March 2012

Volume 17, Issue 1

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Review Article - The Effects of Yoga on Anxiety and Stress by Amber W. Li, PharmD and Carroll-Ann W. Goldsmith, DSc

Abstract

Stress and anxiety have been implicated as contributors to many chronic diseases and to decreased quality of life, even with pharmacologic treatment. Efforts are underway to find non-pharmacologic therapies to relieve stress and anxiety, and yoga is one option for which results are promising. The focus of this review is on the results of human trials assessing the role of yoga in improving the signs and symptoms of stress and anxiety. Of 35 trials addressing the effects of yoga on anxiety and stress, 25 noted a significant decrease in stress and/or anxiety symptoms when a yoga regimen was implemented; however, many of the studies were also hindered by limitations, such as small study populations, lack of randomization, and lack of a control group. Fourteen of the 35 studies reported biochemical and physiological markers of stress and anxiety, but yielded inconsistent support of yoga for relief of stress and anxiety. Evaluation of the current primary literature is suggestive of benefits of yoga in relieving stress and anxiety, but further investigation into this relationship using large, well-defined populations, adequate controls, randomization and long duration should be explored before recommending yoga as a treatment option. (Altern Med Rev 2012;17:21-35.)

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Original Research - Use of a Standardized Extract from Echinacea angustifolia (Polinacea®) for the Prevention of Respiratory Tract Infections by Francesco Di Pierro, Giuliana Rapacioli, Tarcisio Ferrara, Stefano Togni

Abstract

Echinacea preparations are extensively used for the prevention and the management of the common cold. Despite this popularity, the clinical studies on Echinacea have produced mixed results, possibly in part because of the poor characterization of the extracts investigated and the use of different species and/or plant parts for the preparations investigated in the various trials. To address this issue, Polinacea®, a highly standardized extract from a well-defined botanical source (roots of Echinacea angustifolia) with a specific phytochemical profile (presence of the complex polysaccharide IDN5405, the phenylethanoid echinacoside, and substantial lack of alkamides) was developed. We have studied whether Polinacea® could enhance the immune response subsequent to the influenza vaccination, and whether the use of this preparation could translate into a decreased morbidity from influenza. The preliminary results were encouraging, and suggest that Polinacea® could be used for improving the immune response to influenza vaccine. (Altern Med Rev 2012;17-1:36-41)

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Original Research - Nutritional Supplement Therapy Improves Oxidative Stress, Immune Response, Pulmonary Function, and Quality of Life in Allergic Asthma Patients: An Open-Label Pilot Study by Chih-Hung Guo, PhD, Po-Jen Liu, MD, Kuan-Pin Lin, RN, MSN, Pei-Chung Chen, PhD

Abstract

OBJECTIVE: To examine the effects of nutritional supplement therapy on oxidant-antioxidant status, inflammation and immune system responses, pulmonary function, and health-related quality of life in patients with mild to moderate allergic asthma. METHODS: Adult asthma patients (n=30) received daily multiple nutrient supplements for two months. Age- and gender-matched healthy controls (n=30) did not receive any supplements. Enzymatic and non-enzymatic antioxidant status, malondialdehyde (MDA), high-sensitivity C-reactive protein (hs-CRP), immunoglobulin E (IgE) and T-lymphocyte subsets, pulmonary function indices, as well as scores for asthma control and quality of life, were assessed at baseline, at one month of treatment, and at two months of treatment, which was also the end of the study. RESULTS: At baseline, asthma patients had significantly higher IgE, MDA, copper (Cu), hs-CRP, and CD19 and CD4/CD8 lymphocyte ratios, and decreased selenium (Se), zinc (Zn), β-carotene, vitamins C and E, and catalase, glutathione peroxidase (GPx) and glutathione reductase (GR) activities compared to healthy controls (p < 0.05). During the study period, asthmatics showed non-significantly increased pulmonary function and a trend toward lower IgE levels, markedly reduced MDA, Cu, hs-CRP, and CD19 and CD4/CD8 ratios, and increases in levels of Se, Zn, β-carotene, vitamins C and E, and enzymatic antioxidant activities. Also, their asthma control and health-related quality-of-life scores increased significantly by the end of the study. CONCLUSION: Our results indicate that nutritional supplement therapy may improve dysregulated oxidant and antioxidant status, inflammation and immune responses, pulmonary function, and health-related quality of life in patients with mild to moderate allergic asthma. (Altern Med Rev 2012;17:42-56)

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Original Research - A Randomized Controlled Trial of a Multifaceted Integrated Complementary-Alternative Therapy for Chronic Herpes Zoster-Related Pain by Fred Hui, MD, CCFP, Eleanor Boyle, PhD, Eugene Vayda, MD, FRCP, Richard H. Glazier, MD, MPH, FCFP

Abstract

INTRODUCTION: Our objective was to determine whether a three-week complementary and alternative medicine (CAM) approach integrating several therapies from Traditional Chinese Medicine (TCM) along with neural therapy (injection of 1% procaine as local anesthesia) reduces the level of unresolved pain associated with herpes zoster. METHODS: The design was a randomized controlled clinical trial in a community-based primary care clinic in Toronto, Ontario. We studied individuals 18 years of age and older with a confirmed diagnosis of herpes zoster of at least 30 days duration and with at least moderate postherpetic neuralgia pain (≥4) on a 10-point Likert scale. The CAM therapies used were acupuncture, neural therapy (1% procaine injection as a local anesthetic), cupping and bleeding, and TCM herbs. An immediate treatment group (n=32) received the CAM intervention once daily, five days per week, for three weeks. A wait-list (delayed treatment) group (n=27) was used as a control and received the same treatment starting three weeks after randomization. This three-week time period, when one group was receiving active CAM treatment and the other was not, was used as basis of comparison for treatment effects between groups. Pain, quality of life, and depression were measured at baseline, and three, six, and nine weeks post-randomization. Patients were followed for up to two years. RESULTS: Participants had a mean age of 69.8 years (SD=11.1) and had had herpes zoster-related pain for a median of 4.8 months (range: 1 month to 15 years). The immediate treatment and control groups had similar pain levels at baseline (treatment = 7.5; control = 7.8; p=0.5; scores based on the 10-point Likert pain scale). At three weeks post-randomization (i.e., after the immediate treatment group completed treatment) pain scores differed significantly (treatment = 2.3; control = 7.2; p< 0.001). The observed reduction in pain in the immediate treatment group was maintained at nine weeks and at long-term follow-up (one to two years later). The delayed treatment (control) group also had significant reductions in pain after their integrated CAM treatment was completed. CONCLUSION: The described CAM protocol was associated with significantly reduced sub-acute and chronic post-herpes zoster neuralgia pain within three weeks of initiating treatment. Improvements persisted for up to two years. (Altern Med Rev 2012;17:57-68)

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Original Research - Application of the Essential Oil from Copaiba (Copaifera langsdorffii Desf.) for Acne Vulgaris: a Double-Blind, Placebo Controlled Clinical Trial by Ary Gomes da Silva, Paula de Freitas Puziol, Roane Nunes Leitão, Tatiana Rafaela Gomes, Rodrigo Scherer, Mônica Lacerda Lopes Martins, Áurea Scárdua Saade Cavalcanti, Luiz Carlos Cavalcanti

Abstract

Copaiba oil-resin is widely used in traditional medicine due to its anti-inflammatory, healing, and antiseptic activities. This research aims to extract and evaluate the qualitative and quantitative composition of copaiba essential oil from the oil-resin, and test its effects, after incorporation in a gel applied in volunteers with acne, in a double-blind placebo controlled clinical trial. The essential oil was extracted by steam distillation, and purified by freezing to remove the residual remnant water. The density of the essential oil was gravimetrically determined by weighing 1 mL of liquid at 20°C. The identification of the essential oil components was carried out through high-resolution gas chromatography analysis, coupled with mass spectrometry. The essential oil has a density of 0.9175 mg/mL and was composed of 48 substances, 14 of which were the major components representing 95.80% of total essential oil composition. Cis-thujopsene was the main component (46.96% of total essential oil composition). The surface affected with acne decreased when treated with placebo (F = 13.931, p = 0.001, r = 0.518; r² = 0.268), but the linear model could explain only 26.8% of total variance in original data matrix. There was a highly significant decrease in the surface affected with acne in the areas treated with the 1.0% copaiba essential oil preparation (F = 86.494, p = 0.000, r = 0.834; r² = 0.695). (Altern Med Rev 2012;17:69-75)

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Editorial - Atlas Shrugged (Kind Of) by Al Czap, Publisher

Her husband was abusing their daughter, or, perhaps an axe murderer was a nephew, or an embezzler was a brother. When you see one of those stories on television news, the mother “couldn’t believe her husband would do that to her daughter”, the uncle never saw the axe fetish, and the sibling did not relate the brother’s funds, which were well beyond his means, to embezzlement. Sometimes it is the truth; many times it is someone turning a blind eye to something they are intimately aware of.

On March 18, 2012, Dateline NBC weaved their way through a report beginning with the results of an improperly mixed dietary supplement (DS), which led to disastrous consequences. The episode ended with the exposure of a major problem in the DS industry – fraudulent laboratory analysis by “independent laboratories.” This is the very same problem reported in Alternative Medicine Review (AMR) eight years ago (Volume 9, Number 4, 2004) in my editorial entitled “Bursting the Analytical Bubble.” Having authored more than a dozen editorials on DS quality control problems rampant in the industry, I know the problem has not gone away and has been consistently ignored by the DS industry for years. Perhaps this news story will be a kick in the pants.

The Dateline episode began with the life changing consequences of mistakenly putting toxic levels of selenium in a product. This mistake was due to an improper level of selenium called for in the master formula for the product in question. The interviews with the victims, complete with documented hair and fingernail loss and medical nightmares, are heartbreaking. The rest of the episode documents how the analytical quality-control standards, which should have been in place, failed.

The liquid vitamin product, Total Body Formula purchased from General Nutrition Center (GNC), was eventually subject to a recall effort after consumer symptoms caused alarm. The raw material supplier of the selenium, Wright Enrichment, upon learning about the problem, allegedly produced a false certificate of analysis showing acceptable selenium levels, without having an actual laboratory test run. TexAmerican Food Blending was responsible for the blending of the final liquid product. Interviews on camera by the production manager reveal that upon finding “black specks” in the liquid product, the employees strained the product through “women’s panty hose” into buckets to try and remove the contamination.

BUT, what if the raw material supplier, the blender, and the final retail sales giant had submitted the ingredient, the in-process product, and the final product to an independent laboratory for analysis? The problem would have been solved, correct? Well, not necessarily. As the Dateline investigation continued, they carefully set up a sting operation for the laboratory director, Dinesh Patel (Patel), who did the fraudulent analysis mentioned in my AMR editorial (Bursting the Analytical Bubble), albeit under the guise of a new company, now Atlas Bioscience.

Two carefully constructed powder samples were prepared for submission to Atlas for analysis. Unknown to the smiling Patel, there were ingredients for which analysis was requested that were not even in the product and which should have come up with no detectable results. Moreover, both samples had been laced with materials that were not only toxic, but also which were present in high enough levels that no legitimate analytical laboratory on earth could possibly miss them. One sample was spiked with high levels of selenium and the drug sibutramine; the other with high levels of arsenic and lead. Atlas reported analytical results suspiciously close to the levels provided by Dateline on a “suppliers analysis” (i.e., the initial fabricated certificate of analysis) for the two products, even though those levels were fictitious. This was the same thing that Patel did in the “analysis” he provided for the AMR product sting eight years ago, only this time he was missing levels of materials by almost a thousand-fold: toxic levels as it turned out, and he missed the sibutramine entirely, even though it was part of the analytical request.

Imagine yourself now listening to a political speech on television. Close your eyes and pretend it is not the statement Patel used in his defense to Dateline:

“When given misleading information regarding a samples make-up, we would not be aware that the data being observed is being compromised due to the matrix parameters we are not cognizant towards.”

In something imaginable only as the Heisenberg Uncertainty Principle being interpreted by a reincarnated William F. Buckley in the throes of an LSD meltdown, Patel has reduced analytical laboratory science to an internet social standard.

After being visited again by Dateline, Patel admits his initial analysis was wrong, but states:

“When looking at small quantities those values deviate, hugely. In the real world, a shady businessman is not trying to contaminate products with things such as arsenic, cadmium or lead.”

He not only contributes to an industry problem, but also does not understand the very basics of the problem. Shady businessmen do contaminate products with sibutramine, with steroid substances, and with erectile dysfunction drugs. This is well documented. Anything goes with some people when the goal is profit. Poor quality control procedures will miss toxic substances, such as lead in a crop product that is exposed to environmental contamination, or heavy metals provided with loving care by Mother Nature herself, courtesy of naturally occurring soil conditions. Patel was entrusted with an important job; unfortunately he does not seem to properly comprehend this job or its requirements. Atlas shrugged off their responsibility.

And now for the fun part. Since I have mentioned the internet, let’s do a little searching. If you Google “Atlas Bioscience” one of the things you will see are links with (PDF) in front of them. Many of these links once would have taken you to PDFs of Atlas’ “analytical reports,” for products submitted by DS product companies (who shall go unnamed in this particular editorial, but which you can readily see for yourself in the URLs). At one time certain DS companies were proud to display these links from their company websites as a testament to their “product quality.” Many of the links no longer work when you click on them. However, if you move your cursor to the right of each link a double arrow appears and to the right of that a copy of the unlinked PDF will appear, albeit this copy is a little harder to read. Take a bit of time to view these: You will find it an interesting way to spend an hour.

Now for the part that keeps me in the running for the most disliked person in the DS industry: what to do when you have to take your child to the parent-teacher conference knowing full well that the teacher should be fired…

Trade associations that count ingredient suppliers, supplement manufacturers, and retailers, as dues-paying members are often reluctant to step on the toes of those that contribute to their coffers. At no time does this become more obvious than when a negative story about supplements comes out in the national media. Just like Captain Renault in Casablanca, commanding his police force to “round up the usual suspects,” the stomach churning line from some trade associations has always been that “the problem is only caused by a few bad actors.” While Lieutenant Colonel Kilgore, in Apocalypse Now, loved “the smell of napalm in the morning,” I prefer the sound of member toes crunching when stepped upon.

Press releases in response to the Dateline episode (edited for space) included:

The American Herbal Products Association (AHPA):

“Laboratories such as the one depicted on the Dateline NBC show do not represent the mainstream of laboratories that service the food, dietary supplement, drug, and allied industries. … The specific situation of a laboratory’s failings covered by Dateline NBC is not representative of the responsible supplement industry. The show failed to recognize the expertise found in hundreds of supplement companies that understand how to properly qualify a third-party testing laboratory. Knowledgeable manufacturers know how to choose a lab and to verify results.”

The Natural Products Alliance (NPA):

“Consumers can trust what they read on the labels of dietary supplements. We share the concern about the issue of ensuring that products contain what the label claims and are not contaminated… Fortunately, consumers are smart enough to understand that a few or occasional lapses in quality assurance should not translate into suspicion of an entire category of products, especially one with a strong history of safety. … Products that contain undeclared drug ingredients are not dietary supplements. These products are illegal drugs, and they have no place in the legitimate marketplace.”

The Council for Responsible Nutrition (CRN):

“We are concerned, as any industry would be, when a few companies engaging in fraudulent and criminal activity overshadow the legitimate products sold by responsible companies.  … Responsible companies follow the Good Manufacturing Practices (GMPs) regulations that became fully effective in 2010. These rules prescribe step-by-step requirements for the manufacturing and testing of dietary supplements—from the raw ingredients coming into a plant to the finished products headed for consumers—and place absolute responsibility on the manufacturers and distributors, including the actions of any testing labs they hire. We call on FDA to take strong enforcement action against both the companies and the testing labs who do not make safety their top priority…”

United Natural Products Alliance (UNPA):

The UNPA has not issued a press release on the Dateline segment as of the writing of this editorial. One interview with Loren Israelson, UNPA Executive Director, had him stating that the segment was “sobering and distressing and that this issue will hopefully be dealt with.” UNPA has operated an analytical group for its membership and has held analytical lab competence training events for the past eight years. UNPA has maintained a position that:

“FDA (Food and Drug Administration) is set to begin Section 111 GMP inspections of contract analytical laboratories who are seen by FDA as an extension of the manufacturer and thus within the scope of Section 111 inspection… It has become increasingly clear that the large majority of DS manufacturers have no benchmark data to judge whether their spend on inside/outside analytical testing is appropriate based on industry best practices. We believe this should be remedied and have been in discussions with Ole Miss [University of Mississippi, editor] and FDA to provide key benchmark data education for company executives with regard to costs for analytical testing, personnel training, analytical equipment, investments, etc. We believe this will be a critical tool to help companies judge their performance against best practices.”

Meatloaf sang “Two Out of Three Ain’t Bad.” In the case of trade associations one would hope that it was more than “One Out of Four Ain’t Bad.”

Every time that I have attended industry trade events I have heard the “industry leaders” complaining about the problems in the industry, and quality problems in the industry have been at the top of the list over the past 10-15 years. There have always been complaints about how to fix this big, amorphous quality issue in the DS market, the same one the media has been beating the industry over the head with for more than 10 years now. If we just keep telling the press that DS products are great and there are only a handful of bad actors, they will probably just go away. It is obvious that this strategy has been working well thus far…

If the industry keeps wanting to make this a problem too big to fix, nothing will ever get fixed. We need to compartmentalize this into manageable, smaller tasks in order to get to the ultimate goal.

I have some suggestions for the “Three Out of Four” whose responses were a far cry from the accurate and to the point response of UNPA (i.e., that this issue is “sobering and distressing”).

1. Until you have a program in place that, through reliable independent analysis of your members’ products, has shown the quality of said products to be beyond reproach, quit issuing press releases defending those members as “responsible.” You don’t know what is behind door number three unless you walk around backstage and look.

2. Quit pretending that putting some quality assurance program logo from your association on various members’ labels amounts to real quality control review and assurance. Insist that your members be inspected by and trained in quality control by a qualified, independent organization such as NSF or NSF-DBA. And that those members subject themselves to random, unannounced audits by such an organization.

3. Insist that members attend training seminars in conjunction with FDA and/or personnel such as NSF-DBA. These are not just one-hour talks on quality control at an annual trade show by someone who is not qualified and who is affiliated with either a member company or the trade organization.

4. Start issuing press releases whenever there is a bad inspection, detailing what should be done, and I mean really done, to correct the problem.

5. Stop issuing the same press release with only a few words changed whenever there is a bad media story about the DS industry. A third grader might do that in English class. Trade associations and the DS industry, in general, need to be better. Again, detail what should be done, no matter whose toes you step on, to correct the problem.

6. Knock out the dry labs, and you stop the ability of bogus companies to “legitimize” bogus products or ingredients. (See following guest editorial by Frank Jaksch, Founder and Chief Scientific Officer of Chromadex, who was instrumental in the Dateline story).

Don’t shrug it off. Atlas might have shrugged, but the DS industry can no longer afford to.

“Dateline set up a sting operation for the laboratory director, Dinesh Patel, who also did the fraudulent analysis mentioned in my AMR editorial (Bursting the Analytical Bubble)”

e

“in something imaginable only as the Heisenberg Uncertainty Principle being interpreted by a reincarnated William F. Buckley in the throes of an LSD meltdown, Patel has reduced analytical laboratory science to an internet social standard”

e

“Meatloaf sang ‘Two Out of Three Ain’t Bad.’ In the case of trade associations one would hope that it was more than ‘One Out of Four Ain’t Bad’ ”

e

“if the industry keeps wanting to make this a problem too big to fix, nothing will ever get fixed”

Guest Editorial by Frank Jaksch, Founder and Chief Science Officer (CSO), Chromadex

Are you concerned about the practice called “dry labbing” (i.e., fabricating or faking laboratory quality assurance test results) in the dietary supplement (DS) industry?  You should be, as there are probably more than a handful of laboratories that may be operating under these types of practices. Not all dry labs will be operating as blatantly as the lab that was identified in the recent Dateline NBC segment covering that topic. Some labs may in fact be performing selective dry labbing, which means they will do testing on some samples, and not on others, which would make it much more difficult to prove.

Here are a few useful tips for companies using 3rd party contract analytical laboratories. 

1.  When sending samples to independent laboratories, do not tell them exactly what specifications you are expecting for the sample. Bear in mind that you must tell the lab something, as it would make it very difficult for the lab to perform proper analytical testing without having some idea what the concentration range of the analyte (compound of interest) actually is. For example, if you were sending the lab a product which contains 75 mg of caffeine per capsule, you would not want to tell the lab that you expected 75 mg per capsule. It would be better to tell the lab that you were expecting somewhere between 25 mg and 150 mg per capsule. By not providing the laboratory with the exact specification, it makes it very difficult for them to fabricate an expected value.

2. Send challenge samples to all of the contract laboratories you use. Challenge samples are also known as “dummy” samples, and are an intentional effort to misrepresent what you are telling them. For example, send your laboratory a sample of vitamin C capsules, and tell them you would like them to test for caffeine. If the laboratory reports that there was no caffeine, then you are in good shape. The practice of sending challenge samples to your laboratories is something that should be done with some regularity. Challenge samples can also be used to perform a routine checkup on the proficiency of your laboratories. For example, certified reference materials (CRMs) could be purchased from NIST (National Institute of Standards and Technology), where they have very precisely measured and reported the values for various analytes in a botanical matrix sample, such as spinach. By sending your labs such proficiency samples you can find out how accurate their results are as compared to well-established values in CRM materials.

3. Visit, audit, and inspect your contract laboratories. Contract laboratories performing analytical testing services for dietary supplement manufacturers are in fact a part of the good manufacturing practice (GMP) process, which makes them fully accountable for being GMP. Since contract laboratories are accountable for GMPs, companies using the services of contract laboratories should visit, audit, and inspect their labs in order to be GMP compliant themselves.

4. Qualify the contract laboratories your company uses before sending samples and relying on the results they provide. As a matter of fact, it would probably be a good idea to have a standard operating procedure (SOP) for “Qualifying Independent Contract Testing Laboratories,” in which the DS company would provide a checklist for performing due diligence on a laboratory before they were “qualified” for use.

If companies in the DS industry who are utilizing contract testing labs were to follow these four basic rules, it would be very difficult to operate a dry lab without getting caught.

Environmental Medicine - Do Environmental Toxicants Contribute to Allergy and Asthma? by Walter J. Crinnion, ND

Abstract

The rates of asthma and allergy (Type 1 hypersensitivity disorders) have been increasing worldwide for the last few decades. Various theories have been proposed to account for this alarming trend. One of these is the impact of environmental toxicants. Epidemiological research has correlated exposure to environmental chemicals (such as pesticides, solvents, and air pollutants) with increasing rates of both asthma and allergies. Research has documented chemicals as causal agents capable of producing immune system imbalances characteristic of type 1 hypersensitivity. In vitro studies and in vivo animal models have demonstrated that many of the environmental chemicals and pollutants that have been epidemiologically associated with increased allergic tendency have been shown to enhance Type 2 helper T cell (Th2) dominance, which is consistent with the T-helper cell pattern found in asthma, allergic rhinitis, and other Type 1 hypersensitivity disorders. Depletion of glutathione is one possible mechanism for this T-helper cell imbalance. Preliminary evidence suggests the possibility that repletion of glutathione levels (with oral supplementation of N-acetylcysteine), and enhancement of glutathione transferase function (using sulforaphanes), might be therapeutic options for countering type 1 hypersensitivity disorders caused by environmental chemicals. (Altern Med Rev 2012;17:6-18)

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Monograph - Bacillus coagulans by Julie S. Jurenka, MT (ASCP)

Introduction

Probiotics are defined by the World Health Organization as “live microorganisms which, when administered in adequate amounts, confer a health benefit on the host.” Worldwide, there are numerous strains of probiotics used in dietary supplements and foods, but most are unstable at room temperature and need to be freeze dried or encapsulated via special processes to remain viable during manufacturing, storage, and exposure to stomach acid and bile. Consequently, for most probiotics, only a very small percentage of the starting material is actually viable at the end of shelf life. Bacillus coagulans is a notable exception which, due to its sporulated form, survives without special handling and proliferates in the gastrointestinal environment.

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