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Association of differential gene expression with imatinib mesylate and omacetaxine mepesuccinate toxicity in lymphoblastoid cell lines
Functional and structural genomics
Imatinib mesylate is currently the drug of choice to treat chronic myeloid leukemia. However, patient resistance and cytotoxicity make secondary lines of treatment, such as omacetaxine mepesuccinate, a necessity. Given that drug cytotoxicity represents a major problem during treatment, it is essential to understand the biological pathways affected to better predict poor drug response and prioritize a treatment regime.
We conducted cell viability and gene expression assays to determine heritability and gene expression changes associated with imatinib and omacetaxine treatment of 55 non-cancerous lymphoblastoid cell lines, derived from 17 pedigrees. In total, 48,803 transcripts derived from Illumina Human WG-6 BeadChips were analyzed for each sample using SOLAR, whilst correcting for kinship structure.
Cytotoxicity within cell lines was highly heritable following imatinib treatment (h2 = 0.60-0.73), but not omacetaxine treatment. Cell lines treated with an IC20 dose of imatinib or omacetaxine showed differential gene expression for 956 (1.96%) and 3,892 transcripts (7.97%), respectively; 395 of these (0.8%) were significantly influenced by both imatinib and omacetaxine treatment. k-means clustering and DAVID functional annotation showed expression changes in genes related to kinase binding and vacuole-related functions following imatinib treatment, whilst expression changes in genes related to cell division and apoptosis were evident following treatment with omacetaxine. The enrichment scores for these ontologies were very high (mostly >10).
Induction of gene expression changes related to different pathways following imatinib and omacetaxine treatment suggests that the cytotoxicity of such drugs may be differentially tolerated by individuals based on their genetic background.
Chronic myeloid leukemia (CML) represents a myeloproliferative condition characterized by a t(9;22)(q34;q11) translocation that forms the
In addition to resistance, it has been found that 3-8% of imatinib-treated subjects discontinue treatment because of the cytotoxic effects of the drug
We therefore conducted a systematic evaluation of cytotoxicity in imatinib- and omacetaxine-treated cells. In this study we tested two hypotheses. First, we conjectured that the concentration of imatinib or omacetaxine needed to inhibit growth of non-cancerous lymphoblastoid cell lines is a heritable trait. Second, we hypothesized that inhibition of cells by these drugs ensues quantifiable and characteristic changes in gene expression. Using lymphoblastoid cell lines derived from pedigreed individuals,
Cell lines and drugs
Cell lines were derived from Epstein-Barr virus-immortalized lymphoblastoid cells of pedigreed individuals participating in the San Antonio Family Heart Study
Cell viability studies
Cell viability assays were carried out in a similar manner to previous studies
where 117,216 is the molar extinction coefficient of alamarBlue in its oxidized form at 600 nm; 80,586 is the molar extinction coefficient of alamarBlue in its oxidized form at 570 nm; and abs indicates the absorbance. GraphPad PRISM v5 software was used to plot dose response curves and determine IC20 values for both imatinib and omacetaxine for each cell line.
Gene expression assays
Each of the 55 selected cell lines was treated with either imatinib, omacetaxine or was left untreated. Each cell line was treated for 96 hours with a concentration of drug equivalent to the IC20 value (calculated for each cell line individually); additional media containing the appropriate concentration of drug was added after the first 48 hours. A concentration equivalent to IC20 was utilized for two reasons: i) we aimed at maintaining the viability of the majority of cells to make reliable estimates of the gene expression profiles; and ii) previously published drug toxicity studies have used this cut-off in toxicological gene expression studies
Statistical analysis
Analyses were conducted on two sets of experimental results. Using data from Experimental Series 1 (Figure
Additional file 1
Figure S1. Quantile normalization of gene expression data.
Click here for file
Figure 1
Experimental and analytical protocol used in the study
Experimental and analytical protocol used in the study. Experimental series 1 was undertaken to estimate the differential gene expression in 48,803 probes upon treatment with imatinib or omacetaxine. For these experiments both drugs were administered at a dose of IC20. Experimental series 2 was undertaken to measure an individual's sensitivity to drug response (SDR) which was estimated as the slope of the regression line (arrows) between log of dose administered and cell viability. Data from these experiments were also used to estimate the IC20 values used in Experimental Series 1. Differential gene expression (iFC and oFC) was tested for statistical significance for departure from zero as well as for association with the corresponding SDR as shown. Details of the statistical methods mentioned in the figure are provided in the text.
Using data from Experimental Series 2 (Figure
All genetic analyses were conducted using the SOLAR software package
Validation of microarray results by qPCR
To validate results from the Illumina Human WG-6 v3 BeadChips, we performed real-time reverse transcription polymerase chain reaction (quantitative PCR, qPCR) analysis on selected transcripts. We utilized
Assessment of heritability
This study is based on lymphoblastoid cell lines derived from 55 individuals belonging to 17 pedigrees. The kinships included siblings (72), third degree relations (15) and an identical sib pair. A total of 48,803 probes, whose intensities were derived from the microarray experiments, were used for analysis. We first examined the heritability of the IC values obtained from treatment of the cell lines with imatinib (n = 109) and omacetaxine (n = 113). Although both drugs influenced cell viability in a dose-dependent manner, only the IC values for imatinib demonstrated high heritability (range: 0.60 – 0.73), IC values for omacetaxine were consistently non-heritable (Table
Differential gene expression upon treatment
We next examined whether there was a significant difference in gene expression following treatment with either imatinib or omacetaxine at an IC20 equivalent dose. For imatinib, the IC20 values ranged from 8.7×10-6M to 8.7×10-5 M and for omacetaxine, the IC20 values ranged from 1.0×10-8 M to 2.2×10-7 M. Volcano plots (Figure
Figure 2
Differential gene expression response upon treatment with imatinib or omacetaxine
Differential gene expression response upon treatment with imatinib or omacetaxine. (A-B) Volcano plots depicting the extent (x-axis) and significance (y-axis) of differential gene expression for each probe set (n = 48,803) after treatment with either imatinib (A) or omacetaxine (B). (C) Results of k-means clustering of the statistically significant probes based on their differential gene expression in response to imatinib (x-axis) or omacetaxine (y-axis) treatment. The color codes for each cluster are indicated in the index, clusters have been referenced consistently throughout the manuscript. The lack of data towards the center of the scatter plot is due to probes that were not significant (in response to either imatinib or omacetaxine treatment), which are not shown in this figure. (D) Point estimates and 95% confidence ellipses for the association of differential gene expression with sensitivity of drug response (SDR). Plotted in this chart are the regression coefficients from the polygenic models (equation (2)) for the set of probes belonging to the color-coded clusters identified in panel C. (E) Heritability of differential gene expression. The data are shown separately for probe sets belonging to each cluster identified in panel C. Pie charts at the top demonstrate the proportion of probe sets within the corresponding cluster that showed a heritability value exceeding zero for differential gene expression in response to imatinib as well as omacetaxine. The bar charts show the mean heritability of imatinib (blue) and omacetaxine (red) response for genes within each cluster. For reference, color-coded background is shown on the chart corresponding to the clusters. Within each cluster, the difference in the mean heritability for imatinib and omacetaxine response was assessed using a paired Student's
Probes within cluster 1 (n = 1,378, 30.95%) were mildly down regulated by imatinib and mildly up regulated by omacetaxine; those in cluster 2 (n = 2,005, 45.03%) were down regulated by both imatinib and omacetaxine; those in cluster 3 (n = 428, 9.61%) were mainly up regulated by imatinib and those in cluster 4 (n = 642, 14.42%) were mainly up regulated by omacetaxine. Corroborating these conceptual inferences, the mean iFC values and the enrichment scores [mean -log10 (FDR-corrected p-value)] for probes in the four clusters were −0.02 and 0.35 for cluster 1; -0.08 and 0.63 for cluster 2; 0.36 and 4.20 for cluster 3; and 0.13 and 0.67 for cluster 4. The mean oFC values and enrichment scores for these clusters were 0.26 and 4.31 for cluster 1; -0.35 and 5.05 for cluster 2; 0.10 and 0.89 for cluster 3 and 0.5 and 8.44 for cluster 4.
Functional annotation of identified genes
We next considered whether these unsupervised and unbiased clusters of probes indicated any underlying functional similarities. First, we used the DAVID® functional annotation clustering tool
Additional file 2
Table S1. Clusterwise functional annotation of the significant probes.
Click here for file
Second, we examined whether each significantly up regulated probe was associated with iSDR and oSDR. We found that probes in clusters 1 and 4 did not differ from each other with respect to their relation with iSDR and oSDR as indicated by largely overlapping 95% confidence ellipses (Figure
Third, using polygenic models, we found that differential gene expression in response to imatinib (ih2r) and omacetaxine (oh2r) for the majority of probes had measurable (that is exceeded zero) heritability (Figure
Previously, we had identified 750 (3.82%)
Validation of microarray results
We chose five representative genes within the four clusters identified from the microarray results and conducted qPCR assays to validate the differential expression of these genes in response to imatinib and omacetaxine treatment. Amplification plots for a representative sample for all five genes are shown in Supplementary Figure
Additional file 3
Figure S3. Representative amplification plots from RT-PCR for selected genes.
Click here for file
Additional file 4
Table S2. Gene-specific correlation between the results of q-PCR and microarray.
Click here for file
Figure 3
Validation of the microarray results by qPCR
Validation of the microarray results by qPCR. (A) Scatter plot of the differential gene expression in response to imatinib (blue) and omacetaxine (red). Both axes show log-transformed differential gene expression. Results are for all five genes that were assayed by microarray and qPCR. Since qPCR used
Differential gene expression and sensitivity of response
We considered the comparative strength of association of differential gene expression (iFC or oFC) with the sensitivity of drug response (iSDR or oSDR, respectively). For this we selected all probes which showed a FDR-corrected statistically significant correlation between FC and SDR values. We identified 21 genes that showed a significant association between iFC and iSDR and 13 genes that showed a significant association between oFC and oSDR. We annotated these genes using the GeneGO tool (Table
Figure 4
Association between differential gene expression and the SDR in the 34 significant probes
Association between differential gene expression and the SDR in the 34 significant probes. Charts show scatter plots and correspondingly color-coded regression lines. The p-values shown along the regression lines are for a test of the null hypothesis: regression coefficient = 0.
Our study made three novel and interesting observations. First, inhibitory concentration values following treatment with imatinib were highly heritable, although this was not seen for treatment with omacetaxine. This finding implies that in a clinical scenario, determination of a toxic dose of omacetaxine would not need to consider potential familial and heritable influences of drug cytotoxicity. Second, differential gene expression in response to omacetaxine was stronger and more widespread in the genome than for imatinib. Third, the differential gene expression after omacetaxine exposure was a significant determinant of an individual's sensitivity of drug response (defined as the slope of regression line between cell viability and log of drug concentration) but a similar association was not found in the context of imatinib treatment. Together, this suggests that while the dose required to induce cell death is not heritable for omacetaxine, an individual's sensitivity of genomic response to a fixed dose of this drug is heritable. In contrast, while imatinib toxicity was highly heritable, the extent of genomic response was more subdued and was not predictive of the sensitivity of an individual's response to a fixed dose of imatinib. These findings not only demonstrate the differences between the toxicity profiles of imatinib and omacetaxine, but also point towards the possibility of successfully using gene-agnostic drugs as a secondary line of treatment in cases of imatinib resistance.
Functional annotation confirmed results from previous studies that identified kinase binding, apoptosis and vacuole/lysosome related genes as targets of imatinib treatment
In addition to the limitations implicit in any microarray study, our study has further limitations. First, this study was conducted in EBV-transformed lymphoblastoid cell lines and therefore it should be noted that the differential gene expression being ascribed to drug treatment are on the background of an EBV transformation, which may not truly reflect clinical changes. It is noteworthy that imatinib can inhibit the virus-specific proliferation of CD8+ T cells such that there are varying degrees of this inhibitory effect to peptides derived from cytomegalovirus or EBV
Second, the microarray studies were conducted by treating cell lines for 4 days with a preselected concentration equivalent to the IC20 dose for each drug (to avoid excessive cell death). It is possible that clinical gene expression changes would be different from those identified in this study, dependent on the dose chosen and length of treatment. Although our study does not permit interpretation about dose-related differential gene expression, we demonstrate here, examples of pathways that are likely to be altered by imatinib or omacetaxine treatment, many of which have very plausible biological roles in such drug cytotoxicity.
Third, even though the correlations between results of qPCR and microarray estimates can be considered to be modest, these correlations are consistent with those reported in literature
We performed this study to gain a better understanding of the effects of imatinib and omacetaxine treatment on non-cancerous cells in order to identify pathways that might be consistent with drug cytotoxicity. Our results can therefore only be interpreted as potential leads for further research into the cytotoxic effects of two drugs commonly used to treat CML.
We have identified genetic signatures of imatinib and omacetaxine toxicity in non-cancerous cell lines derived from closely related individuals. Identification of the pathways induced by either imatinib or omacetaxine treatment on non-cancerous cell lines may lead to the possibility of early detection of subjects who might be more prone to develop drug cytotoxicity. To our knowledge such a microarray study has not been conducted thus far. Future research should focus on the candidate genes identified in this study as potential determinants of drug toxicity in the treatment of CML. Investigation of such gene expression profiles in CML patients would be particularly interesting, and may be useful in determining a cost/benefit ratio of a treatment regime.
CML: Chronic myeloid leukemia; MCL-1: Myeloid leukemia cell differentiation protein; FC: Fold change; SDR: Sensitivity of drug response; IC: Inhibitory concentration; FDR: False discovery rate; GO: Gene ontology; qPCR: Quantitative polymerase chain reaction.
Competing Interests
The authors declare that they have no competing interests.
Authors' contributions
JB, KRW, GRC and MAC designed the study. SC was responsible for overseeing the generation of cell lines. MAC performed all molecular analyses HK, VD, HHHG and JB performed statistical analysis. HK, MAC and JB wrote the manuscript. All coauthors read and approved the final manuscript.
Financial support for this study was provided by the Max and Minnie Tomerlin Voelcker Fund, the National Heart, Lung and Blood Institute (PO1 HL045522, PI: Dr. Blangero) and the National Institute of Mental Health (R37 MH059490, PI: Dr. Blangero). This investigation was conducted in the facilities constructed with support from Research Facilities Improvement Program Grant Number C06 RR017515 from the National Center for Research Resources, National Institutes of Health.
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First-line therapy for chronic myeloid leukemia: new horizons and an update
Resistance and relapse with imatinib in CML: causes and consequences
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Undetectable molecular residual disease after omacetaxine and nilotinib combination therapy in an imatinib-resistant chronic myeloid leukaemia patient harbouring the BCR-ABL1 T315I gatekeeper mutation
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Pre-publication history
The pre-publication history for this paper can be accessed here:


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text: DEERFIELD, Ill., June 26, 2013 /PRNewswire/ -- In Brazil, there are 32 percent more mobile phones than residents of the country! That's more than 260 million active mobile lines according to research from ANATEL. This is one of the reasons why Mondelez International chose Brazil as the first country to launch a Mobile Futures program after its successful rollout in the United States. (Logo: http://photos.prnewswire.com/prnh/20121003/MM86695LOGO) Mobile Futures aims to ignite the company's consumer connections by collaborating with some of the brightest and most innovative minds in the mobile space – startup entrepreneurs. For the U.S. edition, Mondelez International received hundreds of applications and selected nine startups in the areas of social TV, mobile at retail and SoLoMo (social/location/mobile). This process resulted in the launch of 7 new mobile pilots in just 90 days with Power Brands like Oreo and Chips Ahoy! biscuits as well as Trident and Stride gum. "The Mobile Futures program has been an extraordinary experience for us and we're thrilled to expand to Brazil for the next wave," said Bonin Bough, Vice President of Global Media and Consumer Engagement at Mondelez International. " Brazil not only leads in mobile technology, it's a primary growth market for us. Our goal is to become one of the top mobile marketers in the world, and the expansion of Mobile Futures to Brazil demonstrates our commitment to get there." Mobile Futures – The Future in 90 DaysAnnounced at DEMO Brasil, a global startup event happening for the first time in the country, Mobile Futures Brasil will pair Mondelez International Power Brands with Brazilian startups that have "shelf-ready" technology in some of the most exciting areas of mobile, such as SMS, Mobile at Retail, Social and Apps. Five startups will be selected to partner with some of the largest brands in Brazil such as Bis chocolate , Club Social crackers , Tang powdered beverages , Halls candy and Trident gum. The partnership will kick off with a week-long immersion session, where the brand teams will work alongside their partners to fully experience the startup culture. The teams will then have 90 days to plan and activate mobile pilots. "Today in Brazil, we invest more than 15 percent of our total marketing spending in digital and we believe there are many more opportunities," said Natacha Volpini, Digital Media Manager at Mondelez Brasil. "Through the Mobile Futures Brasil program, not only will we support the startups, but we'll also bring home their innovative spirit. We're creating a culture of 'intrapreneurship,' reflecting new ideas and ways to connect with our consumers." The program is supported by Bob Wollheim, specialist in the digital entrepreneurship area and Chief Executive Officer of S_kull – disruption lab of Flag, in conjunction with Gina Waldhorn, Chief Operating Officer and Co-Founder of Evol8tion, an innovation agency based in New York, that worked on Mobile Futures in the United States. Other partners include: Endeavor; Wayra; 21212; Papaya Ventures; Aceleratech; Pipa; Redpoint e-ventures; Anjos do Brasil; e-bricks digital; .Mobi; Startupi; Demo; Revista Pequenas Empresas Grandes Negocios; ProXXima and BR Innovators. "This initiative demonstrates to the world the level of mobile innovation that can be created by a company like Mondelez International," said Wollhein. "In the future, leading companies should all act like this, taking entrepreneurship inside out."


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A momentous milestone in Shirt.Woot history has passed! And true to form, we haven't bothered to mention it for a couple of weeks now. But let the ages know that at 8:25 AM on January 30, 2009, Alberto of Houston, Texas ordered a single Sun Wukong (The Monkey King) shirt, making it the 1,000,000th wearable offspring Shirt.Woot has hatched and sent into the world!


text: Our server, Patrick, certainly stayed on top of things. We were seated in the very southwest corner (you can't get much farther from the kitchen!) and I feared we would be overlooked. NOT SO! Patrick was very attentive and our food arrived quickly and the order was accurate! I went with the Benedict and the wife had the quiche (her's... More


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Pass by the Guanabara Bay, where you can admire the amazing statue of Christ the Redeemer, its immensity is far outweighed by the beauty of its scenery vegetation wastes.
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PortCityDaily.com is your source for free news and information in the Wilmington area.
Ronald Nash King, of Rocky Point, died Saturday, Aug. 8, 2015, surrounded by family and close friends. He was 72.
He was born Nov. 26, 1942, in Wilmington, son of the late Luther King and Susan Watter King.
Ronald was a skilled cabinet maker and an avid hunter and fisherman.
Survivors include his son, Andy King and his wife Cheryl; daughter, Debbie King; grandchildren, Andrew, Ronnie, Mason and Melody; sister, Jerry Gurganous; and his beloved dog, Peeches.
The family received visitors Sunday, Aug. 9, 2015, at 14060 Ashton Road, Rocky Point, NC 28457.
In lieu of flowers, donations may be made in his name to: NC Wildlife Resources Commission, 1751 Varsity Drive, Raleigh, NC 27606.
Please leave online condolences for the family at Andrews Mortuary.
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Congress to probe Michigan oil spill
DETROIT (Reuters) - A U.S. congressional committee will probe the spill of more than 800,000 gallons (3 million liters) of oil from an Enbridge Inc pipeline in southern Michigan this week, a Michigan congressman said on Saturday.
The House subcommittee on railroads, pipelines, and hazardous materials will launch an investigation into the cause of the spill and the Calgary-based pipeline operator's response, Representative Mark Schauer said on his website.
"Enbridge needs to answer some tough questions about how this happened, and I plan to hold them fully accountable," Schauer, a Democrat, said in a statement.
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Schauer introduced legislation on Friday that would limit the time a company has to report an incident to the government's National Response Center, and increase fines for failure to notify the NRC within that time limit.
The Detroit Free Press, citing a local county official, said that an Enbridge employee talked to firefighters near the spill site on Sunday evening, a day before Enbridge reported the spill.
Enbridge spokeswoman Terri Larson denied that, calling the assertion "completely unsubstantiated," the newspaper said.
Enbridge said in a statement on Saturday that it continues to clean up the Talmadge Creek and Kalamazoo River, where about 19,500 barrels of oil has leaked near the company's pump station. It is using containment and absorbent booms at 28 sites around the spill area to remove oil.
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The leader of an Islamic extremist militia in Libya suspected of involvement in an attack in Benghazi that killed the US ambassador has been shot.
Sufyan bin Qumu, a former Guantanamo Bay detainee, was shot yesterday in the al-Thruwn area of the eastern city of Darna, a stronghold of Islamic extremists.
A security official says he was taken to a nearby hospital and was in the intensive care unit.
Residents of eastern Libya, where the September 11 attack against the US consulate took place, have been standing up to Ansar al-Shariah. Protesters stormed the group's compound in Benghazi days after the attack.
No suspects have been named over the attack that killed ambassador Chris Stevens and three other Americans.
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text:
Stop Smoking
- Constant coughing
- Shortness of Breath
- Paying too much for cigarettes
- Stinky hair, breath and clothes
- Loved ones nagging you to stop smoking
- Loss of limbs due to decreased circulation
- Heart attack
- Lung Cancer
- Emphysema
- Birth defects in children of pregnant smokers
- Death
If you can relate to even one of these smoking-related problems, you know what it's like to suffer from smoking.
And, these are just the basic problems.
The Hypnosis Quit Smoking Plan
You may feel like you are divided. Part of you wants to stop smoking but part of you says it just isn't worth it. Maybe there's a list of reasons and excuses, it's too enjoyable, it's too hard to stop, and you don't care. Maybe you really want to stop, but every time you try, you can't stay stopped. Whatever the reason, why not make it as easy as you possibly can, with hypnosis?
Like any drug, the first week of withdrawal is the hardest. Nicotine withdrawal is a hard thing to live with and Steve G. Jones self-hynosis CDs and MP3s can be with you during the process, giving you support every day, encouraging you that you can do it.
You are probably going to feel frustrated and irritated. You are going to want something to do with your hands, having a stress ball to squeeze may help.
Try to gather support from friends and family. Reach out and call them as often as you can, especially during the first month. Listening to the self-hypnosis CD or MP3, consistently, at least once a day for the first 21 days is highly recommended.
One reason people smoke is to get stress relief. Try the Stress Relief Hypnosis MP3 or CD and the Meditation Hypnosis MP3 or CD and see how much your life improves. The truth is, in our stressful world, the only time most people stop and take a deep breath is when they are inhaling deeply on a cigarette.
Do you want to stop smoking? Are you ready to stop smoking now? Oh, maybe not now. Monday? After Christmas, New Year's, Easter? The truth is sometimes we are truly ready. Sometimes we wish we could stop but we're not ready yet. Even if you are not ready, consider buying and listening to the CD or MP3 now as a way to begin to let your subconscious become willing to get ready. Our brains are complex and often have conflicting desires and emotions. Hypnosis brings those conflicts into synch.
We suggest that you make a list of all the reasons you want to stop smoking. Make a list that is personal to you. You may want to stop and look that list every hour, before the craving hits, because it is very likely that smoking cravings will hit you. Add new reasons every time you think of one. Use your list of reasons as an additional tool to your hypnotherapy CDs.
Your list might be centered on how smoking can be damaging to your health, your looks, and your wallet.
Heart diseases and cancer are the number one and two killers in the U.S. Smoking taxes the heart muscles incredibly. Smokers have three times the likelihood of having a heart attack as non-smokers. The risk of a heart attack drops by 50% one year after quitting. Lung cancer is almost exclusive to smokers (over 90% of lung cancer patients are smokers). All kinds of cancer are now directly linked to smoking including stomach cancer, breast cancer, cervical cancer, kidney, and pancreas, larynx, and cancer of the mouth. In addition to cancer, emphysema, Chronic Obstructive Pulmonary Disorder (COPD)
The 2004 Surgeon General's report linked smoking to over fifty diseases and conditions as varied and wide ranging. They spanned the gamut from mildly annoying to deadly. Besides the more well known, back pain, neck pain, penis erectile dysfunction and low sperm count, immune system malfunctions, and hearing loss, were among some of the surprises.
The good news is that every day you stop smoking and stay stopped, the body begins to rebuild. Quitting cold turkey is hard. For some people that's the best way. They need to pick a date and stick to it. Is it worth it to you to live longer and to stay healthier? How about just to make it through a day without coughing or clearing your throat?
Figure out how much a month of smoking costs you. A lot more than the price of a CD or MP3 to change your life. Then figure out what a year of smoking costs you monetarily.
In the 1940s and 50s, tobacco companies used to tout the virtues of smoking. It was cool the big companies bragged. They even tried to tell you it was healthy for you. We know better now, but science is uncovering more every day. How much of a toll is it taking that we don't know about yet.
Maybe other things will motivate you to give up smoking. Because giving up smoking takes commitment and hypnosis will help but you have to know what your prime reasons are. Ask yourself how much older does my skin look because of your smoking? Does this inconvenience anyone I love? Will food and drink taste better if I stopped? Will my breath, hair and clothes smell better, will anyone notice that? What about the time it takes that you could be doing something else?
How will it feel to have had hypnotherapy help you no longer craving or be distracted by wanting cigarettes when you are not smoking or not able to smoke? What will it be like on long train rides, airplanes, or busses? What will it be like not to have to get up and go out of a restaurant to smoke? Will that matter to you?
Once you educate yourself on reasons to stop smoking, you've talked to your intellectual rational brain. But that's not the part that's craving the cigarette. So hypnosis will give you positive replacement suggestions to add the desire to stop smoking deep into your mind when you are open to having new patterns become a new way of life.
ORDER NOW and begin your NEW LIFE TODAY!!!
Take back the control and begin your lifetime of FREEDOM!
When you listen to this Stop Smoking hypnosis CD or Stop Smoking hypnosis MP3 your mind will very quickly get used to the idea that you don't smoke, and as the title says, you will free yourself from the smoking habit and remain a non smoker forever. This Stop Smoking hypnotherapy CD or Stop Smoking hypnotherapy MP3 also includes positive suggestions to prevent you starting any other negative patterns in place of the smoking habit you leave in the past. In fact when you stop smoking you will feel ever more determined to keep fit and remain healthy.
As a smoking cessation aid, hypnosis has one very important benefit that other quit smoking tools aren't able to offer. Because it uses the power of positive suggestion to help you stop smoking, it actually has the ability to help you develop and strengthen your will and determination to succeed.
Quitting smoking should not be difficult or unpleasant. Granted nicotine is a difficult substance to go without when giving up smoking, but after a few days it is out of your system and most smokers agree that quitting smoking for a few days is difficult but very achievable.
So that's it! A tricky few days and then a lifetime of freedom. So why hasn't it been that easy previously? Simple – you didn't deal with the psychological addiction of smoking. In fact, you probably put cigarettes up on some kind of a pedestal.
If you think that stopping smoking is depriving you of something, then it is just a matter of time until you start again.Using my Hypnotherapy Stop Smoking Cd or MP3 is ideal for this. Using hypnosis, you can deal with all of the emotional and psychological aspects of giving up smoking.
MYTH #1: I will gain weight.
Actually, many people who have used My Stop Smoking hypnosis CD or Stop Smoking Hypnosis MP3 to become non-smokers end up reducing their weight! In my experience, the people afraid of gaining weight are those who gain the weight. You see, here is the predicament that most smokers often find themselves in who have tried to quit "cold turkey" (i.e., without any help or preparation): it becomes a self-fulfilling prophecy. They hear repeatedly from others who have tried the cold turkey method that quitting smoking causes weight gain. So when they stop smoking their fear of weight gain causes them to continue skipping meals like a smoker or they substitute junkfood for cigarettes.
The hitch is this: skipping meals or eating fatty junk foods with too many refined carbohydrates in purchases made from white sugar or white flour causes weight gain! So, without adequate preparation, if you expect to gain weight then you probably will. But it is not a cosmic law; you do have a choice. Drinking water, eating healthier food, and exercising moderately are better subsitutes for smoking, and the best ways to boost your metabolism, keeping your weight in check.
MYTH #2: I can't stop because I'm addicted.
This is simply untrue. You can stop if you really want to stop. The word "can't" is the problem here-I know, I was a smoker for 7 years. The "Addiction Mindset" defeats the will, not the substance itself. What is the addictive substance in gambling or shopping? I have helped 2 pack a day smokers of 40 years walk out of my office feeling like they have never smoked before in their lives.
In fact, in 1997, secret tobacco industry documents revealed that the amount of nicotine found in most brands was not addictive enough, people were still able to stop smoking. So research was conducted at a lab in Oakland, CA on how to genetically alter the tobacco plant to produce even more nicotine! That did not work, so now additives are used to make nicotine become more rapidly absorbed into the bloodstream instead.
MYTH #3: The smoking habit is more difficult to quit than heroin.
Do not fool yourself. It is not because nicotine is more addictive than heroin! Cigarettes are cheap, legal, readily available, glamorized in movies, not debilitating, and easy to use. Heroin is illegal, expensive, not very glamorous, very debilitating, and you have to stick a needle in your arm to use it. It does not take a rocket scientist to understand why some junkies find it is easier to stop using heroin than cigarettes. The fact is, when the price of heroin goes down, the rate of heroin addiction goes up. So now that the price of cigarettes is rising, more and more smokers are quitting!
MYTH #4: I don't want to have to go through withdrawal.
As the body comes back to normal, often new non-smokers mistake both the natural fluctuations in their blood sugar levels and unfamiliar cravings for "withdrawal symptoms". Low blood sugar can cause irritability, nervousness, nausea, headaches, stomachaches, dizziness and cravings. They experience these symptoms because for quite some time they have substituted nicotine (an appetite suppressant and stimulant) for the normal craving for food! Ask a diabetic what it is like to have low blood sugar; for them the symptoms are quite severe. (80 years ago adult onset diabetics were locked up in mental institutions.)
So the people who stop smoking suddenly, unprepared for the blood sugar issue, will relapse when their blood sugar dives because they rationalize that they are "addicted". The fact is, it only takes 3 days (72 hours) for the body to remove the nicotine. Managing your blood sugar with 3 sensible meals a day and healthy snacks in between makes the process a whole lot smoother than you ever thought possible.
The TRUTH is, you already know all you need to know about the dangers of smoking.
It all depends on what you value in your life and what your priorities are. To become a non-smoker, getting your subconscious mind involved is the key! It contains your emotions and habit center, your intellect does not. Why do you think cigarette advertising is now so restricted? Advertising works on the subconscious mind! You need to get the message to your subconscious mind in a way that it can help you, not sabotage your efforts.
With the help of this stop smoking hypnosis MP3 or stop smoking hypnosis CD you can successfully become a non-smoker, focus on eating right, start exercising again, improving your overall health, begin managing your blood sugar like every other non-smoker does, and thus actually end up releasing weight as many of my clients do
This Stop Smoking Hypnotherapy CD and Stop Smoking hypnotherapy MP3 has enjoyed a high success rate with smoking cessation and stopping smoking is one of the most common reasons why people consult hypnotherapists. When quitting smoking, it best not to dwell on negative aspects such as ill health, but instead to aim for positive outcomes such as good health, fitness, freedom and energy.
I know many of you out there are smokers. And I know that you have heard it all before about how bad it is for you and how you need to quit. Most smokers want to quit, they just aren't sure how and they don't know how to cope with the withdrawal from nicotine.
Research has been shown to help smokers quit their habit, using hypnotherapy as an aide. Everything about hypnotherapy is relaxing and encouraging. Relaxation and encouragement is what smokers need to quit smoking! Studies have shown that hypnotherapy is a great tool in helping smokers to quit. Hypnotherapy helps people quit FOR GOOD, not just for a few weeks or months.
If you smoke, I encourage you to look into hypnosis to help you quit smoking. How great would it be to be a non-smoker? Imagine not having to excuse yourself to go on a cigarette break. Imagine no longer having cravings for nicotine. Think about how better you will smell. And most importantly, think about how your body will become healthier as a result of quitting.
No wonder Steve is the leader in hypnotherapy. How lucky are those who have had the benefit of his genius!READ MORE » — Jeraldine Saunders, Creator of "The Love Boat" Series
1. MP3 files are large in file size; therefore broadband is highly recommended.
Here is a sample of the script used in this recording:
Willingness is a state of mind and you are willing to be a non smoker because that is what you want. You will succeed. You are willing to do whatever it takes to produce the results you want. You choose to be a non smoker. Just be willing, be willing. Be willing to do whatever it takes to be a non smoker. Your thoughts create your behavior. When you have a behavior you want to change, you change the thought pattern and the behavior changes automatically. All of your behavior results directly from your thoughts. Therefore, think of yourself as a non smoker. Hear yourself saying I am a non smoker. When someone offers you a cigarette, hear yourself saying, no thanks, I don't smoke. For your body, smoking is poison. You want to live a long and healthy life. You owe your body respect and protection. You have made a commitment to protect and respect your body and when you do that, you then have the power with in you to smoke your last cigarette. You will maintain your non smoking easily and effortlessly. Just relax, let it happen, hear yourself repeating slowly in your subconscious mind, I am a non smoker now and forever more. I am going to make this work. I expect this to work. I now allow myself to be a non smoker. I deserve to be a non smoker. You will maintain your non smoking permanently. You will be relaxed when others are smoking around you. Cigarettes are poison. Cigarettes are filled with over 4,000 substances and then when someone offers you a cigarette, hear yourself say no thank you, I quit. You are now and forever more a non smoker. In the morning, before you can even open your eyes tell yourself, I am strongly motivated to be a non smoker, one day at a time easily and effortlessly. See yourself going through your day and night without a cigarette. That's right, see yourself getting up in the morning without a cigarette. See yourself having coffee or reading the paper, doing what you do in the morning without a cigarette. See yourself on a phone, without a cigarette. See yourself driving, playing your favorite music, relaxed and comfortable, without a cigarette. See yourself after a meal, without a cigarette. Relaxed and comfortable, no interest, no desire. See yourself doing the things that you do throughout the day, whatever they may be, without a cigarette, uninterested, no desire. See yourself out with others, and someone lights up, tell yourself, cigarettes are not a sign of friendship. Cigarettes are poison. You are now and forever more a non smoker. And long ago there is a food that you decided not to eat. Imagine that food now. You made a decision that you would not eat that food and nothing and no one could make you pick up a fork and eat that disgusting and nauseating food. Just as now you have made your choice to be a non smoker and nothing and no one can make you take that first puff. Every time you take a look at a pack of cigarettes you will think of that food and nothing and no one can make you take the first puff. You are now and forever more a non smoker. And as you relax I would like to recall a time in your life, a time in your life when you felt completely confident and proud of yourself. See that moment clearly. Notice the colors in the room. Hear the sounds associated with that event. Notice any odors associated with that event. Feel the atmosphere, your clothes, and the temperature and now make all of those sounds, sights, and smells even more vivid and now allow the feeling of pride associated with this event to build in intensity. And when you feel the pride associated with this event at the maximum level of intensity, make a fist with your former smoking hand and as you hold the fist tightly, take three slow deep breaths, in and out. Feel even more intensely the pride that you felt during the event. That's right, you are there now at that event. Feel that adrenaline rush and as you breathe in and out now. Feel the sense of pride begin to get stronger. Now unclench your fist and relax even more deeply. You are now and forever more a non smoker. I am going to give you a post hypnotic suggestion. A post hypnotic suggestion works long after the hypnosis session is over. For your benefit you will use the suggestion as long as you need it. When you no longer need it, it will just fade away. If you ever feel an urge or a craving for a cigarette, you will make a fist with your former smoking hand, that's right, a tight fist. This is now your power hand. This is a signal to your subconscious mind which says I am powerful. I am a non smoker. Now take three deep breaths in and out. And as you exhale each time, exhale all of that craving out into the atmosphere where it just dissipates and fades away. Remember if you feel a craving, make a fist and take three deep breaths. Tell yourself that a craving for a cigarette lasts for just a few seconds and after you have done this, you can relax that hand. All you need to cope with is a few seconds, so distract yourself. Think of the food you want to eat, this is not deprivation, this is reward. Tell yourself, I am not giving up pleasure, I am giving up poison. Tell yourself, the first puff is the problem. If I never take the first puff, I have no problem. You are now and forever more a non smoker. Imagine yourself one year from now. You are out with friends. You feel great. You look great. It has been a wonderful year. People around you are smoking. As you watch them puff away, you think about how lucky you are to be rid of that dirty, killing habit. Hear someone offer you a cigarette. Hear yourself say no thank you, I stopped smoking. You are now and forever more a non smoker and every night before going to sleep, tell yourself, I am a permanent non smoker. I expect to be a non smoker. I will allow myself to be a non smoker. I deserve to be a non smoker. Relax, let the results take care of themselves. You are a non smoker. You have given up smoking for many reasons. Think of those reasons now. Clean, clear, healthy, pink lungs. More energy, more stamina. Clean smelling mouth. Clean smelling breath. To be a better influence. To reinforce your confidence, to live a longer and healthy life and all the other good, positive, powerful reasons you have. You are now and forever more a non smoker. No matter what is going on in your life you are now and forever more a non smoker. No matter how aggravated you may be, nothing and no one can make you take the first puff. No matter how upset and sad you can be at times, nothing and no one can make you take the first puff. No matter how heart broken or aggravated you may be from time to time, nothing and no one can make you take the first puff. Believe it. Trust yourself. Trust your subconscious mind. A habit that is not fed is soon gone. You are now and forever more a non smoker. Now all thoughts, all cravings, all urges connected to smoking are gone from your mind and your body. Let it happen. Let it happen easily and effortlessly. You have given up smoking for yourself. You are now and forever more a non smoker. Congratulations.
Other information on Stop Smoking Self-Hypnosis CD/MP3:
It is predicted that by 2010 there will be 1.45 billion people in the world who smoke. This is a sad statistic. We all know the dangers of smoking and the negative impact it has on your health. We want to congratulate you on researching your options for quitting. You have taken a big step on the road to becoming a non-smoker.
The important thing is that you quit smoking. You CAN quit! Hypnotherapy has been proven to be effective in helping people quit for good. Research studies have been performed and people who use self-hypnosis to help them quit, are more likely to permanently quit than those who do not use self-hypnosis.
Hypnosis is natural, but so powerful. Under hypnosis, your subconscious mind will listen, understand, and follow the suggestions that it hears. This hypnosis recording is filled with powerful suggestions that will help you to stop smoking.
As of right now, we are assuming that you feel as though smoking is controlling your life. You are right, it is. But realize that it does not have to be that way. Hypnotherapy can put you back in control of your life and more importantly hypnosis can help you say no to smoking.
With this program, you will set a quit date 21 days from the date that you start the hypnosis treatment. Every night for 21 nights, you will listen to this program and your subconscious mind will absorb all of the powerful and positive suggestions on the recording.
After listening to the Stop Smoking self-hypnosis session, you will no longer smoke. You will be repulsed by the idea of smoking and you will want nothing do with it.
Realize that with hypnosis, you can quit smoking for good. You can and will become a non-smoker with this program!
Research demonstrates that hypnosis (especially combined with nicotine patches) compares quite favorably with standard behavioral counseling in generating long-term quit rates. (Nicotine & Tobacco Research, 10 (5): 811-818)
Take back the control and begin your lifetime of FREEDOM!
Steve is among the best in the world.
Being someone who is extremely familiar with the power of hypnosis, I can say without a shadow of a doubt that Clinical Hypnotherapist Steve G. Jones is among the best in the world.— Dr. Joe Vitale
Star of "The Secret"
#1 Best Selling Author of "The Attractor Factor"
the BEST programs out there.
I have purchased 3 products from Steve. I purchased 12 strand DNA activation, Abundance and Psychic Ability…these are the BEST programs out there and I am very picky. I have returned more programs (from other people who claim to help) then I care to count. If you are tired of searching for real programs that help then buy from Steve. You really should be charging alot more…— Karen G
No wonder Steve is the leader in hypnotherapy. How lucky are those who have had the benefit of his genius!— Jeraldine Saunders, Creator of "The Love Boat" Series


text:
"Just don't stay outside by yourself for more than a moment!"
"I won't!"
Vocifer turned her head back forwards. Nophis was always worrying that she was going to do something reckless and get herself killed. Surely she could survive for two nights in a city she had already visited? Her cousin fretted over things too much.
For the first time in a while, Vocifer approached the humongous door of the mansion. She hadn't memorized the exact date she had left here before the year was over, but now that she was back she already felt as though she had been gone for an unimaginably long time. Back at her cousins' house, it didn't seem nearly this long.
Vocifer danced up to the door and paused in front of it. The pathway was still icy, though there hadn't been snow for a few days. Winter tended to do that a lot. If I stand here too long, I'll freeze.
With very little hesitation, Vocifer raised a hand to knock on the gigantic door. At first, nothing happened, and she was worried that she would have to go around the back way. Her worries proved wrong, though, as the door slowly creaked inward, and the unfamiliar shadow of a man slunk back into the darkness of the mansion. There were no lights on. In that sense, Vocifer was thankful for the graying sunlight outside, but there was something more disturbing about the mansion. Apart from whoever had opened the door, it was perfectly silent, and there was no movement anywhere.
She stepped inside, reluctantly closing the door. "Tristis?" she called. "Are you here?"
No answer, apart from the vague, hesitant echo.
Again, no answer.
She allowed her feet to start moving as her eyes scanned the darkened walls. "Tristis!"
At this point she gave up calling for anybody and let her mind work. Surely Drossel has to be here somewhere, right? Why isn't there anyone here?
She paused briefly, and then continued towards the door behind the stairs. They're not gone. He's probably just in the puppet shop, like always… but where's Tristis? If they were going on vacation or something, they would tell me before I got here…
Her pace quickened and she pulled open the door into the dark hallway. This routine seemed so familiar to her, and she remembered doing this so many times back when she was still lost. She couldn't explain her attraction to the puppet shop well, although she had a shadow of an idea forming in her mind that might blossom into the truth later.
She didn't bother to slow down much as she inched down the hallway. She wasn't sure whether her footsteps being loud was a good thing or not – if there was someone here, it might interrupt them, but at the same time she didn't want to startle anybody. Just to be carefull, she restrained her feet a moment before she could see the light of the puppet shop.
Light. Someone is what if it's not Drossel? What will I do?
After a moment's hesitation, Vocifer stepped into the room. At first, she didn't see anything, and relaxed herself, but then –
"Vocifer? Why are you here?"
A familiar, staccato voice came from her left, and when she looked her eyes showed her the colorful garb of the family butler.
"Drossel, you're here," she breathed, suffocated in her own relief. Before she could keep track of what she was doing, her arms were around his torso, and she could feel the hint of his warmth…
"Let go of me."
Vocifer snatched her senses and took a few steps backward. She lingered a moment to allow her thoughts to fall back into place. You idiot, he's a puppet. He doesn't know what that means. Think, Vocifer!
"What are you doing here?" Drossel asked slowly. Vocifer half-expected him to look frustrated with her, but, as always, his face showed nothing but calm.
She cleared her mind again for a moment before replying. "I was coming back to visit Tristis and the others, but they're not here, so I came to find you… where is Tristis?"
Drossel blinked thoughtfully. "She left to find her parents… and she never came back."
Never came back? Vocifer echoed inwardly, trying to register this in her mind. Her thoughts worked through themselves for a minute. Did that mean she wouldn't see Tristis again? How long had this place been practically empty?
"Drossel, you haven't been alone here since I left, have you?"
He nodded slowly, and Vocifer was sure she caught a glint of sadness in his violet eyes. "It's been lonely. Only the dolls kept me –"
Suddenly Drossel appeared to realize something. Either that, or he heard something Vocifer didn't, because his head snapped towards the door and his expression hardened.
Vocifer looked at him unwittingly. Perhaps she was just paying more attention than she had a while back, but… was Drossel being more emotional?
"What's wrong?" she asked quietly, her eyes slowly wandering down to the same table that had always been in the middle of the room. Perched on it was the same box from a while back, with the same familiar blue marking. Again, Vocifer knew she had seen it before. She pondered it briefly, and then the answer came to her.
"Intruders." He looked back at Vocifer, and she returned his glance. Sure enough, she glimpsed the blue marking, just beneath his right eye.
Her gaze drifted for a few moments. His face is so perfect…
Drossel moved towards her, and her mind switched back to the physical world. "What? What do you mean, intruders?"
"Come this way." He stepped past her, evidently determined to leave this room. He appeared as though he had some sort of plan forming, although Vocifer couldn't guess what it might be. She followed him quickly back into the dark passageway.
He shoved open the door into the strange room Vocifer had only seen once before, though this time he clearly wasn't worried about concealing anything. Vocifer paused in the doorway, her eyes wandering the strange, dark room. It looked as if it was designed to be underground, but she was sure that she was breathing the sky's air right now…
Drossel suddenly stopped and turned around, speaking urgently once more. "No. This way."
"Huh?" Vocifer hesitated and followed, pulling the large door closed behind her.
She tailed him out to the main part of the mansion, still as empty as ever. At first she thought that he was leading her to the bedroom she had stayed in when she first came here, but he turned at a different point. There was another small door here on the second level, identical to the one below that led to the puppet shop. Where did this one open to? Phyiscally, it would be somewhere above the other room we were just in…
Drossel tugged the door open and looked at her purposefully. Vocifer stared back for a moment, and then hurried beyond the threshold when Drossel did so first.
As the room before her opened up, she glanced down and to her right. From the looks of this place, it was the strange room from before, although the duo was standing on a sort of upper level. The floor of the room waited far below. From what Vocifer could see, there was no wall or anything protecting her from falling off this upper ledge onto the floor below. Just the thought of it made her bend her knees and almost touch her fingers to the ledge to avoid falling off.
Drossel glanced backwards over his shoulder without relaxing. "Stand up," he told her, and to her surprise he offered a gloved hand for assistance. After a moment of stabilizing herself, Vocifer grasped it tightly. Clearly he had been up here before – otherwise he wouldn't be so confident.
He led her to a corner of the upper ledge so that she could see the large door on the left side of the room. She did not allow her fingers to open, not even when Drossel stopped moving and knelt down, apparently studying either the door or a particular section of the floor. Vocifer followed his gaze, but then drew her eyes away to a wall instead. Just the thought of putting one foot over the edge frightened her, and she followed Drossel to the edge, careful to inch back somewhat from the precipice. Thankfully there was ample space between here and the wall behind her. In response to this, she reluctantly let go of Drossel's hand, instead occupying herself with staying at least a decent third of a meter from the edge.
"Who are the intruders?" she queried quietly, her eyes drifting to Drossel.
He only returned a glance, and then his gaze went back to the room below. He never answered the question, for he was apparently waiting for something.
He's not going to jump down, is he?
A few minutes passed just about as slowly as an hour, and Drossel didn't move an inch. Vocifer watched the room intently, unable to keep her eyes in one place. Then a smaller door she hadn't noticed before swung reluctantly open, admitting three people she couldn't quite see in the light of a small lamp. One was tall and dressed entirely in black and white; the next was shorter and very hard to discern from his surroundings. The third was clad in red from head to toe, and that was all Vocifer could see from this distance.
Those must be the intruders, then, she told herself. But what are they here for? How did Drossel know they were coming? They don't look very extraordinary…
The short one split off from the rest and headed towards the spot where Drossel was perched like a hawk. At first Vocifer worried that the two of them had been spotted, but the short one was focused on something against the wall rather than what was above him.
Nervously, Vocifer peered over the edge, and noticed a strangely colorful object that somewhat resembled a girl in a frilly dress. It was difficult to see exactly what it was from this distance in the dark, though.
She glanced sideways at Drossel, whispering quietly, "What is that?"
He evidently had no trouble keeping his volume down in his reply. "It's one of my puppets." As if in response, he lifted one hand slightly, and Vocifer noticed glinting strings wrapped around his fingers.
Those must be puppet strings, she told herself. Her eyes flicked back down to the three intruders, and then back upwards to Drossel. "What are you going to do?"
"Lure them in." Slowly he rose to his feet. Vocifer could just imagine him saying something along the lines of let the games begin.
But what does he want with them? Wouldn't he try to lure them out?
Vocifer stayed close to the ground, waiting as Drossel paused for around ten seconds. Then he gave the strings a sudden jerk, and whatever they were connected to evidently moved; the three below now cast their eyes somewhat more upward. Vocifer shrank back, but they still seemed oblivious to her presence, and she relaxed gradually.
What is he doing? she asked herself, her eyes flicking back to Drossel. He is a little bit strange, but… that's all right. I'm sure he has a reason for what he's doing with this three.
Drossel raised his voice, evidently focused on the intruders. "That is strange… why does she move against her will?"
Is he taunting them with that puppet? Vocifer concluded that Drossel must have had an idea of what he was doing for a while. He may have been a puppet himself, but that, in addition to many other things she had noticed, made him seem irrefutably human.
He continued to manipulate a rather chaotic scene that went on below, consisting of the three intruders dancing around the room attempting to evade the slices of a large, sharp thing that the frilly puppet was clutching. It looked strangely comedic, and yet disturbingly horrifying.
And was the frilly puppet screeching? Making noise? Is it alive like he is?
Vocifer stared at Drossel again. Once more, his face had regained its stolid expression, and he appeared to have no reaction to what was occuring in the room beneath him (even though he was running the whole thing in the first place – which was strange in itself, since butlers usually weren't the ones running things). Another live puppet? What did that mean?
"Drossel?" she murmured. "Did you make that… out of a real person?"
He only glanced at her briefly, and then continued watching his chaos. Even so, his answer was clearly a yes. This made Vocifer feel an odd frustration with him, and her mind worked furiously to determine how to react. With nobody to keep him company in a small puppet shop, did Drossel really resort to creating things that shouldn't exist? Could he really have found a random little girl out of whom to make… a puppet?
That must be why the intruders are here, Vocifer realized, studying the now somewhat abated havoc beneath her.
She then gazed up at him again, gradually rising to her feet. "You shouldn't do that," she said slowly. "That means you caused this, didn't you?"
His eyes flicked towards her, and he let the string fall from his hand (the scene below had completely calmed down now). Even though the lively fire had returned to his eyes, he didn't respond.
"You knew I was coming back!" Vocifer seethed. "You could have—"
A voice from below interrupted her mid-sentence. "Up there!"
Her head snapped to the room beneath her. Now all three of the intruders were staring at her and Drossel. Instantly she realized why; in her irritation, she had forgotten to keep her voice down, and had revealed their location.
Vocifer's heart sank. Helplessly, she looked back to Drossel, who was glaring at her accusingly. "You blew it," he whispered sharply.
"I… I didn't mean to," Vocifer stammered, her eyes falling to the floor. "I'm sorry, it's just…"
"You're troublesome," the voice from below interceded again. Vocifer looked down; it belonged to the tall one in black. Vocifer looked down; apparently he was referring to Drossel, not her. Vocifer said nothing in response.
At least Drossel wasn't glaring at her anymore. He was peering intently at the tall one wearing black.
"Here, take this," offered the tall one wearing black. Vocifer still couldn't see clearly from here, but he had picked up the big sharp thing, and –
No, he can't!
Her eyes flew to the side. Drossel had stepped back, but nothing more.
From there, everything took place in a split second – at least, that was how Vocifer perceived it. She knew what would happen; the one in black was going to try to hurt them with the sharp thing. In her mind lingered a terrible thought – she knew who he was aiming for.
But she couldn't find her voice. She was too frightened. She could only try to dodge away from the dangerous sharp thing, try not to let herself get hurt. That was the moment she realized she was doing the wrong thing, but the next thing she knew the moment had already passed. Nothing she could do now.
When she looked up again, the three intruders had grouped to one side of the room, worrying about their own puppet. The sharp thing was nowhere to be seen – probably somewhere on the floor below.
Then Vocifer remembered why she really had been so worried. She didn't want to believe that any of this was happening, but this was real… and that was the problem with it.
She turned her head quickly, and her worst fear came true: Drossel was collapsed on the floor (of the ledge, fortunately), and there was a long gash splitting one side of his face where the sharp thing had connected, barely missing his eye. Of course, there was no blood because Drossel didn't have any,but to Vocifer it was still an equally horrifying sight. All of the strength evaporated out of her limbs, and she fell forward next to him, barely supporting herself on her knees. His violet eyes were staring, lifeless, as though he had been a puppet the entire time.
"Drossel, no," she breathed, barely aware of the tears on her own face. "You can't… please don't leave."
She felt as though she would choke on her own existence. She sought comfort, but when she tried, she realized that her most important source of comfort was paralyzed in front of her.
The last thing I did was yell at him…
"Oh, Drossel, please don't die…"
She wasn't sure why she was speaking out loud. Perhaps it was the only thing she could really do now, until something happened to lift her out of this nightmare. Now that she was forced into this bad dream, all she had wanted to do was to be close to him, to feel what little warmth he had…
She leaned in closer, until she could sense his face just beneath her own, trying to scrape out what little warmth she still could from his fading presence.
"Drossel, please stay… you're too talented to leave… and I need you…"
She caught her breath quickly, and went on: "Drossel… I love you."
She pressed his face into her own and kissed him – she didn't care whether he was made of wood or whatever it was; she just wanted her poor heart to stop breaking apart.
What seemed like an hour passed, and she couldn't suppress her pain even by that touch. Reluctantly, she finally drew away. If that was hopeless, then perhaps nothing could stop her tears from flowing. For a last goodbye, she wrapped her arms around him one more time, clutching him as close as possible. The only problem was that she wasn't sure she would ever want to let go.
She was startled out of her breath when she thought she felt Drossel move.
No, that's impossible. Despite her own thoughts, she loosened her grip a little. A few seconds past, and nothing happened. Indeed, it was impossible. She was sure she had witnessed Drossel receive a terrible blow to the head with her own eyes.
Just as that sentence was finished running through her mind, Drossel moved again. This time she was sure that he wasn't dead anymore. But… how can that be?
Vocifer straightened herself, hesitantly returning her arms to her sides. For sure, Drossel had moved – he was kneeling on his own, and before her own eyes he raised one hand to his head. Evidently he was aching there…
"Drossel … you're alive?" She wasn't sure whether to be relieved or skeptical.
Wait. That's not right. Drossel couldn't physically feel pain. He was a puppet, wasn't he?
Once more, she leaned closer to his face. In reaction, he lowered his hand, and looked at her strangely. "Vocifer, what is it?"
For a moment she stopped breathing. There's something different about his voice. It was difficult to think right now, and it was difficult to see in the dim light, but an odd possibility entered her mind. Why would Drossel speak differently like that? He had always sounded hesitant and forced… something about his tone was considerably more relaxed. Considerably more…
Her mind paused for a moment, attempting to calculate whether this whole thing was real.
That's not possible… what's going on?
It may have been a crazy idea, but it was the only explanation she could think of. Drossel watched her intently as she lifted her own hand, gently caressing his face with her fingertips.
As before, her breath caught in her throat.
Of course, Drossel quickly pulled away, but that one touch had been enough…
No, this isn't possible, but…
More nimbly than she thought was possible, she seized one of his hands in her own, using her other to pull off the glove that was still there…
And Vocifer gasped. Though she had told herself it wouldn't happen even in her wildest dreams, it did. Here, in front of her, Drossel's hand was real, flesh and blood, and he looked just as baffled as she was. It still retained all the nimbleness and grace it had as a puppet hand, but it was real.
She let him go and lifted her eyes to his face again. She wasn't sure how this could be happening, but it was, and she definitely wasn't disappointed.
But there's one more thing…
Drossel didn't say anything, so she pressed herself to him again, except this time it was her head to his chest. Thankfully, he still didn't react – Vocifer focused herself, and –
At first, it was a light sense, and then as she wait it, she heard it closer. Never did she think she would be so relieved to hear such a thing. It was the most relaxing thing her ears had picked up in a while, and she actually sighed.
Somehow, Drossel had acquired a heart, and it was beating slow and strong, and it made Vocifer want to cry just thinking about it. But she had had enough of that lately, and so she settled with burying her face in his neck, holding him close once again. And for once, she felt him relax just a little at her touch.
Eventually, her own pulse calmed back down to what it had been before any of this happened, and she allowed herself to back away. Slowly Vocifer was able to rise to her feet, albeit shakily. Drossel quickly followed suit, as easily as he ever had, and swept his fallen hat back upon his head.
Finally, Vocifer's eyes drifted back down to the room below. Where had the intruders gone? Evidently they had left a long time ago. Vocifer had no idea how long she'd been in this room, but with all that had happened, it felt like hours. Oh, well – time didn't seem to matter so much anymore.
Then she recalled that, in this whole mansion, she and Drossel were the only two significant people. What would happen next? Nophis wasn't coming back to get her until the next day at the earliest.
She glanced at Drossel, who was brushing himself off nonchalantly. Well, she wasn't alone in this place. She always had a talented butler with her. Time to get started.
"Drossel," she said sharply, and the butler looked up hurriedly. She smiled; now his fiery violet eyes went with the rest of him: pure and alive. She continued, "My cousins aren't coming back for me until at least tomorrow. Until then, I'm going to need someone to look out for me. Can you be that someone, please?"
Drossel paused for a moment, clearly not expecting the request. But after he had time to register it, he simply allowed himself to genuinely smile, bowing low at the waist. "Yes, milady. I will."
"So then who's this?"
The outside light was warm and welcoming, even though it only barely penetrated the clouds. A soft and comforting fall of snow was descending upon the city. As expected, Nophis had returned to the mansion for Vocifer the next day, although she hadn't anticipated her cousin bringing an unfamiliar man with her.
Vocifer only smiled. "This is Drossel," she explained to Nophis. "He used to be this family's butler, but unfortunately they've all seemed to up and vanished. He can't just stay here alone."
Nophis looked concerned. "But we don't have… accomodations for a butler at our home. There's room in the carriage, of course, but… what are we going to do with him?"
Drossel didn't appear the slightest bit offended. He only glanced at Nophis, slightly confused, and then his eyes went back to Vocifer.
"I actually haven't thought about it much," Vocifer lamented truthfully, not letting her gaze fall to the ground. "But I might have a vague idea."
She looked up at Drossel, into his eyes. She couldn't make it work without his true acceptance, though. Over the last day, he had more than tolerated her; at one point, he had allowed her to bring him close for a moment. Then, a little later, to Vocifer's surprise, he had clutched her in his arms himself, although she couldn't tell what he was really thinking.
Nophis wouldn't mind, would she? No, if she does, Nophis doesn't matter. We can be alone. At this time, Vocifer was so perfectly at peace that she couldn't stop herself from standing up tall just to kiss Drossel one more time…
That's right. All I need is to be close to him. Just to feel him here with me…
She stood on her toes to whisper one thing into his ear, so quietly that she could only hear herself breathe it.
"Drossel… I love you."


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Happy Birthday Xzibit!
Posted 18 September 2016 | | 7 Comments »
All of us here at XzibitCentral.com would like to wish Xzibit a happy birthday for today September 18th!
If you would like to send your birthday wishes to Xzibit, leave a comment on this post or hit him on Twitter at http://twitter.com/#!/xzibit
Justin – XzibitCentral.com
Xzibit Live Show: How The West Was Won – Irvine, California Oct 14
Posted 09 September 2016 | | 3 Comments »
Xzibit will feature at the 'How The West Was Won' concert in Irvine, California on October 14 2016. He will be joined by Ice Cube, Bone Thugs-N-Harmony, Mack 10, Warren G, King Tee, Lighter Shade of Brown, Rodney O, Joe Cooley and many more.
For more information and to buy tickets check with the venue of each show. For all live Xzibit shows go to http://www.xzibitcentral.com/info/xzibit-concert-tour-dates/
Xzibit promoted to series regular for Empire Season 3
Posted 07 July 2016 | | 3 Comments »
Empire fans can expect to see a lot more of Shyne Johnson in Season 3, as rapper-turned-actor Xzibit will be a series regular.
Fans were introduced to Xzibit's character, Shyne Johnson, in the back half of Season 2. There are many famous people and artists that have appeared on Empire, so at first we thought that Xzibit's role would be a brief one. However it's now been reported that Xzibit will be a series regular in Season 3. Shyne Johnson ain't going anywhere baby! (Unless Lucious kills him.) Shyne came into the play in the Season 2 finale, when Lucious admits to Cookie that he did a job for gangsters Tommy and Rosie while she was in prison. The only other person who knows about the hit is Shyne, whom Lucious screwed over. With Tariq and the Feds sniffing around, Lucious and Cookie know that they need to cover their bases and get Shyne on their side. This entails giving him an invite to Hakeem's wedding, but Shyne shows up to the wedding drunk and causes a scene. Now Shyne didn't strike us as the brightest crayon in the box, but more of Shyne's identity is set to be revealed in Empire Season 3.
Source: http://www.melty.com/empire-xzibit-has-been-promoted-to-a-series-regular-for-season-3-a5787.html
Xzibit To Guest Star On FOX TV Show 'Empire'
Posted 26 February 2016 | | 6 Comments »
Xzibit is bringing his acting talents to Empire. Mr. X To The Z, born Alvin Joiner, will be appearing on the FOX drama as a rival to Lucious Lyon (Terrence Howard).
Deadline reports that:
Xzibit will star as Leslie "Shyne" Johnson aside Terrence Howard's polarizing character, Lucious. The rapper will embody a music mogul with a close ear to the streets. "Shyne" also has resentment towards Lucious after getting blackballed for his lifestyle. Leslie "Shyne" Johnson is 100% wolf and 100% gangster. He has managed artists, started record imprints and even sold a few units here and there, but his bread and butter always has been — much to his years-long frustration — drugs, guns and extortion. Feeling shut out by the other heavy hitters in the music industry, he carries a big chip on his shoulder, especially for Lucious.
New Music: Back Up Off Me – Bishop Lamont (Ft. Xzibit & Kaleb Simmonds)
Posted 20 February 2016 | | No Comments »
Just days after a standout feature for Koache, Xzibit does it again. The platinum MC gets down with Bishop Lamont, who is a fellow Dr. Dre affiliate of the mid-2000s. "Back Up Off Me" is a single from Lamont's perceived 2016 debut, The Reformation.
As the title suggests, the record—featuring singer Kaleb Simmonds—is about pushing others for much needed room. X opens things up with a raspy and rowdy verse, talking like he did on his first two solo LPs. Bishop comes in next, showing why he caught the ear of Dre as well as Caltroit in the last decade. This is hard-nosed Hip-Hop that combines B-Boy pride with street-tested bravado.
Listen here: https://soundcloud.com/bishop-lamont/back-up-off-me-bishop-lamont-ft-xzibit-kaleb-simmonds
Source: http://ambrosiaforheads.com/2016/02/mc-eiht-reveals-some-unbelievable-secrets-about-the-casting-of-menace-ii-society-video/


text:
The excitement in the air is palpable as we leave our hotel room to go down to dinner. Women in sparkly frocks stand whispering in the hotel corridors and the waitresses in the restaurant seem in a hurry. We order soup and it arrives within 30 seconds. I overhear one waitress telling a diner, 'I just hope I finish my shift in time to see him.' At 7pm, as if everyone is obeying some invisible signal, the dining room mysteriously empties. We finish our dinner and hurry to the auditorium. There are two hours left before the show starts but there's not an empty seat in the house. One of the staff tells us that jackets and handbags were being placed on chairs as early as 3pm and that couples were dining in shifts so they wouldn't lose their sought-after floor-side tables.
Why such excitement? The answer is in Winifred's handbag. She pulls out a photograph and shows it to me. 'That was taken at a hotel in Chester a couple of years ago. He was lovely and so down-to-earth.' The picture is of Anton du Beke, one of the stars of the BBC's hit show Strictly Come Dancing. And Winifred is not the only member of Anton's fan club present. I am about to discover that women, from 18 to 80 years old, go misty-eyed at the mention of his name.
At 9pm the lights go down and the moment we've all been waiting for arrives. The Ballroom Blitz orchestra strikes up a tango and Anton and his partner, Erin Boag, spin onto the floor in a furious flurry of sequins, feathers and abruptly swivelling heads. They follow it up with a romantic waltz and a jaunty quickstep.
Each time Erin takes to the floor in a new dress, there's a gasp of approval from the women. The dresses can cost as much as £3,000 each and she never wears them twice. The performance ends with a standing ovation.
The dance show had been preceded by a question and answer session. While Erin sat demurely, Anton strutted around, thrilling the audience with his Michael Barrymore-style deadpan delivery and saucy asides. 'How did he meet Erin?' 'She was at the top of a pole in a lapdancing club,' he tells us. 'Who would be his ideal dance partner?' 'Darcy Bussell. I like someone who's a bit bendy.' The women in the audience are loving it. Some are wiping away tears of laughter. He tells us that his new Strictly Come Dancing partner, GMTV host Kate Garraway is on crutches with tendonitis. The young woman sitting next to me sighs: 'I'll be his dance partner.'
Just three years ago, the idea that a ballroom dancer could be a household name and a bona fide heartthrob would have been laughable. Helped in no small part by the Australian film Strictly Ballroom, the world of competitive dancing was seen as camp, dated and definitely not cool. Until, that is, the BBC launched Strictly Come Dancing.
The first two series passed me by but by series three, I found myself being seduced by the tears, the tassles and the torn ligaments. By the time cricketer Darren Gough took the trophy in 2005 with his foxtrot (he may not have been the best dancer but the judges all agreed he'd been on the biggest 'journey' which, roughly translated, means he was the most rubbish to start off with), I was hooked. It had glamour, it had drama and it had Bruce Forsyth. In short, it was the perfect Saturday night entertainment package. Some 12 million viewers tuned in for last year's final and dance schools up and down the country are reporting a surge in students.
Warner Leisure Hotels, which specialise in 'adults-only' holidays (meaning no kids, rather than x-rated content), were quick to pick up on the trend, offering 'Simply Ballroom' breaks, featuring a combination of dance lessons and entertainment by professional ballroom dancers, a guest appearance by Lionel Blair and a performance by Anton and Erin. The weekends have been a huge success, booking up months in advance.
I sign up for one being held at Thoresby Hall in Nottinghamshire. The hotel is an impressive former stately home, with sweeping lawns, ivy-clad turrets and a grand baronial hall with a huge stone fireplace. There's a new wing which houses most of the bedrooms and the auditorium where the classes and evening entertainment take place and there's a spa and swimming pool.
On the Saturday and Sunday there's a choice of masterclasses in everything from the rumba to the jive. My partner and I are ballroom novices so we sign up for beginners' classes in the foxtrot, the tango, the jive and the cha-cha.
Five minutes into the first class and it quickly becomes apparent that our own particular 'journey' is going to be fairly short and bumpy. The young teachers are fantastic - enthusiastic, talented, friendly - but there are so many people in the class and of such mixed ability that the 45-minute lesson feels more like an exercise in crowd control. Our teacher, Crystal, explains that in ballroom dancing the feet should never break contact with the floor. She tells us to imagine we have magnets on the balls of our feet and to glide across the floor with our knees slightly bent. When she does it she looks like Ginger Rogers. When I do it I look like Max Wall. I fare slightly better in the cha cha but only because I am paired with one of the professional dancers, my boyfriend having escaped to the bar.
Never mind. There's plenty of time to practise in the evenings on the dancefloor. Guest star Lionel Blair drops in on the first night and entertains the audience with his showbiz stories before launching into an energetic tap-dancing routine. Then it's the turn of the professional dancers to show us how it should be done. It's joyful, uplifting stuff. The bit I enjoy most, however, is when the ordinary couples take to the dancefloor. A white-haired couple who must have been dancing together for at least 50 years waltz by with a dreamy look on their faces. A mother and daughter practise an energetic jive and a straight-laced middle-aged couple are transformed into fiery Latino lovers as they play out a passionate paso doble.
I'll need a few more lessons before I'm ready to trip the light fantastic myself, but at least when I tune into Strictly Come Dancing tonight for the first results show, I'll know my foxtrot from my quickstep.
Simply Ballroom Breaks (0800 138 8399; arnerbreaks.co.uk) run year-round and cost from £299pp, including three nights' B&B, activities, one dinner and live entertainment. The next is at Cricket St Thomas, Somerset in March; for more dates and locations see the website. Train tickets to Retford courtesy of GNER (08457 225 225;
Simply Ballroom Breaks (0800 138 8399; gner.co.uk).


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