An Emergency Medical Services Toolkit for Improving Systems of Care for Stroke in North Carolina

The Centers for Disease Control and Prevention is partnering with the National Association of Chronic Disease Directors and the North Carolina Office of EMS to design, develop, and implement an emergency medical services (EMS) performance improvement toolkit to evaluate opportunities to improve the emergency identification and treatment of acute stroke. The EMS Acute Stroke Care Toolkit is being developed, tested, and implemented in all 100 counties in the state by the EMS Performance Improvement Center, the agency that provides technical assistance for EMS in North Carolina. The toolkit helps each EMS system in defining, measuring, and analyzing their system of care and promotes collaboration through public education, regional stroke planning with hospitals, EMS service configuration, EMS staffing patterns, EMS education, and timely care delivery. We outline the issues surrounding acute stroke care, the role of emergency medical systems in stroke care, and the components of the EMS Acute Stroke Care Toolkit designed to improve EMS systems and outcomes for stroke patients

Geographic and Sociodemographic Disparities in Drive Times to Joint Commission–Certified Primary Stroke Centers in North Carolina, South Carolina, and Georgia

Introduction: Timely access to facilities that provide acute stroke care is necessary to reduce disabilities and death from stroke. We examined geographic and sociodemographic disparities in drive times to Joint Commission–certified primary stroke centers (JCPSCs) and other hospitals with stroke care quality improvement initiatives in North Carolina, South Carolina, and Georgia. Methods: We defined boundaries for 30- and 60-minute drive-time areas to JCPSCs and other hospitals by using geographic information systems (GIS) mapping technology and calculated the proportions of the population living in these drive-time areas by sociodemographic characteristics. Age-adjusted county-level stroke death rates were overlaid onto the drive-time areas. Results: Approximately 55% of the population lived within a 30-minute drive time to a JCPSC; 77% lived within a 60-minute drive time. Disparities in percentage of the population within 30-minute drive times were found by race/ethnicity, education, income, and urban/rural status; the disparity was largest between urban areas (70% lived within 30-minute drive time) and rural areas (26%). The rural coastal plains had the largest concentration of counties with high stroke death rates and the fewest JCPSCs. Conclusion: Many areas in this tri-state region lack timely access to JCPSCs. Alternative strategies are needed to expand provision of quality acute stroke care in this region. GIS modeling is valuable for examining and strategically planning the distribution of hospitals providing acute stroke care

The Wolbachia endosymbiont as an anti-filarial nematode target

Human disease caused by parasitic filarial nematodes is a major cause of global morbidity. The parasites are transmitted by arthropod intermediate hosts and are responsible for lymphatic filariasis (elephantiasis) or onchocerciasis (river blindness). Within these filarial parasites are intracellular alpha-proteobacteria, Wolbachia, that were first observed almost 30 years ago. The obligate endosymbiont has been recognized as a target for anti-filarial nematode chemotherapy as evidenced by the loss of worm fertility and viability upon antibiotic treatment in an extensive series of human trials. While current treatments with doxycycline and rifampicin are not practical for widespread use due to the length of required treatments and contraindications, anti-Wolbachia targeting nevertheless appears a promising alternative for filariasis control in situations where current programmatic strategies fail or are unable to be delivered and it provides a superior efficacy for individual therapy. The mechanisms that underlie the symbiotic relationship between Wolbachia and its nematode hosts remain elusive. Comparative genomics, bioinfomatic and experimental analyses have identified a number of potential interactions, which may be drug targets. One candidate is de novo heme biosynthesis, due to its absence in the genome sequence of the host nematode, Brugia malayi, but presence in Wolbachia and its potential roles in worm biology. We describe this and several additional candidate targets, as well as our approaches for understanding the nature of the host-symbiont relationship

Assembly and dynamics of the bacteriophage T4 homologous recombination machinery

Homologous recombination (HR), a process involving the physical exchange of strands between homologous or nearly homologous DNA molecules, is critical for maintaining the genetic diversity and genome stability of species. Bacteriophage T4 is one of the classic systems for studies of homologous recombination. T4 uses HR for high-frequency genetic exchanges, for homology-directed DNA repair (HDR) processes including DNA double-strand break repair, and for the initiation of DNA replication (RDR). T4 recombination proteins are expressed at high levels during T4 infection in E. coli, and share strong sequence, structural, and/or functional conservation with their counterparts in cellular organisms. Biochemical studies of T4 recombination have provided key insights on DNA strand exchange mechanisms, on the structure and function of recombination proteins, and on the coordination of recombination and DNA synthesis activities during RDR and HDR. Recent years have seen the development of detailed biochemical models for the assembly and dynamics of presynaptic filaments in the T4 recombination system, for the atomic structure of T4 UvsX recombinase, and for the roles of DNA helicases in T4 recombination. The goal of this chapter is to review these recent advances and their implications for HR and HDR mechanisms in all organisms

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Association between COVID-19 pandemic declaration and depression/anxiety among U.S. adults.

BackgroundAlthough studies have investigated the impact of the COVID-19 on mental health, few studies have attempted to compare the prevalence of depression/anxiety symptoms among U.S. adults before and after the COVID-19 pandemic declaration. We examined the prevalence and association between depression/anxiety symptoms and COVID-19 pandemic declaration among U.S. adult population and subgroups.MethodsA nationally representative cross-sectional study of the Health Information National Trends Survey (HINTS 5, Cycle 4) assessing health-related information and behaviors in U.S. adults aged ≥18 years from February through June 2020. The primary dependent variable was current depression/anxiety derived from Patient Health Questionnaire-4. The main independent variable was responses before and after the COVID-19 pandemic declaration in addition to sexual identity heterosexual identity, /race/ethnicity and rural-urban commuting areas. Covariates were sociodemographic factors, and health risk behaviors. Weighted percentages, multivariable logistic regression, and Chi-square tests were used to establish the prevalence and association between current depression/anxiety and the independent variables and covariates.ResultsA total of 3,865 participants completed the survey and included 35.3% of the participants before the COVID-19 pandemic declaration. Most of the sample were aged 50-64 years [33.0%]; males [51.0%]; and non-Hispanic Whites [70.1%]). The post-pandemic declaration included participants, aged 35-49 years [27.0%]; females [52.6%]; and non-Hispanic Whites [59.6%]). The prevalence of depression/anxiety was higher after the COVID-19 pandemic declaration (32.2%) than before the declaration (29.9%). Higher risks of depression/anxiety symptoms after the declaration were associated with being a sexual minority ([adjusted odds ratio] AOR, 2.91 [95% confidence interval (CI), 1.38-6.14]) and having fair/poor general health (AOR, 2.91 [95% CI, 1.76-4.83]). The probability of experiencing depression/anxiety symptoms after the declaration was highest among homosexuals/lesbians/gays (65.6%) compared to bisexuals (39.6%), and heterosexuals (30.1%).ConclusionsIn this study, young adults, non-Hispanic Whites, and those with fair/poor general health had a higher burden of depression/anxiety symptoms after the pandemic declaration. The development of psychological support strategies to promote wellbeing during the pandemic may reduce psychological distress in the population, especially among at-risk populations