Non-AIDS-related comorbidities in people living with HIV-1 aged 50 years and older: The AGING POSITIVE study.

OBJECTIVE: To characterize the profile of non-AIDS-related comorbidities (NARC) in the older HIV-1-infected population and to explore the factors associated with multiple NARC. METHODS: This was a multicentre, cross-sectional study including HIV-1-infected patients aged ≥50 years, who were virologically suppressed and had been on a stable antiretroviral therapy (ART) regimen for at least 6 months. A multiple regression model explored the association between demographic and clinical variables and the number of NARC. RESULTS: Overall, 401 patients were enrolled. The mean age of the patients was 59.3 years and 72.6% were male. The mean duration of HIV-1 infection was 12.0 years and the median exposure to ART was 10.0 years. The mean number of NARC was 2.1, and 34.7% of patients had three or more NARC. Hypercholesterolemia was the most frequent NARC (60.8%), followed by arterial hypertension (39.7%) and chronic depression/anxiety (23.9%). Arterial hypertension and diabetes mellitus were the most frequently treated NARC (95.6% and 92.6% of cases, respectively). The linear regression analysis showed a positive relationship between age and NARC (B=0.032, 95% confidence interval 0.015-0.049; p=0.0003) and between the duration of HIV-1 infection and NARC (B=0.039, 95% confidence interval 0.017-0.059; p=0.0005). CONCLUSIONS: A high prevalence of NARC was found, the most common being metabolic, cardiovascular, and psychological conditions. NARC rates were similar to those reported for the general population, suggesting a larger societal problem beyond HIV infection. A multidisciplinary approach is essential to reduce the burden of complex multi-morbid conditions in the HIV-1-infected population.info:eu-repo/semantics/publishedVersio

Microbial community succession on developing lesions on human enamel

Dental caries is one of the most common diseases in the world. However, our understanding of how the microbial community composition changes in vivo as caries develops is lacking.An in vivo model was used in a longitudinal cohort study to investigate shifts in the microbial community composition associated with the development of enamel caries.White spot lesions were generated in vivo on human teeth predetermined to be extracted for orthodontic reasons. The bacterial microbiota on sound enamel and on developing carious lesions were identified using the Human Oral Microbe Identification Microarray (HOMIM), which permits the detection of about 300 of the approximate 600 predominant bacterial species in the oral cavity.After only seven weeks, 75% of targeted teeth developed white spot lesions (8 individuals, 16 teeth). The microbial community composition of the plaque over white spot lesions differed significantly as compared to sound enamel. Twenty-five bacterial taxa, including Streptococcus mutans, Atopobium parvulum, Dialister invisus, and species of Prevotella and Scardovia, were significantly associated with initial enamel lesions. In contrast, 14 bacterial taxa, including species of Fusobacterium, Campylobacter, Kingella, and Capnocytophaga, were significantly associated with sound enamel.The bacterial community composition associated with the progression of enamel lesions is specific and much more complex than previously believed. This investigation represents one of the first longitudinally-derived studies for caries progression and supports microbial data from previous cross-sectional studies on the development of the disease. Thus, the in vivo experiments of generating lesions on teeth destined for extraction in conjunction with HOMIM analyses represent a valid model to study succession of supragingival microbial communities associated with caries development and to study efficacy of prophylactic and restorative treatments

Notch signaling in glioblastoma: a developmental drug target?

Malignant gliomas are among the most devastating tumors for which conventional therapies have not significantly improved patient outcome. Despite advances in imaging, surgery, chemotherapy and radiotherapy, survival is still less than 2 years from diagnosis and more targeted therapies are urgently needed. Notch signaling is central to the normal and neoplastic development of the central nervous system, playing important roles in proliferation, differentiation, apoptosis and cancer stem cell regulation. Notch is also involved in the regulation response to hypoxia and angiogenesis, which are typical tumor and more specifically glioblastoma multiforme (GBM) features. Targeting Notch signaling is therefore a promising strategy for developing future therapies for the treatment of GBM. In this review we give an overview of the mechanisms of Notch signaling, its networking pathways in gliomas, and discuss its potential for designing novel therapeutic approaches

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Social and health-related predictors of family function in older spousal caregivers: a cross-sectional study

Given the benefits of adequate family function for the health and well-being of older adults, it is important to understand what factors predict adequate family function in older people who care for their spouses. Objective: Analyse predictors of family function in older spousal caregivers. Methods: A cross-sectional study design was used to investigate a non-probabilistic sample of 298 older spousal caregivers. Home-based face-to-face interviews were used to evaluate sociodemographic variables and care context, family function (Family APGAR), cognitive function, perceived stress, and depressive symptoms. Data were analysed using multiple logistic regression with stepwise forward method for variable section. Results: Older caregivers having some degree of cognitive impairment (OR=-0.160, 95%CI 0.444–0.579), depressive symptoms (OR=-0.848, 95%CI 0.726–0.992) or high levels of stress (OR=-0.955, 95%CI 0.914-0.999) had overall lower levels of family function. Having more children was linked to approximately 1.3 times higher family function (95%CI 1.080–1.057). Conclusion: Stress, depression, cognitive decline, and number of children are predictors of family function and should be considered in social and health care strategies within the family caregiving context