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  • March 12, 2014
  • 06:25 AM

Auckland researchers discover new cell with stem cell properties in human skin

by beredim in Stem Cells Freak

Professor Rod DunbarCreditAuckland researchers have discovered new cells with stem cell properties in human skin, opening the door to a range of new treatments for skin diseases and unhealed wounds.The scientists, Professor Rod Dunbar, Dr Vaughan Feisst, Dr Anna Brooks and Jenni Chen, are members of the Maurice Wilkins Centre for Molecular Biodiscovery, and the research was carried out in the School of Biological Sciences at the University of Auckland.They identified mesenchymal progenitor cells (MPCs) in the dermis, the middle layer of skin, and discovered that these could turn themselves into fat cells. This signals that they can probably become other types of cells that repair and regenerate tissue, like similar stem cells found in fat and bone marrow."Nobody has identified these cells before, so this opens the door to advances in both skin healing and skin diseases. Every time you find new cells with stem cell-like properties, you know you’re onto something that could have major implicationsIt’s a really exciting discovery. We try to avoid getting too carried away about our results because we’re constitutionally cautious - but this discovery is a pretty fundamental finding." said Professor Dunbar.Read More... Read more »

  • March 12, 2014
  • 05:57 AM

Brain cell regeneration may alleviate Alzheimer's symptoms

by beredim in Stem Cells Freak

Alzheimer's disease is the most widespread degenerative neurological disorder in the world. Over five million Americans live with it, and one in three senior citizens will die with the disease or a similar form of dementia. While memory loss is a common symptom of Alzheimer's, other behavioral manifestations — depression, loss of inhibition, delusions, agitation, anxiety, and aggression — can be even more challenging for victims and their families to live with.Today, Professor Daniel Offen and Dr. Adi Shruster from the Tel Aviv University's Sackler School of Medicine announced that they have discovered that by reestablishing a population of new cells in the part of the brain associated with behaviour, some symptoms of Alzheimer's disease significantly decreased or were reversed altogether.Read More... Read more »

  • March 12, 2014
  • 05:46 AM

Optimum-time, Optimum-space, Algorithms for k-mer Analysis of Whole Genome Sequences

by JBCG in JScholar Publishers

The sizable amount of data generated by high throughput cell biology is increasing the demand on traditional computational tools in bioinformatics to handle large input datasets. Large sequence data sets create intractable search spaces that are beyond the scope of many conventional algorithms. One way to address this problem is to transform large sequence data sets to the constituent parts that characterize the features of interest (e.g. transcription factor binding sites, miRNA sites, etc.) of the problem. ... Read more »

Sumedha S. Gunewardena. (2014) Optimum-time, Optimum-space, Algorithms for k-mer Analysis of Whole Genome Sequences. JOURNAL OF BIOINFORMATICS AND COMPARATIVE GENOMICS, 1(1), 1-12. info:/JBCG 1: 101

  • March 12, 2014
  • 05:46 AM

Pain predicting sleep problems in autism

by Paul Whiteley in Questioning Answers

Not so long ago I talked about the paper from Smith and colleagues [1] on autism and obstacles to medical [comorbidity] diagnosis and treatment (see here). Aside from the need for professionals to overcome the issue of "a lack of expressive speech" as an impediment to undertaking a thorough medical work-up when presented with a person with autism, an important theme of that paper was the requirement to see beyond autism as being the 'reason' for every single behaviour or issue that affects a person. It's not.Indeed, the paper by Megan Tudor and colleagues [2] which makes up the material for today's post, adds to that message with their report on pain as being a predictor of sleep problems for some children/young adults with autism. Once again, my thanks go to Natasa for providing the full-text version of the paper for my blogging consumption (yum!).The long-and-short of the Tudor paper was as follows:Take two issues which have cropped up in the autism research literature more than once - sleeping issues and pain - and aim to examine "pain-related behaviors as a predictor of sleep problems in youth with parent-reported ASD using standardized parent-report measurement of both variables".Mothers of a sample of 62 children/young adults drawn from a larger study [3] [note to authors, your date is wrong for this reference] were questioned using several measures including the NCCPC-R (see here) and the CSHQ [4] (open-access) looking at pain and sleep respectively. I should also note that questionnaires were completed on-line and participants received a financial incentive to complete [a large chunk of] questionnaires.Results: parent-reported participant pain levels according to NCCPC-R scores "was high compared to normative information for this measure". Sleep issues were similarly elevated in the sample, particularly parasomnias. The discussion notes that pain scores were gathered across a slightly different timespan to the normative data (1 week retrospective report for the study vs. 2-hour observation period for the normative data) so one perhaps need to be a little cautious about this.Some regression analysis for scores on the two instruments revealed some potentially important results. So higher pain scores "predicted higher scores on CSHQ Total Sleep Disturbance" although with an R-squared value of 0.22 this is not necessarily a straight-forward connection. Specific sleep problems including sleep duration, parasomnias and sleep-disorder breathing were also reported as being accompanied by a previous weeks pain-related behaviours and may well have had some very individual behaviours linked to them e.g. "problems with sleep duration were predicted by social communication of pain, such as comfort-seeking and being difficult to pacify" and "Parasomnias were predicted by facial communication of pain, such as grimacing or brow furrowing".The authors conclude that whilst there is more to do in this area of investigation (including the important use of control groups) their results should serve as a marker for healthcare professionals when dealing with children with autism who also present with sleeping issues. To quote: "how pain and sleep problems relate to one another and may affect children's daytime functioning...". This may have some far-reaching effects in terms of how sleep issues are traditionally managed when it comes to autism and other developmental disorders.Going back to the my starting paragraph about autism not being to blame for every single behavioural manifestation noted among cases, I can't help but ask the question: why were parent-reported indicators of pain-related behaviours seemingly elevated in this sample? As far as I know - and I am just an outsider looking in - autism is not necessarily defined as a painful condition. Indeed, even the authors point to the possibility of a "high threshold for pain" [5] described in the DSM-IV TR diagnostic schedule for autism. Certainly if it was shown that autism 'is a painful condition', it would perhaps change some of the dialogue noted in Dr Insel's Four Kingdoms of Autism.I do have a few theories about this notion of pain and autism however so bear with me. Tudor and colleagues allude to one of them insofar as discussions about "ongoing mild digestive discomfort" and "severe inflammatory bowel disease" with both issues having cropped up before on this blog previously. Thinking back to the paper by Kushak and colleagues [6] discussed in this post on lactase enzymes and autism, there is the suggestion that lactose intolerance (related to the sugar found in milk and dairy produce) "may contribute to abdominal discomfort, pain and observed aberrant behavior". With autism and inflammatory bowel disease in mind, the Walker paper [7] published a while back (discussed in this post) springs to mind.Of course, I don't claim that every expression of pain noted in autism is necessarily one of being related to gastrointestinal (GI) function or dysfunction but one could certainly look to rule these issues out if one were being assiduous. As per some other potentially important issues, I might also refer you to a post I wrote a while back on self-injurious behaviour (see here) and other areas that one might look at when it comes to pain being potentially present in cases of autism.The final angle that is perhaps worthy of exploration has already been touched upon in the additional reference by Allely [5] (see here again) in relation to how one of the core aspects of autism might itself have the ability to induce pain: sensory sensitivity. I say core aspect but am referring to the recent inclusion of sensory issues into DSM-V noting that not everywhere in the world has made the shift over the DSM-5. So, things like over sensitivity to sound for example, I assume may register on someone's behaviour and manner, just as issues with the visual modality might also have the ability to induce something like pain (see here). Indeed, migraine might be something else to look at with pain and autism in mind [8] and not just with the head in mind either [9]. As per previous statements, it all depends on how far one is willing to look into the issue of pain and the potential reasons for its presence...----------[1] Smith MD. et al. Autism and Obstacles to Medical Diagnosis and Treatment. Focus Autism Other Dev Disabl 2012; 27: 189-195.[2] Tudor ME. et al. Pain as a predictor of sleep problems in youth with autism spectrum disorders. Autism. 2014 Feb 4. [Epub ahead of print][3] Walsh CE. et al. Predictors of parent stress in a sample of children with ASD: Pain, problem behavior, and parental coping. Res Autism Spec Disorder. 2013; 7: 256-264.[4] Owens JA. et al. The Children's Sleep Habits Questionnaire (CSHQ): psychometric properties of a survey instrument for school-aged childre... Read more »

Tudor ME, Walsh CE, Mulder EC, & Lerner MD. (2014) Pain as a predictor of sleep problems in youth with autism spectrum disorders. Autism : the international journal of research and practice. PMID: 24497628  

  • March 12, 2014
  • 12:05 AM

Knee Injuries Sustained Prior to Collegiate Athletics may be a Factor in Identifying Athletes at Risk for Reinjury

by Kyle Harris in Sports Medicine Research (SMR): In the Lab & In the Field

College athletes who had orthopaedic surgery in high school miss more days of collegiate competition than athletes without a history of orthopaedic surgery. More specifically, athletes with a history of knee surgery were more likely to sustain another knee injury or require surgery while in college.... Read more »

  • March 11, 2014
  • 11:55 PM

Who Needs a 12 Lead ECG?

by Rogue Medic in Rogue Medic

Do we do too many 12 lead ECGs on patients who do not have chest pain?

This is something that some people worry about.

Save the electrodes!

Those poor little electrodes are being abused!

Are electrodes being abused?... Read more »

  • March 11, 2014
  • 07:33 PM

Training Characteristics Related to Running Related Injuries

by Craig Payne in Running Research Junkie

Training Characteristics Related to Running Related Injuries... Read more »

  • March 11, 2014
  • 11:33 AM

Variant Prioritization in Rare Mendelian Disorders

by Daniel Koboldt in Massgenomics

Few areas of biomedical research have benefited more from next-gen sequencing than studies of rare inherited diseases. Rapid, inexpensive exome sequencing in individuals with rare, presumably-monogenic diseases has been hugely successful over the past few years. There’s been a lot of discussion in the NGS community about the analysis burden of the large-scale whole-genome sequencing […]... Read more »

Koboldt DC, Larson DE, Sullivan LS, Bowne SJ, Steinberg KM, Churchill JD, Buhr AC, Nutter N, Pierce EA, Blanton SH.... (2014) Exome-Based Mapping and Variant Prioritization for Inherited Mendelian Disorders. American journal of human genetics. PMID: 24560519  

  • March 11, 2014
  • 11:09 AM

Depression-related Sleep Abnormalities Vary By Age

by William Yates, M.D. in Brain Posts

This month I will be focusing on sleep and the brain. The importance of sleep to normal and abnormal brain functioning is receiving increased research attention.A variety of sleep abnormalities have been described in major depression and bipolar affective disorder. Depression has been linked to delayed sleep onset, reduced time to first rapid eye movement (REM) period, reduced sleep efficiency and disruption of the circadian rhythm of sleep.Sleep physiology also varies throughout the lifespan. Puberty produces a delay in the sleep-wake cycle while older age is associated with a earlier sleep-wake cycle and reduced total sleep time.Robillard and colleagues recently published a study designed to tease out the effects of depression on sleep across the life cycle. The key elements of the design of their study included the following components:Subjects: 238 treatment-seeking individuals with a lifetime history of mood disorder ranging in age from 12 to 90 years of ageProcedures: Subjects wore an activity watch (actigraphy) for up to 22 days and completed sleep diaries. Additionally, subjects completed the Hamilton Depression Rating Scale a measure of current severity of depression symptomsOutcome variables: sleep onset time, sleep offset time, total time in bed, total sleep time, time awake after sleep onset and sleep efficiency (time asleep divided by time in bed). Additionally, five circadian rhythm parameters were estimated from the dataData analysis: Outcome variables were examined using two-way ANOVA with depression severity and age category as covariatesThe study found significant differences in the depression-related sleep parameters by age and depression severity:Younger age effects: Depression severity in younger adolescents and younger adults was associated with later sleep onset and offset, longer time in bed, longer time awake after sleep onset and lower sleep efficiencyOlder age effects: Depression severity in older adults was associated with reduced circadian rhythm strengthEffects found in all age groups: Depression severity was associated with disruption of sleep consolidationThe authors note in their discussion that sleep offset (later morning awakening) is associated with age and depression severity and "may be especially sensitive to the additive effects of age and depression". This study is limited to use of actigraphy data and did not include more accurate polysomnography (sleep studies). Additionally, the study did not include a non-depressed control sample. Finally, there is limited description of psychotropic drug use in the sample a potentially confounding factor. Nevertheless, this is an important study that helps tease out the effects of depression compared to the effects of age on sleep. Depression appears to adversely effect sleep function across the life cycle. Sleep function can be a valuable tool for assessment and monitoring treatment in mood disorders.Readers with more interest in this research can access the free full-text article by clicking on the link citation link below.Photo of a red shouldered hawk is from the author's files.Follow the author on Twitter @WRY999Robillard, R., Naismith, S., Smith, K., Rogers, N., White, D., Terpening, Z., Ip, T., Hermens, D., Whitwell, B., Scott, E., & Hickie, I. (2014). Sleep-Wake Cycle in Young and Older Persons with a Lifetime History of Mood Disorders PLoS ONE, 9 (2) DOI: 10.1371/journal.pone.0087763... Read more »

Robillard, R., Naismith, S., Smith, K., Rogers, N., White, D., Terpening, Z., Ip, T., Hermens, D., Whitwell, B., Scott, E.... (2014) Sleep-Wake Cycle in Young and Older Persons with a Lifetime History of Mood Disorders. PLoS ONE, 9(2). DOI: 10.1371/journal.pone.0087763  

  • March 11, 2014
  • 06:15 AM

FDA-approved anti-cancer drugs may induce stem cell tumors

by beredim in Stem Cells Freak

Michele MarksteinUsing a new approach to systematically test chemotherapy drugs in an unusual animal model, a research team led by University of Massachusetts Amherst molecular biologist Michele Markstein, with Norbert Perrimon at Harvard Medical School, report that several have a serious side effect: Inducing hyper proliferation in stem cells that could lead to tumor recurrence.Markstein says, “We discovered that several chemotherapeutics that stop fast growing tumors have the opposite effect on stem cells in the same animal, causing them to divide too rapidly. This was a surprise, because it showed that the same drug could have opposite actions on cells in the same animal: Suppressing tumor growth on one cell population while initiating growth in another. Not only is the finding of clinical interest, but with this study we used an emerging new non-traditional tool for assessing drugs using stem cells in the fruit fly gut.” “We did these experiments in the fly because Drosophila stem cells, in the intestine, are very much like the stem cells in our intestine, and it’s a lot easier to do experiments in flies than humans or even mice.” she added.Read More... Read more »

Markstein, M., Dettorre, S., Cho, J., Neumuller, R., Craig-Muller, S., & Perrimon, N. (2014) Systematic screen of chemotherapeutics in Drosophila stem cell tumors. Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.1401160111  

  • March 10, 2014
  • 03:39 PM

Stem cell study opens door to undiscovered world of biology

by beredim in Stem Cells Freak

Dr. Robert A.J. Signer (left) and Dr. Sean MorrisonImage courtesy of UT Southwestern Medical CenterFor the first time, researchers have shown that an essential biological process known as protein synthesis can be studied in adult stem cells – something scientists have long struggled to accomplish. The groundbreaking findings from the Children’s Medical Center Research Institute at UT Southwestern (CRI) also demonstrate that the precise amount of protein produced by blood-forming stem cells is crucial to their function.The discovery, published online yesterday in Nature, measures protein production, a process known as translation, and shows that protein synthesis is not only fundamental to how stem cells are regulated, but also is critical to their regenerative potential.Read More... Read more »

  • March 10, 2014
  • 03:10 PM

Establishing standards for good stem cells

by beredim in Stem Cells Freak

 Kevin Kit ParkerAfter more than a decade of advances in stem cell research, almost anyone with a basic understanding of life sciences understands that stem cells are the basic form of cell from which all the other specialized cells, and eventually organs and body parts, derive.But what makes a "good" stem cell, one that can reliably be used in drug development, and for disease study? Researchers have made enormous strides in understanding the process of cellular reprogramming, and how and why stem cells commit to becoming various types of adult cells. But until now, there have been no standards, no criteria, by which to test these ubiquitous cells for their ability to faithfully adopt characteristics that make them suitable substitutes for patients for drug testing. And the need for such quality control standards becomes ever more critical as industry looks toward manufacturing products and treatments using stem cells.Read More... Read more »

Sheehy, S., Pasqualini, F., Grosberg, A., Park, S., Aratyn-Schaus, Y., & Parker, K. (2014) Quality Metrics for Stem Cell-Derived Cardiac Myocytes. Stem Cell Reports. DOI: 10.1016/j.stemcr.2014.01.015  

  • March 10, 2014
  • 02:55 PM

MYC proteins promote neural stem cell differentiation

by beredim in Stem Cells Freak

A new study by researchers at the Karolinska Institutet,Sweden suggests that the expression of the so called MYC gene is important and necessary for neurogenesis in the spinal cord. The findings appear in the journal EMBO Reports .The MYC gene encodes the protein with the same name, and has an important role in many cellular processes such as proliferation, metabolism, cell death and the potential of differentiation from immature stem cell s to different types of specialized cells . Importantly it is also one of the most frequently activated genes in human cancer.Read More... Read more »

  • March 10, 2014
  • 05:39 AM

Acute psychosis and urinary tract infection

by Paul Whiteley in Questioning Answers

Today I'm highlighting the paper by Krystle Graham and colleagues [1] which talked about a possible association between the presence of urinary tract infections (UTIs) in various types of psychosis. With my interest in all things biology-behaviour, remembering such posts as impulsivity and uric acid (see here), once again we have an example of how the two areas just might fit together.The bullfighter (deceased) @Manet @Wikipedia So, take several groups of adult participants who were admitted "for an acute episode of DSM-IV nonaffective psychosis..., affective psychosis... or alcohol detoxification" and compare with an asymptomatic control group. Analyse for the presence of laboratory-confirmed UTI and voilà, after controlling for potentially confounding variables "UTI was almost 11 times more likely in subjects with nonaffective psychosis than controls". That and the fact that in cases of affective psychosis (major depressive disorder with psychotic features) the odds ratio for a UTI was up at nearly 9x more likely.Coincidence I hear you cry. Well it certainly could be. But the data is strengthened by the fact that this is not the first time that this association has cropped us as per another paper by the same authors [2] covered by Dr Emily Deans over at Evolutionary Psychiatry. The fact that UTIs show more than a passing connection to behavioural and psychiatric features as per the evidence looking at delerium [3] for example should also be mentioned.As to the reason for the association, well to quote from the NHS Choices entry on the causes of UTI: "Most urinary tract infections (UTIs) are caused by bacteria that live in the digestive system". The process of how said bacteria get from bowel to erm, nether regions is slightly more complex and could be related to hygiene practices (remember: wipe from front to back after going to the toilet) or other behaviours. One can't exclude the possibility that where psychosis occurs, such factors might come into play.That being said, I'm also quite interested in whether there may be other reasons for the association made by Graham et al. Readers might remember back to a post I wrote recently on bacterial infections and behaviour (see here) part of which mentioned the paper by Blomström and colleagues [4] on bacterial infections requiring hospital admission and risk of later nonaffective psychosis. Given the focus on childhood in that paper, which I assume to some degree negates the possibility of sexual activity or kidney stones or a urinary catheter as being a primary cause of a bacterial infection like a UTI, one wonders if there may be something more biologically fundamental to account for the association.Indeed, a quick trawl through the collected research literature in this area reveals some potentially relevant findings in relation, for example, to the development of psychosis after a kidney transplant [5] (open-access) and how this particular patient developed anti-NMDAR encephalitis (see here). I'm wondering whether immune suppression may be a contributing factor to the UTI - psychosis correlation, as per data on the infections favoured following something like organ transplant [6] and the degree to which UTIs are involved. That being said, a role for the immune system in psychosis is a mighty complicated subject as per other posts on this blog (see here and see here) and short of suggesting that immune function might be involved in the link with elevated rates of UTIs in cases, there's few comprehensive answers to account for the association at the current time.Still it is an interesting area of work, also raising the question: does the treatment of UTIs have any effect on presented psychosis symptoms? Bearing in mind, the evidence so far seems a little bit contrary... [Finish post with head scratch and confused look].Music to close. Pavement and Cut Your Hair...-----------[1] Graham KL. et al. Urinary tract infections in acute psychosis. J Clin Psychiatry. 2014. Jan 21. [Epub ahead of print][2] Miller BJ. et al. A prevalence study of urinary tract infections in acute relapse of schizophrenia. J Clin Psychiatry. 2013 Mar;74(3):271-7.[3] Lin RY. et al. Clinical associations of delirium in hospitalized adult patients and the role of on admission presentation. Int J Geriatr Psychiatry. 2010 Oct;25(10):1022-9.[4] Blomström A. et al. Hospital Admission With Infection During Childhood and Risk for Psychotic Illness--A Population-based Cohort Study. Schizophr Bull. 2013 Dec 23.[5] Zhao CZ. et al. Clinical reasoning: agitation and psychosis in a patient after renal transplantation. Neurology. 2012 Jul 31;79(5):e41-4.[6] Galindo Sacristán P. et al. Predictive factors of infection in the first year after kidney transplantation. Transplant Proc. 2013 Dec;45(10):3620-3.----------  Graham KL, Carson CM, Ezeoke A, Buckley PF, & Miller BJ (2014). Urinary tract infections in acute psychosis. The Journal of clinical psychiatry PMID: 24499998... Read more »

Graham KL, Carson CM, Ezeoke A, Buckley PF, & Miller BJ. (2014) Urinary tract infections in acute psychosis. The Journal of clinical psychiatry. PMID: 24499998  

  • March 9, 2014
  • 01:00 PM

Prehistoric Giant Virus Found

by Chiara Civardi in United Academics

Prehistoric giant virus buried in the Siberian ice recovered from a scientific expedition. No, it is not the plot of “The Thing”, but the utter truth: a thirty- thousand- year old virus, whose dimensions are 50 times bigger than the ones of average virus from today, was found by Abergel and Claverie’s team in the Russian permafrost.... Read more »

Legendre M, Bartoli J, Shmakova L, Jeudy S, Labadie K, Adrait A, Lescot M, Poirot O, Bertaux L, Bruley C.... (2014) Thirty-thousand-year-old distant relative of giant icosahedral DNA viruses with a pandoravirus morphology. Proceedings of the National Academy of Sciences of the United States of America. PMID: 24591590  

Philippe N, Legendre M, Doutre G, Couté Y, Poirot O, Lescot M, Arslan D, Seltzer V, Bertaux L, Bruley C.... (2013) Pandoraviruses: amoeba viruses with genomes up to 2.5 Mb reaching that of parasitic eukaryotes. Science (New York, N.Y.), 341(6143), 281-6. PMID: 23869018  

  • March 9, 2014
  • 12:49 PM

Matters of Appearance: Eating Disorder Patients’ Interpretations of Therapists’ Bodies

by Andrea in Science of Eating Disorders

Therapeutic alliance is often highlighted in studies looking at treatment effectiveness, both in and beyond the realm of eating disorder therapy. Evidently, there are a number of factors that can impact how well we get along with our therapists, ranging from disagreements with the course of treatment or type of therapy to a simple, unnamable dislike for the person. But what about their appearance? What kind of impact could a therapist’s body size have on the therapy relationship?
Rance, Clarke & Moller (2014) sought out to investigate this issue, looking specifically at how clients evaluate therapists’ body size and speculate on their relationship with food, with an eye to determine what impact this might have on the therapeutic process.
I was immediately drawn to this study when I was browsing the latest literature; I wondered why this hadn’t been studied before. In some ways it seems obvious; we’re bound to compare ourselves with others, social beings that we are. So when looking at the therapeutic alliance, it would be illogical to assume that physical appearance could be left …

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  • March 9, 2014
  • 11:42 AM

Pregnancy and breast cancer risk: why age counts

by EE Giorgi in CHIMERAS

That an early pregnancy is protective against breast cancer is something I've known for ten years now. I remember one of my professors, back when I started studying genetics, saying: "Having a baby at 16 may ruin your life but it sure protects you from breast cancer." Today we know a lot more about the cellular and genetic mechanisms that a first pregnancy triggers in the body. And yet how these mechanisms turn out to be protective against breast cancer is still a mystery. "The ovarian hormones, estrogen and progesterone, play a pivotal role in normal and neoplastic development of the mammary gland. These hormones have a paradoxical role as long duration of estrogen and progesterone are associated with increased breast cancer risk, while short duration of pregnancy level doses are associated with a reduced breast cancer risk [1]."Pregnancy levels of these two hormones induce permanent changes in gene expression that result in the life-long protective effect against breast cancer. This has been achieved in mouse models, too, by mimicking pregnancy through hormonal administration, followed by carcenogenesis challenges (the poor little mice are exposed to stuff that normally raises breast cancer risk). What I found surprising, and that I didn't know ten years ago, is that there is a slight increase in breast cancer risk after pregnancy, and this risk increases with age, as shown in the graph below (from [2]):The graph above, published in [2], is a qualitative summary from various epidemiological studies. The "base-level" risk for breast cancer is by definition the risk of a nulliparous woman (a woman who's never been pregnant). I originally thought that a full term pregnancy had a protective effect on breast cancer, no matter at what age, and that the protection diminished with age. However, there is a temporary increase in risk following the pregnancy, and this temporary increase grows with age. During pregnancy, both estrogen and progesterone levels rise drastically and temporarily increase the risk of breast cancer. The earlier in life the pregnancy, the lower this increase in risk, and, in the long term, the risk gets reversed drastically. However, for first pregnancies at an older age the temporary increase in risk is much higher and it takes much longer to reverse to the protective effect. As a consequence, having a first child after 35 years of age puts a woman at a higher risk compared to a woman who has never been pregnant. Furthermore, the protective effect is negligible in the presence of the BRCA1 and/or BRCA2 mutations, or with breast cancers that are estrogen/progesterone negative (the cancer cells do not have estrogen/progesterone receptors). Finding the epidemiological mechanisms that establish the life-long protection inferred by an early pregnancy could pave the way to better prevention and treatments. Meier-Abt and Bentires-Alj's review [2] is available for free from Cell and I highly recommend it as it has a nice overview of breast cancer risk as well as the current knowledge on the mechanisms that link early pregnancy to protection:"Most probably, the individual mechanisms are not mutually exclusive and the full protective effect results from a combination of several processes [2]."Besides estrogen and progesterone, the growth hormone (GH) and prolactin (PRL) also control the development of the mammary gland. And while estrogen and progesterone levels do not change after a woman has had her first child, PRL levels do. Mouse models have found that decreased PRL and GH levels favor cancer regression in animals with mammary tumors, whereas other studies have associated increased levels of PRL and GH with a higher incidence of breast cancer. Another theory is that mammary cells become less responsive to estrogen and progesterone after pregnancy, and this could be another factor lowering the risk of cancer. It is consistent with the fact that longer exposure to these hormones, on the other hand, increases the risk. In [2], the authors also list some interesting pathway signaling changes observed after early pregnancy that could be associated with breast cancer protection. One pathway in particular, called wingless related protein (Wnt) signaling, is downregulated after early pregnancy. The pathway is involved in binding ligands from the outside surface of the cell and passing the signal to the inside."In women, pregnancy leads to a reduction in the number of hormone-responsive cells and preferential downregulation of protumorigenic genes and pathways in a subset of progenitor cells isolated from normal human breast tissue. The studies point towards the use of Wnt inhibitors to mimic the protective effect against breast cancer of early pregnancy, a finding consistent with the known potent antiproliferation and anticancer activity of Wnt inhibition [2]."The authors conclude with some outstanding questions that still need to be answered before we can use the information to develop a successful preventive strategy. In particular:"Does pregnancy at a late age (late pregnancy) fail to induce similar cellular and molecular changes as pregnancy at an early age? And if so, does this explain the absence of parity-induced protection against breast cancer after late pregnancy?"[1] Medina D (2005). Mammary developmental fate and breast cancer risk. Endocrine-related cancer, 12 (3), 483-95 PMID: 16172188[2] Meier-Abt F, & Bentires-Alj M (2014). How pregnancy at early age protects against breast cancer. Trends in molecular medicine, 20 (3), 143-153 PMID: 24355762... Read more »

Medina D. (2005) Mammary developmental fate and breast cancer risk. Endocrine-related cancer, 12(3), 483-95. PMID: 16172188  

Meier-Abt F, & Bentires-Alj M. (2014) How pregnancy at early age protects against breast cancer. Trends in molecular medicine, 20(3), 143-153. PMID: 24355762  

  • March 7, 2014
  • 07:52 PM

The Effect of Cadence Manipulation on Plantar Pressures

by Craig Payne in Running Research Junkie

The Effect of Cadence Manipulation on Plantar Pressures... Read more »

Wellenkotter, J., Kernozek, T., Meardon, S., & Suchomel, T. (2014) The Effects of Running Cadence Manipulation on Plantar Loading in Healthy Runners. International Journal of Sports Medicine. DOI: 10.1055/s-0033-1363236  

  • March 7, 2014
  • 05:04 AM

Common mutation is responsible for acute leukemia relapse

by beredim in Stem Cells Freak

To identify the mutations that generated the most relapse-prone leukemia, the scientists competed single cancer cells against each other within a zebrafish.Credit: Jessica Blackburn/Massachusetts General HospitalHarvard stem cell scientists have identified a mutation in human cases of acute lymphoblastic leukemia that likely drives relapse. The research, published in Cancer Cell, could translate into improved patient care strategies for this particular blood cancer, which typically affects children but is more deadly in adults.In recent years, a trend toward single-cell analysis has shown that individual cells within a tumor are capable of amassing mutations to make them more aggressive and treatment resistant. So while 99% of a tumor may be destroyed by the initial treatment, a particularly aggressive cell can survive and then cause a cancer patient with the "all clear" to relapse six months later.Harvard Stem Cell Institute Principal Faculty member David Langenau, PhD, and his lab members in the Department of Pathology at Massachusetts General Hospital used zebrafish to search for these rare, relapse-driving leukemia cells and then designed therapies that could kill these cells.Read More... Read more »

Jessica S. Blackburn, Sali Liu, Jayme L. Wilder, Kimberly P. Dobrinski, Riadh Lobbardi, Finola E. Moore, Sarah A. Martinez, Eleanor Y. Chen, Charles Lee, David M. Langenau. (2014) Clonal Evolution Enhances Leukemia-Propagating Cell Frequency in T Cell Acute Lymphoblastic Leukemia through Akt/mTORC1 Pathway Activation. Cancer Cell. info:/10.1016/j.ccr.2014.01.032

  • March 7, 2014
  • 04:40 AM

Autoimmune diseases and schizophrenia

by Paul Whiteley in Questioning Answers

The paper by Michael Benrós and colleagues [1] talking about an "increased risk of subsequent autoimmune diseases in individuals with schizophrenia" caught my eye recently. Based on a trawl of the records of several thousands of people with "schizophrenia-like psychosis" or "individuals with autoimmune disease" derived from Danish nationwide registers (see here for some background), the authors were able to conclude that "Autoimmune diseases developed subsequently in 3.6% of people with schizophrenia, and 3.1% of people with autoimmune diseases had a family history of schizophrenia". By the way, this is not the first time that authors linked to this paper have published on this topic [2] based on similar analyses. Further coverage of this paper can also be found here.And don't forget your lute.. @ Wikipedia As far as I'm aware, I've not yet covered the issue of autoimmune conditions being correlated with a diagnosis of schizophrenia on this blog. Regular readers might already know about my interest in all things autoimmunity when it comes to autism. Be it the markers of autoimmunity (see here and see here) or the seemingly wide range of conditions correlating with the appearance of autism (see here), I certainly believe that there is more to see here from a research point of view. With the schizophrenia data in mind it appears that I should perhaps be casting the research net a little wider; perhaps even talking about some closer links?As Benrós et al note there is already some research form in the area linking schizophrenia and autoimmune conditions. Outside of the autoantibody side of things [3] and that very interesting link to anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis [4] I note some of the data available in this area to be quite nicely summarised by Davison [5] (open-access) specifically with the Chen paper [6] (open-access) in mind. Taking a few conditions noted by Chen and colleagues, I was interested to see that risk of psoriasis was elevated in cases of schizophrenia as per my interest in this skin condition with autism in mind (see here). Given my focus on / obsession with all things gluten too, the fact that a diagnosis of schizophrenia also elevated the risk of coeliac (celiac) disease similarly piqued my interest and brought back floods of memories about the late Curt Dohan and his life's work in this area (see here). In light of the not-quite-coeliac-disease-but-something-else paper on autism and gluten-related serology it also asks the question of how deep the rabbit hole might actually go?The same questions remain about this work as they do when it comes to examining any link between autism and autoimmune conditions - whether first person or familial: What are the common denominators in terms of genes and biochemistry? Are there shared susceptibility factors evident in schizophrenia and selected autoimmune diseases including infection? But also I'm getting pretty interested in some new areas of potential overlap such as any effects from those very old HERVs (human endogenous retroviruses) and whether through expression of HERV proteins, for whatever reason(s), they are participating in a series of events heading towards autoimmunity? Well, it's not as if HERVs haven't been mentioned with schizophrenia [7] or autoimmune diseases in mind [8] but I'll wait and see how this pans out.Fantastic Mr Fox y'say.... Will you join me? (whistle/click)----------[1] Benrós ME. et al. A Nationwide Study on the Risk of Autoimmune Diseases in Individuals With a Personal or a Family History of Schizophrenia and Related Psychosis. Am J Psychiatry 2014;171:218-226.[2] Eaton WW. et al. Association of schizophrenia and autoimmune diseases: linkage of Danish national registers. Am J Psychiatry. 2006 Mar;163(3):521-8.[3] Ezeoke A. et al. A systematic, quantitative review of blood autoantibodies in schizophrenia. Schizophr Res. 2013 Oct;150(1):245-51. [4] Pollak TA. et al. Prevalence of anti-N-methyl-d-aspartate (NMDA) antibodies in patients with schizophrenia and related psychoses: a systematic review and meta-analysis. Psychol Med. 2013 Dec 13:1-13.[5] Davison K. Autoimmunity in psychiatry. Br J Psychiatry. 2012 May;200(5):353-5.[6] Chen SJ. et al. Prevalence of autoimmune diseases in in-patients with schizophrenia: nationwide population-based study. Br J Psychiatry. 2012 May;200(5):374-80.[7] Frank O. et al. Human endogenous retrovirus expression profiles in samples from brains of patients with schizophrenia and bipolar disorders. J Virol. 2005 Sep;79(17):10890-901.[8] Brodziak A. et al. The role of human endogenous retroviruses in the pathogenesis of autoimmune diseases. Med Sci Monit. 2012 Jun;18(6):RA80-8.----------Benrós ME, Pedersen MG, Rasmussen H, Eaton WW, Nordentoft M, & Mortensen PB (2013). A Nationwide Study on the Risk of Autoimmune Diseases in Individuals With a Personal or a Family History of Schizophrenia and Related Psychosis. The American journal of psychiatry PMID: 24129899... Read more »

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