Transplantation-based screen identifies inducers of muscle progenitor cell engraftment across vertebrate species.

Stem cell transplantation presents a potentially curative strategy for genetic disorders of skeletal muscle, but this approach is limited by the deleterious effects of cell expansion in vitro and consequent poor engraftment efficiency. In an effort to overcome this limitation, we sought to identify molecular signals that enhance the myogenic activity of cultured muscle progenitors. Here, we report the development and application of a cross-species small-molecule screening platform employing zebrafish and mice, which enables rapid, direct evaluation of the effects of chemical compounds on the engraftment of transplanted muscle precursor cells. Using this system, we screened a library of bioactive lipids to discriminate those that could increase myogenic engraftment in vivo in zebrafish and mice. This effort identified two lipids, lysophosphatidic acid and niflumic acid, both linked to the activation of intracellular calcium-ion flux, which showed conserved, dose-dependent, and synergistic effects in promoting muscle engraftment across these vertebrate species.

COVID-19 and the reimaging of compassionate release.

PURPOSE: The purpose of this paper is to provide a historical overview of compassionate release policies in the USA and describe how these policies have been used during the COVID-19 pandemic. The authors then describe how these programs have been shaped by COVID-19 and could be reimagined to address the structural conditions that make prisons potentially life limiting for older adults and those with chronic illness. DESIGN/METHODOLOGY/APPROACH: This paper is primarily descriptive, offering an overview of the history of compassionate release policies before and during the COVID-19 pandemic. The authors augmented this description by surveying state Departments of Corrections about their utilization of compassionate release during 2019 and 2020. The findings from this survey were combined with data collected via Freedom of Information Act Requests sent to state Departments of Corrections about the same topic. FINDINGS: The findings demonstrate that while the US federal prison system saw a multifold increase in the number of individuals released under compassionate release policies in 2020 compared to 2019, most US states had modest change, with many states maintaining the same number, or even fewer, releases in 2020 compared with 2019. ORIGINALITY/VALUE: This paper provides both new data and new insight into compassionate release utilization during the COVID-19 pandemic and offers new possibilities for how compassionate release might be considered in the future.

The relative impact of socioeconomic position and frailty varies by population setting.

Introduction: Frailty and socioeconomic position (SEP) are well-established determinants of health. However, we know less about the contributions of frailty and SEP in older adults, especially in acute settings. We set out to answer how frailty and SEP might influence health outcomes in older people, comparing a population sample and patients managed by a speciality acute frailty service. Methods: We used the Delirium and Population Health Informatics Cohort, a population sample of 1510 individuals aged ≥70 years from the London Borough of Camden and 1750 acute frailty patients. SEP was determined using the Index of Multiple Deprivation. Linear and Cox proportional hazard regression models were conducted to assess SEP on frailty, readmission, and mortality outcomes. Results: In the population sample, SEP was significantly associated with frailty and mortality with successive increases in rate of death for each IMD quintile (HR = 1.28, 95% CI 1.11 to 1.49, P < 0.005). Increasing SEP, age, and admission status among hospitalized individuals were associated with greater frailty. For individuals seen by the speciality frailty service, SEP was not associated with frailty, mortality, or readmission. Discussion: When older people experience acute illness severe enough to require secondary care, particularly specialist services, this overcomes any prior advantages conferred by a higher SEP.

Understanding Cancer Survivorship among Firefighters: A Mixed-Method Study.

BACKGROUND: Firefighters are exposed to a unique set of carcinogens through their work environment that predispose them to several cancers, yet there is limited research related to cancer survivorship amongst this occupational group. METHODS: A mixed-method approach was used to assess cancer survivorship amongst firefighters. Four focus groups and one in-depth interview were conducted with 29 active and retired firefighters who have been diagnosed with cancer to understand the experiences and challenges associated with cancer survivorship in the fire service and desired resources. Qualitative data were analyzed using Nvivo software. All participants completed the Functional Assessment of Cancer Therapy-General (FACT-G) survey to assess their quality of life. RESULTS: The primary themes that emerged from the focus groups included managing health and well-being changes, navigating support systems in place, and accessing new resources. FACT-G scores (mean ± standard deviation) of the firefighter cancer survivor sample demonstrate relatively lower levels of emotional well-being (19.26 ± 4.67) and higher quality of life in the physical well-being (23.67 ± 5.08), social well-being (23.38 ± 4.16), and functional well-being (22.6 ± 4.966) domains. CONCLUSIONS: Firefighters requested curated resources, such as support groups and department training resources, supporting the need for more cancer survivorship resources specific to firefighters.

A facile stable-isotope dilution method for determination of sphingosine phosphate lyase activity.

A new technique for quantifying sphingosine phosphate lyase activity in biological samples is described. In this procedure, 2-hydrazinoquinoline is used to convert (2E)-hexadecenal into the corresponding hydrazone derivative to improve ionization efficiency and selectivity of detection. Combined utilization of liquid chromatographic separation and multiple reaction monitoring-mass spectrometry allows for simultaneous quantification of the substrate S1P and product (2E)-hexadecenal. Incorporation of (2E)- d5-hexadecenal as an internal standard improves detection accuracy and precision. A simple one-step derivatization procedure eliminates the need for further extractions. Limits of quantification for (2E)-hexadecenal and sphingosine-1-phosphate are 100 and 50fmol, respectively. The assay displays a wide dynamic detection range useful for detection of low basal sphingosine phosphate lyase activity in wild type cells, SPL-overexpressing cell lines, and wild type mouse tissues. Compared to current methods, the capacity for simultaneous detection of sphingosine-1-phosphate and (2E)-hexadecenal greatly improves the accuracy of results and shows excellent sensitivity and specificity for sphingosine phosphate lyase activity detection.