Stereoisomeric separation of the chiral herbicide profoxydim and residue method development in rice by QuEChERS and LC-MS/MS.

A method for the simultaneous determination of the four stereoisomers of the chiral herbicide profoxydim in rice and husk was developed using the QuEChERS method and LC-tandem mass spectrometry. Four polysaccharide-based chiral stationary phase columns were evaluated. All four stereoisomers were successfully separated on a Chiracel OJ-3R column. The effects of mobile phase, modifiers, mobile phase flow rate and temperature on the separation were also investigated. Different QuEChERS methods were compared for the development of an optimized sample preparation procedure. The method, following SANTE guidelines, showed excellent linearity (R2 ≥ 0.99), the LODs were below 4.0 µg kg-1, and the LOQs did not exceed 12.5 µg kg-1. The overall average recoveries at three levels (12.5, 25.0 and 250 µg kg-1) ranged from 76.77 % to 106.53 %, with RSD values less than 7 %. The method is demonstrated to be convenient and reliable for the routine monitoring of profoxydim stereoisomers in rice and husk.

Assessing the effect of organic amendments on the degradation of profoxydim in paddy soils: Kinetic modeling and identification of degradation products.

The fate and behavior of herbicides can be altered in an unpredictable way when organic amendments are added to soil as a beneficial management tool. The objective of this work was to investigate the effect exerted by the addition of two different organic amendments (alperujo compost and biochar) to soil in the degradation of one of the most relevant new generation rice herbicides, profoxydim. In unamended soils, the degradation of profoxydim was quite fast and was governed by both chemical (DT50steril soil = from 1.52 to 9.21 days) and microbial (DT50nonsterile soil = from 0.47 to 0.53 days) processes. Alperujo- and biochar-amended soils significantly increased the persistence of the herbicide in both soils, especially in the presence of biochar, due to the high capacity absorption of this amendment, increasing DT90 from 1.92 to 3.54 days for DT90unamended to 41.02-48.41 days for DT90biochar amended. Different kinetics models applied to fit the observed dissipation datasets showed that a HS biphasic model fits well with the dissipation of profoxydim in amended and unamended soils. For the first time, five degradation products (DPs) were identified by HPLC-QTOF-MS/MS in soil and a degradation pathway was described. Main DP was generated via oxidation of the sulfur atom to give rise to the corresponding sulfoxide derivative, with this DP being more persistent than the active substance. These outcomes can be very useful for the assessment of the environmental risk associated with the use of profoxydim in rice crops and the application of organic amendments as potential measures for minimizing the risk of contamination of natural water resources.

Impact of outdoor air pollution on severity and mortality in COVID-19 pneumonia.

The relationship between exposure to air pollution and the severity of coronavirus disease 2019 (COVID-19) pneumonia and other outcomes is poorly understood. Beyond age and comorbidity, risk factors for adverse outcomes including death have been poorly studied. The main objective of our study was to examine the relationship between exposure to outdoor air pollution and the risk of death in patients with COVID-19 pneumonia using individual-level data. The secondary objective was to investigate the impact of air pollutants on gas exchange and systemic inflammation in this disease. This cohort study included 1548 patients hospitalised for COVID-19 pneumonia between February and May 2020 in one of four hospitals. Local agencies supplied daily data on environmental air pollutants (PM10, PM2.5, O3, NO2, NO and NOX) and meteorological conditions (temperature and humidity) in the year before hospital admission (from January 2019 to December 2019). Daily exposure to pollution and meteorological conditions by individual postcode of residence was estimated using geospatial Bayesian generalised additive models. The influence of air pollution on pneumonia severity was studied using generalised additive models which included: age, sex, Charlson comorbidity index, hospital, average income, air temperature and humidity, and exposure to each pollutant. Additionally, generalised additive models were generated for exploring the effect of air pollution on C-reactive protein (CRP) level and SpO2/FiO2 at admission. According to our results, both risk of COVID-19 death and CRP level increased significantly with median exposure to PM10, NO2, NO and NOX, while higher exposure to NO2, NO and NOX was associated with lower SpO2/FiO2 ratios. In conclusion, after controlling for socioeconomic, demographic and health-related variables, we found evidence of a significant positive relationship between air pollution and mortality in patients hospitalised for COVID-19 pneumonia. Additionally, inflammation (CRP) and gas exchange (SpO2/FiO2) in these patients were significantly related to exposure to air pollution.

Factores de riesgo de deterioro clínico en pacientes ingresados por COVID-19: estudio caso-control / Risk factors for clinical deterioration in patients admitted for COVID-19: A case-control study

Introducción: Existe controversia sobre los mejores factores predictores de deterioro clínico en la COVID-19. Objetivo: Identificar factores predictores de riesgo de deterioro en pacientes hospitalizados por COVID-19. Métodos Diseño: caso-control anidado dentro de una cohorte. Ámbito: 13 centros de agudos de Osakidetza-Servicio Vasco de Salud. Participantes: se consideró casos a pacientes hospitalizados por COVID-19 con deterioro clínico, definido como la aparición de síndrome de distrés respiratorio del adulto grave, ingreso en UCI o fallecimiento. Se emparejaron 2controles por caso en función de la edad. Se recogieron variables sociodemográficas, comorbilidades, tratamientos basales, síntomas y fecha de inicio, consultas previas, así como variables clínicas, analíticas y radiológicas. Se creó un modelo explicativo del deterioro clínico mediante regresión logística condicional. Resultados: Se incluyeron 99 casos y 198 controles. Mediante análisis de regresión logística las variables independientes asociadas con deterioro clínico fueron: saturación de O2 en Urgencias ≤ 90% (OR=16,6, IC del 95%, 4-68), radiografía de tórax patológica (OR=5,6, IC del 95%, 1,7-18,4), PCR> 100mg/dL (OR=3,62, IC del 95% 1,62-8) y trombocitopenia <150.000 plaquetas (OR=4, IC del 95%, 1,84-8,6) y, entre los antecedentes, haber padecido infarto agudo de miocardio (OR=15,7, IC del 95%, 3,29-75,09), EPOC (OR=3,05, IC del 95%, 1,43-6,5) o hipertensión arterial (OR=2,21, IC del 95%1,11-4,4). El área bajo la curva alcanzado por el modelo fue 0,86. En el análisis univariado, se asociaron con mejor evolución clínica el sexo femenino, la presencia de tos seca y dolor de garganta, pero no resultaron significativas en el análisis multivariado. Conclusiós:Las variables identificadas podrían ser de utilidad en la práctica clínica para la detección de pacientes con alto riesgo de mala evolución (AU)

Introduction: There is controversy regarding the best predictors of clinical deterioration in COVID-19. Objective: This work aims to identify predictors of risk factors for deterioration in patients hospitalized due to COVID-19. Methods Design: Nested case-control study within a cohort. Setting: 13 acute care centers of the Osakidetza-Basque Health Service. Participants: Patients hospitalized for COVID-19 with clinical deterioration—defined as onset of severe ARDS, ICU admission, or death—were considered cases. Two controls were matched to each case based on age. Sociodemographic data; comorbidities; baseline treatment; symptoms; date of onset; previous consultations; and clinical, analytical, and radiological variables were collected. An explanatory model of clinical deterioration was created by means of conditional logistic regression. Results: A total of 99 cases and 198 controls were included. According to the logistic regression analysis, the independent variables associated with clinical deterioration were: emergency department O2 saturation ≤90% (OR 16.6; 95%CI 4-68), pathological chest X-ray (OR 5.6; 95%CI 1.7-18.4), CRP>100mg/dL (OR 3.62; 95%CI 1.62-8), thrombocytopenia with <150,000 platelets (OR 4; 95%CI 1.84-8.6); and a medical history of acute myocardial infarction (OR 15.7; 95%CI, 3.29-75.09), COPD (OR 3.05; 95%CI 1.43-6.5), or HT (OR 2.21; 95%CI 1.11-4.4). The model's AUC was 0.86. On the univariate analysis, female sex and presence of dry cough and sore throat were associated with better clinical progress, but were not found to be significant on the multivariate analysis. Conclusion: The variables identified could be useful in clinical practice for the detection of patients at high risk of poor outcomes (AU)

Risk factors for clinical deterioration in patients admitted for COVID-19: A case-control study.

INTRODUCTION: There is controversy regarding the best predictors of clinical deterioration in COVID-19. OBJECTIVE: This work aims to identify predictors of risk factors for deterioration in patients hospitalized due to COVID-19. METHODS DESIGN: Nested case-control study within a cohort. SETTING: 13 acute care centers of the Osakidetza-Basque Health Service. PARTICIPANTS: patients hospitalized for COVID-19 with clinical deterioration-defined as onset of severe ARDS, ICU admission, or death-were considered cases. Two controls were matched to each case based on age. Sociodemographic data; comorbidities; baseline treatment; symptoms; date of onset; previous consultations; and clinical, analytical, and radiological variables were collected. An explanatory model of clinical deterioration was created by means of conditional logistic regression. RESULTS: A total of 99 cases and 198 controls were included. According to the logistic regression analysis, the independent variables associated with clinical deterioration were: emergency department O2 saturation ≤90% (OR 16.6; 95%CI 4-68), pathological chest X-ray (OR 5.6; 95%CI 1.7-18.4), CRP > 100 mg/dL (OR 3.62; 95%CI 1.62-8), thrombocytopenia with <150,000 platelets (OR 4; 95%CI 1.84-8.6); and a medical history of acute myocardial infarction (OR 15.7; 95%CI, 3.29-75.09), COPD (OR 3.05; 95%CI 1.43-6.5), or HT (OR 2.21; 95%CI 1.11-4.4). The model's AUC was 0.86. On the univariate analysis, female sex and presence of dry cough and sore throat were associated with better clinical progress, but were not found to be significant on the multivariate analysis. CONCLUSION: The variables identified could be useful in clinical practice for the detection of patients at high risk of poor outcomes.

[Risk factors for clinical deterioration in patients admitted for COVID-19: A case-control study]. / Factores de riesgo de deterioro clínico en pacientes ingresados por COVID-19: estudio caso-control.

INTRODUCTION: There is controversy regarding the best predictors of clinical deterioration in COVID-19. OBJECTIVE: This work aims to identify predictors of risk factors for deterioration in patients hospitalized due to COVID-19. METHODS DESIGN: Nested case-control study within a cohort. Setting: 13 acute care centers of the Osakidetza-Basque Health Service. Participants: Patients hospitalized for COVID-19 with clinical deterioration-defined as onset of severe ARDS, ICU admission, or death-were considered cases. Two controls were matched to each case based on age. Sociodemographic data; comorbidities; baseline treatment; symptoms; date of onset; previous consultations; and clinical, analytical, and radiological variables were collected. An explanatory model of clinical deterioration was created by means of conditional logistic regression. RESULTS: A total of 99 cases and 198 controls were included. According to the logistic regression analysis, the independent variables associated with clinical deterioration were: emergency department O2 saturation ≤90% (OR 16.6; 95%CI 4-68), pathological chest X-ray (OR 5.6; 95%CI 1.7-18.4), CRP >100 mg/dL (OR 3.62; 95%CI 1.62-8), thrombocytopenia with < 150,000 platelets (OR 4; 95%CI 1.84-8.6); and a medical history of acute myocardial infarction (OR 15.7; 95%CI, 3.29-75.09), COPD (OR 3.05; 95%CI 1.43-6.5), or HT (OR 2.21; 95%CI 1.11-4.4). The model's AUC was 0.86. On the univariate analysis, female sex and presence of dry cough and sore throat were associated with better clinical progress, but were not found to be significant on the multivariate analysis. CONCLUSION: The variables identified could be useful in clinical practice for the detection of patients at high risk of poor outcomes.

QSAR/QSPR models based on quantum chemistry for risk assessment of pesticides according to current European legislation.

In Europe, agencies and official organizations involved in the pesticide control such as the EFSA, ECHA, JRC and ECETOC or even the OECD are pointing out that the software tools based on quantitative structure relationship models, i.e. QSAR and QSPR, have a huge potential to improve the pesticide risk assessment process. In this sense, these non-animal test methods can promote the competitiveness of agriculture in this region: the consumer safety is increased with them due to the possibility of perform an overall better risk assessment of the degradation products and metabolites from pesticides. However, the use of theses computational-based (in silico) tools must be much more systematised and harmonised, improving their validation and including case studies to test them. To open databases, incorporating critical data in an orderly manner for building the models, becomes also necessary. Moreover, quantum chemistry through the Density Functional Theory should be promoted as tool for calculation of quantum descriptors, especially for the study of similar compounds with the same carbon skeleton but differing substitution patterns, e.g. isomers.

Utility of two biomarkers for directing care among patients with non-severe community-acquired pneumonia.

The aim of the present study is to evaluate the usefulness of two biomarkers-procalcitonin (PCT) and C-reactive protein (CRP)-in addition to the CURB-65 score for assessing the site of care and the etiology of non-severe community-acquired pneumonia (CAP). We conducted a prospective observational study from April 1, 2006, to June 30, 2007, in a single teaching hospital in northern Spain among patients with non-severe CAP. In addition to collecting data needed to determine the CURB-65 score, microbial cultures were taken and levels of PCT and CRP were measured. We compared the prognostic accuracy of these biomarkers with the CURB-65 score to predict hospitalization and microbial etiology using receiver operating characteristic (ROC) curves. A total of 344 patients with non-severe CAP were enrolled; 73 were admitted to the hospital and 271 were treated on an outpatient basis. An etiologic diagnostic was made for 44 %, with atypical pathogens predominating. Levels of PCT and CRP increased with increasing CURB-65 scores. Patients admitted to the hospital had higher PCT and CRP levels than outpatients (p < 0.001). For predicting hospitalization, PCT had a better area under the ROC curve (AUC) (0.81) than the CURB-65 score alone (0.77). For PCT plus the CURB-65 score, the AUC increased significantly from 0.77 to 0.83. In patients with bacterial CAP, the biomarker levels were significantly higher than among patients with atypical or viral etiology (p < 0.001). PCT with a cut-off point of 0.15 ng/mL was the best predictor for bacterial etiology and for select patients eligible for outpatient care. In conclusion, levels of PCT and CRP positively correlate with increasing severity of CAP and may have a role in predicting both patients who can safely receive outpatient care and the microbial etiology in patients with low CURB-65 scores.

Score to identify the severity of adult patients with influenza A (H1N1) 2009 virus infection at hospital admission.

The objective of this paper was to develop a prognostic index for severe complications among hospitalized patients with influenza A (H1N1) 2009 virus infection. We conducted a prospective observational cohort study of 618 inpatients with 2009 H1N1 virus infection admitted to 36 Spanish hospitals between July 2009 and February 2010. Risk factors evaluated included host-related factors and clinical data at admission. We developed a composite index of severe in-hospital complications (SIHC), which included: mortality, mechanical ventilation, septic shock, acute respiratory distress syndrome, and requirement for resuscitation maneuvers. Six factors were independently associated with SIHC: age >45 years, male sex, number of comorbidities, pneumonia, dyspnea, and confusion. From the ß parameter obtained in the multivariate model, a weight was assigned to each factor to compute the individual influenza risk score. The score shows an area under the receiver operating characteristic (ROC) curve of 0.77. The SIHC rate was 1.9 % in the low-risk group, 10.3 % in the intermediate-risk group, and 29.6 % in the high-risk group. The odds ratio for complications was 21.8 for the high-risk group compared with the low-risk group. This easy-to-score influenza A (H1N1) 2009 virus infection risk index accurately stratifies patients hospitalized for H1N1 virus infection into low-, intermediate-, and high-risk groups for SIHC.

The health, activity, dyspnea, obstruction, age, and hospitalization: prognostic score for stable COPD patients.

UNLABELLED: Multidimensional instruments for determining the severity and prognosis of chronic obstructive pulmonary disease (COPD) must be used in daily clinical practice. OBJECTIVE: To develop and validate a new COPD severity score using variables readily obtained in clinical practice and to compare its predictive capacity with that of other multidimensional indexes. Data collected from a prospective cohort of 611 stable COPD patients were used to derive a clinical prediction rule that was later validated in a separate prospective cohort of 348 patients. In the multivariate analyses, six independent predictive factors were correlated with overall and respiratory mortality: health status, physical activity, dyspnea, airway obstruction (FEV(1)), age, and hospitalizations for COPD exacerbations in the previous two years. These create the HADO-AH score. Based on the ß parameter obtained in the multivariate model, a score was assigned to each predictive variable. The area under the curve for 5-year mortality was 0.79 (95% CI, 0.74-0.83) in the derivation cohort and 0.76 (95% CI, 0.71-0.81) in the validation cohort. The HADO-AH score was a significantly better predictor of mortality than the HADO-score and the Body-mass index, Obstruction, Dyspnea, Exercise-index were statistically significant (p < 0.0004 and p = 0.021, respectively), but was similar to the Age, Dyspnea, and Obstruction-index (p = 0.345). The HADO-AH score provides estimates of all-cause and respiratory mortality that are equal to, or better than, those of other multidimensional instruments. Because it uses only easily accessible measures, it could be useful at all levels of care.

Heat shock protein 70 and cellular disturbances in cochlear cisplatin ototoxicity model.

BACKGROUND: Exposure to cisplatin leads to cochlear cell death by apoptosis; these changes are most marked on the seventh day after exposure. Heat shock proteins are induced in inner ear cells in response to a variety of stimuli. This study examined the role of heat shock protein 70 in cisplatin-induced cochlear cell death. METHODS: Fifty-six Sprague-Dawley rats were involved. Some were injected with cisplatin (5 mg/kg body weight), some with cisplatin plus the caspase inhibitor Z-Asp(OMe)-Glu(OMe)-Val-Asp(OME)-fluoromethylketone (5 mg/kg body weight) and others were left as controls (being injected only with saline). Seven days later, we examined the expression of heat shock protein 70 and several other apoptosis-related proteins within the rat cochlear cells; we also assessed total superoxide dismutase activity, auditory brainstem response and auditory steady state response. RESULTS: Seven days after cisplatin injection, significantly increased expression of heat shock protein 70 was found within the rat cochleae. This correlated with increased executioner caspase levels, total superoxide dismutase activity and auditory brainstem response thresholds, and a significant elevation in auditory steady state response thresholds. Inhibition of caspase-3 activity significantly reduced cochlear heat shock protein 70 expression and total superoxide dismutase activity, and improved auditory brainstem response and auditory steady state response thresholds. CONCLUSIONS: Seven days after cisplatin exposure, we found disturbances of the cochlear cellular machinery involving heat shock protein 70, other apoptotic proteins and total superoxide dismutase.

Development of a prognostic index for 90-day mortality in patients discharged after admission to hospital for community-acquired pneumonia.

BACKGROUND: Although patients admitted to hospital for community-acquired pneumonia (CAP) experience substantial short-term mortality following hospital discharge, few studies have focused on identifying factors that predict mortality after admission to hospital in this population. The objective of this study was to develop and validate a prognostic index for 90-day mortality after hospital discharge among patients with CAP. METHODS: The prognostic index was derived in 1117 adult patients discharged between 2003 and 2007 from a general hospital following admission for CAP. It was validated in 646 consecutive patients with CAP discharged from three other hospitals between 1 November 2005 and 31 July 2006. Risk factors evaluated included host-related factors, severity upon admission, in-hospital management and bacteriology. RESULTS: In the derivation cohort, three factors were independently associated with 90-day mortality: pre-illness functional status, Charlson index (composite measure of co-morbid illnesses) and severity on admission. Mortality at 90 days was 0.7% in the low-risk group, 3.5% in the intermediate-risk group and 17.2% in the high-risk group. In the validation cohort, 90-day mortality in the three groups was 0.6%, 3.9% and 19.6%, respectively. Compared with the low-risk group, the odds ratio for mortality was 43.5 for the high-risk group. The risk categories showed an area under the receiver operating characteristic curve of 0.79 in the derivation cohort and 0.82 in the validation cohort. CONCLUSIONS: The prognostic index accurately stratifies patients admitted to hospital for CAP into low-, intermediate- and high-risk groups for 90-day mortality on discharge. The use of this index could help clinicians improve outcomes in this vulnerable population by targeting specific interventions to each group.

Hodgkin's disease and intercurrent processes that may simulate a relapse.

Hodgkin's disease (HD) is an example of a curable disease. In addition, it can serve as a lesson about other pathologies because of the delayed side effects it produces and the appearance of associated processes that may simulate disease progression. Here we provide a case report of a patient who encapsulates a compendium of situations that may occur in HD.

Hodgkin's disease and intercurrent processes that may simulate a relapse

Hodgkin's disease (HD) is an example of a curable disease. In addition, it can serve as a lesson about other pathologies because of the delayed side effects it produces and the appearance of associated processes that may simulate disease progression. Here we provide a case report of a patient who encapsulates a compendium of situations that may occur in HD (AU)

No disponible

The anticancer drug cisplatin induces an intrinsic apoptotic pathway inside the inner ear.

BACKGROUND AND PURPOSE: Ototoxicity is a known adverse effect of cisplatin (CDDP). Since apoptosis is involved in the development of some pathological conditions associated with the administration of anticancer drugs, we examined, using immunohistochemical and electrophysiological techniques, the apoptotic changes in the cochlea of Sprague-Dawley (SD) rats after an injection of CDDP (5 mgkg(-1) body weight). EXPERIMENTAL APPROACH: Luciferase assays were used to determine the different caspase activities and ATP levels in protein extracts of whole cochleae. The expression of several apoptotic-related proteins was measured by means of Western blotting. These analyses were performed 2, 7 and 30 days after the CDDP injection. The auditory brain stem response was obtained before and at the different times after the injection of CDDP, before the animals were killed. KEY RESULTS: CDDP significantly increased the levels of caspase-3/7 activity and active caspase-3 protein expression and caspase-3 immunofluorescence staining, caspase-9 activity, and Bax protein expression but decreased Bcl-2 protein expression within the rat cochleae. Threshold shifts were significantly elevated 2 days after CDDP treatment. CONCLUSIONS AND IMPLICATIONS: These findings support the hypothesis that cisplatin-related apoptosis evokes an intrinsic pathway of pro-apoptotic signalling within the rat cochleae. Thus, selective inhibition of the sequence of events involved in the intrinsic apoptotic pathway could provide a strategy to minimize cisplatin-induced ototoxicity.

alpha-Glucosidase inhibitory activity of the methanolic extract from Tournefortia hartwegiana: an anti-hyperglycemic agent.

Tournefortia hartwegiana is a Mexican medicinal plant that is used for the treatment of diabetes, diarrhea and kidney pain. In a previous investigation, the methanolic extract of Tournefortia hartwegiana (METh) showed significant hypoglycemic and anti-diabetic properties on normoglycemic and alloxanized rats. In this context, the purpose of the present study was to establish one of the possible modes of action of METh to induce anti-diabetic activity. METh (310mg/kg) effect on alpha-glucosidase activity was investigated. METh intragastric administration was conducted to determine oral glucose tolerance test (OGTT), using different substrates: glucose, sucrose and maltose. The increase in plasma glucose level was significantly suppressed (P<0.05) by the extract after substrates administration. On the other hand, METh inhibited alpha-glucosidase activity in vitro, in a concentration-dependent manner (IC(50) of 3.16mg/mL). These results suggest that METh might exert its anti-diabetic effect by suppressing carbohydrate absorption from intestine, and thereby reducing the post-prandial increase of blood glucose. On the other hand, the bio-guided fractionation of this extract led to the isolation of: beta-sitosterol (1), stigmasterol (2), lupeol (3), ursolic acid (4), oleanolic acid (5), saccharose (6) and myo-inositol (7), using various chromatographic techniques.

Optimal growth of Dunaliella primolecta in axenic conditions to assay herbicides.

To develop an assay for herbicides in marine environments using microalgae, we have optimized the specie, cell culture media and physical conditions to obtain maximal cellular densities in a 96 well micro format to allow mass assays. We first surveyed several species of 7 unicellular eukaryotic algae genera (Dunaliella, Tetraselmis, Chlorella, Ellipsoidon, Isochrysis, Nannochloropsis, and Phaeodactylum) for vigorous in vitro axenic growth. Once the genus Dunaliella was selected, Dunaliella primolecta was preferred among 9 species (bioculata, minuta, parva, peircei, polymorpha, primolecta, quartolecta, salina and tertiolecta) because it showed the highest growth rates. The components (oligo elements, sugars, amino acids and vitamins) and conditions (light, CO(2), temperature) of the culture media were further optimized to obtain the highest cellular densities (up to 60x10(6)cellsml(-1)) and the shortest cell cycle duration ( approximately 12h) for D. primolecta. Then the toxicity of four representative herbicides, alloxydim, and sethoxydim (inhibitors of acetyl-coA carboxilase), metamitron (inhibitor of photosynthesis) and clopyralid (inhibitor of respiration), were assayed on the optimal culture conditions for D. primolecta during 96h. The results showed that D. primolecta was susceptible to those herbicides in the following order: metamitron > sethoxydim > alloxydim. In contrast, clopyralid did not have any effects. Therefore, D. primolecta microcultures can be used to assay a large number of samples for the presence of herbicides under a saline environment.

The presence of an intronic deletion in p73 and high levels of ZEB1 alter the TAp73/DeltaTAp73 ratio in colorectal carcinomas.

TAp73 variants largely mimic p53 suppressor activities, while DeltaTAp73 forms act as oncogenes through the inactivation of p53 and TAp73. The present study analysed how TAp73 and DeltaTAp73 levels might be affected by the presence of a 73 bp deletion in a regulatory region of p73. The clinical relevance of this deletion was also examined. ZEB1 can bind to the region repressing p73 transcription in vitro. The relationship between ZEB1 and p73 variant expression levels was studied in the context of this deletion and the levels of the ZEB1 cofactors p300 and CtBP. Tumour and normal tissue from 81 colorectal cancer patients was analysed to evaluate firstly the levels of TAp73, DeltaTAp73 (DeltaEx2p73, DeltaEx2/3p73, and DeltaNp73), ZEB1, p300, and CtBP by quantitative real-time RT-PCR, and secondly the presence of the 73 bp deletion. Tumour characteristics were examined in each patient. Suppressor and oncogenic isoforms of p73 were co-up-regulated in tumour tissues. Overexpression of p73 variants was associated with adverse tumour features. The 73 bp deletion was present in 40% of the patients and was associated with adverse pathological parameters of the tumours and also with TAp73 down-regulation. In those cases harbouring the deletion, the levels of ZEB1 and those of DeltaEx2p73, DeltaEx2/3p73, and DeltaNp73 correlated directly. Variations in the concentration of p300 affected the observed correlations between ZEB1 and the different p73 variants. In conclusion, in colorectal cancer, the 73 bp deletion in the first intron of the p73 gene and different expression levels of ZEB1 and p300 may act in concert to affect the ratio of TAp73/DeltaTAp73 forms, favouring p73 oncogenic variants. In addition, up-regulation of p73 oncogenic isoforms predicts a poor prognosis based on its relationship with advanced tumour stage.

Phase II study: combination of carboplatin and paclitaxel as second-line treatment in metastatic non-small-cell lung cancer

No disponibleEste estudio fue diseñado para determinar la eficacia y seguridad de la combinación de paclitaxel ycarboplatino como quimioterapia de segunda línea de pacientes con cáncer de células no pequeñas depulmón. El tratamiento consistió en la infusión de 175 mg/m2 de paclitaxel durante 1 hora y carboplatinoAUC 5 durante 30 minutos, administrados cada 3 semanas con un máximo de 6 ciclos. Se incluyeronen el estudio tres grupos de pacientes: los diagnosticados de encontrarse en estadio IV; los quepresentaron progresión durante o después de la administración previa de quimioterapia de primera línea;y los que tenían PS ≤ con funciones hepática, renal y ósea normales. Se incluyeron veintidós pacientesentre enero de 2000 y diciembre de 2002. Sus características clínicas fueron: varones 81%/mujeres19%; histología de adenocarcinoma 12 pacientes (55%)/carcinoma escamoso 6 pacientes(27%)/carcinoma de células grandes 2 pacientes (9%)/otros tipos histológicos 2 pacientes (9%). Lostratamientos administrados previamente fueron: combinaciones con cisplatino en 11 pacientes (50%) ycombinaciones sin cisplatino (ifosfamida, gemcitabina, vinorelbina) en 11 pacientes (50%). En la quimioterapiade primera línea, el 50% de los pacientes recibió en promedio 1 a 4 ciclos. Como quimioterapiade segunda línea se administraron 1 a 3 ciclos en el 50% de los casos y 3 a 6 ciclos en el otro50%. Las dosis administradas fueron el 100% de las planeadas en 20 pacientes, en tanto que en 2 fuenecesario reducir las dosis por la aparición de neutropenia y neurotoxicidad de grado 3. El tratamientofue bien tolerado en general, observándose en cuatro pacientes toxicidad de grados 3 y 4: neutropeniaen 2 de ellos (9%) y neuropatía periférica en otros 2 (9%). En conjunto, respondió el 23% de los enfermos(CI 95%, 8-45): 5 pacientes (23%) con respuesta parcial, 9 casos (36%) con enfermedad estable y8 enfermos (31%) con progresión. El tiempo medio de la progresión con el tratamiento de segunda líneafue de 16 semanas, alcanzando una supervivencia global media de 79 semanas. Desde el comienzodel tratamiento de segunda línea la supervivencia media fue de 24,1 semanas (CI 95%, 13,7-34,5).En este estudio se observó que los pacientes con cáncer de células no pequeñas de pulmón que recibieronla combinación de paclitaxel y carboplatino como tratamiento de segunda línea presentaron unarestricción moderada de actividad sin gran toxicidad

This study was designed to determine the efficacy and safety of the paclitaxel and carboplatincombination in second-line chemotherapy treatment of patients with non-small-cell lung cancer.Treatment consisted of 175 mg/m2 paclitaxel infused in 1 hour and carboplatin AUC 5 infused in 30minutes, administered each 3 weeks for a maximum of 6 cycles. The following patient groups wereincluded in the study: those who were stage IV at diagnosis; with progression during or after theadministration of previous first-line chemotherapy; PS ≤ 2 and with normal hepatic, renal and bonemarrow function. Twenty-two patients were included between January 2000 and December 2002. Theirclinical characteristics were: male 81% / female 19%; adenocarcinoma histology in 12 patients (55%) /squamous carcinoma in 6 patients (27%) / large cell carcinoma in 2 patients (9%), and other types in 2patients (9%). The Performance Status (ECOG Scale) was 0 in 5 patients (22%), 1 in 5 patients (22%)and 2 in 12 patients (55%). Previously administered treatments were: combinations with cisplatin in 11patients (50%) and combinations without cisplatin (ifosfamide, gemcitabine, vinorelbine) in 11 patients(50%). The mean number of first-line chemotherapies received was 1 to 4 cycles in 50% patients. Themean number of second-line treatments was 1 to 3 cycles in 50% and 3 to 6 cycles in the others. Thedoses administered were 100% of that planned in 20 patients, with 2 patients requiring dose reductionsdue to neutropenia and grade 3 neurotoxicity. The treatment was well tolerated with presentation of thefollowing grade 3-4 toxicities: neutropenia in 2 patients (9%), peripheral neuropathy in 2 patients (9%).The overall response rate was 23% (CI 95%, 8-45): 5 patients (23%) with partial response, 9 (36%)with stable disease and 8 (31%) with progression. The median time to progression with second-linetreatment was 16 weeks, reaching a median overall survival of 79 weeks. From the initiation of secondlinetreatment median survival was 24.1 weeks (CI 95%, 13.7-34.5).In this study it was observed that the combination of paclitaxel with carboplatin as second-linechemotherapy in patients with non-small-cell lung cancer presented moderate/restrained activitywithout severe toxicity

Validation of a predictive rule for the management of community-acquired pneumonia.

The CURB-65 score (Confusion, Urea > 7 mmol x L(-1), Respiratory rate > or = 30 x min(-1), low Blood pressure, and age > or = 65 yrs) has been proposed as a tool for augmenting clinical judgement for stratifying patients with community-acquired pneumonia (CAP) into different management groups. The six-point CURB-65 score was retrospectively applied in a prospective, consecutive cohort of adult patients with a diagnosis of CAP seen in the emergency department of a 400-bed teaching hospital from March 1, 2000 to February 29, 2004. A total of 1,100 inpatients and 676 outpatients were included. The 30-day mortality rate in the entire cohort increased directly with increasing CURB-65 score: 0, 1.1, 7.6, 21, 41.9 and 60% for CURB-65 scores of 0, 1, 2, 3, 4, and 5, respectively. The score was also significantly associated with the need for mechanical ventilation and rate of hospital admission in the entire cohort, and with duration of hospital stay among inpatients. The CURB-65 score (Confusion, Urea > 7 mmol x L(-1), Respiratory rate > or = 30 x min(-1), low Blood pressure, and age > or = 65 yrs), and a simpler CRB-65 score that omits the blood urea measurement, helps classify patients with community-acquired pneumonia into different groups according to the mortality risk and significantly correlates with community-acquired pneumonia management key points. The new score can also be used as a severity adjustment measure.