Novel phthalazin-1(2H)-one derivatives displaying a dithiocarbamate moiety as potential anticancer agents

Nowadays, cancer disease seems to be the second most common cause of death worldwide. Molecular hybridization is a drug design strategy that has provided promising results against multifactorial diseases, including cancer. In this work, two series of phthalazinone-dithiocarbamate hybrids were described, compounds 6–8, which display the dithiocarbamate scaffold at N2, and compounds 9, in which this moiety was placed at C4. The proposed compounds were successfully synthesized via the corresponding aminoalkyl phthalazinone derivatives and using a one-pot reaction with carbon disulfide, anhydrous H3PO4, and different benzyl or propargyl bromides. The antiproliferative effects of the titled compounds were explored against three human cancer cell lines (A2780, NCI-H460, and MCF-7). The preliminary results revealed significant differences in activity and selectivity depending on the dithiocarbamate moiety location. Thus, in general terms, compounds 6–8 displayed better activity against the A-2780 and MCF-7 cell lines, while most of the analogues of the 9 group were selective toward the NCI-H460 cell line. Compounds 6e, 8e, 6g, 9a–b, 9d, and 9g with IC50 values less than 10 µM were the most promising. The drug-likeness and toxicity properties of the novel phthalazinone-dithiocarbamate hybrids were predicted using Swiss-ADME and ProTox web servers, respectively.Universidade de Vigo, Xunta de Galicia | Ref. ED431C 2022/20Universidade de Vigo, Xunta de Galicia | Ref. ED431G 2019/0

Marketing rural alternativa para el desarrollo rural: caso unidades de producción de lácteos en la zona oriente del Estado De México

De acuerdo a la política pública establecida en el Plan Nacional de Desarrollo (PND), el Plan Estatal de Desarrollo (PED) y los Planes Municipales de Desarrollo (PMD) o llamado Bando Municipal (BM), donde se busca mejorar el bienestar rural y reducir los índices de pobreza, tanto a nivel Nacional, Estatal y Municipal. Es por ello, que surge la necesidad de impulsar el mercadeo de los productos lácteos que se producen en la Zona Oriente del Estado de México, específicamente en el Municipio de Ayapango y las delegaciones que lo integran. El Marketing Rural (MR) representa una opción para el Desarrollo Rural (DR), y específicamente para las Unidades de Producción de Lácteos (UPL) del Municipio de Ayapango Estado de México, para que puedan mercadear los productos que producen y que son el sustento económico de sus familias. Por lo que al formular estrategias de comercialización, le permitan obtener un precio justo y logren posicionarlos en los mercados aledaños, con el propósito de que puedan lograr el retorno de su inversión y sea su actividad primaria, para lograr un ingreso digno para el apoyo de su famili

Characterization of the internal efficiency of public university students using indicators of educational quality models

ABSTRACT Speaking of quality is a topic very important in all organizations because the success of its management depends on it; however, it is even more important to talk about quality in education, the result of which are the professionals who will lead the organizations. The internal efficiency measures and evaluates annually through indicators the situation of the student in the development of their activities in the educational exercise. Taking the quality model of SINEACE as a reference in this work in comparison with other quality models, we talk about the evaluation of internal efficiency within the Accounting and Electrical Engineering programs

Residual Effects of Biosolids Application on Forage Production of Semiarid Grassland in Jalisco, Mexico

Single application of biosolids increases forage production on semiarid grasslands. Residual effects of biosolids on forage production have been scarcely measured in semiarid grasslands. The objective was to evaluate the residual effects of biosolids application on forage production of blue grama (Bouteloua gracilis (Willd. ex Kunth) Lag. ex Griffiths) and other grasses at a semiarid grassland in Jalisco, Mexico. The study was performed at shortgrass prairie in northeast Jalisco. Field plots were selected to include blue grama plants before rainy season in 2002. Aerobic biosolids were applied at 0 (control), 15, 30, 45, 60, 75, or 90 dry Mg ha−1 under a completely random design with five replications. Forage production was estimated by clipping at the end of the growing season during five years. Data analysis was performed with linear mixed model and repeated measures. Forage production was influenced by a rate × year × species interaction (P=0.0001). Blue grama forage production increased with increasing biosolids rates during all years, with the magnitude of this response varying among years. Forage production of other grass species slightly decreased with biosolids application. Single biosolids application had a residual effect on forage production throughout five years in semiarid grasslands

The new pharmacological chaperones PBXs increase α-galactosidase a activity in Fabry disease cellular models

Fabry disease is an X-linked multisystemic disorder caused by the impairment of lysosomal α-Galactosidase A, which leads to the progressive accumulation of glycosphingolipids and to defective lysosomal metabolism. Currently, Fabry disease is treated by enzyme replacement therapy or the orally administrated pharmacological chaperone Migalastat. Both therapeutic strategies present limitations, since enzyme replacement therapy has shown low half-life and bioavailability, while Migalastat is only approved for patients with specific mutations. The aim of this work was to assess the efficacy of PBX galactose analogues to stabilize α-Galactosidase A and therefore evaluate their potential use in Fabry patients with mutations that are not amenable to the treatment with Migalastat. We demonstrated that PBX compounds are safe and effective concerning stabilization of α-Galactosidase A in relevant cellular models of the disease, as assessed by enzymatic activity measurements, molecular modelling, and cell viability assays. This experimental evidence suggests that PBX compounds are promising candidates for the treatment of Fabry disease caused by mutations which affect the folding of α-Galactosidase A, even for GLA variants that are not amenable to the treatment with Migalastat.Fundación Biomédica Galicia Sur | Ref. OT-02-CNFXunta de Galicia | Ref. CN2012 / 18

Clinical characteristics and respiratory care in hospitalized vaccinated SARS-CoV-2 patients

Background: The main objective of the present study was to analyze both clinical characteristics and evolution during hospitalization of a cohort of patients admitted for COVID-19 pneumonia who were not vaccinated, or with a complete or incomplete vaccination schedule. Methods: This COVID-19 specialized single-center cohort study of 1888 COVID-19 patients hospitalized at the “Enfermera Isabel Zendal” Emergencies Hospital (HEEIZ), Madrid (Spain) was performed between July 1 and September 30, 2021. It compared the results of 1327 hospitalized unvaccinated patients to 209 hospitalized fully vaccinated and 352 hospitalized partially vaccinated patients. The four different COVID-19 vaccines authorized in Spain during the time-period studied were: BNT162b2 (Pfizer); ChAdOx1 nCoV-19 (AstraZeneca), mRNA-1273 (Moderna); Ad26.COV2.S (Janssen). Findings: Hospitalized patients’ median age was 41 years (IQR 33–50) for the unvaccinated and 61 years (IQR 53–67) for the fully vaccinated ones. The main comorbidities were obesity, hypertension and diabetes mellitus. 20% of unvaccinated patients (266) required noninvasive respiratory care, as did 14% (51) of partially and 14% (30) of fully vaccinated; 6% (78) of the unvaccinated patients also needed invasive respiratory care, as did 5% (16) of partially and 11 (5%) fully vaccinated. Interpretation: Fully vaccinated patients were 84% (95% CI: 82–86%) less likely to be admitted to hospital, and protection rose for those aged <50 years. Once hospitalized, vaccinated patients displayed more protection against requiring respiratory care than unvaccinated ones, despite being older and having more comorbidities. No differences appeared for the four studied COVID-19 vaccines and complying with vaccination recommendations proved relevant. Funding: The research was funded by the “Plan Propio de Investigación” Program of the Castilla-La Mancha University /European Regional Development Fund (2021-GRIN-31,039

Psicoeducación familiar en esquizofrenia

El propósito del presente capítulo “Psicoeducación Familiar en Esquizofrenia” del Manual para estudiantes de grado de la Cátedra de Psiquiatría, UNC, es incorporar, describir y resaltar esta herramienta terapéutica en el tratamiento de la esquizofrenia. Actualmente es recomendada para un abordaje integral de la enfermedad, por ser considerada complementaria a las terapias psicosociales y los tratamientos psicofarmacológicos, integrándose así a los programas y dispositivos que dan respuesta a las necesidades extrasanitarias de quienes padecen esta enfermedad. La Psicoeducación dirigida a los familiares, también llamada Intervención Familiar Psicoeducacional, es el proceso de capacitación dirigido a los familiares o allegados con funciones de cuidadores de las personas con una enfermedad mental severa, cuyo objetivo inmediato es reducir la brecha de conocimiento entre la información disponible en los profesionales y la que efectivamente posee el familiar. Su propósito final es fortalecer las posibilidades de recuperación de quienes sufren esquizofrenia, con la meta puesta en una vida digna de la persona enferma, procurando que alcance un bienestar pleno y logre un desempeño psicosocial satisfactorio. Corresponde resaltar que la Psicoeducación familiar en esquizofrenia, constituye un recurso de empleo imperativo en las recomendaciones y guías de abordaje de la salud mental de la Organización Mundial de la Salud (OMS, 2013, OMS 2018), apoyado en la sólida evidencia que ofrece la prolífica bibliografía de numerosos investigadores y expertos en gestión de salud mental internacionales, como se describen en este capítulo.Facultad de Ciencias Médica

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of diseas

All Roads Lead to Rome: Results of Non-Invasive Respiratory Therapies Applied in a Tertiary-Care Hospital Without an Intermediate Care Unit During the COVID-19 Pandemic

Introducción. Las terapias respiratorias no invasivas (TRNI) fueron ampliamente utilizadas en la primera ola de la pandemia de COVID-19, en escenarios distintos según los medios disponibles. El objetivo fue presentar la supervivencia a 90 días y los factores asociados a esta de los pacientes tratados con TRNI en un centro de tercer nivel sin Unidad de Cuidados Respiratorios Intermedios. Como objetivo secundario comparar los resultados obtenidos de las distintas terapias. Métodos. Estudio observacional de pacientes tratados con TRNI fuera de un ambiente de Cuidados Intensivos o Unidad de Cuidados Respiratorios Intermedios, diagnosticados de COVID-19 y con síndrome de distrés respiratorio agudo por criterios radiológicos y de ratio SpO2/FiO2. Se desarrolló un modelo multivariante de regresión logística para determinar las variables independientemente asociadas, y se compararon los resultados de la terapia de alto flujo con cánula nasal y la presión positiva continua en la vía aérea. Resultados. Se trataron 107 pacientes y sobrevivieron 85 (79,4%) a los 90 días. Antes de iniciar la TRNI el ratio medio de SpO2/FiO2 fue de 119,8±59,4. Un mayor score de SOFA se asoció significativamente a la mortalidad (OR 2,09; IC95% 1,34 – 3,27), mientras que la autopronación fue un factor protector (OR 0,23; IC95% 0,06 – 0,91). La terapia de alto flujo con cánula nasal fue utilizada en 63 sujetos (58,9%), y la presión positiva continua en la vía aérea en 41 (38,3%). No se encontraron diferencias entre ellas. Conclusión. Aproximadamente cuatro de cada cinco pacientes tratados con TRNI sobrevivieron a los 90 días, y no se encontraron diferencias significativas entre la terapia de alto flujo con cánula nasal y la presión positiva continua en la vía aérea.S

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity &gt; 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI