Tag Archives: medical research

Modeling Weight Loss Over the Long Term

Researchers at the National Institutes of Health have created a mathematical model of what happens when people of varying weights, diets and exercise habits try to change their weight. The findings challenge the commonly held belief that eating 3,500 fewer calories, or burning them off exercising, will result in a pound of weight loss.

Instead, the researchers’ computer simulations indicate that this assumption overestimates weight loss because it fails to account for how metabolism changes. The computer simulations show how these metabolic changes can significantly differ among people.

However, the computer simulation of metabolism is meant as a research tool and not as a weight-loss guide for the public. The computer program can run simulations for changes in calories or exercise that would never be recommended for healthy weight loss. The researchers hope to use the knowledge gained from developing the model and from clinical trials in people to refine the tool for everyone.

“This research helps us understand why one person may lose weight faster or slower than another, even when they eat the same diet and do the same exercise,” said Kevin Hall, Ph.D., an obesity researcher and physicist at the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases. “Our computer simulations can then be used to help design personalized weight management programs to address individual needs and goals.”

The online simulation tool based on the model enables researchers to accurately predict how body weight will change and how long it will likely take to reach weight goals based on a starting weight and estimated physical activity. The tool simulates how factors such as diet and exercise can alter metabolism over time and thereby lead to changes of weight and body fat.

The team found that people’s bodies adapt slowly to changes in dietary intake. They also found heavier people can expect greater weight change with the same change in diet, though reaching a stable body weight will take them longer than people with less fat.

The model also points to a potential simplified method to approximate weight loss in an average overweight person. An adult who has a body mass index (a measure of a person’s weight in relation to his or her height) between 25 and 29.9 is considered overweight. One example: For every pound you want to lose, permanently cut 10 calories from your current intake per day. At that rate, it will take about one year to achieve half of the total weight loss, and almost all of the weight loss will have occurred by three years. This calculation shows how long it takes to achieve a weight-loss goal for a single permanent change of diet or exercise.

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Using Nanocomposites to Improve Dental Filling Performance

After a dentist drills out a decayed tooth, the cavity still contains residual bacteria. Professor Huakun (Hockin) Xu says it is not possible for a dentist to remove all the damaged tissue, so it’s important to neutralize the harmful effects of the bacteria, which is just what the new nanocomposites are able to do.

Rather than just limiting decay with conventional fillings, the new composite he has developed is a revolutionary dental weapon to control harmful bacteria, which co-exist in the natural colony of microorganisms in the mouth.

“Tooth decay means that the mineral content in the tooth has been dissolved by the organic acids secreted by bacteria residing in biofilms or plaques on the tooth surface. These organisms convert carbohydrates to acids that decrease the minerals in the tooth structure,” says Xu, director of the Division of Biomaterials and Tissue Engineering in the School’s Department of Endodontics, Prosthodontics and Operative Dentistry.

The researchers also have built antibacterial agents into primer used first by dentists to prepare a drilled-out cavity and into adhesives that dentists spread into the cavity to make a filling stick tight to the tissue of the tooth. “The reason we want to get the antibacterial agents also into primers and adhesives is that these are the first things that cover the internal surfaces of the tooth cavity and flow into tiny dental tubules inside the tooth,” says Xu.

The main reason for failures in tooth restorations, says Xu, is secondary caries or decay at the restoration margins. Applying the new primer and adhesive will kill the residual bacteria, he says.

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Majority of Clinical Trials Don’t Provide Meaningful Evidence

The largest comprehensive analysis of ClinicalTrials.gov finds that clinical trials are falling short of producing high-quality evidence needed to guide medical decision-making.

The analysis, published today in the Journal of the American Medical Association, found the majority of clinical trials is small, and there are significant differences among methodical approaches, including randomizing, blinding and the use of data monitoring committees.

This is a critical issue as medical studies continue to leave quite a bit to be desired. Even more importantly the failure to systemically study and share evidence of effectiveness once treatments are authorized leaves a great deal to be desired. On top of leaving quite a bit to be desired, the consequences are serious. If we make mistakes for example in how we date fossils it matters but it is unlikely to cause people their lives or health. Failure to adequately manage and analyze health care experiments may very well cost people their health or lives.

“Our analysis raises questions about the best methods for generating evidence, as well as the capacity of the clinical trials enterprise to supply sufficient amounts of high quality evidence to ensure confidence in guideline recommendations,” said Robert Califf, MD, first author of the paper, vice chancellor for clinical research at Duke University Medical Center, and director of the Duke Translational Medicine Institute.

The analysis was conducted by the Clinical Trials Transformation Initiative (CTTI), a public-private partnership founded by the Food and Drug Administration (FDA) and Duke. It extends the usability of the data in ClinicalTrials.gov for research by placing the data through September 27, 2010 into a database structured to facilitate aggregate analysis.

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Is Dirt Healthier Than Broccoli?

That dirt I ate as a kid is maybe why I have been relatively healthy. Ok, probably that hasn’t been the most important factor. But it may be that some dirt and germs (kids licking their dirty hands and the ice cream melts on it, etc.) is actually more important for their long term health than finishing off the broccoli (of course, a healthy diet requires eating a bunch of vegetables, more than most kids eat).

The hygiene hypothesis has become a popular explanation for the boom in asthma, allergies and other health problems. Boiled down to one sentence the hypothesis is that exposure to germs early in life creates a healthy immune system and too little exposure results in a hypersensitive immune system (that is not as effective and leads to things like allergies).

A recent closed science paper, Microbial Exposure During Early Life Has Persistent Effects on Natural Killer T Cell Function, found mice exposed to more germs early on where healthier:

Exposure to microbes during early childhood is associated with protection from immune-mediated diseases such as inflammatory bowel disease (IBD) and asthma. Here, we show that, in germ-free (GF) mice, invariant natural killer T (iNKT) cells accumulate in the colonic lamina propria and lung, resulting in increased morbidity in models of IBD and allergic asthma compared to specific pathogen-free (SPF) mice. This was associated with increased intestinal and pulmonary expression of the chemokine ligand CXCL16, which was associated with increased mucosal iNKT cells. Colonization of neonatal—but not adult—GF mice with a conventional microbiota protected the animals from mucosal iNKT accumulation and related pathology. These results indicate that age-sensitive contact with commensal microbes is critical for establishing mucosal iNKT cell tolerance to later environmental exposures.

The microscopic battles waged in our bodies every day and over our lifetimes are amazing.

NASA Biocapsules Deliver Medical Interventions Based Upon What They Detect in the Body

Very cool innovation from NASA. The biocapsule monitors the environment (the body it is in) and responds with medical help. Basically it is acting very much like your body, which does exactly that: monitors and then responds based on what is found.

The Miraculous NASA Breakthrough That Could Save Millions of Lives

The Biocapsules aren’t one-shot deals. Each capsule could be capable of delivering many metred doses over a period of years. There is no “shelf-life” to the Biocapsules. They are extremely resilient, and there is currently no known enzyme that can break down their nanostructures. And because the nanostructures are inert, they are extremely well-tolerated by the body. The capsules’ porous natures allow medication to pass through their walls, but the nanostructures are strong enough to keep the cells in one place. Once all of the cells are expended, the Biocapsule stays in the body, stable and unnoticed, until it is eventually removed by a doctor back on Earth.
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Dr. Loftus [NASA] thinks we could realistically see wildspread usage on Earth within 10 to 15 years.
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The cells don’t get released from the capsule. The cells inside the capsule secrete therapeutic molecules (proteins, peptides), and these agents exit the capsule by diffusion across the capsule wall.

NASA plans to use the biocapsules in space, but they also have very promising uses on earth. They can monitor a diabetes patient and if insulin is needed, deliver it. No need for the person to remember, or give themselves a shot of insulin. The biocapsule act just like out bodies do, responding to needs without us consciously having to think about it. They can also be used to provide high dose chemotherapy directly to the tumor site (thus decreasing the side effects and increasing the dosage delivered to the target location. Biocapsules could also respond to severe allergic reaction and deliver epinephrine (which many people know have to carry with them to try and survive an attack).

It would be great if this were to have widespread use 15 years from now. Sadly, these innovations tend to take far longer to get into productive use than we would hope. But not always, so here is hoping this innovation from NASA gets into ourselves soon.

Microbiologist Develops Mouthwash That Targets Only Harmful Cavity Causing Bacteria

A new mouthwash developed by a microbiologist at the UCLA School of Dentistry is highly successful in targeting the harmful Streptococcus mutans bacteria that is the principal cause tooth decay and cavities.

In a recent clinical study, 12 subjects who rinsed just one time with the experimental mouthwash experienced a nearly complete elimination of the S. mutans bacteria over the entire four-day testing period.

Dental caries, commonly known as tooth decay or cavities, is one of the most common and costly infectious diseases in the United States, affecting more than 50 percent of children and the vast majority of adults aged 18 and older. Americans spend more than $70 billion each year on dental services, with the majority of that amount going toward the treatment of dental caries.

This new mouthwash is the product of nearly a decade of research conducted by Wenyuan Shi, chair of the oral biology section at the UCLA School of Dentistry. Shi developed a new antimicrobial technology called STAMP (specifically targeted anti-microbial peptides) with support from Colgate-Palmolive and from C3-Jian Inc., a company he founded around patent rights he developed at UCLA; the patents were exclusively licensed by UCLA to C3-Jian.

The human body is home to millions of different bacteria, some of which cause diseases such as dental caries but many of which are vital for optimum health. Most common broad-spectrum antibiotics, like conventional mouthwash, indiscriminately kill both benign and harmful pathogenic organisms and only do so for a 12-hour time period.

The overuse of broad-spectrum antibiotics can seriously disrupt the body’s normal ecological balance, rendering humans more susceptible to bacterial, yeast and parasitic infections.

Shi’s Sm STAMP C16G2 investigational drug, tested in the clinical study, acts as a sort of “smart bomb,” eliminating only the harmful bacteria and remaining effective for an extended period.

“With this new antimicrobial technology, we have the prospect of actually wiping out tooth decay in our lifetime,” said Shi, who noted that this work may lay the foundation for developing additional target-specific “smart bomb” antimicrobials to combat other diseases.

How Lysozyme Protein in Our Tear-Drops Kill Bacteria

A disease-fighting protein in our teardrops has been tethered to a tiny transistor, enabling UC Irvine scientists to discover exactly how it destroys dangerous bacteria. The research could prove critical to long-term work aimed at diagnosing cancers and other illnesses in their very early stages.

Ever since Nobel laureate Alexander Fleming found that human tears contain antiseptic proteins called lysozymes about a century ago, scientists have tried to solve the mystery of how they could relentlessly wipe out far larger bacteria. It turns out that lysozymes have jaws that latch on and chomp through rows of cell walls like someone hungrily devouring an ear of corn.

“Those jaws chew apart the walls of the bacteria that are trying to get into your eyes and infect them,” said molecular biologist and chemistry professor Gregory Weiss, who co-led the project with associate professor of physics & astronomy Philip Collins.

The researchers decoded the protein’s behavior by building one of the world’s smallest transistors – 25 times smaller than similar circuitry in laptop computers or smartphones. Individual lysozymes were glued to the live wire, and their eating activities were monitored.

“Our circuits are molecule-sized microphones,” Collins said. “It’s just like a stethoscope listening to your heart, except we’re listening to a single molecule of protein.”

It took years for the UCI scientists to assemble the transistor and attach single-molecule teardrop proteins. The scientists hope the same novel technology can be used to detect cancerous molecules. It could take a decade to figure out but would be well worth it, said Weiss, who lost his father to lung cancer.

“If we can detect single molecules associated with cancer, then that means we’d be able to detect it very, very early,” Weiss said. “That would be very exciting, because we know that if we treat cancer early, it will be much more successful, patients will be cured much faster, and costs will be much less.”

The project was sponsored by the National Cancer Institute and the National Science Foundation. Co-authors of the Science paper are Yongki Choi, Issa Moody, Patrick Sims, Steven Hunt, Brad Corso and Israel Perez.

Healthy Diet, Healthy Living, Healthy Weight

Living and eating healthily is tricky but not entirely confusing. The whole area of eating healthy food and what is a healthy weight is one where the scientific inquiry process and the complexity of scientific research on what is healthy for us is clear. Scientists study various issues and learn things but creating simple rules has proven difficult. Different studies seem to show benefits of contradictory advice, advice once seen as wise is now seen as wrong…

This is an area I am far from knowledgable about. Still I try to pay some attention as I like being healthy. Being sick is the quickest way to appreciate how great it is to be healthy. From various things I have skimmed it seems there is more evidence from several studies about how difficult it is to lose weight. Our bodies seem to work against our efforts.

And this, it seems to me, makes the problem of increasing childhood and teen obesity even more important to deal with as soon as issues arise.

It seems to me the most important thing to take from this, is the importance of maintaining a healthy weight: since you can’t just easily make up for a bad year of weight gain. I am not sure why I haven’t seen this note in most of what I have read – I suspect it is our reluctance to make value judgements about what is healthy. The problem I see with that is, the best advice we have is confusing enough without people with more knowledge being reluctant to state their best advice given the current knowledge. That doesn’t mean the suggestions are right, but at least they are educated guesses.

I try to eat relatively healthily. Which for me means taking steps to increase the amount of vegetables I eat (especially greens and some fiber) and decrease the amount of sweets and heavily processed food I eat (I still eat way too much heavily processed food). And I try to exercise as it seems to have many benefits including helping make up for some weaknesses in your diet (like eating too many calories and too many “empty calories). In my opinion (which on this topic may well not be worth much) eating a bit more stuff that really isn’t so good for you and exercising more is an easier tradeoff than trying to eat perfectly and do the minimum amount of exercise needed to stay healthy.

I also eat yogurt – I like it and the beneficial benefits of some bacteria seems likely. I heard recently something that surprised me which is that the beneficial bacteria remain for close to 2 weeks. I figured they would be gone in a couple days. I only heard that from one source (I can’t remember now but some seemingly knowledgable source – scientist researching the area), so it might not be accurate but it was interesting.

Here is an example of one of these health studies. They find that a low protein diet resulted in a loss of “lean weight” (muscle…) and more fat than a comparable diet with more protein. The same weight with a higher percentage of fat is not a good thing for human health. Thus the message is that a lower protein diet has this risk that must be considered (and therefor higher protein diets may well be wise). Of course things get much more complicated than that when we actually try to live by a diet.

Effect of Dietary Protein Content on Weight Gain, Energy Expenditure, and Body Composition During Overeating

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Can Just A Few Minute of Exercise a Day Prevent Diabetes?

That just 1 minute of exercise a day could help prevent diabetes seems to good to be true. But research at the University of Bath indicates it might be true. I am a bit of a soft touch for seeing the benefits of exercise. And I also love health care that focuses on achieving healthy lives instead of what most of the spending focuses on: treating illness.

Performing short cycle sprints three times a week could be enough to prevent and possibly treat Type 2 diabetes researchers at the University of Bath believe.

Volunteers were asked to perform two 20-second cycle sprints, three times per week (but really this works out to under 10 minutes of total time including warm up). After six weeks researchers saw a 28% improvement in their insulin function. Type 2 diabetes occurs when blood sugar levels build up to dangerously high levels due to reduced insulin function, often caused by a sedentary lifestyle. The condition can cause life-threatening complications to the heart, kidneys, eyes and limbs, and has huge costs (monetarily and to people’s lives).

Regular exercise can help keep blood sugar levels low but busy lifestyles and lack of motivation mean 66% of the population is not getting the recommended five 30-minute sessions of moderate exercise a week.

Dr Niels Vollaard who is leading the study, said: “Our muscles have sugar stores, called glycogen, for use during exercise. To restock these after exercise the muscle needs to take up sugar from the blood. In inactive people there is less need for the muscles to do this, which can lead to poor sensitivity to insulin, high blood sugar levels, and eventually type 2 diabetes… We already knew that very intense sprint training can improve insulin sensitivity but we wanted to see if the exercise sessions could be made easier and shorter.”

In the study the resistance on the exercise bikes could be rapidly increased so volunteers were able to briefly exercise at much higher intensities than they would otherwise be able to achieve. With an undemanding warm-up and cool-down the total time of each session was only 10 minutes.

This type of study is very helpful in identifying solutions that will allow more people to lead healthy lives and save our economies large amount of money. Medical studies can’t be accepted on face value. They are often not confirmed by future studies and therefore it is unwise to rely on the results of 1 study. The results provide interesting information but need to be confirmed (and in the area of studies on human health this has been shown to be problematic – are health is quite a tricky area to study).

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2011 Nobel Prize in Physiology or Medicine

The Nobel Assembly at Karolinska Institutet has today decided that The Nobel Prize in Physiology or Medicine 2011 shall be divided, with one half jointly to Bruce A. Beutler and Jules A. Hoffmann for their discoveries concerning the activation of innate immunity and the other half to Ralph M. Steinman for his discovery of the dendritic cell and its role in adaptive immunity.

This year’s Nobel Laureates have revolutionized our understanding of the immune system by discovering key principles for its activation.

Scientists have long been searching for the gatekeepers of the immune response by which man and other animals defend themselves against attack by bacteria and other microorganisms. Bruce Beutler and Jules Hoffmann discovered receptor proteins that can recognize such microorganisms and activate innate immunity, the first step in the body’s immune response. Ralph Steinman discovered the dendritic cells of the immune system and their unique capacity to activate and regulate adaptive immunity, the later stage of the immune response during which microorganisms are cleared from the body.

The discoveries of the three Nobel Laureates have revealed how the innate and adaptive phases of the immune response are activated and thereby provided novel insights into disease mechanisms. Their work has opened up new avenues for the development of prevention and therapy against infections, cancer, and inflammatory diseases.

We live in a dangerous world. Pathogenic microorganisms (bacteria, virus, fungi, and parasites) threaten us continuously but we are equipped with powerful defense mechanisms (please see image below). The first line of defense, innate immunity, can destroy invading microorganisms and trigger inflammation that contributes to blocking their assault. If microorganisms break through this defense line, adaptive immunity is called into action. With its T and B cells, it produces antibodies and killer cells that destroy infected cells. After successfully combating the infectious assault, our adaptive immune system maintains an immunologic memory that allows a more rapid and powerful mobilization of defense forces next time the same microorganism attacks. These two defense lines of the immune system provide good protection against infections but they also pose a risk. If the activation threshold is too low, or if endogenous molecules can activate the system, inflammatory disease may follow.

The components of the immune system have been identified step by step during the 20th century. Thanks to a series of discoveries awarded the Nobel Prize, we know, for instance, how antibodies are constructed and how T cells recognize foreign substances. However, until the work of Beutler, Hoffmann and Steinman, the mechanisms triggering the activation of innate immunity and mediating the communication between innate and adaptive immunity remained enigmatic.

Ralph Steinman was awarded the Nobel Prize for his discovery of the dendritic cell and its role in adaptive immunity. He was born in Canada and was a professor at Rockefeller University at the end of his career.

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