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International audience; We conducted a multicentre test negative case control study to estimate the 2013–14 influenza vaccine effectiveness (IVE) against hospitalised laboratory confirmed influenza in 12 hospitals in France, Italy and Spain. We included all ≥18 years hospitalised patients targeted by local influenza vaccination campaign reporting an influenza-like illness within 7 days before admission. We defined as cases patients RT-PCR positive for influenza and as controls those negative for all influenza virus. We used a logistic regression to calculate IVE adjusted for country, month of onset, chronic diseases and age. We included 104 A(H1N1)pdm09, 157 A(H3N2) cases and 585 controls. The adjusted IVE was 42.8% (95%CI: 6.3;65;0) against A(H1N1)pdm09. It was respectively 61.4% (95%CI: −1.9;85.4), 39.4% (95%CI: −32.2;72.2) and 19.7% (95%CI:-148.1;74.0) among patients aged 18–64, 65–79 and ≥80 years. The adjusted IVE against A(H3N2) was 38.1% (95%CI: 8.3;58.2) overall. It was respectively 7.8% (95%CI: −145.3;65.4), 25.6% (95%CI: −36.0;59.2) and 55.2% (95%CI: 15.4;76.3) among patients aged 18–64, 65–79 and ≥80 years. These results suggest a moderate and age varying effectiveness of the 2013–14 influenza vaccine to prevent hospitalised laboratory-confirmed influenza. While vaccination remains the most effective prevention measure, developing more immunogenic influenza vaccines is needed to prevent severe outcomes among target groups. © 2016 Taylor & Francis.

Valproic acid (VPA) is a broad-spectrum antiepileptic drug that is now used commonly for several other neurological and psychiatric indications. While VPA is usually well tolerated, on rare occasions, it has been associated with severe, and sometimes, fatal liver injuries. These complications may also arise due to acute VPA overdose. As a branched chain carboxylic acid, VPA is readily metabolized in the liver via glucuronic acid conjugation, mitochondrial β- and cytosolic ω-oxidation to produce multiple metabolites, and it is probably some of these metabolites that are involved in its toxicity. While the actual mechanism of VPA hepatotoxicity is still not understood, two pathways have been in focus: the first involves the formation of reactive metabolites of VPA (and their subsequent covalent binding to cellular proteins) and the second is the development of oxidative stress in the cell. We describe here a culture system based on 3D spheroid culture of immortal hepatocytes which can determine the toxicity of valproic acid (or structurally or functionally related molecules) in vitro. The spheroids were used to follow changes in ATP production, glucose uptake and adenylate kinase following treatment and can be treated repeatedly with VPA to determine both acutely-lethal and chronically-lethal doses. This system is homeostatic and has been shown to be metabolically stable over at least 24 days and can therefore be used to follow recovery after treatment.

Valproic acid (VPA) is a broad-spectrum antiepileptic drug that is now used commonly for several other neurological and psychiatric indications. While VPA is usually well tolerated, on rare occasions, it has been associated with severe, and sometimes, fatal liver injuries. These complications may also arise due to acute VPA overdose. As a branched chain carboxylic acid, VPA is readily metabolized in the liver via glucuronic acid conjugation, mitochondrial β- and cytosolic ω-oxidation to produce multiple metabolites, and it is probably some of these metabolites that are involved in its toxicity. While the actual mechanism of VPA hepatotoxicity is still not understood, two pathways have been in focus: the first involves the formation of reactive metabolites of VPA (and their subsequent covalent binding to cellular proteins) and the second is the development of oxidative stress in the cell. We describe here a culture system based on 3D spheroid culture of immortal hepatocytes which can determine the toxicity of valproic acid (or structurally or functionally related molecules) in vitro. The spheroids were used to follow changes in ATP production, glucose uptake and adenylate kinase following treatment and can be treated repeatedly with VPA to determine both acutely-lethal and chronically-lethal doses. This system is homeostatic and has been shown to be metabolically stable over at least 24 days and can therefore be used to follow recovery after treatment. © 2013 Nova Science Publishers, Inc. All rights reserved.

There is provided a bioreactor which is provided with a lid (13) that facilitates access to the incubation cavity. Specifically the end wall of the incubation cavity is constituted by the lid (13) so that removal of the cap renders the incubation cavity fully accessible.

It has been estimated that diabetes will affect 439 million adults by 2030, with the major increase occurring in developing countries (Shaw et al., 2010). It is projected that it will rank as the 9th leading cause of death in low-income countries (Mathers & Loncar, 2006). There are two major types of diabetes, i.e. type 1 (T1D) or insulin dependent diabetes and type 2 (T2D) or non-insulin dependent diabetes. The incidence of T2D is reaching epidemic proportions and has been associated with an increase in obesity (Venables & Jeukendrup, 2009). According to the World Health Organisation (WHO, 2011) the main complications associated with diabetes are cardiovascular disease and renal failure. Although genetic factors may play a role, life-style factors, such as reduced exercise and poor diet, specifically a high carbohydrate, high fat diet devoid or low in fruit and vegetables, have been shown to increase the risk of diabetes (Astrup, 2001). Medicinal plants have been used in folk medicine and traditional healing systems such as Ayurveda and Traditional Chinese Medicine (TCM) for the treatment of diabetes (T.S.C. Li, 2003; Modak et al., 2007; Singh et al., 2009; Yen et al., 2003). On the African continent as many as 90% of the populations of some countries relies on plants as the principal source of medicine for the treatment of different diseases, including diabetes (Hostettman et al., 2000), as they provide an affordable alternative to drugs. In South Africa a large number of plants, belonging to plant families such as the Asteraceae and Lamiaceae, amongst others, have been traditionally used for the treatment of diabetes (Deutschländer et al., 2009; Erasto et al., 2005; Thring & Weitz, 2006).

It is widely expected that cells grown in 3D environments (in suspension, on scaffolds etc.) will be superior to growing cells in classical 2D culture flasks. These expectations include the belief that cells grown in 3D culture will possess physiological characteristics that resemble more closely those characteristics expressed by the cells in their native tissue in the organism. Griffith and Swartz 2006]; [Pampaloni et al. 2007] Three dimensional structures therefore may be the missing link to providing in vitro models that sufficiently mimic in vivo conditions. We are developing a new way to grow human liver cells in ‘3 dimensional’ cultures so that they behave very similar to the liver in our bodies. By growing the immortal hepatocytes in specially designed bioreactors they form small pieces of ‘pseudotissue’ which exhibit several of the functions seen in the adult liver.We have grown hepatocytes using the classical approaches (in “2D”) and using a system which leads to the generation of spheroids of cells held in suspension (“3D”). Both approaches gave rise to cultures where the large majority of cells were viable, produced similar amounts of ATP, incorporated similar amounts of methionine, and possessed all the normal ultrastructural organelles seen in eukaryotic cells.Despite these similarities, there were also some striking differences. The first difference was the growth rate. The C3A cells grown in 2D had a high growth rate and a doubling time of about 3 days whereas the cells from the same initial frozen ampoule, in the same media, in the same incubator but grown as 3D spheroids had a doubling time of around 20 days. The second difference is ultrastructural: cells grown in 3D spheroids exhibited extensive tight junctions, microvillae, bile canaliculae-like structrures and glycogen granules. In other words, the cells grown in the classical 2D growth conditions were proliferating rapidly and showing little sign of the differentiated phenotype that hepatocytes in liver tissue show. Conversely the same cells grown as spheroids were proliferating very slowly but were differentiated to a much greater degree and showed many characteristics seen in liver tissue. These results suggest that growth in 2D preferentially supports proliferation whereas growth in 3D preferentially supports cellular differentiation.References:Griffith LG, Swartz MA. (2006): Capturing complex 3D tissue physiology in vitro. Nat Rev Mol Cell Biol. 7(3):211-24Pampaloni F, Reynaud EG, Stelzer EH. (2007): The third dimension bridges the gap between cell culture and live tissue. Nat Rev Mol Cell Biol. 8(10):839-45