Patients' Perspectives on and Experiences of Home Exercise Programmes Delivered with a Mobile Application.

Purpose: We explored patients' perspectives on home exercise programmes (HEPs) and their experiences using a mobile application designed to facilitate home exercise. Method: Data were generated using qualitative, semi-structured, face-to-face interviews with 10 participants who were receiving outpatient physiotherapy. Results: Establishing a therapeutic partnership between physiotherapists and patients enabled therapists to customize the HEPs to the patients' lifestyles and preferences. Analysis suggests that using the mobile application improved participants' ability to integrate the HEP into their daily life and was overwhelmingly preferred to traditional paper handouts. Conclusions: The results suggest that efforts to engage patients in HEPs need to take their daily lives into account. To move in this direction, sample exercise prescription questions are offered. Mobile applications do not replace the clinical encounter, but they can be an effective tool and an extension of delivering personalized HEPs in an existing therapeutic partnership.

Objectif : explorer les points de vue des patients sur les programmes d'exercices à la maison (PEM) et leurs expériences à l'égard d'une application mobile conçue pour faciliter ce type d'exercices. Méthodologie : les chercheurs ont obtenu des données qualitatives semi-structurées en interviewant dix participants qui recevaient des soins ambulatoires en physiothérapie. Résultats : en formant un partenariat thérapeutiques avec leurs patients, les physiothérapeutes pouvaient personnaliser les PEM en fonction du mode de vie et des préférences de leurs patients. Selon l'analyse, une application mobile aidait les participants à intégrer les PEM à leur quotidien. Ceux-ci la préféraient massivement aux feuilles de renseignements habituels. Conclusions : d'après les résultats, les mesures pour que les patients s'investissent dans leur PEM doivent tenir compte du quotidien. Pour aller en ce sens, des questions sur les modèles de prescription d'exercices sont proposées. Les applications mobiles ne remplacent pas la rencontre clinique, mais peuvent constituer un outil efficace et compléter le PEM personnalisé dans le cadre d'un partenariat thérapeutique établi.

Derivation of infectious HIV-1 molecular clones with LTR mutations: sensitivity to the CD8+ cell noncytotoxic anti-HIV response.

CD8(+) cells from healthy, asymptomatic HIV-1-infected individuals can inhibit HIV-1 replication in naturally or acutely infected CD4(+) cells in the absence of cell killing. This CD8(+) cell noncytotoxic anti-HIV response (CNAR) is mediated by a soluble CD8(+) cell antiviral factor (CAF). CNAR/CAF inhibits HIV-1 replication by blocking viral RNA transcription. HIV transcription is regulated by a variety of cis-acting DNA sequence elements within the proviral long terminal repeat (LTR). We hypothesized that one of the HIV-1 LTR proviral DNA sequence elements that binds host cell transcriptional factors is involved in this antiviral activity. To assess this possibility, we constructed full-length infectious HIV-1 molecular clones with mutations in the LTR elements NFAT, AP-1, IL-2 homology region, and the downstream ISRE. We also tested full-length infectious molecular clones that had deletions of either the NF-kappaB or Sp1 sites of the LTR or lacked functional Tat and TAR elements. Viruses generated from these molecular clones were used to acutely infect CD4(+) cells that subsequently were either co-cultured with CD8(+) cells from individuals that exhibited strong CNAR or cultured with CAF-containing fluids. The replication of all of the mutant HIV-1 viruses tested was substantially reduced in the presence of CNAR/CAF. These findings suggest that other regions in the viral LTR or other host cell processes are involved in the transcriptional block elicited by CNAR/CAF.

Differential gene expression in CD8(+) cells from HIV-1-infected subjects showing suppression of HIV replication.

CD8(+) cells from healthy HIV-1-infected individuals suppress human immunodeficiency virus (HIV) replication in infected cells by a non-cytotoxic mechanism. This activity is associated with the production of a soluble CD8(+) cell antiviral factor (CAF) that inhibits viral replication at the level of transcription. Strong CD8(+) cell non-cytotoxic anti-HIV responses (CNARs) correlate with an asymptomatic state and long-term survival of HIV-infected individuals. This antiviral activity is lost when the infected individual advances to disease. In attempts to define the gene(s) mediating CNAR we have evaluated differential gene expression between CD8(+) cells from infected subjects with high CNAR and CD8(+) cells from uninfected controls that lack this activity. The expression analysis, using the Affymetrix GeneChip Human Genome U133 Set, indicated that 18% of the genes were differentially expressed (DE) of which 9.2% were up-regulated. A total of 568 genes were up-regulated with a >2.0-fold difference in expression levels and a >50% concordance of difference call. Stringent selection criteria narrowed down the list to 52 up-regulated 'high confidence genes' (> or = 75% concordance). These genes function in a wide variety of cellular processes and include 13 associated with immunologic activity.

HIV-infected cells are major inducers of plasmacytoid dendritic cell interferon production, maturation, and migration.

Plasmacytoid dendritic cells (PDC), natural type-1 interferon (IFN) producing cells, could play a role in the innate anti-HIV immune response. Previous reports indicated that PDC IFN production is induced by HIV. Our results show a more robust IFN induction when purified PDC (>95%) were exposed to HIV-infected cells. This effect was not observed with non-viable cells, DNA, and RNA extracted from infected cells, and viral proteins. The response was blocked by anti-CD4 and neutralizing anti-gp120 antibodies as well as soluble CD4. IFN induction by HIV-infected cells was also prevented by low-dose chloroquine, which inhibits endosomal acidification. PDC IFN release resulted in reduced HIV production by infected CD4+ cells, supporting an anti-HIV activity of PDC. Stimulated CD4+ cells induced PDC activation and maturation; markers for PDC migration (CCR7) were enhanced by HIV-infected CD4+ cells only. This latter finding could explain the decline in circulating PDC in HIV-infected individuals.

VCAM-1 expression on CD8+ cells correlates with enhanced anti-HIV suppressing activity.

CD8(+) cells from HIV-infected individuals showing the CD8(+) cell noncytotoxic antiviral response unexpectedly revealed mRNA for VCAM-1, a cell surface molecule found on endothelial cells. Uninfected subjects had undetectable levels of VCAM-1 mRNA in their CD8(+) cells. Flow cytometry analysis showed that up to 12% of the CD8(+) cells from HIV-positive individuals expressed VCAM-1 compared with 0.8% of the CD8(+) cells of HIV-negative individuals. Enrichment of the CD8(+)VCAM-1(+) cell population and subsequent coculture with CD4(+) cells acutely infected with HIV-1 showed that the VCAM-1(+)CD8(+) cells were able to suppress viral replication with 50% less input cells than the unseparated CD8(+) cell population. This study demonstrates, for the first time, the expression of VCAM-1 on CD8(+) cells. Moreover, the CD8(+)VCAM-1(+) cells show enhanced CD8(+) cell noncytotoxic antiviral response activity that could have clinical importance in HIV infection.

Low-level HIV infection of plasmacytoid dendritic cells: onset of cytopathic effects and cell death after PDC maturation.

Plasmacytoid dendritic cells (PDC), the natural type-1 interferon (IFN) producing cells, are part of the innate immune defense against human immunodeficiency virus (HIV). PDC numbers are reduced in advanced stages of infection. These cells can be infected in vivo by HIV since highly purified PDC showed evidence of infectious HIV. Moreover, when PDC derived from uninfected donors were exposed to high-titered HIV isolates, productive infection occurred although with low-level replication. Using real-time amplification, PDC and unstimulated CD4+ cells were found equally susceptible to HIV infection; however, HIV replication was considerably limited in the PDC. Virus replication was enhanced after PDC treatment with CD40L and antibodies against IFN-alpha, most likely reflecting the reduction in IFN-alpha activity. On maturation, the infected PDC showed multinuclear cell syncytia formation and death. These findings indicate that PDC can be reservoirs for HIV dissemination and that HIV infection of PDC can contribute to their decline.

Tripeptide interference with human immunodeficiency virus type 1 morphogenesis.

Capsid assembly during virus replication is a potential target for antiviral therapy. The Gag polyprotein is the main structural component of retroviral particles, and in human immunodeficiency virus type 1 (HIV-1), it contains the sequences for the matrix, capsid, nucleocapsid, and several small polypeptides. Here, we report that at a concentration of 100 micro M, 7 of 83 tripeptide amides from the carboxyl-terminal sequence of the HIV-1 capsid protein p24 suppressed HIV-1 replication (>80%). The three most potent tripeptides, glycyl-prolyl-glycine-amide (GPG-NH(2)), alanyl-leucyl-glycine-amide (ALG-NH(2)), and arginyl-glutaminyl-glycine-amide (RQG-NH(2)), were found to interact with p24. With electron microscopy, disarranged core structures of HIV-1 progeny were extensively observed when the cells were treated with GPG-NH(2) and ALG-NH(2). Furthermore, nodular structures of approximately the same size as the broad end of HIV-1 conical capsids were observed at the plasma membranes of treated cells only, possibly indicating an arrest of the budding process. Corresponding tripeptides with nonamidated carboxyl termini were not biologically active and did not interact with p24.