Pharmacokinetic-pharmacodynamic cutoff values for benzylpenicillin in horses to support the establishment of clinical breakpoints for benzylpenicillin antimicrobial susceptibility testing in horses

Introduction: The aim of this international project was to establish a species-specific Clinical Breakpoint for interpretation of Antimicrobial Susceptibility Testing of benzylpenicillin (BP) in horses.Methods: A population pharmacokinetic model of BP disposition was developed to compute PK/PD cutoff values of BP for different formulations that are commonly used in equine medicine around the world (France, Sweden, USA and Japan). Investigated substances were potassium BP, sodium BP, procaine BP, a combination of procaine BP and benzathine BP and penethamate, a prodrug of BP. Data were collected from 40 horses that provided 63 rich profiles of BP corresponding to a total of 1022 individual BP plasma concentrations.Results: A 3-compartment disposition model was selected. For each of these formulations, the PK/PD cutoff was estimated for different dosage regimens using Monte Carlo simulations. The fAUC/MIC or fT>MIC were calculated with a free BP fraction set at 0.4. For fAUC/MIC, a target value of 72 h (for a 72h treatment) was considered. For fT>MIC, efficacy was assumed when free plasma concentrations were above the explored MIC (0.0625-2 mg/L) for 30 or 40 % of the dosing interval. For continuous infusion, a fT>MIC of 90 % was considered. It was shown that a PK/PD cutoff of 0.25 mg/L can be achieved in 90 % of horses with routine regimen (typically 22,000 IU/kg or 12.4 mg/kg per day) with IM procaine BP once a day (France, Japan, Sweden but not USA1) and with IM sodium BP at 14.07 mg/kg, twice a day or IV sodium BP infusion of 12.4 mg/kg per day. In contrast, penethamate and the combination of procaine BP and benzathine BP were unable to achieve this PK/PD cutoff not even an MIC of 0.125 mg/L.Discussion: The PK/PD cutoff of 0.25 mg/L is one dilution lower than the clinical breakpoint released by the CLSI (0.5 mg/ L). From our simulations, the CLSI clinical breakpoint can be achieved with IM procaine BP twice a day at 22,000 IU i.e. 12.4 mg/kg

PERANCANGAN BASIS DATA PERSEDIAAN BARANG STUDI KASUS PADA RIZKY STATIONERY

ABSTRAKSI Laporan Tugas Akhir dengan judul Perancangan Basis Data persediaan barang Studi Kasus pada Rizky Stationery telah dilaksanakan pada tanggal 15 Agustus 2011-20 Januari 2012. Adapun tujuan yang ingin dicapai dalam pembuatan tugas akhir ini adalah menyusun rancangan basis data untuk pengolahan data persediaan barang pada Rizky Stationery yang mampu mengontrol stok barang secara tepat dan menyusun laporan yang tepat waktu tanpa terjadi kesalahan. Dalam laporan ini digambarkan sistem baru yang akan diusulkan melalui desain model data flow diagram. Disamping itu perancangan sistem baru juga dilakukan dengan penyusunan sistem secara umum yang teriri dari data flow diagram, Desain Input Output, Normalisasi, ERD, file database. Metodologi penelitian yang dilakukan adalah meliputi studi lapangan dan studi kepustakaan. Studi lapangan meliputi pengamatan, wawancara. Sedang studi kepustakaan dilakukan dengan penelitian kepustakaan yang relevan dengan masalah tersebut. Setelah rancangan global selesai dibuat maka dapat diketahui bahwa dengan adanya perancangan basis data persediaan pembuatan laporan akan mudah dilakukan, karena semua tabel sudah berelasi, hal ini mempermudah penyediaan laporan yang melibatkan beberapa tabel sekaligus. Kata Kunci : Perancangan, Basis Data, Persediaa

EndoS from Streptococcus pyogenes is hydrolyzed by the cysteine proteinase SpeB and requires glutamic acid 235 and tryptophans for IgG glycan-hydrolyzing activity

ABSTRACT: BACKGROUND: The endoglycosidase EndoS and the cysteine proteinase SpeB from the human pathogen Streptococcus pyogenes are functionally related in that they both hydrolyze IgG leading to impairment of opsonizing antibodies and thus enhance bacterial survival in human blood. In this study, we further investigated the relationship between EndoS and SpeB by examining their in vitro temporal production and stability and activity of EndoS. Furthermore, theoretical structure modeling of EndoS combined with site-directed mutagenesis and chemical blocking of amino acids was used to identify amino acids required for the IgG glycan-hydrolyzing activity of EndoS. RESULTS: We could show that during growth in vitro S. pyogenes secretes the IgG glycan-hydrolyzing endoglycosidase EndoS prior to the cysteine proteinase SpeB. Upon maturation SpeB hydrolyzes EndoS that then loses its IgG glycan-hydrolyzing activity. Sequence analysis and structural homology modeling of EndoS provided a basis for further analysis of the prerequisites for IgG glycan-hydrolysis. Site-directed mutagenesis and chemical modification of amino acids revealed that glutamic acid 235 is an essential catalytic residue, and that tryptophan residues, but not the abundant lysine or the single cysteine residues, are important for EndoS activity. CONCLUSIONS: We present novel information about the amino acid requirements for IgG glycan-hydrolyzing activity of the immunomodulating enzyme EndoS. Furthermore, we show that the cysteine proteinase SpeB processes/degrades EndoS and thus emphasize the importance of the SpeB as a degrading/processing enzyme of proteins from the bacterium itself

"Hvis vi bare ku" få fred til at passe vores arbejdeÉ" — om mening, forandring og psykisk arbejdsmiljø

This article is about meaning and sensemaking in work – as a precondition for employees’ participation and commitment in changing and improving their work. Results from a Danish research project (the BEST project) are presented. Fourteen companies and institutions tried to improve their psychosocial work environment, but many of them failed; even seeing this worsen. Nevertheless, employees everywhere expressed a surprising (desire for) involvement in work – although often frustrated and conflictual. This may indicate a great under-utilised potential for improving work and working conditions. After presenting a specific concept of the work task, a theoretical model is outlined – proposing the work task as pivotal for employees’ creation (or loss) of meaning and sense in their work. This is of special importance when it comes to processes of change: employees’ participation and commitment to change depends on the meaning of the goal. This is crucial when trying to improve the psychosocial work environment. Finally, some consequenses for practise are suggested, as is a wider perspective of democratizing work as a condition for a sustainable psychosocial work environment.Hvordan bliver det meningsfuldt for medarbejdere og ledere at prioritere indsatsen for et bedre psykisk arbejdsmiljø? Det var et underspørgsmål i den nyligt afsluttede VIPS-undersøgelse af 14 danske virksomheder1. Samlet set var resultaterne af virksomhedernes bestræbelser på at forbedre det psykiske arbejdsmiljø skuffende. Men samtidig var der et overraskende højt og udbredt engagement i arbejdsopgaven hos medarbejderne-på tværs af arbejdssektorer. Engagementet var ofte frustreret og forbundet med konfl ikt, men ikke til at overse. Det kan ses som et markant subjektivt potentiale for forbedring af arbejdet. Med udgangspunkt i denne empiri argumenterer denne artikel2 for en forståelsesmodel hvor arbejdsopgaven er den centrale kategori og omdrejningspunkt for skabelse af mening i arbejdet-og mening i udvikling af arbejdet. I praksis indebærer det bla. at arbejdet med at forbedre det psykiske arbejdsmiljø i højere grad end hidtil må fokusere på arbejdets indhold-og give arbejdernes erfaring og indflydelse mere rum

Osteopathic intervention for chronic pain, remaining thoracic stiffness and breathing impairment after thoracoabdominal oesophagus resection: A single subject design study

AbstractBackgroundThoracic surgery can cause negative effects such as chronic pain, impaired thorax movement and/or impaired breathing. There are indications that manual therapies, such as osteopathy, may be beneficial for these conditions.ObjectiveTo investigate effects of osteopathic intervention on chronic pain and remaining limitations to thoracic range of motion and breathing in patients who had undergone thoracoabdominal resection of the oesophagus.DesignIn a single-subject research design (Aa-B-Ab), 8 participants with chronic postoperative thoracic pain, stiffness and/or breathing impairment after standardized oesophagus resection were given 10 sessions of osteopathic treatment of 45 min. Expiratory vital capacity, thorax mobility, pain experience, and subjective perception of treatment were measured on three occasions during each phase. The two-standard deviation band method was used to indicate significant change.ResultsA significantly increased range of motion in the thorax was observed in thoracic excursion and in lateral flexion. A positive change in pain was also noted. The results in expiratory vital capacity were contradictory. The participants were generally positive toward the treatment given.ConclusionOsteopathic intervention may affect thoracic impairment and pain among people with chronic pain and impaired thoracic range of motion after thoracoabdominal resection of the oesophagus

Inclusion of isolated α-amino acids along the polylactide chain through organocatalytic ring-opening copolymerization

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Meet your inside: endoscopic visualizations in contemporary culture

Jan Eric Olsén Meet your inside – endoscopic visualizations in contemporary culture. Visualizations of the body have increasingly become the primary interface between physicians and patients. CT, MRI, PET, ultrasound, scintigraphy, laparoscopy, the list is long of the imaging technologies utilized in hospitals and clinics today. This article deals with the visualization technique described by Bordowitz, namely endoscopy. Since endoscopy is based on the visual examination of the body as such, the shift towards external mediation creates an emotional tension between our embodied sense of corporeal interiority and the live images of soft tissues projected onto TV monitors and computer screens. Drawing on the work of visual cultural scholars such as José van Dijck and Tom Gunning (van Dijck, 2005; Gunning; 2003), the article argues that the technological visualization of the inner flesh yields an estranged relation between what we see on the screen and our unseen insides. The effect of different endoscopic technologies on our perception of the inner body is illustrated with examples from clinical medicine and performance art.&nbsp

Visualizing plasmon-exciton polaritons at the nanoscale using electron microscopy

Polaritons are compositional light-matter quasiparticles that have recently enabled remarkable breakthroughs in quantum and nonlinear optics, as well as in material science. Despite the enormous progress, however, a direct nanometer-scale visualization of polaritons has remained an open challenge. Here, we demonstrate that plasmon-exciton polaritons, or plexcitons, generated by a hybrid system composed of an individual silver nanoparticle and a few-layer transition metal dichalcogenide can be spectroscopically mapped with nanometer spatial resolution using electron energy loss spectroscopy in a scanning transmission electron microscope. Our experiments reveal important insights about the coupling process, which have not been reported so far. These include nanoscale variation of Rabi splitting and plasmon-exciton detuning, as well as absorption-dominated extinction signals, which in turn provide the ultimate evidence for the plasmon-exciton hybridization in the strong coupling regime. These findings pioneer new possibilities for in-depth studies of polariton-related phenomena with nanometer spatial resolution

Forecasting linear aliphatic copolyester degradation through modular block design

AbstractThe development of efficient methods to predict the degradation of renewable polymeric materials is continuously sought in the field of polymer science. Herein, we present a modular build-up approach to create polyester-based materials with forecasted degradation rates based on the hydrolysis of the constituent polymer blocks. This involved the strategic combination of critical factors affecting polyester hydrolysis, i.e. hydrophobicity and degree of crystallinity. The starting point of this method was a toolbox of polymers with different hydrophobicities and degrees of crystallinity, as well as an understanding of their inherent differences in hydrolysis rate. Knowledge of the hydrolysis of each polymer block module enabled the prediction of the overall degradation behavior of the constructed copolymers. Taking advantage of the primary factors that affect polymer degradation, block copolymers could be independently designed to incorporate soft or rigid and faster or slower degradation properties. This approach generated a shift for how molecular design can be used to predict the degradation behavior of intended materials for different applications

Udvikling og solidaritet

I denne artikel belyses samspillet mellem 'udvikling af de menneskelige ressourcer' og de sociale relationer i virksomhederne. Formålet er at undersøge, hvad udviklingen betyder for arbejdernes indbyrdes solidaritet og deres relation til lederne og virksomheden. Afslutningsvis diskuteres udviklingens betydning for den danske fagbevægelse