A Randomized Trial of an Exclusive Human Milk Diet in Neonates with Single Ventricle Physiology.

OBJECTIVE: To determine whether weight gain velocity (g/kg/day) 30 days after the initiation of feeds after cardiac surgery and other clinical outcomes improve in infants with single ventricle physiology fed an exclusive human milk diet compared with a mixed human and bovine diet. STUDY DESIGN: In this multicenter, randomized, single blinded, controlled trial, term neonates 7 days of age or younger with single ventricle physiology and anticipated cardiac surgical palliation within 30 days of birth were enrolled at 10 US centers. Both groups received human milk if fed preoperatively. During the 30 days after feeds were started postoperatively, infants in the intervention group received human milk fortified once enteral intake reached 60 mL/kg/day with a human milk-based fortifier designed for term neonates. The control group received standard fortification with formula once enteral intake reached 100 mL/kg/day. Perioperative feeding and parenteral nutrition study algorithms were followed. RESULTS: We enrolled 107 neonates (exclusive human milk = 55, control = 52). Baseline demographics and characteristics were similar between the groups. The median weight gain velocity at study completion was higher in exclusive human milk vs control group (12 g/day [IQR, 5-18 g/day] vs 8 g/day [IQR, 0.4-14 g/day], respectively; P = .03). Other growth measures were similar between groups. Necrotizing enterocolitis of all Bell stages was higher in the control group (15.4 % vs 3.6%, respectively; P = .04). The incidence of other major morbidities, surgical complications, length of hospital stay, and hospital mortality were similar between the groups. CONCLUSIONS: Neonates with single ventricle physiology have improved short-term growth and decreased risk of NEC when receiving an exclusive human milk diet after stage 1 surgical palliation. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov (www. CLINICALTRIALS: gov, Trial ID: NCT02860702).

Assessment and management of neonates with unrepaired congenital heart disease.

PURPOSE OF REVIEW: To review preoperative assessment and management of neonates with congenital heart disease (CHD). RECENT FINDINGS: The spectrum for neonates with CHD can be wide and complex. An in-depth understanding of their physiology is the first step in assessing their hemodynamics and developing an effective therapeutic strategy. SUMMARY: There is significant heterogeneity in the anatomy and physiology in newborns with CHD. Their complex pathophysiology can be simplified into seven basic subtypes, which include systolic dysfunction, diastolic dysfunction, excessive pulmonary blood flow, obstructed pulmonary blood flow, obstructed systemic blood flow, transposition physiology, and single ventricle physiology. It is important to note these physiologies are not mutually exclusive, and this review summarizes the hemodynamic and therapeutic strategies available for the preoperative neonate with CHD.

Normative Echocardiographic Values for Right and Left Ventricular Function in Extremely Premature Neonates.

OBJECTIVE: To identify the measures of biventricular function and surrogates of pulmonary vascular resistance that can be expected in relatively stable extremely premature neonates, and evaluate maturational changes in myocardial performance in this patient population. STUDY DESIGN: This was a prospective observational study. Clinically stable extremely preterm newborns were divided into 3 cohorts based on gestational age: cohort 1 (240/7-256/7 weeks), cohort 2 (260/7-276/7 weeks), and cohort 3 (280/7-296/7 weeks). Serial echocardiograms were obtained on day of life 3-5, 7-10, and just prior to discharge. RESULTS: In total, 46 subjects met the criteria aimed at capturing only the most clinically healthy and stable newborns less than 296/7 weeks of gestational age. Myocardial performance was reliably assessed by echocardiography with high inter-reader correlation. Normative values were identified for right ventricular function, left ventricular function, and surrogates of pulmonary vascular resistance. CONCLUSIONS: Biventricular systolic performance is significantly different in the clinically stable extremely premature neonate when compared with healthy full-term newborns. All participants had evidence of poor biventricular compliance at birth which improved with maturation. Extreme prematurity does not appear to adversely affect myocardial functional maturation at the time of term corrected age and/or discharge.

Application of Ni0.5Zn0.5Fe2O4 magnetic nanoparticles for diclofenac adsorption: isotherm, kinetic and thermodynamic investigation.

Ni0.5Zn0.5Fe2O4 magnetic nanoparticles were synthesized to obtain a new efficient adsorbent for diclofenac sodium (DF) removal. Fourier Transform Infrared (FTIR), Energy Dispersive Spectrometer (EDS), scanning electron microscope (SEM), Brunauer-Emmett-Teller (BET) and vibrating sample magnetometer (VSM) were applied to characterize the prepared adsorbent. These analyses revealed that adsorbent was successfully prepared with average particle diameter of about 50 nm and a BET surface area of 168.09 m2/g. The saturation magnetization value of magnetic nanoparticles (MNPs) was found to be 24.90 emu/g, thus, adsorbent was efficiently separated from the solution by a facile and rapid magnetic separation process. The effect of adsorption time, amount of adsorbent, initial pH of the solution, initial diclofenac concentration and temperature on the removal of DF were evaluated. Also, the adsorption data were best fitted to the pseudo-first-order kinetic model and Langmuir isotherm model. The thermodynamics studies suggested spontaneous and exothermic adsorption. The maximum diclofenac adsorption amount of the synthesized nanoadsorbent was 52.91 mg/g, which is higher than many recently studied adsorbents.

Management strategies for the preemie ductus.

PURPOSE OF REVIEW: Patent ductus arteriosus (PDA) remains the most common cardiovascular condition afflicting neonates. Despite 5 decades of scientific inquiry pediatric cardiologists and neonatologists still cannot answer the simple question of which PDAs should be treated. RECENT FINDINGS: Although the volume of the shunt is difficult to calculate, echocardiography, biochemical markers, and clinical exam can provide clues to the magnitude and physiologic consequences of the shunt. Epidemiologic data exists showing a positive relationship between a PDA and numerous morbidities. As a result, for most of the 20th and early 21st century, nearly all PDAs where indiscriminately considered to be hemodynamically significant and attempts to close it where initiated shortly after birth. However, no randomized trials of PDA closure have been able to show significant differences between affected and unaffected groups. In fact, surgical ligation has repeatedly been associated with increased morbidities and worse long-term neurodevelopmental outcomes. As a result, most clinicians favor a strategy of watchful waiting. SUMMARY: In this review, we aim to summarize the scientific literature, along with some of the contemporary biases, that exist with regards to the pathophysiology, genetics, and treatment strategies for the neonatal PDA.

Application of the Enzymatic Electrochemical Biosensors for Monitoring Non-Competitive Inhibition of Enzyme Activity by Heavy Metals.

The inhibition effect of the selected heavy metals (Ag+, Cd2+, Cu2+, and Hg2+) on glucose oxidase (GOx) enzyme from Aspergillus niger (EC 1.1.3.4.) was studied using a new amperometric biosensor with an electrochemical transducer based on a glassy carbon electrode (GCE) covered with a thin layer of multi-wall carbon nanotubes (MWCNTs) incorporated with ruthenium(IV) oxide as a redox mediator. Direct adsorption of multi-wall carbon nanotubes (MWCNTs) and subsequent covering with Nafion® layer was used for immobilization of GOx. The analytical figures of merit of the developed glucose (Glc) biosensor are sufficient for determination of Glc in body fluids in clinical analysis. From all tested heavy metals, mercury(II) has the highest inhibition effect. However, it is necessary to remember that cadmium and silver ions also significantly inhibit the catalytic activity of GOx. Therefore, the development of GOx biosensors for selective indirect determination of each heavy metal still represents a challenge in the field of bioelectroanalysis. It can be concluded that amperometric biosensors, differing in the utilized enzyme, could find their application in the toxicity studies of various poisons.

An Investigation on the Application of Pulsed Electrodialysis Reversal in Whey Desalination.

Electrodialysis (ED) is frequently used in the desalination of whey. However, the fouling onto the membrane surface decreases the electrodialysis efficiency. Pulsed Electrodialysis Reversal (PER), in which short pulses of reverse polarity are applied, is expected to decrease the fouling onto membrane surface during ED. Three (PER) regimes were applied in the desalination of acid whey (pH ≤ 5) to study their effects on the membrane fouling and the ED efficiency. The PER regimes were compared to the conventional ED as the control. For each regime, two consecutive runs were performed without any cleaning step in-between to intensify the fouling. After the second run, the membranes were subjected to the Scanning electron microscope (SEM) imaging and contact angle measurement to investigate the fouling on the membrane surface in different regimes. The ED parameters in the case of conventional ED were almost the same in the first and the second runs. However, the parameters related to the ED efficiency including ED capacity, ash transfer, and ED time, were deteriorated when the PER regimes were applied. The contact angle values indicated that the fouling on the diluate side of anion exchange membranes was more intensified in conventional ED compared to the PER regimes. The SEM images also showed that the fouling on the diluate side of both cation and anion exchange membranes under PER regimes was reduced in respect to the conventional ED. However, the back transfer to the diluate compartment when the reverse pulse was applied is dominant and lowers the ED efficiency slightly when the PER is applied.

Preparation and Characterization of Carbon Paste Electrode Bulk-Modified with Multiwalled Carbon Nanotubes and Its Application in a Sensitive Assay of Antihyperlipidemic Simvastatin in Biological Samples.

Determination of an antihyperlipidemic drug simvastatin (SIM) was carried out using a carbon paste electrode bulk-modified with multiwalled carbon nanotubes (MWCNT-CPE). Scanning electrochemical microscopy (SECM), scanning electron microscopy (SEM), and atomic force microscopy (AFM) were used for the characterization of the prepared electrodes. Different electrodes were prepared varying in mass percentage of MWCNTs to find out the optimum amount of MWCNTs in the paste. The MWCNT-CPE in which the mass percentage of MWCNTs was 25% (w/w) was found as the optimum. Then, the prepared electrode was used in a mechanistic study and sensitive assay of SIM in pharmaceutical dosage form and a spiked human plasma sample using differential pulse voltammetry (DPV). The prepared electrode shows better sensitivity compared to the bare carbon paste and glassy carbon electrode (GCE). The detection limit and the limit of quantification were calculated to be 2.4 × 10-7 and 8 × 10-7, respectively. The reproducibility of the electrode was confirmed by the low value of the relative standard deviation (RSD% = 4.8%) when eight measurements of the same sample were carried out. Determination of SIM in pharmaceutical dosage form was successfully performed with a bias of 0.3% and relative recovery rate of 99.7%. Furthermore, the human plasma as a more complicated matrix was spiked with a known concentration of SIM and the spiking recovery rate was determined with the developed method to be 99.5%.

Effect of pump type on outcomes in neonates with congenital diaphragmatic hernia requiring ECMO.

PURPOSE: With the exception of neonatal respiratory failure, most centers are now using centrifugal over roller-type pumps for the delivery of extracorporeal membrane oxygenation (ECMO). Evidence supporting the use of centrifugal pumps specifically in infants with congenital diaphragmatic hernia (CDH) remains lacking. We hypothesized that the use of centrifugal pumps in infants with CDH would not affect mortality or rates of severe neurologic injury (SNI). METHODS: Infants with CDH were identified within the ELSO registry (2000-2016). Patients were then divided into those undergoing ECMO with rollertype pumps or centrifugal pumps. Patients were matched based on propensity score (PS) for the ECMO pump type based on pre-ECMO covariates. This was done for all infants and separately for each ECMO mode, venovenous (VV) and venoarterial (VA) ECMO. RESULTS: We identified 4,367 infants who were treated with either roller or centrifugal pumps from 2000-2016. There was no difference in mortality or SNI between the two pump types in any of the groups (all infants, VA-ECMO infants, VV-ECMO infants). However, there was at least a six-fold increase in the odds of hemolysis for centrifugal pumps in all groups: all infants (odds ratio [OR] 6.99, p<0.001), VA-ECMO infants (OR 8.11, p<0.001 and VV-ECMO infants (OR 9.66, p<0.001). CONCLUSION: For neonates with CDH requiring ECMO, there is no survival advantage or difference in severe neurologic injury between those receiving roller or centrifugal pump ECMO. However, there is a significant increase in red blood cell hemolysis associated with centrifugal ECMO support.

Enhancing the substrate selectivity of enzyme mimetics in biosensing and bioassay: Novel approaches.

A substantial development in nanoscale materials possessing catalytic activities comparable with natural enzymes has been accomplished. Their advantages were owing to the excellent sturdiness in an extreme environment, possibilities of their large-scale production resulting in higher profitability, and easy manipulation for modification. Despite these advantages, the main challenge for artificial enzyme mimetics is the lack of substrate selectivity where natural enzymes flourish. This review addresses this vital problem by introducing substrate selectivity strategies to three classes of artificial enzymes: molecularly imprinted polymers, nanozymes (NZs), and DNAzymes. These rationally designed strategies enhance the substrate selectivity and are discussed and exemplified throughout the review. Various functional mechanisms associated with applying enzyme mimetics in biosensing and bioassays are also given. Eventually, future directives toward enhancing the substrate selectivity of biomimetics and related challenges are discussed and evaluated based on their efficiency and convenience in biosensing and bioassays.

Assessing the role of tracheostomy placement in bronchopulmonary dysplasia with pulmonary hypertension.

OBJECTIVE: Bronchopulmonary dysplasia (BPD) is a common complication of preterm birth and is associated with abnormal vasculature that contributes to pulmonary hypertension (PH). We evaluated how a tracheostomy may alter PH in these patients. METHODS: A retrospective chart review over 15-years identified 17 patients with BPD and PH who underwent tracheostomy. Each patient had four echocardiograms re-reviewed and scored for tricuspid valve regurgitation velocity (TR), tricuspid annular plane systolic excursion (TAPSE), right atrial cross-sectional area (RACA), and left ventricle eccentricity indices (EI). RESULT: There was improvement in TR, TAPSE, RACA, and left ventricle EI indicating reduction in PH after tracheostomy. CONCLUSION: PH improves over time though role of tracheostomy in PH needs to be further defined. The EI may be a sensitive marker to follow over time in these patients.

2D graphene-based advanced nanoarchitectonics for electrochemical biosensors: Applications in cancer biomarker detection.

Low-cost, rapid, and easy-to-use biosensors for various cancer biomarkers are of utmost importance in detecting cancer biomarkers for early-stage metastasis control and efficient diagnosis. The molecular complexity of cancer biomarkers is overwhelming, thus, the repeatability and reproducibility of measurements by biosensors are critical factors. Electrochemical biosensors are attractive alternatives in cancer diagnosis due to their low cost, simple operation, and promising analytical figures of merit. Recently graphene-derived nanostructures have been used extensively for the fabrication of electrochemical biosensors because of their unique physicochemical properties, including the high electrical conductivity, adsorption capacity, low cost and ease of mass production, presence of oxygen-containing functional groups that facilitate the bioreceptor immobilization, increased flexibility and mechanical strength, low cellular toxicity. Indeed, these properties make them advantageous compared to other alternatives. However, some drawbacks must be overcome to extend their use, such as poor and uncontrollable deposition on the substrate due to the low dispersity of some graphene materials and irreproducibility of the results because of the differences in various batches of the produced graphene materials. This review has documented the most recently developed strategies for electrochemical sensor fabrication. It differs in the categorization method compared to published works to draw greater attention to the wide opportunities of graphene nanomaterials for biological applications. Limitations and future scopes are discussed to advance the integration of novel technologies such as artificial intelligence, the internet of medical things, and triboelectric nanogenerators to eventually increase efficacy and efficiency.

Rapid determination of uracil in biological fluids at mercury thin film electrode for early detection of potential 5-fluorouracil toxicity due to dihydropyrimidine dehydrogenase deficiency.

Determination of plasma uracil was reported as a method for evaluation of Dihydropyrimidine dehydrogenase (DPD) activity that is highly demanded to ensure the safe administration of 5-fluorouracil (5-FU)-based therapies to cancer patients. This work reports the development of a simple electroanalytical method based on adsorptive stripping square wave voltammetry (AdSWV) at mercury film-coated glassy carbon electrode (MF/GCE) for the highly sensitive determination of uracil in biological fluids that can be used for diagnosis of decreased DPD activity. Due to the formation of the HgII-Uracil complex at the electrode surface, the accuracy of the measurement was not affected by the complicated matrices in biological fluids including human serum, plasma, and urine. The high sensitivity of the developed method results in a low limit of detection (≈1.3 nM) in human plasma samples, falling below the practical cut-off level of 15 ng mL-1 (≈0.14 µM). This threshold concentration is crucial for predicting 5-FU toxicity, as reported in buffer, and ≤1.15% in biological samples), and accuracy (recovery percentage close to 100%).

Surface modification strategies and the functional mechanisms of gold nanozyme in biosensing and bioassay.

Gold nanozymes (GNZs) have been widely used in biosensing and bioassay due to their interesting catalytic activities that enable the substitution of natural enzyme. This review explains different catalytic activities of GNZs that can be achieved by applying different modifications to their surface. The role of Gold nanoparticles (GNPs) in mimicking oxidoreductase, helicase, phosphatase were introduced. Moreover, the effect of surface properties and modifications on each catalytic activity was thoroughly discussed. The application of GNZs in biosensing and bioassay was classified in five categories based on the combination of the enzyme like activities and enhancing/inhibition of the catalytic activities in presence of the target analyte/s that is realized by proper surface modification engineering. These categories include catalytic activity enhancer, reversible catalytic activity inhibitor, binding selectivity enhancer, agglomeration base, and multienzyme like activity, which are explained and exemplified in this review. It also gives examples of those modifications that enable the application of GNZs for in vivo biosensing and bioassays.

Analysis of semen parameters, and hormonal changes of FSH, LH, testosterone, and libido following bariatric surgery.

Introduction: Although studies have shown that bariatric surgery can have a positive effect on the patient's sexual function, there are still disagreements and contradictions in this regard. The present study is aimed to evaluate semen parameters, hormonal changes of FSH, LH, testosterone, and libido following bariatric surgery. Methods: The present research as a prospective study was performed on 20 male candidates for bariatric surgery referred to Golestan and Aria hospitals in Ahvaz in 2021. Semen parameters (volume, count, motility, and the percentage of sperm with normal morphology), hormonal profile (including FSH, LH test hormones), and sexual function were evaluated using the International Index of Erectile Function (IIEF-5) questionnaire before and 6 months after the surgery. Results: The results of this study indicated that semen parameters did not change significantly 6 months after surgery in comparison with before the surgery (P < 0.05). After the operation, just the total level of testosterone increased significantly (2.23 nmol/L vs. 2.74, P = 0.009). However, LH and FSH levels did not change significantly six months after surgery (P = 0.858 and P = 0.287). The results indicated significant improvement in IIEF score after the operation (P = 0.011). Conclusion: The findings of the present study indicated that the decrement of weight as a result of bariatric surgery had a favorable effect on the levels of serum testosterone and sexual performance, while semen parameters did not improve after surgery.

Efficacy of drug regimen with and without oseltamivir in hospitalized patients with COVID-19: A retrospective study.

Introduction: Coronavirus disease 2019 (COVID-19) is the most critical issue in nowadays medicine. We aimed to evaluate the use and therapeutic outcomes of oseltamivir, an antiviral drug for patients with COVID-19. Materials and method: In an observational study conducted at Imam Khomeini Hospital in Amol, Iran, data for 544 patients with laboratory and CT scan result confirmed COVID-19 were retrospectively collected between February 24th and April 13th 2020. To compare the characteristics of patients based on gender, the chi-square test was used. Logistic regression was used to evaluate the effect of oseltamivir on the outcome of treatment. Logrank test were used to compare the length of hospital stay in people treated with oseltamivir and drugs other than oseltamivir. Results: Kaplan-Meier and logrank test showed no significant reduction in hospitalization time and survival rate following treatment with oseltamivir. However, a significant increase in lymphocytes count and reduction of C-reactive protein (CRP) level detected. Conclusion: Administration of oseltamivir for patients with COVID-19 didn't show any improvement in hospitalization duration and survival rate.

Introducción: la enfermedad por coronavirus 2019 (COVID-19) es el tema más crítico en la medicina actual. Nuestro objetivo fue evaluar el uso y los resultados terapéuticos de oseltamivir, un medicamento antiviral para pacientes con COVID-19. Materiales y método: en un estudio observacional realizado en el Hospital Imam Khomeini en Amol, Irán, los datos de 544 pacientes con resultados de laboratorio y tomografía computarizada confirmados de COVID-19 se recopilaron retrospectivamente entre el 24 de febrero y el 13 de abril de 2020. Para comparar las características de los pacientes en función del género se utilizó la prueba de chi-cuadrado. Se utilizó regresión logística para evaluar el efecto de oseltamivir en el resultado del tratamiento. Se utilizó la prueba de rango logarítmico para comparar la duración de la estancia hospitalaria en personas tratadas con oseltamivir y otros fármacos distintos del oseltamivir. Resultados: Kaplan­Meier y la prueba de rango logarítmico no mostraron una reducción significativa en el tiempo de hospitalización y la tasa de supervivencia después del tratamiento con oseltamivir. Sin embargo, se detectó un aumento significativo en el recuento de linfocitos y una reducción del nivel de proteína C reactiva (PCR). Conclusión: la administración de oseltamivir para pacientes con COVID-19 no mostró ninguna mejora en la duración de la hospitalización y la tasa de supervivencia.

Perioperative Care Models for Neonates With Congenital Heart Disease: Evolving Role of Neonatology Within the Cardiac Intensive Care Unit.

A multidisciplinary team is needed to optimally care for infants with congenital heart disease (CHD). Different compositions of teams trained in cardiology, critical care, cardiothoracic surgery, anesthesia, and neonatology have been identified as being primarily responsible for perioperative care of this high-risk population in dedicated cardiac intensive care units (CICUs). Although the specific role of cardiac intensivists has become more well defined over the past two decades, the responsibilities of neonatologists remain highly variable in the CICU with neonatologists providing care along with a unique spectrum of primary, shared, or consultative care. The neonatologist can function as the primary physician and assume all or share responsibility with the cardiac intensivists for the management of infants with CHD. A neonatologist can provide care as a secondary consultant physician in a supportive role for the primary CICU team. Additionally, neonates with CHD can be mixed with older children in a CICU, cohorted in a dedicated space within the CICU or placed in a stand-alone infant CICU without older children. Although variations exist between centers on which model of care is deployed and the location within a CICU, characterization of current practice patterns represents the initial step required to determine optimal best practices to improve the quality of care for neonates with cardiac disease. In this manuscript, we present four models utilized in the United States in which the neonatologist provides neonatal-cardiac-focused care in a dedicated CICU. We also outline the different permutations of location where neonates can be cared for in dedicated pediatric/infant CICUs.

Correction: Sýs et al. Bis(2,2'-bipyridil)Copper(II) Chloride Complex: Tyrosinase Biomimetic Catalyst or Redox Mediator? Materials 2021, 14, 113.

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Training pathways and careers for neonatologists interested in cardiovascular care.

Neonatologists and neonatal-perinatal trainees continue to be invested in the cardiovascular care of the newborn, many focusing their careers in this area of expertise. Multiple formalized structured and non-structured training pathways have evolved for neonatologists caring for infants with congenital heart disease and other cardiovascular pathologies. Furthermore, the evolution of neonatal hemodynamic science over the past decade has also spawned a formal training pathway in hemodynamics consultation to enhance standard of care and guide the management of infants at risk for cardiovascular compromise. Neonatologists have also chosen to expand upon on their neonatology training with clinical and research exposure to enhance their roles in neonatal cardiovascular care, including fetal care consultation, delivery room management, and perioperative cardiac intensive care consultation. To provide insight and career guidance to interested neonatal trainees and early career physicians, this perspective article highlights several different pathways in the care of neonates with cardiovascular disease.

Preoperative Management of Neonates With Congenital Heart Disease.

Clinicians caring for neonates with congenital heart disease encounter challenges in clinical care as these infants await surgery or are evaluated for further potential interventions. The newborn with heart disease can present with significant pathophysiologic heterogeneity and therefore requires a personalized therapeutic management plan. However, this complex field of neonatal-cardiac hemodynamics can be simplified. We explore some of these clinical quandaries and include specific sections reviewing the anatomic challenges in these patients. We propose this to serve as a primer focusing on the hemodynamics and therapeutic strategies for the preoperative neonate with systolic dysfunction, diastolic dysfunction, excessive pulmonary blood flow, obstructed pulmonary blood flow, obstructed systemic blood flow, transposition physiology, and single ventricle physiology.