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HIV-1 antiretroviral therapy is highly effective but fails to eliminate a reservoir of latent proviruses, leading to a requirement for life-long treatment. How the site of integration of authentic intact latent proviruses might impact their own or neighboring gene expression or reservoir dynamics is poorly understood. Here, we report on proviral and neighboring gene transcription at sites of intact latent HIV-1 integration in cultured T cells obtained directly from people living with HIV, as well as engineered primary T cells and cell lines. Proviral gene expression was correlated to the level of endogenous gene expression under resting but not activated conditions. Notably, latent proviral promoters were 100–10,000× less active than in productively infected cells and had little or no measurable impact on neighboring gene expression under resting or activated conditions. Thus, the site of integration has a dominant effect on the transcriptional activity of intact HIV-1 proviruses in the latent reservoir, thereby influencing cytopathic effects and proviral immune evasion.

Sexual transmission of Zika virus (ZIKV), an important arbovirus, and the virus persistence in semen raise several questions about how and where it circulates in the male reproductive system (MRS). Several studies reported detection of the virus in testes, epididymis, and prostate at 5 days post-infection (dpi) or more in animal models. In the present study, we investigated the interactions of ZIKV with mouse MRS using the AG129 strain, a ZIKV permissive immunodeficient mouse strain, at two dpi. Viral RNA was detected in blood, testes, epididymis, and prostatic complexes (prostate and seminal vesicles). Immunohistochemical (IHC) analyses, based on the envelope protein, showed an early infection in organs of MRS since ZIKV positive antigens were detected in cells within or surrounding blood vessels, Sertoli, and germ cells in testes and epithelial cells in epididymis and prostate. Positive antigens for NS5 protein, the virus RNA-dependent RNA polymerase, were also detected by IHC in these organs and circulating leukocytes, suggesting that the virus replicates in these sites as early as 2 days post-infection. Analysis of the early stages of ZIKV infection in MRS may improve the current knowledge about this issue and contribute to the development of therapies directed to the infection at this site.

•The sustained virological response at 12 weeks post-treatment rate was 92.7% (93.9% for SOF plus DCV and 91.7% for SOF plus SMV).•No clinical or laboratorial factor was statistically associated with SVR.•Out of 144 blood samples, 70 (48.6%) had detected resistance associated substitutions (34.8% treated with SOF+DCV±ribavirin and 61.3% SOF+SMV±ribavirin).•Important mutations associated with resistance against DAAs were detected in NS3 (G122S, I170V, Y56F and V132I), NS5A (R30Q, P58H and Q62E) and NS5B (A421V, L159F and C316N).•Three out of 4 relapsing patients presented virus carrying baseline resistance substitutions.•Substitutions with direct effect on virus resistance were observed occurring simultaneously with compensatory mutations that can improve virus replication.

Analisar e avaliar os resultados funcionais e clínicos em pacientes com pé torto congênito tratados pela técnica de Ponseti.

Avaliar, comparar e identificar a técnica cirúrgica com melhor resultado para o tratamento de fraturas intra‐articulares do calcâneo, levando em consideração evolução pós‐operatória, complicações e pontuação no questionário Aofas.

Demonstrar os resultados obtidos nas reconstruções tendíneas do pé e do tornozelo com o uso do tendão do músculo semitendíneo. Foram avaliados os resultados clínicos, o grau de satisfação do paciente e as complicações da área doadora e receptora do enxerto.

Background:Although a variety of surgical techniques are available for the treatment of ankle degenerative disease, arthrodesis is a common treatment especially for unilateral posttraumatic arthritis in young patients. A clear trend toward internal fixation for ankle arthrodesis is evident, but fusion site compression is known to play an integral role in primary bone healing.Methods:Between September 2001 and October 2009, 17 adults with painful end-stage posttraumatic ankle arthritis were treated with the tension band technique to achieve tibiotalar arthrodesis.Results:Tibiotalar fusion was obtained in all patients at a mean of 16.6 (range, 13 to 28) weeks. No patient had pain at the last postoperative follow-up examination. AOFAS and Mazur scores were preoperatively 29 and 23.1, respectively, and postoperatively 71.1 and 70.7, respectively.Conclusion:Arthrodesis with a tension band was a safe and effective surgical treatment option for posttraumatic ankle arthritis in patients without infection and good bone density, as it was simple, less invasive, and inexpensive and allowed early full weight-bearing.Level of Evidence:Level IV, retrospective case series.