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In response to persistently documented health disparities based on race and other demographic factors, medical schools have implemented “cultural competency” coursework. While many of these courses have focused on strategies for treating patients of different cultural backgrounds, very few have addressed the impact of the physician’s own cultural background and offered methods to overcome his or her own unconscious biases. In hopes of training physicians to contextualize the impact of their own cultural background on their ability to provide optimal patient care, the authors created a 14-session course on culture, self-reflection, and medicine. After completing the course, students reported an increased awareness of their blind spots and that providing equitable care and treatment would require lifelong reflection and attention to these biases. In this article, the authors describe the formation and implementation of a novel medical school course on self-awareness and cultural identity designed to reduce unconscious bias in medicine. Finally, we discuss our observations and lessons learned after more than 10 years of experience teaching the course.

Editor Jeanne Spurlock, a professor of psychiatry at Howard University College of Medicine and George Washington School of Medicine and Health Sciences, has engaged an impressive array of authors whose contributions reflect in content and tone the quiet, determined persistence of these efforts.

The 100-year effort by black psychiatrists to become important contributors to mainstream American psychiatry began with the graduation of Solomon Carter Fuller from Boston University School of Medicine in 1897. The history of that effort is presented in this work, along with reports on the current status of black psychiatrists working in forensics, psychoanalysis, child and adolescent psychiatry, academia, and psychiatric research. Editor Jeanne Spurlock, a professor of psychiatry at Howard University College of Medicine and George Washington School of Medicine and Health Sciences, has engaged an impressive array of authors whose contributions reflect in content and tone the quiet, . . .

Nanomaterials have been part of the Earth system for billions of years, but human activities are changing the nature and amounts of these materials. Hochella Jr. et al. review sources and impacts of natural nanomaterials, which are not created directly through human actions; incidental nanomaterials, which form unintentionally during human activities; and engineered nanomaterials, which are created for specific applications. Knowledge of the properties of all three types as they cycle through the Earth system is essential for understanding and mitigating their long-term impacts on the environment and human health. Science , this issue p. eaau8299 Nanomaterials are critical components in the Earth system’s past, present, and future characteristics and behavior. They have been present since Earth’s origin in great abundance. Life, from the earliest cells to modern humans, has evolved in intimate association with naturally occurring nanomaterials. This synergy began to shift considerably with human industrialization. Particularly since the Industrial Revolution some two-and-a-half centuries ago, incidental nanomaterials (produced unintentionally by human activity) have been continuously produced and distributed worldwide. In some areas, they now rival the amount of naturally occurring nanomaterials. In the past half-century, engineered nanomaterials have been produced in very small amounts relative to the other two types of nanomaterials, but still in large enough quantities to make them a consequential component of the planet. All nanomaterials, regardless of their origin, have distinct chemical and physical properties throughout their size range, clearly setting them apart from their macroscopic equivalents and necessitating careful study. Following major advances in experimental, computational, analytical, and field approaches, it is becoming possible to better assess and understand all types and origins of nanomaterials in the Earth system. It is also now possible to frame their immediate and long-term impact on environmental and human health at local, regional, and global scales.

Crohn's disease and ulcerative colitis are common and debilitating manifestations of inflammatory bowel disease (IBD). IBD is characterized by a radical imbalance in the activation of proinflammatory and anti-inflammatory signaling pathways in the gut. These pathways are controlled by NF-κB, which is a master regulator of gene transcription. In IBD patients, NF-κB signaling is often dysregulated resulting in overzealous inflammation. NF-κB activation occurs through 2 distinct pathways, defined as either canonical or noncanonical. Canonical NF-κB pathway activation is well studied in IBD and is associated with the rapid, acute production of diverse proinflammatory mediators, such as COX-2, IL-1β, and IL-6. In contrast to the canonical pathway, the noncanonical or “alternative” NF-κB signaling cascade is tightly regulated and is responsible for the production of highly specific chemokines that tend to be associated with less acute, chronic inflammation. There is a relative paucity of literature regarding all aspects of noncanonical NF-ĸB signaling. However, it is clear that this alternative signaling pathway plays a considerable role in maintaining immune system homeostasis and likely contributes significantly to the chronic inflammation underlying IBD. Noncanonical NF-κB signaling may represent a promising new direction in the search for therapeutic targets and biomarkers associated with IBD. However, significant mechanistic insight is still required to translate the current basic science findings into effective therapeutic strategies.

Cancer drug delivery remains a formidable challenge due to systemic toxicity and inadequate extravascular transport of nanotherapeutics to cells distal from blood vessels. It is hypothesized that, in absence of an external driving force, the Salmonella enterica serovar Typhimurium could be exploited for autonomous targeted delivery of nanotherapeutics to currently unreachable sites. To test the hypothesis, a nanoscale bacteria‐enabled autonomous drug delivery system (NanoBEADS) is developed in which the functional capabilities of the tumor‐targeting S. Typhimurium VNP20009 are interfaced with poly(lactic‐co‐glycolic acid) nanoparticles. The impact of nanoparticle conjugation is evaluated on NanoBEADS' invasion of cancer cells and intratumoral transport in 3D tumor spheroids in vitro, and biodistribution in a mammary tumor model in vivo. It is found that intercellular (between cells) self‐replication and translocation are the dominant mechanisms of bacteria intratumoral penetration and that nanoparticle conjugation does not impede bacteria's intratumoral transport performance. Through the development of new transport metrics, it is demonstrated that NanoBEADS enhance nanoparticle retention and distribution in solid tumors by up to a remarkable 100‐fold without requiring any externally applied driving force or control input. Such autonomous biohybrid systems could unlock a powerful new paradigm in cancer treatment by improving the therapeutic index of chemotherapeutic drugs and minimizing systemic side effects. Nanoscale bacteria‐enabled autonomous drug delivery system (NanoBEADS) agents are constructed by conjugating poly(lactic‐co‐glycolic acid) nanoparticles with tumor‐targeting Salmonella Typhimurium. NanoBEADS enhance retention and distribution of nanoparticles in solid tumors by up to a remarkable ≈100‐fold, through intercellular (between cells) self‐replication and translocation. This transport enhancement is achieved autonomously, without the need for any externally‐applied driving force or control input.

Background The clustered regularly interspaced short palindromic repeats (CRISPR) and Cas9 protein system is a revolutionary tool for gene therapy. Despite promising reports of the utility of CRISPR–Cas9 for in vivo gene editing, a principal problem in implementing this new process is delivery of high molecular weight DNA into cells. Results Using poly(lactic- co -glycolic acid) (PLGA), a nanoparticle carrier was designed to deliver a model CRISPR–Cas9 plasmid into primary bone marrow derived macrophages. The engineered PLGA-based carriers were approximately 160 nm and fluorescently labeled by encapsulation of the fluorophore 6,13-bis(triisopropylsilylethynyl) pentacene (TIPS pentacene). An amine-end capped PLGA encapsulated 1.6 wt% DNA, with an encapsulation efficiency of 80%. Release studies revealed that most of the DNA was released within the first 24 h and corresponded to ~ 2–3 plasmid copies released per nanoparticle. In vitro experiments conducted with murine bone marrow derived macrophages demonstrated that after 24 h of treatment with the PLGA-encapsulated CRISPR plasmids, the majority of cells were positive for TIPS pentacene and the protein Cas9 was detectable within the cells. Conclusions In this work, plasmids for the CRISPR–Cas9 system were encapsulated in nanoparticles comprised of PLGA and were shown to induce expression of bacterial Cas9 in murine bone marrow derived macrophages in vitro. These results suggest that this nanoparticle-based plasmid delivery method can be effective for future in vivo applications of the CRISPR–Cas9 system.

Nanomedicine has the potential to transform clinical care in the 21(st) century. However, a precise understanding of how nanomaterial design parameters such as size, shape and composition affect the mammalian immune system is a prerequisite for the realization of nanomedicine's translational promise. Herein, we make use of the recently developed Particle Replication in Non-wetting Template (PRINT) fabrication process to precisely fabricate particles across and the nano- and micro-scale with defined shapes and compositions to address the role of particle design parameters on the murine innate immune response in both in vitro and in vivo settings. We find that particles composed of either the biodegradable polymer poly(lactic-co-glycolic acid) (PLGA) or the biocompatible polymer polyethylene glycol (PEG) do not cause release of pro-inflammatory cytokines nor inflammasome activation in bone marrow-derived macrophages. When instilled into the lungs of mice, particle composition and size can augment the number and type of innate immune cells recruited to the lungs without triggering inflammatory responses as assayed by cytokine release and histopathology. Smaller particles (80×320 nm) are more readily taken up in vivo by monocytes and macrophages than larger particles (6 µm diameter), yet particles of all tested sizes remained in the lungs for up to 7 days without clearance or triggering of host immunity. These results suggest rational design of nanoparticle physical parameters can be used for sustained and localized delivery of therapeutics to the lungs.

Systemic Lupus Erythematosus (SLE) is an autoimmune disease in which autoantibody production and cytokine dysregulation leads to systemic organ and tissue damage that can result in mortality. Although various environmental, hormonal, and genetic factors can contribute to disease pathogenesis, the cause of this disease is not known. Traditional treatment for this disease is centered around limiting inflammation using a variety of immunosuppresants including glucocorticosteroids as well as other therapeutics including anti-malarial drugs. More recently, selective immunosuppresives and biologics including Belimumab, a BAFF monoclonal antibody, and Anifrolumab, a monoclonal antibody that selectively binds to type 1 interferon receptor (INFAR1) blocking the biological activity of type 1 IFN, have been used with various success. It should be noted that BAFF is of particular relevance as signaling through BAFFR is a well characterized mechansim for non-canonical NF-κB signaling. While the canonical NF-κB pathway has been well studied and reported, the role of the non-canonical NF-κB pathway has been less investigated as to its role in autoimmunity. This pathway has been implicated in influencing pro-inflammatory immune responses while also regulating lymphocyte development. In this review, we aim to provide clarity on the relationship between the non-canonical NF-κB pathway and the role it plays in pathogenesis of SLE. The objective of this review is to summarize recent findings of the relationship of this pathway in autoimmunity and, more specifically, in lupus pathogenesis.