Professor Troels Jensen‘s clever group of researchers have published an interesting paper in the European Journal of Pain. We were thinking about writing a little spiel on it so you can get the idea and then we thought – what about asking the authors? So we did. Fortunately for us, Lise Gormsen, who has now [...]... Read more »
Gormsen L, Rosenberg R, Bach FW, & Jensen TS. (2010) Depression, anxiety, health-related quality of life and pain in patients with chronic fibromyalgia and neuropathic pain. European journal of pain (London, England), 14(2), 1270-8. PMID: 19473857
A few years ago, I pointed out some speculative work on environmental radiation during embryonic development and its possible effects on later longevity: Speculation on Solar Radiation and Longevity More on Solar Radiation and Life Expectancy The amount of [solar] radiation varies according to where you are in the world, what time of year it is and cyclic changes in the sun’s behaviour. The Equator generally gets the most radiation, and in the northern hemisphere, the usual radiation peaks will be in June and July, but there will be variations from year to year according to "solar cycles." Every 11 years the Sun goes through a cycle when the magnetic field changes and the number of sunspots grows and dwindles. This affects the amounts of radiation produced. The Maine researchers suggest that high radiation levels either stress the immune system of embryos and foetuses or cause small mutations in their DNA, which can either predispose or protect from disease, mould brain characteristics and influence length of life. The reliability theory of aging and longevity models complex organisms such as humans as an array of systems composed of many redundant component parts. It suggests that we are all born with a...... Read more »
Years ago, the relationship between depression and chronic pain was the hot topic, and it’s only more recently that anxiety and pain have become popular. So slightly tangentially, but I think you’ll see how it relates, today I want to muse a bit about health anxiety and some of the findings from this interesting area … Read more... Read more »
Muse, K., McManus, F., Hackmann, A., Williams, M., & Williams, M. (2010) Intrusive imagery in severe health anxiety: Prevalence, nature and links with memories and maintenance cycles. Behaviour Research and Therapy, 48(8), 792-798. DOI: 10.1016/j.brat.2010.05.008
Last month I wrote about how electrical stimulation of the hippocampus causes temporary amnesia - Zapping Memories Away.Now Toronto neurologists Laxton et al have tried to use deep brain stimulation (DBS) to improve memory in people with Alzheimer's disease. Progressive loss of memory is the best-known symptom of this disorder, and while some drugs are available, they provide partial relief at best.This study stems from a chance discovery by the same Toronto group. In 2008, they reported that stimulation of the hypothalamus caused vivid memory recollections a 50 year old man. In that case, the effect was entirely unintended and unexpected. The patient was being given DBS to try to curb his appetite (he weighed 420 pounds.) The hypothalamus is involved in regulating appetite, not memory - but the fornix, a nerve bundle that passes through that area, is. It's the main pathway connecting the hippocampus to the rest of the brain, and the hippocampus is vital for memory.In this new study, Laxton et al implanted electrodes to stimulate the fornix in 6 patients with mild (early-stage) Alzheimer's. What happened? The results, unfortunately, were quite messy. On average, the patients symptoms got worse over the course of the year. Alzheimer's is a progressive degenerative disease, so this is what you'd expect to happen without treatment. The authors say that the decline was a bit slower than you'd expect in these kinds of patients, but to be honest, it's impossible to tell because there was no control group.However, two patients did show memory improvements, and these were the same two who reported vivid recollections when the electrodes were first implanted (similar to the original obese guy):Two of the 6 patients reported stimulation induced experiential phenomena. Patient 2 reported having the sensation of being in her garden, tending to the plants on a sunny day... Patient 4 reported having the memory of being fishing on a boat on a wavy blue colored lake with his sons and catching a large green and white fish. On later questioning in both patients, these events were autobiographical, had actually occurred in the past, and were accurately reported according to the patient’s spouse.Also, the stimulation caused brain activation, generally switching "on" the areas that are turned "off" in Alzheimer's, and this lasted for a year (the length of the study so far). And there were no major side-effects. That's all good.Overall, these results are extremely interesting, but we don't know how well the treatment really works, and we won't know until someone does a randomized controlled trial with a longer follow-up period; something which is, unfortunately, true of a lot of the latest DBS studies.Link: The Neurocritic on the original 2008 paper.Laxton AW, Tang-Wai DF, McAndrews MP, Zumsteg D, Wennberg R, Keren R, Wherrett J, Naglie G, Hamani C, Smith GS, & Lozano AM (2010). A phase I trial of deep brain stimulation of memory circuits in Alzheimer's disease. Annals of neurology PMID: 20687206... Read more »
Laxton AW, Tang-Wai DF, McAndrews MP, Zumsteg D, Wennberg R, Keren R, Wherrett J, Naglie G, Hamani C, Smith GS.... (2010) A phase I trial of deep brain stimulation of memory circuits in Alzheimer's disease. Annals of neurology. PMID: 20687206
There is some evidence to show that hamsters use cortisol as a primary stress endocrine, similar to humans, which would make them a better model for studying stress responses that can be extrapolated onto humans, as opposed to rats and mice, which primarily use corticosterone. There is some debate about the extent to which hamsters use coristol, and both cortisol and corticosterone are present in hamsters, so researchers are currently duking that issue out. In any case, corticosterone is a precursor to cortisol, and both are involved in the stress endocrine cascade, which I have blogged about before.... Read more »
Chelini, M., Otta, E., Yamakita, C., & Palme, R. (2010) Sex differences in the excretion of fecal glucocorticoid metabolites in the Syrian hamster. Journal of Comparative Physiology B, 180(6), 919-925. DOI: 10.1007/s00360-010-0467-9
Dieters on low-fat and low-carb diets both lost the same amount of weight after two years, according to a just-published article in Annals of Internal Medicine. Both groups received intensive behavioral treatment, which may be the key to success for many. Low-carb eating was clearly superior in terms of increased HDL cholesterol, which may help [...]... Read more »
Foster GD, Wyatt HR, Hill JO, Makris AP, Rosenbaum DL, Brill C, Stein RI, Mohammed BS, Miller B, Rader DJ.... (2010) Weight and metabolic outcomes after 2 years on a low-carbohydrate versus low-fat diet: a randomized trial. Annals of internal medicine, 153(3), 147-57. PMID: 20679559
Parkinson's disease (PD) commonly includes a variety of behavioral disturbances related to impulsivity. Impulse control problems noted in (PD) ncludes hypersexuality, compulsive shopping, compulsive eating and pathological gambling.These behavioral problems may be related to the pathophysiology of Parkinson's disease. However, drugs commonly used in Parkinson's disease appear to increase the risk for impulsive behavioral problems. Clinicians face a dilemma in drug-induced behavioral disturbances. The drugs that may be effective for treating the motor symptoms may be causing behavioral problems. Stop the drug and the behavioral symptoms improve but the motor symptoms return.Dysregulation in brain glutamate has been hypothesized to contribute to dyskinesias and behavioral problems in PD. Dopaminergic drugs may alter glutamate regulation as well as sensitizing dopamine and NMDA glutamtergic receptors.Thomas and colleagues from Italy, recently published a clinical trial examining the effect of the antiglutamatergic drug amantadine for pathological gambling in PD. The key elements of the study design included:17 subjects with PDDouble-blind crossover studyAmantadine 200 mg/day vs placebo (50 mg twice daily for two days then 100 mg twice daily)Outcome variables: Yale-Brown Obsessive-Compulsive Scale for Pathological Gambling, Gambling-Symptom Assessment Scale, South Oaks Gambling Screen, time and money spent gamblingAll the subjects were gambling by purchasing scratch off lottery tickets and about a third also were gambling using slot machines. Before the intervention, they were losing 2% of their salary per gambling day. Amantadine treatment produced a significant reduction in the primary psychometric measures and in time and money spent gambling. The effect appeared within two to three days of initiation.Amantadine treatment resulted in five drop-outs during the study. Main adverse effects included: insomnia, visual hallucination, orthostatic hypotension and confusion. It appears that amantadine may not be tolerated by many with PD and this may limit its use.This study needs replication before changing clinical practice approaches. The study does highlight the potential role of glutamatergic drugs in impulse control disorders including pathological gambling. Amantadine may be a promising research drug for clinical trials in pathological gambling in younger populations without PD.Photo of Slot Machine Courtesy of Yates PhotographyThomas A, Bonanni L, Gambi F, Di Iorio A, & Onofrj M (2010). Pathological gambling in Parkinson disease is reduced by amantadine. Annals of neurology PMID: 20687121... Read more »
Thomas A, Bonanni L, Gambi F, Di Iorio A, & Onofrj M. (2010) Pathological gambling in Parkinson disease is reduced by amantadine. Annals of neurology. PMID: 20687121
Sci may have mentioned before just how much she loves Mary Roach’s writing (warning, the webpage has a roach on the front. I’m warning you because if you’re like Sci and have a roach phobia, it can be…unpleasant. Just scroll down to the bottom of the screen and avoid it). Mary Roach, author of Stiff: [...]... Read more »
WARD JE, HAWKINS WR, & STALLINGS HD. (1959) Physiologic response to subgravity. II. Initiation of micturition. Aerospace medicine, 572-5. PMID: 13842868
"The systematic characterization of somatic mutations in cancer genomes is essential for understanding the disease and for developing targeted therapeutics." So began today's journal article from a letter to Nature (link below) from scientists at Genentech. They went on to...... Read more »
Kan, Z., Jaiswal, B., Stinson, J., Janakiraman, V., Bhatt, D., Stern, H., Yue, P., Haverty, P., Bourgon, R., Zheng, J.... (2010) Diverse somatic mutation patterns and pathway alterations in human cancers. Nature. DOI: 10.1038/nature09208
Suppose you do two clinical trials of a drug, and only one of them shows it to work. It would be entirely misleading to only tell people about that one, and sweep the negative result under the carpet - but it happens.That's publication bias. A simple but powerful remedy is to require everyone to publically announce their trials before the data comes in. The USA has led the way in this, with the public clinicaltrials.gov database, and for several years it's been a legal requirement that all clinical trials conducted in the USA must be pre-registered there, and that the results have to be uploaded when they arrive.A new study by Bourgeois et al used this database to assess the scale of non-publication: Outcome Reporting Among Drug Trials Registered in ClinicalTrials.gov. Out of over 500 clinicaltrials.gov trials they looked at, 66% of them ended up getting published eventually. (The trials all ended before 2006, so they've had 5 years to get published and if they haven't by now, it's unlikely they ever will.) Is that a lot? Well, it's better than I'd expected, but it's still 33% too low.The odds of getting published varied depending upon the type of drug, though. Trials of proton-pump inhibitors and cholesterol lowering drugs had the best chances. Antidepressants were a bit less publishable; antipsychotics were markedly worse; and only just over half of the vasodilator trials did.This is interesting data, and it should remind us that publication bias, although often discussed nowadays as a problem with trials of antidepressants, is by no means limited to those drugs and in fact antidepressant trials (at least the ones starting after 2000 and completed by 2006) are fairly middle-of-the-road in terms of % publication rates.Publications resulting from drug company-funded trials were also more likely to be positive (85%) than were trials bankrolled by the government (50%) or non-profit organizations without Pharma "contributions" (61%). This doesn't prove that drug companies are biasing publication - maybe they just really do get more positive results - but, well, it's not exactly reassuring.Why is non-publication still a problem, given that people are required by law to release their trial protocols and results on clinicaltrials.gov? The problem is that clinicaltrials.gov doesn't appear on PubMed, and medical science works on the rule of "PubMed or it didn't happen". Someone searching for papers about "drug X for disease Y" - which I suspect accounts for the vast majority of paper downloads - will still only get told about the trials that the authors chose to publish.Is there an answer? We could in theory force people to write their results up and submit them to a journal, and we force journals to publish them, but that would be unworkable and incredibly unpopular. But why not simply publish the stuff on clinicaltrials.gov?Whenever someone uploads their results to clinicaltrials.gov (as they legally must), clinicaltrials.gov could automatically use them to generate a mini-paper and publish it online. There would be a few tricky issues to sort out - you'd have to be careful that it didn't lead to the same results getting published in multiple places, for one - but so long as these reports were indexed on PubMed, it would solve the fundamental problem.Bourgeois FT, Murthy S, & Mandl KD (2010). Outcome Reporting Among Drug Trials Registered in ClinicalTrials.gov. Annals of internal medicine, 153 (3), 158-66 PMID: 20679560... Read more »
Bourgeois FT, Murthy S, & Mandl KD. (2010) Outcome Reporting Among Drug Trials Registered in ClinicalTrials.gov. Annals of internal medicine, 153(3), 158-66. PMID: 20679560
I hate science press releases.
Well, not exactly. I hate science press releases that hype a study beyond its importance. I hate it even more when the investigators who published the study make statements not justified by the study and use the study as a jumping off point to speculate wildly. True, it's not always the fault of the investigators, particularly if they don't have much experience dealing with the press, but all too often scientists fall prey to the tendency to gab glibly and give the reporter what he or she wants: Pithy, juicy quotes that relate the results to what the reporter wants them related to. It's irritating as hell, not so much because it's pure self-promotion. (After all, self-promotion is not in and of itself a bad thing) but rather because it's almost inevitably an excuse for the investigators to say what they want without peer pesky peer reviewers telling them that they should keep their remarks focused on what the evidence will support. Often these press releases lead to credulous news stories that make conclusions that aren't justified from the actual study. Sometimes an investigators' comments are taken out of context. Sometimes the investigator says something dumb. Sometimes it's all three.
There's a certain Reuters story entitled Cancer cells slurp up fructose, U.S. study finds making the rounds, and it's being represented as yet more evidence about the evils of high fructose corn syrup. That it might be viewed as a few years in the future, after followup studies have been done, but for right now all it is is an intriguing study being used to serve an agenda that it doesn't serve well: Read the rest of this post... | Read the comments on this post...... Read more »
Liu, H., Huang, D., McArthur, D., Boros, L., Nissen, N., & Heaney, A. (2010) Fructose Induces Transketolase Flux to Promote Pancreatic Cancer Growth. Cancer Research, 70(15), 6368-6376. DOI: 10.1158/0008-5472.CAN-09-4615
Andrew Miller (Rice University, United States) and coworkers have developed a remarkably cheap microscope with both the portability and imaging capabilites required for routine slide-based medical diagnostics, an extremely useful development for health professionals in remote regions of the world. This news feature was written on August 4, 2010.... Read more »
Miller, A. R., Davis, G. L., Oden, Z. M., Razavi, M. R., Fateh, A., Ghazanfari, M., Abdolrahimi, F., Poorazar, S., Sakhaie, F., Olsen, R. J.... (2010) Portable, Battery-Operated, Low-Cost, Bright Field and Fluorescence Microscope. PLoS ONE, 5(8). DOI: 10.1371/journal.pone.0011890
Going through the papers cluttering my inbox I found this survey of Australian pharmacy customers relating to their use of CAM and their impressions of how pharmacists should approach the subject. Regular readers of Sciblogs may remember a kerfuffle earlier in the year regarding the sale of homeopathic remedies in pharmacies, I and others were [...]... Read more »
Braun, L., Tiralongo, E., Wilkinson, J., Spitzer, O., Bailey, M., Poole, S., & Dooley, M. (2010) Perceptions, use and attitudes of pharmacy customers on complementary medicines and pharmacy practice. BMC Complementary and Alternative Medicine, 10(1), 38. DOI: 10.1186/1472-6882-10-38
The genetics of dystonia in CRPS - genes don't seem to predispose or cause dystonia in CRPS. This doesn’t mean that there is no genetic contribution, but it does mean that the genes that underpin familial dystonia are not important in CRPS-dystonia.... Read more »
 van Rijn MA, Marinus J, Putter H, & van Hilten JJ. (2007) Onset and progression of dystonia in complex regional pain syndrome. Pain, 130(3), 287-93. PMID: 17499924
Research addressing genetic factors in obesity grows each year. However, there has been limited attention to the other side of the coin, the genetics of thinness and a related body composition variable lean body mass. Some might say, why bother, isn't being thin a good thing?Thinness does confer some advantages with reduced risk of hypertension, diabetes, osteoarthritis and some types of cancer. However, there are some disorders (i.e. osteoporosis) increased in those underweight. And there is some epidemiological data that suggests increased mortality rates for middle-aged and older aged individuals.Additionally, low weight is a hallmark of the eating disorder anorexia nervosa. Anorexia nervosa is likely to have unique risks and mechanisms in producing low weight. Nevertheless, understanding the genetics and mechanisms for low weight in community may provide some insight into eating disorders as well as obesity. For example, a gene found to produce low weight in the general population might provide a clue for the site of a drug target for obesity.A collaborative group from China and the U.S. recently published a genome-wide association study looking for genes important for lean body mass. The primary measure of lean body mass was measured by dual energy X-ray absorption (DXA). This study included three replication studies using independent samples. The primary sample and replication samples all found an association between lean body mass and the TRHR gene. TRHR is thyrotropin-releasing hormone receptor. The TRHR is:Located in the pituitaryResponds to thyrotropin releasing hormone (TRH) produced in the hypothalamusModulates thyroid stimulating hormone (TSH) and therefore thyroid hormone metabolismBelongs to the G protein-coupled receptor 1 familyThyroid hormone is required for the anabolic (muscle building) effect of human growth hormone. Growth hormone acts through insulin-like growth factor 1 in controlling muscle growth. This association may explain some of the effect of TRHR in lean body mass.The authors note lean body mass accounts for about 60% of body weight and significantly contributes to body mass index (BMI). Future genetic studies of lean body mass, leanness and obesity will need to examine thyroid and growth factor pathways.Photo of Lean Triathlete Courtesy of Yates PhotographyLiu XG, Tan LJ, Lei SF, Liu YJ, Shen H, Wang L, Yan H, Guo YF, Xiong DH, Chen XD, Pan F, Yang TL, Zhang YP, Guo Y, Tang NL, Zhu XZ, Deng HY, Levy S, Recker RR, Papasian CJ, & Deng HW (2009). Genome-wide association and replication studies identified TRHR as an important gene for lean body mass. American journal of human genetics, 84 (3), 418-23 PMID: 19268274... Read more »
Liu XG, Tan LJ, Lei SF, Liu YJ, Shen H, Wang L, Yan H, Guo YF, Xiong DH, Chen XD.... (2009) Genome-wide association and replication studies identified TRHR as an important gene for lean body mass. American journal of human genetics, 84(3), 418-23. PMID: 19268274
Early research on the role of the occipitotemporal region in reading often focused on characterizing a single region in the mid fusiform, commonly called the visual word form area. Since then, focus has gradually...
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van der Mark S, Bucher K, Maurer U, Schulz E, Brem S, Buckelmüller J, Kronbichler M, Loenneker T, Klaver P, Martin E.... (2009) Children with dyslexia lack multiple specializations along the visual word-form (VWF) system. NeuroImage, 47(4), 1940-9. PMID: 19446640
The other day I came across an interesting journal article on Hedgehog signalling, how it might be implicated in some cancers, and the potential issues associated with targeting the pathway: "... several issues surrounding the basic biology of the Hh...... Read more »
by email@example.com (Travis Saunders) in Obesity Panacea
This week I am attending the Canadian Obesity Network Student Bootcamp. I know that sounds like some sort of training program, but it's actually a full week of obesity related education with some of Canada's top obesity researchers in a small town outside of Quebec City. Many of my friends and colleagues (Peter included) have attended the bootcamp in the past, and all have told me that its one of their best grad school experiences. Everyday there are lectures from obesity experts like Arya Sharma, JP Depres, and Angelo Tremblay, as well as "journal club" presentations from other students. Below I've embedded a copy of my presentation, which is on the paper "Fitness of Canadian Adults: Results from the 2007-2009 Canadian Health Measures Survey". I discussed the paper in a post a few months ago, but I thought I'd include the full presentation here since it has quite a bit more detail than the original post. I also wanted an excuse to try out SlideShare, which allows you to embed power point (with audio) into a blog post. So feedback would be greatly appreciated.
To follow the goings-on at the bootcamp itself, be sure to check out Arya Sharma's blog, where he will almost certainly be providing updates as the week progresses.
Enjoy the presentation!
Shields, M, Tremblay, MS, Laviolette, M, Craig, CL, Janssen, I, & Connor Gorber, S (2010). Fitness of Canadian adults: Results from the 2007-2009 Canadian
Health Measures Survey Health Reports, 21 (1), 1-15... Read more »
Shields, M, Tremblay, MS, Laviolette, M, Craig, CL, Janssen, I, & Connor Gorber, S. (2010) Fitness of Canadian adults: Results from the 2007-2009 Canadian Health Measures Survey. Health Reports, 21(1), 1-15. info:/
Intravenous Immunoglobulin in Complex Regional Pain Syndrome Andreas Goebel on the results of his latest clinical trial .Just imagine the causes of some chronic pains are completely different from what you had thought. Complex Regional Pain Syndrome is a severe pain which persists after limb trauma. You are unlucky if you develop this nasty condition, [...]... Read more »
 Goebel A, Baranowski A, Maurer K, Ghiai A, McCabe C, & Ambler G. (2010) Intravenous immunoglobulin treatment of the complex regional pain syndrome: a randomized trial. Annals of internal medicine, 152(3), 152-8. PMID: 20124231
I’m pleased to host the very first edition of the MolBio Carnival, your monthly roundup of interesting posts in molecular biology from the science blogosphere. There has been a great response to this initiative and I had a great time reviewing submissions and writing this post.
You can read all about this Carnival here (submission guidelines, scope, etc), but right now, let’s get down to ... Read more »
Niethammer, P., Grabher, C., Look, A., & Mitchison, T. (2009) A tissue-scale gradient of hydrogen peroxide mediates rapid wound detection in zebrafish. Nature, 459(7249), 996-999. DOI: 10.1038/nature08119
Quyn, A., Appleton, P., Carey, F., Steele, R., Barker, N., Clevers, H., Ridgway, R., Sansom, O., & Näthke, I. (2010) Spindle Orientation Bias in Gut Epithelial Stem Cell Compartments Is Lost in Precancerous Tissue. Cell Stem Cell, 6(2), 175-181. DOI: 10.1016/j.stem.2009.12.007
van Bakel H, Nislow C, Blencowe BJ, & Hughes TR. (2010) Most "dark matter" transcripts are associated with known genes. PLoS biology, 8(5). PMID: 20502517
Altschuler, S., & Wu, L. (2010) Cellular Heterogeneity: Do Differences Make a Difference?. Cell, 141(4), 559-563. DOI: 10.1016/j.cell.2010.04.033
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