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El cambio climático es un problema global que altera el funcionamiento de biosferas y ecosistemas enteros, cuyas causas derivan claramente del desarrollo de las diferentes actividades económicas en el mundo, afectando categóricamente a la biodiversidad natural, a los recursos bióticos y abióticos existentes en los sistemas ambientales naturales. El objetivo fue determinar el efecto del cambio climático y la cobertura forestal en la pérdida de bosques en la selva amazónica de Perú, entre los periodos 2003 al 2019, para lo cual se consideró un enfoque cuantitativo, no experimental, descriptivo y longitudinal, se utilizó la información existente en el Instituto Nacional de Estadística e Informática, el Ministerio del Ambiente y Geo-Bosques; se aplicó el modelo econométrico de efectos fijos y aleatorios. Se determinó que la alteración del clima tiene efecto positivo en la pérdida de bosques, mientras que la cobertura forestal tiene un efecto negativo en la perdida de bosques. Además, aun incremento de las precipitaciones pluviales en 1 mm y la temperatura máxima incrementa en 1°C, entonces incrementa la perdida de bosques en 4.3 y 483.9 hectáreas respectivamente; aun incremento de la cobertura forestal en 1 hectárea, entonces disminuye la perdida de bosques el 0.13 hectáreas, la misma que se justifica porque a nivel de las regiones de Perú, no existe una política ambiental que garantice la conservación de las especies forestales, recuperación y protección del recurso forestal en las regiones amazónicas principalmente.

Ofrece una serie de comentarios, aclaraciones y sugerencias a partir de la publicación de los libretos que se desarrollan en un festival escolar para la conmemoración anual de la primera fundación de la ciudad de San Miguel en Tangarará en Sullana (Perú). Se brinda información sobre los principales promotores y los autores del libreto y se revisa la interpretación ofrecida por Luis Millones y Renata Mayer. Pese a algunas inconsecuencias y errores, la representación de Tangarará pretende ofrecer una versión bastante ajustada a la realidad histórica, de breve resistencia y sometimiento pacífico. Pretende afirmar un sentimiento de orgullo local por ser la primera ciudad española, así como promueve la autonomía regional apoyada en la identidad diferencial de los tallanes, frente al centralismo de la capital departamental.

Aims We evaluated two species of human oral commensal streptococci in protection against dental caries induced by Streptococcus mutans. Methods and Results Candidate probiotics, Streptococcus sp. A12, Streptococcus sanguinis BCC23 and an arginine deiminase mutant of BCC23 (∆arcADS) were tested for their ability to reduce S. mutans-induced caries in an established mouse model. Mice were colonized with a probiotic, challenged with S. mutans, then intermittently reinoculated with a probiotic strain. Oral colonization of each strain and autochthonous bacteria was assessed by quantitative polymerase chain reaction. Both BCC23 strains, but not A12, were associated with markedly reduced sulcal caries, persistently colonized mucosal and dental biofilms, and significantly lowered S. mutans counts. All three strains enhanced mucosal colonization of autochthonous bacteria. In a follow-up experiment, when S. mutans was established first, dental and mucosal colonization of S. mutans was unaltered by a subsequent challenge with either BCC23 strain. Results between BCC23 and BCC23 ∆arcADS were equivalent. Conclusions BCC23 is a potential probiotic to treat patients at high caries risk. Its effectiveness is independent of ADS activity, but initial dental cleaning to enhance establishment in dental biofilms may be required. Significance and Impact of the Study In vivo testing of candidate probiotics is highly informative, as effectiveness is not always reflected by genotype or in vitro behaviours

In 2018, we described a robotic natural orifice-assisted left-sided colorectal resection with intracorporeal anastomosis and transrectal extraction of the specimen and termed it the natural orifice intracorporeal anastomosis with transrectal extraction procedure. More recently, we have explored the feasibility, safety, and utility of performing total handsewn intracorporeal anastomosis. We present a technical video and initial experience depicting the unique steps to accomplish this procedure with colorectal end-to-end handsewn anastomosis.Twenty natural orifice intracorporeal anastomosis with transrectal extraction procedures with end-to-end handsewn intracorporeal anastomosis were performed. A video depicting the essential steps with 2 variations of the handsewn techniques is presented along with short-term outcomes.The most common indication was complicated diverticulitis followed by rectal cancer and deep infiltrative endometriosis of the rectum. The mean operative time was 235 minutes (99-294 min), and there were no intraoperative complications or conversions. Handsewn end-to-end intracorporeal anastomosis was successful in all patients. Natural orifice transrectal extraction was successful in 17 of 20 (85%) patients. The mean postoperative length of stay was 2.1 days (±1.05 SD). There were 3 major complications. One patient developed a deep surgical site infection, and another patient had an organ space abscess. Both patients required readmission and were treated with antibiotics alone. One patient, who had a diverting ileostomy performed at the time of the index procedure, developed subclinical dehiscence of the anastomosis, which healed without intervention but resulted in a delay in ileostomy reversal. There were no additional readmissions and no reoperations or mortalities.Robotic natural orifice intracorporeal anastomosis with transrectal extraction procedure and colorectal end-to-end handsewn anastomosis was feasible and safe in this initial series. This technique can be successfully performed in a total intracorporeal manner without the need for an abdominal wall extraction incision or any circular stapling devices.

In myotonic dystrophy type 1 (DM1) quadriceps weakness often results in severe functional limitations and genu recurvatum. To improve quadriceps strength the effects of isometric tetanic contractions using transcutaneous muscle stimulation (TMS) and testosterone enanthate (TE) were assessed. Ten DM1 subjects underwent unilateral TMS 6 hours per day for 14 days. The stimulated leg was randomly assigned and sham stimulation was done on the opposite leg by transcutaneous nerve stimulation. Muscle mass was estimated by cross-sectional area computed tomography and strength was measured by Cybex ergometry. Following the initial TMS period, 8 of 10 subjects were given a 12-week course of TE (3 mg/kg/wk) followed by 14 days of TMS. Neither TMS nor TE improved strength. Following 12 weeks of TE, there was an average increase in muscle mass of at least 8.7 +/- 1.6 cm2. These findings are consistent with the TE—increased muscle mass in DM1 as measured by creatinine clearance and total body potassium. The dissociation of mass and strength following TE and the failure of exercise to improve strength may have significance in characterizing the muscle defect in DM1.

Understanding the metabolic fate of a xenobiotic substance can help inform its potential health risks and allow for the identification of signature metabolites associated with exposure. The need to characterize metabolites of poorly studied or novel substances has shifted exposure studies towards non-targeted analysis (NTA), which often aims to profile many compounds within a sample using high-resolution liquid-chromatography mass-spectrometry (LCMS). Here we evaluate the suitability of suspect screening analysis (SSA) liquid-chromatography mass-spectrometry to inform xenobiotic chemical metabolism. Given a lack of knowledge of true metabolites for most chemicals, predictive tools were used to generate potential metabolites as suspect screening lists to guide the identification of selected xenobiotic substances and their associated metabolites. Thirty-three substances were selected to represent a diverse array of pharmaceutical, agrochemical, and industrial chemicals from Environmental Protection Agency’s ToxCast chemical library. The compounds were incubated in a metabolically-active in vitro assay using primary hepatocytes and the resulting supernatant and lysate fractions were analyzed with high-resolution LCMS. Metabolites were simulated for each compound structure using software and then combined to serve as the suspect screening list. The exact masses of the predicted metabolites were then used to select LCMS features for fragmentation via tandem mass spectrometry (MS/MS). Of the starting chemicals, 12 were measured in at least one sample in either positive or negative ion mode and a subset of these were used to develop the analysis workflow. We implemented a screening level workflow for background subtraction and the incorporation of time-varying kinetics into the identification of likely metabolites. We used haloperidol as a case study to perform an in-depth analysis, which resulted in identifying five known metabolites and five molecular features that represent potential novel metabolites, two of which were assigned discrete structures based on in silico predictions. This workflow was applied to five additional test chemicals, and 15 molecular features were selected as either reported metabolites, predicted metabolites, or potential metabolites without a structural assignment. This study demonstrates that in some–but not all–cases, suspect screening analysis methods provide a means to rapidly identify and characterize metabolites of xenobiotic chemicals.

El propósito del trabajo es explorar la autopercepción de estudiantes de licenciatura, en una universidad de México, sobre su desempeño escolar en el contexto de la pandemia. Se diseñó un cuestionario en línea con preguntas abiertas que exploran la percepción del estudiantado sobre la modalidad a distancia en su proceso de aprendizaje, considerando sus condiciones materiales de vida. El muestreo fue no probabilístico de autoselección, con la participación de 417 estudiantes. Para el análisis se usaron las categorías predefinidas sobre estado de salud, experiencias y dificultades personales en el distanciamiento social, experiencias del semestre pasado, propuestas de mejora y dificultades que pueden afectar el desempeño en el nuevo semestre. Los resultados muestran que aquellos estudiantes capaces de gestionar satisfactoriamente su proceso de aprendizaje perciben como “buenas” sus condiciones materiales de vida, salud personal y familiar. Entre las complicaciones percibidas destacan el servicio de Internet y el uso compartido de dispositivos o espacios. Student perception of school performance during the pandemic experience: a case study in a Mexican public university Abstract The purpose of this work is to explore the perception of undergraduate students, in a mexican university, on their academic performance in the context of the pandemic. An online questionnaire was designed with questions that explore the students' perception of the distance modality in their learning process, considering their structural conditions of life. Non-probabilistic self-selection sampling was carried out, with the participation of 417 students. For the analysis, we used predefined categories of health, personal difficulties, self-regulation, academic performance, and proposals for problem-solving. These categories were detailed as the information was analyzed. The results show that those students capable of satisfactorily managing their learning process perceive their material living conditions, and personal and family health as "good". Among the perceived complications, the Internet service and the shared use of devices or spaces stand out.

Pneumosinus dilatans is a rare disease characterized by air-filled expansion of a paranasal sinus. Approximately 134 cases are reported in the literature, but not only one associated with infantile cerebral palsy (ICP) and nasal polyposis. We herein present this case report aimed to further characterize this uncommon condition: a 28-year-old female diagnosed with infantile cerebral palsy and nasal polyposis, in whom the cranio-facial CT scan revealed the association of a pneumosinus dilatans involving the frontal sinus. The patient is currently undergoing a protocol for endoscopic surgery of the nose and paranasal sinuses.

Parkinson’s disease (PD) is the fastest-growing neurological disease in the world. A key challenge in PD is tracking disease severity, progression, and medication response. Existing methods are semisubjective and require visiting the clinic. In this work, we demonstrate an effective approach for assessing PD severity, progression, and medication response at home, in an objective manner. We used a radio device located in the background of the home. The device detected and analyzed the radio waves that bounce off people’s bodies and inferred their movements and gait speed. We continuously monitored 50 participants, with and without PD, in their homes for up to 1 year. We collected over 200,000 gait speed measurements. Cross-sectional analysis of the data shows that at-home gait speed strongly correlates with gold-standard PD assessments, as evaluated by the Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part III subscore and total score. At-home gait speed also provides a more sensitive marker for tracking disease progression over time than the widely used MDS-UPDRS. Further, the monitored gait speed was able to capture symptom fluctuations in response to medications and their impact on patients’ daily functioning. Our study shows the feasibility of continuous, objective, sensitive, and passive assessment of PD at home and hence has the potential of improving clinical care and drug clinical trials.

Autism spectrum disorder (ASD) affects 1 in 44 children. Chromatin regulatory proteins are overrepresented among genes that contain high risk variants in ASD. Disruption of the chromatin environment leads to widespread dysregulation of gene expression, which is traditionally thought of as a mechanism of disease pathogenesis associated with ASD. Alternatively, alterations in chromatin dynamics could also lead to dysregulation of alternative splicing, which is understudied as a mechanism of ASD pathogenesis. The anticonvulsant valproic acid (VPA) is a well-known environmental risk factor for ASD that acts as a class I histone deacetylase inhibitor. However, the precise molecular mechanisms underlying defects in human neuronal development associated with exposure to VPA are understudied. To dissect how VPA exposure and subsequent chromatin hyperacetylation influence molecular signatures involved in ASD pathogenesis, we conducted RNA sequencing (RNA-seq) in human cortical neurons that were treated with VPA. We observed that differentially expressed genes (DEGs) were enriched for mRNA splicing, mRNA processing, histone modification and metabolism related gene sets. Furthermore, we observed widespread increases in the number and the type of alternative splicing events. Analysis of differential transcript usage (DTU) showed that exposure to VPA induces extensive alterations in transcript isoform usage across neurodevelopmentally important genes. Finally, we find that DEGs and genes that display DTU overlap with known ASD-risk genes. Altogether, these findings suggest that, in addition to differential gene expression, changes in alternative splicing correlated with alterations in the chromatin environment could act as an additional mechanism of disease in ASD.

This study's objective was to compare the total and outside the cleft prevalence of dental anomalies (DA) between patients with cleft lip and palate (CLP) and a control group. This retrospective cross-sectional study was done under a case-control design. The case group consisted of 192 non-syndromic patients with complete CLP, while the control group included 411 patients. All subjects had orthopantomography, intra, and extraoral photographs. The prevalence of dental agenesis, supernumerary teeth, impacted teeth, dental transposition, and microdontia were compared using a chi-squared test (P.05). Next, a second test was made, but only the anomalies outside the cleft were considered for this study. Total prevalence was 89.1% for cases, and 20.9% for controls (P.01). The prevalence of each DA was significantly higher for the case group. In the analysis of DAs outside the cleft, the total prevalence was still significantly associated (P.01); however, only dental agenesis was statistically significant (P.01). Further analysis found that a high rate of upper premolar absence (P.01) could explain this event. Patients with CLP have a higher prevalence of DAs compared to controls. After considering only the DAs outside the cleft, the total prevalence remains significantly higher. However, this phenomenon is explained mainly by the elevated prevalence of upper premolars' agenesis. This study's results suggest that environmental factors are behind the high prevalence of DAs in subjects with CLP.

We investigated the relationship between high carcinoembryonic antigen (CEA) levels and low skeletal muscle mass (LMM) in asymptomatic adults in a population-based study. A total of 202,602 adults (mean age 41.7 years) without malignancy, stroke, cardiovascular disease, or chronic lung/liver disease were included. A high CEA level was defined as ≥5 ng/mL. Skeletal muscle mass index (SMI) was calculated based on appendicular muscle mass (kg)/height (m)2. Participants were classified into three groups based on SMI: “normal”, “mild LMM”, and “severe LMM.” The prevalence of elevated CEA levels was the highest in subjects with severe LMM (4.2%), followed by those with mild LMM (1.6%) and normal muscle mass (1.1%) (p for trend < 0.001). In multivariate logistic regression analysis, high CEA was independently associated with having mild LMM (adjusted odds ratio, 1.139 [95% confidence interval, 1.092–1.188]) and severe LMM (2.611 [2.055–3.319]) compared to normal muscle mass. Furthermore, the association between high CEA and severe LMM was stronger in women than that in men (women, 5.373 [2.705–10.669]; men, 2.273 [1.762–2.933]). Elevated CEA levels were significantly associated with a higher prevalence of LMM. Therefore, increased CEA could be used as a biomarker for detecting LMM in adults without cancer.

El Servicio de Gestión de Emergencias de Copernicus (Copernicus EMS del inglés, Copernicus Emergency Management Service) es un programa financiado con fondos públicos de la Unión Europea y coordinado por la Comisión Europea que proporciona a todos los actores involucrados en la gestión de desastres naturales, situaciones de emergencia y crisis humanitarias información geoespacial, principalmente basada en imágenes de satélite. Incluye componentes de Alerta temprana y Monitoreo, y de Mapeo con un módulo de Validación encargado de la evaluación de la calidad de los productos y el fomento de su mejora, en el marco del cual se realizó este estudio. Dentro del portafolio de productos de mapeo, los productos de clasificación de daños tienen como objetivo evaluar la intensidad y distribución espacial del daño resultante de un evento en edificios, bloques de viviendas o usos del suelo. Las categorías de daños para edificios y bloques de viviendas se definieron inicialmente con base en la Escala Macrosísmica Europea-1998 (EMS-98, del inglés European Macroseismic Scale). Este artículo muestra la función doble del módulo de validación. Por un lado, el artículo muestra los resultados de la validación de cuatro mapas de daños en edificios realizados por Copernicus EMS y por otro analiza la aptitud de la Escala Macrosísmica Europea (EMS-98), concebida para asignar daño in situ, para categorizar daño en edificios a partir de distintos tipos de imágenes (imágenes de satélite, imágenes oblicuas y ortofotos). La principal conclusión es que las categorías EMS-98 no se pueden traducir directamente para la evaluación de daños con base en imágenes de satélite y, en su lugar, se podría utilizar un enfoque operativo, en línea con estudios anteriores.

BACKGROUND: Smac/DIABLO is a proapoptotic protein deregulated in breast cancer, with a controversial role as a tumor marker, possibly due to a lack of correlative mRNA and protein analyses. OBJECTIVE: To investigate the association of Smac/DIABLO gene and protein levels with clinical variables in breast cancer patients. METHODS: Smac/DIABLO mRNA expression was analyzed by qPCR in 57 frozen tissues, whereas protein levels were assessed by immunohistochemistry in 82 paraffin-embedded tissues. Survivin mRNA levels were also measured. In vitro assays were performed to investigate possible regulators of Smac/DIABLO. RESULTS: Higher levels of Smac/DIABLO mRNA and protein were found in estrogen receptor (ER)-positive samples (p= 0.0054 and p= 0.0043, respectively) in comparison to ER-negative tumors. A negligible positive association was found between Smac/DIABLO and survivin expression. In vitro assays showed that Smac/DIABLO is not regulated by ER and, conversely, it does not participate in ER expression modulation. CONCLUSIONS: mRNA and protein levels of Smac/DIABLO were increased in ER-positive breast tumors in comparison with ER-negative samples, although the mechanism of this regulation is still unknown. Public databases showed a possible clinical relevance for this association.

Se ofrece una noticia sobre un crítico literario chileno y una reseña publicada en el New York Times en 1924 sobre el libro Mis últimas tradiciones y Cachivachería de Ricardo Palma, publicado en Barcelona en 1906. Ernesto Montenegro se destacó como difusor de la literatura norteamericana en la gran metrópolis estadounidense, pero en este caso se perciben algunas contradicciones entre el sincero reconocimiento a los méritos del autor y el juicio negativo que merece esta obra crepuscular del tradicionista.

Oxidative stress and inflammation play a pivotal role in ocular diseases. Resveratrol (RSV) is a natural bioactive that has recently attracted attention due to it potent antioxidant and anti-inflammatory properties. However, RSV presents poor aqueous solubility and chemical instability. Besides, effective drug delivery to the posterior segment of the eye is challenge. Nanotechnology emerges as a possible solution to improve both limitations. Here, we developed and characterized nanogels (NG) based on high molecular weight chitosan (HCS) crosslinked with sodium tripolyphosphate. The distribution size of NG presented a major population around 140 nm with a ζ-potential value of 32 ± 2 mV. TEM and AFM images showed that NG exhibited a rounded morphology. RSV encapsulation efficiency was 59 ± 1%. Photodegradation experiments showed that HCS by its own protects RSV from UV light-induced degradation. Biocompatibility assays revealed that NG were not cytotoxic neither inflammatory in human retinal pigment epithelial cells (ARPE-19), which constitutes the outer blood-retinal barrier. After cellular internalization, we report an endo-lysosomal escape of NG, which is crucial for efficient nanocarriers delivery systems. In conclusion, we envision that HCS based NG could constitute novel carriers for RSV, opening the possibility of its application in ocular diseases.

espanolIntroduction. The aim of this study is to assess the value of systematic screening in asymptomatic women admitted for spontaneous delivery with a combination of reverse transcription polymerase chain reaction (RT-PCR) and cycle threshold (Ct) and serum antibodies. Material and methods. Since May 6 all women admitted for spontaneous delivery underwent RT-PCR in nasopharyngeal swabs and specific antibodies IgG of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in serum that were performed as part of routine clinical care in our institution. Ct of the PCR was recorded. We analyzed the first 100 women consecutively admitted for spontaneous delivery at our institution. Results. Nine women were positive for SARS-CoV-2 in nasopharyngeal samples (9%) and 13 (13%) presented positive specific antibodies of the coronavirus. Overall, SAR-CoV-2 prior exposure was 15%. The Ct determination (RT-PCR test) of our 9 positive patients ranged from 36 to 41 cycles with a median of 40. Vaginal delivery occurred in 94% of the cases and only 6% underwent a cesarean section, always for obstetric reasons. No fetal transmission was observed and maternal and neonatal prognosis was excellent. Conclusions. During epidemic episodes in asymptomatic women in labor, universal testing with RT-PCR (considering Ct determination), and the detection of antibodies, permits a better interpretation of the results and avoid unnecessary isolation procedures. EnglishObjetivo. El objetivo de este estudio es evaluar, en mujeres asintomaticas que acuden a urgencias en trabajo de parto, el valor de la deteccion sistematica con una combinacion de reaccion en cadena de la polimerasa con transcriptasa inversa (RT-PCR) y umbral del ciclo (Ct) y anticuerpos sericos. Material y metodos. Desde el 6 de mayo, todas las mujeres ingresadas para parto espontaneo se sometieron a RT-PCR en hisopos nasofaringeos y anticuerpos especificos IgG del sindrome respiratorio agudo severo por coronavirus 2 (SARSCoV-2) en suero que se realizaron como parte de la atencion clinica de rutina en nuestra institucion. Se registro el Ct de la PCR. Analizamos las primeras 100 mujeres admitidas consecutivamente para parto espontaneo en nuestra institucion. Resultados. Nueve mujeres fueron positivas para SARSCoV-2 en muestras nasofaringeas (9%) y 13 (13%) presentaron anticuerpos especificos positivos del coronavirus. En general, la exposicion previa a SARS-CoV-2 fue del 15%. La determinacion de Ct (prueba de RT-PCR) de nuestros 9 pacientes positivos vario de 36 a 41 ciclos con una mediana de 40. El parto vaginal se produjo en el 94% de los casos y solo el 6% se sometio a una cesarea, siempre por razones obstetricas. No se observo transmision fetal y el pronostico materno y neonatal fue excelente. Conclusiones. Durante los episodios epidemicos en mujeres asintomaticas en trabajo de parto, las pruebas universales con RT-PCR (considerando la determinacion de Ct) y la deteccion de anticuerpos, permiten una mejor interpretacion de los resultados y evitan procedimientos de aislamiento innecesarios.

Multicellular tumor spheroids constitute a three-dimensional culture system that recapitulates the in vivo tumor microenvironment. Tumor cells cultured as multicellular tumor spheroids present antineoplastic resistance due to the effect of microenvironmental signals acting upon them. In this work, we evaluated the biological function of a new microenvironment-regulated long non-coding RNA, lncMat2B, in breast cancer. In multicellular tumor spheroids, the expression of lncMat2B presented an increase and a zonal heterogeneity, as it was expressed principally in quiescent cells of hypoxic regions of the multicellular tumor spheroids. As expected, functional assays supported the role of severe hypoxia in the regulation of lncMat2B. Moreover, gain- and loss-of-function assays using a transcriptional silencing CRISPR/Cas9 system and gBlock revealed that lncMAT2B regulates the tumor-initiating phenotype. Interestingly, lncMat2B is overexpressed in a cisplatin-resistant MCF-7 cell line, and its ectopic expression in wild type MCF-7 cells increased survival to cisplatin exposure by reducing DNA damage and reactive oxygen species accumulation. lncMAT2B is a possible link between severe hypoxia, tumor-initiating phenotype, and drug resistance in breast cancer cells.

espanolEn este articulo se presenta el caso de Venezuela, pais que, luego de haber tenido el mayor potencial de desarrollo de Latinoamerica, sufre una debacle politica, economica y social que lo ha llevado a convertirse en el mas pobre de la region, con la inflacion mas elevada, y a ser calificado en “emergencia humanitaria compleja”. Tambien se describen las graves violaciones a los derechos humanos: civiles, politicos, economicos, sociales, culturales y ambientales que ocurren alli sobre la base de la Declaracion Universal sobre Bioetica y Derechos Humanos, de la Unesco (2005). Ademas, se proporciona informacion sobre el desarrollo y la ensenanza de la bioetica en Venezuela. El articulo concluye con el analisis de la situacion del pais desde otras perspectivas bioeticas enfocadas en Latinoamerica: bioetica social y bioetica de intervencion; las repercusiones del problema en la region y la descripcion de los esfuerzos realizados a nivel nacional e internacional para solventar la emergencia humanitaria y recuperar el pais. EnglishThis article presents the case of Venezuela, a country that, after having had the greatest development potential in Latin America, suffers a political, economic and social debacle that led it to become the poorest in the region, with the highest inflation, and to be qualified as a country in a “complex humanitarian emergency”. It also describes the serious violations to human rights – civil, political, economic, social, cultural and environmental – that occur there based on the UniversalDeclaration on Bioethics and Human Rights by Unesco (2005). Additionally, information on the development and teaching of bioethics in Venezuela is provided. The article ends with an analysis of the country situation from other bioethical perspectives focused on Latin-America: social bioethics and intervention bioethics; the repercussions of the problem in the region and the description of the efforts made at national and international level to solve the humanitarian emergency and to recover the country. portuguesEste artigo apresenta o caso da Venezuela que, depois de ter o maior potencial de desenvolvimento da America Latina, sofre um desastre politico, economico e social que a levou a se tornar o pais mais pobre da regiao, alem de apresentar a mais alta taxa de inflacao e estar sob "emergencia humanitaria complexa". Tambem ha relatos de graves violacoes dos direitos humanos (civil, politico, economico, social, cultural e ambiental), com base na Declaracao Universal de Bioetica e Direitos Humanos, da Unesco (2005). Alem disso, algumas informacoes sobre o desenvolvimento e ensino da bioetica na Venezuela sao fornecidas. O artigo e concluido com a analise da situacao desse pais, a partir de outras perspectivas bioeticas que estao enfocadas na America Latina, como a bioetica social e a bioetica de intervencao, as repercussoes do problema na regiao e a descricao dos esforcos realizados, em nivel nacional e internacional, para solucionar a emergencia humanitaria e recuperar esse pais.

Background BRCA genetic testing is recommended by the National Comprehensive Cancer Network (NCCN) in breast cancer patients who meet specific criteria. Limited data are available on the likelihood of detecting a mutation when these guidelines are followed. Methods A retrospective chart review examined patients with breast cancer who underwent BRCA testing based on NCCN guidelines. Results Twelve (6.0%) of the 199 patients had a deleterious BRCA mutation. Family history of BRCA mutations (50%, p = 0.019), age ≤45 at diagnosis (9.7%, p = 0.034) and meeting ≥3 NCCN criteria (13.3%, p = 0.03) yielded the highest rates of BRCA mutation. Having a family history of BRCA mutation and age ≤45 were associated with increased rate of BRCA mutation on multivariate analysis (OR 14.3, CI 1.2–166.3; OR 11.6, CI 1.2–108.6). Conclusion Select NCCN criteria are associated with higher rates of BRCA mutations. Waiting for genetic testing results to guide surgical management may be warranted in this subset of patients.

The ajenjo, Artemisia mendozana DC. var. mendozana (Asteraceae), grows in the Andean foothills of Mendoza and San Juan, Argentina, and is used as a medicinal plant for its antispasmodic and antifungal properties. The aim of this work was to obtain fractions of a chloroform extract of ajenjo leaves and to evaluate the in vitro effects on proliferation, viability and clonogenicity of B16-F0 melanoma cells. Using a silica gel chromatography column, 120 fractions were collected and grouped according to the chromatographic profile in 9 main fractions (F1-F9). Their major compounds identified were: Terpenes (F1), terpenes and sesquiterpene lactones (F2-F3), sesquiterpenes (F4-F6) and phenols and sesquiterpenes (F7-9). B16-F0 cells were incubated for 72 h with DMSO (vehicle) or 0.1 mg/ml F1-F9. At 72 h of culture, F1 decreased both the growing index (GI) and cell viability. F2 and F3 both decreased GI and only F3 decreased clonogenic activity. F4 and F5 both decreased GI. Only F5 decreased cell viability and F4 decreased clonogenicity. Consequently, fractions F6-F8 did not affect any of the cell parameters assayed, while F9 decreased cell viability and inhibited clonogenicity. Fil: Millán, María Elisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina Fil: Marra, María Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina Fil: Salvarredi, Leonardo Andres. Comisión Nacional de Energía Atómica; Argentina. Universidad Nacional de Cuyo; Argentina. Fundación Escuela de Medicina Nuclear; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Lizarraga, Emilio Fernando. Fundación Miguel Lillo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Tucumán; Argentina Fil: Lopez, Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina

El presente trabajo constituye un estudio jurisprudencial sobre la motivación en la contratación pública. La motivación es un requisito esencial, cuya falta da lugar a la anulación del acto impugnado, aunque sus efectos suelen limitarse a la retroacción del procedimiento para que se efectúe una motivación suficiente. La motivación puede sustentarse en los informes técnicos que fundamentan la resolución administrativa. Lan hau kontratazio publikoko motibazioari buruzko azterlan jurisprudentzial bat da. Motibazioa funtsezko baldintza bat da, eta motibaziorik ezak aurkaratutako egintza deuseztatzea dakar; hala ere, ondorioak prozeduraren atzeraeraginera mugatzen dira, behar besteko motibazioa egiteko. Motibazioa administrazio- ebazpenaren oinarri diren txosten teknikoetan oinarritu daiteke. This paper constitutes a jurisprudential study on motivación in public procurement. The statement of reasons is an essential requirement, whose lack leads to the annulment of the challenged act, although its effects are usually limited to the retroaction ot the procedure so as to carry out a sufficient reasoning. The motivation can be based on the technical reports that support the administrative resolution.

PURPOSE Sparse inverse covariance estimation (SICE) is increasingly utilized to estimate inter-subject covariance of FDG uptake (FDGcov) as proxy of metabolic brain connectivity. However, this statistical method suffers from the lack of robustness in the connectivity estimation. Patterns of FDGcov were observed to be spatially similar with patterns of structural connectivity as obtained from DTI imaging. Based on this similarity, we propose to regularize the sparse estimation of FDGcov using the structural connectivity. METHODS We retrospectively analyzed the FDG-PET and DTI data of 26 healthy controls, 41 patients with Alzheimer's disease (AD), and 30 patients with frontotemporal lobar degeneration (FTLD). Structural connectivity matrix derived from DTI data was introduced as a regularization parameter to assign individual penalties to each potential metabolic connectivity. Leave-one-out cross validation experiments were performed to assess the differential diagnosis ability of structure weighted SICE approach. A few approaches of structure weighted were compared with the standard SICE. RESULTS Compared to the standard SICE, structural weighting has shown more stable performance in the supervised classification, especially in the differentiation AD vs. FTLD (accuracy of 89-90%, while unweighted SICE only 85%). There was a significant positive relationship between the minimum number of metabolic connection and the robustness of the classification accuracy (r = 0.57, P < 0.001). Shuffling experiments showed significant differences between classification score derived with true structural weighting and those obtained by randomized structure (P < 0.05). CONCLUSION The structure-weighted sparse estimation can enhance the robustness of metabolic connectivity, which may consequently improve the differentiation of pathological phenotypes.

The assessment of human health hazards posed by chemicals traditionally relies on toxicity studies in experimental animals. However, most chemicals currently in commerce do not meet the minimum data requirements for hazard identification and dose-response analysis in human health risk assessment. Previously, we introduced a read-across framework designed to address data gaps for screening-level assessment of chemicals with insufficient in vivo toxicity information (Wang et al., 2012). It relies on inference by analogy from suitably tested source analogues to a target chemical, based on structural, toxicokinetic, and toxicodynamic similarity. This approach has been used for dose-response assessment of data-poor chemicals relevant to the U.S. EPA's Superfund program. We present herein, case studies of the application of this framework, highlighting specific examples of the use of biological similarity for chemical grouping and quantitative read-across. Based on practical knowledge and technological advances in the fields of read-across and predictive toxicology, we propose a revised framework. It includes important considerations for problem formulation, systematic review, target chemical analysis, analogue identification, analogue evaluation, and incorporation of new approach methods. This work emphasizes the integration of systematic methods and alternative toxicity testing data and tools in chemical risk assessment to inform regulatory decision-making.

In the knowledge society, social progress by nation is measured through the human development index, which includes 3 fundamental aspects, among which is the education index. however, we cannot speak of quality education if it does not contemplate offering accessible inclusive environments for comprehensive student development. the study aims to disseminate experiences of the educational process through virtuality from students with specific needs for educational support due to a disability condition. the methodology consisted of applying a structured interview to 383 students from different regional units that make up the autonomous university of sinaloa, rescuing emotional elements, support received by student care programs, situation regarding the pandemic and use of educational technology tools. instrument validated through expert judgment, and piloted from 30 students under real-world application conditions. the results indicate, 72.1% correspond to the intermediate level, 24.3% higher level, and the rest to postgraduate level. the main conditions that the students said to present are 34.6% psychosocial disability, 10.4% visual, 5.3% intellectual and down syndrome, 7.4% learning disorders, 8.7% hearing disability and 10.4% motor disability. regarding their educational experience, 40.8% presented stress, 37.9% anxiety and 25.4% sadness. it is concluded that a high percentage experienced emotional situations that require attention and follow-up, an aspect that the institution is channeling through the various student support programs, including the attention to diversity program - ADIUAS. En la sociedad del conocimiento, el progreso social por nación se mide a través del Indice de Desarrollo Humano, que incluye 3 aspectos fundamentales, entre los cuales se encuentra el índice de educación. sin embargo, no podemos hablar de educación de calidad si no contempla ofrecer ambientes inclusivos accesibles para el desarrollo integral estudiantil. El estudio tiene como objetivo difundir experiencias del proceso educativo a través de la virtualidad desde los estudiantes con necesidades específicas de apoyo educativo a causa de una condición de discapacidad. La metodología consistió en aplicar una entrevista estructurada a 383 estudiantes de diferentes unidades regionales que conforman la Universidad Autónoma de Sinaloa, rescatando elementos emocionales, de apoyo recibido por programas de atención estudiantil, situación respecto a la pandemia y uso sobre herramientas de tecnología educativa. Instrumento validado a través de juicio de expertos, y piloteado desde 30 estudiantes en condiciones de aplicación en contexto real. Los resultados indican, 72.1% corresponden al nivel medio, 24.3% nivel superior, y el resto a nivel posgrado. Las principales condiciones que los estudiantes manifestaron presentar se encuentran discapacidad psicosocial 34.6%, 10.4% visual, 5.3% intelectual y síndrome de down, 7.4% trastornos del aprendizaje, 8.7% discapacidad auditiva y 10.4% discapacidad motriz. Sobre su experiencia educativa, el 40.8% presentó estrés, 37.9% ansiedad y 25.4% tristeza. Se concluye que un alto porcentaje experimentó situaciones emocionales que requieren atención, aspecto que la institución encauza a través de los diversos programas de apoyo estudiantil, entre ellos, el Programa Atención a la Diversidad – ADIUAS.

En la era del Big Data, una verdadera cultura de la evaluación de las políticas públicas se muestra al alcance de la mano. En el presente documento se plantea el papel que juega la evaluación de políticas públicas en la mejora de las administraciones y la resolución de algunos de los retos socioeconómicos más acuciantes para nuestras sociedades. Se incide asimismo en el gran salto adelante que supondría una mejora del uso de las bases de datos administrativas para la evaluación. De modo ilustrativo, se presenta un estudio de caso para una mejor comprensión de los beneficios potenciales y tangibles de estas inversiones en apertura y conocimiento.

This paper provides a systematic weight-of-evidence method for read-across analyses of data-poor chemicals. The read-across technique extrapolates toxicity from analogous chemicals for which suitable test data are available to a target chemical. To determine that a candidate analogue is the 'best' and is sufficiently similar, the evidence for similarity of each candidate analogue to the target is weighed. We present a systematic weight of evidence method that provides transparency and imposes a consistent and rigorous inferential process. The method assembles relevant information concerning structure, physicochemical attributes, toxicokinetics, and toxicodynamics of the target and analogues. The information is then organized by evidence types and subtypes and weighted in terms of properties: relevance, strength, and reliability into weight levels, expressed as symbols. After evidence types are weighted, the bodies of evidence are weighted for collective properties: number, diversity, and coherence. Finally, the weights for the types and bodies of evidence are weighed for each analogue, and, if the overall weight of evidence is sufficient for one or more analogues, the analogue with the greatest weight is used to estimate the endpoint effect. We illustrate this WoE approach with a read-across analysis for screening the organochlorine contaminant, p,p'-dichlorodiphenyldichloroethane (DDD), for noncancer oral toxicity.

Este estudio tuvo como propósito identificar los efectos del programa ART-EMO en los niveles de inteligencia emocional de jóvenes voluntarios que trabajan con niños en una entidad privada. La muestra fue compuesta por 10 participantes cuyas edades oscilaban los 21 y 30 años; el 10% eran hombres y el 90% mujeres. Se aplicó, en dos condiciones de tiempo, el Inventario de Inteligencia Emocional en adultos: EQ-i-M20 creado por Pérez-Fuentes et al. (2014) y validado en una población de estudiantes peruanos por Domínguez-Lara et al. (2017). Para fines de la presente investigación, en el 2017 se elaboró el programa ART-EMO mediante un diseño cuasi experimental con un solo grupo, considerándose a Guerrón (2015) como referente. El programa tuvo un impacto alto a nivel total de la inteligencia emocional (d=.82) y en sus dimensiones intrapersonal (d=1.04), interpersonal (d=.90) y adaptabilidad (d=1.01); no obstante, en estado de ánimo (d=.67) y manejo de estrés (d=.55), fue moderado. A modo de conclusión, el programa fue eficaz y con ello se busca que las instituciones fomenten el desarrollo emocional en quienes son voluntarios.

OBJECTIVES: Irritable bowel syndrome (IBS) is the most frequently diagnosed functional gastrointestinal disorder, with a prevalence of up to 25% of the global population. IBS patients suffer from abnormal abdominal pain, or visceral hypersensitivity (VHS), associated with altered bowel habits in the absence of an organic detectable cause. The pathophysiology of the disease is incompletely understood, but the dysregulation of the brain-gut axis is well established in IBS. METHODS: IBS onset is mainly triggered by infectious gastroenteritis, psychological factors, and dietary factors, but genetic predispositions and intestinal dysbiosis might also play a role. Additionally, immune activation, and particularly chronic mast cell activation, have been shown to underlie the development of abdominal pain in IBS. RESULTS: By releasing increased levels of mediators, including histamine, mast cells sensitize enteric nociceptors and lead to VHS development. The mechanisms underlying aberrant mast cell activation in IBS are still under investigation, but we recently showed that a local break in oral tolerance to food antigens led to IgE-mediated mast cell activation and food-induced abdominal pain in preclinical models and in IBS patients. CONCLUSION: The concept of food-mediated VHS highlights the potential of therapies targeting upstream mechanisms of mast cell sensitization to treat IBS. ispartof: ACTA CLINICA BELGICA vol:77 issue:5 pages:889-896 ispartof: location:England status: published

El zinc (Zn) es un micromineral esencial y su carencia puede afectar la eficiencia productiva y reproductiva del ganado. Con el objetivo de evaluar el estatus de Zn en vacas de cría de la cuenca deprimida del río Salado (centro este de la provincia de Buenos Aires, Argentina), se realizó un estudio observacional multicén-trico en 110 rebaños en el que se recolectaron muestras de sangre (n = 1.078 vacas) y se analizaron mediante espectrofotometría de absorción atómica. Las vacas se clasificaron según la concentración plasmática de Zn en fisiológicamente adecuadas ≥ 90 μg/dl, marginales entre 80 y 89 μg/dl y carentes, Zinc (Zn) is an essential micromineral and its deficiency can affect the productive and reproductive efficiency in cattle. A multicenter observational study was carried out to evaluate Zn status in breeding cows at Salado River Basin (Buenos Aires, Argentina). The study included 110 cow-calf operations, in which blood samples (n = 1078 cows) were collected and analyzed by using atomic absorption spectrophotometry. Cows were classified according to their plasma Zn concentration values as physiologically adequate (≥ 90 μg/dl), marginal (between 80 to 89 μg/dl) and deficient (, Facultad de Ciencias Veterinarias

Background: We previously showed increased susceptibility to dextran sulfate sodium (DSS)-induced colitis in vagotomized mice. Here, we evaluated whether vagus nerve stimulation (VNS) is able to reduce the severity of DSS colitis and aimed to unravel the mechanism involved.Methods: Colitis was induced in wild type mice by 2.5% DSS administration in drinking water for 5 days. VNS (5 Hz, 1 ms, 1 mA) was applied 1 day prior to and after 4 days of DSS administration to evaluate changes in epithelial integrity and inflammatory response, respectively. Epithelial integrity was assessed using TUNEL and Ki67 staining. Monocytes, immature and mature macrophages were sorted from colonic samples and gene expression levels of pro-inflammatory cytokines were studied.Results: VNS applied prior to DSS administration (i.e., prophylactic VNS) reduced disease activity index (VNS 0.8 ± 0.6 vs. sham 2.8 ± 0.7, p < 0.001, n = 5) and tended to improve histology score. Prophylactic VNS significantly increased epithelial cell proliferation and diminished apoptosis compared to sham stimulation. VNS applied at day 4 during DSS administration (i.e., therapeutic VNS) decreased the influx of monocytes, monocyte-derived macrophages and neutrophils, and significantly reduced pro-inflammatory cytokine expression (i.e., Tnfα and Cxcl1) in immature macrophages compared to sham stimulation.Conclusions: A single period of VNS applied prior to DSS exposure reduced DSS-induced colitis by an improvement in epithelial integrity. On the other hand, VNS applied during the inflammatory phase of DSS colitis reduced cytokine expression in immature macrophages. Our data further underscores the potential of VNS as novel therapeutic approach for inflammatory bowel diseases.

espanolEn diciembre de 1919 la Alianza Internacional para el Sufragio de la Mujer (IWSA) anunciaba oficialmente que su VIII Congreso tendria lugar en Madrid. Su celebracion, finalmente, se frustro como consecuencia de las disputas entre las propias asociaciones feministas espanolas y por la presion de los sectores mas conservadores de la sociedad. Los enfrentamientos entre la Asociacion Nacional de Mujeres Espanolas (ANME) y la Union de las Mujeres de Espana (UME), asi como la oposicion de la Accion Catolica de la Mujer (ACM), determinaron que finalmente el congreso se celebrara en Ginebra en junio de 1920. Alli acudieron importantes representantes del feminismo espanol, como Maria Lejarraga, Isabel Oyarzabal o Magda Donato, que enviaron cronicas a diversos periodicos espanoles sobre los acuerdos alli tomados y sus impresiones del evento. Recogemos sucintamente los aspectos mas destacados de estas cronicas, de una modernidad evidente. EnglishIn December 1919, the International Woman Suffrage Alliance (IWSA) officially announced that their 8th Congress would be held in Madrid. Its celebration was however finally frustrated due to internal disputes within the Spanish feminist associations and pressures from the most conservative sectors of society. The confrontation between the National Association of Spanish Women (ANME) and the Union of Spanish Women (UME), as well as the opposition of the Women Catholic Action (ACM), eventually determined that the Congress would be celebrated in Geneva in June 1920. Important representatives of Spanish feminism attended the conference, such as Maria Lejarraga, Isabel Oyarzabal or Magda Donato. They sent their chronicles out to diverse Spanish newspapers, informing about the agreements reached there and their impressions about the event. We succinctly collect the most outstanding aspects of these chronicles, which reveal an evident modernity

Deriving human health risk estimates for environmental chemicals has traditionally relied on in vivo toxicity databases to characterize potential adverse health effects and associated dose-response relationships. In the absence of in vivo toxicity information, new approach methods (NAMs) such as read-across have the potential to fill the required data gaps. This case study applied an expert-driven read-across approach to identify and evaluate analogues to fill non-cancer oral toxicity data gaps for p,p’-dichlorodiphenyldichloroethane (p,p’-DDD), an organochlorine contaminant known to occur at contaminated sites in the U.S. The source analogue p,p’-dichlorodiphenyltrichloroethane (DDT) and its no-observed-adverse-effect level of 0.05 mg/kg-day were proposed for the derivation of screening-level health reference values for the target chemical, p,p’-DDD. Among the primary similarity contexts (structure, toxicokinetics, and toxicodynamics), toxicokinetic considerations were instrumental in separating p,p’-DDT as the best source analogue from other potential candidates (p,p’-DDE and methoxychlor). In vitro high-throughput screening (HTS) assays from ToxCast were used to evaluate similarity in bioactivity profiles and make inferences toward plausible mechanisms of toxicity to build confidence in the read-across approach. This work demonstrated the value of NAMs such as read-across and in vitro HTS in human health risk assessment of environmental contaminants with the potential to inform regulatory decision-making.

La jurisprudencia constitucional ha examinado desde la perspectiva competencial la nueva regulación del silencio administrativo en la Ley 39/2015, de 1 de octubre, del Procedimiento Administrativo Común de las Administraciones Públicas. A la luz de esa doctrina, este trabajo estudia las novedades consistentes en la restricción de la regla general del silencio positivo y la adición de un nuevo supuesto de silencio negativo, así como la cláusula de prohibición de la adquisición por silencio de facultades o derechos en contra de la legalidad. Jurisprudentzia konstituzionalak eskumenen ikuspegitik aztertu du administrazio-isiltasunaren erregulazio berria (39/2015 Legea, urriaren 1ekoa, Administrazio Publikoen Prozedura Erkidearena). Doktrina hori oinarri, lan honetan berrikuntzak aztertzen dira: isiltasun positiboaren arau orokorra murriztea eta isiltasun negatiboko kasu berri bat eranstea, baita isiltasunagatik ahalmenak edo eskubideak legez kontra eskuratzeko debekuklausula ere. The constitutional jurisprudence has considered from the perspective of the allocation of powers the new regulation of administrative silence as set out by Act 39/2015, of October 1, on the Common Administrative Procedure of Public Administrations. In light of this doctrine, this paper studies the novelties upon the restriction of the general rule of the positive silence and the addition of a new case for negative silence, together with the prohibition clause regarding the acquisition of faculties or rights due to the silence in breach of legality.

A group of 39, 19-22-month-old Friesian bulls were administered an ivermectin/closantel anthelmintic via intended S/C injection in the ischiorectal fossa on 15 June 2017 (Day 0). Over the next 50 days, 22 affected bulls presented various degrees of anorexia, abdominal pain and urine dribbling. Seventeen bulls were examined by transrectal ultrasonography which revealed urinary bladder distension in all 17, and peritoneal fluid accumulation in some. Overall, eight bulls died or were subjected to euthanasia. On-farm postmortem examination of three bulls revealed urinary bladder rupture.On Day 50 one affected live bull was admitted to Massey University for further investigation. This bull continuously dribbled urine and had an overtly distended urinary bladder as determined by rectal palpation and ultrasonography.Postmortem examination of this bull revealed a markedly distended urinary bladder, massive subcapsular and pericapsular renal oedema with retroperitoneal fluid accumulation, minimal hydronephrosis and no evidence of mechanical urinary outflow obstruction. The right ischiorectal fossa contained multifocal areas of tissue fibrosis that extended into areas innervated by the distal cutaneous branch of the pudendal nerve and the pelvic nerve. Histopathological changes consisted of extensive fibrosis, myonecrosis and neurodegeneration, and evidence of granulation tissue and inflammation at the putative injection site and in surrounding tissues.A local inflammatory reaction at the presumed injection site together with localised peripheral neurodegeneration and myelopathy may have led to detrusor-sphincter dyssynergia causing urine retention.These cases of urine retention and bladder rupture in cattle were of putative iatrogenic origin. Veterinarians should be aware of this rare complication after S/C injections in the ischiorectal fossa.

Funding Acknowledgements Type of funding sources: None. Introduction. Pulmonary vascular resistance (PVR) is a hemodynamic parameter with important diagnostic and prognostic implications in patients with heart failure. Currently the gold standard technique for its quantification is right heart catheterization (RHC). However, cardiovascular magnetic resonance imaging (CMR) has been postulated as a non-invasive alternative for its estimation. The aim of this study is to assess the accuracy of a non-invasive model of PVR estimated by CMR in a specific subgroup of patients with acute heart failure (AHF). Methods. Between January 2014 and December 2018, 108 patients with AHF who underwent RHC and CMR on the same day were prospectively included. PVR was assessed by CMR using the model: 19.38 - [4.62 x Ln mean pulmonary artery velocity - 0.08 x right ventricular ejection fraction (RVEF)]. During RHC, PVR were calculated using the ratio between transpulmonary gradient and cardiac output. We evaluated their correlation using the Spearman correlation coefficient, receiver operating characteristic [ROC] curves, and Bland-Altman analysis. Results. The mean age of our cohort was 65 ± 11 years and 64.8% were male. The median PVR (Wood Units, WU) assessed by CMR and RHC were 5.1 WU (3.4 - 6.8) and 3 WU (1.5 - 3.9); p Conclusions. In patients with AHF, the non-invasive estimation of PVR using CMR shows poor accuracy, as well as a limited capacity to discriminate increased PVR values.

Funding Acknowledgements Type of funding sources: None. Introduction Acute pulmonary embolism (PE) is the third cause of cardiovascular mortality, right after acute myocardial infarction and stroke. Systemic thrombolytic therapy (SLT) restores pulmonary perfusion earlier than low molecular-weight heparin, but with a significantly higher risk of major bleeding. Currently, in our area there is a lack of standardized protocols for the management of patients in which SLT is contraindicated. Objective The purpose of our study was to evaluate the safety and efficacy of percutaneous catheter-directed treatment (PCT) for high-intermediate risk PE (HIRPE) patients with hemodynamic deterioration on anticoagulation treatment. Methods We consecutively included all patients with HIRPE patients who underwent PCT in our center. Before and after PCT clinical, echocardiographic and hemodynamic variables were collected, as well as events (major or minor bleeding, death) during follow-up. Results From February 2018 to February 2020, 20 patients with HIRPE underwent PCT. The mean age of our cohort was 62 (52 - 73), and 46.6% were women. The indication for PCT was absolute contraindication for SLT (9 patients, 45%), followed by high bleeding risk (8 patients, 40%) and failure of SLT. Vascular access was mainly performed through femoral vein (12 patients, 60%) followed by a peripheral vein of the superior limb (8 patients, 40%). During pulmonary angiography, lobar arteries occlusion was observed in 60% of the cases, with involvement of main pulmonary arteries in 40% of the cases. Local thrombolysis with Alteplase was performed in 17 cases (85%), and in 8 cases it was decided to carry-out a thrombus fragmentation-aspiration strategy. We observed and early improvement of hemodynamic parameters after PCT, with a significant reduction of mean pulmonary artery pressure before and after PCT (40 +/- 13 mmHg vs. 25 +/- 12 mmHg, p < 0.001, figure 1), as well as an improvement in systolic blood pressure (102 +/- 13 mmHg vs. 129 +/- 14, p < 0.001) and the partial pressure of oxygen (51 +/- 3 vs. 67 +/- 2, p = 0.002). We also observed a significant decrease in NT-proBNP values at admission and 48 hours after PCT (4791 +/- 1077 pg/mL vs. 2311 +/- 680 pg/mL, p = 0.002, figure 2), as well as an improvement in echocardiographic right ventricular function parameters evaluated at admission and 72 hours after PCT, such as TAPSE (15 +/- 2 mm vs 22 +/- 3 mm, p = 0.001) or right ventricle basal diameter (51 +/- 4 mm vs. 41 +/- 2 mm, p = 0.001). During a median follow-up of 7 months (4 - 12 months) one patient died of non-cardiac cause and none of them had a major or minor bleeding event. Conclusion PCT in patients with HIRPE with hemodynamic deterioration on anticoagulation is a simple and effective procedure with an immediate reduction of mean pulmonary pressure and an early improvement of right ventricle-related biochemical, hemodynamic and echocardiographic parameters. Abstract Figure 1: mPAP after and before PCT.

Lobular carcinoma in situ (LCIS), atypical ductal and lobular hyperplasia (AH) increase breast cancer risk. We examined risk management recommendations (RMR) and acceptance in AH/LCIS.All patients with AH/LCIS on core needle biopsy from 2013 to 2016 at our institution were identified; cancer patients were excluded. Univariate and multivariate analysis examined factors associated with management.98 % of patients were evaluated by breast surgeons and 53 % underwent risk model calculation (RC). 77 % had new RMR. RMR of MRI screening (MRI), genetic counselling (GC) and medical oncology (MO) referral were 41 %, 18 %, 77 %, respectively. MRI screening was more likely recommended in those with strong family history (p = 0.01), and high RC (p 0.001). Uptake of at least one RMR did not occur in 84 % of patients. Use of RC correlated with MO acceptance (p = 0.049).Diagnosis of atypia has the potential to change risk management for most, however only 16 % of patients accepted all RMR.

Christianson syndrome (CS), an X-linked neurological disorder characterized by postnatal attenuation of brain growth (postnatal microcephaly), is caused by mutations in SLC9A6 (also termed NHE6), the gene encoding endosomal Na(+)/H(+) exchanger 6 (NHE6). To hasten treatment development, we established CS patient-derived induced pluripotent stem cell (iPSC) lines representing a mutational spectrum, as well as biologically related and isogenic control lines. We demonstrated that pathogenic mutations lead to loss of protein function by a variety of mechanisms: the majority of mutations caused loss of mRNA due to nonsense-mediated mRNA decay; however, a recurrent, missense mutation (the G383D mutation) had both loss-of-function and dominant-negative activities. Regardless of mutation, all patient-derived neurons demonstrated reduced neurite growth and arborization, likely underlying diminished postnatal brain growth in patients. Phenotype rescue strategies showed mutation-specific responses: a gene transfer strategy was effective in nonsense mutations, but not in the G383D mutation, wherein residual protein appeared to interfere with rescue. In contrast, application of exogenous trophic factors (BDNF or IGF-1) rescued arborization phenotypes across all mutations. These results may guide treatment development in CS, including gene therapy strategies wherein our data suggest that response to treatment may be dictated by the class of mutation.

We report on the fabrication of optical waveguides by ultrafast laser ablation of Al2O3. First, a thin film was grown by atomic layer deposition (ALD) on fused silica substrate, followed by laser ablation micromachining the surface material in order to produce a rib waveguide. A multimode behavior of the waveguide and propagation loss of 3.8 dB/cm was measured at 632.8 nm. Microstructural characterization showed that roughness is the major issue to overcome the propagation losses. Results obtained in this work suggest a viable methodology for the fabrication of optical waveguides for potential applications in integrated photonics.

Fundamento. Conocer el nivel de empoderamiento de las personas con insuficiencia cardiaca crónica hospitalizadas es crucial para identificar a las personas con un nivel de empoderamiento más bajo y fundamentar el diseño de estrategias efectivas para mejorar su control sobre las decisiones y acciones que afectan a su salud y bienestar. La falta de estudio de este fenómeno en esta población y contexto, sugiere que estos pacientes no están siendo atendidos adecuadamente. Material y métodos. Estudio descriptivo, prospectivo. Se utilizó el Cuestionario de empoderamiento del paciente con enfermedad crónica, traducido y validado al español, que consta de 47 ítems, agrupados en tres dimensiones: Actitud positiva y sentido del control, Toma de decisiones compartida e informada, y Búsqueda de información y compartir entre iguales. Fue distribuido para su cumplimentación en las 24 horas previas al alta hospitalaria. Resultados. Se recogieron 25 cuestionarios (81%). La puntuación global media de empoderamiento fue de 165,92 ± 20,9. La dimensión Actitud positiva y sentido de control fue la peor puntuada, con una media de 3,4 ± 0,5. Se encontró una relación inversa y débil entre el nivel de empoderamiento y la edad (rho=-0,240; p=0,000) y una relación débil y positiva con la supervivencia a los 10 años (rho=0,316; p=0,01). Conclusión. El nivel de empoderamiento de los pacientes de este estudio fue medio-alto. Las estrategias para abordar la atención de esta población deberían centrarse en trabajar su actitud respecto a la enfermedad y percepción de control de la situación e individualizarse conforme a la edad. Background. Establishing the level of chronic cardiac inpatient empowerment is essential. By doing so, it is possible to identify groups with a lower level. It also provides a basis for designing effective strategies to improve their control over decision making and the actions that affect their health and wellness. The shortage of studies of this phenomenon for this particular population and context suggests that such patients are not receiving proper care. Methods. A prospective and descriptive study was carried out. A validated Spanish version of the Patient empowerment in long-term conditions scale was used. The survey has 47 items, grouped into three dimensions: Positive attitude and feeling of control, Knowledge in shared decision making, and Seeking information and sharing with other patients. It was distributed 24 hours before hospital discharge. Results. Twenty five questionnaires were collected (81%). The mean global empowerment score of the patients was 165.92 ± 20.9. The dimension Positive attitude and sense of control showed the lowest score, with a mean of 3.4 ± 0.5. An inverse weak relationship was found between the level of empowerment and age (rho=-0.240; p=0.000) while a positive one was found with 10-year survival (rho=0,316; p=0.01). Conclusion. The level of empowerment of the patients in this study was medium-high. The strategies used to address the care of this population should focus on working on their attitude towards the disease and perceived control of the situation, and should be individualized according to age.

BACKGROUND: Long-non-coding RNAs, a class of transcripts with lengths > 200 nt, play key roles in tumour progression. Previous reports revealed that LINC00052 (long intergenic non-coding RNA 00052) was strongly downregulated during breast cancer multicellular spheroids formation and suggested a role in cell migration and oxidative metabolism. OBJECTIVE: To examine the function of LINC00052 in MCF-7 breast cancer cells. METHODS: Loss-of-function studies were performed to evaluate LINC00052 role on MCF-7 breast cancer cells. Microarray expression assays were performed to determine genes and cellular functions modified after LINC00052 knockdown. Next, the impact of LINC00052 depletion on MCF-7 cell respiration and migration was evaluated. RESULTS: 1,081 genes were differentially expressed upon LINC00052 inhibition. Gene set enrichment analysis, Gene Ontology and Key Pathway Advisor analysis showed that signalling networks related to cell migration and oxidative phosphorylation were enriched. However, whereas LINC00052 knockdown in MCF-7 cells revealed marginal difference in oxygen consumption rates when compared with control cells, LINC00052 inhibition enhanced cell migration in vitro and in vivo, as observed using a Zebrafish embryo xenotransplant model. CONCLUSION: Our data show that LINC00052 modulates MCF-7 cell migration. Genome-wide microarray experiments suggest that cancer cell migration is affected by LINC00052 through cytoskeleton modulation and Notch/β-catenin/NF-κB signalling pathways.

Purpose Inter-subject covariance of regional 18F-fluorodeoxyglucose (FDG) PET measures (FDGcov) as proxy of brain connectivity has been gaining an increasing acceptance in the community. Yet, it is still unclear to what extent FDGcov is underlied by actual structural connectivity via white matter fiber tracts. In this study, we quantified the degree of spatial overlap between FDGcov and structural connectivity networks. Methods We retrospectively analyzed neuroimaging data from 303 subjects, both patients with suspected neurodegenerative disorders and healthy individuals. For each subject, structural magnetic resonance, diffusion tensor imaging, and FDG-PET data were available. The images were spatially normalized to a standard space and segmented into 62 anatomical regions using a probabilistic atlas. Sparse inverse covariance estimation was employed to estimate FDGcov. Structural connectivity was measured by streamline tractography through fiber assignment by continuous tracking. Results For the whole brain, 55% of detected connections were found to be convergent, i.e., present in both FDGcov and structural networks. This metric for random networks was significantly lower, i.e., 12%. Convergent were 80% of intralobe connections and only 30% of interhemispheric interlobe connections. Conclusion Structural connectivity via white matter fiber tracts is a relevant substrate of FDGcov, underlying around a half of connections at the whole brain level. Short-range white matter tracts appear to be a major substrate of intralobe FDGcov connections.