PURPOSE: The aim of this study was to evaluate whether serum creatinine levels at 3 days after renal transplantation can predict long-term graft survival and its associated clinical aspects. METHODS: Three hundred and seventy six renal transplant recipients who received grafts from living donors were included. Recipients were classified into two groups according to their serum creatinine levels (1.2 mg/dL group) at 3 days after renal transplantations. Demographic characteristics (age, sex, weight, body mass index, donor/recipient body weight ratio, pre-transplant dialysis type, underlying disease and pre-transplant transfusion), transplant variables (immuno-suppressive agents, HLA mismatch and HLA DR mismatch) and post-transplant variables (routine graft biopsy, number of acute rejection episodes within first year after renal transplantation, serum creatinine level and graft survival at each first, second, and fifth years) were assessed. RESULTS: Among total 376 recipients, serum creatinine 1.2 mg/dL groups were 224 (59.6%) recipients. The characteristics of patients with good graft function (serum creatinine 1.2 mg/dL group (first year, 100% vs. 95.7%; fifth year, 96.7% vs. 89.8%; P<0.05). Conclusion: Serum creatinine levels at 3 days after renal transplantation can predict long-term kidney transplant survival. It was associated with immunological (frequency of acute rejection) and non- immunological aspect (match of kidney size and donor's age).
Biopsy ; Body Weight ; Creatinine* ; Dialysis ; Female ; Graft Survival ; Humans ; Kidney ; Kidney Transplantation* ; Living Donors ; Transplantation ; Transplants*

PURPOSE: Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low density lipoprotein receptor (LDLR) and promotes degradation of the LDLR. Inhibition of PCSK9 either by reducing its expression or by blocking its activity results in the upregulation of the LDLR and subsequently lowers the plasma concentration of LDL-cholesterol. As a modality to inhibit PCSK9 action, we searched the chemical library for small molecules that block the binding of PCSK9 to the LDLR. MATERIALS AND METHODS: We selected 100 chemicals that bind to PCSK9 where the EGF-AB fragment of the LDLR binds via in silico screening of the ChemBridge chemical library, using the computational GOLD algorithm analysis. Effects of chemicals were evaluated using the PCSK9-LDLR binding assay, immunoblot analysis, and the LDL-cholesterol uptake assay in vitro, as well as the fast performance liquid chromatography assay for plasma lipoproteins in vivo. RESULTS: A set of chemicals were found that decreased the binding of PCSK9 to the EGF-AB fragment of the LDLR in a dose-dependent manner. They also increased the amount of the LDLR significantly and subsequently increased the uptake of fluorescence-labeled LDL in HepG2 cells. Additionally, one particular molecule lowered the plasma concentration of total cholesterol and LDL-cholesterol significantly in wild-type mice, while such an effect was not observed in Pcsk9 knockout mice. CONCLUSION: Our findings strongly suggest that in silico screening of small molecules that inhibit the protein-protein interaction between PCSK9 and the LDLR is a potential modality for developing hypercholesterolemia therapeutics.
Animals ; Cholesterol/*blood ; Cholesterol, LDL/blood ; Hep G2 Cells ; Humans ; Mice ; Mice, Knockout ; Proprotein Convertases/*metabolism ; Receptors, LDL/*metabolism ; Serine Endopeptidases/*metabolism ; *Small Molecule Libraries

BACKGROUND AND OBJECTIVES: The association between hearing impairment and cognitive function has been established in previous studies. The aim of this study was to compare the effects of conventional hearing aids and middle ear implants on cognitive function. SUBJECTS AND METHOD: This study included 22 participants who underwent middle ear implantation between October 2013 and September 2016. Their mean age at surgery was 70 years. Using Pure tone audiometry (PTA), the Speech discrimination test (SDT), and the Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaire, we compared audiologic benefits of three conditions [without hearing aids, with conventional hearing aids, or with Vibrant Sound bridge (VSB)]. Cognitive ability was evaluated using neuropsychological testings (Seoul Neuropsychological Screening Battery) at intervals of approximately eight weeks. RESULTS: The results of PTA showed a 7.96 dB HL gain with conventional hearing aids and a 10.00 dB HL gain with the use of VSB. SDT results showed a 4.10% gain with conventional hearing aids and a 10% gain with the use of VSB. Results of the APHAB questionnaire showed a significant increase with the use of VSB compared to conventional hearing aids. In the Korean Mini-Mental State Examination, a slight improvement was observed after middle ear implantation. In the Digit Span Test and Korean-Boston Naming Test, a significant improvement was seen with the use of VSB compared to conventional hearing aids. CONCLUSION: The use of middle ear implants in rehabilitation of hearing communication in patients showed improvements in cognitive abilities, compared to the use of conventional hearing aids.
Audiometry ; Cognition* ; Ear, Middle* ; Hearing Aids* ; Hearing Loss ; Hearing* ; Humans ; Mass Screening ; Methods ; Neuropsychological Tests ; Ossicular Prosthesis* ; Rehabilitation ; Speech Discrimination Tests