Evaluation of γ-H2AX foci distribution among different peripheral blood mononucleated cell subtypes.

INTRODUCTION: The detection of γ-H2AX foci in peripheral blood mononucleated cells (PBMCs) has been incorporated as an early assay for biological dosimetry. However, overdispersion in the γ-H2AX foci distribution is generally reported. In a previous study from our group, it was suggested that overdispersion could be caused by the fact that when evaluating PBMCs, different cell subtypes are analyzed, and that these could differ in their radiosensitivity. This would cause a mixture of different frequencies that would result in the overdispersion observed. OBJECTIVES: The objective of this study was to evaluate both the possible differences in the radiosensitivities of the different cell subtypes present in the PBMCs and to evaluate the distribution of γ-H2AX foci in each cell subtype. MATERIALS AND METHODS: Peripheral blood samples from three healthy donors were obtained and total PBMCs, and CD3+, CD4+, CD8+, CD19+, and CD56+ cells were separated. Cells were irradiated with 1 and 2 Gy and incubated at 37 °C for 1, 2, 4, and 24 h. Sham-irradiated cells were also analyzed. γ-H2AX foci were detected after immunofluorescence staining and analyzed automatically using a Metafer Scanning System. For each condition, 250 nuclei were considered. RESULTS: When the results from each donor were compared, no observable significant differences between donors were observed. When the different cell subtypes were compared, CD8+ cells showed the highest mean of γ-H2AX foci in all post-irradiation time points. The cell type that showed the lowest γ-H2AX foci frequency was CD56+. The frequencies observed in CD4+ and CD19+ cells fluctuated between CD8+ and CD56+ without any clear pattern. For all cell types evaluated, and at all post-irradiation times, overdispersion in γ-H2AX foci distribution was significant. Independent of the cell type evaluated the value of the variance was four times greater than that of the mean. CONCLUSION: Although different PBMC subsets studied showed different radiation sensitivity, these differences did not explain the overdispersion observed in the γ-H2AX foci distribution after exposure to IR.

Establishment and validation of surface model for biodosimetry based on γ-H2AX foci detection.

INTRODUCTION: In the event of a radiation accident detecting γ-H2AX foci is being accepted as fast method for triage and dose assessment. However, due to their disappearance kinetics, published calibrations have been constructed at specific post-irradiation times. OBJECTIVES: To develop a surface, or tridimensional, model to estimate doses at times not included in the calibration analysis, and to validate it. MATERIALS AND METHODS: Calibration data was obtained irradiating peripheral mononucleated cells from one donor with radiation doses ranging from 0 to 3 Gy, and γ -H2AX foci were detected microscopically using a semi-automatic method, at different post-irradiation times from 0.5 to 24 h. For validation, in addition to the above-mentioned donor, blood samples from another donor were also used. Validation was done within the range of doses and post-irradiation times used in the calibration. RESULTS: The calibration data clearly shows that at each analyzed time, the γ-H2AX foci frequency increases as dose increases, and for each dose this frequency decreases with post-irradiation time. The γ-H2AX foci nucleus distribution was clearly overdispersed, for this reason to obtain bidimensional and tridimensional dose-effect relationships no probability distribution was assumed, and linear and non-linear least squares weighted regression was used. In the two validation exercises for most evaluated samples, the 95% confidence limits of the estimated dose were between ±0.5 Gy of the real dose. No major differences were observed between donors. CONCLUSION: In case of a suspected overexposure to radiation, the surface model here presented allows a correct dose estimation using γ-H2AX foci as biomarker. The advantage of this surface model is that it can be used at any post-irradiation time, in our model between 0.5 and 24 h.

Charge Disproportionation Triggers Bipolar Doping in FeSb2- xSn xSe4 Ferromagnetic Semiconductors, Enabling a Temperature-Induced Lifshitz Transition.

Ferromagnetic semiconductors (FMSs) featuring a high Curie transition temperature ( Tc) and a strong correlation between itinerant carriers and localized magnetic moments are of tremendous importance for the development of practical spintronic devices. The realization of such materials hinges on the ability to generate and manipulate a high density of itinerant spin-polarized carriers and the understanding of their responses to external stimuli. In this study, we demonstrate the ability to tune magnetic ordering in the p-type FMS FeSb2- xSn xSe4 (0 ≤ x ≤ 0.20) through carrier density engineering. We found that the substitution of Sb by Sn FeSb2- xSn xSe4 increases the ordering of metal atoms within the selenium crystal lattice, leading to a large separation between magnetic centers. This results in a decrease in the Tc from 450 K for samples with x ≤ 0.05 to 325 K for samples with 0.05 < x ≤ 0.2. In addition, charge disproportionation arising from the substitution of Sb3+ by Sn2+ triggers the partial oxidation of Sb3+ to Sb5+, which is accompanied by the generation of both electrons and holes. This leads to a drastic decrease in the electrical resistivity and thermopower simultaneously with a large increase in the magnetic susceptibility and saturation magnetization upon increasing Sn content. The observed bipolar doping induces a very interesting temperature-induced quantum electronic transition (Lifshitz transition), which is manifested by the presence of an anomalous peak in the resistivity curve simultaneously with a reversal of the sign of a majority of the charge carriers from hole-like to electron-like at the temperature of maximum resistivity. This study suggests that while there is a strong correlation between the overall magnetic moment and free carrier spin in FeSb2- xSn xSe4 FMSs, the magnitude of the Curie temperature strongly depends on the spatial separation between localized magnetic centers rather than the concentration of magnetic atoms or the density of itinerant carriers.

Crystal Structure and Thermoelectric Properties of the 7,7L Lillianite Homologue Pb6Bi2Se9.

Pb6Bi2Se9, the selenium analogue of heyrovsyite, crystallizes in the orthorhombic space group Cmcm (#63) with a = 4.257(1) Å, b = 14.105(3) Å, and c = 32.412(7) Å at 300 K. Its crystal structure consists of two NaCl-type layers, A and B, with equal thickness, N1 = N2 = 7, where N is the number of edge-sharing [Pb/Bi]Se6 octahedra along the central diagonal. In the crystal structure, adjacent layers are arranged along the c-axis such that bridging bicapped trigonal prisms, PbSe8, are located on a pseudomirror plane parallel to (001). Therefore, Pb6Bi2Se9 corresponds to a 7,7L member of the lillianite homologous series. Electronic transport measurements indicate that the compound is a heavily doped narrow band gap n-type semiconductor, with electrical conductivity and thermopower values of 350 S/cm and -53 µV/K at 300 K. Interestingly, the compound exhibits a moderately low thermal conductivity, ∼1.1 W/mK, in the whole temperature range, owing to its complex crystal structure, which enables strong phonon scattering at the twin boundaries between adjacent NaCl-type layers A and B. The dimensionless figure of merit, ZT, increases with temperature to 0.25 at 673 K.

Management of sympathetic ophthalmia with the fluocinolone acetonide implant.

OBJECTIVE: We examined whether implantation of the fluocinolone acetonide (Retisert) implant achieved control of inflammation and a reduced need for oral corticosteroids or immunosuppressives in patients with sympathetic ophthalmia (SO). DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Eight patients with active SO. METHODS: The results of fluocinolone acetonide implantation in 8 patients with active SO were studied with a follow-up period of 6 months to 2 years. MAIN OUTCOME MEASURES: Presence or absence of intraocular inflammation, visual acuity, intraocular pressure, need for further surgery, and the need for additional use of oral or locally injected corticosteroids and/or immunosuppressives. RESULTS: All patients demonstrated a significant reduction in the systemic medication required to maintain control of inflammation. Two patients had recurrent inflammatory episodes requiring the resumption of an oral immunosuppressive. Vision improved or was stabilized in all 8 patients. CONCLUSIONS: The fluocinolone acetonide implant provides inflammatory control and reduces the dependence on systemic immunosuppression in patients with SO.

[Prevalence and general features of the metabolic syndrome in the Spanish hypertensive population]. / Prevalencia y características del síndrome metabólico en la población hipertensa española.

BACKGROUND AND OBJECTIVE: Metabolic syndrome (MS) constitutes a risk factor for the development of both type 2 diabetes and cardiovascular disease. The aim of the present study was to assess the prevalence and clinical characteristics of metabolic syndrome in a sample of the hypertensive population. PATIENTS AND METHOD: Cross-sectional epidemiological study in 19,039 hypertensive patients attended in primary care centres. MS was defined using the National Education Cholesterol Program (NCEP) and the International Diabetes Federation (IDF) criteria. RESULT: The 44.6% of patients presented MS using NCEP criteria. This proportion rose to 61.7% when IDF criteria were applied. Compared with hypertensives without MS, those who fulfilled criteria were significantly (p < 0.0001) older, more frequently women, had higher blood pressure values, a poorer blood pressure control (14.4% vs 27.8%) despite the use of more antihypertensive drugs, and suffered more frequently of cardiovascular disease. Other significant abnormalities included higher serum total cholesterol, uric acid, and a decreased estimated glomerular filtration rate. CONCLUSIONS: MS is present in almost half of an unselected hypertensive population (two thirds using the newest criteria). It is more frequent in women than in men and it is associated with mild abnormalities in renal function. MS patients are more refractory to antihypertensive treatment, even with a higher number of antihypertensive drugs.

Prevalencia y características del síndrome metabólico en la población hipertensa española / Prevalence and general features of the metabolic syndrome in the Spanish hypertensive population

Fundamento y objetivo: El síndrome metabólico (SM) incrementa el riesgo de enfermedad cardiovascular y de diabetes mellitus tipo 2. El objetivo del presente estudio ha sido examinar la prevalencia y las características diferenciales de los pacientes afectados de SM en la población hipertensa. Pacientes y método: Encuesta epidemiológica de una muestra de 19.039 hipertensos en atención primaria. Para la definición de SM se siguieron los criterios propuestos por el National Education Cholesterol Program (NCEP) y por la International Diabetes Federation (IDF). Resultado: El SM se diagnosticó en el 44,6% de los pacientes según los criterios del NCEP y en el 61,7%, según los criterios de la IDF. Comparados con los hipertensos no afectados de SM, los que tenían dicho síndrome presentaban de forma significativa (p < 0,0001) una mayor edad, mayor porcentaje de mujeres, cifras más elevadas de presión arterial, un peor control de ésta (el 14,4 frente al 27,8%) a pesar de la utilización de un mayor número de fármacos antihipertensivos y mayor prevalencia de complicaciones cardiovasculares. Igualmente se objetivaron en estos individuos cifras superiores de colesterol total, ácido úrico y un menor filtrado glomerular estimado. Conclusiones: El SM afecta a casi la mitad de la población hipertensa (hasta 2 terceras partes con los nuevos criterios). Existe un predominio del sexo femenino y se detectan alteraciones precoces de la función renal. Por lo que respecta a la hipertensión arterial, los pacientes con SM mantienen cifras de presión arterial superiores y un peor control de la presión a pesar del uso de un mayor número de fármacos antihipertensivos

Background and objective: Metabolic syndrome (MS) constitutes a risk factor for the development of both type 2 diabetes and cardiovascular disease. The aim of the present study was to assess the prevalence and clinical characteristics of metabolic syndrome in a sample of the hypertensive population. Patients and method: Cross-sectional epidemiological study in 19,039 hypertensive patients attended in primary care centres. MS was defined using the National Education Cholesterol Program (NCEP) and the International Diabetes Federation (IDF) criteria. Result: The 44.6% of patients presented MS using NCEP criteria. This proportion rose to 61.7% when IDF criteria were applied. Compared with hypertensives without MS, those who fulfilled criteria were significantly (p < 0.0001) older, more frequently women, had higher blood pressure values, a poorer blood pressure control (14.4% vs 27.8%) despite the use of more antihypertensive drugs, and suffered more frequently of cardiovascular disease. Other significant abnormalities included higher serum total cholesterol, uric acid, and a decreased estimated glomerular filtration rate. Conclusions: MS is present in almost half of an unselected hypertensive population (two thirds using the newest criteria). It is more frequent in women than in men and it is associated with mild abnormalities in renal function. MS patients are more refractory to antihypertensive treatment, even with a higher number of antihypertensive drugs

Quality of life in functional dyspepsia.

Our purpose was to assess the quality of life of functional dyspepsia patients using the SF-36 generic scale and the Gastrointestinal Symptoms Rating Scale (GSRS). In all, 328 dyspeptic patients were included in a multicenter, prospective, observational study. Both scales were filled out at baseline and one and three months after a prokinetic agent was given as a single-drug therapy. A total of 250 patients completed the study. An improvement in all SF-36 dimensions was observed, although the final scores were lower than the population reference values. Physical role (27% change), emotional role (20%), and physical pain (16%) dimensions showed the greater change. The GSRS total and domain scores also showed significant decreases. The best predictors of quality of life improvement were certain basal symptoms, drug compliance, and the absence of idiopathic dyspepsia. In conclusion, both the generic and the specific scales provide useful and sensitive measures of quality of life in functional dyspepsia patients on single-drug treatment.