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Although the cause of neurological disease in patients with chronic kidney disease (CKD) has not been completely identified yet, recent papers have identified accumulated uremic toxin as its main cause. Additionally, omega-3 polyunsaturated fatty acid (ω-3 PUFA) plays an important role in maintaining normal nerve function, but its protective effects against uremic toxin is unclear. The objective of this study was to identify brain damage caused by uremic toxicity and determine the protective effects of ω-3 PUFA against uremic toxin. We divided mice into the following groups: wild-type (wt) sham (n = 8), ω-3 PUFA sham (n = 8), Fat-1 sham (n = 8), ischemia-reperfusion (IR) (n = 20), and ω-3 PUFA+IR (n = 20) Fat-1+IR (n = 20). Brain tissue, kidney tissue, and blood were collected three days after the operation of mice (sham and IR operation). This study showed that Ki67 and neuronal nuclei (NeuN) decreased in the brain of uremic mice as compared to wt mice brain, but increased in the ω-3 PUFA-treated uremic mice and the brain of uremic Fat-1 mice as compared to the brain of uremic mice. The pro-apoptotic protein expressions were increased, whereas anti-apoptotic protein expression decreased in the brain of uremic mice as compared to wt mice brain. However, apoptotic protein expression decreased in the ω-3 PUFA-treated uremic mice and the brain of uremic Fat-1 mice as compared to the brain of uremic mice. Furthermore, the brain of ω-3 PUFA-treated uremic mice and uremic Fat-1 mice showed increased expression of p-PI3K, p-PDK1, and p-Akt as compared to the brain of uremic mice. We confirm that uremic toxin damages the brain and causes cell death. In these injuries, ω-3 PUFA plays an important role in neuroprotection through PI(3)K-Akt signaling.

Accurate dry weight (DW) estimation is important for hemodialysis patients. Although bioimpedance spectroscopy (BIS) is commonly used to measure DW, the BIS-based DW frequently differs from the clinical DW. We analyzed the characteristics of patients whose BIS-based DWs were over- and underestimated. In this retrospective cohort study, we evaluated 1555 patients undergoing maintenance hemodialysis in Chungnam National University Hospital. The gap (DWCP-BIS) was calculated by comparing the BIS and clinical DWs. We analyzed the clinical characteristics of patients with positive (n = 835) and negative (n = 720) gaps. Compared with other patients, the DWCP-BIS-positive group had higher extracellular water (ECW) level and extracellular/intracellular water index (E/I) and had lower weight, body mass index (BMI), lean tissue index (LTI), fat tissue index (FTI), fat mass (FAT), and adipose tissue mass (ATM). The DWCP-BIS-negative group exhibited elevated BMI, FTI, FAT, and ATM, however, it had lower height, ECW, and E/I. Linear regression analysis revealed that FAT significantly predicted DWCP accuracy. The clinical DW of patients with a low fat mass tended to be underestimated, while the clinical DW of patients with comparatively large fat reserves tended to be overestimated. These characteristics will aid in the reduction of BIS-based DW errors.

Background : Kidney transplantation is an effective renal replacement therapy for patients with end-stage renal disease (ESRD). In this study, we assessed the impact of the baseline characteristics and comorbidities of ESRD patients on the probability of deceased donor kidney transplantation (DDKT) and evaluated the morbidity and mortality during the time spent waiting. Methods : The study population consisted of 544 ESRD patients on the waiting list for DDKT at Chungnam National University Hospital in South Korea between February 2000 and October 2015. The patients were observed from the date of transplantation list registration to the date of transplantation. Baseline characteristics and comorbidities were investigated together with new-onset comorbidities that occurred during the waiting time. Results : Diabetes mellitus (39.0%), hypertension (25.2%), and glomerulonephritis (21.3%) were the three most common causes of ESRD in this study, and coronary artery disease (9.4%) was the most common comorbidity. The 115 patients (19.3%) who underwent DDKT had a mean waiting time of 1,711 days (768-2,654 days or 4.68 years [2.10-7.27]). Blood groups other than type O, peritoneal dialysis, and nondiabetic ESRD were significantly associated with a higher likelihood of DDKT. Infection was the leading cause of death and the most common comorbidity that arose during the waiting time. Patients who experienced cardiovascular events during the waiting time showed a lower transplant rate compared with those who did not. Conclusion : The prevalence of comorbidities was high in renal transplantation candidates. During the often-long waiting time, new comorbidities may occur, with long-term sequelae limiting access to kidney transplantation or resulting in death.

Recent studies have implicated mitochondrial disruption in podocyte dysfunction, which is a characteristic feature of primary and diabetic glomerular diseases. However, the mechanisms by which primary mitochondrial dysfunction in podocytes affects glomerular renal diseases are currently unknown. To investigate the role of mitochondrial oxidative phosphorylation (OxPhos) in podocyte dysfunction, glomerular function was examined in mice carrying a loss of function mutation of the gene encoding CR6-interacting factor-1 (CRIF1), which is essential for intramitochondrial production and the subsequent insertion of OxPhos polypeptides into the inner mitochondrial membrane. Homozygotic deficiency of CRIF1 in podocytes resulted in profound and progressive albuminuria from 3 weeks of age, the CRIF1-deficient mice also developed glomerular and tubulointerstitial lesions by 10 weeks of age. Furthermore, marked glomerular sclerosis and interstitial fibrosis were observed in homozygous CRIF1-deficient mice at 20 weeks of age. In cultured mouse podocytes, loss of CRIF1 resulted in OxPhos dysfunction and marked loss or abnormal aggregation of F-actin. These findings indicate that the OxPhos status determines the integrity of podocytes and their ability to maintain a tight barrier and control albuminuria. Analyses of the glomerular function of the podocyte-specific primary OxPhos dysfunction model mice demonstrate a link between podocyte mitochondrial dysfunction, progressive glomerular sclerosis, and tubulointerstitial diseases.

Background and aimsKnowledge of the proper dry weight plays a critical role in the efficiency of dialysis and the survival of hemodialysis patients. Recently, bioimpedance spectroscopy(BIS) has been widely used for set dry weight in hemodialysis patients. However, BIS is often misrepresented in clinical healthy weight. In this study, we tried to predict the clinically proper dry weight (DWCP) using machine learning for patient’s clinical information including BIS. We then analyze the factors that influence the prediction of the clinical dry weight.MethodsAs a retrospective, single center study, data of 1672 hemodialysis patients were reviewed. DWCPdata were collected when the dry weight was measured using the BIS (DWBIS). The gap between the two (GapDW) was calculated and then grouped and analyzed based on gaps of 1 kg and 2 kg.ResultsBased on the gap between DWBISand DWCP, 972, 303, and 384 patients were placed in groups with gaps of DWincreases, it is more difficult to predict the target property. As GapDWincrease, the mean values of hemoglobin, total protein, serum albumin, creatinine, phosphorus, potassium, and the fat tissue index tended to decrease. However, the height, total body water, extracellular water (ECW), and ECW to intracellular water ratio tended to increase.ConclusionsMachine learning made it slightly easier to predict DWCPbased on DWBISunder limited conditions and gave better insights into predicting DWCP. Malnutrition-related factors and ECW were important in reflecting the differences between DWBISand DWCP.

BACKGROUND Outcomes of ABO-incompatible living donor kidney transplantation (ABOi LDKT) in older individuals have not been established. METHODS This multicentric observational study, using data from the Korean Organ Transplantation Registry database, included 634 older patients (≥60 years) undergoing kidney transplantation. We compared clinical outcomes of ABOi LDKT (n = 80) with those of ABO-compatible LDKT (ABOc LDKT, n = 222) and deceased donor kidney transplantation (DDKT, n = 332) in older patients. RESULTS Death-censored graft survival was similar between the three groups (P = 0.141). Patient survival after ABOi LDKT was similar to that after ABOc LDKT (P = 0.489) but higher than that after DDKT (P = 0.038). In multivariable analysis, ABOi LDKT was not risk factor (hazard ratio [HR] 1.73, 95% confidence interval [CI] 0.29-10.38, P = 0.548), while DDKT was significant risk factor (HR 3.49, 95% CI 1.01-12.23, P = 0.049) for patient survival. Although ABOi LDKT showed higher biopsy-proven acute rejection than ABOc LDKT, the difference was not significant after adjustment with covariates. However, ABOi LDKT was significant risk factor for infection (HR 1.66, 95% CI 1.12-2.45, P = 0.012). CONCLUSIONS In older patients, ABOi LDKT was not inferior to ABOc LDKT and was superior to DDKT for patient survival. ABOi LDKT can be recommended for older patients, rather than waiting for DDKT.

Background and Aims Ischemia-reperfusion (I-R)-induced reactive oxygen species (ROS) are thought to be a major factor in the development of acute renal injury by promoting the initial tubular damage. NAD(P)H:quinone oxidoreductase 1 (NQO1) is a well-known antioxidant protein that regulates ROS generation. We investigate whether NQO1 modulates the renal I-R injury. Method C57BL/6N NQO1-deficient mice (NQO1/) were generated. Mice were sacrificed at 4, 12, 24, and 48 h after the surgical procedure. I-R was performed using vascular clamp for 30min. We analyzed renal function, oxidative stress, and tubular apoptosis after I-R injury. Results NQO1/ mice showed increased blood urea nitrogen and creatinine levels, tubular damage, oxidative stress, and apoptosis. In the kidneys of NQO1/ mice, the cellular NADPH/NADPþ ratio was significantly higher and NOX activity was markedly higher than in those of NQO1þ/þ mice. The activation of NQO1 by β-lapachone (βL) significantly improved renal dysfunction and reduced tubular cell damage, oxidative stress, and apoptosis by renal I-R. Moreover, the βL treatment significantly lowered the cellular NADPH/NADPþ ratio and dramatically reduced NOX activity in the kidneys after IRI. From these results, it was concluded that NQO1 has a protective role against renal injury induced by I-R and that this effect appears to be mediated by decreased NOX activity via cellular NADPH/NADPþ modulation. Conclusion NQO1 activation might be beneficial for ameliorating renal injury induced by I-R.

Background and Aims: Hypothermia attenuates the renal injury induced by ischemia-reperfusion(IR). However, the detailed molecular pathway remains unknown. Although there has been reported that hypothermia protects acute renal damage, there is little known that hypothermia reduce renal fibrosis in IR kidney injury. We evaluated hypothermic protection against renal fibrosis in renal IR injury. Method: C57Bl/6 mice were divided into the following groups: sham-operated (cold, 32C) vs normal temperature (37C); IR mice (32C vs 37C). Kidneys were harvested 10 and 27 minutes after induction of renal ischemia and 24, 72, 168 hours after iIR injury. Functional and molecular markers of kidney injury were evaluated. Results: The blood urea nitrogen and serum creatinine levels and the histologic renal injury scores were significantly lower in 32C IR than 37C IR kidneys (all P values < .05).In kidney harvested 10 and 27 min, the extent of renal AMPK,ERK, and HIF1 phosphorylation was significantly increased in the kidneys of 32C compared to 37C IR mice. In kidney harvested 27 min, 24hr, 72hr, and 168hr, the expression levels of SOX9, TGF beta, alpha SMA, collagen IV, and fibrinogen decreased in 32C IR compared to 37C IR mice. In addition, in kidney harvested 72hr, and 168hr, the stained area of TGF beta, alpha SMA, and masson trichrome, were significantly decreased in 32C IR compared to 37C IR mice. Conclusion: Hypothermia attenuates the renal fibrosis induced by Ischemia reperfusion.

Background and Aims Permanent vascular access is important in patients requiring hemodialysis. However, among patients requiring hemodialysis, even if arteriovenous fistula surgery is performed, many are unable to undergo hemodialysis with vascular access due to maturation failure. Method Using 194 patients who underwent arteriovenous fistula surgery, a cilostazol group (n = 107) and a control group (n = 87) were compared and analyzed for the occurrence of vascular complications. Results In the cilostazol group, there were less vascular complications (36.4% vs. 52.9%; p = 0.022), especially maturation failure (2.8% vs. 11.5%; p = 0.016). However, there was no significant difference between the cilostazol group and control group regarding percutaneous transluminal angioplasty (PTA) requirement nor frequency and interval to PTA after vascular surgery. The frequency of reoperations due to vascular injury after the start of hemodialysis after maturation was also significantly lower in the cilostazol group. Conclusion These results suggest that vascular access patients may benefit from postoperative cilostazol therapy.

Background Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This disease, which is quickly spreading worldwide, has high potential for infection and causes rapid progression of lung lesions, resulting in a high mortality rate. This study aimed to investigate the effects of SARS-CoV-2 infection on renal function in patients with COVID-19. Methods From February 21 to April 24, 2020, 66 patients diagnosed with COVID-19 at Chungnam National University Hospital were analyzed; all patients underwent routine urinalysis and were tested for serum creatinine, urine protein to creatinine ratio (PCR), and urine albumin to creatinine ratio (ACR). Results Acute kidney injury (AKI) occurred in 3 (4.5%) of the 66 patients, and 1 patient with AKI stage 3 underwent hemodialysis. Upon follow-up, all 3 patients recovered normal renal function. Compared with patients with mild COVID-19, AKI (n = 3) occurred in patients with severe COVID-19, of whom both urine PCR and ACR were markedly increased. Conclusion The incidence of AKI was not high in COVID-19 patients. The lower mortality rate in SARS-CoV-2 infection compared with previous Middle East respiratory syndrome and SARS-CoV infections is thought to be associated with a low incidence of dysfunction in organs other than the lungs., Graphical Abstract

To evaluate the efficacy and safety of CKD-11101 (biosimilar darbepoetin-alfa, Chong Kun Dang Pharm.) compared with NESP® in treatment of anaemia in patients with chronic kidney disease not on dialysis.NCT03431623.In this multi-centre, randomized, double-blind study, patients were treated with CKD-11101 and NESP. The efficacy evaluation period (EEP) was 24 weeks, during which patients were treated every 2 weeks. All patients who completed the EEP were treated with CKD-11101 every 2 weeks for the first 4 weeks and every 4 weeks for the safety evaluation period (SEP), which was from 24 weeks to 52 weeks. The primary efficacy endpoint was the change in mean haemoglobin (Hb) level from baseline to end of EEP and mean dose needed to achieve the target Hb.The mean Hb level was increased in both groups during the EEP (both p 0.001). The difference in mean Hb level change between the two groups was 0.01 g/dL (95% CI = -0.213-0.242), indicating that CKD-11101 was equivalent to NESP. The difference in mean administration dose between groups was -1.40 mcg (95% CI = -6.859-4.059) included in the equivalent range. The incidence of AEs and ADRs was not different between the two groups, and the frequency of ADRs was favourable in both groups (1.2% in CKD-11101 vs 7.7% in the NESP to CKD-11101 conversion group).CKD-11101 has an equivalent therapeutic effect as NESP in chronic kidney disease patients with renal anaemia. CKD-11101 can be safely used for long-term treatment and in patients converted from NESP.

Although inflammation and fibrosis, which are key mechanisms of chronic kidney disease, are associated with mitochondrial damage, little is known about the effects of mitochondrial damage on the collecting duct in renal inflammation and fibrosis. To generate collecting duct-specific mitochondrial injury mouse models, CR6-interacting factor-1 (CRIF1) flox/flox mice were bred with Hoxb7-Cre mice. We evaluated the phenotype of these mice. To evaluate the effects on unilateral ureteral obstruction (UUO)-induced renal injury, we divided the mice into the following four groups: a CRIF1flox/flox (wild-type (WT)) group, a CRIF1flox/flox-Hob7 Cre (CRIF1-KO) group, a WT-UUO group, and a CRIF1-KO UUO group. We evaluated the blood and urine chemistries, inflammatory and fibrosis markers, light microscopy, and electron microscopy of the kidneys. The inhibition of Crif1 mRNA in mIMCD cells reduced oxygen consumption and membrane potential. No significant differences in blood and urine chemistries were observed between WT and CRIF1-KO mice. In UUO mice, monocyte chemoattractant protein-1 and osteopontin expression, number of F4/80 positive cells, transforming growth factor-β and α-smooth muscle actin staining, and Masson’s trichrome staining were significantly higher in the kidneys of CRIF1-KO mice compared with the kidneys of WT mice. In sham mice, urinary 8-hydroxydeoxyguanosine (8-OHDG) was higher in CRIF1-KO mice than in WT mice. Moreover, CRIF1-KO sham mice had increased 8-OHDG-positive cell recruitment compared with WT-sham mice. CRIF1-KO-UUO kidneys had increased recruitment of 8-OHDG-positive cells compared with WT-UUO kidneys. In conclusion, collecting duct-specific mitochondrial injury increased oxidative stress. Oxidative stress associated with mitochondrial damage may aggravate UUO-induced renal injury.

Myeolchi jeotgals (MJs) were prepared with purified salt (PS), solar salt aged for 1 year (SS), and bamboo salt (BS) melted 3 times at 10% and 20% (w/w) concentrations, and fermented for 28 weeks at 15°C. BS MJ showed higher pH and lower titratable acidities than the other samples because of the alkalinity of bamboo salt. Lactic acid bacteria counts increased until 4-6 weeks and then decreased gradually, and were not detected after 20 weeks from MJs with 10% salt. Yeast counts of PS MJs were higher than those of BS and SS MJs. Bacilli were detected in relatively higher numbers throughout the 28 weeks, like marine bacteria, but archae were detected in lower numbers during the first 10 weeks. When 16S rRNA genes were amplified from total DNA from PS MJ (10% salt) at 12 weeks, Tetragenococcus halophilus was the major species. However, Staphylococcus epidermidis was the dominant species for BS MJ at the same time point. In SS MJ, T. halophilus was the dominant species and S. epidermidis was the next dominant species. BS and SS MJs showed higher amino-type nitrogen, ammonia-type nitrogen, and volatile basic nitrogen contents than PS MJs. SS and BS were better than PS for the production of high-quality MJs.

To develop starters for the production of functional foods or materials, lactic acid bacteria producing γ-aminobutyric acid (GABA) were screened from jeotgals, Korean fermented seafoods. One isolate producing a high amount of GABA from monosodium L-glutamate (MSG) was identified as Enterococcus avium by 16S rRNA gene sequencing. E. avium M5 produced 18.47 ± 1.26 mg/ml GABA when incubated for 48 h at 37°C in MRS broth with MSG (3% (w/v)). A gadB gene encoding glutamate decarboxylase (GAD) was cloned and overexpressed in E. coli BL21 (DE3) using the pET26b (+) expression vector. Recombinant GAD was purified through a Ni-NTA column and the size was estimated to be 53 kDa by SDS-PAGE. Maximum GAD activity was observed at pH 4.5 and 55°C and the activity was dependent on pyridoxal 5'-phosphate. The Km and Vmax values of GAD were 3.26 ± 0.21 mM and 0.0120 ± 0.0001 mM/min, respectively, when MSG was used as a substrate. Enterococcus avium M5 secretes a lot of GABA when grown on MRS with MSG, and the strain is useful for the production of fermented foods containing a high amount of GABA.

Massively parallel chip assembly based on multi-interposer block concept is demonstrated for large-area heterogeneous system integration. The chips are aligned in parallel by liquid surface tension and assembled on the Si interposers through oxide-oxide bonding at room temperature without thermocompression. 3-D Cu sidewall interconnects (the width is approximately $20~\mu \text{m}$ ) climbing over 100- $\mu \text{m}$ -thick self-assembled chips are formed with a spin-on thick photoresist by electroplating. In addition, 3-D Cu interconnects with a width of nearly $10~\mu \text{m}$ are successfully formed across polyimide slopes formed on the sidewall of self-assembled chips. The electrical properties of the 3-D sidewall interconnects are characterized by the daisy chains, resistance distribution, and characteristic fluctuation of CMOS fabricated on the self-assembled chips.

The effects of purified salt (PS) and mineral-rich sea salt (MRS), both with different mineral profiles, on kimchi fermentation were studied using a culture-dependent 16S rRNA sequencing technique and mass-based metabolomic analysis. The different mineral profiles in the fermentation medium caused changes in the bacterial profiles of the 2 kimchi products. An increase of Leuconostoc species in MRS-kimchi decreased the Lactobacillus/Leuconostoc ratio, which led to changes in metabolites (including sugars, amino acids, organic acids, lipids, sulfur compounds, and terpenoids) associated with kimchi quality. Although further studies on the relationship between these salt types and kimchi fermentation are needed, these results suggested that the MRS treatment had positively affected the changes of the kimchi mineral contents, bacterial growth, and metabolite profiles, which are linked to kimchi quality.

This study was focused on developing and obtaining a kimchi starter for use in commercial kimchi production. Kimchi varieties made with selected starters are of high quality, have high levels of mannitol, and extended shelf life. The starters were screened for properties such as mannitol production, low gas/acid production, and acid resistance. Finally, kimchi fermentation testing was performed using selected LAB starters. Kimchi samples were prepared with lactic acid bacteria (LAB) starters, including

Darbepoetin-alfa is an erythropoiesis-stimulating agent (ESA) with a long elimination half-life that achieves better hemoglobin (Hb) stability than short-acting ESAs. We aimed to evaluate the efficacy and safety of intravenous CKD-11101 (a biosimilar of darbepoetin-alfa) compared with those of darbepoetin-alfa in hemodialysis patients. The study was performed in 24 centers in Korea between June 2015 and June 2017. The study subjects were randomized in a double-blind manner. The follow-up duration was 24 weeks, which consisted of 20 weeks of maintenance and 4 weeks of evaluation period. All patients underwent a stabilization period to achieve a target baseline Hb of 10–12 g/dL before randomization. Following randomization, patients received darbepoetin-alfa or CKD-11101 weekly or biweekly. A total of 403 patients were randomized into two groups, and a total of 325 patients (80.6%) completed the investigation. The differences between the two groups in terms of change in the average Hb level from baseline to evaluation were not significant. The average administered dose of ESA was similar between the groups. There was no difference in the proportion of patients who maintained the target Hb during the evaluation period [60.4% vs. 66.2% in the CKD-11101 and darbepoetin-alfa groups, respectively (p = 0.3038)]. In addition, the safety analysis, consisting of adverse events and adverse drug reactions, showed comparable results between the two groups. The changes in the level of Hb, dose of erythropoietin, and achievement rate of the target Hb during the study period were comparable between the groups. CKD-11101 has an equivalent efficacy and safety compared with darbepoetin-alfa in patients undergoing hemodialysis.

BACKGROUND: Tacrolimus is used as a steroid-sparing immunosuppressant in adults with minimal change nephrotic syndrome. However, combined treatment with tacrolimus and low-dose steroid has not been compared with high-dose steroid for induction of clinical remission in a large-scale randomized study. METHODS: In this 24-week open-label noninferiority study, we randomized 144 adults with minimal change nephrotic syndrome to receive 0.05 mg/kg twice-daily tacrolimus plus once-daily 0.5 mg/kg prednisolone, or once-daily 1 mg/kg prednisolone alone, for up to 8 weeks or until achieving complete remission. Two weeks after complete remission, we tapered the steroid to a maintenance dose of 5–7.5 mg/d in both groups until 24 weeks after study drug initiation. The primary end point was complete remission within 8 weeks (urine protein: creatinine ratio 3.0 g/g) after complete remission to within 24 weeks of study drug initiation. RESULTS: Complete remission within 8 weeks occurred in 53 of 67 patients (79.1%) receiving tacrolimus and low-dose steroid and 53 of 69 patients (76.8%) receiving high-dose steroid; this difference demonstrated noninferiority, with an upper confidence limit below the predefined threshold (20%) in both intent-to-treat (11.6%) and per-protocol (17.0%) analyses. Groups did not significantly differ in time until remission. Significantly fewer patients relapsed on maintenance tacrolimus (3–8 ng/ml) plus tapered steroid versus tapered steroid alone (5.7% versus 22.6%, respectively; P=0.01). There were no clinically relevant safety differences. CONCLUSIONS: Combined tacrolimus and low-dose steroid was noninferior to high-dose steroid for complete remission induction in adults with minimal change nephrotic syndrome. Relapse rates were significantly lower with maintenance tacrolimus and steroid compared with steroid alone. No clinically-relevant differences in safety findings were observed.

Background It is well known that renal dysfunction and cerebral small-vessel disease (SVD), including microbleed, lacunar infarction, and white matter lesion (WML), are associated with poor prognosis after ischemic stroke. However, the prognostic relationship between renal dysfunction and SVD has not been well evaluated in acute ischemic stroke survivors. Therefore, in this study, we evaluated the prognostic relationships between estimated glomerular filtration rate (eGFR) and cerebral SVD after acute ischemic stroke. Methods We retrospectively reviewed the clinical and radiological data of acute ischemic stroke survivors with decreased eGFR ( 2 , n = 128) and controls (eGFR ≥60 mL/min/1.73 m 2 , n = 128). The presence of SVD was evaluated according to magnetic resonance imaging performed on admission. Mortality data were obtained from medical chart reviews and telephone interviews. Results Patients with silent lacunar infarction, WML, or microbleed had lower eGFR than patients without such lesions (60.4 ± 34.8 versus 87.5 ± 28.4 mL/min/1.73 m 2 , 60.5 ± 37.1 versus 73.9 ± 33.3 mL/min/1.73 m 2 , and 57.6 ± 33.3 versus 73.9 ± 32.9 mL/min/1.73 m 2 , respectively). In addition, the multivariate adjusted odds ratio for the presence of SVD increased inversely with eGFR. Three-year survival was lower in patients with renal dysfunction and each type of SVD. The presence of WML was an independent risk factor for cardiovascular death. Conclusions Renal impairment was associated with the presence of SVD in acute ischemic stroke survivors. Both renal impairment and the presence of SVD were predictors of poor poststroke survival.

Nine bacilli with fibrinolytic activities were isolated from doenjang, a traditional Korean fermented soy food. Among them, RSB34 showed the strongest activity and was identified as Bacillus amyloliquefaciens by 16S rRNA and recA gene sequencing. During growth on LB up to 96 h, RSB34 showed the highest fibrinolytic activity (83.23 mU/μl) at 48 h. Three bands of 23, 27, and 42 kDa in size were observed when the culture supernatant was analyzed by SDS-PAGE and 27 and 42 kDa bands by fibrin zymography. The gene encoding the 27 kDa fibrinolytic enzyme AprE34 was cloned by PCR. BLAST analyses confirmed that the gene was a homolog to genes encoding AprE-type proteases. aprE34 was overexpressed in Escherichia coli BL21(DE3) using pET26b(+). Recombinant AprE34 was purified and examined for its properties. The Km and Vmax values of recombinant AprE34 were 0.131 ± 0.026 mM and 16.551 ± 0.316 μM/l/min, respectively, when measured using an artificial substrate, N-succinyl-ala-ala-pro-phe-p-nitroanilide. aprE34 was overexpressed in B. subtilis WB600 using pHY300PLK. B. subtilis transformants harboring pHYRSB34 (pHY300PLK with aprE34) showed higher fibrinolytic activity than B. amyloliquefaciens RSB34.

Adhesion is important in many industrial applications including those in the microelectronics industry. Flip-chip assemblies commonly utilize epoxy underfills to promote reliability and the buried interfacial structure of underfills is crucial to device lifetime. Poor adhesion at this interface can cause premature device failure. One method to increase adhesion strength is to plasma treat the substrate attached to underfills, however, the mechanism of this increase in adhesion strength has not been thoroughly investigated at the molecular level in situ, because it is difficult to probe a buried interface where the adhesion occurs. In this work, sum frequency generation (SFG) vibrational spectroscopy was utilized to investigate the buried polymer/epoxy resin interface at the molecular level. Plasma treatment was performed on the polymer surfaces and the effects were examined. The buried interfaces between the polymer surface before and after plasma treatment and epoxy were then investigated to understand if the effects of the treatment can be observed using SFG. It was found that the molecular structure of the buried interface of the pristine polymer surface in contact with epoxy is drastically different from the buried interface of the plasma treated surface with epoxy. The buried interface containing the plasma treated polymer surface was found to be considerably more disordered and had much higher adhesion strength. This research elucidates the plasma treatment effects on structures and properties of buried polymer/epoxy interfaces, providing in-depth understanding on the mechanism of adhesion strength increase facilitated by plasma treatment.

Outcome-based learning is a global trend in medical education. The Korean Association of Medical Colleges (KAMC) has been developing learning objectives for basic medical education (BME) in Korea. In 2012, KAMC published the 1st edition of “Learning outcomes of basic medical education: Clinical competency-centered” in order to promote outcome-based medical education. KAMC has recently revised and updated the learning outcomes of basic medical education in the clinical competency-centered 2nd edition to reflect the suggestions of all medical schools in Korea and improve application of the published learning outcomes for BME in the field of medical education. KAMC has been making efforts to integrate clinical competency-centered learning outcomes with scientific concepts and principle-centered learning outcomes in addition to basic clinical skills and performance in BME.

BACKGROUND 'Spinning' is an indoor cycling regimen. The number of case reports of spinning-induced rhabdomyolysis (SIR) has increased since 2004 in South Korea. AIM The aim of this study is to evaluate the clinical characteristics of SIR and compare it with other causes of rhabdomyolysis. METHODS Patients who were diagnosed with rhabdomyolysis from 1 September 2011 to 30 April 2015 were included. We analysed the incidence of rhabdomyolysis, biochemical parameters and forced hospitalisation, which was defined as the days from admission to creatinine phosphokinase

Three Leuconostoc mesenteroides and a Lactobacillus plantarum strains were isolated from kimchi based on their acid and bile salts tolerances and bile salt hydrolase activities. They also possess β-galactosidase (β-Gal) and β-glucosidase (β-Glu) activities. When exposed to pH 3.0 for 3 h, Lb. plantarum C182 showed the highest survival ratio (52.50%). Lb. plantarum C182 was also the most resistant against 0.3% bile salts (58.53%) followed by Leu. mesenteroides C10 (42.85%), F27 (41.17%) and C4 (30.41%). All strains were sensitive to ampicillin, chloramphenicol, cyclohexamide, erythromycin, neomycin, streptomycin, tetracycline, and rifampicin, but resistant to vancomycin. Three Leuconostoc strains adhered to HT-29 cells (16.3–29.6 CFU/cell) better or similar with Lb. rhamnosus GG (17.1 ± 0.6 CFU/cell). These results indicate that 4 strains might be useful as probiotics.

3D chip stacking approaches with TSV (thorough-silicon vias) are mainly classified into three categories: chip-to-chip, wafer-to-wafer, and chip-to-wafer 3D integration. The chip-to-chip technologies are widely used for traditional microelectronic packaging in which KGDs (known good dies) are assembled using one-by-one pick-and-place techniques. Although the assembly yield is high due to the use of KGDs, the assembly throughput is not sufficiently high, compared with wafer-to-wafer approaches. However, wafer-to-wafer technologies have a serious issue in total production yield that is exponentially decreased with the number of stacked layers because the failure dies cannot be removed from the wafers to be stacked. Therefore, chip-to-wafer 3D integration is thought to be a promising candidate to satisfy both the throughput and yield issues. However, chip-to-wafer 3D integration potentially has a trade-off between assembly throughput and alignment accuracies in the conventional robotic pick-and-place techniques. In order to address the problems, we have proposed and developed multichip-to-wafer 3D integration using liquid surface tension. From the technical point of view of chip-to-wafer bonding, we talk about the basic concept and recent studies of the self-assembly based 3D integration. These approaches using surface tension-driven multichip assembly are divided into two methodologies: one is non-transfer stacking without carrier wafers and the other one is transfer stacking with them. These carrier wafers are typically used for temporary wafer bonding in standard 3D integration processes. Here, we also introduce temporary multichip bonding technologies applicable to 3D integration with multichip transfer stacking in which an inorganic temporary adhesive and a debonding layer sensitive to near UV lasers are utilized. In this presentation, we introduce our multichip-to-wafer 3D integration studies with non-transfer and transfer stacking particularly focused on solder microbump bonding (indium/gold and tin/cupper), CVD (chemical vapor deposition)-oxide/CVD-oxide direct bonding, and hybrid bonding through a new material of Cu nano-pillars that have been most recently reported toward upcoming IoT (internet of things) and trillion sensor societies.

It has been reported that nafamostat mesilate (NM) inhibits inflammatory injury via inhibition of complement activation in ischemic heart, liver, and intestine. However, it is unclear if NM also inhibits apoptosis in ischemia-reperfusion (IR)-injured kidney. We therefore investigated whether NM attenuates IR renal injury that involves inhibition of apoptosis.HK-2 cells and male C57BL/6 mice were used for this study. C57Bl/6 mice were divided into 4 groups: sham, NM (2 mg/kg) + sham, IR injury (IR injury; reperfusion 27 minutes after clamping of both the renal artery and vein), and NM + IR injury. Kidneys were harvested 24 hours after IR injury, and functional and molecular parameters were evaluated. For in vitro studies, HK-2 cells were incubated for 6 hours with mineral paraffin oil to induce hypoxic injury, and then treated with various doses of NM to evaluate the antiapoptotic effects.Blood urea nitrogen, serum creatinine levels, and renal tissue injury scores in NM + IR-injured mice were significantly lower than those of control IR mice (all P .01). NM significantly improved cell survival in hypoxic HK-2 cells (P .01), significantly decreased renal Bax expression (P .05), and increased renal Bcl-2 protein levels in IR kidneys and hypoxic HK-2 cells compared with those of the sham and control groups. The numbers of terminal deoxynucleotide transferase-mediated dUTP nick-end labeling- and 8-oxo-2'-deoxyguanosine-positive cells were significantly lower in NM + IR-injured kidneys compared with those in control IR-injured mice (P .05); NM treatment decreased the expression of inducible and endothelial nitric oxide synthase in IR-injured mice (P .05).NM ameliorates IR renal injury via inhibition of apoptosis by, at least in part, lowering nitric oxide overproduction, reducing Bax, and increasing Bcl-2.

The self-assembly of known good dies (KGDs) on substrates using the liquid capillary method is shown to be a promising technology to achieve three-dimensional (3D) heterogeneous system integration and packaging. Firstly, the effects of the edge structures of self-assembled substrates and chips on alignment accuracies were investigated. When hydrophobic sidewalls with 10-µm-height steps were applied to both chips and assembly sites formed on substrates, the alignment accuracy within 1.0 µm was realized. The alignment accuracies were within 2.0 µm using either substrates or chips having 10-µm-height step structures with hydrophobic sidewalls. Self-assembly of 12-ch vertical-cavity surface-emitting lasers (VCSELs) with a long rectangle shape on glass substrates were also demonstrated. Separation of assembly sites into twelve areas enhanced the resultant force acting on the VCSEL short edge. The enhanced resultant force provided the high alignment accuracies within 2.0 μm. After the self-assembly of the VCSEL and the subsequent thermal compression, the chips successfully exhibited no degradation of their current–voltage (I–V) characteristics and appropriate 850-nm light emission. We demonstrated self-assembly and microbump bonding using non-conductive film (NCF)-covered dies with Cu/Sn microbumps for high-throughput and high-yield multichip-to-wafer 3D integration. The self-assembly of the NCF-covered dies provided high alignment accuracy within 1.1 μm on average. After the self-assembly of NCF-coved dies and thermal compression, microbump chains composed of 7396 bump joints were successfully obtained, resulting in good electrical properties of 32 mΩ/joint without any bridge shorts and failures. The variations of microbump joint resistance were maintained within 5% of the initial value after thermal cycle testing of even 1000 cycles.

To overcome various concerns caused by scaling down the device size in future Large Scale Integrated Circuits (LSIs), it is indispensable to introduce a new concept of heterogeneous 3-D integration in which various kinds of device chips with different sizes, different devices, and different materials are vertically stacked. To achieve such heterogeneous 3-D integration, a key technology of self-assembly and electrostatic bonding has been developed. Exploring new devices for the Internet of Things, we have fabricated several kinds of heterogeneous 3-D LSIs called superchip by stacking compound semiconductor device chip, photonic device chip, and spintronic device chip on CMOS device chips using self-assembly and electrostatic bonding. Furthermore, a new system integration technology using a large-area substrate has been developed to reduce the cost of 2.5-D/3-D system module. A 3-D-stacked image sensor system module for automatic driving vehicle has been fabricated using this technology.

Cheonggukjang, a traditional Korean fermented soy food, was prepared by inoculation of Bacillus subtilis EMD4 or Bacillus amyloliquefaciens EMD17 with anti-bacterial or anti-fungal activities into soybeans. Cheonggukjang was also prepared by co-inoculation of EMD4 and EMD17 (1:1, v/v). Control cheonggukjang was prepared by using B. subtilis KACC16450 (Natto strain). Growth of B. cereus cells spiked with starter organisms was completely inhibited by B. amyloliquefaciens EMD17 after 12 h of fermentation at 37℃. Growth of B. cereus was also inhibited by B. subtilis EMD4, but the degree of inhibition was weaker. After 48 h of fermentation, cheonggukjang samples were stored for 10 days at 4℃. B. cereus cells were not detected from cheonggukjang inoculated with EMD4, whereas significant numbers still present in control. The pH values of cheonggukjang samples were not significantly different. During fermentation, cheonggukjang fermented with EMD17 showed the highest fibrinolytic activity and during storage, cheonggukjang fermented with a Natto strain was the highest. Cheonggukjang fermented with a Natto strain also showed the highest amount of total phenolic compounds. The results show that control of B. cereus in cheonggukjang is possible by using starters such as B. amyloliquefaciens EMD17.

Background/aims Fragmented care in nephrology can cause treatment delays. Nephrologists are qualified to perform vascular access-related procedures because they understand the pathophysiology of renal disease and perform physical examination for vascular access. We compared treatment delays associated with tunneled hemodialysis catheter (TDC) placement between interventional radiologists and nephrologists. Methods We collected data by radiologists from January 1, 2011 through December 31, 2011 and by nephrologists from since July 1, 2012 through June 30, 2013. We compared the duration from the hemodialysis decision to TDC placement (D-P duration) and hemodialysis initiation (D-H duration), catheter success and the complication rate, and the frequency and the usage time of non-tunneled hemodialysis catheters (NDCs) before TDC placement. Results The study analyzed 483 placed TDCs: 280 TDCs placed by radiologists and 203 by nephrologists. The D-P durations were 319 minutes (interquartile range [IQR], 180 to 1,057) in the radiologist group and 140 minutes (IQR, 0 to 792) in the nephrologist group. Additionally, the D-H durations were 415 minutes (IQR,260 to 1,091) and 275 minutes (IQR, 123 to 598), respectively. These differences were statistically significant (p = 0.00). The TDC success rate (95.3% vs. 94.5%, respectively; p = 0.32) and complication rate (16.2% vs. 11%, respectively; p = 0.11) did not differ between the groups. The frequency (24.5 vs. 26%, respectively; p = 0.72) and the usage time of NDC (8,451 vs. 8,416 minutes, respectively; p = 0.91) before TDC placement were not statistically significant. Conclusions Trained interventional nephrologists could perform TDC placement safely, minimizing treatment delays.

This paper provides a new approach for the formation of polymer liner for low- $k$ high-aspect-ratio through-silicon-vias involved in via-last backside-via 3-D integration applications. The approach mentioned, referred to as vacuum-assisted spin coating technique in this paper, is formed by combining a conventional spin coating technique and a vacuum treatment. Silicon blind vias with a diameter of $6~\mu \text{m}$ and an aspect ratio of $\sim 8$ were conformably coated on their sidewall with polyimide liner with the minimum step coverage $\sim 30$ % by this approach. Impacts of via geometric parameters and wafer sizes on step coverage were investigated. Electrical characteristics were evaluated with a trench capacitor structure of which the insulator layer was formed by the vacuum-assisted spin coating technique. The minimum capacitance density of 5.3 nF/cm2 and the leakage current density of $\sim 3$ nA/cm2 at a biased voltage of 5 V were obtained. The proposed vacuum-assisted spin coating technique is a simple, feasible, and cost-effective approach for 3-D integration applications.