Early changes in biochemical markers of bone turnover and their relationship with bone mineral density changes after 24 months of treatment with teriparatide

Summary We report the changes in biochemical markers of bone formation during the first 6 months of teriparatide therapy in postmenopausal women with osteoporosis according to previous antiresorptive treatment. Prior therapy does not adversely affect the response to teriparatide treatment. Similar bone markers levels are reached after 6 months of treatment. Introduction The response of biochemical markers of bone turnover with teriparatide therapy in subjects who have previously received osteoporosis drugs is not fully elucidated. We examined biochemical markers of bone formation in women with osteoporosis treated with teriparatide and determined: (1) whether the response is associated with prior osteoporosis therapy, (2) which marker shows the best performance for detecting a response to therapy, and (3) the correlations between early changes in bone markers and subsequent bone mineral density (BMD) changes after 24 months of teriparatide. Methods We conducted a prospective, open-label, 24-month study at 95 centers in 10 countries in 758 postmenopausal women with established osteoporosis (n = 181 treatment-naïve) who had at least one post-baseline bone marker determination. Teriparatide (20 μg/day) was administered for up to 24 months. We measured procollagen type I N-terminal propeptide (PINP), bone-specific alkaline phosphatase (b-ALP), and total alkaline phosphatase (t-ALP) at baseline, 1 and 6 months, and change in BMD at the lumbar spine, total hip and femoral neck from baseline to 24 months. Results Significant increases in formation markers occurred after 1 month of teriparatide regardless of prior osteoporosis therapy. The absolute increase at 1 month was lower in previously treated versus treatment-naïve patients, but after 6 months all groups reached similar levels. PINP showed the best signal-to-noise ratio. Baseline PINP correlated positively and significantly with BMD response at 24 months. Conclusions This study suggests that the long-term responsiveness of bone formation markers to teriparatide is not affected in subjects previously treated with antiresorptive drugs

AtriplaR/anti-TB combination in TB/HIV patients. Drug in focus

Co-administration of anti-tuberculosis and antiretroviral therapy is often inevitable in high-burden countries where tuberculosis is the most common opportunistic infection associated with HIV/AIDS. Concurrent use of rifampicin and several antiretroviral drugs is complicated by pharmacokinetic drug-drug interaction. Pubmed and Google search following the key words tuberculosis, HIV, emtricitabine, tenofovir efavirenz, interaction were used to find relevant information on each drug of the fixed dose combination AtriplaR RESULTS: Information on generic name, trade name, pharmacokinetic parameter, metabolism and the pharmacokinetic interaction with Anti-TB drugs of emtricitabine, tenofovir, and efavirenz was obtained. Fixed dose combination of emtricitabine/tenofovir/efavirenz (ATRIPLAR) which has been approved by Food and Drug Administration shows promising results as far as safety and efficacy is concerned in TB/HIV co-infection patients, hence can be considered effective and safe antiretroviral drug in TB/HIV management for adult and children above 3 years of age

Potassium and Sodium Transport in Yeast

[EN] As the proper maintenance of intracellular potassium and sodium concentrations is vital for cell growth, all living organisms have developed a cohort of strategies to maintain proper monovalent cation homeostasis. In the model yeast Saccharomyces cerevisiae, potassium is accumulated to relatively high concentrations and is required for many aspects of cellular function, whereas high intracellular sodium/potassium ratios are detrimental to cell growth and survival. The fact that S. cerevisiae cells can grow in the presence of a broad range of concentrations of external potassium (10 M–2.5 M) and sodium (up to 1.5 M) indicates the existence of robust mechanisms that have evolved to maintain intracellular concentrations of these cations within appropriate limits. In this review, current knowledge regarding potassium and sodium transporters and their regulation will be summarized. The cellular responses to high sodium and potassium and potassium starvation will also be discussed, as well as applications of this knowledge to diverse fields, including antifungal treatments, bioethanol production and human disease.L.Y. is funded by grant BFU2011-30197-C03-03 from the Spanish Ministry of Science and Innovation (Madrid, Spain) and EUI2009-04147 [Systems Biology of Microorganisms (SysMo2) European Research Area-Network (ERA-NET)].Yenush, L. (2016). Potassium and Sodium Transport in Yeast. Advances in Experimental Medicine and Biology. 892:187-228. https://doi.org/10.1007/978-3-319-25304-6_8S187228892Ahmed A, Sesti F, Ilan N, Shih TM, Sturley SL et al (1999) A molecular target for viral killer toxin: TOK1 potassium channels. Cell 99:283–291Albert A, Yenush L, Gil-Mascarell MR, Rodriguez PL, Patel S et al (2000) X-ray structure of yeast Hal2p, a major target of lithium and sodium toxicity, and identification of framework interactions determining cation sensitivity. J Mol Biol 295:927–938Albertyn J, Hohmann S, Thevelein JM, Prior BA (1994) GPD1, which encodes glycerol-3-phosphate dehydrogenase, is essential for growth under osmotic stress in Saccharomyces cerevisiae, and its expression is regulated by the high-osmolarity glycerol response pathway. Mol Cell Biol 14:4135–4144Alepuz PM, Cunningham KW, Estruch F (1997) Glucose repression affects ion homeostasis in yeast through the regulation of the stress-activated ENA1 gene. Mol Microbiol 26:91–98Ali R, Brett CL, Mukherjee S, Rao R (2004) Inhibition of sodium/proton exchange by a Rab-GTPase-activating protein regulates endosomal traffic in yeast. J Biol Chem 279:4498–4506Alijo R, Ramos J (1993) Several routes of activation of the potassium uptake system of yeast. Biochim Biophys Acta 1179:224–228Anderson JA, Huprikar SS, Kochian LV, Lucas WJ, Gaber RF (1992) Functional expression of a probable Arabidopsis thaliana potassium channel in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 89:3736–3740Anderson JA, Nakamura RL, Gaber RF (1994) Heterologous expression of K+ channels in Saccharomyces cerevisiae: strategies for molecular analysis of structure and function. Symp Soc Exp Biol 48:85–97André B, Scherens B (1995) The yeast YBR235w gene encodes a homolog of the mammalian electroneutral Na(+)-(K+)-C1- cotransporter family. Biochem Biophys Res Commun 217:150–153Andrés MT, Viejo-Díaz M, Fierro JF (2008) Human lactoferrin induces apoptosis-like cell death in Candida albicans: critical role of K+-channel-mediated K+ efflux. Antimicrob Agents Chemother 52:4081–4088Anemaet IG, van Heusden GP (2014) Transcriptional response of Saccharomyces cerevisiae to potassium starvation. BMC Genomics 15:1040Arino J, Ramos J, Sychrova H (2010) Alkali metal cation transport and homeostasis in yeasts. Microbiol Mol Biol Rev 74:95–120Babazadeh R, Furukawa T, Hohmann S, Furukawa K (2014) Rewiring yeast osmostress signalling through the MAPK network reveals essential and non-essential roles of Hog1 in osmoadaptation. Sci Rep 4:4697Baev D, Rivetta A, Li XS, Vylkova S, Bashi E et al (2003) Killing of Candida albicans by human salivary histatin 5 is modulated, but not determined, by the potassium channel TOK1. Infect Immun 71:3251–3260Baev D, Rivetta A, Vylkova S, Sun JN, Zeng GF et al (2004) The TRK1 potassium transporter is the critical effector for killing of Candida albicans by the cationic protein, Histatin 5. J Biol Chem 279:55060–55072Bagriantsev SN, Ang KH, Gallardo-Godoy A, Clark KA, Arkin MR et al (2013) A high-throughput functional screen identifies small molecule regulators of temperature- and mechano-sensitive K2P channels. ACS Chem Biol 8:1841–1851Bañuelos MA, Sychrová H, Bleykasten-Grosshans C, Souciet JL, Potier S (1998) The Nha1 antiporter of Saccharomyces cerevisiae mediates sodium and potassium efflux. Microbiology 144(Pt 10):2749–2758Bañuelos MA, Ruiz MC, Jiménez A, Souciet JL, Potier S et al (2002) Role of the Nha1 antiporter in regulating K(+) influx in Saccharomyces cerevisiae. Yeast 19:9–15Barnett JA (2008) A history of research on yeasts 13. Active transport and the uptake of various metabolites. Yeast 25:689–731Barreto L, Canadell D, Petrezselyova S, Navarrete C, Maresova L et al (2011) A genomewide screen for tolerance to cationic drugs reveals genes important for potassium homeostasis in Saccharomyces cerevisiae. Eukaryot Cell 10:1241–1250Barreto L, Canadell D, Valverde-Saubí D, Casamayor A, Ariño J (2012) The short-term response of yeast to potassium starvation. Environ Microbiol 14:3026–3042Benito B, Moreno E, Lagunas R (1991) Half-life of the plasma membrane ATPase and its activating system in resting yeast cells. Biochim Biophys Acta 1063:265–268Benito B, Quintero FJ, Rodríguez-Navarro A (1997) Overexpression of the sodium ATPase of Saccharomyces cerevisiae: conditions for phosphorylation from ATP and Pi. Biochim Biophys Acta 1328:214–226Benito B, Garciadeblás B, Rodríguez-Navarro A (2002) Potassium- or sodium-efflux ATPase, a key enzyme in the evolution of fungi. Microbiology 148:933–941Benito B, Garciadeblás B, Schreier P, Rodríguez-Navarro A (2004) Novel p-type ATPases mediate high-affinity potassium or sodium uptake in fungi. Eukaryot Cell 3:359–368Bernardi P (1999) Mitochondrial transport of cations: channels, exchangers, and permeability transition. Physiol Rev 79:1127–1155Bertl A, Slayman CL, Gradmann D (1993) Gating and conductance in an outward-rectifying K+ channel from the plasma membrane of Saccharomyces cerevisiae. J Membr Biol 132:183–199Bertl A, Bihler H, Reid JD, Kettner C, Slayman CL (1998) Physiological characterization of the yeast plasma membrane outward rectifying K+ channel, DUK1 (TOK1), in situ. J Membr Biol 162:67–80Bertl A, Ramos J, Ludwig J, Lichtenberg-Fraté H, Reid J et al (2003) Characterization of potassium transport in wild-type and isogenic yeast strains carrying all combinations of trk1, trk2 and tok1 null mutations. Mol Microbiol 47:767–780Bihler H, Slayman CL, Bertl A (1998) NSC1: a novel high-current inward rectifier for cations in the plasma membrane of Saccharomyces cerevisiae. FEBS Lett 432:59–64Bihler H, Slayman CL, Bertl A (2002) Low-affinity potassium uptake by Saccharomyces cerevisiae is mediated by NSC1, a calcium-blocked non-specific cation channel. Biochim Biophys Acta 1558:109–118Blomberg A (1995) Global changes in protein synthesis during adaptation of the yeast Saccharomyces cerevisiae to 0.7 M NaCl. J Bacteriol 177:3563–3572Blomberg A (2000) Metabolic surprises in Saccharomyces cerevisiae during adaptation to saline conditions: questions, some answers and a model. FEMS Microbiol Lett 182:1–8Borst-Pauwels GW (1981) Ion transport in yeast. Biochim Biophys Acta 650:88–127Botstein D, Fink GR (2011) Yeast: an experimental organism for 21st Century biology. Genetics 189:695–704Bouillet LE, Cardoso AS, Perovano E, Pereira RR, Ribeiro EM et al (2012) The involvement of calcium carriers and of the vacuole in the glucose-induced calcium signaling and activation of the plasma membrane H(+)-ATPase in Saccharomyces cerevisiae cells. Cell Calcium 51:72–81Bowers K, Levi BP, Patel FI, Stevens TH (2000) The sodium/proton exchanger Nhx1p is required for endosomal protein trafficking in the yeast Saccharomyces cerevisiae. Mol Biol Cell 11:4277–4294Breinig F, Tipper DJ, Schmitt MJ (2002) Kre1p, the plasma membrane receptor for the yeast K1 viral toxin. Cell 108:395–405Brett CL, Tukaye DN, Mukherjee S, Rao R (2005) The yeast endosomal Na+K+/H+ exchanger Nhx1 regulates cellular pH to control vesicle trafficking. Mol Biol Cell 16:1396–1405Cagnac O, Leterrier M, Yeager M, Blumwald E (2007) Identification and characterization of Vnx1p, a novel type of vacuolar monovalent cation/H+ antiporter of Saccharomyces cerevisiae. J Biol Chem 282:24284–24293Cagnac O, Aranda-Sicilia MN, Leterrier M, Rodriguez-Rosales MP, Venema K (2010) Vacuolar cation/H+ antiporters of Saccharomyces cerevisiae. J Biol Chem 285:33914–33922Calahorra M, Lozano C, Sánchez NS, Peña A (2011) Ketoconazole and miconazole alter potassium homeostasis in Saccharomyces cerevisiae. Biochim Biophys Acta 1808:433–445Canadell D, González A, Casado C, Ariño J (2015) Functional interactions between potassium and phosphate homeostasis in Saccharomyces cerevisiae. Mol Microbiol 95:555–572Casado C, Yenush L, Melero C, del Carmen Ruiz M, Serrano R et al (2010) Regulation of Trk-dependent potassium transport by the calcineurin pathway involves the Hal5 kinase. FEBS Lett 584:2415–2420Causton HC, Ren B, Koh SS, Harbison CT, Kanin E et al (2001) Remodeling of yeast genome expression in response to environmental changes. Mol Biol Cell 12:323–337Clotet J, Posas F (2007) Control of cell cycle in response to osmostress: lessons from yeast. Methods Enzymol 428:63–76Cornet M, Gaillardin C (2014) pH signaling in human fungal pathogens: a new target for antifungal strategies. Eukaryot Cell 13:342–352Courchesne WE (2002) Characterization of a novel, broad-based fungicidal activity for the antiarrhythmic drug amiodarone. J Pharmacol Exp Ther 300:195–199Courchesne WE, Ozturk S (2003) Amiodarone induces a caffeine-inhibited, MID1-dependent rise in free cytoplasmic calcium in Saccharomyces cerevisiae. Mol Microbiol 47:223–234Crespo JL, Daicho K, Ushimaru T, Hall MN (2001) The GATA transcription factors GLN3 and GAT1 link TOR to salt stress in Saccharomyces cerevisiae. J Biol Chem 276:34441–34444Cunningham KW, Fink GR (1996) Calcineurin inhibits VCX1-dependent H+/Ca2+ exchange and induces Ca2+ ATPases in Saccharomyces cerevisiae. Mol Cell Biol 16:2226–2237Curto M, Valledor L, Navarrete C, Gutiérrez D, Sychrova H et al (2010) 2-DE based proteomic analysis of Saccharomyces cerevisiae wild and K+ transport-affected mutant (trk1,2) strains at the growth exponential and stationary phases. J Proteomics 73:2316–2335D’Avanzo N, Cheng WW, Xia X, Dong L, Savitsky P et al (2010) Expression and purification of recombinant human inward rectifier K+ (KCNJ) channels in Saccharomyces cerevisiae. Protein Expr Purif 71:115–121Daran-Lapujade P, Daran JM, Luttik MA, Almering MJ, Pronk JT et al (2009) An atypical PMR2 locus is responsible for hypersensitivity to sodium and lithium cations in the laboratory strain Saccharomyces cerevisiae CEN.PK113-7D. FEMS Yeast Res 9:789–792Davis DA (2009) How human pathogenic fungi sense and adapt to pH: the link to virulence. Curr Opin Microbiol 12:365–370de Nadal E, Posas F (2011) Elongating under stress. Genet Res Int 2011:326286de Nadal E, Clotet J, Posas F, Serrano R, Gomez N et al (1998) The yeast halotolerance determinant Hal3p is an inhibitory subunit of the Ppz1p Ser/Thr protein phosphatase. Proc Natl Acad Sci U S A 95:7357–7362de Nadal E, Calero F, Ramos J, Ariño J (1999) Biochemical and genetic analyses of the role of yeast casein kinase 2 in salt tolerance. J Bacteriol 181:6456–6462de Nadal E, Alepuz PM, Posas F (2002) Dealing with osmostress through MAP kinase activation. EMBO Rep 3:735–740De Nadal E, Zapater M, Alepuz PM, Sumoy L, Mas G et al (2004) The MAPK Hog1 recruits Rpd3 histone deacetylase to activate osmoresponsive genes. Nature 427:370–374Dimmer KS, Fritz S, Fuchs F, Messerschmitt M, Weinbach N et al (2002) Genetic basis of mitochondrial function and morphology in Saccharomyces cerevisiae. Mol Biol Cell 13:847–853Durell SR, Guy HR (1999) Structural models of the KtrB, TrkH, and Trk1,2 symporters based on the structure of the KcsA K(+) channel. Biophys J 77:789–807Eide DJ, Clark S, Nair TM, Gehl M, Gribskov M et al (2005) Characterization of the yeast ionome: a genome-wide analysis of nutrient mineral and trace element homeostasis in Saccharomyces cerevisiae. Genome Biol 6:R77Elicharova H, Sychrova H (2014) Fluconazole affects the alkali-metal-cation homeostasis and susceptibility to cationic toxic compounds of Candida glabrata. Microbiology 160:1705–1713Endele S, Fuhry M, Pak SJ, Zabel BU, Winterpacht A (1999) LETM1, a novel gene encoding a putative EF-hand Ca(2+)-binding protein, flanks the Wolf-Hirschhorn syndrome (WHS) critical region and is deleted in most WHS patients. Genomics 60:218–225Eraso P, Mazón MJ, Portillo F (2006) Yeast protein kinase Ptk2 localizes at the plasma membrane and phosphorylates in vitro the C-terminal peptide of the H+-ATPase. Biochim Biophys Acta 1758:164–170Erez O, Kahana C (2002) Deletions of SKY1 or PTK2 in the Saccharomyces cerevisiae trk1Deltatrk2Delta mutant cells exert dual effect on ion homeostasis. Biochem Biophys Res Commun 295:1142–1149Estrada E, Agostinis P, Vandenheede JR, Goris J, Merlevede W et al (1996) Phosphorylation of yeast plasma membrane H+-ATPase by casein kinase I. J Biol Chem 271:32064–32072Fairman C, Zhou X, Kung C (1999) Potassium uptake through the TOK1 K+ channel in the budding yeast. J Membr Biol 168:149–157Farnaud S, Evans RW (2003) Lactoferrin – a multifunctional protein with antimicrobial properties. Mol Immunol 40:395–405Fell GL, Munson AM, Croston MA, Rosenwald AG (2011) Identification of yeast genes involved in k homeostasis: loss of membrane traffic genes affects k uptake. G3 (Bethesda) 1:43–56Fernandes AR, Sá-Correia I (2003) Transcription patterns of PMA1 and PMA2 genes and activity of plasma membrane H+-ATPase in Saccharomyces cerevisiae during diauxic growth and stationary phase. Yeast 20:207–219Ferrando A, Kron SJ, Rios G, Fink GR, Serrano R (1995) Regulation of cation transport in Saccharomyces cerevisiae by the salt tolerance gene HAL3. Mol Cell Biol 15:5470–5481Ferrigno P, Posas F, Koepp D, Saito H, Silver PA (1998) Regulated nucleo/cytoplasmic exchange of HOG1 MAPK requires the importin beta homologs NMD5 and XPO1. EMBO J 17:5606–5614Flegelova H, Haguenauer-Tsapis R, Sychrova H (2006) Heterologous expression of mammalian Na/H antiporters in Saccharomyces cerevisiae. Biochim Biophys Acta 1760:504–516Flis K, Hinzpeter A, Edelman A, Kurlandzka A (2005) The functioning of mammalian ClC-2 chloride channel in Saccharomyces cerevisiae cells requires an increased level of Kha1p. Biochem J 390:655–664Forment J, Mulet JM, Vicente O, Serrano R (2002) The yeast SR protein kinase Sky1p modulates salt tolerance, membrane potential and the Trk1,2 potassium transporter. Biochim Biophys Acta 1565:36–40Froschauer E, Nowikovsky K, Schweyen RJ (2005) Electroneutral K+/H+ exchange in mitochondrial membrane vesicles involves Yol027/Letm1 proteins. Biochim Biophys Acta 1711:41–48Fukuda A, Nakamura A, Tagiri A, Tanaka H, Miyao A et al (2004) Function, intracellular localization and the importance in salt tolerance of a vacuolar Na(+)/H(+) antiporter from rice. Plant Cell Physiol 45:146–159Gaber RF (1992) Molecular genetics of yeast ion transport. Int Rev Cytol 137:299–353Gaber RF, Styles CA, Fink GR (1988) TRK1 encodes a plasma membrane protein required for high-affinity potassium transport in Saccharomyces cerevisiae. Mol Cell Biol 8:2848–2859Gaxiola RA, Rao R, Sherman A, Grisafi P, Alper SL et al (1999) The Arabidopsis thaliana proton transporters, AtNhx1 and Avp1, can function in cation detoxification in yeast. Proc Natl Acad Sci U S A 96:1480–1485Gelis S, Curto M, Valledor L, González A, Ariño J et al (2012) Adaptation to potassium starvation of wild-type and K(+)-transport mutant (trk1,2) of Saccharomyces cerevisiae: 2-dimensional gel electrophoresis-based proteomic approach. Microbiologyopen 1:182–193Gómez MJ, Luyten K, Ramos J (1996) The capacity to transport potassium influences sodium tolerance in Saccharomyces cerevisiae. FEMS Microbiol Lett 135:157–160González A, Casado C, Petrezsélyová S, Ruiz A, Ariño J (2013) Molecular analysis of a conditional hal3 vhs3 yeast mutant links potassium homeostasis with flocculation and invasiveness. Fungal Genet Biol 53:1–9Goossens A, de La Fuente N, Forment J, Serrano R, Portillo F (2000) Regulation of yeast H(+)-ATPase by protein kinases belonging to a family dedicated to activation of plasma membrane transporters. Mol Cell Biol 20:7654–7661Gupta SS, Canessa CM (2000) Heterologous expression of a mammalian epithelial sodium channel in yeast. FEBS Lett 481:77–80Gustin MC, Martinac B, Saimi Y, Culbertson MR, Kung C (1986) Ion channels in yeast. Science 233:1195–1197Haass FA, Jonikas M, Walter P, Weissman JS, Jan YN et al (2007) Identification of yeast proteins necessary for cell-surface function of a potassium channel. Proc Natl Acad Sci U S A 104:18079–18084Haro R, Rodríguez-Navarro A (2002) Molecular analysis of the mechanism of potassium uptake through the TRK1 transporter of Saccharomyces cerevisiae. Biochim Biophys Acta 1564:114–122Haro R, Rodríguez-Navarro A (2003) Functional analysis of the M2(D) helix of the TRK1 potassium transporter of Saccharomyces cerevisiae. Biochim Biophys Acta 1613:1–6Haro R, Garciadeblas B, Rodríguez-Navarro A (1991) A novel P-type ATPase from yeast involved in sodium transport. FEBS Lett 291:189–191Hasenbrink G, Schwarzer S, Kolacna L, Ludwig J, Sychrova H et al (2005) Analysis of the mKir2.1 channel activity in potassium influx defective Saccharomyces cerevisiae strains determined as changes in growth characteristics. FEBS Lett 579:1723–1731Herrera R, Álvarez MC, Gelis S, Ramos J (2013) Subcellular potassium and sodium distribution in Saccharomyces cerevisiae wild-type and vacuolar mutants. Biochem J 454:525–532Herrera R, Alvarez MC, Gelis S, Kodedová M, Sychrová H et al (2014) Role of Saccharomyces cerevisiae Trk1 in stabilization of intracellular potassium content upon changes in external potassium levels. Biochim Biophys Acta 1838:127–133Hess DC, Lu W, Rabinowitz JD, Botstein D (2006) Ammonium toxicity and potassium limitation in yeast. PLoS Biol 4:e351Hoeberichts FA, Perez-Valle J, Montesinos C, Mulet JM, Planes MD et al (2010) The role of K+ and H+ transport systems during glucose- and H2O2-induced cell death in Saccharomyces cerevisiae. Yeast 27:713–725Hohmann S (2002) Osmotic stress signaling and osmoadaptation in yeasts. Microbiol Mol Biol Rev 66:300–372Hohmann S, Krantz M, Nordlander B (2007) Yeast osmoregulation. Methods Enzymol 428:29–45Idnurm A, Walton FJ, Floyd A, Reedy JL, Heitman J (2009) Identification of ENA1 as a virulence gene of the human pathogenic fungus Cryptococcus neoformans through signature-tagged insertional mutagenesis. Eukaryot Cell 8:315–326Jung KW, Strain AK, Nielsen K, Jung KH, Bahn YS (2012) Two cation transporters Ena1 and Nha1 cooperatively modulate ion homeostasis, antifungal drug resistance, and virulence of Cryptococcus neoformans via the HOG pathway. Fungal Genet Biol 49:332–345Kafadar KA, Cyert MS (2004) Integration of stress responses: modulation of calcineurin signaling in Saccharomyces cerevisiae by protein kinase A. Eukaryot Cell 3:1147–1153Kahm M, Navarrete C, Llopis-Torregrosa V, Herrera R, Barreto L et al (2012) Potassium starvation in yeast: mechanisms of homeostasis revealed by mathematical modeling. PLoS Comput Biol 8:e1002548Kallay LM, Brett CL, Tukaye DN, Wemmer MA, Chyou A et al (2011) Endosomal Na+(K+)/H+ exchanger Nhx1/Vps44 functions independently and downstream of multivesicular body formation. J Biol Chem 286:44067–44077Kane PM (2007) The long physiological reach of the yeast vacuolar H+-ATPase. J Bioenerg Biomembr 39:415–421Kane PM (2012) Targeting reversible disassembly as a mechanism of controlling V-ATPase activity. Curr Protein Pept Sci 13:117–123Ke R, Ingram PJ, Haynes K (2013) An integrative model of ion regulation in yeast. PLoS Comput Biol 9:e1002879Ketchum KA, Joiner WJ, Sellers AJ, Kaczmarek LK, Goldstein SA (1995) A new family of outwardly rectifying potassium channel proteins with two pore domains in tandem. Nature 376:690–695Kinclová O, Ramos J, Potier S, Sychrová H (2001) Functional study of the Saccharomyces cerevisiae Nha1p C-terminus. Mol Microbiol 40:656–668Kinclova-Zimmermannova O, Sychrova H (2006) Functional study of the Nha1p C-terminus: involvement in cell response to changes in external osmolarity. Curr Genet 49:229–236Kinclová-Zimmermannová O, Flegelová H, Sychrová H (2004) Rice Na+/H+-antiporter Nhx1 partially complements the alkali-metal-cation sensitivity of yeast strains lacking three sodium transporters. Folia Microbiol (Praha) 49:519–525Kinclova-Zimmermannova O, Gaskova D, Sychrova H (2006) The Na+, K+/H+ -antiporter Nha1 influences the plasma membrane potential of Saccharomyces cerevisiae. FEMS Yeast Res 6:792–800Klee CB, Draetta GF, Hubbard MJ (1988) Calcineurin. Adv Enzymol Relat Areas Mol Biol 61:149–200Klipp E, Nordlander B, Krüger R, Gennemark P, Hohmann S (2005) Integrative model of the response of yeast to osmotic shock. Nat Biotechnol 23:975–982Ko CH, Gaber RF (1991) TRK1 and TRK2 encode structurally related K+ transporters in Saccharomyces cerevisiae. Mol Cell Biol 11:4266–4273Ko CH, Buckley AM, Gaber RF (1990) TRK2 is required for low affinity K+ transport in Saccharomyces cerevisiae. Genetics 125:305–312Ko CH, Liang H, Gaber RF (1993) Roles of multiple glucose transporters in Saccharomyces cerevisiae. Mol Cell Biol 13:638–648Kojima A, To

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

The impact of biologics and tofacitinib on cardiovascular risk factors and outcomes in patients with rheumatic disease: a systematic literature review

Introduction Rheumatic diseases are autoimmune, inflammatory diseases often associated with cardiovascular (CV) disease, a major cause of mortality in these patients. In recent years, treatment with biologic and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs), either as monotherapy or in combination with other drugs, have become the standard of treatment. In this systematic literature review, we evaluated the effect of treatment with biologic or tofacitinib on the CV risk and outcomes in these patients. Methods A systematic search was performed in MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews for articles reporting on CV risk and events in patients with rheumatic disease treated with a biologic agent or tofacitinib. Articles identified were subjected to two levels of screening. Articles that passed the first level based on title and abstract were assessed on full-text evaluation. The quality of randomized clinical trials was assessed by Jadad scoring system and the quality of the other studies and abstracts was assessed using the Downs and Black instrument. The data extracted included study design, baseline patient characteristics, and measurements of CV risk and events. Results Of the 5722 articles identified in the initial search, screening yielded 105 unique publications from 90 unique studies (33 clinical trials, 39 prospective cohort studies, and an additional 18 retrospective studies) that reported CV risk outcomes. A risk of bias analysis for each type of report indicated that they were of good or excellent quality. Importantly, despite some limitations in data reported, there were no indications of significant increase in adverse CV events or risk in response to treatment with the agents evaluated. Conclusions Treatment with biologic or tofacitinib appears to be well-tolerated with respect to CV outcomes in these patients

Diagnosis and management of bone fragility in diabetes: an emerging challenge

Fragility fractures are increasingly recognized as a complication of both type 1 and type 2 diabetes, with fracture risk that increases with disease duration and poor glycemic control. Yet the identification and management of fracture risk in these patients remains challenging. This review explores the clinical characteristics of bone fragility in adults with diabetes and highlights recent studies that have evaluated bone mineral density (BMD), bone microstructure and material properties, biochemical markers, and fracture prediction algorithms (i.e., FRAX) in these patients. It further reviews the impact of diabetes drugs on bone as well as the efficacy of osteoporosis treatments in this population. We finally propose an algorithm for the identification and management of diabetic patients at increased fracture risk

EPMA-World Congress 2015: Bonn, Germany. 3-5 September 2015

Table of contents A1 Predictive and prognostic biomarker panel for targeted application of radioembolisation improving individual outcomes in hepatocellular carcinoma Jella-Andrea Abraham, Olga Golubnitschaja A2 Integrated market access approach amplifying value of “Rx-CDx” Ildar Akhmetov A3 Disaster response: an opportunity to improve global healthcare Russell J. Andrews, Leonidas Quintana A4 USA PPPM: proscriptive, profligate, profiteering medicine-good for 1 % wealthy, not for 99 % unhealthy Russell J. Andrews A5 The role of IDO in a murine model of gingivitis: predictive and therapeutic potentials Babak Baban, Jun Yao Liu, Xu Qin, Tailing Wang, Mahmood S. Mozaffari A6 Specific diets for personalised treatment of diabetes type 2 Viktoriia V. Bati, Tamara V. Meleshko, Olga B. Levchuk, Nadiya V. Boyko A7 Towards personalized physiotherapeutic approach Joanna Bauer, Ewa Boerner, Halina Podbielska A8 Cells, animal, SHIME and in silico models for detection and verification of specific biomarkers of non-communicable chronic diseases Alojz Bomba, Viktor O. Petrov, Volodymyr G. Drobnych, Rostyslav V. Bubnov, Oksana M. Bykova, Nadiya V. Boyko A9 INTERACT-chronic care model: Self-treatment by patients with decision support e-Health solution Hans-Peter Brunner-La Rocca, Lutz Fleischhacker, Olga Golubnitschaja, Frank Heemskerk, Thomas Helms, Tiny Jaarsma, Judita Kinkorova, Jan Ramaekers, Peter Ruff, Ivana Schnur, Emilio Vanoli, Jose Verdu A10 PPPM in cardiovascular medicine in 2015 Hans-Peter Brunner-La Rocca A11 Magnetic resonance imaging of nanoparticles in mice, potential for theranostic and contrast media development – pilot results Rostyslav V. Bubnov, Sergiy A. Grabovetskyi, Olena M. Mykhalchenko, Natalia O. Tymoshok, Oleksandr B. Shcherbakov, Igor P. Semeniv, Mykola Y. Spivak A12 Ultrasound diagnosis for diabetic neuropathy - comparative study Rostyslav V. Bubnov, Tetyana V. Ostapenko A13 Ultrasound for stratification patients with diabetic foot ulcers for prevention and personalized treatment - pilot results Rostyslav V. Bubnov, Nazarii M. Kobyliak, Nadiya M. Zholobak, Mykola Ya. Spivak A14 Project ImaGenX – designing and executing a questionnaire on environment and lifestyle risk of breast cancer John Paul Cauchi A15 Genomics – a new structural brand of predictive, preventive and personalized medicine or the new driver as well? Dmitrii Cherepakhin, Marina Bakay, Artem Borovikov, Sergey Suchkov A16 Survey of questionnaires for evaluation of the quality of life in various medical fields Barbara Cieślik, Agnieszka Migasiewicz, Maria-Luiza Podbielska, Markus Pelleter, Agnieszka Giemza, Halina Podbielska A17 Personalized molecular treatment for muscular dystrophies Sebahattin Cirak A18 Secondary mutations in circulating tumour DNA for acquired drug resistance in patients with advanced ALK + NSCLC Marzia Del Re, Paola Bordi, Valentina Citi, Marta Palombi, Carmine Pinto, Marcello Tiseo, Romano Danesi A19 Recombinant species-specific FcεRI alpha proteins for diagnosis of IgE-mediated allergies in dogs, cats and horses Lukas Einhorn, Judit Fazekas, Martina Muhr, Alexandra Schoos, Lucia Panakova, Ina Herrmann, Krisztina Manzano-Szalai, Kumiko Oida, Edda Fiebiger, Josef Singer, Erika Jensen-Jarolim A20 Global methodology for developmental neurotoxicity testing in humans and animals early and chronically exposed to chemical contaminants Arpiné A. Elnar, Nadia Ouamara, Nadiya Boyko, Xavier Coumoul, Jean-Philippe Antignac, Bruno Le Bizec, Gauthier Eppe, Jenny Renaut, Torsten Bonn, Cédric Guignard, Margherita Ferrante, Maria Liusa Chiusano, Salvatore Cuzzocrea, Gerard O'Keeffe, John Cryan, Michelle Bisson, Amina Barakat, Ihsane Hmamouchi, Nasser Zawia, Anumantha Kanthasamy, Glen E. Kisby, Rui Alves, Oscar Villacañas Pérez, Kim Burgard, Peter Spencer, Norbert Bomba, Martin Haranta, Nina Zaitseva, Irina May, Stéphanie Grojean, Mathilde Body-Malapel, Florencia Harari, Raul Harari, Kristina Yeghiazaryan, Olga Golubnitschaja, Vittorio Calabrese, Christophe Nemos, Rachid Soulimani A21 Mental indicators at young people with attributes hypertension and pre-hypertension Maria E. Evsevyeva, Elena A. Mishenko, Zurida V. Kumukova, Evgeniy V. Chudnovsky, Tatyana A. Smirnova A22 On the approaches to the early diagnosis of stress-induced hypertension in young employees of State law enforcement agencies Maria E. Evsevyeva, Ludmila V. Ivanova, Michail V. Eremin, Maria V. Rostovtseva A23 Сentral aortic pressure and indexes of augmentation in young persons in view of risk factors Maria E. Evsevyeva, Michail V. Eremin, Vladimir I. Koshel, Oksana V. Sergeeva, Nadesgda M. Konovalova A24 Breast cancer prediction and prevention: Are reliable biomarkers in horizon? Shantanu Girotra, Olga Golubnitschaja A25 Flammer Syndrome and potential formation of pre-metastatic niches: A multi-centred study on phenotyping, patient stratification, prediction and potential prevention of aggressive breast cancer and metastatic disease Olga Golubnitschaja, Manuel Debald, Walther Kuhn, Kristina Yeghiazaryan, Rostyslav V. Bubnov, Vadym M. Goncharenko, Ulyana Lushchyk, Godfrey Grech, Katarzyna Konieczka A26 Innovative tools for prenatal diagnostics and monitoring: improving individual pregnancy outcomes and health-economy in EU Olga Golubnitschaja, Jan Jaap Erwich, Vincenzo Costigliola, Kristina Yeghiazaryan, Ulrich Gembruch A27 Immunohistochemical assessment of APUD cells in endometriosis Vadym M. Goncharenko, Vasyl O. Beniuk, Olga V. Kalenska, Rostyslav V. Bubnov A28 Updating personalized management algorithm of endometrial hyperplasia in pre-menopause women Vadym M. Goncharenko, Vasyl O. Beniuk, Rostyslav V. Bubnov, Olga Melnychuk A29 The personified treatment approach of polimorbid patients with periodontal inflammatory diseases Irina A. Gorbacheva, Lyudmila Y. Orekhova, Vadim V. Tachalov A30 Ukrainian experience in hybrid war – the challenge to update algorithms for personalized care and early prevention of different military injuries Olena I. Grechanyk, Rizvan Ya. Abdullaiev, Rostyslav V. Bubnov A31 Tear fluid biomarkers: a comparison of tear fluid sampling and storage protocols Suzanne Hagan, Eilidh Martin, Ian Pearce, Katherine Oliver A32 The correlation of dietary habits with gingival problems during menstruation Cenk Haytac, Fariz Salimov, Servin Yoksul, Anatoly A. Kunin, Natalia S. Moiseeva A33 Genomic medicine in a contemporary Spanish population of prostate cancer: our experience Bernardo Herrera-Imbroda, Sergio del Río-González, Maria Fernanda Lara, Antonia Angulo, Francisco Javier Machuca Santa-Cruz A34 Challenges, opportunities and collaborations for personalized medicine applicability in uro-oncological disease Bernardo Herrera-Imbroda, Sergio del Río-González, Maria Fernanda Lara A35 Metabolic hallmarks of cancer as targets for a personalized therapy John Ionescu A36 Influence of genetic polymorphism as a predictor of the development of periodontal disease in patients with gastric ulcer and 12 duodenal ulcer Alfiya Z. Isamulaeva, Anatoly A. Kunin, Shamil Sh. Magomedov, Aida I. Isamulaeva A37 Challenges in diabetic macular edema Tatjana Josifova A38 Overview of the EPMA strategies in laboratory medicine relevant for PPPM Marko Kapalla, Juraj Kubáň, Olga Golubnitschaja, Vincenzo Costigliola A39 EPMA initiative for effective organization of medical travel: European concepts and criteria Vincenzo Costigliola, Marko Kapalla, Juraj Kubáň, Olga Golubnitschaja A40 Design and innovation in e-textiles: implications for PPPM Anthony Kent, Tom Fisher, Tilak Dias A41 Biobank in Pilsen as a member of national node BBMRI_CZ Judita Kinkorová, Ondřej Topolčan A42 Big data in personalized medicine: hype and hope Matthias Kohl A43 The 3P approach as the platform of the European Dentistry Department (DPPPD) Anatoly A. Kunin, Natalia S. Moiseeva A44 The endometrium cytokine patterns for predictive diagnosis of proliferation severity and cancer prevention Andrii I. Kurchenko, Vasyl A. Beniuk, Vadym M. Goncharenko, Rostyslav V. Bubnov, Nadiya V. Boyko, Andriy M. Strokan A45 A monocyte-based in-vitro system for testing individual responses to the implanted material: future for personalized implant construction Julia Kzhyshkowska, Alexandru Gudima, Ksenia S. Stankevich, Victor D. Filimonov4, Harald Klüter, Evgeniya M. Mamontova, Sergei I. Tverdokhlebov A46 Prediction and prevention of adverse health effects by meteorological factors: Biomarker patterns and creation of a device for self-monitoring and integrated care Ulyana B. Lushchyk, Viktor V. Novytskyy, Igor P. Babii, Nadiya G. Lushchyk, Lyudmyla S. Riabets, Ivanna I. Legka A47 Targeting "disease signatures" towards personalized healthcare Mira Marcus-Kalish, Alexis Mitelpunkt, Tal Galili, Neta Shachar, Yoav Benjamini A48 Influence of the skin imperfection on the personal quality of life and possible tools for objective diagnosis Agnieszka Migasiewicz, Markus Pelleter, Joanna Bauer, Ewelina Dereń, Halina Podbielska A49 The new direction in caries prevention based on the ultrastructure of dental hard tissues and filling materials Natalia S. Moiseeva, Anatoly A. Kunin, Dmitry A. Kunin A50 The use of LED radiation in prevention of dental diseases Natalia S. Moiseeva, Yury A. Ippolitov, Dmitry A. Kunin, Alexei N. Morozov, Natalia V. Chirkova, Nakhid T. Aliev A51 Status of endothelial progenitor cells in diabetic nephropathy: predictive and preventive potentials Mahmood S. Mozaffari, Jun Yao Liu, Babak Baban A52 The status of glucocorticoid-induced leucine zipper protein in salivary gland in Sjögren’s syndrome: predictive and personalized treatment potentials Mahmood S. Mozaffari, Jun Yao Liu, Rafik Abdelsayed, Xing-Ming Shi, Babak Baban A53 Maximal aerobic capacity - important quality marker of health Jaroslav Novák, Milan Štork, Václav Zeman A54 The EMPOWER project: laboratory medicine and Horizon 2020 Wytze P. Oosterhuis, Elvar Theodorsson A55 Personality profile manifestations in patient’s attitude to oral care and adherence to doctor’s prescriptions Lyudmila Y. Orekhova, Tatyana V. Kudryavtseva, Elena R. Isaeva, Vadim V. Tachalov, Ekaterina S. Loboda A56 Results of an European survey on personalized medicine addressed to directions of laboratory medicine Mario Pazzagli, Francesca Malentacchi, Irene Mancini, Ivan Brandslund, Pieter Vermeersch, Matthias Schwab, Janja Marc, Ron H.N. van Schaik, Gerard Siest, Elvar Theodorsson, Chiara Di Resta A57 MCI or early dementia predictive speech based diagnosis techniques Matus Pleva, Jozef Juhar A58 Personalized speech based mobile application for eHealth Matus Pleva, Jozef Juhar A59 Circulating tumor cell-free DNA as the biomarker in the management of cancer patients Jiří Polívka jr., Filip Janků, Martin Pešta, Jan Doležal, Milena Králíčková, Jiří Polívka A60 Complex stroke care – educational programme in Stroke Centre University Hospital Plzen Jiří Polívka, Alena Lukešová, Nina Müllerová, Petr Ševčík, Vladimír Rohan A61 Sleep apnea and sleep fragmentation contribute to brain aging Kneginja Richter, Lence Miloseva, Günter Niklewski A62 Personalised approach for sleep disturbances in shift workers Kneginja Richter, Jens Acker, Guenter Niklewski A63 Medical travel and innovative PPPM clusters: new concept of integration Olga Safonicheva, Vincenzo Costigliola A64 Medical travel and women health Olga Safonicheva A65 Continuity of generations in the training of specialists in the field of reconstructive microsurgery Maxim Sautin, Janna Sinelnikova, Sergey Suchkov A66 Telemonitoring of stroke patients – empirical evidence of individual risk management results from an observational study in Germany Songül Secer, Stephan von Bandemer A67 Women’s increasing breast cancer risk with n-6 fatty acid intake explained by estrogen-fatty acid interactive effect on DNA damage: implications for gender-specific nutrition within personalized medicine Niva Shapira A68 Cytobacterioscopy of the gingival crevicular fluid as a method for preventive diagnosis of periodontal diseases Aleksandr Shcherbakov, Anatoly A. Kunin, Natalia S. Moiseeva A69 Use of specially treated composites in dentistry to avoid violations of aesthetics Bogdan R. Shumilovich, Zhanna Lipkind, Yulia Vorobieva, Dmitry A. Kunin, Anastasiia V. Sudareva A70 National eHealth system – platform for preventive, predictive and personalized diabetes care Ivica Smokovski, Tatjana Milenkovic A72 The common energy levels of Prof. Szent-Györgyi, the intrinsic chemistry of melanin, and the muscle physiopathology. Implications in the context of Preventive, Predictive, and Personalized Medicine Arturo Solís-Herrera, María del Carmen Arias-Esparza, Sergey Suchkov A73 Plurality and individuality of hepatocellular carcinoma: PPPM perspectives Krishna Chander Sridhar, Olga Golubnitschaja A74 Strategic aspects of higher medical education reforms to secure newer educational platforms for getting biopharma professionals matures Maria Studneva, Sihong Song, James Creeden, Мark Мandrik, Sergey Suchkov A75 Overview of the strategies and activities of the European Federation of Clinical Chemistry and Laboratory Medicine, (EFLM) Elvar Theodorsson, EFLM A76 New spectroscopic techniques for point of care label free diagnostics Syed A. M. Tofail A77 Tumor markers for personalized medicine and oncology - the role of Laboratory Medicine Ondřej Topolčan, Judita Kinkorová, Ondřej Fiala, Marie Karlíková, Šárka Svobodová, Radek Kučera, Radka Fuchsová, Vladislav Třeška, Václav Šimánek, Ladislav Pecen, Jan Šoupal, Štěpán Svačina2 A78 Modern medical terminology (MMT) as a driver of the global educational reforms Evgeniya Tretyak, Maria Studneva, Sergey Suchkov A79 Juvenile hypertension; the relevance of novel predictive, preventive and personalized assessment of its determinants Francesca M. Trovato, G. Fabio Martines, Daniela Brischetto, Daniela Catalano, Giuseppe Musumeci, Guglielmo M. Trovato A80 Proteomarkers Biotech George Th. Tsangaris, Athanasios K. Anagnostopoulos A81 Proteomics and mass spectrometry based non-invasive prenatal testing of fetal health and pregnancy complications George Th. Tsangaris, Athanasios K. Anagnostopoulos A82 Integrated Ecosystem for an Integrated Care model for Heart Failure (HF) patients including related comorbidities (ZENITH) José Verdú, German Gutiérrez, Jordi Rovira, Marta Martinez, Lutz Fleischhacker, Donna Green, Arthur Garson, Elena Tamburini, Stefano Cuomo, Juan Martinez-Leon, Teresa Abrisqueta, Hans-Peter Brunner-La Rocca, Tiny Jaarsma, Teresa Arredondo, Cecilia Vera, Giuseppe Fico, Olga Golubnitschaja, Fernando Arribas, Martina Onderco, Isabel Vara, on behalf of ZENITH consortium A83 Predictive, preventive and personalized medicine in diabetes onset and complication (MOSAIC project) José Verdú, Francesco Sambo, Barbara Di Camillo, Claudio Cobelli, Andrea Facchinetti, Giuseppe Fico, Riccardo Bellazzi, Lucia Sacchi, Arianna Dagliati, Daniele Segnani, Valentina Tibollo, Manuel Ottaviano, Rafael Gabriel, Leif Groop, Jacqueline Postma, Antonio Martinez, Liisa Hakaste, Tiinamaija Tuomi, Konstantia Zarkogianni, on behalf of MOSAIC consortium A84 Possibilities for personalized therapy of diabetes using in vitro screening of insulin and oral hypoglycemic agents Igor Volchek, Nina Pototskaya, Andrey Petrov A85 The innovative technology for personalized therapy of human diseases based on in vitro drug screening Igor Volchek, Nadezhda Pototskaya, Andrey Petrov A86 Bone destruction and temporomandibular joint: predictive markers, pathogenetic aspects and quality of life Ülle Voog-Oras, Oksana Jagur, Edvitar Leibur, Priit Niibo, Triin Jagomägi, Minh Son Nguyen, Chris Pruunsild, Dagmar Piikov, Mare Saag A87 Sub-optimal health management – global vision for concepts in medical travel Wei Wang A88 Sub-optimal health management: synergic PPPM-TCAM approach Wei Wang A89 Innovative technologies for minimal invasive diagnostics Andreas Weinhäusel, Walter Pulverer, Matthias Wielscher, Manuela Hofner, Christa Noehammer, Regina Soldo, Peter Hettegger, Istvan Gyurjan, Ronald Kulovics, Silvia Schönthaler, Gabriel Beikircher, Albert Kriegner, Stephan Pabinger, Klemens Vierlinger A90 Rare disease diobanks for personalized medicine Ayşe Yüzbaşıoğlu, Meral Özgüç, Member of EuroBioBank - European Network of DNA, Cell and Tissue Banks for Rare Disease