Trans-[Pt(amine)Cl2(PPh3)] Complexes Target Mitochondria and Endoplasmic Reticulum in Gastric Cancer Cells.

Gastric cancer prognosis is still notably poor despite efforts made to improve diagnosis and treatment of the disease. Chemotherapy based on platinum agents is generally used, regardless of the fact that drug toxicity leads to limited clinical efficacy. In order to overcome these problems, our group has been working on the synthesis and study of trans platinum (II) complexes. Here, we explore the potential use of two phosphine-based agents with the general formula trans-[Pt(amine)Cl2(PPh3)], called P1 and P2 (with dimethylamine or isopropylamine, respectively). A cytotoxicity analysis showed that P1 and especially P2 decrease cell viability. Specifically, P2 exhibits higher activity than cisplatin in gastric cancer cells while its toxicity in healthy cells is slightly lower. Both complexes generate Reactive Oxygen Species, produce DNA damage and mitochondrial membrane depolarization, and finally lead to induced apoptosis. Thus, an intrinsic apoptotic pathway emerges as the main type of cell death through the activation of BAX/BAK and BIM and the degradation of MCL1. Additionally, we demonstrate here that P2 produces endoplasmic reticulum stress and activates the Unfolded Protein Response, which also relates to the impairment observed in autophagy markers such as p62 and LC3. Although further studies in other biological models are needed, these results report the biomolecular mechanism of action of these Pt(II)-phosphine prototypes, thus highlighting their potential as novel and effective therapies.

Polylactic acid nanoplastics (PLA-NPLs) induce adverse effects on an in vitro model of the human lung epithelium: The Calu-3 air-liquid interface (ALI) barrier.

The expected increments in the production/use of bioplastics, as an alternative to petroleum-based plastics, require a deep understanding of their potential environmental and health hazards, mainly as nanoplastics (NPLs). Since one important exposure route to NPLs is through inhalation, this study aims to determine the fate and effects of true-to-life polylactic acid nanoplastics (PLA-NPLs), using the in vitro Calu-3 model of bronchial epithelium, under air-liquid interphase exposure conditions. To determine the harmful effects of PLA-NPLs in a more realistic scenario, both acute (24 h) and long-term (1 and 2 weeks) exposures were used. Flow cytometry results indicated that PLA-NPLs internalized easily in the barrier (∼10 % at 24 h and ∼40 % after 2 weeks), which affected the expression of tight-junctions formation (∼50 % less vs control) and the mucus secretion (∼50 % more vs control), both measured by immunostaining. Interestingly, significant genotoxic effects (DNA breaks) were detected by using the comet assay, with long-term effects being more marked than acute ones (7.01 vs 4.54 % of DNA damage). When an array of cellular proteins including cytokines, chemokines, and growth factors were used, a significant over-expression was mainly found in long-term exposures (∼20 proteins vs 5 proteins after acute exposure). Overall, these results described the potential hazards posed by PLA-NPLs, under relevant long-term exposure scenarios, highlighting the advantages of the model used to study bronchial epithelium tissue damage, and signaling endpoints related to inflammation.

Population-based norms for the human papillomavirus-quality of life (HPV-QoL) questionnaire: A cross-sectional multicenter study.

INTRODUCTION: Human papillomavirus (HPV) diagnosis has a considerable emotional and psychological impact on women. To evaluate the impairment this infection leads to regarding quality of life (QoL), several scales have been suggested, such as the human-papillomavirus-quality-of-life (HPV-QoL) questionnaire. This has been validated for the Spanish population and measures the impact of HPV on health-related-quality-of-life (HR-QoL). However, normative values are yet to be developed. Thus, the objective was to describe the population-based norms of the HPV-QoL for Spanish women aged 25-65 years and to test the questionnaire's construct validity. MATERIAL AND METHODS: This was a cross-sectional nationwide multicenter study. Women from outpatient clinics in Spain aged 25-65 years, with a diagnosis of past or active HPV infection were recruited. The central tendency, dispersion, and percentiles were calculated for the total score and its dimensions for each age group. Construct validity was tested by analyzing age groups and their correlations with other related scales (12-Item General Health Questionnaire [GHQ-12], Female Sexual Function Index [FSFI], and Hospital Anxiety and Depression Scale [HADS]). RESULTS: A total of 1352 women were included in the study. The norms showed moderate and significant coefficients of correlation with other related scales. Significant differences between age strata groups were found according to educational level, sexual dysfunction, sexual activity, mental deterioration, and severity of anxiety and depression symptoms (p < 0.001 in all cases). The total score differed significantly between the groups (p = 0.006). Significant differences in the contagiousness, health, and sexuality dimensions (p < 0.05) were found among the groups. It was seen that HPV infection impaired women's QoL. Dimensions within all test age groups (p < 0.001 in all cases) were significantly different, with the health dimension being the highest contributor to women's QoL impairment, whereas social well-being was the main determinant of QoL. CONCLUSIONS: Population-based norms for the novel HPV-QoL questionnaire showed adequate validity and could be a useful tool for assessing the impact of QoL among women with HPV in Spain.

Implementation of Diabetic Retinopathy Screening in Adult Patients With Type 2 Diabetes in a Primary Care Setting.

Diabetic retinopathy (DR) is a microvascular complication of type 2 diabetes and the leading cause of blindness globally. Although diabetes-related eye exams are widely recognized as an effective method for early detection of DR, which can help to prevent eventual vision loss, adherence to screening exams in the United States is suboptimal. This article describes a quality improvement project to increase DR screening rates and increase knowledge and awareness of DR in adults with type 2 diabetes in a primary care setting using mobile DR screening units. This project addressed gaps of care and demonstrated that primary care settings can increase access to DR screening through a patient-centered process and thereby help to prevent irreversible outcomes of DR and improve quality of life.

A novel dissector device that separates anatomic structures during laparoscopic surgery.

OBJECTIVE: To describe a novel dissector device useful in laparoscopy, better definition of anatomic structures to have a better dissection, separation, and cleaning of the structures. METHOD: The endoscopic dissector DisePad was designed and developed at the experimental surgery department of Centro Médico Nacional 20 de Noviembre, and properly patented at Instituto Mexicano de la Propiedad Industrial (title 3512). RESULTS: The tip of the device is the most important component, by its direct contact with the different tissues, consists of a cotton-polyester black cloth impregnated with a special gel immersed into a hot saline solution. Once soaked the tip maintains the solution temperature on itself. CONCLUSIONS: This device has been used in 364 laparoscopic procedures demonstrating, its utility to visualize, separate and clean anatomical structures without thermal lesion, tear, hemorrhage or visceral perforation.

OBJETIVO: Describir un nuevo dispositivo disector en laparoscopia, con una mejor definición de las estructuras anatómicas para obtener una mejor disección,separación y limpieza de las estructuras. MÉTODO: El disector endoscópico DisePad fue diseñado y desarrollado en el servicio de cirugía experimental del Centro Médico Nacional 20 de Noviembre, y patentado ante el Instituto Mexicano de la Propiedad Industrial (registro n.º 3512). RESULTADOS: El componente más importante del disector es la punta que tiene contacto con los tejidos: es una tela de algodón-poliéster negra impregnada en un gel (patentado) que, al ser sumergido en un termo con solución salina caliente, permite retener la temperatura. CONCLUSIONES: Este dispositivo ha sido utilizado en 364 procedimientos quirúrgicos por vía laparoscópica y ha demostrado ser útil para visualizar, separar y limpiar estructuras anatómicas sin producir daño por lesión térmica, desgarre, hemorragia ni perforación visceral.

Acetazolamide encapsulation in elastin like recombinamers using a supercritical antisolvent (SAS) process for glaucoma treatment.

Glaucoma, the second most common cause of blindness worldwide, requires the development of new and effective treatments. This study introduces a novel controlled-release system utilizing elastin-like recombinamers (ELR) and the Supercritical Antisolvent (SAS) technique with supercritical CO2. Acetazolamide (AZM), a class IV drug with limited solubility and permeability, is successfully encapsulated in an amphiphilic ELR at three different ELR:AZM ratios, yielding up to 62 %. Scanning electron microscopy (SEM) reveals spherical microparticles that disintegrate into monodisperse nanoparticles measuring approximately 42 nm under physiological conditions. The nanoparticles, as observed via Transmission Electron Microscopy (TEM) and Atomic Force Microscopy (AFM), do not exhibit aggregates, a fact confirmed by the zeta potential displaying a value of -33 mV over a period of 30 days. Transcorneal permeation tests demonstrate a 10 % higher permeation level compared to the control solution, which increases to 30 % after 2 h. Ocular irritation tests demonstrate no adverse effects or damage. Intraocular pressure (IOP) tests conducted on hypertensive rabbits indicate greater effectiveness for all three analyzed formulations, suggesting enhanced drug bioavailability during treatment. Consequently, the combination of recombinant biopolymers and high-pressure techniques represents a promising approach for advancing glaucoma therapy, emphasizing its potential clinical significance.

Polymer-based antibody mimetics (iBodies) target human PD-L1 and function as a potent immune checkpoint blocker.

Immune checkpoint blockade (ICB) using monoclonal antibodies against programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) is the treatment of choice for cancer immunotherapy. However, low tissue permeability, immunogenicity, immune-related adverse effects, and high cost could be possibly improved using alternative approaches. On the other hand, synthetic low-molecular-weight (LMW) PD-1/PD-L1 blockers have failed to progress beyond in vitro studies, mostly due to low binding affinity or poor pharmacological characteristics resulting from their limited solubility and/or stability. Here, we report the development of polymer-based anti-human PD-L1 antibody mimetics (α-hPD-L1 iBodies) by attaching the macrocyclic peptide WL12 to a N-(2-hydroxypropyl)methacrylamide copolymer. We characterized the binding properties of iBodies using surface plasmon resonance, enzyme-linked immunosorbent assay, flow cytometry, confocal microscopy, and a cellular ICB model. We found that the α-hPD-L1 iBodies specifically target human PD-L1 (hPD-L1) and block the PD-1/PD-L1 interaction in vitro, comparable to the atezolizumab, durvalumab, and avelumab licensed monoclonal antibodies targeting PD-L1. Our findings suggest that iBodies can be used as experimental tools to target hPD-L1 and could serve as a platform to potentiate the therapeutic effect of hPD-L1-targeting small molecules by improving their affinity and pharmacokinetic properties.

Observation of naturally canalized phonon polaritons in LiV2O5 thin layers.

Polariton canalization is characterized by intrinsic collimation of energy flow along a single crystalline axis. This optical phenomenon has been experimentally demonstrated at the nanoscale by stacking and twisting van der Waals (vdW) layers of α-MoO3, by combining α-MoO3 and graphene, or by fabricating an h-BN metasurface. However, these material platforms have significant drawbacks, such as complex fabrication and high optical losses in the case of metasurfaces. Ideally, it would be possible to canalize polaritons "naturally" in a single pristine layer. Here, we theoretically predict and experimentally demonstrate naturally canalized phonon polaritons (PhPs) in a single thin layer of the vdW crystal LiV2O5. In addition to canalization, PhPs in LiV2O5 exhibit strong field confinement ( λ p ~ λ 0 27 ), slow group velocity (0.0015c), and ultra-low losses (lifetimes of 2 ps). Our findings are promising for the implementation of low-loss optical nanodevices where strongly directional light propagation is needed, such as waveguides or optical routers.

Autophagy sustains mitochondrial respiration and determines resistance to BRAFV600E inhibition in thyroid carcinoma cells.

BRAFV600E is the most prevalent mutation in thyroid cancer and correlates with poor prognosis and therapy resistance. Although selective inhibitors of BRAFV600E have been developed, more advanced tumors such as anaplastic thyroid carcinomas show a poor response in clinical trials. Therefore, the study of alternative survival mechanisms is needed. Since metabolic changes have been related to malignant progression, in this work we explore metabolic dependencies of thyroid tumor cells to exploit them therapeutically. Our results show that respiration of thyroid carcinoma cells is highly dependent on fatty acid oxidation and, in turn, fatty acid mitochondrial availability is regulated through macroautophagy/autophagy. Furthermore, we show that both lysosomal inhibition and the knockout of the essential autophagy gene, ATG7, lead to enhanced lipolysis; although this effect is not essential for survival of thyroid carcinoma cells. We also demonstrate that following inhibition of either autophagy or fatty acid oxidation, thyroid tumor cells compensate oxidative phosphorylation deficiency with an increase in glycolysis. In contrast to lipolysis induction, upon autophagy inhibition, glycolytic boost in autophagy-deficient cells is essential for survival and, importantly, correlates with a higher sensitivity to the BRAFV600E selective inhibitor, vemurafenib. In agreement, downregulation of the glycolytic pathway results in enhanced mitochondrial respiration and vemurafenib resistance. Our work provides new insights into the role of autophagy in thyroid cancer metabolism and supports mitochondrial targeting in combination with vemurafenib to eliminate BRAFV600E-positive thyroid carcinoma cells.Abbreviations: AMP: adenosine monophosphate; ATC: anaplastic thyroid carcinoma; ATG: autophagy related; ATP: adenosine triphosphate; BRAF: B-Raf proto-oncogene, serine/threonine kinase; Cas9: CRISPR-associated protein; CREB: cAMP responsive element binding protein; CRISPR: clustered regularly interspaced short palindromic repeats; 2DG: 2-deoxyglucose; FA: fatty acid; FAO: fatty acid oxidation; FASN: fatty acid synthase; FCCP: trifluoromethoxy carbonyl cyanide phenylhydrazone; LAMP1: lysosomal associated membrane protein 1; LIPE/HSL: lipase E, hormone sensitive type; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; OCR: oxygen consumption rate; OXPHOS: oxidative phosphorylation; PRKA/PKA: protein kinase cAMP-activated; PTC: papillary thyroid carcinoma; SREBF1/SREBP1: sterol regulatory element binding transcription factor 1.

Patterns of genetic divergence in the Rio Grande cooter (Pseudemys gorzugi), a riverine turtle inhabiting an arid and anthropogenically modified system.

The lower Rio Grande and Pecos River of the southwest United States have been heavily modified by human activities, profoundly impacting the integrity of their aquatic wildlife. In this context, we focused our study on the population genomics of the Rio Grande Cooter (Pseudemys gorzugi), a freshwater turtle of increasing conservation concern, residing in these two rivers and their tributaries. The genetic data revealed two distinct populations: one in the Pecos and Black Rivers of New Mexico and another in the Rio Grande and Devils River of Texas, with admixed individuals identified at the confluence of the Rio Grande and Pecos River. In addition to having a smaller geographic range, we found lower observed heterozygosity, reduced nucleotide diversity, and a smaller effective population size (Ne) in New Mexico population. Our results depict a significant isolation-by-distance pattern across their distribution, with migration being notably infrequent at river confluences. These findings are pivotal for future conservation and restoration strategies, emphasizing the need to recognize the unique needs of each population.

Valor pronóstico de los parámetros metabólicos medidos en la asistencia inicial a pacientes con trauma grave: asociación con la puntuación de la escala NISS y la mortalidad / Prognostic value of metabolic parameters measured by first responders attending patients with severe trauma: associations with the New Injury Severity Score and mortality

Objetivos. En entornos de emergencia prehospitalarios, la detección temprana de un paciente con trauma grave o potencialmente crítico es un desafío. El objetivo es analizar las posibilidades diagnósticas y pronóstico de los parámetros analíticos obtenidos en los primeros momentos de la asistencia inicial. Métodos. Estudio observacional multicéntrico de la base de datos prospectiva “Código Trauma” de 2016-2019 excluyendo el trauma craneoencefálico aislado. La evaluación de las lesiones se realizó utilizando el New Injury Severity Score (NISS). Los pacientes fueron clasificados en 4 grupos según nivel de gravedad. Para el análisis inferencial, las puntuaciones NISS y el resultado de mortalidad se consideraron variables dependientes. Se realizó el análisis de la curva ROC, puntos de corte óptimos mediante el índice de Youden y se calcularon los valores predictivos positivo (VPP) y negativo. Resultados. De los 1.039 pacientes traumatizados del registro, 709 fueron incluidos en el estudio, con una edad media de 40,4 años (DE 17,3), 77,3% eran varones, el mecanismo lesional principal accidentes de moto (21%) y la mortalidad del 12,1%. El pH, lactato, pCO2, hemoglobina, hematocrito y glucemia influyeron significativamente en gravedad y mortalidad. El VPP de mortalidad para pH fue 61,2, 64,1, 70,7, 62,2 y 66,6 para los grupos de NISS 34-41, 42-49, 50-59 y $ 60 puntos la mortalidad, respectivamente. Las variables clínicas clásicas obtuvieron valores más bajos. Conclusiones. Los pacientes con mayor gravedad presentaron menor pH y concentraciones más altas de pCO2, lactato y exceso de bases. El pH, la pCO2 y la glucemia tuvieron la mayor capacidad predictiva de gravedad. La capacidad predictiva de los valores metabólicos es superior a la de los valores hemodinámicos clásicos. (AU)

Background and objective: Patients with severe or potentially severe trauma must be identified early, a challenge in prehospital settings. This study aimed to analyze the possible diagnostic and prognostic usefulness of analytical markers recorded in the early moments of care. Methods: Observational study of information extracted from the prospective multicenter Code Trauma database for 2016-2019, excluding data for isolated head injuries. Using the New Injury Severity Score (NISS), we classified cases into 4 levels of severity. NISS and mortality were considered the dependent variables in inferential analyses. We calculated the areas under receiver operating characteristic curves, identified optimal cutoff points (Youden index), and calculated positive (PPV) and negative predictive values. Results: Of the 1039 trauma patients in the registry, 709 were included in the study. Their mean (SD) age was 40.4 (17.3) years, and 77.3% were men. Motorcycle accidents were the most common causes of trauma (in 21%), and mortality was 12.1%. Lactate concentration, pH, PCO2, hemoglobin concentration, hematocrit, and blood sugar were significantly associated with severity and mortality. The PPVs corresponding to pH for the 4 NISS score groups (34-41, 42-49, 50-59, and $ 60) and mortality, respectively, were 61.2, 64.1, 70.7, 62.2, and 66.6. The PPVs of traditionally used clinical variables were lower. Conclusions: Patients with more severe trauma had lower pH values and higher PCO2, lactate, and base excess values. PCO2, pH, and blood sugar findings were the best predictors of severity. Metabolic variables are better predictors than traditionally recorded hemodynamic variables. (AU)

Disease burden and costs for patients with hip and knee osteoarthritis and chronic moderate-to-severe refractory pain on treatment with strong opioids in Spain / Carga de la enfermedad y costes en pacientes con osteoartritis de cadera y rodilla con dolor crónico refractario moderado-severo tratados con opioides mayores en España

Introduction and objectives: To determine the disease burden and costs in patients with hip or knee OA and chronic moderate-to-severe refractory pain, receiving strong opioids in Spain. Materials and methods: This was a 36-month longitudinal secondary analysis of the real-word OPIOIDS study. Patients aged ≥18 years with hip or knee OA and chronic moderate-to-severe refractory pain receiving strong opioids were considered. The disease burden included analgesia assessments (NRS scale), cognitive functioning (MMSE scale), basic activities of daily living (Barthel index), and comorbidities (severity and frequency). Costs due to the use of healthcare resources and productivity loss were estimated. Results: 2832 patients were analyzed; age was 72.0 years (SD=14.3), 76.8% were women. Patients had mainly been treated with fentanyl (n=979; 37.6%), tapentadol (n=625; 24.0%), oxycodone (n=572; 22.0%), and buprenorphine (n=425; 16.3%). Pain intensity decreased by 1 point (13.7%), with a 2.6-point decline in the cognitive scale (14.3%, with a 5.3%-increase in patients with cognitive deficit) over a mean treatment period of 384.6 days (SD: 378.8). Barthel scores decreased significantly yielding to a slightly increase in proportion of patients with severe-to-total dependency; 1.2%–2.9%. In the first year of treatment, average healthcare costs were €2013/patient, whereas the average productivity loss cost was €12,227/working-active patient. Discussion and conclusions: Strong opioids resulted in high healthcare costs with a limited reduction in pain, an increase in cognitive deficit, and a slight increase of patients with severe to total dependency over 36 months of treatment.(AU)

Introducción y objetivos: Determinar la carga de la enfermedad y los costes en pacientes con osteoartritis de cadera y rodilla y dolor crónico refractario moderado-severo, en tratamiento con opioides mayores en España. Materiales y métodos: Se trata de un subanálisis de 36 meses de duración, procedente del estudio observacional OPIOIDS. Participaron pacientes con una edad ≥18 años, diagnosticados con osteoartritis de cadera y rodilla y dolor crónico refractario moderado-severo, en tratamiento con opioides mayores. La carga de la enfermedad incluyó la evaluación de la analgesia (escala NRS), del funcionamiento cognitivo (escala MMSE), de la capacidad para realizar las actividades de la vida diaria (índice de Barthel) y de las comorbilidades (gravedad y frecuencia). También se estimaron los costes asociados al uso de recursos sanitarios y a la productividad laboral. Resultados: Se analizaron 2.832 pacientes (edad: 72,0 años [DE: 14,3]; mujeres: 76,8%), que habían sido principalmente tratados con fentanilo (n=979; 37,6%), tapentadol (n=625; 24,0%), oxicodona (n=572; 22,0%) y buprenorfina (n=425; 16,3%). La intensidad del dolor disminuyó una unidad (13,7%), con una reducción de 2,6 unidades en la escala cognitiva (14,3% y aumento del 5,3% en los pacientes con déficit cognitivo) durante una media de 384,6 días (DE: 378,8). Las puntuaciones en la escala de Barthel disminuyeron significativamente, con un ligero aumento en la proporción de pacientes con dependencia grave/total, entre 1,2% y 2,9%. En el primer año, los costes sanitarios medios fueron 2.013€/paciente, mientras que los costes medios de pérdida de productividad fueron 12.227€/trabajador. Discusión y conclusiones: El tratamiento con opioides mayores durante 36 meses implicó elevados costes sanitarios, con una eficacia analgésica limitada, un aumento del déficit cognitivo y un ligero aumento de los pacientes con dependencia grave/total.(AU)

Arteria labial de calibre persistente / Caliber-persistent labial artery

La arteria labial de calibre persistente (ALCP) es una entidad poco común, que se caracteriza por una arteria labial cuyo calibre permanece invariable tras su penetración en la submucosa. El diagnóstico diferencial debe apoyarse en pruebas de imagen pues la biopsia puede ocasionar sangrados importantes. El tratamiento varía desde el seguimiento clínico hasta la escisión quirúrgica. Presentamos el caso de una mujer de 40 años que acude a nuestra consulta por una tumoración lineal submucosa en labio superior, que le ocasionaba problemas estéticos y funcionales. (AU)

Caliber-persistent labial artery is an uncommon lesion of the lip, which consists of a labial arteriy that penetrates into the submucosal tissue of the lip, without a loss of caliber. The differential diagnosis must be supported by image tests, since the surgical biopsy can cause significant bleeding. Treatment varies from clinical follow-up to surgical excision. We present the case of a 40-year-old woman who attends to our consultation for a lineal submucosal lesion that caused her aesthetical and functional compromise. (AU)

Epidemiological Study of Prostate Cancer in the Province of Salamanca (2006-2015)

Objectives: Knowing the incidence of prostate cancer in Salamanca and its evolution, as well as the age at diagnosis and its evolution. In addition, analyzing the mortality from prostate cancer in the province of Salamanca. Methods: Descriptive and analytical, longitudinal and retrospective observational study. From the collection of data from the Pathological Anatomy service and the Clinical Documentation service of the Hospital Complex of Salamanca a database was developed for the calculation of incidence rates. The information collected on mortality was obtained through the National Institute of Statistics. For regression analysis, segmented “jointpoint” models were developed. Results: 2676 males diagnosed with prostate cancer were recorded in the province of Salamanca (period 2006-2015). The risk of prostate cancer up to age 74 in 2006 was 6.23%, almost double in 2010. The evolution of mortality rates adjusted to the European population in the province of Salamanca during the period 2006-2015 showed a slight decrease. Conclusions: In general, Prostate cancer incidence rates increased progressively over the years studied, similar to Spain’s overall rates. These rates increased as age progressed. In general, our incidence rates were lower than those reported by the provinces of northern Spain (except Vizcaya) and higher than those recorded by the provinces of southern Spain. In Europe, our rate was surpassed by countries in northern and western Europe and lower than countries in southern and eastern Europe, and part of central Europe. Countries like U.S.A had rates higher than ours, while Canada accounted for a similar rate. On the other hand, mortality rates remained stable during the middle of the study period, suffering from then on a non-statistically significant anual decrease (AU)

An open-source natural language processing toolkit to support software development: addressing automatic bug detection, code summarisation and code search.

This paper aims to introduce the innovative work carried out in the Horizon 2020 DECODER project - acronym for "DEveloper COmpanion for Documented and annotatEd code Reference" - (Grant Agreement no. 824231) by linking the fields of natural language processing (NLP) and software engineering. The project as a whole addresses the development of a framework, namely the Persistent Knowledge Monitor (PKM), that acts as a central infrastructure to store, access, and trace all the data, information and knowledge related to a given software or ecosystem. This meta-model defines the knowledge base that can be queried and analysed by all the tools integrated and developed in DECODER. Besides, the DECODER project offers a friendly user interface where each of the predefined three roles (i.e., developers, maintainers and reviewers) can access and query the PKM with their personal accounts. The paper focuses on the NLP tools developed and integrated in the PKM, namely the deep learning models developed to perform variable misuse, code summarisation and semantic parsing. These were developed under a common work package - "Activities for the developer" - intended to precisely target developers, who can perform tasks such as detection of bugs, automatic generation of documentation for source code and generation of code snippets from natural languages instructions, among the multiple functionalities that DECODER offers. These tools assist and help the developers in the daily work, by increasing their productivity and avoiding loss of time in tedious tasks such as manual bug detection. Training and validation were conducted for four use cases in Java, C and C++ programming languages in order to evaluate the performance, suitability, usability, etc. of the developed tools.

Software engineers usually spends a lot of time in tedious activities like debugging and documenting code or finding examples of code snippets to use as a basis for their new programmes. Given the large and complex software systems that exist nowadays, being forced to perform these tasks manually causes a considerable drop in the overall productivity of programmers. The models developed in this work target Java, C and C++ programming languages and aim to alleviate software developers', maintainers' and reviewers' efforts, by proposing automatic NLP solutions to carry out tasks such as bug detection, documentation generation and code search.

Incidencia y control de síntomas al final de la vida de pacientes con cáncer

RESUMEN Fundamento: al final de la vida, el paciente con padecimientos oncológicos presenta diversos síntomas físicos, emocionales y espirituales. La medicina paliativa permite un tratamiento continuo e integral para el diagnóstico y control de síntomas. Objetivo: describir la incidencia de síntomas según la localización del tumor inicial y su transición en la última etapa de la enfermedad. Método: se realizó un estudio descriptivo, longitudinal, prospectivo de 100 pacientes con enfermedad terminal, atendidos en el Instituto de Oncología y Radiobiología entre septiembre del 2017 a septiembre del 2019. Se tomó como fuente el registro de la historia clínica con dos evaluaciones, usando la Escala de Evaluación de Síntomas de Edmonton, modificada. Se elaboró un cuestionario mediante la técnica de entrevista en profundidad para recoger la información sobre los síntomas. Con la información se confeccionó una base de datos en Microsoft Excel 16.0 y se procesaron mediante el paquete estadístico de SPSS-PC en su versión 19.0.1 para Windows, que permitió confeccionar tablas y gráficos. Resultados: se describe la incidencia de nueve síntomas, los principales: dolor, cansancio, pérdida de apetito, ansiedad y depresión, independientes a la estructura anatómica afectada por el tumor primario. Se encontró mayor incidencia del dolor de forma general (78 %). Durante la etapa final los síntomas más frecuentes fueron: cansancio, ansiedad, pérdida de apetito y disnea. Conclusión: los síntomas en el paciente terminal con padecimientos oncológicos son múltiples y variables, en ocasiones estrechamente relacionados con la historia natural de su enfermedad. El diagnóstico y control sintomático requiere reconocer las necesidades y generar estrategias colectivas para minimizar el sufrimiento.

ABSTRACT Background: at the end of life, the patient with cancer conditions presents various physical, emotional and spiritual symptoms. Palliative medicine allows a continuous and comprehensive treatment for the diagnosis and control of symptoms. Objective: to describe the incidence of symptoms according to the location of the initial tumor and its transition in the last stage of the disease. Method: a descriptive, longitudinal, prospective study of 100 terminally ill patients treated at the Institute of Oncology and Radiobiology was carried out between September 2017 and September 2019. The medical history record with two evaluations was taken as a source, using Edmonton Symptom Rating Scale, modified. A questionnaire was developed using the in-depth interview technique to collect information on symptoms. With the information, a database was made in Microsoft Excel 16.0 and they were processed using the SPSS-PC statistical package in version 19.0.1 for Windows, which made it possible to make tables and graphs. Results: the incidence of nine symptoms is described, the main ones: pain, fatigue, loss of appetite, anxiety and depression, independent of the anatomical structure affected by the primary tumor. A higher incidence of pain was found in general (78 %). During the final stage, the most frequent symptoms were: fatigue, anxiety, loss of appetite and dyspnea. Conclusion: the symptoms in terminal patients with cancer diseases are multiple and variable, sometimes closely related to the natural history of their disease. Symptomatic diagnosis and control requires recognizing needs and generating collective strategies to minimize suffering.

Dehiscencia de cúpula vaginal y evisceración posquirúrgica: reporte de caso / Vaginal vault dehiscence and postoperative evisceration: case report

RESUMEN La dehiscencia de cúpula vaginal es la separación precoz de la incisión vaginal suturada, que en el 70% de los casos se manifiesta con una evisceración de asas intestinales a través del conducto vaginal. Dentro de sus factores de riesgo, destacan la edad y alteraciones en el lugar postoperatorio de histerectomía. El diagnóstico se realiza mediante un adecuado examen físico, y el tratamiento, netamente quirúrgico, involucra el regresar las vísceras intestinales y corregir la dehiscencia. Describimos el caso de una mujer de 50 años, que presentó dehiscencia de la cúpula vaginal con evisceración de una porción de íleon distal, a quien se le practicó tratamiento quirúrgico y farmacológico.

ABSTRACT Vaginal cuff dehiscence is the premature separation of the sutured vaginal incision, which in 70% of the cases manifests with evisceration of intestinal loops through the vaginal canal. Among its risk factors, age and alterations in the postoperative hysterectomy site stand out. The diagnosis is made by means of an adequate physical examination and the treatment, purely surgical, involves the return of the intestinal viscera and correction of the dehiscence. We describe the case of a 50-year-old woman who presented dehiscence of the vaginal vault with evisceration of a portion of the distal ileum, who underwent surgical and pharmacological treatment.

Estreñimiento crónico debido a síndrome de Currarino / Chronic constipation due to Currarino síndrome

No disponible

Células madre adiposas humanas disminuyen el daño de la fibrosis hepática con baja persistencia de células trasplantadas en ratas / Human adipose stem cells decrease liver fibrosis damage with low persistence of transplanted cells in rats

RESUMEN: En la enfermedad hepática crónica el trasplante ortotópico es la única alternativa terapéutica actual pero es limitada por falta de donantes. Ensayos con células madre adultas en daño hepático agudo evidencian promisorios resultados. El objetivo de este trabajo fue evaluar en ratas con daño hepático crónico la efectividad de la infusión de células madre adiposas humanas (CMAd-h). Ratas con fibrosis hepática inducida por tioacetamida fueron agrupadas en: grupo I control que no recibió tioacetamida ni células madre, grupo II recibió tioacetamida y suero fisiológico i.v., grupo III recibió tioacetamida y células madre adiposas 1 x 106/kg i.v. vía vena de la cola. La regeneración hepática histológica se evaluó por el index METAVIR, mientras las Macrophagocytus stellatus, células estrelladas a- SMA+ y células colágeno I+ por inmunohistoquímica; el daño funcional se evaluó por los niveles sanguíneos de los analitos Aspartato Aminotransferasa (AST), Alanina Aminotransferasa (ALT), Fosfatasa Alcalina (ALP), úrea y nitrógeno ureico (BUN) y hemograma. Los resultados muestran atenuación del daño estructural hepático evidenciado por disminución de los nódulos, del grado de lesión histológica en el score Metavir, y disminución de Macrophagocytus stellatus, células a-SMA+ y células colágeno tipo I+; funcionalmente hay reducción moderada de AST, ALT, urea, BUN y disminución moderada de células blancas pero efecto favorable sobre el volumen corpuscular media y la hemoglobina corpuscular media. Ocho semanas después de la infusión hay escasa población de CMAd-h en el hígado. En conclusión la infusión intravenosa de CMAd-h en ratas disminuye el daño funcional y estructural de la fibrosis hepática con escasa persistencia de CMAd-h en el parénquima hepático. A nuestro conocimiento este es el primer trabajo que evalúa el efecto de las CMAd-h en el modelo daño hepático crónico murino y la persistencia de las células trasplantadas.

SUMMARY: In chronic liver disease, orthotopic transplantation is the only current therapeutic alternative but it is limited due to lack of donors. Trials with adult stem cells in acute liver damage show promising results. The aim of this work was to evaluate the effectiveness of human adipose stem cell (h-ASC) infusion in rats with chronic liver damage. Rats with thioacetamide- induced liver fibrosis were grouped into: group I control that did not receive thioacetamide and h-ASC, group II received thioacetamide and saline i.v., group III received thioacetamide and h-ASC 1 x 106/ kg i.v. via tail vein. Histological liver regeneration was evaluated by METAVIR index, while Macrophagocytus stellatus (Kupffer cells), stellate cells a-SMA+ and collagen I+ cells by immunohistochemistry; functional damage was evaluated by blood levels of the analytes Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Urea and Blood Urea Nitrogen (BUN) and hemogram. The results show attenuation of structural liver damage evidenced by decreased nodules, degree of histologic injury on Metavir score, and decreased Macrophagocytus stellatus, a-SMA+ cells and type I+ collagen cells; functionally there is moderate reduction of AST, ALT, urea, BUN and moderate decrease of white cells but favorable effect on mean corpuscular volume and mean corpuscular hemoglobin. Eight weeks after infusion there is a small population of h-ASC in the liver. In conclusion, intravenous infusion of h-ASC in rats reduces functional and structural damage of hepatic fibrosis with low persistence of h- ASC in the liver parenchyma. To our knowledge this is the first work that evaluates the effect of h-SC in the model of chronic murine liver damage and the persistence of transplanted cells.