Interrelationships between Cellular Density,Mosaic Patterning,and Dendritic Coverage of VGluT3 Amacrine Cells

Amacrine cells of the retina are conspicuously variable in their morphologies, their population demographics, and their ensuing functions. Vesicular glutamate transporter 3 (VGluT3) amacrine cells are a recently characterized type of amacrine cell exhibiting local dendritic autonomy. The present analysis has examined three features of this VGluT3 population, including their density, local distribution, and dendritic spread, to discern the extent to which these are interrelated, using male and female mice. We first demonstrate that Bax-mediated cell death transforms the mosaic of VGluT3 cells from a random distribution into a regular mosaic. We subsequently examine the relationship between cell density and mosaic regularity across recombinant inbred strains of mice, finding that, although both traits vary across the strains, they exhibit minimal covariation. Other genetic determinants must therefore contribute independently to final cell number and to mosaic order. Using a conditional KO approach, we further demonstrate that Bax acts via the bipolar cell population, rather than cell-intrinsically, to control VGluT3 cell number. Finally, we consider the relationship between the dendritic arbors of single VGluT3 cells and the distribution of their homotypic neighbors. Dendritic field area was found to be independent of Voronoi domain area, while dendritic coverage of single cells was not conserved, simply increasing with the size of the dendritic field. Bax-KO retinas exhibited a threefold increase in dendritic coverage. Each cell, however, contributed less dendrites at each depth within the plexus, intermingling their processes with those of neighboring cells to approximate a constant volumetric density, yielding a uniformity in process coverage across the population.SIGNIFICANCE STATEMENT Different types of retinal neuron spread their processes across the surface of the retina to achieve a degree of dendritic coverage that is characteristic of each type. Many of these types achieve a constant coverage by varying their dendritic field area inversely with the local density of like-type neighbors. Here we report a population of retinal amacrine cells that do not develop dendritic arbors in relation to the spatial positioning of such homotypic neighbors; rather, this cell type modulates the extent of its dendritic branching when faced with a variable number of overlapping dendritic fields to approximate a uniformity in dendritic density across the retina.     

某社区2019年第二类疫苗接种疑似预防接种异常反应监测结果

目的了解某社区第二类疫苗接种及疑似预防接种异常反应(AEFI)情况。方法通过查询疫苗出入库系统和中国免疫规划信息管理系统,对2019年该社区第二类疫苗使用及AEFI报告情况进行分析。结果2019年,该社区接种门诊共接种第二类疫苗21种7449剂,接种数最多的是13价肺炎疫苗(784剂)。接种数居前6位的依次为13价肺炎疫苗、ACYW135群流脑多糖疫苗、轮状病毒疫苗、百白破-IPV-HIB五联疫苗、手足口EV71疫苗、九价人乳头瘤疫苗。累计报告AEFI病例94例,发生率为1.26%;一般反应占96.81%,异常反应占3.19%。报告AEFI疫苗共12种,报告发生率居前6位的分别为13价肺炎疫苗、百白破-IPV-HIB五联疫苗、百白破-IPV-HIB四联疫苗、手足口EV71疫苗、九价HPV疫苗、AC结合流脑疫苗。结论第二类疫苗品种接种量均有所增加,AEFI报告发生率有所波动,需加强监测。     

The role of National Immunization Technical Advisory Groups (NITAG) in strengthening health system governance: Lessons from three middle-income countries—Argentina,Jordan, and South Africa (2017–2018)

IntroductionToward the Global Vaccine Action Plan 2020 goal, almost 90% of countries have established a National Immunization Technical Advisory Group (NITAG). However, little is known about NITAG's contributions to governance.MethodsIn 2017–2018, a two-step, qualitative retrospective study was conducted. Jordan (JO), Argentina (AR), and South Africa (SA) were selected owing to government-financed NITAGs from middle-income countries (MICs), geographic diversity, and a vaccine introduction with NITAG support. Country case studies were developed, collecting data through desk review and face-to-face key informant interviews (KIIs) from Ministry of Health (MoH) and NITAG. Case studies were analyzed together, to assess governance applying the European Observatory on Health Systems and Policies framework focusing on transparency, accountability, participation, integrity, and policy capacity (TAPIC).ResultsDocument review and 53 KII (22 AR, 20 SA, 11 JO) showed NITAGs played a pivotal role as advisors promoting a culture of evidence-informed policies. NITAGs strengthened governance, although practices varied among countries. Meetings were conducted behind-closed-doors, participation restricted to members, only in one country agendas, and recommendations were public (AR). To increase participation, policy capacity, and transparency, countries considered adding experts in communications, advocacy, and economics. AR and SA contemplated including community members. NITAGs functioned autonomously from the government, with no established internal or external monitoring or supervision. NITAG meeting minutes allowed the review of integrity, adherence to terms of reference, standard operating procedures, and conflict of interest (CoI). For the most part, NITAGs abided by their mandates. Significant issues were related to the level of MoH support and oversight of CoI declaration and documentation.ConclusionsSystematically implementing governance approaches could improve processes, better tailor policies, and implementation. The long-term survival and resilience of NITAGs in these countries showed they play a significant role in strengthening governance. Lessons learned could be useful to those promoting country-driven evidence-informed decision-making.     

Completeness and timeliness of diphtheria-tetanus-pertussis,measles-mumps-rubella,and polio vaccines in young children with chronic health conditions: A systematic review

Objective

To systematically review literature on uptake and timeliness of diphtheria-tetanus-pertussis, measles-mumps-rubella, and/or polio-containing vaccines in infants who were born preterm, with a low birth weight, and/or with chronic health conditions that were diagnosed within the first 6?months of life.

Encouraging COVID-19 vaccination via an evolutionary theoretical approach: A randomized controlled study in Japan

ObjectiveWe aimed to examine the effect of a message that target the fundamental human motive of kin care on COVID-19 vaccination recommendations among participants with young children, based on an evolutionary theoretical approach.MethodsParticipants with young children (n = 969) were randomly assigned either to a group that received an intervention message that targeted the fundamental motive of kin care, or that targeted the fundamental motive of disease avoidance, or a control message. Intention to receive COVID-19 vaccination was assessed both before and after reading the messages. A one-way ANOVA with Tukey’s or Games–Howell test was conducted.ResultsAn intervention message targeting the fundamental motive of kin care and disease avoidance significantly increased intention of vaccination versus a control message (p < 0.001, respectively).ConclusionThe evolutionary theoretical approach that focuses on fundamental human motives has the potential to extend the communication strategy for COVID-19 vaccination recommendations.Practice implicationsHealth professionals should deliver messages that target the fundamental motive of kin care as well as messages about the susceptibility and severity of COVID-19 and vaccine efficacy (e.g., “Get vaccinated against COVID-19 for your child’s sake, because if you are infected, you will be unable to care for your child.”)     

Moderate protection is induced by a chimeric protein composed of leucine aminopeptidase and cathepsin L1 against Fasciola hepatica challenge in sheep

Leucine aminopeptidase (FhLAP) and cathepsin L1 (FhCL1) of Fasciola hepatica play a critical role in parasite feeding, migration through host tissue, and immune evasion. These antigens have been tested for immune protection as single components with variable degrees of success. The chimeric-protein approach could improve protection levels against fasciolosis. Previously, we reported the design and construction of a chimeric protein composed of antigenic sequences of FhLAP and FhCL1 of F. hepatica. The goal of the present study was to express and evaluate the immune-protective capacity of this chimeric protein (rFhLAP-CL1) in sheep. Animals were randomly allocated into five groups with five animals in each group. Groups 1, 2 and 3 were immunized twice with 100 μg, 200 μg and 400 μg of rFhLAP-CL1 emulsified with Quil A adjuvant, whereas groups 4 and 5 were the adjuvant control and infection control groups, respectively. The animals were then challenged with 200 metacercariae two weeks after the rFhLAP-CL1 booster. The fluke burden was reduced by 25.5%, 30.7% (p < 0.05) and 46.5% (p < 0.01) in sheep immunized with 100 μg, 200 μg and 400 μg of chimeric protein, respectively, in comparison to the infection control group. There was a reduction of 22.7% (p < 0.05) and 24.4% (p < 0.01) in fecal egg count in groups 2 and 3, respectively, compared to the infection control group. Sheep immunized with chimeric protein produced F. hepatica excretion-secretion product-specific total IgG antibody, which were increased after challenge. Moreover, the levels of rFhLAP-CL1-specific IgG1 and IgG2 isotypes in immunized sheep increased rapidly two weeks after the first immunization and were significantly more elevated than those of the control groups, indicating a mixed Th1/Th2 response. This is a preliminary evaluation of the chimeric protein rFhLAP-CL1 as a possible immunogen against F. hepatica infection in sheep.     

Assessing the immunogenicity of three different inactivated polio vaccine schedules for use after oral polio vaccine cessation,an open label,phase IV,randomized controlled trial

BackgroundAfter global oral poliovirus vaccine (OPV) cessation, the Strategic Advisory Group of Experts on Immunization (SAGE) currently recommends a two-dose schedule of inactivated poliovirus vaccine (IPV) beginning ≥14-weeks of age to achieve at least 90% immune response. We aimed to compare the immunogenicity of three different two-dose IPV schedules started before or at 14-weeks of age.MethodsWe conducted a randomized, controlled, open-label, inequality trial at two sites in Dhaka, Bangladesh. Healthy infants at 6-weeks of age were randomized into one of five arms to receive two-dose IPV schedules at different ages with and without OPV. The three IPV-only arms are presented: Arm C received IPV at 14-weeks and 9-months; Arm D received IPV at 6-weeks and 9-months; and Arm E received IPV at 6 and 14-weeks. The primary outcome was immune response defined as seroconversion from seronegative (<1:8) to seropositive (≥1:8) after vaccination, or a four-fold rise in antibody titers and median reciprocal antibody titers to all three poliovirus types measured at 10-months of age.FindingsOf the 987 children randomized to Arms C, D, and E, 936 were included in the intention-to-treat analysis. At 10-months, participants in Arm C (IPV at 14-weeks and 9-months) had ≥99% cumulative immune response to all three poliovirus types which was significantly higher than the 77–81% observed in Arm E (IPV at 6 and 14-weeks). Participants in Arm D (IPV at 6-weeks and 9-months) had cumulative immune responses of 98–99% which was significantly higher than that of Arm E (p value < 0.0001) but not different from Arm C.InterpretationResults support current SAGE recommendations for IPV following OPV cessation and provide evidence that the schedule of two full IPV doses could begin as early as 6-weeks.