Glycocalyx-Mimicking Nanoparticles with Differential Organ Selectivity for Drug Delivery and Therapy.

Organ-selective drug delivery is expected to maximize the efficacy of various therapeutic modalities while minimizing their systemic toxicity. Lipid nanoparticles and polymersomes can direct the organ-selective delivery of mRNAs or gene editing machineries, but their delivery is limited to mostly liver, spleen, and lung. A platform that enables delivery to these and other target organs is urgently needed. Here, a library of glycocalyx-mimicking nanoparticles (GlyNPs) comprising five randomly combined sugar moieties is generated, and direct in vivo library screening is used to identify GlyNPs with preferential biodistribution in liver, spleen, lung, kidneys, heart, and brain. Each organ-targeting GlyNP hit show cellular tropism within the organ. Liver, kidney, and spleen-targeting GlyNP hits equipped with therapeutics effectively can alleviate the symptoms of acetaminophen-induced liver injury, cisplatin-induced kidney injury, and immune thrombocytopenia in mice, respectively. Furthermore, the differential organ targeting of GlyNP hits is influenced not by the protein corona but by the sugar moieties displayed on their surface. It is envisioned that the GlyNP-based platform may enable the organ- and cell-targeted delivery of therapeutic cargoes.

Association between body fat and bone mineral density in Korean adults: a cohort study.

Although obesity was once considered protective against osteoporosis, various factors influence the relationship between fat and bone mineral density (BMD). To establish the importance of healthy body composition in decelerating declines in BMD, we conducted a study to compare the association between body fat composition and BMD in Korean adults. Using data collected from the Kangbuk Samsung Health Study from 2012 to 2019, this cohort study compared the incidence of decreased BMD among the following four groups: normal BMI and normal adiposity (NBMI-NA), normal BMI and high adiposity (NBMI-HA), overweight, and obesity. Decreased BMD was defined as a Z-score ≤ - 2.0 in premenopausal women and men < 50 years of age or a T-score < - 1.0 in postmenopausal women and men ≥ 50 years of age. Individuals who were diagnosed with osteoporosis or compression fracture after their second visit were categorized as having decreased BMD. The incidence rate of decreased BMD in the NBMI-NA group was 3.37, and that in the NBMI-HA group was 4.81, which was the highest among all groups. After adjusting for confounding factors, NBMI-HA led to a significantly greater risk of decreased BMD compared to NBMI-NA (HR 1.47; 95% CI 1.09-1.99). Even with a normal BMI, a high BFP was associated with an increased risk of decreased BMD. Therefore, healthy body composition management, not simply BMI, is important in preventing decreased BMD.

The Adverse Effects and Nonmedical Use of Methylphenidate Before and After the Outbreak of COVID-19: Machine Learning Analysis.

BACKGROUND: Methylphenidate is an effective first-line treatment for attention-deficit/hyperactivity disorder (ADHD). However, many adverse effects of methylphenidate have been recorded from randomized clinical trials and patient-reported outcomes, but it is difficult to determine abuse from them. In the context of COVID-19, it is important to determine how drug use evaluation, as well as misuse of drugs, have been affected by the pandemic. As people share their reasons for using medication, patient sentiments, and the effects of medicine on social networking services (SNSs), the application of machine learning and SNS data can be a method to overcome the limitations. Proper machine learning models could be evaluated to validate the effects of the COVID-19 pandemic on drug use. OBJECTIVE: To analyze the effect of the COVID-19 pandemic on the use of methylphenidate, this study analyzed the adverse effects and nonmedical use of methylphenidate and evaluated the change in frequency of nonmedical use based on SNS data before and after the outbreak of COVID-19. Moreover, the performance of 4 machine learning models for classifying methylphenidate use based on SNS data was compared. METHODS: In this cross-sectional study, SNS data on methylphenidate from Twitter, Facebook, and Instagram from January 2019 to December 2020 were collected. The frequency of adverse effects, nonmedical use, and drug use before and after the COVID-19 pandemic were compared and analyzed. Interrupted time series analysis about the frequency and trends of nonmedical use of methylphenidate was conducted for 24 months from January 2019 to December 2020. Using the labeled training data set and features, the following 4 machine learning models were built using the data, and their performance was evaluated using F-1 scores: naïve Bayes classifier, random forest, support vector machine, and long short-term memory. RESULTS: This study collected 146,352 data points and detected that 4.3% (6340/146,352) were firsthand experience data. Psychiatric problems (521/1683, 31%) had the highest frequency among the adverse effects. The highest frequency of nonmedical use was for studies or work (741/2016, 36.8%). While the frequency of nonmedical use before and after the outbreak of COVID-19 has been similar (odds ratio [OR] 1.02 95% CI 0.91-1.15), its trend has changed significantly due to the pandemic (95% CI 2.36-22.20). Among the machine learning models, RF had the highest performance of 0.75. CONCLUSIONS: The trend of nonmedical use of methylphenidate has changed significantly due to the COVID-19 pandemic. Among the machine learning models using SNS data to analyze the adverse effects and nonmedical use of methylphenidate, the random forest model had the highest performance.

Nanovaccine Displaying Immunodominant T Cell Epitopes of Fibroblast Activation Protein Is Effective Against Desmoplastic Tumors.

Cancer-associated fibroblasts (CAFs), which are dominant cell types in the tumor microenvironment (TME), support tumor growth by secreting cytokines and forming an extracellular matrix (ECM) that hampers the penetration of chemical and biological therapeutics within the tumor and thereby limits their therapeutic efficacy. Here, we report a cancer nanovaccine targeting fibroblast activation protein α (FAP)-expressing CAFs as a potential pan-tumor vaccine. We predicted immunodominant FAP-specific epitope peptides in silico and selected two candidate peptides after in vitro and in vivo screening for immunogenicity and antitumor efficacy. Next, we developed a nanoparticle-based vaccine that displays the two selected epitope peptides on the surface of lipid nanoparticles encapsulating CpG adjuvant (FAPPEP-SLNPs). Immunization with one of two FAPPEP-SLNP nanovaccines led to considerable growth inhibition of various tumors, including desmoplastic tumors, by depleting FAP+ CAFs and thereby reducing ECM production in the TME while causing little appreciable adverse effects. Furthermore, when combined with a chemotherapeutic drug, the FAPPEP-SLNP nanovaccine increased drug accumulation and resulted in a synergistic antitumor efficacy far better than that of each corresponding monotherapy. These findings suggest that our FAPPEP-SLNP nanovaccine has potential for use as an "off-the-shelf" pan-tumor vaccine applicable to a variety of tumors and may be a suitable platform for use in various combination therapies.

Coronary artery calcium and risk of chronic kidney disease in young and middle-aged adults.

BACKGROUND: The role of the coronary artery calcium score (CACS) in incident chronic kidney disease (CKD) in asymptomatic young populations remains unclear. The aim of this study was to evaluate the association between CACSs and CKD development in adults. METHODS: A cohort study of 113 171 Korean adults (mean age 40.6 years) without CKD and proteinuria at baseline who underwent a cardiac tomography estimation of CACSs during health screening examinations was performed (median follow-up 4.2 years). The outcome was CKD, defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 and/or the presence of proteinuria. Hazard ratios (HRs) and 95% confidence intervals (CIs) for CKD were estimated using Cox proportional hazards regression analyses. RESULTS: A higher CACS was moderately associated with an increased risk of CKD in a dose-dependent manner. The multivariable-adjusted HRs for CKD comparing CACSs 1-100, 101-300 and >300 with a CACS of 0 were 1.15 (95% CI 1.05-1.25), 1.37 (95% CI 1.13-1.66) and 1.71 (95% CI 1.32-2.22), respectively (P for trend <.001). When CKD was defined using low eGFR and proteinuria separately, corresponding HRs for low eGFR were 1.31 (95% CI 1.05-1.62), 1.41 (95% CI 0.95-2.11) and 1.86 (95% CI 1.16-3.00), respectively (P for trend = .001), while the HRs for proteinuria were 1.11 (95% CI 1.02-1.21), 1.32 (95% CI 1.07-1.64) and 1.57 (95% CI 1.16-2.12), respectively. CONCLUSIONS: A higher CACS was progressively associated with an increased risk of CKD, even at low CACSs. Individuals with a CACS >0 appear to have an increased risk of CKD and may benefit from preventive measures to reduce CKD risk.

Efficacy, Immunogenicity, and Safety of COVID-19 Vaccines in Randomized Control Trials in the Pre-Delta Era: A Systematic Review and Network Meta-Analysis.

The most effective method of limiting the coronavirus disease pandemic of 2019 (COVID-19) is vaccination. For the determination of the comparative efficacy and safety of COVID-19 vaccines and their platforms during the pre-Delta era, a systematic review and network meta-analysis was conducted. The MEDLINE, Embase, and MedRxiv databases were searched, and the gray literature was manually searched up to 8 July 2021. The review includes the phase II and III randomized controlled trials (RCTs) that assessed the efficacy, immunogenicity, and safety of the COVID-19 vaccines. The network meta-analysis used a Bayesian model and used the surface under the cumulative ranking to rank the comparisons between the vaccines. All included studies were quality appraised according to their design, and the heterogeneity of the analyses was assessed using I2. In terms of vaccine efficacy, the mRNA-1273 vaccine ranked the highest, and the CoronaVac vaccine ranked the lowest. The mRNA-1273 ranked the highest for neutralizing antibody responses to live SARS-CoV-2. The WIV04 vaccine was associated with the lowest incidence of both local and systemic adverse reactions. All studies except one had a low to moderate risk of bias. The mRNA platform vaccines showed higher efficacy and more adverse reactions than the other vaccines.

The association between cotinine-measured smoking intensity and sleep quality.

INTRODUCTION: Cigarette smoking is suggested to be associated with sleep problems. This study evaluated the quantitative association between urinary cotinine-verified smoking intensity and sleep quality assessed by the Pittsburgh Sleep Quality Index (PSQI). METHODS: This was a cross-sectional study of 189970 participants from the Kangbuk Samsung Health Study recruited between 2016 and 2018. Logistic regression analysis adjusted for covariates was performed to estimate the association between urinary cotinine levels assessed by quartiles and poor sleep quality, defined as global PSQI score >5. RESULTS: The odds ratios (OR) and 95% confidence intervals (CI) for poor sleep quality comparing the highest urinary cotinine quartile to non-smokers were: 1.23 (95% CI: 1.16-1.30) for overall, 1.19 (95% CI: 1.12-1.26) for males, and 1.55 (95% CI: 1.29-1.87) for females. Among self-reported never smokers, cotinineverified smokers had higher odds for decreased sleep quality compared to cotinineverified never smokers with OR of 1.26 (95% CI: 1.08-1.46). CONCLUSIONS: Elevated urinary cotinine levels were associated with poor sleep quality in relatively young and middle-aged South Korean adults. Higher odds for poor sleep quality among cotinine-verified smokers who self-reported as never smokers also demonstrate the value of quantitative measurement of urinary cotinine. Prospective studies are warranted to clarify the cause-effect relationship between smoking and sleep quality.

Hypoglycemic agents and glycemic variability in individuals with type 2 diabetes: A systematic review and network meta-analysis.

While hemoglobin A1c (HbA1c) is commonly used to monitor therapy response in type 2 diabetes (T2D), GV is emerging as an essential additional metric for optimizing glycemic control. Our goal was to learn more about the impact of hypoglycemic agents on HbA1c levels and GV in patients with T2D. A systematic review and network meta-analysis (NMA) of randomized controlled trials were performed to assess the effects of glucagon-like peptide 1 receptor agonists (GLP-1 RAs), sodium-glucose cotransporter (SGLT)-2 inhibitors, dipeptidyl peptidase (DPP)-4 inhibitors, sulfonylurea and thiazolidinediones on Mean Amplitude of Glycemic Excursions (MAGE) and HbA1c. Searches were performed using PubMed and EMBASE. A random-effect model was used in the NMA, and the surface under the cumulative ranking was used to rank comparisons. All studies were checked for quality according to their design and also for heterogeneity before inclusion in this NMA. The highest reduction in MAGE was achieved by GLP-1 RAs (SUCRA 0.83), followed by DPP-4 inhibitors (SUCRA: 0.72), and thiazolidinediones (SUCRA: 0.69). In terms of HbA1c reduction, GLP-1 RAs were the most effective (SUCRA 0.81), followed by DPP-4 inhibitors (SUCRA 0.72) and sulfonylurea (SUCRA 0.65). Our findings indicated that GLP-1 RAs have relatively high efficacy in terms of HbA1c and MAGE reduction when compared with other hypoglycemic agents and can thus have clinical application. Future studies with a larger sample size and appropriate subgroup analyses are warranted to completely understand the glycemic effects of these agents in various patients with T2D. The protocol for this systematic review was registered with the International Prospective Register of Systematic Reviews (CRD42021256363).

Systematic Screening and Therapeutic Evaluation of Glyconanoparticles with Differential Cancer Affinities for Targeted Cancer Therapy.

Cancer-targeting ligands used for nanomedicines have been limited mostly to antibodies, peptides, aptamers, and small molecules thus far. Here, a library of glycocalyx-mimicking nanoparticles as a platform to enable screening and identification of cancer-targeting nanomedicines is reported. Specifically, a library of 31 artificial glycopolymers composed of either homogeneous or heterogeneous display of five different sugar moieties (ß-glucose, ß-galactose, α-mannose, ß-N-acetyl glucosamine, and ß-N-acetyl galactosamine) is converted to a library of glyconanoparticles (GlyNPs). GlyNPs optimal for targeting CT26, DU145, A549, and PC3 tumors are systematically screened and identified. The cypate-conjugated GlyNP displaying α-mannose and ß-N-acetyl glucosamine show selective targeting and potent photothermal therapeutic efficacy against A549 human lung tumors. The docetaxel-contained GlyNP displaying ß-glucose, ß-galactose, and α-mannose demonstrate targeted chemotherapy against DU145 human prostate tumors. The results presented herein collectively demonstrate that the GlyNP library is a versatile platform enabling the identification of cancer-targeting glyconanoparticles and suggest its potential applicability for targeting various diseased cells beyond cancer.

Skeletal muscle mass to visceral fat area ratio as a predictor of NAFLD in lean and overweight men and women with effect modification by sex.

The effect of sarcopenic visceral obesity on the risk of nonalcoholic fatty liver disease (NAFLD) is uncertain. We investigated (a) whether the skeletal muscle mass to visceral fat area ratio (SV ratio), as a measure of sarcopenic visceral obesity, is a risk factor for NAFLD; and (b) whether the SV ratio adds to conventional adiposity measures to improve prediction of incident NAFLD. Adults without NAFLD (n = 151,017) were followed up for a median of 3.7 years. Hepatic steatosis was measured using ultrasonography, and liver fibrosis scores were estimated using the Fibrosis-4 index (FIB-4) and the NAFLD Fibrosis Score (NFS). Cox proportional hazards models were used to determine sex-specific adjusted hazard ratios (aHRs) (95% confidence intervals [CIs]). The incremental predictive performance was assessed using the area under the receiver operating characteristic curve, net reclassification improvement, and integrated discrimination improvement. Multivariable aHRs (95% CIs) for incident NAFLD comparing the lowest versus the highest quintile of SV ratio were 3.77 (3.56-3.99) for men and 11.69 (10.46-13.06) for women (p-interaction by sex < 0.001). For incident NAFLD with intermediate/high FIB-4, aHRs were 2.83 (2.19-3.64) for men and 7.96 (3.85-16.44) for women (similar results were obtained for NFS). Associations remained significant even after adjustment for body mass index, waist circumference, and time-varying covariates. These associations were also more pronounced in nonobese than obese participants (p-interaction < 0.001). The addition of SV ratio to conventional adiposity measures modestly improved risk prediction for incident NAFLD. SV ratio was inversely associated with risk of developing NAFLD, with effect modification by sex and obesity. Conclusion: Low SV ratio is a complementary index to conventional adiposity measures in the evaluation of NAFLD risk.

Oral administration of Euglena gracilis paramylon ameliorates chemotherapy-induced leukocytopenia and gut dysbiosis in mice.

Euglena gracilis (EUG) is a food supplement rich in beta-glucans, which are stored in the form of granules called paramylon. We determined whether EUG improved chemotherapy-induced leukocytopenia and dysbiosis. Mice were orally administered EUG prior to gemcitabine treatment. Analyses of the blood cell count, leukocyte population in the spleen, granulocyte/macrophage-colony-stimulating factor (GM-CSF) production by splenocytes, and fecal microbiome were conducted. The recovery of total leukocytes, neutrophils, and monocytes was accelerated after a single gemcitabine treatment. A more rapid lymphocyte recovery rate was observed after four gemcitabine treatments. No difference was observed in the percentage of T, B, or myeloid cells or in the expression of Dectin-1 in the spleens of the gemcitabine and EUG/gemcitabine groups. The EUG/gemcitabine group showed an enhanced GM-CSF production by lipopolysaccharides-stimulated splenocytes. Next-generation sequencing revealed that gemcitabine-induced dysbiosis was alleviated. This study demonstrated that EUG-derived beta-glucans could act as a biological response modifier as well as prebiotics for ameliorating chemotherapy-induced adverse effects.

Fasting ketonuria is inversely associated with coronary artery calcification in non-diabetic individuals.

BACKGROUND AND AIMS: Increased levels of ketone bodies, an alternative fuel when glucose availability is low, may exert beneficial effects on cardiovascular disease (CVD) risk factors. Whether increased ketone bodies are associated with coronary artery calcium (CAC), a recognized and strong cardiovascular risk factor, remains unknown. We investigated the association of fasting ketonuria with CAC and its progression. METHODS: Cross-sectional and longitudinal studies were conducted in adults without diabetes or CVD. Subjects underwent routine health examinations including cardiac computed tomography estimations of CAC scores. Logistic regression models were performed to compute the odds ratios (ORs), 95% confidence intervals (CIs), for prevalent CAC scores >0 according to fasting ketonuria categories (0, 1, and ≥2). Linear mixed models with random intercepts and random slopes were used to estimate CAC progression. RESULTS: Of 144,346 subjects, 12.3% had CAC scores >0 at baseline. Overall, higher fasting ketonuria was associated with decreased prevalence of coronary calcification than no ketonuria. Multivariable-adjusted ORs (95% CIs) for prevalent CAC by comparing ketonuria categories 1 and ≥2 with no ketonuria, were 0.94 (0.84-1.06) and 0.82 (0.71-0.95), respectively. The associations did not differ according to clinically relevant subgroups. Ketonuria was associated with lower CAC progression over time; the multivariable adjusted ratio of progression rates comparing ketonuria ≥2 versus no ketonuria was 0.976 (0.965-0.995). CONCLUSIONS: We found an inverse association between fasting ketonuria and subclinical coronary atherosclerosis, in both prevalence and progression. The potentially protective role of increased ketone body formation in CVD requires further investigation.

Ten-Second Heart Rate Variability, Its Changes Over Time, and the Development of Hypertension.

BACKGROUND: The role of ultrashort-term heart rate variability (HRV) and its temporal changes in incident hypertension are unknown. We aimed to investigate the association between 10-second HRV, its changes, and incident hypertension in adults aged <40 years and older. METHODS: This cohort study included 232 587 Koreans (mean age 37.6 years) without hypertension. Hypertension was defined according to the 2017 American College of Cardiology and American Heart Association hypertension guidelines. HRV, including the root mean square of successive R-R interval differences and the SD of normal-to-normal R-R intervals, was estimated using standard 12-lead, 10-second electrocardiography. RESULTS: During a median follow-up of 3.8 years, 40 268 hypertension cases were identified (incidence rates: 36.1 and 67.9 per 1000 person-years for young and older participants, respectively). An inverse association was observed between HRV and hypertension risk, in a dose-dependent manner. The multivariable-adjusted hazard ratios (95% CIs) for hypertension comparing the first to the fifth quintiles of root mean square of successive R-R interval difference and SD of normal-to-normal R-R interval were 1.58 (1.52-1.63) and 1.35 (1.30-1.39), respectively. These associations were stronger in young adults than in older adults. In a subsample of 150 301 participants, compared with stable HRV, an increase in HRV over time was also inversely associated with incident hypertension. CONCLUSIONS: A higher HRV and its increase over time on a 10-second electrocardiography were associated with a lower risk of hypertension. Our findings indicate that autonomic function, estimated using 10-second standard electrocardiography, plays a role in predicting hypertension, with a stronger effect in young adults.

Long or Irregular Menstrual Cycles and Risk of Prevalent and Incident Nonalcoholic Fatty Liver Disease.

CONTEXT: The association of menstrual cycle length and irregularity with the risk of non-alcoholic fatty liver disease (NAFLD) is unknown. OBJECTIVE: We examined this association in large cross-sectional and cohort studies. METHODS: The cross-sectional study included 72 092 women younger than 40 years who underwent routine health examinations; the longitudinal analysis included the subset of 51 118 women without NAFLD at baseline. Long or irregular cycles were defined as menstrual cycles of 40 days or longer or too irregular to estimate. Abdominal ultrasonography was performed to identify NAFLD. Multivariable Cox proportional hazard regression analyses were performed to estimate hazard ratios (HRs) and 95% CIs for incident NAFLD according to menstrual cycle regularity and length, with 26- to 30-day cycles as the reference. RESULTS: At baseline, 27.7% had long or irregular menstrual cycles and 7.1% had prevalent NAFLD. Long or irregular menstrual cycles were positively associated with prevalent NAFLD. During a median follow-up of 4.4 years, incident NAFLD occurred in 8.9% of women. After adjustment for age, body mass index, insulin resistance, and other confounders, the multivariable-adjusted HR for NAFLD comparing long or irregular menstrual cycles to the reference group was 1.22 (95% CI, 1.14-1.31); this association strengthened in the time-dependent analysis with an HR of 1.49 (95% CI, 1.38-1.60). CONCLUSION: Long or irregular menstrual cycles were associated with increased risk of both prevalent and incident NAFLD in young, premenopausal women. Women with long or irregular menstrual cycles may benefit from lifestyle modification advice to reduce the risk of NAFLD and associated cardiometabolic diseases.

Analysis of GMP for marketing authorization of ATMPs: comparison in the US, the EU, Japan and South Korea.

Aim: This study compared regulatory systems of competent authorities related to GMP for marketing authorization of advanced therapy medicinal products (ATMPs). Methods: Dossiers for GMP and regulations and guidelines for facilities and equipment were analyzed using gap analysis. The risk-based approach (RBA) and GMP inspection were evaluated with regulations and guidelines. Results: The dossier was similar for the competent authorities. However, whereas a site master file is required in the EU, Japan and South Korea, the US requires only a biologics license application. The regulations and guidelines of facilities and equipment emphasized preventing contamination. There are differences among the competent authorities in GMP inspection and RBAs. Conclusion: Differences among the competent authorities in the marketing authorization process related to GMP for ATMPs should be considered.

Low heart rate variability from 10-s electrocardiograms is associated with development of non-alcoholic fatty liver disease.

Reduced heart rate variability (HRV) is reflective of autonomic imbalance. However, its impact on non-alcoholic fatty liver disease (NAFLD) is unknown. We investigated the association between 10-s HRV and incident NAFLD. A cohort of 154,286 Korean adults with no NAFLD at baseline were followed up. 10-s electrocardiograms were used to estimate two time-domain HRV, the standard deviation of normal-to-normal intervals (SDNN) and the root mean square of successive differences in RR intervals (RMSSD). Hepatic steatosis (HS) and liver fibrosis were assessed using ultrasonography and the fibrosis-4 index (FIB-4). A total of 27,279 incident HS (median follow up of 4.2 years) and 1250 incident HS plus high FIB-4 (median follow up of 4.2 years) cases were identified at follow-up. The multivariable adjusted hazard ratios (aHRs) (95% confidence intervals [CIs]) in a model with time-dependent variables for incident HS, comparing the lowest quintile to the highest and reference quintile of the RMSSD, was 1.43 (1.37-1.49), and the corresponding HR for incident HS plus intermediate/high FIB-4 was 1.70 (1.35-2.15). Similarly, SDNN was inversely associated with incident HS and HS plus intermediate/high FIB-4. The results were similar using the NAFLD fibrosis score. Autonomic imbalance assessed by HRV may help to identify individuals at a high risk of HS and its progression and warrant further studies.

Decrease in Sleep Duration and Poor Sleep Quality over Time Is Associated with an Increased Risk of Incident Non-Alcoholic Fatty Liver Disease.

The impact of changes in sleep duration and sleep quality over time on the risk of non-alcoholic fatty liver disease (NAFLD) is not known. We investigated whether changes in sleep duration and in sleep quality between baseline and follow-up are associated with the risk of developing incident NAFLD. The cohort study included 86,530 Korean adults without NAFLD and with a low fibrosis score at baseline. The median follow-up was 3.6 years. Sleep duration and quality were assessed using the Pittsburgh Sleep Quality Index. Hepatic steatosis (HS) and liver fibrosis were assessed using ultrasonography and the fibrosis-4 index (FIB-4). Cox proportional hazard models were used to determine hazard ratios (HRs) and 95% confidence intervals (Cis). A total of 12,127 subjects with incident HS and 559 with incident HS plus intermediate/high FIB-4 was identified. Comparing the decrease in sleep duration of >1 h, with stable sleep duration, the multivariate-adjusted HR (95% CIs) for incident HS was 1.24 (1.15-1.35). The corresponding HRs for incident HS plus intermediate/high FIB-4 was 1.58 (1.10-2.29). Comparing persistently poor sleep quality with persistently good sleep quality, the multivariate-adjusted HR for incident HS was 1.13 (95% CI, 1.05-1.20). A decrease in sleep duration or poor sleep quality over time was associated with an increased risk of incident NAFLD, underscoring an important potential role for good sleep in preventing NAFLD risk.

Risk factors for hemorrhoidal disease among healthy young and middle-aged Korean adults.

Hemorrhoidal disease is a highly prevalent anorectal condition causing substantial discomfort, disability, and decreased quality of life. Evidence on preventable risk factors for hemorrhoidal disease is limited. We conducted a cross-sectional study of 194,620 healthy men and women who completed a health screening exam including colonoscopy in 2011-2017. We evaluated potential risk factors of hemorrhoidal disease, including lifestyle factors, medical history, birth history, gastrointestinal symptoms, and anthropometric measurements. The prevalence of hemorrhoidal disease was 16.6%, and it was higher in females than in males (17.2 vs. 16.3%; P < 0.001). Compared to men, the prevalence of hemorrhoidal disease was higher in parous women (adjusted odds ratio [OR] 1.06; 95% confidence interval [CI] 1.02-1.10), and lower in nulliparous women (adjusted OR 0.92; 95% CI 0.86-0.98). In the adjusted analyses, older age, female sex, smoking, overweight, and being hypertensive were independently associated with the presence of hemorrhoidal disease. The prevalence of hemorrhoidal disease was positively associated with body mass index and waist circumference in parous women. The prevalence of hemorrhoidal disease was higher in older age, females, ever-smokers, and hypertensive participants. The association of excess adiposity with the prevalence of hemorrhoidal disease differed by sex and parity.

Visual acuity and risk of overall, injury-related, and cardiovascular mortality: the Kangbuk Samsung Health Study.

AIMS: The associations of visual impairment (VI) with cardio-metabolic risk factors have been reported but its association with cardiovascular mortality remains uncertain. Therefore, we evaluated the association of visual acuity (VA) with overall, injury-related, and cardiovascular mortality. METHODS AND RESULTS: A cohort study was performed in 580 746 Korean adults (average age, 39.7 years) who were followed for a median of 8.1 years (maximum, 16 years). Presenting VA was measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Visual acuity in the better vision eye was categorized as normal vision (≥0.8), lowered vision (0.5-0.8), mild visual impairment (VI) (0.3-0.5), or moderate to severe VI (<0.3). Vital status and cause of death were ascertained through linkage to national death records. During 4 632 892.2 person-years of follow-up, 6585 overall deaths, 974 cardiovascular deaths, and 1163 injury-related deaths were identified. After adjustment for possible confounders, the multivariable-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for overall mortality among participants with lowered vision, minimal VI, and moderate to severe VI were 1.21 (1.13-1.29), 1.26 (1.15-1.37), and 1.54 (1.40-1.68), respectively, compared with those with normal vision. The corresponding HRs (95% CIs) for injury-related mortality were 1.12 (0.96-1.32), 0.98 (0.76-1.26), and 1.36 (1.04-1.79), respectively, and the corresponding HRs (95% CIs) for cardiovascular mortality were 1.32 (1.12-1.57), 1.43 (1.15-1.77), and 2.41 (1.94-2.99). CONCLUSION: In this large cohort of young and middle-aged individuals, VI was associated with increased risk of mortality especially due to cardiovascular disease.