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  • April 10, 2015
  • 04:34 PM
  • 126 views

Enzyme in cosmetic products can cause allergy

by Dr. Jekyll in Lunatic Laboratories

Papain is found naturally in papaya and is often referred to as a "plant-based pepsin" in reference to the digestive enzyme pepsin that is present in the stomach. Researchers looked at the effect of papain directly on the skin of mice as well as on skin cells in the petri dish. Skin consists of several layers joined via cellular connections called "tight junctions". The project team showed that papain induces a breakdown of these cell-cell junctions. On the skin, papain results in a loss of the barrier function.... Read more »

  • April 10, 2015
  • 05:48 AM
  • 178 views

More ophthalmic findings in autism

by Paul Whiteley in Questioning Answers

"Ophthalmic pathology was noted in 26.9 % of patients with ASD [autism spectrum disorder], of which 22 % had significant refractive errors and 8.6 % had strabismus."That was the conclusion reached in the paper by Emrah Utku Kabatas and colleagues [1] based on the premise that: "Children with autism spectrum disorders (ASD) frequently have ophthalmologic disorders"; that is, issues with the anatomy and function of the eyes.We've been here before. I'll take you back to the post that I wrote around the paper by Ikeda and colleagues [2] and their quite remarkable suggestion that ophthalmic pathology was present in 40% of people with autism or a related disorder. Such cumulative evidence should be enough to convince even the most sceptical healthcare providers that they should be setting up regular eye care appointments for every person diagnosed with autism. More so when perhaps autism is joined with faddy eating habits and the important effects that nutritional deficiency might also bring to eye health (see here).Music: Kate Bush - Hounds of Love.----------[1] Kabatas EU. et al. Initial Ophthalmic Findings in Turkish Children with Autism Spectrum Disorder. J Autism Dev Disord. 2015 Mar 24. [2] Ikeda J. et al. Brief report: incidence of ophthalmologic disorders in children with autism. J Autism Dev Disord. 2013 Jun;43(6):1447-51.----------Kabatas EU, Ozer PA, Ertugrul GT, Kurtul BE, Bodur S, & Alan BE (2015). Initial Ophthalmic Findings in Turkish Children with Autism Spectrum Disorder. Journal of autism and developmental disorders PMID: 25800865... Read more »

Kabatas EU, Ozer PA, Ertugrul GT, Kurtul BE, Bodur S, & Alan BE. (2015) Initial Ophthalmic Findings in Turkish Children with Autism Spectrum Disorder. Journal of autism and developmental disorders. PMID: 25800865  

  • April 9, 2015
  • 03:06 PM
  • 161 views

Do you have the genes of a rapist?

by Dr. Jekyll in Lunatic Laboratories

Rape, it’s so taboo that victims are sometimes shamed for “letting” it happening. It’s a dirty word, no one likes the word rape so we come up with other names for it — sexual assault for example. Well new research shows that close relatives of men convicted of sexual offences commit similar offences themselves more frequently than comparison subjects. The study suggests that this is due to genetic factors rather than shared family environment. The study includes all men convicted of sex crime in Sweden during 37 years.... Read more »

Langstrom, N., Babchishin, K., Fazel, S., Lichtenstein, P., & Frisell, T. (2015) Sexual offending runs in families: A 37-year nationwide study. International Journal of Epidemiology. DOI: 10.1093/ije/dyv029  

  • April 9, 2015
  • 10:38 AM
  • 157 views

Brain Volume Differences in ADHD Normalize By Adulthood

by William Yates, M.D. in Brain Posts

Brain volume differences in ADHD have been documented in some childhood studies.ADHD symptoms diminish with maturation in many but not all individuals. It is unclear whether this improvement in symptoms is also related to maturation of brain regions.A recent study from the Netherlands provides some answers on this issue. A. Marten H. Onnink and colleagues performed a structural MRI study of 119 adults with ADHD compared to a group of controls.This study is important because it examined effects of gender, comorbid depression and treatment history on key brain regions including the basal ganglia, amygdala and hippocampus.The key findings from this study include the following:Women with adult ADHD showed no differences from controls on brain volume measuresMen with adult ADHD showed reduced right caudate volumes and these volumes were negatively correlated with current hyperactivity symptom scoresComorbid major depression in adult ADHD was linked to smaller hippocampus volumes. ADHD without a history of depression was not linked to any differences in hippocampal volumesA history of major depression in ADHD subjects was common (37% of men and 52% of women). Additionally, this sample high rates of current stimulant use (69% of the sample).The authors note their study found essentially no link between adult ADHD and brain volumes. The only exception was the finding of reduced right caudate volumes in men with ADHD. The authors also note:"Although male and female adults with ADHD have similar phenotypic features in terms of symptom rating and comorbidity patterns, the gender-specific finding for caudate nucleus volume suggests that partially distinct neurobiological deficits underlie ADHD in males and females."Structural brain measures are only one element of brain imaging in ADHD and other disorders. In my previous posts, I reviewed studies linking ADHD with functional connectivity (white matter) deficits in both children and adults.Studies of neural networks in ADHD continue to be an important area for future research. Understanding network abnormalities will be key in understanding the pathophysiology of the disorder.Readers with more interest in this topic can access the free full text manuscript by clicking on the PMID link in the citation below.Figure is from a screen shot of the basal ganglia from the iPad app 3D Brain. It illustrates the brain caudate region found to be reduced in adult men but not women with ADHD.Follow the author on Twitter @WRY999.Onnink AM, Zwiers MP, Hoogman M, Mostert JC, Kan CC, Buitelaar J, & Franke B (2014). Brain alterations in adult ADHD: effects of gender, treatment and comorbid depression. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 24 (3), 397-409 PMID: 24345721... Read more »

Onnink AM, Zwiers MP, Hoogman M, Mostert JC, Kan CC, Buitelaar J, & Franke B. (2014) Brain alterations in adult ADHD: effects of gender, treatment and comorbid depression. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 24(3), 397-409. PMID: 24345721  

  • April 9, 2015
  • 03:31 AM
  • 161 views

Effects of prenatal organophosphate pesticide exposure on a mouse model of autism

by Paul Whiteley in Questioning Answers

Pesticides and autism is a topic previously covered on this blog (see here for example). The idea that some of the various preparations that we use to control the pests which have an ability to blight our crops or cause serious health issues could be linked to an increased risk of autism is an area likely to invoke some divisions within elements of the autism and wider scientific community.Part of the problem with the available evidence suggesting a link between autism and pesticide exposure is that it is, to a large extent, observational and correlational. As per the paper from Janie Shelton and colleagues [1], results are based on variables such as looking at what types and amounts of pesticides are used in a specific area and correlating proximity to that area as a function of a diagnosis of autism or not. Similar to the work looking at other environmental factors linked (or not) to autism such as air pollution (see here), it's all about where and when you were, followed by calculations on your probable exposure being tied into risk.The paper from Alessia De Felice and colleagues [2] (open-access) approaches the research area of pesticide exposure and autism (a model of autism) from a slightly different angle. Their findings were based on the use of a mouse model of autism and what happened to mouse offspring when mother mice were exposed to a particular pesticide "at doses devoid of maternal or systemic toxicity."The mouse model in question was a favourite in autism research circles, the BTBR T+tf/J strain (see here). The pesticide used was "the organophosphate insecticide chlorpyrifos (CPF)." Organophosphate (OP) by the way, refers to the chemical make-up of the compound and its particular effects on the enzyme acetylcholinesterase working in a similar fashion to certain warfare agents.The De Felice paper is open-access but as ever, a few details are provided:Recognising that pesticide exposure already has quite a long history in terms of adverse health effects (pesticide applicators of the world take note), the authors set about looking to "evaluate in the offspring of both sexes the effect of the gestational CPF exposure on spontaneous locomotion, ultrasonic vocalization and neurodevelopment during the first two weeks of postnatal life, to evidence early changes in behavioral profile." Further they decided to "evaluate the long-term effects of CPF on selected markers of the peculiar behavioral repertoire of this mouse strain." You'll note that the word autism does not appear in either of those aims.Male and female BTBR mice were allowed to 'get it on' in breeding cages. Females mice were regularly inspected for evidence of carrying a baby mouse and 14 days into the pregnancy were either given peanut oil (vehicle) or CPF dissolved in peanut oil by oral gavage for 4 days. This was given as a single dose.Baby mice were born ("Twenty-four litters (13 Vehicle-treated and 11 CPF-treated"). Various behavioural assessments were conducted including an analysis of ultrasonic vocalisations and spontaneous movements. Various other behavioural measures were also made when the baby mice grew into adult mice.Results: "prenatal CPF exposure significantly modifies spontaneous motor activity in BTBR pups, delaying their motor development and further enhancing the abnormally high vocalization rates." The authors also reported reduced weight gain in CPF exposed offspring during the early days. Looking into adulthood, CPF exposure seemed to show more pronounced effects for males over females with an "altered pattern of investigation of a sexual partner." This finding has however been downplayed by the authors to a certain extent. They conclude with the need for further research in this area "to evaluate the role of environmental chemicals in the etiology of neurodevelopment disorders."Taking a few steps back, one has to remember that this was a study of mouse exposure to pesticides not humans. Indeed, other similar work from some of the authors has also recently seen the light of day [3]. As per other discussions, mice might be good 'models' of something like autism but they are never ever going to reflect autism (and its important comorbidities) in their entirety. Given also that the BTBR mouse "exhibit a 100% absence of the corpus callosum and a severely reduced hippocampal commissure" according to suppliers, one has to be careful about any sweeping generalisations to all autism. The timing and route of CPF exposure described by De Felice et al might also be seen as potentially important variables insofar as their focus some time into pregnancy and sole reliance on the oral route of exposure. That all being said, these are potentially important results not least because of their focus on how both genes and environment might be implicated in [models of] cases of autism. As I've mentioned, this was a study of offspring BTBR mice thus implying that there may be some familial predisposition to mimicking the effects of autism anyway. The idea that in predisposed individuals there may be additional effects from an environmental factor is an important one and perhaps complements the whole 'air pollution effects modified by genotype' suggestion (see here) with autism in mind. Certainly, I think there is quite a bit more research to see and do in this area.Music: Buddy Holly - Rave on!----------[1] Shelton JF. et al. Neurodevelopmental disorders and prenatal residential proximity to agricultural pesticides: The CHARGE study. Environ Health Perspect. 2014: June 23.[2] De Felice A. et al. Prenatal Exposure to a Common Organophosphate Insecticide Delays Motor Development in a Mouse Model of Idiopathic Autism. PLoS One. 2015 Mar 24;10(3):e0121663.[3] Venerosi A. et al. Effects of maternal chlorpyrifos diet on social investigation and brain neuroendocrine markers in the offspring – a mouse study. Environmental Health 2015, 14:32.----------... Read more »

  • April 8, 2015
  • 06:25 PM
  • 156 views

First human HIV-antibody trials, results are promising

by Dr. Jekyll in Lunatic Laboratories

While there is no cure for HIV, a select few known as HIV controllers can literally live with it. Over the years work has been done trying to figure out what makes these individuals so special and it has helped researchers in the fight against HIV. While we are still searching for a vaccine, researchers have now found that a single infusion of an experimental anti-HIV antibody called 3BNC117 resulted in significantly decreased HIV levels that persisted for as long as 28 days in HIV-infected individuals, according to Phase 1 clinical trial findings.... Read more »

Caskey, M., Klein, F., Lorenzi, J., Seaman, M., West, A., Buckley, N., Kremer, G., Nogueira, L., Braunschweig, M., Scheid, J.... (2015) Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117. Nature. DOI: 10.1038/nature14411  

  • April 8, 2015
  • 11:16 AM
  • 177 views

Adult ADHD and Brain White Matter Deficits

by William Yates, M.D. in Brain Posts

In my last post I reviewed a recent diffusion tensor imaging study of ADHD in children. This study found evidence for brain white matter deficits in several ciruitry regions including frontal, temporal and occipital areas.To follow up on this post, I want to highlight a recent study of DTI in adults with ADHD.This study from Brazil recruited 22 drug treatment-naive subjects between the ages of 18 and 50 years of age.This study excluded subjects with a history of substance dependence or other medical or neurological conditions that could confound the findings. However, 7 of the 22 did endorse other axis I mental disorders including 4 with bipolar disorder, 2 with major depression and 1 with anxiety disorder.These adults subjects reported early onset of ADHD symptoms (before age 7) that persisted into adulthood.Using all 22 with ADHD the research team reported multiple areas of differences compared to the healthy control group:Higher fractional anisotropy in ADHD: bilateral frontal gyrus, right middle frontal gyrus, left postcentral gyrus, bilateral cingulate gyrus, bilateral temporal gyrus and right superior temporal gyrusReduced diffusivity measures in ADHD: fronto-striatal-parieto-occipital circuits, corpus callosum circuits, right superior corona radiata and fronto-occipital circuitsA significant finding in this study was the limited findings for ADHD subjects without an axis I comorbidity.Using only these relatively "pure" ADHD subjects most of the findings lost statistical significance although a trend remained for several regions and circuits including:Reduced gray matter volumes in right superior frontal gyrus, right cingulate gyrus and left postcentral gyrusHigher fractional anisotropy in right superior frontal gyrus, right cingulate gyrus and left postcentral gyrusReduced diffusivity in right splenium of the corpus callosum and white matter underlying the right cingulate gyrusThis study highlights some of the research study design problems in adult ADHD. First, many adults with ADHD will have received drug treatment and the effects of drug treatment must be controlled in the analysis. Second, many adults with ADHD will have other significant axis I disorders. These disorders may contribute to white matter deficits found with imaging. It is important to assess for these effects in reporting findings that are felt to be specific to an ADHD diagnosis.One common comorbidity in childhood ADHD is conduct disorder and this disorder needs to be assessed in both children and adults with ADHD.It is challenging to find subjects with only an axis I ADHD diagnosis for imaging and other types of research.The present study supports diffuse white matter deficits in adults with ADHD although the link specifically to an ADHD diagnosis remains unclear.Readers with more interest in this study can access the free full-text manuscript by clicking on the PMID link below.Figure demonstrates the anatomy of the corona radiata white matter tracts in the brain and is a screen shot from the iPad app Brain Tutor. The authors found abnormalities in those with ADHD in the right corona radiata although this finding was not found in the "pure" ADHD group.Follow the author on Twitter @WRY999Chaim TM, Zhang T, Zanetti MV, da Silva MA, Louzã MR, Doshi J, Serpa MH, Duran FL, Caetano SC, Davatzikos C, & Busatto GF (2014). Multimodal magnetic resonance imaging study of treatment-naïve adults with attention-deficit/hyperactivity disorder. PloS one, 9 (10) PMID: 25310815... Read more »

  • April 8, 2015
  • 01:34 AM
  • 169 views

Cleanrooms and autism?

by Paul Whiteley in Questioning Answers

The paper by Scott Faber and colleagues [1] (open-access) is the topic of today's post and the idea that a cleanroom sleeping environment might impact on some important issues accompanying at least some autism.Just in case you hadn't come across the concept of a cleanroom, the concept is that a space is provided where various systems are put in place to control environmental pollutants such as dust, microbes and various chemical emissions. More readily associated with the construction of microchips, satellites or the preparation of various pharmaceutics, I was unable to find any previous studies on the use of cleanrooms 'for autism' so the Faber study seems to represent a bit of a first...The study is open-access but here are a few details:Ten children diagnosed with an autism spectrum disorder (ASD) with "prior evidence of heavy metal and chemical toxicity and immune dysregulation seen through low plasma zinc/serum copper ratios and abnormal T and B cell subsets, respectively" were included for study.Then: "each child and a parent spent two consecutive weeks sleeping in the cleanroom between May and October 2010." The cleanroom in question was based at The Children's Institute and consisted of HEPA filters, cleanroom bedding, a UV water purification system and was "furnished with ash furniture sealed with water soluble polyurethane." Cleanroom status was confirmed via particle counting.Behaviour, blood and hair were collected and tested pre- and post-cleanroom attendance. Blood and hair were analysed for various compounds including nutrients and externally-derived chemicals. Glutathione levels (total, reduced and oxidised) were also assayed for using everyone's favourite analytical method: mass spectrometry.Results: children's results were analysed on the basis of their grouping into a younger age cohort (5 and under) and an older age cohort (6 and older). Bearing in mind the small participant numbers: "The overall pattern of results indicates greater improvements in immune dysregulation and behavior in the younger children, age 5 and under." But: "The older children displayed a worsening in behavioral rating scale performance, which may have been caused by the mobilization of toxins from their tissues."Among the various results presented, glutathione status seemed to change for at least some of the children over the course of cleanroom residence which the authors interpreted as possibly indicating: "a reduction of oxidative stress." The idea that some children actually presented with increased levels of certain toxicants following their cleanroom experience is an interesting one. "Out of the ten participants, eight decreased mean serum benzene, six increased mean serum toluene and five increased serum xylene." Further: "One possible explanation for these results is that, throughout the study, VOCs were mobilized from tissues into the serum at varying rates."The authors conclude: "The performance of a controlled study of 24 hour per day cleanroom exposure for children with autism appears to be an appropriate next step, given the physiologic changes from the limited exposure to a cleanroom environment noted in this study."Whilst I did find this to be an interesting study, there are a couple of caveats to mention. This was a straight forward open trial of cleanrooms for autism so 'preliminary' is an important word to use in relation to the results. I note also that whilst the trial was registered with ClinicalTrials.org (see here) it seems to have been done pretty retrospectively ("First received: July 16, 2014")."The child and parent arrived at TCI and spent approximately ten hours each evening in the cleanroom while wearing silk or cotton clothes." What this means is that during the day, when most people are moving around various environments (including the great outdoors) participants were not contained in that sterile environment. There could have been a myriad of different variables to account for the results during this 'free time' including the idea that parents themselves may have altered their child's routines as a function of being part of the study. I say this not to somehow sabotage the results, merely to say that in a study looking at 'detoxification' in relation to autism, one can't discount other factors coming into play.Insofar as the idea that 'a controlled study of 24 hour per day cleanroom exposure' might be indicated, I think we might have to take a small step back before this is considered. With the limited exposure I've had to cleanrooms during my career I can safely say that I would not take lightly to spending even one day/night in a cleanroom environment. Not least because of the limited living space that would be available as a result of cost considerations but also how the study is potentially talking about housing young children with autism in such an environment and what that might mean for them and an important disruption to their home/school routine among others. That being said I do like one idea discussed by the authors that: "Younger children may have felt an extra closeness to their parents during the study, leading to positive behavioral change." Yes, it's a shocker: children generally love being next to their parents.Music from Ian Dury & The Blockheads.-----------[1] Faber S. et al. A cleanroom sleeping environment’s impact on markers of oxidative stress, immune dysregulation, and behavior in children with autism spectrum disorders. BMC Complementary and Alternative Medicine 2015, 15:71 ----------Faber, S., Zinn, G., Boggess, A., Fahrenholz, T., Kern, J., & Kingston, H. (2015). A cleanroom sleeping environment’s impact on markers of oxidative stress, immune dysregulation, and behavior in children with autism spectrum disorders BMC Complementary and Alternative Medicine, 15 (1) DOI: 10.1186/s12906-015-0564-0... Read more »

  • April 7, 2015
  • 12:59 PM
  • 159 views

Master protein enhances learning, memory and fitness?!

by Dr. Jekyll in Lunatic Laboratories

You're supposed to stay fit, the key to successful aging is to be active. Science doesn't quite understand why, but staying fit helps keep our brain in shape as we get older. I hate to run, hate it, but I exercise my brain often. Truthfully, some people seem built to run marathons and have an easier time going for miles without tiring. Other individuals might be born with a knack for memorizing things, from times tables to trivia facts. These two skills―running and memorizing―are not so different as it turns out.... Read more »

Liming Pei, Yangling Mu, Mathias Leblanc, William Alaynick, Grant D. Barish, Matthew Pankratz, Tiffany W. Tseng, Samantha Kaufman, Christopher Liddle, Ruth T. Yu.... (2015) Dependence of Hippocampal Function on ERRγ-Regulated Mitochondrial Metabolism. Cell metabolism. DOI: http://dx.org/10.1016/j.cmet.2015.03.004  

  • April 7, 2015
  • 11:57 AM
  • 140 views

ADHD and Brain White Matter Deficits

by William Yates, M.D. in Brain Posts

Structural brain imaging studies in ADHD fail to find consistent differences from non-ADHD populations.However, there is increasing evidence linking ADHD to changes in brain white matter function.An example of these findings is a recent study from China examining white matter in children with ADHD.ADHD is typically subgrouped into inattention (ADHD-I), hyperactivity ADHD-H or combined categories (ADHD-C). In the recent Chinese study, inattention and combined subgroups of children were compared to control children without ADHD.Diffusion tensor imaging or DTI was utilized in this study. This imaging techniques allow study of white matter function in various brain regions. A variety of specific connectivy circuits have been identified. The brain white matter connects brain regions in circuits allowing coordinated processing, cognition and behavior.Using DTI measures of white matter integrity and function are calculated. These parameters are known as fractional anisotropy, radial diffusivity and axial diffusivity. The key findings from the Chinese study included the following:ADHD-I children showed white matter abnormalities in the temporo-occipital circuitsADHD-C showed the temporo-occipital abnormalities found in ADHD-I but had additional white matter abnormalities in the frontal-subcortical and fronto-limbic circuit regionsDeficits in the brain region known as the cuneus and precuneus correlated with inattention scores  This study is one of the first to suggest distinct brain white matter regional abnormalities in two subtypes of ADHD. Although both subtypes showed abnormalities in the temporo-occipital circuits, ADHD-C alone showed abnormalities in circuits related to motor function.These brain white matter differences in a group of children of mean age 9 years may represent developmental delays that improve over time. Many adolescents and adults with childhood ADHD symptoms show significant improvement in later stages of development. However, some adolescents and adults will have persistent ADHD symptoms. In the next post, I will summarize a brain imaging study of adults with ADHD.Readers with more interest in this study can access the free full-text manuscript by clicking on the PMID link below.Figure is a screen shot from the iPad app 3D brain. It shows the white matter circuit fibers connecting the temporal lobe and occipital lobe. Deficits in this circuitry were noted in both types of ADHD in the present study.Follow the author on Twitter @WRY999Lei D, Ma J, Du X, Shen G, Jin X, & Gong Q (2014). Microstructural abnormalities in the combined and inattentive subtypes of attention deficit hyperactivity disorder: a diffusion tensor imaging study. Scientific reports, 4 PMID: 25363043... Read more »

  • April 7, 2015
  • 02:45 AM
  • 164 views

Candida albicans triggering coeliac disease?

by Paul Whiteley in Questioning Answers

Will the bafflement around coeliac (celiac) disease ever stop?I want you to cast your eye over the paper from Marion Corouge and colleagues [1] (open-access) and the interesting hypothesis that: "CI [Candida albicans infection] may trigger CeD [coeliac disease] onset in genetically-susceptible individuals."Continuing a theme of 'bafflement' when it comes to the autoimmune condition known as coeliac disease (see here), Corouge et al reported that a protein, hyphal wall protein 1 (Hwp1) present in C. albicans, 'required for hyphal development and yeast adhesion to epithelial cells' "presents sequence analogy with the gluten protein gliadin and is also a substrate for transglutaminase." Further a: "suggestion that C. albicans infection (CI) may be a triggering factor for Celiac disease (CeD) onset."Just in case you aren't au fait with all-things coeliac disease, my training post on the condition might come in useful (see here). Gliadin is a type of protein found in wheat and other cereal produce which together with the glutenins make up gluten. Gluten is the stuff that those with coeliac disease have to avoid as a consequence of the peptides that it eventually is metabolised into meeting a specific (geno)type of immune system. Transglutaminase reflects enzymatic alterations to said gluten peptides and a sort of 'super-charging' of them (deamidation) with reference to that 'coeliac immune system' and the processes it starts/continues.There is quite a bit of chemistry included in the Corouge paper but the main results were:"using recombinant Hwp1" the authors reported "serological cross-reactivity in humans between this C. albicans antigen and gliadin." This translates into Hwp1 and gliadin - peptides from gliadin - potentially having something of a shared ability to invoke an immune response or be involved in immune processes pertinent to coeliac disease.Looking at serum samples from participants diagnosed with coeliac disease or presenting with "systemic CI" researchers also reported that: "CI and CeD patients had higher levels of anti-Hwp1... and anti-gliadin... antibodies" than asymptomatic control specimens. Interestingly, they couldn't [significantly] differentiate between the coeliac and CI samples on these parameters .When plotting Hwp1 levels and anti-gliadin antibodies "during the course of C. albicans infection" they found that the expected increase in anti-Hwp1 antibodies was also accompanied by an "increase in anti-gliadin antibodies that paralleled the anti-Hwp1 response."Finally: "The decrease in levels of anti-gliadin antibodies in GFD [gluten-free diet] -adherent compared to non-adherent CeD patients further validates the clinical classification used." That being said: "the relative independence of anti-Hwp1 antibodies from a GFD" hints that the gluten-free diet might do many things but not necessarily everything in this suggested relationship.A final quote from the paper is worthwhile reproducing: "This study has revealed immune cross-recognition between two substrates of the potential auto-antigen transglutaminase, namely the fungal “invasive” protein Hwp1 and the dietary ‘innocuous” vegetal protein gliadin. Together our data, obtained from a translational comparative analysis of an infectious and an auto-immune disease, support the hypothesis... that the former may trigger the development of the latter."Independent replication is the name of the game when it comes to the Corouge results before anyone gets too carried away with the possible implications. That being said, the idea that in those possessing the risk genotype of coeliac disease a bout of Candida albican infection might have the ability to set the biological wheels in motion in a journey towards the condition (or even perpetuating the condition) represents a potentially important finding [2]. One might also question whether similar cross reactivity (molecular mimicry?) might also be transferable to other autoimmune conditions and whether the agent of choice has to necessarily be just a fungus [3]?Music: Kings Of Leon - The Bucket.----------[1] Corouge M. et al. Humoral Immunity Links Candida albicans Infection and Celiac Disease. PLoS One. 2015 Mar 20;10(3):e0121776.[2] Nieuwenhuizen WF. et al. Is Candida albicans a trigger in the onset of coeliac disease? Lancet. 2003 Jun 21;361(9375):2152-4.[3] Cabrera-Chávez F. et al. Maize prolamins resistant to peptic-tryptic digestion maintain immune-recognition by IgA from some celiac disease patients. Plant Foods Hum Nutr. 2012 Mar;67(1):24, 30.----------Corouge M, Loridant S, Fradin C, Salleron J, Damiens S, Moragues MD, Souplet V, Jouault T, Robert R, Dubucquoi S, Sendid B, Colombel JF, & Poulain D (2015). Humoral Immunity Links Candida albicans Infection and Celiac Disease. PloS one, 10 (3) PMID: 25793717... Read more »

Corouge M, Loridant S, Fradin C, Salleron J, Damiens S, Moragues MD, Souplet V, Jouault T, Robert R, Dubucquoi S.... (2015) Humoral Immunity Links Candida albicans Infection and Celiac Disease. PloS one, 10(3). PMID: 25793717  

  • April 6, 2015
  • 05:54 PM
  • 158 views

It’s all hype: Few commercial weight-loss programs are effective

by Dr. Jekyll in Lunatic Laboratories

In a bid to help physicians guide obese and overweight patients who want to try a commercial weight-loss program, a team of Johns Hopkins researchers reviewed 4,200 studies for solid evidence of their effectiveness but concluded only a few dozen of the studies met the scientific gold standard of reliability.... Read more »

Kimberly A. Gudzune, MD, MPH, Ruchi S. Doshi, BA, Ambereen K. Mehta, MD, MPH, Zoobia W. Chaudhry, MD, David K. Jacobs, BA, Rachit M. Vakil, BS, Clare J. Lee, MD, Sara N. Bleich, PhD, & Jeanne M. Clark, MD, MPH. (2015) Efficacy of Commercial Weight-Loss Programs: An Updated Systematic Review. Annals of Internal Medicine. info:/10.7326/M14-2238

  • April 6, 2015
  • 03:27 PM
  • 171 views

Researchers find protein that triggers lupus-associated immune system activation

by Dr. Jekyll in Lunatic Laboratories

Researchers have identified an inflammatory molecule that appears to play an essential role in the autoimmune disorder systemic lupus erythematosus, commonly known simply as lupus. In their report the team describes finding that a protein that regulates certain cells in the innate immune system – the body’s first line of defense against infection – activates a molecular pathway known to be associated with lupus and that the protein’s activity is required for the development of lupus symptoms in a mouse model of the disease.... Read more »

Ramirez-Ortiz et al. (2015) TREML4 amplifies TLR7. Nature Immunology . info:/10.1038/ni.3143

  • April 6, 2015
  • 04:18 AM
  • 190 views

Assisted Reproductive Technology conception and autism

by Paul Whiteley in Questioning Answers

I noticed recently that the paper by Christine Fountain and colleagues [1] reporting that "incidence of diagnosed autism was twice as high for ART [assisted reproductive technology] as non-ART births" has been making some media headlines.Based on an analysis of an impressive participant number "using linked records from the California Birth Master Files for 1997 through 2007, the California Department of Developmental Services autism caseload for 1997 through 2011, and the Centers for Disease Control and Prevention's National ART Surveillance System for live births in 1997 through 2007" authors looked at nearly 6 million births in California, USA. Including nearly 49,000 "ART-originated infants" and 33,000 "cases of autism diagnosed by the Department of Developmental Services", they set about looking at whether there was any difference between "births originated using ART with births originated without ART for incidence of autism."They concluded that there was perhaps more to see when it came to ART births and autism albeit not necessarily a clear-cut relationship. Multiple births and "adverse prenatal and perinatal outcomes" seemed to play quite an important role in the 'association' reported, leading to quotes like this from others: "The results indicate that reducing multiple births during ART may be beneficial for decreasing the risk of autism."This is not the first time that ART and some of the specific techniques linked to ART such as IVF (in vitro fertilisation) have been talked about with autism in mind. I have discussed the topic previously on this blog (see here) based on the findings reported by Venla Lehti and colleagues [2] for example. In that case, as in other instances [3], the results were less than impressive on any general association. These independent analyses did not rule out specific factors perhaps requiring further investigation, but overall the effect of ART on general autism risk was not particularly great.The take-home message is that whilst ART might impact on autism risk, the techniques themselves included under the ART banner are probably not the primary source of any risk. Rather, as we've seen on quite a few other occasions, issues around gestation and birth (see here) might be the important variables which itself asks some interesting questions about autism research areas such as the use of twins (see here) among other things...Music: Rihanna et al - Umbrella.----------[1] Fountain C. et al. Association Between Assisted Reproductive Technology Conception and Autism in California, 1997-2007. Am J Public Health. 2015 Mar 19:e1-e9.[2] Lehti V. et al. Autism spectrum disorders in IVF children: a national case-control study in Finland. Hum Reprod. 2013 Mar;28(3):812-8.[3] Sandin S. et al. Autism and mental retardation among offspring born after in vitro fertilization. JAMA. 2013 Jul 3;310(1):75-84.----------Fountain C, Zhang Y, Kissin DM, Schieve LA, Jamieson DJ, Rice C, & Bearman P (2015). Association Between Assisted Reproductive Technology Conception and Autism in California, 1997-2007. American journal of public health PMID: 25790396... Read more »

  • April 5, 2015
  • 03:05 PM
  • 212 views

Gender differences in moral judgements linked to emotion

by Dr. Jekyll in Lunatic Laboratories

If a time machine was available, would it be right to kill Adolf Hitler when he was still a young Austrian artist to prevent World War II and save millions of lives? Should a police officer torture an alleged bomber to find hidden explosives that could kill many people at a local cafe? When faced with such dilemmas, men are typically more willing to accept harmful actions for the sake of the greater good than women. For example, women would be less likely to support the killing of a young Hitler or torturing a bombing suspect, even if doing so would ultimately save more lives.... Read more »

  • April 4, 2015
  • 02:53 PM
  • 169 views

Smoking, bad for you, good for MRSA

by Dr. Jekyll in Lunatic Laboratories

Methicillin-resistant Staphylococcus aureus (MRSA), an antibiotic-resistant superbug, can cause life-threatening skin, bloodstream and surgical site infections or pneumonia. It has been a tough battle finding ways to fight it and research now shows, cigarette smoke may make matters worse. The study shows that MRSA bacteria exposed to cigarette smoke become even more resistant to killing by the immune system.... Read more »

McEachern, E., Hwang, J., Sladewski, K., Nicatia, S., Dewitz, C., Mathew, D., Nizet, V., & Crotty Alexander, L. (2015) Analysis of the Effects of Cigarette Smoke on Staphylococcal Virulence Phenotypes. Infection and Immunity. DOI: 10.1128/IAI.00303-15  

  • April 4, 2015
  • 04:55 AM
  • 185 views

No evidence for efficacy of omega-3 fatty acids on [autism] core symptom domains

by Paul Whiteley in Questioning Answers

To quote from the study by Deepali Mankad and colleagues [1] (open-access): "This study does not support high dose supplementation of omega-3 fatty acids in young children with ASD [autism spectrum disorder]."Only yesterday I was discussing the results from Bos and colleagues [2] (see here) and the idea that inattention might be a target behaviour for supplementation with PUFAs [polyunsaturated fatty acids] with (and without) ADHD [attention deficit hyperactivity disorder] in mind. Then today, something completely opposite crops up on this blog...Mankad and colleagues "conducted a 6-month, randomized, placebo controlled trial of omega-3 fatty acid supplements (1.5 g) vs placebo in children 2 to 5 years of age with ASD." The study entry at ClinicalTrials.gov can be seen here. The supplementation in question consisted of "0.75 g of EPA + DHA (1.875 ml once a day) of liquid formulation" rising to "1.5 g (3.5 ml) after 2 weeks" if well tolerated by participants.Various measures were analysed over the course of the trial period beginning at baseline (no intervention). "Autism symptom severity was measured by the autism composite score of the Pervasive Developmental Disorder-Behavioral Inventory (PDDBI)." Further: "The effect of omega-3 fatty acids on externalizing behaviors was measured using the Behavior Assessment System for Children, Second Edition (BASC-2)." Blood draws were also included as part of the study protocol, not only to study EPA and DHA content in "the plasma phospholipid" but also looking at various immune markers such as cytokines too (see here).Results: "There was no significant difference between groups on the 0- to 24-week change in PDDBI autism composite scores." So when it came to the core autism domains, fatty acid supplementation didn't seem to offer anything in excess of the placebo formulation of "refined olive oil and medium chain triglycerides."But: "there was a statistically significant difference in externalizing behaviors, with participants in the placebo group experiencing slight improvements and children in the omega-3 group worsening over the course of the study." Curiously, those receiving the placebo showed some improvement in so-called externalising behaviours (outward behaviours such as hyperactivity, aggression and conduct problems) compared with a worsening of such parameters for those receiving the active intervention. The authors add: "This effect is peculiar in the context of previous studies, but is robust." One possible explanation may lie in the examination of gastrointestinal (GI) issues among the participant groups. So: "8/19 participants in the omega-3 group had GI distress at baseline, and only 1/19 in placebo group had GI distress at baseline. The possibility that preexisting GI distress predisposes to externalizing behaviors cannot be ruled out." Knowing what is known about GI issues in relation to autism and what areas of functioning they can impinge on (see here) I would support the authors' stance on this.Going back to the Bos findings on ADHD and fatty acids, the authors also have some comment on the suggestion that ADHD might be an 'intervention target' for fatty acid supplementation. To quote again: "we explored the effect of this intervention on hyperactivity as measured by the BASC. There was no statistically significant difference between groups and the trend favored placebo." That and the lack of changes to the cytokine profile following intervention and we're just about done.Accepting that there is some research out there that has suggested that fatty acid supplementation might be useful for some on the autism spectrum (see here) including the quite recent results reported by Ooi and colleagues [3] (albeit an open trial), in general the evidence base around this intervention with autism in mind, is perhaps not as favourable as that with something like ADHD in view (see here). I should point out that the dose of fatty acid used by Mankad et al was described as "high dose" and was, eventually, more than double that used in the Bos study but similar to that described by other researchers [4]. Whether there may be merit in looking at smaller doses combined with a greater focus on those presenting with an abnormal fatty acid profile (see here for example) remains to be seen. I might also suggest that lessons could be learned from the paper by Rapaport and colleagues [5] linking inflammatory molecules to best response to fatty acids in relation to depression...Music: Beck - Where It's At.----------[1] Mankad D. et al. A randomized, placebo controlled trial of omega-3 fatty acids in the treatment of young children with autism. Molecular Autism 2015, 6:18.[2] Bos DJ. et al. Reduced symptoms of inattention after Dietary Omega-3 Fatty Acid Supplementation in boys with and without Attention Deficit/Hyperactivity Disorder. Neuropsychopharmacology. 2015 Mar 19.[3] Ooi YP. et al. Omega-3 fatty acids in the management of autism spectrum disorders: findings from an open-label pilot study in Singapore. Eur J Clin Nutr. 2015 Mar 25.[4] Amminger GP. et al. Omega-3 fatty acids supplementation in children with autism: a double-blind randomized, placebo-controlled pilot study. Biol Psychiatry. 2007 Feb 15;61(4):551-3.[5] Rapaport MH. et al. Inflammation as a predictive biomarker for response to omega-3 fatty acids in major depressive disorder: a proof-of-concept study. Molecular Psychiatry. 2015. March 24.----------Mankad, D., Dupuis, A., Smile, S., Roberts, W., Brian, J., Lui, T., Genore, L., Zaghloul, D., Iaboni, A., Marcon, P., & Anagnostou, E. (2015). A randomized, placebo controlled trial of omega-3 fatty acids in the treatment of young children with autism ... Read more »

Mankad, D., Dupuis, A., Smile, S., Roberts, W., Brian, J., Lui, T., Genore, L., Zaghloul, D., Iaboni, A., Marcon, P.... (2015) A randomized, placebo controlled trial of omega-3 fatty acids in the treatment of young children with autism. Molecular Autism, 6(1). DOI: 10.1186/s13229-015-0010-7  

  • April 3, 2015
  • 03:15 PM
  • 140 views

New therapy halts artery plaque growth and suppresses inflammation

by Dr. Jekyll in Lunatic Laboratories

According to the CDC, 1 in 4 deaths are due to heart attacks. In fact it is the leading cause of death for both men and women. Largely attributed to diet, most medications solely aim at lowering cholesterol. However, a research team showed that a nanotherapeutic medicine can halt the growth of artery plaque cells resulting in the fast reduction of the inflammation that may cause a heart attack, offering a new way to treat people at risk for heart disease.... Read more »

Jun Tang, Mark E. Lobatto, Laurien Hassing, Susanne van der Staay, Sarian M. van Rijs, Claudia Calcagno, Mounia S. Braza, Samantha Baxter, Francois Fay, Brenda L. Sanchez-Gaytan.... (2015) Inhibiting macrophage proliferation suppresses atherosclerotic plaque inflammation. Science Advances. info:/10.1126/sciadv.1400223

  • April 3, 2015
  • 04:29 AM
  • 199 views

Improving inattention in boys with and without ADHD

by Paul Whiteley in Questioning Answers

The [truncated] PubMed listing of the abstract by Dienke Bos and colleagues [1] does little justice to the results reported by this group looking at the effects of omega-3 fatty acid supplementation on the behaviour of boys both diagnosed with ADHD (attention-deficit hyperactivity disorder) and those who are described as 'typically developing'.Luckily the paper is open-access (see here) and one can get a true flavour of what happened to this cohort of boys with and without a diagnosis of ADHD following consumption of "10 grams of margarine daily, enriched with either 650mg of EPA/DHA [Eicosapentaenoic Acid / Docosahexaenoic Acid] each or placebo." Indeed, the study is also listed on ClinicalTrials.gov too (see here) and has received some press attention too (see here).So:Authors "set out to investigate the effects of omega-3 PUFA [polyunsaturated fatty acid] dietary supplementation on ADHD symptoms in young boys with and without ADHD in a randomized, placebo-controlled trial." Randomised [placebo-controlled] trials are sweet music to science ears.As mentioned, researchers did not however limit their analysis of any potential effects from fatty acid supplementation to just boys diagnosed with ADHD. No, instead they "included a typically developing reference group to investigate the specificity of treatment to subjects with ADHD."Over 16 weeks of supplementation (or not) and including measures at baseline (before intervention), researchers assessed the strength of any results based on both psychometric and other more physiological measures including buccal (cheek) swabs "for analysis of phospholipid fatty acid levels" and urine samples to "measure the HVA [homovanillic acid] to creatinine ratio, as a proxy for dopamine turnover." They also imaged the brain via fMRI.Results: "Omega-3 PUFA dietary supplementation improved symptoms of inattention in boys with and without ADHD in a double blind randomized controlled trial." This was based on scores on the Child Behavior Checklist (CBCL) and in particular, scores around attention. Inattention scores were not unexpectedly higher in boys diagnosed with ADHD but the authors are pretty adamant that "there was an effect of treatment on parent-rated symptoms of ADHD, regardless of diagnosis.""The dietary intervention affected omega-3 PUFA levels in cheek cell phospholipids." This gives us some idea that the behavioural changes reported also correlated with a physiological difference over placebo. It doesn't confirm the possible mechanism but is a good start linking behaviour and physiology. Other more physiological variables such as urinary HVA and the fMRI results did not show any specific effects following active intervention.The authors conclude: "this study provides new evidence that dietary supplementation using omega-3 PUFAs may be an effective augmentation of pharmacological treatments of ADHD."These are interesting results which add to a growing body of work suggesting that PUFAs may have some important effects when it comes to behaviour. With ADHD specifically in mind, PUFAs have received a mixed response from science albeit with some more recent meta-analyses now starting to come down on the side of (possible) effect over no effect, at least for some (see here). Outside of just ADHD, there is also a bank of research suggesting that skills such as reading ability might also have some connection to PUFA status (see here) again, for some. I say this with the caveat that there is more research to do in these areas.As per the discussions by Bos, their study was of a particularly high methodological standard so that must count in favour of strength of their results. They did note that "a small number of participants with ADHD had changes made to their medication during the intervention" but found similar results without including these participants in separate analysis. With those issues in mind, I'd be inclined to say that we should be paying a lot more attention to fatty acids and behaviour...Music: Bobby Fuller Four - I Fought The Law.----------[1] Bos DJ. et al. Reduced symptoms of inattention after Dietary Omega-3 Fatty Acid Supplementation in boys with and without Attention Deficit/Hyperactivity Disorder. Neuropsychopharmacology. 2015 Mar 19.----------Bos DJ, Oranje B, Veerhoek ES, Van Diepen RM, Weusten JM, Demmelmair H, Koletzko B, de Sain-van der Velden MG, Eilander A, Hoeksma M, & Durston S (2015). Reduced symptoms of inattention after Dietary Omega-3 Fatty Acid Supplementation in boys with and without Attention Deficit/Hyperactivity Disorder. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology PMID: 25790022... Read more »

Bos DJ, Oranje B, Veerhoek ES, Van Diepen RM, Weusten JM, Demmelmair H, Koletzko B, de Sain-van der Velden MG, Eilander A, Hoeksma M.... (2015) Reduced symptoms of inattention after Dietary Omega-3 Fatty Acid Supplementation in boys with and without Attention Deficit/Hyperactivity Disorder. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. PMID: 25790022  

  • April 2, 2015
  • 02:55 PM
  • 160 views

Beta secretase inhibitors to treat Alzheimer's disease

by Dr. Jekyll in Lunatic Laboratories

With each new amyloid-targeting treatment for Alzheimer’s disease that has been developed, there has been a corresponding concern. For example, antibodies targeting amyloid-β peptide (Aβ) produce inflammation in the brain in some patients. Gamma secretase inhibitors tend to produce adverse effects by interacting with Notch, an important pathway for cellular signaling. However, a new target for alzheimer’s is offering some new hope.... Read more »

Filser, S., Ovsepian, S., Masana, M., Blazquez‐Llorca, L., Brandt Elvang, A., Volbracht, C., Müller, M., Jung, C., & Herms, J. (2015) Pharmacological Inhibition of BACE1 Impairs Synaptic Plasticity and Cognitive Functions. Biological Psychiatry, 77(8), 729-739. DOI: 10.1016/j.biopsych.2014.10.013  

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