Robust antibody response after a third BNT162b2 vaccine compared to the second among immunocompromised and healthy individuals,a prospective longitudinal cohort study

PurposeAs protection from COVID-19 following two doses of the BNT162b2 vaccine showed a time dependent waning, a third (booster) dose was administrated. This study aims to compare the antibody response following the third dose versus the second and to evaluate post-booster seroconversion.MethodsA prospective observational study conducted in Maccabi Healthcare Services. Serial SARS-CoV-2 Spike IgG tests, 1,2,3 and 6 months following the second vaccine dose and one month following the third were obtained. Neutralizing antibody levels were measured in a subset of participants. Per individual SARS-CoV-2 Spike IgG titer ratios were calculated one month after the booster administration compared to titers one month following the second dose and prior to booster.ResultsAmong 110 participants, 56 (51%) were women. Mean age was 61.7 ± 1.9 years and 66 (60%) were immunocompromised. One month after third dose, IgG titers were induced 7.83 (95 %CI 5.25–11.67) folds and 2.40 (95 %CI 1.90–3.03) folds compared to one month after the second, in the immunocompromised and immunocompetent groups, respectively. Of the 17 immunocompromised participants who were seronegative after the second dose, 4 (24%) became seropositive following the third. Comparing the titers prior to the third dose, an increase of 50.7 (95 %CI 32.5–79.1) fold in the immunocompromised group and 25.7 (95 %CI 19.1–34.7) fold in and immunocompetent group, was observed.ConclusionA third BNT162b2 vaccine elicited robust humoral response, superior to the response observed following the second, among immunocompetent and immunocompromised individuals.     

NUDT15 is a key genetic factor for prediction of hematotoxicity in pediatric patients who received a standard low dosage regimen of 6-mercaptopurine

6-Mercaptopurine (6-MP) is commonly used for treatment of acute lymphoblastic leukemia (ALL). The incidence of hematotoxicity caused by this drug is quite high in Asians even using a standard low dosage regimen. The present study was aimed to elucidate the impact of thiopurine S-methyltransferase (TPMT), a nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15), inosine triphosphatase (ITPA) and ATP Binding Cassette Subfamily C Member 4 (ABCC4) polymorphisms on hematotoxicity in pediatric patients who received a standard low starting dose of 6-MP. One hundred and sixty-nine pediatric patients were enrolled and their genotypes were determined. Patients who carried NUDT15¹3 and NUDT15¹2 genotypes were at a 10–15 fold higher risk of severe neutropenia than those of the wild-type during the early months of the maintenance phase. Risk of neutropenia was not significantly increased in patients with other NUDT15 variants as well as in patients with TPMT, ITPA or ABCC4 variants. These results suggest that NUDT15 polymorphisms particularly, NUDT15¹3 and NUDT15¹2, play major roles in 6-MP-induced severe hematotoxicity even when using a standard low dosage of 6-MP and genotyping of these variants is necessary in order to obtain precise tolerance doses and avoid severe hematotoxicity in pediatric patients.     

Outcome of conservative treatment of primary vesicoureteral reflux in 87 Thai children in a single center

AIM: To evaluate the outcome of primary vesicoureteral reflux (VUR) using conservative treatment. METHODS: Eighty-seven children with primary VUR who had been treated with a conservative medical regimen and monitored through a yearly cystogram were recruited for the study. The study was conducted at the Pediatric Nephrology Clinic in Songklanagarind Hospital, the major tertiary care center in southern Thailand. Statistical analyses using Kaplan-Meier survival curves, chi-squared test, Fisher's exact test and multivariate analysis with Cox regression were performed. RESULTS: The study group consisted of 41 boys and 46 girls, with a total of 133 VUR. The age of the boys was significantly lower than that of the girls (P < 0.001). Resolution of the low grades (grades I-III) of VUR was significantly more frequent than that of the high grades (grades IV-V) (68/95, 72%vs 14/38, 37%; P < 0.001). Using the Kaplan-Meier survival analysis and log-rank test, the resolutions of VUR in boys versus girls, and age <1 years versus >or=1 years were not significantly different (P = 0.2252 and 0.4756, respectively). Low-grade VUR and unilateral VUR had significantly higher probabilities of resolution than high-grade VUR and bilateral VUR, respectively (P = 0.0041 and 0.0467, respectively). Multivariate Cox regression analysis indicated that among low-grade VUR, boys and unilateral VUR had significantly higher probabilities of resolution. Among the high-grade VUR, neither sex nor laterality had a significant effect on the probabilities of VUR resolution. CONCLUSION: This study offers more evidence that children with low-grade VUR have a higher chance of reflux resolution if they are boys and have only unilateral VUR. There is still no good guide for resolution of reflux in children with high-grade VUR.     

Plaque-forming cell capability in the senescent

The number of plaque-forming cells (PFC) developed in pokeweed mitogen (PWM)-activated unfractionated or T/B separated, 4:1 reconstituted cultures of peripheral blood lymphocytes (PBL) with well-characterized subpopulations obtained from healthy, aged subjects was compared to that of young blood donors. The absolute number of PBL in the aged was reduced by 36%, and the percentage of sheep erythrocyte-rosette-forming cells (E-RFC) by 27%, compared to the percentage obtained in young donors. The IgM-, IgG- and IgA-immunoglobulin (Ig) secretion was monitored with a protein A PFC assay. The number of PFC in PBL cultures of the aged was 58% of the number found in cultures of the young controls. The number of PFC generated in cultures of autologous irradiated T and untreated B cells showed a 104% increase in the aged whereas a 63% increase was obtained using cells from young individuals. Co-cultures of young B cells with untreated or irradiated young or aged T cells showed a significant rise in the PFC response in cultures with irradiated aged T cells, while an equal number of PFC was generated in cultures of young B cells with young or aged untreated T cells. Our results demonstrate a decreased number of PBL, especially T cells, an impaired B cell function and a pronounced enhancement of the PFC response in cultures of irradiated aged T cells and young or aged B cells, whereas the T helper function of untreated cells was found to be normal. The influence of monocytes on the PFC response did not differ in the two groups.     

T cell receptor (TCR) V gene segment use in HLA-typed Japanese healthy subjects

The expression of 13 different α and β V gene segments of the T cell receptor for antigen (TCR) was examined, using V gene-specific MoAbs, on human peripheral blood T lymphocytes from 32 healthy Japanese subjects. In addition, to examine associations between TCR V gene products and HLA alleles, the HLA class I and class II types of all subjects were serologically determined. The reactivities of the anti-TCR V-specific MoAbs were, with some significant exceptions, similar to those previously described in healthy Caucasian subjects. We found a non-random V gene usage as well as a statistically significant bias of the expression of eight Vβ gene products towards the CD4⁺ subpopulation, and a significant skewness in the usage of Vα12 towards the CD8⁺ population. Some subjects showed increased reactivities (above 10%) of certain MoAbs, mainly in the CD8⁺ subpopulation. We found no distinct correlation between any certain HLA class I or II allele and TCR V gene usage in the CD8⁺ or CD4⁺ subpopulations, respectively. In conclusion, the pattern of anti-TCR V-specific MoAb reactivities found in CD4⁺ and CD8⁺ subsets of peripheral blood lymphocytes of healthy Japanese subjects was in general found to match that previously described in healthy Caucasian subjects.     

Strong linkage disequilibrium of a HbE variant with the (AT)9(T)5 repeat in the BP1 binding site upstream of the β-globin gene in the Thai population

A binding site for the repressor protein BP1, which contains a tandem (AT)_x(T)_y repeat, is located approximately 530 bp 5 to the human -globin gene (HBB). There is accumulating evidence that BP1 binds to the (AT)₉(T)₅ allele more strongly than to other alleles, thereby reducing the expression of HBB. In this study, we investigated polymorphisms in the (AT)_x(T)_y repeat in 57 individuals living in Thailand, including three homozygotes for the hemoglobin E variant (HbE; 26Glu->Lys), 22 heterozygotes, and 32 normal homozygotes. We found that (AT)₉(T)₅ and (AT)₇(T)₇ alleles were predominant in the studied population and that the HbE variant is in strong linkage disequilibrium with the (AT)₉(T)₅ allele, which can explain why the ^E chain is inefficiently synthesized compared to the normal ^A chain. Moreover, the mildness of the HbE disease compared to other hemoglobinopathies in Thai may be due, in part, to the presence of the (AT)₉(T)₅ repeat on the HbE chromosome. In addition, a novel (AC)_n polymorphism adjacent to the (AT)_x(T)_y repeat (i.e., (AC)₃(AT)₇(T)₅) was found through the variation screening in this study.MIM and accession numbers and URLs for data presented herein are as follows: Online Mendelian Inheritance of Man (OMIM), (for HBB [MIM 141900]). GenBank, (accession number [NG_000007.2] reference sequence information).     

80例正常人体表标测Q-T_d~p的观察

采用９１ 导联体表电位标测法（ Ｂ Ｓ Ｐ Ｍ） 观察８０ 例正常人 Ｑ Ｔｐｄ（ Ｑ 波起点到 Ｔ 波峰值间期的离散度） ,与同步１２ 导联心电图 Ｑ Ｔ 离散度（ Ｑ Ｔｄ） 对照,探讨 Ｂ Ｓ Ｐ Ｍ 条件下测定 Ｑ Ｔｄ 的可行性。结果：① Ｑ Ｔｐ 、 Ｑ Ｔｐｄ 、 Ｑ Ｔｐｃ１ｄ（ Ｂａｚｚｅｔｔ 公式校正） 、 Ｑ Ｔｐｃ２ｄ（ Ｆｒｉｄｅｒｃｉａ 公式校正） 分别为（２９２ ．６９ ±３７ ．７５） ｍｓ 、（３６ ．７７ ±７ ．４０） ｍｓ 、（４０ ．２３ ±９ ．０４） ｍｓ 和（４０ ．１１ ±７ ．７３） ｍｓ ;② Ｑ Ｔｐｄ 与 Ｑ Ｔｄ 、 Ｑ Ｔｐｃ１ｄ 与 Ｑ Ｔｃ１ｄ 、 Ｑ Ｔｐｃ２ｄ 与 Ｑ Ｔｃ２ｄ 有良好的相关性;③３ 个年龄组（１８ ～３５ 岁、３６ ～６０ 岁、６１ ～７０ 岁） 各参数间无显著性差异;④ Ｑ Ｔｐ 女性明显大于男性（ Ｐ＜ ０ ．０５） ,其余各值男女性之间均无显著性差异。提示： Ｂ Ｓ Ｐ Ｍ 测定 Ｑ Ｔｐｄ 简便可行、较为准确,正常值可暂定为５２ ｍｓ 。     

从泰国传统医药立法探讨我国的中医药知识产权保护方法

近年来传统医药保护问题获得世界各国普遍关注.其中,泰国推出了以国家立法形式对传统医药知识做特殊保护的方法,对发展中国家具有一定借鉴作用.本文在介绍泰国传统医药知识产权保护政策基础上,对我国中医药知识产权保护方法提出了构想.     

Impact of corneal parameters on intraocular pressure measurements in different tonometry methods

AIM: To evaluate the impact of central corneal thickness (CCT) and corneal curvature on intraocular pressure (IOP) measurements performed by three different tonometers. METHODS: IOP in 132 healthy eyes of 66 participants was measured using three different tonometry techniques: Goldmann applanation tonometer (GAT), Pascal dynamic contour tonometer (DCT), and ICare rebound tonometer (RT). CCT and corneal curvature were assessed. RESULTS: In healthy eyes, DCT presents significantly higher values of IOP than GAT (17.34±3.69 and 15.27±4.06 mm Hg, P<0.0001). RT measurements are significantly lower than GAT (13.56±4.33 mm Hg, P<0.0001). Compared with GAT, DCT presented on average 2.51 mm Hg higher values in eyes with CCT<600 μm and 0.99 mm Hg higher results in eyes with CCT≥600 μm. The RT results were lower on average by 1.61 and 1.95 mm Hg than those obtained by GAT, respectively. Positive correlations between CCT in eyes with CCT<600 μm were detected for all IOP measurement techniques, whereas a similar relationship was not observed in eyes with thicker corneas. A correlation between IOP values and keratometry in the group with CCT<600 μm was not detected with any of the tonometry methods. In thicker corneas, a positive correlation was found for GAT and mean keratometry values (R=0.369, P=0.005). CONCLUSION: The same method should always be chosen for routine IOP control, and measurements obtained by different methods cannot be compared. All analysed tonometry methods are dependent on CCT; thus, CCT should be taken into consideration for both diagnostics and monitoring.