Rationale : Abdominal aortic aneurysms constitute a degenerative process in the aortic wall. Both the miR-29 and miR-15 families have been implicated in regulating the vascular extracellular matrix. Objective : Our aim was to assess the effect of the miR-15 family on aortic aneurysm development. Methods and Results : Among the miR-15 family members, miR-195 was differentially expressed in aortas of apolipoprotein E–deficient mice on angiotensin II infusion. Proteomics analysis of the secretome of murine aortic smooth muscle cells, after miR-195 manipulation, revealed that miR-195 targets a cadre of extracellular matrix proteins, including collagens, proteoglycans, elastin, and proteins associated with elastic microfibrils, albeit miR-29b showed a stronger effect, particularly in regulating collagens. Systemic and local administration of cholesterol-conjugated antagomiRs revealed better inhibition of miR-195 compared with miR-29b in the uninjured aorta. However, in apolipoprotein E–deficient mice receiving angiotensin II, silencing of miR-29b, but not miR-195, led to an attenuation of aortic dilation. Higher aortic elastin expression was accompanied by an increase of matrix metalloproteinases 2 and 9 in mice treated with antagomiR-195. In human plasma, an inverse correlation of miR-195 was observed with the presence of abdominal aortic aneurysms and aortic diameter. Conclusions : We provide the first evidence that miR-195 may contribute to the pathogenesis of aortic aneurysmal disease. Although inhibition of miR-29b proved more effective in preventing aneurysm formation in a preclinical model, miR-195 represents a potent regulator of the aortic extracellular matrix. Notably, plasma levels of miR-195 were reduced in patients with abdominal aortic aneurysms suggesting that microRNAs might serve as a noninvasive biomarker of abdominal aortic aneurysms.

Endogenous cardiac progenitor cells, expanded from explants via cardiosphere formation, present a promising cell source to prevent heart failure following myocardial infarction. Here we used cine-magnetic resonance imaging (MRI) to track administered cardiosphere-derived cells (CDCs) and to measure changes in cardiac function over four months in the infarcted rat heart. CDCs, cultured from neonatal rat heart, comprised a heterogeneous population including cells expressing the mesenchymal markers CD90 and CD105, the stem cell marker c-kit and the pluripotency markers Sox2, Oct3/4 and Klf-4. CDCs (2×10⁶) expressing green fluorescent protein (GFP+) were labelled with fluorescent micron-sized particles of iron oxide (MPIO). Labelled cells were administered to the infarcted rat hearts (n = 7) by intramyocardial injection immediately following reperfusion, then by systemic infusion (4×10⁶) 2 days later. A control group (n = 7) was administered cell medium. MR hypointensities caused by the MPIOs were detected at all times and GFP+ cells containing MPIO particles were identified in tissue slices at 16 weeks. At two days after infarction, cardiac function was similar between groups. By 6 weeks, ejection fractions in control hearts had significantly decreased (47±2%), but this was not evident in CDC-treated hearts (56±3%). The significantly higher ejection fractions in the CDC-treated group were maintained for a further 10 weeks. In addition, CDC-treated rat hearts had significantly increased capillary density in the peri-infarct region and lower infarct sizes. MPIO-labelled cells also expressed cardiac troponin I, von Willebrand factor and smooth muscle actin, suggesting their differentiation along the cardiomyocyte lineage and the formation of new blood vessels. CDCs were retained in the infarcted rat heart for 16 weeks and improved cardiac function.

As a minority within a minority, individuals who have a disability and identify as LGBT are at the intersection of multiple stigmatised identities. This brings with it unique challenges, including the possibility of oppression and rejection by both the LGBT and disability communities, which can impact on identity and wider life experiences. While previous reviews have explored issues relating to intersectionality, multiple oppression, identity, acceptance, and sexuality, an overview of the impact on wider life experiences is missing. This narrative review presents empirical findings published since 2000 about the wider everyday experiences relating to attitudes and discrimination, education, employment, finances, health and well-being, support, and intimate relationships among people who identify as LGBT and have a disability.

Background: There has been growing concern about the impact of restrictions put in place to contain the coronavirus pandemic on loneliness, particularly in individuals with disabilities. This study explored the longitudinal impact of the pandemic on loneliness in these individuals, with a focus on those living with visual impairment (VI).Methods: An online survey was conducted in April-2020 and repeated in March 2021 to explore current life circumstances, health-related behaviours, sleep (Pittsburgh Sleep Quality Index) and social well-being, including state anxiety (State-Trait Anxiety Index) and loneliness (UCLA Loneliness scale). A convenience sample of 602 participants completed the first survey. Participants who agreed to be re-contacted were invited to take part in the follow-up survey.Results: Data is presented for the 160 participants who completed both timepoints. At both timepoints, median loneliness was significantly higher in participants with disabilities and those with VI than in participants with no disabilities. While there was no significant change in loneliness in any of the three subgroups, participants with VI experienced the largest increase in median loneliness. Loneliness was associated with having a mental health condition and higher levels of state anxiety at both timepoints.Conclusions: Individuals with disabilities such as VI experienced consistently higher levels of loneliness than those with no disabilities throughout the pandemic. While loneliness remained relatively stable in individuals with no disabilities, it increased, albeit to a non-significant level, in those with disabilities and particularly those with VI. Interventions designed to alleviate loneliness may benefit from addressing state anxiety.

The military population face a unique set of risk factors that may increase the risk of being diagnosed with dementia. Traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) have a higher prevalence in this group in comparison to the civilian population. By delving into the individual relationships between TBI and dementia, and PTSD and dementia, we are able to better explore dementia in the military and veteran populations. While there are some inconsistencies in results, the TBI-dementia association has become more widely accepted. Moderate-to-severe TBI has been found to increase the risk of being diagnosed with Alzheimer’s disease. A correlation between PTSD and dementia has been established, however, whether or not it is a causal relationship remains unclear. Factors such as blast, combat and chemical exposure may occur during a deployment, along with TBI and/or PTSD diagnosis, and can impact the risk of dementia. However, there is a lack of literature exploring the direct effects of deployment on dementia risk. Sleep problems have been observed to occur in those following TBI, PTSD and deployment. Poor sleep has been associated with possible dementia risk. Although limited studies have focused on the link between sleep and dementia in military and veteran populations, sleep is a valuable factor to study due to its association and interconnection with other military/veteran factors. This review aims to inform of various risk factors to the cognitive health of military members and veterans: TBI, PTSD, deployment, and sleep.