mardi 10 janvier 2012

Dématérialisation des factures des fournisseurs des services de l'Etat


Un arrêté publié au Journal Officiel précise les règles applicables aux factures dématérialisées adressées aux administrations d'Etat.
Conformément à la loi de modernisation de l'économie du 4 août 2008 (art.25), l'Etat français s'est mis en capacité d'accepter les factures de ses fournisseurs transmises par voie électronique. Cette nouvelle faculté offerte aux entreprises s'inscrit dans un triple objectif de développement durable, de développement de l'économie numérique et de modernisation de l'administration.
Afin de développer la dématérialisation dite « de bout en bout », l'administration a fait le choix de favoriser la dématérialisation fiscale de factures, sous la forme d'échanges de données structurées, selon les modalités définies par l'article 289 bis du code général des impôts.
Cela signifie d'une part que les factures doivent être transmises dans un format de données prédéfini, d'autre part que les factures électroniques ont une valeur légale permettant de s'affranchir totalement d'un original papier.
L'Etat a choisi également de proposer à ses fournisseurs un portail de saisie de factures.
Au final, quatre possibilités s'offrent aux fournisseurs souhaitant passer à la facturation électronique : 
● la saisie en ligne de factures sur le portail ;
● le dépôt unitaire de factures sur le portail dans l'un des 2 formats acceptés par l'Etat ;
● L'échange EDI (échanges de données informatisé), c'est à dire la transmission des factures directement du fournisseur à l'Etat, dans l'un des deux formats internationaux acceptés par l'administration : UBL Invoice ou CII UNCEFACT ;
● l'échange EDI , dans un format structuré quelconque, via un opérateur de dématérialisation du marché, dans la mesure où cet opérateur est lui même raccordé au système d'information comptable de l'Etat (Chorus).
Les fournisseurs ayant choisi l'un de ces 4 modes de transmission de leurs factures disposent en outre de la possibilité de visualiser sur le portail l'état d'avancement dans l'application Chorus du traitement de ces factures.
La saisie en ligne
Ce service est gratuit.
Pour pouvoir saisir en ligne vos factures, vous devez préalablement :
1°) Créer un compte sur le portail. Ce compte sera validé sans délai par l'administration, et un couple identifiant-mot de passe vous sera transmis par messagerie. Vous devrez ensuite activer votre compte et changer de mot de passe.
2°) Souscrire en ligne un mandat de facturation donnant mandat à l'Etat pour qu'il produise en votre nom les originaux électroniques de vos factures, et qu'il les archive de manière sécurisée pendant 10 ans (durée réglementaire)
Le dépôt de factures
Ce service est gratuit.
Pour pouvoir déposer en ligne vos factures, vous devez préalablement :
1°) Produire vous même vos factures dans l'un des 2 formats internationaux standards requis par l'administration (formats XML UBL INVOICE ou CII-UNCEFACT)
2°) Créer un compte sur le portail. Ce compte sera validé sans délai par l'administration, et un couple identifiant-mot de passe vous sera transmis par messagerie. Vous devrez ensuite activer votre compte et changer de mot de passe.
3°) Souscrire en ligne un mandat de facturation donnant mandat à l'Etat pour qu'il produise en votre nom les originaux électroniques de vos factures, et qu'il les archive de manière sécurisée pendant 10 ans (durée réglementaire), et cela même si vous mettez vous-même en oeuvre un dispositif d'archivage à valeur probante.
L'échange EDI via un opérateur de dématérialisation Cette modalité est la plus adaptée, dès lors que vous émettez un nombre de factures conséquent. Vous devez préalablement acquérir un service de dématérialisation auprès d'un opérateur de dématérialisation du marché et lui donner mandat pour produire les originaux électroniques en votre nom. La plupart des opérateurs sont raccordés au système Chorus ou sont en cours de raccordement. C'est votre opérateur de dématérialisation qui prendra en charge la conversion de vos factures dans les formats attendus par l'administration.
L'échange EDI direct entre le fournisseur et l'Etat Cette modalité suppose que vous procédiez vous-même à votre dématérialisation fiscale et soyez en capacité de produire l'un des 2 formats attendus par l'administration. Vous devrez alors vous raccorder techniquement avec la plate forme de réception des factures côté Chorus (plate forme dite « concentrateur Chorus-factures »).Cet échange peut avoir selon deux modalités de sécurisation : l'usage de protocoles chiffrés FTPS, SFTP, HTTPS, PES-IT avec chiffrement TLS, AS/2 avec chiffrement SSL sur une liaison Internet classique ou bien l'utilisation d'un réseau privé virtuel avec l'Etat et l'un des protocoles X400, HTTP, FTP ou PES-IT.
La consultation des factures sur le portail Quel que soit le mode choisi, vous pouvez suivre sur le portail l'avancement du traitement de vos factures par les services comptables de l'Etat. Pour les factures saisies en ligne ou déposées, vous disposez en outre de la possibilité de visualiser vos factures et de les télécharger. Pour accéder à cette fonctionnalité, vous devez créer un compte sur le portail. Ce compte sera validé sans délai par l'administration, et un couple identifiant-mot de passe vous sera transmis par messagerie. Vous devrez ensuite activer votre compte et changer de mot de passe. 

Arrêté du 30 décembre 2011 déterminant les procédures de transmission des factures des fournisseurs de l'Etat sous forme dématérialisée.


Décret n° 2011-1937 du 22 décembre 2011 relatif aux conditions d'acceptation par l'Etat des factures émises par ses fournisseurs sous forme dématérialisée.


Le portail Chorus.


- Le site PEPPOL

mardi 3 janvier 2012

Google deploying IPV6


In a project that has taken longer than company engineers anticipated, Google is rolling out IPv6 across its entire internal employee network.
Google network engineer Irena Nikolova discussed the company-wide implementation at the Usenix Large Installation System Administration (LISA) conference, being held this week in Boston. There, she shared some lessons that other organizations might benefit from as they migrate their own networks to the next generation Internet Protocol.
From the experience, Google has learned that an IPv6 migration involves more than just updating the software and hardware. It also requires buy-in from management and staff, particularly administrators who already are juggling too many tasks. And, for early adopters, it requires a lot of work with vendors to get them to fix buggy and still-unfinished code. "We should not expect something to work just because it is declared supported," the paper accompanying the presentation concluded.
"I think everyone who has tried to migrate to IPv6 has run into the same problems we have," Nikolova said.
The project, which has been under way for about four years, turned out to be a larger endeavor than the engineering team had anticipated. It is only half way finished. But the company has made significant gains in this time. About 95 percent of Google's engineers now have IPv6 access on their desks. Eventually, the company plans to have an IPv6-only network.
The project was started in 2008 by a small group of Google engineers, some of whom worked on it in the 20 percent of their work time that Google allots for its engineers to pursue their own pet projects. The goal was "IPv6 everywhere," Nikolova said.
Part of the interest in the upgrade was practical. Even though it was a private network, Google's internal network used public IP addresses, and Google was running out of internal IPv4 addresses. Also, Google engineers were developing IPv6 versions of Google's own tools and applications and needed to test this software internally before releasing it to the public.
Lastly, Google engineers realized they faced a chicken-and-egg problem with deploying IPv6. Like many organizations, the company has been slow to adopt IPv6 due to the lack of third party applications running on IPv6, which, in turn, are scarce because few organizations run IPv6 networks.
Google's internal network spans more than 200 offices worldwide, serving about 30,000 employees. It consists of a wide variety of devices from companies such as Cisco Systems, Juniper Networks, and Aruba Networks, hundreds of commercial and home-built applications, and a range of operating systems, including Linux, Mac OS X, and Microsoft Windows.
The engineers modeled the IPv6 network as closely as possible on the existing IPv4 one, to keep the routing and traffic flow largely the same. At first they ran IPv6 over the IPv4 networks, a process called tunneling. Then, in cases where it was feasible, they set up dual stacks, where IPv4 and IPv6 run side by side. Eventually, they want to make the network IPv6 only.
To assign IPv6 numbers to devices, Google followed the guidelines in the Internet Engineering Task Force's RFC 5375. Each campus or office got a /48 address block, which meant that it was allotted 280 addresses. In turn, each building got a /56 block of those addresses (or about 272 addresses) and each VLAN (Virtual Local Area Network) received a /64 block, or about 264 addresses. To assign numbers to specific devices, the engineers used the Stateless Address Auto-Configuration capability (SLAAC), which allows the devices to assign numbers to themselves. This approach eliminated the need to manually assign numbers to each device. It was also necessary in that at least some operating systems do not yet support DHCPv6, the version of Dynamic Host Configuration Protocol server-based addressing mechanism for IPv6 networks.
One of the major issues was inadequate support for IPv6 in network devices and software, Nikolova said.
Many network devices now only support IPv6 in software, meaning that much of the traffic processing is carried out in software, rather than with customized hardware. As a result, IPv6 network operations consume more processor cycles than IPv4 operations do. At least one wireless equipment vendor did not support ACLs (access control lists). Also, the network's WAN (wide area network) acceleration devices can not encrypt IPv6 traffic, because the protocol they use--WCCP (Web Cache Control Protocol)--does not yet work with IPv6. In addition to networking gear, printers remain problematic, in that many do not fully support IPv6.
Application and OS compatibility also proved to be a challenge. The company has been phasing out those applications that do not support IPv6, though many essential tools, such as databases and billing applications, remain in operation because they can not be modified or upgraded easily. And while the current versions of most OSes support IPv6, they do not do so by default, which causes additional work on the part of administrators and users.
"When it comes to technical problems, we can confirm that there is a lot of new, unproven and therefore buggy code, and getting our vendors aligned so that everything supports IPv6 has been a challenge," the Google paper stated.
Google also faced challenges with service providers, those companies that provided network connectivity to Google's offices. The SLAs (Service Level Agreements) were not as rigorous as those for their IPv4 services. They took a longer time connecting separate IPv6 points than they did with IPv4 peering sessions. Google itself had to rewrite its own network monitoring tools to work with IPv6 as well.
Source : http://www.techworld.com.au/article/409851/usenix_google_deploys_ipv6_internal_network

lundi 2 janvier 2012

DMP 2011 : 2012 année de la généralisation


Près d’un an après la mise en service du dossier médical personnel (DMP), plus de 56.000 Français disposent de leur DMP, selon les données présentées par l’agence des systèmes d’information partagés de santé (Asip santé), lors de sa huitième journée nationale des industriels, organisée le 14 décembre à Paris.
Le 12 décembre 2011, soit presque un an jour pour jour, après la "mise en production" du système d’information national DMP, le 16 décembre 2010, exactement 56.362 DMP avaient été créés, a rapporté Anne Monier, directrice du pôle "Territoires" de l’Asip santé.

Le rythme de déploiement du DMP continue donc de croître, puisque les précédents pointages faisaient état de 15.706 dossiers début juillet (voir dépêche TICsanté du 1er août 2011), puis 39.310 mi-octobre (voir dépêche TICsanté du 26 octobre 2011). Si cette progression se poursuit, le seuil des 10.000 créations par mois devrait être rapidement franchi.

Les quatre régions pilotes (Alsace, Aquitaine, Franche-Comté, Picardie) demeurent prépondérantes, mais leur poids relatif s’effrite: 80,7% du total des DMP créés, soit 6,6 points de moins qu’au 25 septembre.

Cette baisse concerne essentiellement l’Alsace (-5,9 points à 27,6%) et un peu la Picardie (-1,9 point à 25,2%), tandis que l’Aquitaine (+0,6 point à 19,2%) et la Franche-Comté (+0,6 point à 8,6%) maintiennent leur position.

Parmi les autres régions, Rhône-Alpes confirme son avance, avec 3.864 DMP, soit 6,8% du total. Derrière, seules les régions Pays de la Loire (1.001), Champagne-Ardenne (995) et Centre (922) approchent la barre du millier de dossiers créés.

A l’opposé, des quantités symboliques sont mentionnées pour La Réunion (7), la Guyane (3) et la Martinique (1), tandis que la Corse est la seule région où aucun DMP n’a encore été créé.

Une courte majorité (51,2%) des DMP provient des "40 établissements utilisateurs" évoqués par l’Asip santé, mais la plupart des documents contenus dans ces dossiers (64,7%) ont été ajoutés par "plus de mille professionnels de santé libéraux".

Sur les 96.332 objets recensés, plus de 35.000 sont des "comptes-rendus ou fiches de visite ou de consultation" et plus de 10.000, des "comptes-rendus hospitaliers de séjour". En outre, les catégories "comptes-rendus d’imagerie médicale", "comptes-rendus d’examens biologiques" et "prescriptions de médicaments" regroupent chacune entre 5.000 et 10.000 items.

Ce sont plus de 15 régions qui seront opérationnelles en 2012 après les 4 premières de 2011. On peut s'attendre à 500 000 DMP pour fin 2012 avant l'arrivée de la prise en compte des ayant-droits qui sera le point de rupture sur les usages.

Bisphénol A et femmes enceintes

Le bisphénol A (ou BPA) est un composant chimique présent dans un type de plastique et certaines résines à usage alimentaire. Par précaution, en France depuis le 30 juin 2010 et au niveau européen depuis juin 2011, la fabrication, l’importation, l’exportation et la mise sur le marché de biberons à base de bisphénol A, sont suspendues. Ils sont remplacés par des biberons principalement en verre ou en polypropylène.

Les contenants alimentaires fabriqués avec du bisphénol A seront prochainement identifiables par des avertissements sanitaires sur les emballages. Par ailleurs, les autorités sanitaires veillent à la poursuite des expertises sur le bisphénol A et des autres substances chimiques susceptibles d’avoir les mêmes effets.

Pour connaître les gestes à adopter, vous pouvez télécharger la brochure.

Pour en savoir plus, rendez-vous sur le site du Ministère en charge de la Santé et sur le site de l’Agence nationale de sécurité sanitaire de l’alimentation, de l’environnement et du travail (ANSES)

jeudi 22 décembre 2011

European Commission starts the eHealth Network


According to the provisions of the Directive 2011/24/EU on Patients' Rights in Cross-border Healthcare, the European Commission has adopted a Decision establishing the eHealth Network. The Network will bring together the national authorities responsible for eHealth on a voluntary basis to work on common orientations for eHealth. The aim of the eHealth Network is to ensure EU wide interoperability of electronic health systems and wider use of eHealth as well as coordination, coherence and consistency of work on eHealth at EU level.
As highlighted by Commissioner for the Digital Agenda, Neelie Kroes, interoperable eHealth can help to improve the safety and efficiency of care of millions of Europeans who travel within the EU every year. The establishment of the Network represents the first time that the European legislator includes provisions on eHealth with a clear objective to achieve modern innovative solutions to deliver better health services to the citizens.
The eHealth Network is expected to translate the results of numerous research projects and pilot projects into real-life accessible services for European citizens. It is mandated to draw up guidelines on a minimum set of common data to be included in patients' summaries as well as effective methods to enable the use of medical information for public health and medical research.
Also, according to the Directive 2011/24/EU on the application of patients’ rights in cross-border healthcare, the eHealth Network will support Member States in developing common identification and authentication measures to facilitate transferability of data in cross-border healthcare.
Source : http://euroalert.net/en/news.aspx?idn=14284

More HTML5 in 2012


After that in 2011 webkit's family of browsers has shown the way, from tech titans like Zynga, Facebook, Microsoft, to startups just launching, the battle lines of 2012 will be drawn across the landscape of HTML5. Below are 14 bold predictions for how HTML5 will evolve in 2012.
Welcome to a more interconnected web:
In 2012, HTML5 will be adding support for some really useful and cool APIs that allow one
website to connect to another.
For example, Zynga games on Facebook run inside of iframes. Using the new postMessage APIthese games will be able to communicate within the containing Facebook frame directly. Before HTML5, inter-window communication had to rely on a remote server – or use unreliable hacks.
Another exciting addition is CORS (Cross Origin Resource Sharing). This will make it much easier for different websites to share information with one another. For example, CORS will enable startups to create photo-editing services that download your photos from Facebook, let you modify them, and then re-upload them – again without having to resort to ugly hacks.
With all of the new semantic information (see Semantics and Microdata) available with HTML5, it will become much easier to create web tools that extract information from web pages. As a result, you can expect to see a plethora of new mashup services, as well as better browser modes (like readers and translators).
Web browsers will look more like iPhones
Everyone loves Apple’s iOS. Now it’s coming to the HTML5 web. In 2012 your browsers will start
sporting push notificationsgeolocation, and offline capable applications. Some browsers will likely adopt a more iOS-like user interface that will make the comparison all the more apt.
More and more applications will just be built in HTML5 instead of downloadable apps
If you’re like me, you already use web apps for email, calendars, and photo-sharing, but in 2012 more classes of applications will be HTML5 enabled. Next up, you can expect to see content creation apps like Inkscape and Illustrator emerge for HTML5 and start to catch on.
Internet Explorer & Microsoft will dramatically improve in coolness.
Internet explorer’s reputation will stop being “the browser where nothing works right” and start being “the fast browser”. Microsoft has made major investments into improving HTML5 performance that will give IE 10 a huge performance lead over competing browsers. Its hardware accelerated “canvas” will blow away all the other browsers in any speed test. Microsoft is also adding interesting ways for the HTML5 web and the desktop to work together that will really spice up its operating system. Having good support from IE will be the impetus that will really turn the tide in favor of authoring HTML5 applications.
Browser manufacturers will get into the App Store business
Taking a cue from Apple, browser manufacturers will start to realize that they are missing out by not being in the app store business. Google Chrome already has an integrated app-store as its splash page. Expect many other browsers to follow. This is actually a good thing for HTML5 application developers – it means more distribution opportunities for apps, although platform specific payment systems and platform revenue-shares will follow later on.
At least one major console game released or re-released using WebGL
In 2012, at least one AAA console game company is going to make the leap and decide to launch a 3D title on the web using WebGL instead of (or in addition to) creating a downloadable client. It might be a re-release of a well-known title (Like “Team Fortress 2″ or “Assassins Creed”), or another way to play a popular MMO (like “Eve Online” or “World of Warcraft”), or it may be an entirely new title launching for the first time.
Many more applications will use offline cache and will work offline
The offline application cache will dramatically improve the usability and speed of HTML5 apps. Querying a local database will allow applications to avoid a round-trip to the server, eliminating that laggy web-app feel that makes us all prefer native apps today.
In 2012, expect to see a few issues arise from this extended usage. You’ll lose your work by clearing your cache at least once or twice. Also expect security vulnerabilities to keep showing up that allow malicious applications to access private files stored on your computer by another
website.
HTML5 ads will become prevalent and overtake Flash ads
Website owners keen to monetize the increasingly large amount of traffic coming from iOS devices will demand HTML5 ads (rather than Flash ads). Startups will emerge to serve this market. These startups will solve the sand boxing, security, and authoring tools issues that this new market will face. Now that HTML5 is capable of doing everything that flash ads commonly do, it’s just a matter of time before they take over.
JavaScript will get a lot faster with better memory management and typed arrays
JavaScript has gotten really, really fast – it’s already among the world’s fastest scripting languages – but there is room for improvement. Google Chrome has started pushing the envelope on better memory management and garbage collection algorithms. This, combined with typed arrays, will bring JavaScript performance closer to more mature languages like Java.
Canvas will get hardware acceleration in more browsers (but no major mobile browsers)
Other browser makers will follow Internet Explorer’s lead and add hardware acceleration to their canvas implementations. Those that don’t will suffer a severe loss in mind-share. Firefox is most at-risk in this regard. If Mozilla fails to accelerate their canvas it risks being portrayed as the new IE — slow and bloated and burdened down with legacy code.
However, in 2012, no major mobile browsers will successfully roll out a hardware-accelerated canvas. We will have to wait until 2013 to start seeing that catch on.
People will play popular HTML5 games on their mobile devices from Zynga and others, but they will be very simple games
You can expect to see your friends playing games like Zynga Poker, Words with Friends, and Mafia Wars on their mobile phones, running purely in HTML5. These games will be played on both destination websites and within native applications (like the Facebook app).
However, successful HTML5 games on mobile devices will be limited to menu-based games, card games, board games, turn-based multiplayer games, and avatar customizer games. More complex and visually intensive Zynga “Ville” style games with isometric worlds or hundreds of animating sprites will not yet strike gold in 2012.
Facebook will release improved HTML5-based APIs that allow for more seamless integration with external websites
In its continued quest to be the de facto social-graph of the web, Facebook Connect will grow and expand to take advantage of new HTML5 features. This will allow even deeper and richer integration of Facebook connect with external websites and services.
Facebook will get a lot more seamlessly integrated with your desktop
Think drag-and-drop, file system access, photo synching, and widgets on your desktop. All of these features (and more) will start to blur the line between desktop and browser, bringing your social graph more closely into contact with your traditional desktop experience.
Apple will NOT fix HTML5 sound in mobile Safari
HTML5 sound used to work well in mobile Safari, back in the days iOS3. However, Apple disabled most of the API in iOS 4 and 5. It just introduces competition for iTunes — both the music store, and the App Store. In its continued fight to maintain total control over the Apple ecosystem, they will refrain from fixing HTML5 sound in 2012.

lundi 19 décembre 2011

L’Uncam rétablit le supplément d’archivage pour des examens d’imagerie médicale


L’Union nationale des caisses d’assurance maladie (Uncam) a entériné la création d’un "supplément pour archivage numérique", applicable à 85 actes d’imagerie médicale à compter du 9 janvier 2012, soit presque 30 mois après l’annulation d’une disposition analogue par le Conseil d’Etat.
La décision du 28 septembre 2011 modifie la liste des actes et prescriptions pris en charge par l’assurance maladie et institue un "supplément pour archivage numérique d’un examen scanographique ou remnographique".

Son contenu est fortement inspiré de l’avenant n°24 à la convention médicale de 2007, qui avait créé une "option archivage" ouvrant droit à deux "suppléments", au profit des seuls radiologues libéraux.

Ces mesures avaient été annulées par le Conseil d’Etat en juillet 2009, en raison d’une "différence de traitement manifestement disproportionnée" avec les praticiens hospitaliers, et parce que la création d’actes nouveaux et la définition de leurs conditions de facturation relève des prérogatives de la seule Uncam.

Plus de deux ans après, la mesure est ainsi restaurée pour 45 actes de scanographie et 40 actes de remnographie et son tarif est fixé à 1,50 euro, contre 4 euros précédemment pour le même type d’examens.

Ce "supplément" est "destiné à financer les coûts d’acquisition et de maintenance du système d’archivage supportés par son exploitant", qui devra fournir "un document de nature comptable attestant de sa participation financière".

En revanche, il "n’est pas pris en charge lorsque le médecin ou la structure (…) a bénéficié d'une subvention, totale ou partielle, pour le système d’archivage et de gestion des images [PACS, ndr], à l’exception des PACS territoriaux intersites ou interétablissements agréés par une agence régionale de santé".

Le texte rappelle que la durée minimale légale d’archivage des données médicales est de vingt ans pour les établissements de santé et stipule que "la durée doit être au minimum de cinq ans" pour les médecins libéraux.

En outre, les images "doivent être disponibles en accès immédiat sur le site pendant au moins trois ans", c’est-à-dire en moins de cinq secondes pour la première image d’un scanner et en moins d’une minute pour une série complète de 600 images.

A cette fin, les données sont archivées "en format DICOM sans compression ou avec compression sans perte (DICOM lossless)". Au-delà des trois premières années, l’accès aux données "peut être différé" et "une compression plus importante sera admise (DICOM lossy)".

En matière d’interopérabilité, le respect de certaines normes HL7 et des profils IHE correspondants (KIN, PAM, PDQ, SWF) est "indispensable", quand "l’utilisation de l’identifiant national de santé (INS) est recommandée". De plus, "le système d’archivage de l’exploitant doit être interopérable avec les PACS qui relèvent de la région où il est implanté".

Enfin, "l’archivage des images doit faire l’objet d’une déclaration" à la Commission nationale de l’informatique et des libertés (Cnil) et "une procédure interne de contrôle qualité du système doit être mise en place".

La décision de l’Uncam est parue au Journal officiel le 10 décembre 2011 et prendra effet "à compter du trentième jour suivant sa publication", soit le lundi 9 janvier 2012.

Source : http://www.ticsante.com/show.php?page=story&id=1131

mercredi 14 décembre 2011

ANTIOXIDANT HAS POTENTIAL IN THE ALZHEIMER’S FIGHT


When you cut an apple and leave it out, it turns brown. Squeeze the apple with lemon juice, an antioxidant, and the process slows down.
Simply put, that same “browning” process — known as oxidative stress — happens in the brain as Alzheimer’s disease sets in. The underlying cause is believed to be improper processing of a protein associated with the creation of free radicals that cause oxidative stress.
Now, a study by researchers in the University of Georgia College of Pharmacy has shown that an antioxidant can delay the onset of all the indicators of Alzheimer’s disease, including cognitive decline. The researchers administered an antioxidant compound called MitoQ to mice genetically engineered to develop Alzheimer’s. The results of their study were published in the Nov. 2 issue of the Journal of Neuroscience.
According to the Alzheimer’s Society, more than 5 million Americans currently suffer from the neurodegenerative disease. Without successful prevention, almost 14 million Americans will have Alzheimer’s by 2050, accounting for healthcare costs of more than $1 trillion a year.
Oxidative stress is believed to cause neurons in the brain to die, resulting in Alzheimer’s. Study author James Franklin, an associate professor of pharmaceutical and biomedical sciences, has studied neuronal cell death and oxidative stress at UGA since 2004.
“The brain consumes 20 percent of the oxygen in the body even though it only makes up 5 percent of the volume, so it’s particularly susceptible to oxidative stress,” said Franklin, coauthor of the study along with Meagan McManus, who received her Ph.D. in neuroscience from UGA in 2010.
The UGA researchers hypothesized that antioxidants administered unsuccessfully by other researchers to treat Alzheimer’s were not concentrated enough in the mitochondria of cells. Mitochondria are structures within cells that have many functions, including producing oxidative molecules that damage the brain and cause cell death.
“MitoQ selectively accumulates in the mitochondria,” said McManus, who is now studying mitochondrial genetics and dysfunction as a postdoctoral researcher at Children’s Hospital of Philadelphia.
“It is more effective for the treatment to go straight to the mitochondria, rather than being present in the cell in general,” she said.
Although he had not previously conducted research on Alzheimer’s disease, Franklin was moved to approve McManus’ research proposal to take his laboratory research in a more clinical direction in part because of her family’s history with the disease.
“Two of my grandparents had Alzheimer’s disease, but they presented with it very differently. While my granddad often couldn’t remember who we were, he was still the same soulful funnyman I’d always loved. But the disease changed my grandmother’s mind in a different way, and turned her into someone we’d never known,” said McManus.
“So the complexity of the disease was most intriguing to me. I wanted to know how and why it was happening, and more importantly, how to stop it from happening to other people,” she said.
In their study, mice engineered to carry three genes associated with familial Alzheimer’s were tested for cognitive impairment using the Morris Water Maze, a common test for memory retention. The mice that had received MitoQ in their drinking water performed significantly better than those that didn’t. Additionally, the treated mice tested negative for the oxidative stress, amyloid burden, neural death and synaptic loss associated with Alzheimer’s.
The full paper is available online at http://www.jneurosci.org/content/31/44/15703.full.

MitoQ


Introduction to Our Platform TechnologyMitochondria, present in all cells, provide energy for life processes. It is now recognized that mitochondrial dysfunction plays a role in the pathogenesis of several degenerative disorders. Antioxidants are the body's defense against free radicals. Antioxidants block the effects of oxidation, a chemical reaction that combines single electrons with oxygen to generate free radicals, which can attack and destroy cells.
Antipodean's proprietary targeted lipophilic cation technology prevents oxidative damage by concentrating antioxidants in mitochondria. MitoQ® is targeted to mitochondria by covalent attachment to a lipophilic triphenylphosphonium cation. Because of the large mitochondria membrane potential, the cations accumulate within cellular mitochondria up to 1,000 fold, compared to non-targeted antioxidants such as Coenzyme Q or its analogues.  This accumulation enables the antioxidant moiety to block lipid peroxidation, and maintain the integrity of the mitochondria membrane by protecting it from oxidative damage.
Antipodean's lead compound MitoQ® (mitoquinone) is a mitochondria-targeted antioxidant that selectively blocks mitochondrial oxidative damage and prevents cell death. Mitochondrial dysfunction underlies a wide range of degenerative diseases, in which oxidative stress plays a key pathogenic role, including such diseases as NASH, Type 2 diabetes, ischemic heart disease, among others. Therefore, protecting mitochondria from oxidative damage is a promising and innovative therapeutic strategy.
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The lipophilic cation is accumulated 5- to 10- fold into the cytoplasm from the extracellular space by the plasma membrane potential and then further accumulated 100- to 500- fold into the mitochondrial matrix by the mitochondrial membrane potential.
MitoQ® is being evaluated as an oral treatment for liver inflammation that leads to fibrosis and is associated with metabolic dysfunction.  The company is also investigating topical indications that involve mitochondrial dysfunction, including dermatologic applications and retinal degeneration. 

BIOCHEMICAL SIGNATURE PREDICTS PROGRESSION TO ALZHEIMER’S DISEASE


A study led by Research Professor Matej Orešič from VTT Technical Research Centre of Finland suggests that Alzheimer’s disease is preceded by a molecular signature indicative of hypoxia and up-regulated pentose phosphate pathway. This indicator can be analysed as a simple biochemical assay from a serum sample months or even years before the first symptoms of the disease occur. In a healthcare setting, the application of such an assay could therefore complement the neurocognitive assessment by the medical doctor and could be applied to identify the at-risk patients in need of further comprehensive follow-up.
Alzheimer’s disease (AD) is a growing challenge to the health care systems and economies of developed countries with millions of patients suffering from this disease and increasing numbers of new cases diagnosed annually with the increasing ageing of populations.
The progression of Alzheimer’s disease (AD) is gradual, with the subclinical stage of illness believed to span several decades. The pre-dementia stage, also termed mild cognitive impairment (MCI), is characterised by subtle symptoms that may affect complex daily activities. MCI is considered as a transition phase between normal aging and AD. MCI confers an increased risk of developing AD, although the state is heterogeneous with several possible outcomes, including even improvement back to normal cognition.
What are the molecular changes and processes which define those MCI patients who are at high risk of developing AD? The teams led by Matej Orešič from VTT and Hilkka Soininen from the University of Eastern Finland set out to address this question, and the results were published on 13th Dec. 2011 in Translational Psychiatry.
The team used metabolomics, a high-throughput method for detecting small metabolites, to produce profiles of the serum metabolites associated with progression to AD. Serum samples were collected at baseline when the patients were diagnosed with AD, MCI, or identified as healthy controls. 52 out of 143 MCI patients progressed to AD during the follow-up period of 27 months on average. A molecular signature comprising three metabolites measured at baseline was derived which was predictive of progression to AD. Furthermore, analysis of data in the context of metabolic pathways revealed that pentose phosphate pathway was associated with progression to AD, also implicating the role of hypoxia and oxidative stress as early disease processes.
The unique study setting allowed the researchers to identify the patients diagnosed with MCI at baseline who later progressed to AD and to derive the molecular signature which can identify such patients at baseline.
Though there is no current therapy to prevent AD, early disease detection is vital both for delaying the onset of the disease through pharmacological treatment and/or lifestyle changes and for assessing the efficacy of potential AD therapeutic agents. The elucidation of early metabolic pathways associated with progression to Alzheimer’s disease may also help in identifying new therapeutic avenues.
This study was supported by the project “From patient data to personalised healthcare in Alzheimer’s disease” (PredictAD) which was supported by the European Commission under the 7th Framework Programme.
Reference:
M. Orešič, T. Hyötyläinen, S.-K. Herukka, M. Sysi-Aho, I. Mattila, T. Seppänan-Laakso, V. Julkunen, P. V. Gopalacharyulu, M. Hallikainen, J. Koikkalainen, M. Kivipelto, S. Helisalmi, J. Lötjönen, H. Soininen, Metabolome in progression to Alzheimer’s disease, Translational Psychiatry, 13th December 2011.
Further information:
VTT Technical Research Centre of Finland
Matej Orešič, Research Professor
tel. +358 20 722 4491, matej.oresic@vtt.fi
University of Eastern Finland
Hilkka Soininen, Professor
tel. +358 40 5735749, hilkka.soininen@uku.fi