The Community Health Response Team: a culturally and linguistically tailored community response to COVID-19 addressing barriers to testing and vaccinations for refugee, immigrant and migrant communities in Atlanta, Georgia

The International Rescue Committee (IRC) in Atlanta and Community Organized Relief Effort (CORE) established a Community Health Response Team in May 2020. The team members represented refugee, immigrant and migrant populations and had expertise in health care and public health. These 18 individuals were recruited from IRC Atlanta's Career Development program, had a variety of backgrounds and spoke 20 languages. They implemented a community-centered COVID-response intervention model of pairing education and outreach efforts with testing and vaccination clinics. Due to their team makeup, the Community Health Response Team conducted tailored outreach and education that was culturally and linguistically congruent with their target communities. They administered over 16,000 COVID-19 tests at mobile community sites within the first 6 months. Once COVID-19 vaccinations were available, the Community Health Response Team coordinated a total of 834 vaccination events in communities with a high number of refugees and in partnership with refugee- and immigrant-trusted community-based organizations, resulting in 31,888 vaccinations. Hiring staff from refugee, immigrant and migrant populations created a sustainable staffing model. Also, embedding culturally specific strategies in their model of pairing education and outreach led to long-term relationships and greater trust with community members. This approach of engaging and empowering community members to create tailored public health responses should serve as guidance for future public health campaigns

DDX3X and specific initiation factors modulate FMR1 repeat‐associated non‐AUG‐initiated translation

A CGG trinucleotide repeat expansion in the 5′ UTR of FMR1 causes the neurodegenerative disorder Fragile X‐associated tremor/ataxia syndrome (FXTAS). This repeat supports a non‐canonical mode of protein synthesis known as repeat‐associated, non‐AUG (RAN) translation. The mechanism underlying RAN translation at CGG repeats remains unclear. To identify modifiers of RAN translation and potential therapeutic targets, we performed a candidate‐based screen of eukaryotic initiation factors and RNA helicases in cell‐based assays and a Drosophila melanogaster model of FXTAS. We identified multiple modifiers of toxicity and RAN translation from an expanded CGG repeat in the context of the FMR1 5′UTR. These include the DEAD‐box RNA helicase belle/DDX3X, the helicase accessory factors EIF4B/4H, and the start codon selectivity factors EIF1 and EIF5. Disrupting belle/DDX3X selectively inhibited FMR1 RAN translation in Drosophila in vivo and cultured human cells, and mitigated repeat‐induced toxicity in Drosophila and primary rodent neurons. These findings implicate RNA secondary structure and start codon fidelity as critical elements mediating FMR1 RAN translation and identify potential targets for treating repeat‐associated neurodegeneration.SynopsisFragile X‐associated tremor/ataxia syndrome is caused by CGG repeat‐associated non‐AUG (RAN) translation that initiates within the 5′UTR of FMR1. A candidate‐based screen identified several initiation factors—DDX3X/Belle, eIF4B, eIF4H, eIF1, and eIF5—critical for FMR1 RAN translation.Knockdown of the RNA helicase DDX3X selectively suppresses FMR1 RAN translation in Drosophila melanogaster, cultured HeLa cells, and in vitro translation assays.DDX3X knockdown reduces CGG repeat‐associated toxicity in Drosophila and mammalian neurons.Eukaryotic initiation factors that modulate RNA‐RNA secondary structure (DDX3X, EIF4B, EIF4H) or start codon fidelity (EIF1, EIF5) impact FMR1 RAN translation.FXTAS is caused by CGG repeat‐associated non‐AUG (RAN) translation that initiates within the 5′UTR of FMR1. A candidate‐based screen identified several initiation factors—DDX3X/Belle, eIF4B, eIF4H, eIF1, and eIF5—critical for FMR1 RAN translation.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151325/1/embr201847498.reviewer_comments.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151325/2/embr201847498-sup-0001-Appendix.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151325/3/embr201847498_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151325/4/embr201847498.pd

DDX

A CGG trinucleotide repeat expansion in the 5′ UTR of FMR1 causes the neurodegenerative disorder Fragile X‐associated tremor/ataxia syndrome (FXTAS). This repeat supports a non‐canonical mode of protein synthesis known as repeat‐associated, non‐AUG (RAN) translation. The mechanism underlying RAN translation at CGG repeats remains unclear. To identify modifiers of RAN translation and potential therapeutic targets, we performed a candidate‐based screen of eukaryotic initiation factors and RNA helicases in cell‐based assays and a Drosophila melanogaster model of FXTAS. We identified multiple modifiers of toxicity and RAN translation from an expanded CGG repeat in the context of the FMR1 5′UTR. These include the DEAD‐box RNA helicase belle/DDX3X, the helicase accessory factors EIF4B/4H, and the start codon selectivity factors EIF1 and EIF5. Disrupting belle/DDX3X selectively inhibited FMR1 RAN translation in Drosophila in vivo and cultured human cells, and mitigated repeat‐induced toxicity in Drosophila and primary rodent neurons. These findings implicate RNA secondary structure and start codon fidelity as critical elements mediating FMR1 RAN translation and identify potential targets for treating repeat‐associated neurodegeneration.SynopsisFragile X‐associated tremor/ataxia syndrome is caused by CGG repeat‐associated non‐AUG (RAN) translation that initiates within the 5′UTR of FMR1. A candidate‐based screen identified several initiation factors—DDX3X/Belle, eIF4B, eIF4H, eIF1, and eIF5—critical for FMR1 RAN translation.Knockdown of the RNA helicase DDX3X selectively suppresses FMR1 RAN translation in Drosophila melanogaster, cultured HeLa cells, and in vitro translation assays.DDX3X knockdown reduces CGG repeat‐associated toxicity in Drosophila and mammalian neurons.Eukaryotic initiation factors that modulate RNA‐RNA secondary structure (DDX3X, EIF4B, EIF4H) or start codon fidelity (EIF1, EIF5) impact FMR1 RAN translation.FXTAS is caused by CGG repeat‐associated non‐AUG (RAN) translation that initiates within the 5′UTR of FMR1. A candidate‐based screen identified several initiation factors—DDX3X/Belle, eIF4B, eIF4H, eIF1, and eIF5—critical for FMR1 RAN translation.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151325/1/embr201847498.reviewer_comments.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151325/2/embr201847498-sup-0001-Appendix.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151325/3/embr201847498_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151325/4/embr201847498.pd

Radial versus femoral access is associated with reduced complications and mortality in patients with non-ST-segment-elevation myocardial infarction: an observational cohort study of 10,095 patients

Background— Compared with transfemoral access, transradial access (TRA) for percutaneous coronary intervention is associated with reduced risk of bleeding and vascular complications. Studies suggest that TRA may reduce mortality in patients with ST-segment–elevation myocardial infarction. However, there are few data on the effect of TRA on mortality, specifically, in patients with non–ST-segment–elevation myocardial infarction. Methods and Results— We analyzed 10 095 consecutive patients with non–ST-segment–elevation myocardial infarction treated with percutaneous coronary intervention between 2005 and 2011 in all 8 tertiary cardiac centers in London, United Kingdom. TRA was a predictor for reduced bleeding (odds ratio=0.21; 95% confidence interval [CI]: 0.08–0.57; P =0.002), access-site complications (odds ratio=0.47; 95% CI: 0.23–0.95; P =0.034), and 1-year mortality (hazard ratio [HR]=0.72; 95% CI: 0.54–0.94; P =0.017). Between 2005 and 2007, TRA did not appear to reduce mortality at 1 year (HR=0.81; 95% CI: 0.51–1.28; P =0.376), whereas between 2008 and 2011, TRA conferred survival benefit at 1 year (HR=0.65; 95% CI: 0.46–0.92; P =0.015). The mortality benefit with TRA at 1 year was not seen at the low-volume centers (HR=0.80; 95% CI: 0.47–1.38; P =0.428) but specifically seen in the high volume radial centers (HR=0.70; 95% CI: 0.51–0.97; P =0.031). In propensity-matched analyses, TRA remained a predictor for survival at 1 year (HR=0.60; 95% CI: 0.42–0.85; P =0.005). Instrumental variable analysis demonstrated that TRA conferred mortality benefit at 1-year with an absolute mortality reduction of 5.8% ( P =0.039). Conclusions— In this analysis of patients with non–ST-segment–elevation myocardial infarction, TRA appears to be a predictor for survival. Furthermore, the evolving learning curve, experience, and expertise may be important factors contributing to the prognostic benefit conferred with TRA. </jats:sec