Inhibition of Methicillin-resistant Staphylococcus aureus-induced cytokines mRNA production in human bone marrow derived mesenchymal stem cells by 1,25-dihydroxyvitamin D3

Background Methicillin-resistant Staphylococcus aureus (MRSA) is the predominant cause of bone infection. Toll like receptors (TLRs) are an important segments of host response to infection and are expressed by a variety of cells including human mesenchymal stem cells (hMSCs). The active form of Vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) has potent immunoregulatory properties, but the mechanism remains poorly understood. The genomic action of 1,25(OH)2D3 is mediated by vitamin D receptor (VDR), hormone-regulated transcription factor. VDR interacts with co-activators and co-repressors are associated with chromatin histone modifications and transcriptional regulation. The aim of our study is to explore MRSA-induced TLRs-mediated pro-inflammatory cytokines expression in hMSCs. Further, we hypothesized that 1,25(OH)2D3 inhibits MRSA-induced cytokines synthesis in hMSCs via inhibition of NF-кB transcription factor. Finally, we explored the regulatory role of 1,25(OH)2D3 in MRSA-mediated global epigenetic histone H3 mark, such as, trimethylated histone H3 lysine 9 (H3K9me3), which is linked to gene silencing. Results Quantitative PCR data revealed that MRSA-infection predominantly induced expression of TLRs 1, 2, 6, NR4A2, and inflammatory cytokines IL-8, IL-6, TNFα in hMSCs. MRSA-mediated TLR ligands reduced osteoblast differentiation and increased hMSCs proliferation, indicating the disrupted multipotency function of hMSCs. Pretreatment of 1,25(OH)2D3 followed by MRSA co-culture inhibited nuclear translocation of NF-кB-p65, reduced expression of NR4A2 and pro-inflammatory cytokines IL-8, IL-6, and TNFα in hMSCs. Further, NF-κB-p65, VDR, and NR4A2 were present in the same nuclear protein complex, indicating that VDR is an active part of the nuclear protein complexes for transcriptional regulation. Finally, 1,25(OH)2D3 activated VDR, restores the global level of H3K9me3, to repress MRSA-stimulated inflammatory cytokine IL-8 expression. Pretreatment of 5-dAZA, DNA methylatransferases (Dnmts) inhibitor, dramatically re-expresses 1,25(OH)2D3-MRSA-mediated silenced IL-8 gene. Conclusions This data indicates that TLR 1, 2, and 6 can be used as markers for localized S. aureus bone infection. 1,25(OH)2D3-VDR may exhibits its anti-inflammatory properties in MRSA-stimulated infection by inhibiting nuclear translocation of NF-kB-p65 and transcripts of IL-8, IL-6, TNFα, and NR4A2 in hMSCs. Finally, 1,25(OH)2D3-activated VDR, acting as an epigenetic regulator, inhibits synthesis of cytokines in MRSA-stimulated infection by restoring the global level of H3K9me3, a histone H3 mark for gene silencing

Midterm Follow Up For Knee Replacement: How Well Do We Follow Our Patients?

The lost to follow up rate specifically for five year post surgical UKAs is significantly higher for this population subset than the most recent published average as seen in a meta analysis review (Callahan et al. 1995). Follow up visits allow for proper assessment of complications such as wear and osteolysis which need early intervention to improve long-term outcomes and reduce the overall cost of care (Bhandari et al. 2012). Eleven patients, 27.5% of those that were lost to follow up, were without a correct or working phone number, which presents a significant barrier to care. Maintaining updated patient contact information and educating patients about the importance of intermittent follow up may aid in compliance. Further research is required to better characterize patients with poor follow up rates so that systematic surveillance methods can be developed to improve the quality of care

Darstellungen von Endphaseverbrechen in Literatur und Film aus Österreich aus vergangenheitspolitischer Perspektive

Mit einer Kombination aus Ansätzen der kulturwissenschaftlichen Gedächtnistheorie und der Vergangenheitspolitik soll in dieser Arbeit die Frage beantwortet werden, welche vergangenheitspolitischen Narrative und Bilder über Endphaseverbrechen in Literatur und Film zur ‚Mühlviertler Hasenjagd‘ konstruiert werden und welche Funktion für das österreichische kulturelle Gedächtnis sie damit einnehmen. Endphaseverbrechen wurden am Ende des Zweiten Weltkrieges vor den Augen und mit Hilfe der lokalen Bevölkerung begangen, weshalb sie eine spezifische Leerstelle im lokalen wie nationalen Gedächtnis darstellen. Denn die Erinnerung an sie hätte die Opferthese bedroht, die bis in die 1980er Jahre nationale Basiserzählung Österreichs war. Die meisten der Arbeiten entstanden in den 1980ern und 90ern von AutorInnen und einem Regisseur, die allesamt der Nachkriegsgeneration angehören. Indem die Werke entweder einen Beitrag zum traumatischen Opfergedächtnis leisten, Täternarrative gestalten oder sich auf den Widerstand konzentrieren, zeigen sie die Bandbreite möglicher Verhaltensweisen auf und setzen Anstöße, um das gespaltene Opfer- und Tätergedächtnis wieder zusammenzuführen.By bringing together theoretical approaches of memory studies and politics of the past, the depictions of final phase crimes in Austrian literature and film, exemplified by the ‘Mühlviertler Hasenjagd’, are examined in this paper. Those crimes were committed with the help of the local population during the final phase of Second World War. Since remembering them would have challenged the ‘victim thesis’ that predominated the official discourse until the 1980s, they represented a specific gap in Austrian local and national memory. The question is asked if the cultural representations provide counter-narratives to the official discourse of the past or if they perpetuate it. What is therefore their function in cultural memory? Most of the works were published or released in the 1980s and 90s by authors and a director of the post-war generation. By either constructing a traumatic victims’ memory, a perpetrator narrative or concentrating on the resistance, they show the different choices people had. All of them challenge the ‘victim thesis’ and therefore function as a critical reminder of the past

Mijenja li ambalaža percipirani okus piva? Rezultati eksperimenta s pivom

Purpose – The purpose of this research was to verify actual consumer behavior concerning different beer packaging material and how it influences the perception of beer taste. More precisely, the main aim of the paper was to explore whether beer packaging can influence consumers’ subjectively perceived taste of the beer they drink. Design/Methodology/Approach – Following the literature research, a questionnaire survey was conducted on a sample of average Czech beer consumers (n=220). A subsequent experiment involving a sample of Czech college students (n=30) aimed at exploring the actual consumer behavior. Findings and implications – The results of the experiment show that beer consumer behavior can be influenced by the beer packaging material. If consumers knew that the beer had been poured from a glass bottle, they assessed its taste better than if they had no information on the type of beer packaging. Similarly, the opposite was found to be true of the plastic bottle – if consumers knew that the beer had been poured from a plastic bottle, they said it tasted worse than if they had no such information. No statistically significant difference was found in the tasting of canned beer with or without the knowledge of the packaging material. Limitation – The main research limitations lie in its regionality as the survey and the experiment were conducted only in the Czech Republic, with college students as participants. Originality – As there is only a limited amount of research available on beer packaging and its influence on consumer behavior, this paper provides a valuable overview of the issue.Svrha – Svrha istraživanja bila je provjeriti ponašanje potrošača ovisno o različitim vrstama ambalaže piva te kako ona utječe na percepciju okusa piva. Preciznije, glavni cilj rada bio je otkriti može li ambalaža piva utjecati na potrošačevu subjektivnu percepciju njegova okusa. Metodološki pristup – Nakon pregleda literature provedeno je anketiranje na uzorku prosječnih čeških potrošača piva (n = 220). Kako bi se otkrilo stvarno ponašanje potrošača, proveden je eksperiment na uzroku čeških studenata (n=30). Rezultati i implikacije – Rezultati eksperimenta pokazuju da ambalaža može utjecati na ponašanje potrošača piva. U situaciji kada su potrošači znali da je pivo točeno iz staklene boce, ocijenili su ga ukusnijim u odnosu na situaciju kada nisu imali informaciju o ambalaži piva, odnosno obratno vrijedi za plastične boce. Kada su potrošači znali da je pivo iz plastične boce, ocijenili su da ima lošiji okus nego kad nisu imali tu informaciju. Nisu pronađene statistički značajne razlike u degustaciji piva iz limenke u odnosu na (ne)posjedovanje informacije o vrsti ambalaže. Ograničenja – Glavna ograničenja istraživanja vezana su uz regionalnost, jer su istraživanje i eksperiment provedeni samo u Republici Češkoj, te činjenicu da su sudionici eksperimenta bili studenti. Doprinos – S obzirom na postojanje ograničenoga broja istraživanja o ambalaži piva i utjecaju na ponašanje potrošača, rad pruža vrijedan pregled problematike

An advanced modeling technique for rolling element bearings in elastohydrodynamic field

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Use of fresh versus frozen or blast-frozen grapes for small-scale fermentation

Background: This paper firstly examines the validity of using laboratory-scale fermentations as a means of correlating winemaking outcomes with larger industrial scale fermentations. Secondly, conventional and blast-freezing of whole bunches were investigated for their relative suitability as methods of preservation as determined by the nature of the resulting wines. Methods: Red must fermentations were compared at the laboratory 80 kg scale, and the more industrially representative 500 kg pilot scale. Fermentation profiles and duration for both scales were found to be very similar. Whole bunches were either slow/conventionally frozen (−20°C), or quickly/blast-frozen (−25°C). Results: Wines made from frozen grapes compared well with the wine made from the fresh must. Color and chemical analyses of the wines revealed few differences. A duo-trio sensory evaluation showed that wine from blast-frozen grapes was more similar to the fresh wines than wines from conventional frozen grapes. Conclusion: The findings of this research suggest that whole-bunch blast-freezing of grapes is preferable to conventional freezing.Frank Schmid, Vladimir Jirane

Retrospective Review of Intra-Articular Hip Steroid Injections and Their Association with Rapidly-Progressive Osteoarthritis

Based on strict inclusion criteria, 109 patients were eligible for analysis in this study. Of these patients, 23 developed RPOA—representing an incidence of 21%. The characteristics of patients who went on to develop RPOA in this study were: worse initial Kellgren-Lawrence grade and older age. Future studies of larger sample size that also include outcomes of patients who did not receive intra-articular injections will be needed to establish a causal relationship between these injections and RPOA