Environmental exposure to manganese and health risk assessment from personal sampling near an industrial source of airborne manganese.

Manganese (Mn), despite being a trace element necessary in small quantities for the correct functioning of the organism, at higher concentrations can induce health disorders, mainly in motor and cognitive functions, even at levels found in non-occupational environments. For this reason, US EPA guidelines define safe reference doses/concentrations (RfD/RfC) for health. In this study, the individualised health risk of exposure to Mn through different media (air, diet, soil) and routes of entry into the organism (inhalation, ingestion and dermal absorption) was assessed according to the procedure defined by the US EPA. Calculations related to Mn present in ambient air were made on the basis of data obtained from size-segregated particulate matter (PM) personal samplers carried by volunteers recruited in a cross-sectional study conducted in the Santander Bay (northern Spain), where an industrial source of airborne Mn is located. Individuals residing in the vicinity of the main Mn source (within 1.5 km) were found to have a hazard index (HI) higher than 1, indicating that there is a potential risk for these subjects to develop health alterations. Also, people living in Santander, the capital of the region, located 7-10 km from the Mn source, may have some risk (HI > 1) under some wind conditions (SW). In addition, a preliminary study of media and routes of entry into the body confirmed that inhalation of PM2.5-bound Mn is the most important route contributing to the overall non-carcinogenic health risk related to environmental Mn.

Short- and long-term exposure to trace metal(loid)s from the production of ferromanganese alloys by personal sampling and biomarkers.

The environmental exposure to trace metal(loid)s (As, Cd, Cu, Fe, Mn, Pb, and Zn) was assessed near a ferromanganese alloy plant using filters from personal particulate matter (PM) samplers (bioaccessible and non-bioaccessible fine and coarse fractions) and whole blood as short-term exposure markers, and scalp hair and fingernails as long-term biomarkers, collected from volunteers (n = 130) living in Santander Bay (northern Spain). Bioaccessible and non-bioaccessible metal(loid) concentrations in coarse and fine PM from personal samplers were determined by ICP-MS after extraction/digestion. Metal(loid) concentration in biomarkers was measured after alkaline dilution (whole blood) and acid digestion (fingernails and scalp hair) by ICP-MS as well. Results were discussed in terms of exposure, considering the distance to the main Mn source, and sex. In terms of exposure, significant differences were found for Mn in all the studied fractions of PM, As in whole blood, Mn and Cu in scalp hair and Mn and Pb in fingernails, with all concentrations being higher for those living closer to the Mn source, with the exception of Cu in scalp hair. Furthermore, the analysis of the correlation between Mn levels in the studied biomarkers and the wind-weighted distance to the main source of Mn allows us to conclude that scalp hair and mainly fingernails are appropriate biomarkers of long-term airborne Mn exposure. This was also confirmed by the significant positive correlations between scalp hair Mn and bioaccessible Mn in coarse and fine fractions, and between fingernails Mn and all PM fractions. This implies that people living closer to a ferromanganese alloy plant are exposed to higher levels of airborne metal(loid)s, mainly Mn, leading to higher levels of this metal in scalp hair and fingernails, which according to the literature, might affect some neurological outcomes. According to sex, significant differences were observed for Fe, Cu and Pb in whole blood, with higher concentrations of Fe and Pb in males, and higher levels of Cu in females; and for Mn, Cu, Zn, Cd and Pb in scalp hair, with higher concentrations in males for all metal(loid)s except Cu.

Empirical monotherapy with meropenem or combination therapy: the microbiological point of view.

The increase in the number of clinical isolates of multiresistant Enterobacteriaceae and Pseudomonas aeruginosa raises problems in decision-making on empirical treatments for severe Gram-negative bacilli-associated infections. The aim of our study is to determine the resistance of meropenem in our setting and the co-resistance of a combination of this compound with two antibiotics from different families: amikacin and ciprofloxacin. Between 2009 and 2013, a total of 81,310 clinical isolates belonging to the main species of Enterobacteriaceae and 39,191 clinical isolates of P. aeruginosa isolated in 28 hospitals in the Valencian Community on the South East Mediterranean Coast of Spain were analyzed using data provided by RedMiva (microbiological surveillance network of the Valencian Community). Meropenem resistance in Enterobacteriaceae increased from 0.16 % in 2009 to 1.25 % in 2013. Very few Enterobacteriaceae strains resistant to meropenem were sensitive to ciprofloxacin; in contrast, the combination of meropenem and amikacin led to a marked decrease in the risk of the microorganisms being resistant to both drugs (RR = 34 in 2013). In the case of P. aeruginosa, meropenem resistance also increased (from 14.32 % in 2009 to 24.52 % in 2013). Most meropenem-resistant P. aeruginosa isolates were also resistant to fluoroquinolones. However, the addition of amikacin led to a more than three-fold decrease in the risk of resistance. In our setting, empirical treatment with meropenem is adequate in enterobacterial infections, but poses difficulties when infection due to P. aeruginosa is suspected, in which case a combination of meropenem and amikacin has been shown to have a higher microbiological success rate.

Kinetics of ascorbate and dithiothreitol oxidation by soluble copper, iron, and manganese, and 1,4-naphthoquinone: Influence of the species concentration and the type of fluid.

An alternative metric to account for particulate matter (PM) composition-based toxicity is the ability of PM-species to generate reactive oxygen species (ROS) and deplete antioxidants, the so-called oxidative potential (OP). Acellular OP assays are the most used worldwide, mainly those based on ascorbic acid (AA) and dithiothreitol (DTT) depletion; OP values are calculated from AA/DTT concentration over time kinetic curves. Since a great variability in OP-DTT and OP-AA values can be found in the literature, the understanding of those factors affecting the kinetic rate of AA and DTT oxidation in the presence of PM-bound species will improve the interpretation of OP values. In this work, a kinetic study of the oxidation rate of AA and DTT driven by species usually found in PM (transition metals and naphthoquinone (NQ)) was carried out. In particular, the influence of the concentration of Cu(II), Fe(II), Fe(III), Mn(II), Mn(III), and 1,4-NQ, and the type of fluid used in the assay (phosphate buffer (PB), phosphate buffer saline (PBS) and artificial lysosomal fluid (ALF)) is analysed and discussed. The reaction orders with respect to the AA/DTT and the active compound, and the kinetic rate constants were also determined. The results show great variability in OP values among the studied species depending on the fluid used; the OP values were mostly higher in PB0.05 M, followed by PBS1x and ALF. Moreover, different species concentration-responses for OP-DTT/OP-AA were obtained. These differences were explained by the different reaction orders and kinetic rate constants obtained for each active compound in each fluid.

Association between ERCC1 and XPA expression and polymorphisms and the response to cisplatin in testicular germ cell tumours.

BACKGROUND: Cisplatin cures over 80% of testicular germ cell tumours (TGCTs), and nucleotide-excision repair (NER) modifies the sensitivity to cisplatin. We explored the association between NER proteins and their polymorphisms with cisplatin sensitivity (CPS) and overall survival (OS) of patients with non-seminomatous (ns)-TGCTs. METHODS: The expression of ERCC1 and XPA and the presence of γH2AX were evaluated in cancer cell lines and in fresh ns-TGCTs. The ERCC1 protein was also determined in ns-TGCTs. The differences between CPS and non-CPS cell lines and patients were analysed by Student's t- or χ(2)-tests. The differences in OS were analysed using the log-rank test, and the hazard ratios (HRs) were calculated using the Cox model. RESULTS: High ERCC1 expression was observed in the non-CPS cells, and both ERCC1 and γH2AX expressions were augmented after cisplatin treatment. Increased ERCC1 expression was also identified in non-CPS patients. Neither polymorphism was associated with either CPS or OS. The presence of ERCC1 was associated with non-CPS (P=0.05) and adjusted in the prognosis groups. The HR in ERCC1-negative and non-CPS patients was >14.43, and in ERCC1-positive and non-CPS patients the HR was >11.86 (P<0.001). CONCLUSIONS: High levels of ERCC1 were associated with non-CPS, suggesting that ERCC1 could be used as a potential indicator of the response to cisplatin and prognosis in ns-TGCTs.

Experimental determination of Gd dose enhancement and Gd dose sparing by 192Ir brachytherapy source with Gafchromic EBT3 dosimeter.

This work evaluates experimentally the dose enhancement factor (DEF) and dose sparing factor (DSF) due to radiation self-shielding, produced by Gd infused in tumor phantom irradiated with brachytherapy HDR 192Ir source by Gafchromic EBT3 dosimeter. The phantom was made of a set of solid water slabs (30 × 30 × 1.0) cm3 and three acrylic slabs of (30 × 30 × 0.5) cm3 machined to contain in the central axis acrylics vials of (1 × 1 × 5) cm3. The first and second acrylic vials were filled with an identical Gd solution of 0, 10 and 20 mg/ml, simulating Gd-doped and undoped tumor, and the third vial was filled in all the measurement only with water, representing an organ at risk. Additional solid water slabs were used to complete a phantom of (30 × 30 × 16) cm3. In the phantom center an acrylic slab was machined to introduce the 2.5 mm flexible guide tube of GammaMed plus iX equipment and positioning the 192Ir source in the phantom central part. EBT3 fragments of (0.9 × 4) cm2 were placed on the inner edge of the second and third vials to measure dose enhancement and dose sparing simultaneously. Phantom CT images were acquired for planning and to prescribe a dose of 6.0 Gy at 2.0 cm of the source, achieving an isodose curve of 44.5% at 3.0 cm (positions of the EBT3 films). Additionally, Monte Carlo simulation of the identical experimental setup was implemented to compare measurement values. The results showed the feasibility of measuring a DEF of 1.15 ± 0.05 in 20 mg/ml of Gd concentration consistent with the Monte Carlo DEF of 1.112 ± 0.005 for the same concentration. DEF value for concentration of 10 mg/ml would not be detected (1.00 ± 0.04) by an expected under measurement of the EBT3 films associated with the non-detection of photoelectrons and Auger electrons of very low energy that cannot reach the radiosensitive substrate.

Understanding how methodological aspects affect the release of trace metal(loid)s from urban dust in inhalation bioaccessibility tests.

The bioaccessibility of metal(loid)s in ambient particulate matter (PM) has been recently used to represent the risk of inhalation exposure. Nevertheless, different methodological factors affect the bioaccessibility values; among these, the type and composition of surrogate biological fluids and the liquid to solid ratio have been revealed to be the most important. To better understand how these methodological aspects affect the bioaccessibility, a reference material corresponding to urban dust (SRM1648a) was contacted with synthetic biological fluids commonly used in the literature representing surrogate fluids that may interact with fine (Gamble's solutions, artificial lysosomal fluid (ALF)) and coarse particles (gastric fluid), for liquid to solid (L/S) ratios ranging from 500 to 20,000. Visual MINTEQ 3.1. was used to enhance the discussion on how the solubility of metals in the leaching solution depends on the composition of the simulated fluids and the speciation of metals. The results obtained indicate that a small change in the composition of Gamble's solution (the presence of glycine) may increase significantly the bioaccessibility at a L/S ratio of 5,000. The highest bioaccessibility of most of the studied metal(loid)s at a L/S ratio of 5,000 was found for ALF fluid. The study of the effect of the L/S ratio showed that metal(loid)s bioaccessibility in Gamble's fluid increased logarithmically with increasing L/S ratio, while it remained practically constant in ALF and gastric fluid. This different behavior is explained assuming that the leaching of metal(loid)s in Gamble's solution is solubility-controlled, while in ALF and gastric fluid is availability-controlled.

Fricke gel xylenol orange dosimeter layers for stereotactic radiosurgery: A preliminary approach.

Investigations regarding the feasibility, reliability, and accuracy of Fricke gel dosimeter layers for stereotactic radiosurgery are presented. A representative radiosurgery plan consisting of two targets has been investigated. Absorbed dose distributions measured using radiochromic films and gelatin Fricke Gel dosimetry in layers have been compared with dose distributions calculated by using a treatment planning system and Monte Carlo simulations. The different dose distributions have been compared by means of the gamma index demonstrating that gelatin Fricke gel dosimeter layers showed agreements of 100%, 100%, and 93%, with dose and distance tolerances of 2% and 2 mm, with respect to film dosimetry, treatment planning system and Monte Carlo simulations, respectively. The capability of the developed system for three-dimensional dose mapping was shown, obtaining promising results when compared with well-established dosimetry methods. The obtained results support the viability of Fricke gel dosimeter layers analyzed by optical methods for stereotactic radiosurgery.

Monte Carlo evaluation of the dose sparing and dose enhancement by combination of Gd-infused tumor and 241Am source for an endocavitary brachytherapy geometry.

In this work, the benefits in terms of dose enhancement and dose sparing via radiation shielding are evaluated, for a combined irradiation scheme with sources of 241Am and tumor-infused with Gd agents, regarding conventional 192Ir treatment. Monte Carlo simulations using PENELOPE code were implemented for endocavitary brachytherapy geometries, configuring a pelvis phantom of 15 cm radius and 30 cm length. Inside, it was defined cylindrical tumor phantoms of 2 cm radius and 4 cm-6 cm length (simulating initial stages) as well as tumors of extensive volume (2.5 and 3.0 cm radius) and difficult coverage. Tumor phantoms were doped with 68 mM and 138 mM of Gd in order to assess the effects of enhancement and protection based on the concentration and emission energy of the isotope. Obtained results for the first tumor group, shown the feasibility of achieving dose enhancements of 94.3%-117% and 160%-194% for 68 mM and 138 mM of Gd infused into the tumor and irradiation with 241Am, respectively. Similarly, reduced dose enhancements of 3.5-5.7% y 8.9%-11.2% for 68 mM and 138 mM of Gd are attained with 192Ir. In terms of dose sparing outer the tumor, the radiation shielding and dose enhancement allowed a higher reduction in the dose by 241Am of 17%-24% for 68 mM and 21%-32% for 138 mM of Gd, and non-negligible dose sparing are produced too by 192Ir of 2% and 5% for the same concentration of Gd. For the second tumors group, the combined use of 241Am and Gd agents simultaneously allowed to improve coverage and reduce the healthy tissue dose, showing the obtained results the possibility of achieving coverage of 95% of the prescribed dose in 100% of tumor volume together with dose sparing factor of 6-21% reduction in isodose of the studied point and dose enhancements of 75%-158% at the prescription point.

Prognostic value of plasma pentraxin 3 levels in patients with septic shock admitted to intensive care.

OBJECTIVE: To evaluate the usefulness of a new marker, pentraxin, as a prognostic marker in septic shock patients. MATERIALS AND METHODS: Single-centre prospective observational study that included all consecutive patients 18 years or older who were admitted to the intensive care unit (ICU) with septic shock. Serum levels of procalcitonin (PCT), C-reactive protein (CRP) and pentraxin (PTX3) were measured on ICU admission. RESULTS: Seventy-five septic shock patients were included in the study. The best predictors of in-hospital mortality were the severity scores: SAPS II (AUC = 0.81), SOFA (AUC = 0.79) and APACHE II (AUC = 0.73). The ROC curve for PTX3 (ng/mL) yielded an AUC of 0.70, higher than the AUC for PCT (0.43) and CRP (0.48), but lower than lactate (0.79). Adding PTX3 to the logistic model increased the predictive capacity in relation to SAPS II, SOFA and APACHE II for in-hospital mortality (AUC 0.814, 0.795, and 0.741, respectively). In crude regression models, significant associations were found between in-hospital mortality and PTX3. This positive association increased after adjusting for age, sex and immunosuppression: adjusted OR T3 for PTX3 = 7.83, 95% CI 1.35-45.49, linear P trend = 0.024. CONCLUSION: Our results support the prognostic value of a single determination of plasma PTX3 as a predictor of hospital mortality in septic shock patients.

Etiology of bloodstream infections at a population level during 2013-2017 in the Autonomous Community of Valencia, Spain.

OBJECTIVE: Bloodstream Infections has become in one of the priorities for the antimicrobial stewardship teams due to their high mortality and morbidity rates. Usually, the first antibiotic treatment for this pathology must be empirical, without microbiology data about the microorganism involved. For this reason, the population studies about the etiology of bacteremia are a key factor to improve the selection of the empirical treatment, because they describe the main microorganisms associated to this pathology in each area, and this data could facilitate the selection of correct antibiotic therapy. METHODS: This study describes the etiology of bloodstream infections in the Southeast of Spain. The etiology of bacteremia was analysed by a retrospective review of all age-ranged patients from every public hospital in the Autonomous Community of Valencia (approximately 5,000,000 inhabitants) for five years. RESULTS: A total of 92,097 isolates were obtained, 44.5% of them were coagulase-negative staphylococci. Enterobacteriales was the most prevalent group and an increase in frequency was observed along the time. Streptococcus spp. were the second microorganisms more frequently isolated. Next, the most prevalent were Staphylococcus aureus and Enterococcus spp., both with a stable incidence along the study. Finally, Pseudomonas aeruginosa was the fifth microorganism more frequently solated. CONCLUSIONS: These data constitute a useful tool that can help in the choice of empirical treatment for bloodstream infections, since the knowledge of local epidemiology is key to prescribe a fast and appropriate antibiotic therapy, aspect capital to improve survival.

Fosfomycin in a single dose versus a 7-day course of amoxicillin-clavulanate for the treatment of asymptomatic bacteriuria during pregnancy.

The purpose of this paper was to compare the efficacy of a single dose of 3 g of fosfomycin to that of a 7-day regimen of amoxicillin-clavulanate in the treatment of asymptomatic bacteriuria during pregnancy. A randomised, prospective, interventional, analytical, longitudinal study was undertaken, in which the efficacy of two antibiotic regimens (one short and the other long) in the treatment of pregnant women with asymptomatic bacteriuria is compared. One hundred and nine patients were randomly assigned to two groups: 56 were treated with amoxicillin-clavulanate and 53 with fosfomycin. The two groups were similar in terms of co-morbidity, treatments received during pregnancy, obstetric, gynaecological and surgical history and laboratory data. The efficacy of the two regimens was similar and the eradication rate was over 80% in both groups (P = 0.720) (relative risk [RR] 1.195, 95% confidence interval [CI]: 0.451-3.165). The number of reinfections was greater in the amoxicillin-clavulanate group (P = 0.045). The secondary effects were lower in the fosfomycin group (P = 0.008). There were no significant differences in the number of persistences (P = 0.39), development of symptomatic urinary infections (P = 0.319) or recurrences (P = 0.96). Treatment with a single dose of fosfomycin is as effective as the standard course of treatment with amoxicillin-clavulanate and may be preferable due to its simpler administration and the smaller number of reinfections.

Experimental determination of the gadolinium dose enhancement in phantom irradiated with low energy X-ray sources by a spectrophotometer -Gafchromic-EBT3 dosimetry system.

This work reports the experimental determination of dose enhancement produced in phantoms containing target volumes doped with Gadolinium and irradiated with low-energy X-ray beams. EBT3 Gafchromic films were immersed into 5 ml target volumes to simulate tumor filling with 100% ultra-pure water (blank sample) and ultra-pure water infused with Gd solution (Omniscan®) in different concentration (9-24 mg/ml). The dose enhancement due to excitation of Gd K-edge (50.2 keV) was evaluated in terms of the increment in optical density, obtained by a Spectrophotometer-Gafchromic-EBT3 dosimetry system calibrated in terms of the dose-response for 1-8 Gy range. The dose enhancement was evaluated in two condition: a beam quality with spectrum above the absorption edge in a medium with and without Gd; and two beam qualities (above and below the absorption edge) in a medium with a fixed Gd concentration (18 mg/ml). The obtained results confirmed increments in relative dose enhancement according to Gd concentrations up to 18 mg/ml, with a dose enhancement of 1.1 Gy and an average percentage enhancement of 28.4%. For higher values of concentration, the attenuation interaction of the primary beam is more relevant instead of dose enhancement process. On the other hand, the dose enhancement obtained to comparison the spectra above and below the absorption edge, shown results up to 3.3 Gy of enhancement and average percentage enhancement of 88%.

A high-sensitivity and low dose energy-dispersive X-ray fluorescence system for identification of gadolium accumulations in planar X-ray fluorescence images.

A new technique, based on in-vivo energy dispersive X-ray fluorescence (EDXRF), has been developed to gadolinium (Gd) concentrations identification in planar X-ray fluorescence (XRF) images. Higher signal-to-noise (SNR) ratios while keeping a low radiation dose were achieved. Experimental validation was performed using tissue equivalent phantoms under two different data acquisition criteria. The first criteria consisted on acquiring the energy spectra from different experimental narrow spectrum beam (FWHM = 2.5 keV) with peak central energy above the L edge energy and determining the spectrum which producing Lowest-Limit-of-Detection (Lowest-LoD) for a specific acquisition time. This also provided the minimum dose expected under the condition of minimum irradiation time. The second criteria consisted on measuring the surface dose required to obtain a specific LoD by different narrow spectrum beam, providing the Lowest-Dose setting. Surface (2D) Gd-doped tissue-equivalent phantoms scanning were performed according to optimized scenarios: Lowest-LoD setting (obtaining to central energy of 10.9 keV) and Lowest-Dose setting (obtaining to central energy 12.9 keV). 625 pixel images were acquired in two different conditions: a pre-defined time (5 s) per pixel was set in the first approach, whereas a pre-defined total surface dose (4 mGy) was set to the second approach. According to the results obtained for the first approach, a 58 times reduction was observed when comparing SNR between the Lowest-LoD and Lowest-Dose settings. On the other hand, for the second approach pre-defining total dose during the whole examination, the best SNR was obtained for the Lowest-Dose configuration exhibiting a 42% of increment respecting to the Lowest-LoD configuration and 47 times higher when compared with the limit case of no optimization.

Clinical practice outcomes and differential results in maternal and neonatal morbidity among pregnant women in Spain who are candidates for a normal birth: a cross-sectional study.

OBJECTIVE: To determine the percentage of pregnant women who are potential candidates for a normal birth in the region of Cantabria, Spain. Also, to compare the main clinical practice outcome indicators and the rates of maternal and neonatal morbidity among the group of candidate women versus non-candidates. DESIGN: A cross-sectional study. SETTING: A tertiary Hospital in Cantabria (Northern region of Spain). PARTICIPANTS: The study population comprised the total number of hospital births that took place between 1 January 2014 and 31 December 2014 (n=3315). RESULTS: Secondary registers were accessed to review the main indicators of care and the outcome of births. The χ2 test or the Student's t-test were used to compare both groups for the categorical and continuous variables, respectively. In total, 1863 births (56.20%) were candidates for applying the strategy of care for a normal birth. In 50.86% of these candidate births, an episiotomy was performed, compared with 60.96% in the group of non-candidates (p<0.001). Regarding caesarean sections, these were carried out in 19.32% of the candidate births, compared with 26.79% of non-candidate births (p<0.001). Furthermore, there were statistically significant differences between the groups according to the type of birth, the need for instrumental birthing methods, the existence of perineal tears, Apgar scores and the requirement for the infant to be admitted to the neonatal intensive care unit. CONCLUSIONS: Our results suggest a differential clinical practice, in line with the recommendations of the Clinical Practice Guidelines for Care of Normal Birth. Nonetheless, improvements are necessary regarding the care provided to women and infants, as the percentages of episiotomies and caesarean sections are still high when compared with current standards and compared with other reports.

[Impact of resistive therapy on gait parameters in children with cerebral palsy: systematic review and meta-analysis]. / Impacto de la terapia resistida sobre los parametros de la marcha en niños con paralisis cerebral: revision sistematica y metaanalisis.

INTRODUCTION: Cerebral palsy is one of the main causes of disability in childhood. Resistive therapy has proved to be beneficial in increasing strength and motor function in these patients, but its impact on gait is not yet clear. AIM: To analyse the impact of resistive therapy on improving gait through a systematic review and meta-analysis. PATIENTS AND METHODS: A search was conducted in Medline, ISI Web of Knowledge and PEDro for clinical trials in which resistive therapy was used and at least one gait parameter was assessed. RESULTS: Nine controlled studies and one single-arm study were identified. In terms of pre-post difference, the overall intragroup effect was in favour of the intervention, with null heterogeneity (standardised mean difference: 0.32; 95% CI: 0.19-0.44). The standardised mean differences were also positive as they restricted each of the gait parameters analysed: 0.36, 0.35 and 0.22 for step cadence, gait speed and step length, respectively. As regards the difference between groups, the results showed high heterogeneity, and the mean difference was also favourable, especially for speed (7.3 cm/s; 95% CI: 2.67-11.92), cadence (5.66 steps; 95% CI: 1.86-9.46) and, to a lesser extent, step length (3.25 cm; 95% CI: -1.69 to 8.19). CONCLUSION: The results support the impact of resistive therapy on gait improvement, especially in terms of the gait speed and step cadence parameters.

TITLE: Impacto de la terapia resistida sobre los parametros de la marcha en niños con paralisis cerebral: revision sistematica y metaanalisis.Introduccion. La paralisis cerebral es una de las principales causas de discapacidad en la infancia. La terapia resistida ha demostrado beneficio en el aumento de la fuerza y la funcion motora de estos pacientes, pero su impacto en la marcha aun no esta claro. Objetivo. Analizar el impacto de la terapia resistida sobre la mejora en la marcha, mediante una revision sistematica y metaanalisis. Pacientes y metodos. Se realizo una busqueda en Medline, ISI Web of Knowledge y PEDro de ensayos clinicos en los que se intervino con terapia resistida y se evaluo al menos un parametro de marcha. Resultados. Se identificaron nueve estudios controlados y uno de un solo brazo. En cuanto a la diferencia pre-post, el efecto global intragrupo fue a favor de la intervencion, con una heterogeneidad nula (diferencia estandarizada de medias: 0,32; IC 95%: 0,19-0,44). Las diferencias estandarizadas de medias fueron asimismo positivas al restringir a cada uno de los parametros de marcha analizados: 0,36, 0,35 y 0,22 para la velocidad de la marcha, la cadencia del paso y la longitud del paso, respectivamente. En relacion con la diferencia entre grupos, los resultados mostraron una heterogeneidad elevada y la diferencia de medias tambien fue favorable, especialmente para la velocidad (7,3 cm/s; IC 95%: 2,67-11,92) y la cadencia (5,66 pasos; IC 95%: 1,86-9,46), y en menor medida para la longitud del paso (3,25 cm; IC 95%: -1,69 a 8,19). Conclusion. Los resultados apoyan el impacto de la terapia resistida en la mejora en la marcha, especialmente en cuanto a los parametros de velocidad de la marcha y cadencia del paso.

Occupational exposures and risk of oesophageal cancer by histological type: a case-control study in eastern Spain.

OBJECTIVE: To explore the relationship between occupations and specific occupational exposures and oesophageal cancer (OC) by histological type. METHODS: A multicentre hospital-based case-control study was conducted in two Mediterranean provinces of Spain. Occupational, sociodemographic and lifestyle information was collected from 185 newly diagnosed male oesophageal cancer patients (147 squamous cell, 38 adenocarcinoma) and 285 frequency matched controls. Occupation was coded according to the Spanish National Classification of Occupations 1994. Occupational exposure to a selection of carcinogenic substances was assessed by the FINJEM job exposure matrix. Odds ratios were calculated by unconditional logistic regression adjusting for age, education, alcohol intake and cigarette smoking. RESULTS: For the squamous cell variety, statistically significant associations were found for waiters and bartenders (OR 8.18, 95% CI 1.98 to 33.75) and miners, shotfirers, stone cutters and carvers (OR 10.78, 95% CI 1.24 to 93.7) in relation to other occupations. For the adenocarcinoma variety, statistically significant associations were observed for carpenters and joiners (OR 9.69), animal producers and related workers (OR 5.61) and building and related electricians (OR 8.26), although these observations were based on a low number of cases. Regarding specific exposures, the study found a statistically significant increased risk of squamous cell carcinoma for ionising radiation, and of adenocarcinoma for high exposure to volatile sulphur compounds (OR 3.12) and lead (OR 5.30). For all histological types of OC combined, a three-fold increase in risk was found with a significant trend for asbestos exposure (OR 3.46, 95% CI 0.99 to 12.10). CONCLUSIONS: The data suggest that some occupational exposures may specifically increase the risk of oesophageal squamous cell carcinoma or adenocarcinoma, while other exposures such as asbestos may increase the overall risk of OC.

Tolerability and effectiveness of 4-factor prothrombin complex concentrate (4F-PCC) for warfarin and non-warfarin reversals.

PURPOSE: Current guidelines favor 4F-PCC over plasma for warfarin reversal. Uncertainty remains on its thrombotic risk and hemostatic effectiveness when used for direct-acting oral anticoagulants (DOACs), transplants, massive transfusion protocols (MTP), and non-anticoagulated patients. This study sought to evaluate the tolerability and effectiveness of 4F-PCC in a real-world setting. MATERIALS AND METHODS: This was a retrospective study of adults who received 4F-PCC from March 2014 to December 2015. The primary outcome was thromboembolic events within 14 days. The secondary outcome was hemostatic effectiveness within 24 h. RESULTS: The final analysis included 212 patients. Primary reversal indication was major bleed in 165 patients (77.8%) and emergent surgery in 47 patients (22.2%). Thromboembolism occurred in 22 patients (10.4%), more in emergent surgery than major bleed reversals (17% and 8.5%, respectively). MTP and heart transplant patients had the highest thromboembolic event rates (44.4% and 28.6%, respectively). Hemostatic effectiveness was 65.8% (68% in major bleed and 58.1% in emergent surgery). DOAC patients achieved hemostasis most often (78.9%). Administration of any reversal agent, major surgery within 14 days, and MTP activation were significant predictors of thromboembolism. CONCLUSIONS: Use of 4F-PCC in this real-world setting was associated with variable thromboembolic and hemostatic effectiveness rates based on the indication for reversal.

Feasibility of dose enhancement assessment: Preliminary results by means of Gd-infused polymer gel dosimeter and Monte Carlo study.

This work reports the experimental development of an integral Gd-infused dosimeter suitable for Gd dose enhancement assessment along with Monte Carlo simulations applied to determine the dose enhancement by radioactive and X-ray sources of interest in conventional and electronic brachytherapy. In this context, capability to elaborate a stable and reliable Gd-infused dosimeter was the first goal aimed at direct and accurate measurements of dose enhancement due to Gd presence. Dose-response was characterized for standard and Gd-infused PAGAT polymer gel dosimeters by means of optical transmission/absorbance. The developed Gd-infused PAGAT dosimeters demonstrated to be stable presenting similar dose-response as standard PAGAT within a linear trend up to 13 Gy along with good post-irradiation readout stability verified at 24 and 48 h. Additionally, dose enhancement was evaluated for Gd-infused PAGAT dosimeters by means of Monte Carlo (PENELOPE) simulations considering scenarios for isotopic and X-ray generator sources. The obtained results demonstrated the feasibility of obtaining a maximum enhancement around of (14 ±â€¯1)% for 192Ir source and an average enhancement of (70 ±â€¯13)% for 241Am. However, dose enhancement up to (267 ±â€¯18)% may be achieved if suitable filtering is added to the 241Am source. On the other hand, optimized X-ray spectra may attain dose enhancements up to (253 ±â€¯22) %, which constitutes a promising future alternative for replacing radioactive sources by implementing electronic brachytherapy achieving high dose levels.

Theory, simulation and experiments for precise deflection control of radiotherapy electron beams.

Conventional radiotherapy is mainly applied by linear accelerators. Although linear accelerators provide dual (electron/photon) radiation beam modalities, both of them are intrinsically produced by a megavoltage electron current. Modern radiotherapy treatment techniques are based on suitable devices inserted or attached to conventional linear accelerators. Thus, precise control of delivered beam becomes a main key issue. This work presents an integral description of electron beam deflection control as required for novel radiotherapy technique based on convergent photon beam production. Theoretical and Monte Carlo approaches were initially used for designing and optimizing device´s components. Then, dedicated instrumentation was developed for experimental verification of electron beam deflection due to the designed magnets. Both Monte Carlo simulations and experimental results support the reliability of electrodynamics models used to predict megavoltage electron beam control.