News Article | May 23, 2017
Each volume focuses on stem cells in an individual organ and how to use them alongside relevant methods and protocols CAMBRIDGE, MA--(Marketwired - May 23, 2017) - Elsevier, the information analytics company specializing in science and health, today announced a new book series, Advances in Stem Cells and their Niches. This series addresses stem cells during development, homeostasis, and disease or injury of the respective organs, presenting new developments in the field, including new data on disease and clinical applications. The first volume in the series, Hematopoietic Stem Cell Niche, is available now. Elsevier also announced the publication of six additional genetics, genomics and stem cell medicine books. Each volume in the Advances in Stem Cells and their Niches series focuses on an individual organ, looking at the stem cells in that organ itself (if they exist), their niches, and how to use them alongside relevant methods and protocols. Edited by Dominique Bonnet, the new series includes video content illustrating such areas as protocols, transplantation techniques, and work with mice. Learn more about stroma cell niche regulation during HSC development in this sample chapter from Volume 1. Dr. Dominique Bonnet is a senior group leader at the Francis Crick Institute in London. Her group is investigating the molecular programs that regulate both human normal and leukemic stem cells. She is also interested in deciphering the role played by the microenvironment or niche in this regulation and finding new potential targets to eradicate the leukemic stem cell pool. Dr. Bonnet is also a professor at the University College of London and a senior lecturer at the Institute of Child Health. The seven new genetics, genomics and stem cell titles are: In order to meet content needs in genetics, genomics and stem cell medicine, Elsevier uses proprietary tools to identify the gaps in coverage of the topics. Editorial teams strategically fill those gaps with content written by key influencers in the field, giving students, faculty and researchers the content they need to answer challenging questions and improve outcomes. These new books, which will educate the next generation of geneticists and genomicists, and provide critical foundational content for information professionals, are key examples of how Elsevier is enabling science to drive innovation. Note for Editors Only credentialed media can request eBook review copies by email, firstname.lastname@example.org About Elsevier Elsevier is a global information analytics company that helps institutions and professionals progress science, advance healthcare and improve performance for the benefit of humanity. Elsevier provides digital solutions and tools in the areas of strategic research management, R&D performance, clinical decision support, and professional education; including ScienceDirect, Scopus, ClinicalKey and Sherpath. Elsevier publishes over 2,500 digitized journals, including The Lancet and Cell, more than 35,000 e-book titles and many iconic reference works, including Gray's Anatomy. Elsevier is part of RELX Group, a global provider of information and analytics for professionals and business customers across industries. www.elsevier.com
News Article | May 17, 2017
Deep in the basement archives of London's Great Ormond Street Hospital for Children reside the patient records that cancer researcher Sam Behjati hopes will put the hospital's past to work for the future. On 2 May, he and his colleagues published the result: DNA sequences from the genomes of three childhood tumour samples collected at the facility almost a century ago1. Those historic cells help to address a modern problem: the small number of tumour samples from rare cancers that are available for researchers to sequence. Behjati knows this problem well. At the Wellcome Trust Sanger Institute in Hinxton, UK, he tracks the genomic miswiring that can lead to rare childhood cancers. And as someone who also treats patients, he has been frustrated by the paucity of evidence backing up much of his practice. “The treatment regimens for children with rare cancers are essentially made up,” Behjati says. “If you’ve got three or four patients nationally, how are you ever going to conduct a reasonable clinical trial?” To expand the pool of samples that he could sequence, he decided in 2014 to harness advances in genome sequencing that had already made it possible to sequence DNA from pathology samples a few decades old. The hospital's 165-year archive of samples and patient records provided the opportunity to see how far back in time he could go. The work highlights the wealth of material that is available in such archives, says Danielle Carrick, a programme director at the US National Cancer Institute in Rockville, Maryland. Mining such archives can expand the options for studying rare conditions and understudied ethnic populations, she notes, and make large, population-scale studies possible. Researchers have analysed DNA from much older specimens: fragments of genome sequence have been used to study ancient human populations from hundreds of thousands of years ago. But DNA tends to degrade over time, and cancer researchers need high-quality sequences to pinpoint the many individual mutations that can contribute to tumour growth. Great Ormond Street Hospital was founded in 1852 on the back of charitable donations raised chiefly by the author Charles Dickens. Behjati and pathologist Neil Sebire of the Great Ormond Street Hospital Institute of Child Health at University College London directed their team to begin searching its archive for samples from the 1920s, however, when the terminology used to classify tumours was more easily comparable to modern diagnoses. The team pored over the patient registry, a well-worn tome with patient names, numbers and diagnoses handwritten in a tiny, precise scrawl. The samples arrived in a small cardboard box filled with dozens of paraffin wax cubes roughly the size of fingernails, with patient numbers handwritten on the sides of each block. Within each chunk of wax was a sample that had been soaked in a solution containing formaldehyde to preserve the tissue and make it rigid. Sebire and his colleagues fished out the blocks they needed, took a thin slice of each and dyed the tissue red and pink with stains. The whole technique — the formaldehyde, the wax, the stains — is well over a century old, Sebire notes. What has changed dramatically, however, is cancer treatment. The children with cancer who came to Great Ormond Street in the 1920s had few options beyond surgery. Chemotherapy was still decades away. And in the absence of modern imaging methods, children who were diagnosed often had advanced disease, their tumours large enough to be felt by the physician. Behjati hopes that those tumours will now help him and others to develop better options for future patients. The team picked three samples: a muscle cancer called rhabdomyosarcoma, a blood-vessel tumour called cellular capillary haemangioma and a lymphoma. After they confirmed the original diagnoses using the stained slices, his team extracted DNA from much of the remaining sample and sequenced 366 genes in each one. They found cancer-associated mutations in all three samples. He plans to keep searching through the Great Ormond Street Hospital collection, and then perhaps to mine the archives of other hospitals for relics of childhood cancers. As his collection grows, he will look for commonalities and potential drug targets. Childhood cancers might be particularly amenable to the approach, notes Sebire. The genomes of adult cancers are often scarred by hundreds of mutations; the genomes of childhood cancers, however, tend to contain far fewer alterations. This makes it easier for researchers to home in on those mutations that are most important, and to sift through the background noise of degraded DNA. But as these centuries-old samples find a modern use, the pathology techniques that were used to create them are on the wane, he adds. Not long from now, Sebire predicts, pathology labs will give up their microscopes altogether in favour of instruments that rapidly sequence DNA and proteins and identify metabolites. “The process hadn’t really changed for over 100 years,” he says. “But by the time I retire, I fully expect that you won’t need to do what I do now.”
News Article | May 26, 2017
A highly anticipated clinical trial has shown that treating patients with epilepsy with a compound derived from marijuana can significantly reduce and, in some cases, eliminate seizures in children and young adults. In the study, children and young adults with a rare and debilitating form of epilepsy called Dravet syndrome who took doses of marijuana extract experienced half as many seizures per month as those who received a placebo. And 5 percent of those treated with the marijuana extract, called cannabidiol, became seizure-free during the study period. [25 Odd Facts About Marijuana] Currently, there aren't any medications that can completely control seizures in children with Dravet syndrome, according to the Epilepsy Foundation. The study, published today (May 24) in the New England Journal of Medicine, is among the first to provide solid, clinical evidence to support a form of treatment that is becoming fairly widespread with the advent of medical marijuana, but which remains largely unregulated. "I can't say enough about the importance of these kinds of medical trials. People have a sense that if 10 people say it works and it's a bad disease like cancer or epilepsy, then it's safe to use. That's just false," said Dr. Orrin Devinsky, the director of NYU Langone's Comprehensive Epilepsy Center and a co-lead author of the study. "Just because it's natural and just because there may be anecdotal support from people, doesn't mean it's effective and safe." Cannabidiol, also known as CBD, is one of dozens of compounds in marijuana called cannabinoids. But unlike tetrahydrocannabinol (THC), which is the main psychoactive chemical in marijuana, CBD does not get users "high." The compound is typically administered in an oil form and is thought to work by interacting with receptors on nerve cells. Interest in using the drug to treat epilepsy grew significantly in 2013 when an 8-year-old girl from Colorado with Dravet syndrome entered the public spotlight. The girl showed remarkable improvement after taking CBD administered by a Denver medical marijuana dispensary. Since then, other anecdotal cases have shown promise and a December 2015 study (also led by Devinsky) suggested positive outcomes from the drug. The 2015 study, however, did not use a placebo. Results, therefore, were vulnerable to a bias since patients and doctors could associate any progress to the drug. The new study was a randomized, double-blind, placebo-controlled trial — a study design that's considered the gold standard for clinical research. That means that neither the researchers nor the participants know if they have been given the drug being studied or a placebo. The study included 120 children and young adults, ages 2 to 18, with Dravet syndrome. Half of the patients received a placebo, while the other half received 20 milligrams per kilogram of body weight per day of the CBD drug, Epidiolex. Epidiolex is a 99 percent cannabidiol preparation made by the U.K.-based company, GW Pharmaceuticals, which funded the study. [Healing Herb? Marijuana Could Treat These 5 Conditions] At the end of the three-month trial, the researchers compared the frequency of patients' seizures to their seizure frequencies from a four-week period before the trial began. Those who received the drug had, on average, 12 seizures per month before the study began. After the study period, the frequency dropped to six seizures per month, on average. Those patients who took CBD showed some side effects, including diarrhea, vomiting, fatigue and abnormal results on liver-function tests. But Devinsky said most of these reactions were mild and could be reduced with an adjustment in dose. Dr. Helen Cross, also a co-lead author of the study, told Live Science that it was critical to measure the effects of a drug with carefully prepared levels of CBD. "We know exactly what’s in every single batch," said Cross, a clinical neuroscientist at University College London's Institute of Child Health. "It's not like the hemp oils that you can buy from the internet, which are so variable in their content." Indeed, in the U.S., CBD oil is legal (with varying limitations) in 44 states, but the substance is not regulated, and many patients and parents of children with elpilepsy are not waiting for clinical data and instead are trying these unregulated versions of the cannabis-derived drug. [3 More States Legalize Recreational Marijuana Use: How the Map Looks Now] “We desperately need other studies like this in other forms of epilepsy and using other cannabis preparations. That should be a priority,” Devinsky told Live Science. While Dravet syndrome is rare, affecting 1 in 40,000 children, epilepsy is the fourth most common neurological condition and affects more than 65 million people worldwide, according to the Epilepsy Foundation. Research from April 2017 showed CBD to be effective in treating another, relatively rare, but severe form of epilepsy, Lennox-Gastaut syndrome. "The big question now is whether this drug is also effective for a larger group of people with epilepsy who don't have these rare syndromes," Devinsky said. In an editorial published in the same journal as the study, Dr. Sam Berkovic, a neurologist and the director of the Epilepsy Research Centre at the University of Melbourne, in Australia,emphasized the importance of the clinical trial ― and the need for more like it. Berkovic was not involved with the new research. "Medical practice cannot be decided by anecdotes," Berkovic told Live Science in an email. "They are subject to many forms of bias." 9 Weird Ways You Can Test Positive for Drugs
News Article | April 17, 2017
Successful clinical trials to create drugs and vaccines for next pandemic disease will rely on building capacity, community engagement, and international collaboration before and during outbreak WASHINGTON - Mobilization of a rapid and robust clinical research program that explores whether investigational therapeutics and vaccines are safe and effective to combat the next infectious disease epidemic will depend on strengthening capacity in low-income countries for response and research, engaging people living in affected communities, and conducting safety trials before an epidemic hits, says a new report from the National Academies of Sciences, Engineering, and Medicine. Using key lessons learned from the Ebola epidemic in West Africa, the report outlines how to improve the speed and effectiveness of clinical trial research while an epidemic is occurring, especially in settings where there is limited health care and research infrastructure. The research and development of therapeutics and vaccines is a long, complex, and expensive process and cannot be compressed into the course of a rapidly progressing outbreak. The development of a drug "from bench to bedside" is estimated, on average, to take at least 10 years and cost $2.6 billion, with less than 12 percent likelihood of eventual licensing. Therefore, making progress on the research and development of products - such as therapeutics and vaccines - before an epidemic breaks is the only way to ensure that promising candidates are ready for trials once an outbreak occurs, said the committee that carried out the study and wrote the report. In addition, clinical trials could be more rapidly planned, approved, and implemented during an outbreak if promising products are studied through Phase 1 or Phase 2 safety trials in advance of an outbreak and if emergency response planning includes clinical research considerations and clinical researchers in the discussions from the beginning. The 2014-2015 Ebola epidemic was the longest and most deadly Ebola outbreak since the virus was first discovered in 1976, resulting in 28,616 cases and 11,310 deaths in Guinea, Liberia, and Sierra Leone. In August 2014, the World Health Organization declared the epidemic a public health emergency of international concern. Researchers discussed how to conduct clinical trials on potential Ebola therapeutics and vaccines in West Africa, and ultimately, several teams conducted formal clinical trials in the Ebola-affected countries during the outbreak. The clinical trial teams overcame immense logistical obstacles encountered while trying to design and implement trials in West Africa in the midst of a rapidly spreading epidemic of a highly dangerous contagious disease. However, none of the therapeutic trials ended with conclusive results on product efficacy, although limited evidence from the trial for the ZMapp treatment did trend toward a possible benefit. Given the resources, time, and effort put into these trials, they were not as successful as they could have been. The results of the vaccine trials were more fruitful. Two Ebola vaccine candidates have data that suggest they may be safe and produce an immune response, and one is most likely protective, but further data are needed. Planning and conducting clinical research during the Ebola epidemic also required confronting a number of ethical issues, such as whether it was ethical to conduct clinical trials at all in the midst of a public health emergency and whether the research activities drew effort away from providing clinical care to the most people possible. There was also disagreement among researchers over how clinical trials should be designed during the Ebola epidemic, particularly whether trials should use randomization and concurrent control groups. Randomized controlled trials are generally the preferred research design, because they allow researchers to directly compare the outcomes of similar groups of people who differ only in the presence or absence of the investigational agent. However, many argued that randomized controlled trials would be unethical during the Ebola epidemic, as this trial design would deprive patients of an agent that could potentially prevent or treat Ebola, given the high mortality rate and lack of known and available treatment options. The committee concluded that randomized controlled trials are both ethical and the fastest and most reliable way to identify the relative benefits and risks of investigational products, and except in rare circumstances, every effort should be made to implement them during epidemics. The issues that influenced choices about trial design during the Ebola epidemic - such as community mistrust, the feasibility of a standard-of-care-only arm, the high and variable mortality rate, limited product availability, and the potential conflicts between research and care - are likely to recur in future epidemics. Nevertheless, the perceived ethical or logistical hurdles that these issues present are not sufficiently compelling to override the benefits of randomized trials. Rather, randomized trials may be the most ethical trial design, because they offer the fastest route to identifying beneficial treatments while minimizing the risks of exposure to potentially harmful investigational agents. To improve the national and international clinical trial response to the next epidemic, the committee focused on three main areas - strengthening capacity, engaging communities, and facilitating international coordination and collaboration - both in the period of time before an outbreak strikes and during the epidemic itself. The committee found major capacity challenges that hindered and slowed the research response to the Ebola epidemic, and recommended developing sustainable health systems and research capabilities, improving capacity to collect and share clinical and epidemiological data, facilitating the mechanisms for rapid ethics reviews and legal agreements before an epidemic occurs, and incorporating research systems into emergency preparedness and response systems for epidemics. Affected communities had considerable fear, mistrust, and misunderstanding of national and international response and research staff. Community members feared going to health care facilities for the treatment of Ebola, rumors spread that Ebola was deliberately brought to the region by foreigners, and initial response efforts did not take into account community traditions and beliefs. For example, mandatory cremation policies countered deeply held religious beliefs. Successful clinical research is dependent on a community's understanding of, engagement in, and sense of involvement and respect in the process of planning and conducting research, the committee found. Community engagement should be prioritized during epidemic responses and be a continuous and evolving effort, starting at the onset of the epidemic. Research and response efforts were also greatly affected by the relationships among international stakeholders and their ability to coordinate and collaborate. For example, there were a few Ebola-specific therapeutic candidates with suggestive efficacy available at the beginning of the outbreak that could have been investigated in clinical trials, but the mechanism to prioritize which should be studied first was limited. The committee recommended the establishment of an international coalition of stakeholders to work between epidemics that would advise and prioritize pathogens to target for research and development, develop generic clinical trial design templates, and identify teams of clinical research experts who could be deployed to assist with research during an outbreak. The committee also highlighted seven critical steps to launching successful clinical trials when the next epidemic first strikes and before it peaks. The steps are to collect and share patient information and establish standards of care, engage communities and establish mutual trust, integrate research efforts into response and facilitate stakeholder coordination, prioritize vaccines and therapies and select trial designs, negotiate contracts, consult with regulators, and perform independent ethics reviews. The study was sponsored by the U.S. Department of Health and Human Services' Office of the Assistant Secretary for Preparedness and Response, National Institutes of Health, and U.S. Food and Drug Administration. The National Academies of Sciences, Engineering, and Medicine are private, nonprofit institutions that provide independent, objective analysis and advice to the nation to solve complex problems and inform public policy decisions related to science, technology, and medicine. The National Academies operate under an 1863 congressional charter to the National Academy of Sciences, signed by President Lincoln. For more information, visit http://national-academies. . A roster follows. Copies of Integrating Clinical Research Into Epidemic Response: The Ebola Experience are available from the National Academies Press at http://www. or by calling 1-800-624-6242. Reporters may obtain a copy from the Office of News and Public Information (contacts listed above). Gerald T. Keusch, M.D.* (co-chair) Professor of Medicine and Global Health Boston University Schools of Medicine and Public Health Boston Keith McAdam, M.D. (co-chair) Emeritus Professor of Clinical and Tropical Medicine London School of Hygiene and Tropical Medicine London Abdel Babiker, Ph.D. Professor of Epidemiology and Medical Statistics Medical Research Council Clinical Trials Unit at University College London London Susan S. Ellenberg, Ph.D. Professor of Biostatistics Perelman School of Medicine University of Pennsylvania Philadelphia Roger J. Lewis, M.D., Ph.D.* Professor and Chair of the Department of Emergency Medicine Harbor-UCLA Medical Center Los Angeles Alex London, Ph.D. Professor of Philosophy, and Director of the Center for Ethics and Policy Carnegie Mellon University Pittsburgh Michelle M. Mello, Ph.D.* Professor of Law Stanford University School of Medicine and School of Law Stanford, Calif. Olayemi Omotade, M.D. Professor of Pediatrics and Child Health Institute of Child Health University College Hospital University of Ibadan Ibadan, Nigeria Fred Wabwire-Mangen, Ph.D. Associate Professor of Epidemiology and Public Health Makerere University School of Public Health Kampala, Uganda
News Article | December 13, 2016
An exciting X-ray imaging technology has been successfully developed to the point where it is now ready for translation into all kinds of beneficial applications, including potentially life-saving uses in security and healthcare. Funded by the Engineering and Physical Sciences Research Council (EPSRC), a major five-year project led by UCL (University College London) has achieved this breakthrough. The work also involved dozens of industrial, academic and research partners in the UK and worldwide. Compared with conventional X-rays, the technology can, for example, identify tumours in living tissue earlier and spot smaller cracks and defects in materials. This is because it excels at determining different shapes and different types of matter - a capability that conventional X-rays could only match by using prohibitively high doses of radiation. The technique at the heart of the advance is called phase-contrast X-ray imaging. Instead of measuring the extent to which tissue or materials absorb radiation - as in conventional X-ray imaging - it measures the physical effect that passing through different types of tissue or material has on the speed of the X-ray itself. Professor Alessandro Olivo, who led the project team, says: "The technique has been around for decades but it's been limited to large-scale synchrotron facilities such as Oxfordshire's Diamond Light Source. We've now advanced this embryonic technology to make it viable for day-to-day use in medicine, security applications, industrial production lines, materials science, non-destructive testing, the archaeology and heritage sector, and a whole range of other fields." This vast potential is already beginning to be explored. For example: Professor Olivo says: "This has the potential to be incredibly versatile, game-changing technology. We're currently negotiating with a number of companies to explore how it could be put to practical use. There's really no limit to the benefits this technique could deliver." For media enquiries contact: Alessandro Olivo, Professor of Applied Physics, UCL, tel: 0207 679 2444, e-mail: email@example.com; or the EPSRC Press Office, tel: 01793 444 404, e-mail: firstname.lastname@example.org The 5-year project Transforming the Use of X-rays in Science and Society ran from November 2011 to October 2016 and received £1.05 million in EPSRC funding under the Challenging Engineering programme. The project created 28 new collaborations and produced around 75 journal papers. Partners and collaborators included: Academia: Imperial College London; Queen Mary University of London; University of Oxford; Ludwig-Maximillian University, Munich; University of Washington in St Louis, Missouri; Kyoto University; Heriot-Watt University; University of Bristol; University of Dundee; University of Glasgow; University of Strathclyde; University of Saskatchewan; University of Trieste; University of Pisa. Research Institutes/Facilities: Diamond Light Source; ELETTRA Sincrotrone Trieste ScpA; European Synchrotron Radiation Facility; Research Complex at Harwell; CNR Institute of Crystallography - Italy; EMPA Switzerland; Barts Health NHS Trust; INFN Istituto Nazionale di Fisica Nucleare, Pisa and Trieste Sections. Within UCL: Department of Mechanical Engineering; Department of Chemical Engineering; Department of Physics and Astronomy; London Centre for Nanotechnology (a joint UCL-Imperial College establishment); Institute of Child Health; Great Ormond Street Hospital. The Engineering and Physical Sciences Research Council (EPSRC): As the main funding agency for engineering and physical sciences research, our vision is for the UK to be the best place in the world to Research, Discover and Innovate. By investing £800 million a year in research and postgraduate training, we are building the knowledge and skills base needed to address the scientific and technological challenges facing the nation. Our portfolio covers a vast range of fields from healthcare technologies to structural engineering, manufacturing to mathematics, advanced materials to chemistry. The research we fund has impact across all sectors. It provides a platform for future economic development in the UK and improvements for everyone's health, lifestyle and culture. We work collectively with our partners and other Research Councils on issues of common concern via Research Councils UK. http://www. UCL (University College London): UCL was founded in 1826. We were the first English university established after Oxford and Cambridge, the first to open up university education to those previously excluded from it, and the first to provide systematic teaching of law, architecture and medicine. We are among the world's top universities, as reflected by performance in a range of international rankings and tables. UCL currently has over 38,000 students from 150 countries and over 12,000 staff. Our annual income is more than £1 billion. Wellcome Trust: Wellcome exists to improve health for everyone by helping great ideas to thrive. We're a global charitable foundation, both politically and financially independent. We support scientists and researchers, take on big problems, fuel imaginations and spark debate.
Saldana L.J.,Institute of Child Health
Journal of laparoendoscopic & advanced surgical techniques. Part A | Year: 2013
Single-incision pediatric endosurgery (SIPES) is defined as minimally invasive surgery performed through a unique incision in the abdomen, chest, or retroperitoneum. Several publications exist, but no previous systematic review has been made to evaluate the real benefits of this approach in terms of feasibility and clinical outcomes. We performed an electronic search in PubMed up to March 2012 with the terms "single AND incision OR site OR port OR trocar AND children" including related articles and obtained 197 articles. After applying our inclusion criteria, 78 articles were reviewed. We identified prospective controlled trials (n=1), case-control studies (n=12), case series (n=49), and case reports (n=16). In total, 4212 patients had been operated on by SIPES and were separated by systems: gastrointestinal (n=2888), urologic (n=390), gynecologic (n=27), other abdominal (n=874), and thoracic (n=33) procedures. The most common procedure was SIPES appendectomy, and a unique prospective controlled trial supports its safety and effectiveness. Technically demanding surgeries such as hepatojejunostomy and colonic surgeries were described. Multichannel ports and multiple ports, standard and articulated instruments, transparietal instruments, retraction sutures, and magnets were used. Operative times, length of stay, and complications similar to standard laparoscopic surgery were described. A low conversion rate (to a reduced port, standard laparoscopy and open procedures) was also mentioned. No comparable measure for pain and cosmesis assessment was used. A wide experience in SIPES and feasibility has already been described with good clinical outcomes and low rate of conversion. Appendectomy is the unique procedure in which SIPES has been demonstrated to be safe and effective. It is pending the execution of prospective controlled trials for other operations to demonstrate, with objective evidence, the real benefits of this less invasive approach.
Mercuri E.,Catholic University |
Mercuri E.,Institute of Child Health |
Muntoni F.,Institute of Child Health
Annals of Neurology | Year: 2012
Congenital muscular dystrophies are a highly heterogeneous group of conditions. In the last few years the identification of several new genes encoding for both glycosyltransferases and structural proteins has expanded the spectrum of the known forms. New classifications based on combined clinical, genetic and pathological data include all the recently discovered genes and allow an easier identification of the different forms and insight on pathogenetic mechanisms. The aim of this review is to discuss the most recent advances in this field, providing a conceptual framework to help the understanding of the responsible mechanisms and, when available, an update on the therapeutic perspectives. © 2012 American Neurological Association.
Kristiansen M.,Institute of Child Health |
Ham J.,Institute of Child Health
Cell Death and Differentiation | Year: 2014
Developing sympathetic neurons of the superior cervical ganglion are one of the best studied models of neuronal apoptosis. These cells require nerve growth factor (NGF) for survival at the time that they innervate their final target tissues during late embryonic and early postnatal development. In the absence of NGF, developing sympathetic neurons die by apoptosis in a transcription- dependent manner. Molecular studies of sympathetic neuron apoptosis began in the 1980s. We now know that NGF withdrawal activates the mitochondrial (intrinsic) pathway of apoptosis in sympathetic neurons cultured in vitro, and the roles of caspases, Bcl-2 (B-cell CLL/lymphoma 2) family proteins and XIAP (X-linked inhibitor of apoptosis protein) have been extensively studied. Importantly, a considerable amount has also been learned about the intracellular signalling pathways and transcription factors that regulate programmed cell death in sympathetic neurons. In this article, we review the key papers published in the past few years, covering all aspects of apoptosis regulation in sympathetic neurons and focusing, in particular, on how signalling pathways and transcription factors regulate the cell death programme. We make some comparisons with other models of neuronal apoptosis and describe possible future directions for the field. © 2014 Macmillan Publishers Limited All rights reserved.
Wells J.C.K.,Institute of Child Health
Reviews in Endocrine and Metabolic Disorders | Year: 2012
The consequences of fetal growth retardation remain unclear, in part because they appear to vary between industrialized and developing countries. Data on body composition offer a new opportunity to investigate this issue, and may be of particular value in addressing the controversial role of nutrition in infancy, which has been proposed by some to boost survival, and by others to increase long-term risk of chronic diseases. The uncertainty regarding the effects of post-natal nutrition is presenting challenges to nutritional policy as many countries undergo the nutrition transition, whereby the nutritional status of individuals may shift within the life-course. A theoretical model, building on the thrifty phenotype hypothesis, is presented to clarify how body composition data can address this dilemma. Measurements of body composition can now be obtained in infants and children using several different technologies, indicating that large-scale studies can now be conducted to investigate objectively the association between early growth patterns and later health. © Springer Science+Business Media, LLC 2012.