Search

We report changes in viral load over time in a 27-day-old neonate with coronavirus disease 2019 who presented with fever, cough, and vomiting. Severe acute respiratory syndrome coronavirus 2 RNA was detected in the nasopharynx, oropharynx, stool, saliva, plasma, and urine. The highest viral RNA copies in nasopharynx decreased over time while viral load in stool remained high., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: The definition of the high-risk group for gestational diabetes mellitus (GDM) defined by the American College of Obstetricians and Gynecologists was changed from the criteria composed of five historic/demographic factors (old criteria) to the criteria consisting of 11 factors (new criteria) in 2017. To compare the predictive performances between these two sets of criteria., Methods: This is a secondary analysis of a large prospective cohort study of non-diabetic Korean women with singleton pregnancies designed to examine the risk of GDM in women with nonalcoholic fatty liver disease. Maternal fasting blood was taken at 10 to 14 weeks of gestation and measured for glucose and lipid parameters. GDM was diagnosed by the two-step approach., Results: Among 820 women, 42 (5.1%) were diagnosed with GDM. Using the old criteria, 29.8% (n=244) of women would have been identified as high risk versus 16.0% (n=131) using the new criteria. Of the 42 women who developed GDM, 45.2% (n=19) would have been mislabeled as not high risk by the old criteria versus 50.0% (n=21) using the new criteria (1-sensitivity, 45.2% vs. 50.0%, P>0.05). Among the 778 patients who did not develop GDM, 28.4% (n=221) would have been identified as high risk using the old criteria versus 14.1% (n=110) using the new criteria (1-specificity, 28.4% vs. 14.1%, P<0.001)., Conclusion: Compared with the old criteria, use of the new criteria would have decreased the number of patients identified as high risk and thus requiring early GDM screening by half (from 244 [29.8%] to 131 [16.0%]).

Induced pluripotent stem cells (iPSCs) have opened up unprecedented opportunities for novel therapeutic options for precision medicine. Hematopoietic stem cell (HSC) donor pools with previously determined HLA types may be ideal sources for iPSC production. Based on the HLA distribution of cryopreserved cord blood units (CBUs) and registered bone marrow (BM) donors, we estimated how much of the Korean population could be covered by HLA-homozygous iPSCs. We analyzed a total of 143,866 Korean HSC donors (27,904 CBUs and 115,962 BM donors). Each donor sample was typed for the HLA-A, -B, and -DRB1 alleles at low to intermediate resolution by DNA-based molecular techniques: PCR sequence-specific oligonucleotide (PCR-SSOP), PCR with sequence-specific primers (PCR-SSP) and PCR with sequence-based typing (PCR-SBT). We also identified individuals possessing homozygous HLA haplotypes by direct counting. The matching probabilities for zero-mismatch transplantation were calculated for 143,866 Koreans and 50 million potential Korean patients. Among the HSC donor pool, 17 HLA-A alleles, 41 HLA-B alleles, and 13 HLA-DRB1 alleles, as well as 128 homozygous HLA-A-B-DRB1 haplotypes, were identified at serologic equivalents, and those haplotypes cumulatively matched 93.20% of the 143,866 Korean donors as zero HLA-mismatch iPSC sources. Among the combinations of 2,056 haplotypes with frequencies ≥ 0.001% in a population of 50 million, those 128 homozygous haplotypes can provide 93.65% coverage for potential Korean recipients. Haplobanking of a reasonable number of HLA-A, -B, and -DRB1 homozygous iPSC lines derived from CBUs and cells of registered BM donors may be an efficient option for allogenic iPSC therapy., (Copyright © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by progressive proximal muscle weakness and atrophy. Given the recent introduction of gene therapies, knowledge of the SMA carrier frequency in various populations has become important for developing screening programs for this disease. In total, 1,581 anonymous DNA samples from an umbilical cord blood bank were tested for SMN1 and SMN2 gene copies using a multiplex ligation-dependent probe amplification assay. Twenty-nine of the 1,581 newborns [1.83%; 95% confidence interval (CI), 1.25-2.66%] were SMA carriers with one copy of SMN1 , and no homozygous SMN1 deletion was detected. The carrier frequency in this population was estimated to be 1,834 per 100,000 (95% CI, 1,254-2,659) or 1 in 55 (95% CI, 1/79-1/38). Our data indicate that SMA carriers are not uncommon in the Korean population and may serve as a reference for designing a population screening program in Korea., Competing Interests: No potential conflicts of interest relevant to this article were reported., (© The Korean Society for Laboratory Medicine.)

The association of anti-MHC class I-related chain A (MICA) and kidney allograft rejection has been reported. However, the associations of antibodies specific to donor MICA (dsMICA) and dsMICA levels with allograft outcome have not been elucidated. From November 2009 to June 2017, 125 sera samples from renal transplantation recipients with no HLA antibodies were screened for MICA antibodies. Patients with positive MICA antibody screening results and available residual donor DNA for MICA geno-typing underwent dsMICA analysis. Among these 125 sera samples, 19 were positive for MICA antibodies. dsMICA was positive in 5 out of the 12 analyzed sera samples. Neither MICA antibodies nor dsMICA were associated with acute rejection. However, interstitial fibrosis and tubular atrophy (IFTA) was significantly associated with MICA antibody positivity (OR=3.84, P =0.009). In addition, the MFI value of dsMICA was significantly higher in patients with IFTA II or III than in patients without IFTA II or III ( P =0.009). The association of MICA antibodies and dsMICA with high grade IFTA (grade II or III) was suggested. The MICA antibody and dsMICA might be useful indicators of chronic renal damage., (© 2020 by the Association of Clinical Scientists, Inc.)

Background: Plasmapheresis (PP) is commonly used for desensitization in highly sensitized patients with donor-specific antibodies (DSA) in living donor kidney transplantation. We analyzed the impact of DSA levels before and after desensitization on renal allograft outcome., Methods: Twenty-three patients who underwent desensitization with PP, intravenous immunoglobulin (IVIG), and rituximab before kidney transplantation in Seoul National University Hospital from August 2006 to August 2016 were enrolled. The association of median fluorescent intensity (MFI) value of DSA with graft outcome was analyzed., Results: The frequency of positive HLA class II DSA after desensitization was lower in patients without antibody-mediated rejection (AMR) compared to those with AMR (p = 0.006). The cutoff value of MFI sum of HLA class II DSA after desensitization for predicting AMR was 2,122 with 63% sensitivity and 94% specificity. The frequency of moderate HLA class II DSA (MFI 5,000 - 10,000) after desensitization was significantly higher in patients with graft loss compared to those without graft loss (p = 0.02)., Conclusions: Weak HLA class II DSA after desensitization including PP, IVIG, and rituximab was related to AMR and moderate levels of HLA class II DSA after desensitization was related to graft loss in living donor kidney transplantation.

Recently, the removal of false reaction from beads 10 ( DRB1 * 04:04), 30 ( DRB1 * 16:01), and 31 ( DRB1 * 16:02) by fetal bovine serum (FBS) treatment in LABScreen Single Antigen Class II Assay was reported. We aimed to confirm the reaction in many cases. Fifty-nine sera showed positivity on at least two among beads 10, 30 and 31 from Nov 2017 to Oct 2018 in Seoul National University Hospital were included. FBS treatment was performed on 59 sera, and Single Antigen Class II Assay was repeated. Among 59 cases, the negative conversion rates of DR16 (57/59, 96.6%), DR4 (37/39, 94.9%), and accompanied other antibodies, e.g.) DP19 (39/45, 86.7%) were very high. The prior use of intravenous immunoglobulin in a non-specific binding group was significantly higher than the sex, age-matched control group ( P =0.005)., (© 2019 by the Association of Clinical Scientists, Inc.)

Dendritic cells (DCs) are key targets for immunity and tolerance induction; they present donor antigens to recipient T cells by donor- and recipient-derived pathways. Donor-derived DCs, which are critical during the acute posttransplant period, can be depleted in graft tissue by forced migration via ultraviolet B light (UVB) irradiation. Here, we investigated the tolerogenic potential of donor-derived DC depletion through in vivo and ex vivo UVB preirradiation (UV) combined with the injection of anti-CD154 antibody (Ab) into recipients in an MHC-mismatched hair follicle (HF) allograft model in humanized mice. Surprisingly, human HF allografts achieved long-term survival with newly growing pigmented hair shafts in both Ab-treated groups (Ab-only and UV plus Ab) and in the UV-only group, whereas the control mice rejected all HF allografts with no hair regrowth. Perifollicular human CD3 + T cell and MHC class II + cell infiltration was significantly diminished in the presence of UV and/or Ab treatment. HF allografts in the UV-only group showed stable maintenance of the immune privilege in the HF epithelium without evidence of antigen-specific T cell tolerance, which is likely promoted by normal HFs in vivo. This immunomodulatory strategy targeting the donor tissue exhibited novel biological relevance for clinical allogeneic transplantation without generalized immunosuppression., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Aims/hypothesis: Although there is substantial evidence that non-alcoholic fatty liver disease (NAFLD) is associated with impaired glucose homeostasis, the clinical significance of NAFLD in pregnant women has not been well determined. This study investigates the relationship between NAFLD in the first trimester and the subsequent development of gestational diabetes mellitus (GDM)., Methods: A multicentre, prospective cohort study was conducted in which singleton pregnant Korean women were assessed for NAFLD at 10-14 weeks using liver ultrasound, fatty liver index (FLI) and hepatic steatosis index (HSI). Maternal plasma adiponectin and selenoprotein P concentrations were measured. Participants were screened for GDM using the two-step approach at 24-28 weeks., Results: Six hundred and eight women were included in the final analysis. The prevalence of NAFLD was 18.4% (112/608) and 5.9% (36/608) developed GDM. Participants who developed GDM had a higher prevalence of radiological steatosis (55.6% vs 16.1%; p < 0.001) and higher FLI (40.0 vs 10.7; p < 0.001) and HSI (35.5 vs 29.0; p < 0.001). The risk of developing GDM was significantly increased in participants with NAFLD and was positively correlated with the severity of steatosis. This relationship between NAFLD and GDM remained significant after adjustment for metabolic risk factors, including measures of insulin resistance. Maternal plasma adiponectin and selenoprotein P levels were also correlated with both NAFLD severity and the risk of developing GDM., Conclusions/interpretation: NAFLD in early pregnancy is an independent risk factor for GDM. Adiponectin may be a useful biomarker for predicting GDM in pregnant women.

Background: Although platelet-rich plasma (PRP) is a popular option for rotator cuff disease, the underlying mechanism of PRP and its clinical indications are unclear. Further, some kinds of PRP might be detrimental to patients. Allogenic PRP prepared through a standardized process and fully characterized could eliminate variations in PRP as well as uncertainties regarding its use in each patient, which could provide clues about its mechanism of action and indications for its use., Purpose: To assess the effects of pure PRP on tenocytes with or without inflammation in an in vitro study and to evaluate the safety and efficacy of a fully characterized pure PRP injection in patients with rotator cuff disease in a clinical study., Study Design: Controlled laboratory study and cohort study; Level of evidence, 3., Methods: For the in vitro study, tenocytes were enzymatically isolated and cultured from patients with rotator cuff tear and treated with or without interleukin 1β (IL-1β) and PRP. Gene expression and protein synthesis of pro- and anti-inflammatory cytokines, enzymes and their inhibitors, matrix synthesis, and cell viability were evaluated. For the clinical study, a total of 17 patients with rotator cuff disease received ultrasonography-guided subacromial PRP injection and were followed for 6 months. Pain, range of motion, muscle strength, shoulder function, and overall satisfaction in patients were compared with the results in a propensity score-matched control group who received corticosteroid (triamcinolone acetonide 40 mg)., Results: PRP induced inflammation in the absence of inflammation and ameliorated inflammation in IL-1β-induced tendinopathic conditions by regulation of cytokines such as IL-1β, cyclooxygenase 2, microsomal prostaglandin E synthase 1, vasoactive intestinal peptide, and downstream matrix metalloproteinases. No general or local adverse events were noted with regard to allogenic PRP injection. Whereas steroid injection showed earlier improvement in some kinds of pain and functional scores, PRP generally showed comparable effects with steroid injection in all clinical outcomes at 6 months., Conclusion: This study showed that allogenic pure PRP had pleiotropic effects on tenocytes depending on inflammation and that it did not cause adverse events but rather decreased pain and improved shoulder function to a degree comparable with steroid injection in patients with rotator cuff disease., Clinical Relevance: Allogenic PRP could be a treatment option for rotator cuff disease.

Background: Forkhead box P3 (FOXP3) is an important marker of regulatory T cells. FOXP3 polymorphisms are associated with autoimmune diseases, cancers, and allograft outcomes. We examined whether single nucleotide polymorphisms (SNPs) at the FOXP3 locus are associated with clinical outcomes after allogenic hematopoietic stem cell transplantation (HSCT)., Methods: Five FOXP3 SNPs (rs5902434, rs3761549, rs3761548, rs2232365, and rs2280883) were analyzed by PCR-sequencing of 172 DNA samples from allogenic HSCT patients. We examined the relationship between each SNP and the occurrence of graft-versus-host disease (GVHD), post-HSCT infection, relapse, and patient survival., Results: Patients with acute GVHD (grades II-IV) showed higher frequencies of the rs3761549 T/T genotype, rs5902434 ATT/ATT genotype, and rs2232365 G/G genotype than did patients without acute GVHD (P=0.017, odds ratio [OR]=5.3; P=0.031, OR=2.4; and P=0.023, OR=2.6, respectively). Multivariate analysis showed that the TT genotype of rs3761549 was an independent risk factor for occurrence of acute GVHD (P=0.032, hazard ratio=5.6). In contrast, the genotype frequencies of rs3761549 T/T, rs5902434 ATT/ATT, and rs2232365 G/G were lower in patients with post-HSCT infection than in patients without infection (P=0.026, P=0.046, and P=0.031, respectively)., Conclusions: rs3761549, rs5902434, and rs2232365 are associated with an increased risk of acute GVHD and decreased risk of post-HSCT infection., Competing Interests: The authors declare that no conflicts of interest exist., (© The Korean Society for Laboratory Medicine.)

Background: Platelet-rich plasma (PRP) stimulates cell proliferation and enhances matrix gene expression and synthesis. However, there have been no comparative study of the PRP effect on the normal and degenerative tenocytes. The purpose of this study was to compare the effect of PRP on tenocytes from normal and degenerative tendon., Methods: Tendon tissues were obtained from patients undergoing arthroscopic repair (n=9) and from healthy donors (n=3). Tenocytes were cultured with 10% (vol/vol) platelet-poor plasma, PRP activated with calcium, and PRP activated with calcium and thrombin. The total cell number was assessed at days 7 and 14. The expressions of type I and III collagen, decorin, tenascin-C, and scleraxis were evaluated by quantitative real-time reverse transcriptase polymerase chain reaction. The total collagen and glycosaminoglycan (GAG) synthesis was evaluated at days 7 and 14., Results: No differences were observed between the groups at day 7, but cell proliferation was remarkably increased in tenocytes from the degenerative tendon at day 14. In both tenocyte groups, the gene expressions of type I and III collagen were up-regulated. GAG synthesis was greater in the normal tendon, whereas the expressions of decorin and tenascin-C were increased in tenocytes from the degenerative tendon. Tenocytes from the degenerative tendon had higher fold-change of GAG synthesis and a lower collagen III/I ratio than normal tenocytes., Conclusions: PRP promoted the cell proliferation and enhanced the synthesis of tendon matrix in both groups. PRP has a greater positive effect on cell proliferation, matrix gene expression and synthesis in tenocytes from degenerative tendon., Competing Interests: Conflict of interest None., (Copyright © 2018 Korean Shoulder and Elbow Society.)

Purpose: Although many hypotheses regarding the pathogenesis of polycystic ovary syndrome (PCOS) have been generated, genetic studies have not identified specific genes that play a role in PCOS etiopathogenesis. This study aimed to investigate the relationship between TGF-β1 gene polymorphism and PCOS in Koreans., Method: A total of 51 Korean women with PCOS and 69 healthy women were enrolled. We analyzed 4 single nucleotide polymorphisms (SNPs) of the TGF-β1 gene (rs11466313, rs1800469, rs2317130, and rs4803457). We also analyzed laboratory measurements, such as free testosterone, glucose, and cholesterol., Results: The frequencies of rs1800469T allele negativity, rs4803457T allele negativity, the rs1800469CC genotype, and the rs4803457CC genotype showed positive associations with PCOS (P = 0.003, P = 0.027, P = 0.009, and P=0.031, respectively), whereas the haplotypes rs1800469C-rs4803457T and rs1800469T-rs4803457T showed negative associations with PCOS. A strong protective effect of the "rs1800469CT-rs4803457TT" combination (OR = 0.09) and a strong risk effect of "rs1800469CC-rs4803457CC" (OR = 6.23) for PCOS were observed. The rs1800469C/T and rs2317130C/T SNPs exhibited associations with several laboratory measurements with various levels of significance., Conclusion: The results demonstrated an association of TGF-β1 gene polymorphisms with the development and/or characteristics of PCOS in the Korean population.

Approximately 10% of individuals do not respond to hepatitis B virus (HBV) vaccination, i.e. non-responders (NRs). We aimed to investigate the association of interleukin (IL)-4 and IL-12B gene polymorphisms with responsiveness to the HBV vaccine in Korean infants. Among 300 healthy infants (9-12 month), SNPs for the IL-4 gene (rs2243250, rs2070874, and rs2227284) and for the IL-12B gene (rs3213094 and rs17860508) were compared between subgroups in terms of the response to HBV vaccination. The percentages of NRs (< 10 mIU/mL), low-titer responders (LRs, 10-100 mIU/mL), and high-titer responders (HRs, ≥ 100 mIU/mL) were 20.3%, 37.7% and 42.0%, respectively. No SNPs differed in frequency between NRs and responders or between LRs and HRs. We divided the subjects into two groups according to the time interval from the 3rd dose of HBV vaccination to Ab quantification: > 6 months from the 3rd dose (n = 87) and ≤ 6 months from the 3rd dose (n = 213). In the ≤ 6 month subjects, rs2243250C and rs2227284G were significantly frequent in the lower-titer individuals (NRs + LR) than HRs (40.1 vs. 25.9%, p = 0.014 and 45.1 vs. 33.0%, p = 0.018, respectively), and the rs2243250C and rs2227284G frequencies were significantly different among the three subgroups (13.2 vs. 26.9 vs. 25.9%, p = 0.040 and 15.5 vs. 29.6 vs. 33.0%, p = 0.038, respectively). In conclusion, those results suggest that IL-4 gene polymorphisms may play a role in the response to the HBV vaccine in Korean infants.

Background: To examine the impact of a single bout of exercise on cardiac function and the blood level of brain natriuretic peptide (BNP) in healthy subjects., Methods: Thirty untrained, healthy young (aged between 20 and 29 years) volunteers (15 men and 15 women) were prospectively recruited. The plasma N-terminal pro-B-type BNP (NT-proBNP) level was checked, cardiac function was assessed using echocardiography in baseline conditions, and the values were compared with those obtained after treadmill exercise according to the Bruce protocol., Results: Left ventricular (LV) ejection fraction decreased after exercise in men, but not in women. Parameters of LV diastolic function were likely to change unfavorably in both sexes after exercise. NT-proBNP levels were significantly elevated by exercise in both sexes (from 22.1±18.3 to 24.7±20.2 pg/mL, P=0.006 in men; from 41.1±21.5 to 46.5±24.9 pg/mL, P<0.001 in women). Changes in NT-proBNP levels were significantly associated with those in E wave velocity, E wave deceleration time, E/e' and E/propagation velocity (Vp) in men (P<0.05 for each) even after controlling for the effects of blood pressure and heart rate. In women, there were no significant associations between changes in parameters of LV diastolic function and those in NT-proBNP levels., Conclusions: LV systolic and diastolic functions may deteriorate, and proBNP levels could be elevated even by a single bout of treadmill exercise in untrained young subjects. Dynamic change in LV diastolic function is a major stimulus to NT-proBNP release following exercise in men but not in women.

Background: The obstetrician's role in vitalizing cord blood (CB) banking is important in both informing donors and beginning CB processing. The aim of the study was to investigate obstetricians' understanding of CB and their roles in informing donors and collection management., Study Design and Methods: Questionnaires examining the management and awareness of CB were distributed to collection centers, and we analyzed 57 respondents who had collection experience., Results: All respondents were experienced, and 82.5% had CB collection experience of at least 4 years. If patients asked for information, one-third provided information about CB themselves, and two-thirds provided CB banks' (CBBs') contact information. Less than half of the respondents knew the legal regulations and had a collection manual. Regarding the awareness of transportation and storage of CB, 58% rated their knowledge as minimal, and respondents who knew the legal regulations rated their knowledge at a higher level. One-fifth of the participants felt that CB collection distracted the labor process, and 16% were concerned about delayed bleeding control. The probability of autologous CB transplantation was overestimated, and the matching probability in public CBBs was underestimated. Approximately 82.7% of the respondents correctly rated the therapeutic use of CB, and 54% rated their knowledge level about CB usefulness as average., Conclusion: Obstetricians' understanding of CB was lower than expected, considering that they are associated with CB collection centers. Obstetricians who provide information and recognize regulations seem to collect CB in compliance with the regulations better. These results will be helpful in CB collection management and education planning for obstetricians., (© 2014 AABB.)

Hepatitis B virus (HBV) vaccination is the most effective means of countering HBV-related morbidity and mortality, and individuals who do not respond to vaccination (non-responders) are problematic. The aim of the present study was to investigate associations between HLA and responsiveness to HBV vaccine in Korean infants. A total of 944 healthy Korean infants 9-12 months old were enrolled, and HLA distribution was compared among subgroups in accordance with the response to HBV vaccination. The HLA distribution of the subjects was similar to known Korean population data and did not deviate from the HWE proportions. The alleles that showed positive associations with non-responsiveness (<10mIU/mL) or low antibody titer (<100mIU/mL) were HLA-A*33, B62, DRB1*04, and DRB1*07, while the alleles A*02 and DRB1*08 showed negative associations. Among these alleles, B62, DRB1*07 and DRB1*08(-) showed significant associations with a poor or decreased response to vaccination even after correction (OR=1.83, 1.99, 5.63; pc<0.05) and also showed dose effects. After stratification by other associated alleles at different loci, B62 and DRB1*07 were independently associated with non-responsiveness, but A*02(-) and DRB1*08(-) lost their individual associations. The combined association of A*02(-)-DRB1*08(-) and B62-DRB1*08(-) was significant (OR=25.2 and 24.5; pc<0.05). Although the hierarchy is not clear, we can assume the following: (i) B62 and DRB1*07 have independent effects, (ii) DRB1*08(-) has a very strong and synergic effect, and (iii) there is probability of a third factor controlling A*02(-) and DRB1*08(-) with an effect on non-responsiveness to HBV vaccination in Korean infants., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: The number of aldehyde dehydrogenase-bright (ALDH(br) ) cells has been suggested as a viable marker of hematopoietic stem cell function. We evaluated the suitability of ALDH(br) cell analysis in the quality assessment of postthaw cord blood (CB) units., Study Design and Methods: A total of 245 CB units were obtained for estimating the numbers of total nucleated cells (TNCs), CD34+ cells, ALDH(br) cells, ALDH(br) cells among CD34+ cells (CD34+ALDH(br) cells), CD34+ cells among ALDH(br) cells (ALDH(br) CD34+ cells), colony-forming unit (CFU)-granulocyte-macrophages (GMs), and CFU-granulocyte-erythrocyte-macrophage-megakaryocytes (GEMMs). Simple linear regression analysis was performed to assess the correlation between the number of TNCs and CD34+ cells before and after crypreservation and CD34+ALDH(br) cells, ALDH(br) cells, and ALDH(br) CD34+ cells after cryopreservation and the number of CFU-GEMMS and CFU-GMs., Results: The number of CFU-GMs was found to be significantly correlated with the number of CD34+ cells before and after cryopreservation (r = 0.418 and r = 0.359, respectively), CD34+ALDH(br) cells, ALDH(br) cells, and ALDH(br) CD34+ cells (r = 0.426, r = 0.455, and r = 0.469, respectively). The number of CFU-GEMMs was found to be significantly correlated with the number of TNCs and CD34+ cells before and after cryopreservation (TNCs, r = 0.251 and r = 0.250, respectively; CD34+ cells, r = 0.391 and r = 0.347, respectively), CD34+ALDH(br) cells, ALDH(br) cells, and ALDH(br) CD34+ cells (r = 0.297, r = 0.297, and r = 0.252, respectively)., Conclusion: The high correlation found between ALDH activity and CFU-GM number supports the suitability of ALDH analysis in the quality assessment of postthaw CB units., (© 2014 AABB.)

Two major genotypes are known to affect the development and progression of Alzheimer's disease (AD) and its response to cholinesterase inhibitors: the apolipoprotein E (ApoE) and butyrylcholinesterase genes (BChE). This study analyzed the effects of the BChE and ApoE genotypes on the cortical thickness of patients with AD and examined how these genotypes affect the neuropsychiatric symptoms of AD. AD-drug-naïve patients who met the probable AD criteria proposed by the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association were recruited. Of 96 patients with AD, 65 were eligible for cortical thickness analysis. 3D T1-weighted images were acquired, and the cortical regions were segmented using the constrained Laplacian-based automated segmentation with proximities (CLASP) algorithm. Neuropsychiatric symptoms were measured by Neuropsychiatric Inventory (NPI) scores. BChE wild-type carriers (BChE-W) showed more thinning in the left dorsolateral prefrontal cortex, including the lateral premotor regions and anterior cingulate cortex, than did BChE-K variant carriers (BChE-K). ApoE-ε4 carriers had a thinner left medial prefrontal cortex, left superior frontal cortex, and left posterior cingulate cortex than did ApoE-ε4 non-carriers. Statistical analyses revealed that BChE-K carriers showed significantly less severe aberrant motor behavioral symptoms and that ε4 non-carriers showed less severe anxiety and indifference symptoms. The current findings show that, similar to ApoE-ε4 non-carriers, BChE-K carriers are protected from the pathological detriments of AD that affect frontal cortical thickness and neuropsychiatric symptoms. This study visually demonstrated the effects of the BChE-K and ApoE genotypes on the structural degeneration and complex aspects of the symptoms of AD.

In the present study, we evaluated the correlation between iron deficiency (ID) and zinc deficiency (ZD) and explored the demographic, anthropometric, and feeding-related factors associated with hypozincemia and hair zinc content in weaning infants. Infants aged 6-24 months were recruited, their feeding history was recorded, and their heights and weights were measured. Hemoglobin content, serum iron/total iron-binding capacity, and ferritin and zinc concentrations of serum and hair (using inductively coupled plasma-mass spectroscopy) were assessed. Among 101 infants, 64 (63.4 %) infants exhibited ID. The median serum zinc concentration in iron-deficient infants was lower than that in non-iron-deficient infants, respectively, 73.5 μg/dL (interquartile range [IQR], 65.0-83.8) vs. 87.0 μg/dL (IQR, 77.5-97.0; p = 0.001). The frequency of hypozincemia was also significantly higher in the iron-deficient group than in the non-iron-deficient group (21 out of 64 [32.8 %] vs. 4 out of 37 [10.8 %], respectively; p = 0.014). In multiple regression analysis, the risk of hypozincemia was significantly increased in infants with ID (p = 0.026), mildly underweight infants (weight-for-age Z score < -1; p = 0.034), and infants with mild wasting (weight-for-height Z score < -1; p = 0.028). Hair zinc concentrations (n = 81) were not significantly associated with ID status (p > 0.1); however, there was an inverse relationship between hair zinc concentrations and age of infants (r = -0.250; p = 0.024). In weaning infants, ID is a risk factor for hypozincemia. Hair zinc concentrations appeared to decrease as the age of infants increased during late infancy. Further large-scale studies are needed to validate the relationship between hypozincemia and mild degrees of weight gain impairment in this age group.

Background: The aim of the study was to investigate the knowledge of cord blood (CB) and attitudes toward CB banking among high-potential donors (i.e., well-educated pregnant Koreans) because their voluntary donation is indispensable to the success of unrelated CB transplantation., Study Design and Methods: Questionnaires examining perspectives on CB were distributed to and completed by 1001 women attending a maternity education program from April to October 2008; 863 women answered that they had heard of CB. We analyzed the 863 questionnaires to identify the sources of information, the plan for CB, the reasons for decisions, beliefs about the potential uses of CB, and knowledge about current therapeutic uses., Results: Most subjects received information from promotional materials distributed by CB banks and the media; however, minimal information was obtained from obstetricians. More than 90% of women who planned to donate cited "altruism," and 75.0% of the "private preservation" group indicated that a desire to "safeguard for the future" was the reason for their decision. The probability of autologous CB transplantation (p = 0.001) and current usefulness were significantly overestimated in the private preservation group (p = 0.02). In addition, 56% of subjects underestimated the probability of identifying a matched CB in the public bank, and the overall rate of correct answers about current usefulness was 57.4%., Conclusions: A considerable portion of educated pregnant Korean women has more than minimal knowledge of CB, but the levels of knowledge regarding the potency of the public bank and the current usefulness and limitations of CB are generally low; in addition, obstetricians play insignificant roles in disseminating knowledge. Providing accurate and detailed information to pregnant women not only via brochures and the media and/or Internet but also by obstetricians would encourage CB donation., (© 2010 American Association of Blood Banks.)

Aim: To investigate the risk factors for Clostridium-difficile-associated diarrhea (CDAD) recurrence, and its relationship with proton pump inhibitors (PPIs)., Methods: Retrospective data of 125 consecutive hospitalized patients diagnosed with CDAD between January 2006 and December 2007 were collected by medical chart review. Collected data included patient characteristics at baseline, underlying medical disease, antibiotic history before receiving a diagnosis of CDAD, duration of hospital stay, severity of CDAD, concurrent treatment with PPIs, laboratory parameters, response to CDAD therapy, and recurrence of disease within 90 d of successful treatment. Various clinical and laboratory parameters were compared in patients in whom CDAD did or did not recur., Results: Of the 125 patients (mean age, 67.6 +/- 13.9 years) that developed CDAD, 98 (78.4%) did not experience recurrence (non-recurrent group) and 27 (21.6%) experienced one or more recurrences (recurrent group). Prior to the development of CDAD, 96% of the 125 patients were prescribed antibiotics, and 56 (44.8%) of the patients received PPIs. Age older than 65 years (P = 0.021), feeding via nasogastric tube (NGT) (P = 0.045), low serum albumin level (P = 0.025), and concurrent use of PPIs (P = 0.014) were found to be risk factors for CDAD recurrence by univariate analysis. However, sex, length of hospital stay, duration and type of antibiotics used, severity of disease, leukocyte count and C-reactive protein (CRP) were not associated with risk of CDAD recurrence. On multivariate analysis, the important risk factors were advanced age (> 65 years, adjusted OR: 1.32, 95% CI: 1.12-3.87, P = 0.031), low serum albumin level (< 2.5 g/dL, adjusted OR: 1.85, 95% CI: 1.35-4.91, P = 0.028), and concurrent use of PPIs (adjusted OR: 3.48, 95% CI: 1.64-7.69, P = 0.016)., Conclusion: Advanced age, serum albumin level < 2.5 g/dL, and concomitant use of PPIs were found to be significant risk factors for CDAD recurrence.

Birthweight and the hematopoietic progenitor cell content in cord blood affect and reflect fetal development, and MHC has been reported to play an important role in intrauterine growth. In this study, we assessed HLA-A, -B and -DRB1 polymorphisms, birthweight and cord blood CD34(+) cell content in 1628 full-term healthy neonates to identify the HLA alleles that are associated with fetal growth in Koreans. HLA-A*31, B*47, B*51, DRB1*04 showed positive association and HLA-A*03, A*24, A*30, B*07, B*52, B*58, DRB1*03 showed negative association with birthweight and/or CD34(+) cell content; additionally, there was a greater association in homozygotes than heterozygotes revealed in the trend analysis of birthweight centile with candidate allele zygosity (A*24, P= 0.018; DRB1*04, P= 0.047). Among these alleles, HLA-A*24 and DRB1*03 showed significant negative association with birthweight and/or CD34(+) cell content after Bonferroni correction, suggesting a significant association of these alleles with fetal growth in late pregnancy (A*24, P= 0.002, P(c) = 0.026; DRB1*03, P < 0.001, P(c) < 0.001). Various populations should be analyzed to identify different or consistent factors among ethnicities. Furthermore, a larger scale study that includes pre-terms will aid in the comprehensive understanding of these associations.

Background: Anti-cyclic citrullinated peptide (CCP) antibody is emerging as an important diagnostic marker for rheumatoid arthritis (RA). We evaluated the analytical and diagnostic performance of the ARCHITECT anti-CCP (Abbott Diagnostics), a new fully automated chemiluminescent microparticle immunoassay., Methods: Serum samples from 69 patients with RA and 86 non-RA patients were used to evaluate the performance of the ARCHITECT anti-CCP assay, and the results were compared with those of EliA CCP (Phadia). The optimal cut-off value was calculated using receiver operating characteristic (ROC) curve analysis., Results: Within-run and total imprecision (%CV) of the ARCHITECT anti-CCP were <6% and good linearity was observed over the claimed range. The areas under the ROC curves for the ARCHITECT anti-CCP and EliA CCP were 0.90 and 0.89, respectively. The sensitivity and specificity were 76.8% and 95.3% for the ARCHITECT anti-CCP and 78.3% and 95.3% for EliA CCP using the manufacturer's cut-off thresholds. Both assays showed sensitivity of 84.1% and specificity of 94.2% using the optimal cut-off values., Conclusions: The analytical performance of the ARCHITECT anti-CCP was satisfactory and diagnostic performance was comparable to that of EliA CCP. The use of optimal cut-off thresholds can yield higher sensitivity with minimal loss of specificity.

Background: In the public cord blood (CB) banks, only safe CB units with adequate cell doses are processed and stored. Complete blood count (CBC) of CB is crucial for estimating total nucleated cells (TNC) and screening suitable CB units without hematologic abnormalities. We analyzed CBC parameters of the donated CB from healthy Korean neonates to establish CBC reference values., Methods: A total of 2,129 Korean CB units, donated and processed during the period from August 2007 to December 2007, were enrolled. We measured hemoglobin (Hb), white blood cell (WBC) count, differential count of WBC, platelets and nucleated red blood cell (nRBC) count by XE-2100 automated hematology analyzer (Sysmex, Japan), and estimated reference value of each parameter by using parametric (Mean+/-2SD) and/or non-parametric methods (2.5-97.5 percentile). And also, we compared the result of each parameter in relation to sex of neonates and delivery method., Results: Because the differences of CBC values among different subgroups were not remarkable, we established the reference intervals as follows without subgroup division: Hb, 9.0-14.4 g/dL; WBC count, 5.6-18.5 x 10(3)/microL; differential count of WBC (neutrophils, 40.8-72.4%; lymphocytes, 17.2-46.7%; monocytes, 4.9-12.8%; eosinophils, 0.7-7.0%; basophils, 0.0-1.6%); platelet, 130-287 x 10(3)/microL; nRBCs, 0.0-13.1/100 WBC., Conclusions: We established cord blood CBC reference values of healthy Korean neonates using a large-scale CB units. The established CBC reference values from our study will be useful as basic data for CBC interpretation and assessment of transplant suitability of donated CB.

The human umbilical cord (hUC) is a source of adult tissue-derived mesenchymal stem cells (MSCs). A pulsed low-intensity ultrasound (PLIUS) method is described for increasing the yield of MSCs from whole hUC without enzymatic digestion or growth factor supplementation. Analysis of the immunophenotype of cells and a differentiation study were performed to show the compatibility of MSCs. The mean number of cells recovered from primocultures of hUC was 6 x 10(5) cells/cm. PLIUS resulted in a 3.3-fold increase in MSC yield at passage 0. PLIUS exposure increases the yield of hUC-MSCs by promoting release and enhancing proliferation.

The Mycobacterium avium complex (MAC) is the most frequently isolated species among non-tuberculous mycobacteria (NTM) clinical isolates. Physicians pay attention to the differential diagnosis of the disease caused by MAC from tuberculosis because of their similar clinical presentations. Expression of the macrophage-induced gene (mig) is one of the virulence phenotypes in MAC, but it has not been determined whether the presence of the mig gene itself has any relationship with clinical disease or whether it is merely a marker for MAC. To uncover the significance of the mig gene among MAC clinical isolates, positive cultures from respiratory specimens from patients in a tertiary referral centre were identified by sequencing the 16S rRNA gene. The mig gene was also evaluated using PCR and sequence analysis. The medical records from the patients were reviewed retrospectively. The diagnostic criteria from the American Thoracic Association were adopted for the diagnosis of NTM lung disease. A total of 45 MAC clinical isolates were identified over a period of 1 year. Following 16S rRNA sequencing, all of the 23 M. avium isolates were categorized as sequevar I. Among the 22 Mycobacterium intracellulare isolates, 18 strains were identified as M. intracellulare sequevar I and the remaining four consisted of one each of sequevars II, III, IV and V. The proportion of cases that fitted the diagnostic criteria of NTM lung disease was 26.7 % (12/45). The mig PCR results were 100 % positive for the MAC isolates studied, irrespective of their species, sequevar or disease-causing properties. However, following bootstrap analysis of the mig sequences, we observed definite grouping between M. avium and M. intracellulare. Thus the mig gene is a species-specific marker with distinct sequence diversity between the two species M. avium and M. intracellulare, but there is poor correlation between disease-causing properties and specific mig sequences.

Background: We evaluated the performance and false positive rate of Mediace RPR test (Sekisui, Japan), a newly introduced nontreponemal test using a chemistry autoanalyzer., Methods: The sensitivity of Mediace RPR test was analyzed using sera from 50 patients with syphilis in different stages (8 primary, 7 secondary, and 35 latent), 14 sera positive with fluorescent treponemal antibody absorption (FTA-ABS) IgM, and 74 sera positive with conventional rapid plasma regain (RPR) card test (Asan, Korea) and also positive with Treponema pallidum hemagglutination (TPHA) test or FTA-ABS IgG test. The specificity was analyzed on 108 healthy blood donors. We also performed RPR card test on 302 sera that had been tested positive with Mediace RPR test and also performed TPHA or FTA-ABS IgG test to analyze the false positive rate of Mediace RPR test. A cutoff value of 0.5 R.U. (RPR unit) was used for Mediace RPR test., Results: Mediace RPR test on syphilitic sera of different stages (primary, secondary, and latent stages) and FTA-ABS IgM positive sera showed a sensitivity of 100%, 100%, 82.9% and 100%, respectively. Among the 74 sera positive with conventional RPR card test and TPHA or FTA-ABS IgG test, 55 were positive with Mediace test. The specificity of Mediace RPR test on blood donors was 97.2%. Among the 302 sera positive with Mediace RPR test, 137 sera (45.4%) were negative by RPR card and TPHA/FTA-ABS IgG tests., Conclusions: Although the sensitivities of Mediace RPR were good for primary and secondary syphilis, due to its high negative rate of Mediace RPR over the conventional RPR positive samples, further studies are necessary whether it can replace conventional nontreponemal test for screening purpose. Moreover, in view of the high false positive rate, positive results by Mediace RPR test should be confirmed with treponemal tests.

Objectives: Methicillin-resistant Staphylococcus aureus (MRSA), originally restricted to hospitals, has emerged as a significant pathogen in the community. Although MRSA accounts for over 60% of S. aureus in tertiary hospitals in Korea, little is known about the epidemiology of community-associated MRSA (CA-MRSA)., Methods: From January to July 2005, a hospital laboratory-based survey was conducted in seven community-based or tertiary hospitals. The medical records and Health Insurance Review Agency databases were reviewed and MRSA isolated from patients without apparent risk factors was defined as CA-MRSA. Susceptibilities to 12 antibiotics were tested by the disc diffusion method. SCCmec typing, Panton-Valentine leucocidin (PVL) gene detection and multilocus sequence typing (MLST) were performed according to published protocols., Results: Of 3,251 S. aureus, 1,900 (58.4%) were MRSA. CA-MRSA accounted for 112 (5.9%) of the MRSA. Of the 112 CA-MRSA isolates, 27 and 33 were found to be pathogens and colonizers, respectively. Fifty-two isolates from the patients with chronic otitis media were classified as 'undetermined'. Most of the 27 CA-MRSA patients had skin and soft tissue infections or acute ear infections. None of the patients died during the study period. Among 72 isolates tested, 64% were multidrug-resistant. SCCmec type IVa was the most common type among the colonizers and pathogens. On MLST analysis, ST72 was predominant, but ST5 and ST239 were prevalent in the 'undetermined' group. None possessed the PVL gene., Conclusions: Despite MRSA-endemic hospital settings, CA-MRSA infections are not common in Korea. A new clone of CA-MRSA, ST72-SCCmec type IVa without the PVL gene, is the most common form.

Mycobacterium lentiflavum has recently been described as an emerging human pathogen without regard to the immune status of the host. We herein report on M. lentiflavum isolated from a respiratory specimen of a patient. Although the organism described in this case seems to be a colonizer of a lung destroyed by tuberculosis, the current methods for species identification of nontuberculous mycobacteria have to be re-evaluated so as not to underestimate these organisms.

Background: The diagnosis of diseases caused by nontuberculous mycobacteria (NTM) is difficult, because NTM are prevalent in the environment such as soil and water, and because they have fastidious properties. In this study we investigated clinical isolates of NTM for their distribution pattern and accurate species identification., Methods: We selected presumptive NTM isolates negative for probe hybridization for M. tuberculosis complex, cultured in a third referral hospital from 21 January 2003 to 20 January 2004. Ninety seven-isolates were identified to the species level by direct sequencing of fragments of 16S rRNA, hsp65 and rpoB genes. A total of 120 isolates were studied for the distribution analysis., Results: Frequently identified NTM species were M. avium (30.8%), M. intracellulare (23.3%) and M. abscessus (18.3%). Others were M. gordonae, M. senegalense, M. fortuitum, M. peregrinum, M. kansasii, M. terrae complex, M. lentiflavum, M. chelonae, and M. szulgai. Three M. tuberculosis complex (2.5%) were also identified among the presumptive NTM isolates. The identification rate by sequencing of 16S rRNA, rpoB, and hsp65 were 65%, 82% and 87%, respectively. The hsp65 or rpoB gene was more efficient than 16S rRNA for the identification of NTM by sequencing., Conclusions: Some NTM are increasingly considered to be the causative organisms in clinical diseases. Thus, direct sequencing could be adapted to routine work of clinical laboratories for accurate identification of NTM to the species level.