Assessment of microcirculatory alteration by a vascular occlusion test using near-infrared spectroscopy in pediatric cardiac surgery: effect of cardiopulmonary bypass.

OBJECTIVES: Cardiopulmonary bypass cause microcirculatory alterations. Near infrared spectroscopic measurement of tissue oxygen saturation and vascular occlusion test are novel technologies for assessing the microcirculatory function of peripheral tissue specifically in patients undergoing cardiac surgery with cardiopulmonary bypass.Our study aimed to evaluate dynamic microcirculatory function using the vascular occlusion testing during cardiac surgery in pediatric patients. METHODS: 120 pediatric patients were scheduled. Children had continuous regional oxygen saturation monitoring using near infrared spectroscopy and vascular occlusion test. Vascular occlusion test was performed five times; before induction (T1), after induction (T2), then during cardiopulmonary bypass with full flow (T3), after the termination of CPB (T4) and after sternum closure (T5). RESULTS: Basal value was the lowest at T3 and this value was significantly different among measurements (p < 0,01).Values for maximum and minimum tissue oxygen saturation were the lowest at T3 (83,4 and 52,9%).The occlusion slope varied significantly among measurements (p < 0,01).Reperfusion slopes were significantly different among measurements (p < 0,01) with a further progressive decrease in reperfusion slope with duration of cardiopulmonary bypass. CONCLUSION: Microcirculatory function can assessed using VOT with forearm Near-infrared spectroscopy derived variables during cardiopulmonary bypass in pediatric cardiac surgery. Noninvasive assessment of microcirculatory perfusion during cardiopulmonary bypass can further help evaluate and improve circulatory support techniques. TRIAL REGISTRATION: The research Project was registered at ClinicalTrials.gov (NCT06191913).

The effect of albumin and total protein values as nutritional markers after Fontan surgery on prognosis.

INTRODUCTION: Children with CHD develop heart failure due to increased pulmonary blood flow, cyanosis, and pulmonary hypertension. The metabolic needs of these children differ from those of healthy children, and malnutrition is common. Protein-losing enteropathy has been reported in 5 to 13% of patients after the Fontan procedure. Serum albumin and total protein levels, which are indicators of the quality of post-operative care, can be useful tools for monitoring and examining the intensive care treatment strategies of these patients. In our retrospective study, the effects of albumin and total protein values, which are two of the markers that give us an idea about diet, nutritional status, and inflammation, on the prognosis of children who underwent the Fontan procedure were investigated. METHOD: In our study, 127 patients who underwent Fontan procedure in our clinic between 2012 and 2021 were analysed retrospectively. Of the patients, 52.7% (n = 67) were male and 47.3% (n = 60) were female. The mean age is 5.83 ± 4.63 years. Patients who underwent albumin replacement were not included in the study. RESULTS: Although the relationship between pre-operative albumin and total protein values and post-operative mortality was not statistically significant, the inverse correlation of post-operative albumin 1st, 2nd, and 3rd-day values and post-operative total protein 1st, 2nd, and 3rd-day values with mortality was found to be statistically significant. In addition, we found that mortality was statistically high in patients whose total protein amount was below 6.65 mg/dl in the early post-operative period. CONCLUSION: Albumin and total protein, whose blood levels can vary with diet, can be used as predictors in the early post-operative prognosis of Fontan patients. In addition, when we examined the exitus patients, it was observed that the total protein amount was below 6.65 mg/dl on the post-operative 1st day. Based on this, we think that a diet with high protein content before surgery will help reduce post-operative early mortality.

3D Printing of continuous fiber composites using two-stage UV curable resin.

3D printing allows for moldless fabrication of continuous fiber composites with high design freedom and low manufacturing cost per part, which makes it particularly well-suited for rapid prototyping and composite product development. Compared to thermal-curable resins, UV-curable resins enable the 3D printing of composites with high fiber content and faster manufacturing speeds. However, the printed composites exhibit low mechanical strength and weak interfacial bonding for high-performance engineering applications. In addition, they are typically not reprocessable or repairable; if they could be, it would dramatically benefit the rapid prototyping of composite products with improved durability, reliability, cost savings, and streamlined workflow. In this study, we demonstrate that the recently emerged two-stage UV-curable resin is an ideal material candidate to tackle these grand challenges in 3D printing of thermoset composites with continuous carbon fiber. The resin consists primarily of acrylate monomers and crosslinkers with exchangeable covalent bonds. During the printing process, composite filaments containing up to 30.9% carbon fiber can be rapidly deposited and solidified through UV irradiation. After printing, the printed composites are subjected to post-heating. Their mechanical stiffness, strength, and inter-filament bonding are significantly enhanced due to the bond exchange reactions within the thermoset matrix. Furthermore, the utilization of the two-stage curable resin enables the repair, reshaping, and recycling of 3D printed thermosetting composites. This study represents the first detailed study to explore the benefits of using two-stage UV curable resins for composite printing. The fundamental understanding could potentially be extended to other types of two-stage curable resins with different molecular mechanisms.

Evaluation of postoperative renal functions and its effect on body perfusion in patients with double aortic cannulation.

BACKGROUND: The optimal visceral preservation method during aortic arch reconstruction is still controversial. It has been thought that double aortic cannulation is effective. Herein, it was aimed to evaluate this technique in providing distal perfusion. METHODS: A total of 74 patients who underwent arch reconstruction between 2011 and 2019 were included. Patients were grouped according to ventricular physiology and cannulation strategies. Group 1 were univentricle patients, and all had double aortic cannulation. Group 2 were biventricular patients. Group 2A double aortic cannulation-done and Group 2B non-double aortic cannulation were included. Lactate, urea, creatinine values, renal functions, and need for peritoneal dialysis of patients were evaluated. RESULTS: There were no complications observed due to descending aortic cannulation in any of the patients. A delayed sternal closure and the need for peritoneal dialysis were more common in the Group 1 (p < 0.01). The preoperative and postoperative 1st- and 2nd-day lactate, urea, and creatinine values in the Group 1 were higher (p < 0.05) when compared with the Group 2A and 2B. The same values were higher in Group 2A than the Group 2B (p < 0.05). CONCLUSION: The positive effect of double aortic cannulation on renal dysfunction could not be demonstrated. This may be associated with a <1 month of age, low weight, complex surgical procedure, and high preoperative lactate, urea, and creatinine values in patients with double aortic cannulation.

Acute Changes in Myocardial Expression of Heat Shock Proteins and Apoptotic Response Following Blood, delNido, or Custodiol Cardioplegia in Infants Undergoing Open-Heart Surgery.

Stress caused by cardioplegic ischemic arrest was shown to alter the expression levels of heat shock proteins (Hsp), but little is known about their effects, particularly on pediatric hearts. This study aimed to investigate whether myocardial cellular stress and apoptotic response changes due to different cardioplegia (CP) solutions during cardiopulmonary bypass (CPB) in infants and to determine their influence on surgical/clinical outcomes. Therefore, twenty-seven infants for surgical closure of ventricular septal defect were randomly assigned to a CP solution: normothermic blood (BCP), delNido (dNCP), and Custodiol (CCP). Hsp levels and apoptosis were determined by immunoblotting in cardiac tissue from the right atrium before and after CP, and their correlations with cardiac parameters were evaluated. No significant change was observed in Hsp27 levels. Hsp60, Hsp70, and Hsp90 levels decreased significantly in the BCP-group but increased markedly in the CCP-group. Decreased Hsp60 and increased Hsp70 expression were detected in dNCP-group. Importantly, apoptosis was not observed in dNCP- and CCP-groups, whereas marked increases in cleaved caspase-3 and -8 were determined after BCP. Serum cardiac troponin-I (cTn-I), myocardial injury marker, was markedly lower in the BCP- and dNCP-groups than CCP. Additionally, Hsp60, Hsp70, and Hsp90 levels were positively correlated with aortic cross-clamp time, total perfusion time, and cTn-I release. Our findings show that dNCP provides the most effective myocardial preservation in pediatric open-heart surgery and indicate that an increase in Hsp70 expression may be associated with a cardioprotective effect, while an increase in Hsp60 and Hsp90 levels may be an indicator of myocardial damage during CPB.

Effects of Subacute Exposure of Dibutyl Phthalate on the Homeostatic Model Assessment, Thyroid Function, and Redox Status in Rats.

Dibutyl phthalate is an endocrine disruptor used in a wide range of industrial and agriculture applications. The present study focuses on elucidating the effect of subacute exposure (4-weeks) of DBP on insulin and its sensitivity indexes, oxidative status, thyroid function, energy metabolites, serum biochemistry, and anthropometry in rats. A total of 64 rats were divided into 4 treatment groups as mg DBP/Kg body weight per day: (a) 0 mg/Kg (control), (b) 10 mg/Kg (DBP-10), (c) 50 mg/Kg (DBP-50), and (d) 100 mg/Kg (DBP-100). The rats in each treatment (n = 16) were further divided into male (n = 8) and female (n = 8) rats for studying treatment and gender interactions. Intraperitoneal glucose tolerance test (IPGTT) was performed on the 21st day. Anthropometry, nutritional determinants, fasting plasma glucose, fasting plasma insulin, homeostatic model assessment (HOMA), thyroid hormones, energy metabolites, and oxidative status were studied during the experimental period. Two-way ANOVA was used to analyze the data (p < 0.05). Tukey's posthoc test was used for pair-wise comparisons. DBP increased body weight gain and feed efficiency in an inverted nonmonotonic U-shaped fashion. Hyperglycemia and increased blood glucose area under the curve were observed in DBP-100 at 120 minutes in IPGTT. The HOMA also showed a linear monotonic contrast. Thyroxin decreased significantly in the DBP-100 rats, whereas malondialdehyde, nonesterified fatty acids, and beta hydroxyl butyrate were increased with the DBP treatments. In conclusion, DBP could be attributed to the development of hyperglycemia and insulin resistance in rats. Further investigations into the lipid peroxidation pathways can improve our understanding of the mechanisms involved in metabolic disruption.

Do platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) have a predictive value on pediatric extracorporeal membrane oxygenation (ECMO) results?

BACKGROUND: It is difficult to predict the complications and prognosis of ECMO, which is gaining widespread use in patients with pediatric surgery. Platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) are emerging inflammatory markers that can be calculated from complete blood count, which is a cheap and easily accessible laboratory analysis. The ratios between cellular elements in peripheral blood have been demonstrated to provide information on inflammation, infection, and immune response. METHODS: Sixty-seven patients who needed ECMO application after undergoing pediatric cardiovascular surgery in our clinic, between May 2005 and April 2020, were included in this study. The age of patients varied between 4 days and 17 years with a mean of 30.59 ± 147.26 months. RESULTS: The relationships between PLR or NLR values and various blood parameters and blood gas results were found to be statistically nonsignificant in our group of pediatric ECMO recipients. Even if the effect of PLR and NLR values on mortality and prognosis is statistically nonsignificant in patients who need ECMO after congenital heart surgery, PLR and NLR are typically elevated in the postoperative period. An increase in these values above a certain threshold may be a statistically significant indicator for the prediction of mortality. CONCLUSIONS: There are few studies in the literature concerning PLR and NLR values in patients with pediatric heart surgery. We consider this study will make way for new studies in the future.

Impact of platelet population behaviours in patients undergoing the Glenn procedure.

Pulmonary pressure is one of the most important parameters in the postoperative follow-up of patients who have undergone the Glenn procedure. Platelet activation markers, which are inexpensive and easily accessible blood count parameters, have been shown to be associated with the aetiology and pathogenesis of primary pulmonary artery hypertension. We examined the relationship between platelet activation markers and pulmonary pressures in the early postoperative period of patients who underwent the Glenn procedure.Eighty-five patients who underwent the Glenn procedure in our clinic between January 2011 and March 2020 were included in the study retrospectively. Fifty-one patients were male and 34 were female, and age varied from 4 to 416 months, with a mean of 28.64 ± 51 months.Patients with increased pulmonary blood flow on palliation before Glenn surgery had higher mean platelet volume values. However, no correlation was found between pulmonary pressures and platelet activation markers in the early postoperative period.There was not similar study evaluating platelet activation markers in the paediatric age group before and after postoperative Glenn surgery in the literature. Therefore, even if platelet activation markers provide information about the pulmonary bed, they may be misleading due to other reasons that trigger bleeding and inflammatory processes in the early postoperative period.

Temperate approach to ASD closure in pulmonary arterial hypertension: the fenestrated patch technique.

The most common CHD in the adult patient population is an atrial septal defect due to its asymptomatic nature in early life. However, when diagnosis and treatment are delayed, pulmonary arterial hypertension may develop as a long-term complication, sometimes before adulthood. The presence of PAH adversely affects the results of surgical treatment and may even eliminate the feasibility of surgery in some patients. In such patients who have high pulmonary artery pressure and pulmonary vascular resistance at the margin of inoperability, the response to the acute vasoreactivity test determines the treatment modality.In our retrospective study, a total of 906 patients who underwent ASD closure between January, 2011 and November, 2020, seven of which had undergone the fenestrated patch procedure after they were identified to have high PAP, but positive AVT test response were included. Short-term follow-up of patients with fenestrated ASD patches revealed decreased pulmonary pressure, regression in NYHA classification, and improvement in symptoms.The fenestrated patch technique should be kept in mind as an option to expand the surgical spectrum in the treatment of patients with high pulmonary pressures, where complete closure is risky. It appears that the fenestrated patch technique is a safe approach in the management of pulmonary hypertension in patients with ASD who have pulmonary hypertension, according to short- and midterm follow-up findings.

Neurological complications after pediatric cardiac surgery.

Background: The number of pediatric patients who survive open-heart surgery has increased in recent years and the complications seen in this patient group continue to decrease with each technological advance, including new surgical and neuroprotective techniques and the improvement in surgeons' experience with this patient population. However, neurological complications, which are the most feared and difficult to manage, require long-term follow-up, and increase hospital costs remain a leading cause of mortality and morbidity in this cohort. Results: We evaluated the neurological physical examination, cranial computed tomography (CT), and magnetic resonance (MRI) records of 162 pediatric patients with neurological symptoms lasting more than 24 h after undergoing heart surgery in our clinic between June 2012 and May 2020. The patients' ages ranged from 0 to 205 months, with a mean of 60.59 ± 46.44 months.Of the 3849 pediatric cardiac surgery patients we screened, 162 had neurological complications in the early period (the first 10 days after surgery). The incidence was calculated as 4.2%; 69 patients (42.6%) experienced seizures, 17 (10.5%) experienced confusion, 39 (24.1%) had stupor, and 37 (22.8%) had hemiparesis. Of the patients who developed neurological complications, 54 (33.3%) died. Patients with neurological complications were divided into 3 groups: strokes (n = 90), intracranial bleeding (n = 37), and no radiological results (n = 35). Thirty-four patients (37.8%) in the stroke group died, as did 15 (40%) in the bleeding group, and 5 (14.3%) in the no radiological results group. Conclusions: Studies on neurological complications after pediatric heart surgery in the literature are currently insufficient. We think that this study will contribute to a more detailed discussion of the issue. Responses to neurological events and treatment in the pediatric group may differ compared to the adult age group. Primary prevention methods should be the main approach in combating neurological complications; their formation mechanisms should be carefully monitored and preventive treatment strategies should be developed.

Organ-on-e-chip: Three-dimensional self-rolled biosensor array for electrical interrogations of human electrogenic spheroids.

Cell-cell communication plays a pivotal role in coordination and function of biological systems. Three-dimensional (3D) spheroids provide venues to explore cellular communication for tissue development and drug discovery, as their 3D architecture mimics native in vivo microenvironments. Cellular electrophysiology is a prevalent signaling paradigm for studying electroactive cells. Currently, electrophysiological studies do not provide direct, multisite, simultaneous investigation of tissues in 3D. In this study, 3D self-rolled biosensor arrays (3D-SR-BAs) of either active field-effect transistors or passive microelectrodes were implemented to interface human cardiac spheroids in 3D. The arrays provided continuous and stable multiplexed recordings of field potentials with high sensitivity and spatiotemporal resolution, supported with simultaneous calcium imaging. Our approach enables electrophysiological investigation and monitoring of the complex signal transduction in 3D cellular assemblies toward an organ-on-an-electronic-chip (organ-on-e-chip) platform for tissue maturation investigations and development of drugs for disease treatment, such as arrhythmias.

Self-Folded Gripper-Like Architectures from Stimuli-Responsive Bilayers.

Self-folding microgrippers are an emerging class of smart structures that have widespread applications in medicine and micro/nanomanipulation. To achieve their functionalities, these architectures rely on spatially patterned hinges to transform into 3D configurations in response to an external stimulus. Incorporating hinges into the devices requires the processing of multiple layers which eventually increases the fabrication costs and actuation complexities. The goal of this work is to demonstrate that it is possible to achieve gripper-like configurations in an on-demand manner from simple planar bilayers that do not require hinges for their actuation. Finite element modeling of bilayers is performed to understand the mechanics behind their stimuli-responsive shape transformation behavior. The model predictions are then experimentally validated and axisymmetric gripper-like shapes are realized using millimeter-scale poly(dimethylsiloxane) bilayers that undergo differential swelling in organic solvents. Owing to the nature of the computational scheme which is independent of length scales and material properties, the guidelines reported here would be applicable to a diverse array of gripping systems and functional devices. Thus, this work not only demonstrates a simple route to fabricate functional microgrippers but also contributes to self-assembly in general.

Proteomic analysis of six- and twelve-month hippocampus and cerebellum in a murine Down syndrome model.

This study was designed to investigate the brain proteome of the Ts65Dn mouse model of Down syndrome. We profiled the cerebellum and hippocampus proteomes of 6- and 12-month-old trisomic and disomic mice by difference gel electrophoresis. We quantified levels of 2082 protein spots and identified 272 (170 unique UniProt accessions) by mass spectrometry. Four identified proteins are encoded by genes trisomic in the Ts65Dn mouse. Three of these (CRYZL11, EZR, and SOD1) were elevated with p-value <0.05, and 2 proteins encoded by disomic genes (MAPRE3 and PHB) were reduced. Intergel comparisons based on age (6 vs. 12 months) and brain region (cerebellum vs. hippocampus) revealed numerous differences. Specifically, 132 identified proteins were different between age groups, and 141 identified proteins were different between the 2 brain regions. Our results suggest that compensatory mechanisms exist, which ameliorate the effect of trisomy in the Ts65Dn mice. Differences observed during aging may play a role in the accelerated deterioration of learning and memory seen in Ts65Dn mice.

Programmable shape transformation of elastic spherical domes.

We investigate mismatch strain driven programmable shape transformation of spherical domes and report the effects of different geometric and structural characteristics on dome behavior in response to applied mismatch strain. We envision a bilayer dome design where the differential swelling of the inner layer with respect to the passive outer layer in response to changes in dome surroundings (such as the introduction of an organic solvent) introduces mismatch strain within the bilayer system and causes dome shape transformation. Finite element analysis reveals that, in addition to snap-through, spherical domes undergo bifurcation buckling and eventually gradual bending to morph into cylinders with increasing mismatch strain. Besides demonstrating how the snap-through energy barrier depends on the spherical dome shape, our analysis identifies three distinct groups of dome geometries based on their mismatch strain-transformed configuration relationships. Our experiments with polymer-based elastic bilayer domes that exhibit differential swelling in organic solvents qualitatively confirm the finite element predictions. We establish that, in addition to externally applied stimuli (mismatch strain), bilayer spherical dome morphing can be tuned and hence programmed through its geometry and structural characteristics. Incorporation of an elastic instability mechanism such as snap-through within the framework of stimuli-responsive functional devices can improve their response time which is otherwise controlled by diffusion. Hence, our proposed design guidelines can be used to realize deployable, multi-functional, reconfigurable, and therefore, adaptive structures responsive to a diverse set of stimuli across multiple length scales.

A proteomic analysis of excreted and circulating proteins from obese patients following two different weight-loss strategies.

Bariatric surgery is the most successful therapeutic approach to weight loss, but how it leads to weight loss, and how it resolves obesity-related complications, including type-2 diabetes, are poorly understood. This study, comprising two groups of individuals, one on a low-calorie diet (n = 5) and one undergoing bariatric surgery (n = 7), used both targeted and untargeted proteomic approaches to determine changes in protein levels pre- and post-intervention (i.e. 3-6 months later). Changes were observed in both circulating and excreted proteins following weight loss. Targeted multiplexed biochip arrays measured 12 plasma peptides/proteins involved in metabolism and inflammation: C-peptide, ferritin, interleukin-6, interleukin-1 alpha, resistin, insulin, tumor necrosis factor alpha, leptin, plasminogen-activator inhibitor-1, adiponectin, cystatin C, and C-reactive protein. Following a low-calorie diet, plasma insulin and C-reactive protein levels were significantly reduced (P = 0.045 and P = 0.030, respectively); adiponectin increased and leptin decreased following surgery (P = 0.014 and P = 0.005, respectively). Untargeted proteomic analysis employing 2D difference in-gel electrophoresis (DIGE) showed 28 protein spots with ≥1.5-fold changes in expression following weight loss by a low-calorie diet; comparison of pre- and post-intervention urine samples from the bariatric surgery group showed changes in excretion of 110 protein spots. The combination of targeted protein analysis by multiplexed arrays and an exploratory (i.e. an unbiased or discovery) proteomic assessment of hundreds of proteins offers valuable insights into the mechanistic differences between alternative weight-loss strategies. This is a powerful hypothesis-generating approach to study complex, multifactorial syndromes such as obesity. The findings that arise from these studies can then be validated in targeted, hypothesis-directed investigations.

Through the eye of an electrospray needle: mass spectrometric identification of the major peptides and proteins in the milk of the one-humped camel (Camelus dromedarius).

The milk of the one-humped camel (Camelus dromedarius) reportedly offers medicinal benefits, perhaps because of its unique bioactive components. Milk proteins were determined by (1) two-dimensional gel electrophoresis and peptide mass mapping and (2) liquid chromatography-tandem mass spectrometry (LC-MS/MS) following one-dimensional polyacrylamide gel electrophoresis. Over 200 proteins were identified: some known camel proteins including heavy-chain immunoglobulins and others exhibiting regions of exact homology with proteins from other species. Indigenous peptides were also identified following isolation and concentration by two strategies: (1) gel-eluted liquid fraction entrapment electrophoresis and (2) small-scale electrophoretic separation. Extracts were analyzed by LC-MS/MS and peptides identified by matching strategies, by de novo sequencing and by applying a sequence tag tool requiring similarity to the proposed sequence, but not an exact match. A plethora of protein cleavage products including some novel peptides were characterized. These studies demonstrate that camel milk is a rich source of peptides, some of which may serve as nutraceuticals.

Cardiac performance is impaired in morbidly obese pregnant females.

AIM: To evaluate the effect of pregnancy on ventricular function in morbidly obese as compared to lean controls. MATERIAL AND METHODS: We serially studied 33 obese and non-obese pregnant females with echocardiography during each trimester of pregnancy and after delivery. Two well-validated, relatively load-independent indices of contractility (systolic shortening index and systolic velocity index) were assessed, along with more traditional echocardiographic parameters. ANOVA for repeated measures was used to compare data between sequential studies in the normal and obese pregnant groups. RESULTS: In lean controls, stroke volume increased and contractility was maintained during pregnancy as compared to pre-pregnancy levels. In contrast, both stroke volume and contractility declined significantly by the third trimester in morbidly obese females. CONCLUSION: There is a maladaptive left ventricular contractile response to pregnancy in morbidly obese patients.

Prevalence of metabolic syndrome in young patients with acute MI: does the Framingham Risk Score underestimate cardiovascular risk in this population?

To assess the prevalence of metabolic syndrome (MS) and estimates of global risk by Framingham Risk Score in young subjects with acute myocardial infarction (MI), we assessed metabolic parameters and global risk assessment in 165 consecutive subjects who presented with myocardial infarction prior to 45 years of age. Nearly 80% of subjects were overweight or obese and at least one cardiovascular risk factor was present in 96% of patients. MS with or without overt diabetes was present in nearly two thirds of subjects. Excluding subjects with diabetes, the mean 10-year Framingham Risk Score estimate in the total cohort was 9.3%, with only 17.1% of subjects having a 10-year risk greater than 20%. Only 28% of subjects with MS had a Framingham Risk Score greater than 20%. Although MS is present in nearly two thirds of young patients with premature myocardial infarction, the Framingham Risk Score appears to underestimate global cardiovascular risk in this population.