Healthy ageing - Adults with intellectual disabilities: Physical health issues

This report has been prepared by the Ageing Special Interest Research Group of the International Association for the Scientific Study of Intellectual Disabilities (IASSID) in collaboration with the Department of Mental Health and Substance Dependence and the Programme on Ageing and Health, World Health Organization (WHO), Geneva, Switzerland, and all rights are reserved by the above mentioned organization. The document may, however, be freely reviewed, abstracted, reproduced or translated in part, but not for sale or use in conjunction with commercial purposes. It may also be reproduced in full by non-commercial entities for information or for educational purposes with prior permission from WHO/IASSID. The document is likely to be available in other languages also.

Genetic and physical interactions between Microphthalmia transcription factor and PU.1 are necessary for osteoclast gene expression and differentiation

The microphthalmia transcription factor (MITF), a basic-helix-loop-helix zipper factor, regulates distinct target genes in several cell types. We hypothesized that interaction with the Ets family factor PU.1, whose expression is limited to hematopoietic cells, might be necessary for activation of target genes like tartrate-resistant acid phosphatase (TRAP) in osteoclasts. Several lines of evidence were consistent with this model. The combination of MITF and PU.1 synergistically activated the TRAP promoter in transient assays. This activation was dependent on intact binding sites for both factors in the TRAP promoter. MITF and PU.1 physically interacted when coexpressed in COS cells or in vitro when purified recombinant proteins were studied. The minimal regions of MITF and PU.1 required for the interaction were the basic-helix-loop-helix zipper domain and the Ets DNA binding domain, respectively. Significantly, mice heterozygous for both the mutant mi allele and a PU.1 null allele developed osteopetrosis early in life which resolved with age. The size and number of osteoclasts were not altered in the double heterozygous mutant mice, indicating that the defect lies in mature osteoclast function. Taken in total, the results afford an example of how lineage-specific gene regulation can be achieved by the combinatorial action of two broadly expressed transcription factors.

Energy cost of physical activity in cystic fibrosis

Objective: The purpose of this study was to compare the energy cost of standardized physical activity (ECA) between patients with cystic fibrosis (CF) and healthy control subjects. Design: Cross-sectional study using patients with CF and volunteers from the community. Setting: University laboratory. Subjects: Fifteen patients (age 24.6 +/- 4.6 y) recruited with consent from their treating physician and 16 healthy control subjects (age 25.3 +/- 3.2) recruited via local advertisement. Interventions. Patients and controls walked on a computerised treadmill at 1.5 km/h for 60 min followed by a 60 min recovery period and, on a second occasion, cycled at 0.5 kp (kilopond), 30 rpm followed by a 60 min recovery. The ECA was measured via indirect calorimetry. Resting energy expenditure (REE), nutritional status, pulmonary function and genotype were determined. Results: The REE in patients was significantly greater than the REE measured in controls (P = 0.03) and was not related to the severity of lung disease or genotype. There was a significant difference between groups when comparing the ECA for walking kg root FFM (P = 0.001) and cycling kg root FFM (P = 0.04). The ECA for each activity was adjusted (ECA(adj)) for the contribution of REE (ECA kJ kg root FFM 120 min(-1) - REE kJ kg root FFM 120 min(-1)). ECA(adj) revealed a significant difference between groups for the walking protocol (P = 0.001) but no difference for the cycling protocol (P = 0.45). This finding may be related to the fact that the work rate during walking was more highly regulated than during cycling. Conclusions ECA in CF is increased and is likely to be explained by an additional energy-requiring component related to the exercise itself and not an increased REE. Sponsorship. The Prince Charles Hospital Foundation; MLR was in receipt of a QUTPRA Scholarship.

Interferon-gamma enhances cytotoxic T lymphocyte recognition of endogenous peptide in keratinocytes without lowering the requirement for surface peptide

Keratinocytes expressing the human papillomavirus (HPV) type 16 E7 protein, as a transgene driven by the K14 promoter, form a murine model of HPV-mediated epithelial cancers in humans. Our previous studies have shown that K14E7 transgenic skin grafts onto syngeneic mice are not susceptible to immune destruction despite the demonstrated presence of a strong, systemic CTL response directed against the E7 protein. Consistent with this finding, we now show that cultured, E7 transgenic keratinocytes (KC) express comparable endogenous levels of E7 protein to a range of CTL-sensitive E7-expressing cell lines but are not susceptible to CTL-mediated lysis in vitro . E7 transgenic and non-transgenic KC are susceptible to conventional mechanisms of CTL-mediated lysis, including perforin and Fas/FasL interaction when an excess of exogenous peptide is provided. The concentration of exogenous peptide required to render a cell susceptible to lysis was similar between KC and other conventional CTL targets (e.g. EL-4), despite large differences in H-2D(b) expression at the cell surface. Furthermore, exposure of KC to IFN-gamma increased H-2D(b) expression, but did not substantially alter the exogenous peptide concentration required to sensitize cells for half maximal lysis. In contrast, the lytic sensitivity of transgenic KC expressing endogenous E7 is modestly improved by exposure to IFN-gamma. Thus, failure of CTL to eliminate KC expressing endogenous E7, and by inference squamous tumours expressing E7, may reflect the need for a sustained, local inflammatory environment during the immune effector phase.

Complementation analysis of the flavivirus Kunjin NS3 and NS5 proteins defines the minimal regions essential for formation of a replication complex and shows a requirement of NS3 in cis for virus assembly

We have previously reported successful trans-complementation of defective Kunjin virus genomic RNAs with a range of large lethal deletions in the nonstructural genes NSI, NS3, and NS5 (A. A. Khromykh et al., J. Virol. 74:3253-3263, 2000). In this study we have mapped further the minimal region in the NS5 gene essential for efficient trans-complementation of genome-length RNAs in repBHK cells to the first 316 of the 905 codons. To allow amplification and easy detection of complemented defective RNAs with deletions apparently affecting virus assembly, we have developed a dual replicon complementation system. In this system defective replicon RNAs with a deletion(s) in the nonstructural genes also encoded the puromycin resistance gene (PAC gene) and the reporter gene for beta-galactosidase (beta-Gal). Complementation of these defective replicon RNAs in repBHK cells resulted in expression of PAC and beta-Gal which allowed establishment of cell lines stably producing replicating defective RNAs by selection with puromycin and comparison of replication efficiencies of complemented defective RNAs by beta-Gal assay. Using this system we demonstrated that deletions in the C-terminal 434 codons of NS3 (codons 178 to 611) were complemented for RNA replication, while any deletions in the first 178 codons were not. None of the genome-length RNAs containing deletions in NS3 shown to be complementable for RNA replication produced secreted defective viruses during complementation in repBHK cells. In contrast, structural proteins produced from these complemented defective RNAs were able to package helper replicon RNA. The results define minimal regions in the NS3 and NS5 genes essential for the formation of complementable replication complex and show a requirement of NS3 in cis for virus assembly.

Energy intake and energy expenditure in elite lightweight female rowers

Purpose: The training program undertaken by many athletes will affect directly the total, habitual energy requirements of that individual. Unless that energy requirement is met via the diet and or supplementation, chronic negative energy balance will ensue, which will have both short-term and long-term effects not only on performance but also on general health. The aim of this research was therefore to determine the energy expenditure (EE) and hence energy requirements of lightweight female rowers and, further, to compare this with their self-reported energy intake (EI). Methods: The El of seven lightweight female rowers was measured using a self-reported 4-d weighed dietary record. EE was determined using the doubly labeled water (DLW) technique over a 14-d period. Results: The mean (+/-SD) age, height, and weight of the subjects was 20 (+/-1.1) yr, 168.8 (+/-4.7) cm, and 60.9 (+/-23) kg, respectively. The rowers self-reported El was 2214 (+/-313) kcal.d(-1) and their total EE was 3957 (+/-1219) kcal.d(-1). After adjusting total EE for changes in body weight (mean (+/-SD) - 1.2 (+/-1.2) kg), the comparison between adjusted El and reported showed a bias to underreporting of 1133 (+/-1539) kcal.d(-1) or 34%. The bias was not consistent across adjusted El, and two of the seven subjects overreported their intake. Conclusions: Due to the underreporting of EI, diet recording may not be an appropriate way of assessing energy requirements in lightweight female rowers. A benefit of accurately determining energy requirements, as with DLW, is that female lightweight rowers will be able to successfully manipulate their EI and achieve the set weight cut-off for participation without compromising their health or performance.

The influence of cis/trans isomerism on the physical properties of a cyano-bridged dinuclear mixed valence complex

The cyano-bridged complexes cis-[L14CoIIINCFeII(CN)5]– and cis-[L14CoIIINCFeIII(CN)5] (L14= 6-methyl-1,4,8,11-tetraazacyclotetradecan-6-amine) are prepared and characterised spectroscopically, electrochemically and structurally: Na{cis-[L14CoIIINCFeII(CN)5]}·9H2O, monoclinic space group P21/c, a= 14.758(3), b= 10.496(1), c= 19.359(3) , = 92.00(2)°, Z= 4; cis-[L14CoIIINCFeIII(CN)5]·4H2O, orthorhombic space group P212121, a= 9.492(1), b= 14.709(2), c= 18.760(3) , Z= 4. In both complexes, the pendant amine is cis to the bridging cyanide ligand. An analysis of the metal-to-metal charge transfer (MMCT) transition in these systems with Hush theory has been carried out. This has revealed that the change in the configuration of the macrocycle both decreases the redox isomer energy difference (E1/2) and increases the reorganisational energy () of the cis-[L14CoIIINCFeII(CN)5]– complex with respect to the trans-[L14CoIIINCFeII(CN)5]– complex, the result being that both isomers display an MMCT transition of similar energy. The variation in redox isomer energy differences of the configurational isomers has been related to strain energy differences by molecular mechanics analysis of the [CoL14Cl]2+/+ precursor complexes.

Child welfare workers' use of theory in working with physical child abuse: Implications for professional supervision

This article examines child welfare workers' understanding of physical child abuse and the Implications for those supervising these workers. The article Is based on the results of a study that involved In-depth Interviews and focus groups with statutory child welfare workers. Analysis revealed that workers' understanding of physical child abuse embodied a wide range of ideas that were generally consistent with existing literature. The study highlights the value and utility of a reflective approach In stimulating and making explicit the theoretical underpinnings of child welfare workers practice. Specific Implications for professional supervision are addressed.

Physical aging of amorphous fructose

Physical aging of amorphous anhydrous fructose at temperature 5 degreesC and at 22 degreesC was studied using differential scanning calorimetry (DSC). The dynamic glass transitions temperature, T-g0 for unaged samples was 16 degreesC and 13.3 degreesC for heating rate of 10 degreesC/min and 1 degreesC/min, respectively. The fictive temperature, T-f0 for unaged samples calculated by Richardson and Savill method was 12 degreesC, which is close to the dynamic value obtained from the lower DSC heating rate. The fictive temperature T-f of the aged fructose glasses at temperatures both below and above the transition region was fitted well by a non-exponential decay function (Williams-Watts form). Aging above the transition region (22 degreesC) for 18 d increased both the dynamic glass transition temperature T and the fictive temperature T-f. However, aging below the transition region (5 degreesC) for I d increased the dynamic glass transition temperature T-g but decreased the fictive temperature T-f.

Up close and personal on physical education teachers' identity: Is conflict an issue?

Much of the research on teachers' work is informed by role theory, that assumes teachers' identity is largely ascribed. When there are inconsistencies in teachers' and others' expectations for different occupational roles such as physical education teacher and sports coach, 'role conflict' is said to occur. This stud), sought to investigate if role conflict was a major concern for Australian physical education teacher/coaches. Findings, informed by case studies with five teacher/coaches, challenge the assumption that moving between professional responsibilities causes role conflict. Rather, in moving across contexts, the physical education teachers managed inconsistencies in ways that resulted in positive and rawarding work experiences.