RESUMO
In the era of combined antiretroviral therapy (CART), many of the complications due to HIV-1 infection have diminished. One exception is HIV-associated neurocognitive disorder (HAND). HAND is a spectrum of disorders in cognitive function that ranges from asymptomatic disease to severe dementia (HAD). The milder form of HAND has actually remained the same or slightly increased in prevalence in the CART era. Even in individuals who have maintained undetectable HIV RNA loads, viral proteins such as Nef and Tat can continue to be expressed. In this report, we show that Nef protein and nef messenger RNA (mRNA) are packaged into exosomes that remain in circulation in patients with HAD. Plasma-derived Nef exosomes from patients with HAD have the ability to interact with the neuroblastoma cell line SH-SY5Y and deliver nef mRNA. The mRNA can induce expression of Nef in target cells and subsequently increase expression and secretion of beta-amyloid (Aß) and Aß peptides. Increase secretion of amyloid peptide could contribute to cognitive impairment seen in HAND.
Assuntos
Complexo AIDS Demência/sangue , Peptídeos beta-Amiloides/biossíntese , Exossomos/metabolismo , Fragmentos de Peptídeos/biossíntese , RNA Mensageiro/biossíntese , RNA Viral/sangue , Produtos do Gene nef do Vírus da Imunodeficiência Humana/genética , Complexo AIDS Demência/tratamento farmacológico , Complexo AIDS Demência/fisiopatologia , Complexo AIDS Demência/virologia , Adulto , Idoso , Peptídeos beta-Amiloides/genética , Peptídeos beta-Amiloides/metabolismo , Fármacos Anti-HIV/uso terapêutico , Linhagem Celular Tumoral , Exossomos/patologia , Feminino , Regulação da Expressão Gênica , Células HEK293 , HIV-1/efeitos dos fármacos , HIV-1/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Neurônios/metabolismo , Neurônios/patologia , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Carga Viral , Produtos do Gene nef do Vírus da Imunodeficiência Humana/metabolismoRESUMO
Problem: The dietitian service at a metropolitan health service in Queensland, Australia has a non-engagement rate for high-risk antenatal women of 50%. Aim: Determine which attributes are related to non-attendance at dietitian appointments, and women's perceptions and attitudes towards dietitian appointments during pregnancy. Methods: An explanatory mixed-methods design was utilised, with first phase including 103 antenatal women referred to a dietitian in 2021 and compared the attributes of those who attended with those who did not engage. Queensland Health electronic databases were used to collect attribute data, which were then analysed with Jamovi (version 1.6) for descriptive, correlational, multivariate analyses of variance MANOVA. Second phase included seven semi-structured interviews with women attending a dietitian appointment, and subsequently analysed through thematic analysis. Results: Distance from clinic was not related to clinic attendance, and women reported they would attend regardless of distance or work status. Non-attendance was related to higher gravidity, parity, and if referred for obesity, but not previous gastric sleeve or underweight referral. Six themes were identified from the interview data: "Women want to be treated like an individual," "It's all about expectations," "Midwives hold the key," "Preferences in receiving dietary information," "Weight has been a long-term problem and is a sensitive topic," and "Barriers to attendance." Conclusion: Antenatal services can adjust service delivery to improve engagement in weight management services during pregnancy. Telehealth appointments may reduce non-engagement due to distance from clinic. Demystifying the dietitian appointment, ensuring non-judgemental referral processes and collaboration between midwives and dietitians will ensure that women value the service.