Techniques to stimulate and interrogate cell–cell adhesion mechanics

Cell–cell adhesions maintain the mechanical integrity of multicellular tissues and have recently been found to act as mechanotransducers, translating mechanical cues into biochemical signals. Mechanotransduction studies have primarily focused on focal adhesions, sites of cell-substrate attachment. These studies leverage technical advances in devices and systems interfacing with living cells through cell–extracellular matrix adhesions. As reports of aberrant signal transduction originating from mutations in cell–cell adhesion molecules are being increasingly associated with disease states, growing attention is being paid to this intercellular signaling hub. Along with this renewed focus, new requirements arise for the interrogation and stimulation of cell–cell adhesive junctions. This review covers established experimental techniques for stimulation and interrogation of cell–cell adhesion from cell pairs to monolayers

High Throughput and Highly Controllable Methods for in Vitro Intracellular Delivery

In vitro and ex vivo intracellular delivery methods hold the key for releasing the full potential of tissue engineering, drug development, and many other applications. In recent years, there has been significant progress in the design and implementation of intracellular delivery systems capable of delivery at the same scale as viral transfection and bulk electroporation but offering fewer adverse outcomes. This review strives to examine a variety of methods for in vitro and ex vivo intracellular delivery such as flow-through microfluidics, engineered substrates, and automated probe-based systems from the perspective of throughput and control. Special attention is paid to a particularly promising method of electroporation using micro/nanochannel based porous substrates, which expose small patches of cell membrane to permeabilizing electric field. Porous substrate electroporation parameters discussed include system design, cells and cargos used, transfection efficiency and cell viability, and the electric field and its effects on molecular transport. The review concludes with discussion of potential new innovations which can arise from specific aspects of porous substrate-based electroporation platforms and high throughput, high control methods in general

Assessing MWCNT-graphene surface energy through in situ SEM peeling

Carbon nanotubes (CNTs) are envisioned as ideal filaments for next-generation nanocomposites due to their high strength-to-weight ratios. However, while individual nanotubes are strong, interfaces between tubes cannot bear significant load due to the weak van der Waals forces that govern their behavior. Premature interfacial failure could thus counteract the inherent strength of carbon nanotubes and, in turn, prevent CNT-based composites from achieving optimal mechanical performance. To increase the load bearing capacity of these interfaces, interlayer crosslinking schemes have been proposed using chemical functionalization. For instance, introduction of hydrogen bonds or additional van der Waals bonds between tubes could improve load transfer between CNTs. While introducing chemical groups on CNT surfaces may enhance intermolecular interactions at these interfaces, a means of quantitatively evaluating changes in interlayer adhesion as a result of to these treatments needs to be defined. In addition, as sizes of CNTs will inherently vary within a composite, it is important that such energy measurements be normalized irrespective of tube dimensions. Here we report an experimental peeling technique that can be used to measure the adhesion energy between multiwalled carbon nanotubes (MWCNTs) and graphene. Peeling tests conducted in situ a scanning electron microscope allow direct visualization of the nanoscale peeling process which, in turn, enables adhesion energy to be estimated through classical fracture analysis. The applicability of this analysis is validated by finite element simulations with boundary conditions derived from experiments. The effective contact width between tubes and graphene is estimated via atomistic simulations, providing a means to normalize interaction energy per unit area. The surface energies of bare MWCNT-graphene interfaces found in this study compare favorably with theoretical and experimental values reported for graphite. This method can serve as a foundation for evaluating the enhancements afforded by chemical functionalization, which is a critical step toward the development of strong, lightweight composites that effectively utilize the full mechanical potential of CNTs

Economía, Sociedad y Procesos Hegemónicos en la Provincia de Misiones (ESOHE). 16H328

Actividades desarrolladas durante el período: Desde mediados de año se ha instalado un Taller Continuo que funciona los días viernes destinado a la puesta en común de información y la discusión de la marcha general del proyecto. El taller, se ha constituido en caja de resonancia de los avances y dificultades que se presentan y como el espacio donde se distribuyen tareas y responsabilices, se analizan las actividades y los aportes personales o de los integrantes de cada grupo responsable de alguna línea de investigación y se incorporan ideas y señalamientos. En este marco, se ha programado también un Ciclo de Lecturas teóricas y metodológicas que colaboran en la construcción de un lenguaje y una mirada común, necesaria para armonizar la labor de investigadores y becarios de postgrado con trayectorias disciplinares y experiencias muy disímiles; En la investigación sobre la historia económica de Misiones se ha avanzado en los siguientes puntos: Construcción de una periodización basada en ciclos económicos. Se trabaja en el reconocimiento y exploración de repositorios y fuentes escritas existentes a nivel local. exhaustivo relevamiento de las tesis de grado y postgrado, tanto en historia como en Antropología, existentes en las bibliotecas de la UNaM, referidas a temas empresariales y o al funcionamiento de las elites del poder. Se ha tomado contacto y accedido a ámbitos empresariales como las cámaras de la construcción, que en Misiones son 5, de PyMES y la Delegación Provincial de la Cámara Argentina de la Construcción que reúne a grandes empresas; Un grupo de investigadores y auxiliares del ESOHE está investigando los procesos de transformación del sistema educativo provincial (incluyendo tanto la componente pública como la privada), entendiendo que el sistema escolar es una de las instancias donde se socializa ideológicamente a la población y se promueven “sentidos de la realidad”; Entre las tareas en ejecución cabe mencionar: Lectura y fichaje de materia bibliográfico destinado a la actualización reajuste del encuadre teórico-metodológico. Identificación y caracterización de diferentes actores: funcionarios gubernamentales, empresas constructoras, e inmobiliarias, medios de comunicación, asociaciones civiles y otras organizaciones, grupos de interés y afectados por las obras que intervienen en la producción, disputa, apropiación y uso del espacio urbano en las ciudades de Encarnación y Posadas, Garupá y Candelaria. Elección y contacto de informantes calificados. Relevamiento de políticas y/o programas de intervención urbana a ambos lados de la frontera y sus procesos resultantes. Geo-referenciamiento de áreas de revalorización urbana, comerciales, de relegación y desplazamiento, así como de asentamientos precarios y zonas residenciales para sectores de alto poder adquisitivo. El trabajo realizado en esta primera etapa ha permitido avanzar en: Revisión bibliográfica; Redefinición del marco teórico de la investigación; Análisis de algunas relaciones concretas establecidas entre el estado y el sector civil organizado, en particular en el campo de las actividades económicas del tercer sector y en el marco de la implementación de planes y programas públicos; Análisis de las tensiones entre prácticas políticas y económicas que se desatan en el proceso de generación y funcionamiento de los emprendimientos productivos auto-gestionados y cooperativas de trabajo

Dendritic cell deficiencies persist seven months after SARS-CoV-2 infection

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection induces an exacerbated inflammation driven by innate immunity components. Dendritic cells (DCs) play a key role in the defense against viral infections, for instance plasmacytoid DCs (pDCs), have the capacity to produce vast amounts of interferon-alpha (IFN-α). In COVID-19 there is a deficit in DC numbers and IFN-α production, which has been associated with disease severity. In this work, we described that in addition to the DC deficiency, several DC activation and homing markers were altered in acute COVID-19 patients, which were associated with multiple inflammatory markers. Remarkably, previously hospitalized and nonhospitalized patients remained with decreased numbers of CD1c+ myeloid DCs and pDCs seven months after SARS-CoV-2 infection. Moreover, the expression of DC markers such as CD86 and CD4 were only restored in previously nonhospitalized patients, while no restoration of integrin β7 and indoleamine 2,3-dyoxigenase (IDO) levels were observed. These findings contribute to a better understanding of the immunological sequelae of COVID-19

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030