What’s new about testosterone?

Dr. Gary Huber recently gave a lecture on what’s new about testosterone. His talk was presented at the 24th Annual World Congress on Anti-Aging Medicine (Dec. 9-11, 2016) in Las Vegas that I attended. It was entitled “Evolution of Testosterone – Dispelling Myths & Charting a Future”.

History of testosterone

There are some notable historic landmarks with respect to the discovery of testosterone.

1869: Dr. Charles Brown-Sequard suggested that the “feebleness of older men” was due to a lack of testosterone. He injected himself with testicular extracts from dogs and guinea pigs.

1912: The Danish physician Dr. Thorkild Rovsing transplanted the testicles of a young soldier killed in battle into an old man with gangrene. The gangrenous wound healed completely.

1918: Dr. Leo Stanley sampled fresh testicles from executed prisoners at the San Quentin Prison and transplanted them to prison inmates. Some regained their sexual potency.

1930’s: Professor Adolf Butenandt collected 25,000 liters of urine from willing policemen. He was able to isolate a breakdown product of testosterone, androsterone. Eventually he isolated both progesterone and testosterone. He received the Nobel prize for his work with sex hormones in 1939.

Historical detours and misguided opinions about testosterone

1935: Because natural hormones cannot be patented, Big Pharma came up with the idea of modifying testosterone by adding a methyl group at the 17-alpha position of testosterone.

This allowed the new substance, 17 alpha-methyltestosterone to be swallowed as a pill. But the liver changed 17 alpha-methyl-testosterone into 17 alpha-methyl-estradiol, a strong estrogenic compound. This was not well metabolized. Shortly after introduction into patients it became evident that 17 alpha-methyl-testosterone caused liver cancers. This “testosterone equivalent” was used for 50 years until the FDA outlawed it because I caused liver cancer. It also caused suspicion among physicians about any testosterone replacement, even the bioidentical hormones that are safe.

Prostate cancer myths

Prostate cancer myth

Conventional medicine teaches (and I have believed this for many years) that testosterone would be the cause for prostate cancer. This was based on old observations by Dr. Huggins, a Canadian born surgeon who practiced in Chicago, that orchiectomy improved the survival of advanced prostate cancer patients a bit. Dr. Lee pointed out that Dr. Huggins neglected to realize that testicles make both testosterone and small amounts of estrogen. When an orchiectomy was done (because of the belief that testosterone production was the culprit) inadvertently the real cause of prostate cancer (an estrogen surplus) was also removed, thus improving the survival of these patients somewhat. Nowadays we have more sophisticated testing methods. Dr. Abraham Morgentaler (Ref. 1) has compiled a lot of evidence about the importance of testosterone in men. He proved, based on a lot of more modern references, that it is not testosterone that is the cause of prostate cancer. We know now that estrogen dominance is responsible for prostate cancer and that this develops as stated above because of the low testosterone and low progesterone during the male menopause (also called “andropause”).

It is important, when testosterone deficiency is present in an aging man, to replace the missing testosterone with bioidentical testosterone.

The old method of hormone depletion therapy in advanced prostate cancer cases is still practiced today, but has been proven wrong by Dr. Morgentaler and other researchers.

10% absorption rule myth

For years there has been a persistent myth that only 10% of testosterone would be absorbed through the skin. This was never proven, and newer studies could demonstrate that about 90% of testosterone gets absorbed through the skin.

Misleading science created myths

Unfortunately three key medical journals, JAMA, NEJM and PLOS ONE have published misleading studies. The content did not discuss physiology, mechanism of actions, appropriate dosing or true science. But their conclusions were that testosterone therapy was associated with heart attacks and strokes. There was an outcry about this particular study in the medical community reflected in the demand to retract this misleading article.

Unfortunately there were more similar false “studies” where controls were wrong or unequal groups were compared that should not have been compared. It is reminiscent of previous effort of the tobacco industry wanting to cover up that cigarette smoke causes lung cancer.

Here we have the problem that testosterone cures so many conditions for which the Pharma industry has many patented medicines that control the symptoms. But testosterone can actually treat the cause of the illness, testosterone deficiency, which leads to a cure of many other symptoms.

For a long time physicians were confused. But younger physicians are replacing the older generation and they treat testosterone deficiency with bioidentical testosterone in the proper dose.

Clinical observations about a lack of testosterone

There is evidence that men have lower testosterone as they age and this has worsened when we compare data from early 2000 to the 1980’s and 1990’s.

As this paper shows, men investigated in the 1980’s were still having higher testosterone levels in older age. But in the 1990’s and more so in 2004 these values have declined even more. This fact coincides also with other studies, showing decreased sperm health and increased infertility. The reason for this is also a lack of testosterone!

Causation of low testosterone

Dr. Huber pointed out that many studies have pointed to a variety of causes for low testosterone levels in men.

  • BPA, toxins and pesticides that occupy testosterone receptors and interfere with the hypothalamus/pituitary hormone function that stimulates the Leydig cells to produce testosterone.
  • The more stress men are under, the less testosterone production there is. Sleep deprivation below 5 hours per night leads to a significant lower testosterone production. Most testosterone is produced during the sleep in the early morning hours.
  • Weight gain and sugar overconsumption poison the testosterone producing Leydig cells.
  • Poly-pharmacy. Many drugs lower testosterone production: statins, diuretics, metformin, spironolactone, opiates, antidepressants, verapamil, alcohol, chemotherapy for cancer, antihistamines, ketoconazole, beta blockers, H2 blockers, finasteride, estrogens and alpha methyldopa.

Many references were provided that support these data. In one paper it was noted that the risk of a heart attack climbs to 4 times the risk of normal, when the man sleeps less than 6 hours per night. As sleep hours lower, the risk for metabolic syndrome increases by 42% and this leads to heart attacks. Testosterone replacement can reverse this risk as it a lack of testosterone production that caused the risk.

Link of low testosterone to cardiovascular disease

The literature is overwhelming that low testosterone has adverse effects on the cardiovascular system. To be more specific, the metabolic syndrome, heart disease (and strokes), diabetes and high blood pressure have their root in low testosterone.

Metabolic syndrome

Inflammation is mediated by cytokines such as IL-6. Dr. Huber mentioned one study where healthy men received IL-6. This promptly suppressed testosterone levels. He said that there are many cytokines that work in concert to suppress testosterone. One useful clinical test for inflammation is the C-reactive protein, which indicates whether or not inflammation is present in a person. Metabolic syndrome is common in obese patients. In a study CRP was found to be significantly associated with obesity. When CRP is high, testosterone levels are low. When the CRP level is high, there is a risk of getting the first heart attack.

On the other hand, when men with high inflammatory markers from low testosterone levels were replaced with testosterone, the tumor necrosis factor was reduced by 50%, IL1b by 37%, triglycerides by 11% and total cholesterol by 6%.

In the Moscow study a group of obese men with low testosterone levels were treated with testosterone injections. There was an impressive reduction of insulin (17%), CRP (35%) weight reduction of 4% and TNF-a reduction of 31% within 16 weeks.

Heart disease (and strokes)

Hardening of the arteries (medically called atherosclerosis) is due to chronic inflammation. A new heart attack/stroke specific biomarker has been developed. It is a ratio of oxidized LDL, divided by HDL. This has an odds ratio of 13.92 compared to a control without a risk for a heart attack or stroke.

Administration of testosterone hormone led to dilatation of coronary arteries. The Rotterdam study showed that low testosterone levels were associated with high risk for heart attacks and strokes, but that treatment with testosterone removed this risk. Testosterone increases AMP kinase for energy production in heart muscle cells, but also dilates coronary arteries for more blood supply to the heart.


Among men with diabetes 20-64% have low testosterone levels. In another study men with higher testosterone levels had a 42% lower diabetes risk. Testosterone levels are inversely related to body mass index and insulin resistance. Men with diabetes have lower testosterone levels than men who were not diabetic and were weight-matched. Most diabetics have high CRP values.

High blood pressure

Experience with androgen deprivation therapy for prostate cancer has shown that blood pressure gets elevated due to testosterone deficiency. Testosterone increases LDH, the protective subunit of cholesterol, and decreases LDL cholesterol and triglycerides. Testosterone also lowers inflammatory markers and reverses clotting factors making blood thinner. All of this leads to a widening of the arteries and lowering of blood pressure.

Treatment options for low testosterone

It is important to support the hypothalamic /pituitary/adrenal gland axis and remove other causes, such as stress and lack of sleep. Younger men can be stimulated in the pituitary gland through Clomiphene. Men older than 60 likely have true secondary hypogonadism and need testosterone replacement. Topical testosterone creams are available commercially or from compounding pharmacies. Injectable testosterone preparations that can be metabolized by the body are available. One such preparation is Delatestryl. A small dose (like 50 mg) is self-injected subcutaneously twice per week, which keeps the testosterone level stable. The last resort, if the creams or injections don’t work, is the use of testosterone pellets that a physician can implant under the skin.

What’s new about testosterone?

What’s new about testosterone?


At a recent Anti-Aging conference in Las Vegas that I attended, Dr. Huber gave an overview of testosterone. There has been an objective reduction of testosterone levels in men since the 1980’s due to pollutants in our environment. Testosterone plays a key role for heart and brain function. It affects sex drive, fertility and potency. But it also prevents diabetes, high blood pressure and weight gain. On top of that it prevents prostate cancer and likely many other cancers. The key with low testosterone is to replace it to high normal levels. Blood levels should be measured every two months, when replacement has been instituted, in order to ensure adequate levels.

References  Ref.1 Abraham Morgentaler, MD “Testosterone for Life – Recharge your vitality, sex drive, muscle mass and overall health”, McGraw-Hill, 2008


Genetic Screening For Better Health

Dr. Matt Pratt-Hyatt gave an overview about genetic screening for better health at the 23rd Annual World Congress on Anti-Aging Medicine on Dec. 13, 2015 in Las Vegas. The talk was entitled ”Genetic Screening: A Tool for Better Health with Age”. He showed that with more sensitive genetic screening techniques minor genetic changes can be detected. These are a lot more common than previously thought of. Matt Pratt-Hyatt, PhD is Associate Laboratory Director for the Great Plains Laboratory in Lenexa, KS.

Specifically, Dr. Pratt-Hyatt explained that single nucleotide polymorphisms, frequently called SNPs (pronounced “snips”) were the most common type of genetic variations among people. These genetic changes in the DNA often cause disease. Different types of genetic testing can identify the gene defects of SNPs. One of the questions is how aging can be better managed when genetic defects are known.

When it comes to our genetic material there are over 3 billion base pairs, all contained in 23 chromosomes. These are home to 20,000-25,000 genes, most of which are normal.

A gene has three regions all of which can have mutations. In the middle there is the coding region; one end is the regulatory region for transcription initiating; at the other end the transcription termination signals are located. Minor mutations in any of these regions can have major implications for the health of the individual or they can stay silent SNPs. SNPs are classified into missense mutation or nonsense mutation. This description just shows how intricate and complex the process of mutations can be!

Three types of sequencing are commonly used:

Three types of genetic screening for better health

  1. Sanger sequencing
 utilizes certain dyes that correspond to specific nucleotides of the DNA. The benefits of Sanger sequencing is that it can cover one gene completely. It can find previously unknown mutations. But the disadvantage of Sanger sequencing is that you cannot process a large number of genes.
  2. The Florophore-base detection looks at multiple SNPs in a single run. This method is cheaper than whole genome sequencing. But one of the disadvantages of Florophore-base detection
is that only a limited number of SNPs can be processed per run. It also can miss new mutations.
  3. Benefits of next generation sequencing 
are that it can look at 1000s of SNPs per run. It is much more accurate than previous technologies. A drawback
though is that the equipment is much more expensive.

Not all of these tests have to be done, but the physician can make the choice of the appropriate one for the patient. The following are some applications with regard to how genetic screening can be useful for better health.

Detoxification as part of genetic screening for better health

Since the 1970’s and 1980’s it has become clear that there are many steps in the detoxification process in the liver. It involves major enzyme systems that are controlled by the P450 genes. Several genetic defects are known that run in different families. These effects are very important for drug detoxification and metabolism. Any mutation in one of the P450 controlling genes will lead to accumulation of the drug that is normally detoxified by this enzyme system. As any drug has toxicity at higher levels, the consequence is possible toxicity, if the drug is not discontinued or lowered. When people age, they often have spontaneous mutations of the P450 detoxification system and this should be taken into account by doctors who prescribe medications. Common drugs that cause problems with the P450 controlled detoxification are antidepressants, the blood thinner Coumadin, the antibiotic erythromycin, the asthma medication Theophylline and many others.

Here is an example of how important this knowledge is in an elderly patient who was sent to the hospital with an irregular heartbeat. The electrocardiogram allowed a diagnosis of atrial fibrillation. The doctor treated the patient with a cautious loading dose of 0.5 mg of Coumadin in an attempt to thin the blood of the patient. This would prevent a blood clot or a stroke due to the arrhythmia. Normally a small dose like this would not do much in terms of blood thinning, as it would take several days of a low dose like this to achieve blood thinning. Unbeknown to the physician, this patient was different as he had a defect in the Cyp2c9 gene, a subtype of the P450 system. Very quickly the patient developed bleeding gums and bruising of the skin in various locations. When blood tests were taken, the INR, a measure of the clotting system, was 3.7, a value that should not have exceeded a level of 2 to 3. Genetic testing confirmed a homogenous mutation of the Cyp2c9 gene that explained the toxicity of Coumadin in this case, one of the many drugs that is detoxified by the P450 system.

Mental health as part of genetic screening for better health

Many mental illnesses can be caused by defects in various parts of the brain metabolism. This is particularly so when it involves the synthesis of brain hormones. If there are genetic defects, this can lead to the particular brain metabolism that is associated with depression or schizophrenia. Even dementia, Alzheimer’s disease and Parkinson’s disease can be caused by genetic defects. Methylation pathway defects are another source of possible genetic defects, which can affect multiple metabolic pathways. This is the cause of many diverse conditions like autism, diabetes and some hereditary cancers. The reason it is important to be aware of such genetic aberrations is that often vitamin B2, B6, niacin, vitamin B12 and the minerals magnesium and zinc can stabilize a person with methylation defects.

Cholesterol as part of genetic screening for better health

People with obesity have problems with their lipid metabolism, diabetes, high blood pressure and often heart disease and strokes. Changes in cholesterol metabolism are at the center of these problems. Cholesterol is one of the building blocks of cell membranes, and cholesterol is one of the normal components in the blood as long as the subfractions are properly balanced (LDL and the HDL cholesterol). Unfortunately many people have minor or major defects of the biosynthetic pathway of cholesterol. There are 5 genes involved in the acetyl CoA biosynthesis. 21 genes are involved in the main cholesterol biosynthesis pathways. Over 10 genes control cholesterol metabolites. Historically these genes were detected because of various familiar gene defects that caused problems with the biochemical processes surrounding cholesterol. Familial high cholesterol levels (familial hypercholesterolemia) is one of these common conditions.

Patients who have this condition will often have high cholesterol and also often have a family history of gall bladder surgery for gallstones and a history of premature heart attacks or strokes. Early diagnosis and careful clinical intervention can improve the outlook for many patients.

Genetic Screening For Better Health

Genetic Screening For Better Health


Not all genetic conditions can be helped by modern medicine. But many minor genetic abnormalities can be worked around or drug interactions can be avoided provided the genetic defect is known. It is encouraging that newer test methods have now shown success, as they are more affordable than in the past. As time progresses the price of these genetic tests will come down even further. Mental health, detoxification pathways and the metabolic syndrome of obesity are practical applications where genetic tests have significance.


Catch Cancer Early

Cancer of the cervix was the first cancer where early diagnosis was practiced and this changed reduced the mortality due to this cancer significantly.

Pap test

When the Pap test was invented and used on a large scale, cervical cancer could be diagnosed at the earliest stage, which is “stage 0” or “cancer in situ” (the earliest local cancer). In 1943 Dr. Papanicolaou published the book “Diagnosis of Uterine Cancer by the Vaginal Smear” where he described in detail how to do the Pap test. This became the norm very quickly and the use of the Pap test spread all around the world following WWII.

This was important, because later it was detected that cure rates of close to 100% could be achieved by removing the tiny accumulation of local cancer cells, which are present with cancer in situ. This could be achieved by surgical removal (cone biopsy), radiation therapy, and cryotherapy or later also with laser treatment. The key to success in cancer treatment is early detection and early treatment.

Other cancer prevention and early detection

  • With melanoma, a darkly pigmented skin cancer, the earliest stage, namely stage 0 or carcinoma in situ is treated by surgical excision leaving a wide margin of healthy skin around it. This is the cure, because it was detected early and had not yet invaded the surrounding tissues.
  • The most common breast cancer type is ductal carcinoma in situ (DCIS), of which 80% are diagnosed by mammography. Treatment for this is usually by local surgical excision, called lumpectomy followed by radiation.
  • Colon cancer typically arises out of colonic polyps. Colonoscopy in high-risk patients with a history of colon cancer in a first degree relative is typically done every three years. Any polyps that are found are removed during the procedure. My mother died at the age 59 of colon cancer. I had colonoscopies every three years since the age of 40 and on several occasions polyps were removed. Had I not had the colonoscopies, an unnoticed carcinoma in situ would have developed within one of the polyps and subsequently invasive colon cancer would have developed. Colonoscopies are a means of true colorectal cancer prevention.

The newest development: Oncoblot test to detect in situ cancers

At the 23rd Annual World Congress on Anti-Aging Medicine in Las Vegas (Dec. 11-13) Dr. Mark Rosenberg spoke about the universal cancer marker ENOX-2 that is only expressed during embryogenesis (the development of the fetus) and in adulthood only again when cancer develops. A test has been developed to check for the ENOX-2 gene, which becomes positive 5 to 7 years before cancer can be detected clinically. This is called Oncoblot test. Sensitivity of ENOX-2 is high and false positives are negligible, which makes the ENOX-2 marker ideal for cancer screening.

There are various isoelectric points for various cancer tissues, so the lab physician can tell the treating physician from which tissue a positive cancer test originates. The interesting aspect is that a combination of green tea and capsicum has been able to suppress the expression of the gene, and the cancer gene can be turned off. Corresponding biopsy samples showed that the cancer cells had disappeared. This is an entirely new concept and will have to be further investigated by clinicians for the various cancer types.

Here are the 25 cancers that are screened with the Oncoblot test: Bladder, Breast, Cervical, Colorectal, Endometrial, Esophageal, Gastric, Hepatocellular (liver), Kidney, Leukemia, Non-Small cell (lung), Lung Small cell, Lymphoma, Melanoma, Mesothelioma, Myeloma, Ovarian, Pancreatic, Prostate, Sarcoma, Squamous Cell, Follicular Thyroid, Papillary Thyroid, Testicular Germ Cell, Uterine. Considering that testing for all of these cancers is 1000 USD, this means that each specific cancer test is only 40 USD per test. I suspect that in future the price will come down as mass screening will be done. But the key is that this test is available right now; it is highly specific and highly sensitive.

But the important finding right now is that we have a very sensitive and very specific cancer screening test for over 25 various cancer types that can detect these cancers in the in situ stage (very early).

This has not been the case in the past except with the introduction of the Pap test for cervical cancer.

Change of treatment protocols may be required

The company producing the Oncoblot test states that the results need to be discussed between patient and treating physician. Although the treatment protocol does not change, there will be a lot more early diagnoses of cancer than in the past. In the past stage 1 and 2 stage cancers were considered to be early cancers and protocols to have these treated have been worked out. But with this very sensitive blood test (Oncoblot test) in situ cancers (stage 0) can be found. Mind you, it sets you back about 1000 USD, the cost for processing your blood and the test. But despite the monetary barrier I believe, that enough people will want this test done, because with the knowledge that cancer is diagnosed, it can be treated effectively with high cure rates.

The down site may be that those who have the test done and are found to be positive may have to undergo additional tests to locate and treat the tumor.

Suggested future approach to cancer detection and treatment

I envisage four steps to the future of cancer diagnosis and treatment.

  1. Screening for cancer using the Oncoblot test and other similar tests that likely will be developed in the future. This will give a tissue specific cancer diagnosis at the earliest possible point in time when clinically in most cases no tumor can be found for another 5 to 7 years.
  2. Staging of the cancer found: this requires confirmation of the cancer by doing imaging studies and possibly biopsies. An MRI scan of the affected area will likely be very useful, also to rule out early lymph gland metastases. Without being certain about the stage of the cancer the treating physician can not be certain what treatment schedule to follow as treatments differ for various stages of a cancer.
  3. Minimal invasive therapy like low-dose laser phototherapy using three different photosensitizers as shown in the example of end stage prostate cancer in this link under the heading “Photodynamic therapy of a group of inoperable prostate cancer patients”. The tragedy in this pilot study was that all of the men presented with end stage prostate cancer, which is difficult to cure. But early prostate cancer is easy to cure with the same method, simply because the cancer cells are local (in situ). Every cancer expert knows that cure rates are very high in the early stages of cancer, with the highest cure rates for cancer in situ (stage 0) and somewhat lower success rates for stages 1 and 2. Stages 3 and 4 have very poor cancer cure rates, as the cancer is already spread into the surrounding area in stage 3 and presents with distant metastases in stage 4. To make an impact in these latter cases requires toxic therapies like chemotherapy, radiotherapy and/or extensive surgery. Having said this, 20% of these end stage prostate cancers still experienced a cure with the triple photosensitizers and low-dose laser therapy (see link above), which conventional therapies would not have achieved.
  4. Retesting for residual cancer using Oncoblot test. Two months after the cancer treatment has been completed, the Oncoblot test should be repeated, which will reassure the patient and physician as well that all of the cancer cells have disappeared. As this test is so sensitive, any remaining cancer cells would shed tumor protein into the blood, which the Oncoblot test would immediately pick up. In the few cases that would remain positive this would enable the physician to do further tests, modify treatment and hopefully get rid of the last cancer cell that way.

Examples of two clinical scenarios

Two common cancers are prostate cancer in men and breast cancer in women.

1. Prostate cancer is very common in older men. From the age of 50 onwards the risk of getting prostate cancer is higher with every decade.

Another problem is that not every prostate cancer is invasive, some cancers are low grade and sit around for a long time and may never metastasize. A cancer expert discusses this here.

To attempt to distinguish between the aggressive form of prostate cancer and the slower “wait and see type”, a score has been developed, called the 4K score. This score combines the PSA test and a prostate specific kallikrein marker within one blood sample. Patients with a high 4K score are the ones who have an aggressive prostate cancer that needs urgent treatment. Patients with a low 4K score are the ones where many urologists recommend to wait and observe.

If I were the patient I would lean towards treating any kind of prostate cancer. Any cancer can do whatever it wants to, and you do not really know how these cancer cells will behave in the future. The only difference in prostate cancer is that the prostate has a tough capsule where the tumor stays localized for a long time, sometimes for decades, but it grows until it breaks out of this shell and metastasizes to the rest of the body. At that point it is often too late to rescue the patient, because it suddenly is a late stage. As stated earlier, late cancer stages are associated with poor treatment successes. Knowing this, I would suggest to use either a radical prostatectomy in a stage I cancer or low-dose laser phototherapy with three photosensitizers and three matching laser frequencies as indicated in the link to my blog mentioned above.

 2. Breast cancer is common in women. Often early cancer is found on a routine mammography or else with the Oncoblot test. An MRI scan can localize the tumor when it has a certain size, but it may take 5 to 7 years following an Oncoblot test to be visualized. This may be a diagnostic dilemma, which has to be worked out in the future. But as most breast cancers develops from the epithelium of the breast ducts, low-dose laser phototherapy with photosensitizers could be given to treat this early cancer stage. If a repeat Oncoblot test 2 months later is negative, the treatment was successful. If not, the clinician will have to closely follow the patient with repeat MRI scans of the breasts. Compared to the present diagnostic system without utilizing the Oncoblot test, this method is still superior, until perhaps in the future another way to localize early cancer becomes available. The fundamental difference between breast cancer and prostate cancer is that breast tissue is very vascular and any cancer of the breast tends to metastasize very early. For this reason it is crucial to treat breast cancer very early to have optimal treatment successes.

Catch Cancer Early

Catch Cancer Early


The introduction of the Oncoblot cancer-screening test may revolutionize diagnosis and treatment of 26 or more cancers that can be screened with this test. I have only highlighted the possibilities with the example of two cancers and explained what this might mean in practical terms. The exciting news is that cancer can now be detected earlier. The confusing part is that it can be diagnosed 5 to 7 years before the cancer is clinical detectable, and many physicians will feel uncomfortable treating cancer that early. Having seen many cancer patients in their end stages in clinical practice, I can only state that you cannot be too early diagnosing cancer. Only stage O (cancer in situ) and stage 1 (and sometimes stage 2) can be treated successfully and guarantee a cure. Experience will teach us what the best way is in the future. In the meantime this is an approach to an early diagnosis without taking any risks.

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