Mechanical Stimulation of Cells Through Scaffold Design for Tissue Engineering

Tissue engineering scaffolds attempt to mimic the stem cell environment by creating different biophysical and chemical signals. On the other hand, stem cells are able to sense these characteristics and change their destiny. Scientists try to explain these phenomena through scaffold design and in vitro experiments, but the mechanisms implicated remain unclear. Moreover, environment-cell interactions are a key process to get organs and tissues arrangement. Therefore, this chapter deals with the mechanical signals and mechanism involved in cell behaviour through scaffolds as a strategy in tissue engineering

Music and emotionality: effects of music on mood and verbal memory

Los estímulos emocionales son mejor recordados que los estímulos neutros. La música, como estímulo emocional, modula la memoria de estímulos de otra modalidad; puede cambiar el estado de ánimo y generar un mejor recuerdo de material congruente con él (hipótesis de congruencia). El objetivo del presente trabajo es estudiar el efecto de la música activante y relajante sobre la memoria verbal emocional en adultos jóvenes, y analizar el efecto de la congruencia del estado de ánimo sobre el tipo de material recordado. Se les administró una lista de palabras, positivas, negativas y neutras, a 33 adultos. Se utilizó música positiva activante yrelajante, o ruido blanco, como tratamiento post-aprendizaje. Se midió el estado de ánimo. Se les tomó una tarea de recuerdo inmediato. Los resultados indicaron un mejor recuerdo de palabras totales y negativas en el recuerdo libre en sujetos expuestos a música activante. La música activante y relajante generó disminución de la ansiedad, en tanto que la condición control generó un aumento de la hostilidad. Estos resultados apoyan la idea de que la música puede ser utilizada como tratamiento para modular recuerdos verbales, aunque no se halló efecto de congruencia con el estado de ánimo.Emotional stimuli are better remembered than neutral stimuli. Music, as an emotional stimulus, modulates memory; it can change the mood and improves memory of material congruent with it (congruence hypothesis). The aim of this work is to study the effect of activating and relaxing music on emotional verbal memory in young adults, and to analyze the effect of mood congruence on the type of material remembered. 33 adults listened to a list of positive, negative and neutral words. Activating and relaxing positive music, or white noise, was used as a post-learning treatment. Mood was measured. We performed an immediate recall task. The results indicated better recall of total and negative words in free recall in subjects exposed to activating music. The activating and relaxing music generated a decrease in anxiety, while the control condition generated an increase in hostility. These results support the idea that music can be used as a treatment to modulate verbal memories, although no effect of congruence with mood was found.Fil: Moltrasio, Julieta. Universidad de Buenos Aires. Facultad de Psicología. Instituto de Investigaciones; ArgentinaFil: Dominguez, Florencia Belén. Universidad de Palermo; ArgentinaFil: Detlefsen, Verónica. Universidad de Buenos Aires. Facultad de Psicología; ArgentinaFil: Rubinstein, Wanda Yanina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; Argentina. Universidad de Palermo; Argentina. Universidad de Buenos Aires. Facultad de Psicología. Instituto de Investigaciones; Argentin

RECENT DISTURBANCE EVENTS RECORDED IN THE SEDIMENTARY INFILL OF LAGO GUILLELMO (ARGENTINA): TEPHRA FALLS AND HYDROGEOMORPHIC PROCESSES

In this work we focus on two natural disturbances that affect the Parque Nacional Nahuel Huapi area: Tephra fall events from Andean volcanoes and hydrogeomorphic processes within catchments related to heavy rains. In order to look for evidence of these disturbance events in the lacustrine sedimentary record, we perform a multi-approach analysis in La Cantera stream watershed, including the subaqueous environment of the distal prodelta area, northwest portion of Lago Guillelmo (Northern Patagonia). We carried out a surface analysis, describing the main morphometric features of the selected watershed, informally called La Cantera stream watershed, and we also analyzed satellite and historical images, looking for evidence of processes related to these disturbance events in the watershed and morphological changes in the distal zone and in the alluvial fan generated over the delta. The subaqueous environment was analyzed by means of expeditive bathymetries, lacustrine cores and Ground Penetrating Radar (GPR) profiles, taken in the distal deltaic environment of the watershed. In the sedimentary record of the lake we identified 10 tephra layers attributed to Cordón Caulle, Calbuco and Osorno Volcanoes for the last 200 years. These were chronologically correlated with previous documented eruptions of these volcanic centers, by means of vitroclast morphology, mineral association and stratigraphic position. Also we identified 10 layers corresponding to sediments with terrigenous components and terrestrial organic matter, interpreted as hyperpycnites. We attribute two hyperpycnite deposits to a debris flow that occurred in the area in February, 2015, based on the magnitude of that event that caused several damages and road cuts and the stratigraphic position of these deposits in the cores. After the correlation between the GPR radargrams with the lacustrine cores we associate one major reflector with a (1) tephra layer and (2) lobe-shaped morphologies, interpreted as a hyperpycnite deposit, located in front of the mouth of an abandoned river course. The anthropic activity in the region associated with the construction of the Ruta Nacional 40 and the gravel mining after 1969, affected the drainage of La Cantera watershed, hindering the possibility that the different types of flows could plunge into the lake. This work also shows the importance of the integration between the processes that occur throughout a basin with the underwater processes that take place in the deltaic environment, to understand the extension and characteristics of the disturbances studied

Methylation of subtelomeric chromatin modifies the expression of the lncRNA TERRA, disturbing telomere homeostasis

The long noncoding RNA (lncRNA) telomeric repeat-containing RNA (TERRA) has been associated with telomeric homeostasis, telomerase recruitment, and the process of chromosome healing; nevertheless, the impact of this association has not been investigated during the carcinogenic process. Determining whether changes in TERRA expression are a cause or a consequence of cell transformation is a complex task because studies are usually carried out using either cancerous cells or tumor samples. To determine the role of this lncRNA in cellular aging and chromosome healing, we evaluated telomeric integrity and TERRA expression during the establishment of a clone of untransformed myeloid cells. We found that reduced expression of TERRA disturbed the telomeric homeostasis of certain loci, but the expression of the lncRNA was affected only when the methylation of subtelomeric bivalent chromatin domains was compromised. We conclude that the disruption in TERRA homeostasis is a consequence of cellular transformation and that changes in its expression profile can lead to telomeric and genomic instability

Heterogeneity and Clonal Evolution of Acquired PARP Inhibitor Resistance in TP53- and BRCA1-Deficient Cells

Homologous recombination (HR)-deficient cancers are sensitive to poly- ADP ribose polymerase inhibitors (PARPi), which have shown clinical efficacy in the treatment of high-grade serous cancers (HGSC). However, the majority of patients will relapse, and acquired PARPi resistance is emerging as a pressing clinical problem. Here we generated seven single-cell clones with acquired PARPi resistance derived from a PARPi-sensitive TP53(-/-) and BRCA1(-/-) epithelial cell line generated using CRISPR/Cas9. These clones showed diverse resistance mechanisms, and some clones presented with multiple mechanisms of resistance at the same time. Genomic analysis of the clones revealed unique transcriptional and mutational profiles and increased genomic instability in comparison with a PARPi-sensitive cell line. Clonal evolutionary analyses suggested that acquired PARPi resistance arose via clonal selection from an intrinsically unstable and heterogenous cell population in the sensitive cell line, which contained preexisting drug-tolerant cells. Similarly, clonal and spatial heterogeneity in tumor biopsies from a clinical patient with BRCA1-mutant HGSC with acquired PARPi resistance was observed. In an imaging-based drug screening, the clones showed heterogenous responses to targeted therapeutic agents, indicating that not all PARPi-resistant clones can be targeted with just one therapy. Furthermore, PARPi-resistant clones showed mechanism-dependent vulnerabilities to the selected agents, demonstrating that a deeper understanding on the mechanisms of resistance could lead to improved targeting and biomarkers for HGSC with acquired PARPi resistance. Significance: This study shows that BRCA1-deficient cells can give rise to multiple genomically and functionally heterogenous PARPi-resistant clones, which are associated with various vulnerabilities that can be targeted in a mechanism-specific manner.Peer reviewe

Telemedicina como estratégia de monitoramento ambulatorial de pacientes covid no Hospital Italiano de San Justo

Fil: Paulin, Pilar. Hospital Italiano Agustín Rocca; Argentina.Fil: Masino, Lucía Antonela. Hospital Italiano de San Justo; Argentina.Fil: Valverde, Julieta. Hospital Italiano de San Justo; Argentina.Fil: Domínguez, María Ercilia. Hospital Italiano de San Justo; Argentina.Fil: Libertella, Florencia Belén. Hospital Italiano de San Justo; Argentina.Fil: Benso, José Daniel. Hospital Italiano de San Justo; Argentina.Fil: Fernández, Verónica. Hospital Italiano de San Justo; Argentina.Fil: Fernández Otero, Lucas Gabriel. Hospital Italiano de San Justo; Argentina.Fil: Funtowicz, Gabriel. Hospital Italiano de San Justo; Argentina.Introducción: Debido a la pandemia por COVID-19 los sistemas sanitarios han tenido que adaptarse a la demanda asistencial. La telemedicina es una herramienta práctica para poder realizar seguimiento ambulatorio de pacientes correctamente seleccionados. Materiales y métodos: Se realizó un estudio descriptivo de una cohorte prospectiva de pacientes en seguimiento por telemedicina en el Hospital Italiano de San Justo. Resultados: Se evaluaron 47 días de seguimiento, un total de 1345 pacientes. De éstos 46,9% (n=631) obtuvieron un resultado de hisopado nasofaríngeo con técnica de PCR positivo y fueron ingresados al sistema de seguimiento por telemedicina. El 10,14% (n=64) requirió una reevaluación clínica en guardia externa. De estos pacientes el 60.1% (n=39) requirió internación en sala general (n=39). Conclusión: Es fundamental poder generar otras formas de cuidado de la salud. El sistema de telemedicina es una herramienta importante a desarrollar en situaciones de sobrecarga del sistema de salud.Introduction: Due to the COVID-19 pandemic, health systems have had to adapt to the growing demand for care. Telemedicine is a practical tool for outpatient monitoring of correctly selected patients. Materials and methods:A descriptive study of a prospective cohort ofpatients under telemedicine follow-up at the Hospital Italiano de San Justo was carried out.Results:47 days of follow-up were evaluated, a total of 1345 patients. Of these, 46.9% (n = 631) obtained a positive nasopharyngeal swab result with PCR technique and were registered in the telemedicine monitoring system, with 10.14% (n = 64) requiring a new clinical evaluation at the emergency center . Of these patients, 60.1% (n = 39) required hospitalization in a general ward (n = 39). Conclusion:It is essential to be able to generate other forms of helth care. The telemedicine system is an important tool to develop in situations of overload of the health system.Introdução: Devido à pandemia de COVID-19, os sistemas de saúde tiveram que se adaptar à crescente demanda por atendimento. A telemedicina é uma ferramenta prática para o monitoramento ambulatorial de pacientes corretamente selecionados. Materiais e métodos: Foi realizado um estudo descritivo de uma coorte prospectiva de pacientes em acompanhamento telemedicina no Hospital Italiano de San Justo. Resultados:foram avaliados 47 dias de seguimento, totalizando 1345 pacientes. Destes, 46,9% (n = 631) obtiveram resultado positivo do swab nasofaríngeo pela técnica de PCR e foram cadastrados no sistema de monitoramento de telemedicina, sendo 10,14% (n = 64) necessitando de nova avaliação clínica no pronto-socorro. Desses pacientes, 60,1% (n = 39) necessitaram de internação em enfermaria geral (n = 39). Conclusão:É fundamental poder gerar outras formas de assistência à saúde. O sistema de telemedicina é uma importante ferramenta a ser desenvolvida em situações de sobrecarga do sistema de saúde.publishedVersionFil: Paulin, Pilar. Hospital Italiano Agustín Rocca; Argentina.Fil: Masino, Lucía Antonela. Hospital Italiano de San Justo; Argentina.Fil: Valverde, Julieta. Hospital Italiano de San Justo; Argentina.Fil: Domínguez, María Ercilia. Hospital Italiano de San Justo; Argentina.Fil: Libertella, Florencia Belén. Hospital Italiano de San Justo; Argentina.Fil: Benso, José Daniel. Hospital Italiano de San Justo; Argentina.Fil: Fernández, Verónica. Hospital Italiano de San Justo; Argentina.Fil: Fernández Otero, Lucas Gabriel. Hospital Italiano de San Justo; Argentina.Fil: Funtowicz, Gabriel. Hospital Italiano de San Justo; Argentina

Conservation of the endemic dwarf carnivores of Cozumel Island, Mexico.

Cozumel Island, Mexico, harbours two endemic species of dwarf procyonids: the Pygmy Raccoon Procyon pygmaeus and the Dwarf Coati Nasua nelsoni. Both species are Critically Endangered, and are among the world&rsquo;s most threatened Carnivora. Here we summarise the research we have been conducting on their ecology, evolution, genetics, and conservation. We also summarise the conservation initiatives we have been undertaking and promoting in order to advance the conservation of these unique species and their habitats. This effort illustrates the importance of an interdisciplinary approach in conservation science and action in maximising effectiveness. Nevertheless, the precarious status of the species make it imperative to continue and expand the work we have carried out in Cozumel to prevent two imminent global extinctions.<br /

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life