Medical marijuana may ease some MS; Little evidence for other complementary or alternative therapies

A new guideline from the American Academy of Neurology suggests that there is little evidence that most complementary or alternative medicine therapies (CAM) treat the symptoms of multiple sclerosis (MS). However, the guideline states the CAM therapies oral cannabis, or medical marijuana pills, and oral medical marijuana spray may ease patients’ reported symptoms of spasticity, pain related to spasticity and frequent urination in multiple sclerosis (MS). The guideline, which is published in the March 25, 2014, print issue of Neurology, the medical journal of the American Academy of Neurology, states that there is not enough evidence to show whether smoking marijuana is helpful in treating MS symptoms.The guideline looked at CAM therapies, which are nonconventional therapies used in addition to or instead of doctor-recommended therapies. Examples include oral cannabis, or medical marijuana pills and oral medical marijuana spray, ginkgo biloba, magnetic therapy, bee sting therapy, omega-3 fatty acids and reflexology.”Using different CAM therapies is common in 33 to 80 percent of people with MS, particularly those who are female, have higher education levels and report poorer health,” said guideline lead author Vijayshree Yadav, MD, MCR, with Oregon Health & Science University in Portland and a member of the American Academy of Neurology. “People with MS should let their doctors know what types of these therapies they are taking, or thinking about taking.”For most CAM therapies, safety is unknown. There is not enough information to show if CAM therapies interact with prescription MS drugs. Most CAM therapies are not regulated by the Food and Drug Administration (FDA). Dronabinol and nabilone are synthetic forms of key ingredients in marijuana. The FDA approved both drugs as treatments for nausea and vomiting associated with cancer chemotherapy that do not respond to standard treatments. Dronabinol also is approved for loss of appetite associated with weight loss in patients with AIDS.The guideline found that certain forms of medical marijuana, in pill or oral spray form only, may help reduce patients’ reported spasticity symptoms, pain due to spasticity, and frequent urination but not loss of bladder control. …

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Do obesity, birth control pills raise risk of multiple sclerosis?

The role of the so-called “obesity hormone” leptin and hormones used for birth control in the development of multiple sclerosis (MS) is examined in two new studies that will be presented at the American Academy of Neurology’s 66th Annual Meeting in Philadelphia, April 26 to May 3, 2014.For the obesity study, BMI was calculated for 210 people with MS and 210 people of the same age and sex who did not have MS at ages 15 and 20 and at the time of the study. The study found that people who are obese at age 20 are twice as likely to later develop MS as people who are not obese. The study found that people with higher BMI levels also had higher levels of leptin, a hormone made by fat tissue that regulates weight, appetite and immune response.”Leptin promotes inflammatory responses in the body, which could potentially explain the link between obesity and MS,” said study author Jorge Correale, MD, of the Ral Carrera Institute for Neurological Research in Buenos Aires, Argentina.For the birth control hormone study, researchers identified 305 women who had been diagnosed with MS or its precursor, clinically isolated syndrome, during a three-year period from the membership of Kaiser Permanente Southern California and who had been members for at least three years before the MS symptoms began. Then they compared them to 3,050 women who did not have MS.A total of 29 percent of the women with MS and 24 percent of those without MS had used hormonal contraceptives for at least three months in the three years before symptoms began. The majority used estrogen/progestin combinations.Women who had used hormonal contraceptives were 35 percent more likely to develop MS than those who did not use them. Those who had used the contraceptives but had stopped at least one month before symptoms started were 50 percent more likely to develop MS.”These findings suggest that using hormonal contraceptives may be contributing at least in part to the rise in the rate of MS among women,” said study lead author Kerstin Hellwig, MD, from Bochum Germany, post-doctoral research fellow, Kaiser Permanente Southern California.Story Source:The above story is based on materials provided by American Academy of Neurology (AAN). Note: Materials may be edited for content and length.

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Sleep apnea may contribute to fatigue in multiple sclerosis: Study

A new study provides evidence that obstructive sleep apnea (OSA) is highly prevalent in people with multiple sclerosis (MS), and it suggests that OSA may be a contributor to the fatigue that is one of the most common and debilitating symptoms of MS.Results show that one-fifth of MS patients surveyed in a large tertiary MS practice carried a diagnosis of OSA, and more than half were found to have an elevated risk for OSA based on a validated screening tool. Further analysis showed that OSA risk was a significant predictor of fatigue severity, even after adjusting for potential confounders such as age, gender, body mass index (BMI), sleep duration and depression.”OSA may be a highly prevalent and yet under-recognized contributor to fatigue in persons with MS,” said lead author and principal investigator Tiffany J. Braley, MD, MS, an Assistant Professor of Neurology from the University of Michigan Multiple Sclerosis and Sleep Disorders Centers in Ann Arbor, Mich. “Our study suggests that clinicians should have a low threshold to evaluate MS patients for underlying sleep disturbances.”The study results appear in the Feb. 15 issue of the Journal of Clinical Sleep Medicine, which is published by the American Academy of Sleep Medicine.”Obstructive sleep apnea is a chronic illness that can have a destructive impact on your health and quality of life,” said American Academy of Sleep Medicine President Dr. M. Safwan Badr. “People with multiple sclerosis who are found to have a high risk of OSA should be referred to a board certified sleep medicine physician for a comprehensive sleep evaluation.”Braley and her colleagues, Benjamin M. Segal, MD (Director of the University of Michigan Multiple Sclerosis Center), and Ronald D. Chervin, MD, MS, (Director of the University of Michigan Sleep Disorders Center) studied 195 MS patients who completed a sleep questionnaire and four validated instruments designed to assess daytime sleepiness, fatigue severity, insomnia severity and OSA risk. …

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Innovative technique creates large skin flaps for full-face resurfacing

Patients with massive burns causing complete loss of the facial skin pose a difficult challenge for reconstructive surgeons. Now a group of surgeons in China have developed an innovative technique for creating a one-piece skin flap large enough to perform full-face resurfacing, reports The Journal of Craniofacial Surgery, published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health.Dr. QingFeng Li and colleagues of Shanghai Jiao Tong University School of Medicine describe their approach to creating “monoblock” flaps for use in extensive face skin resurfacing. In their successful experience with five severely disfigured patients, the full-face tissue flap “provides universally matched skin and near-normal facial contour.”New Technique Grows One-Piece Skin Flaps for Full-Face ResurfacingComplete destruction of the facial skin and underlying (subcutaneous) tissues presents “the most challenging dilemma” in facial reconstructive surgery. Multiple skin flaps and grafts are needed to provide complete coverage, creating a “patchwork” appearance. Standard skin grafts are also too bulky to provide good reconstruction of the delicate features and expressive movement of the normal facial skin.To meet these challenges, Dr. Li and colleagues have developed a new technique for creating a single, large skin flap appropriate for use in full-face resurfacing. Their approach starts with “prefabrication” of a flap of the patient’s own skin, harvested from another part of the body. The skin flap, along with its carefully preserved blood supply, is allowed to grow for some weeks in a “pocket” created under the patient’s skin of the patient’s upper chest.Tissue expanders — balloon-like devices gradually filled with saline solution — are used to enlarge the skin flap over time. While skin expansion is a standard technique for creation of skin flaps, Dr. …

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MS researchers study predictors of employment status

Researchers at Kessler Foundation have studied the measurement tools used in multiple sclerosis for their effectiveness in predicting employment status. They compared the Expanded Disability Status Scale (EDSS), the Multiple Sclerosis Functional Composite (MSFC), the Paced Auditory Serial Addition Task (PASAT), and the Symbol Digit Modalities Test (SDMT), and found the SDMT effective in differentiating employed from unemployed individuals.The article, “Unemployment in multiple sclerosis (MS): utility of the MS Functional Composite and cognitive testing,” was published in the January 2014 issue of Multiple Sclerosis Journal.The authors are Lauren Strober, PhD, Nancy Chiaravalloti, PhD, Nancy Moore, PhD, and John DeLuca, PhD, of Kessler Foundation.”The population with MS comprises people of working age,” noted Dr. Strober, senior research scientist, “which is why factors related to employment status are a major concern for individuals and clinicians.” The researchers studied 77 people with MS; 40 were employed and 37 were unemployed. To determine which factor(s) were predictive of employment status, they compared the two groups in regard to demographic factors, disease variables, MSFC, and cognitive performance. Differences were found in disease duration and progression, upper extremity function, processing speed, verbal learning and memory, and executive function. Analysis revealed the SDMT to be the only predictor of employment status, with an overall accuracy of 67%. “These findings suggest that clinical use of the SDMT may help identify those individuals who are at risk for unemployment,” she explained. “This would allow clinicians to advise them on strategies for maintaining employment.””Unemployment research is a priority at Kessler Foundation,” remarked Dr. Chiaravalloti, “because maintaining employment is such an important factor in the quality of life of persons with MS.”Story Source:The above story is based on materials provided by Kessler Foundation. Note: Materials may be edited for content and length.

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Scientists use blur to sharpen DNA mapping

Oct. 9, 2013 — With high-tech optical tools and sophisticated mathematics, Rice University researchers have found a way to pinpoint the location of specific sequences along single strands of DNA, a technique that could someday help diagnose genetic diseases.Proof-of-concept experiments in the Rice lab of chemist Christy Landes identified DNA sequences as short as 50 nucleotides at room temperature, a feat she said is impossible with standard microscopes that cannot see targets that small, or electron microscopes that require targets to be in a vacuum or cryogenically frozen.The technique called “super-localization microscopy” has been known for a while, Landes said, but its application in biosensing is just beginning. Scientists have seen individual double-stranded DNA molecules under optical microscopes for years, but the ability to see single-stranded DNA is a new achievement, and breaking the diffraction limit of light adds value, she said.The work by Landes, Rice postdoctoral associate Jixin Chen and undergraduate student Alberto Bremauntz is detailed in the American Chemical Society journal Applied Materials and Interfaces.The Rice researchers call their super-resolution technique “motion blur point accumulation for imaging in nanoscale topography” (mbPAINT). With it, they resolved structures as small as 30 nanometers (billionths of a meter) by making, essentially, a movie of fluorescent DNA probes flowing over a known target sequence along an immobilized single strand of DNA.The probes are labeled with a fluorescent dye that lights up only when attached to the target DNA. In the experimental setup, most would flow by unseen, but some would bind to the target for a few milliseconds, just long enough to be captured by the camera before the moving liquid pulled them away. Processing images of these brief events amidst the background blur allows the researchers to image objects smaller than the natural diffraction limits of light-based imaging, which do not allow for the resolution of targets smaller than the wavelength of light used to illuminate them.Even the Landes lab’s system is subject to these physical limitations. Individual images of fluorescing probes on targets are just a pixelated blur. But it’s a blur with a bright spot, and careful analysis of multiple images allows the researchers to pinpoint that spot along the strand.”The probes are moving so fast that in real time, all we would see with the camera is a line,” Chen said. But when the camera firing at 30-millisecond intervals happened to catch a bound probe, it clearly stood out. The probes sometime picked out two sequences along a strand that would have been seen as a single blur via regular fluorescent microscopy.Landes said one goal for mbPAINT is to map ever-smaller fragments of DNA. …

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New explanation for key step in anthrax infection proposed

Aug. 20, 2013 — A new hypothesis concerning a crucial step in the anthrax infection process has been advanced by scientists at the National Institute of Standards and Technology (NIST) and the U.S. Army Medical Research Institute for Infectious Diseases (USAMRIID) at Fort Detrick, Md.The research teams have explored the behavior of the toxins that rapidly overwhelm the body as the often-fatal disease progresses. Their findings suggest a new possible mechanism by which anthrax bacteria deliver the protein molecules that poison victims. Anthrax is easily weaponized; the findings could help lead to a more effective cure.Anthrax bacteria kill by releasing three toxins that work in concert to destroy cells. One toxin, called PA, attaches to the cell membrane, where its surface serves as a sort of landing pad for the other two toxins, called LF and EF. Once several molecules of LF and EF have latched onto PA, the cell membrane tries to destroy these unwanted hangers-on by wrapping them up in an “endosome,” a small bubble of membrane that gets pinched off and moved into the cell’s interior. There, the cell attempts to destroy its contents by a process that includes making the interior of the endosome more acidic. But before the cell can fully carry out its plan, the LF and EF escape from the endosome and wreak havoc in the cell’s interior. The question is: how do these toxins escape?”A recent hypothesis is that LF and EF completely unfold and then squeeze through the narrow hole that PA forms in the endosomal membrane,” says NIST physical scientist John Kasianowicz. …

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Chemists’ work will aid drug design to target cancer and inflammatory disease

Aug. 8, 2013 — Chemists at Indiana University Bloomington have produced detailed descriptions of the structure and molecular properties of human folate receptor proteins, a key development for designing new drugs that can target cancer and inflammatory diseases without serious side effects.The researchers, from the lab of Charles Dann III, assistant professor of chemistry in the College of Arts and Sciences, published their findings in the Proceedings of the National Academy of Sciences. Dann said the results should help chemists create more effective antifolate drugs, which act by interfering with the ability of folates — also called folic acid or vitamin B9 — to perform tasks that are essential for cell growth.The findings could be especially helpful against epithelial cell cancers, including ovarian cancers that are resistant to treatment and nearly always fatal. They could also guide the design of drugs for inflammatory diseases such as rheumatoid arthritis, Crohn’s disease and psoriasis.The article, “Structures of human folate receptors reveal biological trafficking states and diversity in folate and antifolate recognition,” is scheduled to be online this week. Lead author is Soca Wibowo, an IU staff scientist and a former graduate student in Dann’s lab. Co-authors include Dann; postdoctoral fellow Mirage Singh; former IU undergraduate researchers Kristen Reeder, Joshua Carter and Alexander Kovach; former IU researchers Wuyi Meng and Faming Zhang; and Manohar Ratnam of the Karmanos Cancer Institute in Detroit.Physicians have used antifolates for 60 years to treat cancer, and the drugs are often effective at killing cancer cells. The problem is, they aren’t selective.”The antifolates that are currently available also enter normal, healthy cells and kill those as well,” Dann said. “What we’re describing is an entryway into cancer cells that can be exploited to specifically target or attack cancer cells with drugs.”One reason for the multiple chemotherapeutic side effects of current antifolates is that they typically enter cells via routes that are present in most cell types, not just in cancer cells. The PNAS paper, on the other hand, examines the potential for targeting a different entry route in which the molecules bind with human folate receptors, which are widely present in certain cancer cells and in causal cells of inflammatory disease, but not in normal cells.Dann describes the folate receptors as “locks” that can be used to open a door into the cell. By gaining a better understanding of what the lock looks like and how it works, researchers can build a better key — that is, a better antifolate drug — to open the door.The lab does this by taking “molecular snapshots” of the folate receptor proteins, capturing the placement of atoms and the origami-like twists and folds of the molecules to reveal how folates and antifolates are likely to bind with the molecules. …

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Children and magnets have a dangerous attraction, end up in the ER

Aug. 7, 2013 — Cases involving children ingesting magnets quintupled between 2002 and 2011, with ingestion of multiple magnets generally resulting in more serious outcomes, including emergency surgery. The results of a study documenting a rapid rise in pediatric injuries was published online yesterday in Annals of Emergency Medicine.”It is common for children to put things in their mouth and nose, but the risk of intestinal damage increases dramatically when multiple magnets are swallowed,” said lead study author Jonathan Silverman, MD, of the Department of Pediatrics at the University of Washington in Seattle, Wash. “The ingestion of multiple magnets can severely damage intestinal walls to the point that some kids need surgery. The magnets in question were typically those found in kitchen gadgets or desk toys marketed to adults but irresistible to children.”Over a 10-year period, 22,581 magnetic foreign body injuries were reported among children. Between 2002 and 2003, incidence of injury was 0.57 cases per 100,000 children; between 2010 and 2011, that jumped to 3.06 cases per year out of 100,000 children. The majority of the cases occurred in 2007 or later.In cases where children ingested multiple magnets, 15.7 percent were admitted to the hospital (versus 2.3 percent of single magnet ingestions). Nearly three-quarters (74 percent) of magnets were swallowed; twenty-one percent were ingested through the nose. Nearly one-quarter (23.4 percent) of the case reports described the magnets as “tiny,” or other variants on the word “small.””The injuries were not restricted to small children either,” said Dr. Silverman. …

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Breastfeeding may protect against persistent stuttering

Aug. 5, 2013 — A study of 47 children who began stuttering at an early age found that those who were breastfed in infancy were more likely to recover from stuttering and return to fluent speech.”Long-chain fatty acids in human milk play an important role in the development of neural tissue,” said Jamie Mahurin-Smith, who conducted the new study as a doctoral student at U. of I.The analysis, reported in the Journal of Communication Disorders, found a dose-dependent association between breastfeeding and a child’s likelihood of recovering from stuttering, with children who were breastfed longer more likely to recover. Boys, who are disproportionately affected by stuttering, appeared to benefit the most. Boys in the study who breastfed for more than a year had approximately one-sixth the odds of developing persistent stuttering than boys who never breastfed, the team found.The researchers, University of Illinois speech and hearing science professor emerita Nicoline Ambrose and doctoral student Jamie Mahurin-Smith (now at Illinois State University), found no evidence that income or maternal education had any influence on stuttering in their sample. The researchers questioned the mothers about their children’s willingness and ability to breastfeed, and also found no evidence of an underlying neurological problem that could have inhibited the children’s ability to breastfeed and to speak fluently later in life.”We’ve known for years that both genetic and environmental factors contributed to stuttering, but our understanding of the specific environmental variables in play has been murky,” Mahurin-Smith said. “These findings could improve our understanding of stuttering persistence and recovery.”Several earlier studies had found “a consistent association between breastfeeding and improved language development,” the researchers report. A 1997 study found that babies breastfed for more than nine months had a significantly lower risk of language impairment than those breastfed for shorter periods of time. A later study found that infants who breastfed were more likely to produce “variegated babbling at earlier ages,” a key marker of healthy language development.Other studies have found associations between the duration of breastfeeding and verbal IQ or a child’s likelihood of being diagnosed with an autism spectrum disorder.Ambrose and Mahurin-Smith suggest that essential fatty acids found in breast milk but often lacking in infant formulas may help explain why longer duration of breastfeeding is associated with better brain and language development.”Long-chain fatty acids found in human milk, specifically docosahexaenoic acid and arachidonic acid, play an important role in the development of neural tissue,” Mahurin-Smith said. “Fluent speech requires an extraordinarily complex sequence of events to unfold rapidly, and our hypothesis was that early differences in neurodevelopment could cause difficulties with speech fluency later in life.”The infant brain triples in size in its first year of life, and “more than half of the solid weight of that newly built tissue will be lipid,” the researchers wrote. …

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New light shed on cause of pandemic influenza

July 24, 2013 — With the use of sophisticated mathematical modelling techniques, a mathematician at PolyU and his co-researchers have completed a study that explains the phenomenon of multiple waves of influenza pandemic in the last century.With the use of sophisticated mathematical modelling techniques, a mathematician at The Hong Kong Polytechnic University (PolyU) and his co-researchers have completed a study that explains the phenomenon of multiple waves of influenza pandemic in the last century.Taking part in this advanced study is Dr Daihai He, Assistant Professor of PolyU’s Department of Applied Mathematics. He has collaborated with four researchers in Canada to offer an explanation to the worst influenza pandemic in the history of humankind. The research team found that behavioural response has the largest impact among three primary factors causing the waves, thus paving the way for future enhancement on control strategies to the spread of influenza virus.The 1918 flu epidemic was one of the world’s deadliest natural disasters, causing the death of hundred thousands of people. Influenza pandemic appears to be characterized by multiple waves of incidence in one year, but the mechanism that explains this phenomenon has so far been elusive.In explaining the deadly pandemic, Dr Daihai He and his teammates have incorporated in their mathematical model three contributing factors for multiple waves of influenza pandemic in England and Wales: (i) schools opening and closing, (ii) temperature changes during the outbreak, and (iii) changes in human behaviour in response to the outbreak.Dr He and the researchers further applied this model to the reported influenza mortality during the 1918 pandemic in 334 British administrative units and estimate the epidemiological parameters. They have used information criteria to evaluate how well these three factors explain the observed patterns of mortality. The results indicate that all three factors are important, but behavioural responses had the largest effect.The findings have recently been published in the journal Proceedings of the Royal Society Biological Sciences (July 2013 Issue). Dr He’s expertise in advanced mathematics and statistics has helped improve our understanding of the spread of influenza virus at the population level and lead to improved strategies to control and minimize the spread of influenza virus.

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Protein complex linked to cancer growth may also help fight tumors

July 22, 2013 — Researchers at Moffitt Cancer Center and Tianjin Medical University Cancer Institute and Hospital in China have discovered a gene expression signature that may lead to new immune therapies for lung cancer patients. They found that NF-κB, a protein complex known to promote tumor growth, may also have the ability to boost the immune system to eliminate cancerous cells before they harm, as well as promote antitumor responses.The study appeared in the June 3 issue of The Journal of Clinical Investigation.NF-κB is a protein complex that controls gene expression. The regulation of NF-κB also plays an important role in regulating the body’s immune response to infection. Incorrect regulation of NF-kB has been linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development.”New insight into how tumor pathways regulate the anti-tumor immune response may help us to devise new ways for improving immune therapy,” said study lead author Amer Beg, Ph.D., senior member of Moffitt’s Immunology Program. “Studies are now underway to start a clinical trial to determine whether the novel gene expression signature described in this work may help initiate new and better immunotherapy treatments.”According to Beg, NF-κB proteins regulate key genes involved in immune response, inflammation, cell death and cell growth. Work in his lab is aimed at a better understanding of how NF-κB regulates immune response and how the consequences of impaired regulation of responses are related to disease.The researchers analyzed the role of NF-κB in lung cancer cells that were used to develop the NF-κB gene signature. Key studies in mice showed that NF-κB can mediate immune rejection of tumors. The studies were then extended to human tumor specimens. “In this study we found that NF-κB activity is strongly associated with immune system T-cell infiltration in lung cancer,” explained study co-author Dung-Tsa Chen, Ph.D., member of the Biostatistics Department at Moffitt. “Multiple genes, capable of enhancing T-cell responses, were found in the NF-κB signature. …

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Multiple sclerosis research could help repair damage affecting nerves

July 21, 2013 — Multiple sclerosis treatments that repair damage to the brain could be developed thanks to new research.A study has shed light on how cells are able to regenerate protective sheaths around nerve fibres in the brain.These sheaths, made up of a substance called myelin, are critical for the quick transmission of nerve signals, enabling vision, sensation and movement, but break down in patients with multiple sclerosis (MS).The study, by the Universities of Edinburgh and Cambridge, found that immune cells, known as macrophages, help trigger the regeneration of myelin.Researchers found that following loss of or damage to myelin, macrophages can release a compound called activin-A, which activates production of more myelin.Dr Veronique Miron, of the Medical Research Council Centre for Regenerative Medicine at the University of Edinburgh, said: “In multiple sclerosis patients, the protective layer surrounding nerve fibres is stripped away and the nerves are exposed and damaged.”Approved therapies for multiple sclerosis work by reducing the initial myelin injury — they do not promote myelin regeneration. This study could help find new drug targets to enhance myelin regeneration and help to restore lost function in patients with multiple sclerosis.”The study, which looked at myelin regeneration in human tissue samples and in mice, is published in Nature Neuroscience and was funded by the MS Society, the Wellcome Trust and the Multiple Sclerosis Society of Canada.Scientists now plan to start further research to look at how activin-A works and whether its effects can be enhanced.Dr Susan Kohlhaas, Head of Biomedical Research at the MS Society, said: “We urgently need therapies that can help slow the progression of MS and so we’re delighted researchers have identified a new, potential way to repair damage to myelin. We look forward to seeing this research develop further.”Dr Karen Lee, Vice-President, Research at the MS Society of Canada, said: “We are pleased to fund MS research that may lead to treatment benefits for people living with MS. We look forward to advances in treatments that address repair specifically, so that people with MS may be able to manage the unpredictable symptoms of the disease.”

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Women who give birth to multiple babies after IVF are at higher risk of breast cancer

July 9, 2013 — Women who give birth to multiple babies following IVF treatment are at a higher risk of breast cancer than those giving birth to singletons or who remain childless. Dutch investigators from the Omega study group said the explanation may not be the multiple pregnancy per se but a maternal trait related to a higher implantation potential and to breast cancer itself.Although the results were derived from a large nationwide cohort study, the investigators emphasise that the findings should next be replicated in further studies and that presently there is no reason for earlier breast cancer screening than is recommended for the general population.The study, presented today at the annual meeting of ESHRE by Dr Els Groeneveld from the VU University Medical Centre of Amsterdam, the Netherlands, analysed data from the Omega study, a large Dutch nationwide cohort of 19,861 women who received IVF or ICSI treatment between 1983 and 1995. Between 1997 and 1999 all patients were questioned (by questionnaire) about their treatment and its outcome. Those who completed the questionnaire (12,589 women) were cross-referred to the Netherlands Cancer Registry.Cohort analysis showed that over a median 16.7 years of follow-up 1688 women in the study gave birth to multiples (13%), 6027 delivered singletons (48%), and 4874 remained childless (39%). Among these women there were 317 confirmed diagnoses of breast cancer, of whom 57 gave birth to multiples, 155 to singletons, and 105 remained childless. When these findings were analysed statistically, results showed that mothers of multiples had a (44%) higher breast cancer risk than the mothers of singletons (hazard ratio 1.44, statistically significant) when adjusted for year of IVF treatment, number of IVF cycles, height and age at first birth. Nulliparous women were at no increased risk of breast cancer.Remarkably, only multiple pregnancies conceived after the complete implantation of all transferred embryos were associated with an increased breast cancer risk (HR 1.86), whereas multiple pregnancies conceived after incomplete implantation were not (HR 1.31, not statistically significant). This finding, says Dr Groeneveld, supports the hypothesis of a link between high embryo implantation potential and breast cancer risk.She explained: “It has been generally assumed that increased levels of estrogen and progesterone in multiple pregnancies stimulate cellular proliferation in the breast, which increases accumulation of somatic mutations during cell division and leads to the development of breast cancer. Thus, breast cancer could be seen as a consequence of the multiple pregnancy itself. However, we also hypothesise that an additional maternal trait might be associated with an increased breast cancer risk in these women.”Such a trait could be maternal serum concentrations of vascular endothelial growth factor (VEGF), a known protein involved in breast cancer progression and which Dr Groeneveld’s group in Amsterdam has recently found associated with improved embryo implantation potential.”In our study women who developed a multiple pregnancy from all transferred embryos represent women with high embryo implantation potential, possibly through increased levels of VEGF,” said Dr Groeneveld. …

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Higher education may be protective against multiple sclerosis-associated cognitive deficits

July 2, 2013 — Multiple sclerosis (MS) can lead to severe cognitive impairment as the disease progresses. Researchers in Italy have found that patients with high educational levels show less impairment on a neuropsychological evaluation compared with those with low educational levels.Their results are published in Restorative Neurology and Neuroscience.MS is a progressive immunologic brain disorder with neuropsychological deficits including selective attention, working memory, executive functioning, information processing speed, and long term memory. These deficits often impact daily life (ability to do household tasks, interpersonal relationships, employment, and overall quality of life).In this study, investigators first assessed the role of cognitive reserve, the brain’s active attempt to focus on how tasks are processed, in compensating for the challenge represented by brain damage. Earlier studies had reported that higher cognitive reserve protects MS subjects from disease-related cognitive inefficiency but in these studies cognitive reserve was mainly estimated through a vocabulary test. Here, investigators considered educational level and occupational attainment instead of vocabulary. They also evaluated both educational and occupational experience, hypothesizing that an individual’s lifetime occupational attainment could also be considered a good proxy of CR, similar to the way in which higher occupational attainment reduces the risk of Alzheimer’s disease.The second aim of the study was to investigate the possible role of perceived fatigue. Fatigue can have a great negative influence on daily life, so that higher perceived fatigue might result in lower cognitive performance.Fifty consecutive clinically diagnosed MS patients took part in the study. A control group included 157 clinically healthy subjects, with no psychiatric or neurological diagnosis. Individuals in both groups were, on average, of the same age, education level and gender. The mean age was 40.41 (± 9.67) years, with 12.37 (± 4.42) years of education.Cognitive performance was evaluated using the Paced Auditory Serial Addition Test (PASAT), in which a series of single digit numbers are presented and the two most recent digits must be summed. …

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IVF for male infertility linked to increased risk of intellectual disability and autism in children

July 2, 2013 — In the first study to compare all available IVF treatments and the risk of neurodevelopmental disorders in children, researchers find that IVF treatments for the most severe forms of male infertility are associated with an increased risk of intellectual disability and autism in children.Autism and intellectual disability remain a rare outcome of IVF, and whilst some of the risk is associated with the risk of multiple births, the study provides important evidence for parents and clinicians on the relative risks of modern IVF treatments.Published in JAMA today, the study is the largest of its kind and was led by researchers at King’s College London (UK), Karolinska Institutet (Sweden) and Mount Sinai School of Medicine in New York (USA).By using anonymous data from the Swedish national registers, researchers analysed more than 2.5 million birth records from 1982 and 2007 and followed-up whether children had a clinical diagnosis of autism or intellectual disability (defined as having an IQ below 70) up until 2009. Of the 2.5m children, 1.2% (30,959) were born following IVF. Of the 6,959 diagnosed with autism, 103 were born after IVF; of the 15,830 with intellectual disability, 180 were born after IVF. Multiple pregnancies are a known risk factor for pre-term birth and some neurodevelopmental disorders, so the researchers also compared single to multiple births.Sven Sandin, co-author of the study from King’s College London’s Institute of Psychiatry says: “IVF treatments are vastly different in terms of their complexity. When we looked at IVF treatments combined, we found there was no overall increased risk for autism, but a small increased risk of intellectual disability. When we separated the different IVF treatments, we found that ‘traditional’ IVF is safe, but that IVF involving ICSI, which is specifically recommended for paternal infertility is associated with an increased risk of both intellectual disability and autism in children.”Compared to spontaneous conception, children born from any IVF treatment were not at an increased risk of autism, but were at a small increased risk of intellectual disability (18% increase — from 39.8 to 46.3 per 100,000 person years). However, the risk increase disappeared when multiple births were taken into account.Secondly, the researchers compared all 6 different types of IVF procedures available in Sweden — whether fresh or frozen embryos were used; if intracytoplasmic sperm injection (ICSI) was used, and if so, whether sperm was ejaculated or surgically extracted. Developed in 1992, ICSI is recommended for male infertility and is now used in about half of all IVF treatments. The procedure involves injecting a single sperm directly into an egg, rather than fertilization happening in a dish, as in standard IVF.Children born after IVF treatments with ICSI (with either fresh or frozen embryos) were at an increased risk of intellectual disability (51% increase — 62 to 93 per 100,000). This association was even higher when a preterm birth also occurred (73% increase — 96 to 167 per 100,000). …

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In multiple sclerosis animal study, absence of gene leads to earlier, more severe disease

June 24, 2013 — Scientists led by a UCSF neurology researcher are reporting that they have identified the likely genetic mechanism that causes some patients with multiple sclerosis (MS) to quickly progress to a debilitating stage of the disease while other patients progress much more slowly.The team found that the absence of the gene Tob1 in CD4+ T cells, a type of immune cell, was the key to early onset of more serious disease in an animal model of MS.Senior author Sergio Baranzini, PhD, a UCSF associate professor of neurology, said the finding may ultimately lead to the development of a test that predicts the course of MS in individual patients. Such a test could help physicians tailor personalized treatments, he said.The study, done in collaboration with UCSF neurology researchers Scott Zamvil, MD, and Jorge Oksenberg, PhD, was published on June 24, 2013 in the Journal of Experimental Medicine.MS is an inflammatory disease in which the protective myelin sheathing that coats nerve fibers in the brain and spinal cord is damaged and ultimately stripped away — a process known as demyelination. During the highly variable course of the disease, a wide range of cognitive, debilitating and painful neurological symptoms can result.In previously published work, Baranzini and his research team found that patients at an early stage of MS known as clinically isolated syndrome who expressed low amounts of Tob1 were more likely to exhibit further signs of disease activity — a condition known as relapsing-remitting multiple sclerosis — earlier than those who expressed normal levels of the gene.The current study, according to Baranzini, had two goals: to recapitulate in an animal model what the researchers had observed in humans, and uncover the potential mechanism by which it occurs.The authors were successful on both counts. They found that when an MS-like disease was induced in mice genetically engineered to be deficient in Tob1, the mice had significantly earlier onset compared with wild-type mice, and developed a more aggressive form of the disease.Subsequent experiments revealed the probable cause: the absence of Tob1 in just CD4+ T cells. The scientists demonstrated this by transferring T cells lacking the Tob1 gene into mice that had no immune systems but had normal Tob1 in all other cells. They found that the mice developed earlier and more severe disease than mice that had normal Tob1 expression in all cells including CD4+.”This shows that Tob1 only needs to be absent in this one type of immune cell in order to reproduce our initial observations in mice lacking Tob1 in all of their cells,” said Baranzini.The researchers also found the likely mechanism of disease progression in the Tob1-deficient mice: higher levels of Th1 and Th17 cells, which cause an inflammatory response against myelin, and lower levels of Treg cells, which normally regulate inflammatory responses. The inflammation results in demyelination.The research is significant for humans, said Baranzini, because the presence or absence of Tob1 in CD4+ cells could eventually serve as a prognostic biomarker that could help clinicians predict the course and severity of MS in individual patients. “This would be useful and important,” he said, “because physicians could decide to switch or modify therapies if they know whether the patient is likely to have an aggressive course of disease, or a more benign course.”Ultimately, predicted Baranzini, “This may become an example of personalized medicine. When the patient comes to the clinic, we will be able to tailor the therapy based on what the tests tell us. We’re now laying the groundwork for this to happen.”Co-authors of the study are Ulf Schulze-Topphoff, PhD, of UCSF; Simona Casazza, PhD, of UCSF at the time of the study; Michel Varrin-Doyer, PhD; and Kara Pekarek of UCSF; Raymond A. …

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Potential treatment strategies for multiple sclerosis

June 24, 2013 — Myelin, the fatty coating that protects neurons in the brain and spinal cord, is destroyed in diseases such as multiple sclerosis. Researchers have been striving to determine whether oligodendrocytes, the cells that produce myelin, can be stimulated to make new myelin. Using live imaging in zebrafish to track oligodendrocytes in real time, researchers reporting in the June 24 issue of the Cell Press journal Developmental Cell discovered that individual oligodendrocytes coat neurons with myelin for only five hours after they are born. If the findings hold true in humans, they could lead to new treatment strategies for multiple sclerosis.Share This:”The study could help improve our understanding of the triggers needed to encourage cells to produce myelin,” says senior author Dr. David Lyons, of the University of Edinburgh, UK. For example, if scientists could determine what is blocking the cells from making myelin after five hours, they might be able to remove that blockage. Alternatively, treatments could focus on creating more new oligodendrocytes rather than trying to stimulate existing oligodendrocytes.Dr. Lyons and his team used zebrafish to study the formation of myelin sheaths by oligodendrocytes because this laboratory animal is transparent at early stages of its development, which allows investigators to directly observe cells within the organism. It is also known that zebrafish and humans have very similar genes, and these similarities extend to more than 80% of the genes associated with human disease. Zebrafish therefore respond in very similar ways to most drugs used for therapeutic purposes in humans.”In the future, zebrafish will be used to identify new genes and drugs that can influence myelin formation and myelin repair,” says Dr. …

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Commonly-prescribed drugs may influence the onset and progression of Alzheimer’s disease

June 12, 2013 — Multiple drug classes commonly prescribed for common medical conditions are capable of influencing the onset and progression of Alzheimer’s disease, according to researchers at The Mount Sinai Medical Center. The findings are published online in the journal PLoS One.Led by Giulio Maria Pasinetti, MD, PhD, the Saunders Family Chair and Professor in Neurology at Mount Sinai, a research team used a computer algorithm to screen 1,600 commercially-available medications to assess their impact on the brain accumulation of beta-amyloid, a protein abnormally accumulated in the brain of Alzheimer’s disease and implicated in neurodegeneration. They found that currently-available medications prescribed for conditions such as hypertension, depression, and insomnia were found to either to block or to enhance the accumulation of beta-amyloid, the component of amyloid plaques.”This line of investigation will soon lead to the identification of common medications that might potentially trigger conditions associated with the prevention, or conversely the onset, of Alzheimer’s disease,” said Dr. Pasinetti. “They may be a novel reference for physicians to consider when prescribing the most appropriate drug, particularly in subjects at high risk for Alzheimer’s disease.”To validate the screening protocol, Dr. Pasinetti and his colleagues administered these drugs in mice that were genetically engineered to develop the hallmark amyloid plaques associated with Alzheimer’s disease. After six months of treatment with blood pressure medicines, amyloid plaques and neurodegeneration were significantly reduced in the mice. One such medicine was Carvedilol, now under clinical investigation in Alzheimer ‘s disease with the intent to slow down memory deterioration.”In recent years, amyloid plaques have become one of the main focal points in the search to understand and to treat Alzheimer’s disease,” said Dr. Pasinetti. “Thus, identifying novel drug treatments that prevent harmful beta-amyloid generation will help in the development of treatments for Alzheimer’s disease. …

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