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Abstract: Protobothrops (formerly Trimeresurus) elegans, a Crotalinae snake, inhabits Ishigaki and Iriomote islands of the Sakishima Islands of Japan which are located between Okinawa island of Japan and Taiwan. Two phospholipase A2 (PLA2) isozymes were purified to homogeneity from P. elegans venom and sequenced. This led to a discovery of novel PLA2 isozymes with Arg at position 49, that is, [Arg49]PLA2 forms, named PeBP(R)-I and PeBP(R)-II. They are polymorphic at position 3, Val for PeBP(R)-I and Ile for PeBP(R)-II. The cDNAs encoding PeBP(R)-I and PeBP(R)-II were cloned. The cDNA encoding an [Asp49]PLA2 named PePLA2 was also obtained. In contrast to PLA2 isozymes from Protobothrops genus with 122 amino acid residues, PeBP(R)-I and PeBP(R)-II are composed of 121 amino acid residues due to lack of Pro at position 90. They exhibited necrotic and edema-inducing activities but no hemorrhagic activity was detected. A phylogenetic tree constructed for venom PLA2 isozymes of Protobothrops genus and of related genera in the southwestern islands of Japan and Taiwan revealed that PeBP(R)-I and PeBP(R)-II of P. elegans are evolutionarily much closer to PmK49PLA2, a [Lys49]PLA2, from P. mucrosquamatus (Taiwan) than BPI and BPII, both [Lys49]PLA2 forms, from P. flavoviridis (Amami-Oshima and Tokunoshima islands of Japan). Such evolutionary relationships are also seen in neutral [Asp49]PLA2 isozymes from the three Protobothrops species. Thus, P. elegans is the species much closer to P. mucrosquamatus than P. flavoviridis. Their evolutionary distances seem to be well related to geological history of the islands where they have lived. In addition, it was clearly noted that Ovophis okinavensis (Amami-Oshima), which had formerly belonged to the Trimeresurus genus, and Trimeresurus stejnegeri (Taiwan) are the species fairly distant from Protobothrops genus. [Copyright &y& Elsevier]

Information on the epidemiology and cause-specific clinical features of pediatric meningitis and encephalitis is limited, owing to conventional laboratory methods' limitations in identifying causative pathogens. The FilmArray Meningitis/Encephalitis (FA-M/E) panel, a molecular diagnostic tool, can detect 14 pathogens within 1 hour. We investigated meningitis and encephalitis epidemiology among children in Japan and FA-M/E panels' utility in their clinical management. This cross-sectional study was conducted among children aged 0-18 years admitted to seven regional hospitals in western Japan between October 2022 and September 2023. Cerebrospinal fluid (CSF) samples were collected from 221 children and tested using the FA-M/E panel. Clinical and microbiological data were reviewed retrospectively. Fifty-eight patients tested positive using the FA-M/E panel. Viral and bacterial pathogens were detected in 49 and nine cases, respectively. Human parechovirus and enterovirus occurred mainly in epidemic clusters during the summer and were primarily detected in young infants. Patients who tested positive for human parechovirus had a significantly higher frequency of sepsis-like manifestations and a lower frequency of CSF pleocytosis than did those who tested positive for enterovirus. CSF pleocytosis was absent in 30 patients who tested positive using the FA-M/E panel. Among the patients who tested positive for bacteria, three of the nine were not diagnosed using conventional culture methods, owing to prior antimicrobial therapy. The FA-M/E panel can identify bacterial and viral pathogens causing pediatric meningitis and characterize the epidemiology in local communities.IMPORTANCECulture and polymerase chain reactions have traditionally been used to identify microorganisms causing pediatric meningitis and encephalitis. However, the methods currently used to identify the causative microorganisms are limited, particularly in general hospitals. The FilmArray Meningitis/Encephalitis (FA-M/E) panel, a fully automated genetic testing system, can detect 14 pathogens using the multiplex polymerase chain reaction method. This study described the epidemiology of pediatric meningitis and encephalitis in Japan. The microorganisms causing acute meningitis and encephalitis in children in Japan were identified using the FilmArray Meningitis/Encephalitis panel. Testing cerebrospinal fluid using the FA-M/E panel is useful for the identification of the pathogen in children with community-acquired acute meningitis and encephalitis. This increases knowledge on the epidemiology and clinical manifestations of acute meningitis and encephalitis caused by specific pathogens and can be used to facilitate optimal patient management., Competing Interests: The authors declare no conflict of interest.

Objective: This study aimed to evaluate whether elevated urine desmosine levels at 3 weeks of age were associated with severe radiological findings, bronchopulmonary dysplasia (BPD), and post-prematurity respiratory disease (PRD) in extremely preterm (EP) or extremely low birth weight (ELBW) infants., Study Design: This study recruited 37 EP (22-27 completed weeks) or ELBW (<1,000 g) infants. Urine was collected between 21 and 28 postnatal days, and desmosine was measured using an enzyme-linked immunosorbent assay kit; the urine creatinine level was also measured. Bubbly/cystic lungs were characterized by emphysematous chest X-rays on postnatal day 28. Furthermore, provision of supplemental oxygen or positive-pressure respiratory support at 40 weeks' postmenstrual age defined BPD, and increased medical utilization at 18 months of corrected age defined PRD. The desmosine/creatinine threshold was determined by receiver operating characteristic analysis. The adjusted risk and 95% confidence interval (CI) for elevated urine desmosine/creatinine levels were estimated by logistic regression analysis., Results: Elevated urine desmosine/creatinine levels higher than the threshold were significantly associated with bubbly/cystic lungs (8/13 [61.5%] vs. 2/24 [8.3%], p  = 0.001), BPD (10/13 [76.9%] vs. 8/24 [33.3%], p  = 0.02), and PRD (6/13 [46.2%] vs. 2/24 [8.3%], p  = 0.01). After adjusting for gestational age, birth weight, and sex, the urine desmosine/creatinine levels were significantly higher in those who were highly at risk of bubbly/cystic lungs (odds ratio [OR], 13.2; 95% CI, 1.67-105) and PRD (OR, 13.8; 95% CI, 1.31-144)., Conclusion: Elevated urine desmosine/creatinine levels on the third postnatal week were associated with bubbly/cystic lungs on day 28 and PRD at 18 months of corrected age in EP or ELBW infants., Key Points: · Urine desmosine was prospectively measured in 3-week-old EP/ELBW infants.. · Elevated urine desmosine levels were associated with emphysematous radiological findings on day 28, PRD at 18 months of corrected age.. · Urine desmosine may be a promising biomarker indicating lung damage in EP/ELBW infants.., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Although furosemide is used during cyclooxygenase (COX) inhibitor therapy for patent ductus arteriosus (PDA), there are concerns regarding increased ductal closure failure and acute renal failure (ARF). This systematic review explores the effects of furosemide during COX inhibitor therapy., Methods: We searched MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi databases for randomized clinical trials that assessed furosemide during COX inhibitor therapy for PDA in preterm infants. The primary outcome measure was PDA closure failure. Mortality and other complications were also assessed. The risk of bias was assessed using the Cochrane risk-of-bias tool for randomized control trials, and the certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation criteria., Results: Overall, three trials involving 121 patients were included in the analysis. The overall incidence of PDA closure failure was 28%. Although the result of PDA closure failure, mortality, and ARF were obtained, other outcomes were not described in any of the studies. The risk of bias was high. The risk of PDA closure failure did not increase with furosemide administration. Furosemide was not associated with decreased mortality but was associated with an increased risk of ARF (risk ratio, 4.96 [95% confidence interval: 1.80-13.6]). The certainty of evidence for all outcomes was very low., Conclusion: Although furosemide is not associated with an increased risk of PDA closure failure or mortality, the risk of ARF increases after furosemide administration during COX inhibitor therapy., (© 2024 The Author(s). Pediatrics International published by John Wiley & Sons Australia, Ltd on behalf of Japan Pediatric Society.)