What are the benefits and risks of inhaled corticosteroids for COPD?

Q: What are the benefits and risks of inhaled corticosteroids for COPD? A: Inhaled corticosteroids (ICS), either alone or with a long-acting [beta] agonist (LABA), reduce the frequency of exacerbations of chronic obstructive pulmonary disease (COPD) and statistically, but not clinically, improve quality of life (QOL) (strength of recommendation [SOR]: B, meta-analyses of heterogeneous studies). However, ICS have no mortality benefit and don't consistently improve forced expiratory volume in 1 second (FEV1) (SOR: B, meta-analyses of secondary outcomes). They increase the risk of pneumonia, oropharyngeal candidiasis, and bruising (SOR: B, meta-analyses of secondary outcomes). Withdrawal of ICS doesn't significantly increase the risk of COPD exacerbation (SOR: B, a meta-analysis)

Self-Assembly and Biphasic Iron-Binding Characteristics of Mms6, A Bacterial Protein That Promotes the Formation of Superparamagnetic Magnetite Nanoparticles of Uniform Size and Shape

Highly ordered mineralized structures created by living organisms are often hierarchical in structure with fundamental structural elements at nanometer scales. Proteins have been found responsible for forming many of these structures, but the mechanisms by which these biomineralization proteins function are generally poorly understood. To better understand its role in biomineralization, the magnetotactic bacterial protein, Mms6, which promotes the formation in vitro of superparamagnetic magnetite nanoparticles of uniform size and shape, was studied for its structure and function. Mms6 is shown to have two phases of iron binding: one high affinity and stoichiometric and the other low affinity, high capacity, and cooperative with respect to iron. The protein is amphipathic with a hydrophobic N-terminal domain and hydrophilic C-terminal domain. It self-assembles to form a micelle, with most particles consisting of 20–40 monomers, with the hydrophilic C-termini exposed on the outside. Studies of proteins with mutated C-terminal domains show that the C-terminal domain contributes to the stability of this multisubunit particle and binds iron by a mechanism that is sensitive to the arrangement of carboxyl/hydroxyl groups in this domain

Dendritic Cell Responses to Early Murine Cytomegalovirus Infection: Subset Functional Specialization and Differential Regulation by Interferon α/β

Differentiation of dendritic cells (DCs) into particular subsets may act to shape innate and adaptive immune responses, but little is known about how this occurs during infections. Plasmacytoid dendritic cells (PDCs) are major producers of interferon (IFN)-α/β in response to many viruses. Here, the functions of these and other splenic DC subsets are further analyzed after in vivo infection with murine cytomegalovirus (MCMV). Viral challenge induced PDC maturation, their production of high levels of innate cytokines, and their ability to activate natural killer (NK) cells. The conditions also licensed PDCs to efficiently activate CD8 T cells in vitro. Non-plasmacytoid DCs induced T lymphocyte activation in vitro. As MCMV preferentially infected CD8α+ DCs, however, restricted access to antigens may limit plasmacytoid and CD11b+ DC contribution to CD8 T cell activation. IFN-α/β regulated multiple DC responses, limiting viral replication in all DC and IL-12 production especially in the CD11b+ subset but promoting PDC accumulation and CD8α+ DC maturation. Thus, during defense against a viral infection, PDCs appear specialized for initiation of innate, and as a result of their production of IFN-α/β, regulate other DCs for induction of adaptive immunity. Therefore, they may orchestrate the DC subsets to shape endogenous immune responses to viruses

Cobalt ferrite nanocrystals: Out-performing magnetotactic bacteria

Magnetotactic bacteria produce exquisitely ordered chains of uniform magnetite (Fe3O4) nanocrystals, and the use of the bacterial mms6 protein allows for the shape-selective synthesis of Fe 3O4 nanocrystals. Cobalt ferrite (CoFe2O 4) nanoparticles, on the other hand, are not known to occur in living organisms. Here we report on the use of the recombinant mms6 protein in a templated synthesis of CoFe2O4 nanocrystals in vitro. We have covalently attached the full-length mms6 protein and a synthetic C-terminal domain of mms6 protein to self-assembling polymers in order to template hierarchical CoFe2O4 nanostructures. This new synthesis pathway enables facile room-temperature shape-specific synthesis of complex magnetic crystalline nanomaterials with particle sizes in the range of 40 -100 nm that are difficult to produce using conventional techniques

Imaging of Unstained DNA Origami Triangles with Electron Microscopy

Imaging of scaffolded DNA and DNA origami nanostructures has been dominated by atomic force microscopy of samples immobilized on bulk substrates. Less commonly used are electron microscopy techniques, typically carried out after negative staining of DNA structures or by using cryo‐transmission electron microscopy (TEM). Here, direct imaging of unstained DNA origami on common electron‐transparent substrates with utilizing high angular annular dark field scanning transmission electron microscopy (HAADF‐STEM) is reported. This approach establishes a method for depositing and imaging intact DNA triangles with mass‐thickness contrast sufficient to measure the scaffold‐to‐scaffold distances and the length of the triangle\u27s seam. The signal‐to‐noise ratio (SNR) of the DNA supported on amorphous carbon as a function of the carbon thickness is measured on three types of commercially available TEM grids. This allows for edge detection of ≈1 nm height DNA triangles on carbon substrates as thick as ≈25 nm. Observations on the effect on SNR with the imaging modes are discussed. The effect of cation concentration used for pretreating the grid on the image resolution is also explored. This work presents proof‐of‐concept results demonstrating that electron microscopy can be used to resolve key elements of the DNA origami triangle without the use of staining protocols

Managers' and Leaders’ Perceptions of Sexual and Gender-Based Public Harassment in the Veterans Health Administration

PurposeManagers and leaders have a critical role to play in sexual and gender-based harassment prevention within organizations. Although the Veterans Health Administration has committed to eliminating harassment through national directives and training programs, it is unclear how aware local-level managers and leaders are about public harassment at their facilities and how they perceive sexual and gender-based harassment. We examined middle managers' and leaders' views about whether harassment is perceived as a problem locally, and what policies and procedures (if any) are in place to address public harassment.MethodsWe conducted 69 semistructured telephone interviews with middle managers and facility leaders before implementation of an evidence-based quality improvement project designed to improve delivery of comprehensive women's health care. Transcripts were coded using the constant comparative method and analyzed for overarching themes.ResultsPerceptions of the prevalence of sexual and gender-based public harassment varied among middle managers and leaders. A little more than one-half of respondents were unaware of facility-level policies and procedures to address public harassment between patients. To decrease patient-to-patient harassment, both groups generally supported the creation of separate clinical spaces for women. However, middle managers also stated that education was needed to change patient harassing behavior, which they tied to male military culture.ConclusionsAligning divergent perspectives of what constitutes sexual and gender-based harassment and how to address it is a necessary step towards tackling harassment at the local level. Managers and leaders should continue to assess environments of care and share findings widely among employees and leadership to improve awareness and inform a unified response

Collective Power to Create Political Change: Increasing the Political Efficacy and Engagement of Social Workers

Because social workers are called to challenge social injustices and create systemic change to support the well-being of individuals and communities, it is essential that social workers develop political efficacy: belief that the political system can work and they can influence the system. This study explored the impact of an intensive political social work curriculum on political efficacy and planned political engagement among social work students and practitioners. The findings suggest this model of delivering a political social work curriculum effectively increases internal, external, and overall political efficacy, and that increasing political efficacy has promise for increasing future political engagement

Celebrating 20 Years of the ExCEEd Teaching Workshop

In response to the clear need for faculty training, the American Society of Civil Engineers (ASCE) developed and funded Project ExCEEd (Excellence in Civil Engineering Education) which is celebrating its twentieth year of existence. For the past two decades, 38 ExCEEd Teaching Workshops (ETW) have been held at six different universities. The program has 910 graduates from over 267 different U.S. and international colleges and universities. The ExCEEd effort has transformed from one that relied on the grass roots support of its participants to one that is supported and embraced by department heads and deans. This paper summarizes the history of Project ExCEEd, describes the content of the ETW, assesses its effectiveness, highlights changes in the program as a result of the assessment, and outlines the future direction of the program

Marine mammal hotspots across the circumpolar Arctic

Aim: Identify hotspots and areas of high species richness for Arctic marine mammals. Location: Circumpolar Arctic. Methods: A total of 2115 biologging devices were deployed on marine mammals from 13 species in the Arctic from 2005 to 2019. Getis-Ord Gi* hotspots were calculated based on the number of individuals in grid cells for each species and for phyloge-netic groups (nine pinnipeds, three cetaceans, all species) and areas with high spe-cies richness were identified for summer (Jun-Nov), winter (Dec-May) and the entire year. Seasonal habitat differences among species’ hotspots were investigated using Principal Component Analysis. Results: Hotspots and areas with high species richness occurred within the Arctic continental-shelf seas and within the marginal ice zone, particularly in the “Arctic gateways” of the north Atlantic and Pacific oceans. Summer hotspots were generally found further north than winter hotspots, but there were exceptions to this pattern, including bowhead whales in the Greenland-Barents Seas and species with coastal distributions in Svalbard, Norway and East Greenland. Areas with high species rich-ness generally overlapped high-density hotspots. Large regional and seasonal dif-ferences in habitat features of hotspots were found among species but also within species from different regions. Gap analysis (discrepancy between hotspots and IUCN ranges) identified species and regions where more research is required. Main conclusions: This study identified important areas (and habitat types) for Arctic marine mammals using available biotelemetry data. The results herein serve as a benchmark to measure future distributional shifts. Expanded monitoring and teleme-try studies are needed on Arctic species to understand the impacts of climate change and concomitant ecosystem changes (synergistic effects of multiple stressors). While efforts should be made to fill knowledge gaps, including regional gaps and more com-plete sex and age coverage, hotspots identified herein can inform management ef-forts to mitigate the impacts of human activities and ecological changes, including creation of protected areas