Removal of large middle molecules via haemodialysis with medium cut-off membranes at lower blood flow rates: an observational prospective study

BACKGROUND: Online haemodiafiltration (OL-HDF) may improve middle molecular clearance in contrast to conventional haemodialysis (HD). However, OL-HDF requires higher convective flows and cannot sufficiently remove large middle molecules. This study evaluated the efficacy of a medium cut-off (MCO) dialyser in removing large middle molecular uraemic toxins and compared it with that of conventional high-flux (HF) dialysers in HD and predilution OL-HDF. METHODS: Six clinically stable HD patients without residual renal function were investigated. Dialyser and treatment efficacies were examined during a single midweek treatment in three consecutive periods: 1) conventional HD using an HF dialyser, 2) OL-HDF using the same HF dialyser, and 3) conventional HD using an MCO dialyser. Treatment efficacy was assessed by calculating the reduction ratio (RR) for β2-microglobulin (β2M), myoglobin, κ and λ free light chains (FLCs), and fibroblast growth factor (FGF)-23 and measuring clearance for FLCs. RESULTS: All three treatments showed comparable RRs for urea, phosphate, creatinine, and uric acid. MCO HD showed greater RRs for myoglobin and λFLC than did HF HD and predilution OL-HDF (myoglobin: 63.1 ± 5.3% vs. 43.5 ± 8.9% and 49.8 ± 7.3%; λFLC: 43.2 ± 5.6% vs. 26.8 ± 4.4% and 33.0 ± 9.2%, respectively; P <  0.001). Conversely, predilution OL-HDF showed the greatest RR for β2M, whereas MCO HD and HF HD showed comparable RRs for β2M (predilution OL-HDF vs. MCO HD: 80.1 ± 4.9% vs. 72.6 ± 3.8%, P = 0.01). There was no significant difference among MCO HD, HF HD, and predilution OL-HDF in the RRs for κFLC (63.2 ± 6.0%, 53.6 ± 15.5%, and 61.5 ± 7.0%, respectively; P = 0.37), and FGF-23 (55.5 ± 20.3%, 34.6 ± 13.1%, and 35.8 ± 23.2%, respectively; P = 0.13). Notably, MCO HD showed improved clearances for FLCs when compared to HF HD or OL-HDF. CONCLUSIONS: MCO HD showed significantly greater RR of large middle molecules and achieved improved clearance for FLCs than conventional HD and OL-HDF, without the need for large convection volumes or high blood flow rates. This would pose as an advantage for elderly HD patients with poor vascular access and HD patients without access to OL-HDF. TRIAL REGISTRATION: Clinical Research Information Service (CRIS): KCT 0003009. The trial was prospectively registered on the 21 Jul 2018.ope

Association between non-alcoholic fatty liver disease and coronary calcification depending on sex and obesity

Non-alcoholic fatty liver disease (NAFLD) is considered a hepatic manifestation of metabolic syndrome and is associated with cardiovascular outcomes. We investigated whether NAFLD was associated with coronary artery calcification (CAC) in participants without a previous history of cardiovascular disease and whether this association differed according to sex and obesity status after adjustment for other atherosclerosis risk factors, alcohol intake, and liver enzyme levels. Among 67,441 participants, data from 8,705 participants who underwent a fatty liver status and CAC assessment during routine health screening were analysed. CAC scores were calculated using computed tomography. NAFLD was diagnosed in patients with evidence of liver steatosis on ultrasonography. Obesity was defined as a body mass index of ≥25 kg/m2. Multivariate analysis showed a significant association between NAFLD and CAC in non-obese participants (odds ratio, 1.24 [95% confidence interval, 1.01-1.53]), whereas NAFLD and CAC were not associated in obese participants. Interaction analysis showed that the association between NAFLD and CAC was influenced by sex and obesity. Subgroup analysis revealed a significant association between NAFLD and CAC in non-obese male participants (odds ratio, 1.36 [1.07-1.75]), but not in female participants. Our study indicates that non-obese men with NAFLD are prone to CAC.ope

해조류 바이오매스에서 바이오 연료 전환을 위한 휘발성 지방산의 생산 및 농축 공정 개발

학위논문(박사) - 한국과학기술원 : 생명화학공학과, 2015.2 ,[viii, 128 p. :]Declining fossil energy resources and increasing global temperatures have steadily raised concerns on meeting increased future energy demands. Renewed interest in alternative energies has been kindled by environmental concerns and economic challenges. Biofuel, an excellent alternative to traditional fossil fuel-derived energy sources, can be produced from abundant supplies of renewable biomass. Volatile fatty acids (VFAs) are carboxylic acids with less than C6, which can be obtained during anaerobic digestion. VFAs are mainly com-posed of acetic, propionic, and butyric acids with various ratios of 6:1:3, 5:1:5, or 8:1:1. VFAs can be used as precursors for synthesizing mixed alcohols or biochemicals and carbon source for microbial lipid production. In this study, the objective is to optimize VFAs production with various approaches and to enrich VFAs concentration with desalination technology. Numerous attempts have been made to enhance VFAs and $H_2$ production during acidogenesis in the anaerobic digestion processes. This paper implemented response surface methodology (RSM) as statistical tool to optimize VFAs and $H_2$ production from mixed cultures of Saccharina japonica, with respect to two independent variables: methanogenic inhibitor concentration and temperature. When testing the effects of various types of methanogenic inhibitors on acidogenic processes, doses of $beta$ -Cyclodextrin ($beta$ -CD) proved to have greater effects on VFAs concentration compared to other methanogenic inhibitors, showing the highest production of VFAs. RSM showed that VFAs production reached a peak of 12.53 g/L at $38.57^\circ C$ and 7.41 g $beta$ -CD/L, conditions under which $H_2$ production was also nearly maximal. Quantitative polymerase chain reaction showed that the concentration of $beta$ -CD correlated with shifts in the bacterial community population, indicating that $beta$ -CD effectively inhibited methanogens. Additionally, to enhance the VFAs concentration and productivity, bioreactors in four series were developed to implement the MSC-HCDC system. A 4L multistage reactor was constructed, and broth was mixed by an overhead stirrer. In a flask scale, when experiments were conducted at a constant temperature of $45^\circ C$, dilution rate of 0.2/day, feeding ratio of 1:1:1:1, pH in feed stream of pH 10, and methanogenic inhibitor of 7g $beta$ -CD /L, VFAs concentration was measured to be 23.04g/L after 14 days, which was 24% higher than the experiment conducted with only a 1:1:1:1 feeding ratio and a 0.2/day dilution rate. Under this condition, there was a reduction in butyric and lactic acid production. In a four-stage bioreactor, VFAs concentration was 31.17g/L and its productivity was 6.23g/L/day on the 28th day. The composition of VFAs in this bioreactor is completely different than that in the flask scale. Although the concentration of valeric and caproic acids were negligible in the flask scale, VFAs with C4 to C6 were the main soluble compounds generated in this bioreactor. However, the concentration of VFAs in the fermentation broth is generally below 35g/L, which makes the purification process expensive. The series of ordinary distillation columns are hardly applicable to the separation of VFAs. Thus, a cost-effective enrichment process is essential for developing an industrial-scale process. Additionally, several problems exist with VFAs when removing water: hydrophilicity, azeotrope in each acids, and a boiling point near $100^\circ C$. Forward osmosis (FO) has recently become increasingly popular. FO is an osmotic membrane process whereby the driving force for separation is an osmotic pressure gradient between the feed and draw solutions. In this study, to effectively enrich VFAs, permeation characteristics including water flux, reverse salt flux, and rejection of volatile fatty acids (VFAs) in the FO system were investigated. In FO, the pH value of VFAs feed solution affected rejection and water flux most significantly, while temperature, concentration of draw solution, and types of draw solute mainly influenced the water flux. The water flux and rejection of VFAs was also dependent on both membrane orientations. Different types of feed solutes showed different rejection and flux behaviors with either dependence or independence on feed pH. When hydraulic pressure was applied, the PAO system with NH4OH showed higher water flux and a lower rejection rate, while the PAO system with NaOH showed higher water flux and a higher rejection rate. Additionally, not only the chemical solution, but also the real fermentation product can be enriched using the FO system. Furthermore, we investigated the delta pi zero (\Delta \pie =0) reverse osmosis (RO) system. Like reverse osmosis, delta pi zero RO applies lower hydraulic pressure for separation and enrichment since the \Delta \pie =0 RO system has lower or zero osmotic pressure difference. With delta pi zero RO, enrichment of feed solution can be maximized while preserving energy and minimizing operation expenses. In conclusion, these findings paved a new route to produce and enrich VFAs as biofuels and bio-chemicals. If VFAs from Saccharina japonica are converted to biofuels such as mixed alcohol, higher concen-tration and productivity of VFAs will be needed. Thus, these approaches may provide useful information in the extension of a VFAs platform for microbial biodiesels.한국과학기술원 :생명화학공학과

Dopaminergic neuron-like cell cluster and method for preparing the same

Disclosed are a dopaminergic neuron-like cell cluster exhibiting a far higher level of a dopaminergic neuron marker, compared to conventional 2D or 3D cultured cells, and a method for preparing the same. The cell cluster can be more effectively differentiated into dopaminergic neurons in the presence of a differentiation-inducing factor, so that it is suitable for use in studying neurodegenerative diseases such as Parkinson's disease. In addition, the cell cluster can express factors reinforcing intercellular interaction at an improved level, and is free of cellular toxicity and safe to the body, easy to culture with high productivity, superior in biocompatibility, and highly unlikely to undergo mutations. Also provided is a dish for culturing a 3D dopaminergic neuron-like cell cluster on a mass scale; which guarantees the 3D dopaminergic neuron-like cell cluster superior biocompatibility, freedom of cellular toxicity, minimal mutagenicity, and improvement in the expression of factors reinforcing intercellular interaction

Dopaminergic neuron-like cell cluster and method for preparing the same

Disclosed are a dopaminergic neuron-like cell cluster exhibiting a far higher level of a dopaminergic neuron marker, compared to conventional 2D or 3D cultured cells, and a method for preparing the same. The cell cluster can be more effectively differentiated into dopaminergic neurons in the presence of a differentiation-inducing factor, so that it is suitable for use in studying neurodegenerative diseases such as Parkinson's disease. In addition, the cell cluster can express factors reinforcing intercellular interaction at an improved level, and is free of cellular toxicity and safe to the body, easy to culture with high productivity, superior in biocompatibility, and highly unlikely to undergo mutations. Also provided is a dish for culturing a 3D dopaminergic neuron-like cell cluster on a mass scale; which guarantees the 3D dopaminergic neuron-like cell cluster superior biocompatibility, freedom of cellular toxicity, minimal mutagenicity, and improvement in the expression of factors reinforcing intercellular interaction

Dopaminergic neuron-like cell cluster and method for preparing the same

Disclosed are a dopaminergic neuron-like cell cluster exhibiting a far higher level of a dopaminergic neuron marker, compared to conventional 2D or 3D cultured cells, and a method for preparing the same. The cell cluster can be more effectively differentiated into dopaminergic neurons in the presence of a differentiation-inducing factor, so that it is suitable for use in studying neurodegenerative diseases such as Parkinson's disease. In addition, the cell cluster can express factors reinforcing intercellular interaction at an improved level, and is free of cellular toxicity and safe to the body, easy to culture with high productivity, superior in biocompatibility, and highly unlikely to undergo mutations. Also provided is a dish for culturing a 3D dopaminergic neuron-like cell cluster on a mass scale; which guarantees the 3D dopaminergic neuron-like cell cluster superior biocompatibility, freedom of cellular toxicity, minimal mutagenicity, and improvement in the expression of factors reinforcing intercellular interaction

The association between the apolipoprotein B/A-I ratio and coronary calcification may differ depending on kidney function in a healthy population.

BACKGROUND: The apolipoprotein B/A-1 ratio has been reported to be one of the strongest risk predictors of cardiovascular events. However, its prognostic value for cardiovascular disease is still uncertain, especially in patients with chronic kidney disease. This study aimed to investigate whether the association between the apolipoprotein B/A-I ratio and coronary artery calcification differed according to kidney function in a healthy population. METHODS: Of the data from 7,780 participants from the medical records database in Gangnam Severance Hospital from 2005 through 2016, a cross-sectional analysis included participants with an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 determined based on the Chronic Kidney Disease -Epidemiology Collaboration equation (n  =  1,800). Mild renal insufficiency was defined as an eGFR of 60-90 mL/min/1.73 m2. Coronary artery calcification measured with computed tomography was defined as an above-zero score. Logistic regression analyses were used to determine the association between coronary calcification and the apolipoprotein B/A-I ratio according to eGFR by adjusting for the influence of confounders. RESULTS: The mean apolipoprotein B/A-I level was significantly higher in the participants with coronary artery calcification than in the participants without coronary artery calcification. The apolipoprotein B/A-I ratio was significantly different according to coronary artery calcification in the participants with normal kidney function, but in the participants with mild renal insufficiency, it was not different. After adjusting for age, male sex, systolic blood pressure, body mass index, current smoking status, and fasting plasma glucose, the apolipoprotein B/A-I ratio was significantly associated with an increased risk of coronary artery calcification in participants with normal kidney function (odds ratio = 2.411, p = 0.011), while in the participants with mild renal insufficiency, the apolipoprotein B/A-I ratio was not associated with coronary artery calcification. CONCLUSION: Our study showed that the predictive value of apolipoprotein B/A-I ratio for coronary artery calcification may differ according to kidney function.ope

Method of Concentrating Low Titer Fermentation Broths Using Forward Osmosis

본 발명은 발효액의 농축방법에 관한 것으로서, 더욱 상세하게는 정삼투압을 이용한 저농도 발효액의 고농도 농축방법에 관한 것이다. 본 발명에 따른 정삼투압을 이용한 발효액의 농축 방법은 정삼투압막으로 구획되어 있는 피드 챔버 및 드로우 챔버를 포함하는 농축장치의 피드 챔버 및 드로우 챔버에 각각 발효액 및 삼투압 유발액(osmolyte)을 투입한 다음, 정삼투압 반응을 수행함으로써 피드 챔버의 발효액을 농축시키는 것을 특징으로 한다. 저농도 발효액을 역삼투압을 이용하거나 추출용매를 사용하여 농축시킬 경우, 에너지가 많이 소비되거나 추출용매의 가격이 비싸기 때문에 경제적으로 타당하지 않으나, 본 발명에 따른 정삼투압을 이용한 발효액의 농축 방법은 발효액의 농축을 최대화하면서, 에너지 소모 및 운영비용을 최소화할 수 있으므로, 신기술의 산업화에 기여할 수 있다