Thrombopoietin exerts a neuroprotective effect by inhibiting the suppression of neuronal proliferation and axonal outgrowth in intrauterine growth restriction rats.

Chronic hypoxia in utero causes intrauterine growth restriction (IUGR) of the fetus. IUGR infants are known to be at higher risk for neurodevelopmental disorders, but the mechanism is unclear. In this study, we analyzed the structure of the cerebral cortex using IUGR model rats generated through a reduced uterine perfusion pressure operation. IUGR rats exhibited thinner cerebral white matter and enlarged lateral ventricles compared with control rats. Expression of neuron cell markers, Satb2, microtubule-associated protein (MAP)-2, α-tubulin, and nestin was reduced in IUGR rats, indicating that neurons were diminished at various developmental stages in IUGR rats, from neural stem cells to mature neurons. However, there was no increase in apoptosis in IUGR rats. Cells positive for Ki67, a marker of cell proliferation, were reduced in neurons and all glial cells of IUGR rats. In primary neuron cultures, axonal elongation was impaired under hypoxic culture conditions mimicking the intrauterine environment of IUGR infants. Thus, in IUGR rats, chronic hypoxia in utero suppresses the proliferation of neurons and glial cells as well as axonal elongation, resulting in cortical thinning and enlarged lateral ventricles. Thrombopoietin (TPO), a platelet growth factor, inhibited the decrease in neuron number and promoted axon elongation in primary neurons under hypoxic conditions. Intraperitoneal administration of TPO to IUGR rats resulted in increases in the number of NeuN-positive cells and the area coverage of Satb2. In conclusion, suppression of neuronal proliferation and axonal outgrowth in IUGR rats resulted in cortical thinning and enlargement of lateral ventricles. TPO administration might be a novel therapeutic strategy for treating brain dysmaturation in IUGR infants.

Efficacy of tolvaptan in an infant with syndrome of inappropriate antidiuretic hormone secretion associated with holoprosencephaly: A case report.

BACKGROUND: Holoprosencephaly (HPE) is a congenital malformation with various degrees of incomplete separation of the cerebral hemispheres due to differentiation disorders of the forebrain. Although HPE with diabetes insipidus due to associated pituitary dysfunction has been reported, HPE with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) is very rare. Tolvaptan, a vasopressin V2 receptor antagonist, is effective in adults with SIADH. However, there is no report of its efficacy in infants with SIADH. The purpose of this report is to demonstrate that tolvaptan is effective for SIADH in infants and that administration of tolvaptan eliminates the need for restriction of water intake and sodium administration. CASE SUMMARY: A 2414-g female infant was born at 38 wk by normal vaginal delivery. Facial anomalies and head magnetic resonance imaging indicated semilobar HPE. After birth, she had hyponatremia due to SIADH and was treated using water and sodium restriction. However, she developed an exaggerated response to the fluid restrictions, resulting in large fluctuations in serum sodium levels. Subsequent administration of tolvaptan improved the fluctuations in serum sodium levels without the need for adjustment of water or sodium administration. Serum sodium was maintained within the normal range after discontinuation of tolvaptan at 80 d of life. There were no side effects, such as hypernatremia or liver dysfunction, during the administration of tolvaptan. CONCLUSION: This is the first report on the safety and efficacy of tolvaptan in an infant with SIADH associated with HPE.

Successful Noninvasive Respiratory Management of an Infant with Bilateral Choanal Atresia and a Supernumerary Nostril Located on the Columella by a Mouthpiece: A Case Report.

BACKGROUND Choanal atresia with a supernumerary nostril located on the columella is extremely rare. Infants are obligate nasal breathers because the oral airway is invariably blocked during calm respiration. Infants breathe through the mouth only during crying, and they only have nasal breathing until 5 months of life. Congenital nasal anomalies have been reported to be fatal from birth, requiring tracheal intubation or tracheostomy in the early postnatal period. In these cases, it is crucial to maintain an adequate airway. CASE REPORT A 2948-g female infant was born at 40 weeks by normal vaginal delivery. Her Apgar scores were 9 and 9 at 1 and 5 min, respectively. She had retractive breathing, cyanosis, and a supernumerary nostril at birth. She had no other anomalies. Computed tomography showed bilateral membranous choanal atresia. She needed nasal continuous positive pressure or a high-flow nasal canula for oxygen desaturation during crying, apnea, and dyspnea. However, her respiratory symptoms did not improve completely. On day 25 of life, she was given a mouthpiece to support mouth breathing. Her respiratory symptoms improved gradually, and she was discharged on day 73 of life with a mouthpiece. CONCLUSIONS A very rare case of choanal atresia with a supernumerary nostril located on the columella was described. A mouthpiece was effective for breathing, obviating the need for emergency surgical intervention in the early postnatal period. Emergency procedures were avoided, probably because this case involved incomplete bilateral membranous choanal atresia rather than complete bony atresia.

Radial nerve palsy caused by a rapidly growing intramuscular hematoma in an infant with biliary atresia: a case report.

BACKGROUND: Biliary atresia (BA) is a rare cause of persistent jaundice in infants that can result in vitamin K malabsorption and vitamin K deficiency bleeding (VKDB). We present an infant with BA who developed a rapidly growing intramuscular hematoma in her upper arm after a vaccination which caused a radial nerve palsy. CASE PRESENTATION: An 82-day-old girl was referred to our hospital because of a rapidly growing left upper arm mass. She had received three doses of oral vitamin K before age 1 month. At age 66 days, she received a pneumococcal vaccination in her left upper arm. On presentation, she showed no left wrist or finger extension. Blood examination revealed direct hyperbilirubinemia, liver dysfunction, and coagulation abnormalities, indicating obstructive jaundice. Magnetic resonance imaging showed a hematoma in the left triceps brachii. Abdominal ultrasonography revealed an atrophic gallbladder and the triangular cord sign anterior to the portal vein bifurcation. BA was confirmed on cholangiography. VKDB resulting from BA in conjunction with vaccination in the left upper arm were considered the cause of the hematoma. The hematoma was considered the cause of her radial nerve palsy. Although she underwent Kasai hepatic portoenterostomy at age 82 days, the obstructive jaundice did not sufficiently improve. She then underwent living-related liver transplantation at age 8 months. The wrist drop was still present at age 1 year despite hematoma resolution. CONCLUSIONS: Delayed detection of BA and inadequate prevention of VKDB can result in permanent peripheral neuropathy.

Hyperglycemia and Lactic Acidosis Associated with Linezolid Therapy in an Extremely Premature Infant.

The use of linezolid is relatively safe for all age categories, including premature infants. The case of an extremely premature infant with hyperglycemia and lactic acidosis associated with linezolid is reported. A 350-g male infant was born at 24 weeks by cesarean section. His Apgar scores were 1 and 1 at 1 and 5 min, respectively. On the day of life (DOL) 7, linezolid was started at a dose of 10 mg/kg/dose every 8 h for a catheter-related blood stream infection caused by methicillin-resistant coagulase-negative Staphylococci. After linezolid was given, serum lactate and glucose levels increased gradually. After discontinuation of linezolid on DOL 16, hyperglycemia and lactic acidosis improved immediately. In conclusion, a rare case of an extremely premature infant with hyperglycemia and lactic acidosis associated with linezolid was reported. It is crucial to monitor glucose levels along with lactate and pH levels during linezolid therapy.

Usefulness of Q-Probe PCR in Detecting Macrolide-Resistant Mycoplasma pneumoniae Infection in Children.

To investigate the usefulness of quenching probe polymerase chain reaction (Q-probe PCR) for the detection of macrolide-resistant Mycoplasma pneumoniae (MP), we retrospectively analyzed the clinical course of 21 children with MP infection. The rate of macrolide-resistant MP was 66.7%. The duration of pyrexia after the initial antibiotic treatment was longer in patients with macrolide-resistant MP infection than in those with macrolide-sensitive MP infection. The duration of pyrexia after Q-probe PCR was not significantly different between patients with macrolide-resistant and -sensitive MP infection. Antibiotic use based on qPCR may reduce the duration of pyrexia. Q-probe PCR is useful in determining the appropriate antibiotics and improves the clinical course of MP infections.

Serum free carnitine levels in children with Kawasaki disease.

BACKGROUND: Carnitine plays an essential role in the transfer of long-chain fatty acids to the mitochondria for ß-oxidation. No study has characterized carnitine in children with Kawasaki disease (KD). The objective of this study was to elucidate the characteristics of serum free carnitine (FC) in hospitalized pediatric patients with KD. METHODS: We retrospectively analyzed 45 patients with KD in whom serum FC levels were measured. We investigated the clinical and laboratory parameters before intravenous immunoglobulin was administered, including serum FC levels, according to the response to intravenous immunoglobulin (IVIG). We also analyzed the relationship among serum FC, laboratory data, and clinical variables. RESULTS: IVIG was effective in 33 children (responders) and was ineffective in 12 children (non-responders). Serum FC levels were higher in non-responders than in responders: 35.3 µmol/L (range, 26.8-118.4 µmol/L) vs 31.4 µmol/L (range, 20.9-81.2 µmol/L), P <0.05. FC levels before IVIG in 80% of responders were below the normal range. The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, and FC were higher in non-responders than in responders. FC levels were correlated with AST (R2 = 0.364, P = 0.0015) and ALT (R2 = 0.423, P < 0.001) levels. CONCLUSIONS: Free carnitine levels were elevated in some patients with KD, especially in those who were refractory to IVIG. Additionally, FC levels in children with KD correlated with ASL and ALT levels.

Usefulness of brain natriuretic peptide to distinguish Kawasaki disease from cervical lymphadenitis.

BACKGROUND: Cervical lymphadenitis (CL) cannot be easily distinguished from Kawasaki disease (KD). We therefore explored whether brain natriuretic peptide (BNP) levels are useful in this context. METHODS: We retrospectively analyzed 14 children with CL and 177 children with KD. Patients with KD were divided into three groups according to their clinical symptoms at hospitalization - 97 patients had typical KD, 35 had node-first KD (NFKD), and 45 had KD without lymphadenopathy. We reviewed data on clinical and laboratory parameters, including serum BNP levels, at hospitalization together with factors that might distinguish KD from CL. RESULTS: Patients with CL were older than those with KD. Serum BNP levels were higher in all the KD groups than in the CL group. Multivariate logistic regression analyses indicated that higher BNP levels were associated with NFKD (odds ratio: 1.12, 95% confidence interval: 1.01-1.25). The receiver operating characteristic curve yielded a BNP cutoff of 18.3 pg/mL, with a sensitivity of 0.680, a specificity of 0.857, and an area under the curve of 0.806 (95% confidence interval: 0.665-0.947). CONCLUSIONS: Serum BNP levels can be used to distinguish KD from CL, especially in patients with NFKD.

X-Ray Single-Grating Interferometry for Wavefront Measurement and Correction of Hard X-Ray Nanofocusing Mirrors.

X-ray single-grating interferometry was applied to conduct accurate wavefront corrections for hard X-ray nanofocusing mirrors. Systematic errors in the interferometer, originating from a grating, a detector, and alignment errors of the components, were carefully examined. Based on the measured wavefront errors, the mirror shapes were directly corrected using a differential deposition technique. The corrected X-ray focusing mirrors with a numerical aperture of 0.01 attained two-dimensionally diffraction-limited performance. The results of the correction indicate that the uncertainty of the wavefront measurement was less than λ/72 in root-mean-square value.

Focus characterization of an X-ray free-electron laser by intensity correlation measurement of X-ray fluorescence.

This paper proposes and demonstrates a simple method using the intensity correlation of X-ray fluorescence to evaluate the focused beam size of an X-ray free-electron laser (XFEL). This method was applied to the sub-micrometre focused XFEL beam at the SPring-8 Angstrom Compact Free Electron Laser, and the beam size evaluated using the proposed method was consistent with that measured using the knife-edge scan method. The proposed method is readily applicable to extremely small X-ray spots and can be applied for the precise diagnostics of sub-10 nm focused X-ray beams which have recently emerged.

Procalcitonin as a Biomarker of Unresponsiveness to Intravenous Immunoglobulin for Kawasaki Disease.

OBJECTIVE: To investigate the usefulness of procalcitonin (PCT) as predictive factors of intravenous immunoglobulin (IVIG)-resistant Kawasaki disease patients. METHODS: We retrospectively analyzed the laboratory data from 215 children with Kawasaki disease treated with IVIG from 2014 to 2019. We analyzed the clinical and laboratory parameters just before the IVIG including serum levels of PCT with respect to the IVIG response. RESULTS: Eventually, 127 patients were analyzed. The median age was 2.4 years. IVIG was effective in 108 children (responders) and was ineffective in 19 (non-responders). Serum PCT concentration was higher in non-responders than those of responders (P < 0.001). Multivariate logistic regression analyses indicated that higher PCT concentration (odds ratio 1.34, 95% confidence interval 1.10-1.64) were associated with IVIG resistance. Analyses of the receiver operating characteristic curve showed that the cutoff value of PCT 2.18 ng/mL had 46.4% of sensitivity and 93.9% of specificity. Receiver operating characteristic analysis yielded an area under the curve of 0.82 (0.72-0.92) to predict IVIG resistance. CONCLUSIONS: Serum PCT value can be an excellent biomarker for predicting unresponsiveness to IVIG with a good discriminatory ability as well as the existing prediction scores.

Generation of an X-ray nanobeam of a free-electron laser using reflective optics with speckle interferometry.

Ultimate focusing of an X-ray free-electron laser (XFEL) enables the generation of ultrahigh-intensity X-ray pulses. Although sub-10 nm focusing has already been achieved using synchrotron light sources, the sub-10 nm focusing of XFEL beams remains difficult mainly because the insufficient stability of the light source hinders the evaluation of a focused beam profile. This problem is specifically disadvantageous for the Kirkpatrick-Baez (KB) mirror focusing system, in which a slight misalignment of ∼300 nrad can degrade the focused beam. In this work, an X-ray nanobeam of a free-electron laser was generated using reflective KB focusing optics combined with speckle interferometry. The speckle profiles generated by 2 nm platinum particles were systematically investigated on a single-shot basis by changing the alignment of the multilayer KB mirror system installed at the SPring-8 Angstrom Compact Free-Electron Laser, in combination with computer simulations. It was verified that the KB mirror alignments were optimized with the required accuracy, and a focused vertical beam of 5.8 nm (±1.2 nm) was achieved after optimization. The speckle interferometry reported in this study is expected to be an effective tool for optimizing the alignment of nano-focusing systems and for generating an unprecedented intensity of up to 1022 W cm-2 using XFEL sources.

Assessment of renal function in Japanese children with malignancies using serum cystatin C.

Several factors besides renal function influence serum cystatin C (CysC) levels. The present study evaluates the value of serum CysC and the equation for CysC based estimated glomerular filtration rate (CysC-eGFR) for Japanese children with malignancies. We collected information at 36 time points from 13 patients aged ≤ 17 years with malignancies. We assessed tumor activity, cell recovery phase after chemotherapy, neutropenia phase, inflammation response and medication with granulocyte-colony stimulating factor, steroid, and levothyroxine as risk factors associated with serum CysC levels. Although no 24-h creatinine clearance (CCr) data collected at 36 time points indicated renal dysfunction, serum CysC levels were above and below the reference values at four and five time points, respectively. The frequency of elevated serum CysC levels was higher in patients without therapy or with stable or progressive disease than among those with a complete or partial response (p = 0.0046). The correlation coefficient between CCr and CysC-eGFR was 0.355 (p = 0.054), but this improved to 0.663 (p = 0.0010) when restricted to patients with a complete or partial response. Levels of serum CysC might become elevated regardless of renal function, and CysC-eGFR might become unpredictable during the active phase of tumors. J. Med. Invest. 65:231-235, August, 2018.

Organocatalytic asymmetric fluorination of α-chloroaldehydes involving kinetic resolution.

In a previous study it was shown that the enantioselective α-fluorination of racemic α-chloroaldehydes with a chiral organocatalyst yielded the corresponding α-chloro-α-fluoroaldehydes with high enantioselectivity. It was also revealed that kinetic resolution of the starting aldehydes was involved in this asymmetric fluorination. This paper describes the determination of the absolute stereochemistry of a resulting α-chloro-α-fluoroaldehyde. Some information about the substrate scope and a possible reaction mechanism are also described which shed more light on the nature of this asymmetric fluorination reaction.

[The association of hypocarnitinemia with enteral diets and antiepileptic drugs in children and adults with severe physical and mental disabilities].

OBJECTIVE: To examine the risk factors of hypocarnitinemia and hypocarnitinemic symptoms in children and adults with severe physical and mental disabilities. METHODS: The status of hypocarnitinemia as well as the related symptoms were assessed in a total of 78 children and adults with severe physical and mental disabilities who were admitted to National Hospital Organization Iou National Hospital. Their enteral diets and the medication of antiepileptic drugs were evaluated. RESULTS: Markedly decreased blood carnitine levels were noted in patients undergoing an enteral diet without carnitine supplementation as well as in those receiving a combination of valproate sodium (VPA) and phenobarbital (PB). These hypocarnitinemic patients tended to have more frequent episodes of hypoglycemia and hyperammonemia. CONCLUSIONS: Supplemental L-carnitine is needed in patients receiving an enteral diet free of carnitine, those with combination therapy of VPA and PB under oral feeding conditions, and those who develop hyperammonemia during VPA therapy. Patients who received a carnitine-supplemented enteral diet maintained their serum carnitine levels with a relatively low supplemental dose of carnitine.

Usefulness of brush cytology combined with pancreatic juice cytology in the diagnosis of pancreatic cancer: significance of pancreatic juice cytology after brushing.

OBJECTIVES: Pancreatic juice cytology (PJC) and brush cytology (BC) performed during endoscopic retrograde cholangiopancreatography could make a definite diagnosis of pancreatic cancer. The aim of this study was to improve the diagnostic value of cytology performed during endoscopic retrograde cholangiopancreatography in the diagnosis of pancreatic cancer. METHODS: The subjects comprised 127 patients with pancreatic ductal adenocarcinoma (PDAC) and 74 with benign pancreatic duct stricture mimicking PDAC. Final diagnosis was confirmed based on histopathology by resection or on more than 1 year of follow up. Pancreatic juice cytology was examined before and after BC. And the sensitivity of PJC combined with BC was examined. RESULTS: No malignancy was detected by PJC or by BC in patients with benign pancreatic duct strictures (specificity, 100%). In those with PDAC, the sensitivity of PJC before and after brushing was 21.3% and 40.9%, respectively; that of BC was 48.8%. Of 65 patients with PDAC, in whom neither PJC before brushing nor BC indicated malignancy, 16 were diagnosed with pancreatic cancer using PJC after brushing. Brush cytology combined with PJC after brushing significantly raised the diagnostic sensitivity for PDAC to 61.4%. CONCLUSIONS: Diagnosis of pancreatic cancer based on BC combined with PJC after brushing was more reliable than PJC before brushing or BC.

Polychlorinated aromatic hydrocarbons in a soil sample measured using gas chromatography/multiphoton ionization/time-of-flight mass spectrometry.

Gas chromatography/multiphoton ionization/time-of-flight mass spectrometry (GC/MPI/TOF-MS) was applied to a soil sample to survey several groups of polychlorinated aromatic hydrocarbons (polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), polychlorinated naphthalenes (PCNs), polychlorinated diphenylethers (PCDEs), and polychlorinated terphenyls (PCTs)). The signal peaks in the two-dimensional display of GC/MS could be easily and accurately assigned from the intensity distribution of the isotope peaks, even in the presence of numerous interfering species. Using this technology, mutual interferences between organochlorine compounds can be readily recognized from the data of the two-dimensional display after a measurement, although the separation of these compounds is sometimes difficult using high-resolution magnetic-sector-type mass spectrometry. This approach, based on MPI, results in less fragmentation, and is useful for the identification of analytes. Thus, GC/MPI/TOF-MS allows for the simultaneous determination of PCDD/Fs and related compounds in real samples containing numerous interfering species.

Purification and characterization of an N-terminal acidic amino acid-specific aminopeptidase from soybean cotyledons (Glycine max).

A novel enzyme that catalyzes the efficient hydrolysis of Glu-Glu was isolated from soybean cotyledons by ammonium sulfate fractionation and successive column chromatographies of Q-sepharose, Phenyl sepharose, and Superdex 200. The apparent molecular mass of this enzyme was found to be 56 kDa and 510 kDa by SDS-polyacrylamide gel electrophoresis and Superdex 200 HR 10/30 column chromatography respectively. The enzyme had high activity against Glu-p-nitroanilide (pNA) and Asp-pNA, whereas Leu-pNA, Phe-pNA, Ala-pNA, and Pro-pNA were not hydrolyzed. The synthetic dipeptides Glu-Xxx and Asp-Xxx were hydrolyzed, but Xxx-Glu was not. The digestion of a Glu-rich oligopeptide, chromogranin A (Glu-Glu-Glu-Glu-Glu-Met-Ala-Val-Val-Pro-Gln-Gly-Leu-Phe-Arg-Gly-NH(2)) using this purified enzyme was also investigated. Glutamic acid residues were cleaved one by one from the N-terminus. These observations indicate that the enzyme removes glutamyl or aspartyl residues from N-terminal acidic amino acid-containing peptides. It is thought that it was an N-terminal acidic amino acid-specific aminopeptidase from a plant.