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  • October 21, 2014
  • 11:25 AM
  • 6 views

Sleep Problems in Alcoholism Treatment

by William Yates, M.D. in Brain Posts

In a previous post, I summarized a research study six month outcome of insomnia in a group of subjects treated for alcoholism.This study found a high persistence of insomnia despite reduction, and in many cases abstinence, from alcohol.A second study recently published by investigators at the National Institute of Health provides some additional insight into this topic.Gwenyth Wallen and colleagues studied a series of 164 participants admitted to a 4-6 week inpatient program for alcohol dependence.Subjects had an average inpatient length of stay of 32 days. Sleep problems were assessed using a combination of four measures:Pittsburgh Sleep Quality Index (PSQI): The PSQI was completed on the second and 28th day of treatment. A global score of 5 or more is highly reliable as a marker for sleep problems.Epworth Sleepiness Scale (ESS): The ESS is a measure of daytime sleepiness and was collected weekly during the study.Sleep Diaries: Sleep diaries were use to validate actigraphy data and provide an overall subjective rating of nightly sleep on a 0=very poorly to 10=excellent sleep.Actigraphy: Actigraphy data (measurement of activity throughout night) was collected using actigraphy wristbands and analyzed using computerized sleep scoring software.The key findings in the study included:90% of subjects at baseline and 51% at 4 weeks were classified with a sleep disorder by the PSQI25% of subjects reported excessive daytime sleepiness-this rate did not change during the course of treatmentActigraphy data showed improvement in sleep efficiency (sleep time divided by time in bed) and decreased time awake after sleep onsetHowever, total sleep time was low at both 2 and 28 days (about 5.4 hours per night) and subjects did not have a statistically significant mean increase in subjective sleep quality (6.33 at 2 days and 6.5 at 28 days)The authors note their study supports the potential value of actigraphy in identifying persistent sleep problems in alcoholics completing inpatient treatment programs. The actigraphy watches used in this study (Respironics-Actiwatch 2) retails for around $1000. The advent of smart watches and smartphone apps that measure activity during sleep provides an opportunity to extend measurement of sleep variables. I have previous reviewed the iPhone app Sleep Cycle here.The correlation of these consumer activity-based monitors with clinical monitors needs to be studied.Readers with more interest in this research study can access the free full-text manuscript by clicking on the PMID link in the citation below.Photo of grosbeak is from the author's files.Follow the author on Twitter WRY999Wallen GR, Brooks AT, Whiting B, Clark R, Krumlauf MC, Yang L, Schwandt ML, George DT, & Ramchandani VA (2014). The prevalence of sleep disturbance in alcoholics admitted for treatment: a target for chronic disease management. Family & community health, 37 (4), 288-97 PMID: 25167069... Read more »

  • October 21, 2014
  • 10:22 AM
  • 1 view

The Emotions of Paranormal Belief

by Rodney Steadman in Gravity's Pull

Belief in the paranormal may have more to do with a person’s emotional state than what goes bump in the night.... Read more »

  • October 21, 2014
  • 07:00 AM
  • 12 views

Not Quite Dead Yet

by Mark E. Lasbury in The 'Scope

History shows that premature burial was more common than people might want to believe. Many burial traditions, including the Irish wake, stem from trying to prevent someone from being buried alive. How might this happen? Several medical conditions can lead to a poor decision on burial time. ... Read more »

Christopher Dibble. (2010) The Dead Ringer: Medicine, Poe, and the fear of premature burial. Historia Medicinae. info:/

  • October 21, 2014
  • 06:22 AM
  • 14 views

An Om A Day Keeps The Doctor Away

by Chiara Civardi in United Academics

Several studies show how meditating positively influences our minds and bodies. Read which medicines could be partially substituted or helped by a regular meditation practice.... Read more »

Anderson JW, Liu C, & Kryscio RJ. (2008) Blood pressure response to transcendental meditation: a meta-analysis. American journal of hypertension, 21(3), 310-6. PMID: 18311126  

Davidson, R., Kabat-Zinn, J., Schumacher, J., Rosenkranz, M., Muller, D., Santorelli, S., Urbanowski, F., Harrington, A., Bonus, K., & Sheridan, J. (2003) Alterations in Brain and Immune Function Produced by Mindfulness Meditation. Psychosomatic Medicine, 65(4), 564-570. DOI: 10.1097/01.PSY.0000077505.67574.E3  

Delizonna, L., Williams, R., & Langer, E. (2009) The Effect of Mindfulness on Heart Rate Control. Journal of Adult Development, 16(2), 61-65. DOI: 10.1007/s10804-009-9050-6  

Epel E, Daubenmier J, Moskowitz JT, Folkman S, & Blackburn E. (2009) Can meditation slow rate of cellular aging? Cognitive stress, mindfulness, and telomeres. Annals of the New York Academy of Sciences, 34-53. PMID: 19735238  

Gaylord, S., Palsson, O., Garland, E., Faurot, K., Coble, R., Mann, J., Frey, W., Leniek, K., & Whitehead, W. (2011) Mindfulness Training Reduces the Severity of Irritable Bowel Syndrome in Women: Results of a Randomized Controlled Trial. The American Journal of Gastroenterology, 106(9), 1678-1688. DOI: 10.1038/ajg.2011.184  

  • October 21, 2014
  • 04:53 AM
  • 14 views

Antibiotics and childhood obesity: a weighty correlation

by Paul Whiteley in Questioning Answers

It's been a few weeks since the publication of the paper by L. Charles Bailey and colleagues [1] correlating early multiple exposure to broad spectrum antibiotics with obesity in infancy. On purpose I've left it a while before talking about this research so as to let the scientific dust settle a little and get a flavour for some of the discussions about this research (see here and see here).You're a true vulgarian, aren't you?A few details about the Bailey study first:Looking at the electronic records for a large cohort of children (~65,000), researchers picked out "Treatment episodes for prescribed antibiotics" based on prescription data before the age of 2 years.Anthropometric (growth) data was also determined from visits to healthcare providers between the ages of 2 and 5 years and compared with body mass index (BMI) norms derived from a large US-based survey, NHANES.Results: "Sixty-nine percent of children were exposed to antibiotics before age 24 months" with a rough average of 2 antibiotic prescriptions per child. For those who received 4 or more courses of antibiotics, the risk of obesity during early childhood was slightly elevated (11%) compared with those receiving fewer courses.The authors specifically focused on broad spectrum antibiotics as being correlated with infant weight issues; antimicrobials acting against a broad range of bacteria rather than more targeted pharmaceutics.They concluded: "Repeated exposure to broad-spectrum antibiotics at ages 0 to 23 months is associated with early childhood obesity". That being said, they also noted that various other factors seemed to correlate with infant obesity including: "Steroid use, male sex, urban practice, public insurance, Hispanic ethnicity, and diagnosed asthma or wheezing".I'm also minded to pull in a few other findings which did not get so many media headlines such as the reporting that at 4 years of age, 15% of the cohort were found to be obese and 33% overweight (source here).The Bailey results are interesting insofar as the association being made between early antibiotic use and obesity but, as always, a little caution needs to be applied before reading too much into the findings. I note the BBC coverage of this article mentions limitations: "they were not able to look at the children's weight or exercise regimes" so correlation not necessarily being the same as causation comes into play. I might also add that whilst antibiotic stewardship is still a developing area, many/most antibiotic prescriptions are not just given willy-nilly as any parent with a young child suffering from an ear infection for example, will probably be able to attest.I have kinda talked around this area of antibiotics and weight before on this blog (see here) and the implication that antibiotics, broad spectrum, by their very nature have a pretty profound effect on the trillions of bacterial beasties which inhabit places like the gastrointestinal (GI) tract. Carl Zimmer's post on swallowing a grenade (not literally) is a good starting point. The idea being that as well as helping digest our food, said bacteria (whether individual strains or through a more collective action) might also be able to influence a variety of issues like energy homoeostasis, weight management and even our risk of disease (see here and see here). If I take you back to some work looking at a particular bacterium called Akkermansia muciniphila you might get a flavour for this possible connection with weight in mind (at least in rodents).I'm going to finish with another quote included with the BBC report on the Bailey findings. It comes from an independent commentary of the paper and sums up some important issues arising from reading this work:"It would be a concern if parents took from this that they ought to be reluctant to allow antibiotic use in their children. The key risk factors for childhood obesity are over-consumption of high energy, nutrient-poor foods and lack of exercise."Whilst I would perhaps suggest that 'energy in - energy out' is too simplistic an explanation of weight management issues (see here) I would agree that under the right circumstances, antibiotics still make a valuable contribution to the medicines cabinet, and obesity is, very much, a multi-faceted condition.Music... Stevie Wonder and Superstition.----------[1] Bailey LC. et al. Association of Antibiotics in Infancy With Early Childhood Obesity. JAMA Pediatr. 2014. 29 Sept.----------Bailey LC, Forrest CB, Zhang P, Richards TM, Livshits A, & DeRusso PA (2014). Association of Antibiotics in Infancy With Early Childhood Obesity. JAMA pediatrics PMID: 25265089... Read more »

Bailey LC, Forrest CB, Zhang P, Richards TM, Livshits A, & DeRusso PA. (2014) Association of Antibiotics in Infancy With Early Childhood Obesity. JAMA pediatrics. PMID: 25265089  

  • October 20, 2014
  • 04:50 PM
  • 30 views

A Venusian Mystery Explored Once More

by Gabriel in Lunatic Laboratories

Venus, the place where women are from... supposedly. To say Venus has a harsh climate would be an understatement, this is one of many reasons why we will never (or maybe not soon) see a "long lasting" Venus rover counterpart to our Mars rover missions. Still, the planet (much like all the other plants) can teach us a lot about not just our own origins, but the origins of the universe. Also like all our neighbor planets Venus is hiding something beneath its brilliant shroud of clouds, a mystery that might be soon solved, all thanks to a new re-analysis of twenty-year-old spacecraft data.... Read more »

Harrington, E. et. Al. (2014) The puzzle of radar-bright highlands on venus: a high-spatial resolution study in Ovda regio. Geological Society of America. info:other/136-4

  • October 20, 2014
  • 04:21 PM
  • 31 views

Moral Time: Does Our Internal Clock Influence Moral Judgments?

by Jalees Rehman in The Next Regeneration

Does morality depend on the time of the day? The study "The Morning Morality Effect: The Influence of Time of Day on Unethical Behavior" published in October of 2013 by Maryam Kouchaki and Isaac Smith suggested that people are more honest in the mornings, and that their ability to resist the temptation of lying and cheating wears off as the day progresses. In a series of experiments, Kouchaki and Smith found that moral awareness and self-control in their study subjects decreased in the late afternoon or early evening. The researchers also assessed the degree of "moral disengagement", i.e. the willingness to lie or cheat without feeling much personal remorse or responsibility, by asking the study subjects to respond to questions such as "Considering the ways people grossly misrepresent themselves, it's hardly a sin to inflate your own credentials a bit" or "People shouldn't be held accountable for doing questionable things when they were just doing what an authority figure told them to do" on a scale from 1 (strongly disagree) to 7 (strongly agree). Interestingly, the subjects who strongly disagreed with such statements were the most susceptible to the morning morality effect. They were quite honest in the mornings but significantly more likely to cheat in the afternoons. On the other hand, moral disengagers, i.e. subjects who did not think that inflating credentials or following questionable orders was a big deal, were just as likely to cheat in the morning as they were in the afternoons.
... Read more »

  • October 20, 2014
  • 12:12 PM
  • 30 views

How a camera and quantum physics could improve phone security

by This Science is Crazy! in This Science Is Crazy!

New study uses mobile phone camera to detect light, using shot noise to generate true random numbers which researchers hope could be used for encryption in the future.... Read more »

Sanguinetti, B., Martin, A., Zbinden, H., & Gisin, N. (2014) Quantum Random Number Generation on a Mobile Phone. Physical Review X, 4(3). DOI: 10.1103/PhysRevX.4.031056  

  • October 20, 2014
  • 11:59 AM
  • 34 views

Does Literary Fiction Challenge Racial Stereotypes?

by Jalees Rehman in Fragments of Truth

Reading literary fiction can be highly pleasurable, but does it also make you a better person? Conventional wisdom and intuition lead us to believe that reading can indeed improve us. However, as the philosopher Emrys Westacott has recently pointed out in his essay for 3Quarksdaily, we may overestimate the capacity of literary fiction to foster moral improvement. A slew of scientific studies have taken on the task of studying the impact of literary fiction on our emotions and thoughts. Some of the recent research has centered on the question of whether literary fiction can increase empathy. In 2013, Bal and Veltkamp published a paper in the journal PLOS One showing that subjects who read excerpts from literary texts scored higher on an empathy scale than those who had read a nonfiction text. This increase in empathy was predominantly found in the participants who felt "transported" (emotionally and cognitively involved) into the literary narrative. Another 2013 study published in the journal Science by Kidd and Castano suggested that reading literary fiction texts increased the ability to understand and relate to the thoughts and emotions of other humans when compared to reading either non-fiction or popular fiction texts.
... Read more »

Johnson, D., Huffman, B., & Jasper, D. (2014) Changing Race Boundary Perception by Reading Narrative Fiction. Basic and Applied Social Psychology, 36(1), 83-90. DOI: 10.1080/01973533.2013.856791  

  • October 20, 2014
  • 10:56 AM
  • 30 views

Persistent Insomnia and Alcoholism

by William Yates, M.D. in Brain Posts

Sleep problems complicate the treatment and recovery in alcoholism. Heavy alcohol consumption modifies the nature of sleep architecture.A high blood alcohol concentration at bedtime may promote sleep early in the sleep cycle.However, as alcohol levels decline, sleep is often interrupted with limiting rapid eye movement (REM) sleep duration.Shortened total sleep time with alcohol can produce a lack of feeling well rested on awakening.For those with alcoholism or alcohol dependence, successful treatment and alcohol abstinence can restore a normal sleep pattern. However, the clinical picture appears more complicated.Kirk Brower and colleagues at the University of Michigan published an important summary of the effects of alcoholism treatment on sleep.In their study, 267 subject with alcoholism in treatment were assessed for sleep problems at baseline and again six months later.The key findings from their study included:47% of subjects had insomnia at baseline60% of all subjects with insomnia at baseline had persistent insomnia six months laterWomen and those with greater psychiatric severity had higher rates of insomnia persistenceSubjects who reduced drinking quantities had improvement in sleepHowever, a quarter of subjects who maintained abstinence reported persistent insomniaThe authors noted their findings have significant implications for treatment and monitoring of alcohol dependence patient populations.A significant high level of insomnia persistence despite abstinence is important. This group of persistent insomniacs need formal sleep assessment and many might benefit from an overnight sleep lab study known as polysomnography.The current study did not assess specifically for sleep apnea but they note sleep apnea may contribute to sleep problems in many recovered alcoholics.Successful restoration of normal sleep in abstinence may promote higher rates of alcoholism recovery. Readers with more interest in this study can access the free full-text manuscript by clicking on the PMID link in the citation below.Photo of street scene from Galway, Ireland is from the author's files.Follow the author on Twitter WRY999Brower KJ, Krentzman A, & Robinson EA (2011). Persistent insomnia, abstinence, and moderate drinking in alcohol-dependent individuals. The American journal on addictions / American Academy of Psychiatrists in Alcoholism and Addictions, 20 (5), 435-40 PMID: 21838842... Read more »

Brower KJ, Krentzman A, & Robinson EA. (2011) Persistent insomnia, abstinence, and moderate drinking in alcohol-dependent individuals. The American journal on addictions / American Academy of Psychiatrists in Alcoholism and Addictions, 20(5), 435-40. PMID: 21838842  

  • October 20, 2014
  • 07:02 AM
  • 35 views

Morality in everyday life for the religious and the nonreligious

by Rita Handrich in The Jury Room

The researchers recruited a sample of 1,252 adults ranging in age from 18 to 68 years of age who reside in the US and Canada. Each participant completed measures of religiosity and political ideation prior to participation in the actual study. All participants had smartphones and were randomly signaled on their phone for 3 days […]

Related posts:
Should I choose the creative juror, the introvert/extravert, or the religious juror?
“Everyday liars” and “Prolific liars”
“70% of Americans see immigration as threat to American way of life”


... Read more »

Hofmann W, Wisneski DC, Brandt MJ, & Skitka LJ. (2014) Morality in everyday life. Science (New York, N.Y.), 345(6202), 1340-3. PMID: 25214626  

  • October 20, 2014
  • 05:38 AM
  • 37 views

Removing Disease from the Genome

by Gunnar de Winter in United Academics

Using agenetic cut-and-paste system, scientists have removed and replaced the gene causing muscular dystrophy in mice.... Read more »

Long C, McAnally JR, Shelton JM, Mireault AA, Bassel-Duby R, & Olson EN. (2014) Prevention of muscular dystrophy in mice by CRISPR/Cas9-mediated editing of germline DNA. Science (New York, N.Y.), 345(6201), 1184-8. PMID: 25123483  

  • October 20, 2014
  • 04:36 AM
  • 33 views

Reasons for visiting ER by those with autism

by Paul Whiteley in Questioning Answers

ER - Emergency Room - or as we call it here in Blighty Accident & Emergency (A & E), is never a particularly desirable place to visit given the emphasis on illness or injury of yourself or loved one. That being said, staff there do a sterling job sometimes under very stressful circumstances, responding to all-manner of complaints, some of which are life-threatening.The paper by Dorothea Iannuzzi and colleagues [1] sought to identify some of the medical reasons why ER visits were made by people on the autism spectrum. They concluded that, depending on age, epilepsy or seizure-type disorders and "psychiatric conditions" were well represented in cases of autism based on data derived from the US 2010 National Emergency Department database.Realising that epilepsy / seizure-type disorders seem to have more than a passing connection to quite a few cases of autism (see here) and can, in some cases, lead to that most extreme of outcomes (see here), I'm not going to focus any further on this part of the Iannuzzi findings. Rather the finding that: "Psychiatric conditions were primary among ASD individuals aged 12-15 years, accounting for more than 11 % of all visits" merits some further analysis.The findings reported by Kalb and colleagues [2] documenting that: "Thirteen percent of visits among children with ASD [autism spectrum disorder] were due to a psychiatric problem, as compared with 2% of all visits by youths without ASD" provides further evidence for the extent of the Iannuzzi finding. Whilst treading carefully in this area of autism research, one detail stuck out from the Kalb report, whereby ER visits due to psychotic disorders seemed to be increased in likelihood compared to visits by asymptomatic children/youths. This seemed to tie in well with my recent discussions on the observations of Maibing and colleagues [3] and the risk/onset of schizophrenia spectrum disorders following a previous child or adolescent psychiatric diagnosis.Unfortunately, my discussions on the research literature on ER visits and autism do not get any happier as I turn to the body of work looking at suicide attempts and autism, and as per the conclusion from Kato and colleagues [4], "ASDs should always be a consideration when dealing with suicide attempts in adults at the emergency room". Again, I've covered the very sensitive topic of suicide (ideation and attempts) and autism previously on this blog (see here and see here) and as we speak further research has emerged pertinent to this topic [5]. Though sometimes quite uncomfortable to discuss, this collected work emphasises how we all really need to be talking a lot more about this issue and what can be done to divert people away from this most extreme type of behaviour. Admission to the ER - which will often be the first point of contact after such behaviour - could be a good place to start having those discussions.In amongst the literature talking about the ER and autism, there are other details which provide a rather more positive discussion about this topic. Take for example, the paper by Giarelli and colleagues [5] looking at the ways and means ER might be made more comfortable to [some of] those on the autism spectrum. Similarly, the guidance supplied by McGonigle and colleagues [6] talking about ways of managing agitation in the ER for those on the autism spectrum might also be better referenced in this clinical setting. Oh, and a bit more knowledge about medical comorbidities potentially affecting people with autism would probably not go amiss more generally.I should conclude that whilst I've focused on some of the more frequently reported reasons why people with autism might present to the ER, one shouldn't forget that all the other reasons why the general population go to the ER are similarly as pertinent to those on the spectrum. That being said, I very much doubt that "help with removing false nails" would feature on most people's reasons to attend hospital...----------[1] Iannuzzi DA. et al. Brief Report: Emergency Department Utilization by Individuals with Autism. J Autism Dev Disord. 2014 Sep 27.[2] Kalb LG. et al. Psychiatric-related emergency department visits among children with an autism spectrum disorder. Pediatr Emerg Care. 2012 Dec;28(12):1269-76.[3] Maibing CF. et al. Risk of Schizophrenia Increases After All Child and Adolescent Psychiatric Disorders: A Nationwide Study. Schizophr Bull. 2014 Sep 5. pii: sbu119.[4] Kato K. et al. Clinical features of suicide attempts in adults with autism spectrum disorders. Gen Hosp Psychiatry. 2013 Jan-Feb;35(1):50-3.[5] Takar K. & Kondo T. Comorbid atypical autistic traits as a potential risk factor for suicide attempts among adult depressed patients: a case–control study. Annals of General Psychiatry 2014, 13:33.[6] Giarelli E. et al. Sensory stimuli as obstacles to emergency care for children with autism spectrum disorder. Adv Emerg Nurs J. 2014 Apr-Jun;36(2):145-63.[7] McGonigle JJ. et al. Management of agitation in individuals with autism spectrum disorders in the emergency department. Child Adolesc Psychiatr Clin N Am. 2014 Jan;23(1):83-95.----------Iannuzzi DA, Cheng ER, Broder-Fingert S, & Bauman ML (2014). Brief Report: Emergency Department Utilization by Individuals with Autism. Journal of autism and developmental disorders PMID: 25261249... Read more »

Iannuzzi DA, Cheng ER, Broder-Fingert S, & Bauman ML. (2014) Brief Report: Emergency Department Utilization by Individuals with Autism. Journal of autism and developmental disorders. PMID: 25261249  

  • October 20, 2014
  • 12:05 AM
  • 35 views

Novel NSAID has Differential Tissue Effects in the Treatment of Chronic Rotator Cuff Repairs

by Sarah Ilkhanipour Rooney in Sports Medicine Research (SMR): In the Lab & In the Field

Licofelone, a non-steroidal anti-inflammatory treatment, has tissue-specific effects. In a rotator cuff repair rat model, this drug reduces functional muscle regeneration but improves tendon healing.... Read more »

  • October 19, 2014
  • 07:11 PM
  • 53 views

Running Shoes Can Control Motion

by Craig Payne in Running Research Junkie

Running Shoes Can Control Motion... Read more »

  • October 19, 2014
  • 06:39 PM
  • 56 views

Pain is not a "Thing"

by Bronwyn Thompson in Healthskills: Skills for Healthy Living

ResearchBlogging.org
I’m reading some fascinating books at the moment. I’m such a pain geek I take pain books away with me on holiday! Anyway, the two books to hit me between the eyeballs recently are The Pain Chronicles by Melanie Thernstrom (published 2010), and The Story of Pain by Joanna Bourke (published 2014). What makes both of these books fascinating is that these both look at the history of pain and pain management, and explore the “what it is like” to be in pain. Reading them, I’m forcefully reminded that the ways in which we conceptualise pain is an incredibly social process. ... Read more »

Ashton-James, C., Richardson, D., Williams, A., Bianchi-Berthouze, N., & Dekker, P. (2014) Impact of pain behaviors on evaluations of warmth and competence. PAIN®. DOI: 10.1016/j.pain.2014.09.031  

  • October 19, 2014
  • 01:43 PM
  • 47 views

DNA Nanotech: The First Large DNA Crystals

by Gabriel in Lunatic Laboratories

DNA is the stuff of life as we know it, but it is the potential as a programmable material platform that could spawn entire new and revolutionary nanodevices in computer science, microscopy, biology, and more. Researchers have been working to master the ability to coax DNA molecules to self assemble into the precise shapes and sizes needed in order to fully realize these nanotechnology dreams. A dream that been going on for 20 years now and was just realized.... Read more »

Ke, Y., Ong, L., Sun, W., Song, J., Dong, M., Shih, W., & Yin, P. (2014) DNA brick crystals with prescribed depths. Nature Chemistry. DOI: 10.1038/nchem.2083  

  • October 19, 2014
  • 11:00 AM
  • 51 views

Ten years into the making, the HIV-1 mosaic vaccine finally goes into human trial

by EE Giorgi in CHIMERAS

© Bette Korber et al. I hope you will all forgive me if this week I'm gushing over my amazing mentor Bette Korber, as last week she shared some awesome news on Facebook:"A landmark in my life happened yesterday, a major step in a long story. A decade ago I had an idea for making an HIV vaccine that had the potential to work globally. After a struggle (in my first 2 failed proposals, reviewers declared what I proposed was impossible), I got an internal grant from Los Alamos to develop the idea (third time's a charm). With that funding I could bring together a group of computational people to work together on expressing the idea -- a talented guy named Simon Perkins wrote amazing code to make it so, with computational design suggestions from the group, particularly my husband James Theiler. Then James, Will Fischer, Tanmoy Bhattacharya, and I put it through its paces, optimizing running conditions and devising ways to compare mosaics with natural proteins, with additional help from our friends Karina Yusim, Carla Kuiken and Bob Funkhouser. We called it a mosaic vaccine. After so many years of hard work, and with the collaboration of experimentalists at Harvard and at Duke (Drs. Haynes, Letvin, and Barouch), two weeks ago a phase I safety trial finally opened, and an HIV mosaic vaccine went into the arm of a human volunteer for the very first time. "Safety trial" means that this is just the first phase in testing the safety of the vaccine (I explained the three phases of human trials in this post). We will gather immune responses and we are hoping to see the same good results we saw in monkeys [2-5]. If all goes well, HIV mosaics are in the pipeline for 4 more human vaccine studies. I'm so excited about this study and so proud of my mentor.When I explain to people the challenge we are facing when designing an HIV-1 vaccine, I usually make a very simplistic comparison with the flu virus. Influenza evolves from one season to the next, which is why every year we need a new flu shot. So, basically, the flu evolves into a new virus every year. Well, HIV evolves so rapidly that every person has a different virus. In our database alone we have half a million distinct HIV viral sequences: how can you vaccinate people against half a million different viruses? In the past, successful vaccines against diseases like polio or the measles have been made by taking a real virus, inactivating it (for example, you just take one or two of its proteins, but not the whole virus, to ensure it loses its ability to infect cells), and then injecting it into the body. The immune system "sees" the viral proteins and initiates a response. The response is then "saved" into memory cells, which, next time they encounter the pathogen, will remember how to produce the right response that will promptly clear the virus before it can start an active infection. So, as you can see, the problem with HIV is that the viral population is so diverse that no one virus found in nature will protect people from contracting the infection. How to bypass the obstacle, then? Bette's idea is to basically use a computer that mimics HIV's evolutionary mechanisms to create an in-silico virus [1], something I've discussed in this post. The algorithm takes as input a population of, say, 100 different HIV sequences, and then recombines them creating a new population of artificially constructed viral sequences. HIV viruses can naturally recombine when infecting the same cells, and what the algorithm does is mimic this mechanism making sure that after every recombination step the new sequence is still a viable and functional virus. The computer mimics this process, iterates it multiple times and then the best representative is selected as a potential vaccine.The first caveat is: is this new, artificially constructed sequence a real virus? After all, it was never found in nature. It was created by a computer algorithm. It turns out that when reconstructed in a wet lab, the mosaic proteins are functional and viable.The second hurdle was to prove that these artificially constructed sequences are safe to be used in a vaccine and that they do elicit protective responses against not just a few HIV viruses, but many, many HIV viruses -- enough to prevent infection. So, you get an idea of why the mosaic vaccine took 10 years from concept to the first human trial. Animal studies [2-5] demonstrated that mosaic vaccines elicit good immune responses. In one study in particular [3], compared to controls, vaccinated monkeys required many more challenges to get infected (for a risk reduction of 80%), and once infected, they were able to control the viral load and survive the infection. So, as Bette said, we are hopeful. Hopeful and excited![1] Fischer W, Perkins S, Theiler J, Bhattacharya T, Yusim K, Funkhouser R, Kuiken C, Haynes B, Letvin NL, Walker BD, Hahn BH, & Korber BT (2007). Polyvalent vaccines for optimal coverage of potential T-cell epitopes in global HIV-1 variants. Nature medicine, 13 (1), 100-6 PMID: 17187074[2] Nkolola JP, Bricault CA, Cheung A, Shields J, Perry J, Kovacs JM, Giorgi E, van Winsen M, Apetri A, Brinkman-van der Linden EC, Chen B, Korber B, Seaman MS, & Barouch DH (2014). Characterization and immunogenicity of a novel mosaic M HIV-1 gp140 trimer. Journal of virology, 88 (17), 9538-52 PMID: 24965452[3] Barouch DH, Stephenson KE, Borducchi EN, Smith K, Stanley K, McNally AG, Liu J, Abbink P, Maxfield LF, Seaman MS, Dugast AS, Alter G, Ferguson M, Li W, Earl PL, Moss B, Giorgi EE, Szinger JJ, Eller LA, Billings EA, Rao M, Tovanabutra S, Sanders-Buell E, Weijtens M, Pau MG, Schuitemaker H, Robb ML, Kim JH, Korber BT, & Michael NL (2013). Protective efficacy of a global HIV-1 mosaic vaccine against heterologous SHIV challenges in rhesus monkeys. ... Read more »

Fischer W, Perkins S, Theiler J, Bhattacharya T, Yusim K, Funkhouser R, Kuiken C, Haynes B, Letvin NL, Walker BD.... (2007) Polyvalent vaccines for optimal coverage of potential T-cell epitopes in global HIV-1 variants. Nature medicine, 13(1), 100-6. PMID: 17187074  

Nkolola JP, Bricault CA, Cheung A, Shields J, Perry J, Kovacs JM, Giorgi E, van Winsen M, Apetri A, Brinkman-van der Linden EC.... (2014) Characterization and immunogenicity of a novel mosaic M HIV-1 gp140 trimer. Journal of virology, 88(17), 9538-52. PMID: 24965452  

Barouch DH, Stephenson KE, Borducchi EN, Smith K, Stanley K, McNally AG, Liu J, Abbink P, Maxfield LF, Seaman MS.... (2013) Protective efficacy of a global HIV-1 mosaic vaccine against heterologous SHIV challenges in rhesus monkeys. Cell, 155(3), 531-9. PMID: 24243013  

Barouch DH, O'Brien KL, Simmons NL, King SL, Abbink P, Maxfield LF, Sun YH, La Porte A, Riggs AM, Lynch DM.... (2010) Mosaic HIV-1 vaccines expand the breadth and depth of cellular immune responses in rhesus monkeys. Nature medicine, 16(3), 319-23. PMID: 20173752  

  • October 18, 2014
  • 02:55 PM
  • 57 views

New Genetic Test to help Solve Rare Disease Diagnosis

by Gabriel in Lunatic Laboratories

My sister suffers from a rare disease which causes small fiber polyneuropathy, or the killing of nerves in her hands and feet. As it progresses she has trouble standing or using her hands. If that was the worst of it, then it might be liveable given the time between severe attacks is years or more. Unfortunately, it also causes intense and mostly constant pain and burning sensations, pain so bad that conventional narcotic painkillers have trouble controlling it. After some time working with the hospital I narrowed it down to autoimmune mediated. Her Doctors finally agreed, but only after first dismissing it as anything from she was faking it, all the way to lupus.... Read more »

Lee, H., Deignan, J., Dorrani, N., Strom, S., Kantarci, S., Quintero-Rivera, F., Das, K., Toy, T., Harry, B., Yourshaw, M.... (2014) Clinical Exome Sequencing for Genetic Identification of Rare Mendelian Disorders. JAMA. DOI: 10.1001/jama.2014.14604  

  • October 18, 2014
  • 09:45 AM
  • 55 views

Immunoglobulin E: not just a bystander in lupus?

by Aurelie in The Immuno Blog

IgE antibodies are mostly known for their pathophysiological role in allergic reactions and in certain immune deficiencies referred to as hyper-IgE syndromes. In a study published in The Journal of Experimental Medicine in September, Dema et al. find that IgE … Continue reading →... Read more »

Dema B, Charles N, Pellefigues C, Ricks TK, Suzuki R, Jiang C, Scheffel J, Hasni S, Hoffman V, Jablonski M.... (2014) Immunoglobulin E plays an immunoregulatory role in lupus. The Journal of experimental medicine. PMID: 25267791  

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