Cellular cardiomyoplasty with autologous skeletal myoblasts for ischemic heart disease and heart failure

Cell transplantation to repair or regenerate injured myocardium is a new frontier in the treatment of cardiovascular disease. Even though it is based on many years of pre-clinical studies, much remains to be understood about this methodology, even as it progresses to the clinic. For example, controversies exist over the specific cells to be used, the dosages needed for tissue repair, how cells will affect the electrical activity of the myocardium, and even whether the cells can improve myocardial function after transplantation — all of which are briefly reviewed here. Autologous skeletal myoblasts appear to be the most well studied and best first generation cells for cardiac repair. Yet cardiocytes and, more recently, stem cells have been proposed as cell sources for this technology. Their advantages and limitations are also discussed. Although cellular cardiomyoplasty (cell transplantation for cardiac repair) shows great pre-clinical promise, its future will heavily depend on conducting carefully controlled, randomized clinical trials with appropriate endpoints. Utilizing biologically active cells provides both an opportunity for tissue repair and the potential for not yet understood outcomes. As with any frontier, many pioneers will attempt to conquer it. But also as with any frontier, there are pitfalls and consequences to be considered that may surpass those of previous endeavors. The future thus requires careful consideration and well-designed trials rather than haste. The promise for cell transplantation is too great to be spoiled by ill-designed attempts that forget to account for the biology of both the cells and the myocardium

\u27Walkabout Tourism\u27: Is there an Indigenous Tourism Market in Outback Australia?

Outback areas of Australia account for much of the landmass with just 5% of the population, many of whom are Indigenous Australians. Despite tourism being an important industry for Outback economies, it has declined in recent decades prompting a search for new and expanding tourism markets. While Indigenous tourism in the form of visits to Indigenous communities, attractions and sites to obtain the Indigenous ‘experience’ has been pursued it has, along with other niche markets, delivered at best limited and isolated successes. But Indigenous people are themselves highly mobile, making frequent and regular trips away from home. In the past these trips were labelled in a derogatory way as ‘walkabout’. The characteristics of these trips posit them firmly within accepted definitions of tourism but, excepting one study on homelessness, there is a vacuum in research on the potential of people ‘on the move’ as a tourist market. Consequently, we do not know the potential size or characteristics of the market, an awkward contradiction given the historical focus on generating tourism at places where Indigenous people live. This study is the first to analyse data for Outback areas from the perspective of providing baseline information about that market. While results are mixed in terms of the potential to support a flailing tourism industry, this study finds that Indigenous people on the move should not be ignored

Racial Differences in the Effect of Granulocyte Macrophage Colony-Stimulating Factor on Improved Walking Distance in Peripheral Artery Disease: The PROPEL Randomized Clinical Trial.

Background The effects of race on response to medical therapy in people with peripheral artery disease ( PAD ) are unknown. Methods and Results In the PROPEL (Progenitor Cell Release Plus Exercise to Improve Functional Performance in PAD) Trial, PAD participants were randomized to 1 of 4 groups for 6 months: supervised treadmill exercise+granulocyte-macrophage colony-stimulating factor ( GM - CSF ) (Group 1), exercise+placebo (Group 2), attention control+ GM - CSF (Group 3), or attention control+placebo (Group 4). Change in 6-minute walk distance was measured at 12- and 26-week follow-up. In these exploratory analyses, groups receiving GM - CSF (Groups 1 and 3), placebo (Groups 2 and 4), exercise (Groups 1 and 2), and attention control (Groups 2 and 4) were combined, maximizing statistical power for studying the effects of race on response to interventions. Of 210 PAD participants, 141 (67%) were black and 64 (30%) were white. Among whites, GM - CSF improved 6-minute walk distance by +22.0 m (95% CI : -4.5, +48.5, P=0.103) at 12 weeks and +44.4 m (95% CI : +6.9, +82.0, P=0.020) at 26 weeks, compared with placebo. Among black participants, there was no effect of GM - CSF on 6-minute walk distance at 12-week ( P=0.26) or 26-week (-5.0 m [-27.5, +17.5, P=0.66]) follow-up, compared with placebo. There was an interaction of race on the effect of GM - CSF on 6-minute walk change at 26-week follow-up ( P=0.018). Exercise improved 6-minute walk distance in black ( P=0.006) and white ( P=0.034) participants without interaction. Conclusions GM - CSF improved 6-minute walk distance in whites with PAD but had no effect in black participants. Further study is needed to confirm racial differences in GM - CSF efficacy in PAD . Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01408901

Transcription factor MYB26 is key to spatial specificity in anther secondary thickening formation

Successful fertilization relies on the production and effective release of viable pollen. Failure of anther opening (dehiscence), results in male sterility, although the pollen may be fully functional. MYB26 regulates the formation of secondary thickening in the anther endothecium, which is critical for anther dehiscence and fertility. Here, we show that although the MYB26 transcript shows expression in multiple floral organs, the MYB26 protein is localized specifically to the anther endothecium nuclei and that it directly regulates two NAC domain genes, NST1 and NST2, which are critical for the induction of secondary thickening biosynthesis genes. However, there is a complex relationship of regulation between these genes and MYB26. Using DEX-inducible MYB26 lines and overexpression in the various mutant backgrounds, we have shown that MYB26 up-regulates both NST1 and NST2 expression. Surprisingly normal thickening and fertility rescue does not occur in the absence of MYB26, even with constitutively induced NST1 and NST2, suggesting an additional essential role for MYB26 in this regulation. Combined overexpression of NST1 and NST2 in myb26 facilitates limited ectopic thickening in the anther epidermis, but not in the endothecium, and thus fails to rescue dehiscence. Therefore, by a series of regulatory controls through MYB26, NST1, NST2, secondary thickening is formed specifically within the endothecium; this specificity is essential for anther opening

Circulating Biomarkers to Identify Responders in Cardiac Cell therapy.

Bone marrow mononuclear cell (BM-MNC) therapy in ST-elevation acute myocardial infarction (STEMI) has no biological inclusion criteria. Here, we analyzed 63 biomarkers and cytokines in baseline plasma samples from 77 STEMI patients treated with BM-MNCs in the TIME and Late-TIME trials as well as 61 STEMI patients treated with placebo. Response to cell therapy was defined by changes in left ventricular ejection fraction, systolic/diastolic volumes, and wall motion indexes. We investigated the clinical value of circulating proteins in outcome prediction using significance testing, partial least squares discriminant analysis, and receiver operating characteristic (ROC) analysis. Responders had higher biomarker levels (76-94% elevated) than non-responders. Several biomarkers had values that differed significantly (P < 0.05) between responders and non-responders including stem cell factor, platelet-derived growth factor, and interleukin-15. We then used these lead candidates for ROC analysis and found multiple biomarkers with values areas under the curve >0.70 including interleukin 15. These biomarkers were not involved in the placebo-treated subjects suggesting that they may have predictive power. We conclude that plasma profiling after STEMI may help identify patients with a greater likelihood of response to cell-based treatment. Prospective trials are needed to assess the predictive value of the circulating biomarkers

Technology intervention to support caregiving for Alzheimer’s disease (I-CARE): study protocol for a randomized controlled pilot trial

Background: Informal caregivers of patients with Alzheimer's disease and related dementias (ADRD) manage a complex spectrum of patient behavioral and psychological symptoms of dementia (BPSD). Mobile health information technologies have quickly become sources for modern social support and chronic disease management. These technologies can improve our understanding of how to care for patients with ADRD and their informal caregivers. A mobile telehealth intervention could help reduce caregiver burden and BPSD. Methods: This is a pilot randomized controlled trial of 60 dyads of patients living with ADRD and their caregivers, to test the feasibility and estimate the potential effect of the Brain CareNotes (BCN) mobile telehealth system. Participants will be recruited from two health systems. Participants will be randomly assigned to either the BCN intervention arm or usual care comparator. Data will be collected at baseline, 3- and 6-month follow-up. The primary objectives of this trial are to assess feasibility outcomes: (a) recruitment rate, (b) data completion, (c) BCN usability, (d) BCN acceptance, and (e) BCN use and assessed either on an ongoing basis or at 3- and 6-month post-intervention. A secondary objective was to estimate the intervention's effects on caregiver burden and patient BPSD outcomes at 3 and 6 months, assessed by the Neuropsychiatric Inventory. Discussion: The study will assess the intervention feasibility and potential effect size of the BCN telehealth system as a potentially scalable and lower-cost solution for addressing the ADRD public health crisis

Genotype-Independent Transmission of Transgenic Fluorophore Protein by Boar Spermatozoa

Recently, we generated transposon-transgenic boars (Sus scrofa), which carry three monomeric copies of a fluorophore marker gene. Amazingly, a ubiquitous fluorophore expression in somatic, as well as in germ cells was found. Here, we characterized the prominent fluorophore load in mature spermatozoa of these animals. Sperm samples were analyzed for general fertility parameters, sorted according to X and Y chromosome-bearing sperm fractions, assessed for potential detrimental effects of the reporter, and used for inseminations into estrous sows. Independent of their genotype, all spermatozoa were uniformly fluorescent with a subcellular compartmentalization of the fluorophore protein in postacrosomal sheath, mid piece and tail. Transmission of the fluorophore protein to fertilized oocytes was shown by confocal microscopic analysis of zygotes. The monomeric copies of the transgene segregated during meiosis, rendering a certain fraction of the spermatozoa non-transgenic (about 10% based on analysis of 74 F1 offspring). The genotype-independent transmission of the fluorophore protein by spermatozoa to oocytes represents a non-genetic contribution to the mammalian embryo