Low muscle glycogen concentration does not suppress the anabolic response to resistance exercise

We determined the effect of muscle glycogen concentration and postexercise nutrition on anabolic signaling and rates of myofibrillar protein synthesis after resistance exercise (REX). Sixteen young, healthy men matched for age, body mass, peak oxygen uptake (VO2peak) and strength (one repetition maximum; 1RM) were randomly assigned to either a nutrient or placebo group. After 48 h diet and exercise control, subjects undertook a glycogen-depletion protocol consisting of one-leg cycling to fatigue (LOW), whereas the other leg rested (NORM). The next morning following an overnight fast, a primed, constant infusion of L-[ring-13C6] phenylalanine was commenced and subjects completed 8 sets of 5 unilateral leg press repetitions at 80% 1RM. Immediately after REX and 2 h later, subjects consumed a 500 ml bolus of a protein/CHO (20 g whey + 40 g maltodextrin) or placebo beverage. Muscle biopsies from the vastus lateralis of both legs were taken at rest and 1 and 4 h after REX. Muscle glycogen concentration was higher in the NORM than LOW at all time points in both nutrient and placebo groups (P < 0.05). Postexercise Akt-p70S6K-rpS6 phosphorylation increased in both groups with no differences between legs (P < 0.05). mTORSer2448 phosphorylation in placebo increased 1 h after exercise in NORM (P < 0.05), whereas mTOR increased ?4-fold in LOW (P < 0.01) and ?11 fold in NORM with nutrient (P < 0.01; different between legs P < 0.05). Post-exercise rates of MPS were not different between NORM and LOW in nutrient (0.070 ± 0.022 vs. 0.068 ± 0.018 %/h) or placebo (0.045 ± 0.021 vs. 0.049 ± 0.017 %/h). We conclude that commencing high-intensity REX with low muscle glycogen availability does not compromise the anabolic signal and subsequent rates of MPS, at least during the early (4 h) postexercise recovery period.

Response to chemotherapy is predictive in relation to longer overall survival in an individual patient combined-analysis with pleural mesothelioma

Background: There is currently no early predictive marker of survival for patients receiving chemotherapy for malignant pleural mesothelioma (MPM). Tumour response may be predictive for overall survival (OS), though this has not been explored. We have thus undertaken a combined-analysis of OS, from a 42 day landmark, of 526 patients receiving systemic therapy for MPM. We also validate published progression-free survival rates (PFSRs) and a progression-free survival (PFS) prognostic-index model. Methods: Analyses included nine MPM clinical trials incorporating six European Organisation for Research and Treatment of Cancer (EORTC) studies. Analysis of OS from landmark (from day 42 post-treatment) was considered regarding tumour response. PFSR analysis data included six non-EORTC MPM clinical trials. Prognostic index validation was performed on one non-EORTC data-set, with available survival data. Results: Median OS, from landmark, of patients with partial response (PR) was 12·8 months, stable disease (SD), 9·4 months and progressive disease (PD), 3·4 months. Both PR and SD were associated with longer OS from landmark compared with disease progression (both p < 0·0001). PFSRs for platinum-based combination therapies were consistent with published significant clinical activity ranges. Effective separation between PFS and OS curves provided a validation of the EORTC prognostic model, based on histology, stage and performance status. Conclusion: Response to chemotherapy is associated with significantly longer OS from landmark in patients with MPM. © 2012 Elsevier Ltd. All rights reserved.

Gene expression analysis of diagnostic biopsies predicts pathological response to neoadjuvant chemoradiotherapy of esophageal cancer

OBJECTIVE: This study explored gene expression differences in predicting response to chemoradiotherapy in esophageal cancer. PURPOSE:: A major pathological response to neoadjuvant chemoradiation is observed in about 40% of esophageal cancer patients and is associated with favorable outcomes. However, patients with tumors of similar histology, differentiation, and stage can have vastly different responses to the same neoadjuvant therapy. This dichotomy may be due to differences in the molecular genetic environment of the tumor cells. BACKGROUND DATA: Diagnostic biopsies were obtained from a training cohort of esophageal cancer patients (13), and extracted RNA was hybridized to genome expression microarrays. The resulting gene expression data was verified by qRT-PCR. In a larger, independent validation cohort (27), we examined differential gene expression by qRT-PCR. The ability of differentially-regulated genes to predict response to therapy was assessed in a multivariate leave-one-out cross-validation model. RESULTS: Although 411 genes were differentially expressed between normal and tumor tissue, only 103 genes were altered between responder and non-responder tumor; and 67 genes differentially expressed >2-fold. These included genes previously reported in esophageal cancer and a number of novel genes. In the validation cohort, 8 of 12 selected genes were significantly different between the response groups. In the predictive model, 5 of 8 genes could predict response to therapy with 95% accuracy in a subset (74%) of patients. CONCLUSIONS: This study has identified a gene microarray pattern and a set of genes associated with response to neoadjuvant chemoradiation in esophageal cancer. The potential of these genes as biomarkers of response to treatment warrants further investigation. Copyright © 2009 by Lippincott Williams & Wilkins.

A metastatic neuroendocrine anaplastic small cell tumor in a patient with multiple endocrine neoplasia type 1 syndrome : assessment of disease status and response to doxorubicin, cyclophosphamide, etoposide chemotherapy through scintigraphic imaging with 111In-pentetreotide

Extrapulmonary small cell and small cell neuroendocrine tumors of unknown primary site are, in general, aggressive neoplasms with a short median survival. Like small cell lung cancer (SCLC), they often are responsive to chemotherapy and radiotherapy. Small cell lung cancer and well differentiated neuroendocrine carcinomas of the gastrointestinal tract and pancreas tend to express somatostatin receptors. These tumors may be localized in patients by scintigraphic imaging using radiolabeled somatostatin analogues. A patient with an anaplastic neuroendocrine small cell tumor arising on a background of multiple endocrine neoplasia type 1 syndrome is reported. The patient had a known large pancreatic gastrinoma and previously treated parathyroid adenopathy. At presentation, there was small cell cancer throughout the liver and skeleton. Imaging with a radiolabeled somatostatin analogue, 111In- pentetreotide (Mallinckrodt Medical B. V., Petten, Holland), revealed all sites of disease detected by routine biochemical and radiologic methods. After six cycles of chemotherapy with doxorubicin, cyclophosphamide, and etoposide, there was almost complete clearance of the metastatic disease. 111In-pentetreotide scintigraphy revealed uptake consistent with small areas of residual disease in the liver, the abdomen (in mesenteric lymph nodes), and posterior thorax (in a rib). The primary gastrinoma present before the onset of the anaplastic small cell cancer showed no evidence of response to the treatment. The patient remained well for 1 year and then relapsed with brain, lung, liver, and skeletal metastases. Despite an initial response to salvage radiotherapy and chemotherapy with carboplatin and dacarbazine, the patient died 6 months later.

Storylines of institutional responses to climate change as a transformative stressor : the case of regional planning in South East Queensland, Australia

Institutional responses to climate change stresses through planning will require new and amended forms of governance. Institutional framing of change imperatives can significantly condition associated governance responses. This paper builds on scholarly conversations concerning the conceptual role of ‘storylines’ in shaping institutional responses to climate change through governance. It draws on conceptual perspectives of climate change as a ‘transformative stressor’, which can compel institutional transformation within planning. The concepts of storylines and transformative stressors are conceptually linked. The conceptual approach is applied to an empirical enquiry focused on the regional planning regime of South East Queensland (SEQ), Australia. This paper reports and examines three institutional storylines of responding to climate change through planning governance in SEQ. It concludes that the manifestation of climate change as a transformative stressor in SEQ prompted institutional transformation, leading to a dominant storyline focused on climate adaptation as an important facet of regional planning governance.

Community health workers' response to violence against women

This paper reports on a qualitative study of community health workers from a predominantly rural based region in Queensland. The purpose of this study was to determine the community health worker barriers to identification, assessment and intervention on the issue of violence against women. The qualitative research method comprised five structured focus group interviews with 28 community health workers using open-ended questions to explore their perceptions. Analysis of the focus group data revealed that community health workers expressed reluctance to become involved in cases of violence against women. The reasons they provided are grouped under three main themes: barriers to identification; barriers to assessment; and barriers to intervention. Training programs offered to rural community health workers need to be aware of the barriers to identifying, assessing and intervening in cases of violence against women that are highlighted by this study. Further studies are needed to assess the wider relevance of these findings to other groups of community health workers in rural and non-rural settings.

Beyond the ‘three dogmas of juvenile justice’ : a response to Weatherburn, McGrath and Bartels

In 'Three Dogmas of Juvenile Justice', Weatherburn, McGrath and Bartels identify three 'assumptions' or 'dogmas' about youth justice, on which they claim 'juvenile justice policy in Australia currently rests'.

Factors influencing health professionals' response to victims of domestic violence

This thesis examined factors influencing health professional's response to victims of domestic violence in Vietnam. As this is the first time that this type of research has been conducted in Vietnam, it was expected that the results would contribute significantly to local knowledge and should add to global perspectives. Since it is the first questionnaire about this topic to be developed in Vietnam, the psychometric property of the questionnaire was primarily established, resulting in the questionnaire being recommended to use for further study. By explaining the factors that affect the intentions to respond of health workers, this project provides key data for authorities to design intervention strategies to improve the responses of health professionals to victims of domestic violence in Vietnam.

Shadow boxing with an imaginary enemy : a response to "Law and Order Blues"

In our rejoinder to Don Weatherburn's paper,"Law and Order Blues", we do not take issue with his advocacy of the need to take crime seriously and to foster a more rational approach to the problems it poses. Where differences do emerge is (1) with his claim that he is willing to do so whilst we (in our different ways) are not; and (2) on the question of what this involves. Of particular concern is the way in which his argument proceeds by a combination of simple misrepresentation of the positions it seeks to disparage, and silence concerning issues of real substance where intellectual debate and exchange would be welcome and useful. Our paper challenges, in turn, the misrepresentation of Indermaur's analysis of trends in violent crime, the misrepresentation of Hogg and Brown's Rethinking Law and Order, the misrepresentation of the findings of some of the research into the effectiveness of punitive policies and the silence on sexual assault in "Law and Order Blues". We suggest that his silence on sexual assault reflects a more widespread unwillingness to acknowledge the methodological problems that arise in the measurement of crime because such problems severely limit the extent to which confident assertions can be made about prevalence and trends.

No sex difference in body fat in response to supervised and measured exercise

It is often reported that females lose less body weight than males do in response to exercise. These differences are suggested to be a result of females exhibiting a stronger defense of body fat and a greater compensatory appetite response to exercise than males do. Purpose This study aimed to compare the effect of a 12-wk supervised exercise program on body weight, body composition, appetite, and energy intake in males and females. Methods A total of 107 overweight and obese adults (males = 35, premenopausal females = 72, BMI = 31.4 ± 4.2 kg·m−2, age = 40.9 ± 9.2 yr) completed a supervised 12-wk exercise program expending approximately 10.5 MJ·wk−1 at 70% HRmax. Body composition, energy intake, appetite ratings, RMR, and cardiovascular fitness were measured at weeks 0 and 12. Results The 12-wk exercise program led to significant reductions in body mass (males [M] = −3.03 ± 3.4 kg and females [F] = −2.28 ± 3.1 kg), fat mass (M = −3.14 ± 3.7 kg and F = −3.01 ± 3.0 kg), and percent body fat (M = −2.45% ± 3.3% and F = −2.45% ± 2.2%; all P < 0.0001), but there were no sex-based differences (P > 0.05). There were no significant changes in daily energy intake in males or females after the exercise intervention compared with baseline (M = 199.2 ± 2418.1 kJ and F = −131.6 ± 1912.0 kJ, P > 0.05). Fasting hunger levels significantly increased after the intervention compared with baseline values (M = 11.0 ± 21.1 min and F = 14.0 ± 22.9 mm, P < 0.0001), but there were no differences between males and females (P > 0.05). The exercise also improved satiety responses to an individualized fixed-energy breakfast (P < 0.0001). This was comparable in males and females. Conclusions Males and premenopausal females did not differ in their response to a 12-wk exercise intervention and achieved similar reductions in body fat. When exercise interventions are supervised and energy expenditure is controlled, there are no sex-based differences in the measured compensatory response to exercise.

The adaptive metabolic response to exercise-induced weight loss influences both energy expenditure and energy intake

BACKGROUND/OBJECTIVEs A decline in resting energy expenditure (REE) beyond that predicted from changes in body composition has been noted following dietary-induced weight loss. However, it is unknown whether a compensatory downregulation in REE also accompanies exercise (EX)-induced weight loss, or whether this adaptive metabolic response influences energy intake (EI). SUBJECTS/METHODS Thirty overweight and obese women (body mass index (BMI)=30.6±3.6 kg/m2) completed 12 weeks of supervised aerobic EX. Body composition, metabolism, EI and metabolic-related hormones were measured at baseline, week 6 and post intervention. The metabolic adaptation (MA), that is, difference between predicted and measured REE was also calculated post intervention (MApost), with REE predicted using a regression equation generated in an independent sample of 66 overweight and obese women (BMI=31.0±3.9 kg/m2). RESULTS Although mean predicted and measured REE did not differ post intervention, 43% of participants experienced a greater-than-expected decline in REE (−102.9±77.5 kcal per day). MApost was associated with the change in leptin (r=0.47; P=0.04), and the change in resting fat (r=0.52; P=0.01) and carbohydrate oxidation (r=−0.44; P=0.02). Furthermore, MApost was also associated with the change in EI following EX (r=−0.44; P=0.01). CONCLUSIONS Marked variability existed in the adaptive metabolic response to EX. Importantly, those who experienced a downregulation in REE also experienced an upregulation in EI, indicating that the adaptive metabolic response to EX influences both physiological and behavioural components of energy balance.

Effects of scaffold architecture on mechanical characteristics and osteoblast response to static and perfusion bioreactor cultures

Tissue engineering focuses on the repair and regeneration of tissues through the use of biodegradable scaffold systems that structurally support regions of injury whilst recruiting and/or stimulating cell populations to rebuild the target tissue. Within bone tissue engineering, the effects of scaffold architecture on cellular response have not been conclusively characterized in a controlled-density environment. We present a theoretical and practical assessment of the effects of polycaprolactone (PCL) scaffold architectural modifications on mechanical and flow characteristics as well as MC3T3-E1 preosteoblast cellular response in an in vitro static plate and custom-designed perfusion bioreactor model. Four scaffold architectures were contrasted, which varied in inter-layer lay-down angle and offset between layers, whilst maintaining a structural porosity of 60 ± 5%. We established that as layer angle was decreased (90° vs. 60°) and offset was introduced (0 vs. 0.5 between layers), structural stiffness, yield stress, strength, pore size and permeability decreased, whilst computational fluid dynamics-modeled wall shear stress was increased. Most significant effects were noted with layer offset. Seeding efficiencies in static culture were also dramatically increased due to offset (~45% to ~86%), with static culture exhibiting a much higher seeding efficiency than perfusion culture. Scaffold architecture had minimal effect on cell response in static culture. However, architecture influenced osteogenic differentiation in perfusion culture, likely by modifying the microfluidic environment.

The IL-6 response to Chlamydia from primary reproductive epithelial cells is highly variable and may be involved in differential susceptibility to the immunopathological consequences of chlamydial infection

Background Chlamydia trachomatis infection results in reproductive damage in some women. The process and factors involved in this immunopathology are not well understood. This study aimed to investigate the role of primary human cellular responses to chlamydial stress response proteases and chlamydial infection to further identify the immune processes involved in serious disease sequelae. Results Laboratory cell cultures and primary human reproductive epithelial cultures produced IL-6 in response to chlamydial stress response proteases (CtHtrA and CtTsp), UV inactivated Chlamydia, and live Chlamydia. The magnitude of the IL-6 response varied considerably (up to 1000 pg ml-1) across different primary human reproductive cultures. Thus different levels of IL-6 production by reproductive epithelia may be a determinant in disease outcome. Interestingly, co-culture models with either THP-1 cells or autologous primary human PBMC generally resulted in increased levels of IL-6, except in the case of live Chlamydia where the level of IL-6 was decreased compared to the epithelial cell culture only, suggesting this pathway may be able to be modulated by live Chlamydia. PBMC responses to the stress response proteases (CtTsp and CtHtrA) did not significantly vary for the different participant cohorts. Therefore, these proteases may possess conserved innate PAMPs. MAP kinases appeared to be involved in this IL-6 induction from human cells. Finally, we also demonstrated that IL-6 was induced by these proteins and Chlamydia from mouse primary reproductive cell cultures (BALB/C mice) and mouse laboratory cell models. Conclusions We have demonstrated that IL-6 may be a key factor for the chlamydial disease outcome in humans, given that primary human reproductive epithelial cell culture showed considerable variation in IL-6 response to Chlamydia or chlamydial proteins, and that the presence of live Chlamydia (but not UV killed) during co-culture resulted in a reduced IL-6 response suggesting this response may be moderated by the presence of the organism.

Response to re : putting vital stains in context

A response to: "Re: Putting vital stains in context" by Eric Papas & Lyndon Jones, published in the same issue of this journal. "There has been considerable discussion in recent times about the origins of solution-induced corneal staining (SICS) and I welcome this opportunity to further clarify some points raised in my paper1 in relation to certain issues highlighted by Drs Papas and Jones.2 Part of the difficulty in understanding these phenomena relates to the imprecise terminology used. For example, Drs Papas and Jones state ‘. . . SICS..."

Response to re : putting vital stains in context

A response to "Re: Putting vital stains in context" by Charles W McMonnies, published in the same issue of this journal. "I thank Professor McMonnies for his thoughtful comments,1 which rightly forcemeto more directly address the clinical ramifications of solution-induced corneal staining (SICS). I concur with his observation that determining whether the staining can be attributed to preservative-associated transient hyperfluorescence (PATH) or true pathology can be difficult in a typical clinical situation, perhaps requiring two visits in a single day. There is no easy answer to this dilemma..."