Angle-dependent phononic dynamics for data-driven source localization.

The source angle localization problem is studied based on scattering of elastic waves in two dimensions by a phononic array and the exceptional points of its band structure. Exceptional points are complex singularities of a parameterized eigen-spectrum, where two modes coalesce with identical mode shapes. These special points mark the qualitative transitions in the system behavior and have been proposed for sensing applications. The equi-frequency band structures are analyzed with focus on the angle-dependent modal behaviors. At the exceptional points and critical angles, the eigen-modes switch their energy characteristics and symmetry, leading to enhanced sensitivity as the scattering response of the medium is inherently angle-dependent. An artificial neural network is trained with randomly weighted and superposed eigen-modes to achieve deep learning of the angle-dependent dynamics. The trained algorithm can accurately classify the incident angle of an unknown scattering signal, with minimal sidelobe levels and suppressed main lobewidth. The neural network approach shows superior localization performance compared with standard delay-and-sum technique. The proposed application of the phononic array highlights the physical relevance of band topology and eigen-modes to a technological application, adds extra strength to the existing localization methods, and can be easily enhanced with the fast-growing data-driven techniques.

Drying temperatures affect the qualitative-quantitative variation of aromatic profiling in Anethum graveolens L. ecotypes as an industrial-medicinal-vegetable plant.

Introduction: There are several factors that affect the quality and quantity of active ingredients and essential oil (EO) content, including pre and postharvest practices such as drying conditions. One of the most important factors in drying is temperature and then selective drying temperature (DT). In general, DT has a direct effect on the aromatic properties of Anethum graveolens. Methods: On this basis, the present study was conducted to evaluate the effects of different DTs on the aroma profile of A. graveolens ecotypes. Results and discussion: The results showed that different DTs, ecotypes, and their interaction significantly affect EO content and composition. The highest EO yield was obtained from the Parsabad ecotype (1.86%) followed by the Ardabil ecotype (1.4%), both at 40° C. More than 60 EO compounds were identified, mainly monoterpenes and sesquiterpenes, highlighting α-Phellandrene, Germacrene D, and Dill apiole as major components in all treatments. Besides α-Phellandrene, the major EO compounds at shad drying (ShD) were ß-Phellandrene and p-Cymene, while plant parts dried at 40° C showed l-Limonene and Limonene as the main constituents, and Dill apiole was detected in greater amounts in the samples dried at 60 °C. To determine the appropriate DT, simple and factorial based-ANOVA together multivariate analysis demonstrated significant differences in the compounds produced under different DTs. The results indicated that more EO compounds, mainly monoterpenes, were extracted at ShD than other DTs. On the other hand, the content and composition of sesquiterpenes increased significantly when DT was increased to 60 °C. From the genetic backgrounds point of view, the Parsabad ecotype (with 12 similar compounds) and Esfahan ecotype (with 10 similar compounds) were the most suitable ecotypes under all DTs in terms of EO compounds. Accordingly, the present study would help various industries to optimize specific DT(s) to obtain special EO compound(s) from different A. graveolens ecotypes based on commercial requirements.

Comparing the toxicity of tungsten and vanadium oxide nanoparticles on Spirulina platensis.

The production and release of nanoparticles and their impacts on living organisms are among the most important concerns in the world. Spirulina platensis was chosen because of its ability to absorb more elements than other algae. Therefore, an experiment was conducted to improve the product quality of spirulina exposed to new type of nanoparticles. In this experiment, vanadium oxide nanoparticles (VNPs) and tungsten oxide nanoparticles (WNPs) were used at concentrations of 0, 0.001, 0.017, and 0.05 g/l. The measured indices such as protein percentage and concentrations of phycobiliproteins and carbohydrates were the most important parameters of spirulina. Results showed that the concentration of 0.001 g/l of VNPs significantly affected the amounts of protein and phycocyanin. It has also been observed that 0.001 g/l of WNPs significantly influenced the amounts of protein (5.3%) and phycocyanin (90%); however, WNPs at all concentrations increased the concentrations of protein and phycocyanin. A concentration of 0.05 g/l of WNPs increased phycocyanin content by 83% over the control. The examination of nanoparticles by spirulina showed that VNPs were more adsorbed by spirulina than WNPs. In general, VNPs were toxic to algae at concentrations of 0.017 and 0.05 g/l, but WNPs did not show any fatal toxicity.

Leveraging risk assessment for foodborne outbreak investigations: The Quantitative Risk Assessment-Epidemic Curve Prediction Model.

Root cause analysis can be used in foodborne illness outbreak investigations to determine the underlying causes of an outbreak and to help identify actions that could be taken to prevent future outbreaks. We developed a new tool, the Quantitative Risk Assessment-Epidemic Curve Prediction Model (QRA-EC), to assist with these goals and applied it to a case study to investigate and illustrate the utility of leveraging quantitative risk assessment to provide unique insights for foodborne illness outbreak root cause analysis. We used a 2019 Salmonella outbreak linked to melons as a case study to demonstrate the utility of this model (Centers for Disease Control and Prevention [CDC], 2019). The model was used to evaluate the impact of various root cause hypotheses (representing different contamination sources and food safety system failures in the melon supply chain) on the predicted number and timeline of illnesses. The predicted number of illnesses varied by contamination source and was strongly impacted by the prevalence and level of Salmonella contamination on the surface/inside of whole melons and inside contamination niches on equipment surfaces. The timeline of illnesses was most strongly impacted by equipment sanitation efficacy for contamination niches. Evaluations of a wide range of scenarios representing various potential root causes enabled us to identify which hypotheses, were likely to result in an outbreak of similar size and illness timeline to the 2019 Salmonella melon outbreak. The QRA-EC framework can be adapted to accommodate any food-pathogen pairs to provide insights for foodborne outbreak investigations.

Evaluation of Potential Impacts of Free Chlorine during Washing of Fresh-Cut Leafy Greens on Escherichia coli O157:H7 Cross-Contamination and Risk of Illness.

Addition of chlorine-based antimicrobial substances to fresh-cut leafy green wash water is done to minimize microbial cross-contamination during processing. We developed the FDA Leafy Green Risk Assessment Model (FDA-LGRAM) to quantify the impact of free chlorine concentration in wash water during fresh-cut lettuce processing on the extent of water-mediated cross-contamination between shredded lettuce and the associated risk of illness due to exposure to Escherichia coli O157:H7. At different contamination prevalence and levels of E. coli O157:H7 on incoming lettuce heads, the model compared the predicted prevalence of contaminated fresh-cut lettuce packages and the risk of illness per serving between: (1) a scenario where fresh-cut lettuce was packaged without washing; and (2) scenarios involving washing fresh-cut lettuce with different levels of free chlorine (0 ppm, 5 ppm, 10 ppm, 15 ppm, and 20 ppm) prior to packaging. Our results indicate that the free chlorine level in wash water has a substantial impact on the predicted prevalence of contaminated fresh-cut lettuce packages and the risk of illness associated with E. coli O157:H7 in fresh-cut lettuce. Results showed that the required level of free chlorine that can minimize water-mediated cross-contamination and reduce the corresponding risk of illness depended on contamination prevalence and levels of E. coli O157:H7 on incoming lettuce heads. Our model also indicated that the pathogen inactivation rate in wash water via free chlorine was a key model parameter that had a significant impact on the extent of cross-contamination during washing and the predicted associated risk of illness.

Preparation of chitosan/sodium alginate/nano cellulose composite for the efficient removal of cadmium (II) cations from wastewater and soil systems.

In this study, chitosan/sodium alginate/nano cellulose (CSA-N) nanocomposite hydrogels were prepared using a completely green route and used as sorbents to adsorb Cd2+ ions from water and soil systems of an environmental aspect. The sorbents were characterized by FTIR, SEM, and XRD. The influences of initial Cd2+ concentration, the presence of nano cellulose, type of the polluted environment, and ionic strength on adsorption and desorption isotherms were investigated. The maximum adsorption capacity of cadmium onto CSA was significantly increased from 2264.9 to 4380.97 µmol/g when the system was changed from soil to water, respectively. While, the maximum adsorption capacity of cadmium onto CSA-N was almost the same in the soil and wastewater systems, i.e., 3419.5 and 3230.3 µmol/g, respectively. The results indicated that Langmuir and Freundlich models provided the best fit for the experimental adsorption data for CSA and CSA-N, respectively. By comparing the amounts of Δq, the difference between adsorption and desorption amounts, the CSA was not economically feasible sorbent at high initial concentrations of Cd2+ in the wastewater system, while, CSA-N was demonstrated to be a more efficient adsorbent than CSA for cadmium removal from both the soil and wastewater systems.

A multi-method approach to modeling COVID-19 disease dynamics in the United States.

In this paper, we proposed a multi-method modeling approach to community-level spreading of COVID-19 disease. Our methodology was composed of interconnected age-stratified system dynamics models in an agent-based modeling framework that allowed for a granular examination of the scale and severity of disease spread, including metrics such as infection cases, deaths, hospitalizations, and ICU usage. Model parameters were calibrated using an optimization technique with an objective function to minimize error associated with the cumulative cases of COVID-19 during a training period between March 15 and October 31, 2020. We outlined several case studies to demonstrate the model's state- and local-level projection capabilities. We further demonstrated how model outcomes could be used to evaluate perceived levels of COVID-19 risk across different localities using a multi-criteria decision analysis framework. The model's two, three, and four week out-of-sample projection errors varied on a state-by-state basis, and generally increased as the out-of-sample projection period was extended. Additionally, the prediction error in the state-level projections was generally due to an underestimation of cases and an overestimation of deaths. The proposed modeling approach can be used as a virtual laboratory to investigate a wide range of what-if scenarios and easily adapted to future high-consequence public health threats.

3D porous bioadsorbents based on chitosan/alginate/cellulose nanofibers as efficient and recyclable adsorbents of anionic dye.

Natural polysaccharides are attractive materials for fabrication of eco-friendly biodsorbents for efficient water remediation. However, scarcity of adsorbents that possess features of high stability and adsorption capacity at various pH conditions, low-cost, eco-friendly, and recycleability at the same time still remains a great challenge. Herein, porous ionically crosslinked biofoams were prepared by freeze-drying of chitosan (CS)/sodium alginate (SA) complex (CSA). FTIR and XRD were used to characterize the structure of the bioadsorbents. SEM observations revealed that adsorbents have a 3D interconnected porous structure, which is a favorable morphology for dye adsorption. Accordingly, CSA and its nanocomposite containing 15 wt% cellulose nanofibers (CSAC15) exhibited a fast and efficient adsorption behavior with qm values of 2015 and 2297 mg/g for adsorption of the Eriochrome black-T (EBT) anionic dye, respectively, which are quite outstanding among the developed EBT adsorbents in the literature so far. The CSAC15 preserved its stability and high adsorption capacity at various pH solutions. The adsorption of EBT onto the bioadsorbents was well-described with the pseudo-second order kinetics and Freundlich isotherm. The proposed CSAC15 bioadsorbent featured repeated dye removal capability after five cycles of adsorption.

A Predictive Model for Survival of Escherichia coli O157:H7 and Generic E. coli in Soil Amended with Untreated Animal Manure.

This study aimed at developing a predictive model that captures the influences of a variety of agricultural and environmental variables and is able to predict the concentrations of enteric bacteria in soil amended with untreated Biological Soil Amendments of Animal Origin (BSAAO) under dynamic conditions. We developed and validated a Random Forest model using data from a longitudinal field study conducted in mid-Atlantic United States investigating the survival of Escherichia coli O157:H7 and generic E. coli in soils amended with untreated dairy manure, horse manure, or poultry litter. Amendment type, days of rain since the previous sampling day, and soil moisture content were identified as the most influential agricultural and environmental variables impacting concentrations of viable E. coli O157:H7 and generic E. coli recovered from amended soils. Our model results also indicated that E. coli O157:H7 and generic E. coli declined at similar rates in amended soils under dynamic field conditions.The Random Forest model accurately predicted changes in viable E. coli concentrations over time under different agricultural and environmental conditions. Our model also accurately characterized the variability of E. coli concentration in amended soil over time by providing upper and lower prediction bound estimates. Cross-validation results indicated that our model can be potentially generalized to other geographic regions and incorporated into a risk assessment for evaluating the risks associated with application of untreated BSAAO. Our model can be validated for other regions and predictive performance also can be enhanced when data sets from additional geographic regions become available.

An Agent-Based Model for Pathogen Persistence and Cross-Contamination Dynamics in a Food Facility.

We used an agent-based modeling (ABM) framework and developed a mathematical model to explain the complex dynamics of microbial persistence and spread within a food facility and to aid risk managers in identifying effective mitigation options. The model explicitly considered personal hygiene practices by food handlers as well as their activities and simulated a spatially explicit dynamic system representing complex interaction patterns among food handlers, facility environment, and foods. To demonstrate the utility of the model in a decision-making context, we created a hypothetical case study and used it to compare different risk mitigation strategies for reducing contamination and spread of Listeria monocytogenes in a food facility. Model results indicated that areas with no direct contact with foods (e.g., loading dock and restroom) can serve as contamination niches and recontaminate areas that have direct contact with food products. Furthermore, food handlers' behaviors, including, for example, hygiene and sanitation practices, can impact the persistence of microbial contamination in the facility environment and the spread of contamination to prepared foods. Using this case study, we also demonstrated benefits of an ABM framework for addressing food safety in a complex system in which emergent system-level responses are predicted using a bottom-up approach that observes individual agents (e.g., food handlers) and their behaviors. Our model can be applied to a wide variety of pathogens, food commodities, and activity patterns to evaluate efficacy of food-safety management practices and quantify contamination reductions associated with proposed mitigation strategies in food facilities.

A Mathematical Model for Pathogen Cross-Contamination Dynamics during the Postharvest Processing of Leafy Greens.

We developed a probabilistic mathematical model for the postharvest processing of leafy greens focusing on Escherichia coli O157:H7 contamination of fresh-cut romaine lettuce as the case study. Our model can (i) support the investigation of cross-contamination scenarios, and (ii) evaluate and compare different risk mitigation options. We used an agent-based modeling framework to predict the pathogen prevalence and levels in bags of fresh-cut lettuce and quantify spread of E. coli O157:H7 from contaminated lettuce to surface areas of processing equipment. Using an unbalanced factorial design, we were able to propagate combinations of random values assigned to model inputs through different processing steps and ranked statistically significant inputs with respect to their impacts on selected model outputs. Results indicated that whether contamination originated on incoming lettuce heads or on the surface areas of processing equipment, pathogen prevalence among bags of fresh-cut lettuce and batches was most significantly impacted by the level of free chlorine in the flume tank and frequency of replacing the wash water inside the tank. Pathogen levels in bags of fresh-cut lettuce were most significantly influenced by the initial levels of contamination on incoming lettuce heads or surface areas of processing equipment. The influence of surface contamination on pathogen prevalence or levels in fresh-cut bags depended on the location of that surface relative to the flume tank. This study demonstrates that developing a flexible yet mathematically rigorous modeling tool, a "virtual laboratory," can provide valuable insights into the effectiveness of individual and combined risk mitigation options.

Normoxic and hyperoxic cardiopulmonary bypass in congenital heart disease.

Cyanotic congenital heart disease comprises a diverse spectrum of anatomical pathologies. Common to all, however, is chronic hypoxia before these lesions are operated upon when cardiopulmonary bypass is initiated. A range of functional and structural adaptations take place in the chronically hypoxic heart, which, whilst protective in the hypoxic state, are deleterious when the availability of oxygen to the myocardium is suddenly improved. Conventional cardiopulmonary bypass delivers hyperoxic perfusion to the myocardium and is associated with cardiac injury and systemic stress, whilst a normoxic perfusate protects against these insults.

Using a sternocleidomastoid muscle flap to prevent postoperative pharyngocutaneous fistula after total laryngectomy: a study of 88 cases.

Complications of total laryngectomy can have serious implications for the final outcome of treatment, including pharyngocutaneous fistula. We conducted a retrospective study of surgical techniques to determine how to best prevent or decrease the incidence of pharyngocutaneous fistula following total laryngectomy. We reviewed the hospital records of all patients who had undergone total laryngectomy for laryngeal carcinoma at Ghaem Hospital in Mashhad, Iran, from March 1989 through February 2005. We identified 88 such patients-80 men and 8 women. We divided this cohort into two groups according to the type of pharyngeal defect closure they received. A total of 37 patients-31 men and 6 women (mean age: 61.4 ± 5.9 yr) underwent primary closure along with a sternocleidomastoid muscle (SCMM) flap (flap group). The other 51 patients-49 men and 2 women (mean age: 61.3 ± 4.4 yr)-underwent standard primary closure without creation of an SCMM flap (nonflap group). Overall, postoperative pharyngocutaneous fistula occurred in 9 of the 88 patients (10.2%)-1 case in the flap group (2.7%) and 8 cases in the nonflap group (15.7%). The difference between the two groups was statistically significant (p < 0.001; odds ratio = 0.612, 95% confidence interval = 0.451 to 0.832), independent of other factors. We found no correlation between fistula development and age (p = 0.073), sex (p = 0.065), or tumor location (p = 0.435). Likewise, we found no correlation between tumor location and either sex (p = 0.140) or age (p = 0.241). We conclude that including an SCMM flap in the surgical process would significantly decrease the development of fistula, regardless of age, sex, and tumor site.

Controlled reoxygenation during cardiopulmonary bypass decreases markers of organ damage, inflammation, and oxidative stress in single-ventricle patients undergoing pediatric heart surgery.

OBJECTIVE: Single-ventricle patients undergoing pediatric heart surgery are a high-risk group owing to reoxygenation injury during cardiopulmonary bypass (CPB). The present study investigated the effects of controlled reoxygenation CPB on biomarkers of organ damage, inflammation, stress, and long-term functional outcomes in cyanotic patients with either a single or double ventricle during open heart surgery. METHODS: Cyanotic patients with either a single (n = 32) or double (n = 47) ventricle undergoing surgical correction were randomized to receive CPB using either standard oxygen levels or controlled reoxygenation. The markers of cardiac injury, inflammation, stress, and cerebral and hepatic injury were measured preoperatively, at 10 and 30 minutes after starting CPB, and at 10 minutes and 4 and 24 hours after CPB. The data were analyzed using a mixed regression model. RESULTS: No difference was found in the pre- or intraoperative characteristics between the standard and controlled reoxygenation CPB groups for single- or double-ventricle patients. In the single-ventricle patients, controlled reoxygenation CPB significantly (P < .05) decreased the markers of organ damage, inflammation, stress, and oxidative stress. In contrast, the markers of inflammation and cardiac injury were not altered by controlled reoxygenation CPB in the double-ventricle patients. CONCLUSIONS: Controlled reoxygenation CPB decreased the markers of organ damage, stress, inflammation, and oxidative stress in single-ventricle patients undergoing cardiac surgery.

An in vitro evaluation of environmental pH changes after root canal therapy with three different types of calcium hydroxide.

OBJECTIVE: This study determined environmental pH changes after root canal dressing using 3 types of commercial calcium hydroxide pastes. METHODS: Thirty-two extracted single-rooted human premolars with 1 straight root canal were selected. Standard cavities were prepared on root surfaces. All root surfaces, excluding the cavities, were covered with nail polish. Root canals were prepared using the Easy RaCe rotary system. The teeth were randomly divided into 3 experimental groups filled with calcium hydroxide pastes: (Group 1) Sure-Paste, (Group 2) Meta-Paste, and (Group 3) Multi-Cal. The control group had 2 samples. Teeth were then placed in 10 mL of normal saline. Environmental pH values were measured at 1 h, 24 h, 48 h, and 1 week. Statistical evaluations of the results were performed via the ANOVA and Tukey tests. RESULTS: Results demonstrated that groups 3 and 1 showed a significant statistical difference (P<.001) with the pH being greater in group 3. There was no significant difference between groups 2 and 3 (P>.05). Intracanal placement of Multi-Cal compared with that of Sure-Paste and Meta-Paste resulted in a higher pH in simulated root resorption defects. CONCLUSION: In cases, like apexification, that need longer pH changes and higher disinfecting qualities, it might be better to use Multi-Cal, and for short-time use as disinfectant medicament Multi-Cal and Meta-Paste are equally effective.

Controlled reoxygenation cardiopulmonary bypass is associated with reduced transcriptomic changes in cyanotic tetralogy of Fallot patients undergoing surgery.

In cyanotic patients undergoing repair of heart defects, high level of oxygen during cardiopulmonary bypass (CPB) leads to greater susceptibility to myocardial ischemia and reoxygenation injury. This study investigates the effects of controlled reoxygenation CPB on gene expression changes in cyanotic hearts of patients undergoing surgical correction of tetralogy of Fallot (TOF). We randomized 49 cyanotic TOF patients undergoing corrective cardiac surgery to receive either controlled reoxygenation or hyperoxic/standard CPB. Ventricular myocardium biopsies were obtained immediately after starting and before discontinuing CPB. Microarray analyses were performed on samples, and array results validated with real-time PCR. Gene expression profiles before and after hyperoxic/standard CPB revealed 35 differentially expressed genes with three upregulated and 32 downregulated. Upregulated genes included two E3 Ubiquitin ligases. The products of downregulated genes included intracellular signaling kinases, metabolic process proteins, and transport factors. In contrast, gene expression profiles before and after controlled reoxygenation CPB revealed only 11 differentially expressed genes with 10 upregulated including extracellular matrix proteins, transport factors, and one downregulated. The comparison of gene expression following hyperoxic/standard vs. controlled reoxygenation CPB revealed 59 differentially expressed genes, with six upregulated and 53 downregulated. Upregulated genes included PDE1A, MOSC1, and CRIP3. Downregulated genes functionally clustered into four major classes: extracellular matrix/cell adhesion, transcription, transport, and cellular metabolic process. This study provides direct evidence that hyperoxic CPB decreases the adaptation and remodeling capacity in cyanotic patients undergoing TOF repair. This simple CPB strategy of controlled reoxygenation reduced the number of genes whose expression was altered following hyperoxic/standard CPB.

The study of apoptotic bifunctional effects in relationship between host and parasite in cystic echinococcosis: a new approach to suppression and survival of hydatid cyst.

Cystic echinococcosis (hydatidosis) is a zoonotic helminthic disease of human and other intermediated hosts wherein infection is caused by the larval stages of tapeworm Echinococcus granulosus. Growth of the larval stage is formed throughout the internal organs, the liver and lung, causing their destruction. Important pathways are unknown about suppression and survival of cysts in human body. In this study, apoptotic bifunctional effects are evaluated in relationship between host and parasite in cystic echinococcosis. Human lymphocytes were treated with hydatid fluid (HF). After 6 h of exposure, caspase-3 activity was measured by fluorometric assay in the HF-treated lymphocytes and control cells. Also, the expression of Bax (as pro-apoptotic protein) and Bcl-2 (an anti-apoptotic protein) mRNA was assessed by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) after 12 h of exposure. For surveying of apoptosis-inducing ligands TNF-related apoptosis-inducing ligand and Fas-L, germinal layer and accompaniment peripheral tissues as healthy control were separated by scalpel from each cyst in sterile condition, then were assess by semiquantitative RT-PCR method in mRNA expression. Both the ratio of Bax/Bcl-2 mRNA expression and caspase-3 activity were higher in the fertile fluid-treated lymphocytes relative to infertile fluid-treated lymphocytes and control group versus the expression level of apoptosis-inducing ligands having a relatively high level in germinal layer of infertile cyst in comparison to fertile cyst and healthy tissue. Apoptosis of germinal layer of fertile cysts is possibly one of the suppression mechanisms in hydatidosis patients, in contrast to lymphocytes apoptosis by modulator of hydatid fluid, one of the hydatid cyst survival mechanisms.

Transcriptomic analysis of patients with tetralogy of Fallot reveals the effect of chronic hypoxia on myocardial gene expression.

OBJECTIVES: In cyanotic patients undergoing repair of heart defects, chronic hypoxia is thought to lead to greater susceptibility to ischemia and reoxygenation injury. We sought to find an explanation to such a hypothesis by investigating the cardiac gene expression in patients with tetralogy of Fallot undergoing cardiac surgery. METHODS: The myocardial gene profile was investigated in right ventricular biopsy specimens obtained from 20 patients with a diagnosis of cyanotic (n = 11) or acyanotic (n = 9) tetralogy of Fallot undergoing surgical repair. Oligonucleotide microarray analyses were performed on the samples, and the array results were validated with Western blotting and enzyme-linked immunosorbent assay. RESULTS: Data revealed 795 differentially expressed genes in cyanotic versus acyanotic hearts, with 198 upregulated and 597 downregulated. Growth/morphogenesis, remodeling, and apoptosis emerged as dominant functional themes for the upregulated genes and included the apoptotic gene TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), the remodeling factor OPN (osteopontin), and the mitochondrial function gene COX11 (cytochrome-c oxidase 11). In contrast, transcription, mitogen-activated protein kinase signaling, and contractile machinery were the dominant functional classes for the downregulated genes, which included the calcium-handling gene NCX1 (sodium-calcium exchanger). Protein levels of COX11, NCX1, OPN, and LYZ (lysozyme) in the myocardium followed the same pattern obtained by means of transcriptomics. The TRAIL level did not change in myocardium but increased in circulating blood of cyanotic patients, suggesting the myocardium as a possible source. Additionally, our data showed increased protein expression of apoptosis markers in cyanotic myocardium. CONCLUSIONS: Chronic hypoxia in cyanotic children with tetralogy of Fallot induced the expression of genes associated with apoptosis and remodeling and reduced the expression of genes associated with myocardium contractility and function.

Off-pump coronary artery bypass surgery is associated with fewer gene expression changes in the human myocardium in comparison with on-pump surgery.

Off-pump coronary artery bypass surgery reduces the myocardial injury associated with on pump surgery with cardiopulmonary bypass (CPB) and ischemic-cardioplegic arrest (CA). We sought to find a mechanistic explanation for this by comparing the transcriptomic changes in the myocardium of patients undergoing on- and off-pump surgery. Transcriptomic analyses were performed on left ventricular biopsies obtained from patients prior to (pre-op) and after completion of all coronary anastomoses (post-op). Microarray results were validated with real-time polymerase chain reaction. In on-pump group, 68 genes were upregulated in post-op vs. pre-op biopsies (P < 0.01, >or=2-fold). They included inflammatory genes CCL3 and CCL4, apoptotic gene GADD45B and prostaglandin synthesis gene PTGS2 (COX-2). In the off-pump group, 17 genes were upregulated in post-op vs. pre-op biopsies (P < 0.01, >or=2-fold), all shared with on-pump patients. To uncover the genes implicated in CPB and ischemic-CA response, we compared the postoperative gene profiles of the two groups. Thirty-eight genes were upregulated in the on-pump vs. off-pump patients (P < 0.01, >or=2-fold). On-pump surgery induces injury-related response, as demonstrated by the upregulation of apoptosis and remodeling markers, whereas off-pump surgery ameliorates that by mainly upregulating a cytoprotective genetic program. Blood levels of the identified cytokines and chemokines followed the same pattern obtained by transcriptomics, suggesting that the myocardium is a likely source for these proteomic changes. In conclusion, off-pump surgery is associated with fewer alterations in gene expression connected with inflammation, apoptosis, and remodeling seen after on-pump surgery with CPB and ischemic-CA.

The effects of normoxic versus hyperoxic cardiopulmonary bypass on oxidative stress and inflammatory response in cyanotic pediatric patients undergoing open cardiac surgery: a randomized controlled trial.

OBJECTIVES: This study investigates the effects of controlled reoxygenation cardiopulmonary bypass on oxidative stress, inflammatory response, and organ function in children undergoing repair of cyanotic congenital heart defects. METHODS: Sixty-seven cyanotic patients (median age 15 months, interquartile range 6-49 months) undergoing corrective cardiac surgery were randomized to receive either controlled normoxic (50-0 mm Hg; n = 35) or hyperoxic (150-180 mm Hg; n = 32) cardiopulmonary bypass. Troponin I and 8-isoprostane, C3a, interleukins 6, 8, and 10, cortisol, protein S100, and alpha-glutamate transferase were measured preoperatively and 10 and 30 minutes after starting bypass, on removal of the aortic crossclamp, and 12 and 24 hours thereafter. RESULTS: Overall, troponin I and 8-isoprostane levels were lower in the controlled normoxic group (-29%, 95% CI -48% to -3%, P = .03, and -26%, 95% CI -44% to -2%, P = .03, respectively). Protein S100 release was also lower in the normoxic group 10 minutes after starting bypass (-26%, 95% CI -40% to -9%, P = .005) and 10 minutes after aortic crossclamp removal (-23%, 95% CI -38% to -3%, P = .02, respectively), but similar at other time points in the two groups (P >or= .17). The alpha-glutamate transferase release was significantly lower in the normoxic group 10 minutes after aortic crossclamp removal (-28%, 95% CI -44% to -9%, P = .006, respectively) but was similar at other times (P >or= .11). Release of C3a, interleukins 6, 8, and 10, and cortisol was similar in the two groups throughout (P >or= .15). CONCLUSION: Controlled reoxygenation on starting cardiopulmonary bypass is associated with reduced myocardial damage, oxidative stress, and cerebral and hepatic injury compared with hyperoxic bypass and similar whole body inflammatory and stress response in cyanotic children undergoing open cardiac surgery.