Mobile application reinvents health care process
A Scottsdale-based tele-health company is reinventing the way people chose to seek health care with the mobile application Healthiest You. Doctors say health care applications can #39;t replace...
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Fed up! /Health Care Market Place
Tried something different this time so they will not lose my information again.
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Mental health care advocates say patients face challenges in insurance coverage. iStockphoto.com hide caption
Mental health care advocates say patients face challenges in insurance coverage.
By law, many U.S. insurance providers that offer mental health care are required to cover it just as they would cancer or diabetes care. But advocates say achieving this mental health parity can be a challenge. A report released earlier this week by the National Alliance on Mental Illness found that "health insurance plans are falling short in coverage of mental health and substance abuse conditions."
Reporter Jenny Gold of Kaiser Health News tells NPR's Arun Rath that patients are still having trouble getting their care covered. In this interview, she outlines some of the issues confronting both patients and the insurance industry.
Currently, insurers adhering to parity rules is a mixed bag.
Insurance companies used to have a separate deductible or higher copay for mental health or substance abuse visits. That's sort of gone away. For the most part, insurers really have complied. Right now, there really isn't a separate deductible for mental health and there isn't a higher copay, so on that side, you know, they really have complied. But on another sort of subtler and harder-to-pinpoint side, advocates are saying they're really not complying.
Insurance companies, in order to keep down costs, they will do things called "medical necessity" review. Basically, they look at someone's care and ask is it really medically necessary. And advocates say they're applying those sorts of cost-control techniques way more stringently on the mental health side and the substance abuse side than they are on the physical health side. So people are still having trouble getting their care covered.
Insurers say it's complicated to distinguish between physical and mental health
Insurance companies are arguing this is a really hard law to implement. I spoke with Clare Krusing from America's Health Insurance Plans, which is the insurance industry's main trade group, and she says they're really doing their best to make this work:
"The plans have taken tremendous steps since the final rules came out to implement these changes and requirements in a way that is affordable for patients and again this goes back to the fact that we are at a point where health care costs continue to go up."
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When It Comes To Insurance, Mental Health Parity In Name Only?
Gene Therapy (2015) 22, 305315; doi:10.1038/gt.2014.122; published online 15 January 2015
C-SLu1,7, J-LHsieh2,7, C-YLin1, H-WTsai1, B-HSu1, G-SShieh3, Y-CSu1, C-HLee4, M-YChang5, C-LWu1 and A-LShiau6
Hypoxia is a common feature of growing solid tumors. Adaptation to low oxygen condition in cells results in the transcriptional activation of more than 100 genes that regulate key aspects of tumorigenesis, including angiogenesis, metabolism, proliferation, invasion and metastasis.1 Promoters containing hypoxia response element (HRE) can be transactivated by hypoxia and drive-related gene expressions, leading to defective vasculogenesis and abnormal metabolic activity when tumors progress. Hypoxia-inducible factor (HIF)-1, which is an oxygen-sensitive transcriptional activator, primarily mediates this response. HIF-1 consists of two subunits, namely an oxygen-regulated subunit HIF-1 (or its paralogs HIF-2 and HIF-3) and a constitutively expressed subunit HIF-1.2 HIF-1 is degraded via the ubiquitin-proteasome pathway in normoxia. Whereas the HIF-1 subunit becomes stable and regulates the expression of target genes in hypoxia. Furthermore, unusual overexpression of HIF-1 has been found in various cancers. HIF-1 preferentially induces genes encoding glycolytic enzymes, whereas HIF-2 induces genes involved in tumor invasion, such as matrix metalloproteinases and the initiation of cancer stem cell (CSC) factors.3, 4, 5 HIF-2 activates signaling pathways such as Oct4 and Notch, which control the self-renewal and multipotency of CSCs.6 All of the altered characteristics of tumors may impair effective cancer treatment.
Replication-selective oncolytic adenoviruses are an attractive strategy for cancer therapy because they are able to infect, replicate in and lyse tumor cells. Viruses can be modified in various ways to improve their selectivity and therapeutic efficacy. First, viruses have mutated genes that are essential for viral replication in non-tumor cells but can be selectively compensated by specific cellular mutations in cancer cells.7 Second, the enhancer or promoter region of the E1A gene, which is required for adenovirus replication, can be modified with tumor- or tissue-specific promoters. 8, 9, 10, 11, 12 On these modifications, oncolytic adenoviruses are capable of replicating and lysing tumor cells while sparing non-tumor cells. These viruses have shown acceptable anti-tumor activity and overall safety in various cancers, including bladder cancer.13, 14, 15 In the past decade, numerous clinical trials have been conducted to assess the potential of oncolytic viruses for cancer therapy. 16 An oncolytic vaccinia virus, Pexa-Vec (formerly known as JX-594), was engineered to selectively replicate in cells with alterations of the RAS pathway and to express human granulocyte-macrophage colony-stimulating factor (hGM-CSF). Pexa-Vec was employed in clinical trials for the treatment of hepatocellular carcinoma (phase I) and colorectal cancer (phase II).17 An oncolytic herpes simplex virus type 1, Talimogene laherparepvec (T-VEC), which was manipulated to express hGM-CSF, has been tested for the treatment of unresected Stage IIIB, IIIC or IV melanoma. Results from the clinical trials indicated that these oncolytic viruses hold promise as anticancer agents.18, 19
Oct4 is a transcriptional factor that is a key regulator of pluripotency and self-renewal in embryonic stem cells and is also expressed in bladder cancer.20, 21 We have demonstrated that Oct4 expression reflects tumor progression and regulates motility of bladder cancer cells.11 We generated an E1B 55-kDa-deleted adenovirus, designated Ad9OC, which is driven by nine copies of the Oct4 response element (ORE) ligated to a human cytomegalovirus minimal (CMVmini) promoter.10 In addition to Ad9OC, we have also generated another oncolytic adenovirus, named AdWS4, under the control of the Oct4 promoter.11 These two Oct4-regulated oncolytic adenoviruses can specifically kill bladder cancer cells overexpressing Oct4 and exert potent antitumor activity in animal tumor models. 10, 11
Limited viral replication is one of the major obstacles to reaching a highly therapeutic effect. 22 A level of hypoxia similar to that found within solid tumors reduces the replication of adenoviral vectors by reducing E1A expression and hence oncolytic potentials.23, 24 Hypoxia has been exploited to drive the replication of oncolytic adenoviruses aiming at increasing therapeutic efficacy for solid tumors exhibiting significant areas of hypoxia.25, 26, 27 Currently designed oncolytic adenoviruses may require additional modifications to target tumor cells in hypoxic regions. To overcome such drawbacks, in the present study, we generated a new hypoxia-activated oncolytic adenovirus, designated AdLCY, which contains a dual hypoxia/Oct4-responsive promoter composed of the CMVmini promoter ligated with six copies of the HRE and nine copies of the ORE.
Bladder cancer is the most common cancer in the urinary system in the United States.28 Progression to or presentation with muscle-invasive disease usually worsens the survival rate of patients and requires more aggressive therapy. Oct4 and Sox2, which are stemness markers expressed in bladder cancer, have been implicated to be responsible for proliferation and differentiation of CSCs and are correlated to disease prognosis.29, 30 We found that using HRE/ORE segments to transcriptionally regulate adenoviral replication in Oct4-overexpressing cancer cells increased viral replication and oncolytic activities in hypoxic environments, thereby improving antitumor activity against bladder cancer. As Oct4 is expressed in a broad spectrum of cancer and tumor hypoxia increases malignant progression and metastasis,1, 31 Oct4 and hypoxia dual-regulated oncolytic adenoviruses may be broadly applicable.
We first used quantitative real-time reverse transcription (RT)-polymerase chain reaction (PCR) analysis to examine Oct4 mRNA levels in various human and murine bladder cancer cells under normoxic and hypoxic conditions. Levels of Oct4 mRNA expression were higher in hypoxic than in normoxic conditions in all the cells tested (Figure 1a). In human bladder cancer cells, hypoxia induced Oct4 mRNA expression by 4- to 23-folds. Accordingly, higher levels of Oct4, HIF-1 and HIF-2 proteins were also detected in these cell lines under hypoxia than under normoxia (Figure 1b). In the murine MBT-2 cell line and its two sublines, hypoxia also induced Oct4 mRNA expression, albeit at lower levels of induction compared with those in human bladder cancer cells (Figure 1a). Regarding protein expression levels, MBT-2 and MBT-2-LM7 cells under hypoxic conditions expressed higher levels of Oct4, HIF-1 and HIF-2 proteins than those under normoxic conditions (Figure 1b). However, only HIF-2, but not Oct4 and HIF-1 proteins, was elevated following hypoxic induction ( Figure 1b). We next used three different reporter constructs to examine the promoter activities of the CMVmini promoter ligated with either 6 HRE or 9 ORE, or both in hypoxic or normoxic TCC-SUP and MBT-2 cells. As shown in Figure 1c, activities of the three promoters increased when TCC-SUP (upper panel) and MBT-2 (lower panel) cells were under hypoxic conditions. Moreover, the CMVmini promoter ligated with both 6 HRE and 9 ORE exerted higher transcriptional activity than that conjugated with either 6 HRE or 9 ORE. Collectively, these results indicate that the CMVmini-6 HRE-9 ORE promoter was highly responsive to endogenous Oct4 and HIFs in hypoxic cells.
The CMVmini-6 HRE-9 ORE promoter was highly responsive to endogenous Oct4 and HIFs in hypoxic human and murine bladder cancer cells. (a) Expression of Oct4 mRNA in bladder cancer cells under normoxic and hypoxic conditions for 48h, as determined by quantitative real-time RT-PCR. (b) Detection of HIF-1, HIF-2 and Oct4 expression in bladder cancer cells after exposure to normoxia (N) or hypoxia (H) for 48h. The expression of -actin served as the loading control. (c) Determination of promoter activities. TCC-SUP and MBT-2 cells were transfected with single dual-luciferase reporter constructs, which contained the CMVmini promoter ligated with either 6 HRE or 9 ORE, or both to drive firefly luciferase, as well as the CMV promoter to drive Renilla luciferase, and then exposed to normoxia or hypoxia for 48h. Promoter activities were determined by a dual-luciferase reporter assay. The ratio of firefly luciferase activity to Renilla luciferase activity was expressed as relative light units (RLU) (n=4). Values are the means.e.m. of the mean. ***P<0.001; **P<0.01; *P<0.05.
As Oct4 has been identified as a HIF-2-specific target gene,5 we next tested whether silencing HIF-2 expression reduces Oct4 expression and thereby decreases the transcriptional activity of the CMVmini-9 ORE promoter in hypoxic tumor cells. TCC-SUP and MBT-2 cells that have been transfected with a reporter construct containing the CMVmini-9 ORE promoter were transfected with short hairpin RNA (shRNA) constructs specific to HIF-2 (shHIF-2) or green fluorescent protein (GFP) (shGFP) for 24h and then exposed to hypoxia or normoxia for additional 24h. Knockdown of HIF-2 expression resulted in decreased Oct4 expression in TCC-SUP ( Figure 2a, left panel) and MBT-2 ( Figure 2b, left panel) cells under hypoxic conditions. Furthermore, the transcriptional activity of the CMVmini-9 ORE was also downregulated in hypoxic TCC-SUP ( Figure 2a, right panel) and MBT-2 ( Figure 2b, right panel) cells after transduction with shRNA specific to HIF-2. These results confirmed that HIF-2 is involved not only in HRE-dependent transactivation, but also regulates Oct4 transactivation. Given that the transcriptional activity of the CMVmini-6 HRE-9 ORE promoter was higher than that of the CMVmini-9 ORE promoter (Figure 1c), we generated AdLCY, which is an Oct4 and hypoxia dual-regulated oncolytic adenovirus, by adding six copies of the HRE upstream of the CMVmini-9 ORE for driving adenovirus E1A gene expression in the context of the E1B 55-kDa-deleted adenovirus Ad9OC.10
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Image from Chiappini et. al.
Gene therapy, the delivery of genetic material to cells in the form of DNA or RNA, has been explored as a means to treat illnesses. These treatments hinge on ourability to getDNA and RNA inside cells, where they can interact with the cell's machinery. Currently, successful delivery of nucleic acids has been stalled by inefficient insertion of the molecules into cells, safety concerns, limited accessibility of the target cells, and poor scalability.
In order to overcome these limitations, a team of scientists has proposed nanoinjection through a carefully designed array of tiny needles, which they're calling nanoneedles. Nanoinjection provides a more uniform delivery due to the high density of nanoneedles that can occupy a givensurface area. The researchers fabricated biodegradable, porous nanoneedles from silicon with a geometry that was optimized for intracellular delivery.
The nanoneedles had a 5 m length, 50 m width at the sharp end, and 600 nm base diameter, providing a 300-fold increase in surface area for delivery compared to a non-porous wireof equivalent diameter. The porosity of the needles could also be tailored to modulate things likepayload volume, mechanical strength, and how long the needle persists inside cells.
Characterization of the needles demonstrated they could withstand the force required to penetrate cells and were effective in delivering either DNA or RNA. The nanoneedles progressively dissolved over 36 hours in physiological conditions; after 72 hours only the solid stump remained.
Nanoinjection was tested by either placing nanoneedles beneath or on top of a layer of cells. In both cases, nanoinjection did not induce significant toxicitycells continued tofunction and grow normally over the course of five days. Thenanoneedle constructs were also able to load, retain, and deliver nucleic acids over a 12-18 hour period, achieving uniform RNA spread inside the cellafter 48 hours.
The nanoneedles could deliver two separate types of nucleic acids using a RNA strand and a fluorescently labeled DNA strand. These constructsdemonstrated that the molecules were active once inside the cell; they couldmodulate gene activityby either expressing a gene carried on the DNAor silencing expression of genes via RNA interference.
The efficacy of the device was also tested in rats. The nanoneedles could be used for a localized injection, as shown by their ability to carry fluorescent dyes into the skin and muscle of test rats. Nanoinjection was also assessed on ear and muscle to demonstrate that tissue architecture does not influence the delivery process. Injection of fluorescent dyes did not induce local inflammation withina 24 hour period, and imagingof the skin and muscles revealed that the tissue maintained its normal appearanceafter nanoinjection.
Finally, the researchers compared efficiency of nanoinjection todirect injection of DNA. They tested this usingVEGF165, which is a gene that influences the development of blood vessels. While both injections resulted in expression of human VEGF165 for up to one week, the blood vessels formed were very different.Nano injectionpromoted the formation ofhighly interconnected blood vessels near the surface of the skin and a six-fold increase in overall blood perfusion; direct injection did not.
These nano needles could provide a new route totargeted delivery of RNA and DNA, which could lead to major improvements in efficient gene therapy strategies.
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From left: Tushar Menon, Inder Verma and Amy Firth. Salk Institute
From left: Tushar Menon, Inder Verma and Amy Firth. / Salk Institute
Those born with the immune disorder SCID-X1, or "bubble boy disease" may one day benefit from a new treatment to give them a functioning immune system, if new research from the Salk Institute succeeds.
Working with cultures of induced pluripotent stem cells from a patient, Salk scientists led by gene therapy expert Inder Verma repaired the genetic defect that causes the disease. Infants born with this inherited condition have virtually no immune resistance, and can be killed by infections easily defeated by normal immune systems.
Researchers were able to generate what appear to be mature NK, or "natural killer" immune cells, the first time this has been done. They also generated progenitors of T cells. This doesn't repair all the immune system, but it's a big step in that direction.
These preliminary results may pave the way to an alternative from treating these patients, Verma said. At present, patients can be treated with bone marrow transplants, but matching donors are hard to find. Gene therapy using a viral vector to repair the defect has been successful, but has caused leukemia in some patients when the corrective gene went into the wrong place. Newer forms of this therapy appear to have reduced the risk, but long-term followups of those treated are still in progress.
Salk researchers dispensed with viruses entirely by using the TALEN technology, which allows genetic editing without viruses, and is also more precise.
The study was published in the journal Cell Stem Cell on March 12. Tushar Menon and Amy L. Firth are the first authors. Verma is the senior author.
SCID-X1 is caused by an inactivating mutation on a gene called IL-2Rg located on the X chromosome, which means it exclusively affects males. (For females who carry the mutation on one chromosome, the functional gene on the other chromosome suffices).
One-letter mutation
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dr. futurist - alvin toffler
dr. futurist self-release http://www.discogs.com/Dr-Futurist-Alvin-Toffler/release/6221361 http://scapeone.bandcamp.com/album/alvin-toffler.
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Jeremih - Birthday Sex (Andrew Luce Remix)
Jeremih - Birthday Sex (Andrew Luce Remix) Subscribe to Futurism: http://full.sc/1LghY97 SHOW MORE for the download link + more! Download Support Futurism http://soundcloud.com/futur...
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Selena Daly: Mapping the Italian Avant-Garde: Futurism in Space and Time (1909-1944)
Recorded live at the spatial@ucsb Lightning Talks on Feb. 25, 2015. See the full lineup of talks at http://spatial.ucsb.edu/lightning-talks/.
By: Center for Spatial Studies, UCSB
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Selena Daly: Mapping the Italian Avant-Garde: Futurism in Space and Time (1909-1944) - Video
The Great Futurism Debate (w/ Dale Carrico)
Richard and Dale Carrico debate the merits of futurism. Subscribe to The Zero Hour with RJ Eskow for more: http://bit.ly/TheZeroHour If you liked this clip of The Zero Hour with RJ Eskow,...
By: The Zero Hour with RJ Eskow
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How Will People Use Indiana #39;s Religious Freedom Law?
Indiana #39;s religious freedom law has caused plenty of controversy. But how exactly will it work in practice? Our panel broke down the legislation, as well as this week #39;s recently-added clause....
By: The Diane Rehm Show
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How Will People Use Indiana's Religious Freedom Law? - Video
Intuit - #39;Freedom Ringing #39; ::: Second Story Garage
Intuit perform their song "Freedom Ringing" in this music video recorded at the SecondStoryGarage.com studio inside the Daily Camera newsroom in Boulder, Colorado. Intuit #39;s performance in...
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Firestorm Prompts Fix in Indiana #39;s Religious Freedom Bill41:00 | news
Firestorm Prompts Fix in Indiana #39;s Religious Freedom Bill41:00 Please follow me.Rebecca Jarvis goes one-on-one with Vensette CEO Lauren Remington Platt. Breaking news, latest news, current...
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Firestorm Prompts Fix in Indiana's Religious Freedom Bill41:00 | news - Video
Nick Offerman Reveals How Leslie Knope Would Have Reacted to Indiana #39;s Freedom of Religion Act
There were two initial reactions when Indiana first passed the Religious Freedom Restoration Act. The first one was obviously utter disgust. And the second? Someone sic Leslie Knope on them!...
By: wochit Entertainment
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Discrimination: A God-given Right; Religious Freedom in Indiana Arkansas
Liberals have attacked the Religious Freedom Restoration Act (RFRA) in both Indiana and Arkansas as endorsing discrimination against LGBT people. This bill was about freedomnot about same-sex ...
By: Jesse Lee Peterson
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Discrimination: A God-given Right; Religious Freedom in Indiana & Arkansas - Video
Video of adoptable pet named Freedom - Courtesy Post
Freedom - Courtesy Post is an adoptable pet with Ace of Hearts Dog Rescue in Beverly Hills CA. Please visit their website at http://www.aceofheartsdogs.com.
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Video of adoptable pet named Freedom - Courtesy Post - Video
Larry Elder Discusses True Freedom vs. Leftists Ideals
Of course this revolves around the "Freedom of Religion Act" Indiana is trying to implement. I include a parody after Larry Elder brings up an analogy of a black baker and a funeral service...
By: Papa Giorgio
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Larry Elder Discusses True Freedom vs. Leftists Ideals - Video
Enjoy Your Freedom, Oliver
Today we congratulate Oliver Swanick on winning the lottery, and wish him well on his travels.
By: DazPlaysV2
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Driverless Cars Are The Death Of Freedom
David Knight takes the studio for Alex Jones and discusses driverless cars and how they will be used to take your freedoms. http://www.infowars.com/chaos-in-yemen-chinese-troops-arrive-as-us-armed ...
By: The Alex Jones Channel
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Bills enacting Indiana-style religious freedom law dropped
Nevada lawmakers are dropping two bills that would enact religious protections into state law that opponents criticized as opening the door for discrimination.
By: KTNV Channel 13 Las Vegas
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Bills enacting Indiana-style religious freedom law dropped - Video