[the Modified Us7 Score In The Assessment Of Synovitis In Early Rheumatoid Arthritis].

To evaluate the modified US7 score (MUS7 score SYN) in the assessment of patients with early rheumatoid arthritis (ERA). In addition, dorsal and palmar recesses of the wrists as well as of small joints of the hands and feet were examined for the presence of synovitis by means of a global assessment of joints. The study sample comprised 32 patients treated for arthritis, with an average disease duration of 13 months. An ultrasound machine with high frequency transducer was used. Hands were also X-rayed and analysed by Larsen score. Out of the 832 examined joints, synovitis was detected in 173 (20,79%), tenosynovitis in 22 (4,91%), and erosions in 3 (1,56%). Synovitis was predominantly detected in the dorsal recess (73,38%) of MCP and PIP joints, when compared with palmar recess (26%). The presence of synovitis in the joints evaluated correlated with clinical (HAQ-DI, DAS28), laboratory (ACPA, RF, CRP), and ultrasound results (r = 0,37 to r = 0,42; p = 0,04 to p = 0,003). We found correlation of the MUS7 score SYN of the gray scale US or of the power Doppler US with DAS28 (PCR) values (r = 0,38; p = 0,0332), and with CRP results (r = 0,39; p = 0,0280), respectively. The dorsal recess, the wrist, and small joints can be considered as important sites to detect synovitis by the MUS7 score SYN in patients with ERA.

Assessment of ocular surface toxicity after topical instillation of nitric oxide donors

PURPOSE: To evaluate the ocular surface toxicity of two nitric oxide donors in ex vivo and in vivo animal models: S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylcysteine (SNAC) in a hydroxypropyl methylcellulose (HPMC) matrix at final concentrations 1.0 and 10.0 mM. METHODS: Ex vivo GSNO and SNAC toxicities were clinically and histologically analyzed using freshly excised pig eyeballs. In vivo experiments were performed with 20 albino rabbits which were randomized into 4 groups (5 animals each): Groups 1 and 2 received instillations of 150 µL of aqueous HPMC solution containing GSNO 1.0 and 10.0 mM, respectively, in one of the eyes; Groups 3 and 4 received instillations of 150 µL of aqueous HPMC solution-containing SNAC 1.0 and 10.0 mM, respectively, in one of the eyes. The contralateral eyes in each group received aqueous HPMC as a control. All animals underwent clinical evaluation on a slit lamp and the eyes were scored according to a modified Draize eye test and were histologically analyzed. RESULTS: Pig eyeballs showed no signs of perforation, erosion, corneal opacity or other gross damage. These findings were confirmed by histological analysis. There was no difference between control and treated rabbit eyes according to the Draize eye test score in all groups (p>0.05). All formulations showed a mean score under 1 and were classified as non-irritating. There was no evidence of tissue toxicity in the histological analysis in all animals. CONCLUSION: Aqueous HPMC solutions containing GSNO and SNAC at concentrations up to 10.0 mM do not induce ocular irritation.

In Vitro Antifungal Activity and Toxicity of Itraconazole in DMSA-PLGA Nanoparticles

Itraconazole (ITZ) is a drug used to treat various fungal infections and may cause side effects. The aim of this study was to develop and evaluate the in vitro activity of DMSA-PLGA nanoparticles loaded with ITZ against Paracoccidioides brasiliensis, as well as their cytotoxicity. Nanoparticles were prepared using the emulsification-evaporation technique and characterized by their encapsulation efficiency, morphology (TEM), size (Nanosight) and charge (zeta potential). Antifungal efficacy in P brasiliensis was determined by minimal inhibition concentration (MIC), and cytotoxicity using MU assay. ITZ was effectively incorporated in the PLGA-DMSA nanoparticles with a loading efficiency of 72.8 +/- 3.50%. The shape was round with a solid polymeric structure, and a size distribution of 174 +/- 86 nm (Average +/- SD). The particles were negatively charged. ITZ-NANO presented antifungal inhibition (MIC = 6.25 ug/mL) against P brasiliensis and showed lower in vitro cytotoxicity than free drug (ITZ).

Comparison of HRT-3 glaucoma probability score and subjective stereophotograph assessment for prediction of progression in glaucoma

PURPOSE. To assess whether baseline Glaucoma Probability Score (GPS; HRT-3; Heidelberg Engineering, Dossenheim, Germany) results are predictive of progression in patients with suspected glaucoma. The GPS is a new feature of the confocal scanning laser ophthalmoscope that generates an operator-independent, three-dimensional model of the optic nerve head and gives a score for the probability that this model is consistent with glaucomatous damage. METHODS. The study included 223 patients with suspected glaucoma during an average follow-up of 63.3 months. Included subjects had a suspect optic disc appearance and/or elevated intraocular pressure, but normal visual fields. Conversion was defined as development of either repeatable abnormal visual fields or glaucomatous deterioration in the appearance of the optic disc during the study period. The association between baseline GPS and conversion was investigated by Cox regression models. RESULTS. Fifty-four (24.2%) eyes converted. In multivariate models, both higher values of GPS global and subjective stereophotograph assessment ( larger cup-disc ratio and glaucomatous grading) were predictive of conversion: adjusted hazard ratios (95% CI): 1.31 (1.15 - 1.50) per 0.1 higher global GPS, 1.34 (1.12 - 1.62) per 0.1 higher CDR, and 2.34 (1.22 - 4.47) for abnormal grading, respectively. No significant differences ( P > 0.05 for all comparisons) were found between the c-index values ( equivalent to area under ROC curve) for the multivariate models (0.732, 0.705, and 0.699, respectively). CONCLUSIONS. GPS values were predictive of conversion in our population of patients with suspected glaucoma. Further, they performed as well as subjective assessment of the optic disc. These results suggest that GPS could potentially replace stereophotograph as a tool for estimating the likelihood of conversion to glaucoma.

Crotamine toxicity and efficacy in mouse models of melanoma

Objectives: Selective anticancer cell activity for both cell-penetrating and cationic antimicrobial peptides has previously been reported. As crotamine possesses activities similar to both of these, this study investigates crotamine`s anticancer toxicity in vitro and in vivo. Research design and methods: In vitro cancer cell viability was evaluated after treatment with 1 and 5 mu g/ml of crotamine. In vivo crotamine cytotoxic effects in C57Bl/6J mice bearing B16-F10 primary cutaneous melanoma were tested, with two groups each containing 35 mice. The crotamine-treated group received 1 mu g/day of crotamine per animal, subcutaneously which was well tolerated; the untreated group received a placebo. Results: Crotamine at 5 mu g/ml was lethal to B16-F10, Mia PaCa-2 and SK-Mel-28 cells and inoffensive to normal cells. In vivo crotamine treatment over 21 days significantly delayed tumor implantation, inhibited tumor growth and prolonged the lifespan of the mice. Mice in the crotamine-treated group survived at significantly higher rates (n = 30/35) than those in the untreated group (n = 7/35) (significance calculated with the Kaplan-Meier estimator). The average tumor weight in the untreated group was 4.60 g but was only about 0.27 g in the crotamine-treated mice, if detectable. Conclusions: These data warrant further exploration of crotamine as a tumor inhibition compound.

Caenorhabditis elegans mutants resistant to phosphine toxicity show increased longevity and cross-resistance to the synergistic action of oxygen

Phosphine (hydrogen phosphide, PH3) is the fumigant most widely used to protect stored products from pest infestation. Despite the importance of this chemical, little is known about its mode of action. We have created three phosphine-resistant lines (pre-1, pre-7, pre-33) in the model organism C. elegans, with LC50 values 2, 5, and 9 times greater than the fully susceptible parental strain. Molecular oxygen was shown to be an extremely effective synergist with phosphine as, under hyperoxic conditions, 100% mortality was observed in wild-type nematodes exposed to 0.1 mg/l phosphine, a nonlethal concentration in air. All three mutants were resistant to the synergistic effects of oxygen in proportion to their resistance to phosphine with one mutant, pre-33, showing complete resistance to this synergism. We take the proportionality of cross-resistance between phosphine and the synergistic effect of oxygen to imply that all three mutants circumvent a mechanism of phosphine toxicity that is directly coupled to oxygen metabolism. Compared with the wild-type strain, all three mutants have an extended average life expectancy of from 12.5 to 25.3%. This is consistent with the proposed involvement of oxidative stress in both phosphine toxicity and ageing. Because the wild-type and mutant nematodes develop at the same rate, the longevity is unlikely to be caused by a clk-type reduction in oxidative metabolism, a potential alternative mechanism of phosphine resistance.

Adrenocortical tumors: results of treatment and study of Weiss's score as a prognostic factor

PURPOSE: The differential diagnosis between benign and malignant adrenal cortical tumors circumscribed to the gland is controversial. One hundred and seven patients with adrenal cortex tumors (excluding those with primary hyperaldosteronism) were studied to assess the 5-year survival rate of adults, children, patients stratified by pathological stage, and patients stratified according to Weiss's score of <3 or >3. METHODS: The patients were evaluated both clinically and biochemically. One hundred and five patients underwent surgery and were classified pathologically as stages I, II, III, or IV. The tumors were weighed, measured, and classified according to Weiss's criteria and divided into 2 groups: <3 and >3. RESULTS: After 5 years, the survival rate was 77.5% for the whole group, 74.61% for the adults, 84.3% for the children, 100% for stage I, 83.9% for stage II, 33% for stage III, and 11.7% for stage IV groups. Additionally, after 5 years, 100% of the patients with tumors with Weiss's score <3 were alive compared to 61.65% of those with Weiss's score >3. The average weights of the tumors of score <3 and >3 were 23.38 g ± 41.36 g and 376.3 ± 538.76 g, respectively, which is a statistically significant difference. The average sizes of tumors of Weiss's score <3 and >3 were 3.67 ± 2.2 cm and 9.64 ± 5.8 cm, respectively, which is also a statistically significant difference. CONCLUSIONS: Weiss's score may be a good prognostic factor for tumors of the adrenal cortex. Additionally, there was a statistically significant difference between the average weight and size of tumors with benign behavior (Weiss's score <3) and those with malignant behavior (Weiss's score >3).

The Relationship between GRACE Score and Epicardial Fat Thickness in non-STEMI Patients

Abstract Background: GRACE risk score (GS) is a scoring system which has a prognostic significance in patients with non-ST segment elevation myocardial infarction (non-STEMI). Objective: The present study aimed to determine whether end-systolic or end-diastolic epicardial fat thickness (EFT) is more closely associated with high-risk non-STEMI patients according to the GS. Methods: We evaluated 207 patients who had non-STEMI beginning from October 2012 to February 2013, and 162 of them were included in the study (115 males, mean age: 66.6 ± 12.8 years). End-systolic and end-diastolic EFTs were measured with echocardiographic methods. Patients with high in-hospital GS were categorized as the H-GS group (in hospital GS > 140), while other patients were categorized as the low-to-moderate risk group (LM-GS). Results: Systolic and diastolic blood pressures of H-GS patients were lower than those of LM-GS patients, and the average heart rate was higher in this group. End-systolic EFT and end-diastolic EFT were significantly higher in the H-GS group. The echocardiographic assessment of right and left ventricles showed significantly decreased ejection fraction in both ventricles in the H-GS group. The highest correlation was found between GS and end-diastolic EFT (r = 0.438). Conclusion: End-systolic and end-diastolic EFTs were found to be increased in the H-GS group. However, end-diastolic EFT and GS had better correlation than end-systolic EFT and GS.

Individual versus standard quality of life assessment in a phase II clinical trial in mesothelioma patients: feasibility and responsiveness to clinical changes.

BACKGROUND: In patients with malignant pleural mesothelioma undergoing a multimodality therapy, treatment toxicity may outweigh the benefit of progression-free survival. The subjective experience across different treatment phases is an important clinical outcome. This study compares a standard with an individual quality of life (QoL) measure used in a multi-center phase II trial. PATIENTS AND METHODS: Sixty-one patients with stage I-III technically operable pleural mesothelioma were treated with preoperative chemotherapy, followed by pleuropneumonectomy and subsequent radiotherapy. QoL was assessed at baseline, at day 1 of cycle 3, and 1, 3 and 6 months post-surgery by using the Rotterdam Symptom Checklist (RSCL) and the Schedule for the Evaluation of Quality of Life-Direct Weighting (SEIQoL-DW), a measure that is based on five individually nominated and weighted QoL-domains. RESULTS: Completion rates were 98% (RSCL) and 92% (SEIQoL) at baseline and 98%/89% at cycle 3, respectively. Of the operated patients (N=45) RSCL and SEIQoL were available from 86%/72%, 93%/74%, and 94%/76% at months 1, 3, and 6 post-surgery. Average assessment time for the SEIQoL was 24min compared to 8min needed for the RSCL. Median changes from baseline indicate that both RSCL QoL overall score and SEIQoL index remained stable during chemotherapy with a clinically significant deterioration (change>or=8 points) 1 month after surgery (median change of -66 and -14 for RSCL and SEIQoL, respectively). RSCL QoL overall scores improved thereafter, but remained beneath baseline level until 6 months after surgery. SEIQoL scores improved to baseline-level at month 3 after surgery, but worsened again at month 6. RSCL QoL overall score and SEIQoL index were moderately correlated at baseline (r=.30; p<or=.05) and at 6-month follow-up (r=.42; p<or=.05) but not at the other time points. CONCLUSION: The SEIQoL assessment seems to be feasible within a phase II clinical trial, but may require more effort from staff. More distinctive QoL changes in accordance with clinical changes were measured with the RSCL. Our findings suggest that the two measures are not interchangeable: the RSCL is to favor when mainly information related to the course of disease- and treatment is of interest.

In-vitro cell exposure studies for the assessment of nanoparticle toxicity in the lung: a dialog between aerosol science and biology

The introduction of engineered nanostructured materials into a rapidly increasing number of industrial and consumer products will result in enhanced exposure to engineered nanoparticles. Workplace exposure has been identified as the most likely source of uncontrolled inhalation of engineered aerosolized nanoparticles, but release of engineered nanoparticles may occur at any stage of the lifecycle of (consumer) products. The dynamic development of nanomaterials with possibly unknown toxicological effects poses a challenge for the assessment of nanoparticle induced toxicity and safety.In this consensus document from a workshop on in-vitro cell systems for nanoparticle toxicity testing11Workshop on 'In-Vitro Exposure Studies for Toxicity Testing of Engineered Nanoparticles' sponsored by the Association for Aerosol Research (GAeF), 5-6 September 2009, Karlsruhe, Germany. an overview is given of the main issues concerning exposure to airborne nanoparticles, lung physiology, biological mechanisms of (adverse) action, in-vitro cell exposure systems, realistic tissue doses, risk assessment and social aspects of nanotechnology. The workshop participants recognized the large potential of in-vitro cell exposure systems for reliable, high-throughput screening of nanoparticle toxicity. For the investigation of lung toxicity, a strong preference was expressed for air-liquid interface (ALI) cell exposure systems (rather than submerged cell exposure systems) as they more closely resemble in-vivo conditions in the lungs and they allow for unaltered and dosimetrically accurate delivery of aerosolized nanoparticles to the cells. An important aspect, which is frequently overlooked, is the comparison of typically used in-vitro dose levels with realistic in-vivo nanoparticle doses in the lung. If we consider average ambient urban exposure and occupational exposure at 5mg/m3 (maximum level allowed by Occupational Safety and Health Administration (OSHA)) as the boundaries of human exposure, the corresponding upper-limit range of nanoparticle flux delivered to the lung tissue is 3×10-5-5×10-3μg/h/cm2 of lung tissue and 2-300particles/h/(epithelial) cell. This range can be easily matched and even exceeded by almost all currently available cell exposure systems.The consensus statement includes a set of recommendations for conducting in-vitro cell exposure studies with pulmonary cell systems and identifies urgent needs for future development. As these issues are crucial for the introduction of safe nanomaterials into the marketplace and the living environment, they deserve more attention and more interaction between biologists and aerosol scientists. The members of the workshop believe that further advances in in-vitro cell exposure studies would be greatly facilitated by a more active role of the aerosol scientists. The technical know-how for developing and running ALI in-vitro exposure systems is available in the aerosol community and at the same time biologists/toxicologists are required for proper assessment of the biological impact of nanoparticles.

A system to test the toxicity of brake wear particles

Fine particulate matter from traffic increases mortality and morbidity. An important source of traffic particles is brake wear. American studies reported cars to emit break wear particles at a rate of about 11mg/km to 20mg/km of driven distance. A German study estimated that break wear contributes about 12.5% to 21% of the total traffic particle emissions. The goal of this study was to build a system that allows the study of brake wear particle emissions during different braking behaviours of different car and brake types. The particles should be characterize in terms of size, number, metal, and elemental and organic carbon composition. In addition, the influence of different deceleration schemes on the particle composition and size distribution should be studied. Finally, this system should allow exposing human cell cultures to these particles. An exposure-box (0.25 cubic-m volume) was built that can be mounted around a car's braking system. This allows exposing cells to fresh brake wear particles. Concentrations of particle numbers, mass and surface, metals, and carbon compounds were quantified. Tests were conducted with A549 lung epithelial cells. Five different cars and two typical braking behaviours (full stop and normal deceleration) were tested. Particle number and size distribution was analysed for the first six minutes. In this time, two braking events occurred. Full stop produced significantly higher particle concentrations than normal deceleration (average of 23'000 vs. 10'400 #/cm3, p= 0.016). The particle number distribution was bi-modal with one peak at 60 to 100 nm (depending on the tested car and braking behaviour) and a second peak at 200 to 400 nm. Metal concentrations varied depending on the tested car type. Iron (range of 163 to 15'600 μg/m3) and Manganese (range of 0.9 to 135 μg/m3) were present in all samples, while Copper was absent in some samples (<6 to 1220 μg/m3). The overall "fleet" metal ratio was Fe:Cu:Mn = 128:14:1. Temperature and humidity varied little. A549-cells were successfully exposed in the various experimental settings and retained their viability. Culture supernatant was stored and cell culture samples were fixated to test for inflammatory response. Analysis of these samples is ongoing. The established system allowed testing brake wear particle emissions from real-world cars. The large variability of chemical composition and emitted amounts of brake wear particles between car models seems to be related to differences between brake pad compositions of different producers. Initial results suggest that the conditions inside the exposure box allow exposing human lung epithelial cells to freshly produced brake wear particles.

Trabecular bone score (TBS) the new parameter of 2D texture analysis for the evaluation of 3D bone micro architecture status

X-ray is a technology that is used for numerous applications in the medical field. The process of X-ray projection gives a 2-dimension (2D) grey-level texture from a 3- dimension (3D) object. Until now no clear demonstration or correlation has positioned the 2D texture analysis as a valid indirect evaluation of the 3D microarchitecture. TBS is a new texture parameter based on the measure of the experimental variogram. TBS evaluates the variation between 2D image grey-levels. The aim of this study was to evaluate existing correlations between 3D bone microarchitecture parameters - evaluated from μCT reconstructions - and the TBS value, calculated on 2D projected images. 30 dried human cadaveric vertebrae were acquired on a micro-scanner (eXplorer Locus, GE) at isotropic resolution of 93 μm. 3D vertebral body models were used. The following 3D microarchitecture parameters were used: Bone volume fraction (BV/TV), Trabecular thickness (TbTh), trabecular space (TbSp), trabecular number (TbN) and connectivity density (ConnD). 3D/2D projections has been done by taking into account the Beer-Lambert Law at X-ray energy of 50, 100, 150 KeV. TBS was assessed on 2D projected images. Correlations between TBS and the 3D microarchitecture parameters were evaluated using a linear regression analysis. Paired T-test is used to assess the X-ray energy effects on TBS. Multiple linear regressions (backward) were used to evaluate relationships between TBS and 3D microarchitecture parameters using a bootstrap process. BV/TV of the sample ranged from 18.5 to 37.6% with an average value at 28.8%. Correlations' analysis showedthat TBSwere strongly correlatedwith ConnD(0.856≤r≤0.862; p<0.001),with TbN (0.805≤r≤0.810; p<0.001) and negatively with TbSp (−0.714≤r≤−0.726; p<0.001), regardless X-ray energy. Results show that lower TBS values are related to "degraded" microarchitecture, with low ConnD, low TbN and a high TbSp. The opposite is also true. X-ray energy has no effect onTBS neither on the correlations betweenTBS and the 3Dmicroarchitecture parameters. In this study, we demonstrated that TBS was significantly correlated with 3D microarchitecture parameters ConnD and TbN, and negatively with TbSp, no matter what X-ray energy has been used. This article is part of a Special Issue entitled ECTS 2011. Disclosure of interest: None declared.

Fructose toxicity: is the science ready for public health actions?

PURPOSE OF REVIEW: The assumption that fructose may be toxic and involved in the pathogenesis of noncommunicable diseases such as obesity, diabetes mellitus, dyslipidemia, and even cancer has resulted in the call for public health action, such as introducing taxes on sweetened beverages. This review evaluates the scientific basis for such action. RECENT FINDINGS: Although some studies hint towards some potential adverse effects of excessive fructose consumption especially when combined with excess energy intake, the results from clinical trials do not support a significant detrimental effect of fructose on metabolic health when consumed as part of a weight-maintaining diet in amounts consistent with the average-estimated fructose consumption in Western countries. However, definitive studies are missing. SUMMARY: Public health policies to eliminate or limit fructose in the diet should be considered premature. Instead, efforts should be made to promote a healthy lifestyle that includes physical activity and nutritious foods while avoiding intake of excess calories until solid evidence to support action against fructose is available. Public health is almost certainly to benefit more from policies that are aimed at promoting what is known to be good than from policies that are prohibiting what is not (yet) known to be bad.

Nursing Activities Score: an updated guideline for its application in the Intensive Care Unit

ABSTRACT Objective To describe nursing workload in Intensive Care Units (ICU) in different countries according to the scores obtained with Nursing Activities Score (NAS) and to verify the agreement among countries on the NAS guideline interpretation. Method This cross-sectional study considered 1-day measure of NAS (November 2012) obtained from 758 patients in 19 ICUs of seven countries (Norway, the Netherlands, Spain, Poland, Egypt, Greece and Brazil). The Delphi technique was used in expertise meetings and consensus. Results The NAS score was 72.8% in average, ranging from 44.5% (Spain) to 101.8% (Norway). The mean NAS score from Poland, Greece and Egypt was 83.0%, 64.6% and 57.1%, respectively. The NAS score was similar in Brazil (54.0%) and in the Netherlands (51.0%). There were doubts in the understanding of five out 23 items of the NAS (21.7%) which were discussed until researchers’ consensus. Conclusion NAS score were different in the seven countries. Future studies must verify if the fine standardization of the guideline can have a impact on differences in the NAS results.

Prediction of myocardial infarction size using the SYNTAX score in patients treated with primary percutaneous coronary intervention for acute ST- segment elevation myocardial infarction

Objectives The relevance of the SYNTAX score for the particular case of patients with acute ST- segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI)  has previously only been studied in the setting of post hoc analysis of large prospective randomized clinical trials. A "real-life" population approach has never been explored before. The aim of this study was to evaluate the impact of the SYNTAX score for the prediction of the myocardial infarction size, estimated by the creatin-kinase (CK) peak value, using the SYNTAX score in patients treated with primary coronary intervention for acute ST-segment elevation myocardial infarction. Methods The primary endpoint of the study was myocardial infarction size as measured by the CK peak value. The SYNTAX score was calculated retrospectively in 253 consecutive patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) in a large tertiary referral center in Switzerland, between January 2009 and June 2010. Linear regression analysis was performed to compare myocardial infarction size with the SYNTAX score. This same endpoint was then stratified according to SYNTAX score tertiles: low <22 (n=178), intermediate [22-32] (n=60), and high >=33 (n=15). Results There were no significant differences in terms of clinical characteristics between the three groups. When stratified according to the SYNTAX score tertiles, average CK peak values of 1985 (low<22), 3336 (intermediate [22-32]) and 3684 (high>=33) were obtained with a p-value <0.0001. Bartlett's test for equal variances between the three groups was 9.999 (p-value <0.0067). A moderate Pearson product-moment correlation coefficient (r=0.4074) with a high statistical significance level (p-value <0.0001) was found. The coefficient of determination (R^2=0.1660) showed that approximately 17% of the variation of CK peak value (myocardial infarction size) could be explained by the SYNTAX score, i.e. by the coronary disease complexity. Conclusion In an all-comers population, the SYNTAX score is an additional tool in predicting myocardial infarction size in patients treated with primary percutaneous coronary intervention (PPCI). The stratification of patients in different risk groups according to SYNTAX enables to identify a high-risk population that may warrant particular patient care.