CD4-independent protective cytotoxic T cells induced in early life by a non-replicative delivery system based on virus-like particles

The relative immaturity of the neonatal immune system limits CD4(+) Th1 and cytotoxic T lymphocyte (CTL) responses, and represents a significant challenge for the development of vaccines against intracellular pathogens. In this report, we demonstrate the ability of a non-replicative delivery system based on parvovirus-like particles (VLP) to induce CTL responses in the neonatal period. A single immunization of 1-week-old BALB/c mice with recombinant VLP carrying a CD8(+) T cell determinant from lymphocytic choriomeningitis virus (VLP-LCMV) induced antigen-specific CD8(+) cytotoxic T cells that were similar to those elicited by adult immunization, as assessed by cytotoxic activity, interferon (IFN)-gamma secretion, cytotoxic precursor cell frequencies, in vitro avidity for antigen and protective activity against viral challenge. These CTL responses are elicited within 2 weeks of a single immunization, in the absence of adjuvant and independently of the presence and help of CD4(+) T cells, highlighting the potential of VLP as candidate vaccine vectors in early life.     

EB病毒对新生儿脐带血单核细胞来源的树突状细胞表型的影响

从脐带血单核细胞来源树突状细胞(DC)表型变化的角度来探讨EB病毒对DC表型的影响,以阐明其逃逸宿主免疫的机制。将GM-CSF和IL-4、EB病毒和LPS不同组合对单核细胞来源DC进行刺激培养,利用单染色和三染色免疫荧光抗体标记—流式细胞术检测单核细胞来源DC表面CD14、CD11c、CD1a、HLA-DR、CD86、MR和MHCⅠ类分子。加入EB病毒后,DC表面CD14分子表达的下调不明显,CD1a的表达则随病毒加入时细胞的分化阶段有关;同时EB病毒还影响了加入LPS后HLA-DR和CD86的升高和MR的降低;EB病毒还影响了细胞表面MHCⅠ类分子的表达。因此EB病毒可抑制单核细胞来源DC的分化和成熟,这可能是其逃逸宿主免疫的机制之一。     

A Weaning Reaction to Microbiota Is Required for Resistance to Immunopathologies in the Adult

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Increased cyclosporine sensitivity of T cells from cord blood compared with those from the adult.

Despite the increasing numbers of paediatric transplants performed, little is known about the immune responses of T lymphocytes in human neonates. Here we have compared the effects of cyclosporine on the phytohaemagglutinin (PHA) response of immature (cord) and mature (adult) lymphocytes using the following parameters of activation: (i) proliferation, measured by 3H-thymidine uptake; (ii) expression of cell surface IL-2 receptor; (iii) release of IL-2 into the supernatant. Cyclosporine was added to cultures of PHA-stimulated lymphocytes at doses ranging from 5 to 5000 ng/ml. The proliferative response of cord lymphocytes was considerably more sensitive to cyclosporine at each dose, so that 50% inhibition was achieved by 6 ng/ml and 21.5 ng/ml doses of cyclosporine on cord and adult lymphocytes, respectively. Expression of the IL-2 receptor by PHA-activated T cells and their subsets was assessed by flow cytometry. Cyclosporine inhibited IL-2 receptor expression to a significantly greater degree in cord CD4 and CD8 cells (49.7% and 70.1%) than in adults (17.9% and 30.0%). Biologically active IL-2 release was measured using the IL-2-dependent cell line CTLL-2. Cyclosporine at doses 50-5000 ng/ml produced 80-99% inhibition of both cord and adult responses. However, at very low doses (5 ng/ml) cyclosporine produced 69.3% inhibition of cord lymphocytes, compared with 42.0% of adult lymphocytes. These results suggest that the T cells of neonates are considerably more sensitive to cyclosporine than are adult T cells.     

Minor salivary glands: Clinical,histological and immunohistochemical features of common and less common pathologies

Hundreds of minor salivary glands (MiSGs) are scattered in the oral cavity located at the submucosa layer. Beside their role in the oral cavity lubrication and immunity defence system, MiSGs are beneficial tissue source for diagnosing oral and non-oral related diseases. The advantage of MiSGs as a diagnostic tool reside on their fairly simple excisional procedure on one hand and negligible impact of the normal secretion capability of the salivary gland system on the other hand. The review focuses on pathologies related to developmental, reactive, metabolic, inflammatory and immunologic conditions, Iatrogenic causes and other undefined causes.     

经鼻间歇正压通气与大剂量牛肺表面活性剂治疗重症新生儿呼吸窘迫综合征的效果研究

目的 探讨经鼻间歇正压通气与大剂量牛肺表面活性剂治疗重症新生儿呼吸窘迫综合征的应用效果。方法 选取2019年3月—2020年6月在本院就诊的新生儿呼吸窘迫综合征患儿102例,按随机数字表法分为两组,各51例。2组患儿均接受经鼻间歇正压通气辅助呼吸及注射用牛肺表面活性剂治疗,对照组采用标准剂量治疗,观察组采用大剂量治疗。对比2组临床疗效、临床相关指标、血气分析指标,并记录两组不良反应发生情况。结果 观察组治疗总有效率为96.08%,高于对照组的84.31%,(χ2=3.991,P＜0.05)。观察组用药次数、住院时间、氧疗时间及机械通气时间为(1.21±0.26)次、(14.42±2.14)d、(79.25±7.36)h、(65.24±5.01)h,短于对照组的(1.58±0.45)次、(18.74±3.87)d、(88.24±7.85)h、(74.17±6.21)h(t=5.084、6.976、5.966、7.993,P均＜0.05);观察组治疗3 d后血氧分压(partial pressure of oxygen,PaO2)、氧合指数分别为(88.45±6.21)mm Hg、(350.21±12.25)mm Hg,高于对照组的(81.36±5.14)mm Hg、(336.14±11.41)mm Hg,二氧化碳分压(Partial Pressure of Carbon Dioxide,PaCO2)为(43.14±3.65)mm Hg,低于对照组的(50.21±4.35)mm Hg,(t=6.281、6.002、8.892,F=39.446、79.042、36.026,P值均＜0.05)。2组均无严重不良反应发生。结论 经鼻间歇正压通气与大剂量牛肺表面活性剂治疗重症新生儿呼吸窘迫综合征患儿利于改善患儿氧合指数,进而减少机械排气时间及住院时间,值得应用。     

Comparison of the PROMIS Preference Score (PROPr) and EQ-5D-5L Index Value in General Population Samples in the United Kingdom,France, and Germany

ObjectivesThe Patient-Reported Outcome Measurement Information System (PROMIS) Preference score (PROPr) can be used to assess health state utility (HSU) and estimate quality-adjusted life-years in cost-effectiveness analyses. It is based on item response theory and promises to overcome limitations of existing HSU scores such as ceiling effects. The PROPr contains 7 PROMIS domains: cognitive abilities, depression, fatigue, pain, physical function, sleep disturbance, and ability to participate in social roles and activities. We aimed to compare the PROPr with the 5-level EQ-5D (EQ-5D-5L) in terms of psychometric properties using data from 3 countries.MethodsWe collected PROMIS-29 profile and EQ-5D-5L data from 3 general population samples (United Kingdom = 1509, France = 1501, Germany = 1502). Given that cognition is not assessed by the PROMIS-29, it was predicted by the recommended linear regression model. We compared the convergent validity, known-groups construct validity, and ceiling and floor effects of the PROPr and EQ-5D-5L.ResultsThe mean PROPr (0.48, 0.53, 0.48; P<.01) and EQ-5D-5L scores (0.82, 0.85, 0.83; P<.01) showed significant differences of similar magnitudes (d = 0.34; d = 0.32; d = 0.35; P<.01) across all samples. The differences were invariant to sex, income, occupation, education, and most conditions but not for age. The Pearson correlation coefficients between both scores were r = 0.74, r = 0.69, and r = 0.72. PROPr’s ceiling and floor effects both were minor to moderate. The EQ-5D-5L’s ceiling (floor) effects were major (negligible).ConclusionsBoth the EQ-5D-5L and the PROPr assessed by the PROMIS-29 show high validity. The PROPr yields considerably lower HSU values than the EQ-5D-5L. Consequences for quality-adjusted life-year measurements should be investigated in future research.     

A Bayesian Approach for Incorporating the EQ-5D Visual Analog Scale When Estimating the Health-Related Quality of Life

ObjectivesThe EuroQoL 3-level version of EQ-5D and 5-level version of EQ-5D questionnaires are often used to quantify health states. They include ordinal responses across 5 health dimensions (EQ-5D index) and an EQ-visual analog scale (EQ-VAS) overall health rating. We investigated the value of incorporating the EQ-VAS to update health utility estimates using a Bayesian framework.MethodsWe created a joint bivariate normal EQ-VAS and EQ-5D index utility model and compared this to a univariate normal EQ-5D index utility model. We tested these models for 1026 Sri Lankan patients with chronic kidney disease and 94 Australian patients with wounds. We validated our approach by simulating EQ-VAS and EQ-5D index responses and applying our Bayesian model and then comparing the modeled estimates to our observed data.ResultsThe combined model showed a reduction in estimate uncertainty for all respondents. Compared with the EQ-5D index-only model, the mean utility for Sri Lankan respondents dropped from 0.556 (0.534-0.579) to 0.540 (0.521-0.559) in men and increased from 0.489 (0.461-0.518) to 0.528 (0.506-0.550) in women, with reduced credible interval width by 13% and 23%, respectively. The mean utility in Australian respondents moved from 0.715 (0.633-0.800) to 0.716 (0.652-0.782) in men, and 0.652 (0.581-0.723) to 0.652 (0.593-0.711) in women, with reduced credible interval width by 23% and 17%, respectively. The credible interval width for simulated data also narrowed, ranging from 8.3 to 8.5%.ConclusionsIncluding the EQ-VAS through Bayesian methods can add value by reducing requisite sample sizes and decision uncertainty using small amounts of additional data that is often collected but rarely used.     

Impact of maternal pre-pregnancy body mass index on maternal,fetal and neonatal adverse outcomes in the worldwide populations: A systematic review and meta-analysis

ObjectiveSystematic review and meta-analysis conducted to investigate the effect of stratified pre-pregnancy maternal body mass index on twenty maternal and fetal/neonatal adverse outcomes.MethodsPubMed, Google Scholar, Medline, Embase, Web of Science databases were searched from inception till July 11, 2020. Cohort studies were included. The pooled odds ratio with 95% confidence interval was reported considering the random effect and the quality effect model. The sub-group analysis and meta-regression were conducted for BMI cut-offs, geographical region, source of BMI, and sample size.ResultsOverall, 86 studies representing 20,328,777 pregnant women were included in this meta-analysis. Our study reveals that overweight and obese mothers are at increased odds of cesarean delivery, elective cesarean delivery, emergency cesarean delivery, gestational diabetes, gestational hypertension, induction of labor, postpartum hemorrhage, pre-eclampsia, pre-term premature rupture of membrane, and the fetuses/neonates of overweight and obese mothers are at increased risk of admission in the newborn intensive care unit, APGAR scores less than 7 at 5 min, large for gestational age, macrosomia, extreme pre-term birth in pregnant mothers compared with standard BMI mothers. However, the underweight mothers showed increased odds for small for gestational age infant and pre-term birth, whereas obese mothers were at higher risk for post-term birth and stillbirths. The subgroup and meta-regression analyses have shown the impact of BMI cut-offs, geographical region, source of BMI, and sample size on several maternal, fetal/neonatal adverse outcomes.ConclusionThe meta-analysis confirmed the association of elevated pre-pregnancy maternal BMI with higher odds of adverse maternal and fetal/neonatal outcomes.