The promise of chiral electrocatalysis for efficient and sustainable energy conversion and storage: a comprehensive review of the CISS effect and future directions.

The integration of chirality, specifically through the chirality-induced spin selectivity (CISS) effect, into electrocatalytic processes represents a pioneering approach for enhancing the efficiency of energy conversion and storage systems. This review delves into the burgeoning field of chiral electrocatalysis, elucidating the fundamental principles, historical development, theoretical underpinnings, and practical applications of the CISS effect across a spectrum of electrocatalytic reactions, including the oxygen evolution reaction (OER), oxygen reduction reaction (ORR), and hydrogen evolution reaction (HER). We explore the methodological advancements in inducing the CISS effect through structural and surface engineering and discuss various techniques for its measurement, from magnetic conductive atomic force microscopy (mc-AFM) to hydrogen peroxide titration. Furthermore, this review highlights the transformative potential of the CISS effect in addressing the key challenges of the NRR and CO2RR processes and in mitigating singlet oxygen formation in metal-air batteries, thereby improving their performance and durability. Through this comprehensive overview, we aim to underscore the significant role of incorporating chirality and spin polarization in advancing electrocatalytic technologies for sustainable energy applications.

Integrated CO2 capture and electrochemical upgradation: the underpinning mechanism and techno-chemical analysis.

Coupling post-combustion CO2 capture with electrochemical utilization (CCU) is a quantum leap in renewable energy science since it eliminates the cost and energy involved in the transport and storage of CO2. However, the major challenges involved in industrial scale implementation are selecting an appropriate solvent/electrolyte for CO2 capture, modeling an appropriate infrastructure by coupling an electrolyser with a CO2 point source and a separator to isolate CO2 reduction reaction (CO2RR) products, and finally selection of an appropriate electrocatalyst. In this review, we highlight the major difficulties with detailed mechanistic interpretation in each step, to find out the underpinning mechanism involved in the integration of electrochemical CCU to achieve higher-value products. In the past decades, most of the studies dealt with individual parts of the integration process, i.e., either selecting a solvent for CO2 capture, designing an electrocatalyst, or choosing an ideal electrolyte. In this context, it is important to note that solvents such as monoethanolamine, bicarbonate, and ionic liquids are often used as electrolytes in CO2 capture media. Therefore, it is essential to fabricate a cost-effective electrolyser that should function as a reversible binder with CO2 and an electron pool capable of recovering the solvent to electrolyte reversibly. For example, reversible ionic liquids, which are non-ionic in their normal forms, but produce ionic forms after CO2 capture, can be further reverted back to their original non-ionic forms after CO2 release with almost 100% efficiency through the chemical or thermal modulations. This review also sheds light on a focused techno-economic evolution for converting the electrochemically integrated CCU process from a pilot-scale project to industrial-scale implementation. In brief, this review article will summarize a state-of-the-art argumentation of challenges and outcomes over the different segments involved in electrochemically integrated CCU to stimulate urgent progress in the field.

Recurrent C3 Glomerulonephritis along with BK-Virus-Associated Nephropathy after Kidney Transplantation: A Case Report.

C3 glomerulonephritis (C3GN) is a rare cause of end-stage kidney disease and frequently recurrent in allografts following kidney transplantation (KT). Herein, we describe the case of a kidney transplant recipient who developed recurrent C3GN along with BK-virus-associated nephropathy (BKVAN) following KT. A 33-year-old man diagnosed with membranoproliferative glomerulonephritis 17 years ago underwent preemptive KT with a donor kidney from his aunt. Proteinuria gradually increased after 3 months following KT, and graft biopsy was performed 30 months after KT. Histopathological examination revealed recurrent C3GN. The dosages of triple immunosuppressive maintenance therapy agents were increased. Subsequently, serum C3 levels recovered to normal levels. However, at 33 months following KT, the BK viral load increased and graft function gradually deteriorated; a second graft biopsy was performed at 46 months following KT, which revealed BKVAN and decreased C3GN activity. The dosages of immunosuppressive agents were decreased; subsequently, BKVAN improved and graft function was maintained with normal serum C3 levels at 49 months following KT. This case indicates that C3GN is highly prone to recurrence following KT and that immunosuppressive therapy for C3GN increases the risk of BKVAN.

Outbreak of Parainfluenza Virus During the COVID-19 Pandemic at a University Hospital in Korea.

BACKGROUND: The incidence of respiratory viral diseases including parainfluenza virus (PIV) infection has decreased noticeably due to strict quarantine measures during the COVID-19 pandemic. However, the recent outbreak of PIV in children occurred unexpectedly and the distribution pattern showed prominent differences from before the COVID-19 pandemic. PIV is one of the major viral pathogens related to acute lower respiratory infection in young children and the elderly. Accordingly, the authors intended to identify the incidence and distribution pattern of PIV outbreaks and to contribute to public health by providing information on it. METHODS: This study was conducted retrospectively to investigate the incidence and distribution of PIV according to age group, gender, month, and season, and to analyze the co-infections from March 2020 to February 2022. The detection for respiratory microorganisms was performed through FilmArray assay. RESULTS: The overall incidence for at least one respiratory pathogen was 45.9% (665/1,450). PIV was not detected at all from March 2020 to August 2021. However, it was first detected in September 2021 and the rate in the month that followed, October, accounted for 60% (114/190) of the total PIV infections during the entire study period. It also accounted for 44.9% (190/423) of patients with respiratory pathogens from September 2021 to February 2022. It reached the highest proportion at 90.5% (114/126) in October 2021. As for the distribution according to the age groups, group 3 (58.4%) accounted for the highest percentage, followed by group 4 (21.1%). In the PIV positive cases, the overall rate of more than two respiratory pathogens was 32.6% (62/190). The most common pattern of co-infection was PIV3 with rhinovirus/enterovirus (67.7%), followed by PIV3 with adenovirus (8.1%) and PIV3 with rhinovirus/enterovirus and adenovirus (8.1%). CONCLUSIONS: The COVID-19 pandemic has brought about many changes in our daily lives. It has been confirmed that the seasonal distribution of PIV was distinctly different from before the COVID-19 pandemic. It is anticipated that this phenomenon will affect the incidence or distribution of other respiratory pathogens and viral epidemiology. Therefore, clinicians should pay attention to these changes in terms of public health.

Clinical Application of a Solid-Phase Assay for SARS-CoV-2 IgG to Predict a Neutralizing Antibody Titer.

BACKGROUND: To assess protective immunity among a general population against severe acute respiratory syndrome coronavirus 2, the correlation of the commercially available solid-phase assay (SPA) for SARS-CoV-2 IgG with a neutralization assay must be investigated. METHODS: Both the neutralization assay and SPA were performed on samples of 143 recovered coronavirus disease 2019 (COVID-19) patients. SARS-CoV-2 IgG was measured using two SPAs for the chemiluminescence immunoassay principle with different target proteins: nucleocapsid and spike protein (Architect i2000SR [Abbott] and Liaison XL [DiaSorin], respectively). The plaque reduction neutralization test (PRNT) was conducted to obtain titers for the neutralizing antibody. RESULTS: All patients had PRNT titers ranging from 10 to 2,560. Spike Ab SPA had greater sensitivity than nucleocapsid Ab SPA (81.1% [116/143] and 70.6% [101/143], respectively, p = 0.003). The values measured for both SPAs had a positive correlation with the PRNT titers (both R = 0.77, p < 0.001). To predict a high PRNT titer (≥ 160), cutoff values of two SPAs were adjusted based on receiver-operating characteristics curve analysis. The nucleocapsid Ab SPA (cutoff index of 4.17) attained 90.3% sensitivity and 75.9% specificity, whereas the spike Ab SPA (cutoff value of 109 unit/mL) attained 87.1% sensitivity and 89.3% specificity. Therefore, the spike Ab SPA had greater specificity than the nucleocapsid Ab SPA (p = 0.003). CONCLUSIONS: The qualitative SPA for nucleocapsid Ab, as well as the quantitative SPA for spike Ab, had a modest positive correlation with the neutralization assay. However, spike Ab SPA was more suitable for neutralizing capacity.

Age-Related Variation of Syndecan-1 Levels in Saliva and Plasma of Healthy Individuals.

BACKGROUND: Saliva contains various cells, proteins, and molecules, and it is emerging as a material for diagnosing various diseases. Syndecan-1 (SDC-1) is a member of cell surface heparan sulfate proteoglycans and is mainly expressed in epithelial cells and plasma cells. SDC-1 is known to be associated with various cancers and inflammatory response, but there are few studies related to the change of SDC-1 levels in the saliva and plasma of healthy individuals due to aging process. METHODS: The study was conducted on 61 females who were healthy without any metabolic diseases, systemic infection, and oral cavity lesions. The subjects were divided into two groups based on age. Those below 40 years were placed in Group I and those who were 40 years and above were placed in Group II. Saliva was collected according to the guideline and the salivary flow rate (SFR) was determined. SDC-1 levels in the plasma and saliva were measured using a commercially available sandwich ELISA method. RESULTS: Age was significantly different between Group I and II (28.0 ± 2.5 vs. 47.4 ± 5.5, p < 0.001). SFR also showed a significant difference between Group I and II [0.32 (0.13 - 0.39) vs. 0.25 (0.16 - 0.35) ng/mL, p = 0.003]. Salivary SDC-1 level in Group I was significantly higher than that in Group II (p < 0.001). In addition, plasma SDC-1 level in Group I was also higher than that in Group II (p < 0.001). SFR was not significantly correlated as age increased, but it showed a significant negative correlation with salivary SDC-1 (r = -0.607, p < 0.001) and plasma SDC-1 levels (r = -0.373, p = 0.003). Salivary SDC-1 level was significantly correlated with plasma SDC-1 level (r = 0.331, p = 0.012). CONCLUSIONS: In the younger group, the SFR, salivary, and plasma SDC-1 levels were significantly higher than in the older group. Salivary and plasma SDC-1 showed significant negative correlation as age increased. Although this study was not conducted on a large scale, it might be thought to provide information on the age-related variation for salivary and plasma SDC-1 levels in the aging process.

Mycophenolic Acid Trough Concentration and Dose Are Associated with Hematologic Abnormalities but Not Rejection in Kidney Transplant Recipients.

BACKGROUND: Little is known regarding the safe fixed dose of mycophenolic acid (MPA) for preventing biopsy-proven acute rejection (BPAR) in kidney transplant recipients (KTRs). We investigated the correlation of MPA trough concentration (MPA C0) and dose with renal transplant outcomes and adverse events. METHODS: This study included 79 consecutive KTRs who received MPA with tacrolimus (TAC) and corticosteroids. The MPA C0 of all the enrolled KTRs was measured, which was determined monthly by using particle-enhanced turbidimetric inhibition immunoassay for 12 months, and clinical data were collected at each time point. The clinical endpoints included BPAR, any cytopenia, and BK or cytomegalovirus infections. RESULTS: No differences in MPA C0 and dose were observed between KTRs with or without BPAR or viral infections under statistically comparable TAC concentrations. MPA C0 was significantly higher in patients with leukopenia (P = 0.021) and anemia (P = 0.002) compared with those without cytopenia. The MPA dose was significantly higher in patients with thrombocytopenia (P = 0.002) compared with those without thrombocytopenia. MPA C0 ≥ 3.5 µg/mL was an independent risk factor for leukopenia (adjusted odds ratio [AOR], 3.80; 95% confidence interval [CI], 1.24-11.64; P = 0.019) and anemia (AOR, 5.90; 95% CI, 1.27-27.51; P = 0.024). An MPA dose greater than the mean value of 1,188.8 mg/day was an independent risk factor for thrombocytopenia (AOR, 3.83; 95% CI, 1.15-12.78; P = 0.029). However, an MPA dose less than the mean value of 1,137.3 mg/day did not increase the risk of BPAR. CONCLUSION: Either a higher MPA C0 or dose is associated with an increased risk of cytopenia, but neither a lower MPA C0 nor dose is associated with BPAR within the first year of transplantation. Hence, a reduced MPA dose with TAC and corticosteroids might be safe in terms of reducing hematologic abnormalities without causing rejection.

Comparison of Transplant Outcomes for Low-level and Standard-level Tacrolimus at Different Time Points after Kidney Transplantation.

BACKGROUND: Optimal tacrolimus (TAC) trough levels for different periods after kidney transplantation (KT) has not been definitely established. This study aimed to investigate transplant outcomes of low-level (LL) and standard-level (SL) TAC according to post-transplant period. METHODS: A total of 278 consecutive kidney transplant recipients (KTRs) receiving TAC-based immunosuppression were divided into LL and SL-TAC groups (4-7 and 7-12 ng/mL for 0-2 months, 3-6 and 6-10 ng/mL for 3-6 months, 2-5 and 5-8 ng/mL for 7-12 months, respectively) according to TAC trough level at each period. We compared estimated glomerular filtration rate (eGFR), biopsy-proven acute rejection (BPAR), de novo donor-specific antibody (dnDSA), calcineurin inhibitor (CNI) toxicity, opportunistic infection, and allograft survival. RESULTS: SL-TAC group showed significantly higher mean eGFR at 0-2 months than LL-TAC group (72.1 ± 20.3 vs. 64.2 ± 22.7 mL/min/1.73m2; P = 0.003). Incidence of BPAR at 7-12 months was significantly lower in SL-TAC group than in LL-TAC group (0.0% vs. 3.9%; P = 0.039). Patients with persistent SL-TAC lasting 12 months showed higher eGFR at 7-12 months than those with persistent LL-TAC (65.5 ± 13.0 vs. 57.9 ± 13.9 mL/min/1.73m2; P = 0.007). No significant differences in dnDSA, CNI toxicity, serious infections, or allograft survival were observed. CONCLUSIONS: Maintenance of proper TAC trough level after 6 months could reduce BPAR without adverse drug toxicities in KTRs. Moreover, persistent SL-TAC during the first year after KT might have a beneficial effect on a trend for a lower incidence of dnDSA and better renal allograft function.

Characteristics and Clinical Significance of De Novo Donor-Specific Anti-HLA Antibodies after Kidney Transplantation.

BACKGROUND: The association of de novo donor-specific anti-human leukocyte antigens (HLA) antibodies (DSA) and development of antibody-mediated rejection (AMR) in kidney transplant recipients (KTRs) is still undetermined. METHODS: We prospectively screened de novo DSA in 167 KTRs during 32 months after kidney transplantation (KT). Timing of DSA detection was at 3, 6, and 12 months post-transplant and annually thereafter and when clinically indicated. DSA levels were determined by Luminex assays and expressed as mean fluorescence intensity (MFI). We evaluated the incidence, characteristics of DSA, and association between DSA and tacrolimus trough levels or AMR. RESULTS: De novo DSA developed in 16 KTRs (9.6%) and acute AMR occurred more commonly in KTRs with de novo DSA compared to KTRs without de novo DSA (18.8% vs. 0%, P < 0.001). All de novo DSA were against class II antigens. The mean number of DSA was 1.8 ± 1.2 and the average MFI of DSA was 7,399 ± 5,470. Tacrolimus trough level during the first 0-2 months after KT was an independent predictor of DSA development (hazard ratio, 0.70; 95% confidence interval, 0.50-0.99; P = 0.043). No differences were found in the number of DSA, average MFI of DSA, and tacrolimus levels during the first year between de novo DSA-positive KTRs with AMR and those without AMR. CONCLUSION: The results of our study suggest that monitoring of DSA and maintaining proper tacrolimus levels are essential to prevent AMR during the initial period after KT.

Organic-inorganic hybrid photocatalyst for carbon dioxide reduction.

Efficient hybrid photocatalysts for carbon dioxide reduction were developed from dye-sensitized TiO2 nanoparticles and their catalytic performance was optimized by ternary organic/inorganic components. Thus, the hybrid system consists of (E)-2-cyano-3-(5'-(5''-(p-(diphenylamino)phenyl)thiophen-2''-yl)thiophen-2'-yl)-acrylic acid as a sensitizer and fac-[Re(4,4'-bis(diethoxyphosphorylmethyl)-2,2'-bipyridine)(CO)3Cl] as a reduction catalyst (ReP), both of which have been fixed onto TiO2 semiconductors (s-TiO2, h-TiO2, d-TiO2). Mott-Schottky analysis on flat-band potential (Efb) of TiO2 mesoporous films has verified that Efb can be finely modulated by volume variation of water (0 to 20 vol%). The increase of added water resulted in substantial positive shifts of Efb from -1.93 V at 0 vol% H2O, to -1.74 V (3 vol% H2O), to -1.56 V (10 vol% H2O), and to -1.47 V (20 vol% H2O). As a result, with addition of 3-10 vol% water in the photocatalytic reaction, conversion efficiency of CO2 to CO increased significantly reaching a TON value of ∼350 for 30 h. Catalytic activity enhancement is mainly attributed to (1) the optimum alignment of Efb by 3-10 vol% water with respect to the of the dye and Ered of ReP for smooth electron transfer from photo-excited dye to RePvia the TiO2 semiconductor and (2) the water-induced acceleration of chemical processes on the fixed ReP. In addition, the energy level was further tuned by variation of the dye and ReP amounts. We also found that the intrinsic properties of TiO2 sources (morphology, size, agglomeration) exert a great influence on the overall photocatalytic activity of this hybrid system. Implications of the present observations and reaction mechanisms are discussed in detail.

Increased Circulating T Lymphocytes Expressing HLA-DR in Kidney Transplant Recipients with Microcirculation Inflammation.

We consecutively enrolled 82 kidney transplant recipients (KTRs) with stable renal function and 24 KTRs who underwent indication biopsy to compare the histological grading of renal allografts with the activity of circulating T lymphocyte subsets and monocytes determined by flow cytometry, which were obtained at 2 weeks after kidney transplantation (KT) and at the time of indication biopsy, respectively. The sum of the scores of glomerulitis (g) + peritubular capillaritis (ptc), inflammation (i) + tubulitis (t), interstitial fibrosis (ci) + tubular atrophy (ct), and fibrointimal thickening (cv) + arteriolar hyaline thickening (ah) was used to assign a histological grade to the renal allograft samples. The frequencies of CD4⁺HLA-DR⁺/CD4⁺ T cells and CD8⁺HLA-DR⁺/CD8⁺ T cells were significantly increased in KTRs with a microcirculation inflammation (MI) sum score ≥ 1 when compared with KTRs with an MI sum score = 0 as well as stable KTRs. In these 2 subsets, only CD4⁺HLA-DR⁺/CD4⁺ T cells were positively correlated with MI sum scores. Analysis using the receiver operating characteristic (ROC) curve showed that antibody-mediated rejection (AMR) could be predicted with a sensitivity of 80.0% and a specificity of 94.7%, using a cutoff value of 29.6% frequency of CD4⁺HLA-DR⁺/CD4⁺ T cells. MI was significantly associated with an increased frequency of activated T lymphocytes expressing human leukocyte antigen-antigen D related (HLA-DR). Further studies should focus on validating the utility of circulating CD4⁺HLA-DR⁺/CD4⁺ T cells as a noninvasive, immunologic monitoring tool for the prediction of AMR.

Widely Controllable Syngas Production by a Dye-Sensitized TiO2 Hybrid System with ReI and CoIII Catalysts under Visible-Light Irradiation.

Visible-light irradiation of a ternary hybrid catalyst prepared by grafting a dye, an H2 evolving CoIII catalyst and a CO-producing ReI catalyst on TiO2 have been found to produce both H2 and CO (syngas) in CO2 -saturated N,N-dimethyl formamide (DMF)/water solution containing a 0.1 m sacrificial electron donor. The H2 /CO ratios are effectively controlled by changing either the water content of the solvent or the molar ratio of the ReI and CoIII catalysts ranging from 1:2 to 15:1. The controlled syngas formation is discussed in terms of competitive electron flow from TiO2 to each of the CO2 -reduction and hydrogen-evolving sites depending on the efficiencies of the two catalytic reaction cycles under given reaction conditions.

Usefulness of mycophenolic acid monitoring with PETINIA for prediction of adverse events in kidney transplant recipients.

Background Therapeutic drug monitoring of mycophenolic acid (MPA) is required to optimize the immunosuppressive effect and minimize toxicity. We validated a new particle-enhanced turbidimetric inhibition immunoassay (PETINIA) for the determination of MPA levels and evaluated the relationship of MPA trough level with drug-related adverse events. Methods PETENIA and liquid chromatography-mass spectrometry (LC-MS) were used to determine MPA concentrations from 54 kidney transplant recipients (KTRs). Agreement between PETINIA and LC-MS results was assessed by Passing-Bablok regression and the Bland-Altman plot method. The association of adverse events with MPA trough level obtained by PETINIA was analyzed. Results PETINIA revealed a good agreement with the LC-MS; Regression analysis gave an equation of y = 1.27x - 0.12 (r(2) = 0.975, p < 0.001). PETINIA showed a systemic positive bias with a mean difference of 0.66 mg/L compared to LC-MS. However, the magnitude of the positive bias decreased to 0.44 mg/L within the therapeutic range of MPA. Multiple logistic regression showed that MPA trough level determined by PETINIA was an independent risk factor for adverse events (odds ratio 2.28, 95% CI 1.25-4.16, p = 0.007). MPA trough level predicted adverse events with a sensitivity of 77.8% and a specificity of 86.7% using a cut-off level of 5.25 mg/L. Conclusions Good correlation between the two methods indicates that PETINIA is an acceptable method for the monitoring of MPA therapeutic levels. Furthermore, MPA trough level obtained by PETINIA is a useful monitoring tool to minimize toxicity in KTRs.

Highly Robust Hybrid Photocatalyst for Carbon Dioxide Reduction: Tuning and Optimization of Catalytic Activities of Dye/TiO2/Re(I) Organic-Inorganic Ternary Systems.

Herein we report a detailed investigation of a highly robust hybrid system (sensitizer/TiO2/catalyst) for the visible-light reduction of CO2 to CO; the system comprises 5'-(4-[bis(4-methoxymethylphenyl)amino]phenyl-2,2'-dithiophen-5-yl)cyanoacrylic acid as the sensitizer and (4,4'-bis(methylphosphonic acid)-2,2'-bipyridine)Re(I)(CO)3Cl as the catalyst, both of which have been anchored on three different types of TiO2 particles (s-TiO2, h-TiO2, d-TiO2). It was found that remarkable enhancements in the CO2 conversion activity of the hybrid photocatalytic system can be achieved by addition of water or such other additives as Li(+), Na(+), and TEOA. The photocatalytic CO2 reduction efficiency was enhanced by approximately 300% upon addition of 3% (v/v) H2O, giving a turnover number of ≥570 for 30 h. A series of Mott-Schottky (MS) analyses on nanoparticle TiO2 films demonstrated that the flat-band potential (V(fb)) of TiO2 in dry DMF is substantially negative but positively shifts to considerable degrees in the presence of water or Li(+), indicating that the enhancement effects of the additives on the catalytic activity should mainly arise from optimal alignment of the TiO2 V(fb) with respect to the excited-state oxidation potential of the sensitizer and the reduction potential of the catalyst in our ternary system. The present results confirm that the TiO2 semiconductor in our heterogeneous hybrid system is an essential component that can effectively work as an electron reservoir and as an electron transporting mediator to play essential roles in the persistent photocatalysis activity of the hybrid system in the selective reduction of CO2 to CO.

Benefits of fresh-frozen plasma as a replacement fluid to neutralize ABO antibodies.

BACKGROUND: ABO-incompatible organ transplantation requires pre-transplant conditioning to reduce ABO antibody levels in the recipients. With respect to replacement fluids used in plasma exchange, we intended to verify whether fresh-frozen plasma (FFP) containing soluble ABO substance (SAS) is more effective than albumin solution in reducing ABO IgG antibody levels. METHODS: Apheresis data were retrospectively studied for in vivo effects, and in vitro plasma mixing studies were prospectively performed. The amount of ABO IgG antibodies bound to red cells was measured as the mean fluorescence intensity (MFI) using flow cytometry. Neutralization of ABO antibodies in the recipientst plasma by an ABO-incompatible donornc plasma was measured using the inhibition assay principle. The MFI value of the unneutralized control tube was divided by that of the neutralized test tube (neutralizing-capacity index, NCI). RESULTS: The plasma exchange procedures replaced with group AB FFP showed a significantly greater decreased titer than those replaced with albumin (P = 0.010). The in vitro plasma mixing study simulating plasma exchange also produced consistent results. When the pooled group O plasma was neutralized for anti-A by individual group AB plasmas (AB-to-O, N = 30), the NCI was 12.8 ± 5.4 (6.5-29.5). When this group O plasma was neutralized by pooled group AB or A plasma, the repeatedly measured NCI (N = 5) of A-to-O (11.4 ± 1.4) was not significantly different from that of AB-to-O (9.7 ± 1.3, P = 0.074). CONCLUSIONS: ABO antibody levels are reduced more effectively by group AB FFP than by albumin. Either group AB or donor type (group A or B) FFP can be infused to group O recipients. FFP units with higher SAS levels can be selected from multiple available candidate units using our protocol for measuring the neutralizing-capacity.

Prefixation of neutrophils for neutrophil antibody testing.

OBJECTIVE: The granulocyte immunofluorescence test based on flow cytometry is still the most commonly used method for detecting antineutrophil antibodies. We questioned whether neutrophil prefixation is necessary for this test. METHODS: Three pretreatment methods using paraformaldehyde were compared: unfixed, short-fixed (3 minutes 40 seconds), and long-fixed (10 minutes) leukocytes. The mean fluorescence intensity (MFI) of a test sample was divided by the average of negative controls, and this MFI ratio of gated neutrophils or lymphocytes was assessed for its discriminatory value based on the pretreatment method used. RESULTS: In neutrophil antibody positive (Ab+) sera (n = 7), the MFI ratio of unfixed neutrophils (1.97) was higher than that of short- (1.60, P = 0.004) or long- (1.71, P = 0.203) fixed neutrophils. In HLA Ab+ sera (n = 10), the MFI ratio of short-fixed lymphocytes (8.85) was higher than that of unfixed (6.52, P = 0.120) or long-fixed (3.86, P = 0.055) lymphocytes. In antinuclear Ab+ sera (n = 4), the MFI ratio of unfixed neutrophils (2.04) was higher than that of short- (1.23, P = 0.047) or long- (1.14, P = 0.044) fixed neutrophils. CONCLUSION: The benefit of a prefixation step depends on the diagnostic purpose. Unfixed neutrophils are more sensitive, but the prefixed neutrophils are more specific. For the diagnosis of autoimmune neutropenia of childhood, prefixation can be omitted to enhance sensitivity.

Characterization of the novel HLA-DPA1*02:124 allele in a Korean individual by next-generation sequencing.

HLA-DPA1*02:124 differs from HLA-DRB1*02:02:02:01 by one nucleotide substitution in codon 5 in exon 2.

4-Color Flow Cytometric Crossmatch Using Whole Blood Lysis.

BACKGROUND: In lymphocyte crossmatch using flow cytometry (flow cytometric crossmatch, FCXM), the conventional tricolor FCXM protocol requires a mononuclear cell isolation step. To develop a new, more streamlined protocol, we introduced whole blood lysis (WBL) and CD45 fluorescence-triggered acquisition using 4-color flow cytometry. METHODS: A total of 186 donor/recipient pairs for transplantation were classified into donor-specific human leukocyte antigen (HLA) alloantibody-positive (DSA+, n = 78) and DSA-negative (DSA-, n = 108) groups. The latter group was reclassified into blood group ABO-incompatible (ABOi, n = 56) and ABO-compatible (n = 52) subgroups. The WBL FCXM protocol with CD45 V500-C was optimized using a FACSLyric cytometer (BD Biosciences) with 3 lasers. Measurements for T cells or B cells were calculated as a mean fluorescence intensity (MFI) ratio (test divided by control). WBL FCXM was compared with conventional FCXM in each group. RESULTS: WBL FCXM showed no difference quantitatively compared with conventional FCXM, except for the B cell FCXM in the DSA- group (B cell MFI ratio: 1.06 ± 0.44 and 0.92 ± 0.41, respectively [P = .0001]). There was no ABO antibody interference in the ABOi subgroup. Similar results were observed in the qualitative determinations of FCXM as follows: 1) In the DSA+ group, the sensitivity of B cell WBL FCXM (96.2%) showed no difference compared with that of conventional FCXM (91.0%, P = .2188) and 2) In the DSA- group, the specificity of T cell WBL FCXM (96.3%) showed no difference compared with that of conventional FCXM (98.1%, P = .6250). WBL FCXM reduced the turnaround time by 50 min compared with that by conventional FCXM. CONCLUSIONS: WBL FCXM demonstrated comparable assay performance to that of conventional FCXM. Because this new FCXM protocol is simple and does not compromise assay sensitivity, it has the potential to replace the conventional method in histocompatibility laboratory settings.

Safety of the reduced fixed dose of mycophenolate mofetil confirmed via therapeutic drug monitoring in de novo kidney transplant recipients.

Background: Mycophenolate mofetil (MMF) is usually prescribed with a reduced fixed dose in Asian kidney transplant recipients (KTRs). However, the clinical efficacy and safety of the fixed dose have not yet been investigated via therapeutic drug monitoring. We evaluated whether reduced fixed-dose MMF is an optimal dosing strategy to achieve the therapeutic target of mycophenolic acid (MPA) exposure in Korean KTRs. Methods: This open-label, prospective study enrolled 50 de novo KTRs prescribed with tacrolimus, corticosteroid, and fixed-dose MMF (1.0-1.5 g/day). The trough level (C0) and area under the curve (AUC0-12 hr) of MPA were measured at 1 and 24 weeks after kidney transplantation (KT). The relationship of body weight (BW)-adjusted MMF dose with MPA C0 and MPA AUC0-12 hr was assessed using linear regression analysis. Results: The initial fixed dose of MMF of 1.44 ± 0.16 g/day was adjusted in 24 patients (48.0%) and then reduced to a mean dose of 1.19 ± 0.31 g/day at 24 weeks after KT. Most patients (≥84.0%) attained the minimum required MPA C0 of 1.0 µg/mL and MPA AUC0-12 hr of 30 µg × hr/mL at 1 and 24 weeks. The BW-adjusted MMF dose demonstrated significant positive correlations with MPA C0 and MPA AUC0-12 hr at 1 and 24 weeks after KT. Moreover, 14 patients (28.0%) reported MPA-related adverse events that were predictable based on MPA AUC0-12 hr (cutoff level, 46.4 µg × hr/mL). Conclusion: The current reduced fixed-dose MMF strategy can help achieve the therapeutic target of MPA exposure in tacrolimus-treated Korean KTRs during the early posttransplant period.

Characterization of the novel HLA-DRB1*14:252 allele in a Korean individual by next-generation sequencing.

HLA-DRB1*14:252 differs from HLA-DRB1*14:03:01 by one nucleotide substitution in codon 9 in exon 2.