Thirty percent of Americans report insomnia. After eliminating obvious causes, the best therapy for insomnia is cognitive behavioral therapy, but this is not widely available. However, all the known oral sleeping aides are generally unsatisfactory. Recently, a new class of safe, nonaddicting, mechanism-based hypocretin blockers have been developed. Herein we review the information not only for insomnia but also for narcolepsy.
Recent applications of artificial intelligence-derived methods of computational design have permitted de novo creation of proteins that do not exist in nature but have potent effects on human cells and organ systems. These rapid procedures also allow in 1 step protein modifications that optimize function, potency, stability, resistance to biodegradation, cellular and tissue distribution and biological half-time. Such proteins generated to date include cytokines, antibodies, inhibitors of cell death proteins and antagonists of extracellular receptors for growth factors and viruses. Newly designed proteins have broad medical diagnostic and therapeutic potentials, as well as the capacity to alter many normal activities of human cells.
Background/aims: Sera from patients from a single medical institution in New York State with human granulocytic anaplasmosis established by a positive polymerase chain reaction test (PCR) for Anaplasma phagocytophilum were used to assess the performance of serologic testing. All cases were also confirmed by culture in order to eliminate any false positive PCR samples.
Methods: A nested PCR was performed targeting the heat shock operon of A. phagocytophilum. Culture was done using the HL-60 promyelocytic cell line. Serologic testing was performed to detect IgG/A/M using an indirect immunofluorescence assay that incorporated a human isolate of A. phagocytophilum as the source of the antigen.
Results: From 1997 to 2009, 38 human granulocytic anaplasmosis patients were evaluated. On the baseline serum sample 21 (55.3%; 95% CI: 38.3%-71.4%) had a positive serologic test; 7 samples (33.1%) were positive at a titer of 80-320 and 14 samples (66.7%) at a titer of at least 640. Sixteen (94.1%) of the 17 with a negative baseline test had follow-up testing performed. All 16 tested positive on a convalescent phase serum sample obtained from 6 to 45 days later.
Conclusion: PCR testing is the most commonly used direct diagnostic test to diagnose human granulocytic anaplasmosis. Our findings demonstrate that only approximately 55% of the PCR and culture positive cases were also seropositive on blood samples obtained at the same time point, indicating that serologic testing performed at the time of presentation has limited sensitivity. However, all of the 16 evaluable seronegative patients developed antibodies to A. phagocytophilum during convalescence.
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