The FK506 binding protein 5 (FKBP5) is a co-chaperone that regulates the activity of the glucocorticoid receptor (GR) and has been reported to mediate stress resilience. This study aimed to determine the effects of Fkbp5 deletion on acute stress-induced recognition memory impairment and hippocampal GR signaling. Wild-type and Fkbp5-knockout mice were subjected to acute uncontrollable stress induced by restraint and electrical tail shock. First, we assessed the cognitive status of mice using a novel object recognition task. Next, we measured plasma corticosterone, GR levels, and the levels of GR phosphorylation at serine 211 in the hippocampus. Wild-type mice exhibited stress-induced memory impairments, whereas Fkbp5-knockout mice did not. Plasma corticosterone and GR levels did not differ between the non-stressed wild-type and Fkbp5-knockout mice, but the levels of phosphorylated GR were lower in Fkbp5-knockout mice than in wild-type mice. Wild-type and Fkbp5-knockout mice showed increased nuclear GR levels following stress, indicating GR translocation. However, cytosolic phosphorylated GR levels were lower in the hippocampi of Fkbp5-knockout mice following stress than in those of wild-type mice. These results suggest that FKBP5 deficiency increases resilience to acute stress by altering GR signaling.

Patients with end-stage kidney disease face increased risk of cardiovascular events, and left ventricular diastolic dysfunction (LVDD) contributes to the high occurrence of cardiovascular mortality (CM). Although a high serum aldosterone (sALD) level is involved in the development of cardiovascular complications in the general population, this association is unclear in patients undergoing hemodialysis. We aimed to determine the impact of sALD on LVDD and CM among hemodialysis patients (HDPs). Methods: We performed a prospective cohort study of maintenance HDPs without cardiovascular disease. The patients were divided into two groups according to the median level of sALD. All patients underwent baseline echocardiography to evaluate diastolic dysfunction (E/e’ ratio > 15). The LVDD and CM rates were compared between the high and low aldosterone groups. Results: We enrolled a total of 60 adult patients (mean age, 57.9 ± 12.1 years; males, 30.0%). The low aldosterone group had an increased left ventricular diastolic dimension compared with the high aldosterone group (52.2 ± 8.4 mm vs. 50.3 ± 5.2 mm, respectively; p = 0.03). Low log-aldosterone (odds ratio [OR], 0.40; 95% confidence interval [CI], 0.19–0.86) and large left atrial dimension (OR, 1.31; 95% CI, 1.11–1.54) were independent risk factors for LVDD at baseline. In addition, Cox regression analysis demonstrated that low sALD was an independent predictor of CM in HDPs (hazard ratio, 0.46; 95% CI, 0.25–0.85; p = 0.01) during follow-up. Conclusion: Low sALD was not only associated with LVDD but was also an independent predictor of CM among HDPs regardless of their interdialytic weight gain.

Purpose: Atrial fibrillation (AF) patients with low to intermediate risk, defined as non-gender CHA2DS2-VASc score of 0–1, are still at risk of stroke. This study verified the usefulness of ABCD score [age (≥60 years), B-type natriuretic peptide (BNP) or N-terminal pro-BNP (≥300 pg/mL), creatinine clearance (<50 mL/min/1.73 m2 ), and dimension of the left atrium (≥45 mm)] for stroke risk stratification in non-gender CHA2DS2-VASc score 0–1. Materials and Methods: This multi-center cohort study retrospectively analyzed AF patients with non-gender CHA2DS2-VASc score 0–1. The primary endpoint was the incidence of stroke with or without antithrombotic therapy (ATT). An ABCD score was validated. Results: Overall, 2694 patients [56.3±9.5 years; female, 726 (26.9%)] were followed-up for 4.0±2.8 years. The overall stroke rate was 0.84/100 person-years (P-Y), stratified as follows: 0.46/100 P-Y for an ABCD score of 0; 1.02/100 P-Y for an ABCD score ≥1. The ABCD score was superior to non-gender CHA2DS2-VASc score in the stroke risk stratification (C-index=0.618, p=0.015; net reclassification improvement=0.576, p=0.040; integrated differential improvement=0.033, p=0.066). ATT was prescribed in 2353 patients (86.5%), and the stroke rate was significantly lower in patients receiving non-vitamin K antagonist oral anticoagulant (NOAC) therapy and an ABCD score ≥1 than in those without ATT (0.44/100 P–Y vs. 1.55/100 P-Y; hazard ratio=0.26, 95% confidence interval 0.11–0.63, p=0.003). Conclusion The biomarker-based ABCD score demonstrated improved stroke risk stratification in AF patients with non-gender CHA2DS2-VASc score 0–1. Furthermore, NOAC with an ABCD score ≥1 was associated with significantly lower stroke rate in AF patients with non-gender CHA2DS2-VASc score 0–1.

The gut microbiota interacts with the host gut environment, which is influenced by such factors as sex, age, and host diet. These factors induce changes in the microbial composition. The aim of this study was to identify differences in the gut microbiome of Fisher-344 (F344) rats fed a high-fat diet (HFD), depending on their age and sex. Fecal microbiomes from 6-, 31-, and 74-week-old, and 2-year-old both male and female rats (corresponding to 5-, 30-, 60-, and 80-year-old humans) were analyzed using 16S rRNA gene sequencing, phylogenetic investigation of communities by reconstruction of unobserved states, and enterotype (E) assessment. Moreover, the effect of an HFD on colonic epithelial cells was measured using real-time quantitative PCR. Alpha diversity decreased in the HFD group regardless of age and sex. Based on the enterotype clustering of the whole fecal microbiome, clusters from male rats were divided into E1 and E2 enterotypes, while clusters from female rats were divided into E1, E2, and E3 enterotypes. The female E3 group showed a significantly high abundance in the Ruminococcus genus and expression of Tlr2 mRNA, which may reflect compensation to the HFD. Moreover, the female E3 group showed a lower ratio of opportunistic pathogenic strains to commensal strains compared to the female E2 group. Administration of an HFD influenced the rat fecal microbiota in all assessed age groups, which could be further differentiated by sex. In particular, female rats showed a compensatory enterotype response to an HFD compared to male rats.

Background: The Korean Society of Nephrology (KSN) has maintained a nationwide end-stage renal disease (ESRD) registry data from Korean Renal Data System (KORDS) since 1985, as the representative registry of ESRD patients in Korea. This review is aimed to update the status of domestic ESRD and to provide evidence on the direction of dialysis therapy. Methods: The KORDS Committee of KSN has collected data on dialysis centers and patients through an online registry program, and the data from 1986 to 2019 were analyzed. Results: The incidence and prevalence of ESRD patients in Korea are increasing. The ESRD population numbered more than 100,000 in 2019, doubling during the 10 years since 2010. The proportion of diabetes mellitus as a major cause of ESRD seems to have reached a plateau. The increasing number of elderly dialysis patients is a constant trend, with more than half for the proportion of patients older than 65 years old in 2019. All-cause mortality decreased for the last approximately 20 years, regardless of sex, age, and cause of ESRD. The 5-year patient survival rate in both hemodialysis and peritoneal dialysis increased from 2001 to 2013. Since 2013, the patient survival rates in peritoneal dialysis were similar to those in hemodialysis. Cardiovascular complications were the leading cause of death in ESRD patients. Conclusions The incidence and prevalence of Korean ESRD patients have increased over time, although patient survival has also steadily increased. The establishment of a surveillance method to address the major cause of mortality in ESRD patients will help improve outcomes.

Background: The Korean Society of Nephrology (KSN) has maintained a nationwide end-stage renal disease (ESRD) registry data from Korean Renal Data System (KORDS) since 1985, as the representative registry of ESRD patients in Korea. This review is aimed to update the status of domestic ESRD and to provide evidence on the direction of dialysis therapy. Methods: The KORDS Committee of KSN has collected data on dialysis centers and patients through an online registry program, and the data from 1986 to 2019 were analyzed. Results: The incidence and prevalence of ESRD patients in Korea are increasing. The ESRD population numbered more than 100,000 in 2019, doubling during the 10 years since 2010. The proportion of diabetes mellitus as a major cause of ESRD seems to have reached a plateau. The increasing number of elderly dialysis patients is a constant trend, with more than half for the proportion of patients older than 65 years old in 2019. All-cause mortality decreased for the last approximately 20 years, regardless of sex, age, and cause of ESRD. The 5-year patient survival rate in both hemodialysis and peritoneal dialysis increased from 2001 to 2013. Since 2013, the patient survival rates in peritoneal dialysis were similar to those in hemodialysis. Cardiovascular complications were the leading cause of death in ESRD patients. Conclusions The incidence and prevalence of Korean ESRD patients have increased over time, although patient survival has also steadily increased. The establishment of a surveillance method to address the major cause of mortality in ESRD patients will help improve outcomes.

PURPOSE: Data are lacking on the association between the allergic rhinitis (AR) phenotype and sensitization to specific allergens or bronchial hyperresponsiveness (BHR) in children. We here investigated risk factors and comorbidities, including sensitization to specific allergens and BHR, for the AR phenotype by AR and its Impact on Asthma (ARIA) classification in a general population-based birth cohort study. METHODS: We enrolled 606 children aged 7 years from the Panel Study of Korean Children. The AR phenotype was assigned in accordance with the ARIA classification in children. Skin prick tests and Provocholine provocation test were performed. Risk factors and comorbidities for AR phenotypes were then analyzed. RESULTS: The prevalence of mild and moderate to severe AR in our study cohort was 37.2% and 8.8%, respectively. Recent use of analgesics or antipyretics and current cat ownership were associated with the risk of mild persistent AR. Sensitizations to Dermatophagoides Pteronyssinus (Der p), Japanese hop and cat were associated with moderate to severe persistent AR. Children with moderate to severe AR had a higher risk of current asthma and BHR compared to mild AR cases (adjusted odds ratio [aOR], 5.26; 95% confidence interval [CI], 1.77–15.62). Moderate to severe AR with allergic sensitization was associated with the highest risk of BHR (aOR, 11.77; 95% CI, 3.40–40.74). CONCLUSIONS: Moderate to severe-persistent AR is more closely related to respiratory comorbidities and sensitizations than mild AR. Stratifying the AR phenotype by ARIA classification may assist in disease management.
Allergens ; Analgesics ; Animals ; Antipyretics ; Asian Continental Ancestry Group ; Asthma ; Bronchial Hyperreactivity ; Cats ; Child ; Classification ; Cohort Studies ; Comorbidity ; Dermatophagoides pteronyssinus ; Disease Management ; Humans ; Methacholine Chloride ; Odds Ratio ; Ownership ; Parturition ; Phenotype ; Prevalence ; Rhinitis, Allergic ; Risk Factors ; Skin

Background/Aims: This study aimed to evaluate the correlation between clinical risk factors of post-extubation dysphagia (PED) and the severity of impaired pharyngeal swallowing function assessed via videofluoroscopic swallowing studies (VFSSs). Methods: This study was a retrospective review of medical records. Of 116 patients who were admitted to the intensive care unit and underwent VFSS, 32 who had non-neurologic disorders and experienced prolonged intubation (for more than 48 hours) were diagnosed with PED. The severity of PED was evaluated by using a functional dysphagia scale (FDS) and a penetration aspiration scale (PAS), on the basis of VFSS. Results: The Simplified Acute Physiology Score 3 and total FDS score were positively correlated (r = 0.40, p = 0.02). Intubation duration was positively correlated with total PAS and FDS scores (r = 0.62, p < 0.001; r = 0.65, p < 0.001, respectively). The amounts of residue in the valleculae (RV) and pyriform sinuses (RP) were associated with intubation duration (r = 0.58, p < 0.001; r = 0.57, p < 0.001, respectively). Multivariate regression analysis revealed that intubation duration was significantly associated with the total FDS score, RV and RP subscales of the FDS, and total PAS score. Conclusions The severity of impaired swallowing function, particularly the amount of residue in the pharyngeal recesses assessed via VFSS, was strongly associated with both severity of medical illness and intubation duration. Intubation duration could be a prognostic factor for assessing impaired swallowing function on the basis of VFSS.

Background/Aims: Emerging evidence shows that the mechanism of irritable bowel syndrome (IBS) is associated with neurotrophic factors and tight junction proteins (TJPs). It is known that there are sex differences in the pathophysiology of IBS. The aim of the present study is to determine expression levels of neurotrophic factors, TJPs, and cytokines according to IBS subtype and sex. Methods: From 59 IBS (33 IBS-constipation, 21 IBS-diarrhea, and 5 IBS-mixed) and 36 control patients, colonic mucosa mRNA expression levels of transient receptor potential vanilloid-1 (TRPV1), nerve growth factor (NGF), glial cell-derived neurotrophic factor (GDNF), and various TJPs were assessed by real-time polymerase chain reaction. Western blot was performed to determine levels of zonular occludens-1 (ZO-1). Serum levels of cytokines were measured by enzyme-linked immunosorbent assay. Results: TRPV1, GDNF, and NGF mRNA levels were significantly increased in those with IBS-constipation compared to those in controls (all P < 0.05). However, they showed no significant difference between those with IBS-diarrhea and controls. Expression level of TRPV1 correlated with that of GDNF (r = 0.741, P < 0.001) and NGF (r = 0.935, P < 0.001). ZO-1 RNA expression levels were lower (P = 0.021) in female IBS-diarrhea than those in controls, although they showed no significant differences between male IBS-diarrhea and controls. Serum IL-1β levels in female IBS were significantly higher than those of male IBS, especially in IBS-constipation (P < 0.001). Conclusion Our results suggest that neurotrophic factors and IL-1β are closely related to IBS-constipation and that decrease of ZO-1 is an important factor in female with IBS-diarrhea.

PURPOSE: This study demonstrates that estradiol downregulates inflammation and inhibits colorectal cancer (CRC) development in azoxymethane/dextran sulfate sodium (AOM/DSS) mouse model. MATERIALS AND METHODS: AOM/DSS-treated male and female mice were sacrificed at weeks 2, 10, and 16, to assess estrogen effects on colitis and carcinogenesis. Macroscopic and histologic severity of colitis and Western blot and quantitative real-time polymerase chain reaction were evaluated, to measure inflammatory mediators and cytokines. RESULTS: Compared with AOM/DSS-treated male mice (M-AOM/DSS group), AOM/DSS-treated male mice with estradiol administration (M-AOM/DSS+estr group) displayed at week 2 significantly decreased severity of colitis. At weeks 10 and 16, AOM/DSS-treated female mice (F-AOM/DSS group) and the M-AOM/DSS+estr group showed significantly lower tumor multiplicity compared with the M-AOM/DSS group. At week 2, F-AOM/DSS group had a lower level of nuclear factor-κB (NF-κB) expression and higher level of nuclear factor erythroid 2-related factor 2 (Nrf2) expression, compared to the M-AOM/DSS group. At week 2, expression levels of NF-κB and its related mediators decreased in the M-AOM/DSS+estr group, while levels of Nrf2 and Nrf2-related anti-oxidant enzymes increased. In addition, estradiol significantly increased Nod-like receptor protein 3 (NLRP3) inflammasome expressions in AOM/DSS-treated male mice. In contrast, at weeks 10 and 16, Nrf2 and its-related anti-oxidant enzymes and NLRP3 inflammasome were highly expressed in M-AOM/DSS group and in F-AOM/DSS group, who developed cancer. CONCLUSION: The data suggest that estradiol inhibits the initiation of CRC by regulating Nrf2-related pathways. Moreover, these imply the dual role of Nrf2 and NLRP3 inflammasome, including promotion of tumor progression upon tumor initiation.
Animals ; Blotting, Western ; Carcinogenesis ; Colitis ; Colorectal Neoplasms ; Cytokines ; Estradiol ; Estrogens ; Female ; Humans ; Inflammasomes ; Inflammation ; Male ; Mice ; NF-E2-Related Factor 2 ; NF-kappa B ; Real-Time Polymerase Chain Reaction ; Sex Characteristics ; Sodium