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|By PR.com Newswire
Article Rating:
|April 30, 2014 02:21 PM EDT
Edwardsville, IL, April 30, 2014 --(PR.com)-- DataRecovery.com, a world leader in professional data recovery services, released a list of tips for personal computer users to protect against a recently discovered Adobe Flash exploit in Internet Explorer.
The United States Department of Homeland Security recently warned PC users against using Internet Explorer, as a bug discovered by FireEye Research Labs could allow a hacker to circumvent the security protections in various Windows operating systems. The hack uses Adobe Flash, a popular web browser add-on.
"Many users and small businesses are simply not using Internet Explorer to avoid the exploit, but this is not an effective solution," said Michael Katich, Lead Programmer and Analyst at DataRecovery.com. "If Internet Explorer is your default browser, you're one click away from a serious security risk."
"Even if your default browser isn't Internet Explorer, a hacker could still infiltrate your system," Katich explained. "For instance, a program installed on your computer could instruct Internet Explorer to run, which could then allow unauthorized users direct access to your machine."
DataRecovery.com offers the following solutions to the exploit:
● Disable the Adobe Flash Plugin in Internet Explorer. After clicking the Settings menu in Internet Explorer, click "Manage add-ons," then find the Adobe Flash plugin and click "Disable."
● Uninstall Adobe Flash Altogether. Flash can be uninstalled through Windows' Add/Remove Programs interface. As Flash is a commonly used program, this may be an unrealistic solution, but it's a viable option for high-security systems.
● Enable Enhanced Protected Mode in Internet Explorer 10 or Later. DataRecovery.com recommends keeping web browsers updated to prevent security issues. Newer versions of the browser have an enhanced protection feature, accessible through the Internet Options menu. On the "Advanced" tab, click "Enable Enhanced Protected Mode" to add an extra layer of protection to the browser.
● Uninstall Internet Explorer. If you do not use Internet Explorer regularly, you can completely uninstall it. Go to Control Panel, click Add or Remove Programs, then click Turn Windows Features On or Off. Depending on your Windows version, you can then un-click Internet Explorer or select the program to uninstall it.
While these steps can protect against current versions of the exploit, DataRecovery.com also recommends regularly updating web browser software and avoiding potential security issues by using firewalls and third-party security programs to mitigate risks.
Datarecovery.com is a world leader in data recovery and computer forensics. With four locations across the US and Canada, the company provides a variety of data recovery services to thousands of clients each year. Visit www.datarecovery.com for more information.
Contact Information:
Datarecovery.com, Inc.
Ben Carmitchel
Contact via Email
Michael Katich 618-307-0070 ext. 257
Read the full story here: http://www.pr.com/press-release/555943
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In his keynote at 18th Cloud Expo, Andrew Keys, Co-Founder of ConsenSys Enterprise, provided an overview of the evolution of the Internet and the Database and the future of their combination – the Blockchain. Andrew Keys is Co-Founder of ConsenSys Enterprise. He comes to ConsenSys Enterprise with capital markets, technology and entrepreneurial experience. Previously, he worked for UBS investment bank in equities analysis. Later, he was responsible for the creation and distribution of life sett...
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It's easy to assume that your app will run on a fast and reliable network. The reality for your app's users, though, is often a slow, unreliable network with spotty coverage. What happens when the network doesn't work, or when the device is in airplane mode? You get unhappy, frustrated users. An offline-first app is an app that works, without error, when there is no network connection. In his session at 18th Cloud Expo, Bradley Holt, a Developer Advocate with IBM Cloud Data Services, discussed...
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19th Cloud Expo, taking place November 1-3, 2016, at the Santa Clara Convention Center in Santa Clara, CA, will feature technical sessions from a rock star conference faculty and the leading industry players in the world. Cloud computing is now being embraced by a majority of enterprises of all sizes. Yesterday's debate about public vs. private has transformed into the reality of hybrid cloud: a recent survey shows that 74% of enterprises have a hybrid cloud strategy. Meanwhile, 94% of enterpri...
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Our Mission
The Prevention Project believes that in order to eradicate Human Trafficking, the selling of human beings for profit, we must educate young people on the lures of trafficking, and invest in character and leadership development; so we not only prevent sex trafficking from occurring, but create and equip leaders to bring a lasting change for our communities and beyond.
About the Program
The Prevention Project is currently a 6-lesson academic curriculum (with an alternate 4-lesson model) administered to high and middle school students in their classrooms. The program focuses on educating the students on the facts and lures of human trafficking locally and globally; developing healthy self-awareness and boundaries; strengthening character; and fostering leadership amongst the students. The Prevention Project empowers the students to be abolitionists, to take the lead in the fight against human trafficking, and to be the ones who see the final demise of modern day slavery.
Who We Are
The Prevention Project is supported by Richmond Justice Initiative, a grassroots, non-profit organization whose mission is to educate, equip, and mobilize communities to be a force in the global movement to end human trafficking.
Furthermore, The Prevention Project was created, developed, and executed by a committed group of advocates from leading anti-trafficking organizations who have a passion to act against the perils of human trafficking, and who believe that if change is going to happen, it must begin with the young generations.
Interest / Contact
The Prevention Project is continually looking for volunteer abolitionists. From school teachers to parents, from newly-graduated to newly-entered high school, there is a place for you on The Prevention Project team. We are confident that you can be a invaluable partner in a movement that brings justice, freedom, and healing to victims of slavery
Please get in contact with us today, so we can match your greatest talents and gifts, with our greatest needs.
Timeline Photos
#FreedomFriday Read more...
Timeline Photos
Want to help us spread prevention education to more schools? As we celebrate the beginning of our 5th year of the Prevention Project at the end of this summer, join us by asking 5 friends to partner with you in supporting the Richmond Justice Initiative by matching what you give in the month of June. #makemeamatch #JuneJubilee To become a Freedom Keeper or submit your one-time donation, click here: http://richmondjusticeinitiative.com/donate/ Read more...
I survived human trafficking. That makes me the exception to the rule | Crystal Isle
I am one of a handful of victims that has survived to lead a different life. Now, I am determined to be part of the solution Read more...
Timeline Photos
We're proud to say that one of our teachers, Colleen Savino, was selected for a prestigious fellowship from the Lowell Milken Center for Unsung Heroes for her work with spreading the Prevention Project outside the classroom as well as other endeavors to #preventtrafficking. Her drive and compassion is inspiring! Read more...
International Justice Misssion
human rights agency that brings rescue to victims of slavery, sexual exploitation and other forms of violent oppression.

subset: commoncrawl


text:
deep snorkeling
Credit: Andrey Artykov
Creative #: 143916895
License type: Royalty-freeRoyalty-free pricing is based solely on the size of the product you need, not the specific use. You don't have to pay any additional royalties on a use-by-use basis. Once you license a royalty-free product, you may use it multiple times for multiple projects without paying additional fees. (Pornographic, defamatory, libelous or otherwise unlawful use of any image is, of course, prohibited.)
Collection: Vetta
Release info: Model released
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Deep Snorkeling Stock PhotoAdult,Adults Only,Aquatic Sport,Bali,Beautiful Woman,Beauty,Beauty In Nature,Bikini,Blue,Color Image,Coral,Deep,Diving Flipper,Elegance,Fish,Full Length,Healthy Lifestyle,Horizontal,Indian Ocean,Leisure Activity,Lifestyles,One Person,One Woman Only,One Young Woman Only,Only Women,People,Photography,Recreational Pursuit,Reef,Sea,Side View,Snorkel,Snorkeling,Sunbeam,Swimming,Tropical Climate,Undersea,Underwater,Underwater Diving,Vacations,Young AdultPhotographer Andrey ArtykovCollection: Vetta Andrey Artykov


text:
Scoop: THE GOLDBERGS on ABC - Today, June 22, 2016"Weird Al" - Visiting her grandmother from out of town, Dana is not enthusiastic about going to a Weird Al concert, so Adam comes to accept their relationship may end. Meanwhile, when Erica and Barry become peer counselors at school, they soon ... Broadway World, 1 week ago
Scoop: THE GOLDBERGS on ABC - Wednesday, July 6, 2016 - Broadway World, 1 week ago
Indiegogo's Super Troopers 2″ Offers Update: Military Base Visit, Attack Dog/Taser Demonstrations, & Mustache Re-Growths
On Thursday, the casting crew of Indiegogo alum , Super Troopers 2, announced an update about the film's progress which included a very unique items. Last year, production studio Broken Lizard announced the sequel just 14 years after the first ...Crowdfund Insider, 1 month ago
Super Troopers 2 Continues To Move Toward Release With A Brand New Poster
Fox Searchlight Remember that Super Troopers sequel? The one that was a massive crowdfunding smash ? Well, Farva fans, get excited. Were that much closer to seeing Super Troopers 2 . Director and Broken Lizard member Jay Chandrasekhar used the ...Dime Magazine, 1 month ago
DDI acquires international distribution rights for 'Super Troopers 2'
DDI President & CEO, Jason Moring has just announced on May 11 that DDI got a deal to sell the international distribution rights for "Super Troopers 2." DDI will also be launching the picture during the Cannes Film Festival on the Marche du Film.Examiner.com, 1 month ago
Skipper Shinde's makes Thane slip to 91
MUMBAI: Medium pacer and Mumbai Police City Riders skipper Santosh Shinde bowled with fire to help his side score a thumping 98 runs win over Thane Marathas in the Mitsui Shoji T-20 League, at the Police Gymkhana, yesterday. Thane Marathas skipper ...Afternoon Despatch & Courier, 1 month ago
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6 a.m. to 6:30 p.m. PT
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Nintendo DS
Garfield receives a royal invitation from his new friend Prince XII to join him for some lasagne. But when he arrives at Carlyle castle the gates are closed and no one is there to let him in. Help this famished feline use his smarts - and sometimes his weight - to make it inside in time!
• First- person and map overview
• Touch Screen: Smooth mouse-like viewing
• Microphone: Use sound to activate objects found in game
• Game play is a mix of platform activities, puzzles, sliding challenges and mazes.
• Storyline and environmental settings from theatrical release.


text:
Nepal Brass Lionlock With Tail As Loop Rare Unique
This item has been shown 1742 times.
Nepal Brass Lionlock With Tail As Loop Rare Unique:
here to see all my listed items
Welcome !!!
Well, this is my NINTH year as an seller. It is hard to believe that so much time and so many of my goods have reached your collections from my years of collected goods. It is a lot of work to haul these goods out from the boxes and scan, photograph and prepare them for sale, but harder to let go things that have taken me all these years in Asia to accumulate. At least I will be able to have had the pleasure to gather them over the years and cherish the memories associated with their finding. I hope that all of you have been pleasedwith over 3400on my response.
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This is aUNIQUEClassical Nepalese Animal LOCK ( LION ) made more than 30 years ago in Nepal. It has aPERFECTpatina,and was acquired from a village near where I worked in 1978. This very old piece has beautiful patina, is uncleaned.
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Neat work from many travels inSouth and SE Asia ! No one else will get anything like this.
Nepal Brass Lionlock With Tail As Loop Rare Unique:
Burmese 7 Piece Tiffin Box 14.5" X 6" Food Basket
Antique Burmese Shan States Marble Statue Of Buddha, Myanmar, 19th C.
Antique Burmese Nat Riding Horse
Antique Burmese Carved Deva Wood Panel
Antique Burmese Spirit Nat Figure, 18th Century
Vintage Rare And Important Myanmar Burmese Lacquer Painting Of Buddhist Monks


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The Celtics nearly completed the greatest comeback in the team's illustrious history but fell just short, dropping Game 1 of the Eastern Conference semifinal series to the Orlando Magic, 95-90, Monday night at TD Banknorth Garden. Consecutive three-pointers by Brian Scalabrine cut the Magic lead to six, 89-83 with 2:40 remaining and a reverse layup by Glen Davis cut it to four, 89-85, with 2:08 remaining. The Celtics trailed 65-37 with 8:56 remaining in the third quarter. The Celtics began their rally by closing to 78-62 at the end of the third. The comeback would have been even greater than the 26-point deficit overcome in Game 3 of the 2002 Eastern Conference Finals at the Garden. Dwight Howard finished with 16 points and 22 rebounds for Orlando while Paul Pierce led all scorers with 23. For complete coverage, visit the Green Street blog.
Dale, Michael and Jerry dig into the details of this draft for the Patriots with ESPN's Mike Reiss.
Giardi and Price discuss the Tom Brady appeal getting overturned and Roger Goodell's victory tour. The guys can't believe the victory lap and some of his behavior. The more you listen to him, the more frustrating his behavior becomes.
Giardi and Price break down how the teams in the AFC East altered their futures after the NFL Draft weekend.
Danny Ainge joins Glenn and Christian to explain the Celtics draft process; and he also discusses the trade rumors that permeated the night.
Mut is flying solo the last hour, but he's giving reaction and analysis as the Celtics draft a power forward out of France by the name of Guerschon Yabusele and getting some early grades for the Celtics
Mut and Kirk are talking more about the Celtics pick of Jaylen Brown and can't seem to find anyone who thinks it's a good pick or can make a case for why the Celtics took him third overall.
Eduardo Rodriguez and the Sox stumbled in their 13-7 loss to the Rays. Mut recaps the game and takes your calls on all things Boston baseball.
Christian recaps the Red Sox 6-2 loss to the Rangers.
Joe, Tim, and Lou talk with Red Sox shortstop Xander Bogaerts after his walk-off RBI single propelled the Red Sox past the White Sox 8-7.
DJ and Pete continue to assess the season that was for the Bruins and look toward the future for the franchise and how they can improve.
DJ and Pete are together for the final Sunday Skate of the season. They get into their overall thoughts on the season, the Bruins keeping Claude Julien on as head coach and the end-of-season press conferences last week. They discuss the rebuild process, what the Bruins need and how they can obtain it. Plenty of callers have their own theories and opinions on all of these topics as well.
Butch is joined by two-thirds of the Sunday Skate show in DJ and Pete. The guys discuss the problems with Bruins including leadership and grit, who should stay and who should go and if Claude is to blame.
John, Gerry and Kirk open the show Monday discussing the Red Sox slide, as well as WEEI.com beat writer Rob Bradford electing to go to a Texas waterpark by himself.
A conversation about OJ Simpson still being in the Hall of Fame and Peter King's desire to keep character concerns out of HOF voting spurns a discussion about Darren Sharper and others who Minihane wants banned for life from the Hall.
It's quite the Sporty R. McKenzie 8am hour as the guys muscle through Red Sox trade possibilities.
OMF looks at the possibilities for Free Agency, specifically reports out of Canada about the possibility of Steven Stamkos and the Bruins.
We should be closing in on a Deflategate ruling soon, James Harrison will talk PED's on his terms, and $10,000 bongs?
Glenn has an Exclusive BBQ, and Lou whines about Friday's whines
We discuss the reports that Boston is on the short list of cities for both Kevin Durant in the NBA and Steven Stamkos in the NHL to potentially end up in. The chances aren't great but we discuss them and dream about it.
What was meant to be just a small portion of our show exploded in to a huge topic as we comment on and take your reaction to Ray Bourque's DUI arrest this past weekend, and the news that his BAC was 3 times the legal limit.
Boston has had enough of Clay Buchholz, but who else ran out of excuses here through the years?
Former Celtics General Manager Jan Volk joins Kirk Minihane for a discussion that any Celtics fan will love. Kirk and Jan talk about the legendary 85/86 Celtics and how the team was constructed and of course the decision to draft Len Bias and his tragic death.
Kirk Minihane sits down with John Tomase to talk about the current political landscape, John's desire to write about social issues, and of course Spygate is discussed.
Kirk Minihane is joined by one of his radio heroes, Artie Lange. They discuss everything from Artie's comedy career, his time with Howard Stern, his issues with drugs and prostitutes, and the comedy show to benefit slain Officer Ronald Tarentino Jr.
Ben, Russ & Alex recap the 4-0 loss the USMNT suffered to Argentina in the COPA America Centenario semifinal. Then they catch up with the EURO's, and recap if their predicted winners are still in the tournament.
Former Celtics General Manager Jan Volk joins Kirk Minihane for a discussion that any Celtics fan will love. Kirk and Jan talk about the legendary 85/86 Celtics and how the team was constructed and of course the decision to draft Len Bias and his tragic death.
This week we look back at the US Open.
It's quite the Sporty R. McKenzie 8am hour as the guys muscle through Red Sox trade possibilities.More from this show
Gerry Callahan has been invited to Donald Trump's upcoming Wednesday fundraiser. Should he go? Is Trump in trouble per the latest polls?More from this show
Kirk Minihane's Monday 'Headlines' including Bill Clinton's jogging list, Pope Francis apologizing in Italian, and Ray Bourque's DWI apologyMore from this show
Arcand talks about the Sox and their recent struggles on the mound while previewing the Sox/Rangers rubber match today. He also gets into the Celtics and their future.More from this show
With Boston reportedly getting one of five golden tickets to sit down with pending free agent Kevin Durant, the guys discuss what kind of pitch Danny Ainge might make.More from this show


text:
Conflicts of interest: Patent 12B152PRWO; University of South Florida; D.P. D'Agostino, A. Poff, P. Arnold, "Targeting cancer with metabolic therapy and hyperbaric oxygen." P. Arnold (Savind Inc.) has received financial support (ONR N000140910244) from D. D'Agostino (USF) to synthesize ketone esters. The remaining authors have no conflicts of interest
Cancer Therapy
Ketone supplementation decreases tumor cell viability and prolongs survival of mice with metastatic cancer
Version of Record online: 14 MAY 2014
DOI: 10.1002/ijc.28809
© 2014 The Authors Published by Wiley Periodicals, Inc. on behalf of UICC
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
International Journal of Cancer
Volume 135, Issue 7, pages 1711–1720, 01 October 2014
Additional Information
How to Cite
Poff, A.M., Ari, C., Arnold, P., Seyfried, T.N. and D'Agostino, D.P. (2014), Ketone supplementation decreases tumor cell viability and prolongs survival of mice with metastatic cancer. Int. J. Cancer, 135: 1711–1720. doi: 10.1002/ijc.28809
Publication History
- Issue online: 15 JUL 2014
- Version of Record online: 14 MAY 2014
- Accepted manuscript online: 26 FEB 2014 01:41AM EST
- Manuscript Accepted: 11 FEB 2014
- Manuscript Received: 16 SEP 2013
Funded by
- Scivation Inc
- Abstract
- Article
- References
- Cited By
- Warburg effect;
- ketone;
- metastasis
Cancer cells express an abnormal metabolism characterized by increased glucose consumption owing to genetic mutations and mitochondrial dysfunction. Previous studies indicate that unlike healthy tissues, cancer cells are unable to effectively use ketone bodies for energy. Furthermore, ketones inhibit the proliferation and viability of cultured tumor cells. As the Warburg effect is especially prominent in metastatic cells, we hypothesized that dietary ketone supplementation would inhibit metastatic cancer progression in vivo. Proliferation and viability were measured in the highly metastatic VM-M3 cells cultured in the presence and absence of β-hydroxybutyrate (βHB). Adult male inbred VM mice were implanted subcutaneously with firefly luciferase-tagged syngeneic VM-M3 cells. Mice were fed a standard diet supplemented with either 1,3-butanediol (BD) or a ketone ester (KE), which are metabolized to the ketone bodies βHB and acetoacetate. Tumor growth was monitored by in vivo bioluminescent imaging. Survival time, tumor growth rate, blood glucose, blood βHB and body weight were measured throughout the survival study. Ketone supplementation decreased proliferation and viability of the VM-M3 cells grown in vitro, even in the presence of high glucose. Dietary ketone supplementation with BD and KE prolonged survival in VM-M3 mice with systemic metastatic cancer by 51 and 69%, respectively (p < 0.05). Ketone administration elicited anticancer effects in vitro and in vivo independent of glucose levels or calorie restriction. The use of supplemental ketone precursors as a cancer treatment should be further investigated in animal models to determine potential for future clinical use.
- βHB
- AcAc
calorie restriction
fluorodeoxyglucose positron emission tomography
- Glu
histone deacetylase
- i.p.
ketogenic diet
ketone ester
monocarboxylate transporter
- mtDNA
mitochondrial DNA
reactive oxygen species
- s.c.
succinyl CoA 3-ketoacid CoA transferase
A century ago, Otto Warburg discovered that cancer cells display a unique metabolic phenotype of lactate fermentation in the presence of oxygen. This phenotype, known as the Warburg effect, enables tumor visualization using fluorodeoxyglucose positron emission tomography (FDG-PET) scans owing to the elevated rate of glucose consumption in most cancers. Metabolic therapies can exploit this phenotype, offering novel therapeutic directions aside from the classically targeted cytotoxic and gene-based therapies. The Warburg effect exposes a fundamental weakness of cancer cells, reliance on excess glucose for survival and maximal proliferation. Fasting, calorie restriction (CR) and the carbohydrate-restricted ketogenic diet have been successfully used to limit glucose availability and slow cancer progression in a variety of animal models and human studies.[1-9] These dietary manipulations produce a physiological metabolic shift to an unfavorable environment for glucose-dependent cancer cells. Previously, the anticancer effects of these dietary manipulations have largely been attributed to decreased circulating blood glucose, which limits energy substrates for cancer cells. New evidence suggests, however, that the physiological state of ketosis and elevated circulating ketones also have anticancer effects.
Recently, Fine et al. demonstrated that a carbohydrate-restricted ketogenic diet inhibited disease progression and promoted partial remission in patients with advanced metastatic cancers from various tissue origins.[10] On average, the patients did not exhibit a drop in glucose from baseline, suggesting that decreased glucose availability was not the sole or primary cause of efficacy. Interestingly, the study found that the most important factor dictating the patients' response to therapy was the degree of elevated ketosis from baseline. Indeed, a prominent metabolic shift to higher levels of ketosis correlated with reduced disease progression, stable disease or partial regression. A small number of reports have investigated the effects of ketones on cancer growth in vitro. Acetoacetate (AcAc) and β-hydroxybutyrate (βHB) are the two most abundant and physiologically relevant of the three ketone bodies. Acetone is produced as a nonenzymatic byproduct of AcAc metabolism and is rapidly excreted in the lungs. AcAc supplementation inhibited proliferation and ATP production in seven aggressive human colon and breast cancer cell lines but did not affect proliferation in healthy primary fibroblasts.[11] Similarly, βHB inhibited proliferation of transformed lymphoblasts, HeLa cells and melanoma cells in a dose-dependent manner up to 20 mM.[6] In neuroblastoma cells, βHB and AcAc supplementation decreased viability and increased apoptosis, but had no effect on fibroblasts.[12]
Although ketone bodies are efficient energy substrates for healthy extrahepatic tissues, [13] cancer cells cannot effectively use them for energy. Widespread mitochondrial pathology has been observed in most if not all tumors examined, including decreased mitochondrial number, abnormal ultrastructural morphology, mitochondrial swelling, abnormal fusion–fission, partial or total cristolysis, mtDNA mutations, altered mitochondrial membrane potential and abnormal mitochondrial enzyme presence or function, among others.[14-19] These defects in mitochondrial structure and function impair respiratory capacity and force a reliance on substrate-level phosphorylation for survival.[20] As ketone bodies are metabolized exclusively within the mitochondria, cancer cells with impaired mitochondrial function are unable to efficiently metabolize ketone bodies for energy. Indeed, unlike healthy cells, ketone bodies fail to rescue glioma cells from glucose withdrawal-induced death.[21]
Although mitochondrial dysfunction explains the inability of cancer cells to effectively use ketones for energy, the anticancer effects of ketones in a normal glucose in vitro environment are not immediately clear. Upon closer examination, ketone bodies possess many characteristics that can impair cancer cell survival and proliferation. (i) Ketone bodies inhibit glycolysis, thus decreasing the main pathway of energy production for cancer cells.[22] (ii) Cancer cells thrive in an environment of elevated reactive oxygen species (ROS) production but are very sensitive to even small changes in redox status.[23] Ketones decrease mitochondrial ROS production and enhance endogenous antioxidant defenses in normal cells, but not in cancer cells.[13] Ketone metabolism in healthy cells near the tumor may inhibit cancer cell growth by creating a less favorable redox environment for their survival. (iii) Ketone bodies are transported into the cell through the monocarboxylate transporters (MCTs), which are also responsible for lactate export. It has been shown that inhibiting MCT1 activity or inhibiting lactate export from the cell dramatically decreases cancer cell growth and survival.[24] Ketones may impair cancer cells indirectly by competitive inhibition of the MCTs, decreasing critical lactate export from the cell. (iv) Recently, Verdin and coworkers demonstrated that βHB acts as an endogenous HDAC inhibitor at millimolar concentrations easily achieved through fasting, CR or ketone supplementation such as with a ketone ester (KE).[25] Thus, ketone bodies may elicit their anticancer effects by altering the expression of oncogenes and tumor suppressor genes under control of the cancer epigenome.[26] Clearly, ketone bodies exhibit several unique characteristics that support their use as a metabolic therapy for cancer.
The Warburg effect is especially prevalent in aggressive cancers and metastatic cells. Metastasis, the spreading of a primary tumor to distal locations, is the primary cause of cancer morbidity and mortality and is responsible for more than 90% of cancer-related deaths.[27] To make significant strides toward long-term cancer management, we must evaluate therapies that are effective against late-stage metastatic cancers. The major obstacle preventing the discovery of such treatments has been the lack of animal models that mimic the true metastatic phenotype and accurately predict the clinical success of therapeutics. The VM-M3 model of metastatic cancer is a novel murine model that closely mimics the natural progression of cancer invasion and metastasis.[28] The original VM-M3 tumor arose as a spontaneous brain tumor in a VM/Dk inbred mouse. The VM-M3 tumor was adapted to cell culture and transduced with the firefly luciferase gene to allow for in vivo bioluminescent tracking of tumor growth.[29] VM-M3 cells express many in vitro and in vivo characteristics of human glioblastoma multiforme with macrophage or microglial properties.[28-30] When implanted subcutaneously, the VM-M3 cells are morphologically similar to histiocytes and rapidly produce systemic metastasis, forming tumors in all major organ systems, most notably the liver, lung, kidney, spleen, brain and bone.[28] The VM-M3 model of metastatic cancer spreads naturally in an immunocompetent host, and chemotherapeutic agents inhibit metastatic spread in this model similar to their observed effects in humans.[31] The VM-M3 model has many advantages that support its use as a representation of the true metastatic disease state and has therefore been used in our study.
Although the literature strongly suggests that ketone bodies impede cancer growth in vitro, the in vivo efficacy of dietary ketone supplementation has not been adequately examined. It is possible to raise blood ketone levels without the need for carbohydrate restriction by administering a source of supplemental ketones or ketone precursors. 1,3-Butanediol (BD) is a commercially available food additive and hypoglycemic agent that is converted to βHB by the liver.[32, 33] The KE elevates both AcAc and βHB in a dose-dependent manner to levels beyond what can be achieved with the KD or therapeutic fasting.[34] Oral administrations of BD and KE have been shown to elevate blood ketones for at least 240 min in rats.[34] As ketone bodies appear to elicit anticancer effects, and metastasis is the most significant obstacle in the successful treatment of neoplasms, we tested the efficacy of ketone supplementation in the VM-M3 cell line and mouse model of metastatic cancer.
Material and Methods
Cell culture
VM-M3/Fluc cells were received as a gift from T. Seyfried (Boston College) where they were obtained from a spontaneous tumor in a VM/Dk inbred mouse and adapted to cell culture.[28] VM-M3 cells were transduced with a lentivirus vector containing firefly luciferase under control of the cytomegalovirus promoter (VM-M3/Fluc).[28] The VM-M3/Fluc cells were cultured in Eagle's minimum essential medium with 2 mM l-glutamine (ATCC, Manassas, VA), 10% fetal bovine serum (Invitrogen, Grand Island, NY), 1% penicillin–streptomycin (Gibco, Invitrogen) and high glucose (25 mM d-glucose; Fisher Scientific, Waltham, MA). Cells were maintained at 37°C in 95% air and 5% CO2.
VM-M3/Fluc cells were plated into 35-mm six-well plates at a density of 50,000 cells/mL in high (25 mM) or low (3 mM) glucose media with or without ketone supplementation (5 mM βHB; Sigma-Aldrich, St. Louis, MO). Nonketone-supplemented media contained an equal volume of βHB diluent (50 µL dH2O). Cells were grown for 24, 48, 72, 96, 120 and 144 hr to determine a growth curve. All media were replaced with respective treatments every 48 hr. Each time point was run in triplicate. Cells were collected by scraping and counted using standard trypan blue hemocytometry. Plates were visually inspected to ensure all cells were harvested before counting.
Viability was assessed with the LIVE/DEAD® Viability/Cytotoxicity Kit (Invitrogen). VM-M3/Fluc cells were plated into 22-mm 12-well plates containing poly-d-lysine-coated glass coverslips (BrainBits, Springfield, IL) at a density of 50,000/mL in control media and allowed to grow for 24 hr. At 24 hr, media were replaced with treatment [high (25 mM) or low (3 mM) glucose] with or without 5 mM βHB ketone supplementation, and cells were allowed to grow for 24 hr. Nonketone-supplemented media contained an equal volume of βHB diluent (25 µL dH2O). At 48 hr, cells were washed with d-PBS and incubated in 2 µM calcein AM (Ex/Em: 495/515) and 4 µM ethidium homodimer-1 (Ex/Em: 525/590) in Dulbecco's phosphate buffered saline (D-PBS) for 30 min at 37°C. After incubation, wet coverslips were inverted, mounted and sealed on a microscope slide. Cells were visualized using fluorescence confocal microscopy with FIT-C and TRIT-C filters to identify live and dead cells, respectively. Each treatment was run in triplicate with ten frames analyzed per coverslip with a Nikon TE2000E using a 10× objective. The numbers of live and dead cells were counted per frame to determine percent viability.
Three breeding pairs of the VM/Dk inbred strain of mice were used to establish and propagate a VM/Dk mouse colony in the University of South Florida Morsani College of Medicine Vivarium according to standard murine husbandry protocol. Adult male mice (2–4 months of age) were used for our study, with all procedures completed within strict adherence to the NIH Guide for the Care and Use of Laboratory Animals and were approved by the University of South Florida Institutional Animal Care and Use Committee (IACUC; protocol number R4137).
Tumor implantation
Approximately 1 million VM-M3/Fluc cells in 300 µL PBS were implanted s.c. into the abdomen of VM/Dk mice using a 27g needle. VM-M3/Fluc inoculation results in rapid and systemic metastasis as previously described.[28]
Ketone supplementation and diet administration
Mice were fasted overnight before tumor inoculation and randomly assigned to treatment group. Control mice received standard diet (SD) rodent chow (2018 Teklad Global 18% Protein Rodent Diet, Harlan) composed of 60% carbohydrate fed ad libitum. Mice receiving supplemental ketones were administered their respective diet ad libitum in lieu of standard rodent chow. Mice in the BD treatment group received standard rodent chow mixed with BD at 20% by volume and 1% saccharin for palatability (Sigma-Aldrich). Mice in the KE treatment group received standard rodent chow mixed with KE at 10% by volume and 1% saccharin (Sigma-Aldrich) for palatability. The KE was synthesized in collaboration with Savind, Seymour, IL, as previously described.[34] As ketosis has been shown to decrease appetite and food intake,[35] and CR is known to inhibit cancer progression,[2, 36] we included a CR treatment group. CR mice received a daily food allotment of standard rodent chow restricted 40% by weight compared to their normal food consumption. They received their daily food allotment at ∼3 pm. Ad libitum diets were continuously monitored and replaced twice weekly or as needed to maintain freshness.
Blood and weight measurements
Acute metabolic response to diet in healthy VM/dk mice
Blood ketones rise and fall following ingestion of the ketone-supplemented diets, and their levels are affected by the amount of food consumed during a feeding event as well as the time between feeding and blood measurement. Because food was provided ad libitum to mice in the VM-M3 cancer survival study, it was difficult to accurately observe the effects of each diet on blood metabolites. Furthermore, deterioration of health during disease progression affected feeding behavior and, subsequently, blood metabolite concentration. To demonstrate the effects of the diets on blood metabolites without the confounding effects of ad libitum feeding and disease progression, and to demonstrate that oral administration of the ketone supplements given with a standard high-carbohydrate diet is capable of elevating ketones in VM/Dk mice, blood glucose and βHB were measured in a small group of healthy mice following a controlled feeding event. Healthy VM/Dk mice (N = 4 per treatment) were fasted for 8 hr to ensure rapid feeding compliance, and then provided SD, BD or KE diet ad libitum. All mice fed immediately upon return of food (0 hr). Blood glucose and βHB were measured at 0, 1, 4, 8 and 12 hr, and urine AcAc was measured at 12 hr. Blood was collected from the tail using approved methods, and glucose and βHB were measured using the Precision Xtra™ Blood Glucose & Ketone Monitoring System (Abbott Laboratories, Abbott Park, IL). Urine AcAc was measured using Ketocare Reagent Strips for Urinalysis (CVS, Woonsocket, RI).
VM-M3 cancer survival study blood and weight measurements
Blood was collected once weekly from the tail of the VM-M3 cancer mice using approved methods. Blood glucose was measured with the Nova Max® Plus Glucose and β-Ketone Monitoring System (Nova Biomedical, Waltham, MA), and blood βHB was measured with the Precision Xtra™ Blood Glucose & Ketone Monitoring System (Abbott Laboratories). Mice were weighed between 1 and 3 pm, twice weekly, for the duration of the study using the AWS-1KG Portable Digital Scale (AWS, Charleston, SC).
Bioluminescent imaging and tumor growth analysis
Tumor growth and metastatic spread were monitored by in vivo bioluminescent imaging with the Xenogen IVIS Lumina system (Caliper LS, Hopkinton, MA). Bioluminescent signal of the luciferase-tagged cancer was acquired with the Living Image® software (Caliper LS). Mice received an i.p. injection of 50 mg/kg d-luciferin (Caliper LS) 15 min before imaging. Bioluminescent signal was obtained using the IVIS Lumina cooled CCD camera system with a 1-sec exposure time. Whole animal bioluminescent signal was measured in photons/sec once a week as an indicator of overall tumor burden. Bioluminescent signal of key metastatic regions (brain, lungs and liver) was measured in photons/sec as an indicator of metastatic tumor size and spread.[37, 38]
Survival analysis
Health and behavior of the mice were assessed daily for the duration of the study. Upon presentation of defined criteria associated with tumor burden and disease progression (abnormal feeding behavior, diminished response to stimuli and failure to thrive), mice were humanely euthanized according to approved IACUC guidelines and survival time was recorded.
Survival was analyzed with the Kaplan–Meier and log-rank tests for survival distribution. Cell viability was analyzed by unpaired t-test. Cell proliferation, whole animal bioluminescent signal, mean survival, weekly blood measurements, percent body weight change and urine ketones were analyzed by one-way analysis of variance (ANOVA) with Tukey's multiple comparison post hoc test. Acute blood measurements were analyzed by two-way ANOVA with Tukey's multiple comparison post hoc test. Correlation between blood glucose, body weight change and survival times was analyzed by linear regression analysis. Results were considered significant when p < 0.05.
Ketone supplementation decreased VM-M3 cell proliferation and viability in vitro
Proliferation was significantly decreased in VM-M3 cells grown in low (3 mM) glucose conditions and in both low (3 mM) and high (25 mM) glucose conditions with ketone supplementation (5 mM βHB) compared to VM-M3 cells grown in control media (high glucose, 25 mM) at 24, 48, 72, 96, 120 and 144 hr (p < 0.05; one-way ANOVA; Fig. 1a). Although low (3 mM) glucose with ketone supplementation (5 mM βHB) demonstrated a trend of decreased proliferation compared to low (3 mM) glucose alone at all time points, the difference was not statistically significant (one-way ANOVA; Fig. 1a). Viability was significantly decreased in VM-M3 cells treated for 24 hr with low (3 mM) glucose conditions and in both low (3 mM) and high (25 mM) glucose conditions with ketone-supplemented (5 mM βHB) media compared to VM-M3 cells grown in control media (high glucose, 25 mM; p < 0.05; unpaired t-test; Fig. 1b).
Ketone supplementation prolonged survival and induced a trend of reduced tumor burden in mice with metastatic cancer
Bioluminescence of tumor burden varied within and between groups according to disease progression and the health and number of animals remaining in each group over time (Fig. 2b). CR-, BD- and KE-treated mice demonstrated a trend of reduced tumor burden (Figs. 2a and 2b) and metastatic spread (Figs. 2c and 2d) over the course of the survival study; however, bioluminescence was highly variable and not significantly different from controls.
BD- and KE-treated mice demonstrated a significantly prolonged survival curve by log-rank test for survival distribution compared to control animals (p = 0.01 and p = 0.01, respectively, Fig. 3a). They also showed a significant increase in mean survival time compared to control animals (one-way ANOVA; p < 0.05 and p < 0.001, respectively; Fig. 3b). Although previous reports have demonstrated that CR increases survival time in various animal cancer models, in our study, CR-treated mice exhibited a trend of increased latency to disease progression measured as tumor bioluminescence, but survival time was not statistically different from controls (log-rank test for survival distribution and one-way ANOVA; p > 0.05; Figs. 2 and 3). Control (SD) mice lived an average of 31.2 days, whereas CR mice had a nonstatistically significant different mean survival time of 36.9 days (p > 0.05; one-way ANOVA; Fig. 3). BD treatment increased mean survival time by ∼16 days (51%), and KE treatment increased mean survival time by ∼22 days (69%) compared to controls (p < 0.01 and p < 0.001, respectively; one-way ANOVA; Fig. 3b).
Ketone supplementation lowered blood glucose, elevated blood ketones and decreased body weight
Acute ketosis with supplementation in healthy VM/Dk mice
Standard high-carbohydrate rodent chow with ketone supplementation significantly lowered blood glucose for 8 and 4 hr in BD and KE groups, respectively (p < 0.05; two-way ANOVA). BD significantly elevated βHB levels after 1 hr, which further increased in the next 11 hr, whereas KE caused significant βHB elevation only after 4 hr and remained at a similar level after 12 hr (p < 0.05; two-way ANOVA). BD elevated only βHB, whereas KE elevated both βHB and AcAc (p < 0.05; two-way ANOVA and one-way ANOVA, respectively; Figs. 4b and 4c).
Blood and weight measures in VM-M3 cancer survival study mice
Initial blood glucose, βHB and body weights were similar between groups (data not shown). Chronic ketone supplementation at day 7 resulted in lower blood glucose and elevated blood βHB in CR- and KE-treated animals compared to controls (*p < 0.05, **p < 0.01, ***p < 0.001; one-way ANOVA; Figs. 4d and 4e). By day 14, CR- and KE-treated mice lost ∼20% of their initial body weight (p < 0.01; one-way ANOVA; Fig. 4f) and maintained that weight loss for the duration of the study. As expected, blood glucose and βHB were highly variable over the course of the survival study, likely owing to ad libitum feeding, health deterioration and cancer-associated cachexia (Figs. 4g and 4h). Day 7 blood glucose and body weight change were significantly correlated to survival (p = 0.0065 and p = 0.0046, respectively; linear regression analysis; Fig. 5). Interestingly, linear regression analysis of tumor bioluminescence versus blood βHB did not reveal a significant correlation.
The Warburg effect is the most ubiquitous cancer phenotype, exhibited by most if not all cancer types.[1] Exploiting the metabolic deficiencies of cancer cells should be prioritized, because this therapeutic strategy would likely prove effective against most cancers. Mitochondrial dysfunction underlies many aspects of cancer metabolic deficiency and prevents cancer cells from effectively using ketone bodies for energy.[12, 20] In our study, ketone supplementation decreased VM-M3 cell proliferation and viability (Fig. 1), confirming similar results demonstrated in other cancer types in vitro.[6, 11, 12] Therefore, we hypothesized that dietary administration of ketone body precursors would inhibit disease progression in vivo. Indeed, dietary administration of ketone precursors, BD and KE, increased mean survival time by 51 and 69%, respectively, in VM-M3 mice with metastatic cancer (Fig. 3). These data support the use of supplemental ketone administration as a feasible and efficacious cancer therapy, which should be further investigated in additional animal models to determine its potential for clinical use.
Ketone supplementation decreased blood glucose after acute administration, decreased body weight with chronic administration and sustained ketosis in vivo, even when administered with a high-carbohydrate rodent chow in both healthy (VM/Dk) and cancer (VM-M3) mice (Fig. 4). Our study demonstrates the ability of dietary administration of BD and KE to significantly elevate ketone bodies in vivo for at least 12 hr in healthy VM/Dk mice and 7 days in VM-M3 cancer mice (Fig. 4). VM-M3 cancer is very aggressive, and health of control animals declines rapidly after tumor cell inoculation. With onset of disease progression, animal feeding behavior, body weight and blood metabolites vary considerably. Blood and body weight data before the onset of significant disease progression in all treatment groups (Figs. 4d–4f) demonstrate the effects of the dietary therapies on blood metabolites in VM-M3 cancer mice largely aside from the confounding effects of disease progression. Figures 4g and 4h show blood glucose and βHB levels of VM-M3 mice over the course of the survival study. Disease progression altered feeding behavior, and animals often exhibited low blood glucose and elevated blood ketones before euthanasia. For example, nearly all CR mice were euthanized in the fifth week of the study, with their declining health reflected by the marked increase in blood ketones at week 4 (Fig. 4h).
It is important to note that the metabolic changes associated with acute and chronic ketosis are vast and can dramatically affect blood metabolite concentrations. In previous studies, chronic BD and βHB administration has been shown to decrease food intake in the rat and pigmy goat.[39, 40] Similarly, Veech and coworkers demonstrated that feeding a KE-supplemented diet increased malonyl-CoA, an anorexigenic metabolite known to decrease food intake.[41] Ketone-induced appetite suppression may account for the decreased blood glucose and body weight seen in treated VM-M3 cancer mice (Fig. 4f). Additionally, prior studies suggest that ketones increase insulin sensitivity,[41, 42] which may be contributing to the decreased circulating blood glucose in KE-fed mice. Blood metabolite levels are dynamic and change rapidly with food consumption and tissue utilization. Because the VM-M3 cancer mice were fed ad libitum, blood glucose and ketone levels observed at the time of measurement during chronic supplementation were likely affected by variable feeding behavior before blood measurement. As mentioned, health status of the animals also altered feeding behavior. Mice reduced food intake and likely experienced cancer-associated cachexia with disease progression, conditions that elevate blood ketones endogenously through beta-oxidation of stored fats. Furthermore, chronic ketosis enhances ketone utilization by tissues, known as keto-adaptation, resulting in lower blood ketone concentrations.[43] All these factors likely contributed to the observed variability in blood glucose and βHB between acute versus chronic administration of diet and healthy VM/Dk versus VM-M3 cancer mice (Fig. 4).
Previously, dietary intervention in cancer has largely focused on carbohydrate restriction or CR to exploit the Warburg effect. CR has been shown to slow disease progression in a variety of cancer models.[2, 36, 44-46] As described, dietary-induced ketosis often leads to reduced appetite, decreased calorie consumption and decreased body weight, creating the possibility that the effects of ketone supplementation could be indirectly due to CR.[20] Interestingly, although CR decreased blood glucose and elevated blood ketones, CR mice exhibited a trend of increased latency to disease progression and increased survival that was not statistically significant from controls in our study (Figs. 2 and 3). As described, some data suggest that elevated ketones are responsible for much of the anticancer efficacy of the ketogenic diet.[10] Perhaps elevating ketones with exogenous sources such as ketone supplementation or a ketogenic diet, rather than elevating ketones endogenously through lipolysis such as occurs with CR, provides a more effective anticancer strategy. Additionally, ketone supplementation may preserve lean muscle mass to a greater degree than CR, and may therefore support overall health of the organism in this way. Because CR mice demonstrated a trend of increased latency to disease progression and survival time, and body weight change was correlated to survival (Fig. 5), indirect CR likely contributed to the efficacy of ketone supplementation but does not account for the significant increase in survival time in ketone-fed mice. Additionally, although BD increased mean survival time by 51%, blood glucose was not significantly lower than in control animals, suggesting that decreased glucose availability was not the primary mechanism of efficacy (Figs. 3 and 4). KE treatment increased mean survival to a greater extent than BD (69% increase from control; Fig. 3). Notably, blood glucose and body weight were more decreased and ketones were more elevated in KE-treated animals, possibly owing to indirect CR, and perhaps account for the enhanced efficacy of KE compared to BD treatment (Fig. 4). In vitro, 5 mM βHB supplementation decreased proliferation rate and viability of VM-M3 cells even when added to 25 mM glucose media (Fig. 1). Indeed, ketone supplementation was as effective as glucose-restriction (low, 3 mM glu) treatment in decreasing VM-M3 cell proliferation and viability (Fig. 1). These data support the in vitro and in vivo conclusions of Fine et al. suggesting that ketone bodies can inhibit cancer progression independently of other factors such as carbohydrate restriction or CR.[6, 10-12]
Lisanti and coworkers have published reports that tumor-associated fibroblasts produce ketone bodies to fuel nearby cancer cells.[47, 48] In these reports, the authors coculture immortalized fibroblasts genetically altered to overexpress rate-limiting ketone production enzymes with breast cancer cells genetically altered to overexpress ketone utilization enzymes. Although this phenomenon may occur in the system created by the authors, there is no evidence that this situation would occur naturally in vivo. As described, the literature as a whole strongly suggests that cancer cells of various tissue types are unable to effectively use ketone bodies for fuel. Many cancers do not express the succinyl CoA 3-ketoacid CoA transferase (SCOT) enzyme that is necessary for ketone body utilization,[49] while several reports have demonstrated a notable deficiency of cancer cell ketone metabolism in vitro.[12, 21] It is also widely accepted that ketone production occurs nearly exclusively in the liver, and there is no known metabolic pathway by which fibroblasts could produce ketones from glucose. Without evidence to support this phenomenon in a natural cellular environment, we continue to accept the notion that most cancer cells cannot effectively metabolize ketones for energy.
The ketogenic diet has been shown to enhance the efficacy of both radiation and chemotherapy in vivo.[4, 50, 51] As supplemental ketones mimic the physiological ketosis induced by the ketogenic diet, combining supplemental ketone therapy with standard of care could produce similar effects, even if administered with a SD. Furthermore, the neuroprotective effects of ketone metabolism have been widely documented.[52] Ketone metabolism protects normal cells from oxidative damage by decreasing mitochondrial ROS production and enhancing endogenous antioxidant defenses.[13] Radiation and chemotherapy work in large part by inducing ROS production in the tumor, but simultaneously incur damage to normal tissue. Ketone metabolism by healthy tissue would likely mitigate some of the adverse side effects of standard of care as ketones have been shown to protect against oxidative stress.[13, 34] Our data strongly suggest that supplemental ketone administration could provide a safe, feasible and cost-effective adjuvant to standard care that should be further investigated in preclinical and clinical settings.
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- 50Drug/diet synergy for managing malignant astrocytoma in mice: 2-deoxy-D-glucose and the restricted ketogenic diet. Nutr Metab (Lond) 2008;5:33., , .
- 51The ketogenic diet is an effective adjuvant to radiation therapy for the treatment of malignant glioma. PLoS One 2012;7:e36197., , , et al.
- 52The neuroprotective properties of calorie restriction, the ketogenic diet, and ketone bodies. Brain Res Rev 2009;59:293–315., , .


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Welcome. I am a happy creative person from Earth. My name is Juraj Kopačka and I am a freelance SOFTWARE DEVELOPER, illustrator and graphic designer. I love my job and I love bringing new ideas and things to life.
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Jana Valentovičová - responsive MVC CMS with blog
responsive MVC CMS with blog
description: responsive company CMS with blog
technology used: MVC approach, responsivity, PHP, jQuery, ajax, mysql, sass, bootstrap
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Has anyone been to both? My husband and I have 6 days in Jan (without the kids!) and are trying to decide. We aren't sit on the beach types. We prefer architecture, history, kayaking, hiking, and excellent food. I think both Curacao and Puerto Rico have the mix of culture and warm weather but I worry Old San Juan is too touristy and Willemsted won't keep us busy for 6 days. Any thoughts would be appreciated!
Recent ActivityView all Caribbean Islands activity »
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Curacao vs Puerto Rico
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Went to PR in the 80's. We are returning in November. Went to Curacao in 2009. We found it difficult to get to Curacao from Texas. All flights on AA had us overnighting in Miami. We finally flew United (Continental then) to Aruba and then Insel air to Curacao.
Have to say we didn't care for Curacao. There are no long stretches of beach. They are coves/inlets. Most are on the West side of the Island, so you need a car and a good map to get to them or take a tour. The sand is made up of crushed coral, so we felt water shoes were a must. You are correct there was nothing there to keep us busy for 6 nights. You also need a car to get to dining options. The downtown area was very nice and clean with real stores not just tourist trap souvenir shops. No hasseling.
We did enjoy the Aquarium. We did the dive encounter. No certification required, and it was the highlight of the trip. We had fun and was glad we went, but it didn't make our return list. Many people say the snorkeling there is great. Compared to Grand Cayman, Cozumel and the Sian Ka'an Biosphere out side of Playa del Carmen, Mexico is was meh.
If you are interested I have our vacation pictures posted:
The Aquarium Dive:
click "all" to just scroll down through all of them without going through multiple pages.
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Personally don't find Old San Juan too touristy (and I live here in PR) regularly go there with my 5 year old son to check out the forts and just wander around
If you prepared to explore outside of San Juan there are lots of things to see and do
are you looking to do anything in particular?
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Many thanks, KVR & Coqui_07.
We definitely are open to exploring outside of San Juan. I would like to hike in El Yunque and see Ponce and San Germán but I'm not sure how too put that all together without changing hotels four times in six days. Any suggestions on prioritizing or coordinating those places (or other ideas) would be greatly appreciated.
Thanks again!
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You might want to read the forums on Trip Advisor regarding seeing multi areas. A rental car will be a must to do that. We are only staying 6 nights. We have some mobility issues and do not rent cars on vacation. We like guided tours and have planned some sightseeing tours, the El Yunque rain forest and day trips to Culebra and Vieques.
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Thanks, KVR. I realize that we'd be into a rental car. We're in our 30s and enjoy independent travel, non-resort hotels, etc. And I'd appreciate any additional suggestions and feedback from others.
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Quick intro to the various regions of PR http://www.discoveringpuertorico.com/2013/04/regions-of-puerto-rico/
plus more info on that site - just search aroun it
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Thanks so much, coqui_07.
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My recent trips to Curacao and San Juan were brief since we continued on to Bonaire and Culebra, respectively. But Curacao did not have much going on and I felt that the slavery museum in Willemsted, while laudatory in terms of acknowledging slavery - a rarity in the Caribbean, felt a bit like a tax write-off on the part of the wealthy owner who put it together.
Based on your description, I'd think there is a much more diverse range of things to do in Puerto Rico if you rent a car. Also, the duration of flying to Curacao is not to be discounted -- it's a long connection. I loved Bonaire but that was for the endless snorkeling and biking options on that island (good food too...).
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Matt Kuchar reacts to missing a putt on the first hole during the first round of the PGA Colonial golf tournament n Fort Worth, Texas, Thursday, May 22, 2014. (AP Photo/LM Otero)
Matt Kuchar looks back over his shoulder at his shot off the fourth tee during the second round of the Byron Nelson Championship golf tournament, Friday, May 16, 2014, in Irving, Texas. (AP Photo/Tony Gutierrez)
Matt Kuchar hits from the sand onto the eighth green during a practice round for The Players championship golf tournament at TPC Sawgrass in Ponte Vedra Beach, Fla., Wednesday, May 7, 2014. (AP Photo/Gerald Herbert)
Matt Kuchar celebrates after sinking a birdie putt from the bunker on the 18th green to win the final round of the RBC Heritage golf tournament in Hilton Head Island, S.C., Sunday, April 20, 2014. Kuchar won the tournament with 11-under par. (AP Photo/Stephen B. Morton)


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Severe Thunderstorm Watch issued June 29 at 7:08PM MDT expiring June 30 at 2:00AM MDT in effect for: Phillips, Sedgwick
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COMMERCE CITY, Colo. - A motorcyclist was taken to a hospital after being injured in a chain-reaction crash that began when two other vehicles stopped abruptly on Highway 85 in Commerce City.
Commerce City Police said the tractor-trailer was traveling northbound in the left lane when the driver noticed a piece of metal hanging down from a Burlington Northern Railroad bridge. The truck stopped abruptly and so did a Dodge Ram following it.
Police said the motorcyclist hit the back of the Dodge pickup. The rider was wearing a helmet.
Burlington Northern Railroad and CDOT are inspecting the bridge and the left lane of Highway 85. The left lane is closed for that inspection.


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Mariah Carey gifted her fans her latest song video 'you're Mine (Eternal) on Valentine's Eve. The song is from her yet-to-be-named album and has got quite a lot of positive reviews. Check it out right here.
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cdomin01 (Charlie Dominguez)
Last login: Tuesday, June 21, 2016
Comment history
Your Turn: Commissioner addresses code issues
I disagree. Most comments are not about Kobach himself, but about the commission's involvement in providing unbalanced application of processes in place. From Mr. Flory's comments, it is apparent that he did want to please the SOS regardless of the rules in place. There should be an independent 3rd party investigation into this issue as a way to clear the speculation brought on from a couple of individuals breaking protocol and doing what steps it took to ensure the SOS was treated favorably.
June 10, 2015 at 9:03 a.m. ( permalink | suggest removal )
Trio of Lawrence commissioners say they want to get tougher on economic incentives
I hope all public officials will use social media of all types to further communicate their positions; especially when not quoted correctly. Keep it up Matt. Don't let anyone intimidate your choices while on the commission.
June 10, 2015 at 8:36 a.m. ( permalink | suggest removal )
KU chancellor's husband worked closely with people implicated in UNC's massive academic fraud case
Sounds like you must have some really good seats you don't want to lose Joe. The article picks up pieces of a puzzle and starts to put them together; nothing wrong with that. Hard to understand how a well educated individual, at a high management level, and whose spouse was an assistant dean in a program of questionable behavior; was not aware of those issues taking place; especially when high-profile students are involved. And for that same person to then make a statement completely distancing herself from the situation. It used to be long ago, that public figures ensured that their dealing were "above reproach", and today we are stuck with the same public officials making sure their action "were not illegal". Let the investigation move forward, let the freedom of the press continue on without interference.
June 7, 2015 at 12:10 p.m. ( permalink | suggest removal )
Appeals board questions Douglas County codes enforcement policy
Commissioner Gaughan states in today's article, that the commissioners are NOW going to look further into this issue; only last week Commissioner Gaughan was reported as being satisfied with the outcome and accepted the "unwritten change of evaluations"
I am willing to give this same commissioner SOME time to review and get back to the public as to what took place in DETAIL. And then what actions are to be taken to prevent such misconduct from repeating itself. Someone or some people need to be removed from their position in order to ensure that this issue stands out within the county government, so that the next guy doesn't do what someone else told him to do, and in-turn, that procedures are followed by the codes that are written. There has to be some resolution beyond a paper promise of new order by two commissioners and a scrambling administrator. Power has to be shifted in order for justice to be served.
These guys (county personnel and the cover up by the two commissioners) knew what they were doing when they did what they did. And it does no one any good to continue to coat over the truth with deception and excuses. I would like to see the affidavit from the two inspectors as to how and why they felt removed and replaced. Does the current inspector feel he has complete authority to forgive any codes he now finds are being violated and how if he so believes he has such authority, does he determine who gets penalized with re-inspections and which projects are allowed to continue without further evaluation (such as Kobach received)
Should some official be forced to resign or County official is found to have acted illegally, then that will cause other state agencies, review boards and the state media groups to do follow up investigations and in so and if deserving, prosecutions. That is the justice we are all seeking and that is the justice that is deserved. If only Rachel Maddow was in town.....does anyone have those connections?
June 1, 2015 at 12:33 a.m. ( permalink | suggest removal )
Douglas County says Kobach was not shown favoritism in building case; failure to be strict on building codes was result of new, unwritten policy
County Commissioners need to take a look at this with an independent investigator. And the officials knew this would be a highlighted case if they got caught, and still disregarded the rules. And the worst part of this story thus far, is that one man's reputation was questioned and a 'yes' man installed in order to "ensure" that another politician was taken care of.
Time for someone to be let go and set the example that Douglas County does not permit special treatment to anyone.
May 17, 2015 at 10:18 a.m. ( permalink | suggest removal )
Editorial: Questionable leadership
I don't know about bigger lies....try George Bush and Dick, dick, dick, (excuse my stutter) Chaney....their lies cost us a few thousand American lives and the Iraqis, a few hundred thousand lives.....not to mention that trillion dollars plus.
April 7, 2015 at 10:09 p.m. ( permalink | suggest removal )
Select KU, Haskell students get word they'll have preferred seating at Obama event
If only we could all be FREE of you.
January 21, 2015 at 6:26 p.m. ( permalink | suggest removal )
Peaceful march kicks off week of Ferguson-related events at KU
We all know that Fox and O'Reilly are not slanted in their judgement. Come on people, this cop shot an unarmed guy 6 times!! The body was left outside without being picked up, for 4 hours! The prosecuting attorney had experience involving family law enforcement being accused of racism in similar situation.....a trial would have brought transparency. What do people fear to having a trial to temper the rage of injustice. The grand jury was provided a one-sided story without cross examination....
December 2, 2014 at 5:51 p.m. ( permalink | suggest removal )
Lawrence commission takes blame for defeat of police headquarters tax
I don't think the commission or apparently any of those who spoke or reported to have spoken, understand what I think is the reason for the "failure" to raise taxes....
There is no need for a new police station. No evidence that spending $28MM is a reason for what can be done with far less expensive repairs to the existing law enforcement buildings. Absolutely no study done, or documented evidence presented (except their own crafted online video) as to the need for one new $28MM location; the entire argument is based on the police chief's belief that one castle is what the kingdom needs. "Where's the beef"?
After realizing that fact, then there is the wink wink fraternity business acumen that the commission is doing that brings a HUGE distrust from the people as to their fairness in previous appropriations.
It wasn't about Rock Chalk; it was about an over designed building (which provides a fee based on percentage of overall cost for that same design to the design firm) for a need that doesn't exist....sort of like Kris Kobach's need for Voter ID.... and be rest assured, just like Kobach continues to spend taxpayer money for something we don't need, so will this commission continue to push for a headquarters that isn't needed. Somebody get some clothes for the commissioners.
November 11, 2014 at 11:22 p.m. ( permalink | suggest removal )
Q&A on Lawrence police headquarters, sales tax
I would like to know just how much is the A&E fee for the project, and are any of the firms/contracting groups promoting in any way the ballot initiative? The school district had an agreement with their A&E firm, which I find to be a questionable ethics issue if true, as blatant conflict of interest that a firm is promoting for their own fee, the passage of the sales tax which would then benefit the firm, as in attaining said fee, if it is so agreed to assist in the promotion for passage.
October 26, 2014 at 11:27 a.m. ( permalink | suggest removal )
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What does MIBC stand for?
MIBC stands for Medical Insurance Billing and Coding
This definition appears frequently and is found in the following Acronym Finder categories:
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- Business, finance, etc.
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- Malaysian Indian Business Association (est. 1999; Selangor, Malaysia)
- Masters of International Business Administration
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- Marshall and Ilsley Bank
- Misr International Bank (Egypt)
- Military Intelligence Battalion, Air Reconnaissance Support
- Minimally Invasive Breast Biopsy
- Mass Intensity Basketball Club (Massachusetts)
- Member of the Institute of Business Consulting (UK)
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- Moscow International Business Center
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- Master of International Business Economics (degree program)
- Measles Inclusion Body Encephalitis


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Relevant offers
What does every woman want? One French bank thinks it knows the answer: Handbag insurance and a handyman hotline.
The pink-and-gold-coloured "Pour Elle" bank card, part of a cut-price summer offer by Paris-based lender Societe Generale, promises to "simplify" women's lives with up to 200 euros (NZ$300) of handbag theft insurance and a dedicated hotline for up to two electrician, locksmith or other handyman callouts per year.
As useful as these products might be, not all women are happy to be singled out by their bank as needing special help.
"It's a little cheeky to promote both at the same time as 'female crises' that could arise," said Lys-Aelia Hart, a 24-year-old assistant art buyer living in Paris. "In my eyes, many men don't know how to deal with a serious electrical issue - on the contrary, they'd probably get killed."
A spokeswoman for SocGen said the cards had been a "great success" and said the bank did not view them as sexist. "We don't think it's a discriminatory approach," she said. "Those who choose these cards are those who wish to adhere to their femininity."
Even men aren't shy about signing up for the card, added the spokeswoman. "Five percent of cardholders are men," she said.
Despite the noble intentions, the card still looks to some like a misguided attempt to cater to women's needs.
"I don't need my bank to dictate what kind of services I need, but it's kind of them to offer," said Hart.
- Reuters
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