Aims The EURO-ENDO registry aimed to study the management and outcomes of patients with infective endocarditis (IE). Methods and results Prospective cohort of 3116 adult patients (2470 from Europe, 646 from non-ESC countries), admitted to 156 hospitals in 40 countries between January 2016 and March 2018 with a diagnosis of IE based on ESC 2015 diagnostic criteria. Clinical, biological, microbiological, and imaging [echocardiography, computed tomography (CT) scan, 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT)] data were collected. Infective endocarditis was native (NVE) in 1764 (56.6%) patients, prosthetic (PVIE) in 939 (30.1%), and device-related (CDRIE) in 308 (9.9%). Infective endocarditis was community-acquired in 2046 (65.66%) patients. Microorganisms involved were staphylococci in 1085 (44.1%) patients, oral streptococci in 304 (12.3%), enterococci in 390 (15.8%), and Streptococcus gallolyticus in 162 (6.6%). 18F-fluorodeoxyglucose positron emission tomography/computed tomography was performed in 518 (16.6%) patients and presented with cardiac uptake (major criterion) in 222 (42.9%) patients, with a better sensitivity in PVIE (66.8%) than in NVE (28.0%) and CDRIE (16.3%). Embolic events occurred in 20.6% of patients, and were significantly associated with tricuspid or pulmonary IE, presence of a vegetation and Staphylococcus aureus IE. According to ESC guidelines, cardiac surgery was indicated in 2160 (69.3%) patients, but finally performed in only 1596 (73.9%) of them. In-hospital death occurred in 532 (17.1%) patients and was more frequent in PVIE. Independent predictors of mortality were Charlson index, creatinine > 2 mg/dL, congestive heart failure, vegetation length > 10 mm, cerebral complications, abscess, and failure to undertake surgery when indicated. Conclusion Infective endocarditis is still a life-threatening disease with frequent lethal outcome despite profound changes in its clinical, microbiological, imaging, and therapeutic profiles.

No abstract

This study describes the mechanism of homodimer formation of the 90-kDa heat-shock protein (HSP90). In eukaryotic cells, there are two HSP90 isoforms, a and p, encoded by two separate genes.HSP90a exists predominantly as a homodimer, HSP90p mainly as a monomer. Analysis by native PAGE revealed that bacterially expressed HSP90a fused to glutathione S-transferase (GST) existed as a highmolecular-mass oligomer, and was converted to a homodimer following removal of the fusion enzyme by thrombin cleavage. A deletion mutant, HSP90aD44-603, formed a monomer and an N-terminal truncated mutant, HSP90aS33 -732, existed as a dimer, indicating that the dimer-forming ability resides somewhere in the C-terminal 200 amino acids. Limited proteolysis of the C-terminal 200 amino acids of HSP90a with chymotrypsin produced the C-terminal 16-kDa fragment (Met62WAla629-Asp732) and its adjacent more N-terminal 13-kDa fragment (Va1542-Tyr627/Met628). Size-exclusion HPLC and twodimensional PAGE analyses demonstrated that these two chymotryptic fragments bound each other. The C-terminal 198 amino acids as well as the full-length form of HSP90p revealed a lower dimer-forming activity than HSP90u. Expression of the chimeric proteins at the C-terminal 198 amino acids of the a and p isoforrns further indicated that the 16 amino acid substitutions locating between amino acids 561 and 685 account for the impeded dimerization of HSP90p. A leucine zipper motif (Met402-Leu423) was unlikely to be involved in the dimer formation. Taken together, these results indicate that the dimeric structure. of HSP90a is mediated by the C-terminal 191 amino acids and consists of duplicate interactions of the C-terminal region (Met62WAla629-Asp732) of one subunit and the adjacent more N-terminal region (Va1542-Try627/Met628) of the other subunit.Keywords: heat-shock protein 90; isoform; dimerization; leucine-zipper motif; amino acid substitution The 90-kDa heat shock protein (HSP90) is a highly conserved protein that is abundant in cytoplasm of most prokaryotic and eukaryotic cells even under unstressed conditions. In eukaryotic cells, there are two HSP90 genes and, hence, two HSP90 Ahhreviarions. GST, glutathione S-transferase ; HSP90n and HSP90p, the Q and isoforms of the 90-kDa heat-shock protein; GST-HSP90, GST fusion protein of HSP90; HSP90aD48-458 and HSP90aD44-603, mutants of HSP90 with residues 48-458 or 44-603 deleted; HSP90uS33-732, residues 533-732 of HSP90a; LZ, leucine zipper motif; HSP~OQDLZ, mutant of HSP90a with LZ deleted: TosLysCH,CI, N-tosyl-L-lysine chloromethane; TosPheCH2C1, N"-tosyl-1.-phenylalanine chloromethane.Enzymes. Trypsin (EC 3.4.21.4); thrombin (EC 3.4.21.5); chymotrypsin (EC 3.4.21 .1); factor Xa (EC 3.4.21.6); glutathione S-transferase (EC 2.5.1.18).teins [lo, 111. Several lines of evidence indicate a chaperon-like activity of HSP9O that modulates the activity of its associated proteins [9,. For instance, the high-affinity binding for steroid to the glucocorticoid receptor is maintained by the association of HSP90 with the recep...

No abstract

Reference [15] should read as follows:[15] S. M. Bilenky and B.