BVN008, Diphtheria-tetanus-acellular pertussis combined vaccine has no effects on fertility and prenatal and postnatal developmental toxicity in female Sprague-Dawley rats.

Tdap is an acronym for tetanus(T), diphtheria(D), and acellular pertussis(aP), and is a preventive vaccine that combines vaccines against three diseases. BVN008 is a Tdap vaccine designed to protect against three diseases: diphtheria, tetanus, and pertussis. The lower-case "d" and "p" in Td and Tdap means these vaccines use smaller amounts of diphtheria and whooping cough. The lower doses are appropriate for adolescents and adults. The purpose of this study was to identify adverse effects in pregnant or lactating female Sprague-Dawley rats including maternal fertility and toxicity, and development of the embryos, fetus, and pups following intramuscular administration of BVN008. Two groups of 50 female Sprague-Dawley rats were administered four or five intramuscular injections of the vaccine (human dose of 0.5 mL at 4 and 2 weeks before pairing, on gestation day (GD) 8 and 15, and lactation day (LD) 7. A negative control group was administered 0.9% saline at the same dose four or five times. There were no adverse effects on fertility, reproductive performance, or maternal toxicity of the F0 females. There was no effect of developmental toxicity in F1 fetuses and pups including fetal body weight and morphology, postnatal growth, development, and behavior until weaning. Antibodies against tetanus, diphtheria, and pertussis were transferred to the F1 fetuses and F1 pups via placenta and milk. These results demonstrate that BVN008 had no detectable adverse effects in either the F0 female rats, the F1 fetuses or pups.

The effects of parental respect for children's decision-making and respect for human rights on depression in early adolescents: The mediating effect of self-esteem.

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.

Effects of meal type on the bioavailability of vutiglabridin, a novel anti-obesity agent, in healthy subjects.

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.

Effects of transition programmes to adulthood for adolescents and young adults with CHD: a systematic review with meta-analysis.

BACKGROUND: The increased survival rate among individuals with CHD has sparked interest in their transition to adult healthcare. Although there is a general agreement on the importance of transition interventions, the empirical evidence supporting them is insufficient. Therefore, this study aimed to conduct a systematic review and meta-analysis of transition interventions for adult healthcare in adolescents and young adults. METHODS AND RESULTS: A literature search was conducted for studies comparing the quantitative effects of transition interventions with control groups, published up to March 15, 2023, in major databases (CENTRAL, Embase, PubMed, Web of Science, CINAHL, KISS, and KMbase), major clinical trial registries, academic journal sites related to the topic, and grey literature databases. Ten studies involving a total of 1,297 participants were identified. Transition interventions proved effective in enhancing disease-related knowledge (Hedge's g = 0.89, 95% CI = 0.29-1.48) and self-management (Hedge's g = 0.67, 95% CI = 0.38-0.95), as well as reducing loss to follow-up (OR = 0.41, 95% CI = 0.22-0.77). The certainty of evidence for the estimated values of each major outcome was low or very low. CONCLUSIONS: This study supports the implementation of transition interventions by demonstrating that they can improve patients' disease knowledge and self-management, while also promoting treatment continuity. However, since the available data on transition interventions for adolescents and young adults with CHD remain limited, the widespread adoption of structured transition interventions in the future may alter the conclusions of this study. REGISTRATION: URL: https://www.crd.york.ac.uk/PROSPERO. Unique identifier: CRD42023399026.

The impacts of college educational satisfaction and helpfulness of career support on life satisfaction among Korean youth: The mediating role of mental health.

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.

Digital application of three-dimensional diagnosis and treatment with a virtual articulator.

OBJECTIVE: The purpose of this article was to introduce a method for the digital application of three-dimensional (3D) diagnosis and treatment with a virtual articulator and 3D data. CLINICAL CONSIDERATION: With the use of cone-beam computed tomography (CBCT) and intraoral and facial scans, we can create a virtual articulator and evaluate the mandibular position in maximum intercuspation and centric-related occlusion for the patient with an unstable occlusion and temporomandibular disorders (TMD). Based on this, we treated a case using a digital mandibular position indicator (MPI) and fabricated a stabilization splint using a 3D printer. This approach eliminates the traditional impression or model mounting process and the analog face bow transfer. Furthermore, the design of the stabilization splint is accomplished using software. CONCLUSIONS: The approach outlined in this article offers the potential for a digital diagnosis and treatment process by seamlessly integrating CBCT, intraoral scans, and facial scans with a high degree of accuracy. This may enhance precision in diagnosis and treatment planning, especially for patients with complicated TMD, in addition to facilitating effective communication with orthodontic patients who require thorough attention. CLINICAL SIGNIFICANCE: Utilizing a virtual articulator and digital MPI for the occlusal evaluation of patients with TMD and unstable occlusion makes it possible to diagnose and analyze the occlusal condition accurately. This approach also allows for precision and efficiency in treatment.

Draft genome sequences of Listeria monocytogenes strains of sequence type 1733 which constituted a pseudo-outbreak due to contaminated blood agar media.

We report genome sequences of Listeria monocytogenes sequence type (ST) 1733 from a 2013 pseudo-outbreak, where L. monocytogenes isolation from non-sterile sites (urine, wound, or abscess) was an artifact from contaminated sheep blood in the isolation media. Two ST1733 strains from wound and urine in 2005 are also reported.

Impact of moderate-to-late preterm birth on neurodevelopmental outcomes in young children: Results from retrospective longitudinal follow-up with nationally representative data.

This study investigated the relationship between moderate-to-late preterm (MLPT) birth and the risk of neurodevelopmental impairments (NIs) in young children compared with the risks associated with very preterm (VPT) and full-term (FT) birth based on nationally representative large-scale population data. Retrospective follow-up was conducted over 71 months for 738,733 children who were born and participated in the Korean National Health Screening Program for Infants and Children (NHSPIC) between 2011 and 2013. Using a data linkage between the NHSPIC and Korean healthcare claim information, data on birth year, sex, delivery type, birth weight, growth abnormality, gestational age, breastfeeding history, maternal age, NIs, multiple gestation, preterm labor, premature rupture of membranes (PROM), gestational diabetes, gestational hypertension, smoking during pregnancy, and socioeconomic status were collected and included in the final analysis. Cox proportional hazards models were applied to identify the impact of gestational age on NI risk, with all variables adjusted as appropriate. Overall, 0.9% and 3.8% rates of VPT and MLPT births were identified, respectively. NI incidence was highest among VPT children (34.7%), followed by MLPT (23.9%) and FT (18.2%) children. Both VPT (hazard ratio [HR], 1.45; 95% confidence interval [CI], 1.03 to 2.05) and MLPT (HR, 1.21; 95% CI, 1.04 to 1.41) births were associated with increased NI risk. Low birth weight, PROM, and smoking during pregnancy were also associated with increased NI risk, while longer breastfeeding and higher socioeconomic status were associated with decreased risk. Special attention must be given to NIs for both VPT and MLPT children.

Insect collecting bias in Arizona with a preliminary checklist of the beetles from the Sand Tank Mountains.

Background: 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. New information: 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.

The influence of social withdrawal and depression on the self-esteem of female adolescents: The mediating effect of grit.

Previous studies have shown that female adolescents are at a higher risk of low self-esteem than male adolescents, and self-esteem in adolescents is critical for academic performance, adult health, and economic status. Depression, social withdrawal, and grit are predicted to be internal factors that affect self-esteem, and an integrated exploration of the relationship between them is required for a proper approach to enhance self-esteem in female adolescents. Therefore, this study investigated the influence of social withdrawal and depression on self-esteem among female adolescents and explored the mediating effect of grit on self-esteem. Data collected from 1,106 girls in the third year of middle school of the third-year survey (2020) of the Korean Children and Youth Panel Survey 2018 were analyzed in this study. For data analysis, partial least square-structural equation modeling was performed using SmartPLS 3.0. Social withdrawal was negatively related to grit, but not related to self-esteem. Depression was negatively related to grit and self-esteem. Grit was positively related to self-esteem. In addition, grit showed mediating effects in the associations between social withdrawal and self-esteem, and between depression and self-esteem in female adolescents. In conclusion, in female adolescents, the mediating effects of grit attenuated the negative effects of social withdrawal and depression on self-esteem. To enhance self-esteem in female adolescents, it is important to develop and implement strategies to strengthen grit and control negative emotional states, such as depression.

Draft Genome Sequences of Heavy Metal-Resistant Listeria monocytogenes Strains of Sequence Type 14 (Clonal Complex 14) from Human Listeriosis Cases in Sweden.

Listeria monocytogenes of clonal complex 14 (CC14) is a potentially hypervirulent clone of serotype 1/2a but remains poorly characterized. We report the genome sequences of five sequence type 14 (ST14) (CC14) strains from human listeriosis cases in Sweden, which harbor a chromosomal heavy metal resistance island that is generally uncommon in serotype 1/2a.

Whole-genome sequencing of Listeria monocytogenes isolated from the first listeriosis foodborne outbreak in South Korea.

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.

Education of History of Medicine for 80 Years: History and Current Status in Republic of Korea.

Medical history education enables the medical students to understand the humanistic aspects of medicine and also help to promote the professionalism of doctors. It makes them understand the disappearing or emerging diseases by recognizing the historical changes and trends to respond appropriately. Therefore, it is helpful to study and understand modern medicine. As of March 2023, 22 (55.0%) out of 40 medical schools in Republic of Korea have medical history course as an independent subject and two schools have integrated courses with medical ethics. Compared to 53.1% in 1995 and 56.2% in 2010, similar percentage of medical schools maintained the subject independently. However, the average credits of 18 schools in 2023(2.0) are higher than those of 1995(1.4) and 2010(1.2). The number of full-time professor who specialized in the history of medicine was 2 in 1995, 6 in 2010, and 11 in 2023. Generally, a full-time professor majoring medical history tend to have other duties besides the education and research of medical history, depending on the role of the department to which he or she belongs since they are assigned to the humanities education other than medical history education. Currently, the curriculums that have been recommended by Korea Association of Medical Colleges(KAMC), Korean Institute of Medical Education and Evaluation(KIMEE), and The Korean Society of Medical Education(KSMED), emphasize medical humanities but do not necessarily include the medical history. As a result, medical history courses have increased slightly, but the other humanities classes have increased significantly since 2000. The knowledge of medical history will help students become a doctor, and a doctor with professionalism adapting to the rapidly changing medical environment. Students will also be able to establish the ideas they must pursue in the present era when they come into contact with numerous historical situations. And if they share a sense of history, they will inspire a sense of unity as a profession and will be more active in solving social problems such as health equity. It is hoped that The Korean Society for the History of Medicine will step forward to set the purpose and goal of the medical history education, and organize the contents of the education. Classes should be prepared so that students are interested in them, and education should be focused on how the contents of education will be able to be used in medicine. To this end, it is necessary to establish the basic learning outcomes of history of medicine, and prepare learning materials based on these learning outcomes. It is also necessary to increase the competencies of educators for the history of medicine, such as performing workshops. With the dedication of the pioneers who devoted their energy to the education of medical history, it is expected that medical history will find out what to do in medical education to foster better doctors and provide better education.

Emissions and meteorological impacts on PM2.5 species concentrations in Southern California using generalized additive modeling.

The chemical composition of PM2.5 has a significant impact on human health and air quality, and its accurate knowledge can be used to identify contributing emission sources. Assessing and quantifying the impacts of various factors (e.g., emissions, meteorology, and large-scale climate patterns) on the main PM2.5 chemical components can give guidance for implementing effective regulations to improve air quality in the future. In this study, we developed generalized additive models (GAMs) to assess how emissions, meteorological factors, and large-scale climate indices affected ammonium, sulfate, nitrate, elemental carbon, and organic carbon from 2002 to 2019 in the South Coast Air Basin (SoCAB). Concentration trends from three sites in the SoCAB are studied. The statistical results showed that GAMs can capture the variability of these species' daily concentrations (R2 = 0.6 to 0.7) and annual concentrations (R2 = 0.93 to 0.99). Precursor emissions most significantly affect PM2.5 species production, though meteorological factors like maximum temperature, relative humidity, wind speed, and boundary layer height, also influence PM2.5 composition. In the future, these meteorological factors will become more significant in affecting PM2.5 speciation, although emissions will continue to strongly affect formation. Results show that the composition of most PM2.5 species will decrease in the future except for OC, which will become the largest contributor to PM2.5.

A Comparison of the Pharmacokinetics and Safety of Dapagliflozin Formate, an Ester Prodrug of Dapagliflozin, to Dapagliflozin Propanediol Monohydrate in Healthy Subjects.

Background: Dapagliflozin formate (DAP-FOR, DA-2811), an ester prodrug of dapagliflozin, was developed to improve the stability and pharmaceutical manufacturing process of dapagliflozin, a sodium-glucose cotransporter-2 inhibitor. Purpose: This study aimed to evaluate the pharmacokinetics (PKs) and safety of dapagliflozin for DAP-FOR compared to those for dapagliflozin propanediol monohydrate (DAP-PDH, Forxiga) in healthy subjects. Methods: This was an open-label, randomized, single-dose, two-period, two-sequence crossover study. The subjects received a single dose of DAP-FOR or DAP-PDH 10 mg in each period, with a 7-day washout. Serial blood samples for PK analysis were collected up to 48 hours after a single administration to determine plasma concentrations of DAP-FOR and dapagliflozin. PK parameters were calculated using a non-compartmental method and compared between the two drugs. Results: In total, 28 subjects completed the study. DAP-FOR plasma concentrations were not detected in all of the blood sampling time points except for one time point in one subject, and the corresponding DAP-FOR plasma concentration in the subject was close to the lower limit of quantification. The mean plasma concentration-time profiles of dapagliflozin were comparable between the two drugs. The geometric mean ratios and its 90% confidence intervals of the maximum plasma concentration and area under the plasma concentration-time curve of dapagliflozin for DAP-FOR to DAP-PDH were within the conventional bioequivalence range of 0.80-1.25. Both drugs were well-tolerated, with a similar incidence of adverse drug reactions. Conclusion: The rapid conversion of DAP-FOR into dapagliflozin led to the extremely low exposure of DAP-FOR and comparable PK profiles of dapagliflozin between DAP-FOR and DAP-PDH. The safety profiles were also similar between the two drugs. These results suggest that DAP-FOR can be used as an alternative to DAP-PDH.

Investigation of a Listeria monocytogenes Chromosomal Immigration Control Region Reveals Diverse Restriction Modification Systems with Complete Sequence Type Conservation.

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.

Emissions, meteorological and climate impacts on PM2.5 levels in Southern California using a generalized additive model: Historic trends and future estimates.

Annual fine particulate matter (PM2.5) mass concentrations in the South Coast Air Basin (SoCAB) of California decreased from around 30 µg/m3 to 11 µg/m3 between 2000 and 2013 but rose from 11 µg/m3 to 13 µg/m3 between 2014 and 2018, raising important questions about the effectiveness of ongoing emission control policies. A two-step generalized additive model (GAM)-least squares approach was developed to explore the effects of emissions, large-scale climate events and meteorological factors on daily PM2.5 mass concentrations from 2000 to 2019 to quantitatively link impacts of emissions and meteorological on PM2.5 and to assess factors leading to the increase. The GAM had an R2 = 0.99 and root mean square error (RMSE) = 0.7 µg/m3 for the annual average PM2.5 concentrations. The two-step method had an R2 = 0.93 and RMSE = 4.07 µg/m3 for the 98th percentile 24-hr average PM2.5 concentrations. Variations in both emissions and relative humidity were of high importance compared with other included factors. Interactions of NH3 emissions with NOx and SO2 emissions, which lead to ammonium nitrate and sulfate aerosol formation, were the most important factors. Meteorological effects on PM2.5 explained the majority of the daily PM2.5 fluctuations. Emission changes (increases in SO2 and PM2.5) led to increases in predicted PM2.5 between 2014 and 2018. Predicted future PM2.5, using projected emissions and meteorological data from model simulations of representative concentration pathway (RCP) scenarios, are around 12 µg/m3 (annual) and 30 µg/m3 (98th percentile daily), which are both close to the current National Ambient Air Quality Standards (NAAQS) for PM2.5. Meteorological impacts on the predicted PM2.5 in future years lead to variations of ±2 µg/m3 for the annual average and ±5 µg/m3 for the 98th percentile daily level. Future climate changes lead to a probable year-to-year variation that will let PM2.5 levels in some years exceed the standard.

Pharmacokinetics and safety of CT-P17 (40 mg/0.4 ml) versus reference adalimumab: randomized study in healthy Japanese adults.

Aim: Comparing pharmacokinetics and safety of CT-P17 and EU-approved reference adalimumab (EU-adalimumab) in Japan. Materials & methods: Double-blind, parallel-group phase I trial at three hospitals. Healthy Japanese adults were randomized (1:1) to CT-P17 or EU-adalimumab (single 40-mg subcutaneous dose). The primary end point was pharmacokinetic equivalence for area under the concentration-time curve from time zero to infinity and maximum serum concentration. Results: Of the 205 randomized subjects (102 CT-P17, 103 EU-adalimumab), 204 received study drug. CT-P17 and EU-adalimumab were pharmacokinetically equivalent: 90% CIs for geometric least-squares mean ratios were within predefined 80-125% equivalence margins. Secondary pharmacokinetic end points, safety and immunogenicity were similar between the groups. Conclusion: CT-P17 had pharmacokinetics, safety and immunogenicity comparable to EU-adalimumab in healthy Japanese adults.

CT-P17 is a biosimilar that has been determined by the EMA to be highly similar to adalimumab. CT-P17 is approved to treat the same inflammatory conditions as reference adalimumab. CT-P17 is formulated at a high concentration (40 mg/0.4 ml) and may be associated with less injection-site pain than the original lower-concentration formulation of the reference product. In this study, healthy Japanese adults were given a single dose of either CT-P17 or EU-approved reference adalimumab. Pharmacokinetics (drug absorption, distribution, metabolism and excretion), safety and immunogenicity (occurrence of immune response to the drug) were comparable between the two groups. Previous studies with CT-P17 did not take place in Japan. These results support applying the conclusions regarding CT-P17 biosimilarity from other studies to the Japanese population.

Draft Genome Sequences of Three Listeria monocytogenes Strains Isolated from Chicken Carcasses in South Korea.

While Listeria monocytogenes is a foodborne pathogen of global concern, little is known regarding L. monocytogenes populations in Asia. We report the draft genome sequences of three L. monocytogenes strains from chickens in South Korea, which could facilitate understanding the genetic diversity of the regional L. monocytogenes population.

Contrasting Genetic Diversity of Listeria Pathogenicity Islands 3 and 4 Harbored by Nonpathogenic Listeria spp.

Listeria monocytogenes causes the severe foodborne disease listeriosis. Several clonal groups of L. monocytogenes possess the pathogenicity islands Listeria pathogenicity island 3 (LIPI-3) and LIPI-4. Here, we investigated the prevalence and genetic diversity of LIPI-3 and LIPI-4 among 63 strains of seven nonpathogenic Listeria spp. from the natural environment, i.e., wildlife (black bears [Ursus americanus]) and surface water. Analysis of the whole-genome sequence data suggested that both islands were horizontally acquired but differed considerably in their incidence and genetic diversity. LIPI-3 was identified among half of the L. innocua strains in the same genomic location as in L. monocytogenes (guaA hot spot) in a truncated form, with only three strains harboring full-length LIPI-3, and a highly divergent partial LIPI-3 was observed in three Listeria seeligeri strains, outside the guaA hot spot. Premature stop codons (PMSCs) and frameshifts were frequently noted in the LIPI-3 gene encoding listeriolysin S. On the other hand, full-length LIPI-4 without any PMSCs was found in all Listeria innocua strains, in the same genomic location as L. monocytogenes and with ~85% similarity to the L. monocytogenes counterpart. Our study provides intriguing examples of genetic changes that pathogenicity islands may undergo in nonpathogenic bacterial species, potentially in response to environmental pressures that promote either maintenance or degeneration of the islands. Investigations of the roles that LIPI-3 and LIPI-4 play in nonpathogenic Listeria spp. are warranted to further understand the differential evolution of genetic elements in pathogenic versus nonpathogenic hosts of the same genus. IMPORTANCE Listeria monocytogenes is a serious foodborne pathogen that can harbor the pathogenicity islands Listeria pathogenicity island 3 (LIPI-3) and LIPI-4. Intriguingly, these have also been reported in nonpathogenic L. innocua from food and farm environments, though limited information is available for strains from the natural environment. Here, we analyzed whole-genome sequence data of nonpathogenic Listeria spp. from wildlife and surface water to further elucidate the genetic diversity and evolution of LIPI-3 and LIPI-4 in Listeria. While the full-length islands were found only in L. innocua, LIPI-3 was uncommon and exhibited frequent truncation and genetic diversification, while LIPI-4 was remarkable in being ubiquitous, albeit diversified from L. monocytogenes. These contrasting features demonstrate that pathogenicity islands in nonpathogenic hosts can evolve along different trajectories, leading to either degeneration or maintenance, and highlight the need to examine their physiological roles in nonpathogenic hosts.