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In 2019, >90% of new HIV infections in infants globally occurred vertically. Studies suggest intrauterine transmission most often occurs in the third trimester; however, there are no mechanistic studies to support these observations. We therefore obtained early/mid-gestation and term placentae from 20 HIV/Hepatitis B/CMV negative women. Isolated primary placental macrophages (Hofbauer cells [HCs]) were exposed to HIV-1 BaL and/or interferon (IFN)-α, IFN-β, IFN-λ1, and RIG-I-like receptor (RLR) agonists. qRT-PCR, FACS, ELISA, Luminex, and Western blot analyses determined expression of activation markers, co-receptors, viral antigen, cytokines, antiviral genes, and host proteins. Early gestation HCs express higher levels of CCR5 and exhibit a more activated phenotype. Despite downregulation of CCR5, term HCs were more susceptible to HIV replication. Early gestation HCs displayed a more activated phenotype than term HCs and HIV exposure lead to the further up-regulation of T-cell co-stimulatory and MHC molecules. Limited HIV replication in early/mid gestation HCs was associated with increased secretion of anti-inflammatory cytokines, chemokines, and a more robust antiviral immune response. In contrast, term HCs were more susceptible to HIV replication, associated with dampening of IFN-induced STAT1 and STAT2 protein activation. Treatment of early/mid gestation and term HCs, with type I IFNs or RLR agonists reduced HIV replication, underscoring the importance of IFN and RLR signaling in inducing an antiviral state. Viral recognition and antiviral immunity in early gestation HCs may prevent in utero HIV infection, whereas diminished antiviral responses at term can facilitate transmission. Defining mechanisms and specific timing of vertical transmission are critical for the development of specific vaccines and antiviral therapeutics to prevent new HIV infections in children globally.

Introduction African Americans (AA)s have worse inflammation, worse sleep, and a greater incidence of Alzheimer's disease (AD) compared to whites; however, no studies have examined associations between biomarkers, sleep, and cognition, and differences by race. Methods Seventy‐six cognitively normal, middle aged (45–65 years) adults with a parental history of AD were included in this study. Associations between biomarkers (tumor necrosis factor‐α [TNF‐α], interleukin‐10 [IL‐10], intercellular adhesion molecule‐1 [ICAM‐1],, and C‐reactive protein [CRP]) and self‐reported sleep or cognition measures, were assessed. Results Average sleep duration was significantly lower for AA versus whites (average[SD]) in hours: 6.02(1.18) versus 7.23(0.91), P = .000004). We found a statistically significant association between plasma IL‐10 and sleep duration (Spearman's ρ = 0.26, P = .04) and CSF ICAM‐1 and sleep quality (Spearman's ρ = 0.30, P = .03). Discussion Longer sleep duration is positively associated with plasma IL‐10 levels irrespective of race. Sleep quality was positively associated with CSF ICAM‐1 only in African Americans.

While the majority of influenza-infected individuals show no or mild symptomatology, pregnant women are at higher risk of complications and infection-associated mortality. Although enhanced lung pathology and dysregulated hormones are thought to underlie adverse pregnancy outcomes following influenza infection, how pregnancy confounds long-term maternal anti-influenza immunity remains to be elucidated. Previously, we linked seasonal influenza infection to clinical observations of adverse pregnancy outcomes, enhanced lung and placental histopathology, and reduced control of viral replication in lungs of infected pregnant mothers. Here, we expand on this work and demonstrate that lower infectious doses of the pandemic A/California/07/2009 influenza virus generated adverse gestational outcomes similar to higher doses of seasonal viruses. Mice infected during pregnancy demonstrated lower hemagglutination inhibition and neutralizing antibody titers than non-pregnant animals until 63 days post infection. These differences in humoral immunity suggest that pregnancy impacts antibody maturation mechanisms without alterations to B cell frequency or antibody secretion. This is further supported by transcriptional analysis of plasmablasts, which demonstrate downregulated B cell metabolism and post-translational modification systems only among pregnant animals. In sum, these findings corroborate a link between adverse pregnancy outcomes and severe pathology observed during pandemic influenza infection. Furthermore, our data propose that pregnancy directly confounds humoral responses following influenza infection which resolves post-partem. Additional studies are required to specify the involvement of plasmablast metabolism with early humoral immunity abnormalities to best guide vaccination strategies and improve our understanding of the immunological consequences of pregnancy.

Background Black/African American adults (B/AAs) are 64% more likely to develop Alzheimer’s disease (AD) than non‐Hispanic White adults (NHWs), and risk factors, including non‐biological determinants, are not fully delineated. Social determinants of health, such as socioeconomic status and lifetime discrimination, are associated with cognitive decline and increased AD risk. The purpose of this study is to examine the relationships of a perceived discrimination measure with sociodemographic characteristics and cognitive function in a racially diverse cohort of middle‐aged adults with a parental history of AD. Methods Perceived discrimination was assessed utilizing a compilation of self‐reported Perceived Discrimination measures including Expanded Everyday Discrimination, Coping with Discrimination, and Major Experiences of Discrimination from which six discrimination factors were extracted. Cognitive testing consisted of standardized tests in executive function, working memory, and verbal and visuospatial ability. Linear regression models were used to examine associations of perceived discrimination factor scores to cognitive function and sociodemographic characteristics. Results There were no significant differences in Aβ42 between B/AAs and NHWs, but significantly lower levels of total tau (p = 0.004) and p‐tau (p = 0.004) in B/AAs were found. Race was negatively correlated with Disrespect (p = 0.02) and Professional (p = 0.001), and positively correlated with Avoidance (p = 0.04), such that B/AA participants reported more discrimination in these domains. There was a significant correlation between Housing and both MoCA (p = 0.03) and global cognition (p = 0.01). The impact of perceived Housing discrimination on MoCA score approached significant interaction with education (p = 0.051) in the limited participant data. This suggests that perceived housing discrimination is most influential on global cognition in individuals with postgraduate education. These results may reflect prior reports of housing discrimination in B/AAs and housing mobility, even in high SES individuals. Conclusions We found that perceived discrimination influences cognition in a race‐independent manner in this racially diverse middle‐aged cohort with a family history of AD. These results also might be stratified by educational attainment and resulting geographic mobility. This study highlights the importance and impact of social determinants of health on cognition, and overall AD risk.

[...]AI is increasingly enabling data-driven decision-making across the product life cycle, from AI-supported drug candidate selection to real-time clinical trial site monitoring. According to our research, R&D is perceived as 1.5 times more bureaucratic and has a perceived 1.1 times slower execution speed than the combined pharmaceutical and medtech averages. To achieve this, organizations must optimize their organizational structure, behaviors, and skills to drive decisive and transparent decision-making. [...]85 percent of innovation leaders;report that fear often or always holds their personnel back from innovation.

The lipophilicity of two series of thiosemicarbazide derivatives was assessed by the RP-HPLC method with the RP-18 chromatographic column and the methanol–water mixture as the mobile phase. Distribution coefficients logPHPLC were compared to calculated values generated by commonly used AClogP software and quantum chemical calculations. The reliability of the predictions was evaluated using the correlation matrix and PCA. For 4-benzoylthiosemicarbazides, a high correlation between theoretical and experimental logP parameters was obtained using the XlogP3 algorithm, while for 4-aryl/(cyclohexyl)thiosemicarbazides, the XlogP2 parameter was strongly correlated with the experimentally obtained logP.