How to screen the cervix and reduce the risk of spontaneous preterm birth in asymptomatic women without a prior preterm birth.

Preterm birth (PTB) is a leading cause of perinatal morbidity and mortality globally. PTB rates have increased in South Korea despite reduction in birth rates. A history of PTB is a strong predictor of subsequent PTB and screening of cervical length between 16 0/7 weeks and 24 0/7 weeks of gestation is recommended in women with a singleton pregnancy and a prior spontaneous PTB. However, the prediction and prevention of spontaneous PTBs in women without a prior PTB remain a matter of debate. The scope of this review article comprises cervical screening and prevention strategies for PTB in asymptomatic women without a prior PTB, based on recent evidence and guidelines.

Prediction of Pregnancy-Associated Hypertension Using a Scoring System: A Multicenter Cohort Study.

This study aimed to develop an early pregnancy risk scoring model for pregnancy-associated hypertension (PAH) based on maternal pre-pregnancy characteristics, such as mean arterial pressure (MAP), pregnancy-associated plasma protein-A (PAPP-A) or neither. The perinatal databases of seven hospitals from January 2009 to December 2020 were randomly divided into a training set and a test set at a ratio of 70:30. The data of a total pregnant restricted population (women not taking aspirin during pregnancy) were analyzed separately. Three models (model 1, pre-pregnancy factors only; model 2, adding MAP; model 3, adding MAP and PAPP-A) and the American College of Obstetricians and Gynecologists (ACOG) risk factors model were compared. A total of 2840 (8.11%) and 1550 (3.3%) women subsequently developed PAH and preterm PAH, respectively. Performances of models 2 and 3 with areas under the curve (AUC) over 0.82 in both total population and restricted population were superior to those of model 1 (with AUCs of 0.75 and 0.748, respectively) and the ACOG risk model (with AUCs of 0.66 and 0.66) for predicting PAH and preterm PAH. The final scoring system with model 2 for predicting PAH and preterm PAH showed moderate to good performance (AUCs of 0.78 and 0.79, respectively) in the test set. "A risk scoring model for PAH and preterm PAH with pre-pregnancy factors and MAP showed moderate to high performances. Further prospective studies for validating this scoring model with biomarkers and uterine artery Doppler or without them might be required".

Clinical Features and Risk Factors of Uveitis in Korean Children with Juvenile Idiopathic Arthritis: A Retrospective Cohort Study.

This study aimed to investigate the clinical features and risk factors of uveitis in Korean children with juvenile idiopathic arthritis (JIA). The medical records of JIA patients diagnosed between 2006 and 2019 and followed up for ≥1 year were retrospectively reviewed, and various factors including laboratory findings were analyzed for the risk of developing uveitis. JIA-associated uveitis (JIA-U) developed in 30 (9.8%) of 306 JIA patients. The mean age at the first uveitis development was 12.4 ± 5.7 years, which was 5.6 ± 3.7 years after the JIA diagnosis. The common JIA subtypes in the uveitis group were oligoarthritis-persistent (33.3%) and enthesitis-related arthritis (30.0%). The uveitis group had more baseline knee joint involvement (76.7% vs. 51.4%), which increased the risk of JIA-U during follow-up (p = 0.008). Patients with the oligoarthritis-persistent subtype developed JIA-U more frequently than those without it (20.0% vs. 7.8%; p = 0.016). The final visual acuity of JIA-U was tolerable (0.041 ± 0.103 logMAR). In Korean children with JIA, JIA-U may be associated with the oligoarthritis-persistent subtype and knee joint involvement.

Orally bioavailable BTK PROTAC active against wild-type and C481 mutant BTKs in human lymphoma CDX mouse models.

Bruton tyrosine kinase (BTK) is an important signaling hub that activates the B-cell receptor (BCR) signaling cascade. BCR activation can contribute to the growth and survival of B-cell lymphoma or leukemia. The inhibition of the BCR signaling pathway is critical for blocking downstream events and treating B-cell lymphomas. Herein, we report potent and orally available proteolysis-targeting chimeras (PROTACs) that target BTK to inactivate BCR signaling. Of the PROTACs tested, UBX-382 showed superior degradation activity for wild-type (WT) and mutant BTK proteins in a single-digit nanomolar range of half-maximal degradation concentration in diffuse large B-cell lymphoma cell line. UBX-382 was effective on 7 out of 8 known BTK mutants in in vitro experiments and was highly effective in inhibiting tumor growth in murine xenograft models harboring WT or C481S mutant BTK-expressing TMD-8 cells over ibrutinib, ARQ-531, and MT-802. Remarkably, oral dosing of UBX-382 for <2 weeks led to complete tumor regression in 3 and 10 mg/kg groups in murine xenograft models. UBX-382 also provoked the cell type-dependent and selective degradation of cereblon neosubstrates in various hematological cancer cells. These results suggest that UBX-382 treatment is a promising therapeutic strategy for B-cell-related blood cancers with improved efficacy and diverse applicability.

Measles Virus Neutralizing Antibody Response and Durability Two Years after One or Two Doses of Measles-Mumps-Rubella Vaccine among Young Seronegative Healthcare Workers.

Although there have been several studies regarding the immunogenicity of one or two booster doses of the measles−mumps−rubella (MMR) vaccine in measles-seronegative young adults, limited data are available about how long the immune response is sustained compared with natural infection. This study included seronegative healthcare workers (HCWs) (aged 21−38 years) who received one or two doses of the measles−mumps−rubella (MMR) vaccine and HCWs with laboratory-confirmed measles infection during an outbreak in 2019. We compared neutralizing antibody titers measured using the plaque reduction neutralization (PRN) test and measles-specific immunoglobulin G (IgG) using chemiluminescent immunoassays 2 years after vaccination or infection. Among 107 HCWs with seronegative measles IgGs, the overall seroconversion rate of measles IgGs remained 82.2% (88/107), and 45.8% (49/107) of the participants had a medium (121−900) or high (>900) PRN titer after 2 years from one or two booster doses. The measles-neutralizing antibody titers of both PRN titer (ND50) and geometric mean concentration 2 years after natural infection were significantly higher than those of one or two booster doses of the MMR vaccine (p < 0.001 and p < 0.001, respectively). Our results suggest that serologic screening followed by appropriate postexposure prophylaxis can be beneficial for young HCWs without a history of natural infection especially in a measles outbreak setting, because of possible susceptibility to measles despite booster MMR vaccination 2 years ago. Long-term data about sustainable humoral immunity after one or two booster vaccination are needed based on the exact vaccination history.

Effect of Previous COVID-19 Vaccination on Humoral Immunity 3 Months after SARS-CoV-2 Omicron Infection and Booster Effect of a Fourth COVID-19 Vaccination 2 Months after SARS-CoV-2 Omicron Infection.

In this study, we aimed to determine the effect of COVID-19 vaccination on 3-month immune response and durability after natural infection by the Omicron variant and to assess the immune response to a fourth dose of COVID-19 vaccination in patients with prior natural infection with the Omicron variant. Overall, 86 patients aged ≥60 years with different vaccination histories and 39 health care workers (HCWs) vaccinated thrice before Omicron infection were enrolled. The sVNT50 titer was significantly lower in patients with incomplete vaccination before SARS-CoV-2 infection with the S clade (p < 0.001), Delta variant (p < 0.001), or Omicron variant (p = 0.003) than in those vaccinated thrice. The sVNT results against the Omicron variant did not differ significantly in patients aged ≥60 years (p = 0.49) and HCWs (p = 0.17), regardless of the recipient receiving the fourth dose 2 months after COVID-19. Incomplete COVID-19 vaccination before Omicron infection for individuals aged ≥60 years conferred limited protection against homologous and heterologous virus strains, whereas two or three doses of the vaccine provided cross-variant humoral immunity against Omicron infection for at least 3 months. However, a fourth dose 2 months after Omicron infection did not enhance immunity against the homologous strain. A future strategy using the bivalent Omicron-containing booster vaccine with appropriate timing will be crucial.

Neutralizing Antibody Response, Safety, and Efficacy of mRNA COVID-19 Vaccines in Pediatric Patients with Inflammatory Bowel Disease: A Prospective Multicenter Case-Control Study.

The vaccination of immunocompromised children against coronavirus disease 2019 is an important public health issue. We evaluated the serological response, safety, and efficacy of the BNT162b2 vaccine in children with and without inflammatory bowel disease (IBD). A prospective, multicenter, case-control study was conducted in a pediatric population, including patients with IBD, aged 12-18 years. Clinical characteristics, safety profile, and serum samples for surrogate virus-neutralizing antibody testing pre- and post-BNT162b2 vaccination were assessed. The breakthrough infection rate during the Omicron outbreak was calculated to evaluate efficacy. Fifteen controls and twenty-three patients with IBD were enrolled. After two vaccine doses, the median level of percentage inhibition was highly increased, without significant differences between the groups (control 96.9 and IBD 96.3). However, it was significantly reduced in IBD patients receiving combination therapy (anti-tumor necrosis factor-α + immunomodulators) relative to those in other therapies and controls. Serious adverse events were not observed. The breakthrough infection rate was 42.1%, without statistical differences between the groups. Immunization with BNT162b2 in patients with IBD was comparable with that in healthy adolescents in terms of immunogenicity and safety. Nevertheless, the efficacy of BNT162b2 in preventing infection caused by the Omicron variant in the pediatric population was insufficient.

Change of Dendritic Cell Subsets Involved in Protection Against Listeria monocytogenes Infection in Short-Term-Fasted Mice.

The gastrointestinal tract is the first organ directly affected by fasting. However, little is known about how fasting influences the intestinal immune system. Intestinal dendritic cells (DCs) capture antigens, migrate to secondary lymphoid organs, and provoke adaptive immune responses. We evaluated the changes of intestinal DCs in mice with short-term fasting and their effects on protective immunity against Listeria monocytogenes (LM). Fasting induced an increased number of CD103+CD11b- DCs in both small intestinal lamina propria (SILP) and mesenteric lymph nodes (mLN). The SILP CD103+CD11b- DCs showed proliferation and migration, coincident with increased levels of GM-CSF and C-C chemokine receptor type 7, respectively. At 24 h post-infection with LM, there was a significant reduction in the bacterial burden in the spleen, liver, and mLN of the short-term-fasted mice compared to those fed ad libitum. Also, short-term-fasted mice showed increased survival after LM infection compared with ad libitum-fed mice. It could be that significantly high TGF-ß2 and Aldh1a2 expression in CD103+CD11b- DCs in mice infected with LM might affect to increase of Foxp3+ regulatory T cells. Changes of major subset of DCs from CD103+ to CD103- may induce the increase of IFN-γ-producing cells with forming Th1-biased environment. Therefore, the short-term fasting affects protection against LM infection by changing major subset of intestinal DCs from tolerogenic to Th1 immunogenic.

Control of a nosocomial measles outbreak among previously vaccinated adults in a population with high vaccine coverage: Korea, 2019.

We describe a measles outbreak among previously vaccinated healthcare workers (HCWs) and inpatients and the control measures implemented at a tertiary care hospital in 2019. Case-patients were laboratory-confirmed measles with throat swabs tested by quantitative polymerase chain reactions (PCR), during April-May 2019. Medical histories and documented immunization records were obtained. We compared attack rates (ARs) among HCWs by occupational subgroup and age and examined the outbreak-associated costs. The index case was not ascertained. Among 26 measles case-patients (22 HCWs, four inpatients) aged 18-28 years, 25 had previously received measles-mumps-rubella (MMR) vaccine (12/26, 46% (two doses); 13/26, 50% (one dose)), and 16 (62%) had positive results of measles IgG prior to measles diagnosis. ARs were higher among HCWs aged < 30 years (1.88%), especially in the subgroup under 25 years of age (2.22%). Control measures included work restrictions for seronegative HCWs (218/2320, 9.4%) in immunity verification, administration of the MMR vaccine (207 HCWs) or intravenous immunoglobulin (2 HCWs and 11 inpatients), enhanced health surveillance of HCWs, and mandatory assessment of patients with measles-like symptoms at the infectious diseases screening units. The hospital spent 90,417,132 Korean won (US $79,733) in response to the outbreak. Measles outbreaks can occur in healthcare settings despite high population immunity, highlighting the importance of stronger vaccination policies, particularly among young HCWs. Moreover, an effective outbreak response comprising immunization activities and enhanced surveillance of HCWs and patients to rapidly detect measles-like symptoms at a prodromal phase is essential to control nosocomial measles outbreaks.

Clinical Manifestations of Herpes Zoster Associated with Complications in Children.

Herpes zoster (HZ) is caused by latent varicella-zoster virus (VZV) reactivation when VZV-specific cell-mediated immunity declines. Information on HZ in children is limited. Therefore, we retrospectively investigated HZ's clinical course and complications in children. We extracted the outpatient and hospitalization medical records of pediatric patients (<19 years) primarily diagnosed with HZ (ICD-10 B02 code) between January 2010 and November 2020. HZ was defined as a typical unilateral dermatomal vesicular rash where HZ was the treating physician's primary diagnosis. Recognized HZ complications included combined bacterial skin infection, ophthalmic zoster, zoster oticus without facial paralysis, meningitis, and PHN. We identified 602 HZ cases, among which 54 developed HZ complications and were included in our analysis. The median age was 14.7 years, most patients were aged ≥13 years (42, 79%), and none were aged <4 years. Fifty-three were immunocompetent, and only one had systemic lupus erythematosus. The most frequent complication was zoster ophthalmicus (n = 26, 48%). HZ complications were also observed in immunocompetent or vaccinated children exhibiting a head or neck rash before and after VZV immunization. Current VZV vaccination programs may be insufficient in preventing HZ complications. Therefore, close varicella and HZ burden monitoring and the establishment of effective VZV vaccination programs are imperative.

Assignment of opsonic values to pneumococcal reference serum 007sp and a second pneumococcal OPA calibration serum panel (Ewha QC sera panel B) for 11 serotypes.

Pneumococcal conjugate vaccines (PCVs) have been effective in reducing the disease burden caused by Streptococcus pneumoniae. The first licensed PCV (PCV7) was composed of capsular polysaccharides from seven serotypes. This was followed by PCV10, then PCV13, and currently there are a number of higher valency vaccines in development. As part of licensure, new vaccine iterations require assessment of immunogenicity. Since some antibodies can be non-functional, measuring functional antibodies is desirable. To meet this need, opsonophagocytic assays (OPAs) have been developed. Previous studies have shown there can be significant variations in OPA results from different laboratories. We have previously shown that standardizing OPA data using reference serum 007sp can decrease this variation. To extend this approach to additional serotypes, a panel of sera was tested by five laboratories using a multiplexed OPA for serotypes 2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20B, 22F, and 33F. Each sample was tested in five runs with 007sp tested three times in each run. Results were analyzed using a mixed effects ANOVA model. Standardization of the results significantly decreased the inter-laboratory variation for some serotypes. For serotypes 2, 8, and 11A, the variability was reduced by 40%, 45%, and 40%, respectively. For serotypes 12F, 17F, and 20B, the reductions were more modest (14%, 19%, and 24%, respectively). Standardization had little effect for the remaining serotypes. In many cases, the impact of normalization was blunted by the results from five sera that were collected after an extended post-vaccination interval. We have previously reported consensus values for 007sp for 13 serotypes, as well as the creation of a calibration serum panel ("Ewha Panel A"). Here, we report consensus values for 11 additional serotypes for 007sp and the creation of a second serum panel ("Ewha Panel B"). These consensus values will facilitate the development of next-generation PCVs.

Epidemiology and clinical features of coronavirus disease 2019 in children.

Coronavirus disease-2019 (COVID-19), which started in Wuhan, China, in December 2019 and declared a worldwide pandemic on March 11, 2020, is a novel infectious disease that causes respiratory illness and death. Pediatric COVID-19 accounts for a small percentage of patients and is often milder than that in adults; however, it can progress to severe disease in some cases. Even neonates can suffer from COVID-19, and children may spread the disease in the community. This review summarizes what is currently known about COVID-19 in children and adolescents.

Comparison of Immune Responses to Two Quadrivalent Meningococcal Conjugate Vaccines (CRM197 and Diphtheria Toxoid) in Healthy Adults.

BACKGROUND: After the introduction of the meningococcal ACWY-CRM197 conjugate vaccine (MenACWY-CRM) in 2012 and the meningococcal ACWY-diphtheria toxoid conjugate vaccine (MenACWY-DT) in 2014, immunization was recommended for certain high-risk groups including new military recruits in Korea. However, comparative immunogenicity studies for these vaccines have not been performed in Korea. Here, we compared the immunogenicity of these two vaccines in healthy adults. METHODS: A total of 64 adults, 20-49 years of age, were randomly divided into two groups (1:1) to receive either of the two vaccines. The sera were obtained before and 1 month after vaccination and tested for serogroup-specific serum bactericidal activity using baby rabbit complement. RESULTS: There were no significant differences post-vaccination in the geometric mean indices and the seropositive rate to all serogroups between the vaccines. The proportion of seropositive subjects after vaccination ranged from 88% to 100%. CONCLUSION: Both meningococcal conjugate vaccines showed good immunogenicity in healthy Korean adults without statistically significant differences. Further investigations for serotype distribution of circulating meningococci and the immune interference between other diphtheria toxin-containing vaccines concomitantly used for military recruits are needed to optimize immunization policies. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0002460.

Intranasal immunization with pneumococcal surface protein A in the presence of nanoparticle forming polysorbitol transporter adjuvant induces protective immunity against the Streptococcus pneumoniae infection.

Developing effective mucosal subunit vaccine for the Streptococcus pneumoniae has been unsuccessful mainly because of their poor immunogenicity with insufficient memory T and B cell responses. We thus address whether such limitation can be overcome by introducing effective adjuvants that can enhance immunity and show here that polysorbitol transporter (PST) serves as a mucosal adjuvant for a subunit vaccine against the Streptococcus pneumoniae. Pneumococcal surface protein A (PspA) with PST adjuvant induced protective immunity against S. pneumoniae challenge, especially long-term T and B cell immune responses. Moreover, we found that the PST preferentially induced T helper (Th) responses toward Th2 or T follicular helper (Tfh) cells and, importantly, that the responses were mediated through antigen-presenting cells via activating a peroxisome proliferator-activated receptor gamma (PPAR-γ) pathway. Thus, these data indicate that PST can be used as an effective and safe mucosal vaccine adjuvant against S. pneumoniae infection. STATE OF SIGNIFICANCE: In this study, we suggested the nanoparticle forming adjuvant, PST works as an effective adjuvant for the pneumococcal vaccine, PspA. The PspA subunit vaccine together with PST adjuvant efficiently induced protective immunity, even in the long-term memory responses, against Streptococcus pneumoniae lethal challenge. We found that PspA with PST adjuvant induced dendritic cell activation followed by follicular helper T cell responses through PPAR-γ pathway resulting long-term memory antibody-producing cells. Consequently, in this paper, we suggest the mechanism for safe nanoparticle forming subunit vaccine adjuvant against pneumococcal infection.

Signaling pathways associated with macrophage-activating polysaccharides purified from fermented barley.

Barley is commonly used in many food and health products. We have previously demonstrated the macrophage-stimulating properties of polysaccharides derived from fermented barley. In this study, three polysaccharide fractions (BF-I-III) were purified from fermented barley and their monosaccharide composition was analyzed. Their immune-stimulatory activities and intracellular signaling pathways were also studied in RAW264.7 cells. Among the three fractions, BF-I exhibited enhanced macrophage activation properties, such as inducing the production of IL-6, IL-12, and TNF-α. However, BF-II and BF-III showed moderate effects on RAW 264.7 cells. BF-I treatment led to the phosphorylation of MAPKs, NF-κB, and c-Jun (major component of AP-1 transcription factor) and induced the nuclear translocation of p65 in RAW264.7 cells. In addition, experiments with neutralizing antibodies showed that Dectin-1, toll-like receptor (TLR) 4, scavenge receptor (SR), and CD14 were mainly involved in the stimulation of nitric oxide (NO) production by BF-I which was suppressed by the inhibition of JNK phosphorylation. These findings suggest that BF-I, isolated from fermented barley, has an immune potentiation activity on macrophages, where it activates the JNK signaling pathway via several macrophage receptors including dectin-1, TLR4, SR, and CD14.

Zoonotic Staphylococcus pseudintermedius sinonasal infections: risk factors and resistance patterns.

BACKGROUND: Staphylococcus pseudintermedius is a Gram-positive bacteria that colonizes the skin and orifices of healthy canines and felines. It has recently been identified as a cause of sinonasal infections in humans. METHODS: This study was a retrospective review of chronic rhinosinusitis (CRS) patients with S pseudintermedius-positive sinonasal cultures and comparison to a prospectively collected control sample of patients who underwent culture for acute exacerbation of CRS. RESULTS: Thirty-three patients with CRS had nasal cultures positive for S pseudintermedius. Of the positive cultures, 82% demonstrated resistance to penicillin, 58% to clindamycin, 45% to trimethoprim-sulfamethoxazole, 33% to doxycycline, and 27% to oxacillin. Ninety-seven percent of patients with S pseudintermedius were dog owners. There was no significant difference in age, gender, recent endoscopic sinus surgery, or immunosuppression or deficiency between S pseudintermedius patients and patients undergoing culture for acute exacerbation of CRS, but S pseudintermedius infection was associated with dog ownership (p < 0.01). S pseudintermedius infection was not associated with behaviors such as a dog sleeping in the bedroom, routinely licking humans, or being diagnosed with a soft tissue infection. CONCLUSION: Although a rare cause of infection in humans, S pseudintermedius should be considered in sinonasal infections refractory to standard medical management, especially if the patient has regular contact with dogs. S pseudintermedius is not readily identified with routine laboratory diagnostic testing and often demonstrates multidrug resistance, making it a pathogen that is commonly misdiagnosed and difficult to treat.

Comparison of stress distribution in dental crown with different cusp angles: 3D finite element analysis.

The purpose of this study is to measure the failure risk of a crown depending on the cusp angle. Three all-ceramic crown models consisting of CH (high incline), CM (middle incline), and CL (low incline) are designed. Stress is applied to the crown with Loading case-1 (top of cusp tip) and Loading case-2 (middle of cusp ridge) with the use of FEA software. In Loading case-1 and case-2, the CH showed the highest Maximum Principal Stress (MPS) while the CL showed the lowest MPS. The cusp angle is an influential factor affecting stress distribution in dental crowns.

Galectin-9 Induced by Dietary Probiotic Mixture Regulates Immune Balance to Reduce Atopic Dermatitis Symptoms in Mice.

Probiotics can be an effective treatment for atopic dermatitis (AD), while their mechanism of action is still unclear. Here, we induced AD in mice with 2,4-dinitrochlorobenzene and administrated YK4, a probiotic mixture consisting of Lactobacillus acidophilus CBT LA1, L. plantarum CBT LP3, Bifidobacterium breve CBT BR3, and B. lactis CBT BL3. Then, we have validated the underlying mechanism for the alleviation of AD by YK4 from the intestinal and systematic immunological perspectives. Administration of YK4 in AD mice alleviated the symptoms of AD by suppressing the expression of skin thymic stromal lymphopoietin and serum immunoglobulin E eliciting excessive T-helper (Th) 2 cell-mediated responses. YK4 inhibited Th2 cell population through induce the proportion of Th1 cells in spleen and Treg cells in Peyer's patches and mesenteric lymph node (mLN). CD103+ dendritic cells (DCs) in mLN and the spleen were significantly increased in AD mice administered with YK4 when compared to AD mice. Furthermore, galectin-9 was significantly increased in the gut of AD mice administered with YK4. In vitro experiments were performed using bone marrow-derived DCs (BMDC) and CD4+ T cells to confirm the immune mechanisms of YK4 and galectin-9. The expression of CD44, a receptor of galectin-9, together with programmed death-ligand 1 was significantly upregulated in BMDCs following treatment with YK4. IL-10 and IL-12 were upregulated when BMDCs were treated with YK4. Cytokines together with co-receptors from DCs play a major role in the differentiation and activation of CD4+ T cells. Proliferation of Tregs and Th1 cell activation were enhanced when CD4+T cells were co-cultured with YK4-treated BMDCs. Galectin-9 appeared to contribute at least partially to the proliferation of Tregs. The results further suggested that DCs treated with YK4 induced the differentiation of naïve T cells toward Th1 and Tregs. At the same time, YK4 alleviated AD symptoms by inhibiting Th2 response. Thus, the present study suggested a potential role of YK4 as an effective immunomodulatory agent in AD patients.

Validation of a Multiplexed Opsonophagocytic Assay for 11 Additional Pneumococcal Serotypes and Its Application to Functional Antibody Evaluation Induced by Pneumococcal Polysaccharide Vaccine.

BACKGROUND: Various pneumococcal vaccines have been evaluated for immunogenicity by opsonophagocytic assay (OPA). A multiplexed OPA (MOPA) for 13 pneumococcal serotypes was developed by Nahm and Burton, and expanded to 26 serotypes in 2012. The development of new conjugate vaccines with increased valence has necessitated expanded MOPAs to include these additional serotypes. In this study, we validated this expanded MOPA platform and applied to measure antibodies against 11 additional serotypes (2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20B, 22F, and 33F) in human sera. METHODS: All materials, including serum, complement, bacterial master stocks, and HL-60 cells, were evaluated for assay optimization. Following optimization, the assay was validated for accuracy, specificity, and intra- and inter-assay precision with sera from adult donors following standard protocols. The assay was applied to evaluate functional antibodies of 42 sera immunized with 23-valent pneumococcal polysaccharide vaccine (PPV23). RESULTS: The expanded MOPA platform was specific for all serotypes, with the exception of serotype 20. The assay results were highly correlated with those obtained from single-serotype OPA, indicating acceptable accuracy. The coefficients of variation were 7%-24% and 13%-39% in tests of intra- and inter-assay precision, respectively, using three quality-control samples. A MOPA that included 11 additional serotypes in the PPV23 was established and validated with respect to accuracy, specificity, and precision. The opsonic indices of immune sera were obtained using this validated assay. CONCLUSION: The expanded MOPA will be useful for evaluation of the immunogenicity of PPV23 and future conjugate vaccine formulations.

Oral administration of palatinose vs sucrose improves hyperglycemia in normal C57BL/6J mice.

Palatinose is a sucrose analog with a slower digestion rate than that of sucrose. For this reason, palatinose shows better effects on hepatic lipogenesis and cholesterol homeostasis compared with sucrose. We hypothesized that supplementation with palatinose instead of sucrose improves postprandial hyperglycemia and hyperinsulinemia in mice. Herein, we compared the digestion rates in vitro and observed physiological changes in vivo between sucrose- and palatinose-containing diets given to mice. Palatinose was hydrolyzed only by enzymes of the small intestine and was digested more slowly compared with sucrose in vitro. In mice, a diet containing palatinose resulted in significantly lower body weight gain and food efficiency rate values than those given a diet with sucrose. In this study, changes in serum biochemistry; hepatic fatty acid synthesis; cholesterol homeostasis; glucogenic, proinflammatory cytokines; and oxidative stress-related genes and proteins in the palatinose- and sucrose-fed mice were measured. Compared with the mice fed the sucrose diet, the palatinose diet resulted in lower serum glucose, insulin, and total cholesterol levels, as well as lower expression of several lipogenesis-related genes and proteins. Histological analysis of hepatic cells of palatinose-fed mice showed normal morphology. In conclusion, palatinose intake results in lower hepatic lipogenesis and better cholesterol homeostasis than the effects from sucrose.