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The latest in Alzheimer’s disease research

ALZHEIMER

Image shows trees cut to look like heads.

DIABETES DRUG ‘SIGNIFICANTLY REVERSES MEMORY LOSS’ IN ALZHEIMER’S: MOUSE STUDY

NEUROSCIENCE NEWS
Lancaster University researchers report a drug developed to treat diabetes shows promise in reversing memory loss associated with Alzheimer’s in mouse models of the disease. The drug appears to have a neuroprotective effect, enhancing brain growth factors while reducing amyloid plaques, chronic inflammation and oxidative stress. The drug also slows down the rate of neuron loss.… READ MORE…
FEATUREDNEUROLOGYOPEN NEUROSCIENCE ARTICLES6 MIN READ
Image shows a brain scan.

HEALTHY MITOCHONDRIA COULD STOP ALZHEIMER’S

NEUROSCIENCE NEWS
Boosting mitochondria may defend against a form of protein stress that can reduce the formation of amyloid plaques, EPFL researchers report.… READ MORE…

ALZHEIMER

astrocytes are shown

ASTROCYTES LINKED TO ALZHEIMER’S DISEASE

NEUROSCIENCE NEWS
Researchers have discovered a direct association between astrocytes and Alzheimer’s disease. In a new study, researchers report astrocytes in the brains of Alzheimer’s patients produced significantly more amyloid beta than astrocytes in the brains of people without the disease.… READ MORE…

DRUG COULD DERAIL SYNAPSE LOSS IN ALZHEIMER’S

NEUROSCIENCE NEWS
Researchers report a drug called fasudil may help to prevent synapse loss initiated by amyloid beta peptides in early stages of Alzheimer’s disease.… READ MORE…

ALZHEIMER

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CORTICE BIOSCIENCES ANNOUNCES PRESENTATION OF RESULTS FROM PLACEBO-CONTROLLED PHASE 1 CLINICAL TRIALS EVALUATING TPI 287 FOR TREATMENT OF ALZHEIMER’S DISEASE AND RELATED TAUOPATHIES

NEUROSCIENCE NEWS
Cortice Biosciences announced today results from placebo-controlled, double-blinded Phase 1 studies evaluating TPI 287, a brain penetrable microtubule stabilizing agent, for the treatment of Alzheimer’s disease, progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS).… READ MORE…

Alzheimer’s Drug Turns Back Clock in Powerhouse of Cell

Alzheimer’s Drug Turns Back Clock in Powerhouse of Cell

Summary: Researchers have developed a new drug that can help treat Alzheimer’s disease and has been shown to reverse aging in mice.Source: Salk Institute.

The experimental drug J147 is something of a modern elixir of life; it’s been shown to treat Alzheimer’s disease and reverse aging in mice and is almost ready for clinical trials in humans. Now, Salk scientists have solved the puzzle of what, exactly, J147 does. In a paper published January 7, 2018, in the journal Aging Cell, they report that the drug binds to a protein found in mitochondria, the energy-generating powerhouses of cells. In turn, they showed, it makes aging cells, mice and flies appear more youthful.

“This really glues together everything we know about J147 in terms of the link between aging and Alzheimer’s,” says Dave Schubert, head of Salk’s Cellular Neurobiology Laboratory and the senior author on the new paper. “Finding the target of J147 was also absolutely critical in terms of moving forward with clinical trials.”

Schubert’s group developed J147 in 2011, after screening for compounds from plants with an ability to reverse the cellular and molecular signs of aging in the brain. J147 is a modified version of a molecule found in the curry spice curcumin. In the years since, the researchers have shown that the compound reverses memory deficits, potentiates the production of new brain cells, and slows or reverses Alzheimer’s progression in mice. However, they didn’t know how J147 worked at the molecular level.

test tube

In the new work, led by Schubert and Salk Research Associate Josh Goldberg, the team used several approaches to home in on what J147 is doing. They identified the molecular target of J147 as a mitochondrial protein called ATP synthase that helps generate ATP–the cell’s energy currency–within mitochondria. They showed that by manipulating its activity, they could protect neuronal cells from multiple toxicities associated with the aging brain. Moreover, ATP synthase has already been shown to control aging in C. elegans worms and flies.

“We know that age is the single greatest contributing factor to Alzheimer’s, so it is not surprising that we found a drug target that’s also been implicated in aging,” says Goldberg, the paper’s first author.

Further experiments revealed that modulating activity of ATP synthase with J147 changes the levels of a number of other molecules–including levels of ATP itself–and leads to healthier, more stable mitochondria throughout aging and in disease.

“I was very surprised when we started doing experiments with how big of an effect we saw,” says Schubert. “We can give this to old mice and it really elicits profound changes to make these mice look younger at a cellular and molecular level.”

The results, the researchers say, are not only encouraging for moving the drug forward as an Alzheimer’s treatment, but also suggest that J147 may be useful in other age-associated diseases as well.

“People have always thought that you need separate drugs for Alzheimer’s, Parkinson’s, and stroke” says Schubert. “But it may be that by targeting aging we can treat or slow down many pathological conditions that are old age-associated.”

The team is already performing additional studies on the molecules that are altered by J147’s effect on the mitochondrial ATP synthase–which could themselves be new drug targets. J147 has completed the FDA-required toxicology testing in animals, and funds are being sought to initiate phase 1 clinical trials in humans.

ABOUT THIS NEUROSCIENCE RESEARCH ARTICLE

Source: Salk Institute
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is credited to Salk Institute.
Original Research: Full open access research for “The mitochondrial ATP synthase is a shared drug target for aging and dementia” by Joshua Goldberg, Antonio Currais, Marguerite Prior, Wolfgang Fischer, Chandramouli Chiruta, Eric Ratliff, Daniel Daugherty, Richard Dargusch, Kim Finley, Pau B. Esparza-Moltó, José M. Cuezva, Pamela Maher, Michael Petrascheck and David Schubert in Aging Cell. Published online January 7 2018 doi:10.1111/acel.12715

CITE THIS NEUROSCIENCENEWS.COM ARTICLE
Salk Institute “Alzheimer’s Drug Turns Back Clock in Powerhouse of Cell.” NeuroscienceNews. NeuroscienceNews, 9 January 2018.
<http://neurosciencenews.com/atp-synase-mitochondria-8291/&gt;.

Abstract

The mitochondrial ATP synthase is a shared drug target for aging and dementia

Aging is a major driving force underlying dementia, such as that caused by Alzheimer’s disease (AD). While the idea of targeting aging as a therapeutic strategy is not new, it remains unclear how closely aging and age-associated diseases are coupled at the molecular level. Here, we discover a novel molecular link between aging and dementia through the identification of the molecular target for the AD drug candidate J147. J147 was developed using a series of phenotypic screening assays mimicking disease toxicities associated with the aging brain. We have previously demonstrated the therapeutic efficacy of J147 in several mouse models of AD. Here, we identify the mitochondrial α-F1-ATP synthase (ATP5A) as a target for J147. By targeting ATP synthase, J147 causes an increase in intracellular calcium leading to sustained calcium/calmodulin-dependent protein kinase kinase β (CAMKK2)-dependent activation of the AMPK/mTOR pathway, a canonical longevity mechanism. Accordingly, modulation of mitochondrial processes by J147 prevents age-associated drift of the hippocampal transcriptome and plasma metabolome in mice and extends lifespan in drosophila. Our results link aging and age-associated dementia through ATP synthase, a molecular drug target that can potentially be exploited for the suppression of both. These findings demonstrate that novel screens for new AD drug candidates identify compounds that act on established aging pathways, suggesting an unexpectedly close molecular relationship between the two.

“The mitochondrial ATP synthase is a shared drug target for aging and dementia” by Joshua Goldberg, Antonio Currais, Marguerite Prior, Wolfgang Fischer, Chandramouli Chiruta, Eric Ratliff, Daniel Daugherty, Richard Dargusch, Kim Finley, Pau B. Esparza-Moltó, José M. Cuezva, Pamela Maher, Michael Petrascheck and David Schubert in Aging Cell. Published online January 7 2018 doi:10.1111/acel.12715

Soda and Heart Attack

Story at-a-glance

  • Giving up soda — both sugar-sweetened and diet — is one of the most fundamental steps you can take to improve your health. You likely have made that choice long ago, but it is one that is important to many that you know
  • Research suggests sugary beverages are to blame for about 183,000 deaths worldwide each year, including 133,000 diabetes deaths, 44,000 heart disease deaths and 6,000 cancer deaths
  • Men who drank an average of one can of soda per day had a 20 percent higher risk of having a heart attack or dying from a heart attack than men who rarely consumed soda

By Dr. Mercola

One of the most straightforward steps you can take to improve your health in the New Year is to give up soda, and with that I’m talking about both regular and diet varieties. The problem with soda stems from its high sugar content — particularly the liquid high fructose corn syrup (HFCS) variety — and, in the case of diet, its artificial sweetener content, among other issues.

Research suggests sugary beverages are to blame for about 183,000 deaths worldwide each year, including 133,000 diabetes deaths, 44,000 heart disease deaths and 6,000 cancer deaths.1 Even drinking one or more 250 ml (about 8 ounce) servings of soda per day raises your risk of Type 2 diabetes by 18 percent.2 Soda and other sugar-sweetened beverages (SSBs) are a leading source of added sugar in the U.S. diet, with 6 in 10 youth and 5 in 10 adults drinking at least one such beverage on any given day.3

Even the U.S. Centers for Disease Control and Prevention (CDC) states, “Frequently drinking sugar-sweetened beverages is associated with weight gain/obesity, Type 2 diabetes, heart disease, kidney diseases, nonalcoholic liver disease, tooth decay and cavities, and gout, a type of arthritis.”4

However, the CDC only suggests that “limiting the amount of SSB intake can help individuals maintain a healthy weight and have a healthy diet,” stopping far short of advising Americans to ditch these unhealthy drinks to avoid chronic disease.

This isn’t entirely surprising, considering CDC director Dr. Brenda Fitzgerald received $1 million in funding from Coca-Cola5 to combat childhood obesity during her six-year stint as commissioner of Georgia’s public health department and has a history of promoting the soda industry’s “alternative facts.” Her Coke-funded anti-obesity campaign focused on exercise. None of the recommendations involved cutting down on soda and junk food, yet research shows exercise cannot counteract the ill effects of a high-sugar (i.e., high soda) diet.

Health Risks of Drinking Soda

Download Interview Transcript

Downing cans of sugary soda isn’t only a matter of consuming “empty” calories that may lead to weight gain, as some public health organizations would have you believe. You can’t simply undo the effects of soda consumption by cutting back on calories elsewhere in your diet, as the sugar itself wreaks havoc on your body and your gut flora.

Researchers have known since the 1960s that your body metabolizes different types of carbohydrates, like glucose and fructose, in different ways, causing very different hormonal and physiological responses that absolutely may influence fat accumulation and metabolism.6

One 12-ounce can of regular soda has about 33 grams of sugar (8 1/4 teaspoons) and 36 grams of net carbohydrates, which is more than your body can safely handle, especially at one sitting.

The World Health Organization (WHO) recommended that sugar should make up less than 10 percent of your total daily energy intake, with additional benefits to be had if you reduce it to below 5 percent (which amounts to about 25 grams, or 6 teaspoons of sugar a day).7 For optimal health, I recommend limiting your intake of net carbs to under 40 to 50 grams per day, which is virtually impossible to do if you drink soda.

Gary Taubes, co-founder of the Nutrition Science Initiative and the author of “The Case Against Sugar,” expertly documents sugar’s link to chronic disease and much more, including whether sugar should more aptly be described as a drug instead of a food. It doesn’t cause the immediate symptoms of intoxication, like dizziness, staggering, slurring of speech or euphoria, associated with other “drugs,” yet perhaps this only allowed its long-term medical consequences to go “unasked and unanswered.”

Most of us today will never know if we suffer even subtle withdrawal symptoms from sugar, because we’ll never go long enough without it to find out,” Taubes wrote, adding that sugar has likely killed more people than tobacco and that tobacco wouldn’t have killed as many people as it did without sugar.8 Harvard School of Public Health further compiled a list of additional studies demonstrating the link between soda and chronic disease:9

  • Men who drank an average of one can of soda per day had a 20 percent higher risk of having a heart attack or dying from a heart attack than men who rarely consumed soda10
  • Women who consumed a can of soda daily over a 22-year study had a 75 percent higher risk of gout than women who rarely consumed soda11
  • Reducing soda consumption can reduce the prevalence of obesity and obesity-related diseases like Type 2 diabetes12

Why Diet Soda Is Not a ‘Healthier’ Alternative

The idea that diet soda is a healthier option than regular soda is one of the biggest prevailing myths in the nutrition realm today. If you’re one of the nearly half of U.S. adults who consume artificial sweeteners, mostly in the form of diet soda, daily (even one-quarter of kids do so as well),13 it’s important you’re let in on the truth: Drinking diet soda puts your health at risk of the following conditions:

Stroke and Dementia

Drinking one artificially sweetened beverage a day may increase your risk of stroke and dementia by threefold compared to drinking less than one a week.14 Even drinking one to six artificially sweetened beverages a week was linked to 2.6 greater risk of stroke compared to not drinking any. A 2012 study similarly found that people who drank diet soft drinks daily were 43 percent more likely to have suffered a vascular event, including a stroke.15

This significant association persisted even after controlling for other factors that could increase the risk, such as smoking, physical activity levels, alcohol consumption, diabetes, heart disease, dietary factors and more. As for the dementia link, this one is new and no one knows for sure how diet drinks may affect your brain.

Forbes compiled some plausible theories, however, including perhaps via the disruption artificial sweeteners pose to your gut health, via the corresponding gut-brain axis. Alternatively:16

“Diet sodas are designed to trick the brain into thinking it’s getting an extra dose of glucose (the brain’s fuel), but eventually the trick is on us because the brain adapts to not receiving the added glucose by overcompensating in other ways (leading to a variety of effects still under investigation).”

Heart Attack

Research that included nearly 60,000 postmenopausal women who were followed for about 10 years found that drinking just two diet drinks a day can dramatically increase your risk of an early death from heart disease.17

Metabolic Syndrome and Type 2 Diabetes

People with Type 2 diabetes are often advised to consume artificial sweeteners in lieu of sugar, but research shows consumption of diet soda at least daily is associated with a 36 percent greater relative risk of metabolic syndrome and a 67 percent greater relative risk of Type 2 diabetes compared with not consuming any.18

Depression

According to a study that included nearly 264,000 U.S. adults over the age of 50, those who drank more than four cans or glasses of diet soda or other artificially sweetened beverages daily had a nearly 30 percent higher risk of depression compared to those who did not consume diet drinks.19

Weight Gain

In April 2017, research presented at ENDO 2017, the Endocrine Society’s 99th annual meeting in Orlando, Florida, once again found that artificial sweeteners promote metabolic dysfunction that may promote the accumulation of fat.20 A study on mice also revealed that animals fed aspartame-laced drinking water gained weight and developed symptoms of metabolic syndrome while mice not fed the artificial sweetener did not.

Further, the researchers revealed that phenylalanine, an aspartame breakdown product, blocks the activity of a gut enzyme called alkaline phosphatase (IAP). In a previous study, IAP was found to prevent the development of metabolic syndrome (and reduce symptoms in those with the condition) when fed to mice.21 Aspartame likely promotes obesity by interfering with IAP activity.

Industry Ties Perpetuate the Flawed ‘Energy Balance’ Theory

Despite soda’s strong links to disease, public health officials have been slow to place blame on the industry and instead continue to perpetuate the “energy balance theory,” which suggests weight gain is simply a matter of consuming more calories than you burn off, and increasing exercise is therefore the solution to lowering rates of obesity (in lieu of eliminating soda).

The soda industry has been instrumental in shifting the blame away from soda and toward virtually any other scapegoat. In 2015, for instance, Coca-Cola Co. was outed for secretly funding and supporting the now defunct Global Energy Balance Network, a nonprofit front group that promoted exercise as the solution to obesity while significantly downplaying the role of diet and sugary beverages in the weight loss equation.22

Public health authorities accused the group of using tobacco-industry tactics to raise doubts about the health hazards of soda, and a letter signed by more than three dozen scientists said the group was spreading “scientific nonsense.”23 Yet, the soda industry maintains many close ties with organizations that continue to promote the energy balance myth (and directly funds such organizations).24 Among them:

  • The Academy of Nutrition and Dietetics (AND), which was funded by Coca-Cola until 2015. They also founded a program called “Energy Balance 4 Kids With Play” in partnership with the Healthy Weight Commitment Foundation (HWCF), “an industry organization representing Coca-Cola, PepsiCo, Nestle, General Mills and other distributers of sugar-sweetened products.”25
  • The International Food Information Council Foundation, which is funded by Coca-Cola and PepsiCo, promotes the idea that “when it comes to weight management or weight loss, it’s the total calories that matters most.”
  • The National Institutes of Health “We Can!” Campaign. Coca-Cola has donated millions to the NIH Foundation, and the campaign advises drinking soda only “once in a while” and suggests balancing out days when kids eat lots of high-sugar foods/drinks with more physical activity.
  • The American College of Sports Medicine, which is also funded by Coca-Cola, suggests that while water should be your first choice of beverage, “there is no harm in drinking juice or even soda in moderation.”
  • The U.S. Centers for Disease Control and Prevention (CDC), which also receives funding from Coca-Cola via the CDC Foundation, also promotes “energy balance” and the idea that “Healthy eating is all about balance. You can enjoy your favorite foods even if they are high in calories, fat or added sugars. The key is eating them only once in a while … ”26

Try Hibiscus Tea Instead

If the idea of swapping your daily soda with water sounds less than enticing, consider swapping it with tea instead. This gives you the best of both worlds: flavor and a healthy boost to your diet, as high-quality tea can have quite a few health benefits. Hibiscus tea is one such option. It has a pleasingly sharp flavor, similar to the tartness of cranberry, and you can find it in liquid extract form that allows you to add a few pumps to your glass of water.

Unlike soda that will overload you with sugar and/or artificial sweeteners, hibiscus tea is high in vitamin C, minerals and antioxidants, and studies suggest it may improve blood pressure, help prevent metabolic syndrome, protect your liver and even provide anticancer effects.27 It’s the opposite of drinking soda in terms of what it does to your health! It’s not only hibiscus tea that offers benefits, of course. If you prefer green or white tea, these are healthy choices as well.

Studies show green tea consumption improves brain function, as well as staves off cognitive disorders such as Alzheimer’s, helps prevent dental cavities, fights inflammatory disease such as arthritis and even combats several cancers, much like hibiscus tea. The idea is that by making this one healthy switch — swapping your daily soda for a daily cup of tea instead — you can significantly lower your risk of chronic disease and obesity.

In addition, if a soda craving strikes, fit in a quick workout, drink a cup of organic black coffee or consume something sour (like fermented vegetables or lemon water). All can help you to kick your sugar cravings to the curb. The Emotional Freedom Techniques (EFT) is another great option, which has been shown to significantly reduce cravings while increasing peoples’ ability to show restraint — even after six months.28 A video demonstration is below, but here is the basic approach, which you can start using right now:

  • Identify a food or beverage you crave by visualizing it or imagining you’re eating/drinking it
  • Tap on your activated thoughts (for example, “I want this,” “I have to have it”)
  • Tap on each of the specific sensations or thoughts you have about the food (sweetness, saltiness, creaminess, crunchiness, how it feels in your mouth, how it smells)
  • Scan your body for any tension, and tap on that too

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What is the PSA cancer test?

What is the PSA test?

Prostate-specific antigen, or PSA, is a protein produced by normal, as well as malignant, cells of the prostate gland. The PSA test measures the level of PSA in a man’s blood. For this test, a blood sample is sent to a laboratory for analysis. The results are usually reported as nanograms of PSA per milliliter (ng/mL) of blood.

The blood level of PSA is often elevated in men with prostate cancer, and the PSA test was originally approved by the FDA in 1986 to monitor the progression of prostate cancer in men who had already been diagnosed with the disease. In 1994, the FDA approved the use of the PSA test in conjunction with a digital rectal exam (DRE) to test asymptomatic men for prostate cancer. Men who report prostate symptoms often undergo PSA testing (along with a DRE) to help doctors determine the nature of the problem.

In addition to prostate cancer, a number of benign (not cancerous) conditions can cause a man’s PSA level to rise. The most frequent benign prostate conditions that cause an elevation in PSA level are prostatitis (inflammation of the prostate) and benign prostatic hyperplasia (BPH) (enlargement of the prostate). There is no evidence that prostatitis or BPH leads to prostate cancer, but it is possible for a man to have one or both of these conditions and to develop prostate cancer as well.

Is the PSA test recommended for prostate cancer screening?

Until about 2008, some doctors and professional organizations encouraged yearly PSA screening for men beginning at age 50. Some organizations recommended that men who are at higher risk of prostate cancer, including African American men and men whose father or brother had prostate cancer, begin screening at age 40 or 45. However, as more was learned about both the benefits and harms of prostate cancer screening, a number of organizations began to caution against routine population screening. Most organizations recommend that men who are considering PSA screening first discuss the risks and benefits with their doctors.

Currently, Medicare provides coverage for an annual PSA test for all Medicare-eligible men age 50 and older. Many private insurers cover PSA screening as well.

What is a normal PSA test result?

There is no specific normal or abnormal level of PSA in the blood, and levels may vary over time in the same man. In the past, most doctors considered PSA levels of 4.0 ng/mL and lower as normal. Therefore, if a man had a PSA level above 4.0 ng/mL, doctors would often recommend a prostate biopsy to determine whether prostate cancer was present.

However, more recent studies have shown that some men with PSA levels below 4.0 ng/mL have prostate cancer and that many men with higher levels do not have prostate cancer (1). In addition, various factors can cause a man’s PSA level to fluctuate. For example, a man’s PSA level often rises if he has prostatitis or a urinary tract infection. Prostate biopsies and prostate surgery also increase PSA level. Conversely, some drugs—including finasteride and dutasteride, which are used to treat BPH—lower a man’s PSA level. PSA level may also vary somewhat across testing laboratories.

Another complicating factor is that studies to establish the normal range of PSA levels have been conducted primarily in populations of white men. Although expert opinions vary, there is no clear consensus regarding the optimal PSA threshold for recommending a prostate biopsy for men of any racial or ethnic group.

In general, however, the higher a man’s PSA level, the more likely it is that he has prostate cancer. Moreover, a continuous rise in a man’s PSA level over time may also be a sign of prostate cancer.

What if a screening test shows an elevated PSA level?

If a man who has no symptoms of prostate cancer chooses to undergo prostate cancer screening and is found to have an elevated PSA level, the doctor may recommend another PSA test to confirm the original finding. If the PSA level is still high, the doctor may recommend that the man continue with PSA tests and DREs at regular intervals to watch for any changes over time.

If a man’s PSA level continues to rise or if a suspicious lump is detected during a DRE, the doctor may recommend additional tests to determine the nature of the problem. A urine test may be recommended to check for a urinary tract infection. The doctor may also recommend imaging tests, such as a transrectal ultrasound, x-rays, or cystoscopy.

If prostate cancer is suspected, the doctor will recommend a prostate biopsy. During this procedure, multiple samples of prostate tissue are collected by inserting hollow needles into the prostate and then withdrawing them. Most often, the needles are inserted through the wall of the rectum (transrectal biopsy). A pathologist then examines the collected tissue under a microscope. The doctor may use ultrasound to view the prostate during the biopsy, but ultrasound cannot be used alone to diagnose prostate cancer.

What are some of the limitations and potential harms of the PSA test for prostate cancer screening?

Detecting prostate cancer early may not reduce the chance of dying from prostate cancer. When used in screening, the PSA test can help detect small tumors that do not cause symptoms. Finding a small tumor, however, may not necessarily reduce a man’s chance of dying from prostate cancer. Many tumors found through PSA testing grow so slowly that they are unlikely to threaten a man’s life. Detecting tumors that are not life threatening is called “overdiagnosis,” and treating these tumors is called “overtreatment.”

Overtreatment exposes men unnecessarily to the potential complications and harmful side effects of treatments for early prostate cancer, including surgery and radiation therapy. The side effects of these treatments include urinary incontinence (inability to control urine flow), problems with bowel function, erectile dysfunction (loss of erections, or having erections that are inadequate for sexual intercourse), and infection.

In addition, finding cancer early may not help a man who has a fast-growing or aggressive tumor that may have spread to other parts of the body before being detected.

The PSA test may give false-positive or false-negative results. A false-positive test result occurs when a man’s PSA level is elevated but no cancer is actually present. A false-positive test result may create anxiety for a man and his family and lead to additional medical procedures, such as a prostate biopsy, that can be harmful. Possible side effects of biopsies include serious infections, pain, and bleeding.

Most men with an elevated PSA level turn out not to have prostate cancer; only about 25% of men who have a prostate biopsy due to an elevated PSA level actually are found to have prostate cancer when a biopsy is done (2).

A false-negative test result occurs when a man’s PSA level is low even though he actually has prostate cancer. False-negative test results may give a man, his family, and his doctor false assurance that he does not have cancer, when he may in fact have a cancer that requires treatment.

What research has been done to study prostate cancer screening?

Several randomized trials of prostate cancer screening have been carried out. One of the largest is the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, which NCI conducted to determine whether certain screening tests can help reduce the numbers of deaths from several common cancers. In the prostate portion of the trial, the PSA test and DRE were evaluated for their ability to decrease a man’s chances of dying from prostate cancer.

The PLCO investigators found that men who underwent annual prostate cancer screening had a higher incidence of prostate cancer than men in the control group but the same rate of deaths from the disease (3). Overall, the results suggest that many men were treated for prostate cancers that would not have been detected in their lifetime without screening. Consequently, these men were exposed unnecessarily to the potential harms of treatment.

A second large trial, the European Randomized Study of Screening for Prostate Cancer (ERSPC), compared prostate cancer deaths in men randomly assigned to PSA-based screening or no screening. As in the PLCO, men in ERSPC who were screened for prostate cancer had a higher incidence of the disease than control men. In contrast to the PLCO, however, men who were screened had a lower rate of death from prostate cancer (4, 5).

A recent paper analyzed data from the PLCO using a complicated statistical model to account for the fact that some men in the PLCO trial who were assigned to the control group had nevertheless undergone PSA screening. This analysis suggested that the level of benefit in the PLCO and ERSPC trials were similar and that both trials were consistent with some reduction in prostate cancer death in association with prostate cancer screening (6). Such statistical modeling studies have important limitations and rely on unverified assumptions that can render their findings questionable (or more suitable for further study than to serve as a basis for screening guidelines). More importantly, the model could not provide an assessment of the balance of benefits versus harms from screening.

The United States Preventive Services Task Force has analyzed the data from all reported prostate cancer screening trials, principally from the PLCO and ERSPC trials, and estimated that, for every 1,000 men ages 55 to 69 years who are screened every 1 to 4 years for 10 to 15 years (7):

  • About 1 death from prostate cancer would be avoided
  • 120 men would have a false-positive test result that leads to a biopsy, and some men who get a biopsy would experience at least moderately bothersome symptoms from the biopsy
  • 100 men would be diagnosed with prostate cancer. Of those, 80 would be treated (either immediately or after a period of active surveillance) with surgery or radiation. At least 60 of these men would have a serious complication from treatment, such as erectile dysfunction and/or urinary incontinence.
How is the PSA test used in men who have been treated for prostate cancer?

The PSA test is often used to monitor patients who have a history of prostate cancer to see if their cancer has recurred (come back). If a man’s PSA level begins to rise after prostate cancer treatment, it may be the first sign of a recurrence. Such a “biochemical relapse” typically appears months or years before other clinical signs and symptoms of prostate cancer recurrence.

However, a single elevated PSA measurement in a patient who has a history of prostate cancer does not always mean that the cancer has come back. A man who has been treated for prostate cancer should discuss an elevated PSA level with his doctor. The doctor may recommend repeating the PSA test or performing other tests to check for evidence of a recurrence. The doctor may look for a trend of rising PSA level over time rather than a single elevated PSA level.

What does an increase in PSA level mean for a man who has been treated for prostate cancer?

If a man’s PSA level rises after prostate cancer treatment, his doctor will consider a number of factors before recommending further treatment. Additional treatment based on a single PSA test is not recommended. Instead, a rising trend in PSA level over time in combination with other findings, such as an abnormal result on imaging tests, may lead a man’s doctor to recommend further treatment.
How are researchers trying to improve the PSA test?

Scientists are investigating ways to improve the PSA test to give doctors the ability to better distinguish cancerous from benign conditions and slow-growing cancers from fast-growing, potentially lethal cancers. None has been proven to decrease the risk of death from prostate cancer. Some of the methods being studied include:

  • Free versus total PSA. The amount of PSA in the blood that is “free” (not bound to other proteins) divided by the total amount of PSA (free plus bound) is denoted as the proportion of free PSA. Some evidence suggests that a lower proportion of free PSA may be associated with more aggressive cancer.
  • PSA density of the transition zone. The blood level of PSA divided by the volume of the transition zone of the prostate. The transition zone is the interior part of the prostate that surrounds the urethra. Some evidence suggests that this measure may be more accurate at detecting prostate cancer than the standard PSA test.
  • Age-specific PSA reference ranges. Because a man’s PSA level tends to increase with age, it has been suggested that the use of age-specific PSA reference ranges may increase the accuracy of PSA tests. However, age-specific reference ranges have not been generally favored because their use may delay the detection of prostate cancer in many men.
  • PSA velocity and PSA doubling time. PSA velocity is the rate of change in a man’s PSA level over time, expressed as ng/mL per year. PSA doubling time is the period of time over which a man’s PSA level doubles. Some evidence suggests that the rate of increase in a man’s PSA level may be helpful in predicting whether he has prostate cancer.
  • Pro-PSA. Pro-PSA refers to several different inactive precursors of PSA. There is some evidence that pro-PSA is more strongly associated with prostate cancer than with BPH. One recently approved test combines measurement of a form of pro-PSA called [-2]proPSA with measurements of PSA and free PSA. The resulting “prostate health index” can be used to help a man with a PSA level of between 4 and 10 ng/mL decide whether he should have a biopsy.
  • IsoPSA. PSA exists in different structural forms (called isoforms) in the blood. The IsoPSA test, which measures the entire spectrum of PSA isoforms rather than the concentration of PSA in the blood, may improve the selection of men with prostate cancer for biopsy (8).
  • PSA in combination with other protein biomarkers.  Tests that combine measurements of PSA in blood with measurements of other biomarkers linked to prostate cancer in blood or urine are being studied for their ability to distinguish high-risk disease. These other biomarkers include kallikrein-related peptidase 2, prostatecancer antigen 3 (PCA3), and the TMPRSS2-ERG gene fusion.
Selected References
  1. Thompson IM, Pauler DK, Goodman PJ, et al. Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter. New England Journal of Medicine 2004;350(22):2239-2246.

    [PubMed Abstract]

  2. Barry MJ. Clinical practice. Prostate-specific-antigen testing for early diagnosis of prostate cancer. New England Journal of Medicine 2001;344(18):1373-1377.

    [PubMed Abstract]

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How to Prepare Oregano Leaves for Cough Medicine

How to Prepare Oregano Leaves for Cough Medicine

Oregano is an herb that’s not only used in cooking. Oregano is used in natural medicine for many different ailments, from colds and coughs, to digestive issues, to aches and pains. If you have a cough and want to try a natural remedy, you can use oregano to help with your symptoms.

 Making Oregano Oil
  1. Image titled Prepare Oregano Leaves for Cough Medicine Step 1
    1

    Gather the oregano. To make oregano oil, you need to first make sure it is completely dry. If there is any excess water or damp spots, it can cause mold or bacteria to grow in your oil. Gather the amount of oregano you’d like for your oil, such as ½ cup or 1 cup.[1]
  2. Image titled Prepare Oregano Leaves for Cough Medicine Step 2
    2

    Choose your oil. When you make oregano oil, you will use a 1:1 ratio of oil to oregano. This means you will add the same amount of oil as oregano. If you have ½ cup of oregano, you need ½ cup of oil.

    • You can use olive oil, grapeseed oil, avocado oil, or almond oil.[2]
  3. Image titled Prepare Oregano Leaves for Cough Medicine Step 3
    3

    Crush the oregano. You should crush the oregano before you add it to the oil to help it start releasing its own oils. You can do this a couple of different ways. You can tear or cut the leaves with a knife.

    • You can also place the oregano in a plastic bag and smash it with a mallet or rolling pin.[3]
    • If you have a mortar or something similar, you can crush the oregano that way, too.
  4. Image titled Prepare Oregano Leaves for Cough Medicine Step 4
    4

    Warm the oil. Before adding the oil to the oregano, you need make sure it is warm. You can do this by placing it in the microwave, or place the oil in a glass container that you sit in hot water. Just make sure the oil is warm, and not too hot or boiling.[4]

    • Warming the oil helps the oregano and oil infuse better.
    • Alternately, you can place the jar in hot water after you place the oregano inside and seal the jar to infuse it. If you do this, leave the jar in the hot water for up to 10 minutes.[5]
  5. Image titled Prepare Oregano Leaves for Cough Medicine Step 5
    5

    Add the oregano. Once you have warm oil, add the oregano and oil to a sanitized jar. Stir is around to mix the oregano fully. You can even massage the leaves if you want to help release their oils.[6]

    • Place the lid on the jar when the oregano is added.
  6. Image titled Prepare Oregano Leaves for Cough Medicine Step 6
    6

    Infuse the oil for a few weeks. The oil needs to infuse for a few weeks. You want to let it infuse for at least two weeks. You can set it on a sunny windowsill to let the sunlight heat the oil to help it infuse.[7]

    • Make sure to shake the jar every few days.
    • Some people think letting it infuse longer is better for medicinal use. If you want to let it infuse longer, keep it infused for up to six weeks, but no longer. It could go bad.[8]
  7. Image titled Prepare Oregano Leaves for Cough Medicine Step 7
    7

    Strain the oil. After the oil has infused for a number of weeks, you need to strain the oregano from it. Use a strainer or a cheesecloth to strain the oregano from the oil. Make sure to squeeze out all the oil in the oregano leaves.[9]

    • Place the oil in a sanitized jar or a dropper bottle. Store it in a cool, dark place.
    • You can also store it in the refrigerator.

Method2

Making a Cough Syrup With Oregano

  1. Image titled Prepare Oregano Leaves for Cough Medicine Step 8
    1

    Gather the ingredients. To make a natural cough syrup, you need garlic, oregano, and honey. You need ½ cup of honey, 2 cloves of garlic, and 2 sprigs of fresh oregano.[10] You can measure out about one teaspoon to one tablespoon of oregano instead.

    • Garlic, honey, and oregano are antimicrobials that help naturally fight colds and coughs.
    • You can also add ½ cup of onion and one lemon if you want.
  2. Image titled Prepare Oregano Leaves for Cough Medicine Step 9
    2

    Boil oregano and garlic. Boil the garlic cloves and the oregano with about ½ cup of water. Boil for about five minutes.[11]
  3. Image titled Prepare Oregano Leaves for Cough Medicine Step 10
    3

    Combine with honey. Let the boiling mixture cool for a few minutes, then pour into a cup with the honey. Mix together. Now, it is ready to drink.
  4. Image titled Prepare Oregano Leaves for Cough Medicine Step 11
    4

    Steep overnight. An alternate way to make this cough syrup is to let it set overnight. In a jar, put the oregano at the bottom, then the garlic, then lemon and onion. Pour the honey and water over the ingredients, making sure the water covers all the ingredients completely. Put the lid on the jar so it is airtight, and let it steep overnight. Strain the liquid the next morning and only drink the liquid.[12]

    • Store in your refrigerator for a week.
    • This makes an even stronger cough syrup because the garlic and onion (if you add onion) are stronger and have more medicinal properties if they aren’t cooked.

Method3

Using Oregano For Medicinal Purposes

  1. Image titled Prepare Oregano Leaves for Cough Medicine Step 12
    1

    Use oregano cough syrups. The oregano cough syrup can be taken orally. Take a spoonful as often as you need for coughs or sore throats.[13]

    • Don’t give the cough syrup to children under a year old because of the honey.
  2. Image titled Prepare Oregano Leaves for Cough Medicine Step 13
    2

    Take oregano oil for colds and coughs. Oregano oil can be taken orally for any cold or cough symptoms. If you have a dropper, you can take two droppers full if you feel any cold symptoms coming on, including a cough.[14]

    • Another way to use oregano oil for coughs is to take three to five drops daily when you have a cough. You can put the oil in water, tea, orange juice, or directly into your mouth.[15][16]
  3. Image titled Prepare Oregano Leaves for Cough Medicine Step 14
    3

    Use oregano oil only when sick. Some people take oregano oil daily for a general boost. Most people believe you should only take it when you are sick. Oregano oil is considered a powerfully effective herbal remedy, so taking it when you feel a cold or cough coming on, and while you are sick, helps emphasize the effectiveness of the oil.[17]
  4. Image titled Prepare Oregano Leaves for Cough Medicine Step 15
    4

    Know the medicinal properties of oregano oil. Oregano oil is an anti-inflammatory, antifungal, and antibacterial agent. It also is considered a natural pain reliever.[18]

    • Oregano is believed to fight coughs, colds, congestion, sinusitis, allergies, arthritis, sore muscles, tooth aches, burns, ear infections, insect bites, and digestive issues like diarrhea.[19]

Has an Alternative to Table Sugar Contributed to the C. Diff. Epidemic?

Ice cream sundae

Has an Alternative to Table Sugar Contributed to the C. Diff. Epidemic?

Posted on  by 

Most of us know how hard it is to resist the creamy sweetness of ice cream. But it might surprise you to learn that, over the past 15 years or so, some makers of ice cream and many other processed foods—from pasta to ground beef products—have changed their recipes to swap out some of the table sugar (sucrose) with a sweetening/texturizing ingredient called trehalose that depresses the freezing point of food. Both sucrose and trehalose are “disaccharides.” Though they have different chemical linkages, both get broken down into glucose in the body. Now, comes word that this switch may be an important piece of a major medical puzzle: why Clostridium difficile (C. diff) has emerged as a leading cause of hospital-acquired infections.

A new study in the journal Nature indicates that trehalose-laden food may have helped fuel the recent epidemic spread of C. diff., which is a microbe that can cause life-threatening gastrointestinal distress, especially in older patients getting antibiotics and antacid medicines [1, 2]. In laboratory experiments, an NIH-funded team found that the two strains of C. diff. most likely to make people sick possess an unusual ability to thrive on trehalose, even at very low levels. And that’s not all: a diet containing trehalose significantly increased the severity of symptoms in a mouse model of C. diff. infection.

C. diff is a common bacterium that many people already have in their gut. In most cases, the bacterium doesn’t make people sick. The trouble often comes when taking antibiotics, especially in a hospital or nursing home. These drugs can upset the normal balance of healthy gut microbes, and because C. diff. is naturally resistant to many common antibiotics, this opportunistic microbe can multiply and produce toxins that cause inflammation and diarrhea.

Through the 1990s, C. diff. infections were mostly an occasional “nuisance” that would pass quickly. But in the 2000s, that changed. C. diff. infections became far more serious and common, soon emerging as the most frequent hospital-acquired infection in the United States. In 2011 alone, C. diff. sickened roughly a half-million Americans, and about 29,000 died [3].

The recent rise in C. diff. infections has been driven in large part by a particular group of bacterial strains, known collectively as RT027. Their spread may be explained in part by a mutation that lent the bugs resistance to certain antibiotics. But still unanswered was how this strain and another one called RT078 emerged so rapidly and became so prevalent.

An earlier study led by Robert Britton at Baylor College of Medicine, Houston, provided an important lead. He and his colleagues showed that the RT027 strains outcompeted many other C. diff. strains in cell culture and mouse studies [4].

To learn why in the new study, Britton and colleagues tested the strains’ ability to use various sugars that might be present in the gut to fuel their growth and give them a competitive advantage over other bacteria. Those studies suggested that RT027 strains have a special ability to grow on trehalose. In fact, further study of 21 different strains showed that the RT027 and RT078 strains, and only those strains, grow unusually well on a diet of trehalose.

Britton’s team found in the new study that RT027’s ability to grow on trehalose traces to a new mutation in the bacterial DNA. The change allows the bacterium to sense the sugar and produce an enzyme to metabolize it for food, even at extremely low concentrations. In contrast, RT078 is able to grow exceptionally well on low levels of trehalose, thanks to a cluster of four genes involved in metabolizing the sugar that were apparently acquired from another microbe. This shows the two C. diff strains have adapted to feed on trehalose in two completely different ways!

In mouse studies, Britton and colleagues found that a diet including trehalose makes infections with the RT027 strain more severe and sometimes deadly. The researchers also found that when trehalose is present, the epidemic C. diff. strains are not only more abundant, they produce more toxins for reasons that aren’t yet entirely clear. The team also has preliminary evidence from mice and people to suggest that enough dietary trehalose may make its way to the intestine to fuel the growth of those infectious strains.

Britton says the ability of these C. diff strains to grow on trehalose isn’t new. Strains of RT027 that efficiently metabolized trehalose were first isolated in the 1980s. Back then, people got most of their trehalose in small amounts from foods that naturally have it, such as mushrooms and shellfish.

What has changed is the recent addition of man-made trehalose into the food supply, often in large quantities. This shift was prompted by a new method to manufacture trehalose from cornstarch, which made the sugar much less costly. In 2000, FDA approved the sugar as a safe food additive. Trehalose quickly found its way into processed foods in the U.S. and around the world for its mild, flavor-enhancing sweetness and protection of frozen foods. In some store-bought ice creams, it’s found at concentrations of up to 11 percent.

What Britton and colleagues noticed is the more widespread use of manufactured trehalose coincided with early reports of C. diff. outbreaks. Those outbreaks popped up not only in the U.S., but also in countries all around the world where trehalose consumption increased. While more study is surely needed to nail down the possible connection, the circumstantial and experimental evidence has led Britton’s team to propose that widespread use of trehalose inadvertently played a key role in the recent emergence of C. diff infections.

This doesn’t mean that everyone needs to start worrying about trehalose. In fact, Britton says the sugar does have some advantages. For instance, because it’s harder to break down, trehalose doesn’t cause blood glucose to spike in the way some other sugars do.

Britton’s team continues to study the interaction between these C. diff. strains and trehalose. They are especially curious to learn more about how and why trehalose causes some C. diff. strains to produce more toxins in the gut. The findings certainly offer food for thought about the complex interplay between our diets, gut microbes, and health—and the unintended consequences that dietary changes might bring.

References:

[1] Dietary trehalose enhances virulence of epidemic Clostridium difficile. Collins J, Robinson C, Danhof H, Knetsch CW, van Leeuwen HC, Lawley TD, Auchtung JM, Britton RA. Nature. Published online 2018 Jan 3.

[2] Evaluating the risk factors for hospital-onset Clostridium difficile infections in a large healthcare system. Watson T, Hickok J, Fraker S, Korwek K, Poland RE, Septimus E. Clin Infect Dis. 2017 Dec 20.

[3] Clostridium difficile infection. Centers for Dis

California May Accept ‘Charitable’ Donations To Counter GOP Tax Plan

CA May Accept 'Charitable' Donations To Counter GOP Tax Plan

CALIFORNIA — California lawmakers are worried about the impact of the federal GOP tax bill that was just signed into law. In order to fight the pain of the bill, the state may soon begin accepting “charitable” donations, if some state lawmakers have their way.

Senate President pro Tempore Kevin de León (D-Los Angeles), along with Senator Ben Allen (D-Santa Monica) and Senator Jerry Hill (D-San Mateo and Santa Clara), introduced legislation this week “to protect California residents from the targeted federal tax increases that were enacted in the GOP’s recent tax reform,” a press release from the lawmakers states.

SB 227 — dubbed the “Protect California Taxpayers Act” — would make it so taxpayers in the Golden State could make a “charitable donation” to the state, according to the lawmakers. In return, the taxpayer would receive a dollar-for-dollar tax credit on the full amount of their contribution.

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Of the bill, de Leon’s office says:

Taxpayers will then be able to deduct their contribution to the Fund from their federal taxes, as they have historically done with their state tax payments. SB 227 is modeled after laws Senator de León authored in 2014 – SB 798 and SB 174, which provided tax credits on charitable donations made to state college affordability grants, like the Cal Grant program.

“The Republican tax plan gives corporations and hedge-fund managers a trillion-dollar tax cut and expects California taxpayers to foot the bill,” Sen. de León said. “We won’t allow California residents to be the casualty of this disastrous tax scheme.”

Sen. Hill said the legislation will “protect” Californians from losing money in the new tax plan.

The Los Angeles Times first reported on the proposal, noting that charitable donations remain deductible on federal taxes.

“Under the federal measure, residents can deduct $10,000 paid in state and local taxes from their federal taxes. The effects of the new cap would be deeply felt in many suburban areas of California where people typically pay more than that to the state and local governments. Through De León’s plan, the first $10,000 would be paid via regular taxes and people would have the option of making a charitable contribution to the state for the remainder,” according to the Los Angeles Times.

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