SourceFor a while now, the prevailing view has been that the brains of people with autism are "underconnected" and that this lack of communication between different parts of the brain causes at least some of the features of autism. It's an intuitively plausible idea but it was always likely to be an over-simplification.Recently, a number of studies have pointed to the exact opposite - an increase in connectivity in autism. The emerging story is that kids with autism have "hyper connected" brains but they become less connected as they get older.But this is still just a story. It takes the new brain imaging data, which comes from kids, and tries to reconcile it with the older brain imaging data which mainly involves studies of adults. There are, however, lots of other differences between studies in terms of the methods they used and, perhaps most importantly, the way the data were analysed.On top of that, we still don't really understand what many of these "connectivity" measures actually signify. And it's not really clear how changes in connectivity might relate to the development of autism at the behavioural level. Certainly, people with autism change as they get older, but I don't think anyone would argue that autistic adults are the opposite of autistic kids. It's a fascinating area of research but there are still a lot of holes in the plot.Earlier this month I contributed to a "Cross Talk" feature on the SFARI website, in which Damien Fair, Tal Kenet, John Rubenstein, and I gave our thoughts on an earlier post by Vinod Menon, discussing precisely these issues.I was also interviewed by Emily Anthes for a SFARI article on two recent papers providing evidence for hyper connectivity in autism: an fMRI study by Kaustubh Supekar and colleagues at Stanford; and an EEG study by Luis Garcia Dominguez and colleagues in Toronto.Inevitably, my fairly lengthy answers to Emily's questions were edited down to a couple of short quotes. So, with Emily's permission, I'm posting the full email Q&A. I'd be very interested in other people's thoughts.Regarding the Supekar et al paper: The researchers's use of three independent cohorts seems impressive. Is that notable/unusual?This is a really important step, particularly as there are often conflicting findings across studies. It shows that the effect is robust and not just a quirk of the particular sample of children being tested. However, we shouldn't interpret the fact that there are group differences in all three studies as meaning that this is true of all people with autism - or even all people with autism in the studies. Also regarding the Supekar paper: What do you think of the suggestion that connectivity may change as children with autism age? Could that help explain some of the contradictory findings in the literature? It's possible although I think we need a direct comparison with data from adults analysed in exactly the same way as the data from children. Given their argument, I'm surprised Supekar et al didn't look to see if there was a correlation with age within the study. If there really is a change from hyperconnectivity in young children to underconnectivity in adolescents and adults then we would expect to see that hyperconectivity is most pronounced in the youngest children. That wouldn't itself be conclusive evidence - we'd need a longitudinal study to test the idea properly, but it would be the obvious starting point. The PLoS One paper uses EEG to study connectivity--is this unusual? Does EEG have any particular advantages or disadvantages over MRI when it comes to studying connectivity?To me it makes much more sense to use EEG or MEG to look at connectivity. There are lots of studies that have done this before although like the fMRI data the results are quite messy and contradictory. The big advantage of EEG and MEG is that they have very good time resolution so can pick up on the rapid and dynamic changes in connectivity that are involved in cognitive processes. While people often talk about fMRI connectivity in terms of "communication" between the different parts of the brain, it's more accurate to talk about "coactivation". We're really just talking about brain regions increasing and decreasing their activation together at the roughly the same time, roughly once every second or so. In fact, Supekar et al. make a point of filtering the data to look only at very low frequency changes (0.01 to 0.05 Hz) - so they're looking at the extent to which different brain regions are coactivated at the timescale of minutes. One of the problems with EEG is that the signal from any part of the brain is picked up (to different degrees) by all of the electrodes on the scalp. If you find evidence for synchronization between the response at two different electrodes, it's tempting to assume that this means that the parts of the brain underneath the two electrodes are acting together in synchrony. But it could just be that the two electrodes are measuring the same activity from the same source in the brain. The Dominguez paper uses a relatively new mathematical technique that is claimed to eliminate this problem. My understanding is that it effectively looks at the parts of the brain response that are nearly but not perfectly synchronized (on the assumption that perfect synchronization is almost certain to reflect the same brain response being measured at two locations).Going forward, how can we help clear up some of the contradictions in the literature?Researchers need to use the same techniques across different populations. They also need to subject data from the same samples to different analyses. That way we can start to work out how much of the contradictions are due to differences in participant characteristics (eg age, autism severity) and how much is down to the different methods and analyses being used by different research groups. We also need to look at individual as well as group differences - and for that we need to know how reliable these measures are (ie if you test the same person twice, do you get the same result).References: García Domínguez L, Stieben J, Pérez Velázquez JL, & Shanker S (2013). The imaginary part of coherency in autism: differences in cortical functional connectivity in preschool children. PloS one, 8 (10) PMID: 24098409... Read more »
García Domínguez L, Stieben J, Pérez Velázquez JL, & Shanker S. (2013) The imaginary part of coherency in autism: differences in cortical functional connectivity in preschool children. PloS one, 8(10). PMID: 24098409
Supekar K, Uddin LQ, Khouzam A, Phillips J, Gaillard WD, Kenworthy LE, Yerys BE, Vaidya CJ, & Menon V. (2013) Brain hyperconnectivity in children with autism and its links to social deficits. Cell reports, 5(3), 738-47. PMID: 24210821
So, we're here again.The end of another year and time to look back on some of the highlights of the blogging year that was 2013 on Questioning Answers. The question is: are we any further forward when it comes to the autism spectrum, it's aetiology, nature and improving quality of life?Penshaw monument @ Paul Whiteley I'm going to be optimistic this year and say yes in some respects we are. But there is still much further to go...Month by month here's a few posts on research that I thought were pretty important.----------JanuaryWell it all started with a bang. Deborah Fein and colleagues published their optimal outcomes paper detailing how in a well-defined group of children with a previous diagnosis of autism, their autistic symptoms had abated. As you can imagine, the notion that at least some autism might not be as immutable as was first thought caused quite a stir (see here) but the evidence is starting to pile up for at least one developmental trajectory fitting this optimal outcome grouping. Further evidence for a correlation between air pollution and autism was also published. And I was also involved in publishing a review paper on the use of gluten- and casein-free (GFCF) diets for autism (see here) which is a topic I'll be coming back to later in this post.FebruaryFunctional gastrointestinal (GI) problems do seem to be over-represented in cases of autism according to the study by Susie Chandler and colleagues. I know that this is not necessarily new news but from a UK perspective, the source of the message was an important part of this paper, which also applies to later research talked about in December. This month also saw the start of a whole slew of papers in 2013 suggestive of an increased risk of offspring autism where certain antiepileptics were used during the nine months that made us (see here). Maternal autoantibodies to foetal brain tissue also registered on the research radar which again, I'll be coming back to. Personally, I was saddened to hear about the death of Prof. Ann-Mari Knivsberg who was there from the start when it came to the whole GFCF diet and autism research. Rest in peace Ann-Mari.MarchCommon ground was a key message from the consortium looking at the genetic overlap between conditions like autism, ADHD, schizophrenia and the like. In many respects that conclusion set the tone for many debates on clinical nosology vs. real-life presentation which were aired during 2013. Parent-reported autism prevalence figures in the United States suggested that 1 in 50 children presented with an autism spectrum disorder (ASD) in 2011-2012. Transgenerational effects were put forward as another variable influencing autism risk as per the paper by Emma Frans (see here). And that most contentious of topics, bowel disorders and autism, received some welcome attention from Stephen Walker (see here).AprilAutism or the autisms? was a questioned posed by Andrew Whitehouse continuing the theme of real-life autism and all that heterogeneity that accompanies presentation. Many authors have seemingly begun to realise that whilst common symptoms unite under the diagnostic label of autism, the cause and path of those symptoms may very well be numerous. The paper by Chloe Wong and colleagues looking at the methylome and autism continued the rise and rise of epigenetic research in relation to those autisms. The question of a connection between Lyme disease and autism also came under the research spotlight, as did the folding placenta (see here) and some interesting speculations on gut bacteria (see here) though not necessarily portrayed accurately in the accompanying media.MayIMFAR 2013 was held in the beautiful Basque Country. One talk in particular seemed to capture those changing perspectives about autism (sorry, the autisms) as the world was introduced to ESSENCE (see here) by Prof Gillberg. May also saw one of the most significant changes to autism for many years as the latest update to DSM - the DSM-V - came into being, and with it a reshape of how we come to define the condition. Alongside, we were introduced to RDoC (see here) and the diagnostic vs. research battle commenced. Whilst slightly outside of core autism, but nevertheless potentially relevant as comorbidity, Mary Rogers and colleagues talked about depression and its correlation with C.diff infection.JuneFlaming June certainly lived up to its name this year here in the UK. The prevalence of autism in Canada took up two posts in June (see here and here). I was particularly interested to read the paper by Lau and colleagues on immune reactivity to gluten in cases of autism (see here). The implication from their results of a non-coeliac gluten sensitivity as potentially being present in cases set the tone for further interesting work in this area in the following months. Indeed continuing that dietary strand, the study by David Ruskin and colleagues describing the results of a ketogenic diet on a mouse model of autism also provided some rather informative reading.JulyThe gold-standard trial by Cheryl Claiman and colleagues looking at the use of tetrahydrobiopterin (sapropterin or BH4) for cases of autism reported some rather interesting results in terms of a positive impact on presented autism traits. I'm becoming quite interested in what BH4 might be able to do for some cases of autism building on its potential for the archetypal 'diet can affect behaviour' condition that is Phenylketonuria (PKU). Gut bacteria also emerged... Read more »
Fein D, Barton M, Eigsti IM, Kelley E, Naigles L, Schultz RT, Stevens M, Helt M, Orinstein A, Rosenthal M.... (2013) Optimal outcome in individuals with a history of autism. Journal of child psychology and psychiatry, and allied disciplines, 54(2), 195-205. PMID: 23320807
Scientists have successfully administered and utilized insulin through mouth in rats and this would be a huge success against diabetes, if the same experiment will successfully be done on humans.
Something about Insulin therapy:
Scientists are working on and improving insulin therapy for diabetes and one of the most optimized way of insulin therapy could be administration through mouth, i.e. oral administration.
The concept of oral insulin is present since 1930s but it is a complicated thing, as insulin, being a protein, quickly destroys after coming in contact with stomach, and it has a huge size making it difficult to be absorbed through bloodstream.
In the present study, scientists worked on the above mentioned problems by packing insulin in tiny packets of lipids (fats) protecting insulin from stomach enzymes and by attaching it to folic acid to activate a transport mechanism, so that its absorption could be improved.
Scientists found that this strategy worked as effectively after oral administration in rats as injected insulin.
“In vivo pharmacodynamic and pharmacokinetic studies further revealed almost double hypoglycemia and approximately 20% relative bioavailability in comparison with subcutaneously administered standard insulin solution,” Scientists noted.
Although, the dose entering the bloodstream was small as compared to injected insulin but this newly developed oral formulation helped to control blood-sugar level for more than 18 hours as opposed to 6-8 hours after injection.
“Overall the proposed strategy is expected to contribute significantly in the field of designing ligand-anchored, polyelectrolyte-based stable systems in drug delivery,” Scientists wrote.
Insulin pill may soon be a reality - The Conversation (http://goo.gl/YJrBQM)
Ashish Kumar Agrawal et al. (2013). Improved Stability and Antidiabetic Potential of Insulin Containing Folic Acid Functionalized Polymer Stabilized Multilayered Liposomes Following Oral Administration Biomacromolecules DOI: 10.1021/bm401580k... Read more »
Ashish Kumar Agrawal et al. (2013) Improved Stability and Antidiabetic Potential of Insulin Containing Folic Acid Functionalized Polymer Stabilized Multilayered Liposomes Following Oral Administration. Biomacromolecules. DOI: 10.1021/bm401580k
Scientists have found that Lung-Sparing Surgery called P/D is probably the best surgical treatment as it is better than extrapleural pneumonectomy (EPP) for malignant pleural mesothelioma.
It is a lung sparing surgery in which the pleural lining and other diseased tissues are removed while retaining the lung in place.
Extrapleural pneumonectomy (EPP):
It is lung removing surgery, in which the entire pleural lining, the diseased lung, the lymph nodes, portions of the pericardium surrounding the heart and diaphragm (wholly or partially) are removed. Usually, it is followed by some form of chemotherapy and/or radiotherapy to decrease the chances of any form of mesothelioma cells.
In the present study, scientists worked on six electronic databases of medical studies and found seven relevant studies.
They compared lung-sparing extended P/D with lung-removing EPP for malignant pleural mesothelioma and found that the mortality rate with extended P/D is only 2.9% while with EPP, mortality rate is 6.9%. They also found that rate of complications with P/D is also less than EPP, i.e. 27.9% of P/D patients found serious complications while 60% of patients with EPP experience serious complications. Median overall survival among the studies was also higher with P/D, i.e. 13-29 months, as compared to EPP, i.e. 12-22 months.
“The present study indicated that selected patients who underwent extended P/D had lower perioperative morbidity and mortality with similar, if not superior, long-term survival compared to EPP, in the context of multi-modality therapy. This may represent an important paradigm shift in the surgical management of MPM,” Scientists noted.
Cao C et al. (2013). A systematic review and meta-analysis of surgical treatments for malignant pleural mesothelioma. Lung Cancer DOI: 10.1016/j.lungcan.2013.11.026... Read more »
Cao C et al. (2013) A systematic review and meta-analysis of surgical treatments for malignant pleural mesothelioma. Lung Cancer. DOI: 10.1016/j.lungcan.2013.11.026
The latest installment of The Hobbit trilogy has come to theaters. In honor of Bilbo's return to the screen I thought I would do a post about some Middle Earth science.A new article by Joseph and Nicholas Hopkinson, published in The Medical Journal of Australia, asks an interesting question: Why do bad guys always lose? The villain might score some small victories in the beginning, the good guys will stumble along the way, but ultimately the hero will achieve victory in the end. It is a strikingly consistent feature of narratives whether they are on the page, stage, or screen. Most agree that this trope can be attributed to conventions about morality and the necessity of the happy ending. However, the authors of this paper posit that there may be other major factors that lead to the defeat of evildoers: their aversion to sunlight and their poor diet. These factors lead may lead to a vitamin D deficiency that reduces martial prowess.Vitamin D is referred to as the “sunshine vitamin.” It is a fat-soluble vitamin that acts as a steroid hormone. It is produced by the skin in response to ultraviolent light (sunlight). It also occurs naturally in a few foods such as egg yolks, fish oils, and cheese. Vitamin D is essential for strong bones because of its role in calcium metabolism, and it has immune-modulating functions. Vitamin D deficiency (VDD) can result in rickets, osteomalacia, skeletal muscle weakness, and a susceptibility to other conditions ranging from multiple sclerosis to tuberculosis and accelerated lung function decline.The authors first conducted a literature search on “imaginary populations” and “vitamin D” that returned no publications, letting them know that they were on to a novel concept. Then they performed a pilot study using textual analysis to extract data relating to diurnal habits, dwelling, light exposure and diet from The Hobbit by J. R. R. Tolkien. Next, they identified protagonists as good or evil and victorious or defeated on binary scales by consensus. These characters were then scored on (1) sun exposure rated from 3=lots to 0=none, (2) the mention of a vitamin D-containing diet item with 0=no mention and 1=mention, and (3) summing these to give a vitamin D score that was related to victoriousness by unpaired t tests. Let’s break it down by type:The Good Guys -As a hobbit, Bilbo Baggins lives in the ground. However, his hobbit hole has lots of windows and he often smokes his pipe in the sun overlooking his garden. He has a varied diet that includes cake, tea, seed cake, ale, porter, red wine, raspberry jam, mince pies, cheese, pork pie, salad, cold chicken, pickles and apple tarts. And this is simply what he offers the dwarves that invade his household at the beginning of the story. The dwarves are described as a race that likes the dark, but they do spend a lot of time above ground in at least the first part of their journey to the Lonely Mountain. And, as their dinner at Bilbo’s house shows, they eat a variety of food with gusto! As wizards may frequently travel, they will also receive quite a bit of sunlight. And although their diet is not specifically described, Galdalf is often seen appreciating the food and beverage that goes along with any social endeavor he may observe or participate in. Elves, both high and wood, “feast merrily in clearings in the woods” and also receive high vitamin D scores.The Bad Guys -One of the first unsavory creatures that the good guys come across are trolls. Trolls naturally avoid sunlight as it turns them into stone. They live on an exclusively mutton diet, are strong but stupid, and consume jugs of “good drink” that further befuddle their wits. In one of the best scenes (in my humble opinion), Bilbo meets Gollum. Gollum lives in the deep dark of the Misty Mountains. His diet consists of a lot of raw blind fish which may be good, but as all fish do not contain vitamin D it remains unclear as to the advantages of this item. He also eats goblins, on the rare times that they fall into his domain. And, although goblins may also eat some fish (especially the Great Goblin), their proclivity for the dark also gives them a low vitamin D score. Spiders (e.g. Shelob) dwell in the dark and ambush their prey, the vitamin D content depending on what wanders into their territory. And finally, Smaug the dragon lives under his stolen mountain coming out at night to eat people (favoring maidens, but sometimes also ponies and Lake-men). The authors' initial textual analysis supported their hypothesis that the success of the good guys may be assisted, to some extent, by the poor diet and lack of sunlight experienced, and even preferred, by the bad guys. Their scoring results show the mean vitamin D score of the victorious characters to be significantly higher than the non-victorious. However, they note that “the absolute concordance between goodness and victoriousness precludes an assessment of this as an independent effect.” It is important to note that a few things were not taken into account for the purposes of this study. The first are the health issues surrounding smoking which is associated with skeletal muscle dysfunction. Another is the taxanomical classification of creatures (i.e. mammal vs. bird vs. arachnid). In humans, vitamin D is produced by a UVB-induced conversion of 7-dehydrocholesterol into vitamin D. The vitamin then undergoes two hydroxylations in the body for activation. As the physiology of the creatures of Middle Earth is more obscure, it is not known if they produce vitamin D in a similar way. As this is a pilot study, the authors also only look at The Hobbit and so do not include any details on diet and habitat that are further detailed in the other works of Middle Earth. Perhaps future investigations will include these novels and even some other well known bad guys from some of our other favorite tales. I look forward to it!Joseph A Hopkinson, & Nicholas S Hopkinson (2013). The hobbit — an unexpected deficiency The Medical Journal of Australia, 199, 805-806 DOI: 10.5694/mja13.10218More about vitamin D and VDD:Rathish Nair, & Arun Maseeh (2012). Vitamin D: The “sunshine” vitamin J Pharmacol Pharmacother, 3 (2), 118-126 DOI: 10.4103/0976-500X.95506(image via the LOTR Wiki) ... Read more »
PROTIP: When selling your snake oil treatment, try NOT to make wildly outrageous efficacy claims. But if you can’t resist that temptation, try to limit your hard-to-believe, eye-roll-inducing claims to your treatment — there’s no need to go further.
In this post, I’m going to give a brief history of the Mandometer® treatment and its apparent rationale. In the next one or two posts, I will do an analysis of the most recently study by the group that claims to show remission rates of 75% and relapse rates of only 10%. Sounds great, right? Well… we’ll see.
That was written in 1996 by Cecilia Bergh and Per Södersten in, surprisingly, Nature Medicine. Bergh and Södersten are the founders of Mandometer® and Bergh is currently its CEO.
The decision to label something as a mental disorder or not is not a scientific one, and as far as causality is concerned, it really doesn’t matter if we call something a mental disorder or just variation of normal behaviour (perhaps non-neurotypical behaviour). Regardless of the label, the behaviours/cognitions have underlying biological …
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Bergh C, & Södersten P. (1996) Anorexia nervosa, self-starvation and the reward of stress. Nature medicine, 2(1), 21-2. PMID: 8564826
Bergh, C., Brodin, U., Linberg, G., & Sodersten, P. (2002) Randomized controlled trial of a treatment for anorexia and bulimia nervosa. PNAS, 99(14), 9486-9491. DOI: 10.1073/pnas.142284799
Bergh C, Callmar M, Danemar S, Hölcke M, Isberg S, Leon M, Lindgren J, Lundqvist A, Niinimaa M, Olofsson B.... (2013) Effective treatment of eating disorders: Results at multiple sites. Behavioral neuroscience, 127(6), 878-89. PMID: 24341712
The primary cilia were grown on micro-grooves 10 micrometres in sizeIt's a known fact that certain stem cells have the capacity to transform into any cell type within the body through the process of differentiation.This ability may have applications in the development of new therapies for a range of medical treatments where scientists aim to replace or regenerate tissues that have become diseased or dysfunctional.Now, in a new study published in the journal Scientific Reports, researchers at Queen Mary University of London describe that they have found that growing adult mesenchymal stem cells on micro-grooved surfaces disrupts the biochemical pathway that determines the length of the primary cilia.This change in length of the structure ultimately controls the subsequent behaviour of the stem cells.Read More... Read more »
Martin Knight et al. (2013) Surface topography regulates wnt signaling through control of primary cilia structure in mesenchymal stem cells. . Scientific Reports. DOI: 10.1038/srep03545
Scientists have found that even low levels of asbestos exposure can result in mesothelioma and other forms of cancers.
Journal of Occupational and Environmental Medicine
In the present study, scientists used Netherlands Cohort Study on about 60,000 Norwegian men in the age range of 55-69 years. They compared the job history of the participants with the asbestos-exposure and compared the likely levels of asbestos exposure that may result in mesothelioma.
Scientists found that the asbestos levels in the working environment can result in mesothelioma and other cancers such as lung cancer, and laryngeal cancer even in low levels. They found 132 cases of mesothelioma, 2,324 cases of lung cancer, and 166 cases of laryngeal cancer, after about 1.7 decades of follow-up. Of the three types, only two subtypes; lung adenocarcinoma (a form of non-small cell lung cancer) and glottis cancer (a subtype of laryngeal cancer affecting the vocal chords) were found to be related to higher levels of prolonged exposure to asbestos. For all the other forms, even low levels can cause cancer.
“Asbestos levels encountered at the lower end of the exposure distribution may be associated with an increased risk of pleural mesothelioma, lung cancer, and laryngeal cancer,” the researchers concluded.
Offermans NS et al. (2013). Occupational Asbestos Exposure and Risk of Pleural Mesothelioma, Lung Cancer, and Laryngeal Cancer in the Prospective Netherlands Cohort Study. Journal of Occupational and Environmental Medicine DOI: 10.1097/JOM.0000000000000060... Read more »
Offermans NS et al. (2013) Occupational Asbestos Exposure and Risk of Pleural Mesothelioma, Lung Cancer, and Laryngeal Cancer in the Prospective Netherlands Cohort Study. Journal of Occupational and Environmental Medicine. DOI: 10.1097/JOM.0000000000000060
The morning before Christmas eve, I’m sitting here in the dining room munching happily on the bits and pieces of what’s left of our gingerbread house that was only erected to its full glory the night before. I have not consumed this amount of carbohydrates in over a year. Inside, a few species of my […]... Read more »
David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, Ling AV, Devlin AS, Varma Y, Fischbach MA.... (2013) Diet rapidly and reproducibly alters the human gut microbiome. Nature. PMID: 24336217
Today, more than 50% population in the United States use multivitamins, daily or on occasion, to improve body functions. They also believe regular intake of dietary supplements can provide numerous health benefits. But, are those supplements really beneficial in the long run?
Well, the question may seem an easy one to anyone, but the answer is not so simple. In recent years, there has been much debate regarding the question. A new editorial by five doctors published December 17, 2013, in the Annals of Internal Medicine urged that public should stop wasting money on nutritional supplements. ... Read more »
Eliseo Guallar, Saverio Stranges, Cynthia Mulrow, Lawrence J. Appel, & Edgar R. Miller III. (2013) Enough Is Enough: Stop Wasting Money on Vitamin and Mineral Supplements. Annals of Internal Medicine, 159(12), 850-851. DOI: 10.7326/0003-4819-159-12-201312170-00011
Chances are you've never wondered how difficult it is to remove the testes of a hippopotamus. Other people have been thinking hard about it, though, because in fact it's almost impossible.Before sitting down to emasculate a common hippopotamus, Hippopotamus amphibius, it would be reasonable to ask why. They're a threatened species, so usually conservationists try to make more baby hippos—not fewer. But in zoos, hippos turn out to be prolific baby-makers. Females can live for 40 years and may birth 25 calves in that time. This would be great news in the wild, but zookeepers don't always have someplace to store a new two-ton animal.Male hippos can also be aggressive toward each other, at least while they have all their man parts. For both of these reasons, zoos may want to have their male hippos fixed. But there are a few factors working against them, explains a new paper in the journal Theriogenology (that's reproductive science for vets) by an international group of authors.The first challenge is that hippopotamuses hide their genitals. The testes are inside the body, instead of outside in a scrotum. (Other mammals in the internal-testes club, since you asked, include the armadillo, sloth, whale, and platypus.) This makes the hippo's testes totally invisible from the outside. Combined with a penis that the paper's authors describe as "discreet," it means it's hard to tell males from females at a distance.Another problem is that testes aren't in the same place from one hippo to the next, and they may "retract" even farther during surgery. Hippopotamuses are also difficult to safely put to sleep. "In the past, hippopotamus anesthesia has been fraught with serious complications," the authors explain.After moving past the anesthesia problem (they used an apparently safer blend of drugs, delivered via a dart to the hippo's ear), the researchers turned to the anatomical problems. Their answer was ultrasound. Once they had positioned the animal, they used ultrasound imaging to find the testes—then used it again after cutting into the hippo, if the testis they were looking for had scooted farther away from them.Even after finding the sneaky organs, the procedure wasn't simple. The depth of the testes' hiding places varied by as much as 16 inches from one hippo to the next. Everything had to be done deep inside the animal's body, making it hard to see what was going on. "Grasping the testicle with forceps proved laborious" in most of the animals, the authors write. They also mention using a "two-handed technique" and "moderate traction." The whole hour-and-a-half procedure, based on a method for castrating horses, is described in detail for anyone who wants to try it themselves.All ten hippos in the study were successfully castrated, though one died shortly afterward, following a complication from a unknown pre-existing condition. Over the next six months, the authors checked in with the zoos housing the hippos to see whether their behavior or interaction with other animals had changed. There were four cases where zoos wanted their hippos fixed to ease aggression between males; in all four, the problem seemed better. (One zoo, though, reported that castrated males were harassed more by females.) Overall, the authors think their technique will help zoos take better care of their hippos.The final challenge to hippopotamus surgery—what should be a challenge, anyway—is that the animals spend most of their time in a pool of water packed with feces. The animals in the study lowered their stitched-up bellies into this infectious slurry as soon as they had a chance. Yet all of them healed from surgery without trouble. Hippos in general seem to be especially good healers, the authors write.A possible explanation for the animals' healing superpower is the "red sweat" or "blood sweat" that oozes from their skin. It's not really sweat and it doesn't contain blood, though it is red. The pigments in this skin secretion have been found to absorb UV light, making the "sweat" a potential sunscreen. The pigments can also keep bacteria from growing. So a built-in antibiotic may be what keeps hippos from getting infections after they tussle and bite each other (or after meddling vets come and cut out their manhood). However the red sweat works, it shows that a hippo's secrets don't end with the location of his testicles. Images: Charlesjsharp (via Wikimedia Commons); drawings by Eva Polsterer (from Walzer et al.).Walzer C, Petit T, Stalder GL, Horowitz I, Saragusty J, & Hermes R (2013). Surgical castration of the male common hippopotamus (Hippopotamus amphibius). Theriogenology PMID: 24246424
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Chances are you’ve never wondered how difficult it is to remove the testes of a hippopotamus. Other people have been thinking hard about it, though, because in fact it’s almost impossible. Before sitting down to emasculate a common hippopotamus, Hippopotamus amphibius, it would be reasonable to ask why. They’re a threatened species, so usually conservationists […]The post Why It’s Nearly Impossible to Castrate a Hippo appeared first on Inkfish.... Read more »
In the 1940’s, antibiotics were hailed as wonder drugs. “Syphilis is now curable!”, ran the posters. Yet in modern times, several dark sides of these drugs have come to light. The widespread overuse of antibiotic therapy has driven the emergence … Continue reading →... Read more »
Ng KM, Ferreyra JA, Higginbottom SK, Lynch JB, Kashyap PC, Gopinath S, Naidu N, Choudhury B, Weimer BC, Monack DM.... (2013) Microbiota-liberated host sugars facilitate post-antibiotic expansion of enteric pathogens. Nature, 502(7469), 96-9. PMID: 23995682
Dr. Kevin Beaver followed my advice and was able to show that black men with MAOA-2R are especially likely to shoot or stab. Self-righteous critics sternly wag their fingers.... Read more »
Beaver KM, Barnes JC, & Boutwell BB. (2013) The 2-Repeat Allele of the MAOA Gene Confers an Increased Risk for Shooting and Stabbing Behaviors. The Psychiatric quarterly. PMID: 24326626
Piton A, Redin C, & Mandel JL. (2013) XLID-causing mutations and associated genes challenged in light of data from large-scale human exome sequencing. American journal of human genetics, 93(2), 368-83. PMID: 23871722
Tielbeek JJ, Medland SE, Benyamin B, Byrne EM, Heath AC, Madden PA, Martin NG, Wray NR, & Verweij KJ. (2012) Unraveling the genetic etiology of adult antisocial behavior: a genome-wide association study. PloS one, 7(10). PMID: 23077488
Vimaleswaran KS, Tachmazidou I, Zhao JH, Hirschhorn JN, Dudbridge F, & Loos RJ. (2012) Candidate genes for obesity-susceptibility show enriched association within a large genome-wide association study for BMI. Human molecular genetics, 21(20), 4537-42. PMID: 22791748
Given that a certain portly chap with a white beard (yes, one of those fat yet fit types) is heading the way of many a household over the coming hours, I'm going to be quite brief in this post about the paper by Victoria Hallett and colleagues* who concluded that their "findings support previous reports of heightened anxiety in children with ASDs [autism spectrum disorders]". The realisation that Christmas can itself be a significant source of anxiety to many people as per the BBC article (here) is perhaps also worth directing your attention to, given the potential for overlap when discussing autism.By Emile not Santa [Claus] @ Wikipedia I've talked (and talked) about how various forms of anxiety do seem to be over-represented when it comes to autism (see here for the mega-post) and the various ways and means that science has so far offered when it comes to helping to manage or relieve such issues, acknowledging that we still have some distance to go on this topic.The Hallett paper in respect of finding 'parent-reported' anxiety to be present in children with autism is no new thing. That being said, their analysis based on data from TEDS (Twins Early Development Study) adds a new twist to the research in this area, as does their suggestion that "Unaffected co-twins of children with ASDs also showed increased anxiety, generating questions about the potential etiological overlap between ASDs and anxiety". Yes it certainly does generate questions, and in particular, whether the broader autism phenotype (BAP) might have another potential diagnostic string to add to its bow.I note that at least some of this authorship group have previously talked about autism, twins and issues like anxiety (as part of the so-called internalising traits) as per papers like this one** and this one***. I was drawn to a particular quote in one of those papers: "these traits may serve to exacerbate each other over time" suggestive that intervention-wise at least, treating something like anxiety might have some interesting knock-on effects on the presentation of core autism traits and vice-versa. Another discussion for another time methinks, perhaps alongside the recent paper by Boulter and colleagues**** on intolerance of uncertainty in relation to anxiety present in cases of autism?Anyhow, without further ado, I wish you all Happy Christmas or Seasons Greetings if you prefer. Stay tuned for the mega-roundup post of autism research that has appeared on this blog during 2013 coming up in the next few days. I leave you with some sound advice when it comes to cooking that over-sized turkey that you've probably bought to avoid any unfortunate incidents or undesirable trips to the smallest room in the house. Oh, and some research news that will hopefully raise a smile to any Hobbit fan...And just before I go, yet again Shane and Kirsty perform for you the best Christmas song ever...----------* Hallett V. et al. Exploring anxiety symptoms in a large-scale twin study of children with autism spectrum disorders, their co-twins and controls. J Child Psychol Psychiatry. 2013 Nov;54(11):1176-85.** Hallett V. et al. Association of autistic-like and internalizing traits during childhood: a longitudinal twin study. Am J Psychiatry. 2010 Jul;167(7):809-17. *** Hallett V. et al. Investigating the association between autistic-like and internalizing traits in a community-based twin sample. J Am Acad Child Adolesc Psychiatry. 2009 Jun;48(6):618-27.**** Boulter C. et al. Intolerance of Uncertainty as a Framework for Understanding Anxiety in Children and Adolescents with Autism Spectrum Disorders. J Autism Dev Disord. 2013 Nov 24. ----------Hallett V, Ronald A, Colvert E, Ames C, Woodhouse E, Lietz S, Garnett T, Gillan N, Rijsdijk F, Scahill L, Bolton P, & Happé F. (2013). Exploring anxiety symptoms in a large-scale twin study of children with autism spectrum disorders, their co-twins and controls J Child Psychol Psychiatry, 54 (11), 1176-1185 DOI: 10.1111/jcpp.12068... Read more »
Hallett V, Ronald A, Colvert E, Ames C, Woodhouse E, Lietz S, Garnett T, Gillan N, Rijsdijk F, Scahill L.... (2013) Exploring anxiety symptoms in a large-scale twin study of children with autism spectrum disorders, their co-twins and controls. J Child Psychol Psychiatry, 54(11), 1176-1185. DOI: 10.1111/jcpp.12068
Athletes who reported sleeping fewer than 7 hours the night before concussion baseline testing performed worse on ImPACT and reported more symptoms.... Read more »
McClure DJ, Zuckerman SL, Kutscher SJ, Gregory AJ, & Solomon GS. (2013) Baseline Neurocognitive Testing in Sports-Related Concussions: The Importance of a Prior Night's Sleep. The American Journal of Sports Medicine. PMID: 24256713
Garcinia mangostana L.:
Isogarcinol has been obtained from Garcinia mangostana L. also known as mangosteen or the purple mangosteen. It is a tropical evergreen tree that belongs to the family Guttiferae and is found extensively in Southeast Asia. Local people use the pericarp or the ripe fruit of mangosteen to treat abdominal pain, wound infection and in inflammation, as it is found to have anti-inflammatory activity.
Isogarcinol is a newly discovered compound that lowers the natural immunity of the body, i.e. immunosuppressive action. It significantly stops the calcineurin activity that has an important role in immune regulation. It also inhibits murine spleen T-lymphocytes - which is important in organ transplant rejection - induced by concanavalin A (ConA) and the mixed lymphocyte reaction (MLR).
Scientists have found that this compound works much better in acute toxicity tests and if given through mouth in mice as compared to cyclosporin A (CsA) - an immunosuppressive drug for preventing transplant rejection. It has few adverse reactions and low toxicity in lab tests on animals, therefore scientists are of opinion that isogarcinol can be used in place of other commonly used immunosuppressive drugs for preventing transplant rejection and for long-term medication in autoimmune disorders.
“Isogarcinol might protect against organ failure associated with transplantation of other organs,” Researchers noted.
Isogarcinol is also found to have anti-plasmodial, anti-bacterial and anti-cancer activities via inhibition of histone acetyltransferases among other mechanisms.
Researchers have noted that “with further chemical synthesis and modification, isogarcinol may well make a major contribution to future immunosuppression.” So, you can work on the modified forms of this compound and their effects on immunity. Moreover, their effects on different disorders such as against bacteria and in cancer can also be studied.
Juren Cen et al. (2013). Isogarcinol Is a New Immunosuppressant PLoS ONE DOI: 10.1371/journal.pone.0066503... Read more »
injection (Credit: Amy Christensen/Flickr)Main Point:
Scientists have reported the promising results of panobinostat along with cisplatin against mesothelioma tumor cells.
Genetics and Molecular Research
Panobinostat is an experimental drug developed by Novartis - a pharmaceutical company. Although, it is still in its early stages of testing but has shown promising results in combination with cisplatin against mesothelioma.
“Cisplatin and panobinostat exposure of the cells for 24 h resulted in decreased cell survival. The combined treatment was found to be more effective,” Scientists noted.
This drug works by inhibiting the production of enzymes that enable mesothelioma cancer cells to grow at the molecular level. This process inhibits the spread of cancer cells.
After testing the combination against mesothelioma, scientists have found that mesothelioma cells were unable to survive in the laboratory setting but the healthy cells were mostly unaffected.
The same combination has also been tested successfully for other cancers such as multiple myeloma and lymphoma.
Although the results were impressive but these are initial results and scientists are planning to enter into a next phase of research, i.e. research on animals.
Gultekin KE et al. (2013). Effects of cisplatin and panobinostat on human mesothelial (Met-5A) and malignant pleural mesothelioma (MSTO-211H) cells. Genetics and Molecular Research DOI: 10.4238/2013.November.11.2... Read more »
Gultekin KE et al. (2013) Effects of cisplatin and panobinostat on human mesothelial (Met-5A) and malignant pleural mesothelioma (MSTO-211H) cells. Genetics and Molecular Research. DOI: 10.4238/2013.November.11.2
Stem cells, a future treatment for diabetes that emerges from their capacity get transformed to pancreatic cells, capable to produce insulin. Here, scientists describe this breakthough and its potentials for a permanent cure of type 1 diabetes. Another research procedure in mice, that also opens new horizons, refers to the transplantation of pancreatic islets into the anterior chamber of the eye for imaging purposes. This technique can be used to transplant pancreatic buds to study pancreatic development in the anterior chamber of the eye in vivo that means that it could enable real-time visualisation of autoimmune processes underway in the pancreas.
Further reading, 5 scientific research papers.... Read more »
Blair K. Gage, Travis D. Webber, & Timothy J. Kieffer. (2013) Initial Cell Seeding Density Influences Pancreatic Endocrine Development During in vitro Differentiation of Human Embryonic Stem Cells. PLoS ONE. DOI: 10.1371/journal.pone.0082076
Most of us have had frightening nightmares – someone is chasing after us trying to kill us, or the world is coming to an end. Other disturbing dreams are based on real life anxieties – our partner leaves us, we lose our job, we become homeless. One specific psychiatric condition includes nightmares as part of the diagnosis. Individuals with post-traumatic stress disorder (PTSD) often have terrible nightmares that relive the traumatic event (Pigeon et al., 2013)We're always glad to wake up from such nightmares, whether they were of the supernatural or mundane or terrifying variety. "Thank god it was only a dream," we say.But what if waking up from sleep was the nightmare? Hypnopompic hallucinations are unusual sensory phenomena experienced just before or during awakening. Their better known mirror image, hypnagogic hallucinations, are vivid and frightening episodes of seeing or hearing or feeling phantom sensations while falling asleep (or in early stage 1 sleep). Both are frequently associated with sleep paralysis, the terrifying condition of being half awake but unable to move. This is because the complete muscle atonia typically experienced during REM sleep has oozed into lighter stages of non-REM sleep.Hypnagogic and hypnopompic hallucinations are usually associated with narcolepsy, but 37% of a representative community sample reported frequent hypnagogic hallucinations, and 12.5% reported hypnopompic hallucinations (Ohayon et al., 1996).1 This went well beyond the low incidence of narcolepsy in that population. Both types of hallucinations were more common in those with insomnia, excessive daytime sleepiness, anxiety disorders, and depression (according to self-report).Night Terrors 1, by Beth RobinsonNocturnal Episodes of Pain and ScreamingA new case study in the journal Sleep (Mantoan et al., 2013) reports on the terrifying hypnopompic hallucinations of a 43 year old woman who experiences intense limb pain when waking up, which vanishes within 30 seconds. This is a very unusual manifestation of a non-REM parasomnia, a sleep disorder involving partial arousal during the transition between non-REM and wakefulness. The phenomenology might be best characterized as a night terror. According to the case report (Mantoan et al., 2013), the patient had......a history of nocturnal screaming episodes within 1–2 h of sleep onset from the age of 30 years. Her husband was habitually awoken by his wife screaming loudly, usually flapping either her right or left hand against the bed in a semi-purposeful fashion. Her husband reported that the events were sometimes heralded by an inspiratory sigh, she looked terrified and would not respond to him. The screaming would usually last 5–10 sec, and she would then complain to her husband of intense pain affecting the fingers of either hand or arm and occasionally her legs, with no associated numbness or paraesthesia. She would become fully orientated within 30 sec and would be partially amnesic for the event, but would recall an accompanying sense of “fighting to stay alive” associated with intense panic and often accompanied by fast regular palpitations. Otherwise no dream mentation or visualizations were reported in association with the episodes. She initially had these episodes monthly, but they increased in frequency to 2-5 times a week with 1-2 episodes per night.She was unable to identify any triggers for the episodes, and neither she nor her husband considered her to be stressed, anxious, or depressed. There was no history of sleep violence, sleep sex, sleep eating, or any other NREM parasomniac automatisms. The authors could not identify any standard physical source for the pain. Thoracic outlet syndrome, cervical radiculopathy, focal nerve entrapment, and median neuropathy (carpal tunnel syndrome) were all ruled out.Pharmacological treatments were unsuccessful. A low dose (0.5–1 mg) of clonazepam was poorly tolerated (it made her feel depressed) and had no effect on her symptoms. Paroxetine was poorly tolerated (due to sedative effects), and gabapentin was also a complete failure. Trazodone, a sedating antidepressant most often prescribed for insomnia, actually made the symptoms worse.An MRI ruled out a thalamic or hypothalamic lesion. Sleep EEG revealed sudden arousals from deep sleep, accompanied by looks of pain and/or fear on the patient's face. The episodes were consistent with a NREM parasomnia. In the example below, the patient was shaking her arm – muscle activity (EMG) is shown in the green trace.adapted from Fig. 1B (Mantoan et al., 2013). EEG showing delta waves of stage 3 sleep before an episode of arousal with shaking of one arm and looks of fear. Channels 1-12 are EEG; channels 13 and 14 are electro-oculogram (EOG) activity; channel 15 is electromyography (EMG); channel 16 is electrocardiogram (ECG); channel 17 is oxygen saturation by pulse oximetry (SpO2). What did the doctors do to help this poor woman? Nothing, it seems. A few more musculoskeletal causes need to be ruled out. The authors end on a vague note about the possible mechanism(s):In conclusion, to our knowledge this is the first report of a NREM parasomnia associated with painful paroxysms, for which we postulate the following underlying pathophysiological mechanism: an internal or external stimulus triggers arousal, facilitating the activation of innate motor pattern generators in the brainstem and activating somatosensory cortical areas to produce hypnopompic hallucinatory pain.So instead of the more typical visual hallucinations, the patient experiences pain hallucinations that originate.... where?? It seems to me that the sleep EEG could be analyzed more thoroughly, beyond merely ruling out seizure occurrence. Perhaps another imaging modality like PET could be tried (PET would be quieter than fMRI and would better tolerate movement). Identifying the neurophysiological correlates of her phantom night terr... Read more »
Mantoan L, Eriksson SH, Nisbet AP, & Walker MC. (2013) Adult-onset NREM parasomnia with hypnopompic hallucinatory pain: a case report. Sleep, 36(2), 287-90. PMID: 23372277
Ohayon MM, Priest RG, Caulet M, & Guilleminault C. (1996) Hypnagogic and hypnopompic hallucinations: pathological phenomena?. The British journal of psychiatry : the journal of mental science, 169(4), 459-67. PMID: 8894197
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