MedicalResearch.com Interview with: Dr Sandra A. Wilks PhD Senior Research Fellow IfLS Knowledge Mobilisation Fellow in Healthcare Technologies Faculty of Natural and Environmental Science & Faculty of Health Sciences Centre for Biological Sciences, University of Southampton, Southampton, UK Medical Research: … Continue reading →
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Dr Sandra A. Wilks PhD. (2015) Complex Bacterial Biofilms Can Rapidly Obstruct Catheters. MedicalResearch.com. info:/
© Elena E. GiorgiI'm excited to be blogging about science again, albeit only occasionally. Those of you who have been following the blog from its very beginnings, back in 2011, know that I've always been fascinated with epigenetics, one of my favorite topics to discuss. So much so that I've managed to include it into the plot of my detective thriller Chimeras. The thrills in the book are fictional, but the science is all real.I was talking with my colleague Karissa Sanbonmatsu last week, who's been working on RNA and epigenetics since the early 2000s, and she was telling me how the field is still riddled with controversy. There's more and more evidence that environmentally triggered traits like stress, fat storage, and the propensity to acquire certain diseases can be passed on from one generation to the next via activated epigenetic marks, yet many scientists still refuse to believe it. How can things that are not encoded in the DNA be transmitted to the new generation? Germ cells carry epigenetic signatures that have been shaped by the environmental exposures from the parents, but how are these signatures communicated across generations? A little background.Our cells carry long bits of RNA that sense molecules and their changes in concentrations. Depending on the environmental exposures they find, they recruit epigenetic factors that then activate certain genes and/or deactivate others. This happens by inducing changes in the chromatin, the big yarn of DNA that sits inside the nucleus. When a gene needs to be activated, the big yarn moves until that particular gene is exposed on the surface and then translated into proteins. On the other hand, to silence the gene, the chromosome move around again and "hide" the gene deep inside the chromatin. RNA molecule act as regulators of these mechanisms, "deciding" which genes to activate and which ones to silence.A recent study published on PNAS sheds new light on the mechanisms that communicate epigenetic marks from the germ line to the offspring, proving that epigenetic signatures acquired by the parents can be passed onto the offspring. Rodgers et al., from the University of Pennsylvania, used a mouse model to establish the following points:First, they exposed male mice to chronic stress prior to breeding, and then observed reprogramming of certain genes in the hypothalamus of the offspring;Second, they looked at the sperm of the stressed mice and compared it to the sperm of non-stressed mice; they found a change in content of micro RNAs (miRNAs), and 9 miRNA molecules in particular were found in much higher concentrations in the stressed mice's sperm . Rodger et al. hypothesized that the 9 miRNAs were responsible for the genetic reprogramming induced by the chronic stress exposure and passed on through the paternal line.To prove it, they injected the 9 miRNAs into single-cell zygotes that were then implanted into normal female mice, raised with no stress exposure, and then examined to see if they presented the same stress phenotype observed in the stressed male's offspring. Indeed, expression of the target genes in the hypothalamus was reduced in the mice that originated from these zygotes, and the expression patterns observed in these mice recapitulated what they had observed in the offspring of the stressed mice. This study, published in PNAS last october , is a milestone in epigenetics, as it finally shows a molecular mechanism that allows genetic reprogramming in the parent to be transmitted to the offspring. As a final thought, I want to toss in my two cents on the debated rise of autism spectrum and ADHD disorders currently observed in the Western world. Of course, there's the caveat that the diagnostic methods have changed drastically in the past few decades. Still, the increase seems real and the sad truth is that there's probably more than one cause, and the causes lie not just in what the child has been exposed to, but, once you throw in epigenetics into the pictures, his/her parents and grandparents as well. My parents for example grew up at the peak use of asbestos, DDT, and lead in paint. Yes, they survived and, knock on wood, they are quite healthy in fact. But I do fear that we will carry the consequences of those exposures for a few more generations. And who knows what the current exposure to the massive use of corn syrup and antibiotics will do to future generations. Food for thought.  Rodgers AB, Morgan CP, Bronson SL, Revello S, & Bale TL (2013). Paternal stress exposure alters sperm microRNA content and reprograms offspring HPA stress axis regulation. The Journal of neuroscience : the official journal of the Society for Neuroscience, 33 (21), 9003-12 PMID: 23699511 Rodgers, A., Morgan, C., Leu, N., & Bale, T. (2015). Transgenerational epigenetic programming via sperm microRNA recapitulates effects of paternal stress Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.1508347112... Read more »
Rodgers AB, Morgan CP, Bronson SL, Revello S, & Bale TL. (2013) Paternal stress exposure alters sperm microRNA content and reprograms offspring HPA stress axis regulation. The Journal of neuroscience : the official journal of the Society for Neuroscience, 33(21), 9003-12. PMID: 23699511
Rodgers, A., Morgan, C., Leu, N., & Bale, T. (2015) Transgenerational epigenetic programming via sperm microRNA recapitulates effects of paternal stress. Proceedings of the National Academy of Sciences, 201508347. DOI: 10.1073/pnas.1508347112
Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a rare genetic condition caused by mutations in fumarate hydratase (FH). HLRCC patients are at risk of developing type 2 papillary renal cell carcinoma (pRCC2) which typically has an early onset with high metastatic potential. Existing targeted treatments have very limited response rates in both primary and metastatic pRCC2 tumours. Developing more effective treatments relies on preclinical models such as the new FH-deficient cell line derived by Perrier-Trudova et al., (2015).... Read more »
Perrier-Trudova V, Huimin BW, Kongpetch S, Huang D, Ong P, LE Formal A, Poon SL, Siew EY, Myint SS, Gad S.... (2015) Fumarate Hydratase-deficient Cell Line NCCFH1 as a New In Vitro Model of Hereditary Papillary Renal Cell Carcinoma Type 2. Anticancer research, 35(12), 6639-53. PMID: 26637880
The paper by Bradley Brown & Theodore Rais  (open-access available here) lies at the centre of today's brief musings and yet another interesting case report with autism in mind.Detailing the experiences of a 15-year old boy diagnosed with an autism spectrum disorder (ASD) and "neurocardiogenic syncope" (fainting characterised by reduced blood circulation to the brain), authors report on how his admission to hospital for self-injury "secondary to depression" came to reveal some potentially important clinical issues.In particular, the authors detail how some of the stressors potentially pertinent to the reasons for his admission seemed to include an awareness of his mother's "declining health due to a mitochondrial disease" and "his own concerns about his future health, given his previous “spells” (syncopal episodes secondary to his diagnosis of neurocardiogenic syncope)."The mother of the young adult did indeed also suffer from neurocardiogenic syncope alongside various other issues including Ehlers-Danlos syndrome and "a Budd-Chiari type 2 malformation that required surgical decompression." Alongside other symptoms, her profile was considered "typical for a patient with a mitochondrial disease."There is a degree of disconnect in the article by Brown & Rais insofar as how mitochondrial issues and autism are discussed quite a bit but as far as I can see, no specific assessment for such issues was carried out with the young man concerned. Rather, the implication is that a family history of mitochondrial issues should trigger similar assessment in those with autism save viewing such disorders as a zebra - "an obscure diagnosis that is made when a more common explanation is more likely."I've covered some of the literature on mitochondrial issues occurring alongside autism on this blog before (see here and see here for example). Alongside more recent research talking about some fairly non-invasive ways of assessing things like "respiratory complex (RC) activities" in relation to autism  I'd be minded to suggest that quite a few more resources might be ploughed into this area to identify just how people on the autism spectrum might benefit from 'treatment' of said issues bearing in mind what intervention options might be available . Lessons could no doubt be learned from other conditions presenting with a similar profile (at least in some cases).One other detail also caught my eye in terms of how maternal Ehlers-Danlos syndrome (EDS) is discussed by Brown & Rais. I'm particularly interested in the idea that disorders of connective tissue might be something to look at in the context of [some] autism (see here). I say this on the basis of joint mobility issues and gait being something of potential interest to cases of autism and how issues with collagen for example, are more likely present when something like vitamin C deficiency is observed (as it has been in some cases of autism).Physician and researchers alike perhaps should have a high index of suspicion for mitochondrial disease involvement in at least some cases of autism. And just in case this needs reiterating ...Music: Major Lazer & DJ Snake - Lean On (feat. MØ).---------- Brown BD. & Rais T. Autism in the Son of a Woman with Mitochondrial Myopathy and Dysautonomia: A Case Report. Innov Clin Neurosci. 2015 Sep-Oct;12(9-10):29-32. Goldenthal MJ. et al. Mitochondrial enzyme dysfunction in autism spectrum disorders; a novel biomarker revealed from buccal swab analysis. Biomark Med. 2015 Oct;9(10):957-65. Parikh S. et al. A modern approach to the treatment of mitochondrial disease. Curr Treat Options Neurol. 2009 Nov;11(6):414-30. Marin SE. & Saneto RP. Neuropsychiatric Features in Primary Mitochondrial Disease. Neurol Clin. 2016 Feb;34(1):247-94.----------Brown BD, & Rais T (2015). Autism in the Son of a Woman with Mitochondrial Myopathy and Dysautonomia: A Case Report. Innovations in clinical neuroscience, 12 (9-10), 29-32 PMID: 26634179... Read more »
Brown BD, & Rais T. (2015) Autism in the Son of a Woman with Mitochondrial Myopathy and Dysautonomia: A Case Report. Innovations in clinical neuroscience, 12(9-10), 29-32. PMID: 26634179
Scientists showed that they could alter brain activity of rats and either wake them up or put them in an unconscious state by changing the firing rates of neurons in the central thalamus, a region known to regulate arousal. The study was partially funded by the National Institutes of Health.... Read more »
Jia Liu, Hyun Joo Lee, Andrew J Weitz, Zhongnan Fang, Peter Lin, ManKin Choy, Robert Fisher, Vadim Pinskiy, Alexander Tolpygo, Partha Mitra, Nicholas Schiff, Jin Hyung Lee. (2015) Frequency-selective control of cortical and subcortical networks by central thalamus. eLife. DOI: http://dx.org/10.7554/eLife.09215#sthash.uNb2m4j3.dpuf
MedicalResearch.com Interview with: Geert W. Schmid-Schonbein, Ph.D. Distinguished Professor and Chairman Department of Bioengineering Adjunct Professor in Medicine University of California San Diego Medical Research: What is the background for this study? What are the main findings? Dr. Schmid-Schonbein: Most … Continue reading →
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Geert W. Schmid-Schonbein, Ph.D. (2015) Children Can Maintain Healthy Weight By Eating Slowly. MedicalResearch.com. info:/
MedicalResearch.com Interview with: Dr Gerry McCann MD Reader in Cardiovascular Imaging Department of Cardiovascular Sciences University of Leicester Leicester UK Medical Research: What is the background for this study? Dr. McCann: Cardiologists increasingly treat patients who suffer a large heart … Continue reading →
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Dr Gerry McCann MD. (2015) Stenting More Than One Coronary Vessel After Heart Attack Doesn't Add to Damage. MedicalResearch.com. info:/
MedicalResearch.com Interview with: Dr. Jochen Reinöhl Consultant and Head of the ISAH team (intervention for structural and congenital cardiovascular diseases) Department of Cardiology and Angiology I (Medical Director: Prof. Dr. Christoph Bode) University Heart Center Freiburg ∙ Bad Krozingen Medical Research: … Continue reading →
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Dr. Jochen Reinöhl. (2015) Mortality Decreasing From Both Aortic Valve Replacement and TAVR Procedure. MedicalResearch.com. info:/
MedicalResearch.com Interview with: Dr. Li Ding PhD Director, Medical Genomics group McDonnell Genome Institute Department of Medicine Washington University in St. Louis St. Louis, Missouri Medical Research: What is the background for this study? What are the main findings? Dr. … Continue reading →
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Dr. Li Ding PhD. (2015) New Tools Detect Many More Potentially Treatable Cancer Mutations. Eminent Domains Inc. info:/
Of the many important lessons that I've learned down the years of research, perhaps the most important one is that grand over-arching diagnostic labels rarely give a true reflection of the massive heterogeneity that they include in terms of clinical presentation and onwards, discussions about the possibility of differing aetiologies and pathologies. Symptoms, conditions, and diseases are compartmentalised for convenience but that does not mean that everyone shares the same experiences of that label nor arrives at it in exactly the same way.This lesson is no better illustrated than in the paper by Nicholas Higgins and colleagues  (open-access here) who report on how "a 49-year-old woman with a long and debilitating history of chronic fatigue syndrome" was further inspected for "intracranial pressure because of headache, then diagnosed with borderline idiopathic intracranial hypertension after lumbar puncture and cerebrospinal fluid drainage." Further: "Stenting of both transverse sinuses brought about a life-changing remission of symptoms with no regression in 2 years of follow-up."The authors report on how this patient had a 20-year history of fatigue that developed "after a viral illness" (there was evidence of "previous exposure to Epstein-Barr virus") and how after 3 months of "being unable to keep awake" fatigue symptoms fluctuated over several years. When presented to the authors, the woman "complained of being tired all the time, near constant headache, fogginess in the head, an inability to concentrate, muscle and joint aches, shortness of breath, and a sore throat." I had to cast a wry smile at the sentence: "She refused cognitive behavioral therapy" in light of some current goings-on with this and other 'interventions' being discussed in chronic fatigue syndrome (CFS) circles.Kudos to the authors however and their protocol being developed whereby patients who present with chronic fatigue and headaches are "offered investigations to exclude raised intracranial pressure" as a source of their symptoms based on other studies reported by the research team . Indeed, after some further investigations she showed symptoms "consistent with raised intracranial pressure." Treatment followed (although I wouldn't even begin to pretend that I understood it all) and that 'life-changing remission of symptoms' began and continued up to 2 years post diagnosis and intervention.Not surprisingly the authors conclude that: "The unequivocally favorable outcome suggests that this is an area ripe for further study" based on this case report. Yes, one has to be careful not to generalise too much on the basis of the experiences of one patient, but given the current lack of effective interventions for something like CFS (or myalgic encephalomyelitis, ME), I'd suggest that there should be a degree of urgency to undertake additional studies in this area.In addition to providing further evidence to suggest that we need to do more about looking at subgroups when it comes to CFS/ME (see here), I'd also be minded to suggest that this research area might also show more than a passing connection to a few other aspects covered on this blog. So for example, the idea that visual perception might be 'altered' as a symptom in at least some CFS/ME (see here) becomes potentially relevant in light of the link between idiopathic intracranial hypertension (IIH) and vision. The reports that "fogginess in the head" might also be part of the suite of cognitive effects that follow ME/CFS and are to some degree resolved by treatment of IIH in this patient group is also something that I pay quite a bit of attention to (see here). I'll finally direct you to a couple of posts I wrote about some research on Epstein-Barr virus (EBV) and some rather unusual findings (see here and see here) potentially relevant to some cases of CFS/ME with the requirement for quite a bit more research to do as part of a more multi-pronged intervention approach.So, who is going to take up the research gauntlet and put further scientific flesh on the bones pertinent to a possible connection between IIH and [some] cases of CFS?Music: Elle King - Ex's & Oh's.---------- Higgins N. et al. Borderline Intracranial Hypertension Manifesting as Chronic Fatigue Syndrome Treated by Venous Sinus Stenting. J Neurol Surg Rep. 2015 Nov;76(2):e244-e247. Higgins N. et al. Looking for idiopathic intracranial hypertension in patients with chronic fatigue syndrome. Journal of Observational Pain Medicine. 2013; 1: 28-35.----------Higgins N, Pickard J, & Lever A (2015). Borderline Intracranial Hypertension Manifesting as Chronic Fatigue Syndrome Treated by Venous Sinus Stenting. Journal of neurological surgery reports, 76 (2) PMID: 26623235... Read more »
Higgins N, Pickard J, & Lever A. (2015) Borderline Intracranial Hypertension Manifesting as Chronic Fatigue Syndrome Treated by Venous Sinus Stenting. Journal of neurological surgery reports, 76(2). PMID: 26623235
MedicalResearch.com Interview Questions Carlos del Rio, MD Chair, HIV Medicine Association Department of Medicine Hubert Professor and Chair of the Department of Global Health at the Rollins School of Public Health Professor of Medicine in the Division of Infectious Diseases … Continue reading →
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Carlos del Rio, MD. (2015) Medical Societies Discuss Dramatic Increase In Prices For Older Medications For Infectious Diseases. MedicalResearch.com. info:/
MedicalResearch.com Interview with: Luke V. Selby, MD Research Fellow, Department of Surgery Vivian E. Strong, MD FACS Associate Attending Surgeon, Department of Surgery Memorial Sloan Kettering Cancer Center Medical Research: What is the background for this study? What are the … Continue reading →
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Vivian E. Strong, MD FACS. (2015) Pre-op Venous Thromboembolism Prophylaxis Safely Reduced Clots and Pulmonary Emboli. MedicalResearch.com. info:/
MedicalResearch.com Interview with: Dr. Peter C. Minneci, M.D., MHSc Center for Innovation in Pediatric Practice Assistant Professor, Pediatric Surgery The Ohio State’s Wexner Medical Center Medical Research: What is the background for this study? What are the main findings? Dr. Minneci: … Continue reading →
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Dr. Peter C. Minneci, M.D., MHSc. (2015) Some Patients With Appendicitis Can Be Managed Without Surgery. MedicalResearch.com. info:/
MedicalResearch.com Interview with: Dr. Chris J. Hawkey, DM, FRCP, FMedSci. University of Nottingham and Nottingham University Hospital England Medical Research: What is the background for this study? Dr. Hawkey: ASTIC (The Autologous Stem Cell Transplantation International Crohn’s Disease) systematically investigated … Continue reading →
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Dr. Chris J. Hawkey. (2015) Stem Cell Therapy May Be Most Effective, and Most Toxic, Treatment For Crohn's Disease. MedicalResearch.com. info:/
MedicalResearch.com Interview with: Roger Stupp, MD Professor & Chairman Department of Oncology & Cancer Center University of Zurich & University Hospital Zurich (USZ) Zürich / Switzerland Medical Research: What is the background for this study? Dr. Stupp: Tumor Treating Fields … Continue reading →
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Roger Stupp, MD. (2015) Glioblastoma TTF : Alternating Electrical Fields Plus Chemo Extends Survival. MedicalResearch.com. info:/
Gold is not considered a dietary micronutrient, and is the one of the most inert metals. But this is not to say it has no role in living systems; in fact, this metal is a veritable gold mine of biology. New research has led to a greater understanding of how gold can down-regulate inflammatory processes and gold complexes are being used in cancer and infectious disease treatments.... Read more »
Nieminen, R., Korhonen, R., Moilanen, T., Clark, A., & Moilanen, E. (2010) Aurothiomalate inhibits cyclooxygenase 2, matrix metalloproteinase 3, and interleukin-6 expression in chondrocytes by increasing MAPK phosphatase 1 expression and decreasing p38 phosphorylation: MAPK phosphatase 1 as a novel target for antirheumatic drugs. Arthritis , 62(6), 1650-1659. DOI: 10.1002/art.27409
Conservative treatment with early range of motion is equivalent to surgical treatments of Achilles tendon ruptures.... Read more »
Zhang, H., Tang, H., He, Q., Wei, Q., Tong, D., Wang, C., Wu, D., Wang, G., Zhang, X., Ding, W.... (2015) Surgical Versus Conservative Intervention for Acute Achilles Tendon Rupture. Medicine, 94(45). DOI: 10.1097/MD.0000000000001951
Appreciating that the subject matter of today's post might not necessarily align with the season that is upon us, I wanted to bring to your attention the paper by Michael Westerlund and colleagues  (open-access) and some rather disturbing discussions related to a young man who "decided to hang himself and to display the suicidal act" on an internet forum.Published in the British Journal of Psychiatry, the paper set about examining how "participants on an internet forum act and react faced with suicidal communication and while witnessing the suicidal act." This was done via "a qualitative investigation of the messages that were posted before the TS's [thread starter] suicide and a combined qualitative–quantitative analysis of the messages posted during and after the suicide." A total of 30 posts before the suicide and 608 posts during and after the suicide were examined.Several themes are discussed in the paper in terms of the authenticity of the discussions, attitudes towards the suicide, opportunities for prevention and: "Responsibility for the TS's suicide." There are some, quite frankly, awful comments discussed in this paper that I won't be repeating on this blog. Importantly however, the authors highlight a few lessons that might be learned from such events based on the fact that "the internet has developed as the main channel for suicide communication" and the possibility that lives could be potentially saved with the right tools for identifying and responding to "individuals who communicate suicide intentions on different forums on the internet." As per another quote from the paper: "the internet can be a facilitator of the suicidal process, but it can also be a venue where opportunities for prevention of suicide loom large."Although not the main topic of this blog, suicide is something that has cropped up before (see here and see here for example). It is a complicated issue to talk about given that not only are there multiple pathways that bring someone to the position of contemplating taking their own life but also that attempted and completed acts can and do profoundly affect the people around the person in question.The idea that the internet can be a source of positive information when it comes to reducing the risk of suicide is evident in the peer-reviewed domain . Sueki & Ito  discussed the idea of on-line gatekeeping to prevent suicide "by placing advertisements on web search pages to promote consultation service use among Internet users with suicidal ideation." Social media has also been discussed as a good tool to deliver "a range of suicide prevention activities" . The trick, it seems, is getting the relevant information and expertise to those who are currently vulnerable whilst at the same time avoiding issues like possible contagion. I might add that whilst the internet might have a significant role to play in suicide, it does not and should not represent the sum total of discussions about suicide and any potentially related issues (see here).Bearing in mind the caveats of this blog about not giving medical or clinical advice, I did wonder if it might be useful to link to something like this page containing quite a few points and further links if and when discussions about suicide are raised. For anyone here in Blighty in need, details for the Samaritans can also be found here.A song to close from Kate Bush and Peter Gabriel.---------- Westerlund M. et al. Case study of posts before and after a suicide on a Swedish internet forum. Br J Psychiatry. 2015; 207: 476-482. Robert A. et al. Internet use and suicidal behaviors: internet as a threat or opportunity? Telemed J E Health. 2015 Apr;21(4):306-11. Sueki H. & Ito J. Suicide Prevention Through Online Gatekeeping Using Search Advertising Techniques. Crisis. 2015 Jul;36(4):267-73. Robinson J. et al. Social media and suicide prevention: findings from a stakeholder survey. Shanghai Arch Psychiatry. 2015 Feb 25;27(1):27-35.----------Westerlund, M., Hadlaczky, G., & Wasserman, D. (2015). Case study of posts before and after a suicide on a Swedish internet forum The British Journal of Psychiatry, 207 (6), 476-482 DOI: 10.1192/bjp.bp.114.154484... Read more »
Westerlund, M., Hadlaczky, G., & Wasserman, D. (2015) Case study of posts before and after a suicide on a Swedish internet forum. The British Journal of Psychiatry, 207(6), 476-482. DOI: 10.1192/bjp.bp.114.154484
MedicalResearch.com Interview with: Meghan Jeffres, PharmD Assistant Professor | Dept of Clinical Pharmacy Skaggs School of Pharmacy and Pharmaceutical Science University of Colorado Anschutz Medical Campus Aurora, CO 80045 Medical Research: What is the background for this study? What are … Continue reading →
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Meghan Jeffres, PharmD. (2015) Do All Beta Lactam Antibiotics Need To Be Avoided In Patient With Reported Allergy?. MedicalResearch.com. info:/
MedicalResearch.com Interview with: Camron D. Bryant, Ph.D. Assistant Professor Laboratory of Addiction Genetics Department of Pharmacology and Experimental Therapeutics & Psychiatry Boston University School of Medicine Boston, MA 02118 Medical Research: What is the background for this study? What are … Continue reading →
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Camron D. Bryant, Ph.D. (2015) Gene Linked To Methamphetamine Addiction Identified. MedicalResearch.com. info:/
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