Distinct spatiotemporal patterns of cortical thinning in Alzheimer's disease-type cognitive impairment and subcortical vascular cognitive impairment.

Previous studies on Alzheimer's disease-type cognitive impairment (ADCI) and subcortical vascular cognitive impairment (SVCI) has rarely explored spatiotemporal heterogeneity. This study aims to identify distinct spatiotemporal cortical atrophy patterns in ADCI and SVCI. 1,338 participants (713 ADCI, 208 SVCI, and 417 cognitively unimpaired elders) underwent brain magnetic resonance imaging (MRI), amyloid positron emission tomography, and neuropsychological tests. Using MRI, this study measures cortical thickness in five brain regions (medial temporal, inferior temporal, posterior medial parietal, lateral parietal, and frontal areas) and utilizes the Subtype and Stage Inference (SuStaIn) model to predict the most probable subtype and stage for each participant. SuStaIn identifies two distinct cortical thinning patterns in ADCI (medial temporal: 65.8%, diffuse: 34.2%) and SVCI (frontotemporal: 47.1%, parietal: 52.9%) patients. The medial temporal subtype of ADCI shows a faster decline in attention, visuospatial, visual memory, and frontal/executive domains than the diffuse subtype (p-value < 0.01). However, there are no significant differences in longitudinal cognitive outcomes between the two subtypes of SVCI. Our study provides valuable insights into the distinct spatiotemporal patterns of cortical thinning in patients with ADCI and SVCI, suggesting the potential for individualized therapeutic and preventive strategies to improve clinical outcomes.

Clinical and Pathological Validation of CT-Based Regional Harmonization Methods of Amyloid PET.

PURPOSE: The CT-based regional direct comparison Centiloid (dcCL) method was developed to harmonize and quantify regional ß-amyloid (Aß) burden. In the present study, we aimed to investigate correlations between the CT-based regional dcCL scales and Aß pathological burdens and to validate the clinical utility using thresholds derived from pathological assessment. PATIENTS AND METHODS: We included a pathological cohort of 63 cases and a clinical cohort of 4062 participants, and obtained modified Consortium to Establish a Registry for Alzheimer's Disease criteria (mCERAD) scores by assessment of neuritic plaque burdens in multiple areas of each cortical region. PET and CT images were processed using the CT-based regional dcCL method to calculate scales in 6 distinct regions. RESULTS: The CT-based regional dcCL scales were correlated with neuritic plaque burdens represented by mCERAD scores, globally and regionally ( r = 0.56~0.76). In addition, striatum dcCL scales reflected Aß involvement in the striatum ( P < 0.001). The regional dcCL scales could predict significant Aß deposition in specific brain regions with high accuracy: area under the receiver operating characteristic curve of 0.81-0.97 with an mCERAD cutoff of 1.5 and area under the receiver operating characteristic curve of 0.88-0.93 with an mCERAD cutoff of 0.5. When applying the dcCL thresholds of 1.5 mCERAD scores, the G(-)R(+) group showed lower performances in memory and global cognitive functions and had less hippocampal volume compared with the G(-)R(-) group ( P < 0.001). However, when applying the dcCL thresholds of 0.5 mCERAD scores, there were no differences in the global cognitive functions between the 2 groups. CONCLUSIONS: The thresholds of regional dcCL scales derived from pathological assessments might provide clinicians with a better understanding of biomarker-guided diagnosis and distinguishable clinical phenotypes, which are particularly useful when harmonizing different PET ligands with only PET/CT.

Distinct effects of cholesterol profile components on amyloid and vascular burdens.

BACKGROUND: Cholesterol plays important roles in ß-amyloid (Aß) metabolism and atherosclerosis. However, the relationships of plasma cholesterol levels with Aß and cerebral small vessel disease (CSVD) burdens are not fully understood in Asians. Herein, we investigated the relationships between plasma cholesterol profile components and Aß and CSVD burdens in a large, non-demented Korean cohort. METHODS: We enrolled 1,175 non-demented participants (456 with unimpaired cognition [CU] and 719 with mild cognitive impairment [MCI]) aged ≥ 45 years who underwent Aß PET at the Samsung Medical Center in Korea. We performed linear regression analyses with each cholesterol (low-density lipoprotein cholesterol [LDL-c], high-density lipoprotein cholesterol [HDL-c], and triglyceride) level as a predictor and each image marker (Aß uptake on PET, white matter hyperintensity [WMH] volume, and hippocampal volume) as an outcome after controlling for potential confounders. RESULTS: Increased LDL-c levels (ß = 0.014 to 0.115, p = 0.013) were associated with greater Aß uptake, independent of the APOE e4 allele genotype and lipid-lowering medication. Decreased HDL-c levels (ß = - 0.133 to - 0.006, p = 0.032) were predictive of higher WMH volumes. Increased LDL-c levels were also associated with decreased hippocampal volume (direct effect ß = - 0.053, p = 0.040), which was partially mediated by Aß uptake (indirect effect ß = - 0.018, p = 0.006). CONCLUSIONS: Our findings highlight that increased LDL-c and decreased HDL-c levels are important risk factors for Aß and CSVD burdens, respectively. Furthermore, considering that plasma cholesterol profile components are potentially modified by diet, exercise, and pharmacological agents, our results provide evidence that regulating LDL-c and HDL-c levels is a potential strategy to prevent dementia.

Sex-specific relationship between non-alcoholic fatty liver disease and amyloid-ß in cognitively unimpaired individuals.

Background: Non-alcoholic fatty liver disease (NAFLD) is known to be associated with a high risk of clinically diagnosed Alzheimer's disease (AD). Additionally, the prevalence of NAFLD and AD is higher in elderly females than in males. However, a sex-specific association between NAFLD and amyloid-beta (Aß) deposition remains unclear. Therefore, we investigated the sex-specific relationship between NAFLD and Aß deposition in a large-sized cohort of cognitively unimpaired (CU) individuals. Methods: We enrolled 673 (410 [60.9%] females and 263 [39.1%] males) CU individuals aged ≥45 years who underwent Aß positron emission tomography (PET). The presence of NAFLD, assessed using the hepatic steatosis index, and the severity of NAFLD, assessed using the Fibrosis-4 index, were considered predictors. Aß deposition on PET was considered as an outcome. Results: Females had a higher frequency of NAFLD than males (48 and 23.2%, p < 0.001). Among females, the presence of NAFLD (ß = 0.216, p < 0.001) was predictive of increased Aß deposition, whereas among males, the presence of NAFLD (ß = 0.191, p = 0.064) was not associated with Aß deposition. Among females, the presence of NAFLD with low (ß = 0.254, p = 0.039), intermediate (ß = 0.201, p = 0.006), and high fibrosis (ß = 0.257, p = 0.027) was predictive of increased Aß deposition. Aß deposition also increased as the severity of NAFLD increased in females (p for trend = 0.001). Conclusion: We highlight the marked influence of NAFLD and its severity on the risk of Aß deposition in relation to sex. Furthermore, our findings suggest that sex-specific strategies regarding the management of NAFLD are necessary for the prevention of Aß deposition.

H2O2 sulfenylates CHE linking local infection to establishment of systemic acquired resistance.

In plants, a local infection can lead to systemic acquired resistance (SAR) through increased production of salicylic acid (SA). For 30 years, the identity of the mobile signal and its direct transduction mechanism for systemic SA synthesis in initiating SAR have been hotly debated. We found that, upon pathogen challenge, the cysteine residue of transcription factor CHE undergoes sulfenylation in systemic tissues, enhancing its binding to the promoter of SA-synthesis gene, ICS1, and increasing SA production. This occurs independently of previously reported pipecolic acid (Pip) signal. Instead, H2O2 produced by NADPH oxidase, RBOHD, is the mobile signal that sulfenylates CHE in a concentration-dependent manner. This modification serves as a molecular switch that activates CHE-mediated SA-increase and subsequent Pip-accumulation in systemic tissues to synergistically induce SAR.

Correlation analysis between subtest scores of CERAD-K and a newly developed tablet computer-based digital cognitive test (Inbrain CST).

Introduction: The prevalence of Alzheimer's disease (AD) and other dementias is increasing; therefore, identifying individuals at risk for dementia is crucial. Traditional neuropsychological assessments are expensive and time-consuming; however, computerized cognitive testing is becoming popular in clinical and research settings, particularly during the COVID-19 pandemic. This study aimed to investigate the correlation between the computerized cognitive test, Inbrain cognitive screening test (CST), and the traditional neuropsychological battery, the consortium to establish a registry for Alzheimer's disease assessment packet (CERAD-K). Methods: We enrolled 166 participants from five districts in Republic of Korea, including cognitively unimpaired individuals and those with mild cognitive impairment (MCI) diagnosed by experienced neurologists. We used the Inbrain CST and CERAD-K to evaluate the cognitive function of the participants, and the scores of each subtest of the Inbrain CST and CERAD-K were compared. Results: A significant correlation was found between the Inbrain CST and CERAD-K subtests. Furthermore, multivariate analysis revealed a significant correlation between the Inbrain CST and the CERAD-K test pairs after adjusting for age, educational level, and sex. Discussion: In conclusion, this study demonstrates that the Inbrain CST is a reliable tool for detecting cognitive impairment in cognitively unimpaired individuals and patients with MCI, because it has a high correlation and agreement with CERAD-K. Therefore, the Inbrain CST can be a useful, time-efficient, and cost-effective computer-based cognitive test for individuals at risk for cognitive impairment.

Different effects of cardiometabolic syndrome on brain age in relation to gender and ethnicity.

BACKGROUND: A growing body of evidence shows differences in the prevalence of cardiometabolic syndrome (CMS) and dementia based on gender and ethnicity. However, there is a paucity of information about ethnic- and gender-specific CMS effects on brain age. We investigated the different effects of CMS on brain age by gender in Korean and British cognitively unimpaired (CU) populations. We also determined whether the gender-specific difference in the effects of CMS on brain age changes depending on ethnicity. METHODS: These analyses used de-identified, cross-sectional data on CU populations from Korea and United Kingdom (UK) that underwent brain MRI. After propensity score matching to balance the age and gender between the Korean and UK populations, 5759 Korean individuals (3042 males and 2717 females) and 9903 individuals from the UK (4736 males and 5167 females) were included in this study. Brain age index (BAI), calculated by the difference between the predicted brain age by the algorithm and the chronological age, was considered as main outcome and presence of CMS, including type 2 diabetes mellitus (T2DM), hypertension, obesity, and underweight was considered as a predictor. Gender (males and females) and ethnicity (Korean and UK) were considered as effect modifiers. RESULTS: The presence of T2DM and hypertension was associated with a higher BAI regardless of gender and ethnicity (p < 0.001), except for hypertension in Korean males (p = 0.309). Among Koreans, there were interaction effects of gender and the presence of T2DM (p for T2DM*gender = 0.035) and hypertension (p for hypertension*gender = 0.046) on BAI in Koreans, suggesting that T2DM and hypertension are each associated with a higher BAI in females than in males. In contrast, among individuals from the UK, there were no differences in the effects of T2DM (p for T2DM*gender = 0.098) and hypertension (p for hypertension*gender = 0.203) on BAI between males and females. CONCLUSIONS: Our results highlight gender and ethnic differences as important factors in mediating the effects of CMS on brain age. Furthermore, these results suggest that ethnic- and gender-specific prevention strategies may be needed to protect against accelerated brain aging.

Analysis of Natural Organic Matter in Water from Cold and Hot Mineral Springs in South Korea Using 15T FT-ICR-MS.

The natural organic matter (NOM) properties in water from cold and hot mineral springs in South Korea are not well documented. We analyzed the characteristics of NOM in water from 25 cold and hot mineral springs located across South Korea. The NOM of each sample was concentrated using solid-phase extraction and analyzed using 15T Fourier-transform ion cyclotron resonance mass spectrometry. The origin of NOM was identified using van Krevelen diagrams. This study suggests that an analytical method to evaluate the characteristics of water in each region of South Korea can be established and used as a baseline for further research.

Separation of native and C106-oxidized DJ-1 proteins by using column chromatography.

Mutations in PARK7, the gene encoding the DJ-1 protein, are associated with early onset of Parkinson's disease. The C106 residue of DJ-1 is highly susceptible to oxidation, and its oxidation status is essential for various in vivo neuroprotective roles. Since C106 is readily oxidized to sulfinic acid that is not reduced by dithiothreitol, no method to separate native DJ-1 protein from the oxidized one creates challenges in the in vitro study of the biological relevance of C106-oxidation state. Here, we report an efficient column chromatography method to purify native, C106-sulfinic, and mixed (combination of the priors) forms of DJ-1. This method will be useful for systematic in vitro studies of DJ-1 functions by providing specific native and C106-sulfinic DJ-1 proteins.

Bone-density testing interval and transition to osteoporosis in differentiated thyroid carcinoma patients on TSH suppression therapy.

OBJECTIVE: Thyrotropin (TSH) suppression therapy is a standard treatment after surgery for differentiated thyroid carcinoma (DTC). It may be associated with osteoporosis in postmenopausal women. However, there are no guidelines for bone mineral density (BMD) testing intervals to screen for osteoporosis in these patients. Therefore, we evaluated the timing of repeated BMD testing in DTC patients with TSH suppression according to baseline T-scores. DESIGN, PATIENTS, AND MEASUREMENT: We retrospectively evaluated 658 DTC patients who underwent BMD testing more than twice between January 2007 and January 2020. A 1:3 propensity score matching was conducted to compare the timing of repeated BMD tests between the DTC and non-DTC groups. We stratified the participants into four groups based on their baseline T-scores: normal (-1.00 or higher), mild osteopenia (-1.01 to -1.49), moderate osteopenia (-1.50 to -1.99), and severe osteopenia (-2.00 to -2.49). Additionally, the 10% of patients in each group that transitioned to osteoporosis were analysed. RESULTS: The estimated BMD testing interval for 10% of patients who developed osteoporosis was 85 months for patients with initially mild osteopenia, 65 months for those with moderate osteopenia, and 15 months for those with severe osteopenia in the DTC group. In the non-DTC group, the testing intervals for mild, moderate, and severe osteopenia were 98, 57, and 13 months, respectively. On multivariate analysis, baseline T-score (mild osteopenia: hazard ratio [HR] 5.91, p = .105; moderate osteopenia: HR, 25.27, p = .02; and severe osteopenia: HR, 134.82, p < .001) and duration of TSH suppression (tertile 2: HR, 2.25, p = .005; Tertile 3: 1.78, p = .033) were independent risk factors for osteoporosis in the DTC group. CONCLUSION: This study provides guidance for the timing of repeated BMD tests in women over 50 years of age with TSH suppression. The rescreening interval for BMD testing can be modified based on the baseline T-score. The appropriate BMD testing intervals in female DTC patients were similar to those in non-DTC females.

The rice heavy-metal transporter OsNRAMP1 regulates disease resistance by modulating ROS homoeostasis.

Crop diseases threaten food security and sustainable agriculture. Consumption of crops containing nonessential toxic metals leads to health risks for humans. Therefore, cultivation of disease-resistant and toxic metal-safe crops is a double-gain strategy that can contribute to food security. Here, we show that rice heavy-metal transporter OsNRAMP1 plays an important role in plant immunity by modulating metal ion and reactive oxygen species (ROS) homoeostasis. OsNRAMP1 expression was induced after pathogenic bacteria and fungi infections. The osnramp1 mutants had an increased content of H2 O2 and activity of superoxide dismutase, but decreased activity of catalase, showing enhanced broad-spectrum resistance against bacterial and fungal pathogens. RNA-seq analysis identified a number of differentially expressed genes that were involved in metal ion and ROS homoeostasis. Altered expression of metal ion-dependent ROS-scavenging enzymes genes and lower accumulation of cations such as Mn together induced compromised metal ion-dependent enzyme-catalysing activity and modulated ROS homoeostasis, which together contributed towards disease resistance in osnramp1 mutants. Furthermore, the osnramp1 mutants contained lower levels of toxic heavy metals Cd and Pb and micronutrients Ni and Mn in leaves and grains. Taken together, a proof of concept was achieved that broad-spectrum disease-resistant and toxic heavy-metal-safe rice was engineered by removal of the OsNRAMP1 gene.

Using short-term prophylactic antibiotics for prevention of infectious complications after radial endobronchial ultrasound-guided transbronchial biopsy.

BACKGROUND: Radial endobronchial ultrasound-guided transbronchial biopsy (rEBUS-TBB) facilitates the diagnosis of peripheral lung lesions. However, methods to prevent infectious complications afterwards have not been well established. Therefore, we analyzed the efficacy of short-term oral antibiotics for preventing infectious complications. METHODS: We retrospectively analyzed 484 patients. Patients who underwent rEBUS-TBB from March 2018 to March 2019 did not receive prophylactic antibiotics ("no prophylactic" group, n = 233), while patients who underwent rEBUS-TBB from April 2019 to March 2020 did receive prophylactics (oral amoxicillin/clavulanate for 3 days; "prophylactic" group, n = 251). Multivariable logistic regression was used to identify independent factors for infectious complications. RESULTS: The median age was 66 years (IQR: 59-74 years), and 58.9% were male. Slightly over half of the patients (54.4%) were previous or current smokers. In 13% (n = 63) of patients, the procedure was performed using a guide sheath. Infectious complications occurred in 12 (5.2%) and 2 (0.8%) cases in the no prophylactic and prophylactic groups, respectively. In multivariable analysis, infectious complications were significantly associated with a cavity or low-density attenuation (LDA) of the lesion, and with obstructive pneumonic consolidation, but not with prophylactic antibiotics. In subgroup analysis, infectious complications occurred less often when prophylactic antibiotics were used in patients with at least one risk factor (22.4% vs. 0%, p = 0.005). CONCLUSIONS: The risk factors for infectious complications were cavities, LDA in the lesion, and obstructive pneumonic consolidation. Use prophylactic antibiotics might reduce incidence of infectious complications in the presence of these risk factors.

Expansion of CD45RA-FOXP3++ regulatory T cells is associated with immune tolerance in patients with combined kidney and bone marrow transplantation.

OBJECTIVES: Simultaneous transplantation of a solid organ and bone marrow from the same donor is a possible means of achieving transplant tolerance. Here, we attempted to identify biomarkers that indicate transplant tolerance for discontinuation of immunosuppressants in combined kidney and bone marrow transplantation (CKBMT). METHODS: Conventional kidney transplant (KT) recipients (n = 20) and CKBMT recipients (n = 6) were included in this study. We examined various immunological parameters by flow cytometry using peripheral blood mononuclear cells (PBMCs), including the frequency and phenotype of regulatory T (Treg) cell subpopulations. We also examined the suppressive activity of the Treg cell population in the setting of mixed lymphocyte reaction (MLR) with or without Treg cell depletion. RESULTS: Among six CKBMT recipients, three successfully discontinued immunosuppressants (tolerant group) and three could not (non-tolerant group). The CD45RA-FOXP3++ Treg cell subpopulation was expanded in CKBMT recipients compared to conventional kidney transplant patients, and this was more obvious in the tolerant group than the non-tolerant group. In addition, high suppressive activity of the Treg cell population was observed in the tolerant group. The ratio of CD45RA-FOXP3++ Treg cells to CD45RA-FOXP3+ cells indicated good discrimination between the tolerant and non-tolerant groups. CONCLUSION: Thus, our findings propose a biomarker that can distinguish CKBMT patients who achieve transplant tolerance and are eligible for discontinuation of immunosuppressants and may provide insight into tolerance mechanisms in CKBMT.

Overexpression of arogenate dehydratase reveals an upstream point of metabolic control in phenylalanine biosynthesis.

Out of the three aromatic amino acids, the highest flux in plants is directed towards phenylalanine, which is utilized to synthesize proteins and thousands of phenolic metabolites contributing to plant fitness. Phenylalanine is produced predominantly in plastids via the shikimate pathway and subsequent arogenate pathway, both of which are subject to complex transcriptional and post-transcriptional regulation. Previously, it was shown that allosteric feedback inhibition of arogenate dehydratase (ADT), which catalyzes the final step of the arogenate pathway, restricts flux through phenylalanine biosynthesis. Here, we show that in petunia (Petunia hybrida) flowers, which typically produce high phenylalanine levels, ADT regulation is relaxed, but not eliminated. Moderate expression of a feedback-insensitive ADT increased flux towards phenylalanine, while high overexpression paradoxically reduced phenylalanine formation. This reduction could be partially, but not fully, recovered by bypassing other known metabolic flux control points in the aromatic amino acid network. Using comparative transcriptomics, reverse genetics, and metabolic flux analysis, we discovered that transcriptional regulation of the d-ribulose-5-phosphate 3-epimerase gene in the pentose phosphate pathway controls flux into the shikimate pathway. Taken together, our findings reveal that regulation within and upstream of the shikimate pathway shares control over phenylalanine biosynthesis in the plant cell.

Clinical Factors Associated with Renal Outcome After Heart Transplantation.

Cardiorenal syndrome (CRS) frequently occurs in end-stage heart failure patients waiting for heart transplantation (HT). Decision-making regarding simultaneous heart and kidney transplantation is an unresolved issue in these patients. We investigated clinical factors associated with renal outcome after HT. A total of 180 patients who received HT from 1996 to 2015 were included. Factors associated with early post-HT chronic kidney disease (CKD, estimated glomerular filtration rate [eGFR] < 60 mL/minute/1.73 m2 within 1 year post-HT), post-HT end-stage kidney disease (ESKD), and significant renal function improvement (%ΔeGFR > 15%) at 1 year post-HT were analyzed. Early post-HT CKD and post-HT ESKD developed in 61 (33.9%) and 8 (4.4%) of 180 patients, respectively. Old age was only independently associated with early post-HT CKD and preexisting CKD tended to be associated with early post-HT CKD. Old age and preexisting CKD were independently associated with post-HT ESKD. Low pre-HT eGFR and preoperative renal replacement therapy were not associated with early post-HT CKD or post-HT ESKD. Young age, low pre-HT eGFR, and high %ΔeGFR 1 month post-HT were independently associated with significant renal function improvement. Preoperative renal function, including preoperative RRT, was not associated with post-HT mortality. In conclusion, preexisting CKD may impact renal outcomes after HT, but preoperative severe renal dysfunction, even that severe enough to require RRT, may not be a contraindication for HT alone. Our data suggest the necessity of early HT in end-stage heart failure patients with CRS and the importance of careful management during the early postoperative period.

Prediction model for early graft failure after liver transplantation using aspartate aminotransferase, total bilirubin and coagulation factor.

This study was designed to build models predicting early graft failure after liver transplantation. Cox regression model for predicting early graft failure after liver transplantation using post-transplantation aspartate aminotransferase, total bilirubin, and international normalized ratio of prothrombin time was constructed based on data from both living donor (n = 1153) and deceased donor (n = 359) liver transplantation performed during 2004 to 2018. The model was compared with Model for Early Allograft Function Scoring (MEAF) and early allograft dysfunction (EAD) with their C-index and time-dependent area-under-curve (AUC). The C-index of the model for living donor (0.73, CI = 0.67-0.79) was significantly higher compared to those of both MEAF (0.69, P = 0.03) and EAD (0.66, P = 0.001) while C-index for deceased donor (0.74, CI = 0.65-0.83) was only significantly higher compared to C-index of EAD. (0.66, P = 0.002) Time-dependent AUC at 2 weeks of living donor (0.96, CI = 0.91-1.00) and deceased donor (0.98, CI = 0.96-1.00) were significantly higher compared to those of EAD. (both 0.83, P < 0.001 for living donor and deceased donor) Time-dependent AUC at 4 weeks of living donor (0.93, CI = 0.86-0.99) was significantly higher compared to those of both MEAF (0.87, P = 0.02) and EAD. (0.84, P = 0.02) Time-dependent AUC at 4 weeks of deceased donor (0.94, CI = 0.89-1.00) was significantly higher compared to both MEAF (0.82, P = 0.02) and EAD. (0.81, P < 0.001). The prediction model for early graft failure after liver transplantation showed high predictability and validity with higher predictability compared to traditional models for both living donor and deceased donor liver transplantation.

Non-Polar Myxococcus fulvus KYC4048 Metabolites Exert Anti-Proliferative Effects via Inhibition of Wnt/ß-Catenin Signaling in MCF-7 Breast Cancer Cells.

The Wnt/ß-catenin signaling pathway is involved in breast cancer and Myxococcus fulvus KYC4048 is a myxobacterial strain that can produce a variety of bioactive secondary metabolites. Although a previous study revealed that KYC4048 metabolites exhibit anti-proliferative effects on breast cancer, the biochemical mechanism involved in their effects remains unclear. In the present study, KYC4048 metabolites were separated into polar and non-polar (ethyl acetate and n-hexane) fractions via liquid-liquid extraction. The effects of these polar and non-polar KYC4048 metabolites on the viability of breast cancer cells were then determined by MTT assay. Expression levels of Wnt/ß-catenin pathway proteins were determined by Western blot analysis. Cell cycle and apoptosis were measured via fluorescence-activated cell sorting (FACS). The results revealed that non-polar KYC4048 metabolites induced cell death of breast cancer cells and decreased expression levels of WNT2B, ß-catenin, and Wnt target genes (c-Myc and cyclin D1). Moreover, the n-hexane fraction of non-polar KYC4048 metabolites was found most effective in inducing apoptosis, necrosis, and cell cycle arrest, leading us to conclude that it can induce apoptosis of breast cancer cells through the Wnt/ß-catenin pathway. These findings provide evidence that the n-hexane fraction of non-polar KYC4048 metabolites can be developed as a potential therapeutic agent for breast cancer via inhibition of the Wnt/ß-catenin pathway.

A Scoring Model with Simple Clinical Parameters to Predict Successful Discontinuation of Continuous Renal Replacement Therapy.

BACKGROUND: Continuous renal replacement therapy (CRRT) is the standard treatment for severe acute kidney injury in critically ill patients. However, a practical consensus for discontinuing CRRT is lacking. We aimed to develop a prediction model with simple clinical parameters for successful discontinuation of CRRT. METHODS: Adult patients who received CRRT at Samsung Medical Center from 2007 to 2017 were included. Patients with preexisting ESRD and patients who progressed to ESRD within 1 year or died within 7 days after CRRT were excluded. Successful discontinuation of CRRT was defined as no requirement for renal replacement therapy for 7 days after discontinuing CRRT. Patients were assigned to either a success group or failure group according to whether discontinuation of CRRT was successful or not. RESULTS: A total of 1,158 patients were included in the final analyses. The success group showed greater urine output on the day before CRRT discontinuation (D-1) and the discontinuation day (D0). Multivariable analysis identified that urine output ≥300 mL on D-1, and mean arterial pressure 50∼78 mm Hg, serum potassium <4.1 mmol/L, and BUN <35 mg/dL (12.5 mmol/L) on D0 were predictive factors for successful discontinuation of CRRT. A scoring system using the 4 variables above (area under the receiver operating curve: 0.731) was developed. CONCLUSIONS: Scoring system composed of urine output ≥300 mL/day on D-1, and adequate blood pressure, serum potassium <4.1 mmol/L, and BUN <35 mg/dL (12.5 mmol/L) on D0 was developed to predict successful discontinuation of CRRT.

Eradication of Helicobacter pylori infection decreases risk for dyslipidemia: A cohort study.

BACKGROUND: Previous studies have suggested a relationship between Helicobacter pylori infection and dyslipidemia; however, large-scale longitudinal studies have not elucidated this association. This study assessed the longitudinal effects of H. pylori infection and eradication on lipid profiles in a large cohort. METHODS: This cohort study included 2,626 adults without dyslipidemia at baseline, who participated in a repeated, regular health-screening examination, which included upper gastrointestinal endoscopy, between January 2009 and December 2018. The primary outcome was incident dyslipidemia at follow-up. RESULTS: During the 10,324 person-years of follow-up, participants with persistent H. pylori infection had a higher incidence rate (130.5 per 1,000 person-years) of dyslipidemia than those whose infections had been successfully controlled (98.1 per 1,000 person-years). In a multivariable model adjusted for age, sex, waist circumference, smoking status, alcohol intake, and education level, the H. pylori eradication group was associated with a lower risk of dyslipidemia than the persistent group (HR, 0.85; 95% CI, 0.77-0.95; p = 0.004). The association persisted after further adjustment for baseline levels of low-density and high-density lipoprotein cholesterol (HR, 0.87; 95% CI, 0.79-0.97; p = 0.014). CONCLUSIONS: H. pylori infection may play a pathophysiologic role in the development of dyslipidemia, whereas H. pylori eradication might decrease the risk of dyslipidemia.

Risk-Scoring System for Prediction of Non-Curative Endoscopic Submucosal Dissection Requiring Additional Gastrectomy in Patients with Early Gastric Cancer.

PURPOSE: When patients with early gastric cancer (EGC) undergo non-curative endoscopic submucosal dissection requiring gastrectomy (NC-ESD-RG), additional medical resources and expenses are required for surgery. To reduce this burden, predictive model for NC-ESD-RG is required. MATERIALS AND METHODS: Data from 2,997 patients undergoing ESD for 3,127 forceps biopsy-proven differentiated-type EGCs (2,345 and 782 in training and validation sets, respectively) were reviewed. Using the training set, the logistic stepwise regression analysis determined the independent predictors of NC-ESD-RG (NC-ESD other than cases with lateral resection margin involvement or piecemeal resection as the only non-curative factor). Using these predictors, a risk-scoring system for predicting NC-ESD-RG was developed. Performance of the predictive model was examined internally with the validation set. RESULTS: Rate of NC-ESD-RG was 17.3%. Independent pre-ESD predictors for NC-ESD-RG included moderately differentiated or papillary EGC, large tumor size, proximal tumor location, lesion at greater curvature, elevated or depressed morphology, and presence of ulcers. A risk-score was assigned to each predictor of NC-ESD-RG. The area under the receiver operating characteristic curve for predicting NC-ESD-RG was 0.672 in both training and validation sets. A risk-score of 5 points was the optimal cut-off value for predicting NC-ESD-RG, and the overall accuracy was 72.7%. As the total risk score increased, the predicted risk for NC-ESD-RG increased from 3.8% to 72.6%. CONCLUSIONS: We developed and validated a risk-scoring system for predicting NC-ESD-RG based on pre-ESD variables. Our risk-scoring system can facilitate informed consent and decision-making for preoperative treatment selection between ESD and surgery in patients with EGC.