Dysnatremia, its correction, and mortality in patients undergoing continuous renal replacement therapy: a prospective observational study

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Abstract Background Although dysnatremia has been reported to be correlated with mortality risk, this issue remains unresolved in patients undergoing continuous renal replacement therapy (CRRT). Furthermore, it has not been determined whether change in or correction of sodium is related to mortality risk in this subset. Methods A total of 569 patients were prospectively enrolled at the start of CRRT between May 2010 and September 2013. The patients were divided into 5 groups: normonatremia (135–145 mmol/L), mild hyponatremia (131.1–134.9 mmol/L), moderate to severe hyponatremia (115.4–131.0 mmol/L), mild hypernatremia (145.1–148.4 mmol/L), and moderate to severe hypernatremia (148.5–166.0 mmol/L). The non-linear relationship between sodium and mortality was initially explored. Subsequently, the odds ratios (ORs) for 30-day mortality were calculated after adjustment of multiple covariates. Results The relationship between baseline sodium and mortality was U-shaped. The mild hyponatremia, moderate to severe hyponatremia, and moderate to severe hypernatremia groups had greater ORs for mortality (1.65, 1.91, and 2.32, respectively) than the normonatremia group (all P values < 0.05). However, later sodium levels (24 and 72 h after CRRT) did not predict 30-day mortality. Furthermore, the changes in sodium over 24 or 72 h, including the appropriate correction of dysnatremia, did not show any relationships with mortality, irrespective of baseline sodium level. Conclusions Sodium level at the start of CRRT was a strong predictor of mortality. However, changes in sodium level and the degree of sodium correction were not associated with the mortality risk in the patients with CRRT

Co-chaperone BAG2 Determines the Pro-oncogenic Role of Cathepsin B in Triple-Negative Breast Cancer Cells

Triple-negative breast cancer (TNBC) is considered incurable with currently available treatments, highlighting the need for therapeutic targets and predictive biomarkers. Here, we report a unique role for Bcl-2-associated athanogene 2 (BAG2), which is significantly overexpressed in TNBC, in regulating the dual functions of cathepsin B as either a pro- or anti-oncogenic enzyme. Silencing BAG2 suppresses tumorigenesis and lung metastasis and induces apoptosis by increasing the intracellular mature form of cathepsin B, whereas BAG2 expression induces metastasis by blocking the auto-cleavage processing of pro-cathepsin B via interaction with the propeptide region. BAG2 regulates pro-cathepsin B/annexin II complex formation and facilitates the trafficking of pro-cathespin-B-containing TGN38-positive vesicles toward the cell periphery, leading to the secretion of pro-cathepsin B, which induces metastasis. Collectively, our results uncover BAG2 as a regulator of the oncogenic function of pro-cathepsin B and a potential diagnostic and therapeutic target that may reduce the burden of metastatic breast cancer

Urinary adiponectin and albuminuria in non-diabetic hypertensive patients: an analysis of the ESPECIAL trial

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Abstract Background Although adiponectin levels have been reported to be correlated with albuminuria, this issue remains unresolved in non-diabetic hypertensive subjects, particularly when urinary adiponectin is considered. Methods Urinary adiponectin levels were examined using an enzyme-linked immunosorbent assay in 229 participants. who used olmesartan as a hypertensive agent. Their albuminuria levels were measured for 16 weeks after randomization and initiation of conventional or intensive diet education. Linear or logistic regression models were applied, as appropriate, to explore the relationship with albuminuria itself or its response after the intervention. Results Urinary adiponectin levels were positively related to baseline albuminuria level (r = 0.529). After adjusting for several covariates, the adiponectin level was associated with the albuminuria level (β = 0.446). Among the 159 subjects with baseline macroalbuminuria, the risk of consistent macroalbuminuria (> 300 mg/day) at 16 weeks was higher in the 3rd tertile of adiponectin than in the 1st tertile (odds ratio = 6.9), despite diet education. In contrast, among all subjects, the frequency of the normoalbuminuria achievement (< 30 mg/day) at 16 weeks was higher in the 1st tertile than in the 3rd tertile (odds ratio = 13.0). Conclusions Urinary adiponectin may be a useful biomarker for albuminuria or its response after treatment in non-diabetic hypertensive patients

Effect of shared decision-making education on physicians’ perceptions and practices of end-of-life care in Korea

Background Evidence of the ethical appropriateness and clinical benefits of shared decision-making (SDM) are accumulating. This study aimed to not only identify physicians’ perspectives on SDM, and practices related to end-of-life care in particular, but also to gauge the effect of SDM education on physicians in Korea. Methods A 14-item questionnaire survey using a modified Delphi process was delivered to nephrologists and internal medicine trainees at 17 university hospitals. Results A total of 309 physicians completed the survey. Although respondents reported that 69.9% of their practical decisions were made using SDM, 59.9% reported that it is not being applied appropriately. Only 12.3% of respondents had received education on SDM as part of their training. The main obstacles to appropriate SDM were identified as lack of time (46.0%), educational materials and tools (29.4%), and education on SDM (24.3%). Although only a few respondents had received training on SDM, the proportion of those who thought they were using SDM appropriately in actual practice was high; the proportion of those who chose lack of time and education as factors that hindered the proper application of SDM was low. Conclusion The majority of respondents believed that SDM was not being implemented properly in Korea, despite its use in actual practice. To improve the effectiveness of SDM in the Korean medical system, appropriate training programs and supplemental policies that guarantee sufficient application time are required

TRAF6 Mediates IL-1β/LPS-Induced Suppression of TGF-β Signaling through Its Interaction with the Type III TGF-β Receptor

Transforming growth factor-β1 (TGF-β1) is an important anti-inflammatory cytokine that modulates and resolves inflammatory responses. Recent studies have demonstrated that inflammation enhances neoplastic risk and potentiates tumor progression. In the evolution of cancer, pro-inflammatory cytokines such as IL-1β must overcome the anti-inflammatory effects of TGF-β to boost pro-inflammatory responses in epithelial cells. Here we show that IL-1β or Lipopolysaccharide (LPS) suppresses TGF-β-induced anti-inflammatory signaling in a NF-κB-independent manner. TRAF6, a key molecule in IL-1β signaling, mediates this suppressive effect through interaction with the type III TGF-β receptor (TβRIII), which is TGF-β-dependent and requires type I TGF-β receptor (TβRI) kinase activity. TβRI phosphorylates TβRIII at residue S829, which promotes the TRAF6/TβRIII interaction and consequent sequestration of TβRIII from the TβRII/TβRI complex. Our data indicate that IL-1β enhances the pro-inflammatory response by suppressing TGF-βsignaling through TRAF6-mediated sequestration of TβRIII, which may be an important contributor to the early stages of tumor progression

Prevalence and detection of low-allele-fraction variants in clinical cancer samples

Accurate detection of genomic alterations using high-throughput sequencing is an essential component of precision cancer medicine. We characterize the variant allele fractions (VAFs) of somatic single nucleotide variants and indels across 5095 clinical samples profiled using a custom panel, CancerSCAN. Our results demonstrate that a significant fraction of clinically actionable variants have low VAFs, often due to low tumor purity and treatment-induced mutations. The percentages of mutations under 5% VAF across hotspots in EGFR, KRAS, PIK3CA, and BRAF are 16%, 11%, 12%, and 10%, respectively, with 24% for EGFR T790M and 17% for PIK3CA E545. For clinical relevance, we describe two patients for whom targeted therapy achieved remission despite low VAF mutations. We also characterize the read depths necessary to achieve sensitivity and specificity comparable to current laboratory assays. These results show that capturing low VAF mutations at hotspots by sufficient sequencing coverage and carefully tuned algorithms is imperative for a clinical assay

Renoprotective Effect of KLF2 on Glomerular Endothelial Dysfunction in Hypertensive Nephropathy

Kruppel-like factor 2 (KLF2) regulates endothelial cell metabolism; endothelial dysfunction is associated with hypertension and is a predictor of atherosclerosis development and cardiovascular events. Here, we investigated the role of KLF2 in hypertensive nephropathy by regulating KLF2 expression in human primary glomerular endothelial cells (hPGECs) and evaluating this expression in the kidney tissues of a 5/6 nephrectomy mouse model as well as patients with hypertension. Hypertension-mimicking devices and KLF2 siRNA were used to downregulate KLF2 expression, while the expression of KLF2 was upregulated by administering simvastatin. After 4 mmHg of pressure was applied on hPGECs for 48 h, KLF2 mRNA expression decreased, while alpha-smooth muscle actin (&alpha;SMA) mRNA expression increased. Apoptosis and fibrosis rates were increased under pressure, and these phenomena were aggravated following KLF2 knockdown, but were alleviated after simvastatin treatment; additionally, these changes were observed in angiotensin II, angiotensin type-1 receptor (AT1R) mRNA, and interleukin-18 (IL-18), but not in angiotensin type-2 receptor mRNA. Reduced expression of KLF2 in glomerular endothelial cells due to hypertension was found in both 5/6 nephrectomy mice and patients with hypertensive nephropathy. Thus, our study demonstrates that the pressure-induced apoptosis and fibrosis of glomerular endothelial cells result from angiotensin II, AT1R activation, and KLF2 inhibition, and are associated with IL-18

Musical hand shaker toward sustainable behavioral changes : Designing of persuasive interaction through emotion arousing

Context. This paper aims to investigate the potential of sustainable interaction system by employing persuasive design process. Sustainable Human Computer Interaction community (HCI) strives to find effective ways to change human behavior toward pro-environment. The sustainable HCI community seems to propose ambient display interface as one of its major interaction methods, which have an impact in quiet and static surroundings. However, when it comes to crowded public places where public resources are heavily wasted, ambient interfaces hardly get people’s attention and provide timely information to people. Goals. The author proposes an embodied sound interface as an alternative in the crowded places. The embodied sound interface serves to alert people at the right moment in a fun and pleasant way to induce people to engage in an intended behavior spontaneously. A sensor system prototype embedding an embodied sound interface, musical hand shaker (MHS), was developed aiming at reducing the use of paper towels. The MHS is placed near the water tap in a restroom and it respond with a music to the hand shaking of the user in front of the MHS. The system encourages people to experience how easy it is to save paper towel and do a green activity in their daily life. Methods. This study is grounded on three HCI fields: ambient information systems, affective interaction, and persuasive technology. The MHS prototype went through the persuasive design process which includes iterative steps of prototype implementation and evaluation. This design process centered on the eight steps of design process and Fogg behavior model. The persuasive qualities of embodied sound interface such as understandability, recognition of the system goal, and persistency of raised awareness of sustainability were examined. Results. The final outdoor evaluation in the restroom of a mall confirmed the impact of the MHS on people’s habit of using paper towels as well as its effectiveness of persuasion. Since it is a pilot study, there remain some unresolved issues and open questions for researcher in HCI and psychology fields

Musical hand shaker toward sustainable behavioral changes : Designing of persuasive interaction through emotion arousing

Context. This paper aims to investigate the potential of sustainable interaction system by employing persuasive design process. Sustainable Human Computer Interaction community (HCI) strives to find effective ways to change human behavior toward pro-environment. The sustainable HCI community seems to propose ambient display interface as one of its major interaction methods, which have an impact in quiet and static surroundings. However, when it comes to crowded public places where public resources are heavily wasted, ambient interfaces hardly get people’s attention and provide timely information to people. Goals. The author proposes an embodied sound interface as an alternative in the crowded places. The embodied sound interface serves to alert people at the right moment in a fun and pleasant way to induce people to engage in an intended behavior spontaneously. A sensor system prototype embedding an embodied sound interface, musical hand shaker (MHS), was developed aiming at reducing the use of paper towels. The MHS is placed near the water tap in a restroom and it respond with a music to the hand shaking of the user in front of the MHS. The system encourages people to experience how easy it is to save paper towel and do a green activity in their daily life. Methods. This study is grounded on three HCI fields: ambient information systems, affective interaction, and persuasive technology. The MHS prototype went through the persuasive design process which includes iterative steps of prototype implementation and evaluation. This design process centered on the eight steps of design process and Fogg behavior model. The persuasive qualities of embodied sound interface such as understandability, recognition of the system goal, and persistency of raised awareness of sustainability were examined. Results. The final outdoor evaluation in the restroom of a mall confirmed the impact of the MHS on people’s habit of using paper towels as well as its effectiveness of persuasion. Since it is a pilot study, there remain some unresolved issues and open questions for researcher in HCI and psychology fields

Exogenous Glutathione Enhances Mercury Tolerance by Inhibiting Mercury Entry into Plant Cells

Despite the increasing understanding of the crucial roles of glutathione (GSH) in cellular defense against heavy metal stress as well as oxidative stress, little is known about the functional role of exogenous GSH in mercury (Hg) tolerance in plants. Here, we provide compelling evidence that GSH contributes to Hg tolerance in diverse plants. Exogenous GSH did not mitigate the toxicity of cadmium (Cd), copper (Cu), or zinc (Zn), whereas application of exogenous GSH significantly promoted Hg tolerance during seed germination and seedling growth of Arabidopsis thaliana, tobacco, and pepper. By contrast, addition of buthionine sulfoximine, an inhibitor of GSH biosynthesis, severely retarded seed germination and seedling growth of the plants in the presence of Hg. The effect of exogenous GSH on Hg specific tolerance was also evident in the presence of other heavy metals, such as Cd, Cu, and Zn, together with Hg. GSH treatment significantly decreased H2O2 and O2- levels and lipid peroxidation, but increased chlorophyll content in the presence of Hg. Importantly, GSH treatment resulted in significantly less accumulation of Hg in Arabidopsis plants, and thin layer chromatography and nuclear magnetic resonance analysis revealed that GSH had much stronger binding affinity to Hg than to Cd, Cu, or Zn, suggesting that tight binding of GSH to Hg impedes Hg uptake, leading to low Hg accumulation in plant cells. Collectively, the present findings reveal that GSH is a potent molecule capable of conferring Hg tolerance by inhibiting Hg accumulation in plants