Nanoscale-Confined Synthesis of 2D Metal Compounds for Electrochemical Applications.

2D metal compounds, such as transition metal dichalcogenides (TMDs), layered double hydroxides (LDHs), and MXenes, are emerging as important electrocatalyst materials in the transition to a sustainable energy future. Aided by their high surface area, electrical conductivity, and tunable electronic properties, these materials have provided a crucial research thrust in enhancing the efficiency of green hydrogen production, fuel cells, and carbon reduction processes. Most importantly, the synthesis of nanostructured 2D compounds, while challenging, is the key to optimizing their catalytic performance. Recent advancements in this field have highlighted the potential of 2D metal compounds in revolutionizing energy conversion technologies, which entails the discovery of new material compositions, the development of novel synthetic routes, and the integration of these materials into practical energy conversion systems. This review presents an overview of the distinctive characteristics of nanoscale-confined 2D metal compounds, the challenges encountered in their synthesis, and electrochemical applications.

TM4SF19-mediated control of lysosomal activity in macrophages contributes to obesity-induced inflammation and metabolic dysfunction.

Adipose tissue (AT) adapts to overnutrition in a complex process, wherein specialized immune cells remove and replace dysfunctional and stressed adipocytes with new fat cells. Among immune cells recruited to AT, lipid-associated macrophages (LAMs) have emerged as key players in obesity and in diseases involving lipid stress and inflammation. Here, we show that LAMs selectively express transmembrane 4 L six family member 19 (TM4SF19), a lysosomal protein that represses acidification through its interaction with Vacuolar-ATPase. Inactivation of TM4SF19 elevates lysosomal acidification and accelerates the clearance of dying/dead adipocytes in vitro and in vivo. TM4SF19 deletion reduces the LAM accumulation and increases the proportion of restorative macrophages in AT of male mice fed a high-fat diet. Importantly, male mice lacking TM4SF19 adapt to high-fat feeding through adipocyte hyperplasia, rather than hypertrophy. This adaptation significantly improves local and systemic insulin sensitivity, and energy expenditure, offering a potential avenue to combat obesity-related metabolic dysfunction.

A New Equation to Estimate Peripherally Inserted Central Catheter Length.

Background and Objectives: Peripherally inserted central catheter (PICC) placement plays an important role in clinical practice. This study aimed to provide an equation for the proper estimation of catheter length in cases of PICC placement without imaging guidance in relation to patient height, weight, sex, and age. Materials and Methods: For 1137 PICC placement cases in both arm veins of 954 patients at a single center, the elbow crease to the cavoatrial junction length (ECL) was calculated as follows: ECL = (PICC length) + (distance from the elbow crease to the puncture site). We analyzed the relationship between ECL and patient characteristics and suggested a new equation for ECL based on height, weight, sex, and age. Results: The average ECL was 48.0 ± 2.4 cm in the right side and 51.0 ± 3.0 cm in the left side. ECL in the right arm was significantly correlated with patient height, sex, and age, whereas the ECL in the left arm was additionally significantly correlated with patient weight. The ECL (cm) prediction model was as follows: right ECL = 26.32 + 1.33 × (female = 1, male = 2) - 0.02 × age (years) + 0.13 × height (cm); left ECL = 22.09 + 1.28 × (female = 1, male = 2) + 0.02 × age (years) + 0.14 × height (cm) + 0.042 × weight (kg). Conclusions: The appropriate PICC length was predicted based on the patient's height, weight, sex, and age. The equations in our study can help predict the optimal catheter length and can be automatically calculated using computerized patient information for bedside procedures in PICC.

Effect of air temperature on serum 25-hydroxyvitamin D concentrations: A single institutional large-scale study in Korea.

Vitamin D deficiency is a worldwide health issue especially in women. Serum vitamin D concentrations vary depending on the weather. However, the ideal vitamin D supplementation strategy related to weather remains uncertain. We aimed to investigate the relationship between climate factors and serum 25-hydroxy vitamin D [25(OH)D] concentrations. This study included 11,272 women aged 20-79 who visited a health promotion center for annual checkups between January 2013 and December 2015. We reviewed medical records and collected daily meteorological data. We analyzed the association between serum 25(OH)D concentration and climate factors using simple and multiple regression models and then predicted serum 25(OH)D concentration using multiple fractional polynomial models. The median age of the participants was 51 years (20-79 years), and the mean serum 25(OH)D level was 17.4 ± 8.6 ng/mL. The serum 25(OH)D concentration was lower in young women than in older women. The proportions of women with adequate 25(OH)D levels were 14.9% and 47.0% in the age groups 20-29 and 70-79, respectively. The maximum level of predicted log 25(OH)D was found in September, and the minimum was found in January. In multiple regression analysis, age and monthly mean temperature were associated with 25(OH)D concentrations. Serum 25(OH)D level was predicted using the following formula: log (25(OH)D) = 2.144 + 0.009 × age + 0.018 × ((temperature + 12.4)/10)2 (P < 0.001, adjusted R2 = 0.091). Serum 25(OH)D concentrations changed according to air temperature. An adequate strategy for vitamin D supplementation, based on air temperature, is necessary to maintain healthy serum 25(OH)D levels.

Mucosal TLR5 activation controls healthspan and longevity.

Addressing age-related immunological defects through therapeutic interventions is essential for healthy aging, as the immune system plays a crucial role in controlling infections, malignancies, and in supporting tissue homeostasis and repair. In our study, we show that stimulating toll-like receptor 5 (TLR5) via mucosal delivery of a flagellin-containing fusion protein effectively extends the lifespan and enhances the healthspan of mice of both sexes. This enhancement in healthspan is evidenced by diminished hair loss and ocular lens opacity, increased bone mineral density, improved stem cell activity, delayed thymic involution, heightened cognitive capacity, and the prevention of pulmonary lung fibrosis. Additionally, this fusion protein boosts intestinal mucosal integrity by augmenting the surface expression of TLR5 in a certain subset of dendritic cells and increasing interleukin-22 (IL-22) secretion. In this work, we present observations that underscore the benefits of TLR5-dependent stimulation in the mucosal compartment, suggesting a viable strategy for enhancing longevity and healthspan.

Fc-fused IL-7 provides broad antiviral effects against respiratory virus infections through IL-17A-producing pulmonary innate-like T cells.

Repeated pandemics caused by the influenza virus and severe acute respiratory syndrome coronavirus (SARS-CoV) have resulted in serious problems in global public health, emphasizing the need for broad-spectrum antiviral therapeutics against respiratory virus infections. Here, we show the protective effects of long-acting recombinant human interleukin-7 fused with hybrid Fc (rhIL-7-hyFc) against major respiratory viruses, including influenza virus, SARS-CoV-2, and respiratory syncytial virus. Administration of rhIL-7-hyFc in a therapeutic or prophylactic regimen induces substantial antiviral effects. During an influenza A virus (IAV) infection, rhIL-7-hyFc treatment increases pulmonary T cells composed of blood-derived interferon γ (IFNγ)+ conventional T cells and locally expanded IL-17A+ innate-like T cells. Single-cell RNA transcriptomics reveals that rhIL-7-hyFc upregulates antiviral genes in pulmonary T cells and induces clonal expansion of type 17 innate-like T cells. rhIL-7-hyFc-mediated disease prevention is dependent on IL-17A in both IAV- and SARS-CoV-2-infected mice. Collectively, we suggest that rhIL-7-hyFc can be used as a broadly active therapeutic for future respiratory virus pandemic.

Salvage of failed direct lateral sacroiliac joint fixation using a new percutaneous lateral-oblique transfixation technique with two variable-threaded screws: a multicenter case report of three cases.

Background: The direct lateral trans-gluteal muscle splitting transiliac approach was popularized to fixate the sacroiliac joint (SIJ) using three cannulated triangular titanium implants (TTIs) wedges. Publications support efficacy of the direct lateral approach but a paucity of literature to help surgeons revise these implants when they fail. Intuitively the implants can be removed but require an open incision and dissection through the gluteal muscles and scar tissue which can lead to muscle and neurovascular injuries. Our objective was to evaluate the clinical outcome, measured by patient-reported Visual Analog Score (VAS), of three patients who had failed direct lateral SIJ fusions each using three implants and describe a revision technique using a new percutaneous lateral-oblique transfixation technique with two variable-threaded screws while preserving the original implants. Case Description: Two separate orthopedic spine surgeons at different hospitals performed the technique using two SacroFuse® screws for SIJ revision fusion in three patients who had clinical symptoms and radiographic findings of SIJ pseudoarthrosis after direct lateral approach. One 61 years old male patient had a previous surgery with three lateral threaded screw implants. Two females with ages 47 and 40 years old had three TTI wedges. Follow-up from 10 to 26 months. Patients discharged home the same day. Mean procedure time of 20 minutes with blood loss less than five cc. Incision size was approximately 1 inch. Each patient had a 12 mm × 60 mm and a 12 mm × 50 mm screw filled with NanoFuse Biologics synthetic bioactive glass and demineralized bone matrix. Prior implants were left in place. There was an 89% decrease in mean VAS score of 9.5 to 1. Conclusions: This is a clinically valuable report because until now there was no reconstructive surgery to revise direct lateral implants other than removal with potential neurovascular risks. This is the first article to demonstrate a lateral-oblique transfixation technique with two variable-threaded screws for successful salvage of SIJ pseudoarthrosis after direct lateral fixation without implant removal. The Sacrix technique achieved immediate stability and long-term fusion documented on computed tomography (CT) scan as early as 6 months.

Influence of shift work on periodontitis according to the occupation group.

This study aimed to investigate the effects of shift work on periodontal disease in blue-and white-collar workers and to examine the interaction effects between occupation and work patterns. Data were collected from the Korea National Health and Nutrition Examination Survey conducted by the Korean Ministry of Health and Welfare for a total of nine years from 2007 to 2015. Participants with missing outcome variables were excluded from the analysis and a total of 32,336 participants were included in the final analysis. Univariable odds ratios (OR) were calculated using a logistic regression model with 95% confidence interval (CI). A multivariable logistic regression analysis was performed using the backward elimination method. The CONTRAST statement was used to analyze the interaction effect between occupation and work patterns. Multivariable logistic regression analysis revealed that interaction effects are present between the terms, occupational type and work pattern. Crude OR of shift work for periodontitis was 1.269 [CI 1.213-1.327, P < 0.05]. However, following adjustment for multiple confounding factors and the interaction effect term considered, this OR (1.269) increased to 1.381 [CI 1.253-1.523] in white-collar group while it decreased to 1.198 [1.119-1.283] in blue-collar. Crude OR of blue-collar (OR = 3.123, CI 2.972-3.281, P < 0.05) decreased to 1.151 [CI 1.049-1.262] when interaction effect to the shift work was considered. Shift work pattern increases the risk for periodontitis and this adverse effect is greater when white-collar workers are engaged comparing to blue-collar. The result of this study suggests that 24/7 lifestyle of the modern society poses health risks to the relevant people and the potential harm can be greater to white-collar workers.

Periodontitis of maxillary teeth screened by community periodontal index is associated with chronic rhinosinusitis defined by EPOS 2020 guideline.

We aimed to evaluate the association between periodontitis in the upper jaw and chronic rhinosinusitis (CRS) using the nationwide Korean National Health and Nutrition Examination Survey (KNHANES) data. In this cross-sectional study, data of KNHANES participants enrolled between 2008 and 2012 were reviewed. Periodontitis of the upper teeth was diagnosed by dentists according to the community periodontal index with standardized methods. CRS was diagnosed by otorhinolaryngologists according to the European Position Paper on Rhinosinusitis and Nasal Polyps 2020 with nasal endoscopy findings. We also evaluated the association between periodontitis and CRS according to smoking and drinking status. Univariate and multivariate logistic regression analyses were performed. Overall, 28,761 participants were eligible for analysis, and 210 were diagnosed with CRS. Periodontitis was associated with CRS diagnosis (odds ratio [OR] = 1.391, 95% confidence interval [CI] = 1.013-1.912). Non-drinkers showed no significant association between periodontitis and CRS (OR = 1.142, 95% CI 0.746-1.749). However, among drinkers, periodontitis was significantly associated with CRS (OR = 1.733, 95% CI 1.091-2.753). The number of smokers with CRS was not statistically sufficient and a logistic regression model based on smoking status could not be generated. Individuals with periodontitis in the upper jaw may need to consult an otorhinolaryngologist for comorbid CRS especially according to drinking status.

False-positive supraclavicular lymph node detected on chest computed tomography in oncology patients: Clinical implication based on subsequent neck ultrasonography and ultrasonography-guided tissue sampling.

PURPOSE: The purpose of this study was to assess the prevalence and clinical implications of false-positive supraclavicular lymph node (LN) detected on chest computed tomography (CT), using subsequent neck ultrasonography (US) and US-guided tissue sampling. METHODS: Among 172 patients with suspected supraclavicular LNs identified on CT, 87 underwent neck US or US-guided tissue sampling. Receiver operating characteristic curve and logistic regression analyses were performed to determine the diagnostic performance of US and independent predictors of false-positive LNs. RESULTS: Among 87 patients, 49 (56.3%) were pathologically confirmed as metastases, 26 (29.9%) were negative for malignancy, and 12 (13.8%) had pseudolesions or schwannomas. The diagnostic indices were as follows: sensitivity, 91.8%; specificity, 92.3%; PPV, 95.7%; NPV, 85.7%; and accuracy, 92.0% (AUC = 0.921; 95% CI: 0.832-0.970, p < 0.001). The false-positive group had a higher mean age than the true-positive group (mean age, 69.8 ± 9.2 vs. 63.9 ± 9.8, p = 0.003). Logistic regression analyses revealed that age ≥ 65 years was the only independent predictor of false-positive LNs (OR = 4.391; 95% CI: 1.037-18.582; p = 0.044). CONCLUSION: Subsequent US can be helpful for evaluating suspicious supraclavicular LNs detected on CT to establish appropriate management, especially in older patients.

Roles of Heterojunction and Cu Vacancies in the Au@Cu2-xSe for the Enhancement of Electrochemical Nitrogen Reduction Performance.

The utilization of hydrogen (H2) as a fuel source is hindered by the limited infrastructure and storage requirements. In contrast, ammonia (NH3) offers a promising solution as a hydrogen carrier due to its high energy density, liquid storage capacity, low cost, and sustainable manufacturing. NH3 has garnered significant attention as a key component in the development of next-generation refueling stations, aligning with the goal of a carbon-free economy. The electrochemical nitrogen reduction reaction (ENRR) enables the production of NH3 from nitrogen (N2) under ambient conditions. However, the low efficiency of the ENRR is limited by challenges such as the electron-stealing hydrogen evolution reaction (HER) and the breaking of the stable N2 triple bond. To address these limitations and enhance ENRR performance, we prepared Au@Cu2-xSe electrocatalysts with a core@shell structure using a seed-mediated growth method and a facile hot-injection method. The catalytic activity was evaluated using both an aqueous electrolyte of KOH solution and a nonaqueous electrolyte consisting of tetrahydrofuran (THF) solvent with lithium perchlorate and ethanol as proton donors. ENRR in both aqueous and nonaqueous electrolytes was facilitated by the synergistic interaction between Au and Cu2-xSe (copper selenide), forming an Ohmic junction between the metal and p-type semiconductor that effectively suppressed the HER. Furthermore, in nonaqueous conditions, the Cu vacancies in the Cu2-xSe layer of Au@Cu2-xSe promoted the formation of lithium nitride (Li3N), leading to improved NH3 production. The synergistic effect of Ohmic junctions and Cu vacancies in Au@Cu2-xSe led to significantly higher ammonia yield and faradaic efficiency (FE) in nonaqueous systems compared to those in aqueous conditions. The maximum NH3 yields were approximately 1.10 and 3.64 µg h-1 cm-2, with the corresponding FE of 2.24 and 67.52% for aqueous and nonaqueous electrolytes, respectively. This study demonstrates an attractive strategy for designing catalysts with increased ENRR activity by effectively engineering vacancies and heterojunctions in Cu-based electrocatalysts in both aqueous and nonaqueous media.

Milnacipran Has an Antihyperalgesic Effect on Cisplatin-Induced Neuropathy.

(1) Background: Milnacipran is a typical serotonin-norepinephrine reuptake inhibitor and has been shown to have analgesic effects in several pain models. However, its antihyperalgesic effect in cisplatin-induced neuropathy remains unknown. We examined the effects of intraperitoneal (IP) milnacipran on allodynia in cisplatin-induced peripheral neuropathic mice. (2) Methods: Peripheral neuropathy was induced by injecting cisplatin (2.3 mg/kg/day, IP) six times, on every other day. Saline or milnacipran (10, 30, 50 mg/kg, IP) were then administered to the neuropathic mice. We examined mechanical allodynia using von Frey hairs at preadministration and at 30, 60, 90, 120, 180, 240 min and 24 h after drug administration. We also measured the dorsal root ganglion (DRG) activating transcription factor 3 (ATF3) to confirm the analgesic effects of milnacipran. (3) Results: For the milnacipran groups, the decreased paw withdrawal thresholds to mechanical stimuli were significantly reversed when compared to the preadministration values and the values in the saline-injected control group (p < 0.0001). Milnacipran administration to cisplatin-induced peripheral neuropathic mice resulted in a significant suppression of neuronal ATF3 activation (p < 0.01). (4) Conclusions: Milnacipran given via IP injection attenuates mechanical allodynia in mouse models of cisplatin-induced poly-neuropathic pain. These effects were confirmed by significant suppression of neuronal ATF3 activation in the DRG.

Tumor lipid metabolism: a mechanistic link between diet and cancer progression.

The potential for 'anti-cancer' diets to markedly alter cancer risk and prognosis has captured the imagination of patients, physicians, and researchers alike, but many of these dietary recommendations come from correlative studies that attribute certain diets to altered cancer risk. While provocative, little is known about the molecular mechanisms behind how these dietary interventions impact cancer progression. Within this context, however, changes in tumor lipid metabolism are emerging as a key contributor. In this review, we examine the current understanding of lipid metabolism in the tumor microenvironment (TME), suggesting how diet-induced changes in lipid composition may regulate tumor progression and therapeutic efficacy. By dissecting various cellular pathways involved in lipid metabolism, we highlight how diet modulates the balance between saturated and unsaturated fatty acid (FA) species in tumors to impact cancer cell and stromal cell function. Finally, we describe how current cancer therapies may synergize with diet to improve therapeutic efficacy.

Measured sodium excretion is associated with cardiovascular outcomes in non-dialysis CKD patients: results from the KNOW-CKD study.

Background: There are insufficient studies on the effect of dietary salt intake on cardiovascular (CV) outcomes in chronic kidney disease (CKD) patients, and there is no consensus on the sodium (Na) intake level that increases the risk of CV disease in CKD patients. Therefore, we investigated the association between dietary salt intake and CV outcomes in CKD patients. Methods: In the Korean cohort study for Outcome in patients with CKD (KNOW-CKD), 1,937 patients were eligible for the study, and their dietary Na intake was estimated using measured 24h urinary Na excretion. The primary outcome was a composite of CV events and/or all-cause death. The secondary outcome was a major adverse cardiac event (MACE). Results: Among 1,937 subjects, there were 205 (10.5%) events for the composite outcome and 110 (5.6%) events for MACE. Compared to the reference group (urinary Na excretion< 2.0g/day), the group with the highest measured 24h urinary Na excretion (urinary Na excretion ≥ 8.0g/day) was associated with increased risk of both the composite outcome (hazard ratio 3.29 [95% confidence interval 1.00-10.81]; P = 0.049) and MACE (hazard ratio 6.28 [95% confidence interval 1.45-27.20]; P = 0.013) in a cause-specific hazard model. Subgroup analysis also showed a pronounced association between dietary salt intake and the composite outcome in subgroups of patients with abdominal obesity, female, lower estimated glomerular filtration rate (< 60 ml/min per 1.73m2), no overt proteinuria, or a lower urinary potassium-to-creatinine ratio (< 46 mmol/g). Conclusion: A high-salt diet is associated with CV outcomes in non-dialysis CKD patients.

Production and engineering of nanobody-based quenchbody sensors for detecting recombinant human growth hormone and its isoforms.

Due to athletes' misuse of recombinant human growth hormone (rhGH) for performance improvement, the World Anti-Doping Agency has designated rhGH as a prohibited substance. This study focuses on the development and improvement of a simple and fast rhGH detection method using a fluorescence-incorporated antibody sensor "Quenchbody (Q-body)" that activates upon antigen binding. Camelid-derived nanobodies were used to produce stable Q-bodies that withstand high temperatures and pH levels. Notably, pituitary human growth hormone (phGH) comprises two major isoforms, namely 22 and 20 kDa GH, which exist in a specific ratio, and the rhGH variant shares the same sequence as the 22 kDa GH isoform. Therefore, we aimed to discriminate rhGH abuse by analyzing its specific isoform ratio. Two nanobodies, NbPit (recognizing phGH) and NbRec (preferentially recognizing 22 kDa rhGH), were used to develop the Q-bodies. Nanobody production in Escherichia coli involved the utilization of a vector containing 6xHis-tag, and Q-bodies were obtained using a maleimide-thiol reaction between the N-terminal of the cysteine tag and a fluorescent dye. The addition of tryptophan residue through antibody engineering resulted in increased fluorescence intensity (FI) (from 2.58-fold to 3.04-fold). The limit of detection (LOD) was determined using a fluorescence response, with TAMRA-labeled NbRec successfully detecting 6.38 ng/ml of 22 kDa rhGH while unable to detect 20 kDa GH. However, ATTO520-labeled NbPit detected 7.00 ng/ml of 20 kDa GH and 2.20 ng/ml 22 kDa rhGH. Q-bodies successfully detected changes in the GH concentration ratio from 10 to 40 ng/ml in human serum within 10 min without requiring specialized equipment and kits. Overall, these findings have potential applications in the field of anti-doping measures and can contribute to improved monitoring and enforcement of rhGH misuse, ultimately enhancing fairness and integrity in competitive sports.

The Fatal Role of Enterohaemorrhagic Escherichia coli Shiga Toxin-associated Extracellular Vesicles in Host Cells.

Enterohemorrhagic Escherichia coli (EHEC) is a specific subset of Shiga toxin-producing Escherichia coli (STEC) strains that are characterized by their ability to cause bloody diarrhea (hemorrhagic colitis) and potentially life-threatening, extraintestinal complications such as hemolytic uremic syndrome (HUS), which is associated with acute renal failure., contributing to severe clinical outcomes. The Shiga toxins (Stxs), produced by EHEC, are primary virulence factors. These potent cytotoxins are composed of one enzymatically active A subunit (StxA) and five receptor-binding B subunits (StxB). Although the toxins are primarily associated with cytotoxic effects, they also elicit other pathogenic consequences due to their induction of a number of biological processes, including apoptosis through ER-stress, pro-inflammatory responses, autophagy, and post-translational modification (PTM). Moreover, several studies have reported the association between Stxs and extracellular vesicles (EVs), including microvesicles and exosomes, demonstrating that Stx-containing EVs secreted by intoxicated macrophages are taken up by recipient cells, such as toxin-sensitive renal proximal tubular epithelial cells. This mechanism likely contributes to the spreading of Stxs within the host, and may exacerbate gastrointestinal illnesses and kidney dysfunction. In this review, we summarize recent findings relating to the host responses, in different types of cells in vitro and in animal models, mediated by Stxs-containing exosomes. Due to their unique properties, EVs have been explored as therapeutic agents, drug delivery systems, and diagnostic tools. Thus, potential therapeutic applications of EVs in EHEC Stxs-mediated pathogenesis are also briefly reviewed.

Age- and dose-dependent effect of statin use on the risk of osteoporotic fracture in older adults.

Previous studies have revealed the protective effects of statins on bone but the association of statins use with osteoporosis-related measurement has shown controversial results. In this study, we found an age, dose andduration-dependent osteoprotective effect of statins in general older population. PURPOSE: Previous studies have revealed the protective effects of statins on bone but the association of statins use with osteoporotic fractures has shown controversial results. METHODS: In this study with Korean National Health Insurance Service-Senior cohort database, a total of 365,656 elderly without previous history of osteoporosis and who were started on statin since January 1 2004 were included and observed until December 31 2012. Hazard rations (HR) for major osteoporotic fractures were calculated using the weighted Cox proportional hazards model with inverse-probability of treatment weighting method. RESULTS: During 6.27 years of follow-up period, 54,959 osteoporotic fractures occurred and the majority of fractures (69.5%) were vertebral fractures. Compared with non-users, statin use was associated with a decreased risk of all outcomes with adjusted HR (95% CI) of 0.77 (0.72-0.83; P < 0.001) for major osteoporotic fractures, 0.49 (0.38-0.62; P < 0.001) for hip fractures, and 0.70 (0.64-0.77; P < 0.001) for vertebral fractures. When outcomes were examined separately by sex, the results were broadly comparable in terms of patterns of risk reduction by statin use. The patients with statin initiated at age ≥ 80 years had the highest risk reduction for most outcomes relative to non-users. Higher cumulative dose of statin was negatively associated with the osteoporotic fracture risk; 0.97 (0.91-1.02) for 30-364 cumulative daily defined dose (cDDD), 0.45 (0.40-0.51) for 365-1,094 cDDD, and 0.22 (0.15-0.33) for ≥ 1,095 cDDD. CONCLUSIONS: Our results showed that statin use was associated with significant reduction in the risk of osteoporotic fractures in general older population.

Impaired BCAA catabolism in adipose tissues promotes age-associated metabolic derangement.

Adipose tissues are central in controlling metabolic homeostasis and failure in their preservation is associated with age-related metabolic disorders. The exact role of mature adipocytes in this phenomenon remains elusive. Here we describe the role of adipose branched-chain amino acid (BCAA) catabolism in this process. We found that adipocyte-specific Crtc2 knockout protected mice from age-associated metabolic decline. Multiomics analysis revealed that BCAA catabolism was impaired in aged visceral adipose tissues, leading to the activation of mechanistic target of rapamycin complex (mTORC1) signaling and the resultant cellular senescence, which was restored by Crtc2 knockout in adipocytes. Using single-cell RNA sequencing analysis, we found that age-associated decline in adipogenic potential of visceral adipose tissues was reinstated by Crtc2 knockout, via the reduction of BCAA-mTORC1 senescence-associated secretory phenotype axis. Collectively, we propose that perturbation of BCAA catabolism by CRTC2 is critical in instigating age-associated remodeling of adipose tissue and the resultant metabolic decline in vivo.

Association of Chronic Kidney Disease With Atrial Fibrillation in the General Adult Population: A Nationwide Population-Based Study.

Background The incidences of atrial fibrillation (AF) and chronic kidney disease (CKD) are increasing, and AF is prevalent in patients with CKD. However, few studies have investigated the incidence or association of AF in a large CKD population from a longitudinal study. Methods and Results From a nationwide cohort, a total of 4 827 987 Korean individuals without prior AF, who received biennial health checkups provided by the National Health Insurance Service between 2009 and 2012 in Korea, were analyzed. Incidence of AF was ascertained through the end of 2018. During a median follow-up of 8.1 years, the annual incidence rate of AF was 1.17 per 1000 person-years among subjects without CKD, 1.55 for stage 1 CKD, 1.86 for stage 2 CKD, 2.1 for stage 3 CKD, and 4.33 for stage 4 CKD. In Fine-Gray regression models, CKD was associated with an increased risk of AF; the adjusted hazard ratios and 95% CIs of AF occurrence were 1.77 (1.69-1.85), 1.85 (1.80-1.91), 1.99 (1.95-2.04), and 4.04 (3.07-5.33) in individuals with CKD stages 1, 2, 3, and 4, respectively, compared with non-CKD. The association between CKD and incident AF remained statistically significant after adjustment for multiple confounding factors and was consistent across subgroups stratified by sex and age. Conclusions CKD is associated with an increased incidence of AF. Even mild CKD is associated with incident AF, and there was a stepwise increase in the risk of incident AF with a decrease in renal function.

Comparison of cardiovascular event predictability between the 2009 and 2021 Chronic Kidney Disease Epidemiology Collaboration equations in a Korean chronic kidney disease cohort: the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease.

BACKGROUND: The 2009 Chronic Kidney Disease Epidemiology Collaboration creatinine-based estimated glomerular filtration rate (eGFRcr) equation contains a race component that is not based on biology and may cause a bias in results. Therefore, the 2021 eGFRcr and creatinine-cystatin C-based eGFR (eGFRcr-cysC) equations were developed with no consideration of race. This study compared the cardiovascular event (CVE) and all-cause mortality and CVE combined predictability among the three eGFR equations in Korean chronic kidney disease (CKD) patients. METHODS: This study included 2,207 patients from the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease. Receiver operating characteristic (ROC) and net reclassification improvement (NRI) index were used to compare the predictability of the study outcomes according to the 2009 eGFRcr, 2021 eGFRcr, and 2021 eGFRcr-cysC equations. RESULTS: The overall prevalence of CVE and all-cause mortality were 9% and 7%, respectively. There was no difference in area under the curve of ROC for CVE and mortality and CVE combined among all three equations. Compared to the 2009 eGFRcr, both the 2021 eGFRcr (NRI, 0.013; 95% confidence interval [CI], - 0.002 to 0.028) and the eGFRcr-cysC (NRI, -0.001; 95% CI, -0.031 to 0.029) equations did not show improved CVE predictability. Similar findings were observed for mortality and CVE combined predictability with both the 2021 eGFRcr (NRI, -0.019; 95% CI, -0.039-0.000) and the eGFRcr-cysC (NRI, -0.002; 95% CI, -0.023 to 0.018). CONCLUSION: The 2009 eGFRcr equation was not inferior to either the 2021 eGFRcr or eGFRcr-cysC equation in predicting CVE and the composite of mortality and CVE in Korean CKD patients.