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INTERESTING can be three OR four syllables! Learn the simplest way to pronounce this word like a native by making a CH sound for the second T.

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In this American English pronunciation video, we’re going to go over the interesting pronunciation of the word ‘interesting’.

This word can be pronounced a couple of different ways. Thanks for the request for this video.

This word can be four or three syllalbles. If it’s four syllables, it can be pronounced IN-te-res-ting. Interesting. Oh, that’s interesting. Or, as you know, Americans sometimes drop the T after an N. So you’ll definitely hear it pronounced this way: IN-er-es-ting. Interesting.

I pronounce it as just three syllables. And when we do that, we tend to change the T to a CH sound. We do this with the TR cluster a lot, you’ve probably noticed. ‘Train’ usually sounds more like ‘chrain’.

As a three-syllable word, stress is still on the first syllable. DA-da-da. Interesting. In. The IH as in SIT vowel. It can be difficult for non-native speakers. The tendency is to make the EE vowel instead. EE-nteresting. Een. But it should be ‘in’. It’s a little more relaxed. Though the tongue position is similar, it’s not as close to the roof of the mouth, ih, in-. Also, think of droping your jaw just a little bit more. Een-, in-. So the tongue tip is forward, lightly touching the back of the bottom front teeth, while the mid-front part arches up. But again, it doesn’t get too close to the roof of the mouth, ih. For the N, the tongue tip goes to the roof of the mouth. In-ch. Now it’s where it needs to be for the CH: at the roof of the mouth. We stop the air, and pull the tongue back for the R, in-chr. Notice how the lips flare for the CH and the R. In-chr. Now we have the schwa so the tongue relaxes forward again so the tip is down. I’m going to show how the tongue moves in this word with my finger. Interesss. For the S, the tongue tip is also down, and we push air through the teeth, ss. “Inchrusss.”

Now we have a True T, but it’s a little weak. It doesn’t start a stressed syllable, so, (with hand), TT, the escape of air isn’t quite that strong. But the tongue does go to the roof of the mouth and pull away. Interest-. Tt, tt, tt, a little burst of air. Interes-ting, -ting. Now we have the IH vowel, but it does get a little tighter when it’s followed by an NG. So, in this case, maybe you can think of it being like an EE vowel. –Ting, interesting, -ting. It’s unstressed, so it should be fast, -ting. Back of the tongue touches the roof of the mouth for the NG sound at the soft palate. Interesting.

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Hey Dan. . Great article. .

Online reviews are great source for building trust among site visitors. Once a new visitor reads a positive review, the engagement rate increases spontaneously. And negative reviews help the site owner for better improvement. So reviews, no matter Positive or Negative can create a great impact. But ensure you always have a collection of some really good positive reviews.

Thanks. . .

Tino Fernandez

Interesting study Dan!

I when I look for a product or business in google, look down as you pointed out in your studio, the first page of google and whether the second. Rarely I came to the following pages, unless the first two do not find all the information I need.

As for shopping online, I am of the people before purchasing any service or item need to know that opinion is the company among consumers. It gives security to shop online to know those views. It is also true that a negative opinion can throw you back, but if there is 1 negative opinion among 100 positive, the negative for me is not important.

It is difficult for our website, have no client who is not happy with our service, especially if you have heavy traffic. What we have to try is always to make the customer is not satisfied change your opinion of us and give us another chance.

Thank you for your article!

websa100

This article is right on the mark. We're all consumers and we're all looking for information about others for not making any mistakes. This will not only be usefull for improving your SEO ranking (positioning), it'll also come handy to increase customer's satisfaction.

Vishal Mehta

Hi Dan,

Good Article, Best Reviews helps you a lot no doubt about it.

Brian Patterson
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Great stats - I'll definitely be using these when people call asking about Yelp. We've completely changed our reputation management strategy to stop trying to outrank Yelp as it has basically become impossible. Instead, we consult on what needs to change in their business to get better Yelp reviews naturally. We also help them build a process on how to ask people who are happy for Yelp reviews.

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That sounds like a good strategy, as a user I look for businesses that are active on Yelp. They might have a bad review here and there but I am also looking for a business owner that responds to bad/good reviews. That usually means they are taking measures to correct previous bad behavior. I have advised clients to follow a similar ORM strategy because I find Yelp users think like I do.

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» Library » Substance Abuse: The Power of Acceptance
By Darlene Lancer, JD, MFT ~ 4 min read

Accepting reality enables us to live in reality.

What does this mean? When life pleases us and flows in accordance with our needs and desires, we don’t think about acceptance. But when our will is frustrated or we’re hurt in some way, our displeasure causes us to react, ranging from anger to withdrawal.

We might deny or distort what’s happening to lessen our pain. We might blame others or ourselves or we try to change things to our liking and needs.

Denial

Although in some circumstances denial is a useful coping mechanism, it doesn’t help us solve problems. Nor does blame, anger, or withdrawal.

Denial is more common than we may realize. Everyone alters reality somewhat by perceiving events in accordance with our personal biases. Yet, sometimes we unconsciously use the defense of denial to make reality more palatable. Examples are:

Denial helps us cope with a potential threat or uncomfortable facts and feelings, such as our eventual death. We also deny reality when the truth would put us in conflict with someone else or ourselves.

Although denial may be helpful temporarily to cope with stress, a better defense is suppression , which is the conscious decision not to think about something. For example, a cancer patient may be served by deciding not to think all the time about dying, so that she can find the courage to undergo difficult treatment.

Denial is a core symptom of codependency and addiction. We have a distorted relationship to reality — often acting against our best interests. Addicts and codependents use denial to continue addictive behavior. Meanwhile, we endure destructive consequences and painful relationships, partly due to denial and partly due to low self-esteem.

Try to convince an attractive woman who thinks she is unattractive that she isn’t. Try to tell an anorexic that she’s too thin, an alcoholic that he or she drinks too much, or an enabler that he or she is perpetuating his or her child’s drug addiction. The last three examples illustrate how such denial can be viewed as resistance to change. Many people leave when they come to Al-Anon and learn that program is to help them change themselves, because at first, most go mainly to “help” (change) an alcoholic.

Codependents also typically repress their feelings and needs. This denial also postpones real acceptance of a situation. Pretending to ourselves that something doesn’t bother us enables us to take constructive action, set boundaries, or find solutions the problem.

Facing Facts

Paradoxically, all change begins with acceptance of reality. Herein lies our power. Facing facts, including those that we dislike or even abhor, opens us to new possibilities. Acknowledging a painful truth is not easy for most of us, especially if we’re used to denying or controlling our feelings and our circumstances.

C
Circulation on the Run
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Circulation on the Run
Circulation June 5, 2018 Issue

Circulation on the Run
20:04
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By Carolyn Lam, MBBS, PhD. Discovered by Player FM and our community — copyright is owned by the publisher, not Player FM, and audio streamed directly from their servers.

Dr Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. I'm Dr Carolyn Lam, associated editor from the National Heart Center and Duke National University of Singapore. This week's feature paper reports results of the SWAP-4 study, which is the first study to evaluate the pharmacodynamic impact of the timing and dosing of clopidogrel administration when de-escalating from ticagrelor therapy. Extremely important take-home messages for clinicians looking after patients with coronary artery disease and a must listen to. Coming up right after these summaries.

In the first original paper this week, chondroitin sulfate, well known in the context of the monogenic disease mucopolysaccharidosis type 6 may actually represent a novel therapeutic approach for the treatment of general heart failure. First author Dr Zhao, corresponding author Dr Foo, from Genome Institute of Singapore studied changes in myocardial chondroitin sulfate in non-mucopolysaccharidosis failing hearts and assessed its generic role in pathological cardiac remodeling. They found that failing human hearts display an abundant accumulation of chondroitin sulfate proteoglycans in the extracellular matrix largely localized to fibrotic regions.

The main component of chondroitin sulfate glycosaminoglycan chains in human hearts was chondroitin 4 sulfate. TNF alpha was a direct binding partner of glycosaminoglycan chains rich in chondroitin 4 sulfate. Modification of the chondroitin sulfate chain with the recombinant human arylsulfatase B, which is an FDA-approved treatment for mucopolysaccharidosis type 6 that targets chondroitin 4 sulfate, actually ended up reducing myocardial inflammation and overall fibrosis in vivo. In two independent rodent models of pathological cardiac remodeling, this recombinant human arylsulfatase B treatment prevented cardiac deterioration and improved functional recovery. Thus, targeting extracellular matrix chondroitin sulfate represents a novel therapeutic approach for the treatment of heart failure.

The next paper focuses on the subcutaneous ICD, which is an entirely subcutaneous system that does not require intra-procedural vascular access or endovascular defibrillator leads or coils. Now the subcutaneous ICD has a novel mechanism of defibrillation and is associated with an increased energy requirement for defibrillation when compared to traditional transvenous ICDs. Thus, ventricular fibrillation or VF conversion testing at the time of subcutaneous ICD implantation is a class 1 recommendation.

Yet, what is the current adherence to this recommendation? Well, today's paper addresses this question from first and corresponding author Dr. Friedman from Duke Clinical Research Institute. He and his co-authors studied first time subcutaneous ICD recipients between 2012 and 2016 in the National Cardiovascular Database Registry ICD Registry to determine the predictors of use of conversion testing, predictors of an insufficient safety margin during testing and in-hospital outcomes associated with the use of conversion testing.

Results show that use versus non-use of VF conversion testing after subcutaneous ICD implantation in the US was more related to physician preference than patient characteristics. The study also identified several patient characteristics associated with an insufficient defibrillation safety margin. That included increased body mass index, severely decreased ejection fraction, white race, and ventricular pacing on the pre-implantation ECG. Use of VF conversion testing after subcutaneous ICD implantation was not associated with a composite of in hospital complications or death. These data may inform ICD system selection and a targeted approach to conversion testing.

We know that elderly patients are at elevated risk of both ischemic and bleeding complications after an acute coronary syndrome and display higher on clopidogrel platelet reactivity as compared to younger patients. Does prasugrel at five milligrams compared to clopidogrel reduce ischemic events without increasing bleeding in the elderly? Today's paper addresses this question from corresponding from corresponding author Dr Savonitto from Manzoni Hospital Italy and his colleagues.

These authors performed a multicenter randomized open label blinded end point trial comparing a once daily maintenance dose of prasugrel five milligrams with the standard clopidogrel 75 milligrams in patients more than 74 years old with acute coronary syndrome undergoing percutaneous coronary intervention. The primary end point was a composite of mortality, myocardial infarction, disabling stroke and re-hospitalization for cardiovascular causes or bleeding within one year. Enrollment was interrupted due to futility for efficacy according to pre-specified criteria after a planned interim analysis when 1,443 patients had been enrolled with a median follow-up of 12 months.

At this point of interruption, there was no difference in the primary end point between reduced dose prasugrel and standard dose clopidogrel. The results of this Elderly ACS 2 study therefore could not show overall clinical benefit of prasugrel five milligrams versus clopidogrel in elderly ACS patients undergoing early PCI.

The final study is the first to define the cellular and molecular mechanisms of cardiac valve inflammation and fibrosis occurring in the setting of systemic inflammatory disease. First author Dr. Meier, corresponding author Dr Binstadt from University of Minnesota used T-cell receptor transgenic mice which spontaneously developed systemic auto antibody associated autoimmunity leading to fibro inflammatory mitral valve disease and arthritis.

They identified a critical population of CD301b/MGL2 expressing mononuclear phagocytes that orchestrated mitral valve inflammation and fibrosis in this mouse model. They further demonstrated an analogous cell population was present in human inflammatory cardiac valve disease. Finally, they defined key inflammation molecules that drove mitral valve disease in this model, thus providing multiple potential therapeutic targets that are required for mitral valve inflammation and fibrosis.

Dr Carolyn Lam: That wraps it up for your summaries. Now for our feature discussion.

Searching between different classes of P2Y12 inhibitors including de-escalation from ticagrelor to clopidogrel commonly occurs in clinical practice. However, what are the pharmacodynamic profiles of this strategy? Well, today's feature paper is going to provide a lot of insights. I am so pleased to have the corresponding author of the SWAP-4 study, Dr. Dominick Angiolillo from University of Florida College of Medicine Jacksonville, as well as our associate editor Dr. Gabriel Steg from Hôpital Bichat in Paris, France. Dominick, now this is SWAP-4. That means there was a SWAP 1, 2, 3. Could you just paint the background and rationale for SWAP-4 and tell us what you found?

Dr Dominick Angiolillo: We performed this study on the background of a line of research that we've been conducting over the past number of years of switching antiplatelet therapies. There's so many different types of switches that can occur and one of them is that which is defined as a de-escalation which is that from a more potent P2Y12 inhibitor to a less potent and one of those that occur frequently in clinical practice is the switching from a ticagrelor to clopidogrel and this was essentially the rationale for conducting the SWAP-4 study.

Now I want to start off with saying that the reason for doing this study is not to advocate switching because we always recommend that individuals follow guideline recommendations but we performed this study because we wanted to provide clinicians with some additional insights that if you're going to switch particularly from ticagrelor to clopidogrel, which would be the modality which is associated with, put it this way, with the smoothest transition one drug to another.

This is the rationale. What we did was do a pharmacodynamic, conduct a pharmacodynamic study taking patients who were on standard treatment with dual antiplatelet therapy aspirin and clopidogrel and they had a run-in phase with ticagrelor. And the reason why we took patients on the back part of aspirin and clopidogrel is because we then wanted to look at the effects after switching to compare it with a baseline. There have been some discussions about drug-drug interactions. And patients were randomized to either continue with treatment with ticagrelor to switch with a loading dose of clopidogrel, 600 milligrams 12 hours after last dose of ticagrelor. 24 hours after last dose of ticagrelor or directly switch with a maintenance dose. So, the randomization was into four groups.

Essentially to keep a long story short, what we observed was that when de-escalating from ticagrelor to clopidogrel we did see an increase in platelet activity obviously as expected. But the use of a loading was not able to mitigate this increase but there were no differences according to timing of administration of the loading dose clopidogrel 12 or 24 hours. We had anticipated in our study design that with the administration of the loading dose 24 hours after last maintenance dose we could have achieved a smoother transition, but this was not the case.

Nevertheless, the overall conclusions of our study are supported by the pharmacodynamic data in terms of you still achieve a better transition when you give a loading dose than without a loading dose. I was also want a little bit cautious and I think during the review process of the journal and feedback from the editors we kind of phrased in a very cautious way the suggestion for a drug-drug interaction, in fact we suggested because there are other ways to look into this phenomenon in more detailed manner. For example, doing some specific pharmacodynamic analysis which was not done in this study. Nevertheless, the take-home message from a clinical perspective remains unchanged.

Dr Carolyn Lam: Thanks so much, Dominick. That was a very important framing of the paper that you gave us at the start that this trial was not designed to try to say who should be de-escalated or not and that should be in line with the guideline recommendations and yet such an important just take-home message that if there is a need that the 600-milligram loading dose of clopidogrel should be used. You know, Gabriel, you've thought a lot about this and especially the drug-drug interaction question. What are your thoughts there?

Dr Gabriel Steg: Yeah, well first of I think this is an extraordinary, important study even though it's a pharmacodynamic study, which many clinicians might look at and then quickly read the abstract and turn the page I think this is actually one of the most interesting papers we've published in recent months. The reason for this is this is tackling a very common clinical scenario, which is having or desiring or wanting to de-escalate the intensity of platelet therapy after a PCI or ACS from a potent agent such as ticagrelor to a less potent agent such a clopidogrel. And as nicely explained in the paper, there are multiple reasons why this can occur.

A common clinical scenario is that cost is a major issue. Because of the cost patients or physicians may want to switch to clopidogrel, a generic drug as opposed to a branded drug. Another scenario which is fairly common is side effects. Either nuisance bleeding or maybe dyspnea with ticagrelor may prompt some physicians and patients to want to deescalate to clopidogrel. To a less intensive therapy which may not have dyspnea or may not cause as much nuisance bleeding. And finally, sometimes it's done on purpose because some believe that within a few weeks or months following PCI or ACS the benefits of more intensive patient therapy is less, the risk remains the same and therefore maybe we could proposedly de-escalate therapy to clopidogrel and get away with it and there have been a number of randomized studies and observational studies that suggested that this might be feasible although these studies have weaknesses. They're often open label. They're often fairly small and somewhat underpowered.

So, we don't have a definitive answer. Nevertheless, this happens on an everyday basis in most large clinical centers and we don't know exactly how to do it and what the best way to do it and I really want to credit Dominick's team for doing a rigorous series of investigations, including this one, which is the latest one but not the only one in trying to really map out how exactly we should as clinicians manipulate these agents to achieve the best safety and efficacy for our patients. And I think the message here is very clear. Yes, you can de-escalate but you have to be careful on how you do it. And I think you really need to use a loading dose, a 600-milligram loading dose of clopidogrel if you're going to deescalate from ticagrelor to clopidogrel to avoid a gap in protection that might be deleterious to patients.

That does not address all of the questions that are raised by de-escalation and as I pointed out I think outcome trial data are really of paramount importance here, but I think this really important because it has major practical implications for clinicians worldwide on how to do this. So, I think this is a great study. I really want to congratulate Dominick.

Dr Dominick Angiolillo: Thank you.

Dr Carolyn Lam: You looked at the genetic status as well. Could you tell us about your findings there?

Dr Dominick Angiolillo: We in the spirit of trying to perform the most comprehensive possible assessment we have also looked at the genetic background of our patients and in particular looking whether the presence of a loss of function allele for CYP2C19, which is involved with clopidogrel metabolism, could have affected the outcomes. And the reason why we did this there've been a lot of studies clearly showing that if you have a loss of function allele for CYP2C19 you do have higher levels of platelet reactivity. Therefore, we want to see if those carriers would have had even a greater increase in platelet reactivity. And again, we did all this in the spirit of really trying to define again this from a pharmacodynamic standpoint, if there could be any potential safety hazards with such an increase in platelet reactivity with the de-escalation.

When we did our analysis, we did not find any impact of a CYP2C19 on our data. However, I think it's important to underscore that we did not have too many patients with a loss of function allele so clearly the study was not designed or nearly closely powered to look into this assessment. So, I think that aspect does need to be interpreted with caution.

Dr Carolyn Lam: Thanks so much, Dominick. Were there perhaps caveats that clinicians listening in should pay attention to? For example, this study was conducted in stable patients with coronary artery disease. What about patients with recent acute coronary syndrome?

Dr Dominick Angiolillo: That's a great point. The reason why we conducted this study in a more stable setting was largely driven by two aspects. Well first of all, we wanted to have a run-in phase of patients switching from clopidogrel to ticagrelor to have some sort of baseline to reference to after the switch. And this would have been mostly ACS patients that would be less likely to be on clopidogrel. The second is purely a safety issue. We know that patients with acute coronary syndromes are associated with higher levels of platelet reactivity and in the context of a study where we do not know the pharmacodynamic profiles associated with de-escalation or better off we don't know the details.

And so, there was a safety consideration there which is why we did it in stable patients. But what we can say is tied with Gabriel's comment before in all the studies out there are not powered or do not have the rigor of a mega trial. Although we give our suggestions and recommendations, practical recommendations on how to switch, there is an increase in platelet reactivity and we stress in our manuscript that if you are going to switch, please try to delay this as much as possible because those increases in platelet reactivity for example, in a patient with an ACS for example, immediately after PCI, something that we probably would not want for our patients. I'm very happy actually that we conducted the study in the more stable cohort because we had less confounders. This is kind of the reason behind all this.

Dr Gabriel Steg: The last question maybe I would ask Dominick is whether he believe that results would be different if we had the patients on a maintenance therapy for longer with clopidogrel, do you believe that the risk of rebound or drug-drug interaction are the same early on after institution of therapy or later on? Is there any reason to expect a difference?

Dr Dominick Angiolillo: That's a great question. My personal opinion would be that with longer duration the platelet reactivity would have gone back down to baseline. We actually continue to study out up to around 10 days following the switch which we thought would have been sufficient time to get back to baseline and it was not the case particularly in the patients whose switch was a 75 milligram. The answer's probably yes. Probably yes. To redesign the trial again maybe having that 30-day time point as well would have been obviously of added value.

Dr Carolyn Lam: Thank you so much, Gabriel and Dominick. This has been extremely insightful. Fun as always.

You've been to Circulation on the Run. Don't forget to tune in again next week.

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