Low frequency of CHEK2 1100delC allele in Australian multiple-case breast cancer families: functional analysis in heterozygous individuals

A protein-truncating variant of CHEK2, 1100delC, is associated with a moderate increase in breast cancer risk. We have determined the prevalence of this allele in index cases from 300 Australian multiple-case breast cancer families, 95% of which had been found to be negative for mutations in BRCA1 and BRCA2. Only two (0.6%) index cases heterozygous for the CHEK2 mutation were identified. All available relatives in these two families were genotyped, but there was no evidence of co-segregation between the CHEK2 variant and breast cancer. Lymphoblastoid cell lines established from a heterozygous carrier contained approximately 20% of the CHEK2 1100delC mRNA relative to wild-type CHEK2 transcript. However, no truncated CHK2 protein was detectable. Analyses of expression and phosphorylation of wild-type CHK2 suggest that the variant is likely to act by haploinsufficiency. Analysis of CDC25A degradation, a downstream target of CHK2, suggests that some compensation occurs to allow normal degradation of CDC25A. Such compensation of the 1100delC defect in CHEK2 might explain the rather low breast cancer risk associated with the CHEK2 variant, compared to that associated with truncating mutations in BRCA1 or BRCA2.

Global standard for the composition of infant formula: Recommendations of an ESPGHAN coordinated international expert group

The Codex Alimentarius Commission of the Food and Agriculture Organization of the United Nations (FAO) and the World Health Organization (WHO) develops food standards, guidelines and related texts for protecting consumer health and ensuring fair trade practices globally. The major part of the world's population lives in more than 160 countries that are members of the Codex Alimentarius. The Codex Standard on Infant Formula was adopted in 1981 based on scientific knowledge available in the 1970s and is currently being revised. As part of this process, the Codex Committee on Nutrition and Foods for Special Dietary Uses asked the ESPGHAN Committee on Nutrition to initiate a consultation process with the international scientific community to provide a proposal on nutrient levels in infant formulae, based on scientific analysis and taking into account existing scientific reports on the subject. ESPGHAN accepted the request and, in collaboration with its sister societies in the Federation of International Societies on Pediatric Gastroenterology, Hepatology and Nutrition, invited highly qualified experts in the area of infant nutrition to form an International Expert Group (IEG) to review the issues raised. The group arrived at recommendations on the compositional requirements for a global infant formula standard which are reported here.

Arousal and re-feeding rapidly restores digestive tract morphology following aestivation in green-striped burrowing frogs

During aestivation, the gut of the green-striped burrowing frog, Cyclorana alboguttata undergoes significant morphological down-regulation. Despite the potential impact such changes might have on the re-feeding efficiency of these animals following aestivation, they appear to be as efficient at digesting their first meals as active, non-aestivating animals. Such efficiency might come about by the rapid restoration of intestinal morphology with both arousal from aestivation and the initial stages of re-feeding. Consequently, this study sought to determine what morphological changes to the intestine accompany arousal and re-feeding following 3 months of aestivation. Arousal from aestivation alone had a marked impact on many morphological parameters, including small and large intestine masses, small intestinal length, LF heights, enterocyte cross-sectional area and microvilli height and density. In addition, the onset of re-feeding was correlated with an immediate reversal of many morphological parameters affected by 3 months of aestivation. Those parameters that had not returned to control levels within 36 h of feeding generally had returned to control values by the completion of digestion (i.e. defecation of the meal). Re-feeding was also associated with several changes in enterocyte morphology including the incorporation in intracytoplasmic lipid droplets and the return of enterocyte nuclear material to the 'active' euchromatin state: In conclusion, morphological changes to the gut of aestivating frogs which occur during aestivation are transitory and rapidly reversible with both arousal from aestivation and re-feeding. The proximate causes behind these transitions and their functional significance are discussed. (C) 2005 Elsevier Inc. All rights reserved.

Group-directed criticism in Indonesia: Role of message source and audience

Research in individualist cultures has shown that group members are more likely to agree with criticisms of their group when the criticisms are made by another ingroup member as opposed to an outgroup member (the intergroup sensitivity effect). However, evaluations of ingroup critics are often harsher when they take their comments to an outgroup audience. In light of research on facework and tolerance for dissent, it seems important to test whether these effects are generalizable to a collectivist culture. Indonesian Muslims (N = 191) received a criticism of their religion stemming either from another Muslim or a Christian, and published in either a Muslim or a Christian newspaper. Participants agreed with the comments more when they were made by an ingroup as opposed to an outgroup member. Furthermore, consistent with previous research in Australia, the effects of audience on agreement were moderated by levels of group identification. Results are discussed in relation to theory about the functional role internal critics can play in group life.

When group members admit to being conformist: The role of relative intragroup status in conformity self-reports

Five studies examined the hypothesis that people will strategically portray the self as being more g-roup influenced the more junior they feel within the group. Among social psychologists (Study 1), ratings of self-conformity by g-roup members were greater when the status of the participant was low than when it was high. These effects were replicated in Studies 2, 3, and 4 in which relative intragroup status was manipulated. In Study 3, the authors found junior group members described themselves as more conformist than senior members when they were addressing an ingroup audience, but when they were addressing an outgroup audience the effect disappeared. Furthermore, junior members (but not senior members) rated themselves as more conformist when they were led to believe their responses were public than when responses were private (Study 5). The discussion focuses on the strategic processes underlying low-status group members' self-reports of group influence and the functional role of conformity in groups.

The effect of caudal block on functional residual capacity and ventilation homogeneity in healthy children

Caudal block results in a motor blockade that can reduce abdominal wall tension. This could interact with the balance between chest wall and lung recoil pressure and tension of the diaphragm, which determines the static resting volume of the lung. On this rationale, we hypothesised that caudal block causes an increase in functional residual capacity and ventilation distribution in anaesthetised children. Fifty-two healthy children (15-30 kg, 3-8 years of age) undergoing elective surgery with general anaesthesia and caudal block were studied and randomly allocated to two groups: caudal block or control. Following induction of anaesthesia, the first measurement was obtained in the supine position (baseline). All children were then turned to the left lateral position and patients in the caudal block group received a caudal block with bupivacaine. No intervention took place in the control group. After 15 nun in the supine position, the second assessment was performed. Functional residual capacity and parameters of ventilation distribution were calculated by a blinded reviewer. Functional residual capacity was similar at baseline in both groups. In the caudal block group, the capacity increased significantly (p < 0.0001) following caudal block, while in the control group, it remained unchanged. In both groups, parameters of ventilation distribution were consistent with the changes in functional residual capacity. Caudal block resulted in a significant increase in functional residual capacity and improvement in ventilation homogeneity in comparison with the control group. This indicates that caudal block might have a beneficial effect on gas exchange in anaesthetised, spontaneously breathing preschool-aged children with healthy lungs.

In vivo demonstration of load-induced fluid flow in the rat tibia and its potential implications for processes associated with functional adaptation

Load-induced extravascular fluid flow has been postulated to play a role in mechanotransduction of physiological loads at the cellular level. Furthermore, the displaced fluid serves as a carrier for metabolites, nutrients, mineral precursors and osteotropic agents important for cellular activity. We hypothesise that load-induced fluid flow enhances the transport of these key substances, thus helping to regulate cellular activity associated with processes of functional adaptation and remodelling. To test this hypothesis, molecular tracer methods developed previously by our group were applied in vivo to observe and quantify the effects of load-induced fluid flow under four-point-bending loads. Preterminal tracer transport studies were carried out on 24 skeletally mature Sprague Dawley rats. Mechanical loading enhanced the transport of both small- and larger-molecular-mass tracers within the bony tissue of the tibial mid-diaphysis. Mechanical loading showed a highly significant effect on the number of periosteocytic spaces exhibiting tracer within the cross section of each bone. For all loading rates studied, the concentration of Procion Red tracer was consistently higher in the tibia subjected to pure bending loads than in the unloaded, contralateral tibia, Furthermore, the enhancement of transport was highly site-specific. In bones subjected to pure bending loads, a greater number of periosteocytic spaces exhibited the presence of tracer in the tension band of the cross section than in the compression band; this may reflect the higher strains induced in the tension band compared with the compression band within the mid-diaphysis of the rat tibia. Regardless of loading mode, the mean difference between the loaded side and the unloaded contralateral control side decreased with increasing loading frequency. Whether this reflects the length of exposure to the tracer or specific frequency effects cannot be determined by this set of experiments. These in vivo experimental results corroborate those of previous ex vivo and in vitro studies, Strain-related differences in tracer distribution provide support for the hypothesis that load-induced fluid flow plays a regulatory role in processes associated with functional adaptation.

High- and low-volume resistance training similarly enhances functional performance in older adults

It is well known that resistance training improves muscle strength in older adults and may enhance or preserve functional performance. However, it is unclear if the volume of work undertaken in the elderly alters the response in functional performance. PURPOSE: To investigate the effect of a high- versus low-volume resistance training program on functional performance in older adults. METHODS: Thirty-two healthy men and women aged 65-78 years were randomly assigned to either a single-set (SS, n = 16) or 3-set (MS, n = 16) progressive resistance training program for 20 weeks. Groups trained 2 days per week using machine weights at 8 repetitions maximum (8-RM) for 7 upper and lower body exercises. Muscle strength was assessed by the 1-RM and functional performance by a battery of tests (repeated chair rise, usual and fast 6-m walk, 6-m backwards walk, floor rise to standing, stair climb, and 400-m walk time). RESULTS: Twenty-eight subjects completed the study. There was no difference between groups at baseline in muscle strength or functional performance. Whole body muscle strength significantly increased in both groups with greater gains in the 3-set group (MS 32.9 ± 3.1%; SS 18.6 ± 2.7%, mean ± SE; P < 0.01). Significant improvement (time effect, P < 0.01) occurred for both groups in the chair rise (MS 13.6 ± 3.2%; SS 10.2 ± 3.0%), 6-m backwards walk (MS 14.9 ± 3.3%; SS 14.3 ± 4.2%), stair climb (MS 6.4 ± 2.8%; SS 7.7 ± 3.1%) and 400-m walk (MS 7.4 ± 1.4%; SS 3.9 ± 1.2%). There were no interaction (group × time) effects for functional performance and no differences by sex. CONCLUSION: Resistance training that utilizes either a singleset or 3-set regimen may significantly and similarly improve functional performance in community-dwelling older adults. Enhancement of functional performance may prolong independence and improve quality of life. ©2004The American College of Sports Medicine

Evaluation of the effectiveness of enrichment for a group of captive squirrel monkeys (Saimiri sciureus) using time-lapse recording and instantaneous scan sampling

One aim of providing enrichment to captive animals is to promote the expression of behavioural patterns similar to their wild conspecifics. We evaluated the effectiveness of four types of simple feeding enrichment, using surveillance cameras to record the behaviour of 11 captive squirrel monkeys housed in a single enclosure at Alma Park Zoo in Brisbane, Australia. The enrichment involved differences in presentation (whole/chopped) and distribution (localised/scattered) of fruit and vegetables that were part of the normal diet of these animals. Distinguishing between individual squirrel monkeys was not possible from the videos, so Instantaneous Scan Sampling was used to record the numbers of animals performing particular behaviours every 15 minutes over the 24 hour period as well as every 5 minutes for the hour following provision of enrichment. This provided an estimation of the percentage of time spent by the group in various activities. As a result of the enrichment, the activity budget of the group more closely approximated that of wild squirrel monkeys. However on a number of occasions where the enrichment required the squirrel monkeys to work to obtain their food (whole fruit and vegetables), a number of individuals became aggressive towards the zookeepers. This result highlights the variation in responses of individual animals towards enrichment and indicates that in enclosures with large numbers of animals, the response of each individual should be evaluated in addition to the overall benefit of the enrichment for the group. Furthermore, this variation also suggests that it may be beneficial to provide the animals with choices of enrichment as opposed to providing single forms of enrichment that may only be effective for a proportion of the animals in the enclosure, and may even result in undesirable responses from some individuals.

The functional impact of developmental co-ordination disorder during adolescence and early adult life

PURPOSE: The purpose of this study was to increase the understanding of the functional impact that coordination problems have during adolescence and early adult life. In particular, this study aimed to investigate the impact coordination deficits have on day-to-day functioning, activity levels, self-concept with respect to coordination, leisure pursuits, occupational types, accidents and injuries, as well as experiences learning to drive. RELEVANCE: This study may enable clinicians to identify at risk situations, such that appropriate prevention and targeting of treatment can occur. SUBJECTS: The participants involved in this study comprised two groups; 40 subjects previously diagnosed with DCD, and their matched controls. METHODS: Participants were initially contacted by mail for their consent to the study. Consenting participants were then contacted via telephone, and interviewed. ANALYSES: Data analysis was performed using SPSS. Chi squared analysis and Mann Whitney U test was also used to compare groups. RESULTS: During both age periods, the number of DCD subjects participating in sport was significantly less than the number of controls. Although in the 12-14 years age category, the two groups displayed similar results for the type of sport chosen, the 18 – 20 years age group, showed significant differences, with the number of DCD subjects participating in High level coordination activities, being significantly less than controls. Self-perception with respect to coordination was also significantly different amongst groups with more DCD subjects, having perceived themselves as being clumsy. Similarly, a significantly greater number of DCD subjects admitted to tripping over themselves regularly. Some differences have also been noted in the experiences of subjects learning to drive. First, the number of DCD subjects, who had difficulties learning to drive was significantly greater than controls. Second, a much greater number of Control subjects, compared to DCD subjects were successful in obtaining drivers license. Finally, also of interest is the 58% of DCD subjects who have experienced an accident whilst driving, compared to the 35% of controls. The last result of this study was that whilst there was no significant difference between groups, in the number of broken bones, dislocated joints, sprain, burns, stitches, or other significant injuries, the number of control subjects suffering muscle strains was significantly greater than the number of DCD subjects. CONCLUSION: The results of this study indicate that DCD has many implications on day-to-day functioning, both in adolescence and early adulthood. Findings have shown despite the significant sensory-motor deficits displayed by DCD subjects, the impact that this has on day-to-day functioning may be reduced by lifestyle modification.