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'I am accordingly of the opinion that the normal regulation of islet content in the pancreas is by interstitial growth of pre-existing islets and by the formation of new islets [...]

OBJECTIVE--In vitro expansion of β-cells from adult human islets could solve the tissue shortage for cell replacement therapy of diabetes. Culture of human islet cells typically results in RESEARCH DESIGN AND METHODS--Isolated human islets were dissociated into single cells. β-Cells were genetically labeled using a Cre-lox system delivered by lentiviruses. Cells were analyzed for changes in expression of components of the NOTCH pathway during the initial weeks in culture. HES-1 expression was inhibited by a small hairpin RNA (shRNA), and the effects on β-cell phenotype were analyzed. RESULTS--Human β-cell dedifferentiation and entrance into the cell cycle in vitro correlated with activation of the NOTCH pathway and downregulation of the cell cycle inhibitor p57. Inhibition of HES-1 expression using shRNA resulted in significantly reduced β-cell replication and dedifferentiation. CONCLUSIONS--These findings demonstrate that the NOTCH pathway is involved in determining β-cell fate in vitro and suggest possible molecular targets for induction of β-cell redifferentiation following in vitro expansion., Replacement of β-cells by transplantation is a promising approach for treatment of type 1 diabetes; however, its application on a large scale is limited by the availability of pancreas donors. [...]

Understanding and manipulating pancreatic β-cell proliferation is a major challenge for pancreas biology and diabetes therapy. Recent studies have raised the possibility that human β-cells can undergo dedifferentiation and give rise to highly proliferative mesenchymal cells, which retain the potential to redifferentiate into β-cells. To directly test whether cultured β-cells dedifferentiate, we applied genetic lineage tracing in mice. Differentiated β-cells were heritably labeled using the Cre-lox system, and their fate in culture was followed. We provide evidence that mouse β-cells can undergo dedifferentiation in vitro into an insulin-, Pdx1-, and glut2-negative state. However, dedifferentiated β-cells only rarely proliferate under standard culture conditions and are eventually eliminated from cultures. Thus, the predominant mesenchymal cells seen in cultures of mouse islets are not of a β-cell origin., Understanding the mechanisms by which pancreatic β-cells are formed is of great interest because of the importance of this cell type in diabetes. The ability to generate large numbers of [...]

In recent years, the Supreme Court has expanded the Eleventh Amendment concept of state sovereign immunity to limit the extent to which individual litigants may assert federal rights against states in federal courts. In its 1998 term, the Supreme Court extended the sovereign immunity doctrine to shield states from federal claims asserted by individuals in state courts as well. While the court has carved out exceptions to the sovereign immunity doctrine, it has consistently held that if Congress wishes to make states liable in federal court through one of those exceptions, it must do so by clearly expressing its intent to abrogate states' sovereign immunity. This note focuses on one of the exceptions to sovereign immunity - the constructive waiver of sovereign immunity that sometimes occurs when states accept federal funds - and argues that the clear statement requirement should not be applied to federal funding legislation that seeks to provide individual claimants a right to sue their state in state court.

•Bacterial skin infections are common in children, and frequently do not require systemic antibiotic therapy, particularly for superficial forms.•The bacterial species most frequently implicated in skin in children’s skin are Staphylococcus aureusand Streptococcus pyogenes.•Topical antibiotics (mupirocin) are sufficient in most cases of impetigo.•If systemic antibiotics are required, given the low incidence of methicillin-resistant S. aureusin France (<10%), the first-line antibiotic treatment is amoxicillin-clavulanate, to which an anti-toxin treatment such as clindamycin for patients with overt toxin signs may be added.

•Most osteoarticular infections (OAI) occur via the hematogenous route, and most frequently affect children under 5 years of age.•Early diagnosis and prompt treatment are needed to avoid complications.•Staphylococcus aureusis implicated in OAIs in children at all ages and Kingella kingaeis a very common causative pathogen in those from 6 months to 4 years old.•Given its effective activity against K. kingaeand methicillin-susceptible S. aureus(predominant in France) the initial treatment is cefazolin by IV route.•In most children presenting uncomplicated BJI with favorable outcome (disappearance of fever and pain), short intravenous antibiotic therapy for 3 days can be followed by oral therapy. Minimum total duration of antibiotic therapy should be 14 days for septic arthritis, and 3 weeks for osteomyelitis.

Background The best methods of labour induction have still been controversial because of an increased risk of uterine rupture, especially in exposed women of labour induction with prostaglandins. We here attempted to determine, after Dinoprostone Vaginal Insert, previous cesarean women (exposed women), compared with nulliparous women (non-exposed women), are more likely 1) to have the dilated cervix (up to 3 cm or more), and 2) to require cesarean after cervix being dilated 3 cm or more.

How managers of retail operations stock their stores, display their merchandise and group their available products has a direct effect on sales. While sales clerks should offer each customer personal [...]

Issues concerning the hiring and training of staff for the retail operations aquatics centers and waterparks are presented. A merchandise manager should be hired for supervising retail aspects of a large waterpark, including hiring staff and running operations.

Retail shops at aquatic facilities should stock and market items such as beach towels, swimsuits and sunglasses, and other swimming and bathing accessories. Tips for managing an aquatic retail operation are provided.

La réglementation sanitaire française applicable aux eaux potables est codifiée dans le Code de la santé publique et prévoit que le contrôle sanitaire réglementaire est exercé par le préfet; il comprend notamment l’inspection des installations.Parmi les priorités retenues en 2007 par la Ddass de la Gironde, devenue ARS en avril 2010, figurait la réalisation d’une action spécifique de contrôle contradictoire, spécifique sur les conditions d’amé nagement et d’entretien des installations de production et de distribution d’eau potable en utilisant un questionnaire d’enquête. L’action entreprise en Gironde a consisté, d’une part, à vérifier les conditions d’application des arrêtés préfectoraux instaurant les périmètres de protection des captages et, d’autre part, à inspecter les installations de production et de distribution d’eau. Elle avait aussi deux objectifs complémentaires : de mettre à jour les informations techniques détenues par la Ddass et de sensibiliser les collectivités et les exploitants à l’entretien des ouvrages, au risque de malveillance et à sa prévention, à la sécurité des produits chimiques, à la sécurité électrique.Les contrôles réalisés de 2007 à 2010 ont conduit à visiter 82 des 373 captages publics (22 %) et 62 des 256 installations publiques de traitement (24 %) d’eau potable de la Gironde. Les 155 remarques formulées concernant les captages ont porté principalement pour 27 % d’entre elles sur la conception des têtes d’ouvrages, 25 % sur la clôture et 14 % sur l’étanchéité des ouvrages. Les 147 remarques concernant les installations de traitement et/ou de stockage ont quant à elles porté principalement sur la conception et la surveillance des installations vis-à-vis de la malveillance (28 %), la conception des installations (25 %) et la sécurité des produits chimiques (17 %). Les obligations prévues par la réglementation française concernant les points soulevés dans le présent article relèvent plus de l’obligation de résultat que de l’obligation de moyens, le domaine n’étant que très peu encadré par le droit européen. Un partage de culture dans ce domaine est nécessaire, en particulier pour tirer des enseignements des erreurs du passé, valoriser les bonnes expériences, à défaut de disposer de réglementations, guides techniques, codes de bonnes pratiques adaptés.

Acute pancreatitis (AP) is an inflammatory disease in which the regulatory pathways are not clearly elucidated. Activation of interleukin 1β (IL-1β) and immunomodulation via MyD88, the first signaling molecule in the ST2 pathway, seem to be involved. Because IL-33, the ST2 ligand, is an IL-1 family member and acts as an alarmin, we explored the ST2 pathway in human and mouse AP. Soluble ST2 was assayed by enzyme-linked immunosorbent assay (ELISA) in plasma of 44 patients admitted for AP. The levels of soluble ST2 increased early during AP and correlated with parameters of severity. Under two different experimental models of AP (ie, choline-deficient-ethionine-supplemented diet and cerulein injections), ST2-deficient mice (Il1rl1−/−) presented with more severe disease than wild-type mice, with increased activation of mast cells. In vitro, Il1rl1−/−bone-marrow-derived mast cells exhibited exacerbated degranulation, compared with the wild type. Flow cytometry identified mast cells as the main peritoneal population expressing ST2. Using immunohistochemistry and ELISA, we showed constitutive expression of IL-33 in murine pancreas and its release during experimental AP. Correlated with AP severity, increased soluble ST2 levels evoke involvement of the ST2 pathway in human AP. Furthermore, our experimental data suggest a protective role for ST2 during AP, highlighting the potential regulatory role of mast cells and the possibility of the ST2 pathway as a new therapeutic target in AP.

La réglementation sanitaire française applicable aux piscines, autres que celles réservées à l’usage personnel d’une famille, est codifiée dans le code de la Santé Publique et prévoit que le contrôle sanitaire réglementaire est effectué à la diligence de l’ARS qui peut réaliser les prélèvements ou confier leur réalisation au laboratoire agréé chargé du contrôle sanitaire des eaux.Dans ce contexte, en 2009, la réalisation par l’ARS d’Aquitaine de visites techniques de 50 piscines publiques et privées fonctionnant toute l’année en Gironde a été retenue comme un axe prioritaire par l’ex-DDASS de la Gironde dans le but de :•mettre à jour les informations techniques détenues par l’ARS sur les piscines, en particulier celles qui figurent dans les dossiers de déclaration ;•rappeler aux gestionnaires de ces établissements le contexte technique réglementaire auquel ils sont soumis au titre du code de la Santé Publique ;•dresser le constat de la situation au niveau de chaque établissement et plus globalement au niveau de l’ensemble des établissements contrôlés. D’entrée, il a été décidé de ne pas contrôler les règles de sécurité (cette action ne relevant pas des attributions de l’ARS), ni de dresser un bilan des résultats des analyses de contrôle sanitaire réalisées mensuellement sur ces établissements, ou de tenter de croiser ces résultats avec les constats réalisés en matière de conception et d’entretien.Les contrôles réalisés de 2009 à 2010 ont conduit à soulever 214 points majeurs figurant dans les 50 lettres envoyées aux gestionnaires des établissements enquêtés et portent sur le non-respect de règle de conception, mais aussi, dans un certain nombre de cas sur l’entretien des installations, la tenue du carnet sanitaire et l’information du public. Globalement, les 214 points majeurs soulevés se répartissent en 15 thématiques. À eux seuls cinq thèmes « d’inspection » représentent plus de deux tiers des remarques formulées (146/214 = 68,2 %) : le stockage des produits chimiques (21 remarques), le mauvais raccordement sur les réseaux eaux usées/eaux pluviales (24 remarques), la mauvaise réalisation des analyses d’autosurveillance ou mauvaise tenue du carnet sanitaire (24 remarques), l’entretien insuffisant des installations (28 remarques) et les problèmes de conception ou d’entretien des installations de traitement de l’eau des bassins (49 remarques). La réalisation de l’enquête a permis de rappeler aux exploitants la nécessité de veiller au respect de règles qui ne coûtent que peu ou pas d’argent comme l’affichage réglementaire, la tenue du carnet sanitaire, la réalisation de tests de terrain, la régularisation administrative des établissements, l’utilisation de réactifs de traitement homologués et un entretien soutenu des installations.La publication du présent article de synthèse est de nature à sensibiliser les maîtres d’ouvrage, concepteurs et exploitants de ces établissements dont l’encadrement réglementaire date, pour une grande part, de 1981 et qui n’est pas concerné par l’application de directives européennes.

We have reexamined the “uncoupling” of Ca2+ transport from ATP hydrolysis, which has been reported to be caused by trypsin cleavage of the Ca2+-ATPase of sarcoplasmic reticulum (SR) vesicles at the second (slower) of two characteristic tryptic sites (Scott, T. L., and Shamoo, A. E. (1982) J. Membr. Biol. 64, 137-144). We find that the loss of Ca2+ accumulation capacity in SR vesicles is poorly correlated with this cleavage under several conditions. The loss is accompanied by increased Ca2+ permeability but not by changes in the properties of the ATPase or ATP-Pi exchange activities of the vesicles. Proteoliposomes containing purified Ca2+-ATPase which has been cleaved in part at the two tryptic sites are as well coupled and impermeable to Ca2+ as proteoliposomes containing intact Ca2+-ATPase. We conclude that the loss of Ca2+ accumulation capacity in SR vesicles on tryptic treatment is due to cleavage of a SR membrane component other than the Ca2+-ATPase, possibly a component of the gated channels which function in Ca2+ release from SR, which leads to a Ca2+ leak. The hydrolytic and coupled transport functions of the Ca2+-ATPase itself may well be unaffected by the two tryptic cleavages.

The article reviews the Super Deluxe Edition music release of "In Utero," by Nirvana.

The article reviews the music release "New Constellation," by Toad the Wet Sprocket.

The article reviews the music release "...And It Shook Me," by The Postelles.

The article reviews the music release "Promises," by The Boxer Rebellion.

The author expresses his views on the efforts being done by Americans to engage themselves in social movement activities in the U.S. in 2011. He mentions that international indignation against plutocratic rule has already reached its climax. He also offers information on the prevalence of social movements in such countries as Spain and Egypt.

The article reports on the political and economic developments in Spain. It claims that just like other states in Europe, Spain is implementing anti-social-neo-liberal policies that were strongly opposed by its citizens. It cites the protests being staged by the Indignados movement (Indignant Ones) to call for economic democracy, political justice and peace. Among the movement's supporters are Vicent Navarro, Arcadi Oliveras and Eduardo Galeano.

The author discusses the popular uprising in Spain which many feel is the beginning of a European summer of discontent similar to the Arab Spring. He cites the belief of market analysts that previously undeclared debt will surface as the new administration takes control of regional and local governments, making the economic conditions in Spain worse than what has been estimated. He emphasizes the need for a centre-right government to address the people's call of indignation.

The article reports on the protest movement at La Puerta del Sol in Madrid, Spain in 2011. Several people including the disillusioned youth, unemployed, pensioners, students, immigrants and other disenfranchised groups have gathered together at the plaza to demand an opportunity to live with dignity. It compares the Spanish movement to demonstrations held by people across the Arab world.

The article comments on how the Spanish police forces dealt with the non-violent movements calling for economic democracy, political justice and peace at the Plaza Cataluña in Barcelona, Spain. The city government called for the dispersal of the crowds with the excuse of cleaning up the square for security reasons, in preparation for the Champions League soccer final. It suggests that the real aim of the operation was to seize documents from the movement's steering committees.

The article focuses on the U.S.-led war on Libya. The author admits Libyan leader Muammar Qaddafi is a criminal who oppresses his people and steals the country's wealth, but the toppling of corrupt leaders must spread across the region and worldwide in the form of non-violent popular uprisings. The author claims that as Libya's civil war becomes another U.S.-led Western imperial invasion, the people of Libya are no safer and not gaining the kind of democracy they longed for.

The author suggests ways for the citizenry to stop inhumanity in 2011. He encourages readers to coordinate a Global General strike to demonstrate a true sense of solidarity and responsibility. He recommends an organization of a globally coordinated effort to urge citizens to stop paying a proportion of taxes used in defense spending. He adds that not voting can avoid meaningful change.

The article contends that Israel has declared war on the world's citizens in light of the Israeli army's attack on the Turkish humanitarian aid ship Mavi Marmara on international waters. Some of the peace advocates aboard the ship were killed, while the rest were arrested. The author believes the attack is a premeditated one and urges all government to put a stop to Israel's crimes against humanity.

The author focuses on the change in the intellectual community in the U.S. which is said to stem from the 2008 presidential elections. He notes that some of the biggest voices for change has endorsed candidate Barack Obama, which, he claims, reflects the union between those opposed to imperial ideology and those endorsing it. He also provides information on the article written by intellectual James Petras which discusses the reasons why intellectuals have the responsibility of voting against Obama and Republican John McCain.

The author suggests what people can do about the financial crisis. He stresses the importance of acknowledging that the financial panic is deeper than what the media portrays, and understanding that the problem is systematic. In the author's view, it is imperative that people understand that geopolitical events are in some way connected to politics, economy and war, for although the deterioration of the financial systems and economies cannot be prevented, joint and organized collective action is possible to avoid the worse events from happening.