Characterization of enzyme-crosslinked albumin hydrogel for cell encapsulation.

Albumin is an attractive component for the development of biomaterials applied as biomedical implants, including drug carriers and tissue engineering scaffolds, because of its high biocompatibility and low immunogenicity. Additionally, albumin-based gelators facilitate cross-linking reactions under mild conditions, which maintains the high viability of encapsulated living cells. In this study, we synthesized albumin derivatives to undergo gelation under physiological conditions via the peroxidase-catalyzed formation of cross-links. Albumin was modified with phenolic hydroxyl groups (Alb-Ph-OH) using carbodiimide chemistry, and the effect of degree of substitution on gelation was investigated. Various properties of the Alb-Ph-OH hydrogels, namely the gelation time, swelling ratio, pore size, storage modulus, and enzymatic degradability, were easily controlled by adjusting the degree of substitution and the polymer concentration. Moreover, the viability of cells encapsulated within the Alb-Ph-OH hydrogel was high. These results demonstrate the potential applicability of Alb-Ph-OH hydrogels as cell-encapsulating materials for biomedical applications, including tissue engineering.

Catheter Intervention for Flow Regulatory Clips on Palliative Shunts and Conduits in Patients with Congenital Heart Disease.

Catheter intervention (CI) for a Blalock-Taussig shunt (BTS) or a ventricle-to-pulmonary artery conduit (VPC) is often required after a palliative surgery for congenital heart disease. Flow regulatory clips help improve interstage mortality; their use necessitates CIs to prevent cyanosis. To study the CI outcomes in patients who underwent palliative surgery with either BTSs or VPCs with flow regulatory clips. This single-center retrospective study evaluated demographic characteristics and interventional outcomes of 49 consecutive pediatric patients who required CI for BTS (BTS group) or VPC (VPC group) between January 2008 and September 2018. Overall, 34 and 18 procedures were performed in the BTS and VPC groups, respectively. Moreover, 19/32 (59.3%) and 12/17 (70.1%) patients from the BTS and VPC groups had flow regulatory clips, respectively. All clips were unclipped successfully; one patient in each group underwent staged unclipping. A higher proportion of "clipped patients" underwent CI due to desaturation [clipped vs. non-clipped: BTS, 10/20 (50.0%) vs. 3/14 (21.4%), p = 0.092; VPC, 9/13 (69.2%) vs. 1/5 (20.0%), p = 0.060]. Most clipped patients successfully progressed to the next stage [BTS, 19/20 (95.0%); VPC, 12/13 (92.3%)]. Severe adverse events (SAEs) were more frequent in the VPC group than in the BTS group [3/13 (23.1%) vs. 0/20 (0%), p = 0.024]. Two patients developed an atrioventricular block (requiring an atropine infusion), while one died due to pulmonary overcirculation. While the indication of CI was cyanosis for a higher proportion of clipped patients, all clips were unclipped successfully. The incidence of CI-related SAEs was higher in the VPC group than in the BTS group.

Very low birth weight infants with congenital heart disease: A multicenter cohort study in Japan.

BACKGROUND: The frequency, mortality, and morbidity of very low birth weight (VLBW) infants with congenital heart disease (CHD) in Asian countries are limited. In addition, little is known about the risk factors of death in these infants. METHODS: A retrospective, multicenter cohort study was conducted. VLBW infants with CHD born between 2006 and 2010, and followed to 5 years of age, were included in the analysis. Multiple logistic regression analysis was performed to identify the risk factors of death. RESULTS: Among 3247 VLBW infants, 126 various CHDs (3.9 %) were identified. The most common lesions were ventricular septal defect, tetralogy of Fallot (TOF), and coarctation of the aorta/interrupted aortic arch, in that order. The proportions of left-sided and right-sided outflow obstruction (TOF, pulmonary stenosis) were 15.1 % and 15.9 %, respectively. Trisomy 18 and trisomy 13 were present in 32 (25.4 %) of 126 VLBW infants with CHD. Nine patients were lost to follow-up. Overall, 45 patients (35.7 %) died up to 5 years of age. Serious CHD [odds ratio (OR), 19.2; 95 % confidential interval (CI), 3.94-93.11; p < 0.0001], sepsis (OR, 42.3; 95 % CI, 5.39-332.22; p < 0.0001), chromosomal /named anomalies (OR, 7.50; 95%CI, 2.09-26.94; p = 0.001), and no-invasive treatments (OR, 9.89; 95%CI, 2.28-42.91; p = 0.001) were associated with death. On excluding chromosomal anomalies, twelve of 71 patients (16.9 %) died, and only sepsis (OR, 35.5, 95%CI, 2.63-477.1; p = 0.0008) was an independent risk factor. CONCLUSIONS: Trisomy 18 and trisomy 13 of chromosomal anomalies are frequently associated with VLBW infants with CHD. The mortality of VLBW infants with CHD is high, even when chromosomal anomalies are excluded. Sepsis has a significant impact on death in VLBW infants with CHD.

Effects of Screen Viewing Time on Sleep Duration and Bedtime in Children Aged 1 and 3 Years: Japan Environment and Children's Study.

This study aimed to clarify the effects of television/digital versatile disc (TV/DVD) viewing time and portable electronic device (PED) usage time on sleep duration and bedtime and the difference between the effects of TV/DVD and PED on sleep. The effect of TV/DVD viewing time or PED usage time on sleep duration and bedtime was analyzed using a multiple logistic regression analysis adjusted for covariates. A total of 74,525 participants were included in the analysis, using data from Japan Environment and Children's Study. TV/DVD viewing was not associated with short sleep duration, but PED usage was associated with short sleep duration. In addition, the risk of short sleep duration increased as PED usage time increased. We also investigated the effects of sleep habits at age 1 year on sleep at age 3 years. This study showed that late bedtime at age 1 year posed a significant risk of late bedtime at age 3 years. In summary, particular caution should be paid to PED use from a child's health perspective, and sleep habits should be focused on bedtime from the age of 1 year.

Early Developmental Signs in Children with Autism Spectrum Disorder: Results from the Japan Environment and Children's Study.

Autism spectrum disorder (ASD) is a developmental disability in early childhood. Early identification and intervention in children with ASD are essential for children and their families. This study aimed to identify the earliest signs of ASD. Using a large cohort including data from 104,062 fetal records in the Japan Environment and Children's Study, we examined the Ages and Stages Questionnaires® (ASQ-3TM) scores of children with and without ASD. The ASQ-3 comprises five domains: communication, gross motor, fine motor, problem solving, and personal-social. The ASQ-3 scores were obtained at ages 6 months, 1 year, and 3 years. There were 64,501 children with available ASQ-3 data. The number of children diagnosed with ASD was 188 (0.29%) at 3 years of age. The highest relative risk (RR) for any domain below the monitoring score at 6 months was in the communication (RR 1.90, 95% CI 1.29-2.78, p = 0.0041), followed by fine motor (RR 1.50, 95% CI 1.28-1.76, p < 0.0001) domain. A low ASQ-3 score in the communication domain at 6 months was related to an ASD diagnosis at 3 years of age. The ASQ-3 score at 6 months can contribute to the early identification of and intervention for ASD.

Association between maternal insecticide use and otitis media in one-year-old children in the Japan Environment and Children's Study.

Otitis media (OM) is common among young children and is related to hearing loss. We investigated the association between maternal insecticide use, from conception to the first and second/third trimesters, and OM events in children in the first year of age. Data from Japan Environment and Children's Study were used in this prospective cohort study. Characteristics of patients with and without history of OM during the first year of age were compared. The association between history of OM in the first year and insecticide use was evaluated using logistic regression analysis. The study enrolled 98,255 infants. There was no significant difference in the frequency of insecticide use between groups. Insecticide use of more than once a week from conception to the first trimester significantly increased the occurrence of OM in children in the first year (odds ratio [OR] = 1.30, 95% confidence interval [CI] 1.01-1.67). The association between OM in the first year and insecticide use from conception to the first trimester was only significant in the group without daycare attendance (OR 1.76, 95% CI 1.30-2.38). Maternal insecticide use more than once a week from conception to the first trimester significantly increased OM risk in offspring without daycare attendance.

Angiographic diagnosis for accurate assessment of congenital porto-systemic shunt and extrahepatic portal vein obstruction in children.

BACKGROUND: Congenital porto-systemic shunt (CPSS) is a rare disease and can cause fatal complications. Accurate angiographic assessment is mandatory for proper treatment. Although technically difficult, we developed assessment techniques and assessed their accuracy. One technique came from evaluating patients with extrahepatic portal vein obstruction (EHPVO). METHODS: We conducted a single center retrospective study to evaluate the efficacy of angiographic diagnostic procedure for the assessment of CPSS and EHPVO, and its impact on patients' subsequent interventions and clinical course. Eight patients with CPSS and two patients with EHPVO who underwent diagnostic angiography were included. Assessment of the intrahepatic portal vein was performed in all patients. The route of the shunt, and portal vein pressure under shunt occlusion, were also evaluated for patients with CPSS. Evaluation was first attempted with a balloon angiographic catheter (standard method). Three additional techniques were performed as needed: (i) direct wedge-catheter injection without balloon inflation, (ii) use of occlusion balloon in two patients, and (iii) hybrid angiography with sheath placement directly into the superior mesenteric vein. RESULTS: The standard method was sufficient in four patients. On the other hand, all three techniques were required in two patients each. One lost contact during follow up, but all other patients underwent optimal intervention. There were no complications related to the angiographic procedure. CONCLUSIONS: Use of direct wedge-catheter injection without balloon inflation, occlusion balloon, and hybrid catheterization improved the diagnostic yield in patients with CPSS or EHPVO.

Successful transcatheter closure of coronary artery fistula in a patient with anomalous aortic origin of the left main coronary artery from the right aortic sinus.

Transcatheter closure is an established method to treat coronary artery fistula (CAF). We present transcatheter closure in a 6-year-old girl with CAF and anomalous aortic origin of the left main coronary artery from the right aortic sinus. The CAF originated from the left coronary artery (LCA), coursed through the interventricular septum (intraseptal course) with prominent dilation, and drained into the right ventricular outflow tract. She underwent transcatheter closure and was in a stable condition at the 3-year follow-up with regression of the dilated portion of the intraseptal-type LCA. Hence, transcatheter closure of CAF is feasible in patients with anomalous origins of coronary arteries. .

Successful staged repair of pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries in an extremely low birth weight infant.

An extremely low birth weight infant (810 g) was born with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries accompanied by pulmonary overcirculation, which eventually resulted in intestinal hypoperfusion and focal intestinal perforation from the very early stage of life. Based on the echographic findings, we performed banding operations twice to regulate the pulmonary blood flow on day 2 and day 9. At 6 months of age, a definitive repair simultaneous with unifocalization of major aortopulmonary collateral arteries was performed. At 1 year of age, the right ventricle/left ventricle pressure ratio was 0.44 after balloon angioplasty was performed for the right-sided pulmonary artery stenosis. The patient is in a stable condition and was followed-up for more than 2 years after definitive repair. This is the first known successful repair of pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries in an extremely low birth weight infant.

[Joint Cardiovascular Surgeries of Two Hospitals in Shizuoka for Adult Congenital Heart Disease (ACHD) Patients].

BACKGROUND: As for the medical management including surgery for the patients with adult congenital heart disease(ACHD), it may be difficult for most hospitals other than that have both adult/congenital cardiologists/cardiovascular surgeons. Between Shizuoka Prefectural General Hospital and Mt. Fuji Shizuoka Children's Hospital, medical stuff and information have been shared for these 4 years. And joint cardiovascular surgeries have started since 2015 autumn at Shizuoka Prefectural General Hospital. PURPOSE: The contents and the results of these joint operations were evaluated. PATIENTS AND METHODS: Thirteen joint operations were performed and median age at operation was 55 years old( male 3, female 10). The original diagnosis was tetralogy of Fallot/pulmonary atresia with ventricular septal defect 6, ventricular septal defect( VSD)±pulmonary stenosis 4, atrioventicular septal defect/two chamber right ventricle/Ebstein's anomaly 1 ( each). The procedures were pulmonary valve replacement/right ventricle out flow tract reconstruction 7, mitral valve plasty/tricuspid annuloplasty 4, Bentall 2, VSD closure 2 etc.(included multiple choices). RESULTS: There was no early mortality. One late mortality was occurred 17 months after the surgery due to acute myeloid leukemia. General conditions in other patients have been feasible and most of them were followed in Shizuoka Prefectural General Hospital. CONCLUSIONS: The results of the joint operations were feasible in the present study. Our joint project may become more important in the future.

Two closely spaced mutations in cis result in Ullrich congenital muscular dystrophy.

A 2-year-old boy was diagnosed with Ullrich congenital muscular dystrophy (UCMD) by muscle biopsy. COL6A3 gene analysis by next-generation sequencing revealed two heterozygous splice-site mutations (c.6283-1 G > G/T and c.6310-2 A > A/T), whereas normal mRNA was produced. Genomic DNA analysis revealed two mutations located on the same allele; however, no mutation was detected in either parent. These results indicated that two closely spaced de novo mutations resulted in the autosomal dominant UCMD.

Late-onset ornithine transcarbamylase deficiency caused by a somatic mosaic mutation.

An 18-month-old boy was diagnosed with late-onset ornithine transcarbamylase deficiency. Genetic analysis revealed a mosaic frameshift mutation (p.Q279fs) in the OTC gene. Despite the presence of a null mutation, he exhibited a milder phenotype, suggesting that the wild-type allele could rescue the function of OTC. The presence of mosaicism has great effects on the clinical phenotype and recurrence-risk assessment, which should be taken into consideration for genetic counseling.

Liver Cirrhosis and/or Hepatocellular Carcinoma Occurring Late After the Fontan Procedure　- A Nationwide Survey in Japan.

BACKGROUND: Fontan-associated liver disease (FALD) is an important late complication involving liver dysfunction, such as liver cirrhosis (LC) and hepatocellular carcinoma (HCC), in patients undergoing the Fontan procedure. However, the prevalence, clinical manifestation, and methods of diagnosis of FALD are still not well established.Methods and Results:This study comprised 2 nationwide surveys in Japan. First, the prevalence of LC and/or HCC in patients undergoing the Fontan procedure was determined. Second, clinical manifestations in patients with LC and/or HCC were analyzed, along with data from blood tests, echocardiography, and right heart catheterization. In the 1st survey, of the 2,700 patients who underwent the Fontan procedure, 31 were diagnosed with LC and/or HCC (1.15%), and 5 died due to liver diseases (mortality: 0.19%). In the 2nd survey, data were collected from 17 patients (12 with LC, 2 with HCC, and 3 with LC+HCC. Of these 17 patients, 5 died (mortality: 29.4%). The mean age at diagnosis of LC and HCC was 23 and 31 years, respectively. Computed tomography followed by ultrasound was most frequently used for diagnosis. Blood tests revealed low platelet counts, increased hemoglobin, aspartate aminotransferase, γ-guanosine triphosphate, and total bilirubin levels, and an elevated international normalized ratio of prothrombin time. CONCLUSIONS: LC and/or HCC in patients undergoing the Fontan procedure were not rare late complications and were associated with high mortality rates.

Risk factors and prevention for surgical intestinal disorders in extremely low birth weight infants.

PURPOSE: Surgical intestinal disorders (SID), such as necrotizing enterocolitis (NEC), focal intestinal perforation (FIP), and meconium-related ileus (MRI), are serious morbidities in extremely low birth weight (ELBW, birth weight <1000 g) infants. From 2010, we performed enteral antifungal prophylaxis (EAP) in ELBWI to prevent for SID. The aim of this study was to identify disease-specific risk factors and to evaluate the efficacy of prevention for SID in ELBW infants. METHODS: A retrospective chart review of all consecutive patients between January 2006 and March 2015, which included 323 ELBW infants who were admitted to Shizuoka Children's Hospital, was conducted. RESULTS: The number of infants with NEC, FIP, and MRI was 9, 12, and 13, respectively; 28 in 323 ELBW infants died. The control group defined the cases were not SID. In-hospital mortality was higher in infants with NEC relative to those in the control group. On logistic regression analysis, low gestational age and cardiac malformations were associated with increased risk of NEC. IUGR were associated with increased risk of MRI. EAP decreased risk of NEC and FIP. Low gestational weight and NEC were associated with increased risk of death. CONCLUSION: Survival to hospital discharge after operation for NEC in ELBW infants remains poor. EAP decreased risk of NEC and FIP in ELBW infants.

A premature low-birth-weight infant with congenital complete atrioventricular block and myocarditis successfully treated by staged pacemaker implantation.

Congenital complete atrioventricular block is a known lethal condition. Although antenatal diagnosis and the technical advances of pacemaker treatment have reduced its mortality, treatment of premature babies with significant myocardial damage remains a challenge. In this paper, we report the case of a premature low-birth-weight infant with congenital complete atrioventricular block and extremely low ventricular rate, fetal hydrops, and myocarditis who was successfully treated with staged permanent pacemaker implantation.

Cardiac fetal ultrasonographic parameters for predicting outcomes of isolated left-sided congenital diaphragmatic hernia.

BACKGROUND: The purpose of this study was to investigate fetal cardiac ultrasonographic parameters in relation to the outcomes of patients with isolated left-sided congenital diaphragmatic hernia (CDH). METHODS: Subjects comprised 33 fetuses with fetal CDH and 99 control fetuses without cardiac and lung anomalies. Three parameters, cardiothoracic area ratio (CTAR), the ratio of the diameter of the main pulmonary artery to that of the ascending aorta (MPA/AAo), and the ratio of the diameter of the tricuspid valve to that of the mitral valve (TV/MV) were compared between fetal CDH and control subjects and between survival (SG) and non-survival (NSG) groups. RESULTS: All three parameters differed significantly between CDH and control fetuses. Significant differences between SG and NSG were observed in CTAR and TV/MV ratio, but not in MPA/AAo ratio before and after 32 gestational weeks. A significant increase in the TV/MV ratio was noted along with an increase in gestational age. A TV/MV ratio of >1.72 discriminated non-survivors from survivors with better sensitivity and specificity. CONCLUSIONS: Fetal cardiac ultrasonography provides useful information for predicting the outcomes of isolated left-sided CDH. The TV/MV ratio was considered a reliable indicator that reflected outcomes of isolated left-sided CDH.

Laparoscopic Toupet Fundoplication using an Air Seal Intelligent Flow System and Anchor Port in a 1.8-kg infant: A Technical Report.

INTRODUCTION: We report a case of a 1.8-kg infant who had laparoscopic Toupet fundoplication (LTF) using the AirSeal Intelligent Flow System and Anchor Port (AP). MATERIALS AND SURGICAL TECHNIQUE: Our case had severe gastroesophageal reflux in association with genetic and cardiac anomalies. Despite the patient being continuously fed, persistent vomiting caused failure to thrive, and LTF was performed at 4 months of age when he weighed 1.8 kg. The AirSeal Intelligent Flow System is a novel laparoscopic CO2 insufflation system that improves the visual field by constantly evacuating smoke and providing a more stable pneumoperitoneum. The AP is a recently developed, stretchable, elastomeric, low-profile cannula. Three 5-mm AP were inserted: one subumbilically for the scope and one in both the right and left upper abdomen for the surgeon. A 5-mm AirSeal trocar was inserted in the left lower abdomen for the assistant. The gastrosplenic ligament was dissected free, and the intra-abdominal esophagus was prepared. A posterior hiatoplasty was performed, followed by the 270° fundoplication. During the fundoplication, the esophagus was fixed to the crus and then the right and left wraps were fixed to the esophagus. Pneumoperitoneum was maintained stably throughout the LTF procedure, with optimal operative field. Total operating time for LTF was 90 min. Body temperature dropped from 37.4°C to 35.7°C during pneumoperitoneum but resolved once pneumoperitoneum was ceased. Postoperative progress was uneventful, and an upper gastrointestinal study on postoperative day 2 showed no residual gastroesophageal reflux. DISCUSSION: We believe the AirSeal Intelligent Flow System and AP contributed to the successful completion of LTF in a 1.8-kg infant.

Unilateral pulmonary agenesis associated with oesophageal atresia and tracheoesophageal fistula: A case report with prenatal diagnosis.

We describe herein a case of unilateral pulmonary agenesis (PA) with oesophageal atresia (EA)/tracheoesophageal fistula (TEF) that was diagnosed prenatally and repaired by esophagoesophagostomy with stable postoperative course. The patient was born at 34 weeks gestation, after ultrasonography at 22 weeks gestation showed possible right-sided diaphragmatic eventration or PA and EA was subsequently suspected due to hydramnios. The initial X-ray showed mediastinal shift to the right, and coil up sign of the nasogastric tube, without intracardiac anomaly. Immediately after the diagnosis of EA/TEF and unilateral PA on day 0, the patient was intubated in the operating room, and a gastrostomy tube was placed. After pulmonary status stabilized, at 4 days old, EA/TEF was repaired through a thoracotomy in the right 4 th intercostal space. The right main bronchus was noted to continue into the distal oesophagus; this fistula was ligated and divided, and a single-layer esophagoesophagostomy was performed under mild tension with one vertebral gap. The neonate was maintained on mechanical ventilation and gradually weaned to extubation at 7 days old. The postoperative course was uneventful, with the exception of prolonged jaundice that emerged at 3 months old. Laparoscopic cholangiography at that time excluded biliary atresia, and jaundice resolved spontaneously. The patient has not shown any respiratory symptoms or feeding difficulties as of the 12-month follow-up.

Strong micro-dielectric environment effect on the band gaps of (n,m)single-walled carbon nanotubes.

The electronic states of carbon nanotubes are one of the most fundamental properties of the nanotubes. We now describe the finding that the band gaps of (n,m)SWNTs are strongly affected by the change in microdielectric environments around the isolated nanotubes. In situ photoluminescence (PL) spectroelectrochemistry of the films containing 15 isolated (n,m)single-walled carbon nanotubes (SWNTs) cast on ITO electrodes in organic solvents including DMSO, acetonitirile, DMF, THF, and chloroform was completed and then the oxidation and reduction potentials, and band gaps (ΔE(electr)) of the (n,m)SWNTs in the solvents were determined. We have discovered that the ΔE(electr) of the (n,m)SWNTs become greater as the solvent dielectric constants decreased, which is in sharp contrast to the optical band gaps (ΔE(opt)) that show virtually no solvent dependence. Such a strong solvent dependence of the electrochemical band gaps is due to the difference in the solvation energy of the charged SWNTs produced during the electrochemical processes. The ΔE(electr) of both mod types of the SWNTs, mod = 1 and mod = 2, linearly increased versus the reciprocal of the tube diameter, which agrees with the theory. Moreover, the states of the π-electrons in the SWNTs were evaluated from the dependence of the band gaps on the diameter of the SWNTs. Furthermore, the states of the π-electrons on the sidewalls of the SWNTs were evaluated using the γ(0) values, a parameter representing the measure of the stability or the degree of delocalization of π-electrons in the sidewall of the SWNTs, and revealed that the γ(0) values of the mod = 1 and mod = 2 SWNTs increased with a decrease in the dielectric constants of the solvents in the range of 38-79. This study has enabled us to understand the essential electronic properties of the carbon nanotubes.

Efficient solubilization of single-walled carbon nanotubes using tea solutions.

Here we describe the finding that oolong tea and black tea act as excellent carbon nanotube solubilizers to produce individually dissolved single-walled carbon nanotubes (SWNTs), which have been revealed using visible-near IR absorption, photoluminescence and Raman spectroscopy as well as AFM study. The oolong tea solution has a tendency to individually dissolve metallic SWNTs that can be detected by 514 nm-excition, and in solution, the (11,3)SWNTs enriched and (11,0)SWNTs that are contained in as-produced SWNTs were very few. Black tea solution shows similar tendency, while the separation performance was weaker compared to that of the oolong tea. We also used epigallocatechin gallate to solubilize the SWNTs and shed light on the mechanism of the SWNT dissolution. Tea contains numerous components with antioxidant activities; therefore biological and biomedical applications using the present soluble nanotubes might be of interest.