Acceso al diagnóstico rápido de VIH/sífilis en contextos de encierro: relato de experiencia en una unidad penal de la provincia de Buenos Aires en el año 2021 / Access to rapid diagnosis of HIV/syphilis in confinement contexts: an experience report in a penal unit in the province of Buenos Aires in the year 2021

En Argentina se estima que 140 mil personas viven con VIH y de ellas el 17% no conocen su diagnóstico (Ministerio de Salud, 2021). La Dirección de Sida y Enfermedades de Transmisión Sexual (DSyETS) del Ministerio de Salud de la Nación realizó un estudio que mostró una prevalencia global de VIH de 2,68% en unidades del servicio penitenciario federal (DSyETS; 2017). Por ello nuestro objetivo fue favorecer el acceso al testeo y a la prevención de estas enfermedades en personas privadas de su libertad en una unidad penal de la provincia de Buenos Aires en el marco de la pandemia. Relato de experiencia: en diciembre del 2021 se ofreció el testeo voluntario, gratuito y confidencial para VIH y sífilis y accedieron 38 personas. Participaron de la actividad docentes, estudiantes del Departamento de Ciencias de la Salud de la Universidad Nacional del Sur y referentes del programa de VIH-ITS y HV de la Región Sanitaria I del ministerio de salud de la provincia de Buenos Aires. Conclusiones: Esta experiencia mostró la importancia de construcción de redes para la articulación de prácticas que favorezcan el acceso a un diagnóstico temprano y tratamiento oportuno para VIH y sífilis a las personas viviendo en contexto de encierro (AU)

In Argentina, it is estimated that 140 thousand people live with HIV and 17% of them do not know their diagnosis (Ministry of Health, 2021). The Directorate of AIDS and Sexually Transmitted Diseases (DSyETS) of the Ministry of Health of the Nation carried out a study that showed a global prevalence of HIV of 2.68% in units of the federal prison service (DSyETS; 2017). For this reason, our objective was to promote access to testing and the prevention of these diseases in people deprived of their liberty in a penal unit in the province of Buenos Aires in the context of the pandemic. Experience report: in December 2021, voluntary, free and confidential testing for HIV and syphilis was offered and 38 people agreed. Teachers, students from the Department of Health Sciences of the National University of the South and referents of the HIV-STI and HV program of the Sanitary Region I of the Ministry of Health of the province of Buenos Aires participated in the activity. Conclusions: This experience showed the importance of building networks for the articulation of practices that favor access to early diagnosis and timely treatment for HIV and syphilis for people living in a confinement context (AU)

Testosterone-loaded GM1 micelles targeted to the intracellular androgen receptor for the specific induction of genomic androgen signaling.

Androgens play a central role in homeostatic and pathological processes of the prostate gland. At the cellular level, testosterone activates both the genomic signaling pathway, through the intracellular androgen receptor (AR), and membrane-initiated androgen signaling (MIAS), by plasma membrane receptors. We have previously shown that the activation of MIAS induces uncontrolled proliferation and fails to stimulate the beneficial immunomodulatory effects of testosterone in prostatic cells, becoming necessary to investigate if genomic signaling mediates homeostatic effects of testosterone. However, the lack of specific modulators for genomic androgen signaling has delayed the understanding of this mechanism. In this article, we demonstrate that monosialoganglioside (GM1) micelles are capable of delivering testosterone into the cytoplasm to specifically activate genomic signaling. Stimulation with testosterone-loaded GM1 micelles led to the activation of androgen response element (ARE)-regulated genes in vitro as well as to the recovery of normal prostate size and histology after castration in mice. In addition, these micelles avoided MIAS, as demonstrated by the absence of rapid signaling pathway activation and the inability to induce uncontrolled cell proliferation. In conclusion, our results validate a novel tool for the specific activation of genomic androgen signaling and demonstrate the importance of selective pathway activation in androgen-mediated proliferation.

Inefficient N2-Like Neutrophils Are Promoted by Androgens During Infection.

Neutrophils are major effectors of acute inflammation against infection and tissue damage, with ability to adapt their phenotype according to the microenvironment. Although sex hormones regulate adaptive immune cells, which explains sex differences in immunity and infection, little information is available about the effects of androgens on neutrophils. We therefore aimed to examine neutrophil recruitment and plasticity in androgen-dependent and -independent sites under androgen manipulation. By using a bacterial model of prostate inflammation, we showed that neutrophil recruitment was higher in testosterone-treated rats, with neutrophil accumulation being positively correlated to serum levels of testosterone and associated to stronger inflammatory signs and tissue damage. Testosterone also promoted LPS-induced neutrophil recruitment to the prostate, peritoneum, and liver sinusoids, as revealed by histopathology, flow cytometry, and intravital microscopy. Strikingly, neutrophils in presence of testosterone exhibited an impaired bactericidal ability and a reduced myeloperoxidase activity. This inefficient cellular profile was accompanied by high expression of the anti-inflammatory cytokines IL10 and TGFß1, which is compatible with the "N2-like" neutrophil phenotype previously reported in the tumor microenvironment. These data reveal an intriguing role for testosterone promoting inefficient, anti-inflammatory neutrophils that prolong bacterial inflammation, generating a pathogenic environment for several conditions. However, these immunomodulatory properties might be beneficially exploited in autoimmune and other non-bacterial diseases.

The Response of Prostate Smooth Muscle Cells to Testosterone Is Determined by the Subcellular Distribution of the Androgen Receptor.

Androgen signaling in prostate smooth muscle cells (pSMCs) is critical for the maintenance of prostate homeostasis, the alterations of which are a central aspect in the development of pathological conditions. Testosterone can act through the classic androgen receptor (AR) in the cytoplasm, eliciting genomic signaling, or through different types of receptors located at the plasma membrane for nongenomic signaling. We aimed to find evidence of nongenomic testosterone-signaling mechanisms in pSMCs and their participation in cell proliferation, differentiation, and the modulation of the response to lipopolysaccharide. We demonstrated that pSMCs can respond to testosterone by a rapid activation of ERK1/2 and Akt. Furthermore, a pool of ARs localized at the cell surface of pSMCs is responsible for a nongenomic testosterone-induced increase in cell proliferation. Through membrane receptor stimulation, testosterone favors a muscle phenotype, indicated by an increase in smooth muscle markers. We also showed that the anti-inflammatory effects of testosterone, capable of attenuating lipopolysaccharide-induced proinflammatory actions, are promoted only by receptors located inside the cell. We postulate that testosterone might perform prohomeostatic effects through intracellular-initiated mechanisms by modulating cell proliferation and inflammation, whereas some pathological, hyperproliferative actions would be induced by membrane-initiated nongenomic signaling in pSMCs.