Antenatal Growth, Gestational Age, Birth, Enteral Feeding, and Blood Citrulline Levels in Very Low Birth Weight Infants.

Early enteral nutrition using reliable biomarkers of intestinal function must be established to improve neurodevelopmental outcomes in very low birth weight infants (VLBWIs). Serum citrulline levels reflect the intestinal function in adults. To elucidate the relationship among antenatal growth, postnatal enteral nutrition, and blood citrulline levels, a retrospective single-center observational study was conducted on 248 VLBWIs born between April 2014 and March 2021. A mixed effect model and post hoc simple slope analysis were used to estimate the correlations between clinical variables and citrulline levels at Early (day 5.1) and Late (day 24.3) postnatal ages. Greater gestational age, birth weight, and amount of enteral nutrition at the time of blood sampling were associated with lower citrulline levels at the Early postnatal age and higher citrulline levels at the Late postnatal age. Provided that Early citrulline levels predominantly reflect the consequence of antenatal citrulline metabolism, it is suggested that fetal growth and maturation are likely to promote citrulline catabolism in utero and its synthesis after birth. With additional insights into the temporal transition point wherein the maturation-dependent balance of citrulline metabolism shifts from catabolism-dominant to synthesis-dominant, citrulline emerges as a potential biomarker for assessing intestinal function and gastrointestinal disorders.

Novel SPEG variants in a neonate with severe dilated cardiomyopathy and relatively mild hypotonia.

Striated muscle preferentially expressed protein kinase (SPEG) variants have been reported to cause centronuclear myopathy associated with cardiac diseases. The severity of skeletal muscle symptoms and cardiac symptoms are presumably related to the location of the variant. Here, we report novel SPEG compound heterozygous pathological variants in a neonate with severe dilated cardiomyopathy and relatively mild hypotonia. This report expands the genotype-phenotype correlations of patients with SPEG variants.

Early immunological responses to the mRNA SARS-CoV-2 vaccine in patients with neuromuscular disorders.

Backgrounds: Intramuscular injection of the SARS-CoV-2 vaccine has raised concerns about its use in patients with neuromuscular disorders (NMDs). We evaluated the response of patients with NMDs to the BNT162b2 vaccine. Methods: Healthy subjects, patients with spinal muscular atrophy (SMA), and patients with Duchenne muscular dystrophy (DMD) were included. All participants received two BNT162b2 doses. SARS-CoV-2 antibody titers at baseline and 2 weeks after each vaccination were compared between groups. Residual muscle volume was evaluated in NMDs group. A questionnaire documented adverse reactions. Results: Eleven patients with NMDs (9 with SMA, 2 with DMD; 7 males; aged 32.7 ± 19.3 years) and 346 healthy subjects (60 males, aged 40.0 ± 12.4 years) were included. Antibody titers (U/mL) were similar between groups (baseline: <0.40 vs. <0.40, first vaccination, 145 ± 258 vs. 103 ± 1192, and second vaccination, 1528 ± 1265 vs. 1429 ± 944; p = 1.000, 0.909, and 0.736, respectively). A negative correlation was found between antibody titers and residual muscle volume but was not significant (Mercuri scale, r = -0.429, p = 0.249; fat infiltration rate, r = -0.194, p = 0.618). The adverse reactions were comparable between groups. Conclusion: The BNT162b2 vaccine is safe and effective in patients with NMDs.

Echovirus Type 7 Virus-Associated Hemophagocytic Syndrome in a Neonate Successfully Treated With Intravenous Immunoglobulin Therapy: A Case Report.

Virus-associated hemophagocytic syndrome (VAHS) in the neonatal period has a high mortality. Although clear diagnostic criteria and treatment methods have not been established, early diagnosis and treatment are critical. However, treatments for VAHS have potentially serious side effects, especially during the neonatal period. Echovirus type 7 can cause maternal infection around parturition and be vertically transmitted to the neonate and induce VAHS. Intravenous immunoglobulin (IVIG) therapy could be a first-line therapy for neonatal VAHS, so that treatments with potentially serious side effects, including cyclosporine A and etoposide, could be avoided. A case of VAHS associated with echovirus type 7 that was successfully treated with IVIG therapy is reported.

Biallelic mutations in SZT2 cause a discernible clinical entity with epilepsy, developmental delay, macrocephaly and a dysmorphic corpus callosum.

Mutations in SZT2 were first reported in 2013 as a cause of early-onset epileptic encephalopathy. Because only five reports have been published to date, the clinical features associated with SZT2 remain unclear. We herein report an additional patient with biallelic mutations in SZT2. The proband, a four-year-old girl, showed developmental delay and seizures from two years of age. Her seizures were not intractable and readily controlled by valproate. She showed mildly dysmorphic facies with macrocephaly, high forehead, and hypertelorism, and also had pectus carinatum. An EEG showed epileptic discharges which rarely occurred. A brain MRI revealed a short and thick corpus callosum. Whole-exome sequencing detected compound heterozygous biallelic mutations (c.8596dup (p.Tyr2866Leufs∗42) and c.2930-17_2930-3delinsCTCGTG) in SZT2, both of which were novel and predicted to be truncating. This case suggested a broad phenotypic spectrum arises from SZT2 mutations, forming a continuum from epileptic encephalopathy and severe developmental delay to mild intellectual disability without epilepsy. The characteristic thick and short corpus callosum observed in 7/8 cases with epilepsy, including the proband, but not in three non-syndromic cases, appears to be specific, and thus useful for indicating the possibility of SZT2 mutations. This feature has the potential to make loss of SZT2 a clinically discernible disorder despite a wide clinical spectrum.

Evidence of capsaicin synthase activity of the Pun1-encoded protein and its role as a determinant of capsaicinoid accumulation in pepper.

BACKGROUND: Capsaicinoids, including capsaicin and its analogs, are responsible for the pungency of pepper (Capsicum species) fruits. Even though capsaicin is familiar and used daily by humans, the genes involved in the capsaicin biosynthesis pathway have not been well characterized. The putative aminotransferase (pAMT) and Pungent gene 1 (Pun1) proteins are believed to catalyze the second to last and the last steps in the pathway, respectively, making the Pun1 protein the putative capsaicin synthase. However, there is no direct evidence that Pun1 has capsaicin synthase activity. RESULTS: To verify that the Pun1 protein actually plays a role in capsaicin production, we generated anti-Pun1 antibodies against an Escherichia coli-synthesized Pun1 protein and used them to antagonize endogenous Pun1 activity. To confirm the anti-Pun1 antibodies' specificity, we targeted Pun1 mRNA using virus-induced gene silencing. In the Pun1-down-regulated placental tissues, the accumulated levels of the Pun1 protein, which was identified on a western blot using the anti-Pun1 antibodies, were reduced, and simultaneously, capsaicin accumulations were reduced in the same tissues. In the de novo capsaicin synthesis in vitro cell-free assay, which uses protoplasts isolated from placental tissues, capsaicin synthesis was inhibited by the addition of anti-Pun1 antibodies. We next analyzed the expression profiles of pAMT and Pun1 in various pepper cultivars and found that high levels of capsaicin accumulation always accompanied high expression levels of both pAMT and Pun1, indicating that both genes are important for capsaicin synthesis. However, comparisons of the accumulated levels of vanillylamine (a precursor of capsaicin) and capsaicin between pungent and nonpungent cultivars revealed that vanillylamine levels in the pungent cultivars were very low, probably owing to its rapid conversion to capsaicin by Pun1 soon after synthesis, and that in nonpungent cultivars, vanillylamine accumulated to quite high levels owing to the lack of Pun1. CONCLUSIONS: Using a newly developed protoplast-based assay for de novo capsaicin synthesis and the anti-Pun1 antibodies, we successfully demonstrated that the Pun1 gene and its gene product are involved in capsaicin synthesis. The analysis of the vanillylamine accumulation relative to that of capsaicin indicated that Pun1 was the primary determinant of their accumulation levels.

Spontaneous movements in the supine position of healthy term infants and preterm infants with or without periventricular leukomalacia.

AIM: The individual motor elements presumed to be essential for motor development were determined from spontaneous movements involving the entire body of normal term and preterm infants. Then, diagnostic items for motor abnormality in infants with periventricular leukomalacia (PVL) were investigated. METHODS: Video recordings of 24 healthy term infants, 21 normal preterm infants (8 males, 13 females; median gestational age 30 weeks; median birth weight 1216g) and 14 preterm infants with PVL (6 males, 8 females; median gestational age 30 weeks; median birth weight 1360g) were analyzed. RESULTS: In healthy term infants, predominant shoulder rotation was noticed until 1 month of age. After 2 months of age, isolated movements of the shoulder, elbow, hip, knee, and ankle frequently emerged. In preterm infants with PVL at the corrected age of 2 months, startle response and predominant shoulder rotation were more frequently seen and isolated neck, shoulder, elbow, hip, knee, and ankle movements were less frequently seen than in the normal preterm infants (Fisher's exact test, p<0.025). INTERPRETATION: At 2 months of age, isolated movements evolve, and their failure to occur is suggested to be a useful sign for the diagnosis of cerebral motor disorders.

Neurodevelopmental outcomes at 18 months' corrected age of infants born at 22 weeks of gestation.

BACKGROUND: Increased survival rates for extremely low birth weight infants have been reported. However, survival rates and prognoses of extremely preterm infants, such as infants born at 22 weeks of gestation, are still poor. OBJECTIVE: To investigate such infants' long-term outcomes, developmental assessments were performed. METHODS: Seven infants with gestational age of 22 weeks were delivered in our hospital from 2005 to 2008. One infant was a stillbirth despite resuscitation in the delivery room. Six infants, 4 boys and 2 girls, with a gestational age of 22 weeks (range 22(3/7)-22(6/7) weeks), were admitted to the neonatal intensive care unit (NICU). Birth weights ranged from 514 to 710 g. None of the infants suffered from sepsis, necrotizing enterocolitis, or severe intraventricular hemorrhage. RESULTS: The survival rate was 85.7% (6/7) as a percentage of deliveries and 100% (6/6) as a percentage of NICU admissions. None of the infants suffered from deafness, blindness, cerebral palsy, or epilepsy. Six infants were available for developmental assessments at 18 months' corrected age. Three infants showed normal developmental quotients, and 3 infants showed developmental delay. CONCLUSION: In our study, all infants admitted to the NICU at a gestational age of 22 weeks were discharged from the hospital alive. This might suggest that infants after 22 weeks' gestation be considered eligible for active treatment in Japan, though considering the size of the material, generalizibility of the results cannot be considered guaranteed.