Prenatal exposure to Di(2-ethylhexyl) phthalate and high-fat diet synergistically disrupts gonadal function in male mice†.

Prenatal exposure to Di (2-ethylhexyl) phthalate (DEHP) impairs the reproductive system and causes fertility defects in male offspring. Additionally, high-fat (HF) diet is a risk factor for reproductive disorders in males. In this study, we tested the hypothesis that prenatal exposure to a physiologically relevant dose of DEHP in conjunction with HF diet synergistically impacts reproductive function and fertility in male offspring. Female mice were fed a control or HF diet 7 days prior to mating and until their litters were weaned on postnatal day 21. Pregnant dams were exposed to DEHP or vehicle from gestational day 10.5 until birth. The male offspring's gross phenotype, sperm quality, serum hormonal levels, testicular histopathology, and testicular gene expression pattern were analyzed. Male mice born to dams exposed to DEHP + HF had smaller testes, epididymides, and shorter anogenital distance compared with those exposed to HF or DEHP alone. DEHP + HF mice had lower sperm concentration and motility compared with DEHP mice. Moreover, DEHP + HF mice had more apoptotic germ cells, fewer Leydig cells, and lower serum testosterone levels than DEHP mice. Furthermore, testicular mRNA expression of Dnmt1 and Dnmt3a was two to eight-fold higher than in DEHP mice by qPCR, suggesting that maternal HF diet and prenatal DEHP exposure additively impact gonadal function by altering the degree of DNA methylation in the testis. These results suggest that the combined exposure to DEHP and high-fat synergistically impairs reproductive function in male offspring, greater than exposure to DEHP or HF diet alone.

Relationship between short-term ozone exposure, cause-specific mortality, and high-risk populations: a nationwide, time-stratified, case-crossover study.

BACKGROUND: Previous studies reported that short-term exposure to ground-level ozone is associated with mortality risk. However, due to the limited monitored areas, existing studies were limited in assessing the nationwide risk and suggesting specific vulnerable populations to the ozone-mortality risk. METHODS: We performed a nationwide time-stratified case-crossover study to evaluate the association between short-term ozone and cause-specific mortality in South Korea (2015- 2019). A machine learning-ensemble prediction model (a test R2>0.96) was used to assess the short-term ozone exposure. Stratification analysis was conducted to examine the high-risk populations, and the excess mortality due to non-compliance with the WHO guideline was also assessed. RESULTS: For all-cause mortality (1,343,077 cases), the risk associated with ozone (lag0- 1) was weakly identified (odd ratio: 1.005 with 95% CI: 0.997-1.014), and the risk was prominent in mortality with circulatory system diseases. In addition, based on the point estimates, the ozone-mortality risk was higher in people aged less than 65y, and this pattern was also observed in circulatory system disease deaths and urban areas. CONCLUSIONS: This study provides national estimates of mortality risks associated with short-term ozone. Results showed that the benefits of stricter air quality standards could be greater in vulnerable populations.

Air pollution and acute kidney injury with comorbid disease: A nationwide case-crossover study in South Korea.

Emerging evidence suggests that air pollution is a significant contributor to the global burden of kidney disease. Although acute kidney injury (AKI) is a common secondary event in ill patients, evidence regarding the association between air pollution and AKI accompanied by specific comorbidities is limited. This study aimed to estimate the association between short-term exposure to air pollution (fine particulate matter ≤2.5 µm [PM2.5] and ozone [O3]) and incident AKI by comorbid diseases using the Korea National Health Information Database (NHID). Total of 160,390 incident AKI cases, defined as an emergency department (ED) visit due to AKI, were observed within the period 2015-2021 in inland South Korea. A time-stratified case-crossover design was applied for PM2.5 and O3 individually, using a conditional logistic regression model within each case and its own control (three or four days of the same day of the week in the same month) to estimate the association between short-term air pollution exposure and ED visits due to AKI. Short-term exposure to PM2.5 and O3 was associated with ED visits due to AKI with ORs of 1.008 (95% confidence interval [CI]: 0.999, 1.017) and 1.019 (95% CI: 1.005, 1.033) for an interquartile range (IQR) increase in lag 0-1 day PM2.5 and O3 respectively, although OR for PM2.5 was marginally significant. The odds of incident AKI associated with PM2.5 was evident in conjunction with ischemic heart disease, cerebrovascular disease, gastrointestinal bleeding, and pneumonia. For O3, the estimated odds was prominent for AKI with ischemic heart disease. In addition, the comorbid disease-specific odds of AKI attributed to air pollution varied by sex and age. Our findings provide epidemiological evidence of a plausible mechanism between air pollution and incident AKI and suggest the need for personalized AKI prevention strategies attributed to air pollution.

Glomerular crescents are associated with the risk of type 2 diabetic kidney disease progression: a retrospective cohort study.

BACKGROUND: Diabetic kidney disease (DKD) stands as the predominant cause of chronic kidney disease and end-stage kidney disease. Its diverse range of manifestations complicates the treatment approach for patients. Although kidney biopsy is considered the gold standard for diagnosis, it lacks precision in predicting the progression of kidney dysfunction. Herein, we addressed whether the presence of glomerular crescents is linked to the outcomes in patients with biopsy-confirmed type 2 DKD. METHODS: We performed a retrospective evaluation, involving 327 patients diagnosed with biopsy-confirmed DKD in the context of type 2 diabetes, excluding cases with other glomerular diseases, from nine tertiary hospitals. Hazard ratios (HRs) were calculated using a Cox regression model to assess the risk of kidney disease progression, defined as either ≥ 50% decrease in estimated glomerular filtration rates or the development of end-stage kidney disease, based on the presence of glomerular crescents. RESULTS: Out of the 327 patients selected, ten patients had glomerular crescents observed in their biopsied tissues. Over the follow-up period (median of 19 months, with a maximum of 18 years), the crescent group exhibited a higher risk of kidney disease progression than the no crescent group, with an adjusted HR of 2.82 (1.32-6.06) (P = 0.008). The presence of heavy proteinuria was associated with an increased risk of developing glomerular crescents. CONCLUSION: The presence of glomerular crescents is indeed linked to the progression of type 2 DKD. Therefore, it is important to determine whether there is an additional immune-mediated glomerulonephritis requiring immunomodulation, and it may be prudent to monitor the histology and repeat a biopsy.

Intradiscal vacuum phenomenon matches lumbar spine degeneration patterns in an ageing population.

PURPOSE: Intra-Discal Vacuum phenomenon (IDVP) is well-recognised, yet poorly visualised and poorly understood radiological finding in disc degeneration, particularly with regard to its role in spinal alignment. CT analysis of the lumbar spine in an aging population aims to identify patterns associated with IDVP including lumbopelvic morphology and associated spinal diagnoses. METHODS: An analysis was performed of an over-60s population sample of 2020 unrelated abdominal CT scans, without acute spinal presentations. Spinal analysis included sagittal lumbopelvic reconstructions to assess for IDVP and pelvic incidence (PI). Subjects with degenerative pathologies, including previous vertebral fractures, auto-fusion, transitional vertebrae, and listhesis, were also selected out and analysed separately. RESULTS: The prevalence of lumbar spine IDVP was 50.3% (955/1898) and increased with age (125 exclusions). This increased in severity towards the lumbosacral junction (L1L2 8.3%, L2L3 10.9%, L3L4 11.5%, L4L5 23.9%, and L5S1 46.3%). A lower PI yielded a higher incidence of IDVP, particularly at L5S1 (p < 0.01). A total of 292 patients had IDVP with additional degenerative pathologies, which were more likely to occur at the level of isthmic spondylolisthesis, adjacent to a previous fracture or suprajacent to a lumbosacral transitional vertebra (p < 0.05). CONCLUSIONS: This study identified the prevalence and severity of IDVP in an aging population. Sagittal patterns that influence the pattern of IVDP, such as pelvic incidence and degenerative pathologies, provide novel insights into the function of aging spines.

The Impact of Obesity on Kidney Disease: Observational Cohort Study Analyzing 14,492 Kidney Biopsy Cases.

BACKGROUND: The obesity epidemic is associated with the emergence of new kidney diseases including obesity-related glomerulopathy (ORG) and metabolic syndrome-associated disorders. However, the effects of obesity on prevalence and outcome of biopsy-proven kidney disease are not well known. METHODS: We analyzed 14,492 kidney biopsies in 18 hospitals from 1979 to 2018 in Korea. Obesity was defined as a body mass index value of ≥ 30 kg/m². RESULTS: The most common disease was IgA nephropathy (IgAN) in both obese and non-obese participants (33.7% vs. 38.9%). Obesity was associated with a higher risk of focal segmental glomerulosclerosis (FSGS) and hypertensive nephropathy (HT-N) (odds ratio [OR], 1.72, 95% confidence interval [CI], 1.37-2.17; OR, 1.96, 95% CI, 1.21-3.19) and a lower risk of IgAN (OR, 0.74, 95% CI, 0.62-0.88). During the median follow up of 93.1 ± 88.7 months, obesity increased the risk of end-stage kidney disease (ESKD) in patients with IgAN (relative risk [RR], 1.49, 95% CI, 1.01-2.20) and lupus nephritis (LN) (RR, 3.43, 95% CI, 1.36-8.67). Of 947 obese individuals, ORG was detected in 298 (31.5%), and 230 participants had other kidney diseases, most commonly, IgAN (40.9%) followed by diabetic nephropathy (15.2%). Participants with ORG, when combined with other renal diseases, showed higher risks for developing ESKD compared to those with ORG alone (RR, 2.48, 95% CI, 1.09-5.64). CONCLUSION: Obesity is associated with an increased risk of FSGS and HT-N, and also increase the ESKD risk in IgAN and LN patients. ORG in obese participants may have favorable renal outcomes if it occurs alone without any other renal disease.

Systematic Review of Preclinical Studies on the Efficacy and Mechanisms of Herbal Medicines in Post-Myocardial Infarction Heart Failure with Reduced Ejection Fraction.

Background and Objectives: Heart failure with reduced ejection fraction (HFrEF) remains a significant burden. Traditional herbal medicines have shown cardioprotective effects in treating HFrEF. However, the implications of herbal formulation considering the dynamic immunohistological changes in the myocardium following acute ischemic injury have been insufficiently discussed. This review investigated the efficacy and mechanisms reported in studies using rat or mouse models of HFrEF induced by left descending coronary artery ligation. Materials and Methods: A systematic search was conducted using PubMed, Embase, AMED, CINAHL, and CENTRAL databases. Information was extracted regarding study characteristics, disease model induction protocols, intervention characteristics, treatment protocols, outcomes, and suggested mechanisms. Hierarchical cluster analysis of test drugs was performed based on constituent herb similarities. The risk of bias (RoB) was assessed using the Systematic Review Center for Laboratory animal Experimentation RoB tool. Results: Overall, 26 studies met the eligibility criteria. HF model induction periods after LADCA ligation ranged from 1 day to 12 weeks. Most studies administered the test drug for four weeks. Commonly used herbs included Panax ginseng, Astragalus membranaceus, Salvia miltiorrhiza, Carthamus tinctorius, and Lepidium apetalum, which demonstrated anti-fibrotic, anti-inflammatory, and anti-apoptotic effects through various signaling pathways. The overall RoB was relatively high. No significant association was found between model induction periods and herbal formulations or examined mechanisms. Conclusions: Future research should consider the time-dependent immunohistological features of the myocardium during HF treatment.

Association of long-term exposure to air pollution with chronic sleep deprivation in South Korea: A community-level longitudinal study, 2008-2018.

BACKGROUND AND OBJECTIVE: Although there are many findings about the effects of fine particulate matter (PM2.5) and sleep deprivation on health respectively, the association between PM2.5 and chronic sleep deprivation has rarely been investigated. Thus, we aimed to investigate this association using a nationwide survey in South Korea. METHOD: We examined the association between long-term exposure to PM2.5 and chronic sleep deprivation using a national cross-sectional health survey covering the entire 226 districts in inland South Korea from 2008 to 2018, with a machine learning-based national air pollution prediction model with 1 km2 spatial resolution. RESULTS: Chronic sleep deprivation was positively associated with PM2.5 in the total population (odds ratio (OR): 1.09, 95% confidence interval (CI): 1.05-1.13) and sub-population (low, middle, high population density areas with OR: 1.127, 1.09, and 1.059, respectively). The association was consistently observed in both sexes (males with OR: 1.09, females with OR: 1.09)) and was more pronounced in the elderly population (OR: 1.12) than in the middle-aged (OR: 1.07) and young (OR: 1.09) populations. CONCLUSIONS: Our results are consistent with the hypothesis regarding the relationship between long-term PM2.5 exposure and chronic sleep deprivation, and the study provides quantitative evidence for public health interventions to improve air quality that can affect chronic sleep conditions.

The Preventive Effect of Specific Collagen Peptides against Dexamethasone-Induced Muscle Atrophy in Mice.

Muscle atrophy, also known as muscle wasting, is the thinning of muscle mass due to muscle disuse, aging, or diseases such as cancer or neurological problems. Muscle atrophy is closely related to the quality of life and has high morbidity and mortality. However, therapeutic options for muscle atrophy are limited, so studies to develop therapeutic agents for muscle loss are always required. For this study, we investigated how orally administered specific collagen peptides (CP) affect muscle atrophy and elucidated its molecular mechanism using an in vivo model. We treated mice with dexamethasone (DEX) to induce a muscular atrophy phenotype and then administered CP (0.25 and 0.5 g/kg) for four weeks. In a microcomputed tomography analysis, CP (0.5 g/kg) intake significantly increased the volume of calf muscles in mice with DEX-induced muscle atrophy. In addition, the administration of CP (0.25 and 0.5 g/kg) restored the weight of the gluteus maximus and the fiber cross-sectional area (CSA) of the pectoralis major and calf muscles, which were reduced by DEX. CP significantly inhibited the mRNA expression of myostatin and the phosphorylation of Smad2, but it did not affect TGF-ß, BDNF, or FNDC5 gene expression. In addition, AKT/mTOR, a central pathway for muscle protein synthesis and related to myostatin signaling, was enhanced in the groups that were administered CP. Finally, CP decreased serum albumin levels and increased TNF-α gene expression. Collectively, our in vivo results demonstrate that CP can alleviate muscle wasting through a multitude of mechanisms. Therefore, we propose CP as a supplement or treatment to prevent muscle atrophy.

Longitudinal Immune Profiling of a Severe Acute Respiratory Syndrome Coronavirus 2 Reinfection in a Solid Organ Transplant Recipient.

BACKGROUND: The underlying immunologic deficiencies enabling severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection are currently unknown. We describe deep longitudinal immune profiling of a transplant recipient hospitalized twice for coronavirus disease 2019 (COVID-19). METHODS: A 66-year-old male renal transplant recipient was hospitalized with COVID-19 March 2020 then readmitted to the hospital with COVID-19 233 days after initial diagnosis. Virologic and immunologic investigations were performed on samples from the primary and secondary infections. RESULTS: Whole viral genome sequencing and phylogenetic analysis revealed that viruses causing both infections were caused by distinct genetic lineages without evidence of immune escape mutations. Longitudinal comparison of cellular and humoral responses during primary SARS-CoV-2 infection revealed that this patient responded to the primary infection with low neutralization titer anti-SARS-CoV-2 antibodies that were likely present at the time of reinfection. CONCLUSIONS: The development of neutralizing antibodies and humoral memory responses in this patient failed to confer protection against reinfection, suggesting that they were below a neutralizing titer threshold or that additional factors may be required for efficient prevention of SARS-CoV-2 reinfection. Development of poorly neutralizing antibodies may have been due to profound and relatively specific reduction in naive CD4 T-cell pools. Seropositivity alone may not be a perfect correlate of protection in immunocompromised patients.

Excess mortality and the COVID-19 pandemic: causes of death and social inequalities.

BACKGROUND: During the coronavirus diseases 2019 (COVID-19) pandemic, population's mortality has been affected not only by the risk of infection itself, but also through deferred care for other causes and changes in lifestyle. This study aims to investigate excess mortality by cause of death and socio-demographic context during the COVID-19 pandemic in South Korea.  METHODS: Mortality data within the period 2015-2020 were obtained from Statistics Korea, and deaths from COVID-19 were excluded. We estimated 2020 daily excess deaths for all causes, the eight leading causes of death, and according to individual characteristics, using a two-stage interrupted time series design accounting for temporal trends and variations in other risk factors. RESULTS: During the pandemic period (February 18 to December 31, 2020), an estimated 663 (95% empirical confidence interval [eCI]: -2356-3584) excess deaths occurred in South Korea. Mortality related to respiratory diseases decreased by 4371 (3452-5480), whereas deaths due to metabolic diseases and ill-defined causes increased by 808 (456-1080) and 2756 (2021-3378), respectively. The increase in all-cause deaths was prominent in those aged 65-79 years (941, 88-1795), with an elementary school education or below (1757, 371-3030), or who were single (785, 384-1174), while a decrease in deaths was pronounced in those with a college-level or higher educational attainment (1471, 589-2328). CONCLUSION: No evidence of a substantial increase in all-cause mortality was found during the 2020 pandemic period in South Korea, as a result of a large decrease in deaths related to respiratory diseases that offset increased mortality from metabolic disease and diseases of ill-defined cause. The COVID-19 pandemic has disproportionately affected those of lower socioeconomic status and has exacerbated inequalities in mortality.

Comparison of the Efficacy and Safety of Tacrolimus and Low-Dose Corticosteroid with High-Dose Corticosteroid for Minimal Change Nephrotic Syndrome in Adults.

BACKGROUND: Tacrolimus is used as a steroid-sparing immunosuppressant in adults with minimal change nephrotic syndrome. However, combined treatment with tacrolimus and low-dose steroid has not been compared with high-dose steroid for induction of clinical remission in a large-scale randomized study. METHODS: In this 24-week open-label noninferiority study, we randomized 144 adults with minimal change nephrotic syndrome to receive 0.05 mg/kg twice-daily tacrolimus plus once-daily 0.5 mg/kg prednisolone, or once-daily 1 mg/kg prednisolone alone, for up to 8 weeks or until achieving complete remission. Two weeks after complete remission, we tapered the steroid to a maintenance dose of 5-7.5 mg/d in both groups until 24 weeks after study drug initiation. The primary end point was complete remission within 8 weeks (urine protein: creatinine ratio <0.2 g/g). Secondary end points included time until remission and relapse rates (proteinuria and urine protein: creatinine ratio >3.0 g/g) after complete remission to within 24 weeks of study drug initiation. RESULTS: Complete remission within 8 weeks occurred in 53 of 67 patients (79.1%) receiving tacrolimus and low-dose steroid and 53 of 69 patients (76.8%) receiving high-dose steroid; this difference demonstrated noninferiority, with an upper confidence limit below the predefined threshold (20%) in both intent-to-treat (11.6%) and per-protocol (17.0%) analyses. Groups did not significantly differ in time until remission. Significantly fewer patients relapsed on maintenance tacrolimus (3-8 ng/ml) plus tapered steroid versus tapered steroid alone (5.7% versus 22.6%, respectively; P=0.01). There were no clinically relevant safety differences. CONCLUSIONS: Combined tacrolimus and low-dose steroid was noninferior to high-dose steroid for complete remission induction in adults with minimal change nephrotic syndrome. Relapse rates were significantly lower with maintenance tacrolimus and steroid compared with steroid alone. No clinically-relevant differences in safety findings were observed.

Mechanical Stress Improves Fat Graft Survival by Promoting Adipose-Derived Stem Cells Proliferation.

Cell-assisted lipotransfer (CAL), defined as co-transplantation of aspirated fat with enrichment of adipose-derived stem cells (ASCs), is a novel technique for cosmetic and reconstructive surgery to overcome the low survival rate of traditional fat grafting. However, clinically approved techniques for increasing the potency of ASCs in CAL have not been developed yet. As a more clinically applicable method, we used mechanical stress to reinforce the potency of ASCs. Mechanical stress was applied to the inguinal fat pad by needling . Morphological and cellular changes in adipose tissues were examined by flow cytometric analysis 1, 3, 5, and 7 days after the procedure. The proliferation and adipogenesis potencies of ASCs were evaluated. CAL with ASCs treated with mechanical stress or sham control were performed, and engraftment was determined at 4 weeks post-operation. Flow cytometry analysis revealed that mechanical stress significantly increased the number as well as the frequency of ASC proliferation in fat. Proliferation assays and adipocyte-specific marker gene analysis revealed that mechanical stress promoted proliferation potential but did not affect the differentiation capacity of ASCs. Moreover, CAL with cells derived from mechanical stress-treated fat increased the engraftment. Our results indicate that mechanical stress may be a simple method for improving the efficacy of CAL by enhancing the proliferation potency of ASCs.

Standard for the Quantification of a Sterilization Effect Using an Artificial Intelligence Disinfection Robot.

Recent outbreaks and the worldwide spread of COVID-19 have challenged mankind with unprecedented difficulties. The introduction of autonomous disinfection robots appears to be indispensable as consistent sterilization is in desperate demand under limited manpower. In this study, we developed an autonomous navigation robot capable of recognizing objects and locations with a high probability of contamination and capable of providing quantified sterilization effects. In order to quantify the 99.9% sterilization effect of various bacterial strains, as representative contaminants with robots operated under different modules, the operating parameters of the moving speed, distance between the sample and the robot, and the radiation angle were determined. We anticipate that the sterilization effect data we obtained with our disinfection robot, to the best of our knowledge, for the first time, will serve as a type of stepping stone, leading to practical applications at various sites requiring disinfection.

Anti-Gastritis and Anti-Lung Injury Effects of Pine Tree Ethanol Extract Targeting Both NF-κB and AP-1 Pathways.

An ethanol extract (Pd-EE) of Pinus densiflora Siebold and Zucc was derived from the branches of pine trees. According to the Donguibogam, pine resin has the effects of lowering the fever, reducing pain, and killing worms. The purpose of this study is to investigate whether Pd-EE has anti-inflammatory effects. During in vitro trials, NO production, as well as changes in the mRNA levels of inflammation-related genes and the phosphorylation levels of related proteins, were confirmed in RAW264.7 cells activated with lipopolysaccharide depending on the presence or absence of Pd-EE treatment. The activities of transcription factors were checked in HEK293T cells transfected with adapter molecules in the inflammatory pathway. The anti-inflammatory efficacy of Pd-EE was also estimated in vivo with acute gastritis and acute lung injury models. LC-MS analysis was conducted to identify the components of Pd-EE. This extract reduced the production of NO and the mRNA expression levels of iNOS, COX-2, and IL-6 in RAW264.7 cells. In addition, protein expression levels of p50 and p65 and phosphorylation levels of FRA1 were decreased. In the luciferase assay, the activities of NF-κB and AP-1 were lowered. In acute gastritis and acute lung injury models, Pd-EE suppressed inflammation, resulting in alleviated damage.

Cissus subtetragona Planch. Ameliorates Inflammatory Responses in LPS-induced Macrophages, HCl/EtOH-induced Gastritis, and LPS-induced Lung Injury via Attenuation of Src and TAK1.

Several Cissus species have been used and reported to possess medicinal benefits. However, the anti-inflammatory mechanisms of Cissus subtetragona have not been described. In this study, we examined the potential anti-inflammatory effects of C. subtetragona ethanol extract (Cs-EE) in vitro and in vivo, and investigated its molecular mechanism as well as its flavonoid content. Lipopolysaccharide (LPS)-induced macrophage-like RAW264.7 cells and primary macrophages as well as LPS-induced acute lung injury (ALI) and HCl/EtOH-induced acute gastritis mouse models were utilized. Luciferase assays, immunoblotting analyses, overexpression strategies, and cellular thermal shift assay (CETSA) were performed to identify the molecular mechanisms and targets of Cs-EE. Cs-EE concentration-dependently reduced the secretion of NO and PGE2, inhibited the expression of inflammation-related cytokines in LPS-induced RAW264.7 cells, and decreased NF-κB- and AP-1-luciferase activity. Subsequently, we determined that Cs-EE decreased the phosphorylation events of NF-κB and AP-1 pathways. Cs-EE treatment also significantly ameliorated the inflammatory symptoms of HCl/EtOH-induced acute gastritis and LPS-induced ALI mouse models. Overexpression of HA-Src and HA-TAK1 along with CETSA experiments validated that inhibited inflammatory responses are the outcome of attenuation of Src and TAK1 activation. Taken together, these findings suggest that Cs-EE could be utilized as an anti-inflammatory remedy especially targeting against gastritis and acute lung injury by attenuating the activities of Src and TAK1.

Relationship between abdominal aortic calcification on plain radiograph and coronary artery calcification detected by computed tomography in hemodialysis patients
.

PURPOSE: Abdominal aortic calcification (AAC) can be assessed easily using a plain radiograph. We investigated the relationship between AAC assessed by plain radiography and coronary artery calcification (CAC) assessed by computed tomography (CT). MATERIALS AND METHODS: 62 hemodialysis patients who underwent lumbar lateral radiography and multidetector computed tomography (MDCT) were included in this study. We used logistic regression analyses to identify an independent association between AAC and severe CAC (> 400), and assessed the diagnostic performance of the AAC and CAC scores for prediction of cardiovascular disease (CVD) using receiver-operating characteristic (ROC) analysis. RESULTS: The mean age of participants was 55.3 ± 11.2 years, and 30 (48.4%) were men. 17 participants had a previous history of CVD. The mean dialysis duration was 4.3 ± 3.0 years. The mean AAC score was 3.6 ± 4.1. AAC scores were significantly positively correlated with CAC scores (r = 0.464, p < 0.001). In multivariate logistic analysis, AAC score (odds ratio (OR) 1.387, 95% confidence interval (CI) 1.117 - 1.723, p = 0.003) was independently associated with a severe CAC score (> 400). The areas under the ROC curve for CAC and AAC scores were 0.877 (95% CI 0.791 - 0.964, p < 0.001) and 0.723 (95% CI 0.570 - 0.876, p = 0.007), respectively. CONCLUSION: A high AAC score on plain radiograph is an independent risk factor for severe CAC score on CT and can be used to predict CVD.

Long-term Renal Outcome of Biopsy-proven Acute Tubular Necrosis and Acute Interstitial Nephritis.

BACKGROUND: Although emerging evidence suggest acute kidney injury (AKI) progress to chronic kidney disease (CKD), long-term renal outcome of AKI still remains unclear. Acute tubular necrosis (ATN) is the most common cause of AKI due to ischemia, toxin or sepsis. Acute interstitial nephritis (AIN), caused by drugs or autoimmune diseases is also increasingly recognized as an important cause of AKI. Unlike glomerular diseases, AKI is usually diagnosed in the clinical context without kidney biopsies, and lack of histology might contribute to this uncertainty. METHODS: Among 8,769 biopsy series, 253 adults who were histologically diagnosed with ATN and AIN from 1982 to 2018 at five university hospitals were included. Demographic and pathological features that are associated with the development of end stage renal disease (ESRD) were also examined. RESULTS: Rate of non-recovery of renal function at 6 month was significantly higher in the AIN (ATN vs AIN 49.3 vs 69.4%, P = 0.007) with a 2.71-fold higher risk of non- recovery compared to ATN (95% confidence interval [CI], 1.20-6.47). During the mean follow up of 76.5 ± 91.9 months, ESRD developed in 39.4% of patients with AIN, and 21.5% patients of ATN. The risk of ESRD was significantly higher in AIN (23.05; 95% CI, 2.42-219.53) and also in ATN (12.14; 95% CI, 1.19-24.24) compared to control with non-specific pathology. Older age, female gender, renal function at the time of biopsy and at 6 months, proteinuria and pathological features including interstitial inflammation and fibrosis, tubulitis, vascular lesion were significantly associated with progression to ESRD. CONCLUSION: Our study demonstrated that patients with biopsy proven ATN and AIN are at high risk of developing ESRD. AIN showed higher rate of non-renal recovery at 6 month than ATN.

Water Extract of Lotus Leaf Alleviates Dexamethasone-Induced Muscle Atrophy via Regulating Protein Metabolism-Related Pathways in Mice.

Muscle atrophy is an abnormal condition characterized by loss of skeletal muscle mass and function and is primarily caused by injury, malnutrition, various diseases, and aging. Leaf of lotus (Nelumbo nucifera Gaertn), which has been used for medicinal purposes, contains various active ingredients, including polyphenols, and is reported to exert an antioxidant effect. In this study, we investigated the effect of water extract of lotus leaf (LL) on muscle atrophy and the underlying molecular mechanisms of action. Amounts of 100, 200, or 300 mg/kg/day LL were administered to dexamethasone (DEX)-induced muscle atrophy mice for 4 weeks. Micro-computed tomography (CT) analysis revealed that the intake of LL significantly increased calf muscle volume, surface area, and density in DEX-induced muscle atrophy mice. Administration of LL recovered moving distance, grip strength, ATP production, and body weight, which were decreased by DEX. In addition, muscle damage caused by DEX was also improved by LL. LL reduced the protein catabolic pathway by suppressing gene expression of muscle atrophy F-Box (MAFbx; atrogin-1), muscle RING finger 1 (MuRF1), and forkhead box O (FoxO)3a, as well as phosphorylation of AMP-activated kinase (AMPK). The AKT-mammalian target of the rapamycin (mTOR) signal pathway, which is important for muscle protein synthesis, was increased in LL-administered groups. The HPLC analysis and pharmacological test revealed that quercetin 3-O-beta-glucuronide (Q3G) is a major active component in LL. Thus, Q3G decreased the gene expression of atrogin-1 and MuRF1 and phosphorylation of AMPK. This compound also increased phosphorylation levels of mTOR and its upstream enzyme AKT in DEX-treated C2C12 cells. We identified that LL improves muscle wasting through regulation of muscle protein metabolism in DEX-induced muscle atrophy mice. Q3G is predicted to be one of the major active phenolic components in LL. Therefore, we propose LL as a supplement or therapeutic agent to prevent or treat muscle wasting, such as sarcopenia.

Fat-to-Lean Mass Ratio Can Predict Cardiac Events and All-Cause Mortality in Patients Undergoing Hemodialysis.

BACKGROUND: Although higher body mass index (BMI) is associated with better survival in patients undergoing dialysis, BMI is not an adequate obesity indicator. We hypothesized that the fat-to-lean (F/L) mass ratio could be a suitable marker of nutritional status and evaluated its prognostic impact on long-term outcomes in patients undergoing hemodialysis (HD). METHODS: In total, 131 patients undergoing HD were recruited and monitored prospectively for up to 5 years. Body composition was analyzed, and other nutritional and inflammatory parameters were measured. RESULTS: The mean age of the cohort was 60.7 ± 13.6 years, and 65 patients were diabetic. Age, sex, diabetes, comorbidity, and inflammation were associated significantly with the F/L mass ratio. During the follow-up period, 21 patients experienced cardiac events and 22 patients died. Patients with higher F/L mass ratios had significantly higher risks of all-cause death (hazard ratio [HR] 3.61, 95% CI 1.07-12.13; p = 0.038) and cardiac events (HR 3.54, 95% CI 1.05-11.94; p = 0.041) than those with lower F/L mass ratios. CONCLUSIONS: The F/L mass ratio was a useful surrogate marker of nutritional and inflammatory status, and an independent predictor of cardiac events and all-cause mortality, in patients undergoing HD.