fluid flow, and can be used for active control of aerodynamics and heat transfer. In the present work, a modeling framework is presented to study the evolution and interaction of such athermal nonequilibrium plasma discharges in conjunction with low Mach number fluid dynamics and heat transfer. The model is self-consistent, coupling the first-principles-based discharge dynamics with the fluid dynamics and heat transfer equations. Under atmospheric pressure, the discharge can be simulated using a plasma–fluid instead of a kinetic model. The plasma and fluid species are treated as a two-fluid system coupled through force and pressure interactions, over decades of length and time scales. The multiple-scale processes such as convection, diffusion, and reaction/ionization mechanisms make the transport equations of the plasma dynamics stiff. To handle the stiffness, a finite-volume operator-split algorithm capable of conserving space charge is employed. A body force treatment is devised to link the plasma dynamics and thermo-fluid dynamics. The potential of the actuator for flow control and thermal management is illustrated using case studies.
Compressibility and Variable Density Effects in Turbulent Boundary layers
Authors: Liu Kunlun , Pletcher Richard H.
Published: April 2007

Two compressible turbulent boundary layers have been calculated by using direct numerical simulation. One case is a subsonic turbulent boundary layer with constant wall temperature for which the wall temperature is 1.58 times the freestream temperature and the other is a supersonic adiabatic turbulent boundary layer subjected to a supersonic freestream with a Mach number 1.8. The purpose of this study is to test the strong Reynolds analogy (SRA), the Van Driest transformation, and the applicability of Morkovin’s hypothesis. For the first case, the influence of the variable density effects will be addressed. For the second case, the role of the density fluctuations, the turbulent Mach number, and dilatation on the compressibility will be investigated. The results show that the Van Driest transformation and the SRA are satisfied for both of the flows. Use of local properties enable the statistical curves to collapse toward the corresponding incompressible curves. These facts reveal that both the compressibility and variable density effects satisfy the similarity laws. A study about the differences between the compressibility effects and the variable density effects associated with heat transfer is performed. In addition, the difference between the Favre average and Reynolds average is measured, and the SGS terms of the Favre-filtered Navier-Stokes equations are calculated and analyzed.
Analysis of Interfacial Heat Transfer Coefficient of Green Sand Mold Casting for Aluminum and Tin-Lead Alloys by Using a Lump Capacitance Method
Authors: Sun Hsien-Chi , Chao Long-Sun
Published: April 2007

During the casting process of green sand mold, air gaps will form between the metal and sand mold. The air gaps will make it difficult to analyze the heat transfer at the mold/metal interface. Generally, an interfacial heat transfer coefficient is employed to evaluate the heat flux transferred across the air gaps. Though the interfacial heat transfer coefficient is highly important, its value is not easily obtained by using the direct experimental or theoretical method. With temperature-measured data, some inverse methods can be used to predict the coefficient. However, the latent heat released and undercooling during the solidification of the molten metal and the moisture of the green sand mold complicate the associated temperature calculations. To overcome this difficulty, a lump capacitance method is proposed in this study to calculate the interfacial heat transfer coefficient for the casting process in green sand mold. Thermalcouples are utilized to measure the temperatures of sand mold and metal. The geometry of casting is cylindrical and the castings are A356 alloy and Sn-20 wt. % Pb alloy. With the predicted interfacial coefficients, the temperature field of the metal was solved numerically. Based on the solidification time, the numerical results are in good agreement with the experimental ones. This verified the feasibility of the proposed method and it can be applied in the future study or design of a casting process.
A Novel Fluorescence Intensity Screening Assay Identifies New Low-Molecular-Weight Inhibitors of the gp41 Coiled-Coil Domain of Human Immunodeficiency Virus Type 1
Authors: Cai Lifeng , Gochin Miriam
Published: April 2007

A metallopeptide-based fluorescence assay has been designed for the detection of small-molecule inhibitors of human immunodeficiency virus type 1 gp41, the viral protein involved in membrane fusion. The assay involves two peptides representing the inner N-terminal-heptad-repeat (HR1) coiled coil and the outer C-terminal-heptad-repeat (HR2) helical domains of the gp41 six-helix bundle which forms prior to fusion. The two peptides span a hydrophobic pocket previously defined in the literature. The HR1 peptide is modified with a metal-ligated dye complex, which maintains structural integrity and permits association with a fluorophore-labeled HR2 peptide to be followed by fluorescence quenching. Compounds able to disrupt six-helix bundle formation can act as fusion inhibitors, and we show that they can be detected in the assay from an increase in the fluorescence that is correlated with the potency of the compound. Assay optimization and validation have resulted in a simple quantitative competitive inhibition assay for fusion inhibitors that bind in the hydrophobic pocket. The assay has an assay quality factor (
Z
′) of 0.88 and can rank order inhibitors at 10 μM concentration with

K
i

s in the range of 0.2 μM to 30 μM, an ideal range for drug discovery. Screening of a small peptidomimetic library has yielded three new low-molecular-weight gp41 inhibitors. In vitro syncytium inhibition assays confirmed that the compounds inhibited cell-cell fusion in the low micromolar range. These lead compounds provide a new molecular scaffold for the development of fusion inhibitors.
Combined Therapies in a Murine Model of Blastoschizomycosis
Authors: Serena Carolina , Rodríguez M. Mar , Mariné Marçal , Pastor F. Javier , Guarro Josep
Published: April 2007

In a murine model of blastoschizomycosis, amphotericin B combined with micafungin, flucytosine or voriconazole did not improve the efficacy of fluconazole. However, such combinations can constitute therapeutic options for those cases where fluconazole fails.
In Vitro Susceptibilities of 217 Clinical Isolates of Zygomycetes to Conventional and New Antifungal Agents
Authors: Almyroudis Nikolaos G. , Sutton Deanna A. , Fothergill Annette W. , Rinaldi Michael G. , Kusne Shimon
Published: April 2007

We evaluated the in vitro susceptibilities of 217 zygomycetes to amphotericin B, ketoconazole, fluconazole, itraconazole, voriconazole, posaconazole, caspofungin, and flucytosine. The significant in vitro activity of posaconazole against several species appears to support its reported clinical efficacy. Decreased susceptibility to amphotericin B was noted with
Cunninghamella bertholletiae
.
Vancomycin In Vitro Bactericidal Activity and Its Relationship to Efficacy in Clearance of Methicillin-Resistant
Staphylococcus aureus
Bacteremia
Authors: Moise Pamela A. , Sakoulas George , Forrest Alan , Schentag Jerome J.
Published: April 2007

We examined the relationship between the time to clearance of methicillin-resistant
Staphylococcus aureus
(MRSA) bacteremia while patients were receiving vancomycin therapy and the in vitro bactericidal activity of vancomycin. Vancomycin killing assays were performed with 34 MRSA bloodstream isolates (17 accessory gene regulator group II [
agr
-II] and 17 non-
agr
-II isolates) from 34 different patients with MRSA bacteremia for whom clinical and microbiological outcomes data were available. Vancomycin doses were prospectively adjusted to achieve peak plasma concentrations of 28 to 32 μg/ml and trough concentrations of 8 to 12 μg/ml. Bactericidal assays were performed over 24 h with ∼10
7
to 10
8
CFU/ml in broth containing 16 μg/ml vancomycin. The median time to clearance of bacteremia was 6.5 days for patients with MRSA isolates demonstrating ≥2.5 reductions in log
10
CFU/ml at 24 h and >10.5 days for patients with MRSA isolates demonstrating <2.5 log
10
CFU/ml by 24 h (
P
= 0.025). The median time to clearance was significantly longer with MRSA isolates with vancomycin MICs of 2.0 μg/ml compared to that with MRSA isolates with MICs of ≤1.0 μg/ml (
P
= 0.019). The bacteremia caused by MRSA isolates with absent or severely reduced delta-hemolysin expression was of a longer duration of bacteremia (10 days and 6.5 days, respectively;
P
= 0.27) and had a decreased probability of eradication (44% and 78%, respectively;
P
= 0.086). We conclude that strain-specific microbiological features of MRSA, such as increased vancomycin MICs and decreased killing by vancomycin, appear to be predictive of prolonged MRSA bacteremia while patients are receiving vancomycin therapy. Prolonged bacteremia and decreased delta-hemolysin expression may also be related. Evaluation of these properties may be useful in the consideration of antimicrobial therapies that can be used as alternatives to vancomycin for the treatment of MRSA bacteremia.
Heparin-Mimicking Sulfonic Acid Polymers as Multitarget Inhibitors of Human Immunodeficiency Virus Type 1 Tat and gp120 Proteins
Authors: Bugatti Antonella , Urbinati Chiara , Ravelli Cosetta , De Clercq Erik , Liekens Sandra , Rusnati Marco
Published: April 2007

Human immunodeficiency virus (HIV) Tat and gp120 intriguingly share the feature of being basic peptides that, once released by HIV+cells, bind to polyanionic heparan sulfate proteoglycans (HSPGs) on target uninfected cells, contributing to the onset of AIDS-associated pathologies. To identify multitarget anti-HIV prodrugs, we investigated the gp120 and Tat antagonist potentials of a series of polyanionic synthetic sulfonic acid polymers (SSAPs). Surface plasmon resonance revealed that SSAPs inhibit with a competitive mechanism of action the binding of Tat and gp120 to surface-immobilized heparin, an experimental condition that resembles binding to cellular HSPGs. Accordingly, SSAPs inhibited HSPG-dependent cell internalization and the transactivating activity of Tat. Little is known about the binding of free gp120 to target cells. Here, we identified two classes of gp120 receptors expressed on endothelial cells, one of which was consistent with an HSPG-binding, low-affinity/high-capacity receptor that is inhibited by free heparin. SSAPs inhibited the binding of free gp120 to endothelial cells, as well as its capacity to induce apoptosis in the same cells. In all the assays, poly(4-styrenesulfonic acid) (PSS) proved to be the most potent antagonist of Tat and gp120. Accordingly, PSS bound both proteins with high affinity. In conclusion, SSAPs represent an interesting class of compounds that bind both gp120 and Tat and inhibit their HSPG-dependent cell surface binding and pathological effects. As these activities contribute to both AIDS progression and associated pathologies, SSAPs can be considered prototypic molecules for the development of multitarget drugs for the treatment of HIV infection and AIDS-associated pathologies.
Pharmacokinetics and Tolerability of a Higher Rifampin Dose versus the Standard Dose in Pulmonary Tuberculosis Patients
Authors: Ruslami Rovina , Nijland Hanneke M. J. , Alisjahbana Bachti , Parwati Ida , van Crevel Reinout , Aarnoutse Rob E.
Published: April 2007

Rifampin is a key drug for tuberculosis (TB) treatment. The available data suggest that the currently applied 10-mg/kg of body weight dose of rifampin may be too low and that increasing the dose may shorten the treatment duration. A double-blind randomized phase II clinical trial was performed to investigate the effect of a higher dose of rifampin in terms of pharmacokinetics and tolerability. Fifty newly diagnosed adult Indonesian TB patients were randomized to receive a standard (450-mg, i.e., 10-mg/kg in Indonesian patients) or higher (600-mg) dose of rifampin in addition to other TB drugs. A full pharmacokinetic curve for rifampin, pyrazinamide, and ethambutol was recorded after 6 weeks of daily TB treatment. Tolerability was assessed during the 6-month treatment period. The geometric means of exposure to rifampin (area under the concentration-time curve from 0 to 24 h [AUC
0-24
]) were increased by 65% (
P
< 0.001) in the higher-dose group (79.7 mg·h/liter) compared to the standard-dose group (48.5 mg·h/liter). Maximum rifampin concentrations (
C
max
) were 15.6 mg/liter versus 10.5 mg/liter (49% increase;
P
< 0.001). The percentage of patients for whom the rifampin
C
max
was ≥8 mg/liter was 96% versus 79% (
P
= 0.094). The pharmacokinetics of pyrazinamide and ethambutol were similar in both groups. Mild (grade 1 or 2) hepatotoxicity was more common in the higher-dose group (46 versus 20%;
P
= 0.054), but no patient developed severe hepatotoxicity. Increasing the rifampin dose was associated with a more than dose-proportional increase in the mean AUC
0-24
and
C
max
of rifampin without affecting the incidence of serious adverse effects. Follow-up studies are warranted to assess whether high-dose rifampin may enable shortening of TB treatment.
Adapter Protein SH2-Bβ Stimulates Actin-Based Motility of
Listeria monocytogenes
in a Vasodilator-Stimulated Phosphoprotein (VASP)-Dependent Fashion
Authors: Diakonova Maria , Helfer Emmanuele , Seveau Stephanie , Swanson Joel A. , Kocks Christine , Rui Liangyou , Carlier Marie-France , Carter-Su Christin
Published: April 2007

SH2-Bβ (Src homology 2 Bβ) is an adapter protein that is required for maximal growth hormone-dependent actin reorganization in membrane ruffling and cell motility. Here we show that SH2-Bβ is also required for maximal actin-based motility of
Listeria monocytogenes
. SH2-Bβ localizes to
Listeria
-induced actin tails and increases the rate of bacterial propulsion in infected cells and in cell extracts. Furthermore,
Listeria
motility is decreased in mouse embryo fibroblasts from SH2-B
−/−
mice. Both recruitment of SH2-Bβ to
Listeria
and SH2-Bβ stimulation of actin-based propulsion require the vasodilator-stimulated phosphoprotein (VASP), which binds ActA at the surfaces of
Listeria
cells and enhances bacterial actin-based motility. SH2-Bβ enhances actin-based movement of ActA-coated beads in a biomimetic actin-based motility assay, provided that VASP is present. In vitro binding assays show that SH2-Bβ binds ActA but not VASP; however, binding to ActA is greater in the presence of VASP. Because VASP also plays an essential regulatory role in actin-based processes in eukaryotic cells, the present results provide mechanistic insight into the functions of both SH2-Bβ and VASP in motility and also increase our understanding of the fundamental mechanism by which
Listeria
spreads.