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Background: Acanthamoeba and Klebsiella pneumoniae are both environmental commensals. Recently, clinical harm caused by hypermucoviscous K. pneumoniae has been observed. However, the interaction between these microbes and the origin of hypermucoviscous K. pneumoniae have not been reported., Methodology/principal Findings: Here, we report that the bacterial capsule is enlarged when co-cultured with Acanthamoeba using India ink staining, and this effect depends on the number of parasites present. This interaction results in an enhancement of capsular polysaccharide production in the subsequent generations of K. pneumoniae, even without co-culturing with Acanthamoeba. The hypermucoviscosity of the capsule was examined using the sedimentation assay and string test. We also screened other K. pneumoniae serotypes, including K1, K2, K5, and K20, for interaction with Acanthamoeba using India ink staining, and found the same interaction effect., Conclusions/significance: These findings suggest that the interaction between Acanthamoeba and K. pneumoniae could lead to harmful consequences in public health and nosocomial disease control, particularly hypermucoviscous K. pneumoniae infections., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Patients with hypertension are at higher risk for dementia than the general population. We sought to understand the relative importance of various risk factors in the development of dementia among patients with hypertension. This population-based cohort study used data from the Korean National Insurance Service database. Using the Cox proportional hazard model, R2 values for each potential risk factor were calculated to test the relative importance of risk factors for the development of dementia. Eligible individuals were adults 40 to 79 years of age with hypertension and without a history of stroke and dementia between 2007 and 2009. A total of 650,476 individuals (mean age, 60 ± 11 years) with hypertension were included in the analyses. During a mean follow-up of 9.5 years (±2.8 years), 57,112 cases of dementia were observed. The three strongest predictors of dementia were age, comorbidity burden (assessed using the Charlson Comorbidity Index), and female sex (R2 values, 0.0504, 0.0023, and 0.0022, respectively). The next strongest risk factors were physical inactivity, smoking, alcohol consumption, and obesity (R2 values, 0.00070, 0.00024, 0.00021, and 0.00020, respectively). Across all age groups, physical inactivity was an important risk factor for dementia occurrence. In summary, controlling and preventing comorbidities are of utmost importance to prevent dementia in patients with hypertension. More efforts should be taken to encourage physical activity among patients with hypertension across all age groups. Furthermore, smoking cessation, avoiding and limiting alcohol consumption, and maintaining an appropriate body weight are urged to prevent dementia., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Jung et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Angiotensin II receptor blockers (ARBs) are recommended for treating patients with hypertension. However, comparative safety and efficacy of ARB use in elderly patients have not been well established. This study was designed to determine the efficacy of fimasartan, an ARB, in hypertensive elderly patients by measuring clinic and home blood pressures (BPs) and evaluating safety compared to nonelderly patients., Method: In the K-MetS study, a nationwide prospective observational study of hypertensive patients on fimasartan, elderly patients (60 years and older) who were treated for 1 year with fimasartan were recruited. BP was evaluated in clinic and at home., Results: Of the 6 399 enrolled patients, 2 363 were elderly (46.9% males, mean age 67.3 ± 5.7 years). Fimasartan reduced systolic and diastolic BP (SBP and DBP) in clinic from 144.1 ± 17.3 to 127.7 ± 12.9 mmHg and from 85.1 ± 10.4 to 76.8 ± 8.4 mmHg, respectively, (all p<0.0001) in 1 year. Similar results were found in home BPs. These BP changes were consistent with those in nonelderly patients. However, pulse pressure, a better predictor of cardiovascular events in the elderly, decreased more in elderly than in nonelderly patients by -8.2 ± 0.3 in elderly and -7.0 ± 0.2 mmHg (p<0.0001), respectively, after adjustment for confounding factors. Adverse events were reported in 1.6% of elderly hypertensives, independent of dose, which was consistent with results in nonelderly patients., Conclusions: Fimasartan resulted in better pulse pressure reduction with similar BP reduction efficacy and safety in hypertensive elderly patients compared with nonelderly patients., Competing Interests: Although Boryung Pharmaceutical Company in Korea provided the research grant, this does not alter the adherence to PLOS ONE policy on sharing data and materials.

Background: Decreased lung function is associated with non-alcoholic fatty liver disease (NAFLD), based on linking mechanisms such as insulin resistance and systemic inflammation However, its association with the risk of developing NAFLD is unclear. Our aim was to investigate whether baseline lung function is associated with incident NAFLD in middle-aged healthy Koreans., Methods: A cohort study of 96,104 subjects (mean age: 35.7 years) without NAFLD were followed up from 2002 to 2015. NAFLD was diagnosed by ultrasound after the exclusion of other possible causes of liver diseases. Baseline percent predicted forced expiratory volume in one second (FEV1%) and forced vital capacity (FVC%) were categorized in quartiles. Adjusted hazard ratios (aHR) and 95% confidence intervals (CIs) (using the highest quartile as reference) were calculated for incident NAFLD at follow-up, controlling for covariates and potential confounders., Results: During 579,714.5 person-years of follow-up, 24,450 participants developed NAFLD (incidence rate, 42.2 per 1,000 person-years). The mean follow-up period was 5.9±3.4 years. Regardless of smoking history, the risk for incident NAFLD increased with decreasing quartiles of FEV1 (%) and FVC (%) in a dose-response manner (p for trend<0.001). In never smokers, the aHRs (95% CIs) for incident NAFLD were 1.15 (1.08-1.21), 1.11 (1.05-1.18), and 1.08 (1.02-1.14) in quartiles 1-3 for FEV1 (%) and 1.12 (1.06-1.18), 1.11 (1.05-1.18), and 1.09 (1.03-1.15) in quartiles 1-3 for FVC (%), compared with the highest quartile reference. Similar inverse association was present in smoke-exposed subjects (aHR for incident NAFLD were 1.14, 1.21, 1.13 and 1.17, 1.11, 1.09 across FEV1(%) and FVC(%) quartile in increasing order, respectively)., Conclusions: Reduced lung function was a risk factor for incident NAFLD in a large middle-aged Korean cohort with over half a million person-years of follow-up., Competing Interests: The authors have declared that no competing interests exist.

To evaluate the relationships among patient characteristics, irradiation treatment planning parameters, and treatment toxicity of acute radiation dermatitis (RD) after breast hybrid intensity modulation radiation therapy (IMRT). The study cohort consisted of 95 breast cancer patients treated with hybrid IMRT. RD grade ≥2 (2+) toxicity was defined as clinically significant. Patient characteristics and the irradiation treatment planning parameters were used as the initial candidate factors. Prognostic factors were identified using the least absolute shrinkage and selection operator (LASSO)-based normal tissue complication probability (NTCP) model. A univariate cut-off dose NTCP model was developed to find the dose-volume limitation. Fifty-two (54.7%) of ninety-five patients experienced acute RD grade 2+ toxicity. The volume of skin receiving a dose >35 Gy (V35) was the most significant dosimetric predictor associated with RD grade 2+ toxicity. The NTCP model parameters for V35Gy were TV50 = 85.7 mL and γ50 = 0.77, where TV50 was defined as the volume corresponding to a 50% incidence of complications, and γ50 was the normalized slope of the volume-response curve. Additional potential predictive patient characteristics were energy and surgery, but the results were not statistically significant. To ensure a better quality of life and compliance for breast hybrid IMRT patients, the skin volume receiving a dose >35 Gy should be limited to <85.7 mL to keep the incidence of RD grade 2+ toxicities below 50%. To avoid RD toxicity, the volume of skin receiving a dose >35 Gy should follow sparing tolerance and the inherent patient characteristics should be considered., Competing Interests: The authors have declared that no competing interests exist. Parts of the results were presented in an abstract form at Asia Oncology Summit 2016, Kyoto, Japan.

Background: The effect of resolving metabolic syndrome on target organ damage in hypertensive patients is not well described. We evaluated whether treating metabolic syndrome (MetS) with an angiotensin receptor blocker subsequently reduced microalbuminuria in the K-MetS cohort., Methods: Among 10,601 total metabolic syndrome patients, 3,250 (52.2% male, 56.2±10.0 years) with sufficient data on five specific metabolic components were included in this study. Patients were divided into four groups based on MetS status at baseline and 3 months. All patients received an angiotensin receptor blocker, fimasartan, for these 3 months; thereafter, treatment was modified at the discretion of each patient's physician. Microalbuminuria and the albumin/creatine ratio were evaluated as a proxy of organ damage., Results: Blood pressure and waist circumference decreased from baseline to 3 months and 1 year. The average albumin/creatinine ratio significantly improved during the first three months of the study from 36.0±147.4 to 21.0±74.9 mg/g (p<0.05) and was persistently high in patients with MetS at baseline and 3 months versus other groups. Women in comparison with men showed significantly lower ACR among patients with newly developed MetS at 3-month., Conclusions: Treatment of hypertensive patients for one year with the angiotensin receptor blocker fimasartan significantly reduced the albumin/creatine ratio, irrespective of whether the patient had MetS; however, the albumin/creatinine ratio was significantly higher in patents with persistent or newly developed MetS compared to patients without MetS. Additionally, these findings were more prominent in women than in men.

Background: Although non-alcoholic fatty liver disease (NAFLD) is considered to be associated with chronic kidney disease (CKD), long-term follow up data is lacking. We investigated whether NAFLD, as determined by the fatty liver index (FLI), could predict incident CKD in 10-year prospective cohort study. We also assessed the clinical utility of FLI to predict the development of CKD., Methods: 6,238 adults aged 40 to 69 years without baseline CKD from the Ansan-Ansung cohort were examined. Patients were classified according to FLI as follows: FLI<30, no NAFLD; FLI≥60, NAFLD; and 30≤ FLI<60, intermediate. Incident CKD was defined as estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m2. The clinical utility of FLI in predicting incident CKD was estimated via area under the receiver-operating characteristic curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) analyses., Results: During an average of 10 years of follow-up, 724 subjects (15.21%) developed CKD. The adjusted hazard ratio [95% confidence interval (CI)] for incident CKD increased in a graded manner with FLI increased (<30 vs. 30-59 vs. ≥60 = 1 vs. 1.17 [0.997-1.375] vs. 1.459 [1.189-1.791], respectively, P for trend = 0.0012). Incorporation of FLI into traditional risk factors of CKD significantly increased prediction of incident CKD based on NRI (17%; 95% CI, 8.9-25%; P-value <0.001) and IDI (0.002; 95% CI, 0.0046-0.0143; P-value = 0.046)., Conclusions: FLI, a surrogate marker of NAFLD, was an independent risk factor for incident CKD. FLI provides meaningful incremental risk reclassification beyond that of conventional risk factors of CKD.

Aims: The ratio of aspartate aminotransferase (AST) to alanine aminotransferase (ALT) is of great interest as a possible novel marker of metabolic syndrome. However, longitudinal studies emphasizing the incremental predictive value of the AST-to-ALT ratio in diagnosing individuals at higher risk of developing metabolic syndrome are very scarce. Therefore, our study aimed to evaluate the AST-to-ALT ratio as an incremental predictor of new onset metabolic syndrome in a population-based cohort study., Material and Methods: The population-based cohort study included 2276 adults (903 men and 1373 women) aged 40-70 years, who participated from 2005-2008 (baseline) without metabolic syndrome and were followed up from 2008-2011. Metabolic syndrome was defined according to the harmonized definition of metabolic syndrome. Serum concentrations of AST and ALT were determined by enzymatic methods., Results: During an average follow-up period of 2.6-years, 395 individuals (17.4%) developed metabolic syndrome. In a multivariable adjusted model, the odds ratio (95% confidence interval) for new onset of metabolic syndrome, comparing the fourth quartile to the first quartile of the AST-to-ALT ratio, was 0.598 (0.422-0.853). The AST-to-ALT ratio also improved the area under the receiver operating characteristic curve (AUC) for predicting new cases of metabolic syndrome (0.715 vs. 0.732, P = 0.004). The net reclassification improvement of prediction models including the AST-to-ALT ratio was 0.23 (95% CI: 0.124-0.337, P<0.001), and the integrated discrimination improvement was 0.0094 (95% CI: 0.0046-0.0143, P<0.001)., Conclusions: The AST-to-ALT ratio independently predicted the future development of metabolic syndrome and had incremental predictive value for incident metabolic syndrome., Competing Interests: The authors have declared that no competing interests exist.

Background: Although non-alcoholic fatty liver disease is the hepatic manifestation of metabolic syndrome, its influence on hypertension development is poorly understood. We investigated whether fatty liver disease, as assessed by the fatty liver index, could predict the development of hypertension independently of systemic insulin resistance, inflammatory status and adipokine levels., Methods: Prospective cohort study of 1,521 adults (484 men and 1037 women) aged 40 to 70 years without baseline hypertension examined. An equation was used to calculate fatty liver index and classify patients as follows: fatty liver index <30, no non-alcoholic fatty liver disease; fatty liver index ≥ 60, non-alcoholic fatty liver disease; and 30 ≤ fatty liver index <60, intermediate fatty liver index., Results: During an average of 2.6 years of follow-up, 153 subjects (10.06%) developed hypertension. Fatty liver index was positively associated with baseline blood pressure, homeostasis model assessment of insulin resistance, urinary albumin/creatinine excretion, and high sensitivity C-reactive protein. After adjustment for confounding factors, including markers of insulin resistance, systemic inflammation and adiponectin levels, the odds ratio [95% confidence interval] for the incident hypertension increased in a graded manner with fatty liver index (<30 vs. 30-59 vs. ≥ 60 = 1 vs. 1.83 [1.16~2.88] vs. 2.09 [1.08~4.055], respectively)., Conclusions: Non-alcoholic fatty liver disease assessed by fatty liver index was an independent risk factor for hypertension. Our findings suggest that fatty liver index, a simple surrogate indicator of fatty liver disease, might be useful for identifying subjects at high risk for incident hypertension in clinical practice.

Background: The gender disparity in cardiovascular disease (CVD) risk is greatest between young men and women. However, the causes of that are not fully understood. The objective of this study was to evaluate the relationship between insulin resistance and the presence of coronary artery calcium (CAC) to identify risk factors that may predispose young men and women to CVD., Methodology/principal Findings: Insulin resistance and CVD risk factors were examined in 8682 Korean men and 1829 women aged 30-45 years old. Insulin resistance was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR), and CAC was measured using computed tomography. Women were less likely to be insulin resistant (upper quartile of HOMA-IR, 18% vs. 27%, p<0.001) and had a lower prevalence of CAC (1.6% vs. 6.4%, p<0.001). Even when equally insulin resistant men and women were compared, women continued to have lower prevalence of CAC (3.1% vs. 7.2%, p = 0.004) and a more favorable CVD risk profile. Finally, after adjustment for traditional CVD risk factors, insulin resistance remained an independent predictor of CAC only in men (p = 0.03)., Conclusions/significance: Young women have a lower risk for CVD and a lower CAC prevalence compared with men. This favorable CVD risk profile in women appears to occur regardless of insulin sensitivity. Unlike men, insulin resistance was not a predictor of CAC in women in this cohort. Therefore, insulin resistance has less impact on CVD risk and CAC in young women compared with men, and insulin resistance alone does not explain the gender disparity in CVD risk that is observed at an early age.