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Objectives . This study aims to report clinical features and treatment outcomes of 16 cases diagnosed with post-influenza encephalopathy/encephalitis. Methods . We recorded clinical characteristics of 16 pediatric patients diagnosed with post-influenza encephalopathy/encephalitis at the Vietnam National Children's Hospital from January 2019 to January 2021. Results . There were 87.5% infected with influenza A, with influenza A/H1pdm09 and influenza A/H3 accounting for 88.9% and 11.1% respectively, and 12.5% of participants infected with influenza B. The time from onset to the appearance of neurological symptoms was 3 days, of which perceptual changes (93.8%), hypertonia (75%), and seizures (43.8%) were prevalent neurological symptoms. The majority of cases had normal cerebrospinal fluid. Cranial CT/MRI imaging revealed abnormalities in 87.5% of patients. 56.3% of patients had sequelae, including epilepsy and cerebral palsy; 25% recovered, and 18.8% died after treatment. Conclusions . Influenza-associated encephalitis/encephalopathy is a complication occurring early in children, with high mortality and sequelae rates., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Excessive alcohol consumption is a major global health problem. Individuals with alcoholic liver disease often exhibit elevated serum total bile acids (TBAs). Nevertheless, the extent to which high TBA contributes to alcohol-associated liver disease (AALD) remains elusive. To investigate this, wild-type mice were categorized into normal (nTBA) and high (hTBA) TBA groups. Both groups underwent chronic-binge ethanol feeding for 4 weeks, followed by additional weekly ethanol doses. Ethanol feeding worsened AALD in both male and female mice with elevated serum TBA, characterized by liver dysfunction and steatosis. Decreased hepatic expression of genes involved in mitochondrial β-oxidation and lipid transport in ethanol-fed hTBA mice suggests that altered fatty acid metabolism contributed to AALD. Our findings, which represent the first to link high serum TBA to increased AALD susceptibility, underscore the importance of proactive serum TBA screening as a valuable tool for identifying individuals at high risk of developing AALD., Competing Interests: The authors declare that they have no competing interests., (© 2024 The Author(s).)

Introduction and Importance: Chronic extra-articular infections of the tibial tunnel are rare, and there are only a few cases reported in the literature, so the diagnosis and management of these infections are still unclear., Case Presentation: We report a 36-year-old patient with chronic infection of the tibial tunnel after ACL reconstruction surgery. The patient was treated with arthroscopic debridement of the tibial tunnel and antibiotic cement filling. Seven months postoperative, there were no signs of infection at the surgical site and the knee joint. The patient has no pain, no joint instability, no limitation of range of motion, and no limitation in daily activities., Clinical Discussion: The definitive diagnosis of chronic infection of the tibial tunnel should be carefully based on clinical signs, blood tests, and imaging to rule out combined intra-articular infections. The arthroscopic technique can be a favorable method to control and debride the inflammatory tissue of the tibial tunnel, limiting the recurrence rate postoperatively., Conclusion: Arthroscopic debridement and antibiotic-loaded cement can be considered an alternative to traditional surgical methods in the treatment of chronic infection of the tibial bone tunnel after ACL reconstruction., Level of Evidence: A case report., Competing Interests: Conflict of interest statement The authors declare that they have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Vitamin B 12 is essential for deoxyribonucleic acid synthesis and genome stability. A deficiency of vitamin B 12 is associated with telomere shortening, genomic aging, and increased risk of chronic disease and mortality., Objectives: The study aims to determine the effect of vitamin B 12 supplementation on leukocyte telomere length (LTL) in infants at risk of vitamin B 12 deficiency., Methods: The study was a predefined secondary analysis of a randomized controlled trial enrolling 600 Nepalese infants aged 6 -11 mo, who were supplemented with 2 μg (2-3 recommended daily allowances) vitamin B 12 or placebo daily for 1 y. At the end of the study, LTL was measured in 497 participants. Mean LTL was compared between the treatment arms in the full sample and predefined subgroups based on markers of vitamin B 12 status, hemoglobin, sex, and growth indices., Results: LTL at end-study did not differ between the vitamin B 12 and placebo arm with a standardized mean difference (95% confidence interval) of 0.04 (-0.14, 0.21). There was no effect of vitamin B 12 on LTL in any of the subgroups., Conclusions: Providing daily vitamin B 12 for 1 y during infancy in a population at risk of vitamin B 12 deficiency does not affect LTL. This trial was registered at clinicaltrials.gov as NCT02272842., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Leucine rich repeat kinase 2 (LRRK2) is a large multidomain protein containing two catalytic domains, a kinase and a GTPase, as well as protein interactions domains, including a WD40 domain. The association of increased LRRK2 kinase activity with both the familial and sporadic forms of Parkinson's disease has led to an intense interest in determining its cellular function. However, small molecule probes that can bind to LRRK2 and report on or affect its cellular activity are needed. Here, we report the identification and characterization of the first high-affinity LRRK2-binding designed ankyrin-repeat protein (DARPin), named E11. Using cryo-EM, we show that DARPin E11 binds to the LRRK2 WD40 domain. LRRK2 bound to DARPin E11 showed improved behavior on cryo-EM grids, resulting in higher resolution LRRK2 structures. DARPin E11 did not affect the catalytic activity of a truncated form of LRRK2 in vitro but decreased the phosphorylation of Rab8A, a LRRK2 substrate, in cells. We also found that DARPin E11 disrupts the formation of microtubule-associated LRRK2 filaments in cells, which are known to require WD40-based dimerization. Thus, DARPin E11 is a new tool to explore the function and dysfunction of LRRK2 and guide the development of LRRK2 kinase inhibitors that target the WD40 domain instead of the kinase., Competing Interests: Conflicts of interest SRP is a consultant for Schrodinger and Stoke Therapeutics. AP is a co-founder and shareholder of Molecular Partners who are commercializing the DARPin technology. All other authors do not have any conflicts to report with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To improve and rationalize the detection of carbapenemase-producing Enterobacterales (CPE) in rectal swabs in a high-prevalence and resource-constrained setting, addressing surveillance challenges typically encountered in laboratories with limited resources., Methods: A point prevalence survey (PPS) was conducted on 15 August 2022, in a provincial children's hospital in northern Vietnam. Rectal swab samples of all admitted children were collected and plated on a selective medium for carbapenem-resistant Enterobacterales (CRE). Species identification and antimicrobial susceptibility testing (AST) were performed by MALDI-TOF, and VITEK2 XL and interpreted according to CLSI breakpoints (2022). Carbapenemases were detected by the carbapenem inactivation method (CIM) and quantitative real-time PCR (qRT-PCR)., Results: Rectal swab samples were obtained from 376 patients. Of 178 isolates growing on the CRE screening agar, 140 isolates were confirmed as Enterobacterales of which 118 (84.3%) isolates were resistant to meropenem and/or ertapenem. CIM and PCR showed that 90/118 (76.3%) were carbapenemase producers. Overall, 83/367 (22.6%) were colonized by CPE. Klebsiella pneumoniae , Escherichia coli and Enterobacter cloacae complex were the most common CPE detected, with NDM as the predominant carbapenemase (78/90; 86.7%). Phenotypic resistance to meropenem was the best predictor of CPE production (sensitivity 85.6%, specificity 100%) compared with ertapenem resistance (95.6% sensitivity, 36% specificity). CIM was 100% concordant with PCR in detecting carbapenemases., Conclusions: These findings underscore the effectiveness of meropenem resistance as a robust indicator of the production of carbapenemases and the reliability of the CIM method to detect such carbapenemases in resource-limited settings where the performance of molecular methods is not possible., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

The eradication of many cancers has proven challenging due to the presence of functionally and genetically heterogeneous clones maintained by rare cancer stem cells (CSCs), which contribute to disease progression, treatment refractoriness, and late relapse. The characterization of functional CSC activity has necessitated the development of modern clonal tracking strategies. This review describes viral-based and CRISPR-Cas9-based cellular barcoding, lineage tracing, and imaging-based approaches. DNA-based cellular barcoding technology is emerging as a powerful and robust strategy that has been widely applied to in vitro and in vivo model systems, including patient-derived xenograft models. This review also highlights the potential of these methods for use in the clinical and drug discovery contexts and discusses the important insights gained from such approaches., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)