61 research outputs found

    EC80-553 What to Do Until the Doctor Comes....First Aid : A Guide for Emergency Medical Care

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    Extension circular 80-553 discusses What to do until the doctor comes: first aid, a guide for emergency medical care

    The History and Development of a Consolidated Communications System and an Emergency Medical Services System in Nebraska

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    •A Chronology of Events •Nebraska Vital Statistics •A Consolidated Communications Concept •A Total Emergency Medical Service System Concept •The Nebraska Adjutant General\u27s Study of Telecommunications •Nebraska State Civil Defense •The Nebraska Consolidated Communications Corporation •Emergency Telecommunications Service: Planning for the State Disaster Plan •Evolution of Ambulance Service in Nebraska •The Nebraska Committee on Transportation and Communication •The University of Nebraska College of Medicine •Extension Service, the University of Nebraska College of Agriculture •The Nebraska State Department of Health •Area Funding •The Department of Health, Education and Welfare •The Six EMS Regions in Nebraska •The Office of Traffic Highway Safety in Nebraska •The Robert Wood Johnson Foundation •Comprehensive Health Planning •Project 20/20 •Operation Sky-Aid •The Use of Helicopters in EMS Services in Nebraska •The Common Emergency Calling Number-911 •Immediate Dial Tone/Coin Free Telephone •Identification of Calling Number and Ring-back Capability •Visit of DOT People to Nebraska to Inspect Communications •The Omaha Fire Department Ambulance Service •A Paramedic Service for Nebraska •The Nebraska Committee on Trauma, American College of Surgeons •Full-time Emergency Department Staffing (American College of Emergency Physicians) •The Lincoln Medical Education Foundation •Categorization of Hospitals •The American Red Cross Handbook •Veterans Administration TV Network •Some Early Day Activities in Emergency Services in which Nebraskans were Involved •Things That Might Have Been •A Few of Lynn\u27s Comments •Mid-America Research Corporation •Interest in Joint Funding Lincoln/Lancaster Pilot Project •Changes in Pre-hospital Survival in Nebraska •People Involved in Early Day Consolidated Communications •People Involved in Early Day EMS •Appendix A-Original Members of Dr. Thompson\u27s Committee •Appendix B-Professional Staff, EMS Division Department of Health •Appendix C-Report by Del Maier in Washington •Appendix D-Joint Funding Report •Appendix E-ETV Network Development •Bibliographyhttps://digitalcommons.unmc.edu/nehist_books/1000/thumbnail.jp

    Synthetic Analogues of the Snail Toxin 6-Bromo-2-mercaptotryptamine Dimer (BrMT) Reveal That Lipid Bilayer Perturbation Does Not Underlie Its Modulation of Voltage-Gated Potassium Channels

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    Drugs do not act solely by canonical ligand–receptor binding interactions. Amphiphilic drugs partition into membranes, thereby perturbing bulk lipid bilayer properties and possibly altering the function of membrane proteins. Distinguishing membrane perturbation from more direct protein–ligand interactions is an ongoing challenge in chemical biology. Herein, we present one strategy for doing so, using dimeric 6-bromo-2-mercaptotryptamine (BrMT) and synthetic analogues. BrMT is a chemically unstable marine snail toxin that has unique effects on voltage-gated K+ channel proteins, making it an attractive medicinal chemistry lead. BrMT is amphiphilic and perturbs lipid bilayers, raising the question of whether its action against K+ channels is merely a manifestation of membrane perturbation. To determine whether medicinal chemistry approaches to improve BrMT might be viable, we synthesized BrMT and 11 analogues and determined their activities in parallel assays measuring K+ channel activity and lipid bilayer properties. Structure–activity relationships were determined for modulation of the Kv1.4 channel, bilayer partitioning, and bilayer perturbation. Neither membrane partitioning nor bilayer perturbation correlates with K+ channel modulation. We conclude that BrMT’s membrane interactions are not critical for its inhibition of Kv1.4 activation. Further, we found that alkyl or ether linkages can replace the chemically labile disulfide bond in the BrMT pharmacophore, and we identified additional regions of the scaffold that are amenable to chemical modification. Our work demonstrates a strategy for determining if drugs act by specific interactions or bilayer-dependent mechanisms, and chemically stable modulators of Kv1 channels are reported

    Finishing the euchromatic sequence of the human genome

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    The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

    OBSERVE-5: Observational postmarketing safety surveillance registry of etanercept for the treatment of psoriasis final 5-year results

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    BackgroundOBSERVE-5 was a 5-year Food and Drug Administration–mandated surveillance registry of patients with psoriasis.ObjectiveWe sought to assess long-term etanercept safety and effectiveness.MethodsPatients with moderate to severe psoriasis enrolled; a single baseline dose of etanercept was required. Key outcome measures included serious adverse events, serious infectious events, events of medical interest, psoriasis-affected body surface area, physician global assessment score, and Dermatology Life Quality Index score. Safety outcomes were assessed relative to data from the MarketScan database.ResultsFor 2510 patients, 5-year cumulative incidence was 22.2% (95% confidence interval [CI] 20.3%-24.2%) for serious adverse events; 6.5% (95% CI 5.4%-7.7%) for serious infectious events; 3.2% (95% CI 2.3%-4.1%) for malignancies excluding nonmelanoma skin cancer; 3.6% (95% CI 2.7%-4.5%) for nonmelanoma skin cancer; 2.8% (95% CI 2.0%-3.6%) for coronary artery disease; 0.7% (95% CI 0.3%-1.2%) for psoriasis worsening; 0.2% (95% CI 0.0%-0.4%) for central nervous system demyelinating disorder; 0.1% (95% CI 0.0%-0.3%) for lymphoma and for tuberculosis; and 0.1% (95% CI 0.0%-0.2%) for opportunistic infection and for lupus; 55 fatal events were reported. Rates of malignancies, lymphomas, nonmelanoma skin cancer, and hospitalization-associated infections were not higher than expected relative to administrative claims data. The percentage of patients rated as clear/almost clear was 12% at baseline, which increased to 51% at month 6 and remained relatively stable throughout 5 years.LimitationsNo internal comparator group was included; rare events may not have been detected.ConclusionNo new safety signals were observed with long-term, real-world etanercept use

    Synthetic Analogs of the Snail Toxin 6-Bromo-2-Mercaptotryptamine Dimer (BrMT) Reveal That Lipid Bilayer Perturbation Does Not Underlie Its Modulation of Voltage-Gated Potassium Channels

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    Distinguishing membrane perturbation from more direct protein-ligand interactions is an ongoing challenge in chemical biology. Herein, we present one strategy for doing so, using dimeric 6-bromo-2-mercaptotryptamine (BrMT) and synthetic analogs. BrMT is a chemically unstable marine snail toxin that has unique effects on voltage-gated K+ channel proteins, making it an attractive medicinal chemistry lead. BrMT is amphiphilic and perturbs lipid bilayers, raising the question of whether its action against K+ channels is merely a manifestation of membrane perturbation. To determine whether medicinal chemistry approaches to improve BrMT might be viable, we synthesized BrMT and 11 analogs and determined their activities in parallel assays measuring K+ channel activity and lipid bilayer properties. Our work demonstrates a strategy for determining if drugs act by specific interactions or bilayer-dependent mechanisms, and chemically stable modulators of Kv1 channels are reported
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