Objectives: Statins are essential in the prevention of cardiovascular disease; however, their association with type 2 diabetes mellitus (T2DM) risk is concerning. We examined whether genetic susceptibility to T2DM modifies the association between regular statin use and T2DM risk. Methods: This study included 447 176 individuals from the UK Biobank without baseline diabetes or major cardiovascular disease. Statin use was recorded at baseline, and T2DM incidence was determined using clinical records. Polygenic risk scores (PRS) for T2DM risk were provided by the UK Biobank. Using propensity scores adjusted for age, sex, body mass index, and comorbidities, 14 831 statin users were matched with 37 060 non-users. Cox proportional hazards models were used to estimate the interaction effect of statin use and PRS on T2DM incidence, adjusting for key confounders. Results: In the propensity-matched cohort, 3675 of 51 891 participants developed T2DM over a mean follow-up period of 13.7 years. Within the top 5% of the PRS distribution, per 1000 person-years, the incidence of T2DM was 15.42 for statin users versus 12.18 for non-users. Among the lowest 5%, the incidence was 1.90 for statin users and 1.65 for non-users. Based on the Cox proportional hazards model, regular statin use was associated with a 1.24-fold increased T2DM risk (95% confidence interval [CI], 1.15 to 1.33). Furthermore, PRS exhibited a significant multiplicative interaction with regular statin use (odds ratio, 1.10; 95% CI, 1.02 to 1.19). Conclusions PRS may help identify individuals particularly susceptible to the diabetogenic effects of statins, providing a potential path for personalized cardiovascular disease management.

Objectives: Statins are essential in the prevention of cardiovascular disease; however, their association with type 2 diabetes mellitus (T2DM) risk is concerning. We examined whether genetic susceptibility to T2DM modifies the association between regular statin use and T2DM risk. Methods: This study included 447 176 individuals from the UK Biobank without baseline diabetes or major cardiovascular disease. Statin use was recorded at baseline, and T2DM incidence was determined using clinical records. Polygenic risk scores (PRS) for T2DM risk were provided by the UK Biobank. Using propensity scores adjusted for age, sex, body mass index, and comorbidities, 14 831 statin users were matched with 37 060 non-users. Cox proportional hazards models were used to estimate the interaction effect of statin use and PRS on T2DM incidence, adjusting for key confounders. Results: In the propensity-matched cohort, 3675 of 51 891 participants developed T2DM over a mean follow-up period of 13.7 years. Within the top 5% of the PRS distribution, per 1000 person-years, the incidence of T2DM was 15.42 for statin users versus 12.18 for non-users. Among the lowest 5%, the incidence was 1.90 for statin users and 1.65 for non-users. Based on the Cox proportional hazards model, regular statin use was associated with a 1.24-fold increased T2DM risk (95% confidence interval [CI], 1.15 to 1.33). Furthermore, PRS exhibited a significant multiplicative interaction with regular statin use (odds ratio, 1.10; 95% CI, 1.02 to 1.19). Conclusions PRS may help identify individuals particularly susceptible to the diabetogenic effects of statins, providing a potential path for personalized cardiovascular disease management.

Objectives: Statins are essential in the prevention of cardiovascular disease; however, their association with type 2 diabetes mellitus (T2DM) risk is concerning. We examined whether genetic susceptibility to T2DM modifies the association between regular statin use and T2DM risk. Methods: This study included 447 176 individuals from the UK Biobank without baseline diabetes or major cardiovascular disease. Statin use was recorded at baseline, and T2DM incidence was determined using clinical records. Polygenic risk scores (PRS) for T2DM risk were provided by the UK Biobank. Using propensity scores adjusted for age, sex, body mass index, and comorbidities, 14 831 statin users were matched with 37 060 non-users. Cox proportional hazards models were used to estimate the interaction effect of statin use and PRS on T2DM incidence, adjusting for key confounders. Results: In the propensity-matched cohort, 3675 of 51 891 participants developed T2DM over a mean follow-up period of 13.7 years. Within the top 5% of the PRS distribution, per 1000 person-years, the incidence of T2DM was 15.42 for statin users versus 12.18 for non-users. Among the lowest 5%, the incidence was 1.90 for statin users and 1.65 for non-users. Based on the Cox proportional hazards model, regular statin use was associated with a 1.24-fold increased T2DM risk (95% confidence interval [CI], 1.15 to 1.33). Furthermore, PRS exhibited a significant multiplicative interaction with regular statin use (odds ratio, 1.10; 95% CI, 1.02 to 1.19). Conclusions PRS may help identify individuals particularly susceptible to the diabetogenic effects of statins, providing a potential path for personalized cardiovascular disease management.

We analyzed the manner and cause of death in 1,193 forensic autopsies from the Jungbu province (central part of South Korea) conducted by the National Forensic Service Daejeon Institute in 2022. Analysis of the manner of deaths revealed that 43.1% (514/1,193 cases) were natural deaths; 42.8% (511/1,193 cases) were unnatural deaths; and 14.1% (168/1,193 cases) were unknown. Among the unnatural deaths, the major manner of death was 44.6% (228/511 cases) by accidents, 34.1% (174/511 cases) by suicide, 13.5% (69/511 cases) undetermined, and 7.8% (40/511 cases) by homicide. Among the unnatural deaths, the major causes of death was 38.4% (196/511 cases) by trauma, 20.4% (104/511 cases) by poisoning, and 17.6% (90/511 cases) by asphyxia. Falling was the major cause of death by trauma (58.7%, 115/196 cases), and strangulation was the major cause of death by asphyxia (75.6%, 68/90 cases). Among the natural deaths, heart disease was the major cause (46.7%, 240/514 cases), followed by endocrine, nutritional and metabolic diseases (14.0%, 72/514 cases). A time-series statistical analysis and comparison of the manner and cause of deaths in this province may facilitate more advanced interpretations relating to both public safety and healthcare in the future.

We analyzed the manner and cause of death in 1,193 forensic autopsies from the Jungbu province (central part of South Korea) conducted by the National Forensic Service Daejeon Institute in 2022. Analysis of the manner of deaths revealed that 43.1% (514/1,193 cases) were natural deaths; 42.8% (511/1,193 cases) were unnatural deaths; and 14.1% (168/1,193 cases) were unknown. Among the unnatural deaths, the major manner of death was 44.6% (228/511 cases) by accidents, 34.1% (174/511 cases) by suicide, 13.5% (69/511 cases) undetermined, and 7.8% (40/511 cases) by homicide. Among the unnatural deaths, the major causes of death was 38.4% (196/511 cases) by trauma, 20.4% (104/511 cases) by poisoning, and 17.6% (90/511 cases) by asphyxia. Falling was the major cause of death by trauma (58.7%, 115/196 cases), and strangulation was the major cause of death by asphyxia (75.6%, 68/90 cases). Among the natural deaths, heart disease was the major cause (46.7%, 240/514 cases), followed by endocrine, nutritional and metabolic diseases (14.0%, 72/514 cases). A time-series statistical analysis and comparison of the manner and cause of deaths in this province may facilitate more advanced interpretations relating to both public safety and healthcare in the future.

We analyzed the manner and cause of death in 1,193 forensic autopsies from the Jungbu province (central part of South Korea) conducted by the National Forensic Service Daejeon Institute in 2022. Analysis of the manner of deaths revealed that 43.1% (514/1,193 cases) were natural deaths; 42.8% (511/1,193 cases) were unnatural deaths; and 14.1% (168/1,193 cases) were unknown. Among the unnatural deaths, the major manner of death was 44.6% (228/511 cases) by accidents, 34.1% (174/511 cases) by suicide, 13.5% (69/511 cases) undetermined, and 7.8% (40/511 cases) by homicide. Among the unnatural deaths, the major causes of death was 38.4% (196/511 cases) by trauma, 20.4% (104/511 cases) by poisoning, and 17.6% (90/511 cases) by asphyxia. Falling was the major cause of death by trauma (58.7%, 115/196 cases), and strangulation was the major cause of death by asphyxia (75.6%, 68/90 cases). Among the natural deaths, heart disease was the major cause (46.7%, 240/514 cases), followed by endocrine, nutritional and metabolic diseases (14.0%, 72/514 cases). A time-series statistical analysis and comparison of the manner and cause of deaths in this province may facilitate more advanced interpretations relating to both public safety and healthcare in the future.

We analyzed the manner and cause of death in 1,193 forensic autopsies from the Jungbu province (central part of South Korea) conducted by the National Forensic Service Daejeon Institute in 2022. Analysis of the manner of deaths revealed that 43.1% (514/1,193 cases) were natural deaths; 42.8% (511/1,193 cases) were unnatural deaths; and 14.1% (168/1,193 cases) were unknown. Among the unnatural deaths, the major manner of death was 44.6% (228/511 cases) by accidents, 34.1% (174/511 cases) by suicide, 13.5% (69/511 cases) undetermined, and 7.8% (40/511 cases) by homicide. Among the unnatural deaths, the major causes of death was 38.4% (196/511 cases) by trauma, 20.4% (104/511 cases) by poisoning, and 17.6% (90/511 cases) by asphyxia. Falling was the major cause of death by trauma (58.7%, 115/196 cases), and strangulation was the major cause of death by asphyxia (75.6%, 68/90 cases). Among the natural deaths, heart disease was the major cause (46.7%, 240/514 cases), followed by endocrine, nutritional and metabolic diseases (14.0%, 72/514 cases). A time-series statistical analysis and comparison of the manner and cause of deaths in this province may facilitate more advanced interpretations relating to both public safety and healthcare in the future.

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

Purpose: This study reviewed the pathophysiological mechanisms of cellular aging caused by psychological stress and aimed to establish a biobehavioral theoretical framework for nursing interventions to promote autonomic balance based on these mechanisms. Methods: A comprehensive literature review was conducted. Results: A review of the literature showed that the stress response increases the secretion of catecholamines and glucocorticoids, resulting in a greater allostatic load. This load induces inflammatory reactions and oxidative stress, shortening telomere length and damaging mitochondrial DNA, which can lead to cellular aging. Based on this mechanism, a biobehavioral theoretical framework for nursing interventions was established. This framework focuses on delaying or inhibiting the cellular aging process by acting on the stress response stage and improving autonomic balance. Conclusion According to the proposed biobehavioral theoretical framework, stress-relieving nursing interventions may act on the mechanism of cellular aging caused by stress responses. We believe that this framework could expand our understanding of the biobehavioral aspects of stress and would facilitate efforts to use biomarkers to evaluate the effectiveness of stress-related nursing interventions at the cellular level.

Background and Objectives: O-cyclic phytosphingosine-1-phosphate (cP1P) is a synthetic chemical and has a structure like sphingosine-1-phosphate (S1P). S1P is known to promote cell migration, invasion, proliferation, and anti-apoptosis through hippocampal signals. However, S1P mediated cellular-, molecular mechanism is still remained in the lung.Acute lung injury (ALI) and its severe form acute respiratory distress syndrome (ARDS) are characterized by excessive immune response, increased vascular permeability, alveolar-peritoneal barrier collapse, and edema. In this study, we determined whether cP1P primed human dermal derived mesenchymal stem cells (hdMSCs) ameliorate lung injury and its therapeutic pathway in ALI mice. Methods: and Results: cP1P treatment significantly stimulated MSC migration and invasion ability. In cytokine array, secretion of vascular-related factors was increased in cP1P primed hdMSCs (hdMSCcP1P ), and cP1P treatment induced inhibition of Lats while increased phosphorylation of Yap. We next determined whether hdMSCcP1P reduce inflammatory response in LPS exposed mice. hdMSCcP1P further decreased infiltration of macrophage and neutrophil, and release of TNF-α, IL-1β, and IL-6 were reduced rather than naïve hdMSC treatment. In addition, phosphorylation of STAT1 and expression of iNOS were significantly decreased in the lungs of MSCcP1P treated mice. Conclusions Taken together, these data suggest that cP1P treatment enhances hdMSC migration in regulation of Hippo signaling and MSCcP1P provide a therapeutic potential for ALI/ARDS treatment.