#on an unrelated note what's the going rate for a portion of a liver?

[cultivating-wildflowers]

breaking hiatus to beg some first-world level prayers for my menagerie. we're going on three months of Blythe's UTI (have another visit to the vet on Wednesday) and now my dog has a UTI. I am at my wit's end.

[sherristockman]

CRISPR: Crispy Fries Your DNA Dr. Mercola By Dr. Mercola CRISPR gene-editing technology brought science fiction to life with its ability to cut and paste DNA fragments, potentially eliminating serious inherited diseases. CRISPR-Cas9, in particular, has gotten scientists excited because,1 by modifying an enzyme called Cas9, the gene-editing capabilities are significantly improved. That's not to say they're perfect, however, as evidenced by a recent study that showed CRISPR may have significant unintended consequences to your DNA, including large deletions and complex rearrangements.2 Many of the concerns to date regarding CRISPR, or Clustered Regularly Interspaced Short Palindromic Repeat, technology have centered on off-target mutations. The featured study, published in Nature Biotechnology, looked at on-target mutations at the site of the "cuts," revealing potentially dangerous changes that could increase the risk of chronic diseases like cancer. Is CRISPR Scrambling DNA? Researchers at the U.K.'s Wellcome Sanger Institute systematically studied mutations from CRISPR-Cas9 in mouse and human cells, focusing on the gene-editing target site. Large genetic rearrangements were observed, including DNA deletions and insertions, that were spotted near the target site. They were far enough away, however, that standard tests looking for CRISPR-related DNA damage would miss them. The DNA deletions could end up activating genes that should stay "off," such as cancer-causing genes, as well as silencing those that should be "on." One of the study's authors, professor Allan Bradley, said in a statement:3 "This is the first systematic assessment of unexpected events resulting from CRISPR/Cas9 editing in therapeutically relevant cells, and we found that changes in the DNA have been seriously underestimated before now. It is important that anyone thinking of using this technology for gene therapy proceeds with caution, and looks very carefully to check for possible harmful effects." The deletions detected were at a scale of "thousands of bases," which is more than previously thought and enough to affect adjacent genes. For instance, deletions equivalent to thousands of DNA letters were revealed. "In one case, genomes in about two-thirds of the CRISPR'd cells showed the expected small-scale inadvertent havoc, but 21 percent had DNA deletions of more than 250 bases and up to 6,000 bases long," Scientific American reported.4 The cells targeted by CRISPR try to "stitch things back together," according to Bradley, "But it doesn't really know what bits of DNA lie adjacent to each other." As a result, the DNA may be rearranged, previously distant DNA sequences may become attached, or unrelated sections could be incorporated into the chromosome.5 Cas9, a bacteria enzyme that acts as the "scissors" in CRISPR, actually remains in the body for a period of hours to weeks. Even after the initial DNA segment had been cut out and a new section "pasted" into the gap to repair it, Cas9 continued to make cuts into the DNA. "[T]he scissors continued to cut the DNA over and over again. They found significant areas near the cut site where DNA had been removed, rearranged or inverted," The Conversation reported.6 Does This Mean CRISPR Isn't Safe? It's too soon to say what the long-term effects of gene-editing technology will be, and there are many variables to the safety equation. The findings likely only apply to CRISPR-Cas9, which cuts through the DNA's double strand. Other CRISPR technologies exist that may alter only a single strand or not involve cutting at all, instead swapping DNA letters. There are also CRISPR systems that target RNA instead of DNA and those that could potentially involve only cells isolated from the body, such as white blood cells, which could then be analyzed for potential mutations before being put back into the body.7 The Nature study did make waves in the industry, though, such that within the first 20 minutes of the results being made public three CRISPR companies lost more than $300 million in value.8 Some companies using CRISPR have said they're already on the lookout for large and small DNA deletions (including one company using the technology to make pig organs that could be transplanted into humans). One company also claims it hasn't found large deletions in their work on cells that do not divide often (the Nature study used actively dividing cells).9 The researchers are standing by their findings, however, which the journal took one year to publish. During that time, Bradley says, he was asked to conduct additional experiments and "the results all held up."10 Past studies have also found unexpected mutations, including one based on a study that used CRISPR-Cas9 to restore sight in blind mice by correcting a genetic mutation. The researchers sequenced the entire genome of the CRISPR-edited mice to search for mutations. In addition to the intended genetic edit, they found more than 100 additional deletions and insertions along with more than 1,500 single-nucleotide mutations.11 The study was later retracted, however, due to insufficient data and a need for more research to confirm the results.12 CRISPR-Edited Cells Could Cause Cancer Revealing the many complexities of gene editing, CRISPR-Cas9 also leads to the activation of the p53 gene, which works to either repair the DNA break or kill off the CRISPR-edited cell.13 CRISPR actually has a low efficacy rate for this reason, and CRISPR-edited cells that survive are able to do so because of a dysfunctional p53. The problem is that p53 dysfunction is also linked to cancer (including close to half of ovarian and colorectal cancers and a sizable portion of lung, pancreatic, stomach, breast and liver cancers as well).14 In one recent study, researchers were able to boost average insertion or deletion efficiency to greater than 80 percent, but that was because of a dysfunctional p53 gene,15 which would mean the cells could be predisposed to cancer. The researchers noted, " … it will be critical to ensure that [CRISPR-edited cells] have a functional p53 before and after engineering."16 A second study, this one by the Karolinska Institute in Sweden, found similar results and concluded, " … p53 function should be monitored when developing cell-based therapies utilizing CRISPR–Cas9."17 Some have suggested that if CRISPR could cure one chronic or terminal disease at the "cost" of an increased cancer risk later,18 it could still be a beneficial technology, but most agree that more work is needed and caution warranted. A CRISPR clinical trial in people with cancer is already underway in China, and the technology has been used to edit human embryos made from sperm from men carrying inherited disease mutations. The researchers successfully altered the DNA in a way that would eliminate or correct the genes causing the inherited disease.19 If the embryos were implanted into a womb and allowed to grow, the process, which is known as germline engineering, would result in the first genetically modified children — and any engineered changes would be passed on to their own children. A February 2017 report issued by the U.S. National Academies of Sciences (NAS) basically set the stage for allowing research on germline modification (such as embryos, eggs and sperm) and CRISPR, but only for the purpose of eliminating serious diseases. In the U.S., a first of its kind human trial involving CRISPR is currently recruiting participants with certain types of cancer. The trial is going to attempt to use CRISPR to modify immune cells to make them attack tumor cells more effectively. As far as risks from potential mutations, it's anyone's guess, but lead researcher Dr. Edward Stadtmauer of the University of Pennsylvania told Scientific American, "We are doing extensive testing of the final cellular product as well as the cells within the patient."20 Are 'Designer Babies' Next? It's easy to argue for the merits of CRISPR when you put it in the context of curing deafness, inherited diseases or cancer, and at least 17 clinical trials using gene-editing technologies to tackle everything from gastrointestinal cancer to tumors of the central nervous system to sickle cell disease have been registered in the U.S.21 Another use of the technology entirely is the creation of "designer babies" with a certain eye color or increased intelligence. About 40 countries have already banned the genetic engineering of human embryos and 15 of 22 European countries prohibit germ line modification.22 In the U.S., the NAS report specifically said research into CRISPR and germline modification could not be for "enhancing traits or abilities beyond ordinary health." Still, using gene editing to create designer babies is a question of when, not if, with some experts saying it could occur in a matter of decades.23 There are both safety and ethical considerations to think about. With some proponents saying it would be unethical not to use the technology. For instance, Julian Savulescu, an ethicist at the University of Oxford, told Science News he believes parents would be morally obligated to use gene-editing technology to keep their children healthy. "If CRISPR could … improve impulse control and give a child a greater range of opportunities, then I'd have to say we have the same moral obligation to use CRISPR as we do to provide education, to provide an adequate diet …"24 Others have suggested CRISPR could represent a new form of eugenics, especially since it can only be done via in vitro fertilization (IVF), putting it out of reach of many people financially and potentially expanding inequality gaps. On the other hand, some argue that countries with national health care could provide free coverage for gene editing, possibly helping to reduce inequalities.25 It's questions like these that make determining the safety of CRISPR and other gene-editing technology more important now than ever before. What Does a CRISPR-Enabled Future Hold? We've already entered the era of genetic engineering and CRISPR represents just one piece of the puzzle. It's an exciting time that could lead to major advances in diseases such as sickle-cell anemia, certain forms of blindness, muscular dystrophy, HIV and cancer, but also one that brings the potential for serious harm. In addition to work in human and animal cells, gene-edited crops, in which DNA is tweaked or snipped out at a precise location, have already been created — and eaten. To date, the technology has been used to produce soybeans with altered fatty acid profiles, potatoes that take longer to turn brown and potatoes that remain fresher longer and do not produce carcinogens when fried. The latter could be sold as early as 2019. The gene-editing science, in both plants and animals, is progressing far faster than long-term effects can be fully realized or understood. There are many opportunities for advancement to be had, but they must come with the understanding that unintended mutations with potentially irreversible effects could be part of the package.

[sherristockman]

Obesity Responsible for 40 Percent of Diagnosed Cancers Dr. Mercola By Dr. Mercola Nearly 30 percent of the global population is overweight or obese and this has a significant impact on cancer rates, experts say. In a 2014 report, obesity was linked to an estimated 500,000 cancer cases worldwide each year.1,2 More recent statistics from the U.S. Centers for Disease Control and Prevention (CDC) shows the reality is far grimmer than that — at least in the U.S. Obesity-Related Cancers on the Rise in the US While cancers unrelated to obesity declined by 13 percent between 2005 and 2014, obesity-related cancer incidence rose by 7 percent, and in 2014 more than 630,000 people were diagnosed with obesity-related cancer in the U.S. alone.3,4,5 Overall, obesity-related cancers accounted for a whopping 40 percent of all diagnosed cancers in 2014. As reported by Reuters: 6 “According to the International Agency for Research on Cancer, 13 cancers are associated with overweight and obesity. They include meningioma, multiple myeloma, adenocarcinoma of the esophagus, and cancers of the thyroid, postmenopausal breast, gallbladder, stomach, liver, pancreas, kidney, ovaries, uterus and colon and rectum (colorectal).” Previous data from the American Association for Cancer Research (AACR) suggests excess body weight is responsible for about 25 percent of the relative contribution to cancer incidence, ranking second only to smoking.7 When combined with other high-risk behaviors, such as a poor diet and lack of exercise, the relative contribution rises to 33 percent, making optional lifestyle-related factors a significant contributor to many cancers. Obesity-Related Cancers Disproportionally Affect Women Women are at greatest risk. Compared to men, women are more than twice as likely to develop obesity-related cancer,8 and the longer a woman is overweight, the greater her risk.9 The latest CDC data shows that 55 percent of all cancers in women were related to obesity whereas obesity accounted for “just” 24 percent of male cancer cases.10 Overall, endometrial, ovarian and postmenopausal breast cancer accounted for 42 percent of all obesity-related cancers. According to the authors, “Observational studies have provided evidence that even a 5-kg (11-pound) increase in weight since early adulthood is associated with increased risk of overweight- and obesity-related cancers.” Despite such evidence, few people are fully aware of this association. As noted by CDC deputy director Dr. Anne Schuchat,11 “That obesity and overweight are affecting cancers may be surprising to many Americans. The awareness of some cancers being associated with obesity and overweight is not yet widespread.” Considering the fact that nearly 71 percent of American adults are either overweight or obese, and over 20 percent of adolescents are already in the obese category,12 awareness of this link needs to grow if we’re to successfully combat rising cancer rates in coming decades. ‘Fat and Fit’ Myth Promotes Unhealthy Ideals Many still hold fast to the idea that you can be overweight and metabolically healthy, or “fat and fit,” but the cases in which this might be true are few and far in between. While this notion helps combat weight-related depression and poor self-esteem, it ignores the very real health risks associated with excess body weight. As noted in a 2013 review and meta-analysis13 that included data from more than 61,000 people, obese individuals were more likely to die sooner or have heart-related problems than people of normal weight — even if they were otherwise healthy — causing the researchers to conclude that: "Compared with metabolically healthy normal-weight individuals, obese persons are at increased risk for adverse long-term outcomes even in the absence of metabolic abnormalities, suggesting that there is no healthy pattern of increased weight." More recent research confirms that visceral fat — the fat buildup around your internal organs, which typically shows as an increased waist size — is directly associated with insulin resistance, high blood pressure, heart disease, stroke and cancer. In the U.S., Greece, Iceland and New Zealand, over 90 percent of adult men and half of all children were found to have this risk factor.14 Belly Fat Especially Risky for Postmenopausal Women As noted by Medical News Today,15 “So-called metabolically obese normal weight individuals may still have impaired health, and up to 50 percent of these individuals may be ignored by current BMI [body mass index] measurements.” Other recent research has linked excess belly fat alone (regardless of bodyweight) to an increased risk for lung and gastrointestinal cancers in postmenopausal women. According to study author Line Maersk Staunstrup, a doctoral student at Nordic Bioscience ProScion in Denmark:16 "The average elderly women can very much use this information, as it is known that the menopause transition initiates a shift in body fat towards the central trunk area. Therefore, elderly women should be especially aware of their lifestyle when they approach the pre-menopause age." How to Measure Your Body Composition Indeed, BMI has been repeatedly shown to be an unreliable way to measure a person’s body composition as it fails to take into account muscle mass and intra-abdominal (visceral) fat mass. A far more accurate measurement is to measure your waistline (the distance around the smallest area below the rib cage, above your belly button) in relation to your height. Waist circumference is the easiest anthropometric measure of total body fat. A general guide for healthy waist circumference is as follows: Alternatively, you can measure your waist-to-hip ratio. This is done by measuring the circumference of your hips at the widest part, across your buttocks. Then measure your waist at the smallest circumference of your natural waist, just above your belly button. Divide your waist measurement by your hip measurement to get the ratio, or use the University of Maryland’s online waist-to-hip ratio calculator.17 The High Cost of Obesity Other research also deconstructs the “fat and fit” notion, showing obesity eventually takes a toll on health — and finances — even if the person is currently healthy. Using computer modeling, the researchers estimated the financial cost of obesity for different age groups. As an example, a 50-year-old obese individual with normal blood pressure and cholesterol levels has a price tag in excess of $36,000 in direct medical care and lost productivity. Not surprisingly, weight loss was associated with significant savings. Not only could health insurance premiums be lowered across the board if society as a whole did not struggle with an excess of obesity-related health problems, but individuals would also save on co-pays, and they’d be able to maintain their productivity in the workforce. As reported by Medicine Net:18 “The researchers estimated that if an obese 20-year-old shed enough pounds to drop to the overweight category, almost two-thirds of his lifetime costs to society could be avoided … If a healthy but obese 70-year-old crossed to the overweight category, her lifetime costs could be cut by about 40 percent …” How Excess Weight Contributes to Cancer Obesity can raise your risk of cancer in several ways. Some cancers, especially breast and endometrial cancer, are sensitive to the female sex hormone estrogen, and fat cells produce an excess of this hormone. This is also why obesity in young children is such a grave concern. By carrying excess weight (and excess estrogen) for many years, if not decades, they’re at a significantly heightened risk of cancer as adults. Obesity is also associated with elevated inflammation levels in your body, which can contribute to cancer growth. One of the basic reasons why nutritional ketosis works so well against cancer is because it very effectively and efficiently lowers inflammation. A high-sugar diet, which tends to pack on the pounds, also feeds cancer by providing cancer cells with their preferred fuel. A healthy high-fat diet, on the other hand, tends to discourage cancer growth, as cancer cells lack the metabolic flexibility to use ketones derived from fat as fuel. It is likely that obesity represents an indirect marker for the true cause of the problem that contributes to both obesity and cancer, namely insulin resistance, which is also associated with leptin resistance and activation of the mTOR pathway. By lowering your blood sugar levels and normalizing your insulin receptor sensitivity, exercise has a similar effect, as this too creates an environment less conducive to cancer growth. Cutting Carbs Is More Effective Than Cutting Calories Calorie counting used to be the go-to solution for weight loss. However, research shows it’s not the cutting of calories that has the most profound effect, it’s cutting down on net carbs. One of the reasons for this is because, compared to fat and protein, carbohydrates have the greatest effect on insulin, which drives fat storage. Carbohydrate restriction also activates AMPK, an enzyme and powerful signaling protein that monitors cellular energy levels and drives several important metabolic pathways. This includes pathways involved in fat burning, the building of mitochondria, insulin regulation and glycogen breakdown — all of which have important implications not only for fat loss but also for general health. Importantly, recent research19 (summarized in the video above) shows a high-carb diet — even if you reduce calories to a level designed for weight loss — will prevent AMPK activation. What’s more, eating a low-carb diet will activate AMPK even if your calorie count is excessive! This can help explain why it’s so difficult to lose weight on a low-calorie diet when a large portion of those calories come from carbohydrates. That said, calorie restriction does have its merits, especially when you start talking about calorie restriction in terms of cyclical fasting. From my perspective, the timing and frequency of your meals is really the key to unlocking healthy metabolism. Nutritional Ketosis — The Key to Cancer Prevention and Treatment I’ve written a number of articles detailing the anticancer potential of nutritional ketosis. For a more in-depth review, revisit my interview with Thomas Seyfried, one of the leading pioneers in the nutritional treatment of cancer. He's been teaching neurogenetics and neurochemistry as it relates to cancer treatment at Yale University and Boston College for more than 25 years. He wrote an excellent medical textbook for alternative oncologists on this topic called “Cancer as a Metabolic Disease: On the Origin, Management, and Prevention of Cancer,” and is currently involved in preclinical research at Boston College. His book costs over $100 but you can get a free summary20 of it here. Earlier this year, I announced my pledge to raise $1 million to support Seyfried’s work by matching donations. Another front-runner in this field is Dr. Abdul Slocum with the ChemoThermia Oncology Center in Turkey, where they’re reporting remarkable successes using metabolically supported cancer therapies in a broad range of advanced stage cancers, including those involving the pancreas, lung, breasts, ovaries and stomach. Many of Slocum's patients have failed traditional therapies and some have even been sent home to die. When they enter his clinic, they’re immediately placed on a ketogenic diet and remain on it throughout their treatment. By incorporating nutritional ketosis, they’re able to minimize the amount of chemotherapy required without sacrificing effectiveness. On the contrary, effectiveness is massively increased, as their bodies are put into a metabolic state that is inhospitable to cancer cells, making them more vulnerable and easier to eradicate. Cyclical Ketogenic Diet for Optimal Health and Disease Prevention Research reveals a vast majority of Americans eat all day long. Most also consume a majority of their daily calories late in the evening and this type of eating pattern is a recipe for weight gain and metabolic dysfunction. The reason so many struggle with their weight (aside from eating processed foods that have been grossly altered from their natural state) is because they rarely, if ever, skip a meal. As discussed above, carrying excess weight is a significant risk factor for 13 different types of cancer. The good news is that by eating the right foods and reducing the frequency of your eating, you not only will shed weight as a natural side effect of normalizing your metabolism, you’ll also reduce your risk of chronic disease, including cancer, to a significant degree. If you already have cancer, the combination of a ketogenic diet and intermittent fasting can significantly improve your chances of recovery. This is the kind of eating plan I detail in my latest book, “Fat for Fuel.” From my perspective, it's nothing short of medical negligence to fail to integrate this type of dietary strategy into a patient's cancer treatment plan (along with optimizing vitamin D). A ketogenic diet along with intermittent fasting can be easily integrated into whatever cancer treatment plan you decide to follow. Personally, I believe it's absolutely crucial, no matter what type of cancer you're trying to address. To learn more, please see “Burning Fat for Fuel Increases Quality and Quantity of Life.”