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menthol opening your congested nasal airway?

It’s that time of the year again when the dry air irritates your nose and sinuses causing you to feel stuffy.  In all reality, isn’t it always that time of the year?  Allergies, dry air, colds–does it ever end?  I get stuffy a lot so I’m always interested in learning more about how to get some relief. 

Ever wonder why the smell of menthol can cause an enhanced feeling of air moving through your nose?  In another post on the use of nasal irrigation for allergies and sinus problems, I mentioned that nasal rinses with menthol may help with the symptoms of nasal congestion.  Why is that? 

The epithelial cells that comprise your nasal mucosa (the lining on the inside of your nose) have special temperature sensors on them, which belong to a family of proteins called TRP channels.  When you take a deep breath in, cooler air (than the warm air in your nose) whooshes over those receptors which sense “cold”.  This positive “cold” signal is relayed to your brain, which interprets it as “air is moving through my nose”.  Menthol is chemical that activates these receptors without requiring the cold air to move through your nose.  This is why when you are congested (i.e. not moving a lot of air through your nose), but you (for example) use either a nasal rinse with menthol or Vick’s vaporub, your nose feels as though it is opening up.  For more information, check out these studies by Lindemann et al (more clinical) and Bautista et al (more basic science).

Pretty neat, huh?  Now if I can only find something to relieve the sleep deprivation associated with residency.

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advances in cancer genomics webinar

From the Science/AAAS:

Watch Live on Thursday, April 30, 2009
12 noon Eastern, 9 a.m. Pacific, 4 p.m. GMT

Cancer is a complex family of diseases, characterized by the deregulation or dysregulation of the normal control pathways for cellular growth and/or apoptosis. Traditional research programs have focused on identifying and quantifying environmental and inherited factors associated with cancers found in particular tissues. Despite many advances, these approaches have historically been limited in scope due to technological limitations or excessive cost. With next generation genomic platforms, scientists are now able to cost-effectively assay individual cancer genomes and characterize them in terms of the global genetic, epigenetic, and transcriptional changes. In depth characterization of these events—and the relationships between them—will lead to better understanding of the mechanisms of tumorigenesis, metastasis, and therapeutic response. In this timely webinar, a panel of distinguished scientists will share their latest advances in cancer genomics and offer their views on the road ahead for this important area of research.

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only in romania

Just kidding and no offense to my Romanian bretheren. 

I just read an article published in the Dec. 21, 2007 issue of Science Magazine entitled “Cognitive Recovery in Socially Deprived Young Children: The Bucharest Early Intervention Project” which reported the results of a randomized controlled trial looking at the cognitive outcomes of orphan children who were institutionalized versus those who were not.  Wow.  Didn’t know it was ethical to do a randomized controlled trial on that kind of a thing–randomizing orphans to either stay institutionalized or go to a foster family?  Sounds like someone’s IRB dropped the ball on this one…

Anyway, here’s the abstract from the article:

In a randomized controlled trial, we compared abandoned children reared in institutions to abandoned children placed in institutions but then moved to foster care. Young children living in institutions were randomly assigned to continued institutional care or to placement in foster care, and their cognitive development was tracked through 54 months of age. The cognitive outcome of children who remained in the institution was markedly below that of never-institutionalized children and children taken out of the institution and placed into foster care. The improved cognitive outcomes we observed at 42 and 54 months were most marked for the youngest children placed in foster care. These results point to the negative sequelae of early institutionalization, suggest a possible sensitive period in cognitive development, and underscore the advantages of family placements for young abandoned children.

And surprise surprise, the institutionalized orphans did not fare as well.  I guess, as my old friend and mentor who gave this article to me said, you never know the answer until you do the trial.

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new prostate cancer vaccine: is there anything immunology can’t do?

Holy crap!!! Whoever said immunology is useless?  I’ve always been a little wary of cancer immunology because it is a field that is trying to harness the power of a system we still know almost nothing about.  I view Cancer Biology as a high risk, high reward field.  And it sounds like someone might finally be able to get some of that sweet sweet reward.   

Dendreon Corp, a Seattle-based biotech recently released results were from a Phase III clinical trial that included 512 men with late-stage prostate cancer who had not benefited from drugs that lower testosterone (testosterone has a growth/survival effect on most prostate cancers so testosterone blocking agents can often greatly reduce a prostate cancer load).

The new drug by Dendreon Corp is called Provenge (or Sipuleucel-T) and word is that it might become the first therapeutic vaccine for any kind of cancer.  Unlike a prophylactic vaccine, which we have all received as kids to prevent future infection by for example the polio virus, Provenge actually treats it’s target by stimulating the immune system to attack cells expressing certain cancer-specific proteins.  Therapeutic vaccines are also being developed for other cancers where specific tumor antigens exist that can distinguish the tumor from non-cancerous “self”, for example cervical or head and neck cancers caused by HPV.  Of course, the therapeutic benefit of these vaccines will be eliminated if tumors stop expressing those targetted proteins–which will eventually happen through a process of natural selection as long as the proteins are necessary for tumor survival. 

To make Provenge, the patient must undergo leukapheresis, a procedure similar to dialysis, where their blood is taken and their own antigen presenting cells are extracted and incorporated into the vaccine. Provenge is then administered intravenously to the patient, with very few side effect–mostly a few days of flu-like symptoms–but nothing like chemotherapy or hormonal therapy side effects.  And in case you are wondering, the current treatment for advanced prostate cancer is Taxotere, a chemotherapy drug with severe side effects, including neuropathy, hair loss, and vomiting.

Booyah!  Immunology to save the day, as usual.  Come on cancer biologists–let’s get with the program here!  HAHAHAHAHAHAHAHA!!!!!!  Just kidding, much love to the cancer biologists but this is pretty cool.

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obama, stem cells and ending the dark ages

So yesterday President Obama lifted the restrictions on governmental funding for stem cell research imposed by President Bush back in 2001.  We’re all very excited about this and I’m sure we’ve all read about this already, but I will add my two cents anyway. 

In the case you are not too familiar with President Bush’s stem cell research policy, check out this NIH website.  In brief, however, Bush’s executive order severely limited stem cell research primarily by mandating that federal funding (e.g. NIH grants) could only be used to support research performed on stem cell lines created before Aug. 2001.  I don’t remember if anyone ever agreed upon how many stem cell lines this actually was, but the experts (and I had the opportunity to train at an institution with one of the world’s experts on stem cell research so I heard about this a lot) I think largely agreed that these stem cell lines were inferior in quality to what the current technology could produce.

At the time, President Bush instituted this executive order because of the question of when life begins and if it does begin at conception, then is it ethical to destroy embryos for science, despite any future clinical applicability.  Yesterday President Obama declared “Our government has forced what I believe is a false choice between sound science and moral values…  It is about ensuring that scientific data is never distorted or concealed to serve a political agenda and that we make scientific decisions based on facts, not ideology.”  It’s about time.  Last time I checked, we aren’t living in some kind of theocracy where the President dictates scientific policy on his religious beliefs.  If you want to see how well that works, then take a look at the middle east, where despite considerable wealth from oil, the state of science remains in the dark ages. 

You know, I’m sure we all understand the moral and ethical ramifications of stem cell research–and every other kind of research we do.  Anytime we file an IRB application for human or animal research, we are faced with moral considerations.  In the case of stem cell research, religious beliefs have caused substantial controversy.  But I think this was a good thing–anytime conversation is stirred up about potentially dangerous or morally questionable research, it’s a good thing.  It forces us to think about it and make sure we have the right regulatory steps in place.  But, when the president effectively dictates the cessation of this research then there is no longer any conversation, it is simply the execution of the president’s religious beliefs.  It has been an unfortunate situation borne of ignorance and an obstinate belief; and ultimately put us eight years behind in unlocking the potential–or lack thereof (see, I’m open-minded)–of stem cell technology to address numerous human health problems.  Finally, I think one point that is sometimes overlooked in the media is that this eight year delay has also put the U.S. behind in stem cell research and therefore put us at a disadvantage to lead not only in terms of technology but also in terms of the moral/ethical approach to this research.  Since 2001, we have seen fiascos in stem cell research from the french company Clonaid, which supposedly helped the Raelian cult to clone humans back in 2002, to the disgraced South Korean scientist, Hwang Woo-suk, who for some time lead the world in stem cell research by falsifying results that he was able to clone human embryos and extract stem cells from them.  I mean, over the last eight years when I have been watching this B.S. go on, I couldn’t help but shake my head.  It was ridiculous. 

Anyway, all that aside, I’m glad we’re cautiously back on the right track.  And, I’m looking forward to the explosion of stem cell research and results that will come out of President Obama’s executive order.  It’s an exciting time.

For more information on stem cell research, here are some potentially interesting links: California Institute for Regenerative Medicine, the National Institutes of Health resource for stem cell researchUniversity of Wisconsin–Madison Stem Cell and Regenerative Medicine Center, the Harvard Stem Cell Institute and the Penn Institute for Regenerative Medicine.

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to my regular readers

Sorry–it’s been a slow week for new content on mudphudder’s blog.  This has been a really busy week and I’m halfway home now.  I’ll write put some new material up this weekend and ask that you bare with me for the next two days.  It should be smooth sailing from there on out.

For now, if you haven’t already done so, please check out Praxis #6 Blog Carnival (my previous entry).

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this week literature recap

Every week, I scan journals for interesting articles.  Here are some of the really interesting ones I found over the last week…

from Science Magazine:

Serotonin Mediates Behavioral Gregarization Underlying Swarm Formation in Desert Locusts

by Michael L. Anstey, Stephen M. Rogers, Swidbert R. Ott, Malcolm Burrows, and Stephen J. Simpson

Of general interest, serotonin induces the phenotypic switch from solitary to gregarious behavior in desert locusts.

Stretching Single Talin Rod Molecules Activates Vinculin Binding

Armando del Rio, Raul Perez-Jimenez, Ruchuan Liu, Pere Roca-Cusachs, Julio M. Fernandez, and Michael P. Sheetz

Providing evidence for a novel mechanism of protein-protein interactions, force-induced stretching of proteins can expose previous cryptic binding sites and promote binding to their ligands.
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from Nature Magazine

Adaptive immune features of natural killer cells

by Joseph C. Sun, Joshua N. Beilke and Lewis L. Lanier

This study provides evidence for adaptive properties of natural killer cell responses that is a major shift in our understanding of NK cells, which have generally been considered a component of the innate immune response.
   

Allergenicity resulting from functional mimicry of a Toll-like receptor complex protein

by Aurelien Trompette, Senad Divanovic, Alberto Visintin, Carine Blanchard, Rashmi S. Hegde, Rajat Madan, Peter S. Thorne, Marsha Wills-Karp, Theresa L. Gioannini, Jerry P. Weiss and Christopher L. Karp

This study demonstrates a novel mechanism through which allergens (in this case, one of the most common and clinically significant allergic antigens: house dust mite antigen) may trigger allergic responses and therefore suggests another potential therapeutic target for allergies.

Crypt stem cells as the cells-of-origin of intestinal cancer

Nick Barker, Rachel A. Ridgway, Johan H. van Es, Marc van de Wetering, Harry Begthel, Maaike van den Born, Esther Danenberg, Alan R. Clarke, Owen J. Sansom and Hans Clevers

Consistent with the previous literature on cancer stem cells, this study provides more evidence for intestinal stem cells localized to the intestinal crypts as the orginating source for intestinal cancers.
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from Cell

Large-Scale Structural Analysis of the Classical Human Protein Tyrosine Phosphatome

by Alastair J. Barr, Emilie Ugochukwu, Wen Hwa Lee, Oliver N.F. King, Panagis Filippakopoulos, Ivan Alfano, Pavel Savitsky, Nicola A. Burgess-Brown, Susanne Müller and Stefan Knapp

This study sheds insight into the classical PTP family through a comprehensive analysis of 22 human PTP crystal structures in combination with prior structural knowledge. The authors have developed a “phosphatome” resource that may provide insight into intrafamily PTP diversity, catalytic activity, substrate recognition, and autoregulatory self-association.

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despite financial crisis, obama could have major impact on science and technology

With the pressing financial crisis and foreign affair crises facing the country, President-elect Obama has made it clear that he recognizes the importance of science as a practical tool in addressing matters of national and international importance such as energy dependence, global warming and health care.

And while the financial crisis may limit funding for research, hundreds of billions of dollars exist in flexible funding programs that gives Obama plenty of latitude to fund many new projects.  Obama also appears poised to quickly implement many new policy changes that could help to further U.S. research (and undoing George W. Bush’s mess): from expanding embryonic stem cell research to taking a lead role in crafting a replacement for the Kyoto Protocols on global climate change.  Here’s an interesting article from the AAAS about the changes we might expect after Inauguration Day:

http://www.aaas.org/news/releases/2008/1223obama_forecast.shtml

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Sanjay Gupta: i’m too sexy for this job, too sexy for this job, too sexy by far

So, it’s almost official. There was a leak in the Washington Post as well as rumors swirling around the blogosphere all day. Reuters, however, is reporting as of 4 hours ago that Obama has indeed offered the post of Surgeon General to Dr. Sanjay Gupta, who has in return expressed his interest to accept the position.

The choice of Sanjay Gupta for Surgeon General is far from an obvious or conventional one. Seriously, check out the photo to the left; anyone ever remember C. Everett Koop posing for a glamour shot (à la Arthur Fonzerelli)?  I didn’t think so.  

Gupta’s lack of political and public health experience are causing some to wonder whether he is even qualified to be Surgeon General.  Surely, the youth and “coolness” factor played a role in his being chosen, but there is something slightly unsettling about that as well.

He’s had ties to big pharm (specifically Merck) while pushing vaccines (specifically Gardasil HPV) on the air.  Does he have other possible conflicts of interest or skeletons in his closet?  

Also, from naturalnews.com:

“In April, 2008, NaturalNews readers participated in a survey rating various traits of popular health journalists. Here’s how Dr. Sajay Gupta rated:
 


29% Humble / 71% Not
31% Generous / 69% Not
67% Healthy / 33% Not
37% Authentic / 63% Not
77% Intelligent / 23% Not
32% Honest / 68% Not
23% Informed / 77% Not


 
In other words, NaturalNews readers see Dr. Gupta as being intelligent and healthy, but dishonest, misinformed, fake and arrogant.”

I thought the survey results were quite interesting.  That coupled with Gupta’s lack of significant public health experience makes me wonder how the public (and the Senate confirmation committee) will respond to the nomination.

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il-12 and il-23 inhibitor shows promise for severe psoriasis

Ustekinumab is a human monoclonal antibody that antagonizes signalling of the heterodimeric cytokines interleukin 12 (IL-12) and IL-23 by binding to their shared p40 subunit. Previous work has suggested that IL-12 and IL-23 might be particularly important within psoriatic plaques (overexpression in both mice and humans with genetic deficiencies in these genes significantly decreased atopic responses). Phase III trials of ustekinumab have been very promising, with ustekinumab demonstrating significantly better results than etanercept (Enbrel), a soluble TNF-alpha receptor and currently one of the most effective treatments for severe psoriasis. For more information on the phase III clinical trials of ustekinumab, check out these updates:

http://www.nature.com/nrd/journal/v7/n11/full/nrd2753.html

http://www.nature.com/nbt/journal/v26/n12/pdf/nbt1208-1317a.pdf

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milk: the newest sports drink?

got milk?

Evidence has suggested that cow’s milk can be more effective than commercially available sports drinks for recovery after both resistance and endurance exercises. Based on so far limited research, milk appears to be an effective post-resistance exercise beverage that results in favourable acute alterations in protein metabolism: acutely increasing muscle protein synthesis, leading to an improved net muscle protein balance.  Studies have now reported that when postexercise milk consumption is combined with resistance training for at least 12 weeks, greater increases in muscle hypertrophy and lean mass are experienced. Holy smokes! I’m gonna try this out in combination with my weightlifting routine.

There is also some evidence to suggest that milk may be an effective post-exercise beverage for endurance activities. Low-fat milk has been shown to be as effective, if not more effective, than commercially available sports drinks as a rehydration beverage.  Moreover, milk is more nutrient dense for individuals who do both strength and endurance training, compared to traditional sports drinks.

Therefore, bovine low-fat fluid milk is a safe and effective post exercise beverage for most individuals–except for those who are lactose intolerant!

For a recent review article on the evidence supporting the benefits of cow’s milk as an energy drink:

http://www.jissn.com/content/pdf/1550-2783-5-15.pdf

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obesity pandemic

And I wonder how it can be that there is a worldwide obesity problem amongst children of all cultures, including those that have traditionally embraced exercise and healthier foods.

 


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world aids day 2008

December 1 will be the 20th World AIDS Day.  Take some time to think about the fact that over 30 million people are infected with HIV worldwide–as well as the tragic extent of the AIDS epidemic in Sub-Saharan Africa, where 2/3rds of the world’s HIV+ population live and 2/3rds of AIDS-related deaths occur.

For more information and resources, check out:aids red ribbon world aids day

And for those interested, here are links to the first two articles published describing the clinical entity AIDS in the December 10, 1981 issue of the New England Journal of Medicine:

Neither article is available online at nejm.org, so refer to your local medical library but it’ll be well worth the effort.  These articles make for an amazing read and it can be quite eerie–putting yourself in the shoes of the authors who were writing these case reports and then thinking about the extent to which HIV has since spread.

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early loss of mycobacterium tuberculosis–specific helper t cell responses after HIV infection

HIV+ individuals have increased susceptibility to becoming infected with tuberculosis. In fact, a second epidemic of tuberculosis has arisen in the last decade due to the increasing number of people who are immunodeficient from HIV infection. In contrast to many opportunistic infections which occur in late-stage HIV infection (or AIDS), increased tuberculosis susceptibility occurs when HIV+ individuals are largely asymptomatic and not susceptible to many other infections. In the December 1 issue of Journal of Infectious Diseases, Geldmacher et al try to understand the mechanism for the early susceptibility of HIV+ people to tuberculosis. Below are some of the pertinent points from the abstract of that study:

The acid-fast bacillus Mycobacterium tuberculosis is often the first manifestation of acquired immunodeficiency syndrome (AIDS) in patients infected with human immunodeficiency virus (HIV). This study was conducted to better understand the mechanism underlying M. tuberculosis–specific pathogenicity early after onset of HIV infection. In tuberculosis (TB)–asymptomatic subjects (i.e., subjects with unknown TB status who did not show clinical signs suggestive of TB), chronic HIV infection was associated with a decreased percentage of subjects with detectable M. tuberculosis–specific Th1 cells, a decrease which was not observed among subjects with active TB. Acute HIV infection induced a rapid depletion of M. tuberculosis–specific Th1 cells in 4 subjects who remained TB asymptomatic, whereas the population of these cells remained stable in subjects who remained HIV negative. Taken together, these data suggest a mechanism of rapid M. tuberculosis–specific Th1 cell depletion that may contribute to the early onset of TB in individuals with latent M. tuberculosis infection who become HIV infected.

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structure of PPAR-gamma bound to DNA

From Chandra et al in the November 20 issue of the journal Nature:

The peroxisome proliferator-activated receptors (PPARs) are composed of separately encoded genes (PPAR-alpha, PPAR-beta/delta and PPAR-gamma) that have overlapping tissue expression but overall are important regulators of various metabolic pathways, controling cellular processes such as regulation of lipid and carbohydrate metabolism. PPAR-gamma is the best-studied member of the family and is expressed in fat cells and also regulates the generation of fat cells and fat storage. Thiazolidinediones, are a drug class of PPAR-gamma ligands and include the drug rosiglitazone, are effective insulin sensitizers, and have been shown to improve glucose uptake and lower hyperglycemia and hyperinsulinemia. The PPARs have also been suggested to be potential therapeutic targets for atherosclerosis, inflammation and hypertension.

PPARs function as obligate heterodimers with the retinoid X receptors (RXRs). This study by Chandra et al is the first to show the crystal structure of PPAR-gamma with RXR-alpha. Check it out at: http://molvis.sdsc.edu/fgij/fg.htm?mol=3DZY

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informed-consent law enacted by south dakota to restrict abortion

A new informed-consent law in effect as of July in the state of South Dakota states that any physician performing an abortion must provide the following information to the pregnant woman:

(1) A statement in writing providing the following information:

(a) The name of the physician who will perform the abortion;
(b) That the abortion will terminate the life of a whole, separate, unique, living human being;
(c) That the pregnant woman has an existing relationship with that unborn human being and that the relationship enjoys protection under the United States Constitution and under the laws of South Dakota;
(d) That by having an abortion, her existing relationship and her existing constitutional rights with regards to that relationship will be terminated;
(e) A description of all known medical risks of the procedure and statistically significant risk factors to which the pregnant woman would be subjected, including:
(i) Depression and related psychological distress;
(ii) Increased risk of suicide ideation and suicide;
(iii) A statement setting forth an accurate rate of deaths due to abortions, including all deaths in which the abortion procedure was a substantial contributing factor;
(iv) All other known medical risks to the physical health of the woman, including the risk of infection, hemorrhage, danger to subsequent pregnancies, and infertility;
(f) The probable gestational age of the unborn child at the time the abortion is to be performed, and a scientifically accurate statement describing the development of the unborn child at that age;
(g) The statistically significant medical risks associated with carrying her child to term compared to undergoing an induced abortion.  And,

(2) A statement by telephone or in person, by the physician who is to perform the abortion, or by the referring physician, or by an agent of both, at least twenty-four hours before the abortion, providing the following information:

(a) That medical assistance benefits may be available for prenatal care, childbirth, and neonatal care;
(b) That the father of the unborn child is legally responsible to provide financial support for her child following birth, and that this legal obligation of the father exists in all instances, even in instances in which the father has offered to pay for the abortion;
(c) The name, address, and telephone number of a pregnancy help center in reasonable proximity of the abortion facility where the abortion will be performed; and
(d) That she has a right to review all of the material and information described in § 34- 23A.

This is part of a new trend by states to restrict abortion rights around the country. Although this law has been challenged to varying degrees of success by Planned Parenthood, its legality was most recently upheld in June 2008 by the Eighth Circuit Court of Appeals. I have a sneaking suspicion that this will go all the way to the Supreme Court and wonder how it will turn out there. I have said it before and I’ll say it again, informed consent is an integral part of maintaining a patient’s autonomy, one of the 4 tenets of medical ethics, but this law goes way beyond that in my opinion and intrudes upon the sanctity of the doctor-patient relationship by mandating the incorporation of religious and political opinions of others, which may be offensive to the patient.
For more information, there is a recent article in the New England Journal of Medicine about this.

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underlying relationships of multi-university collaborations in academics

In the last 30 years, more and more published scientific articles are a result of collaborations between investigators at different universities, which may suggest a dissemination of research beyond the walls of a few elite universities and/or geographic regions.  A study published in the Nov. 21st issue of the journal Science finds that increased multi-university collaborations are mostly composed of collaborations between geographically close institutions or between institutions of similar status.  It is interesting that collaborations between two elite institution (judged based on the number of citations received by that papers from those institutions) would on average lend greater impact to the work published, while collaborations by lower tier institutions would lead to correspondingly less benefit towards the impact of that work.  In fact, collaborations between the universities of the lowest tiers would, on average, slightly decrease the impact of the work.  Collaborations between universities of differing prestige would lead to work that has impact between that expected from each university–thus on average it does not benefit groups from more elite universities to collaborate with groups at less prestigious universities.  The authors of this study conclude:

“However, whereas the greater geographic interconnectedness of universities would appear to make geography less important, the corresponding intensification of social stratification in multi-university collaboration tends to embed the production of outstanding scientific knowledge in fewer rather than more centers of high-impact science. The dominant role of elite universities suggests several ideas for future research, including scale and resource advantages, social networks, journal leadership, and other factors such as matching based on status or quality, that promote a widening rather than a narrowing of stratification in science through the vehicle of multi-university partnerships.”

Here is the abstract from the study in the Nov. 21st issue of Science:

Multi-University Research Teams: Shifting Impact, Geography, and Stratification in Science

by Benjamin F. Jones, Stefan Wuchty and Brian Uzzi

This paper demonstrates that teamwork in science increasingly spans university boundaries, a dramatic shift in knowledge production that generalizes across virtually all fields of science, engineering, and social science. Moreover, elite universities play a dominant role in this shift. By examining 4.2 million papers published over three decades, we found that multi-university collaborations (i) are the fastest growing type of authorship structure, (ii) produce the highest-impact papers when they include a top-tier university, and (iii) are increasingly stratified by in-group university rank. Despite the rising frequency of research that crosses university boundaries, the intensification of social stratification in multi-university collaborations suggests a concentration of the production of scientific knowledge in fewer rather than more centers of high-impact science.

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physicians/scientists perform the first trachea transplant

Reported online on November 18 on the website of the journal Lancet, physicians from the Hospital Clinic in Barcelona, Spain reported the first trachea transplant.  The transplant trachea that was transplanted was produced from a segment of donor trachea that was denuded of donor cells, leaving a cartilage matrix, and subsequently reseeded with chondrocytes derived from bone marrow stem cells of the recipient, a 30 year old woman who developed significant tracheal stenosis and a hypoplastic left main bronchus secondary to infiltrative tuberculosis. 

Before the transplant, the recipient could not even continue a conversation without becoming short of breath.  In contrast Paolo Macchiarini, the first author of this study, and colleagues report that a few months after the transplant, the patient could “walk up two flights of stairs, walk 500 meters without stopping, and care for her children.”

And because the cells within the tracheal graft are the recipient’s own, she does not have to take anti-rejection medicines/immunosuppressants.

I am extremely excited about this development.  This is only the tip of the iceberg–stem cell technology will only get better with time–this is a great time to be in academic medicine at the forefront of this work!

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what obesity epidemic?

I saw this sign driving through North Carolina:

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vitamins E and C and your cardiovascular health!

You would think that the exclamation point in the title reflects the great benefits of vitamins E and C in decreasing peoples’ risk of cardiovascular events, including heart attack and stroke as well as dying from these events. But sure of enough no, that doesn’t appear to be the case.

The results of a randomized clinical trial (HD Sesso et al) first reported online on November 9 at the Journal of the American Medical Association show that in almost 15,000 men (all of whom were physicians), those taking vitamin E or vitamin C had no advantage in prevention of heart disease or strokes. Even more surprisingly, those taking vitamin E had an increased risk of hemorragic stroke.

It is important to point out that the subjects in this study were all either middle-aged or older men so no statement can be made in regards to women. Moreover, the doses of vitamin E (400 IU) and C (500 mg) aren’t terribly high and many individuals take higher daily doses of these vitamins, and often in combination.

Finally, I also think this highlights an important issue with regard to vitamins and dietary supplements. Many people (myself included) take vitamins and dietary supplements on a daily basis without any real evidence of benefit from ingesting these substances. And in fact, are we more likely exposing ourselves to side effects than any benefit? Something to think about…

keywords: vitamin E, vitamin C, heart disease, stroke, cardiovascular health, supplements

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statins, your cholesterol and your heart

According to a study in the Nov. 6 issue of the New England Journal of Medicine (PM Ridker et al), healthy men and women with normal cholesterol levels may significantly reduce their risk of developing or dying from heart disease (including chest pain, coronary bypass grafting or stenting), heart attacks and stroke by taking a crestor, a member of the cholesterol-lowering drug family of “statins”.  This study by Ridker et al was also described on CNN.com.

While statins are used currently to treat only people with high levels of cholesterol, the people in this study all had healthy cholesterol levels but had an elevated level of high sensitivity C-reactive protein (hs-CRP), which is a non-specific marker of inflammation.  Over the last few years, CRP has become an increasingly important adjunct clinical parameter used to decide whether a person with borderline cholesterol should start statin therapy.  This study further adds significance to the role of CRP in reflecting a person’s risk for cardiovascular disease. 

Moreover, the exact mechanism through which statins exert their beneficial effects remains unclear.  Certainly statins lower cholesterol but they have other ancillary effects as well.  In the laboratory setting, statins have been shown to have pleiotrophic effects–even inhibiting HIV replication!  However, there is now a lot of evidence to suggest statins have a significant anti-inflammatory effect.  And because inflammation is thought to play an important role in atherosclerotic cardiovascular disease, an anti-inflammatory effect by statins may synergize with their cholesterol lowering effects.  This is also consistent with recent controversy over the effectiveness of other cholesterol lowering drug familes (such as fibrates–e.g. TriCor or Lopid, bile acid seqeuestrants–e.g. cholestyramine, and niacin).   

keywords: cholesterol, statins, crestor, heart disease, heart attack, stroke

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myostatin gene and muscle size

This is one of my favorite knockout animal models!

The myostatin gene in mice (and other animals) inhibits muscle growth and instead promotes deposition of fat.  This gene is thought to have been evolutionarily conserved in order to promote formation of energy stores (fat) and restrict calorie consumption (by muscle) in animals who don’t have a guaranteed source of food.  This makes sense because what animal knows for a fact that it will find something to eat every day?  But, if this gene is knocked out in the laboratory setting or as a naturally occurring mutation (myostatin “knockout” mice), check out what happens: there is tremendous muscle hypertrophy and a significant reduction of body fat.  There’s a reason why this animal model is called “Mighty Mouse”!

A view of the chest muscles of these mice:

 

 

A view of the muscles in the front and rear limbs (i.e. arms and legs): 

 

 

 
For a more real-life example, the Belgian Blue Bull is naturally missing the myostatin gene:

 

 

I think I speak for everyone when I say, “Awesome!”

All of these images are taken from the original scientific article, which first described the function of the myostatin gene:

McPherron AC, Lawler AM, Lee S-J. 1997. Regulation of skeletal muscle mass in mice by a new TGF-β superfamily member. Nature 387: 83–90.

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artificial sweeteners: low in calories but high… in weight gain?

Low calorie artificial sweeteners–such as saccharin (e.g. Sweet N’ Low), Aspartame (e.g. Nutrasweet and Equal), or Sucralose (e.g. Splenda)–are used in countless food items including diet sodas and essentially anything labeled as “sugar-free” targeted to consumers as a strategy for reducing calorie intake and thus losing weight.

This is despite the fact that studies have shown numerous side effects to these sugar substitutes.  Most disconcerting: in regards to weight loss, studies have reported essentially no beneficial effects for artificial sweeteners.  And in fact, more recent studies have reported a link between use of these low calorie artificial sweeteners and weight gain.

Low-calorie artificial sweeteners have been linked to both increased appetite as well as metabolic changes in response to calories, both of which promote weight gain rather than weight loss. 

When people eat sweet foods, the sweet taste signals an impending high-calorie bolus to the body, which registers caloric fulfillment of energy needs and also induces metabolic changes for use of the incoming energy.  With use of these low-calorie sweeteners, these natural responses are disrupted because the body can no longer trust a sweet taste to indicate a high-calorie intake.  After a while, the body can no longer accurately gauge daily caloric intake, causing a rise in appetite while burning fewer calories. 

Check out the links below for more info:

http://www.mayoclinic.com/health/artificial-sweeteners/MY00073/UPDATEAPP=false&FLUSHCACHE=0

http://jama.ama-assn.org/cgi/content/full/299/18/2137

These findings emphasize two interesting points:

1) There is an extensive but as of yet mostly uncharacterized connection between the nervous system and the gastrointestinal system.  The effect of artificial sweeteners is just one example of the significance of this neuroendocrine axis.  I actually find this to be one of the more interesting areas for future research with obvious clinical significance and almost immediate impact on the lives of people.  Here is a link to a review paper for those of you who are interested in learning more about this physiology:

http://www.nature.com/nrd/journal/v7/n3/full/nrd2444.html

2) Not only do low-calorie artificial sweeteners not achieve their designed purpose, but apparently do the opposite!  Moreover, these sweeteners have numerous other reported side effects and have been linked to other health problems.  To be fair, the jury is still out on a definitive answer to how sweeteners affect the neuroendocrine axis.  But I think it is fair to say that it doesn’t look promising.  In the medical scientific community at least, there appears to be a growing belief that these substances should be more closely monitored and regulated by the FDA.  However, this is highly unlikely to occur due to the size (i.e. dollar worth) of the sweetener industry…yet another example of the conflicting interests of public health and the dollar…

 
keywords: artificial sweetener, sugar substitute, dieting, weight loss, splenda, equal, sweet n’ low

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president Obama and his impact on medicine and research

Congratulations to President-elect Obama! 

if you missed his victory speech, like I did because I had to get up early today, here is a link to the transcript:  http://www.cnn.com/2008/POLITICS/11/04/obama.transcript/index.html?iref=mpstoryview

I wonder what he will mean to the world of medicine and research?

For high-yield reading, here is a link to his healthcare policy:  http://www.barackobama.com/issues/healthcare/index.php

Here’s a quote off of his website regarding his plan to support biomedical research, including stem-cell research:

  • Advance the Biomedical Research Field:  As a result of biomedical research the prevention, early detection and treatment of diseases such as cancer and heart disease is better today than any other time in history. Obama strongly supports investments in biomedical research, as well as medical education and training in health-related fields. As president, Obama will strengthen funding for biomedical research, and better improve the efficiency of that research by improving coordination both within government and across government/private/non-profit partnerships. An Obama administration will ensure that we translate scientific progress into improved approaches to disease prevention, early detection and therapy that is available for all Americans.
  • Advance Stem Cell Research:Despite recent advances pointing to alternatives like adult stem cell and cord blood, embryonic stem cells remain unmatched in their potential for treatment of a wide variety of diseases and health conditions. Barack Obama has been a long-term supporter of increased stem cell research. He introduced legislation while a member of the Illinois Senate that would allow embryonic stem cell research in Illinois. Obama has cosponsored legislation to allow greater federal government funding on a wider array of stem cell lines. Obama believes we need high ethical standards that allow for research on stem cells derived from embryos produced for in vitro fertilization, embryos that would otherwise be needlessly destroyed.
  • taken from: http://www.barackobama.com/issues/technology/

     

    keywords: Barack Obama, health care, research funding, stem cell research

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    diabetes awareness month! – blood glucose control and major cardiovascular complications in type II diabetes

    red ribbon supporting diabetes cure, research and awareness

    I was walking through the hospital today and saw some big banners announcing “Diabetes Awareness Month,” which got me thinking about some recent and very interesting (in a head scratching kind of way) clinical trials. 

     Within the last year, there have been three major clinical trials reporting on the major cardiovascular benefits (prevention of heart attacks and strokes) of tight blood glucose control in type II diabetes (DMII).  The three major clinical trials all have acronym names: ACCORD, ADVANCE (both published in the June 12, 2008 New England Journal of Medicine: http://content.nejm.org/content/vol358/issue24/index.shtml and VADT (not yet published) studies. 

    These studies compared patients who underwent tight, intensive control of blood glucose with patients who used “standard” methods of blood glucose control.  Controlled glucose levels were defined by hemoglobin A1c levels, which is a measure of long-term (2 to 3 months) blood glucose control, of ~6.5 vs. ~7.5 to 8.5.  These studies were based on the principle and long-believed idea that the major cardiovascular complications of diabetes (heart attack and stroke) are caused by non-physiologically high blood glucose levels. 

    In a surprise to everyone (literally), all three studies found no cardiovascular benefit to tight control of blood glucose.  And in fact, one study–the ACCORD study–was stopped early due to increased death in patients with tight, intensive control of blood glucose!  These results have shocked the entire field and forced physicians and scientists alike to stop and rethink their basic understanding of diabetes.

    How could this be?  Before you stop taking your insulin or glucose lowering medications or recommend the same to your patients, it is important to stop and consider the interpretations of these failed studies–this is exactly what the field of diabetes must do.  In my opinion and many leaders in the field, these studies have uncovered a major flaw in clinical trials: the lack of consideration for the mechanisms through which drugs and interventions act. 

    These studies blindly believed that lower blood glucose would be better without considering pharmacologic mechanisms that were being used to lower blood glucose (e.g. insulin, and the various families of glucose-lowering drugs, all of which were used as needed on a patient by patient basis to meet the hemoglobin A1c targets).  Type II diabetes is increasingly recognized as a state of deranged metabolism with selective insensitivity of some intracellular signaling pathways and over-activity of others–all in the setting of systemic inflammation.  It is very likely that the addition of more drugs/insulin to lower the blood glucose–while achieving the sought after goal of maintaining more physiologic blood glucose–also causes greater stress on an already dysfunctional metabolic environment (e.g. through greater over-stimulation of already hyperactive signaling pathways). 

    Moreover, the level of metabolic disturbance in an individual is highly correlated to how clinically “sick” that person is–a factor that was not really considered in these studies.  (Keep your ears open for possible reports that tighter glucose control may have a beneficial effect in prevention of major cardiovascular complications in sub-groups of those with type II diabetes!)

    In the end, what do we take away from these studies?  Well, not much in terms of prevention heart attack and stroke in type II diabetes with tight glucose control.  For now, the recommendation is to continue to follow the treatment guidelines set by the American Diabetes Association:

    http://www.diabetes.org/for-health-professionals-and-scientists/cpr.jsp

    More importantly though, these studies will hopefully inspire future clinical trials to be more careful in consideration of the molecular mechanisms that are used by therapeutic interventions in the setting of the pathophysiology of the disease being studied.  I won’t get on my soapbox though–for now…

    keywords: diabetes, type 2, insulin, blood glucose, cardiovascular complications, heart attack, stroke

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