Moving beyond size and phosphatidylserine exposure: evidence for a diversity of apoptotic cell-derived extracellular vesicles in vitro

Apoptosis is a form of programmed cell death that occurs throughout life as part of normal development as well as pathologic processes including chronic inflammation and infection. Although the death of a cell is often considered as the only biological outcome of a cell committed to apoptosis, it is becoming increasingly clear that the dying cell can actively communicate with other cells via soluble factors as well as membrane-bound extracellular vesicles (EVs) to regulate processes including cell clearance, immunity and tissue repair. Compared to EVs generated from viable cells such as exosomes and microvesicles, apoptotic cell-derived EVs (ApoEVs) are less well defined and the basic criteria for ApoEV characterization have not been established in the field. In this study, we will examine the current understanding of ApoEVs, in particular, the ApoEV subtype called apoptotic bodies (ApoBDs). We described that a subset of ApoBDs can be larger than 5 μm and smaller than 1 μm based on flow cytometry and live time-lapse microscopy analysis, respectively. We also described that a subset of ApoBDs can expose a relatively low level of phosphatidylserine on its surface based on annexin A5 staining. Furthermore, we characterized the presence of caspase-cleaved proteins (in particular plasma membrane-associated or cytoplasmic proteins) in samples enriched in ApoBDs. Lastly, using a combination of biochemical-, live imaging- and flow cytometry-based approaches, we characterized the progressive lysis of ApoBDs. Taken together, these results extended our understanding of ApoBDs

The Lantern, 2009-2010

• I\u27m Pregnant. It\u27s Yours • The Nightmare • What Death Became After Cyparissus • Substances • Ain\u27t That a Man? • Portrait • The 100th Chemo • Looking into Her Toy Box with a Lover • They Used to Talk About Burning Cities • MESSAGE: Absence for Allen Ginsberg • Lunch with Candide • Behold! Man of Unbelief! Behold! • Dream #1 Final Strophe • Patience (Things You Will Discover) • Four Years • He Falls Like Leaves • The Quilt • Ariel (Turning Tricks at Fisherman\u27s Wharf, Monterey, California) • Extranjera • The Taste of Morning • Fear of Glory • The Rum Bottle\u27s Fortune • While Thinking of What to Write • Dying in Spring • Tutte le Eta di Firenze • Token • A House Grows Into Itself • Gravity • Father with the Skyy • He Says He Dreams of Me • Myth • Sun-Veins and Wishbones • Attempts at Bravery • One Boy in Four Parts • Blacktop Rollin\u27 • Getting My Feet Wet • The Long Ride After Ending • Wet Tongues and Sweaty Cotton • Norman Bates is My Mother • Sims Trek • Tomorrow Comes Today • The Writer\u27s Process • This Too Was Real • Venus from the Waves • Shark • Monday\u27s Expectations • Recognition • The Black Shoes • Climax • Andrew • Bottles • Calle de Cusco • God in the Machine • The 26th of December • Lollipop Lollipop • When Dinosaurs Roamed the Earth • Meaning • Jeffrey • Looking • Jagged Edges • Fading Storm • Shoes • Cover Image: Death by Chocolatehttps://digitalcommons.ursinus.edu/lantern/1175/thumbnail.jp

Treatment of migraine attacks based on the interaction with the trigemino-cerebrovascular system

Primary headaches such as migraine are among the most prevalent neurological disorders, affecting up to one-fifth of the adult population. The scientific work in the last decade has unraveled much of the pathophysiological background of migraine, which is now considered to be a neurovascular disorder. It has been discovered that the trigemino-cerebrovascular system plays a key role in migraine headache pathophysiology by releasing the potent vasodilator calcitonin gene-related peptide (CGRP). This neuropeptide is released in parallel with the pain and its concentration correlates well with the intensity of the headache. The development of drugs of the triptan class has provided relief for the acute attacks but at the cost of, mainly cardiovascular, side effects. Thus, the intention to improve treatment led to the development of small CGRP receptor antagonists such as olcegepant (BIBN4096BS) and MK-0974 that alleviate the acute migraine attack without acute side events. The purpose of this review is to give a short overview of the pathological background of migraine headache and to illustrate the mechanisms behind the actions of triptans and the promising CGRP receptor blockers

CHARACTERISTICS OF THE CURRENT CIVIL SERVICE MILITARY HEALTHCARE WORKFORCE AND DETERMINANTS OF WORKFORCE TURNOVER AND ATTRITION

Fiscal year 2018 marked the onset of a phased transition of command over the Military Treatment Facilities (MTF) to the recently established Defense Health Agency. As the MTF environment goes through a landmark transition, the optimal future functions and capabilities of each MTF remain under planning and evaluation. Strategic decision making requires complete information for future operational planning. Currently, little is known about the baseline demographics, determinants of turnover, attrition rates, and general career life cycle of the civil service healthcare workforce. Using civil service human resource workforce data from the years 2014–2018, this study applies quantitative descriptive and regression analysis methods to achieve an in-depth summary of this workforce’s current condition and career life cycle. The results not only describe the current MTF civilian healthcare labor force but cite workforce planning vulnerabilities. The findings indicate potential risks for a manpower gap in the future MTF environment. The implications of these findings not only provide a workforce baseline for a measurable evaluation of the effect of future policy and transition outcomes, they support the notion that changes in the recruitment and retention policies for federal labor hiring are required if the current civilian medical workforce is to be maintained or increased.http://archive.org/details/characteristicso1094564881Commander, United States NavyApproved for public release; distribution is unlimited

Heparanase: A Novel Therapeutic Target for the Treatment of Atherosclerosis

Cardiovascular disease (CVD) is the leading cause of death and disability worldwide, and its management places a huge burden on healthcare systems through hospitalisation and treatment. Atherosclerosis is a chronic inflammatory disease of the arterial wall resulting in the formation of lipid-rich, fibrotic plaques under the subendothelium and is a key contributor to the development of CVD. As such, a detailed understanding of the mechanisms involved in the development of atherosclerosis is urgently required for more effective disease treatment and prevention strategies. Heparanase is the only mammalian enzyme known to cleave heparan sulfate of heparan sulfate proteoglycans, which is a key component of the extracellular matrix and basement membrane. By cleaving heparan sulfate, heparanase contributes to the regulation of numerous physiological and pathological processes such as wound healing, inflammation, tumour angiogenesis, and cell migration. Recent evidence suggests a multifactorial role for heparanase in atherosclerosis by promoting underlying inflammatory processes giving rise to plaque formation, as well as regulating lesion stability. This review provides an up-to-date overview of the role of heparanase in physiological and pathological processes with a focus on the emerging role of the enzyme in atherosclerosis

Repeatability of Quantitative 18F-NaF PET: A Multicenter Study

PURPOSE In bone-metastatic breast cancer patients, there are no current imaging biomarkers to identify which patients have worst prognosis. The purpose of our study was to investigate if skeletal tumor burden determined by 18F-Fluoride PET/CT correlates with clinical outcomes and may help define prognosis throughout the course of the disease. RESULTS Bone metastases were present in 49 patients. On multivariable analysis, skeletal tumor burden was significantly and independently associated with overall survival (p <0.0001) and progression free-survival (p <0.0001). The simple presence of bone metastases was associated with time to bone event (p = 0.0448). MATERIALS AND METHODS We quantified the skeletal tumor burden on 18F-Fluoride PET/CT images of 107 female breast cancer patients (40 for primary staging and the remainder for restaging after therapy). Clinical parameters, primary tumor characteristics and skeletal tumor burden were correlated to overall survival, progression free-survival and time to bone event. The median follow-up time was 19.5 months. CONCLUSIONS 18F-Fluoride PET/CT skeletal tumor burden is a strong independent prognostic imaging biomarker in breast cancer patients