Donate your body to science?

Ever consider donating your body to science? Your sad little meat suit could advance the cause of human knowledge! Sure, maybe you were a "callow reprobate" in life (the judge's words, not ours), but in death you serve a higher function. Well, unless science decides to use your carcass for one of these things ...

#5. Scientists Tested The Punching Proficiency Of Severed Arms…

David Carrier, a biology professor at the University of Utah -- who doesn't completely buy into the whole "civilized dexterity" thing. He poses another theory: Our hands evolved as they did so that we could more effectively punch each other in the face.

So he gathered up some dismembered arms and started figuring out how to make them deliver haymakers. ..

Researchers attached the arms to a pendulum and tied fishing line to the tendons of the forearm muscles, allowing them to be controlled by guitar tuners like marionettes straight out of a Hellraiser puppet show.

Carrier and Co. then forced the severed arms to slug a force-measuring dumbbell using three hand positions: a clenched fist, a loose fist, and an open-palm slap…

#4. The Military Shot Corpses To Test The Stopping Power Of Handguns…

In 1899, LaGarde and Colonel John T. Thompson (who would later go on to invent the Thompson submachine gun made famous by Al Capone and the like), hung an unspecified number of cadavers from the ceiling and took turns shooting them with .38 and .45 caliber revolvers. Dozens of rounds were fired into each corpse and, based entirely on how much each shot made the body swing, LaGarde and Thompson "calculated" the relative stopping power of the various gun models. Their findings influenced military policies, specifically those dictating that service pistols should be of no less than .45 caliber….

#3. Plastic Surgeons Practice Their Craft On Decapitated Heads…

Countless courses allow surgeons to practice procedures like nose jobs on honest-to-goodness decapitated heads. Why decapitated? Because the rest of the body can be put to better use elsewhere …, and the scientific community is anything but wasteful. Horrific, disturbing, nightmare-inducing -- never wasteful, though…

#2. Scientists Made Corpses Blink (And Now You Never Will Again)…

By screwing one end of a sling into the bone at the corner of the eye and fastening the other end to a pacemaker-like contraption hidden in the natural hollow of the temple, the paralyzed (but now bionic!) eyelid can be made to blink in tandem with the other, healthy eye. That is, if the patient is still alive. When testing the system on a cadaver, the result is one working eyelid and the heavy psychological trauma of having just been hit on by a zombie.

#1. Nearly Everything Around You Has Been Tested On Cadavers

How do you think researchers determine how safe you'll be during a crash? Crash test dummies, right? Even the most technologically advanced dummy can tell you only so much. To get the truest possible picture, sometimes you've got to smash some poor, dead bastard into a brick wall.

Though, officially speaking, car manufacturers will deny it to hell and back, cadaver testing is still alive and well. Because the best way to see how well a new safety feature will protect the human body is to destroy a few human bodies.

http://www.cracked.com/article_23700_did-you-donate-your-body-to-science-maybe-dont-read-this..html

Patent foramen ovale and stroke in childhood

Rubeena Khanemail, Anthony K. Chanemail, Tapas K. Mondalemail, Bosco A. Paes on behalf of the Thrombosis and Hemostasis in Newborns (THIN) Group.  Patent foramen ovale and stroke in childhood: A systematic review of the literature.  European Journal of Paediatric Neurology, 05/10/2016 in press.

Highlights

•Stroke in pediatrics is associated with prothrombotic disorders or arteriopathy.

•Cryptogenic stroke may recur with a patent foramen ovale (PFO) and atrial septal aneurysm.

•Paradoxical embolism from a PFO as a cause for stroke is a diagnosis of exclusion.

•Transthoracic echo and bubble contrast visualizes the atrial septum, PFO and a shunt.

•Closure of a PFO should be individualized in children with cryptogenic stroke.

Abstract

Background

Stroke in association with a patent foramen ovale (PFO) may be due to paradoxical embolization via a right to left intracardiac shunt but the exact contribution of PFO to stroke or stroke recurrence in childhood remains unclear.

Methods

To review the relationship of a PFO with stroke, and evaluate associated co-morbidities. An electronic database literature search of Pubmed, Cochrane and EMBASE was performed from January 2000–December 2014.

Results

149 articles were retrieved, with overlap for diagnosis, management, treatment and outcome. 65 reports were utilized for the comprehensive review. Majority of childhood arterial ischemic stroke and transient ischemic attacks are associated with prothrombotic disorders or arteriopathy. Transthoracic echocardiography with a Valsalva maneuver is highly sensitive as a screening tool but may be falsely positive. Transthoracic echocardiography with color Doppler and a concurrent bubble contrast study are excellent for visualizing the atrial septum and PFO and identifying a right to left shunt. Current literature does not support PFO closure for cryptogenic stroke in young adults without an associated risk of thromboembolism.

Conclusions

High quality research in the pediatric population is lacking and most of the data is extrapolated from adults. Paradoxical embolism from a PFO as a cause of transient ischemic attack or stroke is a diagnosis of exclusion. PFO closure should be individualized based on significant shunting and risk factors such that maximum benefit is derived from the procedure. A young person with a PFO and stroke should be thoroughly investigated to rule out other etiologies.

Courtesy of:  http://www.mdlinx.com/neurology/medical-news-article/2016/05/10/stroke-patent-foramen-ovale-childhood-diagnosis/6652256/?category=sub-specialty&page_id=2&subspec_id=317 

Chronic Lyme disease 2

Berende A, ter Hofstede HJ, Vos FJ, van Middendorp H, Vogelaar ML, Tromp M, van den Hoogen FH, Donders AR, Evers AW, Kullberg BJ. Randomized Trial of Longer-Term Therapy for Symptoms Attributed to Lyme Disease. N Engl J Med. 2016 Mar 31;374(13):1209-20.

Abstract

BACKGROUND:

The treatment of persistent symptoms attributed to Lyme disease remains controversial. We assessed whether longer-term antibiotic treatment of persistent symptoms attributed to Lyme disease leads to better outcomes than does shorter-term treatment.

METHODS:

In a randomized, double-blind, placebo-controlled trial conducted in Europe, we assigned patients with persistent symptoms attributed to Lyme disease--either related temporally to proven Lyme disease or accompanied by a positive IgG or IgM immunoblot assay for Borrelia burgdorferi--to receive a 12-week oral course of doxycycline, clarithromycin plus hydroxychloroquine, or placebo. All study groups received open-label intravenous ceftriaxone for 2 weeks before initiating the randomized regimen. The primary outcome measure was health-related quality of life, as assessed by the physical-component summary score of the RAND-36 Health Status Inventory (RAND SF-36) (range, 15 to 61, with higher scores indicating better quality of life), at the end of the treatment period at week 14, after the 2-week course of ceftriaxone and the 12-week course of the randomized study drug or placebo had been completed.

RESULTS:

Of the 281 patients who underwent randomization, 280 were included in the modified intention-to-treat analysis (86 patients in the doxycycline group, 96 in the clarithromycin-hydroxychloroquine group, and 98 in the placebo group). The SF-36 physical-component summary score did not differ significantly among the three study groups at the end of the treatment period, with mean scores of 35.0 (95% confidence interval [CI], 33.5 to 36.5) in the doxycycline group, 35.6 (95% CI, 34.2 to 37.1) in the clarithromycin-hydroxychloroquine group, and 34.8 (95% CI, 33.4 to 36.2) in the placebo group (P=0.69; a difference of 0.2 [95% CI, -2.4 to 2.8] in the doxycycline group vs. the placebo group and a difference of 0.9 [95% CI, -1.6 to 3.3] in the clarithromycin-hydroxychloroquine group vs. the placebo group); the score also did not differ significantly among the groups at subsequent study visits (P=0.35). In all study groups, the SF-36 physical-component summary score increased significantly from baseline to the end of the treatment period (P<0.001). The rates of adverse events were similar among the study groups. Four serious adverse events thought to be related to drug use occurred during the 2-week open-label ceftriaxone phase, and no serious drug-related adverse event occurred during the 12-week randomized phase.

CONCLUSIONS:

In patients with persistent symptoms attributed to Lyme disease, longer-term antibiotic treatment did not have additional beneficial effects on health-related quality of life beyond those with shorter-term treatment. (Funded by the Netherlands Organization for Health Research and Development ZonMw; PLEASE ClinicalTrials.gov number, NCT01207739.).

______________________________________________________________________________

A number of patients complained of symptoms after initial therapy, a condition known as persistent post-treatment Lyme disease syndrome, or PTLDS, including fatigue, arthralgia, myalgia, or impaired cognition, and they were often severe. Yet, there are little data to support additional antibiotic treatment, and most professional guidelines do not recommend such an approach. Nonetheless, the issue remains controversial, and some physicians continue to prescribe additional regimens when patients continue to experience physical problems.

Paul G. Auwaerter, MD, clinical director of the division, and Michael T. Melia, MD, assistant professor of medicine, first noted that the species of B. burgdorferi bacteria found in Europe are different from those that circulate in North America, including a longer initial duration of illness, they wrote. They also said that only 96 of 280 participants, or 34 percent, had objective evidence of Lyme disease. “This means that nearly two thirds of their study population had nonspecific symptoms that were attributed to Lyme disease solely on the basis of positive IgM or IgG (or both) immunoblot assays for B. burgdorferi,” they wrote. “Such laboratory findings do not necessarily imply causation and could represent either false positive results or remote infection, since antibody titers can remain elevated for decades,” according to the authors.“[This] means that there was no true placebo component [and] the two active oral study regimens ... are both known to produce anti-inflammatory effects in addition to their antimicrobial properties.”Dr. Kullberg said the editorial provided additional perspective. “The authors are correct that the patients' symptoms were not necessarily causally related to their prior Lyme disease, however all of them had a B. burgdorferi infection in their past.” He emphasized that the main conclusion of the study was that long-term antibiotic treatment had no additional beneficial effects on health-related quality of life. “The strength of the study is that the patients themselves have reported multiple aspects of their health status, including physical and mental health, daily activities, pain, and fatigue, over a one-year follow-up period, and consistently reported that they did not experience any benefit from prolonged therapy compared to controls.”

Commenting on the paper, Andrew R. Pachner, MD, the Murray B. Bornstein professor of neurology at Dartmouth University Geisel School of Medicine, in Lebanon, NH, said the study confirms a large body of evidence against prolonged treatment with antibiotics. But, he added, it may not change how some practitioners approach persistent symptoms. “There continues to be the perception, among a small number of practitioners, and certainly some patients, that these symptoms are being caused by persistent infection. But the data against it [are] quite strong,” he told Neurology  Today. “This study is helpful and hopefully will change the practice of prescribing long-term antibiotics for patients who have been initially treated for Lyme disease by a small number of physicians.”…

All of the subjects were initially in the low range for QOL, yet all of them improved. “In the community this is what happens — people tend to get better with any intervention, so the placebo effect is possible,” she said. “I think this will change the practice for most physicians, but not all. People like an explanation for why they feel symptoms, even if the data does not support longer treatment.”

http://journals.lww.com/neurotodayonline/Fulltext/2016/05050/Largest_Lyme_Disease_Trial_Finds_No_Benefit_with.6.aspx

Reduction in mortality after epilepsy surgery

Sperling MR, Barshow S, Nei M, Asadi-Pooya AA. A reappraisal of mortality after epilepsy surgery. Neurology. 2016 Apr 27. pii:10.1212/WNL.0000000000002700. [Epub ahead of print]

Abstract

OBJECTIVE:

To assess whether epilepsy surgery is associated with a reduction in mortality rate and if postoperative seizure frequency and severity affect mortality.

METHODS:

A total of 1,110 patients were evaluated (1,006 surgically and 104 nonsurgically treated) for a total follow-up of 8,126.62 person-years from 1986 to 2013. Deaths were ascertained through database and Social Security Death Index query. Patients were grouped by surgery type and seizure status; standardized mortality ratio and deaths per 1,000 person-years were calculated. Survival analysis and Cox proportional hazard regression were performed.

RESULTS:

Eighty-nine deaths were observed. Surgically treated patients had a lower mortality rate (8.6 per 1,000 person-years [95% confidence interval (CI) 6.58-11.15]) than nonsurgically treated patients (25.3 per 1,000 person-years [14.50-41.17]; p < 0.001). Seizure-free patients had a lower mortality rate (5.2 per 1,000 person-years [95% CI 2.67-9.02]) than non-seizure-free patients (10.4 per 1,000 person-years [95% CI 7.67-13.89] p = 0.03). More frequent postoperative tonic-clonic seizures (>2 per year) were associated with increased mortality (p = 0.006) whereas complex partial seizure frequency was not related to death rate. Mortality was similar in temporal and extratemporal epilepsy patients (p = 0.7).

CONCLUSIONS:

Brain surgery is associated with a reduction in mortality rate in drug-resistant epilepsy, both when seizures are abolished and when it results in significant palliation of tonic-clonic seizure frequency. These observations provide further rationale for earlier consideration of epilepsy surgery.

______________________________________________________________________________

“I see many patients in the office who have had uncontrolled seizures for many years, sometimes for decades, and you really have to wonder why they hadn't been referred sooner,” said Michael R. Sperling, MD, FAAN, professor of neurology and director of the Jefferson Comprehensive Epilepsy Center at the Thomas Jefferson University Hospital in Philadelphia. “We hope this will serve as a wake-up call to neurologists that there is a risk to not referring patients for surgery, said Dr. Sperling, who also serves as editor-in-chief of the journal Epilepsia. “The decision to persist in futile therapy is one with potentially fatal consequences. ”The results of the new study extend results Dr. Sperling reported in a smaller prospective cohort study he published in 2005….

“This paper is incredibly important,” said Steven Karceski, MD, assistant professor of neurology and director of clinical trials at the Weill Cornell Epilepsy Center. “It tells us that we can have a tremendous impact by getting these seizures under control. There has been too much complacency, and this study tells us that complacency has a very real cost.” An accompanying editorial coauthored by Nathalie Jette, MD, of the University of Calgary and Jerome Engel, MD, PhD, of the University of California, Los Angeles, noted that despite surgery's high efficacy and cost effectiveness, no improvement in delays to referral have been observed since the AAN published a practice parameter in 2003 declaring surgery to be the treatment of choice for drug-resistant temporal lobe epilepsy. The editorial noted, however, that despite its strengths, the study did have a few limitations. First, the cause of death was unknown in over half of the patients, precluding stratification into epilepsy-related versus non epilepsy-related causes. Second, the editorial continued, “the surgical and the non-surgical group were not matched, with the non-surgical group having more severe epilepsy and more comorbidity, thus resulting in selection bias. In addition, the surgical group is ten times larger than the non-surgical group. Finally, the lack of risk adjustment for comorbidity is an important limitation, as a number of comorbidities are associated with mortality. There even exists a validated epilepsy-specific comorbidity risk adjustment index for mortality that could have been applied as part of the analysis.” Lara Jehi, MD, research director and head of the outcomes research program at the Cleveland Clinic Epilepsy Center, said that while such limitations are valid, they do not call into question the study's conclusions or its importance to the field…

“Neurologists may feel, despite the publications, that surgery is not right for their patients, that it's too risky,” said Carl W. Bazil, MD, PhD, FAAN, professor of neurology and director of the division of epilepsy and sleep at Columbia University College of Physicians and Surgeons. “They may feel they can take care of it medically. But they owe it to their patients to tell them, ‘If you get your epilepsy cured by surgery, it decreases your chances of death.’ That's a really important message.”“You may be able to identify individuals with medically-refractory epilepsy after the initial two or three antiepileptic medication trials,” said Gregory D. Cascino, MD, FAAN, Whitney Macmillan, Jr., professor of neuroscience and enterprise director of epilepsy at the Mayo Clinic in Rochester, MN.

http://journals.lww.com/neurotodayonline/Fulltext/2016/05050/Mortality_Risk_Found_to_be_Reduced_by_Two_Thirds.3.aspx

Zika virus microcephaly mechanisms

A few weeks ago, Dr. James Bale saw a series of MRI images in a medical journal of MRI scans of babies infected with Zika in the womb.

They scans showed something Bale had seen only a few times in his 30-year career: a phenomenon called fetal brain disruption sequence.

As the fetus's brain starts to grow, it creates pressure, which pushes on the skull and causes it to grow. But if something stops brain growth — such as a virus — pressure on the skull drops. And the skull can collapse down onto the brain.

The skin around the head continues to grow, Bale says. So the baby is born with wrinkles of skin at the back of the neck and a tiny skull. In some cases, the baby's head is as small as an orange, or about half the size of a healthy baby's head.

"It's quite remarkable what the Zika virus is doing to the brain of young infants," Bale says. "Many of them will die often in infancy, and the majority, if not all, will then have a long-term, severe developmental problems."

Now scientists think they have an understanding about how Zika causes these severe brain malformations. The findings come from a series of mouse experiments, published Wednesday in three leading journals.

In one study, published in Nature, Alysson Muotri and his team at the University of California, San Diego, infected pregnant mice with Zika and looked to see how the virus harmed the baby mice.

"We detected the virus all over the mice and in different regions of the body," Muotri says.

But for some reason — and scientists don't know why yet — Zika is particularly attracted to brain cells. And once inside the cells, Muotri says, Zika turns them into viral factories that start producing huge amounts of virus. Until they burst.

"They explode, and more viral particles are released that can infect other cells. And they can just amplify themselves," Muotri says.

More and more brain cells get infected. More die. This cell death is already a problem for the fetus. It scars the brain and creates inflammation.

But the situation gets worse because the brain cells infected by Zika are extremely special. They're called neural progenitor cells. And they're responsible for building a large portion of the brain.

"These are fast-replicating cells that will give rise to billions of cells in our brains," Muotri says.

So if a fetus loses even just a small percentage of these cells, a portion of its brain will never develop. "And the impact later in life would be dramatic," he says.

A second study, published in the journal Cell Stem Cell[see http://childnervoussystem.blogspot.com/2016/03/zika-virus-and-microcephaly-2.html?showComment=1460673838548#c3242958495096400351], confirmed that Zika destroys neural progenitor cells inside a growing embryo. In that experiment, a team of scientists at the Chinese Academy of Sciences, injected the virus directly into the brains of mice embryos, developing inside their moms.

Muortri says death of brain cells is likely the major way that Zika causes microcephaly in babies. But it isn't the full picture.

In the third study, Indira Mysorekar and her colleagues at Washington University in St. Louis, also infected pregnant mice with Zika.

They found the virus not only damages the brain but also attacks the placenta.

"The nutrient and blood exchange that normally happens between the mother and the fetus is reduced," Mysorekar says. This slows down the baby's growth — and may hurt the brain as well.

Mysorekar and her colleagues published their findings in the journal Cell.

She says mouse experiments can never tell us exactly what's happening in people. Human anatomy is more complicated.

But one thing is clear: Once Zika infects the fetus, "it leaves a lot of havoc and devastation in its wake," she says. "It's almost like a tornado or an earthquake. There is death following Zika."

http://www.npr.org/sections/goatsandsoda/2016/05/11/477648872/how-the-zika-virus-damages-the-brain

Brain stimulation and constraint for perinatal stroke hemiparesis

Kirton A, Andersen J, Herrero M, Nettel-Aguirre A, Carsolio L, Damji O, Keess  J, Mineyko A, Hodge J, Hill MD. Brain stimulation and constraint for perinatal stroke hemiparesis: The PLASTIC CHAMPS Trial. Neurology. 2016 May 3;86(18):1659-1667.

Abstract

OBJECTIVE:

To determine whether the addition of repetitive transcranial magnetic stimulation (rTMS) and/or constraint-induced movement therapy (CIMT) to intensive therapy increases motor function in children with perinatal stroke and hemiparesis.

METHODS:

A factorial-design, blinded, randomized controlled trial (clinicaltrials.gov/NCT01189058) assessed rTMS and CIMT effects in hemiparetic children (aged 6-19 years) with MRI-confirmed perinatal stroke. All completed a 2-week, goal-directed, peer-supported motor learning camp randomized to daily rTMS, CIMT, both, or neither. Primary outcomes were the Assisting Hand Assessment and the Canadian Occupational Performance Measure at baseline, and 1 week, 2 and 6 months postintervention. Outcome assessors were blinded to treatment. Interim safety analyses occurred after 12 and 24 participants. Intention-to-treat analysis examined treatment effects over time (linear mixed effects model).

RESULTS:

All 45 participants completed the trial. Addition of rTMS, CIMT, or both doubled the chances of clinically significant improvement. Assisting Hand Assessment gains at 6 months were additive and largest with rTMS + CIMT (β coefficient = 5.54 [2.57-8.51], p = 0.0004). The camp alone produced large improvements in Canadian Occupational Performance Measure scores, maximal at 6 months (Cohen d = 1.6, p = 0.002). Quality-of-life scores improved. Interventions were well tolerated and safe with no decrease in function of either hand.

CONCLUSIONS:

Hemiparetic children participating in intensive, psychosocial rehabilitation programs can achieve sustained functional gains. Addition of CIMT and rTMS increases the chances of improvement.

CLASSIFICATION OF EVIDENCE:

This study provides Class II evidence that combined rTMS and CIMT enhance therapy-induced functional motor gains in children with stroke-induced hemiparetic cerebral palsy.

Autism and DNA methylation

Ciernia AV, LaSalle J. The landscape of DNA methylation amid a perfect storm of autism aetiologies. Nat Rev Neurosci. 2016 May 6. doi: 10.1038/nrn.2016.41. [Epub ahead of print]

Abstract

Increasing evidence points to a complex interplay between genes and the environment in autism spectrum disorder (ASD), including rare de novo mutations in chromatin genes such as methyl-CpG binding protein 2 (MECP2) in Rett syndrome. Epigenetic mechanisms such as DNA methylation act at this interface, reflecting the plasticity in metabolic and neurodevelopmentally regulated gene pathways. Genome-wide studies of gene sequences, gene pathways and DNA methylation are providing valuable mechanistic insights into ASD. The dynamic developmental landscape of DNA methylation is vulnerable to numerous genetic and environmental insults: therefore, understanding pathways that are central to this 'perfect storm' will be crucial to improving the diagnosis and treatment of ASD.

Key points

•The aetiology of autism spectrum disorder is complex: hundreds of genetic variants and various environmental factors have been implicated as risk factors.

•Epigenetic mechanisms such as DNA methylation and chromatin structure are optimally poised at the intersection of genes and environment in autism aetiologies.

•DNA methylation includes multiple modification types, some of which are specifically enriched in the nervous system.

•The association of DNA methylation with gene expression and the dynamics of modification changes during brain development depend on genomic context.

•DNA-methylation patterns are highly dynamic across the lifespan, with the biggest changes occurring around implantation and in the transition between fetal to early postnatal life.

•Alterations in DNA methylation have been observed by both candidate gene and genomic studies of the post-mortem brain in autism. Future investigations of the autistic brain and surrogate tissues using larger sample sizes and whole-genome sequencing approaches hold promise for improved understanding and potential molecular diagnosis of autism risk.

From the article:

Given that most cases of ASD result from a combination of genetic risk and environmental exposures, alterations in DNA methylation serve as an attractive mechanism to link environmental perturbations to lifelong changes in brain function and behaviour. DNA methylation may have various roles in brain development, including directly affecting gene expression by recruiting specific DNA methyl-binding proteins or serving as a mark of previous transcriptional events that are adaptive in poising genomic regions for future events. Examining DNA methylation in the context of developmental gene expression, other epigenomic markers of chromatin state and cell type can predict functional impact. How DNA methylation affects brain function is also inherently tied to genetic variation in transcription factors, methyl-binding proteins and other regulatory proteins and distal DNA regions. The combination of specific inherited genetic variants may make some individuals more susceptible to environmental risk factors such as chemical exposures, maternal infection or low folate levels. Individuals harbouring CNVs or single-nucleotide variants that affect chromatin and synaptic genes might also be especially sensitive to environmental perturbations. Given the widespread and highly dynamic changes in DNA methylation that occur in early fetal life, this time point in development may be particularly vulnerable to the cumulative impact of genetic and environmental risk factors.

Testing the causal relationship between DNA-methylation changes and altered brain development is difficult. DNA methylation is likely to be both a cause and consequence of the developmental regulation of gene expression and occurs in the context of other epigenomic mechanisms of regulation, such as histone modifications. Consequently, differences in methylation at any given point in development may or may not provide mechanistic information on the current state of neurodevelopment. For example, altered brain development caused by a genetic or environmental perturbation may indirectly affect DNA methylation as the brain attempts to compensate for suboptimal conditions. So far, there is only limited evidence of altered DNA-methylation patterns in ASD brain samples, but the levels of methyl donors available to the developing fetus during gestation are related to ASD risk. Although this is hardly causal evidence, it does suggest that supplements containing methyl donors taken before conception may provide some protection against ASD by mitigating the perfect storm of risk factors and aberrant DNA methylation in genetically susceptible individuals.

Courtesy of Doximity