BackgroundOctopamine receptors (OARs) perform key functions in the biological pathways of primarily invertebrates, making this class of G-protein coupled receptors (GPCRs) a potentially good target for insecticides. However, the lack of structural and experimental data for this insect-essential GPCR family has promoted the development of homology models that are good representations of their biological equivalents for in silico screening of small molecules.MethodsTwo Anopheles gambiae OARs were cloned, analysed and functionally characterized using a heterologous cell reporter system. Four antagonist- and four agonist-binding homology models were generated and virtually screened by docking against compounds obtained from the ZINC database. Resulting compounds from the virtual screen were tested experimentally using an in vitro reporter assay and in a mosquito larvicide bioassay.ResultsSix An. gambiae OAR/tyramine receptor genes were identified. Phylogenetic analysis revealed that the OAR (AGAP000045) that encodes two open reading frames is an α-adrenergic-like receptor. Both splice variants signal through cAMP and calcium. Mutagenesis analysis revealed that D100 in the TM3 region and S206 and S210 in the TM5 region are important to the activation of the GPCR. Some 2,150 compounds from the virtual screen were structurally analysed and 70 compounds were experimentally tested against AgOAR45B expressed in the GloResponse™CRE-luc2P HEK293 reporter cell line, revealing 21 antagonists, 17 weak antagonists, 2 agonists, and 5 weak agonists.ConclusionReported here is the functional characterization of two An. gambiae OARs and the discovery of new OAR agonists and antagonists based on virtual screening and molecular dynamics simulations. Four compounds were identified that had activity in a mosquito larva bioassay, three of which are imidazole derivatives. This combined computational and experimental approach is appropriate for the discovery of new and effective insecticides.Electronic supplementary materialThe online version of this article (doi:10.1186/1475-2875-13-434) contains supplementary material, which is available to authorized users.
Objective To assess how use of postpartum contraception (PPC) changed during the COVID‐19 public health emergency. Methods Billing and coding data from a single urban institution (n = 1797) were used to compare use of PPC in patients who delivered from March to June 2020 (COVID Cohort, n = 927) and from March to June 2019 (Comparison Cohort, n = 895). χ2 and multivariable logistic regression models assessed relationships between cohorts, use of contraception, and interactions with postpartum visits and race/ethnicity. Results In the COVID Cohort, 585 women (64%) attended postpartum visits (n = 488, 83.4%, via telemedicine) compared to 660 (74.7%, in‐person) in the Comparison Cohort (P < 0.01). Total use of PPC remained similar: 30.4% (n = 261) in the COVID Cohort and 29.6% (n = 278) in the Comparison Cohort (P = 0.69). Compared to in‐person visits in the Comparison Cohort, telemedicine visits in the COVID Cohort had similar odds of insertion of long‐acting reversible contraception (LARC) (adjusted odds ratio [aOR] 1.13, 95% confidence interval [CI] 0.78–1.6), but higher odds of inpatient insertion (aOR 6.4, 95% CI 1.7–24.9). Black patients compared to white patients were more likely to initiate inpatient LARC (aOR 7.29, 95% CI 1.81–29.4) compared to the Comparison Cohort (aOR 3.63, 95% CI 0.29–46.19). Conclusion Use of PPC remained similar during COVID‐19 with a decrease of in‐person postpartum visits, new adoption of postpartum telemedicine visits, and an increase in inpatient insertion of LARC with higher odds of inpatient placement among black patients.
INTRODUCTION: Seventeen US states have passed legislation requiring insurers to cover dispensation of a full 12-month supply of contraception prescribed at a single time. Such policies are linked to improved contraception continuation and reductions in unintended pregnancy. This study sought to determine if there was a difference in the months of oral contraception prescribed by physicians living in US states with a 12-month supply policy compared to physicians in states without a policy. METHODS: We conducted an exploratory descriptive study using a convenience sample of obstetrics and gynecology resident physicians (n=275) in the United States. Standard bivariate analyses were used to compare the difference between groups and describe the overall prescribing habits of physicians. The study was approved by the institutional review board at Oregon Health & Science University. RESULTS: Of the 275 respondents, 48% resided in a state with a policy requiring insurance coverage of a 12-month supply of contraception and 52% resided in states without such a policy. Few physicians in both groups (3.8% with a policy and 1.4% without a policy) routinely prescribed a 12-month supply of contraception. The mean coverage prescribed by providers in states with and without a policy was 2.81 and 2.07 months (P<.05). CONCLUSION: The majority of physicians were unaware of 12-month contraceptive supply policies and unable to correctly write a prescription for 12 months of contraception. Physician education may be needed to effectively implement 12-month contraceptive supply policies and meaningfully impact contraception access.
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