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Marburg Virus Disease in RwandaA unified response to the global threat posed by a Marburg virus disease outbreak in Rwanda offers reason for hope — and lessons about safeguarding health equity in a time of ascendant isolationism.

Decades of research have pushed us closer to understanding what babies know. However, a powerful approach – representational similarity analysis (RSA) – is underused in developmental research. I discuss the strengths of this approach and what it can tell us about infant conceptual knowledge. As a case study, I focus on numerosity as a domain where RSA can make unique progress.

Opioid use disorder is often a chronic, relapsing condition associated with increased morbidity and death; however, with appropriate treatment and follow-up, individuals can reach sustained long-term remission. This guideline strongly recommends opioid agonist treatment with buprenorphine-naloxone as the preferred first-line treatment when possible, because of buprenorphine's multiple advantages, which include a superior safety profile in terms of overdose risk. Withdrawal management alone is not recommended, because this approach has been associated with elevated risks (e.g., syringe sharing) and death from overdose in comparison to providing no treatment, and high rates of relapse when implemented without immediate transition to long-term evidence-based treatment. Here, Bruneau et al discuss management of opioid use disorders.

Electronic nicotine delivery systems (ENDS) or e-cigarettes have emerged as a popular recreational tool among adolescents and adults. Although the use of ENDS is often promoted as a safer alternative to conventional cigarettes, few comprehensive studies have assessed the long-term effects of vaporized nicotine and its associated solvents, propylene glycol (PG) and vegetable glycerin (VG). Here, we show that compared with smoke exposure, mice receiving ENDS vapor for 4 months failed to develop pulmonary inflammation or emphysema. However, ENDS exposure, independent of nicotine, altered lung lipid homeostasis in alveolar macrophages and epithelial cells. Comprehensive lipidomic and structural analyses of the lungs revealed aberrant phospholipids in alveolar macrophages and increased surfactant-associated phospholipids in the airway. In addition to ENDS-induced lipid deposition, chronic ENDS vapor exposure downregulated innate immunity against viral pathogens in resident macrophages. Moreover, independent of nicotine, ENDS-exposed mice infected with influenza demonstrated enhanced lung inflammation and tissue damage. Together, our findings reveal that chronic e-cigarette vapor aberrantly alters the physiology of lung epithelial cells and resident immune cells and promotes poor response to infectious challenge. Notably, alterations in lipid homeostasis and immune impairment are independent of nicotine, thereby warranting more extensive investigations of the vehicle solvents used in e-cigarettes.

In the tumor microenvironment, local immune dysregulation is driven in part by macrophages and dendritic cells that are polarized to a mixed proinflammatory/immune-suppressive phenotype. The unfolded protein response (UPR) is emerging as the possible origin of these events. Here we report that the inositol-requiring enzyme 1 (IRE1α) branch of the UPR is directly involved in the polarization of macrophages in vitro and in vivo, including the up-regulation of interleukin 6 (IL-6), IL-23, Arginase1, as well as surface expression of CD86 and programmed death ligand 1 (PD-L1). Macrophages in which the IRE1α/X-box binding protein 1 (Xbp1) axis is blocked pharmacologically or deleted genetically have significantly reduced polarization and CD86 and PD-L1 expression, which was induced independent of IFNγ signaling, suggesting a novel mechanism in PD-L1 regulation in macrophages. Mice with IRE1α- but not Xbp1-deficient macrophages showed greater survival than controls when implanted with B16.F10 melanoma cells. Remarkably, we found a significant association between the IRE1α gene signature and CD274 gene expression in tumor-infiltrating macrophages in humans. RNA sequencing (RNASeq) analysis showed that bone marrow-derived macrophages with IRE1α deletion lose the integrity of the gene connectivity characteristic of regulated IRE1α-dependent decay (RIDD) and the ability to activate CD274 gene expression. Thus, the IRE1α/Xbp1 axis drives the polarization of macrophages in the tumor microenvironment initiating a complex immune dysregulation leading to failure of local immune surveillance.

Although environmental justice emerged as a research area in the 1970s, those facing environmental risk had analyzed their problems and mobilized for redress long before that time. In the US, ample research shows that the marginalized and the less affluent are more exposed to environmental threats than others. Pearson et al offer analyses that link the environmental justice literature to environmental social psychology and, in doing so, raise important issues for both research and engagement.

We described public views toward harm reduction among Canadian adults and tested a social exposure model predicting support for these contentious services, drawing on theories in the morality policy, intergroup relations, addiction, and media communication literatures. A quota sample of 4645 adults (18+ years), randomly drawn from an online research panel and stratified to match age and sex distributions of adults within and across Canadian provinces, was recruited in June 2018. Participants completed survey items assessing support for harm reduction for people who use drugs (PWUD) and for seven harm reduction interventions. Additional items assessed exposure to media coverage on harm reduction, and scales assessing stigma toward PWUD (α = .72), personal familiarity with PWUD (α = .84), and disease model beliefs about addiction (α = .79). Most (64%) Canadians supported harm reduction (provincial estimates = 60% - 73%). Five of seven interventions received majority support, including: outreach (79%), naloxone (72%), drug checking (70%), needle distribution (60%) and supervised drug consumption (55%). Low-threshold opioid agonist treatment and safe inhalation interventions received less support (49% and 44%). Our social exposure model, adjusted for respondent sex, household income, political views, and education, exhibited good fit and accounted for 17% of variance in public support for harm reduction. Personal familiarity with PWUD and disease model beliefs about addiction were directly associated with support ( β s = .07 and -0.10, respectively), and indirectly influenced public support via stigmatized attitudes toward PWUD ( β s = 0.01 and -0.01, respectively). Strategies to increase support for harm reduction could problematize certain disease model beliefs (e.g., “There are only two possibilities for an alcoholic or drug addict–permanent abstinence or death”) and creating opportunities to reduce social distance between PWUD, the public, and policy makers.

Bloodborne infections with Candida albicans are an increasingly recognized complication of modern medicine. Here, we present a mouse model of low-grade candidemia to determine the effect of disseminated infection on cerebral function and relevant immune determinants. We show that intravenous injection of 25,000  C. albicans cells causes a highly localized cerebritis marked by the accumulation of activated microglial and astroglial cells around yeast aggregates, forming fungal-induced glial granulomas. Amyloid precursor protein accumulates within the periphery of these granulomas, while cleaved amyloid beta (Aβ) peptides accumulate around the yeast cells. CNS-localized C. albicans further activate the transcription factor NF-κB and induce production of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor (TNF), and Aβ peptides enhance both phagocytic and antifungal activity from BV-2 cells. Mice infected with C. albicans display mild memory impairment that resolves with fungal clearance. Our results warrant additional studies to understand the effect of chronic cerebritis on cognitive and immune function. The potential links between infections and neurodegenerative disorders are unclear. Here, Wu et al. present a mouse model of low-grade candidemia characterized by highly localized cerebritis, accumulation of amyloid precursor protein and beta peptides, and mild memory impairment that resolves with fungal clearance.

BackgroundAdvancing health equity entails reducing disparities in care. African-American patients with chronic kidney disease (CKD) have poorer outcomes, including dialysis access placement and transplantation. Estimated glomerular filtration rate (eGFR) equations, which assign higher eGFR values to African-American patients, may be a mechanism for inequitable outcomes. Electronic health record–based registries enable population-based examination of care across racial groups.ObjectiveTo examine the impact of the race multiplier for African-Americans in the CKD-EPI eGFR equation on CKD classification and care delivery.DesignCross-sectional studySettingTwo large academic medical centers and affiliated community primary care and specialty practices.ParticipantsA total of 56,845 patients in the Partners HealthCare System CKD registry in June 2019, among whom 2225 (3.9%) were African-American.MeasurementsExposures included race, age, sex, comorbidities, and eGFR. Outcomes were transplant referral and dialysis access placement.ResultsOf 2225 African-American patients, 743 (33.4%) would hypothetically be reclassified to a more severe CKD stage if the race multiplier were removed from the CKD-EPI equation. Similarly, 167 of 687 (24.3%) would be reclassified from stage 3B to stage 4. Finally, 64 of 2069 patients (3.1%) would be reassigned from eGFR > 20 ml/min/1.73 m2 to eGFR ≤ 20 ml/min/1.73 m2, meeting the criterion for accumulating kidney transplant priority. Zero of 64 African-American patients with an eGFR ≤ 20 ml/min/1.73 m2 after the race multiplier was removed were referred, evaluated, or waitlisted for kidney transplant, compared to 19.2% of African-American patients with eGFR ≤ 20 ml/min/1.73 m2 with the default CKD-EPI equation.LimitationsSingle healthcare system in the Northeastern United States and relatively small African-American patient cohort may limit generalizability.ConclusionsOur study reveals a meaningful impact of race-adjusted eGFR on the care provided to the African-American CKD patient population.

Virtually all women who have cervical cancer are infected with the human papillomavirus (HPV). Of the 275,000 women who die from cervical cancer every year, 88% live in developing countries. Two vaccines against the HPV have been approved. However, vaccine implementation in low-income countries tends to lag behind implementation in high-income countries by 15 to 20 years. In 2011, Rwanda's Ministry of Health partnered with Merck to offer the Gardasil HPV vaccine to all girls of appropriate age. The Ministry formed a \"public-private community partnership\" to ensure effective and equitable delivery. Thanks to a strong national focus on health systems strengthening, more than 90% of all Rwandan infants aged 12-23 months receive all basic immunizations recommended by the World Health Organization. In 2011, Rwanda's HPV vaccination programme achieved 93.23% coverage after the first three-dose course of vaccination among girls in grade six. This was made possible through school-based vaccination and community involvement in identifying girls absent from or not enrolled in school. A nationwide sensitization campaign preceded delivery of the first dose. Through a series of innovative partnerships, Rwanda reduced the historical two-decade gap in vaccine introduction between high- and low-income countries to just five years. High coverage rates were achieved due to a delivery strategy that built on Rwanda's strong vaccination system and human resources framework. Following the GAVI Alliance's decision to begin financing HPV vaccination, Rwanda's example should motivate other countries to explore universal HPV vaccine coverage, although implementation must be tailored to the local context.