The Strategy of Combining Antidepressants in the Treatment of Major Depression: Clinical Experience in Spanish Outpatients

Introduction. The combination of antidepressants is a useful tool in the treatment of major depression, especially in cases where there is a partial response to antidepressant monotherapy. However, the use of this strategy is a matter of controversy, and its frequency of use in clinical practice is not clear. The aim of our study is to assess the use of antidepressants combination in Spain by reviewing three databases used between 1997 and 2001. Methods. Databases pertain to patients who are study subjects of major depression treatment. These databases are a result of studies performed in Spain and in which 550 psychiatrists participated. The total studied sample was comprised of N = 2, 842 patients, aged over 18, fitting DSM-IV criteria for Major Depressive Episode. The percentage of patients who received more than one antidepressant and the types of combinations used was described. Subsequently, a comparative study between the group which received a combination of antidepressants (N = 64) and the group which received antidepressant monotherapy (N = 775) was performed. Results. 27.1% of patients were on antidepressive monotherapy treatment, and 2.2% were on combination therapy. In the comparison of patients on combination therapy and monotherapy, there were significant differences only in episode duration (P = 0.001). The most frequent combinations are SSRIs and tricyclic antidepressants. The active principle most widely combined is fluoxetine. Conclusions. The prevalence of use of antidepressant combination therapy is 2.2% of the global sample and 8.3% of treated patients. Other than duration of the depressive episode, no clinical characteristics exclusive to patients who received combination rather than monotherapy were found. Our study found that the most frequent combination is SSRIs + TCAs, also being the most studied

Emprendedorismo y políticas públicas. Una introducción a la literatura

In this paper we study entrepreneurship and its relationto public policy through an introductory review of theliterature on the main concepts of entrepreneurship andthe different conceptions of the entrepreneur. We concludethe paper stating that the channels that determine entrepreneurshipand its causal relationship with economic de-velopment are extensive, generating intense debate aboutthe effectiveness and appropriate practices of public policiestherein. In this regard we advocate for the promotionof public policies involving sustainable efforts in bothpublic and private sectors to foster strong entrepreneurshipprocesses.En este trabajo nos proponemos abordar la temáticadel emprendedorismo y su relación con laspolíticas públicas. Para ello, realizamos una revisiónintroductoria de la literatura partiendo de losprincipales conceptos que definen el emprendedorismoy las distintas concepciones del emprendedor.Concluimos el trabajo afirmando que loscanales que determinan la actividad emprendedoray su relación causal con el desarrollo económicoson extensos, generando arduos debates en tornoa la efectividad y prácticas adecuadas de las políticaspúblicas. Es necesario impulsar políticas quecomprometan de manera sostenible esfuerzos delos sectores públicos y privados para mantener vigorososlos procesos de emprendedorismo

CRB2 completes a fully expressed Crumbs complex in the Retinal Pigment Epithelium

The CRB proteins CRB1, CRB2 and CRB3 are members of the cell polarity complex Crumbs in mammals that together with Scribble and Par complexes stablish the polarity of a variety of cell types. Although many members of the Crumbs complex proteins are expressed in the retinal pigment epithelium (RPE), and even though the mRNA of CRB2 has been detected in ARPE-19 cells and in the RPE/Choroid, to date no CRB protein has yet been found in this tissue. To investigate this possibility, we generated an antibody that specifically recognize the mouse CRB2 protein, and we demonstrate the expression of CRB2 in mouse RPE. Confocal analysis shows that CRB2 is restricted to the apicolateral membrane of RPE cells, and more precisely, in the tight junctions. Our study identified CRB2 as the member of the CRB protein family that is present together with the rest of the components of the Crumbs complex in the RPE apico-lateral cell membrane. Considering that the functions of CRB proteins are decisive in the establishment and maintenance of cell-cell junctions in several epithelial-derived cell types, we believe that these findings are a relevant starting point for unraveling the functions that CRB2 might perform in the RPE.This study was supported by grants from Fundación Ramón Areces and Ministerio de Ciencia e Innovación (BFU2008-04490/BFI). S.H.M received support from the Junta de Castilla y León PhD Program.Peer Reviewe

Plataforma Digital para la Gestión de Módulos de Riego en México: SIAM, en México

In Mexico, the traditional management of irrigation modules involves a high consumption of labor, time, and resources, making it costly, slow, and inefficient. To address these challenges, SIAM was developed, a digital platform that facilitates the scheduling, execution, and real-time monitoring of these activities, as well as allowing data collection in the field through electronic devices. This tool, created in the Integrated Development Environment (IDE) of Visual Studio and based on the .Net Framework platform, uses C#, Windows Forms libraries, Syncfusion Essential Studio controls, and MySql databases. Furthermore, SIAM can export ESRI shapefile files with MapWinGis and uses QGis 3.22 for thematic map creation. After being tested in the irrigation modules 3 of D.R. 05 Delicias and III-4 of D.R. 025 Bajo Río Bravo, SIAM proved to be an effective solution, offering a transparent and swift evaluation of the performance of the irrigation modules, thus promoting sustainable and transparent water management.RESUMEN En México, la gestión tradicional de los módulos de riego implica un alto consumo de mano de obra, tiempo y recursos, resultando costosa, lenta e ineficiente. Para abordar estos desafíos, se desarrolló SIAM, una plataforma digital que facilita la programación, ejecución y monitoreo en tiempo real de estas actividades, además de permitir la recopilación de datos en campo a través de dispositivos electrónicos. Esta herramienta, creada en el Entorno de Desarrollo Integrado (IDE) de Visual Studio y basada en la plataforma .Net Framework, utiliza C#, librerías de Windows Forms, controles Syncfusion Essential Studio y bases de datos MySql. Además, SIAM puede exportar archivos ESRI shapefile con MapWinGis y emplea QGis 3.22 para la creación de mapas temáticos. Tras ser probado en los módulos de riego 3 del D.R. 05 Delicias y III-4 del D.R. 025 Bajo Río Bravo, SIAM demostró ser una solución efectiva, proporcionando una evaluación transparente y rápida del desempeño de los módulos de riego, favoreciendo así una gestión sostenible y transparente del agua

Avance tendinoso no convencional para lesiones en las zonas I y II de Verdan. Nueva técnica quirúrgica

Objetivo: Presentar una nueva técnica quirúrgica y los resultados clínicos comparativos de pacientes con roturas de tenorrafia primaria o lesiones crónicas del flexor profundo en las zonas I y II de Verdan, tratados con avance tendinoso no convencional. Materiales y Métodos: Se incluyó a pacientes >18 años, con antecedente de lesiones en las zonas I y II de Verdan y un seguimiento mínimo de 36 meses. La serie estaba formada por 13 pacientes (edad promedio 29 años) que fueron divididos en dos grupos según el tipo de lesión (7 con roturas de tenorrafia primaria y 6 con lesiones crónicas del flexor profundo) y la técnica quirúrgica utilizada (alargamiento en Z más sutura término-terminal y sutura lateral del tendón alargado a un flexor vecino indemne en la zona V, respectivamente). Se empleó la Clasificación de Strickland para la evaluación. Resultados: El seguimiento promedio fue de 51 meses. El intervalo promedio entre la lesión y la cirugía fue de 11.7 semanas. Según la Clasificación de Strickland, 8 pacientes tuvieron resultados excelentes; 4, buenos y uno, pobre. El avance tendinoso promedio fue de 20,5 mm en ambos grupos. Conclusiones: El avance tendinoso no convencional para lesiones en las zonas I y II de Verdan, sea en roturas de tenorrafia primaria o lesiones crónicas del flexor profundo, resultó un tratamiento reproducible y eficaz. Palabras clave: Tendón flexor; alargamiento; zetaplastia. Nivel de Evidencia: II

México y sus Desafíos Hídricos: una mirada a través del ITA y IER en Zonas de Riego

The entirety of the water stress experienced by crops, intensified by the effects of climate change, can be measured through quantitative indicators. In this context, the aim is to introduce and suggest the Water Stress Index (WSI) and the Water Use Efficiency (WUE) based on the water footprint of crops. A study was conducted in the irrigation module III-4 of the Irrigation District 025 Bajo Río Bravo, Tamaulipas, where crops have periodically faced water shortages. A Baseline was defined for situations without water stress, and subsequently, the Current Condition under water stress conditions in the studied crops was estimated. For this, evapotranspiration, water volumes used, and water footprints were measured, and these data were then normalized. Four mathematical formulas were derived to determine the WSI and WUE. The average WSI based on total water footprints was 61.66%, while the average WUE turned out to be 38.34%. These indices provide a tool to effectively analyze total water stress, promoting sustainable water management.La totalidad del estrés hídrico al que están expuestos los cultivos, intensificado por los efectos del cambio climático, puede ser medido a través de indicadores cuantitativos. En este contexto, se busca introducir y sugerir el Índice de Tensión del Agua (ITA) y el Índice de Eficiencia de Riego (IER) basándose en la huella hídrica de los cultivos. Se llevó a cabo un estudio en el módulo de riego III-4 del Distrito de Riego 025 Bajo Río Bravo, Tamaulipas, donde los cultivos han enfrentado periódicamente falta de agua. Se definió una Línea Base para situaciones sin estrés hídrico y posteriormente se estimó la Condición Actual bajo condiciones de estrés hídrico en los cultivos estudiados. Para ello, se midió la evapotranspiración, los volúmenes de agua utilizados y las huellas hídricas, y posteriormente se normalizaron estos datos. Se derivaron cuatro fórmulas matemáticas para determinar el ITA y el IER. El ITA medio basado en las huellas hídricas totales fue del 61.66%, mientras que el IER medio resultó ser del 38.34%. Estos índices ofrecen una herramienta para analizar de manera efectiva el estrés hídrico total, favoreciendo una gestión sostenible del agua

Cognitive Effects of Combined Amisulpride and Quetiapine Treatment in Patients With Refractory Schizophrenia: A Naturalistic, Prospective Study.

Background: There are different treatment options, but little support of evidence in the treatment of patients with resistant schizophrenia. In this study we used antipsychotic polypharmacy (AP) comprising 1200 mg of amisulpride and 600 mg of quetiapine, using neurocognitive evaluations to measure clinical change. Study Question: The AP of amisulpride and quetiapine implicará una mejoría clínica en pacientes with resistant schizophrenia que reflejará especialmente en una mejoría cognitiva. Study Design: Naturalistic and prospective study. 26 patients with no biological response to medication, high social maladjustment, a long history of the disease, to whom Kane's and Brenner's criteria for treatment-resistant schizophrenia were applied and assessed by a battery of neurocognitive evaluations desde a pre-treatment baseline y a los six months treatment. Measures and Outcomes: La mejoría cognitiva implicara una mejora significativa in the cognitive test: Stroop test, WAIS Coding Subtest, Continuous Trail Making Test (CTMT) desde la línea base y los 6 meses de tratamiento. También implicará mejoría en las escalas de Calgary Depression Scale (CDS), Simpson-Angus Scale (SAS) and a Visual Analogue Scale (EVA) con las que fueron evaluados en línea base, a los 3 meses y a los 6 meses. Results: Subjects, after six months treatment with amisulpride and quetiapine, did statistically significant difference in the assessed areas: WAIS Coding Subtest (P <0.001), CTMT A & B (CTMTA P< 0,034; CTMTB P< 0,000) and in Stroop tests: Word (P< 0,001), word-color (P< 0,007) and interference (P< 0,039). Furthermore they showed a statistically significant difference in CDS (P< 0,002), SAS (P< 0,019), and EVA (P < 0.001). Conclusion: The results of this report show a cognitive and clinical improvement in refractory patients after the administration of amisulpride and quetiapine.pre-print523 K

Soluble platelet-endothelial cell adhesion molecule-1, a biomarker of ventilator-induced lung injury

Introduction: Endothelial cell injury is an important component of acute lung injury. Platelet-endothelial cell adhesion molecule-1 (PECAM1) is a transmembrane protein that connects endothelial cells to one another and can be detected as a soluble, truncated protein (sPECAM1) in serum. We hypothesized that injurious mechanical ventilation (MV) leads to shedding of PECAM1 from lung endothelial cells resulting in increasing sPECAM1 levels in the systemic circulation. Methods: We studied 36 Sprague–Dawley rats in two prospective, randomized, controlled studies (healthy and septic) using established animal models of ventilator-induced lung injury. Animals (n = 6 in each group) were randomized to spontaneous breathing or two MV strategies: low tidal volume (VT) (6 ml/kg) and high-VT (20 ml/kg) on 2 cmH2O of positive end-expiratory pressure (PEEP). In low-VT septic animals, 10 cmH2O of PEEP was applied. We performed pulmonary histological and physiological evaluation and measured lung PECAM1 protein content and serum sPECAM1 levels after four hours ventilation period. Results: High-VT MV caused severe lung injury in healthy and septic animals, and decreased lung PECAM1 protein content (P < 0.001). Animals on high-VT had a four- to six-fold increase of mean sPECAM1 serum levels than the unventilated counterpart (35.4 ± 10.4 versus 5.6 ± 1.7 ng/ml in healthy rats; 156.8 ± 47.6 versus 35.6 ± 12.6 ng/ml in septic rats) (P < 0.0001). Low-VT MV prevented these changes. Levels of sPECAM1 in healthy animals on high-VT MV paralleled the sPECAM1 levels of non-ventilated septic animals. Conclusions: Our findings suggest that circulating sPECAM1 may represent a promising biomarker for the detection and monitoring of ventilator-induced lung injury

VITAL phase 2 study: Upfront 5-fluorouracil, mitomycin-C, panitumumab and radiotherapy treatment in nonmetastatic squamous cell carcinomas of the anal canal (GEMCAD 09-02)

Aim: VITAL, a phase II single-arm study, aimed to evaluate efficacy and safety of panitumumab addition to 5-fluorouracil (5-FU), mitomycin-C (MMC) and radiotherapy (RT) in patients with localized squamous cell carcinoma of the anal canal (SCCAC). Methods: Adult, treatment-naïve SCCAC patients (Stage T2-T4, any N, M0) and ECOG-PS ≤2, received panitumumab (6 mg/kg, day 1 and Q2W; 8 weeks), 5-FU (1000 mg/m2/d, days 1-4 and 29-32), MMC (10 mg/m2, days 1 and 29) and RT 45 Gy (1.8 Gy/fraction) to the primary tumor and mesorectal, iliac and inguinal lymph nodes, plus 10-15 Gy boost dose to the primary tumor and affected lymph nodes. The primary objective was disease free survival rate (DFS) at 3-years (expected 3-year DFS rate: 73.7 ± 12%). Results: Fifty-eight patients (31 women; median age: 59 years; ECOG-PS 0-1:98%; TNM II [29%] (T2 or T3/N0/M0)/IIIA (T1-T3/N1/M0 or T4/N0/M0) [21%]/IIIB (T4/N1/M0 or any T/N2 or N3/M0) [47%]/nonevaluable [4%]) were included. The median follow-up was 45 months. The 3-year DFS rate was 61.1% (95% CI: 47.1, 72.4). The 3-year overall survival rate was 78.4% (95% CI: 65.1, 87.1). Eighteen patients (31.0%) required a colostomy within 2 years posttreatment. Grade 3-4 toxicities were experienced by 53 (91%) patients. Most common grade 3-4 treatment-related events were radiation skin injury (40%) and neutropenia (24%). No toxic deaths occurred. Improved efficacy in colostomy-free survival and complete response rate was observed in human papilloma virus positive patients. Conclusions: Panitumumab addition to MMC-5FU regimen in SCCAC patients increases toxicity and does not improve patients’ outcomes. RT plus MMC-5FU remains the standard of care for localized SCCAC patients.This work was supported by Amgen S.A