Core set of unfavorable events of shoulder arthroplasty: an international Delphi consensus process

BackgroundShoulder arthroplasty (SA) complications require standardization of definitions and are not limited to events leading to revision operations. We aimed to define an international consensus core set of clinically relevant unfavorable events of SA to be documented in clinical routine practice and studies.MethodsA Delphi exercise was implemented with an international panel of experienced shoulder surgeons selected by nomination through professional societies. On the basis of a systematic review of terms and definitions and previous experience in establishing an arthroscopic rotator cuff repair core set, an organized list of SA events was developed and reviewed by panel members. After each survey, all comments and suggestions were considered to revise the proposed core set including local event groups, along with definitions, specifications, and timing of occurrence. Consensus was reached with at least two-thirds agreement.ResultsTwo online surveys were required to reach consensus within a panel involving 96 surgeons. Between 88% and 100% agreement was achieved separately for local event groups including 3 intraoperative (device, osteochondral, and soft tissue) and 9 postoperative event groups. Experts agreed on a documentation period that ranged from 3 to 24 months after SA for 4 event groups (peripheral neurologic, vascular, surgical-site infection, and superficial soft tissue) and that was lifelong until implant revision for other groups (device, osteochondral, shoulder instability, pain, late hematogenous infection, and deep soft tissue).ConclusionA structured core set of local unfavorable events of SA was developed by international consensus to support the standardization of SA safety reporting. Clinical application and scientific evaluation are needed.</div

A Simple & Convenient Solid Phase Synthesis of Bacterial Origin Octapeptide Sequence, Glu-Asp-Gly-Asn-Lys-Pro-Gly-Lys-OH

The repeating octapeptide sequence, Glu-Asp-Gly-Asn-Lys-Pro-Gly-Lys-OH derived from the glycoprotein found in Staphylococcus aureus cell wall is assembled by simple solid phase peptide synthesis methodology using a base labile linker

New Noncovalent Inhibitors of Penicillin-Binding Proteins from Penicillin-Resistant Bacteria

BACKGROUND: Penicillin-binding proteins (PBPs) are well known and validated targets for antibacterial therapy. The most important clinically used inhibitors of PBPs beta-lactams inhibit transpeptidase activity of PBPs by forming a covalent penicilloyl-enzyme complex that blocks the normal transpeptidation reaction; this finally results in bacterial death. In some resistant bacteria the resistance is acquired by active-site distortion of PBPs, which lowers their acylation efficiency for beta-lactams. To address this problem we focused our attention to discovery of novel noncovalent inhibitors of PBPs. METHODOLOGY/PRINCIPAL FINDINGS: Our in-house bank of compounds was screened for inhibition of three PBPs from resistant bacteria: PBP2a from Methicillin-resistant Staphylococcus aureus (MRSA), PBP2x from Streptococcus pneumoniae strain 5204, and PBP5fm from Enterococcus faecium strain D63r. Initial hit inhibitor obtained by screening was then used as a starting point for computational similarity searching for structurally related compounds and several new noncovalent inhibitors were discovered. Two compounds had promising inhibitory activities of both PBP2a and PBP2x 5204, and good in-vitro antibacterial activities against a panel of Gram-positive bacterial strains. CONCLUSIONS: We found new noncovalent inhibitors of PBPs which represent important starting points for development of more potent inhibitors of PBPs that can target penicillin-resistant bacteria.Eur-Intafa

Researching Memory in Early Modern Studies

This essay pursues the study of early modern memory across a chronologically, conceptually and thematically broad canvas in order to address key questions about the historicity of memory and the methodologies of memory studies. First, what is the value for our understanding of early modern memory practices of transporting the methodologies of contemporary memory studies backwards, using them to study the memorial culture of a time before living memory? Second, what happens to the cross-disciplinary project of memory studies when it is taken to a distant period, one that had its own highly self-conscious and much debated cultures of remembering? Drawing on evidence and debates from a range of disciplinary locations, but primarily focusing on literary and historical studies, the essay interrogates crucial differences and commonalities between memory studies and early modern studies

The syntax of ‘-cā’ (*-kwe) in Ahunavaiti Gāthā

This paper seeks to provide a full description of the syntactic behaviour of the enclitic co-ordinate conjunction -cā in the earliest stage of the Avestan language. By studying the occurrences of the particle in Ahunavaiti Gāthā, a distributive analysis is provided together with an interpretative hypothesis of its distributive dynamics. Two syntactic levels, phrase and sentence, are taken into consideration. Finally, a syntactic domain-based variation is argued and two clitic functional variants are identified as synchronically operating conjunction strategies

Happy heart syndrome. role of positive emotional stress in takotsubo syndrome

AIMS: Takotsubo syndrome (TTS) is typically provoked by negative stressors such as grief, anger, or fear leading to the popular term 'broken heart syndrome'. However, the role of positive emotions triggering TTS remains unclear. The aim of the present study was to analyse the prevalence and characteristics of patients with TTS following pleasant events, which are distinct from the stressful or undesirable episodes commonly triggering TTS. METHODS AND RESULTS: Takotsubo syndrome patients with preceding pleasant events were compared to those with negative emotional triggers from the International Takotsubo Registry. Of 1750 TTS patients, we identified a total of 485 with a definite emotional trigger. Of these, 4.1% (n = 20) presented with pleasant preceding events and 95.9% (n = 465) with unequivocal negative emotional events associated with TTS. Interestingly, clinical presentation of patients with 'happy heart syndrome' was similar to those with the 'broken heart syndrome' including symptoms such as chest pain [89.5% (17/19) vs. 90.2% (412/457), P = 1.0]. Similarly, electrocardiographic parameters, laboratory findings, and 1-year outcome did not differ. However, in a post hoc analysis, a disproportionate higher prevalence of midventricular involvement was noted in 'happy hearts' compared with 'broken hearts' (35.0 vs. 16.3%, P = 0.030). CONCLUSION: Our data illustrate that TTS can be triggered by not only negative but also positive life events. While patient characteristics were similar between groups, the midventricular TTS type was more prevalent among the 'happy hearts' than among the 'broken hearts'. Presumably, despite their distinct nature, happy and sad life events may share similar final common emotional pathways, which can ultimately trigger TTS

The spin label amino acid TOAC and its uses in studies of peptides: chemical, physicochemical, spectroscopic, and conformational aspects

We review work on the paramagnetic amino acid 2,2,6,6-tetramethyl-N-oxyl-4-amino-4-carboxylic acid, TOAC, and its applications in studies of peptides and peptide synthesis. TOAC was the first spin label probe incorporated in peptides by means of a peptide bond. In view of the rigid character of this cyclic molecule and its attachment to the peptide backbone via a peptide bond, TOAC incorporation has been very useful to analyze backbone dynamics and peptide secondary structure. Many of these studies were performed making use of EPR spectroscopy, but other physical techniques, such as X-ray crystallography, CD, fluorescence, NMR, and FT-IR, have been employed. The use of double-labeled synthetic peptides has allowed the investigation of their secondary structure. A large number of studies have focused on the interaction of peptides, both synthetic and biologically active, with membranes. In the latter case, work has been reported on ligands and fragments of GPCR, host defense peptides, phospholamban, and β-amyloid. EPR studies of macroscopically aligned samples have provided information on the orientation of peptides in membranes. More recent studies have focused on peptide–protein and peptide–nucleic acid interactions. Moreover, TOAC has been shown to be a valuable probe for paramagnetic relaxation enhancement NMR studies of the interaction of labeled peptides with proteins. The growth of the number of TOAC-related publications suggests that this unnatural amino acid will find increasing applications in the future