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Objectives Patients with inflammatory arthritis (IA) have a high risk of sleep disturbances and disorders. The objective was to evaluate the evidence of non-pharmacological interventions targeting sleep disturbances or disorders in patients with IA. Methods A systematic search was undertaken from inception to September 8th, 2020. We included randomized trials concerning non-pharmacological interventions applied in adults with IA and concomitant sleep disturbances or disorders. Primary outcome was the sleep domain while secondary outcomes were core outcome domains for IA trials and harms. The Cochrane Risk of Bias tool was applied, and the overall quality of the evidence was assessed using GRADE. Effect sizes for continuous outcomes were based on the standardized mean difference, combined using random-effects meta-analysis. Results Six trials (308 patients) were included in the quantitative synthesis; three of these reported improvement in sleep in favor of the non-pharmacological intervention(s). The meta-analysis of the sleep domains indicated a large clinical effect of -0.80 (95 -1.33 to -0.28) in favor of non-pharmacological interventions targeting sleep disturbances or disorders. The estimate was rated down twice for risk of bias, and unexplained inconsistency; this was assessed as corresponding to low quality evidence. None of the secondary core outcomes used in contemporary IA trials indicated clinical benefit in favor of non-pharmacological interventions targeting sleep. Conclusion Non-pharmacological interventions targeting sleep disturbances/disorders in patients with IA indicated a promising effect on sleep outcomes, but not yet with convincing evidence. ObjectivesPatients with inflammatory arthritis (IA) have a high risk of sleep disturbances and disorders. The objective was to evaluate the evidence of non-pharmacological interventions targeting sleep disturbances or disorders in patients with IA.MethodsA systematic search was undertaken from inception to September 8th, 2020. We included randomized trials concerning non-pharmacological interventions applied in adults with IA and concomitant sleep disturbances or disorders. Primary outcome was the sleep domain while secondary outcomes were core outcome domains for IA trials and harms. The Cochrane Risk of Bias tool was applied, and the overall quality of the evidence was assessed using GRADE. Effect sizes for continuous outcomes were based on the standardized mean difference, combined using random-effects meta-analysis.ResultsSix trials (308 patients) were included in the quantitative synthesis; three of these reported improvement in sleep in favor of the non-pharmacological intervention(s). The meta-analysis of the sleep domains indicated a large clinical effect of -0.80 (95% CI, -1.33 to -0.28) in favor of non-pharmacological interventions targeting sleep disturbances or disorders. The estimate was rated down twice for risk of bias, and unexplained inconsistency; this was assessed as corresponding to low quality evidence. None of the secondary core outcomes used in contemporary IA trials indicated clinical benefit in favor of non-pharmacological interventions targeting sleep.ConclusionNon-pharmacological interventions targeting sleep disturbances/disorders in patients with IA indicated a promising effect on sleep outcomes, but not yet with convincing evidence.

The non-pharmacological treatment of osteoarthritis (OA) includes exercise therapy; however, little is known about the specific effect of exercise on the joint per se. The purpose of the present study was to investigate the direct effects of a load-bearing exercise upon cartilage in a single, human osteoarthritic joint determined by biochemical markers of cartilage turnover and inflammation in the synovial fluid (SF), serum and urine. Eleven subjects with OA of the knee(s), but with no other joint- or inflammatory disorders, volunteered for the study and had samples of blood, urine and synovial fluid drawn both at baseline and following 30-min one-legged knee-extension exercise. Workload: 60% of 1 RM (Repetition Maximum). Determination of cartilage oligomeric matrix protein (COMP), aggrecan, C-terminal collagen II peptide (CTX-II) and interleukin (IL)-6 were performed in synovial fluid (SF), serum and urine. A significant decrease was found in SF concentration of COMP following exercise, whereas aggrecan, CTX-II and IL-6 remained unchanged. No differences in any of the tested markers were found in serum and urine between baseline and post-exercise. Thirty minutes of mechanical loading of a single knee joint in human subjects with knee OA resulted in a reduced COMP concentration in SF.

This book is concerned with the 2008 Quality Procedures survey on quality assurance agencies within the European Higher Education Area (EHEA). Undertaken by the European Association for Quality Assurance in Higher Education (ENQA), it collates and analyses responses from 51 agencies and related bodies, and provides an update on a similar survey undertaken in 2002. The initial chapter identifies the responding agencies, their countries and their ENQA status, and the extent of their remits. Most but not all agencies work within a national remit but a few also have international ones as well. Remits vary from those covering only one type of institution to those with a far wider range of responsibilities, often encompassing essentially all higher education provision, and in some cases various support services as well. The ‘ level’ at which quality assurance responsibilities are held shows some interesting patterns ; in about half of the cases the institutions are responsible for approval of new subject areas, but when it comes to programmes the role of the relevant QA agency rises markedly. Approval of new institutions is typically done by central or regional government, but not in all cases. Chapter 2 provides details on the status, structures, activities and resources of the QA agencies. It pays particular attention to those issues covered by Part 3 of the European Standards and Guidelines (ESG), and is of interest regarding criteria that are also used for ENQA membership. The analysis and commentary acknowledge that there can be a strained relationship between national traditions, legislation and the ESG. The responses illustrate that almost all agencies are formally recognised, either under a specific law (most) or by public authorities. The number of agencies within a country varies ; in most cases there is a single agency, but regional and other dimensions can result in there being multiple agencies within a country. The analysis of the types of activities covered by agencies shows that, whilst two-thirds of agencies use programme level procedures, just less than half work at institutional level. Some agencies cover both. QA procedures are generally undertaken on a cyclical rather than one-off basis, and generally result in formal consequences. One of the significant sets of responses in this part of the survey indicates that, within a five year period, three-quarters of the agencies have undertaken or are undertaking change, or planning changes to their procedures. Data on staffing, funding and other resources provide an interesting snap-shot of generally adequate provision, but also illustrate some constraints under which agencies are working. The third and most extensive chapter is concerned with structure(s), functions, decision making and methodological approaches to external quality assurance. A very rich source of data illustrates the increasing extent to which stakeholders are now involved within agency structures, although the main functions of agencies (external quality assurance and improvement, and dissemination of information about quality) remain much the same as in 2003. Agencies have however taken on, or become involved in, a wider range of additional functions, particularly in relation to the development of the Bologna Process. One interesting finding is that the 4-stage theoretical model of quality assurance, presented in an annex of the ESG, is applied by most but not all of the responding agencies. Within the details of what is examined during the external evaluations, research strategies and assessment ranked highly, but a surprising 20% of agencies indicated that they do not include institutions’ assessments of students in their evaluations. A variety of mechanisms is used by agencies to look at their own internal quality assurance procedures with, as might be expected, the more developed agencies having a wider range of measures than those established more recently. Chapter 4 provides further evidence that builds upon important aspects coming from Chapter 3. It describes and discusses a number of critical areas relating to the division of responsibilities within the methodological frameworks and procedures used by agencies. It reports on: the membership of external panels [there is clear evidence of an increase in student membership but a (corresponding?) decrease in the direct involvement of agency staff on panels)] ; the training of panels ; the responsibilities exercised in determining what QA method(s) will be applied (mostly the agency’ s) and the writing of reports (mostly the panel’ s). Legal regulations provide a reference frame for many agencies in determining their methodologies, but there are other important factors as well. An interesting comparison with the 2003 survey may be drawn from the now wider availability and use of ‘ specific criteria and standards’ for QA. The quality assurance of collaborative provision between (providing) institutions (including trans-national delivery) was not covered in 2003 ; the data provided here may act as a baseline for future comparisons in an area that is becoming of increasing importance. Chapter 5 focuses on just one critical aspect of QA – site visits, and the preparatory work undertaken before them. Evidence suggests that the development of the self-evaluation reports is done by institutions in much the same way as in 2003 ; sources for data collection are much as might be expected and the people and panels interviewed much as in 2003. The site visits themselves are generally, but not always, accompanied by agency staff, and whilst averages can be distorting it was perhaps interesting to see that site visits for institutional evaluations are only one day longer than those for programme evaluations. Class room observations were used in a small proportion of methodologies / cases only. The sixth chapter covers the extent to which, and the ways in which, the outcomes of the QA procedures are reported. Most agencies provide public reports on their evaluations, with those that do not yet do so are planning to. The majority of reports, which include data analyses, recommendations, and conclusions, are subject to some form of ‘ consultation’ with the institution before final publication. It is usually the agency that published the report, with the number of reports published clearly depending on the size of an agency’ s ‘ jurisdiction’ and whether it is involved in only institutional evaluation or programme evaluations, when the number of reports rises considerably, or both. This is followed in Chapter 7, as in any typical QA methodology, by consideration of follow-up procedures after any judgements and recommendations have been made. Various responsibilities lie with both agencies and institutions, and there are a range of actions that can be asked for or required of institutions. Some preliminary thoughts about possible future developments are covered briefly in the penultimate chapter. Revisions to external QA procedures figure highly in the responses, as does the development of national qualifications frameworks. Almost all agencies have undergone, are undergoing, or are planning to undergo an external evaluation themselves, although a small proportion do not, as yet, intend to apply for membership of the European Quality Assurance Register (EQAR). The final chapter aims to summarise the key findings not in a repetitive way but by seeking to provide interesting insights into similarities and differences through cross referring detailed findings and discussion points that have arisen from various parts of the survey.

Insulin-like growth factor-II mRNA-binding proteins 1, 2 and 3 (IMP1, IMP2 and IMP3) belong to a family of RNA-binding proteins implicated in mRNA localization, turnover and translational control. We examined their expression pattern during development of murine and human testis and ovaries. In the mouse, IMPs were expressed in male and female gonadal cells at embryonic day 12.5 (E12.5). From E16.5, IMP1 and IMP3 became restricted to the developing germ cells, whereas IMP2 expression persisted in the interstitial cells. In mature mouse and human ovaries, IMP1, IMP2 and IMP3 were detected in resting and growing oocytes and in the granulosa cells. In testis, IMP1 and IMP3 were found mainly in the spermatogonia, whereas IMP2 was expressed in the immature Leydig cells. Moreover, all three IMPs were detected in human semen. The developmental expression pattern of IMP1 and IMP3 in the human testis prompted us to examine their possible involvement in testicular neoplasia. IMPs were detected primarily in germ-cell neoplasms, including preinvasive testicular carcinomain situ, classical and spermatocytic seminoma, and nonseminomas, with particularly high expression in undifferentiated embryonal carcinoma. The relative expression of IMP1, IMP2 and IMP3 varied among tumor types and only IMP1 was detected in all carcinomain situcells. Thus IMPs, and in particular IMP1, may be useful auxiliary markers of testicular neoplasia.

The expression of the gene for vasoactive intestinal polypeptide (VIP) and peptide histidine methionine (PHM) in the human gastrointestinal tract was studied by in situ hybridization and Northern blotting for PHM/ VIP mRNA and immunocytochemistry using specific antisera against the bioactive peptides PHM and VIP. In the colon sigmoideum, antisera against all five putative processing products of the VIP precursor (prepro-VIP) were used, namely prepro-VIP 22–79, PHM, prepro-VIP 111–122, VIP and prepro-VIP 156–170. Furthermore, RNA extracted from various regions of the gastrointestinal tract was examined by Northern blots and hybridization to a VIP-cDNA probe. Throughout the gastrointestinal tract, PHM/VIP mRNA was found in neurons only. Using single-or double-staining methods, we demonstrated both PHM/VIP mRNA and the corresponding peptides PHM and VIP in the neurons. In the sigmoideum, the single-staining methods were extended to investigate whether the neurons simultaneously contained PHM/VIP mRNA and each of the five prepro-VIP-derived peptides. Only one major band of PHM/VIP mRNA (1.9 kb) was found by Northern blotting in the tissue of the gastrointestinal tract.

The effect of vasoactive intestinal polypeptide on vaginal blood flow was investigated in postmenopausal women. In women who were receiving hormonal replacement therapy the vasodilatory response induced by vasoactive intestinal polypeptide was identical to that of young women, whereas in postmenopausal women who were receiving no replacement therapy, the response induced by vasoactive intestinal polypeptide was absent. Plasma levels of vasoactive intestinal polypeptide and systemic cardiovascular effects were identical in the two groups.