Differences in Physical Activity Levels by Sociodemographic and Health Risk Factors Among Persons With Disabilities in South Korea.

The World Health Organization (WHO) recommends physical activity for more than 150 minutes a week to improve health and reduce disease burden; however, previous studies have shown a lack of participation among persons with disabilities. Logistic regression analysis was performed on National Health Insurance Service data to analyze the relationship between physical activity levels by disability type and socioeconomic factors. The results showed that women with disabilities exercised 0.663 times compared to men with disabilities (95% confidence interval [CI] = [0.659, 0.668]), and individuals with severe disabilities exercised 0.719 times compared to those with mild disabilities (95% CI = [0.71, 0.727]). Those from the highest income level households (adjusted odds ratio [AOR] = 1.442, 95% CI = [1.424, 1.46]) and the re-employed (AOR = 1.119, 95% CI = [1.095, 1.145]) exercised adequately. Thus, physical activity levels and socioeconomic factors are related in persons with disabilities. Exercise policies and programs are required to support persons with disabilities by income level.

Comparative analysis of genetic testing utilization rates among people with and without disabilities in South Korea from 2016 to 2019, focusing on malignant neoplasms: A national population-based study.

INTRODUCTION: Oncogene testing is widely used to detect or direct cancer treatments. Compared to people without disabilities, people with disabilities in Korea have a lower cancer incidence rate but a fivefold higher cancer mortality rate, implying delayed detection. METHODS: We used an administrative database combining disability status and care utilization to analyze every case of cancer-related genetic testing paid for by the National Health Insurance Services of Korea between 2016 and 2019. We first compared percentages of individuals who had taken a registered genetic test by their disability statuses. We then compared the most frequently utilized tests between individuals with and without disabilities. RESULTS: Korean citizens, 175,000 in total, underwent at least one of the 192 registered cancer-related genetic tests between 2016 and 2019. People with disabilities utilized these genetic tests at higher rates than those without disabilities, regardless of sex or age. Among people aged ≥40 years, lung and colorectal cancer-related tests were most frequently utilized, regardless of disability status. CONCLUSION: Although the cancer-related genetic test uptake rate is higher among people with disabilities than among those without disabilities, it is still possible that information on these tests is not as readily available to people with disabilities. Therefore, it is imperative for the government to actively devise strategies to enhance national cancer screening rates among people with disabilities.

Design, synthesis, and evaluation of purine and pyrimidine-based KRAS G12D inhibitors: Towards potential anticancer therapy.

Oncogenic RAS mutations, commonly observed in human tumors, affect approximately 30% of cancer cases and pose a significant challenge for effective cancer treatment. Current strategies to inhibit the KRAS G12D mutation have shown limited success, emphasizing the urgent need for new therapeutic approaches. In this study, we designed and synthesized several purine and pyrimidine analogs as inhibitors for the KRAS G12D mutation. Our synthesized compounds demonstrated potent anticancer activity against cell lines with the KRAS G12D mutation, effectively impeding their growth. They also exhibited low toxicity in normal cells, indicating their selective action against cancer cells harboring the KRAS G12D mutation. Notably, the lead compound, PU1-1 induced the programmed cell death of KRAS G12D-mutated cells and reduced the levels of active KRAS and its downstream signaling proteins. Moreover, PU1-1 significantly shrunk the tumor size in a pancreatic xenograft model induced by the KRAS G12D mutation, further validating its potential as a therapeutic agent. These findings highlight the potential of purine-based KRAS G12D inhibitors as candidates for targeted cancer therapy. However, further exploration and optimization of these compounds are essential to meet the unmet clinical needs of patients with KRAS-mutant cancers.

Disability-Related Mortality Inequity in South Korea: Comparison in Terms of Seoul Metropolitan/Non-Metropolitan Areas and Income Levels.

Despite the improved living standards in South Korea, people with disabilities still experience health disparities. Therefore, we analyzed differences in mortality rates among people with disabilities according to income level and residential area using representative data from the National Health Insurance Service in South Korea. Descriptive statistics and Cox proportional risk models were used to identify the risk factors for mortality affecting people with disabilities stratified by income level and residential area. Those living in non-metropolitan areas and low-income households had high mortality risks, suggesting that income level and residential area were related to mortality risk. The mortality risk of those with a high-income level was 1.534 times higher in non-metropolitan areas than in Seoul metropolitan areas (95% confidence interval [CI] = 1.44-1.63). Among people with low income living in non-metropolitan areas, the crude hazard ratios of mortality risk were 1.26 (95% CI = 1.14-1.39), 1.44 (95% CI = 1.34-1.54), and 1.39 (95% CI = 1.20-1.61) for those with brain lesions, sensory impairment (visual/hearing/speech impairment), and kidney failure, respectively. No significant differences were observed between people with autism in non-metropolitan and Seoul metropolitan areas and those with low- and high-income levels. Health issues and countermeasures are crucial to reduce mortality risk among people with disabilities.

Hypertension Prevalence and Control Among U.S. Women of Reproductive Age.

INTRODUCTION: Hypertension is a risk factor for cardiovascular disease, a leading cause of death among women of reproductive age (women aged 18-44 years). This study estimated hypertension prevalence and control among women of reproductive age at the national and state levels using electronic health record data. METHODS: Nonpregnant women of reproductive age were included in this cross-sectional study using 2019 IQVIA Ambulatory Electronic Medical Records - U.S. national data (analyzed in 2023). Suspected hypertension was identified using any of these criteria: ≥1 hypertension diagnosis code, ≥2 blood pressure readings ≥140/90 mmHg on separate days, or ≥1 antihypertensive medication. Among women of reproductive age with hypertension, the latest blood pressure in 2019 was used to identify hypertension control (blood pressure <140/90 mmHg). Estimates were age standardized and stratified by race or Hispanic ethnicity, region, and states with sufficient data. Tukey tests compared estimates by race or Hispanic ethnicity, region, and comorbidities. RESULTS: Among 2,125,084 women of reproductive age (62.1% White, 8.8% Black, and 29.1% other [including Hispanic, Asian, other, or unknown]) with a mean age of 31.7 years, hypertension prevalence was 14.5%. Of those with hypertension, 71.9% had controlled blood pressure. Black women of reproductive age had a higher hypertension prevalence (22.3% vs 14.4%, p<0.05) but lower control (60.6% vs 74.0%, p<0.05) than White women of reproductive age. State-level hypertension prevalence ranged from 13.7% (Massachusetts) to 36% (Alabama), and control ranged from 82.9% (Kansas) to 59.2% (the District of Columbia). CONCLUSIONS: This study provides the first state-level estimates of hypertension control among women of reproductive age. Electronic health record data complements traditional hypertension surveillance data and provides further information for efforts to prevent and manage hypertension among women of reproductive age.

State-Level Hypertension Prevalence and Control Among Adults in the U.S.

INTRODUCTION: Improving hypertension control is a national priority. Electronic health record data have the potential to augment traditional surveillance systems. This study aimed to assess hypertension prevalence and control at the state level using a previously established electronic health record-based phenotype for hypertension. METHODS: Adult patients (N=11,031,368) were included from the IQVIA ambulatory electronic medical record-U.S. 2019 data set. IQVIA ambulatory electronic medical record comprises electronic health records from >100,000 providers and includes patients from every U.S. state and Washington DC. Authors compared hypertension prevalence and control estimates against those from the Behavioral Risk Factor Surveillance System 2019. Results were age-standardized and stratified by state and sociodemographic characteristics. Statistical analyses were conducted in 2022-2023. RESULTS: IQVIA ambulatory electronic medical record-U.S. patients had a median age of 55 years, and 56.7% were women. Overall age-standardized hypertension prevalence was higher in IQVIA ambulatory electronic medical record-U.S. (35.0%) than in the Behavioral Risk Factor Surveillance System (29.7%), however, state-level geographic patterns were similar, with the highest burden in the South and Appalachia. Similar patterns were also observed by sociodemographic characteristics in both data sets: hypertension prevalence was higher in older age groups (than younger), men (than women), and Black patients (than other races). Hypertension control varied widely across states: among states with >1% data coverage, control rates were lowest in Nevada (51.1%), Washington DC (52.0%), and Mississippi (55.2%); highest in Kansas (73.4%), New Jersey (72.3%), and Iowa (71.9%). CONCLUSIONS: This study provided the first-ever estimates of hypertension control for all states and Washington DC. Electronic health record-based surveillance could support hypertension prevention and control efforts at the state level.

Leveraging Electronic Health Records to Construct a Phenotype for Hypertension Surveillance in the United States.

BACKGROUND: Hypertension is an important risk factor for cardiovascular diseases. Electronic health records (EHRs) may augment chronic disease surveillance. We aimed to develop an electronic phenotype (e-phenotype) for hypertension surveillance. METHODS: We included 11,031,368 eligible adults from the 2019 IQVIA Ambulatory Electronic Medical Records-US (AEMR-US) dataset. We identified hypertension using three criteria, alone or in combination: diagnosis codes, blood pressure (BP) measurements, and antihypertensive medications. We compared AEMR-US estimates of hypertension prevalence and control against those from the National Health and Nutrition Examination Survey (NHANES) 2017-18, which defined hypertension as BP ≥130/80 mm Hg or ≥1 antihypertensive medication. RESULTS: The study population had a mean (SD) age of 52.3 (6.7) years, and 56.7% were women. The selected three-criteria e-phenotype (≥1 diagnosis code, ≥2 BP measurements of ≥130/80 mm Hg, or ≥1 antihypertensive medication) yielded similar trends in hypertension prevalence as NHANES: 42.2% (AEMR-US) vs. 44.9% (NHANES) overall, 39.0% vs. 38.7% among women, and 46.5% vs. 50.9% among men. The pattern of age-related increase in hypertension prevalence was similar between AEMR-US and NHANES. The prevalence of hypertension control in AEMR-US was 31.5% using the three-criteria e-phenotype, which was higher than NHANES (14.5%). CONCLUSIONS: Using an EHR dataset of 11 million adults, we constructed a hypertension e-phenotype using three criteria, which can be used for surveillance of hypertension prevalence and control.

Risk of Cardiovascular Disease After COVID-19 Diagnosis Among Adults With and Without Diabetes.

Background Growing evidence suggests incident cardiovascular disease (CVD) may be a long-term outcome of COVID-19 infection, and chronic diseases, such as diabetes, may influence CVD risk associated with COVID-19. We evaluated the postacute risk of CVD >30 days after a COVID-19 diagnosis by diabetes status. Methods and Results We included adults ≥20 years old with a COVID-19 diagnosis from March 1, 2020 through December 31, 2021 in a retrospective cohort study from the IQVIA PharMetrics Plus insurance claims database. A contemporaneous control group comprised adults without recorded diagnoses for COVID-19 or other acute respiratory infections. Two historical control groups comprised patients with or without an acute respiratory infection. Cardiovascular outcomes included cerebrovascular disorders, dysrhythmia, inflammatory heart disease, ischemic heart disease, thrombotic disorders, other cardiac disorders, major adverse cardiovascular events, and any CVD. The total sample comprised 23 824 095 adults (mean age, 48.4 years [SD, 15.7 years]; 51.9% women; mean follow-up, 8.5 months [SD, 5.8 months]). In multivariable Cox regression models, patients with a COVID-19 diagnosis had a significantly greater risk of all cardiovascular outcomes compared with patients without a diagnosis of COVID-19 (hazard ratio [HR], 1.66 [1.62-1.71], with diabetes; HR, 1.75 [1.73-1.78], without diabetes). Risk was attenuated but still significant for the majority of outcomes when comparing patients with COVID-19 to both historical control groups. Conclusions In patients with COVID-19 infection, postacute risk of incident cardiovascular outcomes is significantly higher than among controls without COVID-19, regardless of diabetes status. Therefore, monitoring for incident CVD may be essential beyond the first 30 days after a COVID-19 diagnosis.

Trends and Characteristics of Blood Pressure Prescription Fills Before and During the COVID-19 Pandemic in the United States.

BACKGROUND: The COVID-19 pandemic disrupted healthcare in the United States and raised concerns about certain antihypertensives, and may have impacted both prescribing practices and access to blood pressure (BP) medications. METHODS: We assessed trends in BP prescription fills before and during the first year of the COVID-19 pandemic, using cross-sectional data for BP fills and tablets in the IQVIA (IMS Health) National Prescription Audit® database. Drugs filled via retail (92% coverage), mail-order (78% coverage), and long-term care (72% coverage) channels from January 2018 through December 2020 were included. Data were projected nationally and by state. RESULTS: Between 2.9 and 3.4 billion BP tablets were dispensed monthly until February 2020, increasing sharply to 3.8 billion in March 2020 and declining to 3.5 billion in April, then increasing at 3-month intervals until December 2020. The number of tablets per fill increased slightly over time, with the largest increase (from 66.7 to 68.6) during February-March, 2020. Tablets were dispensed through retail channels (99.7 billion), mail-order (14.7 billion), and long-term care (5.3 billion). Rates of patients initiating new medications decreased during 2020 compared to prior years. Fills did not vary significantly by drug class. CONCLUSIONS: A sharp increase in BP fills occurred with COVID-19 emergence, suggesting patients may have secured medications in preparation for potential access limitations. A decrease in new fills, indicating decreased initiation and/or modification of treatment regimens, suggests need for efforts to re-engage patients in the healthcare system and provide alternative ways to obtain medication refills and adjustments.

Pre-pandemic physical activity as a predictor of infection and mortality associated with COVID-19: Evidence from the National Health Insurance Service.

Introduction: During the coronavirus disease 2019 (COVID-19) pandemic, many populations have experienced reduced physical activity (PA) levels, weight gain, and increased anxiety and depression. However, according to a previous study, engaging in PA has a positive effect on damages caused by COVID-19. Therefore, this study aimed to investigate the association between PA and COVID-19 using the National Health Insurance Sharing Service Database in South Korea. Methods: Logistic regression analysis was used to analyze the association of PA with COVID-19 and mortality. The analysis was adjusted for body mass index, sex, age, insurance type, comorbidity, and region of residence at baseline. Disability and lifestyle (weight, smoking, and drinking status) were adjusted consecutively. Results: The results indicated that engaging in insufficient PA as per the WHO guidelines predicts a higher risk of COVID-19 when controlling for personal characteristics, comorbidity, lifestyle, disability, and mortality. Discussion: This study revealed the need to engage in PA and manage weight to reduce the risk of infection and mortality associated with COVID-19. Because engaging in PA is an important component of weight management and can help restore physical and mental health after the COVID-19 pandemic, it should be emphasized as a pillar of recovery after COVID-19.

Genomic and phenotypic profiling of Staphylococcus aureus isolates from bovine mastitis for antibiotic resistance and intestinal infectivity.

BACKGROUND: Staphylococcus aureus is one of the prevalent etiological agents of contagious bovine mastitis, causing a significant economic burden on the global dairy industry. Given the emergence of antibiotic resistance (ABR) and possible zoonotic spillovers, S aureus from mastitic cattle pose threat to both veterinary and public health. Therefore, assessment of their ABR status and pathogenic translation in human infection models is crucial. RESULTS: In this study, 43 S. aureus isolates associated with bovine mastitis obtained from four different Canadian provinces (Alberta, Ontario, Quebec, and Atlantic provinces) were tested for ABR and virulence through phenotypic and genotypic profiling. All 43 isolates exhibited crucial virulence characteristics such as hemolysis, and biofilm formation, and six isolates from ST151, ST352, and ST8 categories showed ABR. Genes associated with ABR (tetK, tetM, aac6', norA, norB, lmrS, blaR, blaZ, etc.), toxin production (hla, hlab, lukD, etc.), adherence (fmbA, fnbB, clfA, clfB, icaABCD, etc.), and host immune invasion (spa, sbi, cap, adsA, etc.) were identified by analyzing whole-genome sequences. Although none of the isolates possessed human adaptation genes, both groups of ABR and antibiotic-susceptible isolates demonstrated intracellular invasion, colonization, infection, and death of human intestinal epithelial cells (Caco-2), and Caenorhabditis elegans. Notably, the susceptibilities of S. aureus towards antibiotics such as streptomycin, kanamycin, and ampicillin were altered when the bacteria were internalized in Caco-2 cells and C. elegans. Meanwhile, tetracycline, chloramphenicol, and ceftiofur were comparatively more effective with ≤ 2.5 log10 reductions of intracellular S. aureus. CONCLUSIONS: This study demonstrated the potential of S. aureus isolated from mastitis cows to possess virulence characteristics enabling invasion of intestinal cells thus calling for developing therapeutics capable of targeting drug-resistant intracellular pathogens for effective disease management.

Trends in Lipid-Lowering Prescriptions: Increasing Use of Guideline-Concordant Pharmacotherapies, U.S., 2017‒2022.

INTRODUCTION: Almost one third of U.S. adults have elevated low-density lipoprotein cholesterol, increasing their risk of atherosclerotic cardiovascular disease. The 2018 American College of Cardiology/American Heart Association Multisociety Cholesterol Management Guideline recommends maximally tolerated statin for those at increased atherosclerotic cardiovascular disease risk and add-on therapies (ezetimibe and PCSK9 inhibitors) in those at very high risk and low-density lipoprotein cholesterol ≥70 mg/dL. Prescription fill trends are unknown. METHODS: Using national outpatient retail prescription data from the first quarter of 2017 to the first quarter of 2022, authors determined counts of patients who filled low-, moderate-, or high-intensity statins alone and with add-on therapies. The overall percentage change and joinpoint regression were used to assess trends. Analyses were conducted in March 2022-May 2022. RESULTS: During the first quarter of 2017 to the first quarter of 2022, patients filling a statin increased by 25.0%, with the greatest increase in high-intensity statins (64.1%, range=6.6-10.9 million). Low-intensity statins decreased by 29.2% (range=3.3-2.4 million). Concurrent fills of high-intensity statin and ezetimibe rose by 210% to 579,012 patients by the first quarter of 2022, with an increase in slope by the first quarter of 2019 for all statin intensities (p<0.01). Concurrent fills of a statin and PCSK9 inhibitor increased to 2,629, 16,169, and 28,651 by the first quarter of 2022 for low-, moderate-, and high-intensity statins, respectively. For patients on all statin intensities and PCSK9 inhibitor, there were statistically significant increases in slope in the second quarter of 2019 and decreases in the first quarter of 2020. CONCLUSIONS: Patients filling moderate- and high-intensity statins and add-on ezetimibe and PCSK9 inhibitors have increased, indicating uptake of guideline-concordant lipid-lowering therapies. Improvements in the initiation and continuity of these therapies are important for atherosclerotic cardiovascular disease prevention.

Pharmacy Students' Attitudes Toward Persons With Disabilities and Perceptions of Right to Self-Determination.

Objective. As the number of persons with disabilities increases, pharmacists are responsible for providing optimal pharmaceutical care services to more patients in this population. The purpose of this study was to assess pharmacy students' perceptions of the right of persons with disabilities to self-determination and to identify factors that affect pharmacists' attitudes and perceptions.Methods. A survey of 370 pharmacy students was conducted. The revised Korean versions of the Scale of Attitudes Towards Disabled Persons (SADP) and the Attitudes Toward Disabled Persons Form O (ATDP-O) were used to measure attitudes toward persons with disabilities. Pharmacy students' perception of the right of persons with disabilities to self-determination was measured in 2 subdomains developed by education and ethics experts: absoluteness of right and social support.Results. Responses from 363 pharmacy students were included in the analysis. We found that the more contact students had with persons with disabilities in the past, the more positive attitudes they had toward this patient group. In addition, students' understanding of self-determination and positive attitudes toward persons with disabilities were determined to be statistically significant factors affecting pharmacy students' perceptions of both the absoluteness of right of persons with disabilities and the level of social support that should be given to this patient group.Conclusion. Since experience relating to people with disabilities is associated with pharmacy students' positive perceptions about the right of persons with disabilities to self-determination, education and activities are needed in the pharmacy curriculum to ensure students have experiences with this patient group.

A longitudinal census of the bacterial community in raw milk correlated with Staphylococcus aureus clinical mastitis infections in dairy cattle.

BACKGROUND: Staphylococcus aureus is a common cause of clinical mastitis (CM) in dairy cattle. Optimizing the bovine mammary gland microbiota to resist S. aureus colonization is a growing area of research. However, the details of the interbacterial interactions between S. aureus and commensal bacteria, which would be required to manipulate the microbiome to resist infection, are still unknown. This study aims to characterize changes in the bovine milk bacterial community before, during, and after S. aureus CM and to compare bacterial communities present in milk between infected and healthy quarters. METHODS: We collected quarter-level milk samples from 698 Holstein dairy cows over an entire lactation. A total of 11 quarters from 10 cows were affected by S. aureus CM and milk samples from these 10 cows (n = 583) regardless of health status were analyzed by performing 16S rRNA gene amplicon sequencing. RESULTS: The milk microbiota of healthy quarters was distinguishable from that of S. aureus CM quarters two weeks before CM diagnosis via visual inspection. Microbial network analysis showed that 11 OTUs had negative associations with OTU0001 (Staphylococcus). A low diversity or dysbiotic milk microbiome did not necessarily correlate with increased inflammation. Specifically, Staphylococcus xylosus, Staphylococcus epidermidis, and Aerococcus urinaeequi were each abundant in milk from the quarters with low levels of inflammation. CONCLUSION: Our results show that the udder microbiome is highly dynamic, yet a change in the abundance in certain bacteria can be a potential indicator of future S. aureus CM. This study has identified potential prophylactic bacterial species that could act as a barrier against S. aureus colonization and prevent future instances of S. aureus CM.

Exposure to COVID-19 Infection and Mortality Rates Among People With Disabilities in South Korea.

BACKGROUND: With the delayed eradication of coronavirus disease 2019 (COVID-19), people with disabilities, a socially vulnerable class of individuals, face aggravated hardships caused by a pause in support services and lack of care due to stricter social distancing policies combined with the challenges of their disabilities. Given this background, we aim to investigate COVID-19 infection and mortality rates among people with disabilities, who face heightened physical and mental health threats amidst the COVID-19 pandemic. METHODS: Gender, age, health insurance premiums, the Charlson Comorbidity Index (CCI), the severity of the disability, and the type of disability were compared among people with disabilities who had been infected with or died from COVID-19 using the nationally representative National Health Insurance Service (NHIS)-COVID-19 database (DB). RESULTS: We found that the COVID-19 infection rate was higher among those with low income, those with severe disability, and those with "other" disabilities (ie, speech disabilities, hepatic dysfunction, respiratory dysfunction, facial disfigurement, intestinal fistular/urinary disability, epilepsy, intellectual disability, autistic disorder, and mental disorders). The mortality rate was markedly higher (ie, 15.90 times higher, odds ratio [OR]: 15.90, 95% confidence interval [CI]: 6.16 - 41.06) among people aged 80 years or older as compared with those aged 60 years or younger. The odds for mortality were 2.49 times higher (OR: 2.49, 95% CI: 1.33 - 4.64) among people with severe disabilities as compared with mild disabilities. CONCLUSION: Among people with disabilities, we found that COVID-19 infection rates differed according to income level, severity of the disability, and disability type, while the COVID-19 mortality rates differed according to age and severity of the disability.

Genetic Testing on Patients with Developmental Delay: A Preliminary Study from the Perspective of Physicians.

This study aimed to discover and propose solutions to various decision-making problems, including obtaining consent, encountered by physicians when administering genetic testing to patients with disabilities. A preliminary survey and focus group interviews (FGIs) were conducted with 27 specialists who had 5-25 years of clinical experience in rehabilitation medicine, pediatrics, and obstetrics and gynecology, regarding their experience in providing genetic testing to people with developmental disabilities. This included the "role of medical staff in the patient's decision-making process", "difficulty of the consent process for genetic testing", and so forth. Some limitations were identified in the genetic testing communication process for patients with disabilities. Although providing information corresponding to the level of understanding of each person and accurately evaluating the correct consenting ability is important, the usage rate of auxiliary tools, such as booklets and videos, was only 50.0%. Additionally, there were concerns regarding the marriage prospects of people with disabilities. For people with developmental disabilities to provide consent for genetic testing, legal consent forms and explanation aids that consider individual characteristics are necessary. Moreover, education on disability awareness throughout society, including cost support, is needed.

Exploring the Relationship between Physical Activities and Health-Related Factors in the Health-Related Quality of Life among People with Disability in Korea.

The purpose of this study is to explore the relationship between modes (e.g., frequency and total time) of physical activity and health-related conditions of disabled people on their health-related quality of life (HRQoL) in Korea. This study is a cross-sectional research funded by the Ministry of Health and Welfare. Data was obtained from the 2017 disability survey. A total of 6549 people with disabilities (Mage = 61.92, SD = 17.36; Male = 55.98%) were analyzed in this study. The higher the frequency of physical activity for the disabled in Korea, the more positive the HRQoL (p < 0.001). Among the elderly disabled, the higher the severity of disability and educational degree, the lower the HRQoL (all p < 0.05). Disabled people who had fewer diseases and lived an independent socio-economic and cultural life had a higher HRQoL (all p < 0.001). This study revealed different dimensions of how health-related factors influence the quality of life of people with disabilities. More attention should be paid to supporting people in being independent and active, in order to help them maintain a healthy life. Especially, the barriers to physical activity faced by disabled people are multi-layered and multifaceted. Increasing the frequency of physical activity for disabled people is not only beneficial for their physical function, but also for their HRQoL. This study enables welfare promotion for disabled people through various policies and incentives. Further, this will be an opportunity to reduce the socio-economic burden on medical and health-related services related to the disabled population.

Comparative genomic analysis of Staphylococcus aureus isolates associated with either bovine intramammary infections or human infections demonstrates the importance of restriction-modification systems in host adaptation.

Staphylococcus aureus is a major etiological agent of clinical and subclinical bovine mastitis. The versatile and adaptative evolutionary strategies of this bacterium have challenged mastitis control and prevention globally, and the high incidence of S. aureus mastitis increases concerns about antimicrobial resistance (AMR) and zoonosis. This study aims to describe the evolutionary relationship between bovine intramammary infection (IMI)-associated S. aureus and human pathogenic S. aureus and further elucidate the specific genetic composition that leads to the emergence of successful bovine IMI-associated S. aureus lineages. We performed a phylogenomic analysis of 187 S. aureus isolates that originated from either dairy cattle or humans. Our results revealed that bovine IMI-associated S. aureus isolates showed distinct clades compared to human-originated S. aureus isolates. From a pan-genome analysis, 2070 core genes were identified. Host-specific genes and clonal complex (CC)-specific genes were also identified in bovine S. aureus isolates, mostly located in mobile genetic elements (MGEs). Additionally, the genome sequences of three apparent human-adapted isolates (two from CC97 and one from CC8), isolated from bovine mastitis samples, may provide an snapshot of the genomic characteristics in early host spillover events. Virulence and AMR genes were not conserved among bovine IMI-associated S. aureus isolates. Restriction-modification (R-M) genes in bovine IMI-associated S. aureus demonstrated that the Type I R-M system was lineage-specific and Type II R-M system was sequence type (ST)-specific. The distribution of exclusive, virulence, and AMR genes were closely correlated with the presence of R-M systems in S. aureus, suggesting that R-M systems may contribute to shaping clonal diversification by providing a genetic barrier to the horizontal gene transfer (HGT). Our findings indicate that the CC or ST lineage-specific R-M systems may limit genetic exchange between bovine-adapted S. aureus isolates from different lineages.