Extent of rescue of F508del-CFTR function by VX-809 and VX-770 in human nasal epithelial cells correlates with SNP rs7512462 in SLC26A9 gene in F508del/F508del Cystic Fibrosis patients.

BACKGROUND: We analyzed the CFTR response to VX-809/VX-770 drugs in conditionally reprogrammed cells (CRC) of human nasal epithelium (HNE) from F508del/F508del patients based on SNP rs7512462 in the Solute Carrier Family 26, Member 9 (SLC26A9; MIM: 608481) gene. METHODS: The Isc-eq measurements of primary nasal epithelial cells from F508del/F508del patients (n = 12) for CFTR function were performed in micro Ussing chambers and compared with non-CF controls (n = 2). Data were analyzed according to the rs7512462 genotype which were determined by real-time PCR. RESULTS: The CRC-HNE cells from F508del/F508del patients evidenced high variability in the basal levels of CFTR function. Also, the rs7512462*C allele showed an increased basal CFTR function and higher responses to VX-809 + VX-770. The rs7512462*CC + CT genotypes together evidenced CFTR function levels of 14.89% relatively to wt/wt (rs7512462*CT alone-15.29%) i.e., almost double of rs7512462*TT (7.13%). Furthermore, sweat [Cl-] and body mass index of patients also evidenced an association with the rs7512462 genotype. CONCLUSION: The CFTR function can be performed in F508del/F508del patient-derived CRC-HNEs and its function and responses to VX-809 + VX-770 combination as well as clinical data, are all associated with the rs7512462 variant, which partially sheds light on the generally inter-individual phenotypic variability and in personalized responses to CFTR modulator drugs.

The Peer and Non-peer: the potential of risk management for HIV prevention in contexts of prostitution.

Sex workers have been the protagonists and focus of HIV prevention campaigns and research since the late 1980s in Brazil. Through a review of national and international literature, combined with a history of sex workers' involvement in the construction of the Brazilian response, this article explores the overlaps and disconnects between research and practice in contexts of prostitution over the past three decades. We review the scientific literature on the epidemiology of HIV among sex workers and prevention methodologies. We conclude that although research focus and designs often reinforce the idea that sex workers' vulnerability is due to their sexual relationships with clients, their greatest vulnerability has been found to be with their nonpaying intimate partners. Few studies explore their work contexts and structural factors that influence safe sex practices with both types of partners. The negative effects of criminalization, stigma, and exclusively biomedical and peer education-based approaches are well documented in the scientific literature and experiences of sex worker activists, as is the importance of prevention programs that combine empowerment and human rights-based approach to reduce HIV infection rates. We conclude that there is a need for actions, policies, and research that encompass the environment and context of sex workers' lives and reincorporate the human rights and citizenship frame that dominated the Brazilian response until the end of the 2000s. As part of HIV prevention efforts, female sex workers need to be considered above all as women, equal to all others.

The Peer and Non-peer: the potential of risk management for HIV prevention in contexts of prostitution / O Par e o Ímpar: o potencial de gestão de risco para a prevenção de DST/HIV/AIDS em contextos de prostituição

ABSTRACT Sex workers have been the protagonists and focus of HIV prevention campaigns and research since the late 1980s in Brazil. Through a review of national and international literature, combined with a history of sex workers' involvement in the construction of the Brazilian response, this article explores the overlaps and disconnects between research and practice in contexts of prostitution over the past three decades. We review the scientific literature on the epidemiology of HIV among sex workers and prevention methodologies. We conclude that although research focus and designs often reinforce the idea that sex workers' vulnerability is due to their sexual relationships with clients, their greatest vulnerability has been found to be with their nonpaying intimate partners. Few studies explore their work contexts and structural factors that influence safe sex practices with both types of partners. The negative effects of criminalization, stigma, and exclusively biomedical and peer education-based approaches are well documented in the scientific literature and experiences of sex worker activists, as is the importance of prevention programs that combine empowerment and human rightsbased approach to reduce HIV infection rates. We conclude that there is a need for actions, policies, and research that encompass the environment and context of sex workers' lives and reincorporate the human rights and citizenship frame that dominated the Brazilian response until the end of the 2000s. As part of HIV prevention efforts, female sex workers need to be considered above all as women, equal to all others.

RESUMO Prostitutas têm sido protagonistas e foco de campanhas de prevenção de HIV desde o final da década de 1980 no Brasil. Com base em um levantamento da literatura nacional e internacional, combinada com a trajetória do movimento de prostitutas na construção da resposta brasileira à epidemia, este artigo explora as sobreposições e incoerências entre pesquisa e prática em contextos de prostituição nas últimas três décadas. Na revisão da literatura científica, verificamos que a maior vulnerabilidade desse grupo social ocorre com os parceiros íntimos, não-comerciais; entretanto, o foco das pesquisas e a forma que são feitas geralmente reforçam a ideia de que a vulnerabilidade decorre de seus clientes. Ao mesmo tempo, há poucos estudos sobre seus contextos de trabalho e fatores estruturais que influenciam práticas sexuais mais seguras com ambos os tipos de parceiros. Os efeitos negativos da criminalização, do estigma, e de abordagens exclusivamente biomédicas e baseadas de uma forma isolada na metodologia de educação pelos pares estão bem documentados na literatura científica e nas experiências de ativistas, assim como a importância de programas de prevenção baseados em direitos humanos e sexuais. Concluímos que há necessidade de ações, políticas e pesquisas que incluam o ambiente e contexto nos quais profissionais do sexo trabalham, que reincorporem o arcabouço de direitos humanos e cidadania que dominou a resposta brasileira até o final da década de 2000, e que prostitutas devem ser consideradas e tratadas como mulheres, iguais a todas as outras.