Dissemination of the high-risk cloneST147 carbapenem-resistant klebsiella pneumoniae from a local tertiary care hospital in the Republic of Korea.

BACKGROUND: The emergence of carbapenem-resistant Enterobacterales (CRE) infections is rapidly increasing and represents a serious public threat. In 2020, a total of 16,883 carbapenemase-producing Enterobacterales strains were collected; among these isolates, 21 strains were repeatedly isolated in a local tertiary care hospital. METHODS: Antimicrobial susceptibility testing was performed using the broth microdilution method. All 21 strains of CRKP were analyzed by PFGE after XbaI digestion. The 21 CRKP strains were sequenced on the Illumina Miseq and Oxford Nanopore GridION platforms. RESULTS: These 21 CRKP isolates showed an identical antimicrobial resistance profile, including resistance to ampicillin, carbapenems, cephems, chloramphenicol, fluoroquinolone, macrolides and trimethoprim/sulfamethoxazole. Based on whole-genome analysis, these 21 CRKP isolates shared a common genetic structure (ISAba125-IS630-blaNDM-1-bleMBL) and harbored additional resistance determinants (blaOXA-1, blaCTX-M-15, blaSHV-11, blaSHV-67, aac(6')-Ib-cr, qnrS1, OqxA, OqxB, catB3, mph(A), sul1, and dfrA12) and mutations in the quinolone resistance-determining regions of gyrA (S83I) and parC (S80I). These isolates belonged to the ST147 and KL64 capsular types, which were carried on IncFIB replicon plasmids. The 21 CRKP strains collected from one hospital were divided into five PFGE patterns, and they were closely related with a minimum similarity value of 95.2%. These isolates were found to be highly related based on the presence of between 2 and 27 SNPs. CONCLUSIONS: These findings indicate that NDM-1-producing K. pneumoniae ST147 may have been introduced via a common source, implying nosocomial transmission; furthermore, continuous monitoring is necessary to prevent endemic transmission.

Decrease in Weekly Working Hours of Korean Workers From 2010 to 2020 According to Employment Status and Industrial Sector.

BACKGROUND: The present study examined changes in the working hours of Korean workers from 2010 to 2020 according to employment status and industrial sector. METHODS: This was a secondary analysis of data from the third (2010), fourth (2014), fifth (2017) and sixth (2020) Korean Working Conditions Surveys, which were conducted by the Korea Occupational Safety and Health Agency. RESULTS: During the past 10 years, workers classified as employees, self-employed, or employers experienced clear declines in average weekly working hours and in the percentages of individuals who worked more than 48 hours per week. During 2020, the largest proportion of employees (52.8%) had 40-hour work weeks, whereas the largest proportions of self-employed individuals (26.8%) and employers (25.1%) had very long work weeks (≥ 60 h/week). Also during 2020, individuals who were self-employed or employers in the sectors of 'Accommodation and food service' had the longest weekly work hours, whereas employees in the sector of 'Transportation' had the longest weekly work hours. All three groups (employees, self-employed, and employers) in all 21 industrial sectors experienced declines in average weekly working hours from 2017 to 2020. CONCLUSION: From 2010 to 2020, employees, self-employed individuals, and employers experienced clear declines in average weekly working hours, and in the percentages of individuals with long weekly working hours. However, there were also differences in the weekly working hours of those who had different employment status and who worked in different industrial sectors. The implementation of the 40-hour work-week and the 52-hour maximum work-week in Korea reduced excessive work hours by individuals who had different employment status and who worked in different industrial sectors, and probably improved worker quality-of-life. We recommend extension of these regulations to workplaces with fewer than 5 employees.

Association of Participation in Health Check-ups with Risk Factors for Cardiovascular Diseases.

BACKGROUND: We compared the risk factors for cardiovascular diseases (CVDs) among Koreans who did and did not participate in national periodic health check-ups, after adjustment for demographic factors, socioeconomic status, and lifestyle factors. METHODS: This cross-sectional study used data from the Korea National Health and Nutrition Examination Survey (KNHANES) from 2007 to 2018. Study subjects were classified as participants or non-participants in health check-ups, based on attendance at national periodic health check-ups during the previous two years. RESULTS: Comparison of participants and non-participants in health check-ups indicated statistically significant differences in age, gender, region, education level, monthly income, employment status, obesity, smoking, alcohol consumption, exercise, and marital status. After adjustment for demographic, socioeconomic factors, and health-related behaviors, woman non-participants were more likely to have metabolic syndrome, pre-hypertension, hypertension, prediabetes, and diabetes, and man non-participants were more likely to have pre-diabetes and diabetes. CONCLUSION: Subjects who participated in periodic health check-ups had fewer CVD-related risk factors than non-participants. Thus, health care providers should encourage non-participants to attend periodic health check-ups so that appropriate interventions can be implemented and decrease the risk for CVDs in these individuals.

Association of poor psychological well-being with co-exposure to psychosocial factors at work in Korean regular workers.

BACKGROUND: This study evaluated the association of co-exposure to different psychosocial factors with poor psychological well-being of Korean regular workers. METHODS: This was a secondary analysis of data from the fifth Korean Working Conditions Survey, conducted in 2017. Multiple logistic regression was used to determine adjusted odd ratios (aORs) and 95% confidence intervals for poor psychological well-being associated with self-reported psychosocial factors. Poor psychological well-being was measured using the Well-Being Index of the World Health Organization. For each question on psychosocial factors (long weekly working hours, lack of decision latitude, work pressure, lack of autonomy, lack of role clarity, organizational injustice, lack of reward, and lack of support from managers), answers of "always" and "most of the time" were classified as affirmative and answers of"sometimes," "rarely," and "never" were classified as negative. RESULTS: Poor psychological well-being was significantly associated with most individual work stressors for both sexes (aORs = 1.22-1.83). Furthermore, poor psychological well-being had a positive association with co-exposure to different psychosocial factors (aORs = 1.71-8.08). Co-exposure to an increasing number of psychosocial factors showed greater association with poor psychological well-being. CONCLUSION: We found that poor psychological well-being was associated with co-exposure to psychosocial factors in Korean workers in regular employment. Thus, we suggest that employers provide comprehensive measures that will protect workers from simultaneous exposure to adverse psychosocial factors.

Factors Related to Subjective Well-being in Workers Who Interact with Angry Clients.

BACKGROUND: Among workers who interact with angry clients, there is limited information about the characteristics of workers who are most vulnerable to mental health problems. Thus, we determined the association of multiple demographic, socioeconomic, and modifiable work-related psychosocial factors with the subjective well-being of workers who interact with angry clients. METHODS: This was a secondary analysis of data from the fifth Korean Working Conditions Survey, conducted in 2017. The study focused on workers who interacted with angry clients during 25% or more of their work time. Multiple logistic regression was used to determine odds ratios (ORs) and 95% confidence intervals for the association of multiple factors with self-reported subjective well-being after adjustment for demographic, socioeconomic, and modifiable psychosocial factors. RESULTS: Overall, 9.6% of men and 7.4% of women who interacted with angry clients reported poor subjective well-being. Poor well-being was significantly more likely to be reported by men who worked 40 hours or more per week (aOR, 3.97-5.37) and by men who were daily workers (aOR, 2.21). Poor subjective well-being had a significantly positive association with exposure to adverse social behaviors by clients (men: aOR, 1.54, women: aOR, 1.58), and significantly negative associations with unskilled manual work (women only: aOR, 0.30), job satisfaction (men: aOR, 0.70, women: aOR, 0.52), and good social climate (men: aOR, 0.70, women: aOR, 0.44). CONCLUSION: Workers who interact with angry clients were widely distributed over non-manual labor and manual labor, but not limited to service and sales job. We identified modifiable factors that affect the subjective well-being of workers who interact with angry clients. We suggest that employers provide protection to prevent adverse social behaviors by clients, and also make an effort to establish a good social climate at the workplace.

Nonstandard workers and differential occupational safety and health vulnerabilities.

BACKGROUND: Permanent jobs are in decline world-wide, and are being replaced with temporary, casual, part-time, and contract jobs. We investigated the characteristics and occupational safety and health (OSH) vulnerabilities of workers with nonstandard and standard employment. METHODS: We used the Korean Working Conditions Survey of 2017 to compare working conditions and OSH vulnerabilities of workers with standard and nonstandard employment in five major job categories. RESULTS: Workers with nonstandard employment were older, less educated, had lower monthly incomes, were employed in smaller businesses, worked fewer hours per week, had shorter work durations, and were more likely to report exposure to physical/chemical and ergonomic hazards, and musculoskeletal and mental symptoms. Among nonstandard workers, the rates of occupational hazards and work-related health problems depended on the type of work performed. In particular, nonstandard male workers who were unskilled manual workers, older, had less education, and earned low wages had a greater risk of working in unstable occupations, greater exposures to occupational hazards, and more musculoskeletal pain (back pain: odds ratio [OR], 2.4; upper extremity pain: OR, 2.1; and lower extremity pain: OR, 1.7) than those performing other types of work. CONCLUSION: Male unskilled manual workers with nonstandard employment were most vulnerable to OSH problems. Our findings suggest the need for OSH programs that specifically target nonstandard workers especially those in manual unskilled occupations.

Clinical Validation of Non-Invasive Prenatal Testing for Fetal Common Aneuploidies in 1,055 Korean Pregnant Women: a Single Center Experience.

BACKGROUND: Non-invasive prenatal testing (NIPT) using cell-free fetal DNA from maternal plasma for fetal aneuploidy identification is expanding worldwide. The objective of this study was to evaluate the clinical utility of NIPT for the detection of trisomies 21, 18, and 13 of high-risk fetus in a large Korean population. METHODS: This study was performed retrospectively, using stored maternal plasma from 1,055 pregnant women with singleton pregnancies who underwent invasive prenatal diagnosis because of a high-risk indication for chromosomal abnormalities. The NIPT results were confirmed by karyotype analysis. RESULTS: Among 1,055 cases, 108 cases of fetal aneuploidy, including trisomy 21 (n = 57), trisomy 18 (n = 42), and trisomy 13 (n = 9), were identified by NIPT. In this study, NIPT showed 100% sensitivity and 99.9% specificity for trisomy 21, and 92.9% sensitivity and 100% specificity for trisomy 18, and 100% sensitivity and 99.9% specificity for trisomy 13. The overall positive predictive value (PPV) was 98.1%. PPVs for trisomies 21, 18, and 13 ranged from 90.0% to 100%. CONCLUSION: This study demonstrates that our NIPT technology is reliable and accurate when applied to maternal DNA samples collected from pregnant women. Further large prospective studies are needed to adequately assess the performance of NIPT.

Self-employed individuals performing different types of work have different occupational safety and health problems.

INTRODUCTION: We assessed the occupational safety and health (OSH) issues of self-employed individuals in Korea. METHODS: The working conditions and OSH issues in three groups were analyzed using the Korean Working Conditions Survey of 2014. RESULTS: Among self-employed individuals, "Physical work" was more common among males, whereas "Emotional work" was more common among females. Self-employed individuals performing "Mental work" had more education, higher incomes, and the lowest exposure to physical/chemical and ergonomic hazards in the workplace. In contrast, those performing "Physical work" were older, had less education, lower incomes, greater exposure to physical/chemical and ergonomic hazards in the workplace, and more health problems. Individuals performing "Physical work" were most vulnerable to OSH problems. CONCLUSION: The self-employed are a heterogeneous group of individuals. We suggest development of specific strategies that focus on workers performing "Physical work" to improve the health and safety of self-employed workers in Korea.

Association of Blood Pressure with Blood Lead and Cadmium Levels in Korean Adolescents: Analysis of Data from the 2010-2016 Korean National Health and Nutrition Examination Survey.

BACKGROUND: We evaluated the association of blood pressure (BP) with blood levels of cadmium, lead, and cadmium and lead together (cadmium + lead) in a representative sample of adolescents from Korea. METHODS: We used 2010-2016 data from the Korean National Health and Nutrition Examination Survey. This cross-sectional study enrolled adolescents aged at 10-18 years-old who completed a health examination survey and had blood measurements of lead and cadmium. The association of adjusted mean differences in diastolic and systolic BP with doubling of blood lead and cadmium were estimated by regression of BP against log2-transformed blood metals and their quartiles after covariate adjustment. Adjusted odds ratio for prehypertension were calculated for log2-transformed blood levels of lead and cadmium and their quartiles. RESULTS: Our analysis of adolescents in Korea indicated that blood levels of lead and cadmium were not significantly associated with increased BP or risk of prehypertension. However, the cadmium + lead level was associated with prehypertension. Previous studies showed that blood levels of lead and cadmium were associated with increased BP and risk of hypertension in adult populations. We found no such association in Korean adolescents. CONCLUSION: We found that the cadmium + lead level was associated with prehypertension. The differences between adults and adolescents are because adolescents generally have lower levels of these blood metals or because adolescents only rarely have hypertension.

Outbreak of CTX-M-15-Producing Enterotoxigenic Escherichia coli O159:H20 in the Republic of Korea in 2016.

We investigated an outbreak of enterotoxigenic Escherichia coli (ETEC) O159:H20 associated with the consumption of a tossed-noodle dish in a high school in 2016. Thirty-three ETEC strains isolated from clinical and food samples were genetically indistinguishable. The outbreak strains were resistant to third-generation cephalosporins and harbored a blaCTX-M-15 gene on a 97-kb self-transferable IncK plasmid. This is the first outbreak caused by CTX-M-15-producing ETEC strains.

Environmental exposures to lead, mercury, and cadmium among South Korean teenagers (KNHANES 2010-2013): Body burden and risk factors.

INTRODUCTION: Limited information is available on the association of age and sex with blood concentrations of heavy metals in teenagers. In addition, factors such as a shared family environment may have an association. We analyzed data from the Korean National Health and Nutrition Examination Survey (KNHANES, 2010-2013) to determine whether blood levels of heavy metals differ by risk factors such as age, sex, and shared family environment in a representative sample of teenagers. METHODS: This study used data obtained in the KNHANES 2010-2013, which had a rolling sampling design that involved a complex, stratified, multistage, probability-cluster survey of a representative sample of the non-institutionalized civilian population in South Korea. Our cross-sectional analysis was restricted to teenagers and their parents who completed the health examination survey, and for whom blood measurements of cadmium, lead, and mercury were available. The final analytical sample consisted of 1585 teenagers, and 376 fathers and 399 mothers who provided measurements of blood heavy metal concentrations. RESULTS: Male teenagers had greater blood levels of lead and mercury, but sex had no association with blood cadmium level. There were age-related increases in blood cadmium, but blood lead decreased with age, and age had little association with blood mercury. The concentrations of cadmium and mercury declined from 2010 to 2013. The blood concentrations of lead, cadmium, and mercury in teenagers were positively associated with the levels in their parents after adjustment for covariates. CONCLUSION: Our results show that blood heavy metal concentrations differ by risk factors such as age, sex, and shared family environment in teenagers.

Gender differences in occupations and complaints of musculoskeletal symptoms: Representative sample of South Korean workers.

INTRODUCTION: The present study examines gender differences in occupations, occupational hazards, and musculoskeletal symptoms in Korean workers. METHODS: We performed a secondary analysis of data from the fourth Korean Working Conditions Survey (KWCS). RESULTS: Relative to "managers," men who were "craft and related trades workers," "equipment, machine operating and assembling workers," and in "elementary occupations" were more likely to report back pain (ORs: 2.08, 2.33, and 2.71, respectively); women who were "skilled agricultural, forestry, and fishery workers" were more likely to report back pain (OR: 3.96). Back pain was more likely to be reported in men exposed to "carrying/moving heavy loads," "painful/tiring postures," and "repetitive hand/arm movements" (ORs: 1.20, 2.26, and 1.28, respectively). CONCLUSION: Men and women workers differed in their reporting of ergonomic risk factors, and complaints of musculoskeletal symptoms. Am. J. Ind. Med. 60:342-349, 2017. © 2017 Wiley Periodicals, Inc.

Vulnerability of employees in businesses with fewer than five workers (micro-enterprises) to occupational safety and health problems.

INTRODUCTION: We assessed the characteristics of micro-enterprises (businesses with fewer than five workers) focusing on occupational safety and health (OSH) issues. METHODS: We performed a secondary analysis of data from the Economically Active Population Supplementary Survey and the fourth Korean Working Conditions Survey of 2014. RESULTS: Relative to larger businesses, micro-enterprises employ more women, temporary workers, and older workers (>55 years). In addition, more workers in micro-enterprises held "elementary occupations" (unskilled or under-skilled) or "sales and service jobs." Key sectors of such employment included the sectors of "wholesale and retail trade" and "hotel and restaurants." Furthermore, lower skilled workers in such micro-enterprises more frequently reported exposure to ergonomic risk factors and subsequent musculoskeletal disorders, and they also experienced a much higher fatality rate due to occupational injuries. CONCLUSION: Our results indicate that Korean workers in micro-enterprises are more vulnerable to OSH problems than workers in larger businesses.

Noninvasive prenatal diagnosis of duchenne muscular dystrophy: comprehensive genetic diagnosis in carrier, proband, and fetus.

BACKGROUND: Noninvasive prenatal diagnosis of monogenic disorders using maternal plasma and targeted massively parallel sequencing is being investigated actively. We previously demonstrated that comprehensive genetic diagnosis of a Duchenne muscular dystrophy (DMD) patient is feasible using a single targeted sequencing platform. Here we demonstrate the applicability of this approach to carrier detection and noninvasive prenatal diagnosis. METHODS: Custom solution-based target enrichment was designed to cover the entire dystrophin (DMD) gene region. Targeted massively parallel sequencing was performed using genomic DNA from 4 mother and proband pairs to test whether carrier status could be detected reliably. Maternal plasma DNA at varying gestational weeks was collected from the same families and sequenced using the same targeted platform to predict the inheritance of the DMD mutation by their fetus. Overrepresentation of an inherited allele was determined by comparing the allele fraction of 2 phased haplotypes after examining and correcting for the recombination event. RESULTS: The carrier status of deletion/duplication and point mutations was detected reliably through using a single targeted massively parallel sequencing platform. Whether the fetus had inherited the DMD mutation was predicted correctly in all 4 families as early as 6 weeks and 5 days of gestation. In one of these, detection of the recombination event and reconstruction of the phased haplotype produced a correct diagnosis. CONCLUSIONS: Noninvasive prenatal diagnosis of DMD is feasible using a single targeted massively parallel sequencing platform with tiling design.

What are the determinants of gene expression levels and breadths in the human genome?

In complex organisms, different tissues express different genes, which ultimately shape the function and phenotype of each tissue. An important goal of modern biology is to understand how some genes are turned on and off in specific tissues and how the numbers of different gene expression products are determined. These aspects are named 'expression breadth' (or 'tissue specificity') and 'expression level', respectively. Here, we show that we can predict substantial amount of variation in levels and breadths of gene expression using genomic information of each gene. Interestingly, many genomic traits are correlated with both aspects of gene expression in similar directions, suggesting shared molecular pathways. However, to elucidate distinctive molecular mechanisms governing gene expression levels and breadths, we need to identify the relative significance of each genomic trait on these two aspects of gene expression. To this end, we developed a novel multivariate multiple regression method. Using this new method, we show that gene compactness (in particular, the mean size of exons), codon usage bias and non-synonymous rates have a stronger influence on expression levels compared with their effects on expression breadths. In contrast, the propensity of promoter DNA methylation is a stronger indicator of expression breadths than of expression levels. Interestingly, intron DNA methylation exhibits an opposite pattern to the promoter DNA methylation in the human genome, suggesting that DNA methylation may play multiple roles depending upon its genomic targets. Furthermore, synonymous rates have stronger associations with expression breadths than with expression levels in the human genome. These findings provide clues toward distinctive molecular mechanisms regulating different aspects of gene expression.

Murine Th9 cells promote the survival of myeloid dendritic cells in cancer immunotherapy.

Dendritic cells (DCs) are professional antigen-presenting cells to initiate immune responses, and DC survival time is important for affecting the strength of T-cell responses. Interleukin (IL)-9-producing T-helper (Th)-9 cells play an important role in anti-tumor immunity. However, it is unclear how Th9 cells communicate with DCs. In this study, we investigated whether murine Th9 cells affected the survival of myeloid DCs. DCs derived from bone marrow of C57BL/6 mice were cocultured with Th9 cells from OT-II mice using transwell, and the survival of DCs was examined. DCs cocultured with Th9 cells had longer survival and fewer apoptotic cells than DCs cultured alone in vitro. In melanoma B16-OVA tumor-bearing mice, DCs conditioned by Th9 cells lived longer and induced stronger anti-tumor response than control DCs did in vivo. Mechanistic studies revealed that IL-3 but not IL-9 secreted by Th9 cells was responsible for the prolonged survival of DCs. IL-3 upregulated the expression of anti-apoptotic protein Bcl-xL and activated p38, ERK and STAT5 signaling pathways in DCs. Taken together, our data provide the first evidence that Th9 cells can promote the survival of DCs through IL-3, and will be helpful for designing Th9 cell immunotherapy and more effective DC vaccine for human cancers.

Factors affecting work-related non-fatal injuries among aged workers in South Korea.

Introduction: The objective of this paper is to investigate whether an aging workforce is associated with an increase in work-related non-fatal injuries and to explore the underlying reasons for this potential increase. Methods: Aged workers were defined as those who were at least 55-years-old. Work-related non-fatal injuries were assessed in aged and young workers who were registered with the workers' compensation system from 2017 to 2021 of South Korea. Results: The mean estimated rate of work-related non-fatal injuries of aged workers (0.88/100) was about 2.5-times higher than that of younger workers (0.35/100). Most work-related non-fatal injuries in the older adults were in individuals working in the "construction sector" (36.0%), those with "elementary occupations (unskilled workers)" (45.0%), and those with employment status of "daily worker" (44.0%). "Trip & slip" (28.7%) and "falling" (19.6%) were more frequent types of work-related non-fatal injuries in aged workers relative to young workers. The category of "buildings, structures, and surfaces" was a more frequent cause of work-related non-fatal injuries in aged workers than young workers. Discussion: The incidence of non-fatal work-related injuries is higher among aged workers compared to their younger counterparts. The increased occurrence of aged workers participating in precarious employment and jobs, along with the greater physical vulnerability, is likely the cause of their higher rate of work-related non-fatal injuries.

Distribution of Extended-Spectrum-ß-Lactamase-Producing Diarrheagenic Escherichia coli Clonal Complex 10 Isolates from Patients with Diarrhea in the Republic of Korea.

ESBL-producing E. coli is a public health concern in healthcare settings and the community. Between 2009 and 2018, a total of 187 ESBL-producing pathogenic E. coli isolates were identified, and clonal complex (CC) 10 was the predominant clone (n = 57). This study aimed to characterize the ESBL-producing pathogenic E. coli CC10 strains obtained from patients with diarrhea to improve our understanding of CC10 distribution in the Republic of Korea. A total of 57 CC10 strains were selected for comprehensive molecular characterization, including serotype identification, the analysis of antibiotic resistance genes, the investigation of genetic environments, the determination of plasmid profiles, and the assessment of genetic correlations among CC10 strains. Among the CC10 isolates, the most prevalent serotype was O25:H16 (n = 21, 38.9%), followed by O6:H16 (10, 19.6%). The most dominant ESBL genes were blaCTX-M-15 (n = 31, 55%) and blaCTX-M-14 (n = 15, 27%). Most blaCTXM genes (n = 45, 82.5%) were located on plasmids, and these incompatibility groups were confirmed as IncB/O/K/Z, IncF, IncI1, and IncX1. The mobile elements located upstream and downstream mainly included ISEcp1 (complete or incomplete) and IS903 or orf477. Phylogenetic analysis showed that the CC10 strains were genetically diverse and spread among several distinct lineages. The results of this study show that ESBL-producing pathogenic E. coli CC10 has been consistently isolated, with CTX-M-15-producing E. coli O25:H16 isolates being the major type associated with the distribution of CC10 clones over the past decade. The identification of ESBL-producing pathogenic E. coli CC10 isolates underscores the possible emergence of resistant isolates with epidemic potential within this CC. As a result, continuous monitoring is essential to prevent the further dissemination of resistant ESBL-producing E. coli CC10 strains.

Multiparity increases the risk of diabetes by impairing the proliferative capacity of pancreatic ß cells.

Pregnancy imposes a substantial metabolic burden on women, but little is known about whether or how multiple pregnancies increase the risk of maternal postpartum diabetes. In this study, we assessed the metabolic impact of multiple pregnancies in humans and in a rodent model. Mice that underwent multiple pregnancies had increased adiposity, but their glucose tolerance was initially improved compared to those of age-matched virgin mice. Later, however, insulin resistance developed over time, but insulin secretory function and compensatory pancreatic ß cell proliferation were impaired in multiparous mice. The ß cells of multiparous mice exhibited aging features, including telomere shortening and increased expression of Cdkn2a. Single-cell RNA-seq analysis revealed that the ß cells of multiparous mice exhibited upregulation of stress-related pathways and downregulation of cellular respiration- and oxidative phosphorylation-related pathways. In humans, women who delivered more than three times were more obese, and their plasma glucose concentrations were elevated compared to women who had delivered three or fewer times, as assessed at 2 months postpartum. The disposition index, which is a measure of the insulin secretory function of ß cells, decreased when women with higher parity gained body weight after delivery. Taken together, our findings indicate that multiple pregnancies induce cellular stress and aging features in ß cells, which impair their proliferative capacity to compensate for insulin resistance.