Comparative Analysis of Muscle Atrophy During Spaceflight, Nutritional Deficiency and Disuse in the Nematode Caenorhabditis elegans.

While spaceflight is becoming more common than before, the hazards spaceflight and space microgravity pose to the human body remain relatively unexplored. Astronauts experience muscle atrophy after spaceflight, but the exact reasons for this and solutions are unknown. Here, we take advantage of the nematode C. elegans to understand the effects of space microgravity on worm body wall muscle. We found that space microgravity induces muscle atrophy in C. elegans from two independent spaceflight missions. As a comparison to spaceflight-induced muscle atrophy, we assessed the effects of acute nutritional deprivation and muscle disuse on C. elegans muscle cells. We found that these two factors also induce muscle atrophy in the nematode. Finally, we identified clp-4, which encodes a calpain protease that promotes muscle atrophy. Mutants of clp-4 suppress starvation-induced muscle atrophy. Such comparative analyses of different factors causing muscle atrophy in C. elegans could provide a way to identify novel genetic factors regulating space microgravity-induced muscle atrophy.

Associations of Perioperative Red Blood Cell Transfusion With Outcomes of Kidney Transplantation in Korea Over a 16-Year Period.

BACKGROUND: This study investigated the associations between transfusion of different types of red blood cell (RBC) preparations and kidney allograft outcomes after kidney transplantation (KT) over a 16-year period in Korea using a nationwide population-based cohort. METHODS: We investigated the reported use of RBCs during hospitalization for KT surgery, rejection, and graft failure status using nationwide data from the National Health Information Database (2002-2017). The associations between the type of perioperative RBC product and transplant outcomes were evaluated among four predefined groups: no RBC transfusion, filtered RBCs, washed RBCs, and packed RBCs (pRBCs). RESULTS: A total of 17,754 KT patients was included, among which 8,530 (48.0%) received some type of RBC transfusion. Of the patients who received RBC transfusion, 74.9%, 19.7%, and 5.4% received filtered RBCs, pRBCs, or washed RBCs, respectively. Regardless of the type of RBC products, the proportions of acute rejection and graft failure was significantly greater in patients receiving transfusion (P < 0.001). Cox proportional hazards regression analyses showed that the filtered RBC and pRBC groups were significantly associated with both rejection and graft failure. The washed RBC group also had hazard ratios greater than 1.0 for rejection and graft failure, but the association was not significant. Rejection-free survival of the pRBC group was significantly lower than that of the other groups (P < 0.001, log-rank test), and graft survival for the no RBC transfusion group was significantly greater than in the other groups (P < 0.001, log-rank test). CONCLUSION: Perioperative RBC transfusion was associated with poor graft outcomes. Notably, transfusion of pRBCs significantly increased transplant rejection. Therefore, careful consideration of indications for RBC transfusion and selection of the appropriate type of RBCs is necessary, especially for patients at high risk of rejection or graft failure.

De Novo Cancer Incidence after Kidney Transplantation in South Korea from 2002 to 2017.

Advances in patient care and immunosuppressive drugs have improved graft survival, resulting in an increase in kidney transplantation (KT); however, persistent immunosuppression is thought to cause late occurrence of cancer. This population-based study consisted of a total of 14,842 patients whose data from the years 2002 to 2017 were collected from the National Health Information Database in South Korea. Malignancies occurred in 7.6% of the total KT patients. Prostate and thyroid cancers were the most common in males and females, respectively. From the age-adjusted incidence analysis, Kaposi's sarcoma showed the highest standardized incidence ratio in both male and female patients. According to the linear regression model, cancer incidence in KT recipients under immunosuppressive conditions increased by approximately 0.1% each month. Patients' age over 39 and the use of prednisolone as an initial steroid regimen were associated with increased risk of cancer development after KT. Our regression and proportional hazards models will help clinicians to predict the approximate cancer incidence risk when monitoring KT recipients. Based on the largest available national database, screening or monitoring methods for cancer detection and prevention can be established for KT patients by considering the factors involved in cancer development.

Outcomes of kidney transplantation over a 16-year period in Korea: An analysis of the National Health Information Database.

BACKGROUND: This study investigated the outcomes of kidney transplantation (KT) over a 16-year period in Korea and identified risk factors for graft failure using a nationwide population-based cohort. METHODS: We investigated the Korean National Health Insurance Service-National Health Information Database. Health insurance claims for patients who underwent KT between 2002 and 2017 were analyzed. RESULTS: The data from 18,331 patients who underwent their first KT were reviewed. The percentage of antithymocyte globulin (ATG) induction continuously increased from 2.0% in 2002 to 23.5% in 2017. Rituximab began to be used in 2008 and had increased to 141 patients (9.6%) in 2013. Acute rejection occurred in 17.3% of all patients in 2002 but decreased to 6.3% in 2017. The rejection-free survival rates were 78.8% at 6 months after KT, 76.1% after 1 year, 67.5% after 5 years, 61.7% after 10 years, and 56.7% after 15 years. The graft survival rates remained over 80% until 12 years after KT, and then rapidly decreased to 50.5% at 16 years after KT. In Cox's multivariate analysis, risk factors for graft failure included being male, more recent KT, KT from deceased donor, use of ATG, basiliximab, or rituximab, tacrolimus use as an initial calcineurin inhibitor, acute rejection history, and cytomegalovirus infection. CONCLUSIONS: ATG and rituximab use has gradually increased in Korea and more recent KT is associated with an increased risk of graft failure. Therefore, meticulous preoperative evaluation and postoperative management are necessary in the case of recent KT with high risk of graft failure.

Perioperative blood usage and therapeutic plasma exchange in kidney transplantation during a 16-year period in South Korea.

BACKGROUND: The frequency of kidney transplantation (KT) is increasing. Blood transfusion plays an important role in the success of KT. Therapeutic plasma exchange (TPE) is also used for desensitisation in ABO-incompatible KT and treatment of antibody-mediated rejection. MATERIALS AND METHODS: We analysed red blood cell (RBC), platelet, and fresh frozen plasma (FFP) usage and the number of TPE procedures performed during the hospitalisation of KT patients from 2002 to 2017 using the Korean National Health Insurance Service-National Health Information Database. RESULTS: A total of 18,331 KT patients were included in this study. The number of transfused RBCs continued to increase from 4,806 units in 2002-2005 to 12,390 units in 2014-2017. However, the average number of RBCs transfused per patient decreased from 2.17 to 1.79 units. Estimated platelet usage increased from 4,259 units in 2002-2005 to 11,519 units in 2014-2017, and the proportion of filtered platelets increased from 72.6% to 83.4% during the same period. There was a huge increase in the total number of FFP units used, from 2,255 units in 2002-2005 to 51,531 units in 2014-2017. The number of TPE procedures performed also increased from 296 to 6,479 during the same period. Patients with acute rejection accounted for 8.8% of all KT patients, and more RBC and FFP were used for these patients and a greater number of TPE procedures were performed compared to those who did not experience rejection. DISCUSSION: Blood usage and TPE have increased steadily with the increasing numbers of KTs. Therefore, continuous efforts are needed to ensure appropriate perioperative blood preparation and usage for KT patients.

Muscle and epidermal contributions of the structural protein ß-spectrin promote hypergravity-induced motor neuron axon defects in C. elegans.

Biology is adapted to Earth's gravity force, and the long-term effects of varying gravity on the development of animals is unclear. Previously, we reported that high gravity, called hypergravity, increases defects in the development of motor neuron axons in the nematode Caenorhabditis elegans. Here, we show that a mutation in the unc-70 gene that encodes the cytoskeletal ß-spectrin protein suppresses hypergravity-induced axon defects. UNC-70 expression is required in both muscle and epidermis to promote the axon defects in high gravity. We reveal that the location of axon defects is correlated to the size of the muscle cell that the axon traverses. We also show that mutations that compromise key proteins of hemidesmosomal structures suppress hypergravity-induced axon defects. These hemidesmosomal structures play a crucial role in coupling mechanical force between the muscle, epidermis and the external cuticle. We speculate a model in which the rigid organization of muscle, epidermal and cuticular layers under high gravity pressure compresses the narrow axon migration pathways in the extracellular matrix hindering proper axon pathfinding of motor neurons.

Prevalence and Risk Factors for Extended-Spectrum ß-Lactamase-Producing Klebsiella pneumoniae Colonization in Intensive Care Units.

Active surveillance culture (ASC) can help detect hidden reservoirs, but the routine use of ASC for extended spectrum ß-lactamase-producing Enterobacteriaceae is controversial in an endemic situation. We aimed to determine the prevalence and risk factors of extended spectrum ß-lactamase-producing Klebsiella pneumoniae (EBSL-Kpn) colonization among intensive care unit (ICU)-admitted patients. Prospective screening of ESBL-Kpn colonization was performed for ICU-admitted patients within 48 hours for two months. A perirectal swab sample was inoculated on MacConkey agar supplemented with 2 µg/mL ceftazidime. ESBL genotype was determined by PCR-sequencing, and clonal relatedness was evaluated by pulsed-field gel electrophoresis (PFGE). The risk factors of ESBL-Kpn colonization were evaluated. The ESBL-Kpn colonization rate among the 281 patients at ICU admission was 6.4% (18/281), and blaCTX-M-15 was detected in all isolates. ESBL producers also showed resistance to fluoroquinolone (38.9%, 7/18). All isolates had the same ESBL genotype (blaCTX-M-15) and a highly clustered PFGE pattern, suggesting cross-transmission without a documented outbreak. In univariate analysis, the risk factor for ESBL-Kpn colonization over the control was the length of hospital stay (odds ratio=1.062; P=0.019). Routine use of ASC could help control endemic ESBL-Kpn for ICU patients.

Diagnostic performance of CA 125, HE4, and risk of Ovarian Malignancy Algorithm for ovarian cancer.

OBJECTIVE: We evaluated the diagnostic performance of CA 125, HE4, and ROMA for ovarian cancer in Koreans and set optimal cutoffs. METHOD: Serum levels of HE4 and CA 125 and the ROMA score were determined in 762 patients with benign gynecological disease and 70 with ovarian cancer. Receiver operating characteristic curves were constructed to calculate the areas under the curve (AUC). CA 125, HE4, and ROMA exhibiting maximum Youden index were determined, respectively, as the optimal cutoffs, and sensitivity and specificity were evaluated by applying those cutoffs. RESULTS: In benign diseases, CA 125 significantly increased in patients with uterine myoma, adenomyosis, endometrial pathology, or endometriosis, but HE4 only increased in patients with adenomyosis. For the diagnosis of ovarian cancer, the combination of CA 125, HE4, and age showed the highest AUC value of 0.892 in the premenopausal group, and ROMA demonstrated the best diagnostic performance, with an AUC of 0.935 in postmenopausal patients. When the optimal cutoff values for CA 125 and HE4 were applied, the sensitivities of CA 125, HE4, and ROMA in premenopausal women were all the same at 0.714, while the specificities were 0.841, 0.974, and 0.972, respectively. In the postmenopausal group, the sensitivities of these markers were 0.857, 0.804, and 0.929, and the specificities were 0.836, 0.887, and 0.800, respectively. CONCLUSION: Although all markers demonstrated good diagnostic performance, they varied depending on the pathologic types of benign diseases and ovarian cancer. For accurate diagnosis of ovarian cancer, CA 125, HE4, and ROMA should be used complementarily.

Superhydrophobic Water-Solid Contact Triboelectric Generator by Simple Spray-On Fabrication Method.

Energy harvesting is a method of converting energy from ambient environment into useful electrical energy. Due to the increasing number of sensors and personal electronics, energy harvesting technologies from various sources are gaining attention. Among energy-harvesting technologies, triboelectric nanogenerator (TENG) was introduced as a device that can effectively generate electricity from mechanical motions by contact-electrification. Particularly, liquid-solid contact TENGs, which use the liquid itself as a triboelectric material, can overcome the inevitable friction wear between two solid materials. Using a commercial aerosol hydrophobic spray, liquid-solid contact TENGs, with a superhydrophobic surface (contact angle over 160°) can be easily fabricated with only a few coating processes. To optimize the fabrication process, the open-circuit voltage of sprayed superhydrophobic surfaces was measured depending on the number of coating processes. To demonstrate the simple fabrication and applicability of this technique on random 3D surfaces, a liquid-solid contact TENG was fabricated on the brim of a cap (its complicated surface structure is due to the knitted strings). This simple sprayed-on superhydrophobic surface can be a possible solution for liquid-solid contact TENGs to be mass produced and commercialized in the future.

Analysis of red blood cell use in elective surgeries over 12 years in Korea.

BACKGROUND: Red blood cell (RBC) transfusion is a lifesaving process for patients with perioperative bleeding, but transfusion can cause adverse events. Effective utilization and management of blood products as a limited resource is essential when considering cost-efficiency and patient safety. STUDY DESIGN AND METHODS: We analyzed the number of RBC units used during the hospitalization of patients who had undergone surgical procedures from 2002 to 2013 using National Health Insurance Service-National Sample Cohort data, which include a total of 487,238 cases for 206 selected operations. RESULTS: RBC units were used in 39,637 (8.1%) cases. A total of 60,815 RBC units were transfused with a mean of 0.13 units per patient overall and a mean of 1.53 units per case receiving RBC transfusion. In addition, 56.7% of the RBC units were transfused for females, and 60.1% of RBC units were transfused into patients aged 60 or older. RBC units were used most often in orthopedic surgeries (33.8%), followed by general surgeries (12.0%) and vascular surgeries (11.8%). The number of operations performed in the cohort increased from 27,690 in 2002 to 49,473 in 2013, and the mean number of RBC units used per operation also increased from 0.08 units in 2002 to 0.15 units in 2013. CONCLUSION: Continuous management for blood preparation and transfusion is needed for efficient utilization of blood. Periodic investigation on the use of blood products through nationwide studies could suggest data applicable to blood product preparation for various elective surgical operations.

Laboratory and Clinical Performance of the ADVIA Centaur Anticyclic Citrullinated Peptide Assay for Rheumatoid Arthritis Diagnosis.

CONTEXT.­: Anticyclic citrullinated peptide antibodies are important serologic markers for the diagnosis of rheumatoid arthritis. Several kinds of test reagents for automated immunoassay systems have been developed and used in recent years. OBJECTIVE.­: To evaluate the analytic and diagnostic performance of the new ADVIA Centaur anticyclic citrullinated peptide assay (Siemens Healthineers, Erlangen, Germany) compared with the Elecsys assay (Roche Diagnostics, Mannheim, Germany). DESIGN.­: A total of 576 serum samples were collected from subjects, including 156 patients (27%) with rheumatoid arthritis. Precision performance and analytical measurement range for the ADVIA assay were evaluated. Diagnostic performance of the 2 assays was compared based on sensitivity, specificity, and area under the receiver operating characteristic curves. RESULTS.­: The ADVIA assay showed a within-laboratory imprecision of 3.4% coefficient of variation for levels of 3.36 and 24.99 U/mL. This assay was demonstrated to be linear from 0.4 to 180.0 U/mL. With default cutoff values, sensitivity and specificity for diagnosing rheumatoid arthritis were 71.2% and 97.9%, respectively, for the ADVIA assay and 73.1% and 96.9%, respectively, for the Elecsys assay. With the best cutoff values from the analyses of the receiver operating characteristic curve, the sensitivity of the 2 assays was the same at 75.6%. However, the specificity of the ADVIA assay was 96.4%, whereas that of the Elecsys assay was 94.3%. The area under the receiver operating characteristic curve value for the ADVIA assay was 0.867, which was not significantly different from that of the Elecsys assay (0.865). CONCLUSIONS.­: The ADVIA Centaur anticyclic citrullinated peptide assay showed good analytic and diagnostic performance in diagnosing rheumatoid arthritis.

Energy-loss return gate via liquid dielectric polarization.

There has been much research on renewable energy-harvesting techniques. However, owing to increasing energy demands, significant energy-related issues remain to be solved. Efforts aimed at reducing the amount of energy loss in electric/electronic systems are essential for reducing energy consumption and protecting the environment. Here, we design an energy-loss return gate system that reduces energy loss from electric/electronic systems by utilizing the polarization of liquid dielectrics. The use of a liquid dielectric material in the energy-loss return gate generates electrostatic potential energy while reducing the dielectric loss of the electric/electronic system. Hence, an energy-loss return gate can make breakthrough impacts possible by amplifying energy-harvesting efficiency, lowering the power consumption of electronics, and storing the returned energy. Our study indicates the potential for enhancing energy-harvesting technologies for electric/electronics systems, while increasing the widespread development of these systems.

Retrospective analysis on the diagnostic performances and signal-to-cut-off ratios of the Elecsys Anti-HCV II assay.

BACKGROUND: Anti-HCV assays are widely used as a screening tool for HCV infection. However, diagnostic performances and effective signal-to-cut-off ratios (S/COs) for predicting true HCV infections would vary according to the assays used. Thus, we evaluated the diagnostic performances of the new Elecsys Anti-HCV assay. METHODS: A total of 41 694 cases tested by the Elecsys Anti-HCV II assay (Roche Diagnostics, Germany) during January 2013 to December 2015 were retrospectively analyzed by comparing with the diagnosis on HCV infections determined by patients' medical records and results of laboratory tests. RESULTS: Excluding 62 cases with unclear history of HCV infection, 430 and 41 202 cases were respectively assorted as "true infection" and "no evidence of infection," and 99.85% of the initial results by the Elecsys assay were concordant with the diagnosis on HCV infection. Sensitivity, specificity, positive and negative predictive values were respectively 99.30%, 99.86%, 88.04%, and 99.99%, where the prevalence of the HCV infection was 1.0%. The area under the receiver operating characteristics curve value of the Elecsys assay was 0.9980 (95% confidence interval [CI]=0.9944 to 1.0017). The S/CO by the Elecsys assay for predictive of a true-positive ≥95% of the time was 19.0 (95% CI=15.0 to 25.1). CONCLUSION: The Elecsys Anti-HCV II assay showed excellent diagnostic performances, particularly in terms of sensitivity, specificity, and NPV. However, the results obtained by this assay with S/CO less than a certain value would need to be retested by HCV RNA PCR or another anti-HCV assay.

Application of Multiplex Ligation-Dependent Probe Amplification Assay for Genotyping Major Blood Group Systems Including DEL Variants in the D-Negative Korean Population.

BACKGROUND: The DEL blood type, a very weak D variant, is a major concern in the field of transfusion medicine because of its potential to cause anti-D alloimmunization. We investigated the molecular basis of serologically D-negative phenotypes, including the DEL type, and the distribution of other blood group systems in the Korean population using the recently developed multiplex ligation-dependent probe amplification (MLPA) assay. METHODS: Blood group genotyping using the MLPA assay and RhCE phenotyping were performed on randomly selected 95 D-negative red blood cell products. The MLPA results were verified by multiplex PCR for the RHD promoter, exons 4, 7, and 10 and by direct sequencing of RHD exon 9. RESULTS: Out of 95 cases, total deletion of the RHD was observed in 74 cases (77.9%) and four cases (4.2%) had an RHD-CE-D hybrid allele. The other 17 cases (17.9%) had an RHD(1227G>A) allele, which was further confirmed by sequencing analysis. The RhCE phenotypes of RHD(1227G>A) alleles were composed of 14 Cce and 3 CcEe, and all 60 cases of the ce phenotype were revealed to have a total deletion of the RHD. Genotyping results and allele distribution of the other 17 blood group systems were consistent with previous reports on the East Asian population. CONCLUSIONS: MLPA assay correctly determined RHD genotype, including RHD-CE-D hybrid alleles or RHD(1227G>A) allele, and other clinically relevant blood group genotypes in D-negative Koreans. The use of MLPA assay on serologically D-negative individuals may help improve transfusion safety by preventing anti-D alloimmunization.