The acute response of tendon to loading: implications for rehabilitation

Achilles tendinopathy is a common disorder involving physically active and sedentary individuals alike. Although the processes underlying its development are poorly understood, tendinopathy is widely regarded as an ‘overuse’ injury in which the tendon fails to adapt to prevalent loading conditions. Paradoxically, there is emerging evidence that heavy eccentric loading of the Achilles tendon may be an effective conservative approach for treatment of tendinopathy, with success rates of 60–80% reported. Interestingly, loading exercises involving other forms of muscle action, such as concentric activation, have been shown to be less effective treatment options. However, little is known about the acute response of tendon to exercise at present, and there are few plausible explanatory mechanisms for the observed beneficial effects of eccentric exercise, as opposed to other forms of strain stimuli. This paper presents the findings from a series of experiments undertaken to evaluate the effect of various strain stimuli on the time-dependent response of human Achilles tendon in vivo. It was shown for the first time, that heavy resistive ankle plantarflexion/ dorsiflexion exercises induced an immediate and significant decrease in Achilles tendon thickness (~15%). While thickness returned to pre-exercise levels within 24 hours, the recovery was exponential, with primary recovery occurring in less than 6 hours post-exercise. We proposed that such a diametral strain response with tensile loading reflects collagen realignment, Poison’s effects and radial extrusion of water from the tendon core. With unloading, the recovery of tendon dimensions likely reflects the re-diffusion of water via osmotic and/or inflammatory driven processes. Interestingly, prolonged walking was found to induce a similar diametral strain response. In subsequent studies, we demonstrated that eccentric exercise resulted in a greater reduction (-21%) in Achilles tendon thickness than isolated concentric exercise alone (-5%), despite a similar loading impulse. These novel findings, coupled with observations of a reduced diametral strain response with tendon pathology, highlight the importance of fluid movement to tendon function, nutrition and health. They also provide new insights into potential mechanisms underlying Achilles tendinopathy that impact rehabilitation strategies

Affinities of the family Sollasellidae (Porifera, Demospongiae). II. Molecular evidence

This is the second part of a revision and re-classification of the demosponge family Sollasellidae, and an example of a successful use of combined morphological and molecular data. Sollasella had been a poorly known, long forgotten taxon, placed incertae sedis in the order Hadromerida in the last major revision of the demosponges. It has recently been suggested to belong to Raspailiidae in the order Poecilosclerida due to striking morphological similarities. The present analysis verified this re-classification using molecular markers. Comparing 28S rDNA fragments of Sollasella cervicornis, a newly described species S. moretonensis and a representative set of raspailiid and hadromerid samples. In our analyses Sollasella clearly clusters inside the Raspailiidae clade, and distantly from hadromerid taxa. Supporting morphological hypothesis of Van Soest et al. (2006), that Sollasella is a raspailiid sponge

Environmental Scan: Metro Regional Report

In 2010, the Extension Center for Family Development of the University of Minnesota launched a project to learn more about the current and future issues affecting families in Minnesota. During this environmental scan project, community-level interviews were conducted in 11 different regions of the state. This report summarizes the community-level interviews conducted in metro Minnesota. University of Minnesota Extension Center for Family Development staff members — Ali Shurilla, Mary Marczak, Jon Fu, and Heather Lee — assisted in the development of this report.This archival publication may not reflect current scientific knowledge or recommendations. Current information available from the University of Minnesota Extension: https://www.extension.umn.edu

Feasibility of an Intervention to Support Hearing and Vision in Dementia:The SENSE-Cog Field Trial

OBJECTIVES: People with dementia (PwD) frequently experience hearing and vision impairment that is underrecognized and undertreated, resulting in reduced quality of life. Managing these impairments may be an important strategy to improve outcomes in PwD. Our objective was to field-trial a multifaceted sensory intervention (SI) to enhance hearing and vision in PwD. DESIGN: An international single-arm open-label feasibility, acceptability, and tolerability study. SETTING: Home-based setting in the United Kingdom, France, and Cyprus. PARTICIPANTS: Adults aged 60 years and older with mild-to-moderate dementia and uncorrected or suboptimally corrected hearing and/or vision impairment, and their study partners (n = 19 dyads). INTERVENTION: A sensory intervention (SI), comprising assessment of hearing and vision, fitting of corrective devices (glasses, hearing aids), and home-based support from a sensory support therapist for device adherence and maintenance, communication training, referral to support services, environmental sensory modification, and optimization of social inclusion. MEASUREMENTS: Ratings of study procedure feasibility, and intervention acceptability/tolerability, ascertained through questionnaires, participant diaries, therapist logbooks, and semistructured interviews. RESULTS: We successfully delivered all intervention components, and these were received and enacted as intended in all those who completed the intervention. No serious adverse events were reported. Acceptability (ie, understanding, motivation, sense of achievement) and tolerability (ie, effort, fatigue) ratings of the intervention were within a priori target ranges. We met recruitment and retention (93.8%) targets in two of the three sites. Participants completed more than 95% of diary entries, representing minimal missing data. Delays in the logistics circuit for the assessment and delivery of hearing aids and glasses were identified, requiring modification. The need for minor modifications to some outcome measures and the inclusion criteria were identified. CONCLUSION: This is the first study combining home-based hearing and vision remediation in PwD. The positive feasibility, acceptability, and tolerability findings suggest that a full-scale efficacy trial, with certain modifications, is achievable

Antibody-mediated disruption of the interaction between PCSK9 and the low-density lipoprotein receptor

PCSK9 (proprotein convertase subtilisin/kexin type 9) promotes degradation of the LDLR [LDL (low-density lipoprotein) receptor] through an as-yet-undefined mechanism, leading to a reduction in cellular LDLc (LDL-cholesterol) and a concomitant increase in serum LDLc. Central to the function of PCSK9 is a direct protein–protein interaction formed with the LDLR. In the present study, we investigated a strategy to modulate LDL uptake by blocking this interaction using specific antibodies directed against PCSK9. Studies using surface plasmon resonance demonstrated that direct binding of PCSK9 to the LDLR could be abolished with three different anti-PCSK9 antibodies. Two of these antibodies were raised against peptide epitopes in a region of the catalytic domain of PCSK9 that is involved in the interaction with the LDLR. Such antibodies restored LDL uptake in HepG2 cells treated with exogenous PCSK9 and in HepG2 cells engineered to overexpress recombinant PCSK9. This latter observation indicates that antibodies blocking the PCSK9–LDLR interaction can inhibit the action of PCSK9 produced endogenously in a cell-based system. These antibodies also disrupted the higher-affinity interaction between the natural gain-of-function mutant of PCSK9, D374Y, and the LDLR in both the cell-free and cell-based assays. These data indicate that antibodies targeting PCSK9 can reverse the PCSK9-mediated modulation of cell-surface LDLRs

A systematic review and meta-synthesis of the impact of low back pain on people's lives

Copyright @ 2014 Froud et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Background - Low back pain (LBP) is a common and costly problem that many interpret within a biopsychosocial model. There is renewed concern that core-sets of outcome measures do not capture what is important. To inform debate about the coverage of back pain outcome measure core-sets, and to suggest areas worthy of exploration within healthcare consultations, we have synthesised the qualitative literature on the impact of low back pain on people’s lives. Methods - Two reviewers searched CINAHL, Embase, PsycINFO, PEDro, and Medline, identifying qualitative studies of people’s experiences of non-specific LBP. Abstracted data were thematic coded and synthesised using a meta-ethnographic, and a meta-narrative approach. Results - We included 49 papers describing 42 studies. Patients are concerned with engagement in meaningful activities; but they also want to be believed and have their experiences and identity, as someone ‘doing battle’ with pain, validated. Patients seek diagnosis, treatment, and cure, but also reassurance of the absence of pathology. Some struggle to meet social expectations and obligations. When these are achieved, the credibility of their pain/disability claims can be jeopardised. Others withdraw, fearful of disapproval, or unable or unwilling to accommodate social demands. Patients generally seek to regain their pre-pain levels of health, and physical and emotional stability. After time, this can be perceived to become unrealistic and some adjust their expectations accordingly. Conclusions - The social component of the biopsychosocial model is not well represented in current core-sets of outcome measures. Clinicians should appreciate that the broader impact of low back pain includes social factors; this may be crucial to improving patients’ experiences of health care. Researchers should consider social factors to help develop a portfolio of more relevant outcome measures.Arthritis Research U

By staff and for staff: building, sustaining and empowering a community of practice in teaching and learning for all university staff

VicTeach was established in 2013 as a part of a Learning and Teaching Development initiative. VicTeach promotes cross-disciplinary dialogue between Victoria staff who are interested in pedagogy, sharing best practice, implementing new teaching approaches, and participating in and disseminating research on teaching and learning. It has become a particularly helpful network for academics interested in developing and informing their own teaching practice, but for whom education is not their main disciplinary focus; and for general staff supporting these academics in their teaching and student support. Regular bi-monthly meetings have addressed issues such as: new technologies and pedagogies, supporting Maori and Pasifika students, large classes, internships and placements, social media, flipped teaching, active learning and transition from high school. Meetings are held around the distributed VUW campus, streamed live, and archived for future-viewing. The community itself also continually tests, promotes, and profiles new technologies that all Victoria staff can use in teaching. Every seminar in the VicTeach programme attempts to include: • Best practice examples from a real teaching scenario Pedagogical grounding / research related to the topic, technology, or teaching concept Academic staff championing the topic/ technology / teaching concept Support staff with expertise in the area, or able to support development of this technology/ concept Time for discussion Over 200 academic and general staff members from across the university voluntarily subscribe to the VicTeach listserv and approximately 20-45 attend each event. The group is led by a volunteer steering committee consisting of academics from all Faculties, teaching award winners, and representatives from the Centre for Academic Development, Student Learning, the Library, and IT Support. This structure has been designed to ensure the organisation is sustainable and can continually respond to staff needs in learning and teaching. Future plans include the development and support of research hubs which will foster cross–disciplinary initiatives into particular aspects of teaching and learning. VicTeach appears to address an unfilled professional development need for Victoria University staff. In a survey conducted at the end of the first year the community reported that they had gained value from VicTeach, and most appreciated that it is pan-University, pan-staff, self-selecting, occurring at a regular time, gras

Valacyclovir in the treatment of acute retinal necrosis

Background: To report the outcome of oral valacyclovir as the sole antiviral therapy for patients with acute retinal necrosis (ARN). Methods: This study reports a retrospective, interventional case series of nine consecutive patients with ten eyes with newly diagnosed ARN treated with oral valacyclovir as the sole antiviral agent. Eight patients received oral valacyclovir 2 g tid (Valtrex, GlaxoSmithKline) and one patient with impaired renal function received oral 1 g tid. The main outcome measures were response to treatment, time to initial response to treatment, time to complete resolution of retinitis, best corrected visual acuity (BCVA) at final follow-up, retinal detachment and development of recurrent or second eye disease. Results: Retinitis resolved in ten of ten (100%) affected eyes. The median time to initial detectable response was seven days and the median time to complete resolution was 21 days. A final BCVA of 20/40 or better was achieved in 6/10 (60%) of eyes. 3/10 eyes (30%) developed a retinal detachment. No patients developed either disease reactivation or second eye involvement over the course of the study (mean follow up 31 weeks, range 7 to 104 weeks). Conclusions: Treatment with oral valacyclovir as the sole antiviral therapy resulted in complete resolution of retinitis. Final BCVA and retinal detachment rate were comparable with previously reported outcomes for intravenous acyclovi

Dynamin I phosphorylation by GSK3 controls activity-dependent bulk endocytosis of synaptic vesicles.

Glycogen synthase kinase 3 (GSK3) is a critical enzyme in neuronal physiology; however, it is not yet known whether it has any specific role in presynaptic function. We found that GSK3 phosphorylates a residue on the large GTPase dynamin I (Ser-774) both in vitro and in primary rat neuronal cultures. This was dependent on prior phosphorylation of Ser-778 by cyclin-dependent kinase 5. Using both acute inhibition with pharmacological antagonists and silencing of expression with short hairpin RNA, we found that GSK3 was specifically required for activity-dependent bulk endocytosis (ADBE) but not clathrin-mediated endocytosis. Moreover we found that the specific phosphorylation of Ser-774 on dynamin I by GSK3 was both necessary and sufficient for ADBE. These results demonstrate a presynaptic role for GSK3 and they indicate that a protein kinase signaling cascade prepares synaptic vesicles for retrieval during elevated neuronal activity

Cell salvage and donor blood transfusion during cesarean section: A pragmatic, multicentre randomised controlled trial (SALVO)

BACKGROUND: Excessive haemorrhage at cesarean section requires donor (allogeneic) blood transfusion. Cell salvage may reduce this requirement. METHODS AND FINDINGS: We conducted a pragmatic randomised controlled trial (at 26 obstetric units; participants recruited from 4 June 2013 to 17 April 2016) of routine cell salvage use (intervention) versus current standard of care without routine salvage use (control) in cesarean section among women at risk of haemorrhage. Randomisation was stratified, using random permuted blocks of variable sizes. In an intention-to-treat analysis, we used multivariable models, adjusting for stratification variables and prognostic factors identified a priori, to compare rates of donor blood transfusion (primary outcome) and fetomaternal haemorrhage ≥2 ml in RhD-negative women with RhD-positive babies (a secondary outcome) between groups. Among 3,028 women randomised (2,990 analysed), 95.6% of 1,498 assigned to intervention had cell salvage deployed (50.8% had salvaged blood returned; mean 259.9 ml) versus 3.9% of 1,492 assigned to control. Donor blood transfusion rate was 3.5% in the control group versus 2.5% in the intervention group (adjusted odds ratio [OR] 0.65, 95% confidence interval [CI] 0.42 to 1.01, p = 0.056; adjusted risk difference -1.03, 95% CI -2.13 to 0.06). In a planned subgroup analysis, the transfusion rate was 4.6% in women assigned to control versus 3.0% in the intervention group among emergency cesareans (adjusted OR 0.58, 95% CI 0.34 to 0.99), whereas it was 2.2% versus 1.8% among elective cesareans (adjusted OR 0.83, 95% CI 0.38 to 1.83) (interaction p = 0.46). No case of amniotic fluid embolism was observed. The rate of fetomaternal haemorrhage was higher with the intervention (10.5% in the control group versus 25.6% in the intervention group, adjusted OR 5.63, 95% CI 1.43 to 22.14, p = 0.013). We are unable to comment on long-term antibody sensitisation effects. CONCLUSIONS: The overall reduction observed in donor blood transfusion associated with the routine use of cell salvage during cesarean section was not statistically significant. TRIAL REGISTRATION: This trial was prospectively registered on ISRCTN as trial number 66118656 and can be viewed on http://www.isrctn.com/ISRCTN66118656