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Abstract Vutiglabridin, which affects the pharmacokinetics (PKs) of food, is currently under clinical development for the treatment of obesity. This study aimed to evaluate the effects of low‐ and high‐fat meals on PKs of vutiglabridin in healthy male subjects. A randomized, open‐label, single‐dose, three‐period, six‐sequence crossover study was conducted. The subjects received a single oral dose of vutiglabridin 480 mg in a fasted state, 30 min after the intake of a low‐fat meal (total 500–600 kcal, fat content 100–125 kcal) and high‐fat meal (total 800–1000 kcal, fat content 500–600 kcal), with a 21‐day washout period. Geometric mean ratios (GMRs) and 90% confidence intervals (CIs) for maximum plasma concentration (Cmax) and area under the plasma concentration‐time curve to the last measurable timepoint (AUClast) were calculated. After intake of low‐ and high‐fat meals, systemic exposure to vutiglabridin was increased, and the time to reach Cmax (Tmax) was delayed compared to that in the fasted state. The GMRs (90% CIs) of low‐fat meal to fasted state for Cmax and AUClast were 2.14 (1.76–2.60) and 2.15 (1.92–2.42), respectively, and those of high‐fat meal to fasted state were 3.07 (2.53–3.72) and 3.00 (2.67–3.37), respectively. The median Tmax was delayed by 1.5 h in both fed states compared with that in the fasted state. The study drug was well‐tolerated after administration in both the fed and fasted states. Food ingestion substantially increased the extent of oral vutiglabridin absorption in healthy subjects, and this enhancement increased with the fat content of the meal.

The State of Arizona in the south-western United States supports a high diversity of insects. Digitised occurrence records, especially from preserved specimens in natural history collections, are an important and growing resource to understand biodiversity and biogeography. Underlying bias in how insects are collected and what that means for interpreting patterns of insect diversity is largely untested. To explore the effects of insect collecting bias in Arizona, the State was regionalised into specific areas. First, the entire State was divided into broad biogeographic areas by ecoregion. Second, the 81 tallest mountain ranges were mapped on to the State. The distribution of digitised records across these areas were then examined.A case study of surveying the beetles (Insecta, Coleoptera) of the Sand Tank Mountains is presented. The Sand Tanks are a low-elevation range in the Lower Colorado River Basin subregion of the Sonoran Desert from which a single beetle record was published before this study.The number of occurrence records and collecting events are very unevenly distributed throughout Arizona and do not strongly correlate with the geographic size of areas. Species richness is estimated for regions in Arizona using rarefaction and extrapolation. Digitised records from the disproportionately highly collected areas in Arizona represent at best 70% the total insect diversity within them. We report a total of 141 species of Coleoptera from the Sand Tank Mountains, based on 914 digitised voucher specimens. These specimens add important new records for taxa that were previously unavailable in digitised data and highlight important biogeographic ranges.Possible underlying mechanisms causing bias are discussed and recommendations are made for future targeted collecting of under-sampled regions. Insect species diversity is apparently at best 70% documented for the State of Arizona with many thousands of species not yet recorded. The Chiricahua Mountains are the most densely sampled region of Arizona and likely contain at least 2,000 species not yet vouchered in online data. Preliminary estimates for species richness of Arizona are at least 21,000 and likely much higher. Limitations to analyses are discussed which highlight the strong need for more insect occurrence data.

This study aimed to investigate the structural relationships between college educational satisfaction, the helpfulness of career support, and mental health, and how these factors influence the life satisfaction of late adolescents and young adults. The study utilized data from 550 Korean individuals 18-24 years of age who have experienced going to college, collected in the "2021 Youth Socio-Economic Reality Survey" conducted by the National Youth Policy Institute. Data analysis was conducted with SmartPLS 3.0 software, using a structural equation model with the partial least squares method. The mediating impact of mental health was validated using bootstrapping. The study yielded several key findings. First, college educational satisfaction, the helpfulness of career support, and mental health all exerted a significant and positive influence on the life satisfaction of young people. Second, college educational satisfaction was found to significantly positively affect youth's mental health. Third, mental health was identified as playing a significant positive mediating role in the connection between college educational satisfaction and the life satisfaction of young people. The study underscores the importance of enhancing mental health, alongside improving college educational satisfaction and career support, to boost the life satisfaction of young people. Suggestions based on these findings are discussed.

This study investigated the structural relationships among parental respect for children's decision-making, respect for human rights, and self-esteem, and their impact on depression in early adolescents. The study utilized data from 2,747 middle school students who participated in the 2020 Survey on the Current Status of Korean Children's and Youth's Rights conducted by the National Youth Policy Institute. The data were analyzed using a structural equation model based on partial least squares with SmartPLS 3.0. The analysis revealed that both parental respect for children's decision-making and respect for human rights perceived by middle school students had a significant positive impact on self-esteem and a significant negative impact on depression. Furthermore, self-esteem was found to have a significant negative effect on depression. Importantly, self-esteem also played a significant mediating role in the relationship between parental respect for children's decision-making and depression, as well as the relationship between respect for human rights and depression. Therefore, in order to manage depression, it is necessary to develop strategies that encourage parental respect for children's decision-making, promote respect for human rights, and foster self-esteem in early adolescents.

Abstract Therapeutic drug monitoring (TDM) is performed for drugs with narrow therapeutic indices. At Seoul National University Hospital (SNUH) and Seoul National University Bundang Hospital (SNUBH), TDM services are provided for various drugs such as antibiotics and antiepileptics. This study aimed to identify prescription patterns over time using electronic medical records and analyze their relationship with TDM practice. Data were collected from a clinical data warehouse from 2007 to 2020, and the number of patients, total number of drug administration days, serum level tests, and TDM were calculated. The ratio was calculated as the number of serum level tests or TDM to the total number of drug administration days. The study included 136,427 and 162,927 patients from SNUH and SNUBH who were prescribed 11 specified drugs. Each drug showed different prescription patterns over time, and the serum level test and TDM also changed with prescription pattern changes. Serum level test or TDM of antibiotics was frequently used compared to antiepileptics. As some drugs’ usage and test for drugs have decreased newly developed drugs are replacing old drugs. It is recommended that TDM services include these new drugs as well for an effective and safe therapy.

Purpose This study investigated the parenting experiences of mothers of young children born moderate-to-late preterm (MLPT) in South Korea. Methods In this qualitative study, semi-structured focus group interviews were conducted with 10 mothers of MLPT children from infancy to preschool age. The interviews were video-recorded, transcribed verbatim, and analyzed using qualitative content analysis. Results Four categories resulted from the analysis of parenting experiences of mothers with young MLPT children, as follows: "becoming a mother of an early-born child", "difficulties as the primary caregiver for a high-risk child", "helpful social support, but still a lack of professional support for parenting a high-risk child", and "mothers and children growing together". Conclusion Mothers of young MLPT children experienced difficulties due to concerns about their child's health, growth and development, and insufficient child-rearing support. Therefore, social support systems should be strengthened and more aggressive nursing strategies should be adopted for mothers of young MLPT children.

Listeria monocytogenes is a foodborne pathogen that causes listeriosis in humans with severe symptoms. In South Korea, listeriosis had only been reported sporadically among hospitalized patients until the first foodborne outbreak occurred in 2018. In this study, a L. monocytogenes strain responsible for this outbreak (FSCNU0110) was characterized via whole genome sequencing and compared with publicly available L. monocytogenes genomes of the same clonal complex (CC). Strain FSCNU0110 belonged to multilocus sequence typing (MLST)-based sequence type 224 and CC224, and core genome MLST-based sublineage 6,178. The strain harbored tetracycline resistance gene tetM, four other antibiotic resistance genes, and 64 virulence genes, including Listeria pathogenicity island 1 (LIPI-1) and LIPI-3. Interestingly, llsX in LIPI-3 exhibited a characteristic SNP (deletion of A in position 4, resulting in a premature stop codon) that was missing among all CC224 strains isolated overseas but was conserved among those from South Korea. In addition, the tetM gene was also detected only in a subset of CC224 strains from South Korea. These findings will provide an essential basis for assessing the characteristics of CC224 strains in South Korea that have shown a potential to cause listeriosis outbreaks.

Acute intermittent porphyria (AIP) is characterized by acute neurovisceral attacks that are precipitated by the induction of hepatic 5-aminolevulinic acid synthase 1 (ALAS1). In erythropoietic protoporphyria (EPP), sun exposure leads to skin photosensitivity due to the overproduction of photoreactive porphyrins in bone marrow erythroid cells, where heme synthesis is primarily driven by the ALAS2 isozyme. Cimetidine has been suggested to be effective for the treatment of both AIP and EPP based on limited case reports. It has been proposed that cimetidine acts by inhibiting ALAS activity in liver and bone marrow for AIP and EPP, respectively, while it may also inhibit the hepatic activity of the heme catabolism enzyme, heme oxygenase (HO). Here, we show that cimetidine did not significantly modulate the activity or expression of endogenous ALAS or HO in wildtype mouse livers or bone marrow. Further, cimetidine did not effectively decrease hepatic ALAS activity or expression or plasma concentrations of the putative neurotoxic porphyrin precursors 5-aminolevulinic acid (ALA) and porphobilinogen (PBG), which were all markedly elevated during an induced acute attack in an AIP mouse model. These results show that cimetidine is not an efficacious treatment for acute attacks and suggest that its potential clinical benefit for EPP is not via ALAS inhibition.

Traumatic brain injury (TBI) is a major public health problem. Despite considerable research deciphering injury pathophysiology, precision therapies remain elusive. Here, we present large-scale data sharing and machine intelligence approaches to leverage TBI complexity. The Open Data Commons for TBI (ODC-TBI) is a community-centered repository emphasizing Findable, Accessible, Interoperable, and Reusable data sharing and publication with persistent identifiers. Importantly, the ODC-TBI implements data sharing of individual subject data, enabling pooling for high-sample-size, feature-rich data sets for machine learning analytics. We demonstrate pooled ODC-TBI data analyses, starting with descriptive analytics of subject-level data from 11 previously published articles (N?=?1250 subjects) representing six distinct pre-clinical TBI models. Second, we perform unsupervised machine learning on multi-cohort data to identify persistent inflammatory patterns across different studies, improving experimental sensitivity for pro- versus anti-inflammation effects. As funders and journals increasingly mandate open data practices, ODC-TBI will create new scientific opportunities for researchers and facilitate multi-data-set, multi-dimensional analytics toward effective translation.

Listeria monocytogenes is a Gram-positive pathogen responsible for the severe foodborne disease listeriosis. A chromosomal hotspot between lmo0301 and lmo0305 has been noted to harbor diverse restriction modification (RM) systems. Here, we analyzed 872 L. monocytogenes genomes to better understand the prevalence and types of RM systems in this region, designated the immigration control region (ICR). Type I, II, III and IV RM systems were found in 86.1% of strains inside the ICR and in 22.5% of strains flanking the ICR. ICR content was completely conserved within the same multilocus sequence typing-based sequence type (ST), but the same RM system could be identified in diverse STs. The intra-ST conservation of ICR content suggests that this region may drive the emergence of new STs and promote clone stability. Sau3AI-like, LmoJ2 and LmoJ3 type II RM systems as well as type I EcoKI-like, and type IV AspBHI-like and mcrB-like systems accounted for all RM systems in the ICR. A Sau3AI-like type II RM system with specificity for GATC was harbored in the ICR of many STs, including all strains of the ancient, ubiquitous ST1. The extreme paucity of GATC recognition sites in lytic phages may reflect ancient adaptation of these phages to preempt resistance associated with the widely distributed Sau3AI-like systems. These findings indicate that the ICR has a high propensity for RM systems which are intraclonaly conserved and may impact bacteriophage susceptibility as well as ST emergence and stability.

microRNAs (miRNAs) and small interfering RNAs (siRNAs) are 21- to 22-nucleotide RNAs that guide Argonaute-class effectors to targets for repression. In this work, we uncover 5-aminolevulinic acid synthase 1 (ALAS1), the initiating enzyme for heme biosynthesis, as a general repressor of miRNA accumulation. Although heme is known to be a positive cofactor for the nuclear miRNA processing machinery, ALAS1—but not other heme biosynthesis enzymes—limits the assembly and activity of Argonaute complexes under heme-replete conditions. This involves a cytoplasmic role for ALAS1, previously considered inactive outside of mitochondria. Moreover, conditional depletion of ALAS activity from mouse hepatocytes increases miRNAs and enhances siRNA-mediated knockdown. Notably, because ALAS1 is the target of a Food and Drug Administration–approved siRNA drug, agents that suppress ALAS may serve as adjuvants for siRNA therapies. [ABSTRACT FROM AUTHOR]