BackgroundThe United States' COVID-19 epidemic has grown extensively since February 2020, with substantial associated hospitalizations and mortality; New York State (NYS) has emerged as the national epicenter. We report on the extent of testing and test results during the month of March in NYS, along with risk factors, outcomes, and household prevalence among initial cases subject to indepth investigations. MethodsSpecimen collection for COVID-19 testing was conducted in healthcare settings, community-based collection sites, and by home testing teams. Information on demographics, risk factors, and hospital outcomes of cases was obtained through epidemiological investigations and an electronic medical records match, and summarized descriptively. Active testing of initial case's households enabled estimation of household prevalence. ResultsDuring March In NYS, outside of New York City, a total of 47,326 persons tested positive for SARS-CoV-2, out of 141,495 tests (33% test-positive), with the highest number of cases located in the metropolitan region counties. Among 229 initial cases diagnosed through March 12, by March 30 13% were hospitalized and 2% died. Testing conducted among 498 members of these case's households found prevalent infection among 57%; excluding first-reported cases 38%. In these homes, we found a significant age gradient in prevalence, from 23% among those <5 years to 68% among those ≥65 years (p<.0001). ConclusionsNew York State faced a substantial and increasing COVID-19 outbreak during March 2020. The earliest cases had high levels of infection in their households and by the end of the month, the risks of hospitalization and death were high.
Evidence from studies with phenylisopropylamine hallucinogens indicates that the 5HT2A receptor is the likely target for the initiation of events leading to hallucinogenic activity associated with LSD and related drugs. Recently, lisuride (a purported non-hallucinogenic congener of LSD) was reported to be a potent antagonist at the 5HT2C receptor and an agonist at the 5HT2A receptor. LSD exhibited agonist activity at both receptors. These data were interpreted as indicating that the 5HT2C receptor might be the initiating site of action for hallucinogens. To test this hypothesis, recombinant cells expressing 5HT2A and 5HT2C receptors were used to determine the actions of LSD and lisuride. LSD and lisuride were potent partial agonists at 5HT2A receptors with EC50 values of 7.2 nM and 17 nM, respectively. Also, LSD and lisuride were partial agonists at 5HT2C receptors with EC50 values of 27 nM and 94 nM, respectively. We conclude that lisuride and LSD have similar actions at 5HT2A and 5HT2C receptors in recombinant cells. As agonist activity at brain 5HT2A receptors has been associated with hallucinogenic activity, these results indicate that lisuride may possess hallucinogenic activity, although the psychopharmacological effects of lisuride appear to be different from the hallucinogenic effects of LSD.
Zika virus (ZIKV) is implicated in fetal stillbirth, microcephaly, intracranial calcifications, and ocular anomalies following vertical transmission from infected mothers. In adults, infection may trigger autoimmune inflammatory polyneuropathy. Transmission most commonly follows the bite of infected mosquitoes but may also occur through sexual intercourse or receipt of blood products. Definitive diagnosis through detection of viral RNA is possible in serum or plasma within 10 days of disease onset, in whole blood within 3 weeks of onset, and in semen for up to 3 months. Serological diagnosis is nonetheless critical because few patients have access to molecular diagnostics during the acute phase of infection and infection may be associated with only mild or inapparent disease that does not prompt molecular testing. Serological diagnosis is confounded by cross-reactivity of immune sera with other flaviviruses endemic in the areas where ZIKV has recently emerged. Accordingly, we built a high-density microarray comprising nonredundant 12-mer peptides that tile, with one-residue overlap, the proteomes of Zika, dengue, yellow fever, West Nile, Ilheus, Oropouche, and chikungunya viruses. Serological analysis enabled discovery of a ZIKV NS2B 20-residue peptide that had high sensitivity (96.0%) and specificity (95.9%) versus natural infection with or vaccination against dengue, chikungunya, yellow fever, West Nile, tick-borne encephalitis, or Japanese encephalitis virus in a microarray assay and an enzyme-linked immunosorbent assay (ELISA) of early-convalescent-phase sera (2 to 3 weeks after onset of symptomatic infection). The emergence of Zika virus (ZIKV) as a teratogen is a profound challenge to global public health. Molecular diagnosis of infection is straightforward during the 3-week period when patients are viremic. However, serological diagnosis thereafter of historical exposure has been confounded by cross-reactivity. Using high-density peptide arrays that tile the proteomes of a selection of flaviviruses to identify a ZIKV-specific peptide, we established two assays that enable sensitive and specific diagnosis of exposure to ZIKV. These assays may be useful in guiding clinical management of mothers at risk for potential exposure to ZIKV and enable insights into the epidemiology of ZIKV infections.
Phenylalkylamines such as 1-(4-bromo-2, 5-dimethoxyphenyl)-2-aminopropane (DOB; 1a) and its corresponding iodo derivative DOI (2) are commonly used 5-HT(2) serotonin agonists. Previous studies have established that the 2,5-dimethoxy substitution pattern found in these compounds is optimal for high affinity at 5-HT(2A) receptors and that substituents at the 4-position can modulate affinity over a wide range. We have previously shown, however, that when the 4-position is substituted with a 3-phenylpropyl substituent (i.e., 3), the compound binds with an affinity comparable to that of 1a but that it possesses 5-HT(2A) antagonist character. The present study examined the structure-affinity relationships of 3, and the results were very much unexpected. That is, the 2,5-dimethoxy substitution pattern of 3 is not required for high affinity. Either of the two methoxy groups can be removed without untoward effect on affinity, and relocation of the methoxy substituents actually enhances affinity by as much as an order of magnitude. None of the compounds displayed more than 20-fold selectivity for 5-HT(2A) over 5-HT(2C) receptors. In addition, several were demonstrated to act as 5-HT(2A) partial agonists. As such, the results of this study suggest that the structure-affinity relationships of phenylalkylamines as 5-HT(2A) ligands now be reinvestigated in greater detail.
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