Human ß2-defensin in oral lichen planus expresses the degree of inflammation.

Syndrome (BMS). Seventeen OLP patients, with a positive histopathologic diagnosis of the disease, were recruited into this study in order to measure the relative quantity of HBD-2 in their saliva and crevicular fluid. The values were compared with those collected from a group of 9 patients affected by the Burning Mouth Syndrome (BMS) and with a control group (CTRL) of 9 patients. There was no statistically significant difference between the groups (p=0.523; p=0.897). However, patients affected by OLP showed a dycotomic distribution of values: while 10 of them showed similar values to those found out in the other two groups, 7 patients expressed high levels of HBD-2 and 3500 pg/ml was the threshold to distinguish the subgroups. During the dental visit the clinician classified OLP patients into two groups according to the clinical presentation of the disease: reticular and hyperplastic (white OLP), atrophic and erosive forms (red OLP). There was a statistical significant correlation between the clinical and numeric classification of the patients (p=0.004; p=0.001), and the expression of HBD-2 was higher in the red OLP group than in the white OLP group (p=0.000; p=0.000). In conclusion, this study shows that HBD-2 represents an index to assess active inflammation and it is probably linked to the presence of the typical band-like CD8+ infiltrate in Oral Lichen Planus.

The risk of venous thromboembolism in renal cell carcinoma patients with residual tumor thrombus.

BACKGROUND: The clinical importance of tumor thrombus in patients with renal cell carcinoma is unknown. We sought to determine the long-term risk of venous thromboembolism (VTE) in patients with residual tumor thrombus postextraction, and to evaluate the impact of residual tumor thrombus on overall survival. PATIENTS/METHODS: A cohort study of patients with stage III-IV renal cell carcinoma undergoing nephrectomy was undertaken. The primary endpoint was the risk of VTE during a 2-year follow-up period. The secondary endpoint was 2-year overall survival. RESULTS: A total of 170 surgical renal cell carcinoma patients were included, 97 (57.1%) of whom had tumor thrombus. Patients with residual tumor thrombus following surgery had a higher risk of developing VTE than those with complete tumor thrombus resection (hazard ratio [HR] 8.7, 95% confidence interval [CI] 1.7-43.4) and no tumor thrombus (HR 6.5, 95% CI 1.7-24.7). Patient with residual tumor thrombus did not have worse overall survival than those with tumor thrombus completely resected or those without tumor thrombus. CONCLUSIONS: The presence of residual tumor thrombus is an important risk factor for VTE among renal cell carcinoma patients.

Increased risk of preoperative venous thromboembolism in patients with renal cell carcinoma and tumor thrombus.

BACKGROUND: The clinical impact of a tumor thrombus in renal cell carcinoma (RCC) patients awaiting radical nephrectomy and thrombectomy is unknown. OBJECTIVE: To determine the incidence of venous thromboembolism (VTE) in RCC patients with tumor thrombus prior to nephrectomy. PATIENTS AND METHODS: We conducted a retrospective cohort study including all late-stage (stage 3-4 excluding T1-2 N0M0) RCC patients who underwent radical nephrectomy at our institution between 1 January 2005 and 1 July 2012. Tumor thrombus was defined as the presence of an intraluminal filling defect in the renal vein, hepatic vein, portal vein, or inferior vena cava, directly extending from a renal mass detected on computed tomography. RESULTS: A total of 176 patients were included in the study. Fifty-three (30.1%) patients had tumor thrombus diagnosed on imaging Three patients with tumor thrombus (5.7%; 95% confidence interval [CI] 1.4-16.8) developed a VTE while awaiting radical nephrectomy, whereas none (0%; 95% CI 0-2.9) of the patients without a tumor thrombus had an event (P = 0.026). All three events were deep vein thrombosis. Times from tumor thrombus diagnosis to VTE were 5, 15 and 21 days. CONCLUSIONS: Tumor thrombus on imaging is a frequent finding among RCC patients awaiting nephrectomy. The presence of tumor thrombus in these patients increases the incidence of preoperative VTE.

Management of penoscrotal extramammary Paget disease: case series and review of the literature.

Extramammary Paget disease (empd) is a rare, slow-growing neoplasm, considered to be an adenocarcinoma of the apocrine glands. In men, the penoscrotal region is the most commonly affected area. The disease can present as carcinoma in situ or as invasive disease that can subsequently metastasize to lymph nodes and distant sites. Because of the rarity of empd, the medical literature available to guide management of the disease is limited, particularly in patients with metastases. In addition, metastatic disease may pose a diagnostic challenge, because invasive cancer of the genitourinary or gastrointestinal tract can occur in association with empd. In the present case series, we describe our experience in treating penoscrotal empd with multimodality therapy, and we review the existing literature concerning its diagnosis and management.

Incidence, consequences and treatment of bone metastases in breast cancer patients-Experience from a single cancer centre.

BACKGROUND: There is a paucity of literature about the benefits of bone-targeted agents for breast cancer patients with bone metastases treated in the non-trial setting. We explored the incidence, consequences, and treatment of bone metastases at a single cancer centre. METHODS: Electronic records of metastatic breast cancer patients were reviewed and pertinent information was extracted. RESULTS: Of 264 metastatic breast cancer patients, 195 (73%) developed bone metastases. Of these patients, 176 were eligible for analysis. Median age at bone metastases diagnosis was 56.9 years (IQR 48-67) and initial presentation of bone metastases included asymptomatic radiological findings (58%), bone pain (40%), or a SRE (12.5%). Most patients (88%) received a bone-targeted agent, starting a median of 1.5 months (IQR 0.8-3.30) after bone metastasis diagnosis. 62% of patients had ≥1 SRE. The median time from bone metastasis diagnosis to first SRE was 1.8 months (IQR 0.20-8.43 months). Median number of SREs per patient was 1.5 (IQR 0-3). Overall, 26.8% of all SREs were clinically asymptomatic. Within the entire cohort, 51% required opioids and 20% were hospitalized due to either an SRE or bone pain. CONCLUSIONS: Despite extensive use of bone-targeted agents, the incidence of SREs remains high. Nearly half of SREs occur prior to starting a bone-targeted agent. Use of opioids and hospitalizations secondary to bone metastases remain common. More effective treatment options are clearly needed.

Investigation of low-energy proton effects on aptamer performance for astrobiological applications.

Biochips are promising instruments for the search for organic molecules in planetary environments. Nucleic acid aptamers are powerful affinity receptors known for their high affinity and specificity, and therefore are of great interest for space biochip development. A wide variety of aptamers have already been selected toward targets of astrobiological interest (from amino acids to microorganisms). We present a first study to test the resistance of these receptors to the constraints of the space environment. The emphasis is on the effect of cosmic rays on the molecular recognition properties of DNA aptamers. Experiments on beam-line facilities have been conducted with 2 MeV protons and fluences much higher than expected for a typical mission to Mars. Our results show that this irradiation process did not affect the performances of DNA aptamers as molecular recognition tools.

Comparison of GEANT4 very low energy cross section models with experimental data in water.

PURPOSE: The GEANT4 general-purpose Monte Carlo simulation toolkit is able to simulate physical interaction processes of electrons, hydrogen and helium atoms with charge states (H0, H+) and (He0, He+, He2+), respectively, in liquid water, the main component of biological systems, down to the electron volt regime and the submicrometer scale, providing GEANT4 users with the so-called "GEANT4-DNA" physics models suitable for microdosimetry simulation applications. The corresponding software has been recently re-engineered in order to provide GEANT4 users with a coherent and unique approach to the simulation of electromagnetic interactions within the GEANT4 toolkit framework (since GEANT4 version 9.3 beta). This work presents a quantitative comparison of these physics models with a collection of experimental data in water collected from the literature. METHODS: An evaluation of the closeness between the total and differential cross section models available in the GEANT4 toolkit for microdosimetry and experimental reference data is performed using a dedicated statistical toolkit that includes the Kolmogorov-Smirnov statistical test. The authors used experimental data acquired in water vapor as direct measurements in the liquid phase are not yet available in the literature. Comparisons with several recommendations are also presented. RESULTS: The authors have assessed the compatibility of experimental data with GEANT4 microdosimetry models by means of quantitative methods. The results show that microdosimetric measurements in liquid water are necessary to assess quantitatively the validity of the software implementation for the liquid water phase. Nevertheless, a comparison with existing experimental data in water vapor provides a qualitative appreciation of the plausibility of the simulation models. The existing reference data themselves should undergo a critical interpretation and selection, as some of the series exhibit significant deviations from each other. CONCLUSIONS: The GEANT4-DNA physics models available in the GEANT4 toolkit have been compared in this article to available experimental data in the water vapor phase as well as to several published recommendations on the mass stopping power. These models represent a first step in the extension of the GEANT4 Monte Carlo toolkit to the simulation of biological effects of ionizing radiation.

Step-to-step reproducibility and asymmetry to study gait auto-optimization in healthy and cerebral palsied subjects.

OBJECTIVE: The purpose of our study was to compare plantar pressure asymmetry and step-to-step reproducibility in both able-bodied persons and two groups of hemiplegics. The relevance of the research was to determine the efficiency of asymmetry and reproducibility as indexes for diagnosis and rehabilitation processes. MATERIAL AND METHOD: This study comprised 31 healthy young subjects and 20 young subjects suffering from cerebral palsy hemiplegia assigned to two groups of 10 subjects according to the severity of their musculoskeletal disorders. The peaks of plantar pressure and the time to peak pressure were recorded with an in-shoe measurement system. The intra-individual coefficient of variability was calculated to indicate the consistency of plantar pressure during walking and to define gait stability. The effect size was computed to quantify the asymmetry and measurements were conducted at eight footprint locations. RESULTS: Results indicated few differences in step-to-step reproducibility between the healthy group and the less spastic group while the most affected group showed a more asymmetrical and unstable gait. CONCLUSION: From the concept of self-optimisation and depending on the neuromotor disorders the organism could make priorities based on pain, mobility, stability or energy expenditure to develop the best gait auto-optimisation.

Investigation of neutron radiation effects on polyclonal antibodies (IgG) and fluorescein dye for astrobiological applications.

Detecting life in the Solar System is one of the great challenges of new upcoming space missions. Biochips have been proposed as a way to detect organic matter on extraterrestrial objects. A biochip is a miniaturized device composed of biologically sensitive systems, such as antibodies, which are immobilized on a slide. In the case of in situ measurements, the main concern is to ensure the survival of the antibodies under space radiation. Our recent computing simulation of cosmic ray interactions with the martian environment shows that neutrons are one of the dominant species at soil level. Therefore, we have chosen, in a first approach, to study antibody resistance to neutrons by performing irradiation experiments at the Applications Interdisciplinaires des Faisceaux d'Ions en Région Aquitaine (AIFIRA) platform, a French ion beam facility at the Centre d'Etudes Nucléaires de Bordeaux-Gradignan in Bordeaux. Antibodies and fluorescent dyes, freeze-dried and in buffer solution, were irradiated with 0.6 MeV and 6 MeV neutrons. Sample analyses demonstrated that, in the conditions tested, antibody recognition capability and fluorescence dye intensity are not affected by the neutrons.

Monte Carlo simulation of the radiation environment encountered by a biochip during a space mission to Mars.

Simulations with a Monte Carlo tool kit have been performed to determine the radiation environment a specific device, called a biochip, would face if it were placed into a rover bound to explore Mars' surface. A biochip is a miniaturized device that can be used to detect organic molecules in situ. Its specific detection part is constituted of proteins whose behavior under cosmic radiation is completely unknown and must be investigated to ensure a good functioning of the device under space conditions. The aim of this study is to define particle species and energy ranges that could be relevant to investigate during experiments on irradiation beam facilities. Several primary particles have been considered for galactic cosmic ray (GCR) and solar energetic particle (SEP) contributions. Ionizing doses accumulated in the biochip and differential fluxes of protons, alphas, neutrons, gammas, and electrons have been established for both the Earth-Mars transit and the journey at Mars' surface. Neutrons and gammas appear as dominant species on martian soil, whereas protons dominate during the interplanetary travel. Depending on solar event occurrence during the mission, an ionizing dose of around a few Grays (1 Gy = 100 rad) is expected.

The effects of fatigue on plantar pressure distribution in walking.

The purpose of this study was to assess plantar pressure deviations due to fatigue. Plantar pressure was assessed using a portable system while eleven healthy subjects performed three walking tests, one before, one immediately after and another 30-min after intensive running. Pressure peak, intra-subject coefficient of variation and relative impulse were recorded. Significant decrease in pressure peak and the relative impulse under the heel and the midfoot along with significant increase in pressure peak and relative impulse under the forefoot were observed 30 min after the run. After a 30-min rest, the heel and forefoot loading remained significantly affected compared to the pre-test conditions while variability, step length and frequency remained unchanged. The study demonstrates short- and long-term plantar pressure deviations due to fatigue induced by an intensive 30-min run, while previous studies showed negligible deviation of the ground reaction force.

The toxic benthic dinoflagellate Ostreopsis ovata: quantification of proliferation along the coastline of Genoa, Italy.

Toxic harmful algal bloom (HAB) occurrence is becoming more frequent and problematic in highly urbanized coastal zones. In summer 2005 along the urbanized Genoa coastline (Ligurian Sea, North western Mediterranean Sea), local first aid stations treated about 200 people, who all showed similar symptoms following exposure to marine aerosols. The link with proliferation of Ostreopsis ovata was made, and it highlighted for the first time, the risks that benthic HABs may represent in highly urbanised temperate areas. Subsequently, a specific monitoring plan was designed and implemented in the same area in July 2006, before the first signs of Ostreopsis proliferation were detected. Here we report on this quantification of an Ostreopsis ovata bloom in the Ligurian Sea. Cells were quantified both in the water column and in the epiphytic community on macrophytes. Our results suggest a role of sea water temperature and weather conditions in favouring bloom development.

[Development and test of a new plantar pressure control device for foot unloading]. / Elaboration et validation d'un nouveau dispositif de surveillance des pressions plantaires: application à la décharge du pied.

OBJECTIVE: To validate a new plantar pressure control device able to detect excessive plantar pressure on-line and to improve the subject's awareness of the gait pattern in order to correct and optimize the load distribution patterns. The aim of this study was to verify the feasibility of a deliberate and partial unload of the first metatarsal head. MATERIAL AND METHOD: Eight healthy subjects were equipped with the plantar pressure sensors integrated in customized insoles. They were told to unload the first metatarsal head of the right foot by 5%. During the trials, the auditory and visual signals inform the subject of an excessive, insufficient or correct unload. RESULTS: Five subjects over eight succeeding in modifying significantly their gait pattern and in unloading by 5% the first metatarsal head. The unload is effective in 70.7% of the trials. However, the subjects were spontaneously inclined to reduce peak pressure under the first metatarsal head beyond the critical peak plantar pressure threshold (48.2% of the trials). DISCUSSION - CONCLUSION: The results showed the feasibility of a partial and deliberate foot unloading in using biofeedback device but emphasized the subject's difficulty to control a discriminated and accurate unload of the first metatarsal head. That points out the necessity of learning period. The baropodometric biofeedback rehabilitation focuses on the subject's capacities to modify its own locomotor pattern. It would be used as primary and secondary prevention means of diabetic foot ulceration.

Froude number fractions to increase walking pattern dynamic similarities: application to plantar pressure study in healthy subjects.

The purpose of this study was to determine if using similar walking velocities obtained from fractions of the Froude number (N(Fr)) and leg length can lead to kinematic and kinetic similarities and lower variability. Fifteen male subjects walked on a treadmill at 0.83 (VS(1)) and 1.16ms(-1) (VS(2)) and then at two similar velocities (V(Sim27) and V(Sim37)) determined from two fractions of the N(Fr) (0.27 and 0.37) so that the average group velocity remained unchanged in both conditions (VS(1)=V (Sim27)andVS(2)=V (Sim37)). N(Fr) can theoretically be used to determine walking velocities proportional to leg lengths and to establish dynamic similarities between subjects. This study represents the first attempt at using this approach to examine plantar pressure. The ankle and knee joint angles were studied in the sagittal plane and the plantar pressure distribution was assessed with an in-shoe measurement device. The similarity ratios were computed from anthropometric parameters and plantar pressure peaks. Dynamically similar conditions caused a 25% reduction in leg joint angles variation and a 10% significant decrease in dimensionless pressure peak variability on average of five footprint locations. It also lead to heel and under-midfoot pressure peaks proportional to body mass and to an increase in the number of under-forefoot plantar pressure peaks proportional to body mass and/or leg length. The use of walking velocities derived from N(Fr) allows kinematic and plantar pressure similarities between subjects to be observed and leads to a lower inter-subject variability. In-shoe pressure measurements have proven to be valuable for the understanding of lower extremity function. Set walking velocities used for clinical assessment mask the effects of body size and individual gait mechanics. The anthropometric scaling of walking velocities (fraction of N(Fr)) should improve identification of unique walking strategies and pathological foot functions.

In vitro percutaneous absorption and in vivo stratum corneum distribution of an organic and a mineral sunscreen.

Sunscreens, whose main function is to protect the skin against the harmful effects of solar irradiation, should remain at the skin surface or impregnate the first layers of the stratum corneum only and not penetrate into the underlying living tissue. The goal of this work was to assess the penetration of titanium dioxide (TiO(2)) and methylene bis-benzotriazoyl tetramethylbutylphenol (MBBT), included in a broad-spectrum sunscreen formulation, into human skin in vivo, using the tape stripping method, and in vitro, using a compartmental approach. An additional objective was to propose an easy and minimally invasive approach to determining the percutaneous uptake of sunscreens following topical application. TiO(2) and MBBT were quantified using colorimetric assay and HPLC analysis, respectively. The transmission electron microscopy and particle-induced X-ray emission techniques were used to localize the TiO(2) in skin sections. More than 90% of both sunscreens was recovered in the first 15 tape strippings. In addition we have shown that the remaining 10% did not penetrate the viable tissue, but was localized in the furrows and in the opened infundibulum. Less than 0.1% of MBBT was detected in the receptor medium, and no TiO(2) was detected in the follicle, viable epidermis or dermis. Thus, this in vivo and in vitro penetration study showed an absence of TiO(2) penetration into the viable skin layers through either transcorneal or transfollicular pathways and negligible transcutaneous absorption of MBBT. However, differences in distribution within the stratum corneum reinforced the need for a complementary approach, using minimally invasive in vivo methodology and in vitro compartmental analysis. This combination represents a well-adapted method for testing the safety of topically applied sunscreen formulations in real-life conditions.

An interdisciplinary approach to investigate the impact of cobalt in a human keratinocyte cell line.

Since in nuclear power plants, risks of skin contact contamination by radiocobalt are significant, we focused on the impact of cobalt on a human cutaneous cell line, i.e. HaCaT keratinocytes. The present paper reports an interdisciplinary approach aimed at clarifying the biochemical mechanisms of metabolism and toxicity of cobalt in HaCaT cells. Firstly, a brief overview of the used instrumental techniques is reported. The following parts present description and discussion of results concerning: (i) toxicological studies concerning cobalt impact towards HaCaT cells (ii) structural and speciation fundamental studies of cobalt-bioligand systems, through X-ray absorption spectroscopy (XAS), ab initio and thermodynamic modelling (iii) preliminary results regarding intracellular cobalt speciation in HaCaT cells using size exclusion chromatography/inductively coupled plasma-atomic emission spectroscopy (SEC/ICP-AES) and direct in situ analysis by ion beam micropobe analytical techniques.

[Parkinson gait analysis using in-shoe plantar pressure measurements]. / Analyse de la marche dans la maladie de Parkinson par enregistrement baropodométrique à l'aide de semelles embarquées.

INTRODUCTION: The literature reports some studies describing the walking pattern of patients with Parkinson's disease, its deterioration with disease severity and the effects of various treatments. Other studies concerned the plantar pressure distribution when walking. The aim of this study was to validate the use of baropodometric measurements for gait analysis of parkinsonian patients at various stages of disease severity and in on and off phases. METHODS: Fifteen normal control subjects and fifteen parkinsonian patients equipped with a plantar pressure measurement system performed walking tests. The parkinsonian patients performed the walking tests in off phase then in on phase. A clinical examination was performed to score the motor handicap on the UPDRS scale. RESULTS: Analysis of the plantar pressures of the parkinsonian subjects under various footprint areas detected significant baropodometric differences compared with controls, between groups with different UPDRS scores, and before and after L-Dopa treatment. CONCLUSIONS: Plantar pressures measurements allow a sufficiently fine discrimination for using it to detect parkinsonism and monitor patients with Parkinson's disease.