Adults with cerebral palsy benefit from participating in a strength training programme at a community gymnasium

Purpose : This study examined whether a community-based progressive resistance strength training programme could improve muscle strength and functional activity in a group of adults with cerebral palsy with high support needs.

Method : Using a single group pre-post clinical design, 10 adults (7 males, 3 females; mean age 47.8 SD 5.7 years) with cerebral palsy and high support needs completed 4 weeks of introduction and familiarization, followed by a 10-week progressive resistance strength training programme in a community gymnasium. Participants were measured for muscle strength, locomotion speed and timed sit-to-stand.

Results : After establishment of a stable baseline from weeks 2 to 5 with no systematic change and a high degree of association ( r  > 0.86), participants increased leg strength by 22.0% ( p  = 0.02), arm strength by 17.2% ( p  = 0.01) and improved performance of sit-to-stand ( p  = 0.02) during the 10-week strength training intervention.

Conclusions : This study adds to the accumulating evidence that strength training can be beneficial for people with cerebral palsy by demonstrating benefits for adults with cerebral palsy and high support needs who are subject to decline in physical function associated with the ageing process.

Distributional overlap rather than habitat differentiation characterizes co-occurrence of bivalves in intertidal soft sediment systems

Diverse species assemblages are often associated with a diversity of habitat structures. Sedimentary systems seem to be no exception, as within sedimentary systems benthic species diversity within a sample point appears to correlate with sediment grain size complexity. However, it remains to be shown whether total benthic species diversity relates to a system’s sediment heterogeneity across multiple systems. In the present paper we examined whether bivalve diversity is associated with: (1) sediment heterogeneity across systems and (2) sediment grain size complexity within systems, at 9 temperate and tropical tidal flat systems. Although bivalve life-history strategies, like post-settlement habitat selection, might suggest that sediment heterogeneity should be important for bivalve species, bivalve diversity and sediment heterogeneity were not associated across systems. Interestingly, the association between total benthic diversity and sediment heterogeneity was also not significant, suggesting that changing species composition across systems does not account for the lack of a correlation between bivalve diversity and sediment heterogeneity. Instead of habitat differentiation, bivalve diversity within a sample point was highest in ‘complex’ fine-grained sediments and bivalve distributions showed a large degree of distributional overlap in all systems. The results of this study at both smaller and larger spatial scales suggest that coexistence between bivalve species in diverse tidal flats is not associated with increased sediment heterogeneity.

Identification and disruption of the gene encoding the third member of the low-molecular-mass rhoptry complex in Plasmodium falciparum

The low-molecular-mass rhoptry complex of Plasmodium falciparum consists of three proteins, rhoptry-associated protein 1 (RAP1), RAP2, and RAP3. The genes encoding RAP1 and RAP2 are known; however, the RAP3 gene has not been identified. In this study we identify the RAP3 gene from the P. falciparum genome database and show that this protein is part of the low-molecular-mass rhoptry complex. Disruption of RAP3 demonstrated that it is not essential for merozoite invasion, probably because RAP2 can complement the loss of RAP3. RAP3 has homology with RAP2, and the genes are encoded on chromosome 5 in a head-to-tail fashion. Analysis of the genome databases has identified homologous genes in all Plasmodium spp., suggesting that this protein plays a role in merozoite invasion. The region surrounding the RAP3 homologue in the Plasmodium yoelii genome is syntenic with the same region in P. falciparum; however, there is a single gene. Phylogenetic comparison of the RAP2/3 protein family from Plasmodium spp. suggests that the RAP2/3 duplication occurred after divergence of these parasite species.

RAP1 controls rhoptry targeting of RAP2 in the malaria parasite Plasmodium falciparum

Rhoptry associated protein 1 (RAP1) and 2 (RAP2), together with a poorly described third protein RAP3, form the low molecular weight complex within the rhoptries of Plasmodium falciparum. These proteins are thought to play a role in erythrocyte invasion by the extracellular merozoite and are important vaccine candidates. We used gene-targeting technology in P.falciparum blood-stage parasites to disrupt the RAP1 gene, producing parasites that express severely truncated forms of RAP1. Immunoprecipitation experiments suggest that truncated RAP1 species did not complex with RAP2 and RAP3. Consistent with this were the distinct subcellular localizations of RAP1 and 2 in disrupted RAP1 parasites, where RAP2 does not traffic to the rhoptries but is instead located in a compartment that appears related to the lumen of the endoplasmic reticulum. These results suggest that RAP1 is required to localize RAP2 to the rhoptries, supporting the hypothesis that rhoptry biogenesis is dependent in part on the secretory pathway in the parasite. The observation that apparently host-protective merozoite antigens are not essential for efficient erythrocyte invasion has important implications for vaccine design.

A probabilistic framework for extracting narrative act boundaries and semantics in motion pictures

This work constitutes the first attempt to extract the important narrative structure, the 3-Act storytelling paradigm in film. Widely prevalent in the domain of film, it forms the foundation and framework in which a film can be made to function as an effective tool for story telling, and its extraction is a vital step in automatic content management for film data. The identification of act boundaries allows for structuralizing film at a level far higher than existing segmentation frameworks, which include shot detection and scene identification, and provides a basis for inferences about the semantic content of dramatic events in film. A novel act boundary likelihood function for Act 1 and 2 is derived using a Bayesian formulation under guidance from film grammar, tested under many configurations and the results are reported for experiments involving 25 full-length movies. The result proves to be a useful tool in both the automatic and semi-interactive setting for semantic analysis of film, with potential application to analogues occuring in many other domains, including news, training video, sitcoms.

Adolescent substance use and educational attainment: an integrative data analysis comparing cannabis and alcohol from three Australasian cohorts

BACKGROUND: The relative contributions of cannabis and alcohol use to educational outcomes are unclear. We examined the extent to which adolescent cannabis or alcohol use predicts educational attainment in emerging adulthood. METHODS: Participant-level data were integrated from three longitudinal studies from Australia and New Zealand (Australian Temperament Project, Christchurch Health and Development Study, and Victorian Adolescent Health Cohort Study). The number of participants varied by analysis (N=2179-3678) and were assessed on multiple occasions between ages 13 and 25. We described the association between frequency of cannabis or alcohol use prior to age 17 and high school non-completion, university non-enrolment, and degree non-attainment by age 25. Two other measures of alcohol use in adolescence were also examined. RESULTS: After covariate adjustment using a propensity score approach, adolescent cannabis use (weekly+) was associated with 1½ to two-fold increases in the odds of high school non-completion (OR=1.60, 95% CI=1.09-2.35), university non-enrolment (OR=1.51, 95% CI=1.06-2.13), and degree non-attainment (OR=1.96, 95% CI=1.36-2.81). In contrast, adjusted associations for all measures of adolescent alcohol use were inconsistent and weaker. Attributable risk estimates indicated adolescent cannabis use accounted for a greater proportion of the overall rate of non-progression with formal education than adolescent alcohol use. CONCLUSIONS: Findings are important to the debate about the relative harms of cannabis and alcohol use. Adolescent cannabis use is a better marker of lower educational attainment than adolescent alcohol use and identifies an important target population for preventive intervention.

Retirement patterns of Australian doctors aged 65 years and older.

OBJECTIVE: To investigate retirements over a 4-year period among Australian general practitioners (UPs) and specialists aged 65 years and over, and factors influencing retirement. METHODS: Data from Medicine in Australia: Balancing Employment and Life (MABEL) for the years 2009-12 were analysed for 435 GPs and 643 specialists aged 65 years and over at the time of entry to the MABEL survey. Discrete time survival analysis was used. RESULTS: The retirement rates were 4.1% (2009), 5.1% (2010), 4.2% (2011) and 10.4% (2012). Retirement was associated with: (1) the intention to leave medical work in 2009 and 2010; (2) working fewer hours in private consulting rooms in 2010 and 2012; (3) having lower job satisfaction in 2009 and 2011; (4) being older in 2009; (5) working fewer hours in a public hospital in 2012; and (6) working fewer hours in a private hospital in 2010. Doctors who intended to reduce their working hours were less likely to retire in 2009. CONCLUSIONS: Strategies to support doctors at the late career stage to provide their valued contributions to the medical workforce for as long as possible may include increasing job satisfaction and addressing barriers to reducing work hours.

Psychosocial working conditions and suicide ideation: evidence from a cross-sectional survey of working Australians

OBJECTIVES: This study examined the relationship between psychosocial working factors such as job control, job demands, job insecurity, supervisor support, and workplace bullying as risk factors for suicide ideation. METHODS: We used a logistic analytic approach to assess risk factors for thoughts of suicide in a cross-sectional sample of working Australians. Potential predictors included psychosocial job stressors (described above); we also controlled for age, gender, occupational skill level, and psychological distress. RESULTS: We found that workplace bullying or harassment was associated with 1.54 greater odds of suicide ideation (95% confidence interval 1.64 to 2.05) in the model including psychological distress. Results also suggest that higher job control and security were associated with lower odds of suicide ideation. CONCLUSIONS: These results suggest the need for organizational level intervention to address psychosocial job stressors, including bullying.

Impact of early valve surgery on outcome of Staphylococcus aureus prosthetic valve infective endocarditis: analysis in the International Collaboration of Endocarditis-Prospective Cohort Study

BACKGROUND: The impact of early valve surgery (EVS) on the outcome of Staphylococcus aureus (SA) prosthetic valve infective endocarditis (PVIE) is unresolved. The objective of this study was to evaluate the association between EVS, performed within the first 60 days of hospitalization, and outcome of SA PVIE within the International Collaboration on Endocarditis-Prospective Cohort Study. METHODS: Participants were enrolled between June 2000 and December 2006. Cox proportional hazards modeling that included surgery as a time-dependent covariate and propensity adjustment for likelihood to receive cardiac surgery was used to evaluate the impact of EVS and 1-year all-cause mortality on patients with definite left-sided S. aureus PVIE and no history of injection drug use. RESULTS: EVS was performed in 74 of the 168 (44.3%) patients. One-year mortality was significantly higher among patients with S. aureus PVIE than in patients with non-S. aureus PVIE (48.2% vs 32.9%; P = .003). Staphylococcus aureus PVIE patients who underwent EVS had a significantly lower 1-year mortality rate (33.8% vs 59.1%; P = .001). In multivariate, propensity-adjusted models, EVS was not associated with 1-year mortality (risk ratio, 0.67 [95% confidence interval, .39-1.15]; P = .15). CONCLUSIONS: In this prospective, multinational cohort of patients with S. aureus PVIE, EVS was not associated with reduced 1-year mortality. The decision to pursue EVS should be individualized for each patient, based upon infection-specific characteristics rather than solely upon the microbiology of the infection causing PVIE.

Risk factors for female sexual dysfunction in the general population : exploring factors associated with low sexual function and sexual distress

Introduction. No previous population-based studies have used validated instruments to measure female sexual dysfunction (FSD) in Australian women across a broad age range.
Aim. To estimate prevalence and explore factors associated with the  components of FSD.
Main Outcome Measures. Sexual Function Questionnaire measured low sexual function. Female Sexual Distress Scale measured sexual distress.
Methods. Multivariate analysis of postal survey data from a random sample of 356 women aged 20–70 years.
Results. Low desire was more likely to occur in women in relationships for 20–29 years (odds ratio 3.7, 95% confidence intervals 1.1–12.8) and less likely in women reporting greater satisfaction with their partner as a lover (0.3, 0.1–0.9) or who placed greater importance on sex (0.1, 0.03–0.3). Low genital arousal was more likely among women who were perimenopausal (4.4, 1.2–15.7), postmenopausal (5.3, 1.6–17.7), or depressed (2.5, 1.1–5.3), and was less likely in women taking hormone therapy (0.2, 0.04–0.7), more educated (0.5, 0.3–0.96), in their 30s (0.2, 0.1–0.7) or 40s (0.2, 0.1–0.7), or placed greater importance on sex (0.2, 0.05–0.5). Low orgasmic function was less likely in women who were in their 30s (0.3, 0.1–0.8) or who placed greater importance on sex (0.3, 0.1–0.7). Sexual distress was positively associated with depression (3.1, 1.2–7.8) and was inversely associated with better communication of sexual needs (0.2, 0.05–0.5). Results were adjusted for other covariates including age, psychological, socioeconomic, physiological, and relationship factors.
Conclusions. Relationship factors were more important to low desire than age or menopause, whereas physiological and psychological factors were more important to low genital arousal and low orgasmic function than relationship factors. Sexual distress was associated with both psychological and relationship factors.

Effects of survivin antagonists of growth of established tumors and B7-1 immunogene therapy

Background: Survivin, a member of the inhibitor of apoptosis (IAP) protein family, is detectable in most types of cancer, and its presence is associated with a poor prognosis. We determined the effects of gene-based therapies that inhibit survivin function in a mouse tumor model. Methods: Using five to six mice per treatment group, we injected tumors derived from mouse EL-4 thymic lymphoma cells with plasmids encoding antisense survivin, a dominant-negative mutant survivin, and the T-cell costimulator B7-1. Expression of endogenous survivin and the proteins encoded by the injected plasmids were examined by immunohistochemical staining of tumor sections and by western blot and flow cytometry analyses of isolated tumor cells. Tumor growth, the generation of antitumor cytotoxic T-lymphocyte (CTL) activity, apoptosis, and the contribution of leukocyte subsets to antitumor activity were measured. All statistical tests were two-sided. Results: Large (1.0-cm diameter) tumors had approximately 10-fold more survivin than small (0.2-cm diameter) tumors. At 28 days after injection, antisense and dominant-negative mutant survivin plasmids statistically significantly inhibited the growth of both small (P = .006 and P = .0018, respectively) and large (P<.001 for both plasmids) EL-4 tumors compared with tumors injected with empty plasmid. The growth of large tumors was further inhibited by intratumoral injection with antisense survivin and B7-1 (P = .004); thus, inhibition of survivin expression renders large tumors susceptible to B7-1-mediated immunotherapy. Mice whose tumors were completely eradicated by injection of B7-1 remained tumor free for 26 days after re-injection with EL-4 cells (when the experiment ended). Compared with tumors injected with empty plasmid, tumors injected with survivin-based plasmids had increased apoptosis, and animals bearing such tumors generated more antitumor CTLs. Conclusion: Intratumoral injection of plasmids that block survivin expression and stimulate the generation of tumor-specific CTLs may be beneficial for the treatment of large lymphomas.

Fructose-1,6-Bisphosphatase overexpression in pancreatic [beta]-cells results in reduced insulin secretion : a new mechanism for fat-induced impairment of [beta]-cell function

Fructose-1,6-bisphosphatase (FBPase) is a gluconeogenic enzyme that is upregulated in islets or pancreatic beta-cell lines exposed to high fat. However, whether specific beta-cell upregulation of FBPase can impair insulin secretory function is not known. The objective of this study therefore is to determine whether a specific increase in islet beta-cell FBPase can result in reduced glucose-mediated insulin secretion.

To test this hypothesis, we have generated three transgenic mouse lines overexpressing the human FBPase (huFBPase) gene specifically in pancreatic islet beta-cells. In addition, to investigate the biochemical mechanism by which elevated FBPase affects insulin secretion, we made two pancreatic beta-cell lines (MIN6) stably overexpressing huFBPase.

FBPase transgenic mice showed reduced insulin secretion in response to an intravenous glucose bolus. Compared with the untransfected parental MIN6, FBPase-overexpressing cells showed a decreased cell proliferation rate and significantly depressed glucose-induced insulin secretion. These defects were associated with a decrease in the rate of glucose utilization, resulting in reduced cellular ATP levels.

Taken together, these results suggest that upregulation of FBPase in pancreatic islet beta-cells, as occurs in states of lipid oversupply and type 2 diabetes, contributes to insulin secretory dysfunction.

Gag-Pol supplied in trans is efficiently packaged and supports viral function in human immunodeficiency virus type 1

The intracellular trafficking and subsequent incorporation of Gag-Pol into human immunodeficiency virus type 1 (HIV-1) remains poorly defined. Gag-Pol is encoded by the same mRNA as Gag and is generated by ribosomal frameshifting. The multimerization of Gag and Gag-Pol is an essential step in the formation of infectious viral particles. In this study, we examined whether the interaction between Gag and Gag-Pol is initiated during protein translation in order to facilitate the trafficking and subsequent packaging of Gag-Pol into the virion. A conditional cotransfection system was developed in which virion formation required the coexpression of two HIV-1-based plasmids, one that produces both Gag and Gag-Pol and one that only produces Gag-Pol. The Gag-Pol proteins were either immunotagged with a His epitope or functionally tagged with a mutation (K65R) in reverse transcriptase that is associated with drug resistance. Gag-Pol packaging was assessed to determine whether the Gag-Pol incorporated into the virion was preferentially packaged from the plasmid that expressed both Gag and Gag-Pol or whether it could be packaged from either plasmid. Our data show that translation of Gag and Gag-Pol from the same mRNA is not critical for virion packaging of the Gag-Pol polyprotein or for viral function.

Leukocyte numbers and function in subjects eating n-3 enriched foods: selective depression of natural killer cell levels

Introduction : While consumption of omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) has been recommended for those at risk of inflammatory disease such as rheumatoid arthritis, the mechanism of their anti-inflammatory effect remains to be clearly defined, particularly in relation to the dose and type of n-3 LCPUFA. The objective of this study was to determine whether varying the levels of n-3 LCPUFA in erythrocyte membrane lipids, following dietary supplementation, is associated with altered numbers and function of circulating leukocytes conducive to protection against inflammation. Methods : In a double-blind and placebo-controlled study, 44 healthy subjects aged 23 to 63 years consumed either standard or n-3 LCPUFA-enriched versions of typical processed foods, the latter allowing a target daily consumption of 1 gram n-3 LCPUFA. After six months, peripheral blood leukocyte and subpopulation proportions and numbers were assessed by flow cytometry. Leukocytes were also examined for lymphoproliferation and cytokine production, neutrophil chemotaxis, chemokinesis, bactericidal, adherence and iodination activity. Erythrocytes were analyzed for fatty-acid content. Results : Erythrocyte n-3 LCPUFA levels were higher and absolute leukocyte and lymphocyte numbers were lower in subjects consuming n-3 enriched foods than in controls. There were no changes in the number of neutrophils, monocytes, T cells (CD3+), T-cell subsets (CD4+, CD8+) and B cells (CD19+). However, natural killer (NK) (CD3-CD16+CD56+) cell numbers were lower in n-3 supplemented subjects than in controls and were inversely related to the amount of eicosapentaenoic acid or docosahexaenoic acid in erythrocytes. No significant correlations were found with respect to lymphocyte lymphoproliferation and production of IFN-γ and IL-2, but lymphotoxin production was higher with greater n-3 LCPUFA membrane content. Similarly, neutrophil chemotaxis, chemokinesis, bactericidal activity and adherence did not vary with changes in erythrocyte n-3 LCPUFA levels, but the iodination reaction was reduced with higher n-3 LCPUFA content. Conclusion : The data show that regular long-term consumption of n-3 enriched foods leads to lower numbers of NK cells and neutrophil iodination activity but higher lymphotoxin production by lymphocytes. These changes are consistent with decreased inflammatory reaction and tissue damage seen in patients with inflammatory disorders receiving n-3 LCPUFA supplementation.

N-Acetylcysteine improves mitochondrial function and ameliorates behavioral deficits in the R6/1 mouse model of Huntington's disease

Huntington's disease (HD) is a neurodegenerative disorder, involving psychiatric, cognitive and motor symptoms, caused by a CAG-repeat expansion encoding an extended polyglutamine tract in the huntingtin protein. Oxidative stress and excitotoxicity have previously been implicated in the pathogenesis of HD. We hypothesized that N-acetylcysteine (NAC) may reduce both excitotoxicity and oxidative stress through its actions on glutamate reuptake and antioxidant capacity. The R6/1 transgenic mouse model of HD was used to investigate the effects of NAC on HD pathology. It was found that chronic NAC administration delayed the onset and progression of motor deficits in R6/1 mice, while having an antidepressant-like effect on both R6/1 and wild-type mice. A deficit in the astrocytic glutamate transporter protein, GLT-1, was found in R6/1 mice. However, this deficit was not ameliorated by NAC, implying that the therapeutic effect of NAC is not due to rescue of the GLT-1 deficit and associated glutamate-induced excitotoxicity. Assessment of mitochondrial function in the striatum and cortex revealed that R6/1 mice show reduced mitochondrial respiratory capacity specific to the striatum. This deficit was rescued by chronic treatment with NAC. There was a selective increase in markers of oxidative damage in mitochondria, which was rescued by NAC. In conclusion, NAC is able to delay the onset of motor deficits in the R6/1 model of Huntington's disease and it may do so by ameliorating mitochondrial dysfunction. Thus, NAC shows promise as a potential therapeutic agent in HD. Furthermore, our data suggest that NAC may also have broader antidepressant efficacy.