Cadmium (Cd) exposure primarily occurs through inhalation, either by smoking or occupational exposure to contaminated air. Upon inhalation, Cd ultimately reaches the prostate through the bloodstream. In this review, we investigate the carcinogenic potential of Cd in both respiratory organs and the prostate. Specifically, this review examines cellular metabolism, comprehensive toxicity, and carcinogenic mechanisms by exploring gene ontology, biological networks, and adverse outcome pathways. In the respiratory organs, Cd induces lung cancer by altering the expression of IL1B and FGF2, causing DNA damage, reducing cell junction integrity, and promoting apoptosis. In the prostate, Cd induces prostate cancer by modifying the expression of EDN1 and HMOX1, leading to abnormal protein activities and maturation, suppressing tumor suppressors, and inducing apoptosis. Collectively, this review provides a comprehensive understanding of the carcinogenic mechanisms of Cd in two different organs by adopting toxicogenomic approaches. These insights can serve as a foundation for further research on cadmium-induced cancer, contributing to the establishment of future cancer prevention strategies.

Long-term outcomes of live kidney donors remain controversial, although this information is crucial for selecting potential donors. Thus, this study compared the long-term risk of all-cause mortality between live kidney donors and healthy control. Methods: We performed a retrospective cohort study including donors from seven tertiary hospitals in South Korea. Persons who underwent voluntary health screening were included as controls. We created a matched control group considering age, sex, era, body mass index, baseline hypertension, diabetes, estimated glomerular filtration rate, and dipstick albuminuria. The study outcome was progression to end-stage kidney disease (ESKD), and all-cause mortality as identified in the linked claims database. Results: We screened 1,878 kidney donors and 78,115 health screening examinees from 2003 to 2016. After matching, 1,701 persons remained in each group. The median age of the matched study subjects was 44 years, and 46.6% were male. Among the study subjects, 2.7% and 16.6% had underlying diabetes and hypertension, respectively. There were no ESKD events in the matched donor and control groups. There were 24 (1.4%) and 12 mortality cases (0.7%) in the matched donor and control groups, respectively. In the age-sex adjusted model, the risk for all-cause mortality was significantly higher in the donor group than in the control group. However, the significance was not retained after socioeconomic status was included as a covariate (adjusted hazard ratio, 1.82; 95% confidence interval, 0.87–3.80). Conclusion: All-cause mortality was similar in live kidney donors and matched non-donor healthy controls with similar health status and socioeconomic status in the Korean population.

Background/Aims: Renal recovery of a kidney donor after undergoing nephrectomy though challenging is essential. We aimed to examine the effect of estimated glomerular filtration rate (eGFR) percent change at 1-month post-donation on insufficient kidney function after kidney donation. Methods: A total of 3,952 living kidney donors who underwent donor nephrectomy from 1982 to 2019 from eight different tertiary hospitals in Korea were initially screened. Percent changes in the eGFR from baseline to 1-month post-donation were calculated. The degree of percent changes was categorized by quartile, and the 1st quartile was regarded as the group with the lowest decreased eGFR at 1-month after donation. The remaining eGFR less than 60 mL/min/1.73 m2 was the end-point. The Cox proportional hazard model was used for evaluating the impact of initial eGFR and eGFR percent change at 1-month post-donation on the condition with remaining eGFR < 60 mL/ min/1.73 m2. In the multivariate analysis, we used variables with a p < 0.1 in the univariate analysis. Results: A total of 1,585 donors were included in the analysis. During 62.2 ± 49.3 months, 13.7% of donors showed renal insufficiency. The 4th (adjusted hazard ratio [aHR], 10.41; 95% confidence interval [CI], 5.15 to 21.04) and the 3rd (aHR, 4.29; 95% CI, 2.15 to 8.56) quartiles of percent change in eGFR and the pre-donation eGFR (aHR, 0.90; 95% CI, 0.88 to 0.92) were associated with the development of renal insufficiency. Conclusions The impact of worse initial renal recovery on renal insufficiency was pronounced in donors with lower pre-donation eGFRs. Additionally, worse initial renal recovery of remaining kidney affected the long-term development of renal insufficiency in kidney donors.

Background/Aims: PPARγ, farnesoid X receptor (FXR) and CYP7A1 are associated with solubility of bile. This study was performed to understand a mechanism and interactions of statin-induced PPARγ, PGC-1α and HNF-4α related to the statin-induced activation of FXR and CYP7A1, and verify whether the mevalonate pathway is involved in the mechanism. Methods: MTT assays were performed using cultured human Hep3B cells to determine the effect of atorvastatin on the cell proliferation. Expression levels of indicated proteins were measured using Western blotting assays by inhibiting the protein expression or not. Results: Atorvastatin increased expression of PPARγ, PGC-1α, HNF-4α, FXR, and CYP7A1 in Hep3B cells. PPARγ ligand of troglitazone upregulated the expression of PGC-1α, HNF-4α, FXR, and CYP7A1 in Hep3B cells. Silencing of PPARγ, PGC1α, and HNF4α using respective siRNA demonstrated that atorvastatin-induced FXR and CYP7A1 activation required sequential action of PPARγ /PGC-1α/HNF-4α. The silencing of PPARγ completely inhibited atorvastatin-induced PGC-1α expression, and the PGC1α silencing partially inhibited atorvastatin-induced PPARγ expression. The inhibition of HNF4α did not affect atorvastatin-induced PPARγ expression, but partially inhibited atorvastatin-induced PGC-1α expression. Besides, mevalonate completely reversed the effect of atorvastatin on PPARγ, PGC-1α, HNF-4α, FXR, and CYP7A1. Conclusions Atorvastatin induces FXR and CYP7A1 activation as a result of sequential action of PPARγ/PGC-1α/HNF-4α in human hepatocytes. We propose that atorvastatin enhances solubility of cholesterol in bile by simultaneously activating of FXR and CYP7A1.

Background: Considering the growing prevalence of Western lifestyles and related chronic diseases occurring in South Korea, this study aimed to explore the progression of metabolic risk factors in living kidney donors compared to a control group. Methods: This study enrolled living kidney donors from seven hospitals from 1982 to 2016. The controls were individuals that voluntarily received health check-ups from 1995 to 2016 that were matched with donors according to age, sex, diabetes status, baseline estimated glomerular filtration rate, and date of the medical record. Data on hyperuricemia, hypertension, hypercholesterolemia, and overweight/obesity were collected to determine metabolic risks. The proportion of individuals with three or more metabolic risk factors was evaluated. Logistic regressions with interaction terms between the medical record date and donor status were used to compare the trends in metabolic risks over time in the two groups. Results: A total of 2,018 living kidney donors and matched non-donors were included. The median age was 44.0 years (interquartile range, 34.0–51.0 years) and 54% were women. The living kidney donors showed a lower absolute prevalence for all metabolic risk factors, except for those that were overweight/obese, than the non-donors. The proportion of subjects that were overweight/obese was consistently higher over time in the donor group. The changes over time in the prevalence of each metabolic risk were not significantly different between groups, except for a lower prevalence of metabolic risk factors ≥ 3 in donors. Conclusion Over time, metabolic risks in living kidney donors are generally the same as in non-donors, except for a lower prevalence of metabolic risk factors ≥ 3 in donors.

Background: The effect of each health-related quality of life (HRQOL) component on hemodialysis prognosis has not been well studied. We aimed to investigate the clinical factors associated with HRQOL and the effect of HRQOL after dialysis initiation on long-term survival in an Asian population. Methods: A total of 568 hemodialysis patients were included from a nationwide prospective cohort study. HRQOL was evaluated using the Kidney Disease Quality of Life (KDQOL) Short FormTM 1.3 at 3 months after dialysis initiation. The effect of each KDQOL item score on mortality was analyzed. Multivariable Cox analysis was performed after adjusting for age, sex, modified Charlson comorbidity index, and causes of primary kidney disease. Results: Old age, diabetes mellitus, high comorbidities, and low serum albumin levels were associated with poor physical health status. Decreased urine output was associated with both poor physical and mental health status.The scores of 3 indices in the kidney disease domain (effect of kidney disease, social support, and dialysis staff encouragement) showed significant associations with mortality, as did the 3 indices (physical function, physical role limitation, and body pain) in the physical health domain. Neither the 4 indices in the mental health domain nor the mental composite score showed a significant association with mortality. However, a high physical composite score was associated with decreased overall patient mortality (P = 0.003). The effect of physical composite score on survival was prominent among young or middle-aged groups. Conclusion Poor physical health status 3 months after hemodialysis start correlates significantly with overall mortality.

Background: The effect of each health-related quality of life (HRQOL) component on hemodialysis prognosis has not been well studied. We aimed to investigate the clinical factors associated with HRQOL and the effect of HRQOL after dialysis initiation on long-term survival in an Asian population. Methods: A total of 568 hemodialysis patients were included from a nationwide prospective cohort study. HRQOL was evaluated using the Kidney Disease Quality of Life (KDQOL) Short FormTM 1.3 at 3 months after dialysis initiation. The effect of each KDQOL item score on mortality was analyzed. Multivariable Cox analysis was performed after adjusting for age, sex, modified Charlson comorbidity index, and causes of primary kidney disease. Results: Old age, diabetes mellitus, high comorbidities, and low serum albumin levels were associated with poor physical health status. Decreased urine output was associated with both poor physical and mental health status.The scores of 3 indices in the kidney disease domain (effect of kidney disease, social support, and dialysis staff encouragement) showed significant associations with mortality, as did the 3 indices (physical function, physical role limitation, and body pain) in the physical health domain. Neither the 4 indices in the mental health domain nor the mental composite score showed a significant association with mortality. However, a high physical composite score was associated with decreased overall patient mortality (P = 0.003). The effect of physical composite score on survival was prominent among young or middle-aged groups. Conclusion Poor physical health status 3 months after hemodialysis start correlates significantly with overall mortality.

BACKGROUND: In the present multi-institutional study, the prevalence and clinicopathologic characteristics of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) were evaluated among Korean patients who underwent thyroidectomy for papillary thyroid carcinoma (PTC).METHODS: Data from 18,819 patients with PTC from eight university hospitals between January 2012 and February 2018 were retrospectively evaluated. Pathology reports of all PTCs and slides of potential NIFTP cases were reviewed. The strict criterion of no papillae was applied for the diagnosis of NIFTP. Due to assumptions regarding misclassification of NIFTP as non-PTC tumors, the lower boundary of NIFTP prevalence among PTCs was estimated. Mutational analysis for BRAF and three RAS isoforms was performed in 27 randomly selected NIFTP cases.RESULTS: The prevalence of NIFTP was 1.3% (238/18,819) of all PTCs when the same histologic criteria were applied for NIFTP regardless of the tumor size but decreased to 0.8% (152/18,819) when tumors ≥1 cm in size were included. The mean follow-up was 37.7 months and no patient with NIFTP had evidence of lymph node metastasis, distant metastasis, or disease recurrence during the follow-up period. A difference in prevalence of NIFTP before and after NIFTP introduction was not observed. BRAF(V600E) mutation was not found in NIFTP. The mutation rate for the three RAS genes was 55.6% (15/27).CONCLUSIONS: The low prevalence and indolent clinical outcome of NIFTP in Korea was confirmed using the largest number of cases to date. The introduction of NIFTP may have a small overall impact in Korean practice.
Carcinoma, Papillary ; Diagnosis ; Follow-Up Studies ; Genes, ras ; Hospitals, University ; Humans ; Korea ; Lymph Nodes ; Mutation Rate ; Neoplasm Metastasis ; Pathology ; Prevalence ; Protein Isoforms ; Recurrence ; Retrospective Studies ; Thyroid Gland ; Thyroid Neoplasms ; Thyroidectomy

BACKGROUND: Appropriate immunosuppressive therapy for patients with idiopathic membranous nephropathy (MN) remains controversial. The effect of mycophenolate mofetil (MMF) versus cyclosporine (CsA) combined with low-dose corticosteroids was evaluated in patients with idiopathic MN in a multi-center randomized trial (www.ClinicalTrials.gov NCT01282073). METHODS: A total of 39 biopsy-proven idiopathic MN patients with severe proteinuria were randomly assigned to receive MMF combined with low-dose corticosteroids (MMF group) versus CsA combined with low-dose corticosteroids (CsA group), respectively, and followed up for 48 weeks. Complete or partial remission rate of proteinuria and estimated glomerular filtration rate (eGFR) at 48 weeks were compared. RESULTS: The level of proteinuria at baseline and at 48 weeks was 8.9 ± 5.9 and 2.1 ± 3.1 g/day, respectively, in the MMF group compared to 8.4 ± 3.5 and 3.2 ± 5.7 g/day, respectively, in the CsA group. In total, 76.1% of the MMF group and 66.7% of the CsA group achieved remission at 48 weeks (95% confidence interval, −0.18 to 0.38). There was no difference in eGFR between the two groups. Anti-phospholipase A2 receptor Ab levels at baseline decreased at 48 weeks in the complete or partial remission group (P = 0.001), but were unchanged in the no-response group. There were no significant differences between the two groups in changes in the Gastrointestinal Symptom Rating Scale and Gastrointestinal Quality of Life Index scores from baseline to 48 weeks. CONCLUSION: In combination with low-dose corticosteroids, the effect of MMF may not be inferior to that of CsA in patients with idiopathic MN, with similar adverse effects including gastrointestinal symptoms. Trial registry at ClinicalTrials.gov (www.ClinicalTrials.gov NCT01282073).
Adrenal Cortex Hormones ; Cyclosporine ; Glomerular Filtration Rate ; Glomerulonephritis, Membranous ; Humans ; Proteinuria ; Quality of Life

OBJECTIVES: In an effort to improve hearing aid users’ satisfaction, recent studies on trainable hearing aids have attempted to implement one or two environmental factors into training. However, it would be more beneficial to train the device based on the owner’s personal preferences in a more expanded environmental acoustic conditions. Our study aimed at developing a trainable hearing aid algorithm that can reflect the user’s individual preferences in a more extensive environmental acoustic conditions (ambient sound level, listening situation, and degree of noise suppression) and evaluated the perceptual benefit of the proposed algorithm. METHODS: Ten normal hearing subjects participated in this study. Each subjects trained the algorithm to their personal preference and the trained data was used to record test sounds in three different settings to be utilized to evaluate the perceptual benefit of the proposed algorithm by performing the Comparison Mean Opinion Score test. RESULTS: Statistical analysis revealed that of the 10 subjects, four showed significant differences in amplification constant settings between the noise-only and speech-in-noise situation (P<0.05) and one subject also showed significant difference between the speech-only and speech-in-noise situation (P<0.05). Additionally, every subject preferred different β settings for beamforming in all different input sound levels. CONCLUSION: The positive findings from this study suggested that the proposed algorithm has potential to improve hearing aid users’ personal satisfaction under various ambient situations.
Acoustics ; Classification ; Hearing Aids* ; Hearing* ; Humans ; Noise ; Patient Preference ; Personal Satisfaction ; Signal Processing, Computer-Assisted