bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence that periodontal treatment improves diabetes outcomes: a systematic review and meta‐analysis
Authors: Engebretson Steven , Kocher Thomas
Published: April 2013

Context

The effect of periodontal therapy on diabetes outcomes has not been established.

Objective

This update examines the effect of periodontal treatment on diabetes outcomes.

Data sources

Literature since October 2009 using MEDLINE.

Study eligibility criteria

Published RCTs including periodontal therapy for diabetic subjects, a metabolic outcome, an untreated control group, and follow‐up of 3 months.

Data extraction

Pre‐defined data fields, including study quality indicators were used.

Data synthesis

A search revealed 56 publications of which 9 met inclusion criteria. Mean change of HbA1c from baseline was compared across treatment groups. Pooled analysis was based on random effects models.

Results

A meta‐analysis indicated a mean treatment effect of −0.36% HbA1c (CI −0.54, −0.19) compared to no treatment after periodontal therapy (p < 0.0001). Heterogeneity tests revealed only minimal evidence of publication bias (I2 = 9%).

Limitations

Small sample size and high risk of bias remain problematic for studies of this type. Periodontal therapy varied considerably.

Conclusion

The modest reduction in HbA1c observed as a result of periodontal therapy in subjects with type 2 diabetes is consistent with previous systematic reviews. Despite this finding, there is limited confidence in the conclusion due to a lack of multi‐centre trials of sufficient sample size are lacking.
Periodontitis and atherosclerotic cardiovascular disease: consensus report of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases
Authors: Tonetti Maurizio S. , Van Dyke Thomas E. ,   working group 1 of the joint EFP/AAP workshop
Published: April 2013

Background

This consensus report is concerned with the association between periodontitis and atherosclerotic cardiovascular disease (ACVD). Periodontitis is a chronic multifactorial inflammatory disease caused by microorganisms and characterized by progressive destruction of the tooth supporting apparatus leading to tooth loss; as such, it is a major public health issue.

Aims

This report examined biological plausibility, epidemiology and early results from intervention trials.

Plausibility

Periodontitis leads to entry of bacteria in the blood stream. The bacteria activate the host inflammatory response by multiple mechanisms. The host immune response favors atheroma formation, maturation and exacerbation.

Epidemiology

In longitudinal studies assessing incident cardiovascular events, statistically significant excess risk for ACVD was reported in individuals with periodontitis. This was independent of established cardiovascular risk factors. The amount of the adjusted excess risk varies by type of cardiovascular outcome and across populations by age and gender. Given the high prevalence of periodontitis, even low to moderate excess risk is important from a public health perspective.

Intervention

There is moderate evidence that periodontal treatment: (i) reduces systemic inflammation as evidenced by reduction in C‐reactive protein (CRP) and improvement of both clinical and surrogate measures of endothelial function; but (ii) there is no effect on lipid profiles – supporting specificity. Limited evidence shows improvements in coagulation, biomarkers of endothelial cell activation, arterial blood pressure and subclinical atherosclerosis after periodontal therapy. The available evidence is consistent and speaks for a contributory role of periodontitis to ACVD. There are no periodontal intervention studies on primary ACVD prevention and there is only one feasibility study on secondary ACVD prevention.

Conclusions

It was concluded that: (i) there is consistent and strong epidemiologic evidence that periodontitis imparts increased risk for future cardiovascular disease; and (ii) while in vitro, animal and clinical studies do support the interaction and biological mechanism, intervention trials to date are not adequate to draw further conclusions. Well‐designed intervention trials on the impact of periodontal treatment on prevention of ACVD hard clinical outcomes are needed.
Sensitivity to Organic Acids In Vitro and In Situ of Salmonella spp. and Escherichia coli Isolated from Fresh Pork Sausages
Authors: de Ávila Amanda Rejane Alves , Marques Simone Cristina , Piccolli Roberta Hilsdorf , Schwan Rosane Freitas
Published: April 2013

The production of fresh pork sausages inoculated with different multi‐resistant bacterial strains, isolated from sausage commercially purchased from Brazil, was conducted to evaluate microbial inhibition by lactic acid. The isolates were identified through 16S rDNA region sequencing and the bacteria with antimicrobial multi‐resistance profiles were selected. The minimum bactericidal concentration was determined using lactic and acetic acids. Samples were contaminated by Salmonella Typhi, Salmonella Typhimurium, Salmonella Paratyphi, Escherichia coli and high counts of aerobic mesophilic bacteria. Antibiotic resistance was detected in 21 of the 27 analyzed isolates (six Salmonella spp. and 21 E. coli). In the minimum bactericidal concentration test, lactic acid was more effective than acetic acid in the reduction of the bacterial population. The food matrix inoculated with two bacterial strains (E. coli, Salmonella spp.) was treated with lactic acid at the concentrations of 1.5 and 4.0 M and showed no significant effect on the bacterial population.

Practical Application

Fresh sausages are potential vehicles for pathogenic microorganisms, which are frequently associated with foodborne diseases. Organic acids have been used to improve the microbiological quality of food products including meat. Bacteria were isolated from fresh pork sausages and antibiotic resistance and susceptibility of lactic and acetic acids in vitro of the identified strains were tested. The best results were used to test the functionality in fresh pork sausages inoculated with Escherichia coli and Salmonella spp. These results may be applied by local producers of fresh pork sausages.
An Optimization Study on the Ultrasonic Treatments for Saccharomyces cerevisiae Inactivation in Red Grape Juice with Maintaining Critical Quality Attributes
Authors: Nafar Maryam , Emam‐Djomeh Zahra , Yousefi Shima , Hashemi Ravan Mahnaz
Published: April 2013

This study was conducted to decrease Saccharomyces cerevisiae cell count and to maximize levels of quality characteristics in red grape juice during ultrasound process using response surface methodology (RSM). The effects of three process parameters (considered as independent variables), namely temperature (25–50C), time (20–40 min) and frequency (0–135 Hz), on the yeast inactivation, total anthocyanin content (TAC), total color difference (TCD), antioxidant activity (AA), polymeric color content (PCC), pH, total titratable acidity (TTA) and total soluble solids (TSS) (considered as dependent variables) were studied based on RSM. The optimum operating conditions for the maximum yeast inactivation and the optimal juice quality characteristics were found to be frequency of 135.0 kHz, temperature of 30.9C and time of 40.0 min. In these conditions, the yeast inactivation, TAC, PCC, AA, TCD, pH, TTA and TSS were 1 cfu/mL, 808.0 mg/g, 67.85%, 0.94 mmol/L, 1.64, 3.47, 977.4 mg citric acid/100 mL and 20.04, respectively.

Practical Applications

In recent years, emerging nonthermal methods, such as ultrasound (US), for inactivating microorganisms have been developed in food industries to manufacture natural products. Red grape juice, due to the presence of anthocyanins and flavonoids, has many health‐promoting effects. As the nutritive and organoleptic characteristics of grapes decrease during storage and ripening periods because of their high susceptibility to pathogenic infection and physiological deterioration, the use of US method as a potential technology can inactive foodborne spoilage or pathogenic microorganisms and produce juices with organoleptic and nutritional qualities. Moreover, the optimization of US conditions enabled us to shorten the process duration and to reduce the production costs while maintaining the quality at a relatively high level.
Differences in energy and nutrient‐intake among Greek children between 1992/93 and 2006/07
Authors: Smpokos E. A. , Linardakis M. , Papadaki A. , Theodorou A. S. , Havenetidis K. , Kafatos A.
Published: April 2013

Background

There is lack of data in Greece on the trends in energy and nutrient intake. The present study aimed to examine differences in these parameters among first‐grade children of Crete, Greece, between 1992/93 and 2006/07.

Methods

Children (aged 5.7–7.6 years) from two‐representative cross‐sectional samples participated during 1992/93 (n = 245) and 2006/07 (n = 257). Nutrient and food intakes were assessed using estimated 3‐day‐food records. Nutrient intakes were estimated as amounts per 4185 kJ (1000 kcal) of energy intake (EI), whereas macronutrients were estimated as percentage of total EI.

Results

Between 1992/93 and 2006/07, respectively, significant increases (P < 0.05) were observed in the intake of energy (boys: 7996 versus 8646 kJ; girls: 7265 versus 7963 kJ), calcium (boys: 488 versus 587 mg; girls: 464 versus 594 mg), iron (boys: 5.8 versus 7.3 mg; girls: 5.7 versus 7.4 mg) and vitamins B2 (boys: 1.01 versus 1.17 mg; girls: 1.0 versus 1.16 mg) and B6 (boys: 0.80 versus 0.87 mg; girls: 0.75 versus 0.95 mg), for boys and girls, respectively. Among boys, the intake of protein (13.6 versus 14.6% of EI) and total trans fatty acids (TTFA) (0.84 versus 0.99 g) was also significantly lower in 1992/93 (P < 0.016). Between 1992/93 and 2006/07, total fat (boys: 42.9% versus 42.8%, girls: 42% versus 43.1%) and saturated fat (boys: 15.5% versus 15.4%, girls: 15% versus 15.3%) exceeded the 30–35% and <10% dietary recommendations, respectively, A significantly higher proportion of children in 2006/07, compared to 1992/93, had a higher intake of total energy (>120% of the recommended energy allowance).

Conclusions

The intake of several macronutrients (protein, TTFA, total and saturated fat) in this sample of children did not meet the recommended intakes in either time period.
Health Literacy and Women's Health: Challenges and Opportunities
Authors: Corrarino Jane E.
Published: April 2013

Introduction

This article describes the impact of health literacy on women's health and provides strategies for addressing this public health issue.

Methods

A comprehensive literature review was conducted of peer‐reviewed journals. Multiple electronic databases were used, including CINAHL, MEDLINE, PubMed, and Google Scholar. Key words were used to identify articles and were combined to include health literacy, health behavior, women's health, patient education, and professional role. Additional articles were identified as a result of reviewing reference lists found during the electronic search.

Results

Health literacy is a complex issue that affects many women and can adversely affect women's knowledge, ability to adhere to clinical plans of care, and health outcomes for women and their children. It is estimated that 36% of adults in the United States possess limited health literacy skills. Effective strategies can be used by health care providers to address this serious problem, including clear and effective communication, development of health education materials, professional education, and development of community partnerships.

Discussion

Health literacy is a serious problem. Effective approaches can be employed to blunt the adverse effect on women's health. Health care providers are well positioned to demonstrate leadership within the health care system regarding health literacy.
Interconception Care for Women With Prior Gestational Diabetes Mellitus
Authors: Mielke Ruth T. , Kaiser Deborah , Centuolo Rhonda
Published: April 2013

The diagnosis of gestational diabetes mellitus (GDM) signals greater pregnancy risk but also increased lifelong risk of developing diabetes and cardiovascular disease. In women with GDM, insulin resistance exceeds that observed in normal pregnancy and to varying degrees may persist or worsen after birth. Therefore, during postpartum and interconception periods, women with a history of GDM must be monitored for manifestations of increasing insulin resistance, hyperglycemia, dyslipidemia, hypertension, and increased adiposity. Care of women with prior GDM in the postpartum and interconception periods affords clinicians a unique opportunity for targeted screening and health promotion. The objective of this review was to synthesize evidence related to interconception care for women following a pregnancy complicated by GDM and to suggest principles of care: 1) case finding and multiple patient/clinician reminders for women with prior GDM are necessary so that screening occurs in the postpartum through interconception periods; 2) monitoring of metabolic (glucose) and cardiovascular risk (lipids, blood pressure, adiposity) should occur at regular intervals and more often in women with additional risk factors such as insulin use during pregnancy, early diagnosis of GDM, obesity, prediabetes, and dyslipidemia; 3) breastfeeding and use of long‐term contraception should be encouraged; and 4) lifestyle modifications that are effective in preventing and delaying disease should be encouraged.
Tuning of Acoustic Bandgaps in Phononic Crystals With Helmholtz Resonators
Authors: Li Jian-Bao , Wang Yue-Sheng , Zhang Chuanzeng
Published: April 2013

In this paper, acoustic wave propagation in a two- or three-dimensional phononic crystal consisting of Helmholtz resonators embedded in a fluid matrix is studied. The band structures are calculated to discuss the influence of the geometry topology of Helmholtz resonators on the bandgap characteristics. It is shown that a narrow bandgap will appear in the lower frequency range due to the resonance of the Helmholtz resonators. The width and position of this resonance bandgap can be tuned by adjusting the geometrical parameters of the Helmholtz resonator. The position of the resonance bandgap can be evaluated by the resonance frequency of the Helmholtz resonator. A decrease in the size of the opening generally results in a lower position and a smaller width of the bandgap. The system with one opening exhibits a wider bandgap in a lower position than the system with two openings.
Po‐Poster ‐ 29: Radiation‐induced apoptosis of lymphocytes to predict late toxicity from radiotherapy
Authors: Schnarr K , Dayes I , Sathya J , McFarlane N , Boreham D
Published: April 2013

An important challenge arises in radiotherapy when certain individuals present with abnormal radiosensitivities. Radiosensitive individuals may not tolerate normal therapy and encounter complications whereas radioresistant patients may not respond adequately to standard treatments regimes because of intrinsic cellular resistance. It has been shown (Crompton et al. IJROBP 2003; 45:707–714 and IJROBP 2001; 49:547–554) that late normal tissue toxicity was correlated to low level apoptosis in CD4 and CD8 lymphocytes. The assay developed by this group used a simple flow cytometry based assay. Our group has researched the sensitivity of alternative apoptosis assays (DiOC6, Caspase‐3, Annexin‐V, PI, 7AAD and Comet), and have shown that both the Annexin V‐FITC and the DiOC6 assay have the greatest suitability in clinical use with respect to speed, simplicity and sensitivity. In our present study, 80 prostate cancer patients will be tested for radiosensitivity using lymphocyte apoptosis assays. These patients were formerly enrolled in a randomized dose‐escalation study (Sathya et al. JCO 2005; 45:1192–1199). Toxicity was recorded prospectively. The aim of this study is to determine a correlation between the proportion of T‐lymphocytes undergoing apoptosis when irradiated (2, 4 and 8Gy) and the occurrence of late toxicity (Grade II and above). We will present our current results showing a large inter‐individual variation within our patient cohort. Data obtained using the Annexin Assay measuring CD4 lymphocyte apoptosis receiving 8Gy show a wide range of responses (mean = 34% apoptosis, σ = 8.2) with z‐scores ranging from −1.5 to 2.4.
Sci‐PM Fri ‐ 04: A three‐dimensional micro‐ultrasound image‐guided and robotically assisted needle positioning system
Authors: Waspe A , Cakiroglu H , Lacefield J , Fenster A
Published: April 2013

Biomedical research using small animals often requires interventional procedures such as biopsies and injections. When performed inaccurately, these procedures can produce poor results, jeopardizing the study. A needle‐positioning robot for three‐dimensional micro‐ultrasound guided interventions was developed to improve the accuracy of needle insertion. The robot has three degrees of freedom for positioning the needle in three dimensions. Two rotational joints are used to control orientation (roll and pitch), while another joint linearly translates the needle to perform insertion. The three axes intersect at a single point, producing a remote centre of motion (RCM) that acts as a fulcrum for the three‐dimensional orientation of the needle. The RCM corresponds to the insertion point of the needle into the animal. The robot was calibrated to ensure that the three axes intersected at a single point, and that the needle tip was positioned at the RCM. The calibration was performed using a high‐resolution digital camera to find the centre of rotation about the pitch and roll axes separately. The position of the needle was adjusted until it was aligned with the RCM. Calibration results indicate that the distance from the needle to the pitch and roll axes are 24±30 μm and 18±15 μm, respectively. The pitch and roll axes are separated by 11±3 μm. The calibration procedure allowed us to detect and correct manufacturing and design errors. The expected maximum needle positioning error computed from the calibration is 32 μm when the needle tip is moved to the boundary of the workspace.
Sci‐AM1 Sat ‐ 05: Fractal and motion modeling of PET/CT tumours
Authors: Kusano M , Caldwell C , Ravi A
Published: April 2013

Objective: To generate realistic computer‐simulated PET/CT tumour images with characteristics typical of the tumour (shape, pixel intensity and movement over time) and of the imaging system (acquisition parameters and resolution). Methods: An initial tumour volume was segmented from the CT scan of a lung cancer patient via region growing. To improve the axial resolution and mimic the contour curvature and pixel variations in the transaxial plane, fractal analysis and interpolation was used. Breathing motion with a period and extents typical of lung cancer patients was then applied to the fractal tumour. To produce PET and CT images, the moving tumour was sampled according to acquisition characteristics typical of the two modalities. For CT, a slice thickness of 3.0mm, acquisition time of 0.7s and resolution of 2mm was assumed. For PET, it was assumed that tumour motion was captured within one bed position over an acquisition time of 180s, and the imager resolution was 6mm. Results: Following fractal interpolation, the tumour exhibited similar curvature and gray‐level gradation in all three imaging planes. Application of motion and blurring produced CT images different in appearance from the stationary fractal tumour volume and the total volume traced by the moving object. Motion and blurring produced PET images similar to the volume traced by the moving object, graded by the time spent in each location within the volume and blurred due to the degraded resolution of the scanner. Conclusions: Realistic computer‐simulated PET/CT tumour images can be generated using fractal analysis and motion modeling.
Sci‐AM1 Sat ‐ 06: Improved absorbed dose calculations incorporating internal organ motion
Authors: Jiang R , Barnett R , Chow J , Grigorov G , Chen J
Published: April 2013

The goal of radiation therapy is to deliver a highly conformal dose to a prescribed target volume and to spare surrounding healthy tissue as much as possible. Present commercial dose planning systems assume that patient's anatomy is static over the course of treatment. During treatment delivery, however, dosimetric uncertainties arising from patient repositioning and internal organ motion are unavoidable practically. The purpose of this study is to evaluate the effect of prostate motion on the physical dose distribution by model based on the Pinnacle treatment planning system. Prostate motion, within the PTV, was represented by a weighted average of seven individually shifted PTVs As already well known, internal organ motion always leads to blurred contour surfaces. The dose coverage of PTV and critical organs is less as indicated by dose at “edge” of contours and also by decreased DVH particularly at high dose region. The averaged decrease of TCP between the static planning and model is 2.9%, and the rectum is spared if motion is equally weighted and symmetric. The configurations yield a better estimate of the actual dose in the rectal wall with decreasing NTCP. The effects of different shifting weight to TCP and NTCP in L‐R, A‐P and S‐I directions were also quantitatively analyzed. The calculation of the cumulative dose incorporating internal organ motion plays an important role in pursuing adaptive radiation therapy and dose escalation for IMRT with the goal of decreasing the dose delivered to the normal critical structures.
Sci‐AM2 Sat ‐ 02: Energy optimization for inverse planning
Authors: Sévigny C , Beaulieu L , Beaulieu F
Published: April 2013

Purpose: To simultaneously optimize the photon beam energy, orientations(gantry, table), wedge filters and beam weights in aperture‐based IMRT, a new inverse planning system has been developed. This system, Ballista, uses anatomy‐based MLC fields as aperture. It is an alternative for beamlet‐based IMRT. The aim of this study is to include the photon energy in the optimization process. Method and Materials: Ballista uses a fast simulated annealing algorithm to select the optimal configuration of beams with respect to the objectives specified by the planner. To include the energy as a free parameter in the existing overall optimization system, this variable is interpreted by the algorithm as an angle. That is, each eligible energy is assigned to a circular section of the space of all possible solutions. In addition to varying the energy of the individual beams, an option was added to the process which allows associating a combination of energies to various segments of a single field. Results: The effectiveness of energy optimization has been tested on several sites. The lung cancer has provided good results. The value of V20(29.6%vs.35%) is reduced as well as the mean dose to the heart(14.5%vs.21.5%). Also, a better tumor coverage (V95%=97.8%vs.96.6% and IH=1.07vs.1.10) is obtained in the case of a non‐coplanar plan realized with this new approach in comparison with a standard plan (23MV only). Conclusion: The inclusion of energy gives the optimization process an additional advantage over standard planning, and better close the gap between the optimized approach and the clinical treatment methods.
Sci‐AM2 Sat ‐ 05: Dose verification for rotating multileaf collimator IMRT
Authors: Schmuland M , Otto K
Published: April 2013

A new method of delivering IMRT has been proposed in which the entire MLC is rotated between each segment. Current linacs were not designed for IMRT delivery with collimator rotation and extensive quality assurance testing must be done before it can be used clinically. This work describes the different areas of testing that need to be considered, namely (1) the commissioning and QA of the Dynamic Beam Delivery (DBD) Toolbox (Varian Medical Systems, Palo Alto) required for collimator rotation control on a Varian CL21EX linac, (2) accurate fluence modeling of rotated apertures, and (3) dosimetric verification of full IMRT treatments delivered with a rotating MLC (RMLC). The DBD toolbox was tested and the collimator rotation angle was found to be accurate and reproducible to within 0.5 degrees. Fluence distributions of varying complexity were generated using the RMLC algorithm and the accuracy of the fluence modeling was validated using film based verification methods. IMRT treatment plans for a prostate, nasopharynx, and c‐shape target were generated with the RMLC segmentation algorithm and were delivered to a phantom. Measured and calculated dose distributions were compared using dose difference, distance‐to‐agreement, gamma factor maps and two‐dimensional profiles. The level of agreement was comparable to clinically accepted plans. Our results show that we can accurately control collimator rotation and precisely model fluence distributions generated from rotating MLC apertures. We also show that the RMLC technique is capable of delivering 3D clinical dose distributions accurately and reproducibly. This work was supported in part by Varian Medical Systems.
Sci‐AM2 Sat ‐ 09: Towards objective plan comparisons in radiation therapy
Authors: Yartsev S , Chen J , Yu E , Kron T , Rodrigues G , Coad T , Trenka K , Wong E , Bauman G , Van Dyk J
Published: April 2013

In recent years, various novel techniques for radiation treatment of cancer patients have been introduced to clinical practice: intensity‐modulated radiation therapy (IMRT), intensity‐modulated arc therapy (IMAT), helical tomotherapy (HT), light ions irradiation, etc. Such variety of instrumentation possibilities requires some initial comparative assessment of which particular technique would be the most beneficial for a given patient case. In clinical practice a balanced trade‐off between homogeneous and sufficient tumour irradiation and maximal sparing of sensitive structures is needed. A dose quality factor (DQF) was introduced to evaluate the plan quality for different treatment techniques based on realistic clinical requirements for target and organs at risk irradiation. A correlation between plan quality quantified by DQF with some set of patient specific features characterised by patient feature factor (PFF) is analysed in a comparative planning studies for 15 patients with stage III inoperable non‐small cell lung cancer using 3D conformal technique, IMRT and HT. For this set of patients, PFF is chosen as the product of three patient characteristics: the target complexity parameter, overlap between target and lungs, and the ratio between involved and non‐involved lungs. Future work would require validation in larger patient data sets, other disease sites and weighting of different factors of the PFF. This approach can help to select the most beneficial treatment technique prior to actual planning.
Sci‐PM Sat ‐ 01: Imaging performance of a bench‐top megavoltage CT scanner
Authors: Monajemi T , Tu D , Fallone B , Rathee S
Published: April 2013

The ultimate goal of this project is to create a focused 2D MV detector with high detective quantum efficiency so reasonable low contrast resolution (LCR) at low dose can be obtained in MVCT. As an initial step an 80‐element detector is fabricated by tiling 8‐element (element size 0.275 × 0.8 × 1 cm3) and photodiode arrays on an arc (radius = 110 cm). A precision rotary stage and its control are added to create a third generation CT scanner. The attenuation of and 6 MV beams are measured as a function of solid water thickness, fit to a second order polynomial to correct for spectral hardening artifacts. A calibration procedure was established to remove ring artifacts caused by distinctly asymmetric line spread functions at the ends of 8‐element blocks. Low contrast resolution as a function of dose and object size, the signal to noise ratio (SNR) as a function of dose, and linearity of CT numbers with density were quantified. Throwing away one‐ninth of collected projection angles to reduce the dose per image adversely affects the resolution in 6 MV images; 15 mm targets at 1.5% are visible at 7cGy. Low contrast target of 1.5% at 6 mm is visible in at 2cGy. LCR in objects stays approximately constant while dose is reduced from 17 to 2cGy. Contrast decreases with diameter decrease. SNR2 from a uniform phantom increases linearly with dose (R2=0.9977). CT numbers as a function of the density show a linear trend (R2=0.9923).
Sci‐PM Sat ‐ 03: Conformal dose verification using cone beam optical computed tomography and polymer gel dosimeters: A feasibility study
Authors: Schreiner J , Rogers M , Senden R , McAuley K , Miller J
Published: April 2013

The advent of image guided radiotherapy, particularly with intensity modulation techniques, offers the potential to improve patient outcomes by conforming the dose to a tumour thereby decreasing irradiation of surrounding tissues. This potentially reduces complication rates and enables dose escalation. However, intensity modulated radiation therapy necessarily requires far greater complexity in treatment planning and dose delivery and, ideally, delivery must be verified directly in three‐dimensions to ensure that the planning objectives are achieved. Currently no convenient system exists for such 3D dosimetry. In this work we provide an initial assessment of a modality that could provide exactly this functionality using polymer gel dosimeters that polymerize when exposed to radiation. Two dosimeters based on polyacrylamide gelatin (PAG) and on a new formulation using N‐vinylFormamide are investigated. The dosimeters are prepared with Tetrakis to enable preparation in conventional fumehoods in an oxygen environment. A novel cone beam optical CT unit designed in London Ontario specifically for gel dosimetry provides dose measurements. The radiation induced polymerization, and hence dose, affects light attenuation and, hence CT numbers in optical CT, since the polymers act as scattering centres for light. We will show that apart from an initial threshold region, the relationship between dose and optical CT numbers is linear over the range investigated. An example of the visualization of a treatment failure will be illustrated. Though preliminary, these results suggest that cone beam optical CT polymer gel dosimetry could provide an efficient and economical method for 3D dose delivery verification.
Sci‐PM Sat ‐ 05: Differential absorption of radiochromic plastic dosimeter: Presage™
Authors: Jordan K , Adamovics J
Published: April 2013

Radiochromic plastics are a physically robust alternative to radiation sensitive hydrogels such as the polymerization gels (BANG®, PAG) and ferrous xylenol orange gels for 3D dosimetry. Plastics simplify optical computed tomography (CT) scanning by eliminating reflections and refraction at the optical interfaces associated with sample vessels. Presage™ is a patented radiochromic plastic based on the radiation‐induced conversion of the colourless dye precursor, luecomalachite green, into malachite green within a transparent solid, polyurethane. Since Presage™ is transparent, it is optimal for readout with fast broad beam (cone beam) optical CT scanners where scattering materials degrade quantitative transmission measurements. Differential absorption with multiple wavelengths can simplify optical CT scanning by eliminating pre‐irradiation scans. Fractionated irradiation of Presage™, to a maximum dose of 10 Gy, in 1 cm cuvettes demonstrates a linear response. Absorption spectrum recorded at 0 and 6 Gy demonstrate that optical CT scanning near 630 nm with reference scans near 520 nm or 700 nm are optimum for maximizing dynamic range. In the particular case of laser CT with He‐Ne lasers 633 and 543 nm provide the optimum scan wavelengths. Statement: J. Adamovics is President of Heuris Pharma LLC, and has a patent pending concerning Presage™.
Identification of PTC725, an Orally Bioavailable Small Molecule That Selectively Targets the Hepatitis C Virus NS4B Protein
Authors: Gu Zhengxian , Graci Jason D. , Lahser Frederick C. , Breslin Jamie J. , Jung Stephen P. , Crona James H. , McMonagle Patricia , Xia Ellen , Liu Shaotang , Karp Gary , Zhu Jin , Huang Song , Nomeir Amin , Weetall Marla , Almstead Neil G. , Peltz Stuart W. , Tong Xiao , Ralston Robert , Colacino Joseph M.
Published: April 2013

While new direct-acting antiviral agents for the treatment of chronic hepatitis C virus (HCV) infection have been approved, there is a continued need for novel antiviral agents that act on new targets and can be used in combination with current therapies to enhance efficacy and to restrict the emergence of drug-resistant viral variants. To this end, we have identified a novel class of small molecules, exemplified by PTC725, that target the nonstructural protein 4B (NS4B). PTC725 inhibited HCV 1b (Con1) replicons with a 50% effective concentration (EC
50
) of 1.7 nM and an EC
90
of 9.6 nM and demonstrated a >1,000-fold selectivity window with respect to cytotoxicity. The compounds were fully active against HCV replicon mutants that are resistant to inhibitors of NS3 protease and NS5B polymerase. Replicons selected for resistance to PTC725 harbored amino acid substitutions F98L/C and V105M in NS4B. Anti-replicon activity of PTC725 was additive to synergistic in combination with alpha interferon or with inhibitors of HCV protease and polymerase. Immunofluorescence microscopy demonstrated that neither the HCV inhibitors nor the F98C substitution altered the subcellular localization of NS4B or NS5A in replicon cells. Oral dosing of PTC725 showed a favorable pharmacokinetic profile with high liver and plasma exposure in mice and rats. Modeling of dosing regimens in humans indicates that a once-per-day or twice-per-day oral dosing regimen is feasible. Overall, the preclinical data support the development of PTC725 for use in the treatment of chronic HCV infection.
Candida glabrata Drug:H
+
Antiporter CgQdr2 Confers Imidazole Drug Resistance, Being Activated by Transcription Factor CgPdr1
Authors: Costa Catarina , Pires Carla , Cabrito Tânia R. , Renaudin Adeline , Ohno Michiyo , Chibana Hiroji , Sá-Correia Isabel , Teixeira Miguel C.
Published: April 2013

The widespread emergence of antifungal drug resistance poses a severe clinical problem. Though predicted to play a role in this phenomenon, the drug:H
+
antiporters (DHA) of the major facilitator superfamily have largely escaped characterization in pathogenic yeasts. This work describes the first DHA from the pathogenic yeast
Candida glabrata
reported to be involved in antifungal drug resistance, the
C. glabrata QDR2
(
CgQDR2
) gene (ORF
CAGL0G08624g
). The expression of
CgQDR2
in
C. glabrata
was found to confer resistance to the antifungal drugs miconazole, tioconazole, clotrimazole, and ketoconazole. By use of a green fluorescent protein (GFP) fusion, the CgQdr2 protein was found to be targeted to the plasma membrane in
C. glabrata
. In agreement with these observations,
CgQDR2
expression was found to decrease the intracellular accumulation of radiolabeled clotrimazole in
C. glabrata
and to play a role in the extrusion of this antifungal from preloaded cells. Interestingly, the functional heterologous expression of
CgQDR2
in the model yeast
Saccharomyces cerevisiae
further confirmed the role of this gene as a multidrug resistance determinant: its expression was able to complement the susceptibility phenotype exhibited by its
S. cerevisiae
homologue,
QDR2
, in the presence of imidazoles and of the antimalarial and antiarrhythmic drug quinidine. In contrast to the findings reported for Qdr2, CgQdr2 expression does not contribute to the ability of yeast to grow under K
+
-limiting conditions. Interestingly,
CgQDR2
transcript levels were seen to be upregulated in
C. glabrata
cells challenged with clotrimazole or quinidine. This upregulation was found to depend directly on the transcription factor CgPdr1, the major regulator of multidrug resistance in this pathogenic yeast, which has also been found to be a determinant of quinidine and clotrimazole resistance in
C. glabrata
.
Mapping and Regulation of Genes within Salmonella Pathogenicity Island 12 That Contribute to
In Vivo
Fitness of Salmonella enterica Serovar Typhimurium
Authors: Tomljenovic-Berube Ana M. , Henriksbo Brandyn , Porwollik Steffen , Cooper Colin A. , Tuinema Brian R. , McClelland Michael , Coombes Brian K.
Published: April 2013

Salmonella
pathogenicity island 12 (SPI-12) of
Salmonella enterica
serovar Typhimurium is a 15-kb region that encompasses genes
STM2230
to
STM2245
and encodes a remnant phage known to contribute to bacterial virulence. In mouse infection experiments and replication assays in macrophages, we demonstrated a role for four genes in SPI-12 for bacterial survival in the host. STM2239, a potential Q antiterminator, showed a prominent contribution to bacterial fitness. Transcriptional reporter experiments, quantitative reverse transcription-PCR (RT-PCR), and immunoblotting demonstrated that the virulence regulator SsrB and STM2239 contribute to transcriptional activation of genes in SPI-12. SsrB was found to indirectly regulate this locus by transcriptional read-through from the
sspH2
(
STM2241
) promoter. Chromatin immunoprecipitation showed that STM2239 copurified with the promoter regulating
STM2237
, suggesting that STM2239 may function as an antiterminator to activate adjacent genes. These results demonstrate that bacteriophage genes may be adapted by pathogenic bacteria to improve fitness in the host.
Aspirin treatment and risk of first incident cardiovascular diseases in patients with type 2 diabetes: an observational study from the Swedish National Diabetes Register
Authors: Ekström Nils , Cederholm Jan , Zethelius Björn , Eliasson Björn , Fhärm Eva , Rolandsson Olov , Miftaraj Mervete , Svensson Ann-Marie , Gudbjörnsdottir Soffia
Published: April 2013

Objectives

To investigate the benefits and risks associated with aspirin treatment in patients with type 2 diabetes and no previous cardiovascular disease (CVD) in clinical practice.

Design

Population-based cohort study between 2005 and 2009, mean follow-up 3.9 years.

Setting

Hospital outpatient clinics and primary care in Sweden.

Participants

Men and women with type 2 diabetes, free from CVD, including atrial fibrillation and congestive heart failure, at baseline, registered in the Swedish National Diabetes Register, with continuous low-dose aspirin treatment (n=4608) or no aspirin treatment (n=14 038).

Main outcome measures

Risks of CVD, coronary heart disease (CHD), stroke, mortality and bleedings, associated with aspirin compared with no aspirin, were analysed in all patients and in subgroups by gender and estimated cardiovascular risk. Propensity scores were used to adjust for several baseline risk factors and characteristics at Cox regression, and the effect of unknown covariates was evaluated in a sensitivity analysis.

Results

There was no association between aspirin use and beneficial effects on risks of CVD or death. Rather, there was an increased risk of non-fatal/fatal CHD associated with aspirin; HR 1.19 (95% CI 1.01 to 1.41), p=0.04. The increased risk of cardiovascular outcomes associated with aspirin was seen when analysing women separately; HR 1.41 (95% CI 1.07 to 1.87), p=0.02, and HR 1.28 (95% CI 1.01 to 1.61), p=0.04, for CHD and CVD, respectively, but not for men separately. There was a trend towards increased risk of a composite of bleedings associated with aspirin, n=157; HR 1.41 (95% CI 0.99 to 1.99).

Conclusions

The results support the trend towards more restrictive use of aspirin in patients with type 2 diabetes and no previous CVD. More research is needed to explore the differences in aspirin's effects in women and men.
Heterogeneity of characteristics, structure, and dynamics of male andhijrasex workers in selected cities of Pakistan
Authors: Thompson Laura H , Salim Momina , Baloch Chaker Riaz , Musa Nighat , Reza Tahira , Dar Nosheen , Arian Shahzad , Blanchard James F , Emmanuel Faran
Published: April 2013

Background

We sought to describe the characteristics and operational dynamics of male sex workers (MSW) andhijrasex workers (HSWs) in 11 cities across Pakistan in 2011.

Methods

We report descriptive statistics of self-reported sexual behaviour data from cross-sectional mapping and biological and behavioural surveys conducted among 1431 MSWs and 1415 HSWs in four cities across Pakistan in 2011.

Results

While Karachi had the largest numbers of MSWs and HSWs, Quetta had the largest relative population sizes, with 3.6 MSWs per 1000 male adults and 3.3 HSWs per 1000 male adults. There was considerable variability in the proportion of HSWs who operate throughderas, ranging from 2.2% in Peshawar to 62.7% in Karachi. The number of HSWs perguruvaries by city, from 1.5 in Quetta to 16.5 HSWs perguruin Karachi. Among HSWs, the use of mobile phones for solicitation ranged from 37.6% in Quetta to 83% in Peshawar and among MSWs the use of mobile phones ranged from 27% in Karachi to 52% in Quetta. In Quetta, a large proportion of HSWs (41%) find clients throughgurus. Client volume tended to be higher among HSWs and among both MSWs and HSWs in Quetta and Peshawar. Condom use with clients was most consistent in Quetta, with 31% of MSWs and 41% of HSWs reporting always using condoms with clients. Peshawar had the greatest proportion reporting never using condoms.

Conclusions

There is considerable geographic heterogeneity in the characteristics and operational dynamics of MSWs and HSWs across Pakistan.
A new rapid molecular point-of-care assay forTrichomonas vaginalis: preliminary performance data
Authors: Pearce David M , Styles David N , Hardick Justin P , Gaydos Charlotte A
Published: April 2013

Objective

Trichomonas vaginalisinfection is the most prevalent treatable sexually transmitted infection (STI) in the world. An accurate point-of-care (PoC) molecular test would enable patients to be tested and treated forT vaginalisin a single visit to the genitourinary medicine clinic, community STI clinic, pharmacy or doctor's office. In this report, we describe a rapid prototype assay forT vaginalisdesigned for use in conjunction with the Atlas io PoC platform, and initial verification of its performance using 90 clinical samples.

Methods

A rapid prototypeT vaginalisassay was designed. The test, featuring novel electrochemical end-point detection, used a multi-copy region of theT vaginalisgenome as the assay target. Ninety clinical vaginal swab samples were used to verify the performance of the prototype assay.

Results

The assay demonstrated a sensitivity and specificity of 95.5% (42/44) and 95.7% (44/46), respectively, when tested using clinical samples. Assay inclusivity was demonstrated for a number of geographically diverseT vaginalisisolates, and the test showed no cross-reactivity with either human DNA or a panel of DNAs isolated from common cross-reactants.

Conclusions

The sensitivity and specificity achieved using this prototype assay is comparable with that achieved for existing central laboratory nucleic acid amplification tests used for screening patients forT vaginalis.
Survival ofTrichomonas vaginalisin wet preparation and on wet mount
Authors: Stoner Kevin A , Rabe Lorna K , Meyn Leslie A , Hillier Sharon L
Published: April 2013

Objectives

Microscopy is an insensitive method for detection ofTrichomonas vaginalis, but is widely used because it is both rapid and inexpensive. Diagnosis of trichomoniasis by microscopy requires that motile forms be identified in vaginal fluid samples. However, microscopy cannot always be performed immediately after sample collection. The objective of this study was to assess the impact of sample storage at room temperature on trichomonad motility.

Methods

Vaginal swab samples from 77 women positive forT vaginalisinfection were collected to determine the impact of storage on wet preparations (swabs in plastic tubes with saline) and wet mounts (samples placed onto a glass slide with a coverslip). Samples were read at 400× every 30 min for the first hour and then once per hour thereafter until there were no motile trichomonads observed.

Results

For wet preparations, motility was 100% at 30 min, 99% at 60 min and decreased by 3%–15% each subsequent hour, with samples having a lower density of trichomonads losing motility more quickly. Trichomonad motility diminished more rapidly in wet mounts compared with wet preparations, with a 20% decrement in motility in 60 min.

Conclusions

These data suggest that vaginal fluid samples for diagnosis of trichomoniasis should be stored in saline rather than on microscope slides until they are examined under the microscope and samples should be evaluated by microscopy within an hour of collection. These findings also suggest that clinical sites which cannot perform microscopy within 1 h of sample collection should consider the use of other diagnostic tests.
Trichomoniasis and HIV interactions: a review
Authors: Kissinger Patricia , Adamski Alys
Published: April 2013

Objective

To discuss the epidemiology ofTrichomonas vaginalis(TV) and HIV co-infections, the role of TV in acquisition and transmission of HIV, special treatment considerations for TV among women with HIV and the prevention of TV among HIV-infected persons.

Design

Systematic review.

Data source

Review of literature of EMBASE and PubMed databases from January 1990 to February 2013. Search keywords included TV,HIV co-infections, HIV acquisition, HIV transmission, HIV shedding, TV treatment, HIV and couples studies.

Review method

We included studies of any design that contained the selected search words and were published during the specified time frame. We then searched the reference lists of included papers for additional papers and included these when relevant.

Results

There is strong evidence that TV increases both transmission and acquisition of HIV among women, and that successful treatment for TV can reduce HIV genital shedding. Single dose metronidazole (MTZ) should no longer be used for HIV+ women with TV given the high rates of asymptomatic bacterial vaginosis co-infections and other factors that may render MTZ less effective in HIV+ women. Prevention of TV among HIV+ persons is similar to among HIV, including promotion of condoms as well as regular screening and prompt treatment. There may be a role for expedited partner treatment for the prevention of repeat infections, but most repeat infections are clinical treatment failures. Diligence in screening and treating TV among both HIV- susceptible and HIV+ persons is an important public health strategy.
In vitro bactericidal activity of enrofloxacin againstgyrAmutant andqnr‐containingEscherichia coliisolates from animals
Authors: Cengiz M. , Sahinturk P. , Sonal S. , Buyukcangaz E. , Sen A. , Arslan E.
Published: April 2013

The objective of this work was to investigate the bactericidal activity of enrofloxacin againstgyrAmutant andqnr‐containingEscherichia coliisolates from animals. The minimum inhibitory concentrations (MICs) ofgyrAmutant andqnr‐containingE coliisolates ranged from 1 µg/ml to 32 µg/ml for enrofloxacin. Time‐kill experiments were performed using selectedE coliisolates. For the time‐kill experiments, the colony counts were determined by plating each diluted sample onto plate count agar and an integrated pharmacokinetic/pharmacodynamics area measure (log ratio area) was applied to the colony‐forming units (cfu) data. In general, enrofloxacin exhibited bactericidal activity against all thegyrAmutantE coliisolates at all concentrations greater than four times the MIC. However, the bactericidal activity of enrofloxacin for all theqnr‐containingE coliisolates was less dependent on concentration. The results of the present study indicated that the genetic mechanism of resistance might account for the different bactericidal activities of enrofloxacin observed for thegyrAmutant and theqnr‐containingE coliisolates. Therefore, in addition to MIC assays, genetic mechanism‐based pharmacodynamic models should be used to provide accurate predictions of the effects of drugs on resistant bacteria.