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Leading the way in experimental and clinical research in hematology

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Daniela E. Egas Bejar , Joy M. Fulbright , Fernando F. Corrales-Medina , Mary E. Irwin , Blake Johnson and Joya Chandra
Blood 2013 122:1293;
Daniela E. Egas Bejar
Department of Pediatrics Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA,
Joy M. Fulbright
Department of Pediatrics Research, University of Texas MD Anderson Cancer Center, Houston, TX, USA
Fernando F. Corrales-Medina
Department of Pediatrics Research, University of Texas MD Anderson Cancer Center, Houston, TX, USA
Mary E. Irwin
Department of Pediatrics Research, University of Texas MD Anderson Cancer Center, Houston, TX, USA
Blake Johnson
Department of Pediatrics Research, University of Texas MD Anderson Cancer Center, Houston, TX, USA
Joya Chandra
Department of Pediatrics Research, University of Texas MD Anderson Cancer Center, Houston, TX, USA

Anthracyclines are among the most powerful drugs used for the treatment of leukemia, however their use has been associated with cardiotoxicity. Reactive oxygen species (ROS) are generated in both cancer and normal cells after anthracycline exposure and have been implicated in both early and late onset cardiotoxicity. Counteracting this ROS generation are intracellular antioxidants such as the ubiquitous antioxidant glutathione (GSH), levels of which are depleted upon anthracycline exposure. Basal expression of GSH pathway components and other antioxidants vary greatly between different cell types. Due to this differential expression of cellular antioxidants in cardiomyocytes versus leukemia cells, we posit that anthracyclines exert distinct effects on oxidative stress and consequent apoptosis induction in leukemia cells and nontransformed hematopoietic cells (PBMC) relative to cardiomyocytes. As a result, we expect potentially varied mechanisms of cell death induction in these cell lines after anthracycline treatment. To test this hypothesis, the acute leukemia cell lines Jurkat and ML-1 and the cardiomyocyte line H9C2 were used. Dose responses with the anthracyclines, doxorubicin and daunorubicin, were carried out and trypan blue exclusion and propidium iodide staining followed by flow cytometry were used to assess viability and DNA fragmentation respectively. Cardiomyocytes had a 25-150 fold higher IC 50 value than the acute leukemia cell lines, indicating selectivity. To assess whether apoptosis was induced by anthracyclines, caspase 3 activity was measured and found to be increased at 24 hours in Jurkat cells which preceded decreases in viability, supporting an apoptotic mechanism of cell death. GSH levels also decreased markedly after 24 hours of treatment with anthracyclines in this cell line, however, a pan-caspase inhibitor did not block GSH depletion, indicating that these events occur independent of each other. To evaluate whether antioxidants conferred protection against loss of viability in all cell types, cells were pretreated for at least 30 minutes with antioxidants and then treated with doxorubicin and daunorubicin for 24 hours. Antioxidants used were N-acetylcysteine (NAC, a GSH precursor and amino acid source), GSH ethyl ester (cell permeable form of GSH), tiron (free radical scavenger) and trolox (a water soluble form of vitamin E). GSH ethylester did not prevent cytotoxicity of anthracyclines in acute leukemia lines or cardiomyocytes. Therefore boosting GSH levels in leukemia cells does not reverse cytotoxicity. Trolox, however, did block anthracycline induced cell death in ML-1 cells, suggesting that vitamin E supplementation would counteract leukemia cell specific effects of anthracyclines on AML cells. Tiron protected PBMC from doxorubicin cytotoxicity but did not protect leukemia cells or cardiomyocytes, hinting at a protective strategy for normal non-leukemia blood cells. Interestingly, NAC did not interfere with the cytotoxic effects of anthracyclines on acute leukemia cells or PBMC, but protected H9C2 cells from daunorubicin cytotoxicity. Taken together, these data reveal differential protective effects of antioxidants in cardiomyocytes and PBMCs relative to ALL and AML cells. Our work indicates that NAC can protect cardiomyocytes without interfering with anthracycline cytotoxicity in acute leukemia cells. In humans, one randomized control trial tested the addition of NAC to doxorubicin therapy, detecting no evidence of cardioprotective activity by chronic administration of NAC. However, the schedule used for administration of NAC in that study may not have been optimal, and biomarkers for oxidative stress reduction by NAC were not incorporated into the trial. Previously, other antioxidants have been used with very limited clinical success and possible contributing factors include inadequate sample size, choice of agent, dose used, duration of intervention and the lack of biomarker endpoints. Designing a cardioprotective and antioxidant strategy with attention to these factors may prove to be efficacious in protecting cardiac cells without interfering with the antitumoral effect of anthracyclines. To this end, our data suggests that trolox and vitamin E analogues should not be used in acute leukemia as they may interfere with the cytotoxic action of anthracyclines but NAC or cysteine may be used as cardioprotectants.

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QA: Jordan Spieth Shares a Coke with Special Olympics Athlete and Employee Matthew Wynne

Well before PGA TOUR golfer, three-time major champion and Ambassador Jordan Spieth made TOUR history, he knew he wanted to make a difference on and off the course. The source of his inspiration? His sister Ellie.Born with a neurological disorder, Ellie challenged her older brother to prioritize

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Coca-Cola is incentivizing recycling at the 2018 Special Olympics USA Games through “reverse” vending machines that let fans give back in more ways than one. Attendees can stop by the two recycling stations in Seattle to deposit PET bottles or aluminum cans. Each recycled package triggers a $.05 donation to Special Olympics Washington through the Coca-Cola Give platform, and consumers will be prompted to text “give” to 2653 to learn about additional opportunities to support their local communities. The

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Between fielding grounders and taking cuts at Atlanta Braves spring training camp in Kissimmee, Fla., Dansby Swanson got an idea. The 24-year-old shortstop and Atlanta native wanted to both celebrate and give back to his beloved hometown through a charitable brand borrowing the city’s nickname: #AllThingsLoyal (ATL). The goal? To give shouts-out to the unique aspects of Atlanta culture – from music to sports to brands that call the city home – that have been a part of Swanson’s life. On every Braves

Blog Home / Knitting Blog / Mystery Stash Yarns: Determining Yarn Weights

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It’s difficult to organize your yarn, especially ifmost of it has been given to you by family members cleaning out their attics. Or maybe your stash is composed ofskeins you picked up from secondhand stores along withscrap yarnfrom old knittingorcrochetprojects.

Inheriting yarn and having a huge stash to choose from is great, especially for LOLLIPOPS Ankle boots outlet classic 100% original cheap price wiki cheap price discount excellent 08zDLC
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, and often this information isn’t available on the yarn. It could be because the label is torn or yellowed — or maybe there’s no label at all.

Yarn weight is determined by the diameter of a yarn strand? Bulky-weight yarns work up quickly because the yarn strand is thick in diameter. Lace weights are airy because their strands are thinner.

Wrapping the yarn around the pencil determines whether the yarn wraps many times around the pencil, like a lighter-weight yarn would,or the yarn doesn’t wrapas many times around the pencil, like a heavier-weight yarn would.

See the difference between the two yarn weights here? The first is a DK weight and the second is a super-bulky yarn.

It’s also an option to wrap your mystery yarn around a ruler, eliminating the need for an object with a consistent circumference. You can even buy a special clearance under really cheap price BCBGeneration BgNomad B2 Black Casual Sneakers clearance 100% original IuU5X
that has notches to hold the yarn in place while you wrap and comes with a handy card to help you categorize.

You can wrap the yarn around your knitting needle or crochet hook — but only if the tools has a consistent circumference. If it tapers or has an ergonomic handle, it won’t work.

Begin by wrapping the yarn around thepencil. Don’t wrap too tightly.The goal is to get the yarn strands as close as possible without overlapping them or leaving holes.

Usually wrapping about an inch should give you an accurate measurement, but if you’re using a yarn with a shape that isn’t consistent, like an eyelash yarn, you should wrap it for more than an inch to get the most accurate measurement possible.

Once you’ve wrapped your yarn, count the number of times you wrapped it around the pencil within the first inch. Then, compare that number with the numbers on the WPI chart below.

So for example, if your yarn wrapped around the pencil eight times in one inch, your yarn is bulky-weight. Ifthe yarnwrapped around the pencil 16 times in an inch, it’s a sport weight yarn.

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You may not be the only one reading your messages in your Gmail account.

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. In some cases, it's not just the developers' computers but their human employees who are reading Gmail users' messages, according to the report.

Google has long allowed software developers the ability to access users' accounts as long as users gave them permission. That ability was designed to allow developers to create apps that consumers could use to add events to their Google Calendars or to send messages from their Gmail accounts.

But marketing companies have created apps that take advantage of that access to get insights into consumers' behavior, according to the report. The apps offer things such as price-comparison services or travel-itinerary planning, but the language in their service agreements allows them to view users' email as well. In fact, it's become a "common practice" for marketing companies to scan consumers' email, The Journal reported.

It isn't clear how carefully Google is monitoring such uses. Many consumers may not be aware that they've given apps such access to their accounts. Even if they are, Facebook's new cheap online Top Quality Kanye West Wave Runner 700 Boots Grey Casual Shoes for men 700s womens mens Sports Sneakers trainers outdoor designer shoes original online best sale latest collections sale online YWUaXxQ8
offers a worrisome example of how similar access to consumer data can be abused.

Here's how to see which apps have access to your Google account and how to block them from accessing it in the future.

From your Google Account homepage, go to the Sign-in Security section.

To get to your Google Account page, select the "Account" icon from the app menu in the top right-hand corner of your Gmail account or navigate to myaccount.google.com .

In that section, you'll see all of the apps to which you've given any kind of access since you created your account.

You'll see what kinds of information and services inside your Google account to which the apps have access.

The three groups are apps that allow for "Signing in with Google," "Third-party apps with account access," and "Google apps."

It's obvious what Google apps are — things like Chrome and Drive. But here's how the two other groups differ:

Apps in the "Signing in with Google" section have access to your name, email address, and profile picture. But in some cases they may have access to more of your information — potentially a lot more, such as the ability to read and delete your email messages.

You most likely gave the "Signing in with Google" apps permission to access such data because you wanted to use your Google login to sign into your accounts with them instead of having to create separate user accounts and passwords. But some companies that use Google's apps in their workplaces also require their employees to use their Google login to sign in to other apps and services.

The "Third-party apps with account access" typically have access to much more than just your basic profile information. In fact, according to a Google support page , these apps often "can see and change nearly all information in your Google Account."

Developers whose apps have such access to your account can't change your password, delete your account, or use Google Pay on your behalf, but they can read your email — or have their employees do it.

Some apps require those kinds of permissions to do what you've asked them to do. If you want to be able to use a mail app on your computer to manage your Gmail account or your Google calendar, it needs to be able to read and delete messages or appointments.

But you should make sure you trust the apps and developers that have such access to your accounts and that you are giving them only as much access as they need.

After clicking on that button you'll have to click "OK" to confirm that you really want to block the app. The app should then disappear from the list of apps that have access to your account and should no longer have any ability to view or do anything else with your email or other data.

It's a good idea to check the "Apps with access to your account" page every few months to keep your account safe from wandering eyes.

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