Is heavy eccentric calf training superior to wait-and-see, sham rehabilitation, traditional physiotherapy and other exercise interventions for pain and function in mid-portion Achilles tendinopathy?

Background: Mid-portion Achilles tendinopathy (AT) is prevalent amongst athletic and non-athletic populations with pain, stiffness and impaired function typically reported. While different management options exist, loading protocols remain the best available intervention and have been shown to be effective in the management of AT. Trials investigating loading in AT have used a variety of different protocols, and recent narrative reviews suggest that no protocol is superior to another when comparing outcomes in pain and function. However, there has been no systematic review or meta-analysis completed to determine this. Furthermore, the narrative review did not consider wait-and-see or sham interventions, thus a systematic review and met-analysis which includes wait-and see or sham interventions is warranted. Methods: A systematic review and meta-analyses will be conducted as per the PRISMA guidelines. The databases PUBMED, CINAHL (Ovid) and CINAHL (EBSCO) will be searched for articles published from inception to 31 December 2017. Our search focuses on studies examining the improvement of pain and function when completing a loading program for mid-portion AT. Only randomised/ quasi-randomised trials will be included while case reports and case series will be excluded. The primary outcome assessing pain and function will be the Victorian Institute Sports Assessment - Achilles (VISA-A). Two reviewers will screen articles, extract data and assess the risk of bias independently with a third reviewer resolving any disagreements between the two reviewers. A meta-analysis will then be performed on the data (if appropriate) to determine if the traditional heavy load calf training protocol described by Alfredson is superior to wait-and-see, sham intervention, traditional physiotherapy, and other forms of exercise rehabilitation. Discussion: This systematic review and meta-analysis will allow us to investigate if there are difference in pain and function when comparing wait-and-see, sham interventions, traditional physiotherapy and different exercise interventions to the traditional heavy eccentric calf training protocol for mid-portion Achilles tendon pain. Systematic review registration: PROSPERO registration number CRD42018084493

Perceptions of Problem Behavior in Adolescents’ Families: Perceiver, Target, and Family Effects

Considerable research has focused on the reliability and validity of informant reports of family behavior, especially maternal reports of adolescent problem behavior. None of these studies, however, has based their orientation on a theoretical model of interpersonal perception. In this study we used the social relations model (SRM) to examine family members’ reports of each others’ externalizing and internalizing problem behavior. Two parents and two adolescents in 69 families rated each others’ behavior within a round-robin design. SRM analysis showed that within-family perceptions of externalizing and internalizing behaviors are consistently due to three sources of variance; perceiver, target, and family effects. A family/contextual effect on informant reports of problem behavior has not been previously reported

Ser649 and Ser650 Are the Major Determinants of Protein Kinase A-Mediated Activation of Human Hormone-Sensitive Lipase against Lipid Substrates

BACKGROUND: Hormone-sensitive lipase (HSL) is a key enzyme in the mobilization of fatty acids from stored triacylglycerols. Its activity is regulated by reversible protein phosphorylation. In rat HSL Ser563, Ser659 and Ser660 have been shown to be phosphorylated by protein kinase A (PKA) in vitro as well as in vivo. METHODOLOGY/PRINCIPAL FINDINGS: In this study we employed site-directed mutagenesis, in vitro phosphorylation and mass spectrometry to show that in vitro phosphorylation of human HSL by PKA occurs primarily on Ser649 and Ser650 (Ser659 and Ser660 in rat HSL). The wild type enzyme and four mutants were expressed in C-terminally His-tagged form in Sf9 insect cells and purified to homogeneity. HSL variants in which Ser552 and/or Ser554 were mutated to Ala or Glu retained both lipolytic and non-lipolytic activity and were phosphorylated by PKA and activated to a similar extent as the wild type enzyme. (32)P-labeling studies revealed that the bulk of the phosphorylation was on the Ser649/Ser650 site, with only a minor phosphorylation of Ser552 and Ser554. MS/MS analysis demonstrated that the peptide containing Ser649 and Ser650 was primarily phosphorylated on Ser650. The mutant lacking all four serines had severely reduced lipolytic activity, but a lesser reduction in non-lipolytic activity, had S(0.5) values for p-nitrophenol butyrate and triolein comparable to those of wild type HSL and was not phosphorylated by PKA. PKA phosphorylation of the wild type enzyme resulted in an increase in both the maximum turnover and S(0,5) using the TO substrate. CONCLUSIONS: Our results demonstrate that PKA activates human HSL against lipid substrates in vitro primarily through phosphorylation of Ser649 and Ser650. In addition the results suggest that Ser649 and Ser650 are located in the vicinity of a lipid binding region and that PKA phosphorylation controls the accessibility of this region

Autism as a disorder of neural information processing: directions for research and targets for therapy

The broad variation in phenotypes and severities within autism spectrum disorders suggests the involvement of multiple predisposing factors, interacting in complex ways with normal developmental courses and gradients. Identification of these factors, and the common developmental path into which theyfeed, is hampered bythe large degrees of convergence from causal factors to altered brain development, and divergence from abnormal brain development into altered cognition and behaviour. Genetic, neurochemical, neuroimaging and behavioural findings on autism, as well as studies of normal development and of genetic syndromes that share symptoms with autism, offer hypotheses as to the nature of causal factors and their possible effects on the structure and dynamics of neural systems. Such alterations in neural properties may in turn perturb activity-dependent development, giving rise to a complex behavioural syndrome many steps removed from the root causes. Animal models based on genetic, neurochemical, neurophysiological, and behavioural manipulations offer the possibility of exploring these developmental processes in detail, as do human studies addressing endophenotypes beyond the diagnosis itself

Acceptance of technology-enhanced learning for a theoretical radiological science course: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Technology-enhanced learning (TEL) gives a view to improved education. However, there is a need to clarify how TEL can be used effectively. The study compared students' attitudes and opinions towards a traditional face-to-face course on theoretical radiological science and a TEL course where students could combine face-to-face lectures and e-learning modules at their best convenience.</p> <p>Methods</p> <p>42 third-year dental students were randomly assigned to the traditional face-to-face group and the TEL group. Both groups completed questionnaires before the beginning and after completion of the course on attitudes and opinions towards a traditional face-to-face lectures and technology-enhanced learning. After completion of the course both groups also filled in the validated German-language TRIL (Trierer Inventar zur Lehrevaluation) questionnaire for the evaluation of courses given at universities.</p> <p>Results</p> <p>Both groups had a positive attitude towards e-learning that did not change over time. The TEL group attended significantly less face-to-face lectures than the traditional group. However, both groups stated that face-to-face lectures were the basis for education in a theoretical radiological science course.</p> <p>The members of the TEL group rated e-mail reminders significantly more important when they filled in the questionnaire on attitudes and opinions towards a traditional face-to-face lectures and technology-enhanced learning for the second time after completion of the course.</p> <p>The members of the technology-enhanced learning group were significantly less confident in passing the exam compared to the members of the traditional group. However, examination results did not differ significantly for traditional and the TEL group.</p> <p>Conclusions</p> <p>It seems that technology-enhanced learning in a theoretical radiological science course has the potential to reduce the need for face-to-face lectures. At the same time examination results are not impaired. However, technology-enhanced learning cannot completely replace traditional face-to-face lectures, because students indicate that they consider traditional teaching as the basis of their education.</p

HEALTH:laparoscopic supracervical hysterectomy versus second-generation endometrial ablation for the treatment of heavy menstrual bleeding: study protocol for a randomised controlled trial

Peer reviewedPublisher PD

Alternatively Activated Mononuclear Phagocytes from the Skin Site of Infection and the Impact of IL-4Rα Signalling on CD4+T Cell Survival in Draining Lymph Nodes after Repeated Exposure to Schistosoma mansoni Cercariae

In a murine model of repeated exposure of the skin to infective Schistosoma mansoni cercariae, events leading to the priming of CD4 cells in the skin draining lymph nodes were examined. The dermal exudate cell (DEC) population recovered from repeatedly (4x) exposed skin contained an influx of mononuclear phagocytes comprising three distinct populations according to their differential expression of F4/80 and MHC-II. As determined by gene expression analysis, all three DEC populations (F4/80-MHC-IIhigh, F4/80+MHC-IIhigh, F4/80+MHC-IIint) exhibited major up-regulation of genes associated with alternative activation. The gene encoding RELMα (hallmark of alternatively activated cells) was highly up-regulated in all three DEC populations. However, in 4x infected mice deficient in RELMα, there was no change in the extent of inflammation at the skin infection site compared to 4x infected wild-type cohorts, nor was there a difference in the abundance of different mononuclear phagocyte DEC populations. The absence of RELMα resulted in greater numbers of CD4+ cells in the skin draining lymph nodes (sdLN) of 4x infected mice, although they remained hypo-responsive. Using mice deficient for IL-4Rα, in which alternative activation is compromised, we show that after repeated schistosome infection, levels of regulatory IL-10 in the skin were reduced, accompanied by increased numbers of MHC-IIhigh cells and CD4+ T cells in the skin. There were also increased numbers of CD4+ T cells in the sdLN in the absence of IL-4Rα compared to cells from singly infected mice. Although their ability to proliferate was still compromised, increased cellularity of sdLN from 4x IL-4RαKO mice correlated with reduced expression of Fas/FasL, resulting in decreased apoptosis and cell death but increased numbers of viable CD4+ T cells. This study highlights a mechanism through which IL-4Rα may regulate the immune system through the induction of IL-10 and regulation of Fas/FasL mediated cell death

Strengthening the Reporting of Genetic Risk Prediction Studies: The GRIPS Statement

Cecile Janssens and colleagues present the GRIPS Statement, a checklist to help strengthen the reporting of genetic risk prediction studies

Posterior shoulder tightness; an intersession reliability study of 3 clinical tests.

Background Although posterior shoulder tightness (PST) has been associated with shoulder pathology and altered glenohumeral joint kinematics, uncertainty remains regarding its cause and definition. To understand the efficacy of treatments for PST, it must be possible to identify people with PST for the purposes of research and clinical decision-making. Clinical tests for PST must demonstrate acceptable levels of measurement reliability in order to identify the condition and to evaluate the response to intervention. There is currently a lack of research describing intersession reliability for measures of PST. The aim of this study was to quantify the inter-session reliability for three clinical tests used to identify PST over a 6–10 week interval. Methods A convenience sample of 26 asymptomatic adult participants (52 shoulders) were recruited from a university setting over a five-month duration. Participants attended the human movement laboratory for measurement of glenohumeral joint internal rotation, horizontal adduction and low flexion on two occasions separated by an interval of 6–10 weeks. Intra-class correlation coefficients were calculated from the mean square values derived from the within-subject, single factor (repeated measures) ANOVA. Test-retest measurement stability was evaluated by calculating the standard error of measurement and the minimum detectable change for each measurement. Results All 3 tests demonstrated good intersession intra-rater reliability (0.86–0.88), and the standard error of measurement (95%) were 7.3° for glenohumeral horizontal adduction, 9.4° for internal rotation, and 6.9° for low flexion. The minimum detectable change for glenohumeral horizontal adduction was 10.2°, internal rotation was 13.3°, and low flexion was 9.7°. Conclusion In this population of people without symptoms, the 3 measures of PST all demonstrated acceptable inter-session reliability. The standard error of measurement and minimum detectable change results can be used to determine if a change in measures of PST are due to measurement error or an actual change over time.Peer reviewe