RESUMEN
Biological sex affects adaptive immune responses, which could impact influenza infection and vaccine efficacy. Infection of mice with 2009 H1N1 induced antibody responses, CD4+ T cell and CD8+ T cell memory responses that were greater in females than males; both sexes, however, were equally protected against secondary challenge with an H1N1 drift variant virus. To test whether greater antibody in females is sufficient for protection against influenza, males and females were immunized with an inactivated H1N1 vaccine that induced predominantly antibody-mediated immunity. Following vaccination, females had greater antibody responses and protection against challenge with an H1N1 drift variant virus than males. Antibody derived from vaccinated females was better at protecting both naïve males and females than antibody from males, and this protection was associated with increased antibody specificity and avidity to the H1N1 virus. The expression of Tlr7 was greater in B cells from vaccinated females than males and was associated with reduced DNA methylation in the Tlr7 promoter region, higher neutralizing antibody, class switch recombination, and antibody avidity in females. Deletion of Tlr7 reduced sex differences in vaccine-induced antibody responses and protection following challenge and had a greater impact on responses in females than males. Taken together, these data illustrate that greater TLR7 activation and antibody production in females improves the efficacy of vaccination against influenza.
Asunto(s)
Subtipo H1N1 del Virus de la Influenza A/genética , Vacunas contra la Influenza/inmunología , Infecciones por Orthomyxoviridae/prevención & control , Animales , Femenino , Inmunidad Humoral , Subtipo H1N1 del Virus de la Influenza A/inmunología , Masculino , Ratones , Infecciones por Orthomyxoviridae/inmunología , Factores SexualesRESUMEN
PURPOSE: To assess persistent and de novo rates of overactive bladder (OAB) and urgency urinary incontinence (UUI) in patients with incontinence after prostate treatment (IPT) focusing on differences between surgical intervention vs radiation. METHODS: We performed a retrospective review of 79 patients who underwent primary artificial urinary sphincter (AUS) placement and activation from a single surgeon between February 2012 and November 2017. Four patients with neurogenic bladder were excluded and two with insufficient follow-up. The primary outcome measures were persistent OAB, persistent UUI, and pad usage before and after AUS placement. RESULTS: After activation of the AUS, 67% of non-radiated patients had resolution of urgency incontinence vs only 31% of the radiated patients (P = .096). After activation of the AUS, resolution of OAB symptoms was more common in the non-radiated group. We found 53% of the non-radiated group vs only 22% of the radiated group had resolution of their urinary urgency (P = .045). Previous history of radiation was a risk factor for OAB after implantation of AUS (odds ratio [OR], 3.63; P = .010). Postoperative oral medical pharmacotherapy for OAB was higher in those with previous radiation vs those without prior radiation (66.7% vs 25.7%, P = .001). A history of OAB or UUI did not affect social continence after AUS placement. CONCLUSION: Radiation is a risk for continued OAB after AUS activation. Appropriate counseling is necessary pre- and postoperatively to manage patient expectations and provide additional medical therapies. Mixed urinary incontinence or OAB symptoms should not exclude patients from undergoing AUS placement.
Asunto(s)
Próstata/cirugía , Prostatectomía/efectos adversos , Vejiga Urinaria Hiperactiva/cirugía , Incontinencia Urinaria de Urgencia/cirugía , Esfínter Urinario Artificial , Anciano , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Vejiga Urinaria Hiperactiva/etiología , Incontinencia Urinaria de Urgencia/etiologíaRESUMEN
Both sex (i.e., biological construct of male and female) and gender (i.e., social construct of masculine and feminine) impact the pathogenesis of diseases, including those caused by microbial infections. Following the 2015 NIH policy for consideration of sex as a biological variable in preclinical research, in 2018, authors of papers published in primary-research American Society for Microbiology (ASM) journals will be asked to report the sex of the research subjects and animals and of materials derived directly from them. To address the need for sex reporting in ASM journals, we systematically reviewed 2,928 primary-research articles published in six primary-research ASM journals (Antimicrobial Agents and Chemotherapy, Clinical and Vaccine Immunology, Infection and Immunity, Journal of Bacteriology, Journal of Virology, and mBio) in 2016. Approximately 37% of animal studies and 9% of primary cell culture papers published in 2016 would have been affected by the new sex-reporting policy. For animal studies (i.e., studies with any nonhuman vertebrate hosts), most published papers either did not report the sex of the animals or used only female animals, and a minority used only males or both sexes. For published studies using primary cells from diverse animal species (i.e., humans and nonhuman vertebrates), almost all studies failed to report the sex of donors from which the cells were isolated. We believe that reporting the sex of animals and even of the donors of derived cells could improve the rigor and reproducibility of research conducted in microbiology and immunology and published in ASM journals.