Empirical model to assess leaching of pesticides in soil under a steady-state flow and tropical conditions.

Abstract: An empirical model of leaching of pesticides was developed to simulate the concentration of fungicides throughout unsaturated soil. The model was based on chemical reactions and the travel time of a conservative tracer to represent the travel time required for water to flow between soil layers. The model's performance was then tested using experimental data from dimethomorph and pyrimethanil applied to the soil under field and laboratory conditions. The empirical model simulated fungicide concentration on soil solids and in soil solution at different depths over time (mean square error between 2.9 mg2 kg-2 and 61mg2 kg-2) using sorption percentages and degradation rates under laboratory conditions. The sorption process was affected by the organic carbon, clay, and the effective cation exchange capacity of the soil. The degradation rate values of dimethomorph (0.039 d-1-0.009 d-1) and pyrimethanil (0.053 d-1-0.004 d-1) decreased from 0 to 40 cm and then remained constant in deeper soil layers (60-80 cm). Fungicide degradation was a critical input in the model at subsurface layers. The model was determined to be a reliable mathematical tool to estimate the leachability of pesticides in tropical soil under a steady-state flow. It may be extended to other substances and soils for environmental risk assessment projects. Supplementary Information: The online version contains supplementary material available at 10.1007/s13762-023-05038-w.

Experiencia inicial del uso de SelectMDx(R) en el diagnóstico de cáncer de próstata en un entorno de práctica clínica habitual «real-world evidence» / Initial experience with SelectMDx(R) in the diagnosis of prostate cancer in a real-world evidence clinical practice setting

INTRODUCCIÓN: El uso de biomarcadores en la detección del cáncer de próstata (CP) puede disminuir el sobrediagnóstico y sobretratamiento de CP no significativos. Analizamos la utilidad y aplicabilidad del marcador SelectMDx® en un entorno de práctica clínica habitual. MATERIAL Y MÉTODOS: Estudio retrospectivo de 48 pacientes evaluados mediante el test SelectMDx® entre julio de 2017 y abril de 2019. Los pacientes se estratificaron en dos grupos según el riesgo estimado por el test de CP clínicamente significativo (CP-CS): < 2% o «muy bajo riesgo», y > 2%. Los resultados se expresaron en función de los antecedentes de biopsia prostática (BP) y resonancia magnética multiparamétrica (RMmp). RESULTADOS: En pacientes con BP negativa y RMmp normal/dudosa el riesgo fue < 2% en 7/9 casos. En pacientes sin BP y RMmp normal/dudosa el riesgo fue < 2% en 12/18 casos, y 2/6 casos con un riesgo % presentaron un CP-CS. De los 14 pacientes sin BP ni RMmp previas, 9 presentaron un riesgo < 2%, con 2 casos diagnosticados de CP en los 5 pacientes con riesgo > 2%. En el resto de subgrupos el número de pacientes es pequeño como para poder extraer conclusiones. En todos los casos con tacto rectal patológico el test demostraba un riesgo de padecer CP > 2%. CONCLUSIÓN: SelectMDx® es un test prometedor para detectar pacientes con un riesgo muy bajo de CP-CS, especialmente en pacientes con sospecha de CP con o sin BP negativas, en los que la RMmp muestre un resultado normal/dudoso. La presencia de un tacto rectal patológico puede condicionar el resultado del test

INTRODUCTION: The use of biomarkers in the detection of prostate cancer (PC) can decrease overdiagnosis and overtreatment of non-significant PC. We analyze the usefulness and applicability of the SelectMDx® marker in a routine clinical practice setting. MATERIAL AND METHODS: Retrospective study of 48 patients evaluated by the SelectMDx® test between July 2017 and April 2019. Patients were stratified into two groups according to the risk estimated by the clinically significant CP test (CS-PC): < 2% or 'very low risk', and > 2%. Results were expressed based on previous prostate biopsy (PB) and multi-parametric magnetic resonance imaging (mpMRI) outcomes. RESULTS: Patients with negative PB and normal/doubtful mpMRI had < 2% risk in 7/9 cases. Patients without PB and normal/doubtful mpMRI had < 2% risk in 12/18 cases, and 2/6 cases with a > 2% risk presented CS-PC. Of the 14 patients with no previous PB or mpMRI, 9 had < 2% risk, and 2 cases were diagnosed with PC from the group of patients (5) with risk >2%. The number of patients in the remaining subgroups is too small to draw any conclusions. In all cases with pathological digital rectal examination, the test showed a > 2% PC risk. CONCLUSION: SelectMDx® is a promising test for detecting patients with a very low risk of CS-PC, especially in patients with suspected PC, with or without negative PB, with normal/doubtful mpMRI. The presence of a pathological digital rectal examination may condition the result of the test

Initial experience with SelectMDx® in the diagnosis of prostate cancer in a real-world evidence clinical practice setting. / Experiencia inicial del uso de SelectMDx® en el diagnóstico de cáncer de próstata en un entorno de práctica clínica habitual «real-world evidence¼.

INTRODUCTION: The use of biomarkers in the detection of prostate cancer (PC) can decrease overdiagnosis and overtreatment of non-significant PC. We analyze the usefulness and applicability of the SelectMDx® marker in a routine clinical practice setting. MATERIAL AND METHODS: Retrospective study of 48 patients evaluated by the SelectMDx® test between July 2017 and April 2019. Patients were stratified into two groups according to the risk estimated by the clinically significant CP test (CS-PC): <2% or 'very low risk', and >2%. Results were expressed based on previous prostate biopsy (PB) and multi-parametric magnetic resonance imaging (mpMRI) outcomes. RESULTS: Patients with negative PB and normal/doubtful mpMRI had <2% risk in 7/9 cases. Patients without PB and normal/doubtful mpMRI had <2% risk in 12/18 cases, and 2/6 cases with a >2% risk presented CS-PC. Of the 14 patients with no previous PB or mpMRI, 9 had <2% risk, and 2 cases were diagnosed with PC from the group of patients (5) with risk >2%. The number of patients in the remaining subgroups is too small to draw any conclusions. In all cases with pathological digital rectal examination, the test showed a >2% PC risk. CONCLUSION: SelectMDx® is a promising test for detecting patients with a very low risk of CS-PC, especially in patients with suspected PC, with or without negative PB, with normal/doubtful mpMRI. The presence of a pathological digital rectal examination may condition the result of the test.

[Cognitive-behavioural group therapy for insomnia: evaluation of the results after its implementation in a health department]. / Terapia grupal cognitivo-conductual para el insomnio: evaluación de resultados tras su introducción en un departamento de salud.

INTRODUCTION: Cognitive-behavioural therapy (CBT) is the preferred treatment in cases of chronic insomnia disorder in adults. PATIENTS AND METHODS: Open pragmatic study of 32 patients after eight sessions of group CBT for insomnia. RESULTS: Remission (insomnia severity index: 0-7 points) and response (insomnia severity index drops to > 8) were 31.3% and 46.9% at one month (n = 32) and 42.8% and 52.4% at one year (n = 21), respectively, with an effect size of 1.9 at one month and 2.3 at one year. At one month, 40.6% met the criteria for a case of insomnia (according to the insomnia symptoms questionnaire), and at one year, 19%, with a significant improvement in the symptoms at night and the consequences during the day. The questions of the Pittsburgh Sleep Quality Index on insomnia and sleep efficiency also improved. The pre-sleep arousal scale (n = 7) showed a shift from significant somatic and cognitive arousal to no arousal at one month. In the sleep diaries, total sleep time increased by an average of 53 minutes at one month (n = 14) and 76 minutes at one year (n = 10), with an increase of more than 10% in 71.4% of patients at one month and at one year, and an average sleep efficiency of more than 85%. The effect size for total sleep time and sleep efficiency was between 0.7 and 1. CONCLUSIONS: Group CBT for insomnia appears to be an effective treatment option in a clinical setting.

TITLE: Terapia grupal cognitivo-conductual para el insomnio: evaluación de resultados tras su introducción en un departamento de salud.Introducción. La terapia cognitivo-conductual (TCC) es el tratamiento de elección en el trastorno de insomnio crónico en adultos. Pacientes y métodos. Estudio pragmático abierto de 32 pacientes tras ocho sesiones de TCC grupal para el insomnio. Resultados. La remisión (índice de gravedad del insomnio: 0-7 puntos) y la respuesta (caída del índice de gravedad del insomnio > 8) fue del 31,3% y 46,9% al mes (n = 32) y del 42,8% y 52,4% al año (n = 21), respectivamente, con un tamaño del efecto de 1,9 al mes y 2,3 al año. Al mes, el 40,6% cumplía criterios de caso de insomnio (según el cuestionario de síntomas de insomnio), y al año, el 19%, con una mejoría significativa de síntomas nocturnos y consecuencias diurnas. También mejoraron las preguntas del índice de calidad de sueño de Pittsburgh sobre el insomnio y la eficiencia del sueño. La escala de activación previa al sueño (n = 7) mostró un trasvase desde activación significativa somática y cognitiva a ausencia de activación al mes. En los diarios de sueño, el tiempo total de sueño aumentó 53 minutos de media al mes (n = 14) y 76 al año (n = 10), con un aumento superior al 10% en el 71,4% de los pacientes al mes y al año, y una eficiencia del sueño media superior al 85%. El tamaño del efecto para el tiempo total de sueño y la eficiencia del sueño estuvo entre 0,7 y 1. Conclusiones. La TCC grupal para el insomnio parece una opción terapéutica eficaz en un entorno clínico.

Ultra-selection of metastatic colorectal cancer patients using next-generation sequencing to improve clinical efficacy of anti-EGFR therapy.

BACKGROUND: Extended RAS analysis is mandatory in metastatic colorectal cancer (mCRC) patients. The optimal threshold of RAS mutated subclones to identify patients most likely to benefit from antiepidermal growth factor receptor (EGFR) therapy is controversial. Our aim was to assess the clinical impact of detecting mutations in RAS, BRAF, PIK3CA and EGFRS492R in basal tissue tumour samples by using a highly sensitive next-generation sequencing (NGS) technology in mCRC patients treated with chemotherapy plus anti-EGFR or anti-vascular endothelial growth factor. PATIENTS AND METHODS: Five hundred and eighty-one tumour samples from untreated mCRC patients from 7 clinical studies were collected. Mutational analysis was carried out by standard-of-care (therascreen pyro) with a sensitivity detection of 5% mutant allele fraction (MAF), and compared with NGS technology using 454GS Junior platform (Roche Applied Science, Germany) with a sensitivity of 1%. Molecular results were correlated with clinical outcomes. RESULTS: After quality assessment, 380 samples were evaluable for molecular analysis. Standard-of-care mutational analysis detected RAS, BRAFV600E or PIK3CA mutations in 56.05% of samples compared with 69.21% by NGS (P = 0.00018). NGS identified coexistence of multiple low-frequency mutant alleles in 96 of the 263 mutated cases (36.5%; range 2-7). Response rate (RR), progression-free survival (PFS) and overall survival (OS) were increasingly improved in patients with RAS wild-type, RAS/BRAF wild-type or quadruple (KRAS/NRAS/BRAF/PIK3CA) wild-type tumours treated with anti-EGFR, assessed by standard-of-care. No additional benefit in RR, PFS or OS was observed by increasing the detection threshold to 1% by NGS. An inverse correlation between the MAF of the most prevalent mutation detected by NGS and anti-EGFR response was observed (P = 0.039). EGFRS492Rmutation was not detected in untreated samples. CONCLUSIONS: No improvement in the selection of patients for anti-EGFR therapy was obtained by adjusting the mutation detection threshold in tissue samples from 5% to 1% MAF. Response to anti-EGFR was significantly better in patients with quadruple wild-type tumours.

Reversible solvatomagnetic switching in a single-ion magnet from an entatic state.

A vast impact on molecular nanoscience can be achieved using simple transition metal complexes as dynamic chemical systems to perform specific and selective tasks under the control of an external stimulus that switches "ON" and "OFF" their electronic properties. While the interest in single-ion magnets (SIMs) lies in their potential applications in information storage and quantum computing, the switching of their slow magnetic relaxation associated with host-guest processes is insufficiently explored. Herein, we report a unique example of a mononuclear cobalt(ii) complex in which geometrical constraints are the cause of easy and reversible water coordination and its release. As a result, a reversible and selective colour and SIM behaviour switch occurs between a "slow-relaxing" deep red anhydrous material (compound 1) and its "fast-relaxing" orange hydrated form (compound 2). The combination of this optical and magnetic switching in this new class of vapochromic and thermochromic SIMs offers fascinating possibilities for designing multifunctional molecular materials.

The single water-surface sweep estimation method accurately estimates very low (n = 4) to low-moderate (n = 25-100) and high (n > 100) Aedes aegypti (Diptera: Culicidae) pupae numbers in large water containers up to 13 times faster than the exhaustive sweep and total count method and without any sediment contamination.

OBJECTIVE: To confirm that a single water-surface sweep-net collection coupled with three calibration factors (2.6, 3.0 and 3.5 for 1/3, 2/3 and 3/3 water levels, respectively) (WSCF) could accurately estimate very low to high Aedes aegypti pupae numbers in water containers more rapidly than the exhaustive 5-sweep and total count (ESTC) method recommended by WHO. METHODS: Both methods were compared in semi-field trials using low (n = 25) to moderate (n = 50-100) pupae numbers in a 250-l drum at 1/3, 2/3 and 3/3 water levels, and by their mean-time determinations using 200 pupae in three 220- to 1024-l water containers at these water levels. Accuracy was further assessed using 69.1% (393/569) of the field-based drums and tanks which contained <100 pupae. RESULTS: The WSCF method accurately estimated total populations in the semi-field trials up to 13.0 times faster than the ESTC method (all P < 0.001); no significant differences (all P-values ≥ 0.05) were obtained between the methods for very low (n = 4) to low-moderate (n = 25-100) and high (n > 100) pupae numbers/container and without sediment disturbance. CONCLUSION: The simple WSCF method sensitively, accurately and robustly estimated total pupae numbers in their principal breeding sites worldwide, containers with >20 l water volumes, significantly (2.7- to 13.0-fold: all P-values <0.001) faster than the ESTC method for very low to high pupae numbers/container without contaminating the clean water by sediment disturbance which is generated using the WHO-recommended ESTC method. The WSCF method seems ideal for global community-based surveillance and control programmes.

Optimization of DNA extraction from fresh leaf tissues of Melanoxylon brauna (Fabaceae).

Melanoxylon brauna (Fabaceae - Caesalpinioideae) is an endemic and valuable hardwood tree species in the Brazilian Atlantic rainforest; it is comparable to African ebony wood. We tested three protocols of DNA extraction based on the citrimonium bromide (CTAB) method and evaluated the quantity, purity and integrity of the DNA. We also determined whether these procedures interfere with PCR amplification in order to develop a protocol for M. brauna. We found that the quality and integrity of DNA were improved with the use of proteinase K in the extraction buffer and by modifications in the centrifugation speed. The lowest concentration of DNA was obtained with Doyle and Doyle's protocol (5.42 ng/µL). Ferreira and Grattapaglia's protocol modified for M. brauna provided the most DNA (36.89 ng/µL) and the highest quality DNA (purity ratio of 1.80 nm). The original Ferreira and Grattapaglia protocol provided 13.42 ng/µL DNA; however, the purity ratio (1.44 nm) indicates protein contamination. PCR results showed that Ferreira and Grattapaglia's protocol modified for M. brauna gave satisfactory quantity and purity of DNA for molecular studies.

Three calibration factors, applied to a rapid sweeping method, can accurately estimate Aedes aegypti (Diptera: Culicidae) pupal numbers in large water-storage containers at all temperatures at which dengue virus transmission occurs.

The ability of a simple sweeping method, coupled to calibration factors, to accurately estimate the total numbers of Aedes aegypti (L.) (Diptera: Culicidae) pupae in water-storage containers (20-6412-liter capacities at different water levels) throughout their main dengue virus transmission temperature range was evaluated. Using this method, one set of three calibration factors were derived that could accurately estimate the total Ae. aegypti pupae in their principal breeding sites, large water-storage containers, found throughout the world. No significant differences were obtained using the method at different altitudes (14-1630 m above sea level) that included the range of temperatures (20-30 degrees C) at which dengue virus transmission occurs in the world. In addition, no significant differences were found in the results obtained between and within the 10 different teams that applied this method; therefore, this method was extremely robust. One person could estimate the Ae. aegypti pupae in each of the large water-storage containers in only 5 min by using this method, compared with two people requiring between 45 and 90 min to collect and count the total pupae population in each of them. Because the method was both rapid to perform and did not disturb the sediment layers in these domestic water-storage containers, it was more acceptable by the residents, and, therefore, ideally suited for routine surveillance purposes and to assess the efficacy of Ae. aegypti control programs in dengue virus-endemic areas throughout the world.

Sample sizes for identifying the key types of container occupied by dengue-vector pupae: the use of entropy in analyses of compositional data.

A method has been developed for estimating the sample sizes needed to identify categories that comprise a large proportion of a compositional data-set. The method is to be used in the design of surveys of mosquito pupae, for identifying the key container types from which the majority of adult dengue vectors emerge. Although a finite-population correction was devised for estimating the mean of a negative binomial distribution, other complications of parametric approaches make them unlikely to yield methods simple enough to be practically applicable. The Shannon-Wiener index was therefore investigated as a more useful alternative, at the cost of theoretical generalizability, in an approach based on re-sampling methods in conjunction with the use of entropy. This index can be used to summarize the degree to which pupae are either concentrated in a few container types, or dispersed among many. An empirical relationship between the index and the repeatability of surveys of differing sample sizes was observed. A step-wise rule, based on the entropy of the cumulative data, was devised for determining the sample size, in terms of the number of houses positive for pupae, at which a pupal survey might reasonably be stopped.

Pupal-productivity surveys to identify the key container habitats of Aedes aegypti (L.) in Barranquilla, the principal seaport of Colombia.

Surveys were conducted in three neighbourhoods of Barranquilla, the main seaport of Colombia, to identify, using counts of pupae in water containers during the wet and dry seasons, the most productive Aedes aegypti breeding sites. Overall, 3,433 premises were investigated in the wet season and 3,563 in the dry, representing, respectively, 82.3% and 84.6% of the total numbers of premises in the study areas. Despite a reasonably reliable supply of piped water, there were still some large storage containers for domestic water (cement ground tanks and plastic, metal and cement drums) in the area. Although such containers represented only 1.8%-16.3% of the total number of containers observed, they contributed 72.0%-78.2% and 65.0%-95.8% of the total Ae. aegypti pupal population in the three study neighbourhoods during the wet and dry seasons, respectively. In contrast, bottles represented 23.0%-88.9% of the total number of containers but produced no more than 0.1% of the total Ae aegypti pupal populations in these neighbourhoods. Other containers (tyres, vases, 'other discarded' and 'other used') generally produced only low numbers of pupae. In some settings, however, containers in the 'other discarded' category could contribute up to 19% of the total pupal population, and in one survey of one neighbourhood a single container in this category held 9.1% of all the pupae collected. These results, from a city where dengue fever is endemic, will help to focus local campaigns for Ae. aegypti source-reduction on the most productive categories of container.

The cost of steroid-free protocols in primary cadaver kidney transplantation.

Steroid-free immunosuppression regimens have been enjoying recent success in clinical transplantation. The use of antibodies required for such protocols can be an economic burden. We proposed to study their cost in our center. This retrospective study involved 147 consecutive patients subjected to 4 protocols of immunosuppression. The first received triple therapy. The second group received induction with basiliximab, whereas the third received Basiliximab plus cyclosporine (CSA) plus mycophenolate mofetil (MMF), and the fourth received Thymoglobulin plus CSA plus MMF in conjuction with only 4 days of steroid. Rejection episodes were treated with Solumedrol. Six-month charges were obtained from computerized records of the finance department, the in-house laboratories, and the transplantation service registry. All charges were expressed in 2004 dollars. Statistical analyses were obtained using chi-square, analysis of variance (ANOVA) and Kaplan-Meier tests. The 4 groups were similar with regard to donor and/or recipient gender, race, panel reactive antibodies, cold ischemia, dialysis requirements length of stay and readmission, graft survival, and function. Charges were significantly higher in the last 2 groups as compared with triple therapy.

Estudio experimental para comprobar la efectividad de los ácidos grasos hiperoxigenados en la prevención de las úlceras por presión en pacientes ingresados / Experimental study to test the effectiveness of hyperoxygenated fatty acids in the prevention of pressure sores in hospitalized patients

Objetivo: Identificar si hay diferencias en la incidencia de úlceras por presión en los enfermos a los que se realiza prevención con aplicación de ácidos grasos hiperoxigenados y a los que no se les aplica. Diseño: Estudio experimental, aleatorizado, controlado, con grupo control y grupo experimental. Ámbito de estudio: Hospital General Vall d'Hebron, entre diciembre de 1999 y mayo de 2000.Sujetos de estudio: Tras calcular el tamaño de la muestra necesario, se estudiaron a 192 pacientes que ingresaron en el centro sin úlceras por presión y que tenían la movilidad y la actividad alteradas (según la escala de riesgo EMINA©). La técnica de muestreo utilizada ha sido accidental, a medida que iban ingresando los pacientes en el hospital. Intervención: Al grupo control se le realizó la prevención habitual para las úlceras por presión que se lleva a cabo en el hospital. Al grupo experimental, además de esta prevención, se le aplicaron ácidos grasos hiperoxigenados según el protocolo establecido para el estudio. La asignación de los pacientes a los 2 grupos se realizó de manera aleatoria. Resultados y conclusiones: Se estudiaron a 192 pacientes (96 por grupo). La incidencia de úlceras por presión en el grupo control fue del 35 por ciento (intervalo de confianza [IC] del 95 por ciento, 27-47 por ciento) y en el grupo experimental del 19 por ciento (IC del 95 por ciento, 12-29 por ciento), siendo esta diferencia estadísticamente significativa (*2 = 6,8; gl = 1; p = 0,007).La incidencia de úlceras por presión es menor en el grupo experimental, lo que indica que los ácidos grasos hiperoxigenados son útiles para prevenir el desarrollo de este tipo de úlceras (AU)

Reversal of steroid- and anti-lymphocyte antibody-resistant rejection using intravenous immunoglobulin (IVIG) in renal transplant recipients.

BACKGROUND: Despite the recent advances in immunosuppression, steroid-resistant rejection remains a difficult problem in renal transplant recipients. METHODS: We reviewed our experience with i.v. immunoglobulin (IVIG) in the treatment of steroid- and antilymphocyte antibody-resistant rejection in renal transplant patients. Between September 1996 and March 1999, 17 patients were treated with IVIG to reverse steroid- or antilymphocyte antibody-resistant rejection. A total of 2 g/kg of IVIG was administered to patients during each treatment course. RESULTS: With a mean follow-up of 21.5+/-9.5 months from the time of IVIG administration, patient and graft survival rates were 94% (16/17) and 71% (12/17), respectively. The baseline mean serum creatinine level prior to rejection was 2.2+/-0.7 mg/dl and peaked at 3.3+/-1.1 mg/dl at the time of the diagnosis of refractory rejection. IVIG therapy was associated with a fall in the mean creatinine to 2.8+/-1.1 mg/dl. The most recent serum creatinine in patients with functioning grafts was 2.8+/-1.6 mg/dl. In 82% of allograft biopsies after IVIG, reversal or reduction in the severity of rejection was demonstrated. In addition, IVIG therapy rescued three of four patients with antilymphocyte antibody-resistant rejection. CONCLUSIONS: IVIG rescue therapy for steroid- or antilymphocyte antibody-resistant rejection is associated with resolution or improvement of rejection severity, stable renal function, and reasonable graft survival.