Validity of the activPAL3 activity monitor in people moderately affected by Multiple Sclerosis

Background: Walking is the primary form of physical activity performed by people with Multiple Sclerosis (MS), therefore it is important to ensure the validity of tools employed to measure walking activity. The aim of this study was to assess the criterion validity of the activPAL3 activity monitor during overground walking in people with MS.\ud Methods: Validity of the activPAL3 accelerometer was compared to video observation in 20 people moderately affected by MS. Participants walked 20-30m twice along a straight quiet corridor at a comfortable speed.\ud Results: Inter-rater reliability of video observations was excellent (all intraclass correlations > 0.99). The mean difference (activPAL3- mean of raters) was -4.70 ± 9.09, -4.55 s ± 10.76 and 1.11 s ± 1.11 for steps taken, walking duration and upright duration respectively. These differences represented 8.7, 10.0 and 1.8% of the mean for each measure respectively. The activPAL3 tended to underestimate steps taken and walking duration in those who walked at cadences of ≤ 38 steps/minute by 60% and 47% respectively.\ud Discussion: The activPAL3 is valid for measuring walking activity in people moderately affected by MS. It is accurate for upright duration regardless of cadence. In participants with slow walking cadences, outcomes of steps taken and walking duration should be interpreted with caution

Dephosphorylation of YB-1 is Required for Nuclear Localisation During G2 Phase of the Cell Cycle

Elevated levels of nuclear Y-box binding protein 1 (YB-1) are linked to poor prognosis in cancer. It has been proposed that entry into the nucleus requires specific proteasomal cleavage. However, evidence for cleavage is contradictory and high YB-1 levels are prognostic regardless of cellular location. Here, using confocal microscopy and mass spectrometry, we find no evidence of specific proteolytic cleavage. Doxorubicin treatment, and the resultant G2 arrest, leads to a significant increase in the number of cells where YB-1 is not found in the cytoplasm, suggesting that its cellular localisation is variable during the cell cycle. Live cell imaging reveals that the location of YB-1 is linked to progression through the cell cycle. Primarily perinuclear during G1 and S phases, YB-1 enters the nucleus as cells transition through late G2/M and exits at the completion of mitosis. Atomistic modelling and molecular dynamics simulations show that dephosphorylation of YB-1 at serine residues 102, 165 and 176 increases the accessibility of the nuclear localisation signal (NLS). We propose that this conformational change facilitates nuclear entry during late G2/M. Thus, the phosphorylation status of YB-1 determines its cellular location

Critical Role for Cold Shock Protein YB-1 in Cytokinesis

High levels of the cold shock protein Y-box-binding protein-1, YB-1, are tightly correlated with increased cell proliferation and progression. However, the precise mechanism by which YB-1 regulates proliferation is unknown. Here, we found that YB-1 depletion in several cancer cell lines and in immortalized fibroblasts resulted in cytokinesis failure and consequent multinucleation. Rescue experiments indicated that YB-1 was required for completion of cytokinesis. Using confocal imaging we found that YB-1 was essential for orchestrating the spatio-temporal distribution of the microtubules, β-actin and the chromosome passenger complex (CPC) to define the cleavage plane. We show that phosphorylation at six serine residues was essential for cytokinesis, of which novel sites were identified using mass spectrometry. Using atomistic modelling we show how phosphorylation at multiple sites alters YB-1 conformation, allowing it to interact with protein partners. Our results establish phosphorylated YB-1 as a critical regulator of cytokinesis, defining precisely how YB-1 regulates cell division

Critical Role for Cold Shock Protein YB-1 in Cytokinesis

High levels of the cold shock protein Y-box-binding protein-1, YB-1, are tightly correlated with increased cell proliferation and progression. However, the precise mechanism by which YB-1 regulates proliferation is unknown. Here, we found that YB-1 depletion in several cancer cell lines and in immortalized fibroblasts resulted in cytokinesis failure and consequent multinucleation. Rescue experiments indicated that YB-1 was required for completion of cytokinesis. Using confocal imaging we found that YB-1 was essential for orchestrating the spatio-temporal distribution of the microtubules, β-actin and the chromosome passenger complex (CPC) to define the cleavage plane. We show that phosphorylation at six serine residues was essential for cytokinesis, of which novel sites were identified using mass spectrometry. Using atomistic modelling we show how phosphorylation at multiple sites alters YB-1 conformation, allowing it to interact with protein partners. Our results establish phosphorylated YB-1 as a critical regulator of cytokinesis, defining precisely how YB-1 regulates cell division

Technologies to Support Assessment of Movement During Video Consultations: Exploratory Study

Background Understanding and assessing patients’ body movements is essential for physical rehabilitation but is challenging in video consultations, as clinicians are frequently unable to see the whole patient or observe the patient as they perform specific movements. Objective The objective of this exploratory study was to assess the use of readily available technologies that would enable remote assessment of patient movement as part of a video consultation. Methods We reviewed the literature and available technologies and chose four technologies (Kubi and Pivo desktop robots, Facebook Portal TV, wide-angle webcam), in addition to help from a friend or a simple mobile phone holder, to assist video consultations. We used 5 standard assessments (sit-to-stand, timed “Up &amp; Go,” Berg Balance Test, ankle range of motion, shoulder range of motion) as the “challenge” for the technology. We developed an evaluation framework of 6 items: efficacy, cost, delivery, patient setup, clinician training and guidance, and safety. The coauthors, including 10 physiotherapists, then took the roles of clinician and patient to explore 7 combinations of 5 technologies. Subsequently, we applied our findings to hypothetical patients based on the researchers’ family members and clinical experience. Results Kubi, which allowed the clinician to remotely control the patient’s device, was useful for repositioning the tablet camera to gain a better view of the patient’s body parts but not for tracking movement. Facebook Portal TV was useful, but only for upper body movement, as it functions based on face tracking. Both Pivo, with automated full body tracking using a mobile phone, and the wide-angle webcam for a laptop or desktop computer show promise. Simple solutions such as having a friend operate a mobile phone and use of a mobile phone holder also have potential. The setup of these technologies will require better instructions than are currently available from suppliers, and successful use will depend on the technology readiness of patients and, to some degree, of clinicians. Conclusions Technologies that may enable clinicians to assess movement remotely as part of video consultations depend on the interplay of technology readiness, the patient’s clinical conditions, and social support. The most promising off-the-shelf approaches seem to be use of wide-angle webcams, Pivo, help from a friend, or a simple mobile phone holder. Collaborative work between patients and clinicians is needed to develop and trial technological solutions to support video consultations assessing movement. </jats:sec

Using a Delphi process to determine optimal care for patients with pancreatic cancer

Aim Overall 5-year survival for pancreatic cancer is ~5%. Optimising the care that pancreatic cancer patients receive may be one way of improving outcomes. The objective of this study was to establish components of care which Australian health professionals believe important to optimally manage patients with pancreatic cancer. Methods Using a Delphi process, a multi-disciplinary panel of 250 health professionals were invited to provide a list of factors they considered important for optimal care of pancreatic cancer patients. They were then asked to score and then rescore (from one (no importance/disagree) to 10 (very important/agree) the factors. The mean and coefficient of variation scores were calculated and categorised into three levels of importance. Results Overall 63 (66% of those sent the final questionnaire; 25% of those initially invited) health professionals from 9 disciplines completed the final scoring of 55 statements/factors encompassing themes of presentation/staging, surgery and biliary obstruction, multi-disciplinary team details and oncology. Mean scores ranged from 3.7 to 9.7 with the highest related to communication and patient assessment. There was substantial intra- and inter- disciplinary variation in views about MDT membership and roles. Conclusion Overall the opinions of Australian health professionals reflect international guideline recommended care; however they identified a number of additional factors focusing on where patients should be treated, the importance of clear communication and the need for multi-disciplinary care which were not included in current clinical practice guidelines. Differences in priorities between specialty groups were also identified