These guidelines for the treatment of persons who have or are at risk for sexually transmitted infections (STIs) were updated by CDC after consultation with professionals knowledgeable in the field of STIs who met in Atlanta, Georgia, June 11-14, 2019. The information in this report updates the 2015 guidelines. These guidelines discuss 1) updated recommendations for treatment of Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis; 2) addition of metronidazole to the recommended treatment regimen for pelvic inflammatory disease; 3) alternative treatment options for bacterial vaginosis; 4) management of Mycoplasma genitalium; 5) human papillomavirus vaccine recommendations and counseling messages; 6) expanded risk factors for syphilis testing among pregnant women; 7) one-time testing for hepatitis C infection; 8) evaluation of men who have sex with men after sexual assault; and 9) two-step testing for serologic diagnosis of genital herpes simplex virus. Physicians and other health care providers can use these guidelines to assist in prevention and treatment of STIs. BOX 1. The Five P's approach for health care providers obtaining sexual histories: partners, practices, protection from sexually transmitted infections, past history of sexually transmitted infections, and pregnancy intention Additional information about external condoms is available at https://www.cdc.gov/condomeffectiveness. Internal CondomsCondoms for internal vaginal use, also known as female condoms, are available worldwide (e.g., the FC2 Female Condom, Reddy condom, Cupid female condom, and Woman's condom) (31,32). Use of internal condoms can provide protection from acquisition and transmission of STIs, although data are limited. Internal condoms are more costly compared with external condoms; however, they offer the advantage of being controlled by the receptive partner as an STI and HIV prevention method, and the newer versions might be acceptable to all persons. Although the internal condom also has been used during receptive anal intercourse, efficacy associated with this practice remains unknown (33). Additional information about the internal condom is available at http://www.ashasexualhealth. org/pdfs/Male_and_Female_Condoms.pdf. Cervical DiaphragmsIn observational studies, diaphragm use has been demonstrated to protect against cervical gonorrhea, chlamydia, and trichomoniasis (34). However, a trial examining the effect of a diaphragm plus lubricant on HIV acquisition among women in Africa reported no additional protective effect when compared with the use of male condoms alone. Likewise, no difference by study arm in the rate of acquisition of chlamydia, gonorrhea, or herpes occurred (35,36). Diaphragms should not be relied on as the sole source of protection against HIV and other STIs.

This study reports further evidence as to the determinants of the audit fees paid by quoted companies in the UK. It outlines a framework based on the findings from semi‐structured interviews with partners in four large audit firms and the results of previous research, and tests this framework by means of multivariate analysis using 1987 data for a large sample of quoted UK companies. A model explaining 87 per cent of the variation in audit fees is constructed. The principal explanatory variables are found to be auditee size, return on shareholders equity, the number of subsidiaries, the lag between the year end and the date of the audit report, the size of the auditor, a measure of auditee diversification, the ownership structure of the auditee, and whether the auditor was based in London, with the last three being new variables introduced in this study.

Infectious Disease and EMS (PRIDEMS)*Authors contributed equally to this work.

contributed equally to this workThe catalytic determinants for the cleavage and ligation reactions mediated by the hairpin ribozyme are integral to the polyribonucleotide chain. We describe experiments that place G8, a critical guanosine, at the active site, and point to an essential role in catalysis. Cross-linking and modeling show that formation of a catalytic complex is accompanied by a conformational change in which N1 and O6 of G8 become closely apposed to the scissile phosphodiester. UV cross-linking, hydroxyl-radical footprinting and native gel electrophoresis indicate that G8 variants inhibit the reaction at a step following domain association, and that the tertiary structure of the inactive complex is not measurably altered. Rate±pH pro®les and¯uores-cence spectroscopy show that protonation at the N1 position of G8 is required for catalysis, and that modi®cation of O6 can inhibit the reaction. Kinetic solvent isotope analysis suggests that two protons are transferred during the rate-limiting step, consistent with rate-limiting cleavage chemistry involving concerted deprotonation of the attacking 2¢-OH and protonation of the 5¢-O leaving group. We propose mechanistic models that are consistent with these data, including some that invoke a novel keto±enol tautomerization.

Background: Excessive use of the Internet has been associated with attention deficit hyperactivity disorder (ADHD), but the relationship between video games and ADHD symptoms in adolescents is unknown.

The human genome contains frequent single-basepair variants that may or may not cause genetic disease. To characterize benign vs. pathogenic missense variants, numerous computational algorithms have been developed based on comparative sequence and/or protein structure analysis. We compared computational methods that use evolutionary conservation alone, amino acid (AA) change alone, and a combination of conservation and AA change in predicting the consequences of 254 missense variants in the CDKN2A (n = 92), MLH1 (n = 28), MSH2 (n = 14), MECP2 (n = 30), and tyrosinase (TYR) (n = 90) genes. Variants were validated as either neutral or deleterious by curated locus-specific mutation databases and published functional data. All methods that use evolutionary sequence analysis have comparable overall prediction accuracy (72.9-82.0%). Mutations at codons where the AA is absolutely conserved over a sufficient evolutionary distance (about one-third of variants) had a 91.6 to 96.8% likelihood of being deleterious. Three algorithms (SIFT, PolyPhen, and A-GVGD) that differentiate one variant from another at a given codon did not significantly improve predictive value over conservation score alone using the BLOSUM62 matrix. However, when all four methods were in agreement (62.7% of variants), predictive value improved to 88.1%. These results confirm a high predictive value for methods that use evolutionary sequence conservation, with or without considering protein structural change, to predict the clinical consequences of missense variants. The methods can be generalized across genes that cause different types of genetic disease. The results support the clinical use of computational methods as one tool to help interpret missense variants in genes associated with human genetic disease.

PrEP implementation in the United States is moving forward with the development of diverse models of delivery. Optimal scale-up will require learning about the best features of each model and providing choices to consumers that enhance engagement and uptake.

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