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

Comparison of Xpert MTB/RIF with Other Nucleic Acid Technologies for Diagnosing Pulmonary Tuberculosis in a High HIV Prevalence Setting: A Prospective Study

In this prospective, real-world cohort study nested within a national screening program for tuberculosis, Lesley Scott and colleagues compare the performance of Xpert MTB/RIF on a single sputum sample with different TB sputum detection technologies

A cross-sectional survey of the knowledge, attitudes and practices regarding tuberculosis among general practitioners working in municipalities with and without asylum centres in eastern Norway

TB survey among Norwegian GPs survey questionnaire NOR: The survey questionnaire in Norwegian. (PDF 208 kb

Glacial vicariance drives phylogeographic diversification in the amphi-boreal kelp Saccharina latissima

Glacial vicariance is regarded as one of the most prevalent drivers of phylogeographic structure and speciation among high-latitude organisms, but direct links between ice advances and range fragmentation have been more difficult to establish in marine than in terrestrial systems. Here we investigate the evolution of largely disjunct (and potentially reproductively isolated) phylogeographic lineages within the amphi-boreal kelp Saccharina latissima s.l. Using molecular data (COI, microsatellites) we confirm that S. latissima comprises also the NE Pacific S. cichorioides complex and is composed of divergent lineages with limited range overlap and genetic admixture. Only a few genetic hybrids were detected throughout a Canadian Arctic/NW Greenland contact zone. The degree of genetic differentiation and sympatric isolation of phylogroups suggest that S. latissima s.l. represents a complex of incipient species. Phylogroup distributions compared with paleo-environmental reconstructions of the cryosphere further suggest that diversification within S. latissima results from chronic glacial isolation in disjunct persistence areas intercalated with ephemeral interglacial poleward expansions and admixture at high-latitude (Arctic) contact zones. This study thus supports a role for glaciations not just in redistributing pre-existing marine lineages but also as a speciation pump across multi-glacial cycles for marine organisms otherwise exhibiting cosmopolite amphi-boreal distributions.Pew Foundation (USA); Portuguese FCT (Fundacao para a Ciencia e a Tecnologia) through program GENEKELP [PTDC/MAR-EST/6053/2014]; Portuguese FCT (Fundacao para a Ciencia e a Tecnologia) through program MARFOR [Biodiversa/0004/2015]; Portuguese FCT (Fundacao para a Ciencia e a Tecnologia) [UID/Multi/04326/2013, SFRH/BPD/88935/2012, SFRH/BPD/111003/2015]; NSERC; FRQNT; Canada Foundation for Innovation; New Brunswick Innovation Foundation; European Union's Seventh Framework Programme [226248]; Danish Environmental Protection Agency within the Danish Cooperation for Environment in the Arctic (DANCEA)info:eu-repo/semantics/publishedVersio

Perivascular Fat and the Microcirculation: Relevance to Insulin Resistance, Diabetes, and Cardiovascular Disease

Type 2 diabetes and its major risk factor, obesity, are a growing burden for public health. The mechanisms that connect obesity and its related disorders, such as insulin resistance, type 2 diabetes, and hypertension, are still undefined. Microvascular dysfunction may be a pathophysiologic link between insulin resistance and hypertension in obesity. Many studies have shown that adipose tissue-derived substances (adipokines) interact with (micro)vascular function and influence insulin sensitivity. In the past, research focused on adipokines from perivascular adipose tissue (PVAT). In this review, we focus on the interactions between adipokines, predominantly from PVAT, and microvascular function in relation to the development of insulin resistance, diabetes, and cardiovascular disease

Influence of Psychological Factors on Pain and Disability in Anterior Knee Pain Patients

AKP patients express chronic pain but also disability. However, the correlation between pain and disability is not complete and linear. Some patients with a lot of pain show mild disability while others with much less pain also show great disability. The disability is profoundly influenced by other emotional and cognitive factors that are associated with the perception of pain. Therefore, the clinical efforts do not have to be focused only on treating the pain as a feeling but on identifying and modifying these factor

Perspectives from the 2nd International Post-Tuberculosis Symposium: mobilising advocacy and research for improved outcomes

In 2020, it was estimated that there were 155 million survivors of TB alive, all at risk of possible post TB disability. The 2nd International Post-Tuberculosis Symposium (Stellenbosch, South Africa) was held to increase global awareness and empower TB-affected communities to play an active role in driving the agenda. We aimed to update knowledge on post-TB life and illness, identify research priorities, build research collaborations and highlight the need to embed lung health outcomes in clinical TB trials and programmatic TB care services. The symposium was a multidisciplinary meeting that included clinicians, researchers, TB survivors, funders and policy makers. Ten academic working groups set their own goals and covered the following thematic areas: 1) patient engagement and perspectives; 2) epidemiology and modelling; 3) pathogenesis of post-TB sequelae; 4) post-TB lung disease; 5) cardiovascular and pulmonary vascular complications; 6) neuromuscular & skeletal complications; 7) paediatric complications; 8) economic-social and psychological (ESP) consequences; 9) prevention, treatment and management; 10) advocacy, policy and stakeholder engagement. The working groups provided important updates for their respective fields, highlighted research priorities, and made progress towards the standardisation and alignment of post-TB outcomes and definitions