Antimalarial Drug Combination Predictions Using the Machine Learning Synergy Predictor (MLSyPred©) tool.

PURPOSE: Antimalarial drug resistance is a global public health problem that leads to treatment failure. Synergistic drug combinations can improve treatment outcomes and delay the development of drug resistance. Here, we describe the implementation of a freely available computational tool, Machine Learning Synergy Predictor (MLSyPred©), to predict potential synergy in antimalarial drug combinations. METHODS: The MLSyPred© synergy prediction method extracts molecular fingerprints from the drugs' biochemical structures to use as features and also cleans and prepares the raw data. Five machine learning algorithms (Logistic Regression, Random Forest, Support vector machine, Ada Boost, and Gradient Boost) were implemented to build prediction models. Implementation and application of the MLSyPred© tool were tested using datasets from 1540 combinations of 79 drugs and compounds biologically evaluated in pairs for three strains of Plasmodium falciparum (3D7, HB3, and Dd2). RESULTS: The best prediction models were obtained using Logistic Regression for antimalarials with the strains Dd2 and HB3 (0.81 and 0.70 AUC, respectively) and Random Forest for antimalarials with 3D7 (0.69 AUC). The MLSyPred© tool yielded 45% precision for synergistically predicted antimalarial drug combinations that were annotated and biologically validated, thus confirming the functionality and applicability of the tool. CONCLUSION:  The MLSyPred© tool is freely available and represents a promising strategy for discovering potential synergistic drug combinations for further development as novel antimalarial therapies.

Global dataset of soil organic carbon in tidal marshes.

Tidal marshes store large amounts of organic carbon in their soils. Field data quantifying soil organic carbon (SOC) stocks provide an important resource for researchers, natural resource managers, and policy-makers working towards the protection, restoration, and valuation of these ecosystems. We collated a global dataset of tidal marsh soil organic carbon (MarSOC) from 99 studies that includes location, soil depth, site name, dry bulk density, SOC, and/or soil organic matter (SOM). The MarSOC dataset includes 17,454 data points from 2,329 unique locations, and 29 countries. We generated a general transfer function for the conversion of SOM to SOC. Using this data we estimated a median (± median absolute deviation) value of 79.2 ± 38.1 Mg SOC ha-1 in the top 30 cm and 231 ± 134 Mg SOC ha-1 in the top 1 m of tidal marsh soils globally. This data can serve as a basis for future work, and may contribute to incorporation of tidal marsh ecosystems into climate change mitigation and adaptation strategies and policies.

Immobilization of Cr3+, Cd2+, and Pb2+ added to calcareous soil amended with composted agro-industrial residues.

The bioavailability of trace metals in soils poses a major threat to the environment, especially with massive mineral fertilizers added to increase plant yield. A plot experiment was conducted for the effectiveness evaluation of compost and vermicompost, recycled from agro-industrial wastes, in immobilizing chromium, cadmium, and lead added to calcareous soil (artificially contaminated). Moreover, immobilization efficiency was compared to the natural occurrence of these metals in the soil without metal addition (uncontaminated soil). In both soils, amendments and mineral fertilizers were applied at three different levels alone and combined to each other. The experimental design was arranged in factorial complete randomized blocks using contamination, organic and mineral fertilizer levels, and their combination as categorical factors. The distribution of metal fractions and their bioavailability in soils and bioaccumulation in wheat grains were evaluated. Soil alkalinity, the contents of soil organic carbon and nitrogen, available phosphorus, and soil micronutrients were significantly improved under vermicompost and compost compared to mineral fertilizer and control. Vermicompost was more effective than compost in reducing metals bioavailability in contaminated soils by increasing the immobilized organic fractions, but it regressed when combined with mineral fertilizers. The bioavailability of the naturally occurring metal levels in uncontaminated soil did not change significantly compared to contaminated soil. Likewise, wheat yield, plant biomass, and nutrient enrichment in wheat grains improved due to enhanced soil nutrient availability. These composted agro-industrial residues, by-products from food industries, can be classified as environmentally-friendly soil amendments for their great potential to enrich soil nutrients, reduce mineral fertilizer addition, enhance plant growth, and stabilize Cr, Cd, and Pb in contaminated calcareous soils under wheat plants.

Litter decomposition of three halophytes in a Mediterranean salt marsh: Relevance of litter quality, microbial activity and microhabitat.

Studies of litter decomposition in salt marshes have been mainly focused on the measurement of decomposition rates, being litter quality, the type of microbial decomposers and their extracellular enzyme activity, rarely considered. Moreover, most of these studies have been conducted in Poaceae and Cyperaceae species, being scarce the literature on Chenopodiaceae species, which are abundant in Mediterranean salt marshes. Here we analyse the litter decomposition process of two Chenopodiaceae (Sarcocornia fruticosa and Halimione portulacoides) and one Poaceae (Elytrigia atherica) species, belonging S. fruticosa to a halophilous scrub habitat and the other two to a salt meadow habitat of a Mediterranean salt marsh. For each species, we analysed litter decomposition rates, litter quality, fungal and bacterial biomass and potential extracellular enzymes activities. In order to embrace the spatial heterogeneity, two zones were considered within each habitat. Litter of E. atherica decomposed 7- and 13-fold slower than those of S. fruticosa and H. portulacoides, respectively, suggesting that this species is the one that would favour most the carbon sequestration into the soil. The different decomposition rates would be explained by the higher initial lignin and cellulose content of E. atherica rather than by the initial carbon and nitrogen content and C/N ratio. Moreover, enzyme efficiency, compared to enzyme activity, better contributes to explain the different decomposition rates observed. Bacteria dominated throughout the litter decomposition process regardless the species, but fungi increased their relevance in the later stages, when the relative lignin litter content increased. Litter decomposition was affected by microhabitat spatial differences, although the responses depended on the species. Hence, flooding (in the habitat of S. fruticosa) or soil texture (in the habitat of E. atherica and H. portulacoides) might have modulated the decomposition process, being H. portulacoides the most sensitive species to the spatial differences of the salt meadow habitat.

Grado de conocimiento de la detección de drogas en orina entre médicos que atienden a pacientes intoxicados / Level of knowledge of urine drug screening among physicians who treat patients with drug poisoning

No disponible

Cirugía conservadora y mastectomía radical modificada en el cáncer de mama de etapas I y II / Conservative surgery and radical mastectomy in stage I and II breast cancer

INTRODUCCIÓN. El cáncer de mama es la primera causa de muerte por cáncer en la mujer y se ha convertido en una pandemia que amenaza continuar si no se halla la forma de prevenirlo. El objetivo de este trabajo fue evaluar la supervivencia global y el intervalo libre de enfermedad en pacientes que recibieron como tratamiento inicial cirugía conservadora más radioterapia y mastectomía radical modificada; y determinar otras variables pronósticas, como la edad, clínicas histológicas, recaídas y tiempo entre la cirugía y la radioterapia. MÉTODOS. Entre enero del 2000 y diciembre del 2005 se realizó en el Hospital «Julio Trigo López¼ un estudio retrospectivo y descriptivo de un grupo de pacientes con cáncer primario de mama, en etapas I y II. Los datos se extrajeron de las historias clínicas y de encuestas. Se creó una base de datos y se realizó un análisis descriptivo de los datos, frecuencia y porcentajes para el caso de las variables cualitativas y medias, y desviaciones estándares para las cuantitativas. Se estimó la supervivencia y el intervalo libre de enfermedad utilizando el método de Kaplan Meir y se compararon en curvas según las variables de interés de Sug Rank. El análisis de las variables pronósticas de supervivencia e intervalo libre de enfermedad se realizó mediante análisis de regresión de Cox. RESULTADOS. El intervalo libre de enfermedad fue mayor en la cirugía conservadora que en la mastectomía radical modificada, y de igual manera se comporto la supervivencia global. Las pacientes con Rh positivo presentaron mayor intervalo libre de enfermedad (88 por ciento). El carcinoma infiltrante fue la variedad más frecuente y de mayor número de recaídas, en las cuales influyó el tiempo entre la cirugía y la radioterapia. La frecuencia más alta de cáncer de mama se observó en las mujeres mayores de 50 años. En la cirugía conservadora predominó la conducta terapéutica de cirugía más radioterapia y quimioterapia y en la mastectomía radical modificada, la quimioterapia. En la cirugía conservadora fueron más frecuentes las recaídas locorregionales, mientras que en la mastectomía radical, las recaídas más frecuentes se registraron a distancia. CONCLUSIONES. El tipo de cirugía no influyó significativamente en el intervalo libre de enfermedad, pero sí hubo diferencias entre las técnicas conservadoras. Los factores pronósticos tamaño del tumor, estado ganglionar y receptores hormonales influyeron en la supervivencia y en el intervalo libre de enfermedad en todas las pacientes(AU)

INTRODUCTION. Breast cancer is the first cause of death from cancer in females and it has become a pandemic threatening to continue if the way to prevent it is not found. The objective of this paper was to evaluate global survival and the disease free interval in patients that underwent conservative surgery plus radiotherapy and modified radical mastectomy as initial treatment, and to determine other prognostic variables, such as age, histological clinics, relapses and time elapsed between surgery and radiotherapy. METHODS. A retrospective and descriptive study was conducted in a group of patients with stage I and II primary breast cancer at «Julio Trigo López¼ Hospital from January 2000 to December 2005. Data were taken from the medical histories and surveys. A database was created and a descriptive analysis was made of the data, frequency and percentages for the case of qualitative and mean variables, and of the standard deviations for the quantitative variables. Survival and the disease free interval were estimated by Kaplan Meir's method and they were compared by curves according to the Sug Rank's variables of interest. The analysis of the prognostic variables of survival and disease free interval was carried out by Cox's regression analysis. RESULTS. The disease free interval was longer in conservative surgery than in the modified radical mastectomy. Global survival had a similar behaviour. Patients with positive Rh presented a longer disease free interval (88 percent). The infiltrating carcinoma was the most frequent variety and it had the greatest number of relapses, which were influenced by the time elapsed between surgery and radiotherapy. The highest frequency of breast cancer was observed in females over 50. The therapeutic conduct of surgery plus radiotherapy and chemotherapy prevailed in conservative surgery, whereas chemotherapy predominated in the modified radical mastectomy. The locoregional relapses were more common in conservative surgery; however, the most frequent relapses in radical mastectomy were registered at a distance. CONCLUSIONS. The type of surgery did not exert a significant influence on the disease free interval, but there were differences among the conservative techniques. The prognostic factors size of the tumor, ganglionic state and hormone recipients influenced on the survival and on the disease free interval of all patients(AU)

Cirugía conservadora y mastectomía radical modificada en el cáncer de mama de etapas I y II / Conservative surgery and radical mastectomy in stage I and II breast cancer

El intervalo libre de enfermedad fue mayor en la cirugía conservadora que en la mastectomía radical modificada, y de igual manera se comporto la supervivencia global. Las pacientes con Rh positivo presentaron mayor intervalo libre de enfermedad (88 por ciento). El carcinoma infiltrante fue la variedad más frecuente y de mayor número de recaídas, en las cuales influyó el tiempo entre la cirugía y la radioterapia. La frecuencia más alta de cáncer de mama se observó en las mujeres mayores de 50 años. En la cirugía conservadora predominó la conducta terapéutica de cirugía más radioterapia y quimioterapia y en la mastectomía radical modificada, la quimioterapia. En la cirugía conservadora fueron más frecuentes las recaídas locorregionales, mientras que en la mastectomía radical, las recaídas más frecuentes se registraron a distancia...(AU)

The disease free interval was longer in conservative surgery than in the modified radical mastectomy. Global survival had a similar behaviour. Patients with positive Rh presented a longer disease free interval (88 per cent). The infiltrating carcinoma was the most frequent variety and it had the greatest number of relapses, which were influenced by the time elapsed between surgery and radiotherapy. The highest frequency of breast cancer was observed in females over 50. The therapeutic conduct of surgery plus radiotherapy and chemotherapy prevailed in conservative surgery, whereas chemotherapy predominated in the modified radical mastectomy. The locoregional relapses were more common in conservative surgery; however, the most frequent relapses in radical mastectomy were registered at a distance...(AU)

Importancia de algunos medios auxiliares de diagnóstico en la enfermedad inflamatoria pélvica aguda / Importance of some diagnostic aids in the acute pelvic inflammatory disease

INTRODUCCIÓN. Hoy día la enfermedad inflamatoria pélvica aguda se considera un síndrome clínicamente atribuido al paso ascendente de microorganismos desde la vagina al cérvix, hasta el endometrio y las trompas de Falopio, y que es capaz de diseminarse a las estructuras vecinas. Fueron objetivos de esta publicación conocer el comportamiento de la enfermedad, la eficiencia de algunos medios y procedimientos diagnósticos y el comportamiento de las pruebas hematológicas e identificar los gérmenes más frecuentes para definir la conducta posterior. MÉTODOS. El universo estuvo conformado por 108 mujeres atendidas en el Hospital «Julio Trigo López¼ a causa de una enfermedad inflamatoria pélvica aguda. Se seleccionó la muestra aleatoriamente y se registraron en una encuesta variables como datos generales y de salud y de la historia ginecoobstétrica. Para el diagnóstico clínico se realizó tacto vaginal, con anestesia o sin ella, punción del saco de Douglas, ultrasonido, laparoscopia, hemograma, leucograma y eritrosedimentación. En todos los casos se utilizó la laparoscopia como prueba comprobatoria. RESULTADOS. La mayoría de las pacientes tenían edades entre los 20 y 25 años. El dolor abdominal (98,1 por ciento) y la leucorrea (30,6 por ciento) predominaron como sintomatología clínica. Se encontró una alta incidencia de esta enfermedad en mujeres en edad reproductiva, con dos o más embarazos y abortos y el antecedente de dispositivo intrauterino implantado. Además, hubo concordancia diagnóstica entre los resultados aportados por el tacto vaginal y el ultrasonido, al compararlos con la laparoscopia. La prueba menos específica fue el tacto vaginal (20,5 por ciento) y los valores predictivos de la prueba positiva más baja también lo aportó el mismo proceder (64,6 por ciento), así como la eritrosedimentación (70 por ciento). Por tanto, después de la laparoscopia, el medio más efectivo fue el ultrasonido (87,5 por ciento). CONCLUSIONES. Se concluyó que la prueba más eficiente en comparación con la laparoscopia es el ultrasonido (77 por ciento), al cual siguió el tacto vaginal (70 por ciento)(AU)

INTRODUCTION. At present, the acute pelvic inflammatory disease is considered a syndrome clinically attributed to the ascending passage of microorganisms from the vagina to the cervix, the endometrium and the Fallopian's tubes. It is also capable of disseminating to the neighbouring structures. The objective of this paper was to know the behaviour of the disease, the efficiency of some diagnostic aids and procedures, the performance of the haematological tests, and to identify the most common germs to define the further conduct. METHODS. The study group consisted of 108 females seen at "Julio Trigo López" Hospital due to an acute inflammatory pelvic disease. The sample was selected at random and variables such as general and health data and data from the gynecoobstetric history were registered. Vaginal manipulation, with anaesthesia or without it, puncture of Douglas' pouch, ultrasound, laparoscopy, red-blood cell count, white-blood cell count, and erythrosedimentation were used to make the diagnosis. Laparoscopy was used in all cases as a confirmatory test. RESULTS. Most of the patients were aged 20-25. Abdominal pain (98.1 percent) and leucorrhoea (30.6 percent) predominated as clinical symptomatology. A high incidence of this disease was observed in females at reproductive age, with 2 or more pregnancies and abortions and history of implanted intrauterine device. Moreover, there was a diagnostic concordance between the results of the vaginal manipulation and ultrasound, on comparing them with laparoscopy. The least specific test was vaginal manipulation (20.5 percent) and the predictive values of the lowest positive test were obtained with the same procedure (64.6 percent), as well as with erythrosedimentation (70 percent). Therefore, ultrasound proved to be the most effective diagnostic aid (87,5 percent) after laparoscopy. CONCLUSIONS. It was concluded that ultrasound (77 percent) is the most effective test compared with laparoscopy, followed by vaginal manipulation (70 percent)(AU)

Importancia de algunos medios auxiliares de diagnóstico en la enfermedad inflamatoria pélvica aguda / Importance of some diagnostic aids in the acute pelvic inflammatory disease

El universo estuvo conformado por 108 mujeres atendidas en el Hospital Julio Trigo López a causa de una enfermedad inflamatoria pélvica aguda. Se seleccionó la muestra aleatoriamente y se registraron en una encuesta variables como datos generales y de salud y de la historia ginecoobstétrica. Para el diagnóstico clínico se realizó tacto vaginal, con anestesia o sin ella, punción del saco de Douglas, ultrasonido, laparoscopia, hemograma, leucograma y eritrosedimentación. En todos los casos se utilizó la laparoscopia como prueba comprobatoria. La mayoría de las pacientes tenían edades entre los 20 y 25 años. El dolor abdominal (98,1 por ciento) y la leucorrea (30,6 por ciento) predominaron como sintomatología clínica. Se encontró una alta incidencia de esta enfermedad en mujeres en edad reproductiva, con dos o más embarazos y abortos y el antecedente de dispositivo intrauterino implantado. Además, hubo concordancia diagnóstica entre los resultados aportados por el tacto vaginal y el ultrasonido, al compararlos con la laparoscopia. La prueba menos específica fue el tacto vaginal (20,5 por ciento) y los valores predictivos de la prueba positiva más baja también lo aportó el mismo proceder (64,6 por ciento), así como la eritrosedimentación (70 por ciento). Por tanto, después de la laparoscopia, el medio más efectivo fue el ultrasonido (87,5 por ciento)(AU)

The study group consisted of 108 females seen at Julio Trigo López Hospital due to an acute inflammatory pelvic disease. The sample was selected at random and variables such as general and health data and data from the gynecoobstetric history were registered. Vaginal manipulation, with anaesthesia or without it, puncture of Douglas' pouch, ultrasound, laparoscopy, red-blood cell count, white-blood cell count, and erythrosedimentation were used to make the diagnosis. Laparoscopy was used in all cases as a confirmatory test. Most of the patients were aged 20-25. Abdominal pain (98,1 per cent) and leucorrhoea (30,6 per cent) predominated as clinical symptomatology. A high incidence of this disease was observed in females at reproductive age, with 2 or more pregnancies and abortions and history of implanted intrauterine device. Moreover, there was a diagnostic concordance between the results of the vaginal manipulation and ultrasound, on comparing them with laparoscopy. The least specific test was vaginal manipulation (20,5 per cent) and the predictive values of the lowest positive test were obtained with the same procedure (64,6 per cent), as well as with erythrosedimentation (70 per cent). Therefore, ultrasound proved to be the most effective diagnostic aid (87,5 per cent) after laparoscopy(AU)

Relative influence of wildfire on soil properties and erosion processes in different Mediterranean environments in NE Spain.

Abandonment of terraced soils and increased brushland cover has increased wildfire occurrence to almost an annual rate in the Cap de Creus Peninsula, NE Pyrenees Range, Province of Girona, Spain. A wildfire occurred in August 2000 and affected an area of 6760 ha of shrubs and cork trees, whereas still cultivated plots were only slightly affected. Five stations of erosion measurements, corresponding to five different environments (from present cultivation to late abandonment) were destroyed by the passage of fire, and were promptly replaced to allow to monitoring post-fire effects on soil erosion. Selected soil properties were determined monthly before the fire and during 6 months after the fire at a monthly rate. Runoff and sediment yield together with dissolved organic carbon (DOC) in runoff water and organic carbon losses in eroded sediments (EOC) were evaluated throughout 2000. The last stage of abandonment, stands of cork trees, had the highest soil stability. Nevertheless, evidence of unfavourable soil conditions was detected at the shrub stage, when Cistus monspeliensis cover was the dominant opportunistic plant. This stage was considered to be a critical threshold leading either to degradation or regeneration processes according to fire frequency. A drastic change in soil properties, erosion and nutrient depletion occurred after the fire in all the environments. Statistics enabled to state that environments differed significantly in main soil properties. By statistically comparing the measured variables between the environments before and after the fire, DOC was found to be the soil parameter showing the highest significance between environments. Absolute values of erosion were low with respect to other Mediterranean environments although the shallow nature of these soils might deserve special attention because of a comparatively higher risk of degradation.

Runoff erosion and nutrient depletion in five Mediterranean soils of NE Spain under different land use.

We investigated the influence of agricultural management and various plant covers related to the period of abandonment on soil properties, erosion and nutrient depletion in a typical Mediterranean area with sandy loam shallow soils. Cultivated soils (CS) with insufficient management, 5 year abandoned soils covered with meadow (A5), 25 year abandoned soils covered with dense scrubs (A25), 50 year abandoned soils covered with cork trees (A50) and soils in a 50 year pine reforested area (P50) were studied over a period of 6 months (May-October 1999). The soils were classified as Lithic Xerorthents. Both the differences in soil properties and response to rainfall events were mainly attributed to the different vegetation types and stages in land management. Principal components analysis (PCA) was performed on the results, by running the overall data determined after five rainfall events. The factors extracted by PCA of the samples by variables matrix represented the response of the environments to different rainfall intensities as a function of management or natural evolution after abandonment. CS environments showed the highest runoff and sediment yield as well as the highest amount of dissolved organic carbon (DOC) and nitrogen in runoff water. The sequence of abandonment (A5, A25 and A50) showed approximately the same runoff production, whereas eroded sediments (ES) and DOC were inversely correlated. Organic carbon in the ES and DOC in runoff water always increased with the period of abandonment, which accounted for consistent nutrient depletion. Nevertheless, the A50 environment (dominated by Quercus suber) showed the best soil properties, whilst the A25 environment with dense cover of Cistus monspeliensis and Calicotome espinosa seemed to cause a worsening effect on the soil's physical and chemical properties. This is probably because these environments are more severely damaged by wild fire occurrence. In terms of sediment yield, the P50 environment followed CS environment, indicating that reforestation followed by insufficient forest management may negatively affect both soil properties and response to the erosive action of rainfall.