Early inflammatory and myogenic responses to resistance exercise in the elderly

Introduction and Methods: This study compared changes in myokine and myogenic genes following resistance exercise (3 sets of 12 repetitions of maximal unilateral knee extension) in 20 elderly men (67.8 ± 1.0 years) and 15 elderly women (67.2 ± 1.5 years). Results: Monocyte chemotactic protein (MCP)-1, macrophage inhibitory protein (MIP)-1β, interleukin (IL)-6 and MyoD mRNA increased significantly (P < 0.05), whereas myogenin and myostatin mRNA decreased significantly after exercise in both groups. Macrophage-1 (Mac-1) and MCP-3 mRNA did not change significantly after exercise in either group. MIP-1β, Mac-1 and myostatin mRNA were significantly higher before and after exercise in men compared with women. In contrast, MCP-3 and myogenin mRNA were significantly higher before and after exercise in the women compared with the men. Conclusions: In elderly individuals, gender influences the mRNA expression of certain myokines and growth factors, both at rest and after resistance exercise. These differences may influence muscle regeneration following muscle injury

Wolbachia-mediated resistance to dengue virus infection and death at the cellular level

Dengue is currently the most important arthropod-borne viral disease of humans. Recent work has shown dengue virus displays limited replication in its primary vector, the mosquito Aedes aegypti, when the insect harbors the endosymbiotic bacterium Wolbachia pipientis. Wolbachia-mediated inhibition of virus replication may lead to novel methods of arboviral control, yet the functional and cellular mechanisms that underpin it are unknown.

Inflammatory cytokine responses to progressive resistance training and supplementation with fortified milk in men aged 50+ years : an 18-month randomized controlled trial

We examined the effects of progressive resistance training (PRT) and supplementation with calcium-vitamin D(3) fortified milk on markers of systemic inflammation, and the relationship between inflammation and changes in muscle mass, size and strength. Healthy men aged 50-79 years (n = 180) participated in this 18-month randomized controlled trial that comprised a factorial 2 x 2 design. Participants were randomized to (1) PRT + fortified milk supplement, (2) PRT, (3) fortified milk supplement, or (4) a control group. Participants assigned to PRT trained 3 days per week, while those in the supplement groups consumed 400 ml day(-1) of milk containing 1,000 mg calcium plus 800 IU vitamin D(3). We collected venous blood samples at baseline, 12 and 18 months to measure the serum concentrations of IL-6, TNF-alpha and hs-CRP. There were no exercise x supplement interactions, but serum IL-6 was 29% lower (95% CI, -62, 0) in the PRT group compared with the control group after 12 months. Conversely, IL-6 was 31% higher (95% CI, -2, 65) in the supplement group compared with the non-supplemented groups after 12 and 18 months. These between-group differences did not persist after adjusting for changes in fat mass. In the PRT group, mid-tibia muscle cross-sectional area increased less in men with higher pre-training inflammation compared with those men with lower inflammation (net difference similar to 2.5%, p < 0.05). In conclusion, serum IL-6 concentration decreased following PRT, whereas it increased after supplementation with fortified milk concomitant with changes in fat mass. Furthermore, low-grade inflammation at baseline restricted muscle hypertrophy following PRT.

'It had to be my choice' Indigenous smoking cessation and negotiations of risk, resistance and resilience

While Australia is considered a world leader in tobacco control, smoking rates within the Aboriginal and Torres Strait Islander population have not declined at the same rate. This failure highlights an obvious shortcoming of mainstream anti-smoking efforts to effectively understand and engage with the socio-cultural context of Indigenous smoking and smoking cessation experiences. The purpose of this article is to explore the narrative accounts of 20 Indigenous ex-smokers within an urban community and determine the motivators and enablers for successful smoking cessation. Our findings indicated that health risk narratives and the associated social stigma produced through anti-smoking campaigns formed part of a broader apparatus of oppression among Indigenous people, often inspiring resistance and resentment rather than compliance. Instead, a significant life event and supportive relationships were the most useful predictors of successful smoking cessation acting as both a motivator and enabler to behavioural change. Indigenous smoking cessation narratives most commonly involved changing and reordering a person’s life and identity and autonomy over this process was the critical building block to reclaiming control over nicotine addiction. Most promisingly, at an individual level, we found the important role that individual health professionals played in encouraging and supporting Indigenous smoking cessation through positive rather than punitive interactions. More broadly, our findings highlighted the central importance of resilience, empowerment, and trust within health promotion practice.

Serine protease inhibition and mitochondrial dysfunction associated with cisplatin resistance in human tumor cell lines : targets for therapy

Indicators of mitochondrial function were studied in two different cell culture models of cis-diamminedichloroplatinum-II (CDDP) resistance: the intrinsically resistant human ovarian cancer cell line CI-80-13S, and resistant clones (HeLa-S1a and HeLa-S1b) generated by stable expression of the serine protease inhibitor—plasminogen activator inhibitor type-2 (PAI-2), in the human cervical cancer cell line HeLa. In both models, CDDP resistance was associated with sensitivity to killing by adriamycin, etoposide, auranofin, bis[1,2-bis(diphenylphosphino)ethane]gold(I) chloride {[Au(DPPE)2]Cl}, CdCl2 and the mitochondrial inhibitors rhodamine-123 (Rhl23), dequalinium chloride (DeCH), tetraphenylphosphonium (TPP), and ethidium bromide (EtBr) and with lower constitutive levels of ATP. Unlike the HeLa clones, CI-80-13S cells were additionally sensitive to chloramphenicol, 1-methyl-4-phenylpyridinium ion (MPP+), rotenone, thenoyltrifluoroacetone (TTFA), and antimycin A, and showed poor reduction of 1-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT), suggesting a deficiency in NADH dehydrogenase and/or succinate dehydrogenase activities. Total platinum uptake and DNA-bound platinum were slightly lower in CI-80-13S than in sensitive cells. The HeLa-S1a and HeLa-S1b clones, on the other hand, showed poor reduction of triphenyltetrazolium chloride (TTC), indicative of low cytochrome c oxidase activity. Total platinum uptake by HeLa-S1a was similar to HeLa, but DNA-bound platinum was much lower than for the parent cell line. The mitochondria of CI-80-13S and HeLa-S1a showed altered morphology and were fewer in number than those of JAM and HeLa. In both models, CDDP resistance was associated with less platinum accumulation and with mitochondrial and membrane defects, brought about one case with expression of a protease inhibitor which is implicated in tumor progression. Such markers may identify tumors suitable for treatment with gold phosphine complexes or other mitochondrial inhibitors.

Oblique-Shock-Wave/Boundary-Layer Interaction Using Near-Wall Reynolds-Stress Models

A synthesis is presented of the predictive capability of a family of near-wall wall-normal free Reynolds stress models (which are completely independent of wall topology, i.e., of the distance fromthe wall and the normal-to-thewall orientation) for oblique-shock-wave/turbulent-boundary-layer interactions. For the purpose of comparison, results are also presented using a standard low turbulence Reynolds number k–ε closure and a Reynolds stress model that uses geometric wall normals and wall distances. Studied shock-wave Mach numbers are in the range MSW = 2.85–2.9 and incoming boundary-layer-thickness Reynolds numbers are in the range Reδ0 = 1–2×106. Computations were carefully checked for grid convergence. Comparison with measurements shows satisfactory agreement, improving on results obtained using a k–ε model, and highlights the relative importance of redistribution and diffusion closures, indicating directions for future modeling work.

Influence of inflow turbulence in shock-wave/turbulent-boundary-layer interaction computations

The influence of inflow turbulence on the results of Favre–Reynolds-averaged Navier–Stokes computations of supersonic oblique-shock-wave/turbulent-boundary-layer interactions (shock-wave Mach-number MSW ∼2.9), using seven-equation Reynolds-stress model turbulence closures, is studied. The generation of inflow conditions (and the initialization of the flowfield) for mean flow, Reynolds stresses, and turbulence length scale, based on semi-analytic grid-independent boundary-layer profiles, is described in detail. Particular emphasis is given to freestream turbulence intensity and length scale. The influence of external-flow turbulence intensity is studied in detail both for flat-plate boundary-layer flow and for a compression-ramp interaction with large separation. It is concluded that the Reynolds-stress model correctly reproduces the effects of external flow turbulence.

A home-based progressive resistance exercise programme for patients with venous leg ulcers : a feasibility study

This study aimed to assess the feasibility of a home-based exercise program and examine the effects on the healing rates of venous leg ulcers. A 12 –week randomised controlled trial was conducted investigating the effects of an exercise intervention compared to a usual care group. Participants in both groups (n = 13) had active venous ulceration and were treated in a metropolitan hospital outpatients clinic in Australia. Data were collected on recruitment from medical records, clinical assessment and questionnaires. Follow-up data on progress in healing and treatments were collected fortnightly for 12 weeks. Calf muscle pump function data were collected at baseline and 12 weeks from recruitment. Range of ankle motion data were collected at baseline, 6 and 12 weeks from recruitment. This pilot study indicated that the intervention was feasible. Clinical significance was observed in the intervention group with a 32% greater decrease in ulcer size (p=0.34) than the control group, and a 10% (p=0.74) improvement in the number of participants healed in the intervention group compared to the control group. Significant differences between groups over time were observed in calf muscle pump function parameters; (ejection fraction [p = 0.05]; residual volume fraction [p = 0.04]) and range of ankle motion (p = 0.01). This pilot study is one of the first studies to examine and measure clinical healing rates for participants involved in a home-based progressive resistance exercise program. Further research is warranted with a larger multi-site study.

2nd Australian producer survey 2012 : understanding Australian screen content producers : wave 2

This report presents the top-line findings of the Australian Screen Producer survey conducted in December 2011. The report was prepared by Bergent Research and commissioned by the ARC Centre of Excellence for Creative Industries and Innovation (CCI), Queensland University of Technology, with assistance from the Centre for Screen Business, Australian Film Television and Radio School (AFTRS). The 2011 producer survey was a national study of the demographics, motivations, sentiments and activities of screen producers across four industry segments: Film, Television, Commercial and Digital Media. This survey is the second Australian Screen Producer survey and builds upon research undertaken in the Australian Screen Content Producer Survey conducted in 2009. The 2011 study is referred to in this report as Wave 2 and the 2009 study is referred to as Wave 1.

Paclitaxel resistance and multicellular spheroid formation are induced by kallikrein-related peptidase 4 in serous ovarian cancer cells in an ascites mimicking microenvironment

High tumor kallikrein-related-peptidase 4 (KLK4) levels are associated with a poor outcome for women with serous epithelial ovarian cancer (EOC), for which peritoneal dissemination and chemoresistance are key events. To determine the role of KLK4 in these events, we examined KLK4-transfected SKOV-3 and endogenous KLK4 expressing OVCA432 cells in 3-dimensional (3D) suspension culture to mimic the ascites microenvironment. KLK4-SKOV-3 cells formed multicellular aggregates (MCAs) as seen in ascites, as did SKOV-3 cells treated with active KLK4. MCA formation was reduced by treatment with a KLK4 blocking antibody or the selective active site KLK4 sunflower trypsin inhibitor (SFTI-FCQR). KLK4-MCAs formed larger cancer cell foci in mesothelial cell monolayers than those formed by vector and native SKOV-3 cells, suggesting KLK4-MCAs are highly invasive in the peritoneal microenvironment. A high level of KLK4 is expressed by ascitic EOC cells compared to matched primary tumor cells, further supporting its role in the ascitic microenvironment. Interestingly, KLK4 transfected SKOV-3 cells expressed high levels of the KLK4 substrate, urokinase plasminogen activator (uPA), particularly in 3D-suspension, and high levels of both KLK4 and uPA were observed in patient cells taken from ascites. Importantly, the KLK4-MCAs were paclitaxel resistant which was reversed by SFTI-FCQR and to a lesser degree by the general serine protease inhibitor, Aprotinin, suggesting that in addition to uPA, other as yet unidentified substrates of KLK4 must be involved. Nonetheless, these data suggest that KLK4 inhibition, in conjunction with paclitaxel, may improve the outcome for women with serous epithelial ovarian cancer and high KLK4 levels in their tumors.

Inflammation, hepatic enzymes and resistance training in individuals with metabolic risk factors

AIMS: Increases in inflammatory markers, hepatic enzymes and physical inactivity are associated with the development of the metabolic syndrome (MetS). We examined whether inflammatory markers and hepatic enzymes are correlated with traditional risk factors for MetS and studied the effects of resistance training (RT) on these emerging risk factors in individuals with a high number of metabolic risk factors (HiMF, 2.9 +/- 0.8) and those with a low number of metabolic risk factors (LoMF, 0.5 +/- 0.5). METHODS: Twenty-eight men and 27 women aged 50.8 +/- 6.5 years (mean +/- sd) participated in the study. Participants were randomized to four groups, HiMF training (HiMFT), HiMF control (HiMFC), LoMF training (LoMFT) and LoMF control (LoMFC). Before and after 10 weeks of RT [3 days/week, seven exercises, three sets with intensity gradually increased from 40-50% of one repetition maximum (1RM) to 75-85% of 1RM], blood samples were obtained for the measurement of pro-inflammatory cytokines, C-reactive protein (CRP), gamma-glutamyltransferase (GGT) and alanine aminotransferase (ALT). RESULTS: At baseline, HiMF had higher interleukin-6 (33.9%), CRP (57.1%), GGT (45.2%) and ALT (40.6%) levels, compared with LoMF (all P < 0.05). CRP, GGT and ALT correlated with the number of risk factors (r = 0.48, 0.51 and 0.57, respectively, all P < 0.01) and with other anthropometric and clinical measures (r range from 0.26 to 0.60, P < 0.05). RT did not significantly alter inflammatory markers or hepatic enzymes (all P > 0.05). CONCLUSIONS: HiMF was associated with increased inflammatory markers and hepatic enzyme concentrations. RT did not reduce inflammatory markers and hepatic enzymes in individuals with HiMF.

Free-surface flow past arbitrary topography and an inverse approach for wave-free solutions

An efficient numerical method to compute nonlinear solutions for two-dimensional steady free-surface flow over an arbitrary channel bottom topography is presented. The approach is based on a boundary integral equation technique which is similar to that of Vanden-Broeck's (1996, J. Fluid Mech., 330, 339-347). The typical approach for this problem is to prescribe the shape of the channel bottom topography, with the free-surface being provided as part of the solution. Here we take an inverse approach and prescribe the shape of the free-surface a priori while solving for the corresponding bottom topography. We show how this inverse approach is particularly useful when studying topographies that give rise to wave-free solutions, allowing us to easily classify eleven basic flow types. Finally, the inverse approach is also adapted to calculate a distribution of pressure on the free-surface, given the free-surface shape itself.

Genetic variability and antimicrobial resistance of Ureaplasma parvum in response to maternal erythromycin treatment : a study in pregnant sheep

Background: Ureaplasmas are the most frequently isolated microorganisms from the amniotic fluid (AF) of pregnant women and can cause chronic infections that are difficult to eradicate with standard macrolide treatment. We tested the effects of erythromycin treatment on phenotypic and genotypic markers of ureaplasmal antimicrobial resistance in sheep. Method: At 50 days of gestation (d, term=145d) 12 pregnant ewes received intra-amniotic injections of U. parvum serovar 3 (erythromycin-sensitive, 2x104 colony-forming-units). At 100d ewes received: erythromycin treatment (500 mg, q3h for 4 days, IM, n=6) or no treatment (n=6). Fetuses were delivered surgically (125d) and AF and chorioamnion were collected for: culture, minimum inhibitory concentration (MIC) and minimum biofilm inhibitory concentration (MBIC) testing; 23S rRNA sequencing; and detection of macrolide-lincosamide-streptogramin resistance (MLSr) genes. Results: MICs of erythromycin, azithromycin and roxithromycin against AF isolates were low (range = 0.06 mg/L to 1.0 mg/L); however, chorioamnion isolates demonstrated increased resistance to roxithromycin (0.13 – 5.33 mg/L). 62.5% of chorioamnion ureaplasmas formed biofilms in vitro and mutations (125 nucleotides, 29.6%) were found in the 23S rRNA gene (domain V) of chorioamnion (but not AF) ureaplasmas. MLSr genes (ermB, msrC and msrD) were detected in 100% of chorioamnion isolates and only msrD was detected in AF isolates (40%). Conclusions: 23S rRNA mutations and MLSr genes occurred independently of erythromycin treatment, suggesting that the anatomical site of infection and microenvironment may exert selective pressures on ureaplasmas that cause genetic changes and alter antimicrobial sensitivity profiles. These results have serious implications for treatment of in utero infections.