Notes

Mansur ibn Ilyas Shirazi (1380-1422 AD), a pioneer associated with neuroanatomy.
Super-resolution microscopy techniques are versatile and powerful tools for visualizing organelle structures, interactions, and protein functions in biomedical research. However, whole-cell and tissue specimens challenge the achievable resolution and depth of nanoscopy methods. We focus on three-dimensional single-molecule localization microscopy and review some of the major roadblocks and developing solutions to resolving thick volumes of cells and tissues at the nanoscale in three dimensions. These challenges include background fluorescence, system- and sample-induced aberrations, information carried by photons, as well as drift correction, volume reconstruction, and photobleaching mitigation. We also highlight examples of innovations that have demonstrated significant breakthroughs in addressing the above-mentioned challenges together with their core concepts as well as their trade-offs. Expected final online publication date for the Annual Review of Biomedical Engineering, Volume 22 is June 4, 2020. Please see http//www.annualreviews.org/page/journal/pubdates for revised estimates.The National Heart, Lung, and Blood Institute (NHLBI) convened a working group on October 23, 2019 to identify the most relevant and urgent research priorities, and prevailing challenges in e-cigarette or vaping product use associated lung injury (EVALI). Experts across multiple disciplines discussed the complexities of the EVALI outbreak, identified research priorities, and recommended strategies to address most effectively its causal factors, improve diagnosis, treatment, and prevention of this disease. Many research priorities were identified, including the need to create national and international registries of EVALI patients, to track accurately those affected, and assess outcomes. The group concluded that biospecimens from EVALI subjects are urgently needed to help define EVALI pathogenesis, and that vaping has disease risks which are disparate from smoking, with the occurrence of EVALI highlighting the importance of broadening e-cigarette research beyond comparators to smoking-related diseases.Generating the barriers that protect our inner surfaces from bacteria and other challenges requires large glycoproteins called mucins. These come in two types, gel-forming and transmembrane, all characterized by large, highly O-glycosylated mucin domains that are diversely decorated by Golgi glycosyltransferases to become extended rodlike structures. The general functions of mucins on internal epithelial surfaces are to wash away microorganisms and, even more importantly, to build protective barriers. The latter function is most evident in the large intestine, where the inner mucus layer separates the numerous commensal bacteria from the epithelial cells. The host's conversion of MUC2 to the outer mucus layer allows bacteria to degrade the mucin glycans and recover the energy content that is then shared with the host. The molecular nature of the mucins is complex, and how they construct the extracellular complex glycocalyx and mucus is poorly understood and a future biochemical challenge. selleck chemicals Expected final online publication date for the Annual Review of Biochemistry, Volume 89 is June 22, 2020. Please see http//www.annualreviews.org/page/journal/pubdates for revised estimates.OBJECTIVES The spread of Zika virus throughout Latin America and parts of the United States in 2016 and 2017 presented a challenge to public health communicators. The objective of our study was to describe emergency risk communication practices during the 2016-2017 Zika outbreak to inform future infectious disease communication efforts. METHODS We conducted semi-structured telephone interviews with 13 public health policy makers and practitioners, 10 public information officers, and 5 vector-control officials from May through August 2017. RESULTS Within the public health macro-environment, extended outbreak timeframe, government trust, US residence status, and economic insecurity set the backdrop for Zika communication efforts. Limited resources, staffing, and partnerships negatively affected public health structural capacity for communication efforts. Public health communicators and practitioners used a range of processes and practices to engage in education and outreach, including fieldwork, community meetings, and contact with health care providers. Overall, public health agencies' primary goals were to prevent Zika infection, reduce transmission, and prevent adverse birth outcomes. CONCLUSIONS Lessons learned from this disease response included understanding the macro-environment, developing partnerships across agencies and the community, and valuing diverse message platforms. These lessons can be used to improve communication approaches for health officials at the local, state, and federal levels during future infectious disease outbreaks.Pseudomonas aeruginosa is a lethal pathogen that causes high mortality and morbidity in immunocompromised and critically ill patients. The Type III secretion system (T3SS) of P. aeruginosa mediates many of the adverse effects of infection with this pathogen including increased lung permeability in a toll-like receptor 4/Rho A/plasminogen activator inhibitor (PAI)-1-dependent manner. Alpha-tocopherol has anti-inflammatory properties that may make it a useful adjunct in treatment of this moribund infection. We measured transendothelial and transepithelial resistance, Rho A and PAI-1 activation, stress fiber formation, P. aeruginosa T3SS exoenzyme (Exo Y) intoxication into host cells, and survival in a murine model of pneumonia in the presence of P. aeruginosa and pretreatment with α-tocopherol. We found that α-tocopherol alleviated P. aeruginosa-mediated alveolar endothelial and epithelial paracellular permeability by inhibiting RhoA, in part, via PAI-1 activation and increased survival in a mouse model of P. aeruginosa pneumonia. Furthermore, we found that α-tocopherol decreased the activation of RhoA and PAI-1 by blocking the injection of T3SS exoenzymes into alveolar epithelial cells. P. aeruginosa is becoming increasingly antibiotic-resistant. We provide evidence that α-tocopherol could be a useful therapeutic agent for individuals that are susceptible to infection with P. aeruginosa such as those who are immunocompromised or critically ill.
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