The Risk of Sympathetic Ophthalmia Associated with Open-Globe Injury Management Strategies: A Meta-analysis.

TOPIC: Sympathetic ophthalmia (SO) is a sight-threatening granulomatous panuveitis caused by a sensitizing event. Primary enucleation or primary evisceration, versus primary repair, as a risk management strategy after open-globe injury (OGI) remains controversial. CLINICAL RELEVANCE: This systematic review was conducted to report the incidence of SO after primary repair compared with that of after primary enucleation or primary evisceration. This enabled the reporting of an estimated number needed to treat. METHODS: Five journal databases were searched. This review was registered with International Prospective Register of Systematic Reviews (identifier, CRD42021262616). Searches were carried out on June 29, 2021, and were updated on December 10, 2022. Prospective or retrospective studies that reported outcomes (including SO or lack of SO) in a patient population who underwent either primary repair and primary enucleation or primary evisceration were included. A systematic review and meta-analysis were carried out in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Random effects modelling was used to estimate pooled SO rates and absolute risk reduction (ARR). RESULTS: Eight studies reporting SO as an outcome were included in total. The included studies contained 7500 patients and 7635 OGIs. In total, 7620 OGIs met the criteria for inclusion in this analysis; SO developed in 21 patients with OGI. When all included studies were pooled, the estimated SO rate was 0.12% (95% confidence interval [CI], 0.00%-0.25%) after OGI. Of 779 patients who underwent primary enucleation or primary evisceration, no SO cases were reported, resulting in a pooled SO estimate of 0.05% (95% CI, 0.00%-0.21%). For primary repair, the pooled estimate of SO rate was 0.15% (95% CI, 0.00%-0.33%). The ARR using a random effects model was -0.0010 (in favour of eye removal; 95% CI, -0.0031 [in favor of eye removal] to 0.0011 [in favor of primary repair]). Grading of Recommendations, Assessment, Development, and Evaluations analysis highlighted a low certainty of evidence because the included studies were observational, and a risk of bias resulted from missing data. DISCUSSION: Based on the available data, no evidence exists that primary enucleation or primary evisceration reduce the risk of secondary SO. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

"Young at heart": Regenerative potential linked to immature cardiac phenotypes.

The adult human myocardium is incapable of regeneration; yet, the zebrafish (Danio rerio) can regenerate damaged myocardium. Similar to the zebrafish heart, hearts of neonatal, but not adult mice are capable of myocardial regeneration. We performed a proteomics analysis of adult zebrafish hearts and compared their protein expression profile to hearts from neonatal and adult mice. Using difference in-gel electrophoresis (DIGE), there was little overlap between the proteome from adult mouse (>8weeks old) and adult zebrafish (18months old) hearts. Similarly, there was a significant degree of mismatch between the protein expression in neonatal and adult mouse hearts. Enrichment analysis of the selected proteins revealed over-expression of DNA synthesis-related proteins in the cardiac proteome of the adult zebrafish heart similar to neonatal and 4days old mice, whereas in hearts of adult mice there was a mitochondria-related predominance in protein expression. Importantly, we noted pronounced differences in the myofilament composition: the adult zebrafish heart lacks many of the myofilament proteins of differentiated adult cardiomyocytes such as the ventricular isoforms of myosin light chains and nebulette. Instead, troponin I and myozenin 1 were expressed as skeletal isoforms rather than cardiac isoforms. The relative immaturity of the adult zebrafish heart was further supported by cardiac microRNA data. Our assessment of zebrafish and mammalian hearts challenges the assertions on the translational potential of cardiac regeneration in the zebrafish model. The immature myofilament composition of the fish heart may explain why adult mouse and human cardiomyocytes lack this endogenous repair mechanism.

Role of miR-195 in aortic aneurysmal disease.

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.

Prevalence of dual sensory impairment in veterans: a rapid systematic review.

Dual sensory impairment (DSI) is prevalent in the older population, but due to exposure to military-related risk factors, it is a particular problem for veterans, older and younger. This rapid review aimed to critically review and summarise the prevalence of DSI in military veteran populations, as well as any associative factors and outcomes that were assessed. This was done in accordance with the Preferred Reporting Items for Systematic Reviews (PRISMA) statement. Several databases (Scopus, Web of Science, AMED, CINAHL Plus, Ultimate, and MEDLINE via EBSCOHost) were searched and five studies were selected for final review. All studies provided a prevalence rate for DSI in a veteran sample. One study also looked at functional independence as an outcome. Three of the studies considered blast injuries and traumatic brain injury (TBI) by using samples from TBI patient populations. Overall, results of this review suggest that age and presence of TBI and/or exposure to blast may increase prevalence of DSI in veterans. Prevalence rates ranged from 5.0-34.6% but there are caveats. There is a lack of universal or standardised definition for DSI, making it difficult to determine true prevalence. Future research should also include veterans who may not be receiving support from Veterans Affairs, consider factors such as TBI aetiology and severity based on clinical measures, and utilise a more standardised definition for DSI based on clinical measures.

How does the UK public think and feel about people with visual impairment: a review of existing evidence.

Despite legislation to protect people with visual impairment (V.I.) from discrimination in the United Kingdom (UK), the latter continue to experience overt and covert negative behaviours. Perceived discrimination has been associated with an adverse impact on identity, health and well-being, while negative attitudes have been identified as the biggest barrier to participation in everyday life. This article provides a narrative review of existing evidence of how the UK public treats (behaviours), thinks (perceptions) and feels (attitudes) about people with V.I. Despite limitations, the findings suggest that there is a gap between the behaviours reported by people with V.I. and the attitudes expressed by members of the UK public. Social psychological theories are used to explore possible reasons for this gap, and ways in which it may be addressed. As such, the article provides an example of how social psychological theories can be used to address problems in an applied context.

A cross-sectional study of sleep, mood, well-being, motivations, and perceived support in Ukrainian veterans and active-duty military personnel with disability, and their supporters, preparing for a sporting event.

Purpose: The benefits of sports and exercise to the lives and rehabilitative journeys of military veterans with disabilities is increasingly well-documented but veteran sporting events remain underexplored. Addressing this topic, the current article seeks to provide insight into the health and well-being of Team Ukraine during a 5-week preparatory camp in the UK before attendance at the 2022 Warrior Games. Materials and methods: Two surveys were run, one toward the beginning and one toward the end of the camp. Eighteen of the 55 veterans and serving personnel (with disability), support staff, and family members in attendance responded to both surveys. Data on sleep, mood, and competition-related emotions, motivations for participation and perceived support were gathered. Data were analysed descriptively, and sleep, mood, and competition-related emotion responses were categorised to explore improvements, maintenance, or worsening in these areas. Results and conclusion: Sleep, mood, and competition-related emotions were relatively stable, although sleep duration was low, and there were some increases in daytime dysfunction, anxiety, nervousness, and feeling tense. Family was the most important source of support and representation of one's country and raising awareness of Ukraine's circumstances were the most important motivational factors. Findings offer insight into not only the health and well-being experiences associated with participation in this disabled veteran sporting event, but also the important role played by this event in meeting collective goals relating to this unique time in Ukraine's history.

Exposure to war and conflict: The individual and inherited epigenetic effects on health, with a focus on post-traumatic stress disorder.

War and conflict are global phenomena, identified as stress-inducing triggers for epigenetic modifications. In this state-of-the-science narrative review based on systematic principles, we summarise existing data to explore the outcomes of these exposures especially in veterans and show that they may result in an increased likelihood of developing gastrointestinal, auditory, metabolic and circadian issues, as well as post-traumatic stress disorder (PTSD). We also note that, despite a potential "healthy soldier effect", both veterans and civilians with PTSD exhibit the altered DNA methylation status in hypothalamic-pituitary-adrenal (HPA) axis regulatory genes such as NR3C1. Genes associated with sleep (PAX8; LHX1) are seen to be differentially methylated in veterans. A limited number of studies also revealed hereditary effects of war exposure across groups: decreased cortisol levels and a heightened (sex-linked) mortality risk in offspring. Future large-scale studies further identifying the heritable risks of war, as well as any potential differences between military and civilian populations, would be valuable to inform future healthcare directives.

The Use of Preoperative Prophylactic Systemic Antibiotics for the Prevention of Endopthalmitis in Open Globe Injuries: A Meta-Analysis.

TOPIC: This study reports the effect of systemic prophylactic antibiotics (and their route) on the risk of endophthalmitis after open globe injury (OGI). CLINICAL RELEVANCE: Endophthalmitis is a major complication of OGI; it can lead to rapid sight loss in the affected eye. The administration of systemic antibiotic prophylaxis is common practice in some health care systems, although there is no consensus on their use. METHODS: PubMed, CENTRAL, Web of Science, CINAHL, and Embase were searched. This was completed July 6, 2021 and updated December 10, 2022. We included randomized and nonrandomized prospective studies which reported the rate of post-OGI endophthalmitis when systemic preoperative antibiotic prophylaxis (via the oral or IV route) was given. The Cochrane Risk of Bias tool and ROBINS-I tool were used for assessing the risk of bias. Where meta-analysis was performed, results were reported as an odds ratio. PROSPERO registration: CRD42021271271. RESULTS: Three studies were included. One prospective observational study compared outcomes of patients who had received systemic or no systemic preoperative antibiotics. The endophthalmitis rates reported were 3.75% and 4.91% in the systemic and no systemic preoperative antibiotics groups, a nonsignificant difference (P = 0.68). Two randomized controlled trials were included (1555 patients). The rates of endophthalmitis were 17 events in 751 patients (2.26%) and 17 events in 804 patients (2.11%) in the oral antibiotics and IV (± oral) antibiotics groups, respectively. Meta-analysis demonstrated no significant differences between groups (odds ratio, 1.07; 95% confidence interval, 0.54-2.12). CONCLUSIONS: The incidences of endophthalmitis after OGI were low with and without systemic antibiotic prophylaxis, although high-risk cases were excluded in the included studies. When antibiotic prophylaxis is considered, there is moderate evidence that oral antibiotic administration is noninferior to IV. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Conceptualizations of well-being in adults with visual impairment: A scoping review.

Background: Despite its ubiquity, it is often not clear what organizations and services mean by well-being. Visual impairment (VI) has been associated with poorer well-being and well-being has become a key outcome for support and services for adults living with VI. A shared understanding of what well-being means is therefore essential to enable assessment of well-being and cross-service provision of well-being support. Objectives: To provide an overview of the ways in which well-being has been conceptualized in research relating to adults living with VI. Eligibility criteria: Articles were included in the review if the article discussed well-being in the context of adults living with VI, was available in English and as a full text. Data sources: A systematic search using search terms relating to VI and well-being was conducted in EBSCOHost (Medline, CINHL) and Ovid (Embase Classic, Embase, Emcare 1995, Health + Psychosocial, HMIC Health Management Info, APA, PsycArticles, PsycInfo, PsycTests). Charting: A team of three reviewers screened titles, abstracts and full-texts articles and extracted data. Ambiguous articles were referred to the research group and discussed. Results: Of 10,662 articles identified in the search, 249 were included in the review. These referred to 38 types of well-being. The most common types were general well-being (n = 101; 40.6%) emotional well-being (n = 86, 34.5%) and psychological well-being (n = 66, 26.5%). Most articles (n = 150; 60.2%) referred to one type only, with a maximum of 9 listed in one article. A large number of articles did not clearly define well-being. A wide range of indicators of well-being related to the domains of hedonia, mood, positive and negative affect, quality of life, mental health, eudaimonia, self/identity, health, psychological reactions to disability and health problems, functioning, social functioning and environment, were extracted, many of which were used just once. Conclusions: There remains a lack of consensus on how well-being is conceptualized and assessed in the context of adult VI. A standardized multi-domain approach derived with input from adults with VI and practitioners working with them is required to enable comparison of findings and cross-organizational provision of support.

Scoping review of remote rehabilitation (telerehabilitation) services to support people with vision impairment.

OBJECTIVE: Telerehabilitation for individuals with vision impairment aims to maintain maximum physical and/or psychological functioning through remote service delivery. This review aims to describe the type of telerehabilitation services available to people with vision impairment and summarise evidence on health-related outcomes, well-being and cost-effectiveness. DESIGN: Scoping review. DATA SOURCES: CINAHL Plus, MEDLINE, PsycARTICLES, PsychINFO, Embase, PubMed, HMIC and Ovid Emcare were searched, without date restrictions up to 24 May 2021. Charity and government websites, conference proceedings and clinical trial databases were also examined. ELIGIBILITY CRITERIA: Eligible studies evaluated benefits of telerehabilitation services for adults with vision impairment. Studies were excluded if they were not available in English, or focused on distance learning of visually impaired students. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers screened articles and extracted data. A risk of bias analysis was performed. OUTCOME MEASURES: Measures of benefit included performance-based assessment, patient-reported outcomes and cost-effectiveness. RESULTS: Of 4472 articles, 10 eligible studies were included. Outcomes addressed patient satisfaction (n=4;33.3%), quality-of-life, activities of daily living and well-being (n=4;33.3%), objective visual function (n=2;16.6%) and knowledge relating to ocular symptoms (n=1;8.3%). Two studies addressed multiple outcomes. Cost-effectiveness was addressed in one article (8.3%). Patients were generally satisfied with their experiences, which had a range of positive benefits on functional and quality-of-life outcomes in areas relating to daily activities (eg, reading, making phone calls). Telerehabilitation allowed patients to undertake vision optimisation training to prevent vision deterioration. Grey literature indicated that there are no completed clinical trials relating to low vision telerehabilitation. Charity services had implemented digital skills training to help beneficiaries communicate remotely. CONCLUSION: While acceptability of telerehabilitation was mostly high, limited real-world data are available which raises questions around the long-term desirability of this approach. Further trials are needed to evaluate telerehabilitation using a robust set of outcome measures. PROSPERO REGISTRATION NUMBER: CRD42021254825.

Snapshot of health-related behaviours in adults living with disabilities 1 year into the COVID-19 pandemic: a cross-sectional survey study.

OBJECTIVES: This survey aimed to assess the status of a range of health-related behaviours 1 year after the coronavirus outbreak was declared a pandemic in adults living with disabilities comparative with those with no disabilities. DESIGN: This cross-sectional study reports findings from an online survey conducted in March 2021. Mann-Whitney U and Χ2 tests were used to compare a range of health behaviours including time spent self-isolating, smoking, alcohol consumption, exercise frequency and diet in adults with and without disabilities. SETTING: A convenience sample of UK adults was recruited through the researchers' personal and professional networks including UK-based sight loss sector charities, social media platforms and professional forums. PARTICIPANTS: A total of 123 UK participants completed the survey. OUTCOME MEASURES: COVID-19 diagnosis, time spent self-isolating, alcohol consumption frequency, exercise frequency, change in smoking habit and eating habits. RESULTS: No significant differences were found in alcohol consumption, smoking, water intake, breakfast, or fruit and vegetable intake. There were statistically significant differences in the time spent self-isolating (U=2061, p=0.001), exercise frequency (U=1171.5, p=0.005) and the amount of food eaten (χ2 (2)=9.60, p=0.008, Cramer's V=0.281). Although the majority in both groups reported exercising three to four times per week and eating what they should, those with disabilities were more likely to eat less than they should, not exercise at all and to have been self-isolating for over 6 months than participants with no disabilities. CONCLUSIONS: The data in this study present some key differences between the two groups, with those living with disabilities being more likely to report that they had been self-isolating for prolonged periods of time, not exercising at all, and not eating as much as they should . This raises concerns for the health and well-being of individuals with disabilities.

The Long-Term Impact of the COVID-19 Pandemic on Loneliness in People Living With Disability and Visual Impairment.

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.

Dementia in military and veteran populations: a review of risk factors-traumatic brain injury, post-traumatic stress disorder, deployment, and sleep.

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.

Traumatic brain injury and sight loss in military and veteran populations- a review.

War and combat exposure pose great risks to the vision system. More recently, vision related deficiencies and impairments have become common with the increased use of powerful explosive devices and the subsequent rise in incidence of traumatic brain injury (TBI). Studies have looked at the effects of injury severity, aetiology of injury and the stage at which visual problems become apparent. There was little discrepancy found between the frequencies or types of visual dysfunctions across blast and non-blast related groups, however complete sight loss appeared to occur only in those who had a blast-related injury. Generally, the more severe the injury, the greater the likelihood of specific visual disturbances occurring, and a study found total sight loss to only occur in cases with greater severity. Diagnosis of mild TBI (mTBI) is challenging. Being able to identify a potential TBI via visual symptoms may offer a new avenue for diagnosis.

The Impact of COVID-19 on Sleep Quality in People Living With Disabilities.

Background: Research exploring the impact of the COVID-19 pandemic on sleep in people with disabilities has been scarce. This study provides a preliminary assessment of sleep in people with disabilities, across two timepoints during the pandemic, with a focus on those with visual impairment (VI). Methods: Two online surveys were conducted between April 2020 and March 2021 to explore sleep quality using the Pittsburgh Sleep Quality Index (PSQI). A convenience sample of 602 participants completed the first survey and 160 completed the follow-up survey. Results: Across both timepoints, participants with disabilities reported significantly poorer global sleep quality and higher levels of sleep disturbance, use of sleep medication and daytime dysfunction than those with no disabilities. Participants with VI reported significantly higher levels of sleep disturbance and use of sleep medication at both timepoints, poorer global sleep quality, sleep duration and latency at time 1, and daytime dysfunction at time 2, than those with no disabilities. Global sleep quality, sleep duration, sleep efficiency, and self-rated sleep quality deteriorated significantly in participants with no disabilities, but daytime dysfunction increased in all three groups. Disability and state anxiety were significant predictors of sleep quality across both surveys. Conclusion: While sleep was consistently poorer in people with disabilities such as VI, it appears that the COVID-19 pandemic has had a greater impact on sleep in people with no disabilities. State anxiety and, to a lesser extent, disability, were significant predictors of sleep across both surveys, suggesting the need to address anxiety in interventions targeted toward improving sleep.

Preconditioning of Cardiosphere-Derived Cells With Hypoxia or Prolyl-4-Hydroxylase Inhibitors Increases Stemness and Decreases Reliance on Oxidative Metabolism.

Cardiosphere-derived cells (CDCs), which can be isolated from heart explants, are a promising candidate cell source for infarcted myocardium regeneration. However, current protocols used to expand CDCs require at least 1 month in vitro to obtain sufficient cells for transplantation. We report that CDC culture can be optimized by preconditioning the cells under hypoxia (2% oxygen), which may reflect the physiological oxygen level of the stem cell niche. Under hypoxia, the CDC proliferation rate increased by 1.4-fold, generating 6 × 10(6) CDCs with higher expression of cardiac stem cell and pluripotency gene markers compared to normoxia. Furthermore, telomerase (TERT), cytokines/ligands involved in stem cell trafficking (SDF/CXCR-4), erythropoiesis (EPO), and angiogenesis (VEGF) were increased under hypoxia. Hypoxic preconditioning was mimicked by treatment with two types of hypoxia-inducible factor (HIF) prolyl-4-hydroxylase inhibitors (PHDIs): dimethyloxaloylglycine (DMOG) and 2-(1-chloro-4-hydroxyisoquinoline-3-carboxamido) acetic acid (BIC). Despite the difference in specificity, both PHDIs significantly increased c-Kit expression and activated HIF, EPO, and CXCR-4. Furthermore, treatment with PHDIs for 24 h increased cell proliferation. Notably, all hypoxic and PHDI-preconditioned CDCs had decreased oxygen consumption and increased glycolytic metabolism. In conclusion, cells cultured under hypoxia could have potentially enhanced therapeutic potential, which can be mimicked, in part, by PHDIs.

Chronic High-Fat Feeding Affects the Mesenchymal Cell Population Expanded From Adipose Tissue but Not Cardiac Atria.

UNLABELLED: Mesenchymal stem cells offer a promising approach to the treatment of myocardial infarction and prevention of heart failure. However, in the clinic, cells will be isolated from patients who may be suffering from comorbidities such as obesity and diabetes, which are known to adversely affect progenitor cells. Here we determined the effect of a high-fat diet (HFD) on mesenchymal stem cells from cardiac and adipose tissues. Mice were fed a HFD for 4 months, after which cardiosphere-derived cells (CDCs) were cultured from atrial tissue and adipose-derived mesenchymal cells (ADMSCs) were isolated from epididymal fat depots. HFD raised body weight, fasted plasma glucose, lactate, and insulin. Ventricle and liver tissue of HFD-fed mice showed protein changes associated with an early type 2 diabetic phenotype. At early passages, more ADMSCs were obtained from HFD-fed mice than from chow-fed mice, whereas CDC number was not affected by HFD. Migratory and clonogenic capacity and release of vascular endothelial growth factor did not differ between cells from HFD- and chow-fed animals. CDCs from chow-fed and HFD-fed mice showed no differences in surface marker expression, whereas ADMSCs from HFD-fed mice contained more cells positive for CD105, DDR2, and CD45, suggesting a high component of endothelial, fibroblast, and hematopoietic cells. Both Noggin and transforming growth factor ß-supplemented medium induced an early stage of differentiation in CDCs toward the cardiomyocyte phenotype. Thus, although chronic high-fat feeding increased the number of fibroblasts and hematopoietic cells within the ADMSC population, it left cardiac progenitor cells largely unaffected. SIGNIFICANCE: Mesenchymal cells are a promising candidate cell source for restoring lost tissue and thereby preventing heart failure. In the clinic, cells are isolated from patients who may be suffering from comorbidities such as obesity and diabetes. This study examined the effect of a high-fat diet on mesenchymal cells from cardiac and adipose tissues. It was demonstrated that a high-fat diet did not affect cardiac progenitor cells but increased the number of fibroblasts and hematopoietic cells within the adipose-derived mesenchymal cell population.

Investigating mitochondrial metabolism in contracting HL-1 cardiomyocytes following hypoxia and pharmacological HIF activation identifies HIF-dependent and independent mechanisms of regulation.

Hypoxia is a consequence of cardiac disease and downregulates mitochondrial metabolism, yet the molecular mechanisms through which this occurs in the heart are incompletely characterized. Therefore, we aimed to use a contracting HL-1 cardiomyocyte model to investigate the effects of hypoxia on mitochondrial metabolism. Cells were exposed to hypoxia (2% O2) for 6, 12, 24, and 48 hours to characterize the metabolic response. Cells were subsequently treated with the hypoxia inducible factor (HIF)-activating compound, dimethyloxalylglycine (DMOG), to determine whether hypoxia-induced mitochondrial changes were HIF dependent or independent, and to assess the suitability of this cultured cardiac cell line for cardiovascular pharmacological studies. Hypoxic cells had increased glycolysis after 24 hours, with glucose transporter 1 and lactate levels increased 5-fold and 15-fold, respectively. After 24 hours of hypoxia, mitochondrial networks were more fragmented but there was no change in citrate synthase activity, indicating that mitochondrial content was unchanged. Cellular oxygen consumption was 30% lower, accompanied by decreases in the enzymatic activities of electron transport chain (ETC) complexes I and IV, and aconitase by 81%, 96%, and 72%, relative to controls. Pharmacological HIF activation with DMOG decreased cellular oxygen consumption by 43%, coincident with decreases in the activities of aconitase and complex I by 26% and 30%, indicating that these adaptations were HIF mediated. In contrast, the hypoxia-mediated decrease in complex IV activity was not replicated by DMOG treatment, suggesting HIF-independent regulation of this complex. In conclusion, 24 hours of hypoxia increased anaerobic glycolysis and decreased mitochondrial respiration, which was associated with changes in ETC and tricarboxylic acid cycle enzyme activities in contracting HL-1 cells. Pharmacological HIF activation in this cardiac cell line allowed both HIF-dependent and independent mitochondrial metabolic changes to be identified.

Murine cardiosphere-derived cells are impaired by age but not by cardiac dystrophic dysfunction.

To be clinically relevant as a therapy for heart failure, endogenous progenitor cells must be isolated and expanded from aged and/or diseased tissue. Here, we investigated the effect of age and cardiac impairment resulting from lack of dystrophin on murine cardiosphere-derived cells (CDCs). CDCs were isolated and expanded from atrial biopsies from wild-type mice aged 1.5, 6, 18, and 24 months and from mdx mice aged 6 and 18 months. Cardiac function was measured in mdx mice and age-matched wild-type mice using high-resolution cine magnetic resonance imaging. CDCs could be isolated and expanded from all mice, however, the number of cells obtained, and their regenerative potential, decreased with age, as demonstrated by decreased expression of stem cell markers, c-kit and Sca-1, and decreased cell proliferation, migration, clonogenicity, and differentiation. Six-month-old mdx mice showed right ventricular (RV) dilation and reduced RV ejection fraction (EF) in comparison to wild-type mice. Older mdx mice displayed significant RV and left ventricular dilation and decreased EF in both ventricles, compared with age-matched wild-type mice. Mdx mouse hearts contained significantly more fibrotic tissue than age-matched wild-type mouse hearts. However, CDCs isolated from mice aged 6 and 18 months had the same number and regenerative potential from mdx mice and age-matched wild-type mice. Thus, the cardiac progenitor cell population is impaired by age but is not substantially altered by the progressive deterioration in function of the dystrophic heart.

Efficient pro-survival/angiogenic miRNA delivery by an MRI-detectable nanomaterial.

Herein, we report the use of biodegradable nanoparticles (NPs) containing perfluoro-1,5-crown ether (PFCE), a fluorine-based compound (NP170-PFCE) with the capacity to track cells in vivo by magnetic ressonance imaging (MRI) and efficiently release miRNA. NP170-PFCE complexed with miRNAs accumulate whitin the cell's endolysosomal compartment and interact with higher frequency with argonaute2 (Ago2) and GW182 proteins, which are involved in the biological action of miRNAs, than commercial complexes formed by commercial reagents and miRNA, which in turn accumulate in the cell cytoplasm. The release of miRNA132 (miR132) from the NPs increased 3-fold the survival of endothelial cells (ECs) transplanted in vivo and 3.5-fold the blood perfusion in ischemic limbs relatively to control.