SARS-CoV-2 pathogenesis in an angiotensin II-induced heart-on-a-chip disease model and extracellular vesicle screening.

Adverse cardiac outcomes in COVID-19 patients, particularly those with preexisting cardiac disease, motivate the development of human cell-based organ-on-a-chip models to recapitulate cardiac injury and dysfunction and for screening of cardioprotective therapeutics. Here, we developed a heart-on-a-chip model to study the pathogenesis of SARS-CoV-2 in healthy myocardium established from human induced pluripotent stem cell (iPSC)-derived cardiomyocytes and a cardiac dysfunction model, mimicking aspects of preexisting hypertensive disease induced by angiotensin II (Ang II). We recapitulated cytopathic features of SARS-CoV-2-induced cardiac damage, including progressively impaired contractile function and calcium handling, apoptosis, and sarcomere disarray. SARS-CoV-2 presence in Ang II-treated hearts-on-a-chip decreased contractile force with earlier onset of contractile dysfunction and profoundly enhanced inflammatory cytokines compared to SARS-CoV-2 alone. Toward the development of potential therapeutics, we evaluated the cardioprotective effects of extracellular vesicles (EVs) from human iPSC which alleviated the impairment of contractile force, decreased apoptosis, reduced the disruption of sarcomeric proteins, and enhanced beta-oxidation gene expression. Viral load was not affected by either Ang II or EV treatment. We identified MicroRNAs miR-20a-5p and miR-19a-3p as potential mediators of cardioprotective effects of these EVs.

Developing STEM Career Identities among Latinx Youths: Collaborative Design, Evaluations, and Adaptations during COVID-19.

In response to the low representation of Latinx adults in STEM occupations, this community-based participatory action research study aims to increase the number of middle school youths developing STEM career identities and entering high school with the intention to pursue STEM careers. The students were provided with summer and after-school activities focusing on network science and career development curricula. Using a quasi-experimental pretest-posttest design and career narratives, this study examined the changes in STEM and career self-efficacy, as well as career identity. The results show improvements in self-efficacy, an increased number of youths with intentions of pursuing future STEM career opportunities, and deeper reflections on their talents and skills after program participation. This paper also describes the program development and implementation in detail, as well as the adaptations that resulted from COVID-19, for scholars and educators designing similar programs. This study provides promising evidence for the quality of STEM and career development lessons in supporting the emergence of a STEM career identity and self-efficacy.

Occurrence of pathogenic microorganisms in small drinking-water systems in Costa Rica.

This study describes the quality of drinking water sampled over 2 years (2018 and 2019) from 20 ASADAS (Spanish acronym for Administrative Associations for Water and Sewer Systems) in Costa Rica. The analysis included Rotavirus (RV), somatic coliphages, fecal coliforms, and Escherichia coli. The ASADAS were categorized into three regions as temperate rainy (region 1), tropical rainy (region 2), and tropical rainy and dry (region 3) according to biogeographic classification. The concentrations of fecal coliforms and E. coli were higher in samples from surface water sources from the ASADAS in region 3 compared to regions 1 and 2. RV-positive samples (24/296) were detected in drinking-water samples from regions 2 and 3 during dry and transition seasons, with higher concentrations more frequently in the dry season. In addition, somatic coliphages were detected in samples from the three regions, with higher concentrations in region 2. Furthermore, a statistically significant relationship was found between somatic coliphages and diarrheal cases, classified as outbreaks or alerts in the region. Thus, the results confirmed that somatic coliphages are a good indicator of the presence of diarrhea cases in a specific region.

Modeling the formation of trihalomethanes in rural and semi-urban drinking water distribution networks of Costa Rica.

Chlorination is one of the most important stages in the treatment of drinking water due to its effectiveness in the inactivation of pathogenic organisms. However, the reaction between chlorine and natural organic matter (NOM) generates harmful disinfection by-products (DBPs), such as trihalomethanes (THMs). In this research, drinking water quality data was collected from the distribution networks of 19 rural and semi-urban systems that use water sources as springs, surfaces, and a mixture of both, in three provinces of Costa Rica from April 2018 to September 2019. Twelve models were developed from four data sets: all water sources, spring, surface, and a mixture of spring and surface waters. Linear, logarithmic, and exponential multivariate regression models were developed for each data set to predict the concentration of total trihalomethanes (TTHMs) in the distribution networks. Concentrations of TTHMs were found between < 0.20 and 91.31 µg/L, with chloroform being the dominant species accounting for 62% of TTHMs on average. Turbidity, free residual chlorine, total organic carbon (TOC), dissolved organic carbon (DOC), and ultraviolet absorbance at 254 nm (UV254) showed a significant correlation with TTHMs. In all the data sets the linear models presented the best goodness-of-fit and were moderately robust. Four models, the best of each data set, were validated with data from the same systems, and, according to the criteria of R2, standard error (SE), mean square error (MSE), and mean absolute error (MAE), spring water and mixed spring/surface water models showed a satisfactory level of explanation of the variability of the data. Moreover, the models seem to better predict TTHM concentrations below 30 µg/L. These models were satisfactory and could be useful for decision-making in drinking water supply systems.

Application of Cell, Tissue, and Biomaterial Delivery in Cardiac Regenerative Therapy.

Cardiovascular diseases (CVD) are the leading cause of death around the world, being responsible for 31.8% of all deaths in 2017 (Roth, G. A. et al. The Lancet 2018, 392, 1736-1788). The leading cause of CVD is ischemic heart disease (IHD), which caused 8.1 million deaths in 2013 (Benjamin, E. J. et al. Circulation 2017, 135, e146-e603). IHD occurs when coronary arteries in the heart are narrowed or blocked, preventing the flow of oxygen and blood into the cardiac muscle, which could provoke acute myocardial infarction (AMI) and ultimately lead to heart failure and death. Cardiac regenerative therapy aims to repair and refunctionalize damaged heart tissue through the application of (1) intramyocardial cell delivery, (2) epicardial cardiac patch, and (3) acellular biomaterials. In this review, we aim to examine these current approaches and challenges in the cardiac regenerative therapy field.

z-Wire: A Microscaffold That Supports Guided Tissue Assembly and Intramyocardium Delivery for Cardiac Repair.

Tissue engineering holds promise to replace damaged tissues for repair of vital organs in the human body. In cardiac repairs specifically, approaches are developed for intramyocardial delivery of cells and the epicardial delivery of tissue-engineered cardiac patches, providing benefit of cell localization and tissue structure, respectively. However, to improve cell retention and integration, there is a need for the intramyocardial delivery of functional tissues while preserving anisotropic muscle alignment. Here, a biodegradable z-wire scaffold that supports the scalable gel-free production of an array of functional cardiac tissues in a 384-well plate format is developed. The z-wire scaffold design supports cellular alignment, provides tunable mechanical support, and allows for tissue contraction. When the scaffold is imparted with magnetic properties, individual tissues can be assembled with macroscopic alignment under magnetic guidance. When used in combination with a customized surgical delivery tool, z-wire tissues can be injected directly into the myocardial wall, with controlled tissue orientation according to the injection path. This modular tissue engineering approach, in combination with the use of smart scaffolds, can expand opportunity in functional tissue delivery.

Coating polystyrene beads with iron oxide for the adsorption of carbofuran from the water supply.

Population growth requires more food production and as a consequence, there is the indiscriminate use of agrochemicals, among them major group are carbamates. At times, runoff of pesticides leads to surface water pollution that serves as a source of public supply. Thus, the presence of these microcontaminants in surface water has become increasingly frequent. The treatment developed in this work uses the principle of adsorption as a technology for the removal of carbamates, more specifically carbofuran. Two methods of coating the polystyrene beads with iron oxide were used to adsorb these microcontaminants from the water. The coating was evaluated through the chemical extraction of iron, analysis by scanning electron microscopy and BET analysis. The metallurgy that presented the best coating was the one that used the ferric chloride. The beads coated by this methodology were used for adsorption tests of carbofuran and showed positive results after verification of the influence of pH on the adsorption process.

Characteristics of hemolytic activity induced by the aqueous extract of the Mexican fire coral Millepora complanata.

BACKGROUND: Millepora complanata is a plate-like fire coral common throughout the Caribbean. Contact with this species usually provokes burning pain, erythema and urticariform lesions. Our previous study suggested that the aqueous extract of M. complanata contains non-protein hemolysins that are soluble in water and ethanol. In general, the local damage induced by cnidarian venoms has been associated with hemolysins. The characterization of the effects of these components is important for the understanding of the defense mechanisms of fire corals. In addition, this information could lead to better care for victims of envenomation accidents. METHODS: An ethanolic extract from the lyophilized aqueous extract was prepared and its hemolytic activity was compared with the hemolysis induced by the denatured aqueous extract. Based on the finding that ethanol failed to induce nematocyst discharge, ethanolic extracts were prepared from artificially bleached and normal M. complanata fragments and their hemolytic activity was tested in order to obtain information about the source of the heat-stable hemolysins. RESULTS: Rodent erythrocytes were more susceptible to the aqueous extract than chicken and human erythrocytes. Hemolytic activity started at ten minutes of incubation and was relatively stable within the range of 28-50°C. When the aqueous extract was preincubated at temperatures over 60°C, hemolytic activity was significantly reduced. The denatured extract induced a slow hemolytic activity (HU50 = 1,050.00 ± 45.85 µg/mL), detectable four hours after incubation, which was similar to that induced by the ethanolic extract prepared from the aqueous extract (HU50 = 1,167.00 ± 54.95 µg/mL). No significant differences were observed between hemolysis induced by ethanolic extracts from bleached and normal fragments, although both activities were more potent than hemolysis induced by the denatured extract. CONCLUSIONS: The results showed that the aqueous extract of M. complanata possesses one or more powerful heat-labile hemolytic proteins that are slightly more resistant to temperature than jellyfish venoms. This extract also contains slow thermostable hemolysins highly soluble in ethanol that are probably derived from the body tissues of the hydrozoan.

Characteristics of hemolytic activity induced by the aqueous extract of the Mexican fire coral Millepora complanata

Background Millepora complanata is a plate-like fire coral common throughout the Caribbean. Contact with this species usually provokes burning pain, erythema and urticariform lesions. Our previous study suggested that the aqueous extract of M. complanata contains non-protein hemolysins that are soluble in water and ethanol. In general, the local damage induced by cnidarian venoms has been associated with hemolysins. The characterization of the effects of these components is important for the understanding of the defense mechanisms of fire corals. In addition, this information could lead to better care for victims of envenomation accidents.Methods An ethanolic extract from the lyophilized aqueous extract was prepared and its hemolytic activity was compared with the hemolysis induced by the denatured aqueous extract. Based on the finding that ethanol failed to induce nematocyst discharge, ethanolic extracts were prepared from artificially bleached and normal M. complanata fragments and their hemolytic activity was tested in order to obtain information about the source of the heat-stable hemolysins.Results Rodent erythrocytes were more susceptible to the aqueous extract than chicken and human erythrocytes. Hemolytic activity started at ten minutes of incubation and was relatively stable within the range of 28-50°C. When the aqueous extract was preincubated at temperatures over 60°C, hemolytic activity was significantly reduced. The denatured extract induced a slow hemolytic activity (HU50= 1,050.00 ± 45.85 μg/mL), detectable four hours after incubation, which was similar to that induced by the ethanolic extract prepared from the aqueous extract (HU50= 1,167.00 ± 54.95 μg/mL). No significant differences were observed between hemolysis induced by ethanolic extracts from bleached and normal fragments, although both activities were more potent than hemolysis induced by the denatured extract.Conclusions The results showed that the aqueous extract of M. complanata possesses one or more powerful heat-labile hemolytic proteins that are slightly more resistant to temperature than jellyfish venoms. This extract also contains slow thermostable hemolysins highly soluble in ethanol that are probably derived from the body tissues of the hydrozoan.(AU)

Characteristics of hemolytic activity induced by the aqueous extract of the Mexican fire coral Millepora complanata

Background Millepora complanata is a plate-like fire coral common throughout the Caribbean. Contact with this species usually provokes burning pain, erythema and urticariform lesions. Our previous study suggested that the aqueous extract of M. complanata contains non-protein hemolysins that are soluble in water and ethanol. In general, the local damage induced by cnidarian venoms has been associated with hemolysins. The characterization of the effects of these components is important for the understanding of the defense mechanisms of fire corals. In addition, this information could lead to better care for victims of envenomation accidents.Methods An ethanolic extract from the lyophilized aqueous extract was prepared and its hemolytic activity was compared with the hemolysis induced by the denatured aqueous extract. Based on the finding that ethanol failed to induce nematocyst discharge, ethanolic extracts were prepared from artificially bleached and normal M. complanata fragments and their hemolytic activity was tested in order to obtain information about the source of the heat-stable hemolysins.Results Rodent erythrocytes were more susceptible to the aqueous extract than chicken and human erythrocytes. Hemolytic activity started at ten minutes of incubation and was relatively stable within the range of 28-50°C. When the aqueous extract was preincubated at temperatures over 60°C, hemolytic activity was significantly reduced. The denatured extract induced a slow hemolytic activity (HU50= 1,050.00 ± 45.85 g/mL), detectable four hours after incubation, which was similar to that induced by the ethanolic extract prepared from the aqueous extract (HU50= 1,167.00 ± 54.95 g/mL). No significant differences were observed between hemolysis induced by ethanolic extracts from bleached and normal fragments, although both activities were more potent than hemolysis induced by the denatured extract...

Hydroxocobalamin and epinephrine both improve survival in a swine model of cyanide-induced cardiac arrest.

STUDY OBJECTIVE: To determine whether hydroxocobalamin will improve survival compared with epinephrine and saline solution controls in a model of cyanide-induced cardiac arrest. METHODS: Forty-five swine (38 to 42 kg) were tracheally intubated, anesthetized, and central venous and arterial continuous cardiovascular monitoring catheters were inserted. Potassium cyanide was infused until cardiac arrest developed, defined as mean arterial pressure less than 30 mm Hg. Animals were treated with standardized mechanical chest compressions and were randomly assigned to receive one of 3 intravenous bolus therapies: hydroxocobalamin, epinephrine, or saline solution (control). All animals were monitored for 60 minutes after cardiac arrest. Additional epinephrine infusions were used in all arms of the study after return of spontaneous circulation for systolic blood pressure less than 90 mm Hg. A sample size of 15 animals per group was determined according to a power of 80%, a survival difference of 0.5, and an α of 0.05. Repeated-measure ANOVA was used to determine statistically significant changes between groups over time. RESULTS: Baseline weight, time to arrest, and cyanide dose at cardiac arrest were similar in the 3 groups. Coronary perfusion pressures with chest compressions were greater than 15 mm Hg in both treatment groups indicating sufficient compression depth. Zero of 15 (95% confidence interval [CI] 0% to 25%) animals in the control group, 11 of 15 (73%; 95% CI 48% to 90%) in the hydroxocobalamin group, and 11 of 15 (73%; 95% CI 48% to 90%) in the epinephrine group survived to the conclusion of the study (P<.001). The proportion of animals with return of spontaneous circulation at 5 minutes was 4 of 15 (27%; 95% CI 10% to 52%), and that of return of spontaneous circulation at 10 minutes was 11 of 15 (73%; 95% CI 48% to 90%) in the 2 treatment groups. Additional epinephrine infusion after return of spontaneous circulation was administered for hypotension in 2 of 11 (18%; 95% CI 4% to 48%) hydroxocobalamin animals and in 11 of 11 (100%; 95% CI 70% to 100%) of the epinephrine animals (P<.001). At 60 minutes, serum lactate was significantly lower in the hydroxocobalamin group compared with the epinephrine group (4.9 [SD 2.2] versus 12.3 [SD 2.2] mmol/L), and the pH was significantly higher (7.34 [SD 0.03] versus 7.15 [SD 0.07]). Serial blood cyanide levels in the hydroxocobalamin group were also lower than that of the epinephrine group from cardiac arrest through the conclusion of the study. CONCLUSION: Intravenous hydroxocobalamin and epinephrine both independently improved survival compared with saline solution control in our swine model of cyanide-induced cardiac arrest. Hydroxocobalamin improved mean arterial pressure and pH, decreased blood lactate and cyanide levels, and decreased the use of rescue epinephrine therapy compared with that in the epinephrine group.

Síntomas de rebeldía, depresión y aislamiento asociados al consumo de drogas en adolescentes costarricenses / Rebel conduct, depresion and isolation symptoms and its association to drug use in Costarrican teenagers

Objetivo: Determinar la relación entre le consumo de drogas y la presencia de síntomas de rebeldía, depresión y aislamiento entre los adolescentes costarricenses. Diseño: Estudio descriptivo. Sitio: Instituciones de III y IV ciclos de Costa Rica. Pacientes: Muestra nacional representativa de 1186 estudiantes, estratificada por tipo de colegio y región. Resultados: Se encontró una asociación estadísticamente significativa, entre el consumo de drogas y la encia de síntomas de rebeldía y depresión. Los adolescentes que refirieron consumo de tabaco y alcohol en los últimos doce meses mostraron una probabilidad fue casi seis veces mayor. Los estudiantes que reportaron consumo de alcohol y de tabaco tenían el doble de probabilidad de presentar síntomas de depresión, y cinco veces más posibilidades de presentar este síntoma si habían consumido drogas ilícitas. Con respecto a los síntomas de aislamiento mostraron una fuerza de asociación mayor pero no estadísticamente significativa con el consumo de drogas ilícitas. Este estudio determinó que los síntomas de depresión y rebeldía en los estudiantes constituyen señales de alerta para la identificación temprana de problemas asociados con el consumo de drogas

Violencia en pediatría: análisis regional para la planificación de acciones de prevención / Violence in pediatrics: regional analysis for prevention planning

Con el objeto de estudiar los caracteres epidemiológicos predominantes de la población infantil expuesta a accidentes y violencias, para establecer factores regionales de riesgo, se evaluaron retrospectivamente tres niveles de atención a niños lesionados: consultorio de urgencias 4398, internación común 891, terapia intensiva 56. Destacamos niveles de riesgo según edad, sexo y "urbanización" del niño. Así como factores ambientales e inherentes al agente. Señalamos las formas de lesión más frecuentes para cada grupo etário, y los índices de morbimortalidad. Se detectó una importante número de lesiones intencionales. El presente trabajo es un primer análisis de una patología médico-social que aquí dimensionamos, y que es considerada "evitable"