Let’s Get Moving- Exercise is critical for health AND disease therapy

We still live in an age where we expect instant cures- a pill or a shot NOW to fix our ailments.  Yet, we overeat and live flaccid lives- which make us more susceptible to diseases.  Recently, the government has suggested that we need 150 minutes of exercise a week and to give up sugary drinks.  Not only does that work to reduce our girth- but data are now showing that exercise is critical to preclude- and improve-  the treatment and rehabilitation of devastating diseases. We have known for years that exercise is a critical regimen in the treatment of cardiac patients. Many asthmatics have proven that swimming precludes attacks and alleviates symptoms.  We can now expand the use of exercise to cancer, autoimmune diseases, Parkinson’s disease, and, even, dialysis patients.

We used to limit breast cancer survivors to lifting less than 15 pounds.  Dr. Schmitz (University of Pennsylvania) and her research group have shown that slow, progressive weight lifting is not only safe, but beneficial. With their compromised lymphatic systems, localized fluid retention and tissue swelling (lymphedema) flared occasionally; this regimen precluded such flare-ups.  The exercise may also reduce recurrence by some 40% (however, this part of the data needs more study).

Dr. Comella (Rush University Medical Center) has been involved with Parkinson’s Disease studies for years.  She has now found (animal studies) that exercise can slow the process of cellular

 

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loss associated with Parkinson’s; exercise helps with neuroplasticity and the ability of the brain to repair itself. It seems that exercise stimulates dopamine synthesis (reducing symptoms) and causes the release of neurotrophic factors and augments cerebral oxygenation that promotes cell growth and survival.  Her studies will now progress to humans; personal trainers will be used to improve patient participation.

Dr. Wilund of the University of Illinois (Urbanna-Champaign) is conducting a study with dialysis patients in Champaign and Chicago (both sites of U of I campuses).  With a more than $ 2 million NIH grant, he will lead the study to determine if bicycling (with some protein supplements) during dialysis therapy helps.  The anemic dialysis patients, who suffer from a loss of muscle tissue, will be studied to see if this regimen reverses such trends.  (Dialysis does remove amino acids [unintended circumstances, again], which is why protein supplements are part of the regimen.] The research will also see if vascular calcification will be reversed (blood vessel constriction and dilation affects blood pressure; blood pressure control is important in dialysis).  Part of this study will include personal trainers to induce the patients to use the modified bicycle units.

Exercise is able to work at both the physical and emotional levels; it has been found to reduce aggression and perfectionist tendencies.  But, the real trick in getting it to work is to choose specific goals (improve blood pressure, reduce blood sugar by 10 points) and employing a personal trainer to keep the patient (or us) on track.  Studies as to the mode and duration of exercise are critical, too. Many physicians have been leery of providing a stressor to the body during life-threatening illnesses.  However, as you can see, the data clearly indicates that the avoidance of inactivity is essential.  Let’s get moving…

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Laser Probes Being Developed for Early Detection of Cancer, Osteoporosis, and Dental Caries

 

Molecular energy levels and Raman effect

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Light scattering from laser probes (fiber optics) are being developed as diagnostic tools to differentiate between healthy and diseased cells.   These tools would be a (safer) replacement for the ubiquitous x-ray machines that have been used; moreover, the device provides more accurate information at a lower cost.  Preliminary results for a variety of diseases were presented at this year’s International Conference on Raman Spectroscopy (ICORS).

Raman Spectroscopy (RS) measures the changes in wavelength and intensity from the laser probe, after it becomes scattered from the target. The positive attribute of RS is that sample preparation is not required (nor is it an invasive technique); the negative aspect is that RS is not particularly sensitive.  However, RS can detect changes in cell composition, due to illness or cancer, as compared to their healthy state; those changes alter the spectrum results.

Researchers at the University of Michigan (under the direction of Dr. Michael Morris) found that RS is particularly effective for bone analysis (osteoporosis); the minerals within the bone provide clearly distinguishable Raman bands, which differ according to age, diet, degree of loading and exercise, as well as disease. RS is capable of predicting susceptibility to fracture and the effectiveness of a therapeutic regimen.  Currently, X-ray systems are used to predict therapeutic outcomes with moderate success; RS would greatly surpass this as a predictor.

Research groups from Rutherford Appleton Laboratory and Gloucestershire Royal Hospital (both in the UK) have employed RS to determine breast tissue calcification.  As is true for bone, the calcifications are primarily deposits of hydroxyapatite.  The calcifications are what is observed in positive mammograms.  Other research groups in Singapore and at Vanderbilt University are examining the use of RS for stomach and cervical cancers (as opposed to Pap smears), respectively).

Tooth decay (dental caries) was the target for  Dr. Choo-Smith at Canada’s National Research Council (Winnipeg) research.  As with bone, the primary component of teeth is hydroxyapatite, which has that strong Raman band.  Tooth decay involves the acid leaching (by Streptococcus mutans and others) of the minerals. Very small decay pits (100 to 250 μm) can be detected; in these cases sealants or antimicrobial treatments would be viable as opposed to drill and fill techniques that we commonly employ now.  The researchers hope to begin work with live subjects very shortly.

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New Method to Produce Pluripotent Stem Cells- quicker and more efficiently.

 

Illustration of mRNA transcription, an overview

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Dr. Derrick J. Rossi (Children’s Hospital Boston) along with a team of researchers from Children’s, Harvard, MIT, and Boston University, published  results in Cell demonstrating that skin cells can be reprogrammed into stem cells that seem virtually identical to embryonic ones.  These cells can also be used to develop transplant organs. While very exciting, the issue is that we have found that iPS (induced Pluripotent Stem) cells are not totally identical to embryonic ones; the cells seem to retain some memory of their tissue of origin.

Instead of using viri to manipulate the cell back to its embryonic capabilities, messenger RNA (mRNA) was inserted to effect the conversion; an interferon inhibitor was also employed.  The mRNA are involved in transcription (the formation of RNA from the DNA template) and translation (the formation of proteins); these conversions occurs in ribosomes among the cytoplasm.  In this case, the mRNA are involved in the translation of four key proteins (genes) that reprogram the cells into the iPS state.  The time frame involved is about 17 days from start to finish (about ½ the time for the viral method) and this process produces some 50-100 times more iPS cells.

Studies were done to see if differences between these iPS and embryonic cells would be easily manifested.  However, none were readily found.  In addition, the cells have been converted into cardiomyocetes (heart muscle cells) from their stem cell state.

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We are not crazy- overheard cell phone conversations are VERY distracting

I spend most mornings before visiting with clients at St. Elmo’s (my local coffee shop). Besides reading the paper and discussing politics with friends (and, of course, the coffee), what I like most about St. Elmo’s is its firm NO CELLPHONE POLICY.  I am sure you, too, feel that overheard cell phone conversations are very distracting.  Well, Lauren Embersen, while she was an undergraduate at the University of British Columbia, thought so, too.  The difference is that she performed the research to find out why  (for her Ph.D. at Cornell University).  The study results (co-authors are Michael Goldstein [Cornell University], Michael Spivey [University of California at Merced] and Gary Lupyan [University of Wisconsin-Madison]) are published in Psychological Science (September 2010; one needs to be a subscriber to read the document).  It turns out hearing half a conversation is much more distracting than hearing the entire discourse.

Ms. Embersen recording two pairs of female roommates holding a cell conversation- as a dialogue (both sides heard) and a “halfalogue” (only one side of the conversation could be

Pictogram: use of cellphones is prohibited

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heard, i.e., a simulated overheard cell phone conversation).  A monologue version (one person recapping the conversation) was also recorded.

These recordings were then played for 24 volunteers at modulating volumes (and silence,

as the control), who performed two different tasks on a computer.  One test involved tracking a moving dot on the monitor with the

mouse.  The other test required them to push a button whenever they saw four specific letters flash on the monitor.  The volunteers were requested to ignore the sounds and just concentrate on the assignment.

Performance (missed responses, incorrect hits) was the worst when the “halfalogue” was heard.  Overhearing the dialogue provided a six-fold response for the moving dot test when compared to the “halfalogue”.  The letter response test performance dropped 10% during the “halfalogue” (when compared to the dialogue, silence, or monologues).  The “halfalogues” were also adjusted to sound muffled (as if underwater) to test if the acoustic characteristics of the voice affected performance (and not the unpredictability); there was no significant effect.

Ms. Embersen postulates that our brains tend to ignore predictable items, but pays closer attention to those items that are not predictable.  A dialogue flows predictably, so we tend to ignore it.  However, overheard cell conversations, with varying bursts of noise and silence, are much less predictable to our brains.

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Take Me Out to the Ballgame…

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Another slightly off topic discussion today, because it’s getting near the baseball playoffs.  My team is in them- for the fourth year in a row. It’s also been a year when pitchers have really been in the news- and the number of pitcher injuries has been accelerating over the years.  The Phillies (Let’s Go Phils) have lost for most of this season the talents of baseball’s oldest pitcher- Jamie Moyer, and many of its players were out for weeks on end (but returned in time to prove that September is our favorite month).  (Our other three aces- Roy Halliday, Roy Oswalt, and Cole Hamels have been healthy and in great shape.)  The league bottom-dweller lost its hope when Steve Stasberg blew his arm.  And, therein lies the problem.

There are all kinds of theories as to what’s the best pitching technique and style.  But, we really don’t know.  What we do know is that pitching injuries are cumulative from microtrauma to soft tissues over the course of time.  Theories about the overuse have ranged from pitch counts, types, mechanics, as well as physical conditioning and nutrition, among others.  We need to understand the biomechanics of pitching to minimize injury, preclude overuse syndrome, and evaluate the rehabilitation.

Enter Drs. Berkson and Gill (Massachusetts General Hospital) and Paradiso (MIT).  They have developed a compact, wireless, wearable system that can monitor pitching and batting (among other physical activities that require bursts of action). This IMU (Inertial Measurement Unit) system is capable of employing six degree-of-freedom, battery-powered nodes that are worn on various places of the athlete’s body, coupled with sensors for both slow and fast motion.  The data are acquired wirelessly and analyzed off-line.  Previous to this development, pitching (as the example here) was analyzed in a controlled laboratory setting with various high-speed cameras tracking the action.  Acceleration and velocity were derived from positional data.

In this case, the motions are picked up with an array of cameras and sensors, creating a series of dots that are then analyzed by computer.  A biomechanical avatar of the individual is then produced that provides for 3-D imaging, demonstrating stresses and velocities (wrists, shoulders, arms, as well as other parts of the body).    Now, we can monitor pitchers when they are healthy- and stressed- comparing the results.  The athlete can compare the sequences in precise detail, determining what rehabilitation or re-learning steps are needed.  Also, by know what puts too much stress on an elbow or a wrist, one can correct actions and preclude injuries.  (You can see one short analysis of an ODU college pitcher here.)

All this while, we rabid Phanatics can enjoy our baseball.  Let’s go enjoy the playoffs and the World Series.

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the economy and our country Need Rethinking (the lower case was chosen on purpose)

American Manufacturing Jobs Rebounding

Image by Speaker Pelosi via Flickr

I have been trying to keep my politics out of this blog.  If you don’t know me, you have NO idea how hard this is for me.  And, I am not really going to break that rule, but it may strain those confines a little right now.

I was listening to Morning Joe (the absolutely best news discussion program on TV, hands down; Charlie Rose is probably second) when I heard Mayor Bloomberg make a statement that made me stop dead in my tracks earlier this week.   Now, I have a great deal of respect for the Mayor (one of the few NY Mayors to earn that in four decades), but I really thought he was exaggerating.  He wasn’t.  [OK, maybe just a little.]

Michael Bloomberg said that 10% of the private job growth in the US was in New York City.  Let me repeat the actual facts:  Of all the new jobs created in the US in 2010, 8.8% of them were created in New York City (67000 NYC and 736000 US) .  When you couple that with the fact that the metropolitan DC area had about 2% of the total private sector growth, you can see that private sector employment for the rest of the US is barely moving up at all.

It also points to the depletion of our manufacturing base in America.  Neither of these two regions are hotbeds for manufacturing; as a matter of fact, they generally are hotbeds for office jobs.  And, yes, our manufacturing base has dropped from 22 to 10% of total employment this past decade.  (While part of the drop was due to the Great Recession, the trend was clearly definite throughout the decade.)

I don’t care what your politics are (OK, I do- really), but this is a real problem.  Our politicians have to stop running for office (every minute of the day) and start working together to solve this problem.  I have started a feasibility study for a new venture, a small manufacturing firm.  It won’t employ thousands, but ten is a good start.  All of us so talented individuals should consider what effort they can contribute to restore American competency and strategic advantages.

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Our choice of branded objects provides self-affirmation

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Ron Shachar (Tel Aviv University), Gavan Fitzsimmons (Duke) and Tulin Erdem (NYU) published a study in Marketing Science that has ramifications for each of us in business.  They found that the more religious a person is, the less brand affiliation seems to matter.  Basically, they found that for non-religious persons, brand affiliation provides self-worth, similar to the affirmation that religion affords the religious.

One test monitored the number of Apple, Macy’s and Gap stores per million people in various regions.  This was compared with self-reported attended at religious services and the number of congregations per thousand residents.  They routinely found a negative correlation between brand reliance and religiosity.

Another test employed two groups of students (45 in total).  One group wrote essays on “What your religions means to you personally”; the other group “How they spent their days”.  All the students were sent on an imaginary shopping trip; the choices were among functional items (bread, batteries, ibuprofen) and self-expression items  (watches, socks, and sunglasses).  The choices were among national brands and store brands. Those that wrote about religion were less likely to choose national brands (choosing generic, store brands) for the self-expression items.

A third test involved 356 students (via the internet) that were queried as to their religious beliefs.   They then went on the same imaginary shopping trip.  Again, for the functional products there was not much difference, but the religious group more likely chose the store, rather than the national, branded items.

Similar results were found by Martin Lindstrom, reported in his book “Buyology” several years ago.  He found (using fMRI brain scanning) that the affinity of devout Christians for religion and the affinity for a brand name by non-religious had similar brain scans.   (He also found that we remain brand loyal until they sell us three bad products.)

This takes the old adage of “location, location, location” one step further.  We need to determine the religious demographic of the targeted region.   If the citizenry are more religious, a generic or store brand would be the product of choice; branded items seem to appeal more to those of us that feel less religious.

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New Applications for Pluripotent Stem Cells

organ regeneration example from induced plurip...

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While the US Court of Appeals has lifted (temporarily) the ban on stem cell research imposed by Judge Lamberth on my birthday (not the kind of present for which I had hoped), the case will probably proceed to the U.S. Supreme Court to settle the issue. As such, firms are reluctant to employ fetal stem cells as part of their research protocols.  Instead, the use of pluripotent stem cells that can differentiate into three different germ layers (endoderm- stomach and GI tract lining, lungs; mesoderm- muscle, bone, blood; or ectoderm-epidermal or nervous system) are being used;  there are no legal restrictions on their use.

As a means to save money- and to determine potential deleterious effects early and safely- drugs are now being tested using human tissues generated from stem cells. Companies such as Pfizer, Roche, and GlaxoSmithKline are employing tissues derived from pluripotent stem cells upon which they can test new drugs.  The goal is to determine- early on- if there are potential side effects to these new drugs.  Often, development proceeded beyond the laboratory and animal testing only to find deleterious effects.   Using tissues developed from pluripotent stem cells is one way to get those results earlier.

It had been found that stem cell generated heart cells and animals both had irregular heartbeats develop after an antiviral drug was administered.  (The antiviral drug development had been abandoned after the animal testing; stem cell-derived heart tissue was tested to see if the results mimicked the animal testing- it did.)

This nascent development in stem cell usage is being fed by two vendors (at present).  Cellular Dynamics International, founded in 2004, provides cardiomyocytes now and will be producing liver and nerve tissues generated from pluripotent stem cells.  Their stem cells are derived from blood or skin.  iPierian, only two years old,  has chosen a different approach for the derivation of their stem cells.  They have elected to obtain their stem cells from subjects who have ailments (diabetes, heart disorders, Alzheimer’s, among other choices).

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Bone metabolism and Energy metabolism- linked? Data says yes, but how tightly?

Bone is broken down by osteoclasts, and rebuil...

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Gerard Karsenty, now at Columbia (with various cohorts, the most common being Patricia Ducy, his now-wife) has spent some 15 years investigating the interactions and regulations effected by osteocalcin (controls the processes by which calcium phosphate is deposited onto bone cells). In a fairly radical theory (even to this day) Karsenty has been studying the links between osteocalcin (which affects the skeletal system (bone) and energy metabolism. Energy metabolism is a process that goes askew in diabetes.  (Our bones are involved with dynamic processes: Osteoblasts form and shape bone tissue, while osteoclasts break it down; the system is called “remodeling”.)

Karsenty also found that leptin (which suppresses appetite) blocks bone growth, even though there is no direct signal from leptin to the bone cells. Moreover, once leptin is infused into mouse brains, bone growth returns to normal).  It seems that leptin inhibits the synthesis of serotonin (in the brain, where most homeostatic processes¹ are regulated), which then attenuates bone growth. But, since homeostatic processes are part of feedback loops, there must be a mechanism by which bone growth affects energy metabolism. It turns out that osteocalcin deficiency is related to insulin-resistant, glucose intolerance (diabetes).

Karsenty determined that eating promotes the release of insulin, which then activates bone remodeling. Osteoblasts produce osteocalcin when forming bone; bone resorption activates the hormone (releases it into the blood stream) which then notifies the β-cells (in the pancreas) to boost insulin production (and glucose uptake). [These two articles referenced above have a great graphical depiction.] This regulatory mechanism operates on a longer-term basis than the normal insulin response.

These mice studies seem to have the most relevance to overweight humans, where insulin resistance and low bone turnover is common.

¹Homeostasis refers to the ability to regulate an organisms interior milieu, ensuring stability due to fluctuations in the environmental surrounding it.

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Creative Enterprises Are The Province of Everyone- Age is NOT a barrier!

Quarter (Canadian coin)

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When I was organizing (ok, dreaming up) my professional career, I made a decision that I needed to develop two new products or processes every single year.  Not a running average- a minimum.  If I failed to do so, it was time to consider changing foci.  And, thanks to a great deal of luck, I managed to do just that for more than three decades.  (Unfortunately, I feel my self-generated onus more and more lately.)

Imagine my surprise, when I was re-reading a 2008 Kauffman Foundation report (Vivek Wadhwa, Richard Friedman, Ben Rissing), to see that, contrary to my (and, I believe, popular) belief, high-tech startups were not the province of the young and single, but the 39 or 40 year old married professional (engineer, business major).  And, these folks are more successful than their younger counterparts, because of their accumulated expertise, networking (both peers and potential venture backers), and customer knowledge.  Moreover, there has been an additional shift in the census over the past few years.  Folks over 55 are now twice as likely to be starting new ventures, when compared to those among 20-34 year range (presumably due to the changing economy and/or the buy-outs offered by larger firms).

Why are we not hearing more about this phenomenon?  It probably has a lot to do with the fact that the older entrepreneurs are not part of the Web-based industries, but traverse among the biotech, energy, or hardware technology sectors.  And, these enterprises tend to be part of the B2B (business to business) sector, and not the B2C (business to consumer) end.

Actually, this substantiates a credo I have always nurtured:  Creativity is the ability to employ a concept or practice in a dramatically new setting. One does not have to develop a radical new concept to develop a creative enterprise. What’s holding you back?

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