Long-term clinical, immunologic and virologic impact of glucocorticoids on the chronic phase of HIV infection

BACKGROUND: To test the hypothesis of down-regulating the increased immune system activation/destruction process associated with chronic HIV infection, we focused our interest on prednisolone (PDN), because we had showed that, in vitro, PDN had a strong anti-apoptotic activity on activated T cells of HIV-infected patients and no effect on viral replication. We thus designed in 1992 a pilot study to evaluate the clinical, immunologic and virologic effects of PDN. The drug was given to a group of 44 patients with CD4 T cells over 200/μl. After one year, no patient had developed clinical AIDS and the mean CD4 T cell count of the group had increased from 441 ± 21 cells/μl to 553 ± 43 cells/μl. Moreover, markers of immune activation had dropped back to normal levels while the mean viral load of the group had remained unchanged. Here we explore the long-term clinical, immunologic, and virologic impact of prednisolone on the chronic phase of HIV infection. METHODS: Retrospective study over 10 years starting between July 1992 and February 1993. A total of 44 patients with CD4 cells/μl ranging from 207 to 775 were treated with prednisolone, 0.5 mg/kg/d, over 6 months and 0.3 mg/kg/d thereafter. RESULTS: No clinical AIDS developed under prednisolone; side effects of the drug were mild. CD4 cells which increased from 421 cells/μl at entry to 625 cells/μl at day 15, slowly decreased to reach 426 cells/μl after two years; T cell apoptosis and activation markers dropped within 15 days to normal levels and reincreased slowly thereafter. Serum viral loads remained stable. The percentage of patients maintaining CD4 cells over entry was 43.2% at two years, 11.4% at five years and 4.6% at 10 years. Initial viral load was highly predictive of the rate of CD4 decrease under prednisolone. CONCLUSIONS: Prednisolone postponed CD4 cell decrease in a viral load dependent manner for a median of two years and for up to 10 years in a fraction of the patients with a low viral load. These findings might stimulate clinical trials as well as biological research on the role of antiapoptotic drugs in HIV infection

Latent HIV in primary T lymphocytes is unresponsive to histone deacetylase inhibitors

Recently, there is considerable interest in the field of anti-HIV therapy to identify and develop chromatin-modifying histone deacetylase (HDAC) inhibitors that can effectively reactivate latent HIV in patients. The hope is that this would help eliminate cells harboring latent HIV and achieve an eventual cure of the virus. However, how effectively these drugs can stimulate latent HIVs in quiescent primary CD4 T cells, despite their relevant potencies demonstrated in cell line models of HIV latency, is not clear. Here, we show that the HDAC inhibitors valproic acid (VPA) and trichostatin A (TSA) are unable to reactivate HIV in latently infected primary CD4 T cells generated in the H80 co-culture system. This raises a concern that the drugs inhibiting HDAC function alone might not be sufficient for stimulating latent HIV in resting CD4 T cells in patients and not achieve any anticipated reduction in the pool of latent reservoirs

A collaboratively derived international research agenda on legislative science advice

© 2019, The Author(s). The quantity and complexity of scientific and technological information provided to policymakers have been on the rise for decades. Yet little is known about how to provide science advice to legislatures, even though scientific information is widely acknowledged as valuable for decision-making in many policy domains. We asked academics, science advisers, and policymakers from both developed and developing nations to identify, review and refine, and then rank the most pressing research questions on legislative science advice (LSA). Experts generally agree that the state of evidence is poor, especially regarding developing and lower-middle income countries. Many fundamental questions about science advice processes remain unanswered and are of great interest: whether legislative use of scientific evidence improves the implementation and outcome of social programs and policies; under what conditions legislators and staff seek out scientific information or use what is presented to them; and how different communication channels affect informational trust and use. Environment and health are the highest priority policy domains for the field. The context-specific nature of many of the submitted questions—whether to policy issues, institutions, or locations—suggests one of the significant challenges is aggregating generalizable evidence on LSA practices. Understanding these research needs represents a first step in advancing a global agenda for LSA research

Understanding the Use of Crisis Informatics Technology among Older Adults

Mass emergencies increasingly pose significant threats to human life, with a disproportionate burden being incurred by older adults. Research has explored how mobile technology can mitigate the effects of mass emergencies. However, less work has examined how mobile technologies support older adults during emergencies, considering their unique needs. To address this research gap, we interviewed 16 older adults who had recent experience with an emergency evacuation to understand the perceived value of using mobile technology during emergencies. We found that there was a lack of awareness and engagement with existing crisis apps. Our findings characterize the ways in which our participants did and did not feel crisis informatics tools address human values, including basic needs and esteem needs. We contribute an understanding of how older adults used mobile technology during emergencies and their perspectives on how well such tools address human values.Comment: 10 page

Guiding principles for rewilding

There has been much recent interest in the concept of rewilding as a tool for nature conservation, but also confusion over the idea, which has limited its utility. We developed a unifying definition and 10 guiding principles for rewilding through a survey of 59 rewilding experts, a summary of key organizations’ rewilding visions, and workshops involving over 100 participants from around the world. The guiding principles convey that rewilding exits on a continuum of scale, connectivity, and level of human influence and aims to restore ecosystem structure and functions to achieve a self-sustaining autonomous nature. These principles clarify the concept of rewilding and improve its effectiveness as a tool to achieve global conservation targets, including those of the UN Decade on Ecosystem Restoration and post-2020 Global Biodiversity Framework. Finally, we suggest differences in rewilding perspectives lie largely in the extent to which it is seen as achievable and in specific interventions. An understanding of the context of rewilding projects is the key to success, and careful site-specific interpretations will help achieve the aims of rewilding