The Potential of Pulsed Low Intensity Ultrasound to stimulate Chondrocytes in a 3D Model System

PhDPulsed low intensity ultrasound (PLIUS) is used clinically to accelerate fracture healing. although the mode of action is unclear. However studies suggest that PLIUS may stimulate endochondral ossification and consequently PLIUS may also be beneficial for cartilage regeneration, either in vivo or as part of a tissue engineered approach. Preyious studies using chondrocytes cultured in monolayer have suggested that PLIUS may stimulate glycosaminoglycan (GAG) synthesis, and that calcium signalling is implicated in this process. Therefore the present studies set out to investigate the influence of PLIUS on bovine articular chondrocytes in monolayer and agarose culture. This required the design of a bioreactor system which enabled cell-agarose constructs to be subjected to PLIUS, as well as a microscope-mounted test rig enabling confocal visualisation of intracellular calcium dynamics. A PLIUS system and signalling characteristics were provided by Smith and Nephew, Inc. (York, UK). Chondrocytes in agarose demonstrated a reduction in cell viability associated with PLIUS above a spatial averaged time averaged (SAT A) intensity of 200m W /cm2 , presumably associated with transducer heating. In subsequent studies, 30 and 100mW/cm2 were applied to monolayer and agarose cultures for up to 20 days, and biosynthesis was examined by assessment of GAG synthesis and cell proliferation using biochemical and radio-labelling protocols. Intracellular calcium signalling was investigated as a possible mechanotransduction pathway, using confocal mIcroscopy and the calcium indicator Fluo-4. In monolayer culture PLIUS did not stimulate total GAG content or cell proliferation at either 30 or 100 mW/cm2 • In agarose cultures, PLIUS had no effect on total GAG content at 30 mW/cm2 • At 100 mW/cm2 PLIUS induced a very small increase in total GAG content but there was no detectable effect on the rate of GAG synthesis in either model system at either 30 or 100 mW/cm2 . There were no PLIUS associated changes in the levels of intracellular calcium signaling in either monolayer or agarose cultures. Preliminary studies using Fluorescent Recovery after Photobleaching (FRAP) showed that PLIUS at 30mW/cm2 increased diffusion of 70kDa FITC-dextrans, although this clearly had no effect on GAG synthesis or cell proliferation. These studies indicate that PLIUS-induced fracture healing, or any potential use of PLIUS for cartilage repair. is unlikely to involve direct stimulation of proteoglycan synthesis or cell proliferation. Indeed the proposed use of PLIUS in cartilage tissue engineering is more limited than previously suggested

Improving children’s and their visitors’ hand hygiene compliance

Background: Numerous interventions have tried to improve healthcare workers' hand hygiene compliance, however little attention has been paid to children's and their visitors’ compliance.Aim: To increase children’s and visitors’ compliance using interactive educational interventions. Methods: This was an observational study of hand hygiene compliance before and after the introduction of educational interventions. Qualitative data in the form of Questionnaires and interviews was obtained.Findings: Hand hygiene compliance increased by 21.4% (P [less than] 0.001) following the educational interventions, with children's compliance reaching 40.8% and visitors' being 50.8%. Compliance varied depending on which of the five moments of hygiene was observed (P [less than] 0.001), with the highest compliance was ‘after body fluid exposure’ (96%). Responses from questionnaires showed educational interventions raised awareness of the importance of hand hygiene (69%, 57%) compared to those who hadn't experienced the educational intervention (50%). Conclusion: Educational interventions may result in a significant increase in children's and visitors' hand hygiene (P [less than] 0.001)

A discovery down under: decoding the draft genome sequence of Pantoea stewartii from Australia's Critically Endangered western ground parrot / kyloring (Pezoporus flaviventris)

Pantoea stewartii, a plant pathogen, is primarily transmitted through contaminated seeds and insect vectors, with the corn flea beetle (Chaetocnema pulicaria) being the primary carrier. P. stewartii is a bacterium belonging to the order Enterobacterales and can lead to crop diseases that have a significant economic impact worldwide. Due to its high potential for spread, P. stewartii is classified as a quarantine organism in numerous countries. Despite its impact on agriculture, the limited genome sequences of P. stewartii hamper understanding of its pathogenicity and host specificity, and the development of effective control strategies. In this study, a P. stewartii strain (C10109_Jinnung) was discovered in the faecal matter of the Critically Endangered western ground parrot/kyloring (Pezoporus flaviventris) in Australia, which to our knowledge is the first reported P. stewartii genome from a bird source. Whole-genome sequencing and phylogenomic analysis of strain C10109_Jinnung, obtained from a captive psittacine, provides new insights into the genetic diversity and potential transmission route for the spread of P. stewartii beyond insects and plants, where P. stewartii is typically studied. Our findings provide new insights into the potential transmission route for spread of P. stewartii and expand the known transmission agents beyond insects and plants. Expanding the catalogue of P. stewartii genomes is fundamental to improving understanding of the pathogenicity, evolution and dissemination, and to develop effective control strategies to reduce the substantial economic losses associated with P. stewartii in various crops and the potential impact of endangered animal species

Trauma, Memory and Religion

How can we screen trauma? This question might lead the perception of documentary films about atrocities in the 20th and 21st centuries, like S21 THE KHMER ROUGE KILLING MACHINE (Rithy Panh, CAMB/FR 2003) about Cambodia, THE LOOK OF SILENCE (Joshua Oppenheimer, ID/DK 2014) about Indonesia or DAS RADIKAL BÖSE (Stefan Ruzowitzky, AT 2013) about Nazi-Europe. A concern that may emerge as we watch films on atrocities is whether these artistic representations perhaps guide the public away from what “really happened”. There certainly is a huge gap between, on the one hand, the immediate experience of the event that lies behind the interpretative screening and, on the other hand, watching the director’s material while neither being a part nor ever having been part of the event. Yet often filmic representations are not intended to show what happened; instead they present case studies to be explored in the present. Often the films contain an inherent critique of genocidal violence and present humanistic perspectives on obedience. Mostly, these films underline the humanity of the victims, seeking to give names, faces and biographies so that they are much more than just numbers. What appears on the screen therefore challenges the audience with a moral question: what would you do

Physiotherapy and occupational therapy vs no therapy in mild to moderate Parkinson disease: a randomized clinical trial

IMPORTANCE It is unclear whether physiotherapy and occupational therapy are clinically effective and cost-effective in Parkinson disease (PD). OBJECTIVE To perform a large pragmatic randomized clinical trial to evaluate the clinical effectiveness of individualized physiotherapy and occupational therapy in PD. DESIGN, SETTING, AND PARTICIPANTS The PD REHAB Trial was a multicenter, open-label, parallel group, controlled efficacy trial. A total of 762 patients with mild to moderate PD were recruited from 38 sites across the United Kingdom. Recruitment took place between October 2009 and June 2012, with 15 months of follow-up. INTERVENTIONS Participants with limitations in activities of daily living (ADL) were randomized to physiotherapy and occupational therapy or no therapy. MAIN OUTCOMES AND MEASURES The primary outcome was the Nottingham Extended Activities of Daily Living (NEADL) Scale score at 3 months after randomization. Secondary outcomes were health-related quality of life (assessed by Parkinson Disease Questionnaire–39 and EuroQol-5D); adverse events; and caregiver quality of life. Outcomes were assessed before trial entry and then 3, 9, and 15 months after randomization. RESULTS Of the 762 patients included in the study (mean [SD] age, 70 [9.1] years), 381 received physiotherapy and occupational therapy and 381 received no therapy. At 3 months, there was no difference between groups in NEADL total score (difference, 0.5 points; 95%CI, −0.7 to 1.7; P = .41) or Parkinson Disease Questionnaire–39 summary index (0.007 points; 95%CI, −1.5 to 1.5; P = .99). The EuroQol-5D quotient was of borderline significance in favor of therapy (−0.03; 95%CI, −0.07 to −0.002; P = .04). The median therapist contact time was 4 visits of 58 minutes over 8 weeks. Repeated-measures analysis showed no difference in NEADL total score, but Parkinson Disease Questionnaire–39 summary index (diverging 1.6 points per annum; 95%CI, 0.47 to 2.62; P = .005) and EuroQol-5D score (0.02; 95%CI, 0.00007 to 0.03; P = .04) showed small differences in favor of therapy. There was no difference in adverse events. CONCLUSIONS AND RELEVANCE Physiotherapy and occupational therapy were not associated with immediate or medium-term clinically meaningful improvements in ADL or quality of life in mild to moderate PD. This evidence does not support the use of low-dose, patient-centered, goal-directed physiotherapy and occupational therapy in patients in the early stages of PD. Future research should explore the development and testing of more structured and intensive physical and occupational therapy programs in patients with all stages of PD

The SysteMHC Atlas project.

Mass spectrometry (MS)-based immunopeptidomics investigates the repertoire of peptides presented at the cell surface by major histocompatibility complex (MHC) molecules. The broad clinical relevance of MHC-associated peptides, e.g. in precision medicine, provides a strong rationale for the large-scale generation of immunopeptidomic datasets and recent developments in MS-based peptide analysis technologies now support the generation of the required data. Importantly, the availability of diverse immunopeptidomic datasets has resulted in an increasing need to standardize, store and exchange this type of data to enable better collaborations among researchers, to advance the field more efficiently and to establish quality measures required for the meaningful comparison of datasets. Here we present the SysteMHC Atlas (https://systemhcatlas.org), a public database that aims at collecting, organizing, sharing, visualizing and exploring immunopeptidomic data generated by MS. The Atlas includes raw mass spectrometer output files collected from several laboratories around the globe, a catalog of context-specific datasets of MHC class I and class II peptides, standardized MHC allele-specific peptide spectral libraries consisting of consensus spectra calculated from repeat measurements of the same peptide sequence, and links to other proteomics and immunology databases. The SysteMHC Atlas project was created and will be further expanded using a uniform and open computational pipeline that controls the quality of peptide identifications and peptide annotations. Thus, the SysteMHC Atlas disseminates quality controlled immunopeptidomic information to the public domain and serves as a community resource toward the generation of a high-quality comprehensive map of the human immunopeptidome and the support of consistent measurement of immunopeptidomic sample cohorts