Physical activity and health characteristics : a survey among Dutch elderly women and men

To study physical activity of elderly people and its relationship with health characteristics, a cross-sectional study was conducted in 1991/1992 in Arnhem, the Netherlands, among 515 women and 497 men, aged 65 to 85 years. Habitual physical activity was assessed with a questionnaire, previously validated for elderly, and including questions on household activities, sports and other physically active leisure time activities like walking, bicycling and gardening. Health characteristics were assessed by interview (reported disability, chronic diseases, perceived health and respiratory complaints) and physical examination (anthropometry, blood pressure measurements, electrocardiography, and spirometry).Light housework was carried out by 90% of the women and 61% of the men. 87% of the women and 91% of the men were involved in sports or other physically active leisure time activities. Physical activity (including household activities) is related to favorable health characteristics e.g. absence of disability and chronic diseases, and high subjective health in both women and men. Only in men it is as well associated with high heart rate variability, high forced vital capacity and high forced expiratory volume in one second. Performance of household activities might be regarded as an indicator of independence. We found non-performers to be characterized by high age, high socio-economic status, unfavorable reported health, and living with someone else, the latter only for men.Our findings suggest that physically inactive elderly are in general characterized by older age and a less favorable health. From this cross-sectional study it is not clear whether physical activity may positively affect health, or the reverse or whether both effects are present. Independence, represented by performance of household activities, probably is primarily influenced by health. Longitudinal studies are needed to clarify the direction of causal pathways. For reasons of maintaining health, well- being and independence, we recommend promotion of physical activity in old age. In addition we suggest to stimulate independence of men by training them in preparing cooked meals and doing other traditionally "female" housework

An analysis of the proteolytic system in Aspergillus in order to improve protein production

The filamentous fungus Aspergillus niger is capable of producing and secreting large amounts of homologous proteins (2040 g/l; Montenecourt and Eveleigh, 1985; Nevalainen et al., 1991). Because of this very efficient secretion large effort is being made to use Aspergilli as hosts for expression of many heterologous products. Especially A. niger is an interesting option because of the very high secretion capacity and because it has GRAS (Generally Regarded As Safe) status, which enables food-grade applications. Unfortunately, in spite of the very high expression and secretion capacity of A. niger , it has been shown both in homologous and heterologous expression studies that overexpression of gene products is often hampered by homologous proteases. The Aspergillus expression strains produce several proteases which cause partial or complete degradation of target products. In order to study these protease-related problems and to construct Aspergillus strains in which proteolytic degradation is decreased or absent, the protease project was started. The results of these elaborate studies to improve protein production in relation to proteolytic degradation are presented in this thesis.Aspergillus strains express many different proteolytic activities as discussed in the introduction (chapter I). Therefore, the protease spectra of A.nidulans and A. niger have been characterized (chapter III). The very different protease spectra, the differences in acidification of the growth medium and glycosylation of the proteins produced, caused large differences in expression yields, stability and activities of the expressed products. This clearly proved the importance of the choice of expression strain for heterologous expression. Many different proteolytic activities, comprising acid, semi-alkaline and alkaline proteases and serine carboxpeptidases, have been isolated from A. niger . Some of these activities were cloned ( pep A; Berka et al., 1990; pep B, Inoue et al., 1991 and pep C, Frederick et al., 1993) at the beginning of the protease project in which five additional A. niger protease genes were cloned, pep D, pep E, pep F, pep H and pal B (van den Hombergh et al., unpublished results). In chapter IV the cloning of a pepstatin-repressible intracellular acid protease, pep E, is described. The PEPE protein is probably located in the vacuole and involved in the cascade activation of two additional vacuolar proteolytic enzymes (PEPC and CPY, carboxypeptidase Y). After cloning and characterization of pep F an extracellular serine carboxypeptidase it was shown that this extracellular exo-protease was regulated in a very complex manner (chapter V). Both carbon catabolite repression and nitrogen metabolite repression are involved in the regulation of pep F at the level of mRNA amounts. Furthermore, pathway specific induction by protein and regulation by external pH have been described. Additionally, an extracellular metallo protease, pep H, was cloned from A.niger. This endo-protease was cloned after the observation that in the residual activities of some isolated protease ( prt ) mutants, metallo protease activities were still present (see also chapter VIII). Cloning of the responsible gene(s) and subsequent disruption enables specific strain improvement of these protease mutants. Gene disruption of the three cloned acid proteases (two extracellular ( pep A and pep B) and one intracellular ( pep E), resulted in a significant reduction of degradation of 'a-specific' proteins (chapter VII). Also, for specific tester-proteins such as PELB a similar reduced in vitro degradation was observed. Furthermore, it was shown that disruption of pep E inactivated the cascade activation of Pro-PEPC and Pro-CPY, resulting in a strongly reduced vacuolar proteolytic activity. Besides generating specific gene disruptions, a large number of protease ( prt ) deficient mutants were isolated (chapter VIII). Classical genetic analyses of the prt mutants identified at least seven complementation groups ( prt A-G). Residual activities in some of these prt mutants varied from 2-80 % compared to wild type and in vitro degradation of tester proteins was reduced 500-1000 fold in some of these mutants. Construction of multiple prt deficient mutants, either by recombination of characterized mutations or by additional mutagenesis in existing prt mutants, resulted in further reduction of degradation. For six prt complementation groups transformable strains were constructed and subsequently expression of a pkipel B expression-secretion cassette was studied (chapter IX). These experiments proved that in vivo degradation of PELB was also significantly reduced and overall expression yields were improved. The highest expression was observed in the prt F28 mutant and the overall expression was improved by a factor of 13 compared to expression in wild type. The regulation of several proteases in A. niger is very complex, as already mentioned in chapters I, IV, V and VI. The observed pH regulation of several extracellular proteases combined with the fact that A. niger acidifies its medium very rapidly, initiated analysis of pH regulation which finally resulted in the isolation of the wide domain pH regulatory gene, pac C, in A.niger (chapter X). The pac C gene encodes a zinc-finger regulator protein which binds to specific sequences (5'-GCCA/GG-3') in the promoters of target genes. A disruption construct, designed in a way that upon integration at the homologous pac C locus a C-terminally truncated PacC protein is produced, resulted in constitutive expression of pac C (chapter XI). From expression studies with this pac 2C cdisruptant it was concluded that the pac C gene is auto-regulated and that the C-terminal part of PacC (deleted in the pac 2C cstrain) has a negative regulatory effect. Expression of several phosphatases identified at least three acid phosphatases (PI, PII and PIII) which are regulated both by phosphate and by pH. The observed pH regulatory effects were shown to be pac C mediated, as expression of PI, PII and PIII decreased severely in the pac 2C cdisruptant. The recent isolation of both cre A and are A mutants in A. niger combined with the construction of a pac 2C cdisruption strain enabled a detailed analysis of protease expression at the level of mRNA content (chapter XII). Northern analyses using the wide domain regulatory mutants and disruptant proved that the observed regulatory effects for extracellular proteases (carbon catabolite repression, nitrogen metabolite repression and pH regulation) were indeed mediated by the cre A, are A and pac C genes, respectively. Apart from identification of severe cre A and are A alleles and the expected derepression phenomena for carbon catabolite repression and nitrogen metabolite repession of extracellular protease, also elevated mRNA levels for the vacuolar proteases were observed. Possibly, the derepressed strains need higher degradation capacities in order to remove the increased levels of damaged or unwanted protein. Furthermore, in the pac 2C cdisruption strain the expression of the extracellular acid proteases is increased upon transfer to alkaline pH. As the current model for pH regulation predicts a strong reduced expression for acid target genes in pac C cstrains, this observation could imply that for acid pH regulation not all the components involved have been identified.A. nidulans has a very different protease spectrum compared to A. niger (chapter III). However, although the pH optimum for degradation of 'a-specific' proteins is much higher than for A. niger , A.nidulans can also express an acid protease gene, pep A, which is probably regulated in a similar complex way as described for the A.niger extracellular proteases (chapter XIII). Cloning and characterization of two novel metallo protease genes, pep I and pep J , from A.nidulans is described in chapter XIV. These two metallo proteases appear (together with the A.oryzae neutral protease II, the A.fumigatus and A.flavus mp20 and the P. citrinum neutral metallo protease) to belong to a novel class of metallo proteases, as no significant homologies with any of the known metallo protease families can be detected. As the metallo protease genes are expressed in A.nidulans and metallo proteases in general have neutral pH optima, these metallo proteases could well be involved in the overall degradation of expressed heterologous proteins, which is also observed in A.nidulans. Disruption of these metallo proteases together with the major extracellular serine protease could be a starting point for construction of A.nidulans expression strains with reduced proteolytic activities

High workload and job stress are associated with lower practice performance in general practice: an observational study in 239 general practices in the Netherlands

Contains fulltext : 80493.pdf (publisher's version ) (Open Access)BACKGROUND: The impact of high physician workload and job stress on quality and outcomes of healthcare delivery is not clear. Our study explored whether high workload and job stress were associated with lower performance in general practices in the Netherlands. METHODS: Secondary analysis of data from 239 general practices, collected in practice visits between 2003 to 2006 in the Netherlands using a comprehensive set of measures of practice management. Data were collected by a practice visitor, a trained non-physician observer using patients questionnaires, doctors and staff. For this study we selected five measures of practice performance as outcomes and six measures of GP workload and job stress as predictors. A total of 79 indicators were used out of the 303 available indicators. Random coefficient regression models were applied to examine associations. RESULTS AND DISCUSSION: Workload and job stress are associated with practice performance.Workload: Working more hours as a GP was associated with more positive patient experiences of accessibility and availability (b = 0.16). After list size adjustment, practices with more GP-time per patient scored higher on GP care (b = 0.45). When GPs provided more than 20 hours per week per 1000 patients, patients scored over 80% on the Europep questionnaire for quality of GP care.Job stress: High GP job stress was associated with lower accessibility and availability (b = 0.21) and insufficient practice management (b = 0.25). Higher GP commitment and more satisfaction with the job was associated with more prevention and disease management (b = 0.35). CONCLUSION: Providing more time in the practice, and more time per patient and experiencing less job stress are all associated with perceptions by patients of better care and better practice performance. Workload and job stress should be assessed by using list size adjusted data in order to realise better quality of care. Organisational development using this kind of data feedback could benefit both patients and GP

Can we import quality tools? a feasibility study of European practice assessment in a country with less organised general practice

<p>Abstract</p> <p>Background</p> <p>Quality is on the agenda of European general practice (GP). European researchers have, in collaboration, developed tools to assess quality of GPs. In this feasibility study, we tested the European Practice Assessment (EPA) in a one-off project in Belgium, where general practice has a low level of GP organisation.</p> <p>Methods</p> <p>A framework for feasibility analysis included describing the recruiting of participants, a brief telephone study survey among non-responders, organisational and logistic problems. Using field notes and focus groups, we studied the participants' opinions.</p> <p>Results</p> <p>In this study, only 36 of 1000 invited practices agreed to participate. Co-ordination, administrative work, practice visits and organisational problems required several days per practice. The researchers further encountered technical problems, for instance when entering the data and uploading to the web-based server. In subsequent qualitative analysis using two focus groups, most participant GPs expressed a positive feeling after the EPA procedure. In the short period of follow-up, only a few GPs reported improvements after the visit. The participant GPs suggested that follow-up and coaching would probably facilitate the implementation of changes.</p> <p>Conclusion</p> <p>This feasibility study shows that prior interest in EPA is low in the GP community. We encountered a number of logistic and organisational problems. It proved attractive to participants, but it can be augmented by coaching of participants in more than a one-off project to identify and achieve targets for quality improvement. In the absence of commitment of the government, a network of universities and one scientific organisation will offer EPA as a service to training practices.</p

Gender shift in realisation of preferred type of gp practice: longitudinal survey over the last 25 years

<p>Abstract</p> <p>Background</p> <p>An increasing number of newly trained Dutch GPs prefer to work in a group practice and as a non-principal rather than in a single-handed practice. In view of the greater number of female doctors, changing practice preferences, and discussions on future workforce problems, the question is whether male and female GPs were able to realise their initial preferences in the past and will be able to do so in the future.</p> <p>Methods</p> <p>We have conducted longitudinal cohort study of all GPs in the Netherlands seeking a practice between 1980 and 2004. The Netherlands Institute of Health Services Research (NIVEL) in Utrecht collected the data used in this study by means of a postal questionnaire. The overall mean response rate was 94%.</p> <p>Results</p> <p>Over the past 20 years, an increasing proportion of GPs, both male and female, were able to achieve their preference for working in a group practice and/or in a non-principal position. Relatively more women than men have settled in group practices, and more men than women in single-handed practices; however, the practice preference of men and women is beginning to converge. Dropout was highest among the GPs without any specific practice preference.</p> <p>Conclusion</p> <p>The overwhelming preference of male and female GPs for working in group practices is apparently being met by the number of positions (principal or non-principal) available in group practices. The preference of male and female GPs regarding the type of practice and job conditions is expected to converge further in the near future.</p