An engineered cardiac reporter cell line identifies human embryonic stem cell-derived myocardial precursors.

Unlike some organs, the heart is unable to repair itself after injury. Human embryonic stem cells (hESCs) grow and divide indefinitely while maintaining the potential to develop into many tissues of the body. As such, they provide an unprecedented opportunity to treat human diseases characterized by tissue loss. We have identified early myocardial precursors derived from hESCs (hMPs) using an α-myosin heavy chain (αMHC)-GFP reporter line. We have demonstrated by immunocytochemistry and quantitative real-time PCR (qPCR) that reporter activation is restricted to hESC-derived cardiomyocytes (CMs) differentiated in vitro, and that hMPs give rise exclusively to muscle in an in vivo teratoma formation assay. We also demonstrate that the reporter does not interfere with hESC genomic stability. Importantly, we show that hMPs give rise to atrial, ventricular and specialized conduction CM subtypes by qPCR and microelectrode array analysis. Expression profiling of hMPs over the course of differentiation implicate Wnt and transforming growth factor-β signaling pathways in CM development. The identification of hMPs using this αMHC-GFP reporter line will provide important insight into the pathways regulating human myocardial development, and may provide a novel therapeutic reagent for the treatment of cardiac disease

Long term in vitro expansion of epithelial stem cells enabled by pharmacological inhibition of PAK1-ROCK-Myosin II and TGF-β signaling

Summary: Despite substantial self-renewal capability in vivo, epithelial stem and progenitor cells located in various tissues expand for a few passages in vitro in feeder-free condition before they succumb to growth arrest. Here, we describe the EpiX method, which utilizes small molecules that inhibit PAK1-ROCK-Myosin II and TGF-β signaling to achieve over one trillion-fold expansion of human epithelial stem and progenitor cells from skin, airway, mammary, and prostate glands in the absence of feeder cells. Transcriptomic and epigenomic studies show that this condition helps epithelial cells to overcome stresses for continuous proliferation. EpiX-expanded basal epithelial cells differentiate into mature epithelial cells consistent with their tissue origins. Whole-genome sequencing reveals that the cells retain remarkable genome integrity after extensive in vitro expansion without acquiring tumorigenicity. EpiX technology provides a solution to exploit the potential of tissue-resident epithelial stem and progenitor cells for regenerative medicine. : Zhang et al. screen a small-molecule collection and find that pharmacologic inhibition of TGF-β and PAK1-ROCK-Myosin II, in low calcium conditions, supports extended expansion of epithelial stem cells in 2D format. This approach enhances the potential of tissue-resident epithelial stem cells for cell therapy. Keywords: epithelial stem and progenitor cells, cell culture method, TGF-β, PAK1/ROCK/Myosin II, feeder-free, regenerative medicine, cell therap

Gravitational Radiation Instability in Hot Young Neutron Stars

We show that gravitational radiation drives an instability in hot young rapidly rotating neutron stars. This instability occurs primarily in the l=2 r-mode and will carry away most of the angular momentum of a rapidly rotating star by gravitational radiation. On the timescale needed to cool a young neutron star to about T=10^9 K (about one year) this instability can reduce the rotation rate of a rapidly rotating star to about 0.076\Omega_K, where \Omega_K is the Keplerian angular velocity where mass shedding occurs. In older colder neutron stars this instability is suppressed by viscous effects, allowing older stars to be spun up by accretion to larger angular velocities.Comment: 4 Pages, 2 Figure

The Sleep Or Mood Novel Adjunctive therapy (SOMNA) trial: a study protocol for a randomised controlled trial evaluating an internet-delivered cognitive behavioural therapy program for insomnia on outcomes of standard treatment for depression in men

BACKGROUND: Insomnia is a significant risk factor for depression onset, can result in more disabling depressive illness, and is a common residual symptom following treatment cessation that can increase the risk of relapse. Internet-based cognitive behavioural therapy for insomnia has demonstrated efficacy and acceptability to men who are less likely than women to seek help in standard care. We aim to evaluate whether internet delivered cognitive behavioural therapy for insomnia as an adjunct to a standard depression therapeutic plan can lead to improved mood outcomes.METHODS/DESIGN: Male participants aged 50 years or more, meeting Diagnostic and Statistical Manual of Mental Disorders criteria for current Major Depressive Episode and/or Dysthymia and self-reported insomnia symptoms, will be screened to participate in a single-centre double-blind randomised controlled trial with two parallel groups involving adjunctive internet-delivered cognitive behavioural therapy for insomnia and an internet-based control program. The trial will consist of a nine-week insomnia intervention period with a six-month follow-up period. During the insomnia intervention period participants will have their depression management coordinated by a psychiatrist using standard guideline-based depression treatments. The study will be conducted in urban New South Wales, Australia, where 80 participants from primary and secondary care and direct from the local community will be recruited. The primary outcome is change in the severity of depressive symptoms from baseline to week 12. DISCUSSION: This study will provide evidence on whether a widely accessible, evidence-based, internet-delivered cognitive behavioural therapy for insomnia intervention can lead to greater improvements than standard treatment for depression alone, in a group who traditionally do not readily access psychotherapy. The study is designed to establish effect size, feasibility and processes associated with implementing e-health solutions alongside standard clinical care, to warrant undertaking a larger more definitive clinical trial.Trial registration: Australian and New Zealand Clinical Trials Registry ACTRN12612000985886.The study is supported by beyondblue: the national depression and anxiety initiative National Priority Driven Research Program and funded through a donation from the Movember Foundation

Lower Levels of Glutathione (GSH) in the Brains of Secondary Progressive Multiple Sclerosis Patients Measured by 1H Magnetic Resonance Chemical Shift Imaging at 3 T

BACKGROUND: Disability levels for patients with secondary progressive multiple sclerosis (SPMS) often worsen despite a stable MRI T2 lesion burden. The presence of oxidative stress in the absence of measurable inflammation could help explain this phenomenon. In this study, the assessment of an in vivo marker of oxidative stress, cerebral glutathione (GSH), using magnetic resonance chemical shift imaging (CSI) is described, and GSH levels were compared in patients with SPMS and healthy controls. OBJECTIVE: To assess whether GSH, a key antioxidant in the brain, is lower in the SPMS patients compared to matched controls. METHODS: Seventeen patients with SPMS (Expanded Disability Status Scale = 4.0–7.0; length of MS diagnosis = 19.4±7 years) and 17 age- and gender-matched healthy controls were studied. GSH levels were measured in the fronto-parietal regions of the brain using a specially designed magnetic resonance spectroscopy technique, CSI of GSH, at 3T. RESULTS: The levels of GSH were lower for SPMS patients than for controls, the largest reduction (18.5%) being in the frontal region (p=0.001). CONCLUSION: The lower GSH levels in these patients indicate the presence of oxidative stress in SPMS. This process could be at least partially responsible for ongoing functional decline in SPMS

A proposed approach to monitor private-sector policies and practices related to food environments, obesity and non-communicable disease prevention

Private-sector organizations play a critical role in shaping the food environments of individuals and populations. However, there is currently very limited independent monitoring of private-sector actions related to food environments. This paper reviews previous efforts to monitor the private sector in this area, and outlines a proposed approach to monitor private-sector policies and practices related to food environments, and their influence on obesity and non-communicable disease (NCD) prevention. A step-wise approach to data collection is recommended, in which the first (‘minimal’) step is the collation of publicly available food and nutrition-related policies of selected private-sector organizations. The second (‘expanded’) step assesses the nutritional composition of each organization’s products, their promotions to children, their labelling practices, and the accessibility, availability and affordability of their products. The third (‘optimal’) step includes data on other commercial activities that may influence food environments, such as political lobbying and corporate philanthropy. The proposed approach will be further developed and piloted in countries of varying size and income levels. There is potential for this approach to enable national and international benchmarking of private-sector policies and practices, and to inform efforts to hold the private sector to account for their role in obesity and NCD prevention

Monitoring the impacts of trade agreements on food environments

The liberalization of international trade and foreign direct investment through multilateral, regional and bilateral agreements has had profound implications for the structure and nature of food systems, and therefore, for the availability, nutritional quality, accessibility, price and promotion of foods in different locations. Public health attention has only relatively recently turned to the links between trade and investment agreements, diets and health, and there is currently no systematic monitoring of this area. This paper reviews the available evidence on the links between trade agreements, food environments and diets from an obesity and non-communicable disease (NCD) perspective. Based on the key issues identified through the review, the paper outlines an approach for monitoring the potential impact of trade agreements on food environments and obesity/NCD risks. The proposed monitoring approach encompasses a set of guiding principles, recommended procedures for data collection and analysis, and quantifiable ‘minimal’, ‘expanded’ and ‘optimal’ measurement indicators to be tailored to national priorities, capacity and resources. Formal risk assessment processes of existing and evolving trade and investment agreements, which focus on their impacts on food environments will help inform the development of healthy trade policy, strengthen domestic nutrition and health policy space and ultimately protect population nutrition.The following organizations provided funding support for the travel of participants to Italy for this meeting and the preparation of background research papers: The Rockefeller Foundation, International Obesity Taskforce (IOTF), University of Auckland, Deakin University, The George Institute, University of Sydney, Queensland University of Technology, University of Oxford, University of Pennsylvania Perelman School of Medicine, World Cancer Research Fund International, University of Toronto, and The Australian National University. The Faculty of Health at Deakin University kindly supported the costs for open access availability of this paper, and the Australian National Health and Medical Research Council Centre for Research Excellence in Obesity Policy and Food Systems (APP1041020) supported the coordination and finalizing of INFORMAS manuscripts

Lost in the system : responsibilisation and burden for women with multiple long-term health conditions during pregnancy

We would like to thank our patient and public involvement representatives for their input into the design, conduct and analysis of this work. Thanks also to our participants who took part in the study. This work was funded by the Strategic Priority Fund “Tackling multimorbidity at scale” programme (grant number MR/W014432/1) delivered by the Medical Research Council and the National Institute for Health Research in partnership with the Economic and Social Research Council and in collaboration with the Engineering and Physical Sciences Research Council.Peer reviewe

Health and Economic Burden of Post-Partum Staphylococcus aureus Breast Abscess

Objectives: To determine the health and economic burdens of post-partum Staphylococcus aureus breast abscess. Study design We conducted a matched cohort study (N = 216) in a population of pregnant women (N = 32,770) who delivered at our center during the study period from 10/1/03–9/30/10. Data were extracted from hospital databases, or via chart review if unavailable electronically. We compared cases of S. aureus breast abscess to controls matched by delivery date to compare health services utilization and mean attributable medical costs in 2012 United States dollars using Medicare and hospital-based estimates. We also evaluated whether resource utilization and health care costs differed between cases with methicillin-resistant and -susceptible S. aureus isolates. Results: Fifty-four cases of culture-confirmed post-partum S. aureus breast abscess were identified. Breastfeeding cessation (41%), milk fistula (11.1%) and hospital readmission (50%) occurred frequently among case patients. Breast abscess case patients had high rates of health services utilization compared to controls, including high rates of imaging and drainage procedures. The mean attributable cost of post-partum S. aureus breast abscess ranged from $2,340–$4,012, depending on the methods and data sources used. Mean attributable costs were not significantly higher among methicillin-resistant vs. –susceptible S. aureus cases. Conclusions: Post-partum S. aureus breast abscess is associated with worse health and economic outcomes for women and their infants, including high rates of breastfeeding cessation. Future study is needed to determine the optimal treatment and prevention of these infections