Liver transplantation (LT) recipients are known to require less anesthetic agents. Providing minimally required anesthetics while avoiding awareness is especially important in LT recipients because it would help manag...Liver transplantation (LT) recipients are known to require less anesthetic agents. Providing minimally required anesthetics while avoiding awareness is especially important in LT recipients because it would help manage perioperative hemodynamic instability with less vasopressor and fast track recovery. This study aims to compare state entropy (SE) against bispectral index (BIS) during isoflurane anesthesia in LT. We adjusted anesthesia to BIS values 40 - 60, and compared it with concomitant SE values. BIS, SE values, and anesthetic requirements according to liver failure severity, etiology and LT stages were analyzed. For BIS-SE differences, SE value that is different from the concomitant BIS by more than 15 was defined as a significant disagreement. Mann Whitney, Kruskal Wallis test and a Poisson exact test were used for analysis. The BIS-SE pair sets of 2895 from 38 patients were analyzed. BIS, SE values and anesthetic requirements were significantly lower in MELD ≥ 20 (p < 0.001 in all) and in alcoholic etiology (p < 0.001 in all). For BIS-SE differences, 320 disagreement data pairs were seen at a rate of 1.33 times/hr (95% CI = [1.19, 1.48], p < 0.001). A significant disagreement was delineated in MELD score ≥ 20 (3.04 times/hr, CI = [2.64, 3.49], p < 0.001), alcoholic etiology (3.19 times/hr, [2.67, 3.78], p < 0.001) and postreperfusion stage (1.63 times/hr, [1.43, 1.85], p < 0.001). In these significant BIS-SE differences, 95.9% (307/320 disagreement data pairs) showed higher BIS than SE. In conclusion, in high MELD and alcoholic etiology, anesthetic requirements were significantly less, and BIS and SE showed great discrepancy with lower SE values. Therefore, when SE monitoring is used during LT, anesthesiologists may need to consider that in high MELD and alcoholic etiology, SE tends to show lower values than the concomitant BIS values that are within optimal anesthetic depth ranges.展开更多
BACKGROUND There is limited evidence regarding the association between muscle strength and metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To investigate the association between muscle strength and MAF...BACKGROUND There is limited evidence regarding the association between muscle strength and metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To investigate the association between muscle strength and MAFLD in the general population in Korea.METHODS This nationwide representative cross-sectional study included 31649 individuals aged≥19 years who participated in the Korea National Health and Nutrition Examination Survey between 2015 and 2018.Odds ratios(ORs)and 95%confidence intervals(95%CIs)for MAFLD according to sex-specific quartiles of muscle strength,defined by relative handgrip strength,were calculated using multivariable logistic regression analysis.Additionally,multivariable logistic regression analysis was used to assess the association between muscle strength and probable liver fibrosis in patients with MAFLD.RESULTS Of all the participants,29.3%had MAFLD.The prevalence of MAFLD was significantly higher in the lower muscle strength quartile groups for all participants,sexes,and age groups(P<0.001).A 1.92-fold(OR=1.92,95%CI:1.70–2.16)and 3.12-fold(OR=3.12,95%CI:2.64–3.69)higher risk of MAFLD was observed in the lowest quartile(Q1)group than in the other groups(Q2–Q4)and the highest quartile(Q4)group,respectively.The ORs of MAFLD were significantly increased in the lower muscle strength quartile groups in a dose-dependent manner(P for trend<0.001).These associations persisted in both sexes.An inverse association between muscle strength and the risk of MAFLD was observed in all subgroups according to age,obesity,and diabetes mellitus.In patients with MAFLD,the odds of severe liver fibrosis were higher in Q1(OR=1.83,95%CI:1.25–2.69)than in other groups(Q2–Q4).CONCLUSION Among Korean adults,low muscle strength was associated with an increased risk of MAFLD and liver fibrosis in patients with MAFLD.展开更多
Protein phosphatase 2A （PP2A） accounts for the majority of total Ser/Thr phosphatase activities in most cell types and regulates many biological processes. PP2A holoenzymes contain a scaffold A subunit, a cat- alyti...Protein phosphatase 2A （PP2A） accounts for the majority of total Ser/Thr phosphatase activities in most cell types and regulates many biological processes. PP2A holoenzymes contain a scaffold A subunit, a cat- alytic C subunit, and one of the regulatory/targeting B subunits. How the B subunit controls PP2A localization and substrate specificity, which is a crucial aspect of PP2A regulation, remains poorly understood. The kine- tochore is a critical site for PP2A functioning, where PP2A orchestrates chromosome segregation through its interactions with BubR1. The PP2A-BubR1 interac- tion plays important roles in both spindle checkpoint silencing and stable microtubule-kinetochore attach- ment. Here we present the crystal structure of a PP2A B56-BubRI complex, which demonstrates that a con- served BubRl LxxlxE motif binds to the concave side of the B56 pseudo-HEAT repeats. The BubR1 motif binds to a groove formed between B56 HEAT repeats 3 and 4, which is quite distant from the B56 binding surface for PP2A catalytic C subunit and thus is unlikely to affect PP2A activity. In addition, the BubR1 binding site on B56 is far from the B56 binding site of shugoshin, another kinetochore PP2A-binding protein, and thus BubR1 and shugoshin can potentially interact with PP2A-B56 simultaneously. Our structural and biochemical analysis indicates that other proteins with the LxxlxE motif may also bind to the same PP2A B56 surface. Thus, our structure of the PP2A B56-BubR1 complex provides important insights into how the B56 subunit directs the recruitment of PP2A to specific targets.展开更多
1. Evaluating the U.S.-DPRK Singapore Summit Finally, U.S. President Donald Trump and North Korea’s Chairman Kim Jong-un met for a historic summit on June 12 in Singapore. The summit was indeed a ‘historic’ in the ...1. Evaluating the U.S.-DPRK Singapore Summit Finally, U.S. President Donald Trump and North Korea’s Chairman Kim Jong-un met for a historic summit on June 12 in Singapore. The summit was indeed a ‘historic’ in the sense that the leaders of two enemy states met for the first time face-to-face.展开更多
文摘Liver transplantation (LT) recipients are known to require less anesthetic agents. Providing minimally required anesthetics while avoiding awareness is especially important in LT recipients because it would help manage perioperative hemodynamic instability with less vasopressor and fast track recovery. This study aims to compare state entropy (SE) against bispectral index (BIS) during isoflurane anesthesia in LT. We adjusted anesthesia to BIS values 40 - 60, and compared it with concomitant SE values. BIS, SE values, and anesthetic requirements according to liver failure severity, etiology and LT stages were analyzed. For BIS-SE differences, SE value that is different from the concomitant BIS by more than 15 was defined as a significant disagreement. Mann Whitney, Kruskal Wallis test and a Poisson exact test were used for analysis. The BIS-SE pair sets of 2895 from 38 patients were analyzed. BIS, SE values and anesthetic requirements were significantly lower in MELD ≥ 20 (p < 0.001 in all) and in alcoholic etiology (p < 0.001 in all). For BIS-SE differences, 320 disagreement data pairs were seen at a rate of 1.33 times/hr (95% CI = [1.19, 1.48], p < 0.001). A significant disagreement was delineated in MELD score ≥ 20 (3.04 times/hr, CI = [2.64, 3.49], p < 0.001), alcoholic etiology (3.19 times/hr, [2.67, 3.78], p < 0.001) and postreperfusion stage (1.63 times/hr, [1.43, 1.85], p < 0.001). In these significant BIS-SE differences, 95.9% (307/320 disagreement data pairs) showed higher BIS than SE. In conclusion, in high MELD and alcoholic etiology, anesthetic requirements were significantly less, and BIS and SE showed great discrepancy with lower SE values. Therefore, when SE monitoring is used during LT, anesthesiologists may need to consider that in high MELD and alcoholic etiology, SE tends to show lower values than the concomitant BIS values that are within optimal anesthetic depth ranges.
文摘BACKGROUND There is limited evidence regarding the association between muscle strength and metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To investigate the association between muscle strength and MAFLD in the general population in Korea.METHODS This nationwide representative cross-sectional study included 31649 individuals aged≥19 years who participated in the Korea National Health and Nutrition Examination Survey between 2015 and 2018.Odds ratios(ORs)and 95%confidence intervals(95%CIs)for MAFLD according to sex-specific quartiles of muscle strength,defined by relative handgrip strength,were calculated using multivariable logistic regression analysis.Additionally,multivariable logistic regression analysis was used to assess the association between muscle strength and probable liver fibrosis in patients with MAFLD.RESULTS Of all the participants,29.3%had MAFLD.The prevalence of MAFLD was significantly higher in the lower muscle strength quartile groups for all participants,sexes,and age groups(P<0.001).A 1.92-fold(OR=1.92,95%CI:1.70–2.16)and 3.12-fold(OR=3.12,95%CI:2.64–3.69)higher risk of MAFLD was observed in the lowest quartile(Q1)group than in the other groups(Q2–Q4)and the highest quartile(Q4)group,respectively.The ORs of MAFLD were significantly increased in the lower muscle strength quartile groups in a dose-dependent manner(P for trend<0.001).These associations persisted in both sexes.An inverse association between muscle strength and the risk of MAFLD was observed in all subgroups according to age,obesity,and diabetes mellitus.In patients with MAFLD,the odds of severe liver fibrosis were higher in Q1(OR=1.83,95%CI:1.25–2.69)than in other groups(Q2–Q4).CONCLUSION Among Korean adults,low muscle strength was associated with an increased risk of MAFLD and liver fibrosis in patients with MAFLD.
文摘Protein phosphatase 2A （PP2A） accounts for the majority of total Ser/Thr phosphatase activities in most cell types and regulates many biological processes. PP2A holoenzymes contain a scaffold A subunit, a cat- alytic C subunit, and one of the regulatory/targeting B subunits. How the B subunit controls PP2A localization and substrate specificity, which is a crucial aspect of PP2A regulation, remains poorly understood. The kine- tochore is a critical site for PP2A functioning, where PP2A orchestrates chromosome segregation through its interactions with BubR1. The PP2A-BubR1 interac- tion plays important roles in both spindle checkpoint silencing and stable microtubule-kinetochore attach- ment. Here we present the crystal structure of a PP2A B56-BubRI complex, which demonstrates that a con- served BubRl LxxlxE motif binds to the concave side of the B56 pseudo-HEAT repeats. The BubR1 motif binds to a groove formed between B56 HEAT repeats 3 and 4, which is quite distant from the B56 binding surface for PP2A catalytic C subunit and thus is unlikely to affect PP2A activity. In addition, the BubR1 binding site on B56 is far from the B56 binding site of shugoshin, another kinetochore PP2A-binding protein, and thus BubR1 and shugoshin can potentially interact with PP2A-B56 simultaneously. Our structural and biochemical analysis indicates that other proteins with the LxxlxE motif may also bind to the same PP2A B56 surface. Thus, our structure of the PP2A B56-BubR1 complex provides important insights into how the B56 subunit directs the recruitment of PP2A to specific targets.
文摘1. Evaluating the U.S.-DPRK Singapore Summit Finally, U.S. President Donald Trump and North Korea’s Chairman Kim Jong-un met for a historic summit on June 12 in Singapore. The summit was indeed a ‘historic’ in the sense that the leaders of two enemy states met for the first time face-to-face.
