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  • February 3, 2016
  • 04:29 AM
  • 118 views

Estimated autism rate in 2 regions of Poland

by Paul Whiteley in Questioning Answers

"The average prevalence of ASD [autism spectrum disorder] was 35/10 000 children and was about 4-fold higher in males."I don't have too much to add to the findings reported by Karolina Skonieczna-Żydecka and colleagues [1] who estimated the prevalence of ASD in two regions of Poland: "West Pomeranian and Pomeranian regions." Based on the analysis of data from "Provincial Disability Services Commissions", researchers concluded that approximately 3 children in 1000 in those regions have a diagnosis on the autism spectrum. As always: "More studies are necessary."Accepting that there may true geographical variations in the rate of autism around the globe [2] (including effects potentially related to factors such as migration for example), these figures are surprisingly conservative compared with what has been mentioned in other parts of the world in recent times (see here). Yes, one could eventually look at issues around the identification and diagnosis of autism (including translation of the appropriate screening and assessment instruments), what criteria you use to define autism, the potential effect(s) of service availability and delivery following a diagnosis and specific cultural factors to account for the low estimates, but at the moment we can only go with the data that is available. Indeed, this is not the first time that I've talked about other geographic areas also reporting a low prevalence of autism and the possible factors around that example (see here).I do expect to see the autism prevalence estimates increase in Poland as more detailed study is done such as that actually going looking for those who possibly fall on the autism spectrum (see here) rather than relying on more passive methods of reporting. As per previous peer-reviewed research coming out of Poland [3], fulfilling the criteria for autism and actually receiving a diagnosis are not necessarily one and the same for whatever reason(s).But again, we can only go with the available data...Music: Frank Sinatra - Come Fly With Me.----------[1] Skonieczna-Żydecka K. et al. The Prevalence of Autism Spectrum Disorders in West Pomeranian and Pomeranian Regions of Poland. J Appl Res Intellect Disabil. 2016 Jan 14.[2] Fombonne E. et al. Prevalence of Autism Spectrum Disorders in Guanajuato, Mexico: The Leon survey. J Autism Dev Disord. 2016 Jan 21.[3] Wolańczyk T. et al. Features of autism, autistic traits, autism: retrospective analysis of clinical symptoms in children treated in the Pediatric Psychiatric Clinic. Psychiatr Pol. 2001 Jan-Feb;35(1):59-69.----------Skonieczna-Żydecka K, Gorzkowska I, Pierzak-Sominka J, & Adler G (2016). The Prevalence of Autism Spectrum Disorders in West Pomeranian and Pomeranian Regions of Poland. Journal of applied research in intellectual disabilities : JARID PMID: 26771078... Read more »

Skonieczna-Żydecka K, Gorzkowska I, Pierzak-Sominka J, & Adler G. (2016) The Prevalence of Autism Spectrum Disorders in West Pomeranian and Pomeranian Regions of Poland. Journal of applied research in intellectual disabilities : JARID. PMID: 26771078  

  • February 2, 2016
  • 05:20 PM
  • 142 views

How Not to Get Killed by a Cow

by Elizabeth Preston in Inkfish



Between 1993 and 2015, cattle killed 13 people who were out for walks in the United Kingdom. Dozens more walkers received broken bones or other injuries from the animals.

Murderous cattle are an understudied phenomenon, say veterinarian Angharad Fraser-Williams and other researchers at the University of Liverpool in the United Kingdom. So they scoured news articles and scientific literature to learn about cattle attacks over two decades. They turned up some advice for people wishing to av... Read more »

Fraser-Williams, A., McIntyre, K., & Westgarth, C. (2016) Are cattle dangerous to walkers? A scoping review. Injury Prevention. DOI: 10.1136/injuryprev-2015-041784  

  • February 2, 2016
  • 03:03 PM
  • 139 views

Depressed or inflamed? Inflammation attacks brain’s reward center

by Dr. Jekyll in Lunatic Laboratories

Inflammation is a good thing, it helps the body fight disease, and without it we wouldn't survive. Unfortunately, when inflammation isn't kept under control it can wreak havoc on the body. From potentially causing alzheimer's to arthritis it seems that unchecked inflammation can cause all sorts of issues. In fact, a new study adds to the list of issues out of control inflammation causes in the body.

... Read more »

  • February 2, 2016
  • 12:35 PM
  • 102 views

Weird small holes in the woods

by Rosin Cerate in Rosin Cerate

Within the ground beneath our feet lie dark cavities of various shapes and sizes. They're home to pale and eyeless creatures living a midnight existence. Natural holes in the ground, filled with air and/or water, can be roughly categorized into three types based on the particular habitat they provide for subterranean organisms:(1) Caves are large, deep, and tend not to contain much organic matter for organisms to munch on. They're often found in karst and volcanic areas prone to developing big holes. Caves tend to get all the attention because we can squeeze into them and wander around.(2) Interstitial spaces are tiny. They're the gaps between particles making up soils or underlying water-filled layers of gravel and sand (aquifers). Interstitial spaces are usually not much larger than the organisms found within them. Being hemmed in on all sides has resulted in these organisms typically being smaller and having shortened appendages compared to the inhabitants of larger underground spaces.(3) Unlike caves and interstitial spaces, shallow subterranean habitats are always found near (<10 m from) the surface, are small but not tiny, and usually contain lots of organic matter for critters to eat. Examples include holes in bedrock created by weathering (e.g. limestone being slowly eaten away at by rainwater), cavities within a pile of rocks (e.g. lava clinker), and the space beside and underneath streams through which water flows (the hyporheic zone).Another type of shallow subterranean habitat is a seepage spring (see plate 1). It's essentially a very small yet persistent wetland where water slowly flows to the surface from a shallow underground source (the flow can stop when it's hot and dry). The fancy term for the underground part is a hypotelminorheic habitat. If you've ever been out walking in a temperate forest full of deciduous trees and spotted an isolated dark wet spot where there is a slight depression in the leaf-covered ground, you may have been looking at a seepage spring. They're typically full of blackened, decaying leaves. At the base of the spring, usually less than 50 cm beneath the surface, lies an impermeable layer of clay. This clay keeps the water where it is, blocking it from moving deeper into the ground (it's a sort of small perched aquifer).Seep-dwelling Stygobromus kenki measures just a couple of millimeters in length (Source)Seepage springs are inhabited by leaf-eating crustaceans such as amphipods and isopods. They hang out in spaces between decomposing leaves, feeding on their surroundings. Even though their home is near the surface, some of these creatures resemble the inhabitants of much deeper and consistently dark caves in that they lack eyes and pigmentation. In other words, they exhibit troglomorphism.One of the dark-adapted residents of seepage springs is Stygobromus kenki (aka Kenk's amphipod) (see above photo), which only occurs within a couple dozen square miles of land draining to the Potomac River near Washington, DC. Due to its highly constrained and easily disturbed habitat, this amphipod is at risk of becoming extinct.ReferencesCulver D, Pipan T, Gottstein S. 2006. Hypotelminorheic - A unique freshwater habitat. Subterranean Biology 4(59):1-7.Pipan T, Fišer C, Novak T, Culver DC. 2012. Fifty years of the hypotelminorheic: What have we learned? Acta Carsologica 41(2-3):275–285. [Full text]Pipan T, Culver DC. 2014. Shallow subterranean habitats. Oxford University Press. [Link]http://www.american.edu/americantoday/campus-news/20090821-David-Culver-NPS.cfm... Read more »

  • February 2, 2016
  • 05:14 AM
  • 75 views

Computational Tools from Biophysical Journal

by ragothamanyennamalli in Getting to know Structural Bioinformatics

Biophysical Journal has created a collection of papers that describe tools and software that can be routinely used in biological research. Editor Prof. Leslie Loew mentions that the full-text of articles in this collection will be freely available until February 25, 2016.... Read more »

Qi Y, Cheng X, Lee J, Vermaas JV, Pogorelov TV, Tajkhorshid E, Park S, Klauda JB, & Im W. (2015) CHARMM-GUI HMMM Builder for Membrane Simulations with the Highly Mobile Membrane-Mimetic Model. Biophysical journal, 109(10), 2012-22. PMID: 26588561  

McGibbon RT, Beauchamp KA, Harrigan MP, Klein C, Swails JM, Hernández CX, Schwantes CR, Wang LP, Lane TJ, & Pande VS. (2015) MDTraj: A Modern Open Library for the Analysis of Molecular Dynamics Trajectories. Biophysical journal, 109(8), 1528-32. PMID: 26488642  

Hertig S, Goddard TD, Johnson GT, & Ferrin TE. (2015) Multidomain Assembler (MDA) Generates Models of Large Multidomain Proteins. Biophysical journal, 108(9), 2097-102. PMID: 25954868  

de Vries SJ, Schindler CE, Chauvot de Beauchêne I, & Zacharias M. (2015) A web interface for easy flexible protein-protein docking with ATTRACT. Biophysical journal, 108(3), 462-5. PMID: 25650913  

  • February 2, 2016
  • 04:29 AM
  • 102 views

Risk of cancer in autism: probably not excessive as more data emerge

by Paul Whiteley in Questioning Answers

A quote to begin: "Taken together, there are no published evidence to suggest that there is a high overall concordance between ASD [autism spectrum disorders] and cancer or between ASD and specific cancers."Those words reported by Svend Erik Mouridsen and colleagues [1] (who knows a thing or two about autism research) should offer some relief to both people on the autism spectrum and their loved ones.Based on the analysis of over 100 adults "diagnosed with infantile autism (IA) in childhood" compared with over 330 asymptomatic (not-autism) controls in Denmark, researchers found that 8 adults (6.8%) with autism has registered at least one cancer diagnosis and 17 people (5.1%) of the comparison group the same over a 30+ year period. The authors suggest that although there was no statistically significant increased risk in their cohort of people with autism "it is important to recognize that adults with IA [infantile autism] are at similar risk for these diseases." Once again, a diagnosis of autism is seemingly protective against nothing when it comes to other diseases/conditions/labels appearing.Although to some degree reassuring about the excess risk of cancer in cases of autism, I am minded to bring in a previous post I wrote on this topic (see here) based on some important work coming out of the research powerhouse that is Taiwan [2]. Based on a considerably larger participant sample (~8400 people diagnosed with autism), the numbers of those with autism developing cancer were equally small to that of Mouridsen but greater than generally expected. The excess cancer risk on that occasion seemed to be specifically linked to being male and also covered a younger age group. I say this accepting that cancer risk with autism in mind might not be the same the world over.The currently available peer-reviewed research literature in this population does not seem to indicate any wildly significantly greater risk of cancer as a function of being diagnosed on the autism spectrum. What it does suggest is that outside of specific overlap between cancer genes and so-called autism genes (see here) is that people with autism need to be screened the same way everyone else is for their risk of cancer save any health inequalities emerging, particularly as the population ages and eyes start to turn towards ageing and autism (see here). I might also add that if there is certain psychiatric comorbidity attached to a diagnosis of autism, one may need to be mindful that this could potentially impact on mortality rates (see here) and therefore adjust care accordingly.----------[1] Mouridsen SE. et al. Risk of cancer in adult people diagnosed with infantile autism in childhood: A longitudinal case control study based on hospital discharge diagnoses. Research in Autism Spectrum Disorders. 2016; 23: 203-209.[2] Chiang H-L. et al. Risk of Cancer in Children, Adolescents, and Young Adults with Autistic Disorder. J Pediatrics. 2014. 18 November.----------Mouridsen, S., Rich, B., & Isager, T. (2016). Risk of cancer in adult people diagnosed with infantile autism in childhood: A longitudinal case control study based on hospital discharge diagnoses Research in Autism Spectrum Disorders, 23, 203-209 DOI: 10.1016/j.rasd.2015.12.010... Read more »

  • February 1, 2016
  • 04:14 PM
  • 75 views

Schizophrenia, Hubris and Science

by Neuroskeptic in Neuroskeptic_Discover





A press-release from the Harvard-MIT Broad Institute reaches astonishing heights of hyperbole in announcing a new schizophrenia study (Sekar et al. 2016). Here's the release:
Genetic study provides first-ever insight into biological origin of schizophrenia

Landmark analysis reveals excessive "pruning" of connections between neurons in brain predisposes to schizophrenia

A landmark study, based on genetic analysis of nearly 65,000 people, has revealed that a person’s risk of schizo... Read more »

Sekar A, Bialas AR, de Rivera H, Davis A, Hammond TR, Kamitaki N, Tooley K, Presumey J, Baum M, Van Doren V.... (2016) Schizophrenia risk from complex variation of complement component 4. Nature. PMID: 26814963  

  • February 1, 2016
  • 03:59 PM
  • 71 views

The tegu lizard and the origin of warm-blooded animals

by Piter Boll in Earthling Nature

by Piter Kehoma Boll Warm blood is the popular way to refer to endothermy, the ability that certain animals have to maintain a high body temperature by the use of heat generated via metabolism, especially in internal organs. Mammals and birds … Continue reading →... Read more »

  • February 1, 2016
  • 03:41 PM
  • 110 views

Blood pressure medicine may improve conversational skills of individuals with autism

by Dr. Jekyll in Lunatic Laboratories

An estimated 1 in 68 children in the United States has autism. The neurodevelopmental disorder, which impairs communication and social interaction skills, can be treated with medications and behavioral therapies, though there is no cure. Now, University of Missouri researchers have found that a medication commonly used to treat high blood pressure and irregular heartbeats may have the potential to improve some social functions of individuals with autism.

... Read more »

  • February 1, 2016
  • 10:28 AM
  • 67 views

A True Underdog…or Undermouse

by Miss Behavior in The Scorpion and the Frog

By Spencer Henkel People love a good underdog story, and nowhere is that image more embodied than in the rodents that live in deserts. In the desert there are two main problems that animals must face: it is way too hot and way too dry. You would think that rodents, the smallest of mammals, would not have much difficulty surviving in this kind of habitat. You might think that they would need far less food and water than their larger neighbors like reptiles and birds. Unfortunately, this is not the case; in fact, rodents’ small size actually makes life harder for them in such harsh conditions. Rodents gain and lose body heat faster through surface exchange with their environment, their highly active lifestyle requires a lot of food and a high metabolism, which generates a lot of extra heat that must be dispersed, and the distance they can travel to find food and water is extremely limited. Desert rodents must find ways to deal with all these issues, a tremendous feat for such tiny creatures. Photo of a Golden Spiny Mouse (Acomys russatus) in Israel by Mickey Samuni-Blank at Wikimedia Commons.The most pressing concern of any animal that lives in the desert is making sure its body has enough water to carry it through the day. Needless to say, water can be hard to come by in such arid lands, and what water is present is usually found in seeds, tubers, and other plant material. Rodents will find and take in this water, but they face another problem: the contents of their diet are very salty. The rodents must now find a way to get rid of this excess salt while still holding onto a fair amount of water, for they cannot afford to simply excrete a steady stream of urine like we can. They must call upon a chemical from their brain, vasopressin, to help them out with this process. Vasopressin is an antidiuretic hormone, what I like to call an “anti-makes-you-pee”. It is made in the hypothalamus part of the brain, and when called upon it exits the pituitary gland and travels by blood to the kidneys. Once there, vasopressin causes the tiny blood vessels in the kidneys to clench up, slowing the flow of blood and increasing the time water has to be reabsorbed before urine is produced. When Nature eventually does call, the rodents will have made a small amount of urine that rids them of a whole lot of salt. Now the rodents must turn to the other issue at hand: keeping cool. Water plays an active role in cooling an animal’s body by evaporation through sweating, panting, urinating, and defecating. Unfortunately, as with the salt in their diet, rodents can’t afford to lose all that water if they want their insides to keep functioning. So instead, rodents will lower their metabolisms. This reduces the amount of heat generated inside the body, so their core temperatures will decrease. A lower metabolism will also reduce the amount of water the rodents need to cool themselves down. However, if this process keeps up, the animal could die of hypothermia, ironically. So to keep that from happening, these rodents increase the amount of heat generated by their brown fat, masses of fat found primarily in animals that hibernate. This tissue will keep the animal’s core body temperature stable even when their metabolism slows way down. In spite of their size, rodents actually have a rather tough time surviving in the desert. Yet they have found efficient ways of dealing with such extreme challenges. They can conserve enough water to live while still filtering out a great deal of salt, and they can slow down their own heat production while maintaining stable body temperatures. It is indeed quite a feat when the smallest of mammals succeeds in living in one of the harshest places on earth! Sources CitedSCHWIMMER, H., & HAIM, A. (2009). Physiological adaptations of small mammals to desert ecosystems Integrative Zoology, 4 (4), 357-366 DOI: 10.1111/j.1749-4877.2009.00176.x ... Read more »

  • February 1, 2016
  • 02:47 AM
  • 133 views

On (pre)pregnancy obesity and inflammation and offspring autism risk

by Paul Whiteley in Questioning Answers

At the time of writing this [long read] post there has been a flurry of autism research articles making news.The headline: 'Scientists create the first ever autistic monkeys' referring to the work published by Liu and colleagues [1] who reported on "lentivirus-based transgenic cynomolgus monkeys (Macaca fascicularis) expressing human MeCP2 in the brain exhibit autism-like behaviours and show germline transmission of the transgene" started the ball rolling. Anyone who knows a little bit about autism will realise that mutations in the MeCP2 gene generally refers to Rett syndrome. Whilst linked to the expression of certain autistic-like behaviours, Rett syndrome is but one part of the very heterogeneous spectrum called autism. I'd also suggest that other primate research had previously 'modelled' autism, or at least, certain facets of autism (see here).Next up was the headline: 'Autism Diets: Can Nutrition Have An Impact On Autism Risk?' portraying the findings reported by Xie and colleagues [2] (open-access) who talked about inborn errors of carnitine metabolism potentially being linked to some autism. This follows some important research history in this area (see here) specifically linked to a gene called trimethyllysine hydroxylase, epsilon (TMLHE) (see here). Inborn errors of metabolism potentially linked to autism (some autism) is a woefully under-researched and under-screened area (see here).And then we have two papers that make up the core of today's post. The first by Mengying Li and colleagues [3] continues something of an important theme in autism research circles these days on how mum's weight and risk of diabetes during pregnancy might have a bearing on offspring development [4], and specifically the risk of autism and comorbid learning disability. This time around researchers "examined the independent and combined effects of maternal prepregnancy obesity and maternal diabetes on the risk of autism spectrum disorder (ASD) in parallel with other developmental disorders (DDs)." They did this by analysing data - "a subset of the Boston Birth Cohort who completed at least 1 postnatal study visit at Boston Medical Center between 1998 and 2014" - and comparing rates of autism ("based on physician diagnoses as documented in electronic medical records") and other diagnoses "among 6 groups defined by maternal prepregnancy obesity and diabetes status." They found that yes, those mums who were obese and presented with pregestational diabetes (PGDM) had a [significantly] increased risk of offspring autism as were those with both obesity and gestational diabetes. Interestingly: "This pattern of risk was mostly accounted for by cases with co-occurring ASD and ID."Before heading further into the potential whys and wherefores to account for the Li results, I want to bring in another paper making news. Gloria Choi and colleagues [5] report results that have created headlines such as: 'Autism caused by immune response to viral infection during pregnancy?' Accepting that again, the use of the singular term 'autism' in that media piece does little to accentuate the degree of diversity that the label includes and the various 'routes' that might bring someone to a diagnosis (see here for example), I found this to be an interesting paper.Building on the idea that viral infection during pregnancy might be able to affect offspring risk of autism or other behavioural outcomes (see here), researchers set about looking at some of the possible mechanisms involved in this process. The work of the late Paul Patterson (see here) gets a mention in the Choi study write-up and the concept of maternal immune activation (MIA). Pregnant mice were initially artificially 'immune stimulated' and offspring were found to display the sorts of behaviours that had previously been mentioned in the science literature in this area. Researchers then took out some key elements of the cells involved in the inflammatory response to immune activation - specifically Th17 cells - and repeated the artificial immune activation procedure. Offspring mice did not appear to show the same behavioural issues as those whose mother mice possessed their Th17 cells intact. Further, when pregnant mother mice were given an antibody that blocks interleukin-17 (IL-17) (produced by Th17 cells), offspring mice also showed behavioural differences compared with those offspring whose mother mice received immune stimulation but nothing else. Ergo, the suggestion that: "therapeutic targeting of TH17 cells in susceptible pregnant mothers may reduce the likelihood of bearing children with inflammation-induced ASD-like phenotypes." The idea of an 'inflammation-induced autism phenotype' by the way is not a new one (see here).Whilst remembering that mice are mice (and monkeys are monkeys) and so not necessarily able to model all of the complexity of human autism (and its important comorbidities), these are potentially important findings. I've covered the idea that immune function and inflammatory processes might be part and parcel of some autism previously on this blog (see here for example) as part of a larger shift in psychiatry circles (see here). Indeed, some of that research has specifically talked about IL-17 and at least some autism (see here for example) and the idea that levels might be increased compared to other groups. Insofar as the notion of blocking the effects of IL-17 (or Th17), I'm minded to suggest that we need a lot more data first before specific interventions are discussed or attempted including looking at compounds linked to the maturation of Th17 cells [6] as possible targets.What the Li and Choi papers share in common are several variables. First is the idea that 'the nine months that made us' might indeed be an important time insofar as future behavioural outcome. Indeed the Li results also suggest that what happens prepregnancy might also exert a significant effect. Second is the notion that inflammation (or response to inflammation) in-utero might be an important concept for at least some 'types' of autism and indeed other future diagnoses (see here). If you're wondering what obesity might have to do with inflammation, well, let's just say that qu... Read more »

Li, M., Fallin, M., Riley, A., Landa, R., Walker, S., Silverstein, M., Caruso, D., Pearson, C., Kiang, S., Dahm, J.... (2016) The Association of Maternal Obesity and Diabetes With Autism and Other Developmental Disabilities. PEDIATRICS, 137(2), 1-10. DOI: 10.1542/peds.2015-2206  

Choi GB, Yim YS, Wong H, Kim S, Kim H, Kim SV, Hoeffer CA, Littman DR, & Huh JR. (2016) The maternal interleukin-17a pathway in mice promotes autismlike phenotypes in offspring. Science (New York, N.Y.). PMID: 26822608  

  • January 31, 2016
  • 08:08 PM
  • 94 views

Zika Virus (ZIKV): similarities to other arboviruses

by thelonevirologist in Virology Tidbits

Zika Virus (ZIKV) is an arbovirus belonging to the Flaviviridae transmitted primarily by mosquitoes (including Aedes Agypti). Although first identified in a resuscitate monkey from the forests in Uganda in the year 1947 with estimated first emergence probably in 1920, the first human case was only reported in 1964. ZIKV has been shown to be distributed Northern Africa as well as in Southeast Asia; however only a few human cases in Africa and Asia were identified until 2007, when a ZIKV outbreak was reported in Yap/Micronesia followed by an outbreak in French Polynesia and New Caledonia 2013 and currently in Central and South America as well as the Caribbean. Most epidemiological studies are based on the seroprevalence of neutralising antibodies, suggest that up to 73% of the population (6.1-73%) have been exposed to ZIKV.


Being a Flavivirus, ZIKV -like the related West Nile Virus (WNV), Japanese Encephalitis Virus (JEV), Chikungunya (CHIKV) and Dengue Virus (DENGV)- has a single strand, positive sense RNA genome, encoding for a polyprotein that ultimately is processed into three structural proteins, the Capsid (C), precursor of Membrane protein (prM), and Envelope (E) protein as well as seven non-structural proteins (NS1-5). Here the similarities to other members of the Flaviviridae are discussed.... Read more »

Ioos S, Mallet HP, Leparc Goffart I, Gauthier V, Cardoso T, & Herida M. (2014) Current Zika virus epidemiology and recent epidemics. Medecine et maladies infectieuses, 44(7), 302-7. PMID: 25001879  

Gannage M, & Münz C. (2010) MHC presentation via autophagy and how viruses escape from it. Seminars in immunopathology, 32(4), 373-81. PMID: 20857294  

Bell TM, Field EJ, & Narang HK. (1971) Zika virus infection of the central nervous system of mice. Archiv fur die gesamte Virusforschung, 35(2), 183-93. PMID: 5002906  

Foy BD, Kobylinski KC, Chilson Foy JL, Blitvich BJ, Travassos da Rosa A, Haddow AD, Lanciotti RS, & Tesh RB. (2011) Probable non-vector-borne transmission of Zika virus, Colorado, USA. Emerging infectious diseases, 17(5), 880-2. PMID: 21529401  

Salvetti A, & Greco A. (2014) Viruses and the nucleolus: the fatal attraction. Biochimica et biophysica acta, 1842(6), 840-7. PMID: 24378568  

Martín-Acebes MA, Blázquez AB, & Saiz JC. (2015) Reconciling West Nile virus with the autophagic pathway. Autophagy, 11(5), 861-4. PMID: 25946067  

  • January 31, 2016
  • 02:57 PM
  • 168 views

The brains of patients with schizophrenia vary depending on the type of schizophrenia

by Dr. Jekyll in Lunatic Laboratories

I have a friend who lost an eye to his brother. Yes, you read that correctly, his brother tried to kill him and in the process he lost his eye. I’ve told this story before, but whenever new schizophrenia research comes out I feel the need to tell it again. While he has forgiven his brother (partly because not long after, he was diagnosed as schizophrenic), he will not be able to see him again until he is released from prison. A tragedy that could’ve been avoided had he been diagnosed sooner. Sadly now that he is treated, most days, you wouldn’t know he’s schizophrenic.

... Read more »

  • January 31, 2016
  • 07:09 AM
  • 99 views

Coal tar, dyes, and the unlikely origins of psychotherapeutic drugs

by neurosci in Neuroscientifically Challenged










While it may be difficult to imagine in a day and age when psychiatric medicines are advertised as a way to treat nearly every mental disorder, only 65 years ago targeted and effective psychiatric medicines were still just an unrealized aspiration. In fact, until the middle of the 20th century, the efficacy and safety of many common approaches to treating mental illness were highly questionable. For example, one method of treating schizophrenia that was common in the 1940s and 1950s, known as insulin coma therapy, involved the repeated administration of insulin to precipitate a coma---and then rousing the patient out of the coma with a sugar solution. Although in hindsight this was an ineffective and dangerous way of treating the disorder, that realization didn't spread throughout the medical community until the late 1950s (about 30 years after the introduction of the procedure). Other methods used at the time (e.g. lobotomy, electroconvulsive therapy) were applied in a similarly precarious fashion while providing little to no real improvement in symptomatology. Pharmacological approaches weren't much better, as the drugs used to treat psychiatric disorders tended to be very non-specific, and often dangerous. For example, agents like chloral hydrate or barbiturates might be used to calm a schizophrenic patient whose erratic symptoms made him difficult to pacify. These drugs, however, didn't target any pathology specific to schizophrenia; they simply caused massive sedation and in the process posed a variety of risks ranging from dependence to overdose.In the 1950s, however, treatment of psychiatric disorders began to change. The decade saw the identification of the first true antipsychotic drugs to treat schizophrenia, the first antidepressants, and the first benzodiazepines to treat insomnia and anxiety. Indeed, the 1950s ushered in what many refer to as the "psychopharmacological revolution," an appellation that began to be used as the second half of the 20th century saw the development of an unprecedented number pharmacological treatments for psychiatric illnesses. Over this time, pharmacological treatments would surpass all other approaches as the most common ways to address psychiatric disorders. And many point to the first antipsychotic drug, chlorpromazine, as the drug that started it all. Considering the major impact it had on psychiatry, medicine, and society, it is perhaps surprising to consider the humble origins of chlorpromazine: the discovery of the drug can be traced back to a black sludge formed in the process of converting coal to fuel.From coal tar to dyesWhen coal is transformed into fuel, one of the byproducts left behind is a thick brown or black liquid known as coal tar. Coal tar smells strongly of naphthalene---one of its chemical constituents and the main ingredient in mothballs---and its appearance and odor probably wouldn't give anyone the impression that there was anything extraordinary about it. Coal tar, however, is made up of a very rich mixture of organic chemicals. Over the years, many of these chemicals---like naphthalene and benzene--were isolated from coal tar and found domestic or industrial uses either in their unaltered form or as starting points for other derivative chemicals. One such use was as synthetic dyes for clothing or other fabrics.In the 1800s, dyes had to be obtained from natural sources; for example, blue or indigo dye was extracted from tropical plants of the Indigofera genus while yellow was obtained from the flowers of Crocus sativus, or the saffron plant. Relying solely on natural sources for dyes was expensive and resource dependent; the process of extracting dyes from natural sources also tended to be somewhat complicated. Thus, when chemists began to discover ways of creating synthetic dyes from cheap and readily-available substrates, synthetic dyes quickly supplanted natural dyes as the most common method for staining a variety of products ranging from clothing to upholstery. In the process, dye synthesis became the foundation on which a new industry that dealt in the production and use of chemicals was built. The growth of the chemical industry would not just change manufacturing and commerce, but also science---as for many it provided a necessary justification for the existence of chemistry as a scientific field in its own right.The pioneering chemists in the work on dye synthesis had unintentionally found that aniline, one of the organic constituents of coal tar, could---with the appropriate reaction---produce dyes that were brilliantly purple, magenta, red, or really almost any color imaginable. Then it was discovered that many of the components of coal tar---like benzene, toluene, naphthalene, phenol, and anthracene---could be used to synthesize dyes as well. These discoveries made dyestuffs an extraordinarily lucrative industry in the second half of the twentieth century. The money made selling synthetic dyes helped several major firms like BASF, Bayer, and Sandoz become global powers; the fact that these companies (in some form---Sandoz is now Novartis) are still extremely influential in the chemical and/or pharmaceutical markets indicates that the impact of synthetic dye production can still be felt today.From dyes to pharmaceuticalsThe use of coal tar wasn't limited to dyes, however. Scientists found the rich organic makeup of coal tar could be exploited to produce a variety of substances ranging from paints to cosmetics. As they experimented with this bountiful substrate, researchers also began to find that some of the products they derived had potential as medicines. The first of these substances that were marketed for medicinal purposes were antipyretic, or fever-reducing drugs. The commercial success of some of these drugs led to it being commonplace to test dyes and related compounds for potential therapeutic effects.At around the same time these antipyretic substances were discovered, chemists were working with another coal tar derivative dye called methylene blue. While examining the structure of methylene blue, the German chemist August Bernthsen discovered that it was a derivative of a previously unknown compound that would come to be called phenothiazine. Phenothiazine derivatives were subsequently found to have antiparasitic properties, and many were synthesized in the hopes of finding treatments for malaria. At the time quinine was the only available antimalarial treatment, and the need for an alternative was acutely felt when events like the World Wars limited access to the natural source of quinine, the tree quina cinchona.Investigation of the phenothiazines led to some successes in malaria treatment. One in particular was the drug quinacrine, a methylene blue derivative that ended up being used to treat malaria as much as quinine itself. Many of the drugs that came out of these investigations, however, did not prove to be effective antimalarials. Instead of abandoning them altogether, though, researchers investigated their potential uses in treating other ailments. In the process, it was noted that some of the drugs had sedative properties, and one line of research explored their potential use in preventing surgical shock, a condition that can cause extremely low blood pressure during surgery and carries a significant risk of death. One hypothesis at the time, proposed by French surgeon Henri-Marie Laborit, was that surgical shock was precipitated by an excessive defensive reaction to stress, and that this exaggerated reaction might be inhibited through the use of sedatives. Laborit found that one of the phenothiazine derivatives, promethazine, was useful for this purpose when mixed with an opioid drug. Under the influence of this drug combination, patients were much calmer going into surgical procedures and the occurrence of shock was significantly reduced.The success of promethazine in lowering the risk of surgical shock led to the investigation of other phenothiazine derivatives for their sedative effects. One of the resultant substances, a chlorinated derivative of promazine called chlorpromazine, seemed not only to be an ideal candidate for use in preventing surgical shock, but also to possess some other unique pharmacological characteristics. For example, while other drugs of a sedative nature (like barbiturates) inhibited all behavioral responses in experimental animals, chlorpromazine only inhibited certain learned responses. This suggested the drug was having a more targeted effect on the brain and thus that it might have a more specific mechanism than something like a barbiturate, which caused widespread central nervous system sedation.As Laborit began to use chlorpromazine to prevent the occurrence of surgical shock, he was amazed at the degree of calmness and relaxation patients who were treated with it felt before, during, and after the surgery. These observations led Laborit to suggest the use of chlorpromazine be explored for the treatment of other psychiatric conditions that required sedation. It didn't take long before chlorpromazine was investigated as a potential treatment for psychosis.Chlorpromazine as an antipsychoticThe symptoms schizophrenic patients present with are very di... Read more »

López-Muñoz, F., Alamo, C., cuenca, E., Shen, W., Clervoy, P., & Rubio, G. (2005) History of the Discovery and Clinical Introduction of Chlorpromazine. Annals of Clinical Psychiatry, 17(3), 113-135. DOI: 10.1080/10401230591002002  

  • January 30, 2016
  • 03:21 PM
  • 151 views

Neurological adaptations to the presence of toxic HIV protein

by Dr. Jekyll in Lunatic Laboratories

Nearly half of HIV infected patients suffer from impaired neurocognitive function. The HIV protein transactivator of transcription (Tat) is an important contributor to HIV neuropathogenesis because it is a potent neurotoxin that continues to be produced despite treatment with antiretroviral therapy.

... Read more »

  • January 30, 2016
  • 01:17 PM
  • 124 views

This Month in Blastocystis Research (JAN 2016)

by Christen Rune Stensvold in Blastocystis Parasite Blog

The first post in the This Month in Blastocystis Research series in 2016 is about Blastocystis epidemiology in India (including IBS patients), views on treatment, and Blastocystis in non-human primates.... Read more »

Pandey PK, Verma P, Marathe N, Shetty S, Bavdekar A, Patole MS, Stensvold CR, & Shouche YS. (2015) Prevalence and subtype analysis of Blastocystis in healthy Indian individuals. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 296-9. PMID: 25701123  

Kurt Ö, Doğruman Al F, & Tanyüksel M. (2016) Eradication of Blastocystis in humans: Really necessary for all?. Parasitology international. PMID: 26780545  

  • January 30, 2016
  • 07:01 AM
  • 115 views

The Automatic Neuroscientist

by Neuroskeptic in Neuroskeptic_Discover

We've learned this week that computers can play Go. But at least there's one human activity they will never master: neuroscience. A computer will never be a neuroscientist. Except... hang on. A new paper just out in Neuroimage describes something called The Automatic Neuroscientist. Oh.



So what is this new neuro-robot? According to its inventors, Romy Lorenz and colleagues of Imperial College London, it's a framework for using "real-time fMRI in combination with modern machine-learning te... Read more »

  • January 30, 2016
  • 04:00 AM
  • 121 views

Autism in phenylketonuria (PKU)

by Paul Whiteley in Questioning Answers

"Autism has been reported in untreated patients with phenylketonuria."Indeed it has, as the paper by Sameh Khemir and colleagues [1] revisits something of a long known about association whereby the archetypal inborn error of metabolism that is phenylketonuria (PKU) has been linked to the presentation of autism or autistic traits [2].Looking at 18 participants diagnosed with PKU, Khemir et al "report their clinical, biochemical and molecular peculiarities" (authors words not mine) and how 15 of the 18 presented with autism as per assessment with "The Childhood Autism Rating Scale and the Autism Diagnostic Interview-Revised." Following some molecular biological analysis specifically with the "phenylalanine hydroxylase gene" in mind (a key player in PKU), the authors reported on various potentially important issues but "no correlation between autism and mutations affecting the phenylalanine hydroxylase gene."I have a lot of time for PKU on this blog. Not only because PKU represents one of the best examples of how certain foods for some can affect development and onwards mental health (see here) but also because some of the other intervention options for PKU (outside of low phenyalanine diet) might hold some promise for some autism too (see here). Indeed, the idea that tetrahydrobiopterin (BH4) - an important cofactor for phenyalanine hydroxylase and related aromatic amino acid hydroxylase enzymes - might be quite good at helping to mop up excess phenylalanine and other compounds continues to find favour in some autism research circles. Dare I also mention the effects of BH4 on tryptophan and 5-HTP as potentially being relevant to some autism too? (see here)In many parts of the world, the advent of the newborn screening program (built on the genius of people like Robert Guthrie and others) has all but eradicated untreated PKU and perhaps impacted on the number of people presenting with autism too. There remain however, challenges in certain areas of the globe, where people are not so fortunate to have such screening measures in place. Indeed, Khemir and colleagues report their results based in Tunisia and Algeria; other geographically related areas might also benefit from the implementation of such screening practices [3].     Just before I go, there is one last comment to make on something discussed by Khemir and colleagues: "age of diet onset was the determining factor in autistic symptoms' evolution." Diet, as I've mentioned, refers to the low phenylalanine (low protein) diet commonly used to manage PKU. It appears that there might be more to see in terms of how long PKU goes untreated and the progression of autistic traits similar to other descriptions, particularly the findings reported by Baieli and colleagues [4]: "None out of 62 patients with classic PKU diagnosed early met criteria for autism. In the group of 35 patients diagnosed late, two boys (5.71%) ages 16 and 13 years fulfilled the diagnostic criteria for autism."Diet potentially affecting the presentation of autism eh? I'll be coming to the paper by Oyarzabal and colleagues [5] soon enough built on some related research...Music: Led Zeppelin - Rock And Roll.----------[1] Khemir S. et al. Autism in Phenylketonuria Patients: From Clinical Presentation to Molecular Defects. J Child Neurol. 2016 Jan 12. pii: 0883073815623636.[2] Miladi N. et al. Phenylketonuria: an underlying etiology of autistic syndrome. A case report. J Child Neurol. 1992 Jan;7(1):22-3.[3] Saad K. et al. ADHD, autism and neuroradiological complications among phenylketonuric children in Upper Egypt. Acta Neurol Belg. 2015 Dec;115(4):657-63.[4] Baieli S. et al. Autism and phenylketonuria. J Autism Dev Disord. 2003 Apr;33(2):201-4.[5] Oyarzabal A. et al. Mitochondrial response to the BCKDK-deficiency: Some clues to understand the positive dietary response in this form of autism. Biochim Biophys Acta. 2016 Jan 22. pii: S0925-4439(16)30003-5.----------Khemir S, Halayem S, Azzouz H, Siala H, Ferchichi M, Guedria A, Bedoui A, Abdelhak S, Messaoud T, Tebib N, Belhaj A, & Kaabachi N (2016). Autism in Phenylketonuria Patients: From Clinical Presentation to Molecular Defects. Journal of child neurology PMID: 26759449... Read more »

Khemir S, Halayem S, Azzouz H, Siala H, Ferchichi M, Guedria A, Bedoui A, Abdelhak S, Messaoud T, Tebib N.... (2016) Autism in Phenylketonuria Patients: From Clinical Presentation to Molecular Defects. Journal of child neurology. PMID: 26759449  

  • January 29, 2016
  • 01:51 PM
  • 147 views

How to unlock inaccessible genes

by Dr. Jekyll in Lunatic Laboratories

An international team of biologists has discovered how specialized enzymes remodel the extremely condensed genetic material in the nucleus of cells in order to control which genes can be used. It was known that the DNA in cells is wrapped around proteins in structures called nucleosomes that resemble beads on a string, which allow the genetic material to be folded and compacted into a structure called chromatin.

... Read more »

de Dieuleveult, M., Yen, K., Hmitou, I., Depaux, A., Boussouar, F., Dargham, D., Jounier, S., Humbertclaude, H., Ribierre, F., Baulard, C.... (2016) Genome-wide nucleosome specificity and function of chromatin remodellers in ES cells. Nature. DOI: 10.1038/nature16505  

  • January 29, 2016
  • 12:29 PM
  • 127 views

Lizards Overcome Lack of Mirrors to Find Rocks That Match Their Colors

by Elizabeth Preston in Inkfish



Think about the last time you stood squinting in front of a full-length mirror, trying to decide whether the colors in your outfit went together. Now imagine you're a reptile, and you wouldn't even understand a mirror if you saw one, but somehow you need to find a rock that matches your skin color. Otherwise you might get eaten by a bird today. Oh, and the skin color you need to match is on your back.

Certain lizards in Greece manage to pull this off every day, though how they do it is a ... Read more »

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