VDA Net Rassegna Stampa Internazionale del 11/02/2013

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1 CENTER FOR INFECTIOUS DISEASE RESEARCH&POLICY Study details age-related differences in flu vaccination response Lisa Schnirring * Staff Writer Feb 6, 2013 (CIDRAP News) A detailed inventory of antibodies in the blood of people before and after flu vaccination found that the number of antibody types shrink with age, suggesting that vaccines may work differently in older people, a research team reported today. The immune systems of older people don't respond to flu vaccination as well as those of younger people, and people age 65 and older are at greater risk of serious complications from the disease. Scientists haven't completely pieced together why seniors have a less robust immune response to flu vaccine, but new studies are starting to shed some light on age-related antibody changes that may play a role. In the current study, researchers based at Stanford University analyzed blood samples from 17 volunteers from different age-groups who were immunized against flu with the 2009 or 2010 seasonal flu vaccines. Their findings appear today in Science Translational Medicine. The group noted that it's difficult to measure and analyze the human antibody repertoire, because the genome for each B cell encodes a distinct, personalized antibody sequence, the antibody repertoire changes over time, and antibody sequences are highly similar. To address the challenges. the scientists used high-throughput long-read sequencing and analyzed 5 million antibody heavy chain sequences, which allowed them to characterize the sequences, determine lineage structures, and measure age- and antigen-related mutation activity. The volunteers were recruited from three age-groups: children (ages 8 to 17 years old), young adults (ages 18 to 30), and older people (ages 70 to 100). The cohort included three sets of twins in the youngest age-group to allow researchers to analyze the antibody profiles of people with identical genetic backgrounds. Subjects were randomly vaccinated with either trivalent inactivated influenza vaccine (TIV) or live-attenuated influenza vaccine (LAIV), although the older group could only receive TIV. Blood samples were collected from each person at three points: right before vaccination, at 7 or 8 days after vaccination, and 28 days after vaccination. The researchers found significant differences in antibody composition by different age-groups. For example, the relative percentage of immunoglobulin M (IgM) sequences dropped after vaccination in all volunteers except one and reduction in IgM usage decreased with age. These findings are consistent with the hypothesis that older people are more likely to use memory B calls than naive NB cells to respond to flu vaccination, according to the study. Though the results lend support to the theory that flu vaccines may work differently in seniors, the authors noted in summary ed to journalists that the findings don't suggest that older people should stop getting vaccinated. They suggested that elderly people avoid activities that expose them to flu viruses and seek medical care when the first symptoms of flulike illness surface. Jiang N, He J, Weinstein JA, et al. Lineage structure of the human antibody repertoire in response to influenza vaccination. Sci Transl Med 2013 Feb 6;5(171)

2 EUROPEAN COMMISSION - EACH Patient Safety: New EU Rapid Alert platform for human Tissues and Cells A secure alert platform launched by the European Commission will improve the safety of patients undergoing transplantation and medical procedures involving human tissues and cells, e.g. bone marrow, cornea, skin, oocytes, sperm, etc. From today, national health authorities can use the web-based Rapid Alert system for Tissues and Cells (RATC) in case of alerts relating to human tissues or cells transferred across borders. Timely exchange of urgent information between Member States can ensure that cross-border incidents are prevented or contained and immediate measures taken to ensure the safety of patients. The RATC will be used in parallel with existing national vigilance systems which collect and manage alerts on tissues and cells donated and used within a Member State. A high volume of tissues and cells are donated and transplanted every year in the EU. More than units of tissues and cells were donated and over transplants performed in 2011 alone. Many of these tissues and cells pass national borders during these processes. Vigilance beyond national borders, as provided by the RATC, is therefore extremely important. In addition to quality and safety defects of tissues/cells, the RATC can be used to raise the alarm on illegal and fraudulent activities in this field, as well as on developing epidemiological situations (e.g. disease outbreaks) which may have cross-border implications. AMERICAN ACADEMY OF NEUROLOGY Can nerve stimulation help prevent migraine? MINNEAPOLIS Wearing a nerve stimulator for 20 minutes a day may be a new option for migraine sufferers, according to new research published in the February 6, 2013, online issue of Neurology, the medical journal of the American Academy of Neurology. The stimulator is placed on the forehead, and it delivers electrical stimulation to the supraorbital nerve. For the study, 67 people who had an average of four migraine attacks per month were followed for one month with no treatment. Then they received either the stimulation 20 minutes a day for three months or sham stimulation, where they wore the device but the stimulation given was at levels too low to have any effect. Those who received the stimulation had fewer days with migraine in the third month of treatment compared to the first month with no treatment. The number of days with migraine decreased from 6.9 days to 4.8 days per month. The number did not change for those who received the sham treatment. The study also looked at the number of people who had 50 percent or higher reduction in the number of days with migraine in a month. That number was 38 percent for those who had the stimulation compared to 12 percent of those who received the sham treatment. There were no side effects from the stimulation. "These results are exciting, because the results were similar to those of drugs that are used to prevent migraine, but often those drugs have many side effects for people, and frequently the side effects are bad enough that people decide to quit taking the

3 drug," said study author Jean Schoenen, MD, PhD, of Lie'ge University in Belgium and a member of the American Academy of Neurology. The study was supported by the Walloon Region, Department of Economy, Employment and Research in Belgium. INSERM.FR Syndrome des ovaires polykystiques : un nouveau facteur implique' dans l'absence d'ovulation L'absence d'ovulation chez les femmes atteintes d'un syndrome des ovaires polykystiques serait lie'e a' une perturbation de la production d'hormone anti-mulle'rienne et de son re'cepteur. Une e'quipe de l'inserm montre que l'hormone sexuelle LH jouerait un rôle dans cette de're'gulation. Ces travaux contribuent a' clarifier les me'canismes implique's dans ce syndrome. Les proble'mes d'ovulation des femmes pre'sentant un syndrome des ovaires polykystiques restent aujourd'hui difficiles prendre en charge. Ils sont ne'anmoins de mieux en mieux compris sur le plan biologique. Une e'quipe de l'inserm vient en effet de montrer que, chez ces patientes qui n'ovulent pas, l'hormone sexuelle hypophysaire LH produite au niveau du cerveau entraine la surexpression d'une autre hormone et de son re'cepteur, produits par les follicules ovariens*. Un syndrome associe' a' la stérilité Le syndrome des ovaires polykystiques est très fre'quent puisqu'il est responsable de problèmes de fertilite' chez 5 a' 10 % des femmes. Il se caracte'rise par la pre'sence de très nombreux follicules ovariens de petite taille et immatures. Les formes mode're'es permettent une ovulation, tandis que les formes plus se'vères empêchent le déroulement de cette étape nécessaire a' la reproduction. De pre'ce'dents travaux ont montre' que les femmes touche'es par ce syndrome pre'sentent un taux se'rique d'hormone anti-mulle'rienne (AMH) plus e'leve' que les autres. Le dosage de l'amh est même devenu un outil de diagnostic de la pathologie. Les experts ont longtemps estime' que ce taux e'tait lie' au nombre excessif de follicules qui produisent l'hormone. Mais des travaux re'cents ont e'galement rapporté un dysfonctionnement des follicules, sans que les me'canismes n'en soient connus. "L'hormone anti-mullerienne freine la croissance des follicules. Cela pourrait contribuer au fait qu'ils restent immatures chez les femmes pre'sentant un taux d'amh e'leve'", explique Nathalie di Clemente**, co-auteur des travaux. Les hormones sexuelles s'en mêlent Les hormones sexuelles LH et FSH ayant un rôle pre'ponde'rant dans le cycle de reproduction et dans le de'clenchement de l'ovulation, les chercheurs ont e'tudie' leur impact sur la production d'amh et de son re'cepteur spe'cifique au niveau des cellules du follicule ovarien. Ils ont pour cela travaille' sur des échantillons issus de ponctions ovariennes effectue'es chez des femmes suivant un protocole de fe'condation in vitro. Ils ont inclus dans leur étude des patientes pre'sentant un syndrome polykystique, avec ou sans ovulation, ainsi que des patientes "te'moins ". Après avoir laisse' des cellules issues des follicules en pre'sence des hormones LH ou FSH, les auteurs ont constate' une de're'gulation de l'expression de l'amh et de son re'cepteur spe'cifique chez les femmes anovulantes atteintes de polykystose ovarienne. "Chez elles, et uniquement chez elles, nous avons observe' une stimulation de l'expression d'amh en pre'sence de l'hormone LH et pas de re'trocontrôle ne'gatif de son re'cepteur, sense' re'guler l'effet de l'amh", explique la chercheuse. Reste a' comprendre les me'canismes responsables de ce phe'nomène pour parvenir a' mieux traiter cette pathologie.

4 AIDSMEDS.COM People With HIV have a doubled risk of non-melanoma skin cancers The incidence of two non-melanoma skin cancers basal cell and squamous cell carcinomas is more than twice as high among people with HIV as compared with the general population, according to study findings published in the Journal of the National Cancer Institute and reported by Kaiser Permanente, which conducted the research. The study included a cohort of 6,560 HIV-positive and nearly 37,000 HIV-negative members of Kaiser Permanente Northern California between 1996 and The study, which is the first to identify with such specificity the nature of this increased skin cancer risk, found that the HIV-positive participants' rate of basal cell carcinomas was 2.1 times higher than those without HIV, and their risk of squamous cell carcinomas 2.6 times greater. The researchers also found that squamous cell carcinomas were associated with lowered CD4 counts. The study's authors note these findings fall in line with HIV-positive people's increased risk for a wide variety of cancers, which is likely a consequence of damage to the immune system. In press materials, senior author Maryam M. Asgari, MD, MPH, a Kaiser Permanente dermatologist and investigator at its Division of Research, called for "increased vigilance in skin-cancer screening for HIV-positive individuals" for these common and typically curable cancers, "particularly for those who are not on antiretroviral therapy or who were diagnosed late and have more advanced HIV/AIDS." GARVAN INSTITUTE The brain circuit that makes it hard for obese people to lose weight Imagine you are driving a car, and the harder you press on the accelerator, the harder an invisible foot presses on the brake. That's what happens when obese people diet the less food they eat, the less energy they burn, and the less weight they lose. While this phenomenon is known, scientists at Sydney's Garvan Institute of Medical Research and the University of NSW have pinpointed the exact brain circuitry behind it and have published their findings in the prestigious international journal Cell Metabolism, now online. Dr Shu Lin, Dr Yanchuan Shi and Professor Herbert Herzog and his team have been studying the complex processes behind energy balance using various mouse models. They have shown that the neurotransmitter Neuropeptide Y (NPY), known for stimulating appetite, also plays a major role in controlling whether the body burns or conserves energy. The researchers found that NPY produced in a particular region of the brain the arcuate nucleus (Arc) of the hypothalamus inhibits the activation of brown fat'1, one of the primary tissues where the body generates heat. "This study is the first to identify the neurotransmitters and neural pathways2 that carry signals generated by NPY in the brain to brown fat cells in the body. It is also the first to show a direct connection between Arc NPY, the sympathetic nervous system and the control of energy expenditure." said Professor Herzog. "We know that NPY also influences other aspects of the sympathetic nervous system such

5 as heart rate and gut function but its control of heat generation through brown fat seems to be the most critical factor in the control of energy expenditure." "When you don't eat, or dramatically curtail your calorie intake, levels of NPY rise sharply. High levels of NPY signal to the body that it is in starvation mode' and should try to replenish and conserve as much energy as possible. As a result, the body reduces processes that are not absolutely necessary for survival." "Evolution has provided us with these mechanisms to help us survive famine, and they are strictly controlled. When people had to survive by finding food or hunting game, they could not afford to run out of energy and die of exhaustion, so their bodies evolved to cope." "Until the twentieth century, there were no fast food chains and people did not have ready access to high fat, high sugar, foods. So in evolutionary terms, it was unlikely that people were going to get very fat and mechanisms were only put in place to prevent you losing weight." "Obesity is a modern epidemic, and the challenge will be to find ways of tricking the body into losing weight and that will mean somehow circumventing or manipulating this NPY circuit, probably with drugs." UNIVERSITAT AUTONOMA DE BARCELONA 07/02/2013 Aconsegueixen curar la diabetis tipus 1 en gossos Investigadors de la UAB han aconseguit curar completament la diabetis tipus 1 en gossos mitjançant una u'nica sessio' de tera'pia ge'nica. Es tracta de la primera vegada que s'aconsegueix curar la malaltia en animals grans, un pas fonamental per a l'aplicacio' de la tera'pia en humans. La investigacio', basada en la introduccio' d'un "sensor de glucosa" en el mu'scul, ha estat publicada a la revista Diabetis, la me's prestigiosa del mo'n en aquest camp. Investigadors de la Universitat Auto'noma de Barcelona, liderats per la professora Fa'tima Bosch, han demostrat per primer cop que e's possible curar la diabetis en animals grans amb un sol tractament, mitjançant tera'pia ge'nica. Segons publiquen aquesta setmana a Diabetis, la revista me's prestigiosa en recerca sobre la malaltia, despre's d'un sol tractament de tera'pia ge'nica, els gossos recuperen el seu estat de salut i deixen de patir els símptomes de la diabetis. El seguiment s'ha realitzat durant me's de quatre anys en alguns exemplars, i en cap cas han reaparegut els símptomes de la malaltia. La tera'pia e's molt poc invasiva. Consisteix en una sola sessio' de diverses injeccions en les potes del darrere de l'animal mitjançant agulles senzilles, del tipus que s'utilitza en tractaments d'este'tica. Mitjançant aquestes injeccions s'introdueixen vectors de tera'pia ge'nica amb un doble objectiu: expressar el gen de la insulina, per una banda, i de la glucoquinasa, de l'altra. La glucoquinasa, un enzim, actua com a regulador de la captacio' de glucosa de la sang. Quan ambdo's gens actuen simulta'niament fan la funcio' d'un "sensor de glucosa", tot aconseguint una regulacio' automa'tica de la captacio' de la glucosa de la sang i reduint així la hipergluce'mia diabe'tica (l'exce's de glucosa associat a la malaltia). Segons destaca Fa'tima Bosch, directora de la investigacio', "l'estudi representa la primera demostracio' de curacio' de diabetis a llarg termini en un model animal gran utilitzant tera'pia ge'nica." Aquest tipus de tera'pia ja havia estat assajada en ratolins amb anterioritat pel mateix grup d'investigadors, pero' els excel lents resultats obtinguts per primera vegada amb animals grans senten les bases per a la transfere'ncia clínica d'aquesta aproximacio' de tera'pia ge'nica a la medicina veterina'ria i la seva futura aplicacio' en

6 pacients diabe'tics. En la investigacio', liderada per la directora del Centre de Biotecnologia Animal i Tera'pia Ge'nica de la UAB (CBATEG) Fa'tima Bosch, han participat el Departament de Bioquímica i de Biologia Molecular de la UAB, el Departament de Medicina i Cirurgia Animal de la UAB, la Facultat de Veterina'ria de la UAB, el Departament de Sanitat i d'anatomia Animals de la UAB, el CIBER de Diabetis i Malalties Metabo'liques Associades (CIBERDEM), el Children 's Hospital of Philadelphia (EUA) i el Howard Hughes Medical Institute of Philadelphia (EUA). Tera'pia ge'nica segura i efectiva L'estudi proveeix moltes dades que avalen la seguretat del tractament amb tera'pia ge'nica per mitja' de vectors adenoassociats (AAV) en gossos diabe'tics. La tera'pia ha demostrat ser segura i efectiva: es basa en la transfere'ncia de dos gens al mu'scul d'animals adults emprant una nova generacio' de vectors molt segurs denominats vectors adenoassociats. Aquests vectors deriven de virus no pato'gens, so'n a'mpliament usats en tera'pia ge'nica, i han demostrat e'xit en el tractament diverses malalties. De fet, el primer medicament de tera'pia ge'nica aprovat per l'age'ncia europea del medicament, anomenat Glybera, es basa en vectors adenoassociats per tractar una malaltia metabo'lica, causada per la deficie'ncia de lipoproteinlipasa i la consegüent acumulacio' de triglice'rids a la sang. Control de la malaltia a llarg termini Els gossos tractats amb una u'nica administracio' de tera'pia gènica van mostrar en tot moment un bon control glucèmic, tant en deju' com en alimentacio', millor que els gossos tractats amb injeccions dia'ries d'insulina i sense l'aparicio' d'episodis d'hipogluce'mia, ni tan sols despre's de realitzar exercici. A me's, els gossos tractats amb vectors adenoassociats van normalitzar el pes corporal i no van desenvolupar complicacions secunda'ries despre's de quatre anys des del tractament. Es tracta de la primera publicacio' que descriu un control adequat de la diabetis a llarg termini en animals grans. Aixo' mai havia estat aconseguit abans amb cap de les tera'pies innovadores per a la diabetis. Al seu torn, e's la primera publicacio' que descriu que una u'nica administracio' de gens a gossos diabètics e's capaç d'aconseguir el manteniment de la normoglice'mia a llarg termini (me's de 4 anys). A me's d'aconseguir la normoglice'mia, els gossos presentaven nivells normals de proteïnes glucosilades i no van desenvolupar complicacions secunda'ries de la diabetis despre's de me's de 4 anys d'evolucio' de la seva diabetis. Aplicacio' en pacients diabe'tics Fins ara, s'han dut a terme mu'ltiples assaigs clínics amb vectors AAV administrats directament al mu'scul esquele'tic per al tractament d'altres malalties, de manera que l'estrate'gia descrita en aquest treball es pot transferir a la clínica. Futurs estudis de seguretat i efica'cia proporcionaran les bases per a la iniciacio' d'un assaig clínic veterinari per al tractament de la diabetis en animals de companyia, la qual cosa proporcionara' informacio' clau per al possible assaig d'aquesta estrate'gia en humans. En conclusio', aquest treball posa les bases per a la transfere'ncia clínica d'aquesta aproximacio' de tera'pia ge'nica a la medicina veterina'ria i, en un futur, en pacients diabe'tics. Diabetis mellitus La diabetis mellitus e's la malaltia metabo'lica més comuna, i un gran nombre de pacients requereixen tractament amb insulina per sobreviure. Malgrat el control de la malaltia mitjançant les injeccions d'insulina, aquests pacients solen desenvolupar greus complicacions secunda'ries com ara ceguesa, dany renal o amputacio' d'extremitats. A me's, per aconseguir un bon control gluce'mic, la insulina s'ha d'injectar dues o tres vegades al dia, el que comporta un risc de patir hipogluce'mies (baixades del sucre en sang), un problema afegit a la pro'pia incomoditat del tractament.

7 THE SCRIPPS RESEARCH INSTITUTE 07/02/2013 Compound developed by Scripps Florida Scientists protects heart cells during and after attack JUPITER, FL, February 7, 2013 Using two different compounds they developed, scientists from the Florida campus of The Scripps Research Institute (TSRI) have been able to show in animal models that inhibiting a specific enzyme protects heart cells and surrounding tissue against serious damage from heart attacks. The compounds also protect against additional injury from restored blood flow after an attack, a process known as reperfusion. The study, which was led by Philip LoGrasso, a professor and senior scientific director of discovery biology at Scripps Florida, appears in the February 8, 2013 print edition of The Journal of Biological Chemistry. A heart attack severely restricts blood supply, starving heart cells and surrounding tissue of oxygen, which can cause enormous damage in relatively little time sometimes in just a few minutes. Known as an ischemic cascade, this drop-off of oxygen results in a sudden crush of metabolic waste that damages cell membranes as well as the mitochondria, a part of the cell that generates chemical energy and is involved in cell growth and death. Unfortunately, restoring blood flow adds significantly to the damage, a serious medical issue when it comes to treating major ischemic events such as heart attack and stroke. Reperfusion re-invigorates production of free radicals and reactive oxygen species that attack and damage cells, exacerbating inflammation, turning loose white blood cells to attack otherwise salvageable cells and maybe even inducing potentially fatal cardiac arrhythmias. The new study found that inhibiting the enzyme, c-jun-n-terminal kinase (JNK), pronounced "junk," protected against ischemic/reperfusion injury in rats, reducing the total volume of tissue death by as much as 34 percent. It also significantly reduced levels of reactive oxygen species and mitochondrial dysfunction. In earlier studies, TSRI scientists found that JNK migrates to the mitochondria upon oxidative stress. That migration, coupled with JNK activation, they found, is associated with a number of serious health issues, including liver damage, neuronal cell death, stroke and heart attack. The peptide and small molecule inhibitor (SR3306) developed by LoGrasso and his colleagues blocks those harmful effects, thereby reducing programmed cell death four-fold. "This is the same story, said LoGrasso. These just happen to be heart cells, but we know that oxidative stress kills cells, and JNK inhibition protects against this stress. Blocking the translocation of JNK to the mitochondria is essential for stopping this killing cascade and may be an effective treatment for damage done to heart cells during an ischemic/reperfusion event." In addition, LoGrasso said, biomarkers that rise during a heart attack shrink in the presence of JNK inhibition, a clear indication that blocking JNK reduces the severity of the infarction. The first author of the study, "Inhibition of JNK Mitochondrial Localization and Signaling is Protective Against Ischemia-Reperfusion Injury in Rats," is Jeremy W. Chambers of TSRI. Other authors include Alok Pachori, Shannon Howard and Sarah Iqbal, also of TSRI. This work was supported by the National Institutes of Health (grant number NS057153) and by the Saul and Theresa Esman Foundation. INSTITUT PASTEUR

8 07/02/2013 L'histoire evolutive et l'emergence de la tuberculose retracees Des scientifiques de l'institut Pasteur a' Paris, du CNRS, de l'inserm, de l'institut Pasteur de Lille, de l'universite' Lille 2, en collaboration avec le CEA-Genoscope et le Sanger Institute, viennent de de'terminer l'origine de l'e'mergence de la bacte'rie Mycobacterium tuberculosis, principal agent de la tuberculose. Les chercheurs apportent e'galement des indices sur les raisons de son succe's e'volutif. Ils ont identifie' plusieurs me'canismes ge'ne'tiques ayant pu contribuer a' la disse'mination mondiale du pathoge'ne, qui infecte actuellement jusqu'a' 2 milliards d'individus. Ces travaux, publie's online le 6 janvier sur le site de Nature Genetics, ouvrent des perspectives pour identifier de nouvelles cibles pour lutter contre la tuberculose. Mycobacterium tuberculosis (M. tuberculosis) est responsable de la grande majorite' des cas de tuberculose. Environ un tiers de la population mondiale est infecte'e par ce micro-organisme. En 2011, la tuberculose a fait 1,4 millions de victimes et ce chiffre pourrait augmenter en raison de l'e'mergence de souches multi-re'sistantes aux antibiotiques. D'autant plus que le seul vaccin disponible, le BCG, n'est que partiellement efficace et prote'ge les adultes dans un cas sur deux seulement. En France, on compte environ 5000 nouveaux cas et 650 de'ce's chaque anne'e, l'ile-de-france e'tant 2 a' 4 fois plus touche'e en terme d'incidence que le reste du territoire. Les personnes au syste'me immunitaire fragile sont les plus vulne'rables. Parmi les sous-espe'ces de bacilles tuberculeux capables de provoquer la tuberculose chez l'homme, la plus re'pandue et la plus pathoge'ne est de loin M. tuberculosis. Les e'quipes de Roland Brosch, a' l'institut Pasteur a' Paris et de Philip Supply, a' l'institut Pasteur de Lille, en collaboration avec le CEA-Genoscope et le Sanger Institute, sont parvenues a' retracer l'histoire e'volutive de M. tuberculosis. Leur e'tude a permis de confirmer l'hypothèse de pre'ce'dents travaux sugge'rant que les souches de M. tuberculosis, ge'ne'tiquement très conserve'es, sont issues d'une branche e'volutive commune aux souches de Mycobacterium canettii (1) (M. canettii). Ces dernières, qui entraînent e'galement la tuberculose, pre'sentent une très large diversite' ge'ne'tique et certaines caractéristiques de leurs génomes indiquent qu'elles sont d'une origine beaucoup plus ancienne. Les scientifiques fournissent e'galement des indications possibles sur les facteurs qui ont contribue' au succès évolutif de M. tuberculosis, qui a fait de la tuberculose une pande'mie mondiale, alors que les souches de M. canettii sont reste'es majoritairement cantonne'es dans les re'gions de l'est de l'afrique. L'e'quipe de chercheurs, mene'e par Philip Supply et Roland Brosch, suggère notamment que les souches de M. tuberculosis ont acquis leur virulence et leur persistance par une combinaison de plusieurs me'canismes ge'ne'tiques, tels que : une perte de fonction de certains ge'nes ou encore l'acquisition de nouveaux ge'nes par transfert horizontal. Grâce a' l'identification de ge'nes possiblement implique's chez M. tuberculosis, l'ensemble de ces travaux ouvre des perspectives pour la lutte contre la tuberculose, dont l'oms a fait l'une de ses priorite's. Illustration - Copyright Institut Pasteur Le'gende : Mycobacterium tuberculosis, agent de la tuberculose. Microscopie e'lectronique a' balayage. ARTHRITIS RESEARCH UK 07/02/2013 Children with ACL injuries need special care to prevent future knee problems

9 Children with an injury to their anterior cruciate ligament (ACL) need special treatment and care to prevent long-term complications and knee problems in the future, experts have claimed. A review article in the Journal of the American Academy of Orthopaedic Surgeons has considered the problem, which is not uncommon among children and adolescents who play sports. Dr Jeremy Frank, a paediatric orthopaedic surgeon at the Joe DiMaggio Children's Hospital in Florida, says that special consideration is needed in girls under the age of 14 and boys under the age of 16, as their bones have not yet fully matured. Without the appropriate care, children with ACL injuries may face a heightened risk of complications and early-onset osteoarthritis of the knee in the future, he warns. Dr Frank and co-author Peter Gambacorta, from the Women and Children's Hospital of Buffalo in New York State, make a number of recommendations to avoid future complications, including the use of a specialist orthopaedic surgeon with expertise in the treatment of children. They say that non-surgical management - including activity modification, bracing and physiotherapy - can be considered for children with partial ACL tears affecting less than 50 per cent of the diameter of the ligament. However, reconstructive surgery that partially or completely spares the femoral physis (growth plate) and adult-type open or keyhole surgery for those nearing skeletal maturity should be performed in cases of complete ACL rupture. Dr Frank insists that surgery-related complications are rare as long as the right operation is performed on the right patient. He notes: "There are currently numerous safe and effective surgical techniques to reconstruct the ACL in the skeletally immature sportsperson to restore stability and forestall the early progression towards meniscal and chondral (cartilage) pathologies (disease)." The experts also recommend weight-bearing exercises and activity modifications following surgery, along with bracing, progressive physiotherapy emphasising range-of-motion, and other suitable exercises. Arthritis Research UK is currently funding research that aims to reduce the increased risk of osteoarthritis in young people who have suffered a knee injury and have damaged their meniscus - which acts as a shock absorber in the knee. They are looking at the effectiveness of meniscal transplant surgery in these patients. NEWS-MEDICAL.NET 07/02/2013 Study finds two biomarkers of acute kidney injury Acute kidney injury strikes large numbers of hospitalized patients, including those with no prior kidney-related illness, and is one of the most costly and deadly conditions affecting critically ill patients. Findings published today in Critical Care from a Mayo Clinic-led, multicenter study identify two biomarkers of acute kidney injury that can be easily measured in urine and detect affected patients roughly 12 to 36 hours earlier than current tests. "Failure to recognize and manage acute kidney injury in the early stages can lead to devastating outcomes for patients and increased costs to the health care system. Unfortunately, current blood and urine tests are not able to detect it early enough to avoid further complications or provide any chance for intervention," says lead author Kianoush B. Kashani, M.D., a nephrologist and intensivist at Mayo Clinic. The study's findings give physicians a tool to determine early on whether a patient is at risk, Dr. Kashani says. Researchers evaluated nearly 340 biomarkers to find the two with the highest correlation to kidney injury risk. The markers, Insulin Growth Factor Binding Protein-7 (IGFBP-7) and Tissue Inhibitor of

10 Metalloproteinases-2 (TIMP-2), were later validated by another multicenter study known as the Sapphire Trial. Source: Mayo Clinic