"This paper provides an overview of the benefits and drawbacks of the current clinical pathway that places primacy on a diagnostic assessment for triggering the commencement of therapy. The paper then presents an alternative clinical pathway - the identification and provision of therapy to infants at risk of ASD [autism spectrum disorder] - and provides a critical review of current evidence supporting this model."So said the 'lecture paper' by Andrew Whitehouse  and, as per the title of this short post, another peer-reviewed critical look at an autism status quo from this author (see here) who does not seem to be afraid to rock the boat (NB. see Cordelia Fine's new book for further discussion on the idea that there probably is no 'male' and female' binary brain differentiation).Bearing in mind this was a paper based on a lecture given at a speech and language conference in Australia, I'm once again intrigued with the sentiments expressed by Prof. Whitehouse, who really does seem to be quite clued into how (a) an autism / autism spectrum diagnosis is for many children, happening 'too late' in terms of the time between when symptoms start manifesting and them getting an 'official' label, and (b) how quite a few children are entering into early intervention programs (for autism) before formal diagnosis is given (see here). I'm not going to go into the possible reasons 'why' the diagnostic pathway seems to be such a long one for so many (although there are clues outside of 'we're just better at recognising autism') but it strikes me as eminently sensible that if a child presents with autistic traits/behaviours, why wait for formal assessment but rather set plans in motion to 'zoom in' on specific areas where intervention might be required. Yes, there will be cost implications - without sounding too conspiracy-like, I've often wondered whether the 'queues' of those waiting for diagnosis at least here in Blighty is partly because the powers-that-be know that there will be cost implications following a diagnosis - but if one assumes that early intervention might have some long-term positive effects (see here) even the bean counters might see some benefits. I might add that whilst behavioural intervention is probably important, this should not be at the expense of other 'types' of intervention for some 'types' of autism (see here) and the value of other screening programs outside of just asking 'is it autism' (see here)?'Nuff said, for now at least but I will be coming to another Whitehouse paper quite soon on this blog...---------- Whitehouse AJ. Elizabeth Usher Memorial Lecture: Rethinking the clinical pathway for autism spectrum disorder and challenging the status quo. Int J Speech Lang Pathol. 2017 Jan 13:1-10.----------Whitehouse AJ (2017). Elizabeth Usher Memorial Lecture: Rethinking the clinical pathway for autism spectrum disorder and challenging the status quo. International journal of speech-language pathology, 1-10 PMID: 28084105... Read more »
Whitehouse AJ. (2017) Elizabeth Usher Memorial Lecture: Rethinking the clinical pathway for autism spectrum disorder and challenging the status quo. International journal of speech-language pathology, 1-10. PMID: 28084105
I've talked about 'fecal microbial transplants' a.k.a the poo(p) transplant before on this blog (see here). That previous entry was about the more typical (and potentially life-saving) use of a poo transplant - where stool from one person is extracted, 'repackaged' and transferred to another person - albeit with caveats in terms of possible long-term side-effects. Now it appears that poo transplants are being investigated with something rather more central to the typical contents of the blog...The paper by Dae-Wook Kang and colleagues  (open-access) has already been picked up by some media (see here) and it seems, also has a following from likely proponents and detractors particularly on social media. Including one James Adams on the authorship list, someone who is quite well-known in autism research circles (see here and see here for examples) alongside some other notable inclusions (Alessio Fasano, Thomas Borody, etc), the authors describe the results of small open-label study - I repeat, a small open-label trial - of 18 participants diagnosed with an autism spectrum disorder (ASD) who underwent a 10-week program characterised by the use of antibiotics, a bowel cleanse and then regular poo transplants for approximately 8 weeks. Additional information about the study and its results can be found here or if you wish, you can see the ClinicalTrials.gov entry here.Tapping into a growing interest in how the gut (and its contents) might be important for at least some autism (see here for example) the aims of the trial were to "follow gut microbiota in healthy and treated children with ASD longitudinally as well as to evaluate an investigational new treatment, MTT [Microbiota Transfer Therapy], for its effectiveness in children with ASD in treating both GI [gastrointestinal] symptoms (primary outcome) and ASD-related symptoms (secondary outcomes), and to determine the effect of MTT on the gut microbiome."The study included children diagnosed on the autism spectrum - ADI-R diagnosed - aged between 7-16 years old. All presented with moderate to severe functional bowel issues alongside their autism (something not unusual it seems). The authors also report using a control group of "20 age- and gender-matched neurotypical children without GI disorders" who were monitored but not treated as part of their study design.The study first involved the administration of the antibiotic vancomycin for 2 weeks (something that has, on its own, some peer-reviewed research history with autism in mind ) used to 'profoundly suppress' pathogenic bacteria. Prilosec, the brand name for omeprazole was also administered towards the end of the bacterial washout phase initiated by the use of vancomycin. Prilosec is a medicine traditionally used to suppress stomach acid secretions and was used to "remove most remaining gut bacteria and vancomycin" and aid the passage and survival of the donor stool to the wider gastrointestinal (GI) tract. I say all that knowing that such medicines can affect the composition of the gut microbiota. Then came the bowel cleanse (Moviprep) complete with a fasting from food day, followed by the main [research] event: oral or rectal administration of donor stool and an initial high dose followed by maintenance doses. I know some people might be slightly uncomfortable with the idea of the rectal administration of medicines but there are some common-sense reasons behind this form of medicines delivery particularly where oral dosage forms (tablets, capsules) might not be well tolerated. As for the initial oral dosage form: "the participants began either oral administration of SHGM [Standardized Human Gut Microbiota] (2.5 × 1012 cells/day) mixed in a chocolate milk, milk substitute, or juice for 2 days (divided into three daily doses)." I have to say that whilst I initially envisaged Austin Powers and his 'tastes a bit nutty' scene, this was very much NOT how things actually were.Alongside the donor stool formulation being trialled predominantly with regards to safety and initial efficacy, researchers also surveyed participants in relation to (i) effects on their gut microbiota (diversity and species present), (ii) the presentation of bowel symptoms/habits and (iii) behavioural outcomes covering autism-specific issues (via the CARS) and more general adaptive behaviours (via the Vineland scales for example). I was also happy to see a section included in their paper labelled 'virome bioinformatics' hat-tipping the idea that gut bacteria are not the only passengers we carry in our deepest, darkest recesses.Results: well something certainly seemed to happen when looking at before, during and after results of this case series trial. First and foremost adverse effects were small and limited (hyperactivity, irritability) meaning that in the short term at least, the poo transplants and pre-poo transplant protocols were tolerated quite well. This is also evident in the 0% study attrition rate (i.e. everyone who started the study stayed in the study).So: "Substantial changes in GI and ASD symptoms were observed. GI symptoms, as assessed by the GSRS [Gastrointestinal Symptom Rating Scale], significantly improved for abdominal pain, indigestion, diarrhea, and constipation." The authors report some significant differences in scores over the course of the intervention period such that: "The average GSRS score dropped 82% from the beginning to end of the treatment and remained improved (77% decrease from baseline) even 8 weeks after treatment stopped." That is a helluva placebo effect! Indeed, only 2 participants from the cohort were classified as 'non-responders' on the basis of their GSRS scores over the course of the study.Also: "Beyond these GI improvements, ASD-related behavior also improved following MTT." The sorts of changes to CARS scores being reported were in the region of a 20% reduction in 'core ASD' symptoms at 8 weeks compared to baseline reports. Further, 8 weeks after the intervention had been completed the behavioural gains ("relative to baseline") were still evident based on CARS scoring. These ratings also did not depend on whether the poo transplant was administered orally or rectally.The authors also discuss some not unexpected changes to gut bacterial profiles in their cohort over the intervention period. At baseline: "gut bacteria were significantly less diverse in children with ASD than neurotypical controls." This finding is in line with other study results from the authors (see here). Bacterial diversity did (slowly) change over the intervention period to a point where at 18 weeks after baseline median richness "was statistically indistinguishable between the ASD and control groups." This was noted in 16 of the 18 participants with ASD.Finally: "Specific genera that significantly changed in their relative abundances with treatment included Bifidobacterium, Prev... Read more »
Kang, D., Adams, J., Gregory, A., Borody, T., Chittick, L., Fasano, A., Khoruts, A., Geis, E., Maldonado, J., McDonough-Means, S.... (2017) Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study. Microbiome, 5(1). DOI: 10.1186/s40168-016-0225-7
Epigenetic regulation is thought to be one of the most important mechanisms contributing to the development and clinical course of chronic immunological diseases like allergies and asthma. DNA methylation has been extensively studied in this context, which has not been a case of histone modifications such as histone acetylation or methylation.
Early epigenetic studies from our lab conducted in mouse models demonstrated a role for histone acetylation in mediating bacteria-induced protection against asthma.1 Subsequently, apart from the continuation of animal investigations, we also launched human studies. The need of reproducible, quick, and cost-effective methods that allow the analysis of multiple human samples from larger cohorts, led us to the establishment of our own, in-house chromatin immunoprecipitation (ChIP) assay2 that utilizes a relatively low input of cells. Although it was originally optimized for CD4 T-cells, other types of cells can be also studied with small modifications to the protocol.2... Read more »
Harb H, Alashkar Alhamwe B, Garn H, Renz H, & Potaczek DP. (2016) Recent developments in epigenetics of pediatric asthma. Current opinion in pediatrics, 28(6), 754-763. PMID: 27662207
Harb, H., Amarasekera, M., Ashley, S., Tulic, M., Pfefferle, P., Potaczek, D., Martino, D., Kesper, D., Prescott, S., & Renz, H. (2016) Epigenetic Regulation in Early Childhood: A Miniaturized and Validated Method to Assess Histone Acetylation. International Archives of Allergy and Immunology, 168(3), 173-181. DOI: 10.1159/000442158
Harb, H., Raedler, D., Ballenberger, N., Böck, A., Kesper, D., Renz, H., & Schaub, B. (2015) Childhood allergic asthma is associated with increased IL-13 and FOXP3 histone acetylation. Journal of Allergy and Clinical Immunology, 136(1), 200-202. DOI: 10.1016/j.jaci.2015.01.027
Stefanowicz, D., Lee, J., Lee, K., Shaheen, F., Koo, H., Booth, S., Knight, D., & Hackett, T. (2015) Elevated H3K18 acetylation in airway epithelial cells of asthmatic subjects. Respiratory Research, 16(1). DOI: 10.1186/s12931-015-0254-y
Of the various autism science journals out there in peer-reviewed (La-La!) land, one journal in particular is really starting to grow on me: [The] Review Journal of Autism and Developmental Disorders.I like this journal because it is basically systematic review and meta-analysis heaven when it comes to the quite voluminous autism research literature and seems to publish some real gems (see here for example).Another paper from this journal caught my eye recently by Maggie Butchart and colleagues  (open-access) synthesising the collected research on "the prevalence of visual impairments in children and adults with Autism Spectrum Disorder (ASD), and the similar behavioural traits associated with both visual impairment and autism." Affiliated with the RNIB - Royal National Institute of Blind People - Scotland among other groups, the authors trawled the research literature looking at reported visual impairments in relation to the autism spectrum and provide quite a nice overview of 'where we're at' with regards to "papers published from 2000-2015."The paper is open-access but a few comments are required bearing in mind my relative lack of knowledge on the complexities of visual impairments.First: "Collating the evidence from six of the seven prevalence studies suggests a refractive error rate in the childhood ASD population studied at 22.9–32.7%, which is comparable with general childhood refractive error rates in 6–7 year olds at 29%, and 32.3% in 12–13 year olds." What this means is that a diagnosis of autism does not protect against the presence of refractive errors ('when the shape of the eye prevents light from focusing directly on the retina').Second: "Estimates of childhood strabismus in the UK is 1.5 to 5.3%... but in the evidence collated in this review, the incidence of strabismus amongst autistic participants is higher at 8.3%." Strabismus, where the eyes don't align properly, seems to be a little bit more prevalent when it comes to autism compared with general population statistics. This is a topic that I've talked about before on this blog in relation to correcting such an issue with autism in mind (see here).Finally: "There were no studies examining ophthalmic conditions and adult autistic populations who are more at risk of age-related visual impairments." Bearing in mind the search parameters included in the Butchart paper, I'm kinda dismayed that this is the current state of affairs. You'd have thought with all the money and resources being thrown into autism research that someone, somewhere might have thought more about eye health in adults with autism? Eye-tracking, reading the mind in the eyes test... the word 'eye' or 'eyes' is prominent in autism research but just not in relation to eye health it seems. And bear in mind that issues with eye health probably will affect the results of some of those autism 'eye' studies.Eye or vision issues related to autism have often been a topic of discussion on this blog (see here and see here for examples) and so I'm glad that someone has finally brought a review of this area into the peer-reviewed arena. Screening is important; even if some of those on the autism spectrum may not always be by first sight (pardon the pun) particularly amenable to taking part in an eye exam - adjustments can and should be made.And finally consider this: "Undiagnosed visual impairment is likely to severely impact quality of life. There is a need therefore for education and training that equip autism support practitioners with the awareness and skills to identify potential visual impairment, to refer individuals to optometry professionals if necessary, and to make necessary adjustments to service environments and support practices for individuals identified as having a visual impairment." Not much more to say really is there aside from 'make it so'.---------- Butchart M. et al. Autism and Visual Impairment: a Review of the Literature. Review Journal of Autism and Developmental Disorders. 2017. Jan 5.----------Butchart, M., Long, J., Brown, M., McMillan, A., Bain, J., & Karatzias, T. (2017). Autism and Visual Impairment: a Review of the Literature Review Journal of Autism and Developmental Disorders DOI: 10.1007/s40489-016-0101-1... Read more »
Butchart, M., Long, J., Brown, M., McMillan, A., Bain, J., & Karatzias, T. (2017) Autism and Visual Impairment: a Review of the Literature. Review Journal of Autism and Developmental Disorders. DOI: 10.1007/s40489-016-0101-1
Competition for government research grants to fund scientific research remains fierce in the United States. The budget of the National Institutes of Health (NIH), which constitute the major source of funding for US biological and medical research, has been increased only modestly during the past decade but it is not even keeping up with inflation. This problem is compounded by the fact that more scientists are applying for grants now than one or two decades ago, forcing the NIH to enforce strict cut-offs and only fund the top 10-20% of all submitted research proposals. Such competition ought to be good for the field because it could theoretically improve the quality of science. Unfortunately, it is nearly impossible to discern differences between excellent research grants. For example, if an institute of the NIH has a cut-off at the 13 percentile range, then a grant proposal judged to be in the top 10% would receive funding but a proposal in top 15% would end up not being funded. In an era where universities are also scaling back their financial support for research, an unfunded proposal could ultimately lead to the closure of a research laboratory and the dismissal of several members of a research team. Since the prospective assessment of a research proposal’s scientific merits are somewhat subjective, it is quite possible that the budget constraints are creating cemeteries of brilliant ideas and concepts, a world of scientific what-ifs that are forever lost.... Read more »
After a late dinner, a jungle-dwelling whip spider can't rely on an Uber driver to get her home. She has to find the way herself, in the pitch-black, picking her way over thick undergrowth to reach the tree she lives on. It's a trick she can even manage when plucked from her home tree and tossed into the forest at random, up to 10 meters away. Now scientists think whip spiders don't use her eyes for this homing feat—they use their feet.
Whip spiders hunt by night and hunker down at dawn u... Read more »
Bingman VP, Graving JM, Hebets EA, & Wiegmann DD. (2016) Importance of the antenniform legs, but not vision, for homing by the neotropical whip spider, Paraphrynus laevifrons. The Journal of experimental biology. PMID: 28011820
"Because of the limited number of included studies and small sample sizes, no firm conclusions can be drawn. However, the limited data currently available suggest that ω-3 FA [fatty acid] supplementation does not enhance the performance of children with ASD [autism spectrum disorder]."Those were the conclusions reached in the systematic review and meta-analysis paper published by Andrea Horvath and colleagues  looking at the collected peer-reviewed literature on the topic up to August 2016. Specifically focused on randomised-controlled trials (RCTs), where participants are randomly allocated to receive a treatment - in this case ω-3 (omega-3) FA supplementation - or no treatment/placebo, researchers identified 5 studies where ω-3 supplements had been delivered to children diagnosed as being on the autism spectrum. The authors add: "With 4 exceptions, there were no statistically significant differences in ASD symptoms between groups measured by validated scales."I'm not too surprised by these findings given some previous discussion on this topic (see here). I would however point out a few relevant issues that should be considered when it comes to fatty acids and autism: (i) Despite core symptoms not necessarily showing any general 'improvement' following fatty acid supplementation, this does not mean that other non-core features might not be affected by such supplements. Take for example, the collected data on what fatty acid supplementation might do for [some] attention-deficit hyperactivity disorder (ADHD) for example (see here), allied to the idea that ADHD might be 'over-represented' when it comes to autism (see here). Same goes for fatty acids and reading ability (see here) and indeed, into adulthood, the possibility of a connection between fatty acids and conditions such as bipolar disorder (see here) or psychosis (see here) (bearing in mind some recent discussions on the psychosis 'association'). Both bipolar disorder and psychosis have cropped up in relation to autism (see here and see here respectively). (ii) Horvath and colleagues report that: "Adverse effects were similar in both groups" meaning that fatty acid supplementation is probably not any more 'dangerous' than the placebos or 'no supplementation' used in the reviewed studies when it comes to autism. Given the growing literature suggesting that everyone should be eating a little more fish for heart health for example, supplementing those who don't like fish or who don't seem to eat enough fish is not ruled out. This is particularly relevant when one talks about autism and some peculiar eating habits (see here). (iii) There is a sizeable peer-reviewed literature talking about alterations in the levels of essential fatty acids in cases of autism (see here). Allied to the idea that there is no 'one-size-fits-all' intervention for 'the autisms', it is conceivable that selected supplementation on the basis of those presenting with deficiency could be considered advantageous. Much like when another nutrient of the hour - vitamin D - is shown to be deficient in relation to autism (see here), the onus should surely be to correct the deficiency when found, albeit under appropriate medical supervision (see here).I don't disagree with the findings reported by Horvath and colleagues and, as I've said a few times before, vitamins and other supplements should be treated in the same way as other 'medicines' in terms of their use and safety (even if they don't typically come as a prescription). But I'd hate to think that the message 'fish oils generally don't benefit autism' gets translated into those on the autism spectrum potentially ignoring what are some potentially important nutrients for general health and wellbeing ...---------- Horvath A. et al. ω-3 Fatty Acid Supplementation Does Not Affect Autism Spectrum Disorder in Children: A Systematic Review and Meta-Analysis. J Nutr. 2017 Jan 11. pii: jn242354. Alexander DD. et al. A Meta-Analysis of Randomized Controlled Trials and Prospective Cohort Studies of Eicosapentaenoic and Docosahexaenoic Long-Chain Omega-3 Fatty Acids and Coronary Heart Disease Risk. Mayo Clinic Proceedings. 2017; 92: 15-29.----------Horvath A, Łukasik J, & Szajewska H (2017). ω-3 Fatty Acid Supplementation Does Not Affect Autism Spectrum Disorder in Children: A Systematic Review and Meta-Analysis. The Journal of nutrition PMID: 28077731... Read more »
Horvath A, Łukasik J, & Szajewska H. (2017) ω-3 Fatty Acid Supplementation Does Not Affect Autism Spectrum Disorder in Children: A Systematic Review and Meta-Analysis. The Journal of nutrition. PMID: 28077731
"From 2006 to 2012, the prevalence of autism spectrum disorder diagnoses in 0- to 24-year-olds increased from 0.22% to 0.38%."That was one of the details included in the rather interesting paper by Christian Bachmann and colleagues  who provided some introductory information on the the trends in autism diagnoses in Germany. I say 'introductory information' because it appears that autism or autism spectrum disorder (ASD) has not exactly received the research attention in Germany that it perhaps has in other similarly developed nations such as the United States or here in Blighty. Indeed, as Bachmann et al note: "Due to the only available study to date, the prevalence of ASD in Germany is estimated to be about 0.25% in 0- to 24-year-olds in 2009" and even that was taken from another study by the author .This time around, the authors listed two primary aims for their research: (a) "to establish the time trends in the administrative prevalence of autism spectrum disorder diagnoses" and (b) "to assess the stability of autism spectrum disorder diagnoses over time." I'm interested in both these areas on this blog (see here for example). Data for the time trends part of this research came from "the German statutory health insurance company Allgemeine Ortskrankenkassen (AOK) from the years 2006 to 2012" where a diagnosis of ASD was registered by ICD-10 definition. Data for the stability side of their research was via a "cohort with a first-time diagnosis of autism spectrum disorder in 2007 through 2012, investigating the percentage of retained autism spectrum disorder diagnoses."Results: well as per the opening sentence to this post, the only way is up when it comes to the estimated prevalence of autism or ASD despite the figures being a tad lower than those for other countries. Those percentages were based on nearly 15,000 ASD diagnoses being recorded in 2006 out of 6.9 million insurees, and nearly 22,000 ASD diagnoses in 2012 out of 6.4 million insurees. Males were quite a bit more likely to be diagnosed with autism/ASD and prevalence peaked for the age group 6-11 year olds.Then to that stability part of the study and from "3927 patients (mean age: 8.7 years, 68.9% males)" with a specific ASD diagnosis in 2007 only a third 'carried on' with a specific diagnosis by 2012. The authors note: "This figure is lower than the usual persistence for ASD diagnoses, which is about 73%–100%." Lower? Yes, I'd say. The reasons for this quite notable lack of diagnostic stability? Well, the authors note that there is probably going to be more than one (before anyone makes any sweeping generalisations). They talk about the lack of "specialised mental health services that are competent to diagnose ASD according to international standards and guidelines" as one factor. They talk about diagnoses "often made by paediatricians or occupational therapists, without employing diagnostic gold standards like Autism Diagnostic Observation Schedule (ADOS)." They even talk about diagnostic switching between ASD subgroups as potentially also being a factor to consider. And then another possibility: "Other reasons include improvement of symptoms because of successful therapeutic interventions" without any specific mention of what types of therapeutic intervention might be involved. Sounds very 'optimal outcome' to me (see here). In short, it's probably going to be complicated.Bearing in mind those diagnostic stability figures and the authors reliance on a database that relied on those unstable figures for prevalence estimates, this is interesting research. It shows that even a social and economic powerhouse like Germany still has some way to go in many areas not least with that related to autism. Where next? Well, as per the authors suggestion: "one possible option could be to establish standardised diagnostic algorithms and certify ASD diagnostic centres who employ these standards." Sounds good but in amongst the chatter about autism 'misdiagnosis' and seemingly 'ill-trained' professionals diagnosing, I do wonder whether further, more detailed, investigations are needed on the autism diagnostic stability figures of Germany and whether it's all just due to administrative errors...Music to close, and this guy was/is apparently quite big in Germany... Permit denied!---------- Bachmann CJ. et al. Diagnoses of autism spectrum disorders in Germany: Time trends in administrative prevalence and diagnostic stability. Autism. 2016. Dec 20. Bachmann CJ. et al. Psychopharmacological treatment in children and adolescents with autism spectrum disorders in Germany. Res Dev Disabil. 2013 Sep;34(9):2551-63.----------Christian J Bachmann, Bettina Gerste, & Falk Hoffmann (2016). Diagnoses of autism spectrum disorders in Germany: Time trends in administrative prevalence and diagnostic stability Autism: International Journal of Research & Practice : 10.1177/1362361316673977... Read more »
Christian J Bachmann, Bettina Gerste, & Falk Hoffmann. (2016) Diagnoses of autism spectrum disorders in Germany: Time trends in administrative prevalence and diagnostic stability. Autism: International Journal of Research . info:/10.1177/1362361316673977
Among monogamous animals, some individuals are more faithful than others. Could these differences in fidelity be, in part, because of differences in our brains? And if so, why does this diversity in brain and behavior exist?A snuggly prairie vole family. Photo from theNerdPatrol at Wikimedia Commons.Prairie voles are small North American rodents that form monogamous pair bonds, share parental duties, and defend their homes. Although prairie voles form monogamous pairs, that does not mean they are sexually exclusive. About a quarter of prairie vole pups are conceived outside of their parents’ union.Not all male prairie voles cheat on their partners at the same rates. In fact, some males are very sexually faithful. It turns out, there are both costs and benefits to being faithful and to cheating. Mariam Okhovat, Alejandro Berrio, Gerard Wallace, and Steve Phelps from the University of Texas at Austin, and Alex Ophir from Cornell University used radio-telemetry to track male prairie voles for several weeks to explore what some of these costs and benefits might be. Compared to males that only sired offspring with their own partner, unfaithful males had larger home ranges, intruded on more territories of other individuals, and encountered females more often. However, these unfaithful males were also more likely to be cheated on when they were away (probably because they were away more). I guess even rodents live by The Golden Rule.Maps of how paired male voles in this study used space. The solid red/orange/yellow peaks show where a faithful male (in the left map) and unfaithful male (in the right map) spent their time in relation to where other paired males spent their time (showed by open blue peaks). Image from the Okhovat et al. Science paper (2015).Vasopressin is a hormone that has been found to affect social behaviors such as aggression and pair bonding when it acts in the brain. Mariam, Alejandro, Gerard, Alex, and Steve all set out to determine how vasopressin in the brain may relate to sexual fidelity in prairie voles. They found that faithful males had lots of a particular type of vasopressin receptor (called V1aR) in certain brain areas involved in spatial memory. Surprisingly, faithful males did not have more V1aR in brain regions typically associated with pair bonding and aggression. A male that has more V1aR in spatial memory regions might better remember where his own mate is and where other males have been aggressive, which would decrease the chances that he would intrude on other territories in search of other females and increase the time that he spends home with his own mate. A male that has less V1aR in spatial memory regions might be less likely to learn from his negative experiences and more likely to sleep around.Photos of a brain section from a faithful male (left) and unfaithful male (right). The dark shading shows the density of V1aR vasopressin receptors. The arrows show the location of the retrosplenial cortex (RSC), a brain area involved in spatial memory. Faithful males had significantly more V1aR receptors in the RSC compared to unfaithful males. Image from the Okhovat et al. Science paper (2015). The research team then found genotype variations that related to having lots or not much V1aR in one of these spatial memory regions (called retrosplenial cortex … but we’ll just call it RSC). They confirmed these findings with a breeding study, in which they reared siblings that were genetically similar, but some had the genotype they predicted would result in lots of V1aR in RSC and some had the genotype they predicted would result in very little V1aR in RSC. They confirmed that these genetic variations correspond with the amount of vasopressin receptor in this specific spatial memory area.The researchers then looked closer at the different versions of this vasopressin receptor gene in the RSC brain region to see if differences in the amount of vasopressin receptors in RSC may be caused by the epigenetic state of the gene (i.e. how active the gene is). They found that the genotype that results in very little V1aR in RSC had many more potential methylation sites, which can repress gene activity.All of this data together tells a very interesting story. Male prairie voles that have the genotype for more V1aR vasopressin receptors in their RSC part of their brain are more likely to remember where their home and mate are and to remember where other aggressive prairie voles are, which will make them more likely to spend more time with their partner, to be sexually faithful and to have sexually faithful partners. Male prairie voles that have the genotype for less V1aR in their RSC are more likely to forget where their home and mate are and where other aggressive prairie voles are, which will make them more likely to cheat and to be cheated on. Overall, faithful and unfaithful male prairie voles have roughly the same number of offspring, but advantages may emerge with changes in population density. Prairie vole populations vary anywhere from 25 to 600 voles per hectare from year to year. When population densities are high, you (and your partner) are more likely to encounter more potential mates and it may benefit you to cheat (and have a “cheater’s brain”). When population densities are low, you (and your partner) are less likely to encounter more potential mates and it may benefit you to be faithful (and have a “faithful brain”). But when populations fluctuate between high and low densities, both faithful and unfaithful genotypes will get passed along from generation to generation. Want to know more? Check this out:Okhovat, M., Berrio, A., Wallace, G., Ophir, A., & Phelps, S. (2015). Sexual fidelity trade-offs promote regulatory variation in the prairie vole brain Science, 350 (6266), 1371-1374 DOI: 10.1126/science.aac5791 ... Read more »
Okhovat, M., Berrio, A., Wallace, G., Ophir, A., & Phelps, S. (2015) Sexual fidelity trade-offs promote regulatory variation in the prairie vole brain. Science, 350(6266), 1371-1374. DOI: 10.1126/science.aac5791
by Piter Kehoma Boll If you think spiders are scary creatures, today you will learn that they are scared too. But what could scary a spider? Well, a web bug! We usually think of spider webs as an astonishing evolutionary … Continue reading →... Read more »
PAPE, R. (2013) Description and Ecology of A New Cavernicolous, Arachnophilous Thread-legged Bug (Hemiptera: Reduviidae: Emesini) from Kartchner Caverns, Cochise County, Arizona. Zootaxa, 3670(2), 137. DOI: 10.11646/zootaxa.3670.2.2
Resende, L., Zepon, T., Bichuette, M., Pape, R., & Gil-Santana, H. (2016) Associations between Emesinae heteropterans and spiders in limestone caves of Minas Gerais, southeastern Brazil. Neotropical Biology and Conservation, 11(3). DOI: 10.4013/nbc.2016.113.01
Wignall, A., & Taylor, P. (2010) Predatory behaviour of an araneophagic assassin bug. Journal of Ethology, 28(3), 437-445. DOI: 10.1007/s10164-009-0202-8
I'm a great believer in balance when it comes to this blog and its content. As enthusiastic as I might be about a particular topic or topics, I don't want to lose sight of the fact that peer-reviewed science is a messy business and often filled with contrary findings.With 'contrary' in mind, I want to talk today about a paper by Amy Romijn and colleagues  detailing the results of a double-blind, randomised, placebo-controlled trial of a probiotic mix which contained "freeze-dried L. helveticus R0052 (strain I-1722 in the French National Collection of Cultures of Microorganisms [CNCM], Institut Pasteur, Paris, France) and B. longum R0175 (CNCM strain I-3470) bacteria at a dosage of three billion colony-forming units (⩾3 × 109 CFU) per 1.5 g sachet" with a sample of participants selected for 'low mood'. Probiotics, just in case you don't know, are those various live bacteria and yeasts that are supposed to confer some health benefit.The reason for this study? Well, as the authors note, the specific probiotics under study were "previously found to improve emotional behaviour in animals and psychological outcomes and humans" as per other findings . So with [prospective] trial registration (see here) in hand, researchers set out to look at what 8 weeks worth of probiotics might do for 'low mood' and other psychological parameters when pitted against a placebo formulation (that contained only the excipients included in the probiotic formulation). Blood samples were also provided by participants at baseline (before intervention) and at 8 weeks post-intervention "to measure levels of high-sensitivity C-reactive protein (hsCRP), IL-1β, IL-6, TNF-α, vitamin D and BDNF."Results: "Intent-to-treat analysis (n = 79) showed no significant group differences on any outcome measure." The scores for the groups - probiotic (n=40) & placebo (n=39) - did not seem to differ significantly on any of the measures used during the trial. Indeed, when taking into account individual scores on the primary outcome measures called the Montgomery–Åsberg Depression Rating Scale (MADRS) - something used to measure "the severity of depressive episodes" - the results actually (non-significantly) seemed to favour the placebo in terms of those who "showed a ⩾60% change on the MADRS (responders)."Insofar as adverse effects, well taking this probiotic probably won't do any harm if we rely on the Romijn findings, as authors describe "three serious adverse events over the course of the trial, all of which were suicide attempts by one participant from the placebo group. There were no serious adverse events in the probiotic group."But all was not completely negative when it came to the trial as a little gem was potentially uncovered: "Among those randomized to the probiotic group, those who had high vitamin D at baseline showed greater improvement in mood and functioning than those who had low vitamin D at baseline." Without trying to make mountains out of molehills, the authors speculate that: "the vitamin D status of the host could have an effect on the relationship between the gut microbiota and the immune system: low vitamin D could limit response to probiotic treatment as any changes to the microbiome composition would not necessarily be translated to the immune system." A rather interesting sentiment given the increasingly vocal link between vitamin D and depression for example in the research literature (see here).These results do represent a bit of a set-back for the idea of psychobiotics  but I'm not ready to poo-poo the whole area just yet. Among the various caveats raised by the study authors (samples size, length of intervention, etc) it is possible that 'low mood' over and above something a little more clinically 'transforming', might not be a suitable target for such intervention (indeed, other research might also be relevant ) despite the fact that other research on subclinical psychological symptoms have been seemingly affected by probiotic administration (see here). The specific formulation used might also be a factor as the authors quite correctly suggest that: "It is important that the results of the current study are not generalized to all potential probiotic strains." Baby and bathwater eh?But these results stand, and given some important names on the authorship list (see here), this is one study that cannot and should not be just swept under the scientific carpet...---------- Romijn AR. et al. A double-blind, randomized, placebo-controlled trial of Lactobacillus helveticus and Bifidobacterium longum for the symptoms of depression. Aust N Z J Psychiatry. 2017 Jan 1:4867416686694. Messaoudi M. et al. Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. Br J Nutr. 2011 Mar;105(5):755-64. Dinan TG. et al. Psychobiotics: a novel class of psychotropic. Biol Psychiatry. 2013 Nov 15;74(10):720-6. Kleiman SC. et al. The Gut-Brain Axis in Healthy Females: Lack of Significant Association between Microbial Composition and Diversity with Psychiatric Measures. PLoS One. 2017 Jan 19;12(1):e0170208.----------Romijn AR, Rucklidge JJ, Kuijer RG, & Frampton C (2017). A double-blind, randomized, placebo-controlled trial of Lactobacillus helveticus and Bifidobacterium longum for the symptoms of depression. The Australian and New Zealand journal of psychiatry PMID: 28068788... 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Romijn AR, Rucklidge JJ, Kuijer RG, & Frampton C. (2017) A double-blind, randomized, placebo-controlled trial of Lactobacillus helveticus and Bifidobacterium longum for the symptoms of depression. The Australian and New Zealand journal of psychiatry, 2147483647. PMID: 28068788
The European Association of Urology (EAU) Renal Cell Carcinoma (RCC) guidelines panel has recently updated its recommendation on adjuvant therapy with sunitinib in non-metastatic RCC after surgical tumour removal (Bex et al., 2016). These clinical guidelines provide urologists with evidence-based information and recommendations for the management of RCC and the panel includes urological surgeons, oncologists, pathologists, radiologists and patient advocates. Based on the conflicting results of two available clinical studies (ASSURE and S-TRAC), the panel rated the quality of the evidence of the trials, the harm-to-benefit ratio, the patient preferences and the costs. As a result, the EAU panel, including representatives from a patient advocate group (International Kidney Cancer Coalition) voted and reached a consensus recommendation that adjuvant therapy with sunitinib for patients with high-risk RCC after nephrectomy should not be given.... Read more »
Bex A, Albiges L, Ljungberg B, Bensalah K, Dabestani S, Giles RH, Hofmann F, Hora M, Kuczyk MA, Lam TB.... (2016) Updated European Association of Urology Guidelines Regarding Adjuvant Therapy for Renal Cell Carcinoma. European urology. PMID: 27986369
Meric-Bernstam, F., Tannir, N., Harding, J., Voss, M., Mier, J., DeMichele, A., Munster, P., Patel, M., Iliopoulos, O., Owonikoko, T.... (2016) Phase 1 study of CB-839, a small molecule inhibitor of glutaminase, in combination with everolimus in patients (pts) with clear cell and papillary renal cell cancer (RCC). European Journal of Cancer. DOI: 10.1016/S0959-8049(16)32626-0
by Piter Kehoma Boll This week we’ll stay in the sea and meet on of the most impressive algae, the giant kelp, Macrocystis pyrifera. It is called giant for a good reason, since it can grow up to 50 m in … Continue reading →... Read more »
In today's post I want to draw your attention to the findings reported by Diana Ohanian and colleagues  (open-access available here) talking about "the use of machine learning to further explore the unique nature"of various conditions/labels including those typically headed under the label of chronic fatigue syndrome / myalgic encephalomyelitis (CFS/ME).Including one 'Jason LA' on the authorship list, researchers set about looking at "what key symptoms differentiate Myalgic Encephalomyelitis (ME) and Chronic Fatigue syndrome (CFS) from Multiple Sclerosis (MS)."You may be wondering why such a comparative study was undertaken but a quick trawl of the research literature reveals that these different clinical labels may well have some important commonalities .This was an internet-based research project whereby "106 people with MS and 354 people with ME or CFS fully completed the [DePaul Symptom Questionnaire] questionnaire" and based on the responses received "decision trees were used to determine what symptoms differentiated those with MS from those with ME or CFS." Decision trees, as the name suggests, is a statistical technique where binary (0 or 1, no or yes) choices make branches and: "At each branch the computer decides what symptom would best predict classifications, in this case whether someone has MS or ME or CFS." This process continues and continues through the different levels of branches "until the tree reaches a balance between classification accuracy and generalizing to new data." Such a machine learning tool has been previously discussed quite recently on this blog (see here).Results: "Five symptoms best differentiated the groups." These were: flu-like symptoms, tender lymph nodes, alcohol intolerance, inability to tolerate upright position and next day soreness after strenuous activity. The first two symptoms - flu-like symptoms and tender lymph nodes - were pretty good by themselves at correctly categorising MS or CFS/ME (~80% correct). Indeed, these seemed to be the core differentiators that were examined and as the authors note: "The most important two symptoms that differentiated MS versus ME or CFS existed within the immune domain."Of course further investigations are warranted to potentially build on these findings. One has however to be slightly cautious about the use of the internet and social media when undertaking such research, especially when very little information about the formal diagnoses of participants is included in the current paper. This is a particular issue when it comes to CFS/ME and the various ways that it can be defined and diagnosed .Still, I can't quibble with the continued rise and rise of machine learning being applied to many areas of medicine, and not before time that it starts to reach ME/CFS. And just before I go, it appears that the research team at DePaul University have been quite busy...To close, on what retiring Presidents of the USA should do next. I think I would go with George Washington and his whisky business... 🍻---------- Ohanian D. et al. Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis. Neurology (ECronicon). 2016;4(2):41-45. Morris G. & Maes M. Myalgic encephalomyelitis/chronic fatigue syndrome and encephalomyelitis disseminata/multiple sclerosis show remarkable levels of similarity in phenomenology and neuroimmune characteristics. BMC Medicine. 2013; 11: 205. Jason LA. et al. Case definitions integrating empiric and consensus perspectives. Fatigue. 2016;4(1):1-23.----------Ohanian D, Brown A, Sunnquist M, Furst J, Nicholson L, Klebek L, & Jason LA (2016). Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis. Neurology (E-Cronicon), 4 (2), 41-45 PMID: 28066845... Read more »
Ohanian D, Brown A, Sunnquist M, Furst J, Nicholson L, Klebek L, & Jason LA. (2016) Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis. Neurology (E-Cronicon), 4(2), 41-45. PMID: 28066845
"A more homogeneous subgroup with regression between 18 and 36 months (n = 48) had higher rates of intellectual disability, epilepsy, and special education, more socially restrictive educational settings, and more severe ASD [autism spectrum disorder] communication deficits and schizophrenia spectrum symptoms than non-regressed youth (n = 136)."So said the findings reported by Kenneth Gadow and colleagues  taking on one of the more important issues in relation to autism: developmental regression (see here). I say 'more important' in that last sentence because whilst it has taken autism research and science quite a while to accept that regression in skills/behaviour can occur in cases of autism, there is now a realisation that such regression can impact on various other areas of investigation, not least the discussions on the potential [very] early detection of autism (see here). And still researchers continue to talk about very early autism detection...Gadow (a name not unfamiliar to this blog in terms of autism and schizophrenia spectrums potentially colliding) et al set out to examine "the psychiatric and clinical correlates of loss of previously acquired skills (regression) as reported by parents of youth with autism spectrum disorder (ASD)." They relied to quite a large extent on data derived from the Child and Adolescent Symptom Inventory partly created by Dr Gadow, that assesses for the presence of various behaviours linked to various developmental and psychiatric labels. Some 213 6- to 18-year old children and adolescents with ASD were included for study; 77 (36%) of them defined as showing some parent-reported regression in skills coincidental to the presentation of their autism.As per that opening sentence, there did appear to be some differences in clinical presentation when using regression as a characterising feature. A few additional details: 37% of those "whom parents indicated had regressed (whether or not they indicated age of regression and type of skill)" fell into the intellectual/learning disability category vs. 18-19% of non-regressed participants. Significantly more participants who regressed were 'ever hospitalised' (48% vs 29%); a statistic that probably ties into the rates of epilepsy/seizure disorder also described in this cohort (18% vs 5-6%). Although the authors talk about 'a more severe ASD communication deficit' being linked to reports of regression, the data obtained from both parent and teacher ratings in relation to the presentation of autistic traits were mainly 'more severe' in the regression group when examined as a whole: social deficits, communication deficits and perseverative behaviours; albeit not significantly so.Then to the suggestion that schizophrenia spectrum symptoms were more pronounced in the regression group. Appreciating that there is some history when it comes to autism and schizophrenia (think Mildred Creak for example) but also some controversy, this is something potentially quite important, not least when one considers the rise and rise of research interest into something like psychosis and [some] autism (see here and see here) and also how [some] regressive autism might not be a million miles away from a condition like anti-NMDA-receptor encephalitis (see here) typically encompassing a psychotic element to it. I also wonder whether the talk about regression accompanying autism might set the tone for further regression potentially accompanying the onset of something like schizophrenia for example. Could a life of 'regression in skills' be a feature of this group?Of course further investigations are required to independently verify the findings reported by Gadow and colleagues; such work should really also include more professionally-derived ratings (bearing in mind parents are generally the experts on their own children). I wonder too if it's time to start including a few more 'biological' measures when it comes to looking at regression vs. no regression in the context of autism to see if genetics/epigenetics/biochemistry variables might also tie up with some of the behavioural findings. Indeed, this should really be a must.Finally: "A brief parent report of developmental regression may be a useful clinical indicator of later general functioning." I agree that this might be a rather good idea based on the current data; perhaps allied to some further chatter about ESSENCE and autism also (see here).---------- Gadow KD. et al. Parent-Reported Developmental Regression in Autism: Epilepsy, IQ, Schizophrenia Spectrum Symptoms, and Special Education. J Autism Dev Disord. 2017 Jan 10.----------Gadow KD, Perlman G, & Weber RJ (2017). Parent-Reported Developmental Regression in Autism: Epilepsy, IQ, Schizophrenia Spectrum Symptoms, and Special Education. Journal of autism and developmental disorders PMID: 28074354... Read more »
Gadow KD, Perlman G, & Weber RJ. (2017) Parent-Reported Developmental Regression in Autism: Epilepsy, IQ, Schizophrenia Spectrum Symptoms, and Special Education. Journal of autism and developmental disorders. PMID: 28074354
"Adolescents with ASD [autism spectrum disorder] spent less time in MVPA [moderate and vigorous physical activity] compared to TD [typically developing] adolescents (29 min/day vs. 50 min/day, p < 0.001) and fewer met the Physical Activity Guidelines for Americans (14 vs. 29%, p > 0.05)."So said the study results published by Heidi Stanish and colleagues  adding yet more to another growth autism research area - physical activity and exercise - a topic also fast becoming a repetitive blogging issue for me.It's not necessarily new news that physical activity and exercise levels are not what they could or should be for many people on the autism spectrum (see here) but rather that the use of objective measures such as accelerometers for data collection are starting to put some scientific flesh on previous 'what exercise did you do' type questionnaire studies. And the trend that is being revealed really is quite a disturbing one if one assumes that physical activity is a significant gateway to rude health and well-being, particularly in the context of ever-increasing waistlines and onward longitudinal effects. I might even point you in the direction of some new research hinting that MVPA in childhood might predict "fewer symptoms of major depressive disorders" later on; something that could be particularly relevant to autism in light of those over-represented comorbidities that I keep going on about (see here).Stanish et al have been mentioned before on this blog in the context of physical activity / exercise and autism and particularly the ways that said activity could be made more attractive to teens diagnosed on the autism spectrum (see here). Small steps and finding the right activity were some of the routes offered in that previous paper .Before I go I do want to briefly mention one point raised in the latest Stanish paper: "Walking/hiking and active video gaming were among the top activities for both groups." Both groups refers to adolescents with autism (n=35) and those described as typically developing (n=60) who were included for study (although much like the term 'neurotypical' I'm still at a loss as to the precise meaning of 'typically developing'). Walking/hiking... great, really worthwhile encouraging (see here) including exposing people to the great outdoors and that yellow thing usually high in the sky. 'Active videogaming' is something I'm a little less sure of at the moment and indeed, some people have talked about such 'exergaming' as being a poor substitute for the real thing . I don't doubt that one can build up a sweat on something like those new-fangled 'watch my movement' games consoles that abound these days, but might such exergaming just further feed into the 'screen time' narrative that typically accompanies sedentary behaviours?And of the multiple correlates potentially attached to low levels of physical activity, one might also count bone health  among them as being relevant to at least some autism...---------- Stanish HI. et al. Physical Activity Levels, Frequency, and Type Among Adolescents with and Without Autism Spectrum Disorder. J Autism Dev Disorders. 2017. Jan 9. Stanish H. et al. Enjoyment, Barriers, and Beliefs About Physical Activity in Adolescents With and Without Autism Spectrum Disorder. Adapt Phys Activ Q. 2015 Oct;32(4):302-17. Daley AJ. Can Exergaming Contribute to Improving Physical Activity Levels and Health Outcomes in Children? Pediatrics. 2009; 124: 2. Neumeyer AM. et al. Bone microarchitecture in adolescent boys with autism spectrum disorder. Bone. 2017 Jan 11. pii: S8756-3282(17)30009-1.----------Stanish, H., Curtin, C., Must, A., Phillips, S., Maslin, M., & Bandini, L. (2017). Physical Activity Levels, Frequency, and Type Among Adolescents with and Without Autism Spectrum Disorder Journal of Autism and Developmental Disorders DOI: 10.1007/s10803-016-3001-4... Read more »
Stanish, H., Curtin, C., Must, A., Phillips, S., Maslin, M., & Bandini, L. (2017) Physical Activity Levels, Frequency, and Type Among Adolescents with and Without Autism Spectrum Disorder. Journal of Autism and Developmental Disorders. DOI: 10.1007/s10803-016-3001-4
Zika Virus (ZIKV) is a positive sense RNA virus that belongs to the Flavivirus genus of the Flaviviridae family that includes other human pathogens including Hepatitis C Virus (HCV), Yellow Fever Virus (YFV), West Nile Virus, Dengue Virus (DENV), Tick Borne Encephalitis Virus (TBEV), and Japanese Encephalitis Virus (JEV).
Although being first isolated in 1947, until recently ZIKV was not associated with severe disease; following the introduction of ZIKV in the Americas however, foetal ZIKV infection became associated with neonatal cognitive defects, including viral Microcephaly as well as GBS in adult patients.
Like other flaviviruses such as DENV or JEV, ZIKV entry into host cells is mediated by several cell surface receptors that belong to the Tyro3-Axl-Mer (TAM) family of receptor tyrosine kinases, T cell immunoglobulin and mucin domain (TIM) phosphatidylserine (PS) and C-type lectin receptor families followed by endocytosis of the viral particle. As discussed in this post, activation of at least one of these receptors, Axl, by ZIKV might promote the inhibition of the secretion of pro-inflammatory cytokines.
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Retallack H, Di Lullo E, Arias C, Knopp KA, Laurie MT, Sandoval-Espinosa C, Mancia Leon WR, Krencik R, Ullian EM, Spatazza J.... (2016) Zika virus cell tropism in the developing human brain and inhibition by azithromycin. Proceedings of the National Academy of Sciences of the United States of America, 113(50), 14408-14413. PMID: 27911847
Brault JB, Khou C, Basset J, Coquand L, Fraisier V, Frenkiel MP, Goud B, Manuguerra JC, Pardigon N, & Baffet AD. (2016) Comparative Analysis Between Flaviviruses Reveals Specific Neural Stem Cell Tropism for Zika Virus in the Mouse Developing Neocortex. EBioMedicine, 71-6. PMID: 27453325
El Costa H, Gouilly J, Mansuy JM, Chen Q, Levy C, Cartron G, Veas F, Al-Daccak R, Izopet J, & Jabrane-Ferrat N. (2016) ZIKA virus reveals broad tissue and cell tropism during the first trimester of pregnancy. Scientific reports, 35296. PMID: 27759009
Quicke KM, Bowen JR, Johnson EL, McDonald CE, Ma H, O'Neal JT, Rajakumar A, Wrammert J, Rimawi BH, Pulendran B.... (2016) Zika Virus Infects Human Placental Macrophages. Cell host , 20(1), 83-90. PMID: 27247001
Wells MF, Salick MR, Wiskow O, Ho DJ, Worringer KA, Ihry RJ, Kommineni S, Bilican B, Klim JR, Hill EJ.... (2016) Genetic Ablation of AXL Does Not Protect Human Neural Progenitor Cells and Cerebral Organoids from Zika Virus Infection. Cell stem cell, 19(6), 703-708. PMID: 27912091
Leake DS, & Peters TJ. (1982) Lipid accumulation in arterial smooth muscle cells in culture. Morphological and biochemical changes caused by low density lipoproteins and chloroquine. Atherosclerosis, 44(3), 275-91. PMID: 7150393
Savidis, G., Perreira, J., Portmann, J., Meraner, P., Guo, Z., Green, S., & Brass, A. (2016) The IFITMs Inhibit Zika Virus Replication. Cell Reports, 15(11), 2323-2330. DOI: 10.1016/j.celrep.2016.05.074
Brass AL, Huang IC, Benita Y, John SP, Krishnan MN, Feeley EM, Ryan BJ, Weyer JL, van der Weyden L, Fikrig E.... (2009) The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus. Cell, 139(7), 1243-54. PMID: 20064371
Nour AM, Li Y, Wolenski J, & Modis Y. (2013) Viral membrane fusion and nucleocapsid delivery into the cytoplasm are distinct events in some flaviviruses. PLoS pathogens, 9(9). PMID: 24039574
Bailey CC, Zhong G, Huang IC, & Farzan M. (2014) IFITM-Family Proteins: The Cell's First Line of Antiviral Defense. Annual review of virology, 261-283. PMID: 25599080
Mercer, J. (2011) Viral Apoptotic Mimicry Party: P.S. Bring Your Own Gas6. Cell Host , 9(4), 255-257. DOI: 10.1016/j.chom.2011.04.002
Mercer J, & Helenius A. (2010) Apoptotic mimicry: phosphatidylserine-mediated macropinocytosis of vaccinia virus. Annals of the New York Academy of Sciences, 49-55. PMID: 20958316
Desai TM, Marin M, Chin CR, Savidis G, Brass AL, & Melikyan GB. (2014) IFITM3 restricts influenza A virus entry by blocking the formation of fusion pores following virus-endosome hemifusion. PLoS pathogens, 10(4). PMID: 24699674
Morizono K, Xie Y, Olafsen T, Lee B, Dasgupta A, Wu AM, & Chen IS. (2011) The soluble serum protein Gas6 bridges virion envelope phosphatidylserine to the TAM receptor tyrosine kinase Axl to mediate viral entry. Cell host , 9(4), 286-98. PMID: 21501828
Meertens L, Carnec X, Lecoin MP, Ramdasi R, Guivel-Benhassine F, Lew E, Lemke G, Schwartz O, & Amara A. (2012) The TIM and TAM families of phosphatidylserine receptors mediate dengue virus entry. Cell host , 12(4), 544-57. PMID: 23084921
Abderrazak A, Syrovets T, Couchie D, El Hadri K, Friguet B, Simmet T, & Rouis M. (2015) NLRP3 inflammasome: from a danger signal sensor to a regulatory node of oxidative stress and inflammatory diseases. Redox biology, 296-307. PMID: 25625584
Bhattacharyya S, Zagórska A, Lew ED, Shrestha B, Rothlin CV, Naughton J, Diamond MS, Lemke G, & Young JA. (2013) Enveloped viruses disable innate immune responses in dendritic cells by direct activation of TAM receptors. Cell host , 14(2), 136-47. PMID: 23954153
Wang J, Qiao L, Hou Z, & Luo G. (2017) TIM-1 Promotes Hepatitis C Virus Cell Attachment and Infection. Journal of virology, 91(2). PMID: 27807228
Han J, Bae J, Choi CY, Choi SP, Kang HS, Jo EK, Park J, Lee YS, Moon HS, Park CG.... (2016) Autophagy induced by AXL receptor tyrosine kinase alleviates acute liver injury via inhibition of NLRP3 inflammasome activation in mice. Autophagy, 12(12), 2326-2343. PMID: 27780404
"Vitamin D treatment significantly improved fatigue in otherwise healthy persons with vitamin D deficiency."Supplementation details, described in the paper by Albina Nowak and colleagues  (open-access available here), were a single dose of 100,000 IU [international units] of vitamin D or a placebo (mannitol) administered to 120 adult participants who presented with "fatigue and vitamin D deficiency (serum 25(OH)D < 20 μg/L)." This was a double-blind trial and self-perceived fatigue was measured using the fatigue assessment scale (FAS) at baseline (before intervention) and after 4 weeks.This is an interesting paper but not without some issues. Use of the FAS is OK but I would have preferred to see something else accompanying the data derived from this schedule when it comes to something like self-reported fatigue. The authors did rely on a "short self-developed fatigue test (fatigue course assessment; FCA)" too during their study but I was thinking of something a little more standardised. Although data for some 120 participants were available for the study results , I was a little surprised to see that some 280 participants were initially screened for study inclusion; most of whom did not make the cut. The vast majority (n=103) were cut because "25-OH vitamin D levels >20 μg/L" or in other words, they were not classified as vitamin D deficient based on analysis by immunoassay. Bearing in mind the idea that deficiency is not the only categorisation when it comes to vitamin D and not everyone agrees where deficiency actually starts and stops, I'd perhaps have liked to have seen some more information about those excluded, particularly those on the periphery of being classified as deficient and what supplementation might have meant for them.It's also interesting to see the strength of the placebo effect when it came to the study results as alongside the 70%+ who reported "amelioration" of fatigue who were actually in receipt of vitamin D, so half of the placebo group also registered the same/similar improvement. As far as I know mannitol is not known as a fatigue reducing agent so there's potentially something more going on here. "A significant increase in 25-OH vitamin D was observed in vitamin D but not in placebo-treated participants." Given the supplementation of vitamin D at such a high dose it's perhaps not surprising that vitamin D levels went up for those consuming the supplement.The Nowak results do stand, and even though they were based on self-reported fatigue in an otherwise healthy cohort, I do wonder whether there may be some tie-ups with other independent study (see here for example). Accepting that there may be many reasons for fatigue, I'm also inclined to point out that for perhaps at least a subset of those diagnosed with something like chronic fatigue [syndrome], there could be some additional studies to undertake bearing in mind the authors assertion that: "our study results are not generalizable to CFS [chronic fatigue syndrome]."To close, what if ‘There's Something About Mary’ was trailed as a Psychological Thriller?---------- Nowak A. et al. Effect of vitamin D3 on self-perceived fatigue: A double-blind randomized placebo-controlled trial. Medicine (Baltimore). 2016 Dec;95(52):e5353.----------Nowak A, Boesch L, Andres E, Battegay E, Hornemann T, Schmid C, Bischoff-Ferrari HA, Suter PM, & Krayenbuehl PA (2016). Effect of vitamin D3 on self-perceived fatigue: A double-blind randomized placebo-controlled trial. Medicine, 95 (52) PMID: 28033244... Read more »
Nowak A, Boesch L, Andres E, Battegay E, Hornemann T, Schmid C, Bischoff-Ferrari HA, Suter PM, & Krayenbuehl PA. (2016) Effect of vitamin D3 on self-perceived fatigue: A double-blind randomized placebo-controlled trial. Medicine, 95(52). PMID: 28033244
"Rates of ASD [autism spectrum disorder] and ASD traits are elevated in a psychosis population."The paper by Debbie Kincaid and colleagues  provides yet more [short] blogging material pertinent to the increasing interest in how psychosis may be yet another comorbidity over-represented when it comes to autism (see here) and vice-versa. I know this is another topic that has to be treated with some caution in terms of concepts like stigma but more discussions - science discussions - are needed to ensure that appropriate screening, diagnosis and also management is available to those who might need it.A systematic review was the name of the research game for Kincaid et al as seven studies "reporting prevalence rates of Autistic-like Traits (ALTs) and ASD in populations with a diagnosis of schizophrenia or other psychotic disorder" were included. The results weren't exactly precise in terms of what was reported as anywhere between 9-61% of those diagnosed with psychosis presented with those ALTs and between 1-52% of those with psychosis were also diagnosed with an autism spectrum disorder (ASD). The authors however are correct when they point out that the "prevalence rates of ALTs and ASD in psychosis populations are much higher than in the general population." Quite a bit higher if one looks at the top end of those prevalence stats.I'll leave it at that for now.---------- Kincaid DL. et al. What is the prevalence of Autism Spectrum Disorder and ASD traits in psychosis? A systematic review. Psychiatry Research. 2017. Jan 6.----------Kincaid, D., Doris, M., Shannon, C., & Mulholland, C. (2017). What is the prevalence of Autism Spectrum Disorder and ASD traits in psychosis? A systematic review Psychiatry Research DOI: 10.1016/j.psychres.2017.01.017... Read more »
Kincaid, D., Doris, M., Shannon, C., & Mulholland, C. (2017) What is the prevalence of Autism Spectrum Disorder and ASD traits in psychosis? A systematic review. Psychiatry Research. DOI: 10.1016/j.psychres.2017.01.017
The bacterium, Deinococcus radiodurans, is thought to be discovered as a contaminant in radiation-sterilized cans in 1960s. The name of the bacterium comes from the Ancient Greek, i.e. deinos and kokkos meaning “terrible grain/berry”, and the Latin language, i.e. radius and durare, meaning “radiation surviving”. The bacterium is also known as Conan the Bacterium.
Deinococcus radiodurans is a comparatively larger bacterium having spherical shape. It is a red-pigmented bacterium that does not cause diseases. The bacterium also possesses a highly efficient DNA repair system that is thought to be responsible for the unbelievable survival strategies.
It is considered as the toughest bacterium in the world as it is highly resistant to radiations, i.e. it can resist thousand times more radiation as compared to a normal person. The bacterium also has a strong ability to survive in conditions of cold, vacuum, dehydration, and acid. Therefore, it is also known as polyextremophile.
Deinococcus radiodurans in a dish (Source: science.nasa.gov)
Deinococcus radiodurans in a dish (Source: science.nasa.gov)
Deinococcus radiodurans has also been used by scientists for the consumption and digestion of solvents as well as heavy metals. It is also thought to have an ability to store information that can survive even after huge catastrophes.
Data stored in multiplying bacteria – https://www.newscientist.com/article/dn3243-data-stored-in-multiplying-bacteria/
Genome News Network – http://www.genomenewsnetwork.org/articles/07_02/deinococcus.shtml
The Possible Mechanisms Involved in the Protection Strategies against Radiation-Induced Cellular Damage by Carnitines – http://file.scirp.org/Html/1-2101023_53873.htm
Krisko, A., & Radman, M. (2013). Biology of Extreme Radiation Resistance: The Way of Deinococcus radiodurans Cold Spring Harbor Perspectives in Biology, 5 (7) DOI: 10.1101/cshperspect.a012765
Meet Conan the Bacterium – https://science.nasa.gov/science-news/science-at-nasa/1999/ast14dec99_1... Read more »
Krisko, A., & Radman, M. (2013) Biology of Extreme Radiation Resistance: The Way of Deinococcus radiodurans. Cold Spring Harbor Perspectives in Biology, 5(7). DOI: 10.1101/cshperspect.a012765
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