PLGA nanoparticles of a new cinnamic acid derivative inhibits cellular proliferation on breast cancer cell line MCF-7 in a PPARγ dependent way.

Currently, cancer treatments are highly invasive, and they have been associated with a lot of adverse effects that put patient integrity at risk. Therefore, research of novel molecules and delivery systems capable of achieving a therapeutic effect that modifies inhibits and reduces the proliferative activity in cancer cells and, at the same time, reduce adverse effects associated with conventional therapies is imperative. In this study, we analyzed the biological effect of a novel cinnamic acid derivative, 3,4-dichlorobencil-p-phenoxylcilamide, in polymeric nanoparticles over MCF-7 breast cancer cells. The nanoparticulated system showed an inhibitory influence over cellular metabolism at equal or higher concentrations than 25 µM of 3,4-dichlorobencil-p-phenoxylcilamide, which is associated with PPARγ transcriptional activity, in addition to the decrease in the proliferation antigen Ki-67 basal levels. Those results position this kind of nanoscale system as an alternative on breast cancer treatment and lay the basis for research on the action mechanism associated with its cellular metabolism modulation and relationship with another hallmark on breast cancer cellular models.

International league of associations for rheumatology recommendations for the management of psoriatic arthritis in resource-poor settings.

BACKGROUND: Psoriatic arthritis (PsA) is a challenging heterogeneous disease. The European League Against Rheumatism (EULAR) and the Group for Research and Assessment of Psoriasis and PsA (GRAPPA) last published their respective recommendations for the management of PsA in 2015. However, these guidelines are primarily based on studies conducted in resource replete countries and may not be applicable in countries in the Americas (except Canada and USA) and Africa. We sought to adapt the existing recommendations for these regions under the auspices of the International League of Associations for Rheumatology (ILAR). PROCESS: The ADAPTE Collaboration (2009) process for guideline adaptation was followed to adapt the EULAR and GRAPPA PsA treatment recommendations for the Americas and Africa. The process was conducted in three recommended phases: set-up phase; adaptation phase (defining health questions, assessing source recommendations, drafting report), and finalization phase (external review, aftercare planning, and final production). RESULT: ILAR recommendations have been derived principally by adapting the GRAPPA recommendations, additionally, EULAR recommendations where appropriate and supplemented by expert opinion and literature from these regions. A paucity of data relevant to resource-poor settings was found in PsA management literature. CONCLUSION: The ILAR Treatment Recommendations for PsA intends to serve as reference for the management of PsA in the Americas and Africa. This paper illustrates the experience of an international working group in adapting existing recommendations to a resource-poor setting. It highlights the need to conduct research on the management of PsA in these regions as data are currently lacking.Key Points• The paper presents adapted recommendations for the management of psoriatic arthritis in resource-poor settings.• The ADAPTE process was used to adapt existing GRAPPA and EULAR recommendations by collaboration with practicing clinicians from the Americas and Africa.• The evidence from resource-poor settings to answer clinically relevant questions was scant or non-existent; hence, a research agenda is proposed.

Influence of germination time on the morphological, morphometric, structural, and physicochemical characteristics of Esmeralda and Perla barley starch.

The aim of this study was to analyzing the impact of germination time on the morphology, crystallinity, gelatinization and viscosity properties on the starch of Esmeralda and Perla barley variety. The two barley were germinated for 1 to 8 days, at 26 °C and 65% relative humidity. Micrographs showed the presence of pinholes and eroded surfaces. Starch in Esmeralda was hydrolyzed completely at 8 days of germination. Birefringence was reduced from day 4, losing molecular structuring of the crystalline area. Morphometric data: fractal dimension, area, perimeter, circularity, and roundness decreased significantly along germination time in both varieties. The entropy increased significantly, from 0.79 to 10.09 in Esmeralda and from 0.46 to 7.57 in Perla. Relative crystallinity decreased significantly in the Perla from 24.7% to 23.6%. Viscosity peaks were also significantly reduced, pasting temperature was constant in Esmeralda but in Perla was significantly reduced from 95.43 to 95.19 °C with germination, the gelatinization temperature increased significantly in the Esmeralda while in Perla it remained constant. Enthalpy decreased significantly to 75.8% and 37% in Esmeralda and Perla respectively. The study of germination impact on structural and physicochemical properties is important to identify the use of hydrolyzed starches in the food industry or others.

Genetic parameters and direct, maternal and heterosis effects on litter size in a diallel cross among three commercial varieties of Iberian pig.

The Iberian pig is one of the pig breeds that has the highest meat quality. Traditionally, producers have bred one of the available varieties, exclusively, and have not used crosses between them, which has contrasted sharply with other populations of commercial pigs for which crossbreeding has been a standard procedure. The objective of this study was to perform an experiment under full diallel design among three contemporary commercial varieties of Iberian pig and estimate the additive genetic variation and the crossbreeding effects (direct, maternal and heterosis) for prolificacy. The data set comprised 18 193 records for total number born and number born alive from 3800 sows of three varieties of the Iberian breed (Retinto, Torbiscal and Entrepelado) and their reciprocal crosses (Retinto × Torbiscal, Torbiscal × Retinto, Retinto × Entrepelado, Entrepelado × Retinto, Torbiscal × Entrepelado and Entrepelado × Torbiscal), and a pedigree of 4609 individuals. The analysis was based on a multiple population repeatability model, and we developed a model comparison test that indicated the presence of direct line, maternal and heterosis effects. The results indicated the superiorities of the direct line effect of the Retinto and the maternal effect of the Entrepelado populations. All of the potential crosses produced significant heterosis, and additive genetic variation was higher in the Entrepelado than it was in the other two populations. The recommended cross for the highest yield in prolificacy is a Retinto father and an Entrepelado mother to generate a hybrid commercial sow.

Recommendations for the prevention and diagnosis of asthma in children: Evidence from international guidelines adapted for Mexico

BACKGROUND: With the availability of high-quality asthma guidelines worldwide, one possible approach of developing a valid guideline, without re-working the evidence, already analysed by major guidelines, is the ADAPTE approach, as was used for the development of National Guidelines on asthma. METHODS: The guidelines development group (GDG) covered a broad range of experts from medical specialities, primary care physicians and methodologists. The core group of the GDG searched the literature for asthma guidelines 2005 onward, and analysed the 11 best guidelines with AGREE-II to select three mother guidelines. Key clinical questions were formulated covering each step of the asthma management. RESULTS: The selected mother guidelines are British Thoracic Society (BTS), GINA and GEMA 2015. Responses to the questions were formulated according to the evidence in the mother guidelines. Recommendations or suggestions were made for asthma treatment in Mexico by the core group, and adjusted during several rounds of a Delphi process, taking into account: 1. Evidence; 2. Safety; 3. Cost; 4. Patient preference - all these set against the background of the local reality. Here the detailed analysis of the evidence present in BTS/GINA/GEMA sections on prevention and diagnosis in paediatric asthma are presented for three age-groups: children with asthma ≤5 years, 6-11 years and ≥12 years. CONCLUSIONS: For the prevention and diagnosis sections, applying the AGREE-II method is useful to develop a scientifically-sustained document, adjusted to the local reality per country, as is the Mexican Guideline on Asthma

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Novel Supramolecular Nanoparticles Derived from Cucurbit[7]uril and Zwitterionic Surfactants.

Binding constants, log K ≈ 6.6 M-1, and NMR characterization of the complexes formed by sulfobetaines and cucurbit[7]uril (CB7) support the electrostatic interaction as the major driving force. This very strong binding motif is cross-linked by additional CB7 molecules, resulting in the formation of supramolecular nanoparticles (SNPs) with an average diameter of 172 nm and a negative surface potential. The time course evolution of the particle size and the surface potential suggests the very fast formation of an amorphous aggregate that absorbs an additional amount of sulfobetaine. These aggregates afford very stable (more than 2 weeks) nanoparticles in an aqueous dispersion. The reversibility of the sulfobetaine/CB7 host/guest complexes allows SNP disaggregation by adding a competitive guest as shown by treatment with tetraethylammonium chloride. The addition of this competitive cation triggers a SNP-to-micelle transition. The potential application of these nanoparticles as drug delivery vehicles was investigated by using carboxyfluorescein. These experiments revealed that upon externally induced disruption of the SNPs (by tetraethylammonium chloride) the fluorescent dye was trapped in micellar aggregates that can be further disrupted by cyclodextrin addition.

Recommendations for the prevention and diagnosis of asthma in children: Evidence from international guidelines adapted for Mexico.

BACKGROUND: With the availability of high-quality asthma guidelines worldwide, one possible approach of developing a valid guideline, without re-working the evidence, already analysed by major guidelines, is the ADAPTE approach, as was used for the development of National Guidelines on asthma. METHODS: The guidelines development group (GDG) covered a broad range of experts from medical specialities, primary care physicians and methodologists. The core group of the GDG searched the literature for asthma guidelines 2005 onward, and analysed the 11 best guidelines with AGREE-II to select three mother guidelines. Key clinical questions were formulated covering each step of the asthma management. RESULTS: The selected mother guidelines are British Thoracic Society (BTS), GINA and GEMA 2015. Responses to the questions were formulated according to the evidence in the mother guidelines. Recommendations or suggestions were made for asthma treatment in Mexico by the core group, and adjusted during several rounds of a Delphi process, taking into account: 1. Evidence; 2. Safety; 3. Cost; 4. Patient preference - all these set against the background of the local reality. Here the detailed analysis of the evidence present in BTS/GINA/GEMA sections on prevention and diagnosis in paediatric asthma are presented for three age-groups: children with asthma ≤5 years, 6-11 years and ≥12 years. CONCLUSIONS: For the prevention and diagnosis sections, applying the AGREE-II method is useful to develop a scientifically-sustained document, adjusted to the local reality per country, as is the Mexican Guideline on Asthma.

Comparación de la respuesta clínica a la aplicación de hilano G-F 20 y colágeno-PVP en pacientes con artrosis de rodilla / Comparison of the clinical response to the application of Hylan G-F 20 and collagen-PVP in patients with knee osteoarthritis

Resumen: Antecedentes: La osteoartritis de rodilla es una enfermedad articular caracterizada por degeneración, pérdida del cartílago y alteración del hueso subcondral asociadas a cambios en los tejidos blandos. En una muestra de 2,500 individuos se encontró una prevalencia de artrosis de 2.3% (IC 95% 1.7 a 2.9) en adultos. En nuestro hospital representa la segunda causa de consulta. Material y métodos: Se tomaron dos grupos de pacientes: el primero, de 70 pacientes a los que se les aplicó hilano G-F 20 en tres infiltraciones; al otro grupo, de 40 pacientes, se le aplicó colágeno-PVP en cuatro aplicaciones. Se les realizó un interrogatorio basado en el cuestionario de WOMAC, con el cual pudimos valorar dolor, rigidez y capacidad funcional antes y después de la aplicación de los medicamentos. Resultados: Nuestro estudio presentó que en ambos grupos hubo mejora de la calidad de vida al disminuir los síntomas tales como dolor, rigidez y limitación funcional; el colágeno fue más eficiente para la disminución del dolor y el hialino G-F 20, para la disminución de la rigidez y la limitación funcional. Conclusiones: Ambos tratamientos mostraron seguridad y eficacia. Su uso en nuestro instituto para los pacientes fuera de tratamiento quirúrgico puede disminuir de manera importante los internamientos por dolor, con lo que podemos hacer un uso más eficiente de los recursos con que contamos.

Abstract: Background: Knee osteoarthritis is a joint disease characterized by degeneration, loss of cartilage and subchondral bone alteration associated with changes in the soft tissues. In a sample of 2,500 individuals, the prevalence of osteoarthritis was found in 2.3% (IC 95% 1.7 a 2.9) in adults; it represents the second cause of consultation in our hospital. Material and methods: Two groups of patients were studied: the first included 70 patients who received hylan G-F 20 in three infiltrations; the other group, of 40 patients, received collagen-PVP in four applications. A subjective questionnaire based on the WOMAC evaluation was applied, with which we could assess pain, stiffness and functional capacity before and after the application. Results: Both hylan G-F 20 and collagen-PVP improved the quality of life of our patients by reducing symptoms such as pain, stiffness and functional limitation, collagen being more efficient for reducing pain and hylan G-F 20 for reducing stiffness and functional limitation. Conclusions: Both treatments were safe and effective; they can be used in our institute as a conservative treatment to decrease hospitalizations for pain management.

Serum ferritin thresholds for the diagnosis of iron deficiency in pregnancy: a systematic review.

The aim of this review was to understand the landscape of serum ferritin in diagnosing iron deficiency in the aetiology of anaemia in pregnancy. Iron deficiency in pregnancy is a major public health problem leading to the development of anaemia. Reducing the global prevalence of anaemia in women of reproductive age is a 2025 global nutrition target. Bone marrow aspiration is the gold standard test for iron deficiency but requires an invasive procedure; therefore, serum ferritin is the most clinically useful test. We undertook a systematic search of electronic databases and trial registers from inception to January 2016. Studies of iron or micronutrient supplementation in pregnancy with pre-defined serum ferritin thresholds were included. Two independent reviewers selected studies, extracted data and assessed quality. There were 76 relevant studies mainly of observational study design (57%). The most commonly used thresholds of serum ferritin for the diagnosis of iron deficiency were <12 and <15 ng mL-1 (68%). Most primary studies provided no justification for the choice of serum ferritin threshold used, but 25 studies (33%) used thresholds defined by expert consensus in a guideline development process. There were five studies (7%) using a serum ferritin threshold defining iron deficiency derived from primary studies of bone marrow aspiration. Unified international thresholds of iron deficiency for women throughout pregnancy are required for accurate assessments of the global disease burden and for evaluating effectiveness of interventions addressing this problem.

[Comparison of the clinical response to the application of Hylan G-F 20 and collagen-PVP in patients with knee osteoarthritis]. / Comparación de la respuesta clínica a la aplicación de hilano G-F 20 y colágeno-PVP en pacientes con artrosis de rodilla.

BACKGROUND: Knee osteoarthritis is a joint disease characterized by degeneration, loss of cartilage and subchondral bone alteration associated with changes in the soft tissues. In a sample of 2,500 individuals, the prevalence of osteoarthritis was found in 2.3% (IC 95% 1.7 a 2.9) in adults; it represents the second cause of consultation in our hospital. MATERIAL AND METHODS: Two groups of patients were studied: the first included 70 patients who received hylan G-F 20 in three infiltrations; the other group, of 40 patients, received collagen-PVP in four applications. A subjective questionnaire based on the WOMAC evaluation was applied, with which we could assess pain, stiffness and functional capacity before and after the application. RESULTS: Both hylan G-F 20 and collagen-PVP improved the quality of life of our patients by reducing symptoms such as pain, stiffness and functional limitation, collagen being more efficient for reducing pain and hylan G-F 20 for reducing stiffness and functional limitation. CONCLUSIONS: Both treatments were safe and effective; they can be used in our institute as a conservative treatment to decrease hospitalizations for pain management.

ANTECEDENTES: La osteoartritis de rodilla es una enfermedad articular caracterizada por degeneración, pérdida del cartílago y alteración del hueso subcondral asociadas a cambios en los tejidos blandos. En una muestra de 2,500 individuos se encontró una prevalencia de artrosis de 2.3% (IC 95% 1.7 a 2.9) en adultos. En nuestro hospital representa la segunda causa de consulta. MATERIAL Y MÉTODOS: Se tomaron dos grupos de pacientes: el primero, de 70 pacientes a los que se les aplicó hilano G-F 20 en tres infiltraciones; al otro grupo, de 40 pacientes, se le aplicó colágeno-PVP en cuatro aplicaciones. Se les realizó un interrogatorio basado en el cuestionario de WOMAC, con el cual pudimos valorar dolor, rigidez y capacidad funcional antes y después de la aplicación de los medicamentos. RESULTADOS: Nuestro estudio presentó que en ambos grupos hubo mejora de la calidad de vida al disminuir los síntomas tales como dolor, rigidez y limitación funcional; el colágeno fue más eficiente para la disminución del dolor y el hialino G-F 20, para la disminución de la rigidez y la limitación funcional. CONCLUSIONES: Ambos tratamientos mostraron seguridad y eficacia. Su uso en nuestro instituto para los pacientes fuera de tratamiento quirúrgico puede disminuir de manera importante los internamientos por dolor, con lo que podemos hacer un uso más eficiente de los recursos con que contamos.

Behavior and Inactivation of Enterotoxin-Positive Clostridium perfringens in Pork Picadillo and Tamales Filled with Pork Picadillo under Different Cooking, Storage, and Reheating Conditions.

This study analyzed the behavior of Clostridium perfringens in individual ingredients and tamales containing different pathogen concentrations upon exposure to different temperatures and methods of cooking, storage, and reheating. In ground pork, C. perfringens cells were inactivated when exposed to 95°C for 30 min. Three lots of picadillo inoculated with 0, 3, and 5 log CFU/g C. perfringens cells, respectively, were exposed to different storage temperatures. At 20°C, cell counts increased 1 log in all lots, whereas at 8°C, counts decreased by 2 log. Four lots of tamales prepared with picadillo inoculated with 0, 2, 3, and 7 log CFU/g prior to the final cooking step exhibited no surviving cells (91°C for 90, 45, or 35 min). Four lots of tamales were inoculated after cooking with concentrations of 0, 0.6, 4, and 6 log CFU/g of the pathogen and then stored at different temperatures. In these preparations, after 24 h at 20°C, the count increased by 1.4, 1.7, and 1.8 log in the tamales inoculated with 0.6, 4, and 6 log inoculum, respectively. When they were stored at 8°C for 24 h, enumerations decreased to <1, 2.5, and 1.9 log in the tamales inoculated with 0.6, 4, and 6 log of C. perfringens cells, respectively. However, when the lots were exposed to 20°C and then 8°C, 0.8, 1.8, and 2.4 log changes were observed for the tamales inoculated with 0.6, 4, and 6 log, respectively. Microwaving, steaming, and frying to reheat tamales inoculated with 6 log CFU/g C. perfringens cells showed that the pathogen was inactivated after 2 min of exposure in the microwave and after 5 min of exposure to steam. In contrast, no inactivation was observed after 5 min of frying. The tamales inoculated with spores (7 log most probable number [MPN]/g) showed a decrease of 2 log after steaming or frying, and no survival was observed after microwaving. Tamales inoculated with spores (7 log MPN/g) after cooking were susceptible to microwaves, but 2.4 and 255 MPN/g remained after frying and steaming, respectively.

Anaerobic Codigestion of Sludge: Addition of Butcher's Fat Waste as a Cosubstrate for Increasing Biogas Production.

Fat waste discarded from butcheries was used as a cosubstrate in the anaerobic codigestion of sewage sludge (SS). The process was evaluated under mesophilic and thermophilic conditions. The codigestion was successfully attained despite some inhibitory stages initially present that had their origin in the accumulation of volatile fatty acids (VFA) and adsorption of long-chain fatty acids (LCFA). The addition of a fat waste improved digestion stability and increased biogas yields thanks to the higher organic loading rate (OLR) applied to the reactors. However, thermophilic digestion was characterized by an effluent of poor quality and high VFA content. Results from spectroscopic analysis suggested the adsorption of lipid components onto the anaerobic biomass, thus disturbing the complete degradation of substrate during the treatment. The formation of fatty aggregates in the thermophilic reactor prevented process failure by avoiding the exposure of biomass to the toxic effect of high LCFA concentrations.

Antibacterial effect of roselle extracts (Hibiscus sabadariffa), sodium hypochlorite and acetic acid against multidrug-resistant Salmonella strains isolated from tomatoes.

UNLABELLED: Antibiotic-resistant Salmonella strains were isolated from saladette and red round type tomatoes, and an analysis done of the antibacterial activity of roselle calyx extracts against any of the identified strains. One hundred saladette tomato samples and 100 red round tomato samples were collected from public markets. Each sample consisted of four whole tomatoes. Salmonella was isolated from the samples by conventional culture procedure. Susceptibility to 16 antibiotics was tested for the isolated Salmonella strains by standard test. The antibacterial effect of four roselle calyx extracts (water, methanol, acetone and ethyl acetate), sodium hypochlorite and acetic acid against antibiotic-resistant Salmonella isolates was evaluated on contaminated tomatoes. Twenty-four Salmonella strains were isolated from 12% of each tomato type. Identified Salmonella serotypes were Typhimurium and Typhi. All isolated strains exhibited resistance to at least three antibiotics and some to as many as 12. Over contaminated tomatoes, the roselle calyx extracts produced a greater reduction (2-2·6 log) in antibiotic-resistant Salmonella strain concentration than sodium hypochlorite and acetic acid. SIGNIFICANCE AND IMPACT OF THE STUDY: The presence of multidrug-resistant Salmonella in vegetables is a significant public health concern. Multidrug-resistant Salmonella strains were isolated from raw tomatoes purchased in public markets in Mexico and challenged with roselle Hibiscus sabdariffa calyx extracts, sodium hypochlorite and acetic acid. On tomatoes, the extracts caused a greater reduction in the concentration of antibiotic-resistant Salmonella strains than sodium hypochlorite and acetic acid. Roselle calyx extracts are a potentially useful addition to disinfection procedures of raw tomatoes in the field, processing plants, restaurants and homes.

Investigating the link between disease activity and infliximab serum levels in rheumatoid arthritis patients.

OBJECTIVES: The aim of this study was to examine the extent to which infliximab (IFX) serum levels impact disease activity in rheumatoid arthritis (RA) patients. METHODS: In this cross sectional study, serum samples were taken prior to drug infusion from 60 RA patients who had been undergoing IFX therapy > 12 months as a first line of biological treatment. Patient IFX levels were tested and then associated with clinical disease activity. Three DAS28 cut-off points, <2.6, <3.2 and <5.1 were used to determine whether detectable IFX levels were any predictor of clinical disease activity. Logistic regression analysis was run to check other possible factors associated with RA clinical outcomes such as MTX concomitant use, CRP and ESR. RESULTS: Sixteen (27%) out of the 60 patients tested negative; 28 (46%) presented subtherapeutic and 16 (27%) therapeutic IFX levels. Median IFX levels were higher in patients either in remission or showing low disease activity than in those with moderate and high disease activity (p=0.014). Significant association was found between IFX levels and clinical disease activity (p=0.001). Detectable levels of IFX shows better sensitivity and specificity to identify patients with DAS28<3.2 than to identify patients with DAS28<2.6 or DAS28<5.1. Conversely, the best DAS28 cut-off to identify detectable/undetectable IFX was 3.19, with AUC under ROC curve 0.804 (Sd.E 0.070), 76% specificity and 83% sensitivity (p<0.001). MTX use, CRP and ESR did not interfere with this association. Seven out of the 8 patients with anti-IFX antibodies presented DAS28>3.2 (p=0.005). CONCLUSIONS: DAS28 and IFX serum levels were shown to have an inverse correlation. Undetectable IFX serum levels were associated to RA patients presenting DAS28>3.2 meaning that DAS28 <3.2 may be useful to clinicians to evaluate patient response to drug therapy.

γ-Cyclodextrin modulates the chemical reactivity by multiple complexation.

Multiple complexation by γ-CD has been studied by self-diffusion coefficients (DOSY) and chemical kinetics experiments in which 4-methoxybenzenesulfonyl chloride (MBSC) solvolysis was used as a chemical probe. The addition of a surfactant as a third component to the reaction mixture induced a very complex reactivity pattern that was explained on the basis of multiple complexation phenomena and surfactant self-assembly to form micelles. A cooperative effect that yielded a ternary complex formed by cyclodextrin-surfactant-MBSC was observed. The larger cavity of γ-CD in comparison with ß-CD is responsible for the change from the competitive complexation mechanism predominant with ß-CD to a cooperative/competitive mixed mechanism operating for the larger derivative. The cavity size in γ-CD is large enough to bind two surfactant alkyl chains with a cooperative effect. Water molecules released by the formation of 1:1 host-guest complexes made the cavity more hydrophobic and promoted further inclusion. A reduction in the available volume of the cavity should be considered on binding a second guest.

Analysis of disease activity and response to treatment in a large Spanish cohort of patients with systemic lupus erythematosus.

OBJECTIVES: The objectives of this paper are to study the impact of disease activity in a large cohort of patients with systemic lupus erythematosus (SLE) and estimate the rate of response to therapies. METHODS: We conducted a nationwide, retrospective, multicenter, cross-sectional cohort study of 3658 SLE patients. Data on demographics, disease characteristics: activity (SELENA-SLEDAI), damage, severity, hospitalizations and therapies were collected. Factors associated with refractory disease were identified by logistic regression. RESULTS: A total of 3658 patients (90% female; median SLE duration (interquartile range): 10.4 years (5.3-17.1)) were included. At the time of their last evaluation, 14.7% of the patients had moderate-severe SLE (SELENA-SLEDAI score ≥6). There were 1954 (53.4%) patients who were hospitalized for activity at least once over the course of the disease. At some stage, 84.6% and 78.8% of the patients received glucocorticoids and antimalarials, respectively, and 51.3% of the patients received at least one immunosuppressant. Owing to either toxicity or ineffectiveness, cyclophosphamide was withdrawn in 21.5% of the cases, mycophenolate mofetil in 24.9%, azathioprine in 40.2% and methotrexate in 46.8%. At some stage, 7.3% of the patients received at least one biologic. A total of 898 (24.5%) patients had refractory SLE at some stage. Renal, neuropsychiatric, vasculitic, hematological and musculoskeletal involvement, a younger age at diagnosis and male gender were associated with refractory disease. CONCLUSIONS: A significant percentage of patients have moderately-to-severely active SLE at some stage. Disease activity has a big impact in terms of need for treatment and cause of hospitalization. The effectiveness of the standard therapies for reducing disease activity is clearly insufficient. Some clinical features are associated with refractory SLE.

Using (222)Rn as a tracer of geodynamical processes in underground environments.

Radon levels in two old mines in San Luis, Argentina, were measured and analyzed, with the aim to assess the potential use of this radioactive noble gas as a tracer of geological processes in underground environments. La Carolina gold mine and Los Cóndores tungsten mine are today used as tourism mines. CR-39 nuclear track detectors were used for this purpose. Measurements were performed during both winter and summer seasons. The findings show that in these environments, significant radon concentrations are subject to large seasonal fluctuations, due to the strong dependence on natural ventilation with the outside temperature variations. For both mines, higher concentration values of (222)Rn were observed in summer than in winter; with an extreme ratio of 2.5 times between summer and winter seasons for Los Cóndores mine. The pattern of radon transport inside La Carolina mine revealed, contrary to what was believed, that this mine behaves as a system with two entrances located at different levels. However, this feature can only be observed in the winter season, when there is a marked difference between the inside and outside temperatures of the mine. In the case of Los Cóndores mine, the radon concentration pattern distribution is principally established by air current due to chimney-effect in summer and winter seasons. In both cases, the analyses of radon pattern distribution appear as a good method to trace air currents, and then localize unknown ducts, fissures or secondary tunnels in subterranean environments.