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Background and purposeSignal transducer and activator of transcription 3 (STAT3) may contribute to the proinflammation in the central nervous system diseases by modulating the microglial responses. Thus, this study was intended to investigate the effect of STAT3 on microglia-dependent neuroinflammation and functional outcome after experimental subarachnoid haemorrhage (SAH).MethodsThe SAH model was established by endovascular perforation in the mouse. Real-time PCR (RtPCR) and western blot were used to examine the dynamic STAT3 signalling pathway responses after SAH. To clarify the role of the STAT3 signalling pathway in the microglia-dependent neuroinflammation after SAH, the microglia-specific STAT3 knockout (KO) mice were generated by the Cre-LoxP system. The neurological functions were assessed by Catwalk and Morris water maze tests. Neuronal loss after SAH was determined by immunohistochemistry staining. Microglial polarisation status after STAT3 KO was then examined by RtPCR and immunofluorescence.ResultsThe STAT3 and Janus kinase-signal transducer 2 activated immediately with the upregulation and phosphorylation after SAH. Downstream factors and related mediators altered dynamically and accordingly. Microglial STAT3 deletion ameliorated the neurological impairment and alleviated the early neuronal loss after SAH. To investigate the underlying mechanism, we examined the microglial reaction after STAT3 KO. STAT3 deletion reversed the increase of microglia after SAH. Loss of STAT3 triggered the early morphological changes of microglia and primed microglia from M1 to M2 polarisation. Functionally, microglial STAT3 deletion suppressed the SAH-induced proinflammation and promoted the anti-inflammation in the early phase.ConclusionsSTAT3 is closely related to the microglial polarisation transition and modulation of microglia-dependent neuroinflammation. Microglial STAT3 deletion improved neurological function and neuronal survival probably through promoting M2 polarisation and anti-inflammatory responses after SAH. STAT3 may serve as a promising therapeutic target to alleviate early brain injury after SAH.

The induction of broadly neutralizing antibodies (bNAbs) is a potential strategy for a vaccine against HIV-1. However, most bNAbs exhibit features such as unusually high somatic hypermutation, including insertions and deletions, which make their induction challenging. VRC01-class bNAbs exhibit extraordinary breadth and potency, but also rank among the most highly somatically-mutated bNAbs. Here we describe a VRC01-class antibody isolated from a viremic controller, BG24, that has less than half the mutations of most other relatives of its class, while achieving comparable breadth and potency. A 3.8 Å X-ray crystal structure of a BG24-BG505 Env trimer complex revealed conserved contacts at the gp120 interface characteristic of the VRC01-class Abs, despite lacking common CDR3 sequence motifs. The existence of moderately-mutated CD4-binding site (CD4bs) bNAbs such as BG24 provides a simpler blueprint for CD4bs antibody induction by a vaccine, raising the prospect that such an induction might be feasible with a germline-targeting approach.TeaserAn anti-HIV-1 antibody with comparable neutralization breadth and potency to similarly-classed antibodies, with half as many mutations.

Neuroinflammation plays a critical role in the pathogenesis of subarachnoid hemorrhage (SAH). Microglia, as the resident immune cells, orchestrate neuroinflammation distinctly in neurological diseases with different polarization statuses. However, microglial polarizations in the neuroinflammatory responses after SAH are not fully understood. In this study, we investigated the dynamics of microglial reaction in an endovascular perforated SAH model. By using the Cx3cr1GFP/GFP Ccr2RFP/RFP transgenic mice, we found that the reactive immune cells were largely from resident microglia pool rather than infiltrating macrophages. Immunostaining and real-time PCR were employed to analyze the temporal microglial polarization and the resulting inflammatory responses. Our results showed that microglia accumulated immediately after SAH with a centrifugal spreading through the Cortex Adjacent to the Perforated Site (CAPS) to the remote motor cortex. Microglia polarized dynamically from M1 to M2 phenotype along with the morphological transformation from ramified to amoeboid shapes. The ramified microglia demonstrated the M1 property, which suggested the function-related microglial polarization occurred prior to morphological transformation after SAH. Bipolar-shaped microglia appeared as the intermediate and transitional status with the capacity of bidirectional polarization. The microglial polarization status is distinct in molecular inflammatory responses; M1-related pro-inflammation was predominant in the early phase and subsequently transited to the M2-related anti-inflammation. The systematic characterization of the dynamics of microglial polarization in this study contributes to the understanding of the origin of neuroinflammatory responses after SAH and provides key foundation for further investigations to develop target treatment.

Background: CDC estimates that in the 2015-2016 flu season, vaccination prevented 3,000 pneumonia and influenza-associated deaths and more than 5 million influenza illnesses. The American Academy of Pediatrics recommends that all children over 6 months of age receive influenza vaccinations annually; however, less than 50% of children in the US receive influenza vaccination, making interventions to increase vaccination rates of great public health importance.Purpose: To identify household-, parent-, and child-level factors associated with influenza vaccination, using nationally representative data, to ultimately inform the development of behavioral interventions.Methods: Using pooled data from the 2011-2014 National Health Interview Survey (NHIS; n=34,843 children under 18), we compared parent reports of child’s influenza vaccination across categories of gender, age (0-2, 3-5, 6-11, 12-17 years), race-ethnicity (Black, Hispanic, White, other), child’s health status, child’s health insurance status, household income, parents’ education level, and parental status (single parent vs. two parent households). Statistical significance was assessed using chi-squared tests with pResults: Influenza vaccination was received by 14,890 (46.0%) children. Influenza vaccination rates were significantly associated with age, race-ethnicity, child health insurance status, parent’s education level, and parental status in bivariate analyses (all pConclusion: This study identified several subgroups with low influenza vaccination rates, particularly children ages 12-17 and those without health insurance. However, the overall low rates observed in this US population-based sample highlight an important need for interventions to increase the receipt of influenza vaccination for all children. Efforts to increase child influenza vaccination rates could include programs to educate parents about the importance of regular influenza vaccination and that address misconceptions about vaccination. Further studies should be conducted to investigate how factors that were not measured by the NHIS are associated with child influenza vaccination.

Despite the prevalence of depressive symptoms and increased risk for future cardiovascular events, depressive symptoms frequently go underrecognized in patients hospitalized for acute coronary syndrome (ACS). Identifying an effective approach to depressive symptom screening is imperative in this population.The purpose of this cross-sectional study was to explore the agreement between Beck Depression Inventory-II (BDI-II) scores and a single screening question for depressive symptoms in 1122 patients hospitalized for ACS.Independent-samples t tests and χ tests were used to compare the groups with BDI-II scores of 14 or higher and lower than 14. Three separate agreement analyses were conducted using categorized BDI-II scores (≥14, ≥20, and ≥29). Agreement of the BDI-II categories with the responses to the single screening question was assessed with the simple κ statistic. Sensitivity and specificity were calculated using the BDI-II categories as the criterion standards for depressive symptom screening.The agreement analysis revealed a moderate level of agreement (κ coefficient = 0.42) between the BDI-II scores of 14 or higher and the single screening question. Of the participants who reported a BDI-II score of 14 or higher, 61.65% answered yes to the single screening question (sensitivity, 0.62). For those who had BDI-II scores of lower than 14, a total of 82% responded no to the single screening question (specificity, 0.82). When using higher BDI-II scores to define depressive symptoms (≥20 and ≥29), the level of agreement decreased, whereas sensitivity increased to 0.76 and 0.90, with a trade-off in specificity (0.79 and 0.74, respectively).These results suggest that the single screening question for depressive symptoms correctly identifies depressive symptoms 62% of the time but inappropriately identifies depressive symptoms 18% of the time in patients hospitalized for ACS. This suggests that the single screening question for depressive symptoms may be used with caution to initially screen patients with ACS, who can then undergo a more thorough assessment for clinical depression.