La generación e implementación de estrategias para disminuir la transmisión de SARS-CoV-2 son un reto imperante para el país. Las estrategias deben ser dinámicas y específicas para cada región ...buscando equilibrar el impacto en la salud y en la economía. Esta tarea debe abordarse desde un enfoque interdisciplinario con el fin de estudiar la problemática de manera holística. En el presente artículo se presentan algunos hallazgos y revisiones realizadas en el marco del proyecto SISCOVID, en el cual se utilizan modelos sistémicos de simulación computacional para apoyar la toma de decisiones para el control y mitigación de la pandemia en Colombia. El proyecto está conformado por investigadores de la Universidad de Los Andes, el Centro Nacional de Consultoría (CNC) y la Universidad de Ibagué, en alianza con universidades internacionales y empresas. El proyecto ha logrado apoyar a los tomadores de decisiones en formular estrategias para disminuir la transmisión de SARS-CoV-2 en contextos urbanos en las ciudades de Barranquilla, Bogotá, Cali, Cartagena y Medellín. Palabras clave: SARS-CoV-2, Epidemiología, Prevención, Modelos sistémicos, Sistemas Complejos The development and implementation of strategies to reduce SARS-CoV2 transmission is a prevailing challenge for Colombia. These strategies ought to be dynamic and specific to each region, seeking to balance health and economic impacts. This task calls for an interdisciplinary approach to ensure a holistic view of the problem. This article presents findings and results obtained from the SISCOVID project, which used simulated systemic models to support decision making and efforts to mitigate the pandemic in Colombia. The project included researchers from Universidad de Los Andes, the Centro Nacional de Consultoría (CNC) and Universidad de Ibagué, in alliance with several international universities and companies. SISCOVID helped decision makers design strategies to reduce SARS-CoV-2 transmission in urban contexts for the cities of Barranquilla, Bogotá, Cali, Cartagena, and Medellín. Key words: SARS-CoV-2, Epidemiology, Prevention, Systemic Models, Complex Systems
Recycled concrete aggregate (RA) from pavement demolition was used to make concrete. Ten concrete mixtures with different replacement percentages of RA (coarse and fine) were made. The corrosion rate ...of steel and the electrical resistivity of concrete were determined on reinforced concrete specimens subjected to wetting-drying cycles (3.5% solution of NaCl). Corrosion rate was determined using the electrochemical technique of linear polarization resistance, while the electrical resistivity was measured by electrochemical impedance spectroscopy. The results show that the use of RA introduces more interfaces in concrete, which accelerates the steel corrosion process because the porosity increases and the electrical resistivity decreases. However, steel corrosion and the electrical resistivity in concrete are not significantly influenced by replacing a maximum 30% of coarse aggregate or 20% of fine aggregate with RA.
The acute respiratory distress syndrome (ARDS) is a highly lethal condition that impairs lung function and causes respiratory failure. Mechanical ventilation (MV) maintains gas exchange in patients ...with ARDS but exposes lung cells to physical forces that exacerbate injury. Our data demonstrate that mTOR complex 1 (mTORC1) is a mechanosensor in lung epithelial cells and that activation of this pathway during MV impairs lung function. We found that mTORC1 is activated in lung epithelial cells following volutrauma and atelectrauma in mice and humanized in vitro models of the lung microenvironment. mTORC1 is also activated in lung tissue of mechanically ventilated patients with ARDS. Deletion of Tsc2, a negative regulator of mTORC1, in epithelial cells impairs lung compliance during MV. Conversely, treatment with rapamycin at the time MV is initiated improves lung compliance without altering lung inflammation or barrier permeability. mTORC1 inhibition mitigates physiologic lung injury by preventing surfactant dysfunction during MV. Our data demonstrate that, in contrast to canonical mTORC1 activation under favorable growth conditions, activation of mTORC1 during MV exacerbates lung injury and inhibition of this pathway may be a novel therapeutic target to mitigate ventilator-induced lung injury during ARDS.
The maturation of genomic surveillance in the past decade has enabled tracking of the emergence and spread of epidemics at an unprecedented level. During the COVID-19 pandemic, for example, genomic ...data revealed that local epidemics varied considerably in the frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage importation and persistence, likely due to a combination of COVID-19 restrictions and changing connectivity. Here, we show that local COVID-19 epidemics are driven by regional transmission, including across international boundaries, but can become increasingly connected to distant locations following the relaxation of public health interventions. By integrating genomic, mobility, and epidemiological data, we find abundant transmission occurring between both adjacent and distant locations, supported by dynamic mobility patterns. We find that changing connectivity significantly influences local COVID-19 incidence. Our findings demonstrate a complex meaning of "local" when investigating connected epidemics and emphasize the importance of collaborative interventions for pandemic prevention and mitigation.
Acute respiratory distress syndrome (ARDS) is a prevalent disease with significant mortality for which no effective pharmacologic therapy exists. Low-dose inhaled carbon monoxide (iCO) confers ...cytoprotection in preclinical models of sepsis and ARDS.
We conducted a phase I dose escalation trial to assess feasibility and safety of low-dose iCO administration in patients with sepsis-induced ARDS. Twelve participants were randomized to iCO or placebo air 2:1 in two cohorts. Four subjects each were administered iCO (100 ppm in cohort 1 or 200 ppm in cohort 2) or placebo for 90 minutes for up to 5 consecutive days. Primary outcomes included the incidence of carboxyhemoglobin (COHb) level ≥10%, prespecified administration-associated adverse events (AEs), and severe adverse events (SAEs). Secondary endpoints included the accuracy of the Coburn-Forster-Kane (CFK) equation to predict COHb levels, biomarker levels, and clinical outcomes.
No participants exceeded a COHb level of 10%, and there were no administration-associated AEs or study-related SAEs. CO-treated participants had a significant increase in COHb (3.48% ± 0.7% cohort 1; 4.9% ± 0.28% cohort 2) compared with placebo-treated subjects (1.97% ± 0.39%). The CFK equation was highly accurate at predicting COHb levels, particularly in cohort 2 (R2 = 0.9205; P < 0.0001). Circulating mitochondrial DNA levels were reduced in iCO-treated participants compared with placebo-treated subjects.
Precise administration of low-dose iCO is feasible, well-tolerated, and appears to be safe in patients with sepsis-induced ARDS. Excellent agreement between predicted and observed COHb should ensure that COHb levels remain in the target range during future efficacy trials.
ClinicalTrials.gov NCT02425579.
NIH grants P01HL108801, KL2TR002385, K08HL130557, and K08GM102695.
Ventilator-associated pneumonias (VAPs) are a worldwide problem that significantly increases patient morbidity, mortality, and length of stay (LoS), and their effects should be estimated to account ...for the timing of infection. The purpose of the study was to estimate extra LoS and mortality in an intensive-care unit (ICU) due to a VAP in a cohort of 69 248 admissions followed for 283 069 days in ICUs from 10 countries. Data were arranged according to the multi-state format. Extra LoS and increased risk of death were estimated independently in each country, and their results were combined using a random-effects meta-analysis. VAP prolonged LoS by an average of 2·03 days (95% CI 1·52–2·54 days), and increased the risk of death by 14% (95% CI 2–27). The increased risk of death due to VAP was explained by confounding with patient morbidity.
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