Elevated cholesterol in ATAD3 mutants is a compensatory mechanism that leads to membrane cholesterol aggregation.

Aberrant cholesterol metabolism causes neurological disease and neurodegeneration, and mitochondria have been linked to perturbed cholesterol homeostasis via the study of pathological mutations in the ATAD3 gene cluster. However, whether the cholesterol changes were compensatory or contributory to the disorder was unclear, and the effects on cell membranes and the wider cell were also unknown. Using patient-derived cells, we show that cholesterol perturbation is a conserved feature of pathological ATAD3 variants that is accompanied by an expanded lysosome population containing membrane whorls characteristic of lysosomal storage diseases. Lysosomes are also more numerous in Drosophila neural progenitor cells expressing mutant Atad3, which exhibit abundant membrane-bound cholesterol aggregates, many of which co-localize with lysosomes. By subjecting the Drosophila Atad3 mutant to nutrient restriction and cholesterol supplementation, we show that the mutant displays heightened cholesterol dependence. Collectively, these findings suggest that elevated cholesterol enhances tolerance to pathological ATAD3 variants; however, this comes at the cost of inducing cholesterol aggregation in membranes, which lysosomal clearance only partly mitigates.

Favorable Prognostic Factors for Survival Outcomes of Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis After Hepatectomy.

BACKGROUND: This study aimed to investigate prognostic factors of recurrence and survival associated with hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). PATIENTS AND METHODS: This retrospective study included 161 patients with HCC with PVTT who underwent hepatectomy between January 2003 and January 2014 at the Asan Medical Center. Regression analyses were conducted to identify favorable predictive factors for overall survival (OS) and recurrence-free survival (RFS). RESULTS: The median follow-up was 15.9 months, while 1-, 3-, and 5-year OS was 65.0%, 38.4%, and 36.0%, respectively, and 1-year RFS was 25.5%. There were no significant differences in OS and RFS between the patients with portal vein invasion (Vp) 1-2 and Vp3-4 PVTT. Patients with intrahepatic recurrence had significantly better overall survival than patients with extrahepatic recurrence. Transcatheter arterial chemoembolization and radiofrequency ablation were the most effective treatments for intrahepatic metastasis, and surgery was the most effective treatment for extrahepatic metastasis. On multivariate analysis, absence of esophageal varices, maximal tumor size < 5 cm, tumor location in single lobe, and anatomical resection were favorable prognostic factors for OS and R0 resection, and absence of microvascular invasion was a favorable prognostic factor for RFS. CONCLUSION: The long-term outcome of patients with HCC with PVTT can be improved under consideration of favorable prognostic factors including absence of esophageal varices, maximal tumor size < 5 cm, tumor location in single lobe, and anatomical resection, R0 resection, and absence of microvascular invasion. In addition, recurrent HCC required aggressive management to prolong overall survival.

Provably Secure Lightweight Mutual Authentication and Key Agreement Scheme for Cloud-Based IoT Environments.

A paradigm that combines cloud computing and the Internet of Things (IoT) allows for more impressive services to be provided to users while addressing storage and computational resource issues in the IoT environments. This cloud-based IoT environment has been used in various industries, including public services, for quite some time, and has been researched in academia. However, various security issues can arise during the communication between IoT devices and cloud servers, because communication between devices occurs in open channels. Moreover, issues such as theft of a user's IoT device or extraction of key parameters from the user's device in a remote location can arise. Researchers interested in these issues have proposed lightweight mutual authentication key agreement protocols that are safe and suitable for IoT environments. Recently, a lightweight authentication scheme between IoT devices and cloud servers has been presented. However, we found out their scheme had various security vulnerabilities, vulnerable to insider, impersonation, verification table leakage, and privileged insider attacks, and did not provide users with untraceability. To address these flaws, we propose a provably secure lightweight authentication scheme. The proposed scheme uses the user's biometric information and the cloud server's secret key to prevent the exposure of key parameters. Additionally, it ensures low computational costs for providing users with real-time and fast services using only exclusive OR operations and hash functions in the IoT environments. To analyze the safety of the proposed scheme, we use informal security analysis, Burrows-Abadi-Needham (BAN) logic and a Real-or-Random (RoR) model. The analysis results confirm that our scheme is secure against insider attacks, impersonation attacks, stolen verifier attacks, and so on; furthermore, it provides additional security elements. Simultaneously, it has been verified to possess enhanced communication costs, and total bit size has been shortened to 3776 bits, which is improved by almost 6% compared to Wu et al.'s scheme. Therefore, we demonstrate that the proposed scheme is suitable for cloud-based IoT environments.

Provably Secure Mutual Authentication and Key Agreement Scheme Using PUF in Internet of Drones Deployments.

Internet of Drones (IoD), designed to coordinate the access of unmanned aerial vehicles (UAVs), is a specific application of the Internet of Things (IoT). Drones are used to control airspace and offer services such as rescue, traffic surveillance, environmental monitoring, delivery and so on. However, IoD continues to suffer from privacy and security issues. Firstly, messages are transmitted over public channels in IoD environments, which compromises data security. Further, sensitive data can also be extracted from stolen mobile devices of remote users. Moreover, drones are susceptible to physical capture and manipulation by adversaries, which are called drone capture attacks. Thus, the development of a secure and lightweight authentication scheme is essential to overcoming these security vulnerabilities, even on resource-constrained drones. In 2021, Akram et al. proposed a secure and lightweight user-drone authentication scheme for drone networks. However, we discovered that Akram et al.'s scheme is susceptible to user and drone impersonation, verification table leakage, and denial of service (DoS) attacks. Furthermore, their scheme cannot provide perfect forward secrecy. To overcome the aforementioned security vulnerabilities, we propose a secure mutual authentication and key agreement scheme between user and drone pairs. The proposed scheme utilizes physical unclonable function (PUF) to give drones uniqueness and resistance against drone stolen attacks. Moreover, the proposed scheme uses a fuzzy extractor to utilize the biometrics of users as secret parameters. We analyze the security of the proposed scheme using informal security analysis, Burrows-Abadi-Needham (BAN) logic, a Real-or-Random (RoR) model, and Automated Verification of Internet Security Protocols and Applications (AVISPA) simulation. We also compared the security features and performance of the proposed scheme and the existing related schemes. Therefore, we demonstrate that the proposed scheme is suitable for IoD environments that can provide users with secure and convenient wireless communications.

Visible-Light-Induced Organophotocatalytic Difunctionallization: Open-Air Hydroxysulfurization of Aryl Alkenes with Aryl Thiols.

Herein, we report a regioselective visible-light-induced organophotoredox catalytic difunctionalization method to prepare ß-hydroxysulfides using aryl alkenes and aryl thiols as substrates. The reaction provides a wide substrate scope of aryl alkenes (from simple styrene to complex bioactive compounds) and aryl thiols (from diverse heteroaromatic thiols to nonheteroaromatic thiols) (total 45 examples, up to 88% yield). Based on the combined experimental and computational studies, we demonstrate that in situ generated hydroperoxyl radicals from O2 in air react with benzylic radicals, which restrains the reaction between benzylic radicals and the acidic form of thiols in a classical thiol-ene radical reaction. We show that difunctionalization is possible due to the choice of bases, diluted substrate concentrations, increment in catalyst loading, and selection of suitable aryl thiols under aerobic conditions. Considering the biological importance of heteroaromatic thiols and the lack of methods to install them, our approach offers a platform to derive various ß-hydroxysulfides that contain aromatic elements.

Machine learning-based survival rate prediction of Korean hepatocellular carcinoma patients using multi-center data.

AIM: To predict survival time of Korean hepatocellular carcinoma (HCC) patients using multi-center data as a foundation for the development of a predictive artificial intelligence model according to treatment methods based on machine learning. METHODS: Data of patients who underwent treatment for HCC from 2008 to 2015 was provided by Korean Liver Cancer Study Group and Korea Central Cancer Registry. A total of 10,742 patients with HCC were divided into two groups, with Group I (2920 patients) confirmed on biopsy and Group II (5562 patients) diagnosed as HCC according to HCC diagnostic criteria as outlined in Korean Liver Cancer Association guidelines. The data were modeled according to features of patient clinical characteristics. Features effective in predicting survival rate were analyzed retrospectively. Various machine learning methods were used. RESULTS: Target was overall survival time, which divided into approximately 60 months (= /< 60 m, > 60 m). Target distribution in Group I (total 514 samples) was 28.8%: (148 samples) less than 60 months, 71.2% (366 samples) greater than 60 months, and in Group II (total 757 samples) was 66.6% (504 samples) less than 60 months, 33.4% (253 samples) greater than 60 months. Using NG Boost method, its accuracy was 83%, precision 84%, sensitivity 95%, and F1 score 89% for more than 60 months survival time in Group I with surgical resection. Moreover, its accuracy was 79%, precision 82%, sensitivity 87%, and F1 score 84% for less than 60 months survival time in Group II with TACE. The feature importance with gain criterion indicated that pathology, portal vein invasion, surgery, metastasis, and needle biopsy features could be explained as important factors for prediction in case of biopsy (Group I). CONCLUSION: By developing a predictive model using machine learning algorithms to predict prognosis of HCC patients, it is possible to project optimized treatment by case according to liver function and tumor status.

Ceria-Zirconia nanoparticles reduce intracellular globotriaosylceramide accumulation and attenuate kidney injury by enhancing the autophagy flux in cellular and animal models of Fabry disease.

BACKGROUND: Fabry disease (FD) is a lysosome storage disease (LSD) characterized by significantly reduced intracellular autophagy function. This contributes to the progression of intracellular pathologic signaling and can lead to organ injury. Phospholipid-polyethyleneglycol-capped Ceria-Zirconia antioxidant nanoparticles (PEG-CZNPs) have been reported to enhance autophagy flux. We analyzed whether they suppress globotriaosylceramide (Gb3) accumulation by enhancing autophagy flux and thereby attenuate kidney injury in both cellular and animal models of FD. RESULTS: Gb3 was significantly increased in cultured human renal proximal tubular epithelial cells (HK-2) and human podocytes following the siRNA silencing of α galactosidase A (α-GLA). PEG-CZNPs effectively reduced the intracellular accumulation of Gb3 in both cell models of FD and improved both intracellular inflammation and apoptosis in the HK-2 cell model of FD. Moreover these particles attenuated pro fibrotic cytokines in the human podocyte model of FD. This effect was revealed through an improvement of the intracellular autophagy flux function and a reduction in reactive oxygen species (ROS). An FD animal model was generated in which 4-week-old male B6;129-Glatm1Kul/J mice were treated for 8 weeks with 10 mg/kg of PEG-CZNPs (twice weekly via intraperitoneal injection). Gb3 levels were reduced in the kidney tissues of these animals, and their podocyte characteristics and autophagy flux functions were preserved. CONCLUSIONS: PEG-CZNPs alleviate FD associated kidney injury by enhancing autophagy function and thus provide a foundation for the development of new drugs to treat of storage disease.

Combined Analysis of HLA Class II Eplet Mismatch and Tacrolimus Levels for the Prediction of De Novo Donor Specific Antibody Development in Kidney Transplant Recipients.

We investigated whether HLA class II eplet mismatch was related to dnDSA development and analyzed its combined impact with tacrolimus levels for kidney transplantation outcomes. A total of 347 kidney transplants were included. HLA Matchmaker was used for the single molecular eplet, total eplet, antibody (Ab)-verified eplet mismatch analyses, and Ab-verified single molecular analysis to identify HLA-DR/DQ molecular thresholds for the risk of dnDSA development. A time-weighted tacrolimus trough level (TAC-C0) of 5 ng/mL and a TAC-C0 time-weighted coefficient variability (TWCV) of 20% were applied to find the combined effects on dnDSA development. A high level of mismatch for single molecular eplet (DQ ≥ 10), total eplet (DQ ≥ 12), Ab-verified eplet (DQ ≥ 4), and Ab-verified single molecular eplet (DQ ≥ 4) significantly correlated with HLA class II dnDSA development. Class II dnDSA developed mostly in patients with low TAC-C0 and high eplet mismatch. In the multivariable analyses, low TAC-C0 and high eplet mismatch showed the highest hazard ratio for the development of dnDSA. No significant combined effect was observed in dnDSA development according to TWCV. In conclusion, the determination of HLA class II eplet mismatch may improve the risk stratification for dnDSA development, especially in conjunction with tacrolimus trough levels.

Single-Step Approach toward Nitrones via Pyridinium Ylides: The DMAP-Catalyzed Reaction of Benzyl Halides with Nitrosoarenes.

A single-step approach is reported for the preparation of nitrones from benzyl halides and nitrosoarenes via pyridinium ylides, utilizing 4-dimethylaminopyridine (DMAP) catalyst and mild reaction conditions (Li2CO3, dimethylacetamide, and room temperature). The reaction provides both keto- and aldonitrones in high yields with a wide scope for benzyl halides and nitrosoarenes. In the same reaction system, 2-methyl-2-nitrosopropane, which does not have an aryl group, also affords the corresponding N-tert-butyl nitrones from primary benzyl bromides that have an electron-withdrawing group. As an application of the reaction, methyl 2-bromo-2-phenylacetate was used to prepare the corresponding isoxazolidine by a sequential one-pot synthesis.

Enantioselective Total Synthesis of Nitraria Alkaloids: (+)-Nitramine, (+)-Isonitramine, (-)-Isonitramine, and (-)-Sibirine via Asymmetric Phase-Transfer Catalytic α-Allylations of α-Carboxylactams.

Many optically active 2-azaspirocyclic structures have frequently been found in biologically active natural products. In particular, Nitraria alkaloids, (+)-nitramine, (+)-isonitramine, (-)-isonitramine, and (-)-sibirine, have stereogenicity on their quaternary carbon of the 2-azaspiro[5,5]undecane-7-ol structure. To synthesize Nitraria alkaloids, we developed a new enantioselective synthetic method for chiral α-quaternary lactams via the α-alkylation of α-tert-butoxycarbonyl lactams. α-Alkylation of α-tert-butoxycarboxylactams in the circumstances of phase-transfer catalytic (PTC) system (solid KOH, toluene, and -40 °C) by virtue of the catalytic action of (S,S)-NAS bromide (5 mol %) furnished the corresponding α-alkyl-α-tert-butoxycarbonyl lactams in very high chemical (<99%) and enantioselectivity (<98% ee). Our catalytic methodology was successfully applied for the enantioselective total synthesis of Nitraria alkaloids. (+)-Isonitramine was obtained in 12 steps (98% ee, 43% yield) from δ-valerolactam through enantioselective phase-transfer catalytic allylation, Dieckmann condensation, and diastereoselective reduction as the key reactions. (-)-Sibirine and (+)-nitramine were prepared from (-)-isonitramine or its intermediate. Switching the phase-transfer catalyst from (S,S)-NAS bromide to (R,R)-NAS bromide afforded (-)-isonitramine (98% ee, 41% yield). (-)-Sibirine was synthesized by N-ethoxycarbonylation of (-)-isonitramine followed by reduction (98% ee, 14 steps, 32% yield). Furthermore, the diastereoselective reduction of (R)-2-benzhydryl-2-azaspiro[5.5]undecane-1,7-dione [(R)-15] followed by reductive removal of the diphenylmethyl group successfully gave (+)-nitramine (98% ee, 11 steps, 40% yield).

Enhanced anti-angiogenic activity of novel melatonin-like agents.

Hypoxia-inducible factor-1 (HIF-1) plays an important role in cellular responses to hypoxia, including the transcriptional activation of several genes involved in tumor angiogenesis. Melatonin, also known as N-acetyl-5-methopxytryptamine, is produced naturally by the pineal gland and has anti-angiogenic effects in cancer through its ability to modulate HIF-1α activity. However, the use of melatonin as a therapeutic is limited by its low oral bioavailability and short half-life. Here, we synthesized melatonin-like molecules with enhanced HIF-1α targeting activity and less toxicity and investigated their effects on tumor growth and angiogenesis, as well as the underlying molecular mechanisms. Among melatonin derivatives, N-butyryl-5-methoxytryptamine (NB-5-MT) showed the most potent HIF-1α targeting activity. This molecule was able to (a) reduce the expression of HIF-1α at the protein level, (b) reduce the transcription of HIF-1α target genes, (c) reduce reactive oxygen species (ROS) generation, (d) decrease angiogenesis in vitro and in vivo, and (e) suppress tumor size and metastasis. In addition, NB-5-MT showed improved anti-angiogenic activity compared with melatonin due to its enhanced cellular uptake. NB-5-MT is thus a promising lead for the future development of anticancer compounds with HIF-1α targeting activity. Given that HIF-1α is overexpressed in the majority of human cancers, the melatonin derivative NB-5-MT could represent a novel potent therapeutic agent for cancer.

Clinical significance of heart rate variability for the monitoring of cardiac autonomic neuropathy in end-stage renal disease patients.

BACKGROUND AND AIMS: The aim of this study is to determine whether the measurement of continuous heart rate variability (HRV) is useful in the evaluation of cardiac autonomic neuropathy (CAN) in end-stage renal disease (ESRD) patients. METHODS AND RESULTS: This cross-sectional study was performed at Seoul St. Mary's hospital between June 2017 and February 2018. Seventy-seven ESRD patients, and 29 healthy controls (HCs) were asked to wear a continuous ambulatory HRV monitor for 24 h. General cardiac function was evaluated using transthoracic echocardiogram (TTE), pulse wave velocity (PWV), coronary calcium scoring (CCS), and 24-h ambulatory blood pressure monitoring (ABPM). HRV parameters of ESRD patients and HCs, and the correlation of HRV parameters with cardiovascular screening methods were observed. All HRV parameters were significantly decreased in ESRD patients compared to HCs (P < 0.001). In the correlation analysis between TTE results and HRV parameters, 24-h standard deviation of all N-N intervals (24SDNN), 24-h standard deviation of sequential 5-min N-N interval means (24DANN) and Low Frequency Power/High Frequency Power (LF/HF) ratio showed negative correlations with E/e', LAVI and TR velocity which are representative indices for the diastolic function of the heart (P < 0.05). HRV parameters showed negative correlations with baPWV, CCS, and 24-h ABPM results as well (P < 0.05). Hemoglobin and serum albumin showed positive correlations with HRV parameters, and glucose, BUN, creatinine, and iPTH levels showed negative correlations (P < 0.05). CONCLUSION: Continuous HRV monitoring may be a useful tool for the evaluation of CAN in ESRD.

Prognostic Impact of Resection Margin Length in Patients Undergoing Resection for Mid-Common Bile Duct Cancer: A Single-Center Experience.

INTRODUCTION: The purpose of this study was to analyze survival outcomes after segmental bile duct resection (BDR) for mid-common bile duct cancer according to the length of the tumor-free BDR margins. METHOD: A total of 133 consecutive patients underwent BDR for mid-bile duct cancers between December 2007 and June 2017. The Cox proportional hazard model was used to verify the cutoff value of the R0 resection margin. The patients were divided into 3 groups according to resection margin status (group 1; R0 resection margin ≥5 mm; group 2, R0 resection margin <5 mm; and group 3, R1 resection margin). RESULTS: The median follow-up period of the study cohort was 24 months. A resection margin of 5 mm in length was verified to be suitable as a reliable cutoff value. The median disease-free and overall survival (OS) periods were 32 and 49 months in group 1, 13 and 20 months in group 2, and 23 and 30 months in group 3, respectively (p = 0.03 and p < 0.001). The length of the tumor-free resection margin (hazard ratio, 2.01; 95% confidence interval, 1.10-3.67; p = 0.022) was independent factor affecting OS. CONCLUSIONS: BDR for mid-bile duct cancer appears to be a feasible surgical option in selected patients with careful preoperative imaging assessment and intraoperative frozen-section diagnosis. Our results suggest achieving a BDR margin ≥5 mm to improve survival outcomes.

Provably Secure Three-Factor-Based Mutual Authentication Scheme with PUF for Wireless Medical Sensor Networks.

Wireless medical sensor networks (WMSNs) are used in remote medical service environments to provide patients with convenient healthcare services. In a WMSN environment, patients wear a device that collects their health information and transmits the information via a gateway. Then, doctors make a diagnosis regarding the patient, utilizing the health information. However, this information can be vulnerable to various security attacks because the information is exchanged via an insecure channel. Therefore, a secure authentication scheme is necessary for WMSNs. In 2021, Masud et al. proposed a lightweight and anonymity-preserving user authentication scheme for healthcare environments. We discover that Masud et al.'s scheme is insecure against offline password guessing, user impersonation, and privileged insider attacks. Furthermore, we find that Masud et al.'s scheme cannot ensure user anonymity. To address the security vulnerabilities of Masud et al.'s scheme, we propose a three-factor-based mutual authentication scheme with a physical unclonable function (PUF). The proposed scheme is secure against various security attacks and provides anonymity, perfect forward secrecy, and mutual authentication utilizing biometrics and PUF. To prove the security features of our scheme, we analyze the scheme using informal analysis, Burrows-Abadi-Needham (BAN) logic, the Real-or-Random (RoR) model, and Automated Verification of Internet Security Protocols and Applications (AVISPA) simulation. Furthermore, we estimate our scheme's security features, computation costs, communication costs, and energy consumption compared with the other related schemes. Consequently, we demonstrate that our scheme is suitable for WMSNs.

Insulin induces phosphorylation of pyruvate dehydrogenase through RhoA activation pathway in HepG2 cells.

Insulin is a critical signaling molecule in reducing blood glucose levels, and pyruvate dehydrogenase (PDH) is an essential enzyme in regulating glucose metabolism. However, the insulin effect on PDH function has not been well established. We observed that insulin attenuated the phosphorylation (p) of Ser264 (p-Ser264) in the PDH E1α subunit (PDHA1) in normal rat hepatocyte. In contrast, insulin induced an increase of p-Ser264 PDHA1 levels in hepatocellular carcinoma HepG2 and Huh7 cells. Insulin activated RhoA and Rho-dependent coiled coil kinase, an effector protein of active RhoA, which regulated p-Ser264 PDHA1 levels, along with both p-Ser9 and p-Tyr216 forms of glycogen synthase kinase-3ß (GSK-3ß) in HepG2 cells. Only p-Tyr216 GSK-3ß, the active form was involved in an increase of p-Ser264 PDHA1. Akt was also engaged in p-Ser9 of GSK-3ß, but neither in p-Tyr216 of GSK-3ß nor p-Ser264 of PDHA1 upon insulin. Reconstituted dephospho-mimic forms PDHA1 S264A and GSK-3ß Y216F impaired, but wild-types PDHA1 and GSK-3ß and phospho-mimic forms PDHA1 S264D and GSK-3ß Y216E increased cell proliferation upon insulin through expression of c-Myc and cyclin D1. Therefore, we propose that insulin-mediated p-PDHA1 is involved in the regulation of HepG2 cell proliferation through RhoA signaling pathway.-Islam, R., Kim, J.-G., Park, Y., Cho, J.-Y., Cap, K.-C., Kho, A.-R., Chung, W.-S., Suh, S.-W., Park, J.-B. Insulin induces phosphorylation of pyruvate dehydrogenase through RhoA activation pathway in HepG2 cells.

The impact of cytomegalovirus infection on clinical severity and outcomes in kidney transplant recipients with Pneumocystis jirovecii pneumonia.

Cytomegalovirus (CMV) infection is associated with Pneumocystis jirovecii pneumonia (PJP) in kidney transplant recipients (KTRs), but its impact on clinical severity and outcomes in KTRs with PJP is unknown. We reviewed 1994 medical records of KTRs from January 1997 to March 2019. PJP or CMV infection was diagnosed by polymerase chain reaction or culturing using blood or respiratory specimens. We divided patients into PJP and PJP+CMV groups, and evaluated the clinical severity and outcomes. Fifty two patients had PJP (2.6%) in the whole study cohort. Among patients with PJP, 38 (73.1%) had PJP alone and 14 (26.9%) had combined PJP and CMV co-infection. The PJP+CMV group showed worse laboratory findings (serum albumin and C-reactive protein, P = 0.010 for both) and higher requirement of continuous renal replacement therapy than the PJP group (P = 0.050). The pneumonia severity was worse in the PJP+CMV group than in the PJP group (P < 0.05), and CMV infection was a high risk factor of pneumonia severity (odds ratio 16.0; P = 0.002). The graft function was worse in the PJP+CMV group (P < 0.001), and the incidence of graft failure was higher in the PJP+CMV group than in the PJP group (85.7% vs 36.8%; P < 0.001). Mortality was double in the PJP+CMV group than in the PJP group, but not statistically significant (21.4% vs 10.5%; P = 0.370). Our results show that approximately one in four patients with PJP after kidney transplantation develops CMV with increased clinical severity and risk of graft failure. The possibility of increased clinical severity and worse clinical outcomes by CMV co-infection should be considered in KTRs with PJP.

Acute kidney injury with extreme hyperuricemia after antithymocyte globulin treatment in a kidney transplant recipient with underlying aplastic anemia: a case report.

BACKGROUND: The occurrences of hyperuricemia and acute kidney injury after antithymocyte globulin treatment are unusual in kidney transplant recipients. Here, we report a unique case of acute kidney injury with extreme hyperuricemia after antithymocyte globulin treatment in a kidney transplant recipient with underlying aplastic anemia. CASE PRESENTATION: A 40-year-old woman with aplastic anemia who received a kidney transplant 5 years 6 months before presented to our emergency department with complaints of oliguria, generalized edema, and general weakness 6 days after receiving antithymocyte globulin treatment for acute T-cell-mediated rejection. Urinalysis revealed 100 uric acid crystal particles. The blood chemistry test results showed rapid increases in serum creatinine (from 2.86 mg/dL to 5.58 mg/dL) and uric acid levels (from 10.2 mg/dL to 32.7 mg/dL), which suggested acute uric acid nephropathy. Tumor lysis syndrome was suspected to be the cause of the acute uric acid nephropathy; hence, the patient was reevaluated for aplastic anemia. Human leukocyte antigen-DR15 was positive, and flow cytometry revealed a low percentage of glycophosphatidyl inositol-deficient granulocytes (2.9%), which suggested paroxysmal nocturnal hemoglobinuria clones. These findings indicate that the previously diagnosed aplastic anemia had either originally been hypocellular myelodysplastic syndrome (MDS) or later transformed into hypocellular MDS, which is a type of bone marrow failure syndrome. CONCLUSIONS: Clinicians should consider unexpected tumor lysis syndrome to be the cause of complications after antithymocyte globulin treatment in kidney transplant recipients with underlying bone marrow failure syndrome.

Development of End Stage Renal Disease after Long-Term Ingestion of Chaga Mushroom: Case Report and Review of Literature.

Chaga mushrooms are widely used in folk remedies and in alternative medicine. Contrary to many beneficial effects, its adverse effect is rarely reported. We here report a case of end-stage renal disease after long-term taking Chaga mushroom. A 49-year-old Korean man with end stage renal disease (ESRD) was transferred to our hospital. Review of kidney biopsy finding was consistent with chronic tubulointerstitial nephritis with oxalate crystal deposits and drug history revealed long-term exposure to Chaga mushroom powder due to intractable atopic dermatitis. We suspected the association between Chaga mushroom and oxalate nephropathy, and measured the oxalate content of remained Chaga mushroom. The Chaga mushroom had extremely high oxalate content (14.2/100 g). Estimated daily oxalate intake of our case was 2 times for four years and 5 times for one year higher than that of usual diet. Chaga mushroom is a potential risk factor of chronic kidney disease considering high oxalate content. Nephrologist should consider oxalate nephropathy in ESRD patients exposed to Chaga mushrooms.

Design of Secure Protocol for Cloud-Assisted Electronic Health Record System Using Blockchain.

In the traditional electronic health record (EHR) management system, each medical service center manages their own health records, respectively, which are difficult to share on the different medical platforms. Recently, blockchain technology is one of the popular alternatives to enable medical service centers based on different platforms to share EHRs. However, it is hard to store whole EHR data in blockchain because of the size and the price of blockchain. To resolve this problem, cloud computing is considered as a promising solution. Cloud computing offers advantageous properties such as storage availability and scalability. Unfortunately, the EHR system with cloud computing can be vulnerable to various attacks because the sensitive data is sent over a public channel. We propose the secure protocol for cloud-assisted EHR system using blockchain. In the proposed scheme, blockchain technology is used to provide data integrity and access control using log transactions and the cloud server stores and manages the patient's EHRs to provide secure storage resources. We use an elliptic curve cryptosystems (ECC) to provide secure health data sharing with cloud computing. We demonstrate that the proposed EHR system can prevent various attacks by using informal security analysis and automated validation of internet security protocols and applications (AVISPA) simulation. Furthermore, we prove that the proposed EHR system provides secure mutual authentication using BAN logic analysis. We then compare the computation overhead, communication overhead, and security properties with existing schemes. Consequently, the proposed EHR system is suitable for the practical healthcare system considering security and efficiency.

Epidemiologic study on changes in occurrence of hemorrhagic fever with renal syndrome in Republic of Korea for 17 years according to age group: 2001-2017.

BACKGROUND: The potential effect of the inactivated hantavirus vaccine (IHV) remains controversial; however, it appears to be moderately effective for patients at high risk of hemorrhagic fever with renal syndrome (HFRS). This study of the epidemiology of HFRS from 2001 to 2017 aimed to examine those at high risk of HFRS in the Republic of Korea (ROK), particularly in terms of disease distribution according to age. METHODS: Raw data of HFRS patients recorded in Korea from 2001 to 2017 were obtained from the Korean Center for Disease Control and Prevention. Patients were divided into three age groups: ≤39, 40-69, and ≥ 70 years. The incidence rate per 100,000 individuals in each age group was calculated using population data. The 12-month year was divided into three-month quarters, and the number and proportion of patients corresponding to each quarter were calculated. The effects of time, sex, and quarter on HFRS incidence were assessed in a Poisson regression analysis. RESULTS: From 2001 to 2017, 7048 HFRS patients were recorded nationwide. Among these patients, the proportion of patients aged ≥70 years increased gradually from 16.4% in 2001 to 43.9% in 2017. Regarding the quarter-year periods, the fourth quarter contained a significantly higher proportion of patients in the ≥70 years group (69.4%) compared to the other age groups. In the Poisson regression analysis, patients aged ≥70 years had a significantly higher relative risk of HFRS incidence within each quartile compared to those in the other age groups (2.102- and 10.029-fold in the third and fourth quarters, respectively). An analysis of disease incidence revealed a more distinct pattern in seasonal variation among those aged ≥70 years compared with other age groups. CONCLUSIONS: In this study of the incidence of HFRS in the ROK, subjects aged ≥70 years exhibited a gradual increase in incidence and a distinct pattern of seasonal variation. These results may be important to identify individuals in Korea who are at high risk of developing HFRS. In future, active immunization programs will be needed to control HFRS among these high-risk groups in Korea.