Erratum: Correction of the Text in the Article "Table": Discordance between Physician and the General Public Perceptions of Prognostic Disclosure to Children with Serious Illness: a Korean Nationwide Study.

This corrects the article on e327 in vol. 33, PMID: 30505258.

Comparison and correlation among in vitro and in vivo assays to assess cord blood quality according to delivery temperature and time after collection.

Cord blood (CB) has been used as an alternative source for unrelated allogeneic hematopoietic stem cell transplantation. To determine which assay was useful for predicting the successful outcome of CB transplantation, CBs were grouped according to the temperature (4 °C, 24 °C, and 37 °C) and time (24, 48, and 72 h) after collection. The viability, early apoptosis, and colony forming units (CFUs) were ascertained for the total nucleated cells (TNCs) and CD34+ cells; in addition, the engraftment of infused CD34+ cells in NSG mice was determined. The viability of the TNCs and CD34+ cells and total CFUs were significantly decreased whereas the early apoptosis was significantly increased in the 72 h group at 37 °C compared to that of the 24 h group at 24 °C. The viability and early apoptosis of the TNCs correlated with those of CD34+ cells. In addition, the viability and early apoptosis correlated with the number of granulocyte/monocyte progenitor CFUs. In transplanted NSG mice, the frequency of human CD45+ cells decreased in the 72 h group at 24 °C compared to that of the 24 h group at 24 °C and was negatively correlated with early apoptosis of TNCs and CD34+ cells. This study demonstrated that the early apoptosis of TNCs and CD34+ cells constitutes a useful marker for predicting the engraftment of HSCs and may provide helpful data for standard assessment regarding CB quality by analyzing the correlation between in vitro and in vivo assays using NSG mice.

Erratum: Correction of Ethics Statement: Discordance between Physician and the General Public Perceptions of Prognostic Disclosure to Children with Serious Illness: a Korean Nationwide Study.

[This corrects the article e327 in vol. 33, PMID: 30505258.].

Purification and characterization of the thermostable protease produced by Serratia grimesii isolated from channel catfish.

BACKGROUND: Microbial spoilage of fishery products accounts for significant financial losses, yearly on a global scale. Psychrotrophic spoilage bacteria often secrete extracellular enzymes to break down surrounding fish tissue, rendering the product unsuitable for human consumption. For a better understanding of bacterial spoilage due to enzymatic digestion of fish products, proteases in Serratia grimesii isolated from North American catfish fillets (Ictalurus punctatus) were investigated. RESULTS: Mass spectrometric evidence demonstrated that S. grimesii secretes two distinct extracellular proteases and one lipase. Protease secretion displayed broad thermostability in the 30-90 °C range. The major protease-secretion (O-1) was most active under alkaline conditions and utilized manganese as a co-factor. Organic solvents significantly disrupted the efficacy of S. grimesii extracellular enzymes and, in a series of bactericidal detergents, protease activity was highest when treated with Triton X-100. Ethylenediaminetetraacetic acid (EDTA) and phenylmethylsulfonyl fluoride (PMSF) significantly inhibited the enzyme activity, while protease was moderately stable under freeze-thaw and refrigerated storage. CONCLUSION: The influence of fish spoilage-related enzymes, depending on various factors, is discussed in this paper. This study will provide new insight into enzymatic spoilage and its control, which can be exploited to enhance food safety and the shelf-life of fishery products worldwide. © 2018 Society of Chemical Industry.

Discordance between Physician and the General Public Perceptions of Prognostic Disclosure to Children with Serious Illness: a Korean Nationwide Study.

BACKGROUND: It is difficult to decide whether to inform the child of the incurable illness. We investigated attitudes of the general population and physicians toward prognosis disclosure to children and associated factors in Korea. METHODS: Physicians working in one of 13 university hospitals or the National Cancer Center and members of the general public responded to the questionnaire. The questionnaire consisted of the age appropriate for informing children about the prognosis and the reason why children should not be informed. This survey was conducted as part of research to identify perceptions of physicians and general public on the end-of-life care in Korea. RESULTS: A total of 928 physicians and 1,241 members of the general public in Korea completed the questionnaire. Whereas 92.7% of physicians said that children should be informed of their incurable illness, only 50.7% of the general population agreed. Physicians were also more likely to think that younger children should know about their poor prognosis compared with the general population. Physicians who opposed incurable illness disclosure suggested that children might not understand the situation, whereas the general public was primarily concerned that disclosure would exacerbate the disease. Physicians who were women or religious were more likely to want to inform children of their poor prognosis. In the general population, gender, education, comorbidity, and caregiver experience were related to attitude toward poor prognosis disclosure to children. CONCLUSION: Our findings indicate that physicians and the general public in Korea differ in their perceptions about informing children of poor prognosis.

Comparison of extracellular DNase- and protease-producing spoilage bacteria isolated from Delaware pond-sourced and retail channel catfish (Ictalurus punctatus).

BACKGROUND: Spoilage of fishery products begins immediately following filleting due to microbial growth that degrades fish tissue quality prior to consumption. Extensive research has been conducted to identify such bacterial populations. A better understanding of the mechanisms involved in fish spoilage is necessary as a novel remedy for microbial spoilage inhibition has yet to be established for fish tissue. The present study identified, for the first time, bacterial populations that produce extracellular DNase and protease from Delaware and local retail distributed channel catfish (Ictalurus punctatus) fillets. RESULTS: A clear trend was identified between bacteria derived from catfish filleted under aseptic conditions where Pseudomonas was the dominant genus. Bacteria isolated from retail catfish contained high quantities of DNase-producing isolates, in contrast to aseptic-filleted catfish tissue which had none. Both types of catfish sample maintained high populations of protease-producing bacterial colonies throughout the duration of the study. Most bacteria isolated from catfish intestines exhibited DNase production with no protease production. CONCLUSION: Specific spoilage organism populations were significantly higher on retail-derived catfish in comparison to lab-filleted Delaware cultured catfish tissue. It is suggested that DNase production and protease production contribute to the spoilage of fish tissue as a result of mishandling and septic filleting being the major cause of rapid catfish tissue spoilage.

Multipurpose assessment for the quantification of Vibrio spp. and total bacteria in fish and seawater using multiplex real-time polymerase chain reaction.

BACKGROUND: This study describes the first multiplex real-time polymerase chain reaction assay developed, as a multipurpose assessment, for the simultaneous quantification of total bacteria and three Vibrio spp. (V. parahaemolyticus, V. vulnificus and V. anguillarum) in fish and seawater. The consumption of raw finfish as sushi or sashimi has been increasing the chance of Vibrio outbreaks in consumers. Freshness and quality of fishery products also depend on the total bacterial populations present. RESULTS: The detection sensitivity of the specific targets for the multiplex assay was 1 CFU mL⁻¹ in pure culture and seawater, and 10 CFU g⁻¹ in fish. While total bacterial counts by the multiplex assay were similar to those obtained by cultural methods, the levels of Vibrio detected by the multiplex assay were generally higher than by cultural methods of the same populations. Among the natural samples without Vibrio spp. inoculation, eight out of 10 seawater and three out of 20 fish samples were determined to contain Vibrio spp. CONCLUSION: Our data demonstrate that this multiplex assay could be useful for the rapid detection and quantification of Vibrio spp. and total bacteria as a multipurpose tool for surveillance of fish and water quality as well as diagnostic method.

Current Status and Barriers of Exercise in Individuals with Spinal Cord Injuries in Korea: A Survey.

This study investigated exercise participation, health status, and barriers to exercise in 109 individuals with spinal cord injury (SCI) using a self-report questionnaire. The responses of the exercise and non-exercise groups were statistically analyzed using t-tests or Fisher's exact test. Significant differences were observed in the cause of injury and the American Spinal Injury Association Impairment Scale between the groups. The non-exercise group had a higher incidence of traumatic and complete injuries. Demographic factors such as gender, age, income level, and marital status did not significantly influence exercise participation. The exercise group reported lower pain scores, less inconvenience from complications, and higher activity and participation scores. However, less than half of the individuals with SCI met the recommended exercise intensity, and community facility usage was low. Barriers to exercise participation included severe disabilities, lack of time, insufficient exercise information, and lack of facility accessibility. To enhance exercise among individuals with SCI, it is essential to develop and extend exercise programs tailored to individual physical factors and a comprehensive understanding of barriers. Prioritizing community-based data management, alongside developing social systems and health policies, is crucial to overcome barriers to exercise participation for individuals with SCI.

Status and Barriers of Physical Activity and Exercise in Community-Dwelling Stroke Patients in South Korea: A Survey-Based Study.

This study aimed to examine the physical activity and exercise status of stroke patients in the community after discharge and the need for community-based exercises. This study included 100 community-dwelling patients with stroke in South Korea. The survey investigated the self-assessment of health status and physical activity, demand for community-based exercise after discharge, quality of life, and social participation. Overall, 96% of the respondents recognized the need to exercise, and two-thirds exercised. The third who did not exercise cited disability (29%), lack of facilities (22%), and health concerns (13%); only 21% of participants had ever used a community exercise facility, and their satisfaction with the facility was low. The main reasons for not using community exercise facilities were concerns about accidents during exercise and accessibility issues. Among real-world community stroke patients, those who exercised regularly had higher EuroQol-5D and reintegration to normal living indices than those who did not exercise (p < 0.05). Although community-dwelling stroke patients were highly aware of the need for physical activity and exercise, few engaged in adequate exercise. This lack of engagement is directly linked to identifiable personal and socio-structural barriers. Addressing these barriers will improve the quality of life and social participation of patients with stroke.

Computationally designed peptide inhibitors of the ubiquitin E3 ligase SCF(Fbx4).

A structure-based computational approach was used to rationally design peptide inhibitors that can target an E3 ligase (SCF(Fbx4) )-substrate (TRF1) interface and subsequent ubiquitylation. Characterization of the inhibitors demonstrates that our sequence-optimization protocol results in an increase in peptide-TRF1 affinity without compromising peptide-protein specificity.

A randomized trial comparing standard versus high-dose daunorubicin induction in patients with acute myeloid leukemia.

We conducted a phase 3 randomized trial comparing 2 different doses of daunorubicin as induction chemotherapy in young adults (60 years of age or younger) with acute myeloid leukemia (AML). Of 383 patients who were analyzed, 189 received standard-dose daunorubicin (SD-DN, 45 mg/m² per day times 3 days) and 194 received high-dose daunorubicin (HD-DN, 90 mg/m² per day times 3 days) in addition to cytarabine (200 mg/m² per day times 7 days) to induce complete remission (CR). The CR rates were 72.0% in the SD-DN arm and 82.5% in the HD-DN arm (P = .014). At a median follow-up of 52.6 months, overall (OS) and event-free (EFS) survival were higher in the HD-DN arm than in the SD-DN arm (OS, 46.8% vs 34.6%, P = .030; EFS, 40.8% vs 28.4%, P = .030). Differences in CR rate and both OS and EFS remained significant after adjusting for other variables (CR, hazard ratio [HR], 1.802, P = .024; OS, HR, 0.739, P = .032; EFS, HR, 0.774, P = .048). The survival benefits of HD-DN therapy were evident principally in patients with intermediate-risk cytogenetic features. The toxicity profiles were similar in the 2 arms. In conclusion, HD-DN improved both the CR rate and survival duration compared with SD-DN in young adults with AML. This study is registered at www.clinicaltrials.gov as #NCT00474006.

APRIL stimulates NF-κB-mediated HoxC4 induction for AID expression in mouse B cells.

Activation-induced cytidine deaminase (AID) plays a key role in B cell immunoglobulin (Ig) class switch recombination (CSR) and somatic hypermutation (SHM). We have previously reported that the highly conserved homeodomain HoxC4 transcription factor binds to the Aicda (AID gene) promoter to induce AID expression. Here, we investigated the regulation of HoxC4 transcription by a proliferation-inducing ligand (APRIL) and B cell-activating factor belonging to the TNF family (BAFF) in mouse B cells. APRIL substantially increased both HoxC4 and AID expression, whereas BAFF induced the expression of AID but not HoxC4. To elucidate the underlying mechanisms, we constructed a HoxC4 gene promoter reporter vector and analyzed the promoter induction after APRIL stimulation. APRIL enhanced the HoxC4 promoter activity by 2.3-fold, and this increase disappeared when the second putative NF-κB-binding promoter element (NBE2) was mutated. Based on ChIP assays, we found that NF-κB bound to the HoxC4 promoter NBE2 region. Furthermore, the overexpression of NF-κB augmented the APRIL-induced HoxC4 promoter activity, while the expression of dominant negative-IκBα suppressed it. Taken together, our findings suggest that NF-κB mediates APRIL-induced HoxC4 transcription.

Essential role of toll-like receptor 4 in Acinetobacter baumannii-induced immune responses in immune cells.

TLR4 is a membrane sensor for lipopolysaccharide (LPS), a major cell wall component of gram-negative bacteria. In this study, we investigated the role of TLR4 on innate immune responses in immune cells against Acinetobacter baumannii. Bone marrow-derived macrophages (BMDMs) and dendritic cells (BMDCs) were isolated from WT and TLR4-deficient mice and infected with A. baumannii ATCC 15150. ELISA assay revealed that the production of IL-6 and TNF-α by A. baumannii was impaired in TLR4-deficient macrophages. However, absence of TLR2 did not affect A. baumannii-induced cytokines production in BMDMs. In addition, TLR4 was required for the optimal production of IL-6, TNF-α, and IL-12 in BMDCs in response to A. baumannii. Western blot analysis showed that A. baumannii leads to the activation of NF-κB and MAPKs (p38, ERK, and JNK) in macrophages via TLR4-dependent pathway. mRNA expression of iNOS and NO production was elicited in WT BMDMs in response to A. baumannii, which was abolished in TLR4-deficienct cells. Bacterial killing ability against A. baumannii was impaired in TLR4-deficient BMDMs. In addition, A. baumannii induced apoptosis in BMDMs via TLR4-independent pathway. Our results demonstrate that TLR4 is essential for initiating innate immune response of macrophages against A. baumannii infection.

Detection of 5 CFU/g of Escherichia coli O157:H7 on lettuce using activated charcoal and real-time PCR without enrichment.

A sample treatment method which separates Escherichia coli O157:H7 from lettuce and removes PCR inhibitors allowing 5 CFU/g of target cells to be detected using real-time PCR is described. Lettuce leaves inoculated with E. coli O157:H7 were rinsed with 0.025% sodium dodecyl sulfate (SDS). In this study, there were two major factors that strongly affected the recovery of E. coli O157:H7 during sample preparation, the amount of bentonite coated activated charcoal used to remove PCR inhibitors and the agitated contact time of the samples with the coated charcoal. When 3.0 g of activated carbon coated with bentonite were mixed with target cell suspensions (30 ml) derived from 50 g of lettuce, a high recovery of E. coli O157:H7 (93%) was obtained. Sample agitation with bentonite coated activated charcoal for 15 min resulted in 95% recovery of E. coli O157:H7. When a commercial DNA purification resin was used for detection of E. coli O157:H7 without the use of the bentonite treated charcoal, the real-time PCR (Rti-PCR) failed to detect 1 × 10(2) CFU/g. In contrast, with the use of use of bentonite coated activated charcoal and a commercial DNA purifying resin together, Rti-PCR was able to detect 5 CFU of E. coli O157:H7/g of lettuce which was equivalent to 2.8 CFU/Rti-PCR. Such a successful detection level was the result of the bentonite coated activated charcoal's ability to absorb the PCR inhibitors released from seeded lettuce during detachment. A standard curve was generated by plotting the Ct values against the log of CFU of target bacterial cells. A linear range of DNA amplification was exhibited from 5.0 × 10(0) to 1.0 × 10(4) CFU/g by using Rti-PCR.

2020 Korean guidelines for the management of metastatic prostate cancer.

In 2017, Korean Society of Medical Oncology (KSMO) published the Korean management guideline of metastatic prostate cancer. This paper is the 2nd edition of the Korean management guideline of metastatic prostate cancer. We updated recent many changes of management in metastatic prostate cancer in this 2nd edition guideline. The present guideline consists of the three categories: management of metastatic hormone sensitive prostate cancer; management of metastatic castration resistant prostate cancer; and clinical consideration for treating patients with metastatic prostate cancer. In category 1 and 2, levels of evidence (LEs) have been mentioned according to the general principles of evidence-based medicine. And grades of recommendation (GR) was taken into account the quality of evidence, the balance between desirable and undesirable effects, the values and preferences, and the use of resources and GR were divided into strong recommendations (SR) and weak recommendations (WR). A total of 16 key questions are selected. And we proposed recommendations and described key evidence for each recommendation. The treatment landscape of metastatic prostate cancer is changing very rapid and many trials are ongoing. To verify the results of the future trials is necessary and should be applied to the treatment for metastatic prostate cancer patients in the clinical practice. Especially, many prostate cancer patients are old age, have multiple underlying medical comorbidities, clinicians should be aware of the significance of medical management as well as clinical efficacy of systemic treatment.

Minor H antigen HA-1-specific regulator and effector CD8+ T cells, and HA-1 microchimerism, in allograft tolerance.

The role of the hematopoietic lineage-restricted minor histocompatibility (H) antigen HA-1 in renal allograft tolerance was explored. We obtained peripheral blood samples from three recipients of histocompatibility leukocyte antigen (HLA)-matched, HA-1-mismatched renal transplants, one of which had discontinued immunosuppression >30 yr ago while sustaining normal kidney function. Peripheral blood mononuclear cells (PBMCs) were injected into the footpads of severe combined immunodeficiency mice to measure human delayed type hypersensitivity (DTH) responses. All three patients manifested regulated DTH responses to HA-1H peptide. By differential tetramer staining intensities, we observed two distinct minor H antigen HA-1-specific CD8+ T cell subsets. The one that stained dimly had the characteristics of a T regulatory (TR) cell and produced interleukin (IL) 10 and/or transforming growth factor (TGF) beta. These HA-1-specific TR cells coexisted with bright tetramer-binding CD8+ T effector (TE) cells. The CD8+ TE cells mediated HA-1-specific DTH and produced interferon-gamma. Suppression of these TE functions by TR cells was TGFbeta, IL-10, and cytotoxic T lymphocyte-associated antigen 4 dependent. In addition, HA-1 microchimerism was detected in two recipients, primarily in the dendritic cell fraction of the PBMCs. This is the first demonstration of coexisting CD8+ memory TR and TE cells, both specific for the same HA-1 antigen, in the context of renal allograft tolerance.

Optimizing Preparative Regimen for Umbilical Cord Blood Transplantation in Adult Acute Leukemia Patients: Acute Lymphoblastic Leukemia Requires Myeloablative Conditioning but Not Acute Myeloid Leukemia.

Cord blood transplantation (CBT) is a valuable alternative to bone marrow transplantation in adults without readily available donors. We conducted this study to investigate the feasibility of CBT for adult patients with acute leukemia with regards to impact of different conditioning and graft-versus-host disease (GVHD) prophylaxis regimens on clinical outcomes. From 16 centers in Korea, 41 acute myeloid leukemia (AML) and 29 ALL (acute lymphoblastic leukemia) patients undergoing CBT were enrolled. For AML patients, the neutrophil engraftment was observed in 87.5% of reduced intensity conditioning (RIC) and 72.0% of myeloablative conditioning (MAC) (p = 0.242). The median RFS was 5 months and OS 7 months. Conditioning regimen did not affect relapse free survival (RFS) or overall survival (OS). GVHD prophylaxis using calcineurin inhibitors (CNI) plus methotrexate was associated with better RFS compared to CNI plus ATG (p = 0.032). For ALL patients, neutrophil engraftment was observed in 55.6% of RIC and 90.0% of MAC (p = 0.034). The median RFS was 5 months and OS 19 months. MAC regimens, especially total body irradiation (TBI)-based regimen, were associated with both longer RFS and OS compared to other conditioning regimens. In conclusion, individualized conditioning regimens will add value in terms of enhancing safety and efficacy of CBT.

Analysis of indirect pathway CD4+ T cells in a patient with metastable tolerance to a kidney allograft: possible relevance to superior graft survival of HLA class II closely matched renal allografts.

MHC class I mismatched, but class II matched kidney transplants are tolerogenic in large animal models. CD4(+) T regulatory cells specific for HLA-B1501-derived peptide p37-MA (DSDAASPRMAPRAPWIEQ) developed in a long term (>12 years) tolerant patient who received an HLA-B1501 mismatched, HLA class II closely matched renal allograft. We hypothesized that class II matching favored T regulatory cell development by allowing allopeptide presentation on either recipient (DR4/DQ7(+)) or donor (DR4/DQ8(+)) antigen presenting cells (APC). Indirect pathway CD4(+) T cell clones were generated from recipient PBMC by sorting antigen-stimulated, proliferating cells. Most clones responded to p37-MA-pulsed B1501(-) autologous, but not to DQ8(+)B1501(+) donor B-lymphoblastoid cell lines (B-LCL). However, some clones responded to both; in fact, one responded even more strongly to donor B-LCL than to p37-MA-pulsed autologous B-LCL. P37-MA contained a DQ8-binding motif and induced strong TH1 responses from DQ8 but not DQ6 transgenic mice. Microchimerism was found to be enriched in the dendritic cells (DC) cultured from adherent PBMC. This indicates donor APC could possibly present p37-MA peptide directly to p37-MA specific T cells. These data support the concept that, when the donor is MHC class II closely matched, a "hybrid" form of allorecognition (direct/indirect) occurs. This may favor the generation of a beneficial form of indirect pathway alloreactivity, i.e. allopeptide-specific CD4(+) T regulatory cells, in the context of long term DC microchimerism.

A comparative study of the ability of EMA and PMA to distinguish viable from heat killed mixed bacterial flora from fish fillets.

Ethidium bromide monoazide (EMA) and propidium monoazide (PMA) were utilized to selectively allow real-time PCR (Rti-PCR) amplification of target DNA from viable but not heat killed cells from the mixed bacterial flora derived from cod fillets. A linear range of DNA amplification was exhibited from 3.2x10(2) to 1.0x10(5) genomic targets per Rti-PCR. Following the heat treatment of cell suspensions the surviving populations with the EMA and PMA Rti-PCR method were evaluated by comparison with plate counts and MPN assays following different heat exposures (45 to 95 degrees C) for 5 min. The percent of erroneous survival with PMA Rti-PCR was higher than with EMA treatment. Cellular leakage was examined by following the extracellular increase of 260 and 280 nm absorbing materials. Initial leakage of protein and nucleic acids occurred at 50 degrees C, the maximal amount of leakage occurred at 70 degrees C.

Clinical features and survival outcomes in patients with multiple myeloma: analysis of web-based data from the Korean Myeloma Registry.

AIM: The Korean Multiple Myeloma Working Party performed a nationwide registration of multiple myeloma patients via a web-based data bank system. METHODS: We retrospectively analyzed registered data from 3,209 patients since 1999. RESULTS: The median overall survival (OS) was 50.13 months (95% confidence interval: 46.20-54.06 months). Patients < or =40 years demonstrated a longer OS than patients >65 years of age (median OS 71.13 vs. 36.73 months, p < 0.001). Patients who received novel agents at any time during their treatments showed a longer OS than patients who did not (median OS 42.23 vs. 55.50 months, p < 0.001). Response to treatment was associated with OS, with tandem autologous stem cell transplantation (SCT) producing longer OS than single autologous SCT. CONCLUSIONS: We demonstrated associations between survival outcomes and treatment modalities as well as baseline disease characteristics in a registry of multiple myeloma patients using a web-based data analysis.