Early time course of Akt phosphorylation after endurance and resistance exercise

Purpose The aim of this study was to determine the early time course of exercise-induced signaling after divergent contractile activity associated with resistance and endurance exercise. Methods Sixteen male subjects were randomly assigned to either a cycling (CYC; n = 8, 60 min, 70% V?O2peak) or resistance (REX; n = 8, 8×5 leg extension, 80% one-repetition maximum, 3-min recovery) exercise group. Serial muscle biopsies were obtained from vastus lateralis at rest before, immediately after, and after 15, 30, and 60 min of passive recovery to determine early signaling responses after exercise. Results There were comparable increases from rest in AktThr308/Ser473 and mTORSer2448 phosphorylation during the postexercise time course that peaked 30-60 min after both CYC and REX (P<0.05). There were also similar patterns in p70S6K Thr389 and 4E-BP1Thr37/46 phosphorylation, but a greater magnitude of effect was observed for REX and CYC, respectively (P<0.05). However, AMPKThr172 phosphorylation was only significantly elevated after CYC (P<0.05), and we observed divergent responses for glycogen synthaseSer641 and AS160 phosphorylation that were enhanced after CYC but not REX (P<0.05). Conclusions We show a similar time course for Akt-mTOR-S6K phosphorylation during the initial 60-min recovery period after divergent contractile stimuli. Conversely, enhanced phosphorylation status of proteins that promote glucose transport and glycogen synthesis only occurred after endurance exercise. Our results indicate that endurance and resistance exercise initiate translational signaling, but high-load, low-repetition contractile activity failed to promote phosphorylation of pathways regulating glucose metabolism.

High rates of muscle glycogen resynthesis after exhaustive exercise when carbohydrate is coingested with caffeine

We determined the effect of coingestion of caffeine (Caff) with carbohydrate (CHO) on rates of muscle glycogen resynthesis during recovery from exhaustive exercise in seven trained subjects who completed two experimental trials in a randomized, double-blind crossover design. The evening before an experiment subjects performed intermittent exhaustive cycling and then consumed a low-CHO meal. The next morning subjects rode until volitional fatigue. On completion of this ride subjects consumed either CHO [4 g/kg body mass (BM)] or the same amount of CHO + Caff (8 mg/kg BM) during 4 h of passive recovery. Muscle biopsies and blood samples were taken at regular intervals throughout recovery. Muscle glycogen levels were similar at exhaustion [?75 mmol/kg dry wt (dw)] and increased by a similar amount (?80%) after 1 h of recovery (133 ± 37.8 vs. 149 ± 48 mmol/kg dw for CHO and Caff, respectively). After 4 h of recovery Caff resulted in higher glycogen accumulation (313 ± 69 vs. 234 ± 50 mmol/kg dw, P < 0.001). Accordingly, the overall rate of resynthesis for the 4-h recovery period was 66% higher in Caff compared with CHO (57.7 ± 18.5 vs. 38.0 ± 7.7 mmol·kg dw-1·h-1, P < 0.05). After 1 h of recovery plasma Caff levels had increased to 31 ± 11 ?M (P < 0.001) and at the end of the recovery reached 77 ± 11 ?M (P < 0.001) with Caff. Phosphorylation of CaMKThr286 was similar after exercise and after 1 h of recovery, but after 4 h CaMKThr286 phosphorylation was higher in Caff than CHO (P < 0.05). Phosphorylation of AMP-activated protein kinase (AMPK)Thr172 and AktSer473 was similar for both treatments at all time points. We provide the first evidence that in trained subjects coingestion of large amounts of Caff (8 mg/kg BM) with CHO has an additive effect on rates of postexercise muscle glycogen accumulation compared with consumption of CHO alone.

Characterisation of microvasulature changes after closed soft tissue trauma by contrast enhanced micro-CT imaging

INTRODUCTION It is known that the vascular morphology and functionality are changed following closed soft tissue trauma (CSTT) [1], and bone fractures [2]. The disruption of blood vessels may lead to hypoxia and necrosis. Currently, most clinical methods for the diagnosis and monitoring of CSTT with or without bone fractures are primarily based on qualitative measures or practical experience, making the diagnosis subjective and inaccurate. There is evidence that CSTT and early vascular changes following the injury delay the soft tissue tissue and bone healing [3]. However, a precise qualitative and quantitative morphological assessment of vasculature changes after trauma is currently missing. In this research, we aim to establish a diagnostic framework to assess the 3D vascular morphological changes after standardized CSTT in a rat model qualitatively and quantitatively using contrast-enhanced micro-CT imaging. METHODS An impact device was used for the application of a controlled reproducible CSTT to the left thigh (Biceps Femoris) of anaesthetized male Wistar rats. After euthanizing the animals at 6 hours, 24 hours, 3 days, 7 days, or 14 days after trauma, CSTT was qualitatively evaluated by macroscopic visual observation of the skin and muscles. For visualization of the vasculature, the blood vessels of sacrificed rats were flushed with heparinised saline and then perfused with a radio-opaque contrast agent (Microfil, MV 122, Flowtech, USA) using an infusion pump. After allowing the contrast agent to polymerize overnight, both hind-limbs were dissected, and then the whole injured and contra-lateral control limbs were imaged using a micro-CT scanner (µCT 40, Scanco Medical, Switzerland) to evaluate the vascular morphological changes. Correlated biopsy samples were also taken from the CSTT region of both injured and control legs. The morphological parameters such as the vessel volume ratio (VV/TV), vessel diameter (V.D), spacing (V.Sp), number (V.N), connectivity (V.Conn) and the degree of anisotropy (DA) were then quantified by evaluating the scans of biopsy samples using the micro-CT imaging system. RESULTS AND DISCUSSION A qualitative evaluation of the CSTT has shown that the developed impact protocols were capable of producing a defined and reproducible injury within the region of interest (ROI), resulting in a large hematoma and moderate swelling in both lateral and medial sides of the injured legs. Also, the visualization of the vascular network using 3D images confirmed the ability to perfuse the large vessels and a majority of the microvasculature consistently (Figure 1). Quantification of the vascular morphology obtained from correlated biopsy samples has demonstrated that V.D and V.N and V.Sp were significantly higher in the injured legs 24 hours after impact in comparison with the control legs (p<0.05). The evaluation of the other time points is currently progressing. CONCLUSIONS The findings of this research will contribute to a better understanding of the changes to the vascular network architecture following traumatic injuries and during healing process. When interpreted in context of functional changes, such as tissue oxygenation, this will allow for objective diagnosis and monitoring of CSTT and serve as validation for future non-invasive clinical assessment modalities.

Long-term survival after intensive care unit discharge in Thailand : a retrospective study

Introduction Economic evaluations of interventions in the hospital setting often rely on the estimated long-term impact on patient survival. Estimates of mortality rates and long-term outcomes among patients discharged alive from the intensive care unit (ICU) are lacking from lower- and middle-income countries. This study aimed to assess the long-term survival and life expectancy (LE) amongst post-ICU patients in Thailand, a middle-income country. Methods In this retrospective cohort study, data from a regional tertiary hospital in northeast Thailand and the regional death registry were linked and used to assess patient survival time after ICU discharge. Adult ICU patients aged at least 15 years who had been discharged alive from an ICU between 1 January 2004 and 31 December 2005 were included in the study, and the death registry was used to determine deaths occurring in this cohort up to 31st December 2010. These data were used in conjunction with standard mortality life tables to estimate annual mortality and life expectancy. Results This analysis included 10,321 ICU patients. During ICU admission, 3,251 patients (31.5%) died. Of 7,070 patients discharged alive, 2,527 (35.7%) were known to have died within the five-year follow-up period, a mortality rate 2.5 times higher than that in the Thai general population (age and sex matched). The mean LE was estimated as 18.3 years compared with 25.2 years in the general population. Conclusions Post-ICU patients experienced much higher rates of mortality than members of the general population over the five-year follow-up period, particularly in the first year after discharge. Further work assessing Health Related Quality of Life (HRQOL) in both post-ICU patients and in the general population in developing countries is needed.

HPLC method for preliminary analysis of constituents in rat blood after oral administration of the extract of Acanthopanax senticosus

An HPLC with SPE method has been developed for analysis of constituents in rat blood after oral administration of the extract of Acanthopanax senticosus (ASE). The plasma sample was prepared by SPE method equipped with Oasis HLB cartridge (3cc, 60 mg). The analysis was performed on a Dikma Diamonsil RP(18) column (4.6 mmx150 mm, 5 microm) with the gradient elution of solvent A (ACN) and solvent B (0.1% aqueous phosphoric acid, v/v) and the detection wavelength was set at 270 nm. The calibration curve was linear over the range of 0.156-15.625 microg/mL. The LOD was 60 ng/mL. The intraday precision was less than 5.80%, and the interday precision was less than 6.0%. The recovery was (87.30 +/- 1.73)%. As a result, 19 constituents were detected in rat plasma after oral administration of the ASE, including 11 original compounds in ASE and eight metabolites, and three of the metabolites originated from syringin in ASE. Six constituents were identified by comparing with the corresponding reference compounds.

Can vasculature changes be characterised morphologically after closed soft tissue trauma?

INTRODUCTION Closed soft tissue trauma (CSTT) can be the result of a blunt impact, or a prolonged crush injury and involves damage to the skin, muscles and the neurovascular system. It causes a variety of symptoms such as haematoma and in severe cases may result in hypoxia and necrosis. There is evidence that early vasculature changes following the injury delays the tissue healing [1]. However, a precise qualitative and quantitative morphological assessment of vasculature changes after trauma and the effect of this on CSTT healing is currently missing. Research aims: Developing an experimental rat model to characterise the structural changes to the vasculature after trauma qualitatively and quantitatively using micro CT. MATERIAL AND METHODS An impact device was developed to apply a controlled reproducible CSTT to the left thigh (Biceps Femoris) of anaesthetised rats [3]. After euthanizing the animals at 6 hours after trauma, CSTT was qualitatively evaluated by macroscopic observations of the skin and muscles. For vasculature visualisation, the blood vessels of sacrificed rats were flushed with heparinised saline and then perfused with a radio-opaque contrast agent (Microfil) using an infusion pump (Figure 4). The overall changes to the vasculature as a result of impact trauma were characterised qualitatively based on the 3D reconstructed images of the vasculature (Figure 5). For a smaller region of interest, the morphological parameters such as vessel thickness (diameter), spacing, and average number per volume were quantified using the scanner’s software. RESULTS AND DISCUSSION Visual observation of CSTT has revealed a haematoma in some animals (Figure 3). Micro CT images indicate good perfusion of the vasculature with contrast agent, allowing the major vessels to be identified (Figure 5). Qualitatively and quantitatively, no differences between injured and non-injured legs were observed at 6 h after trauma. Further time points of 12h, 24h, 3 days and 14 days after trauma will be characterised for identifying temporal changes of the vasculature during healing. Histomorphometical studies are required for validation of the results derived from the micro CT imaging. CONCLUSION AND FUTURE DIRECTION Findings of this research may contribute towards the establishment of a fundamental basis for the quantitative assessment and monitoring of CSTT based on microvasculature changes after trauma, which will ultimately allow for optimising the clinical treatment and improve patient outcomes.

Review : "Quality of life: the assessment, analysis and interpretation of patient-reported outcomes (2nd Ed.)" by Peter M. Fayers & David Machin

An updated version, this excellent text is a timely addition to the library of any nurse researching in oncology or other settings where individuals’ quality of life must be understood. Health-related quality of life should be a central aspect of studies concerned with health and illness. Indeed, considerable evidence has recently emerged in oncology and other research settings that selfreported quality of life is of great prognostic significance and may be the most reliable predictor of subsequent morbidity and mortality. From a nursing perspective, it is also gratifying to note that novel therapy and other oncology studies increasingly recognize the importance of understanding patients’ subjective experiences of an intervention over time and to ascertain whether patients perceive that a new intervention makes a difference to their quality of life and treatment outcomes. Measurements of quality of life are now routine in clinical trials of chemotherapy drugs and are often considered the prime outcome of interest in the cost/benefit analyses of these treatments. The authors have extensive experience in qualityof- life assessment in cancer clinical trials, where most of the pioneering work into quality of life has been conducted. That said, many of the health-related qualityof- life issues discussed are common to many illnesses, and researchers outside of cancer should find the book equally helpful.

Risk factors for ocular surface squamous neoplasia recurrence after treatment with topical mitomycin C and interferon alpha-2b

Purpose To determine the rate of recurrence and associated risk factors following the use of mitomycin C (MMC) and/or interferon alpha-2b (IFN) for management of non-invasive ocular surface squamous neoplasia (OSSN). Design Retrospective non-comparative interventional case series. Methods Clinical practice setting of 135 patients treated consecutively with topical MMC (0.4 mg/mL) and/or IFN (1 million units/mL) for OSSN observed for clinical recurrence. Results Clinical recurrences were diagnosed in 19 of 135 (14.1%) eyes following topical treatment. The mean time to recurrence was 17.2 months (range 4 - 61) with 14 (73.7%) recurring within a two year period. There was no greater risk of recurrence identified for variables including lesion size, lesion location, gender, age, treatment type or duration. Post-hoc log-Rank pairwise comparisons revealed that lesions initially treated using surgery alone had significantly reduced time to recurrence (21.1 ± 5.6 months) compared to previous topical treatment with MMC (with or without surgery) (29.6 ± 4.7 months) (p = 0.04) and primary OSSN (23.2 ± 1.8 months) (p = 0.09). Conclusions Topical MMC and IFN are an effective treatment modality for a wide range of non-invasive OSSN. Topical therapy avoids the morbidity of excisional surgery with equivalent or reduced recurrence rates and should be considered as primary therapy.

Assessment of traffic noise level before and after freeway widening using traffic microsimulation and a refined classic noise prediction method

In this paper, a refined classic noise prediction method based on the VISSIM and FHWA noise prediction model is formulated to analyze the sound level contributed by traffic on the Nanjing Lukou airport connecting freeway before and after widening. The aim of this research is to (i) assess the traffic noise impact on the Nanjing University of Aeronautics and Astronautics (NUAA) campus before and after freeway widening, (ii) compare the prediction results with field data to test the accuracy of this method, (iii) analyze the relationship between traffic characteristics and sound level. The results indicate that the mean difference between model predictions and field measurements is acceptable. The traffic composition impact study indicates that buses (including mid-sizedtrucks) and heavy goods vehicles contribute a significant proportion of total noise power despite their low traffic volume. In addition, speed analysis offers an explanation for the minor differences in noise level across time periods. Future work will aim at reducing model error, by focusing on noise barrier analysis using the FEM/BEM method and modifying the vehicle noise emission equation by conducting field experimentation.

The Law of Real Property Mortgages [2nd. Ed.]

This book examines the principles and practice of real estate mortgages in an easily accessible text referenced to all the Australian States. It specifically deals with the major theoretical and practical aspects of the land mortgage, including vitiating factors in formation, mortgagees’ powers and duties and mortgagors’ rights – both statutory and other – as well as assignment, insurance and discharge. It focuses exclusively on real estate mortgages and provides a thorough account of the law through analysis of the plethora of court decisions and statutory provisions in this area. Duncan and Dixon analyse the substance of the mortgage transaction from creation through to rights of enforcement. In its detailed consideration of the rights and obligations of mortgagors and mortgagees, it covers topics such as priorities and tacking, insurance, variation and assignment, rights of discharge, entry into possession, foreclosure and power of sale. In addition, the book contains a separate chapter on factors that may affect the validity and enforcement of a mortgage, together with separate consideration of a mortgagee’s right to enforce a guarantee provided on behalf of a mortgagor, and the rights and liabilities associated with a receivership regime initiated by

Reduced biceps femoris myoelectrical activity influences eccentric knee flexor weakness after repeat sprint running

The aim of this study was to determine whether declines in knee flexor strength following overground repeat sprints were related to changes in hamstrings myoelectrical activity. Seventeen recreationally active males completed maximal isokinetic concentric and eccentric knee flexor strength assessments at 1800.s-1 before and after repeat sprint running. Myoelectrical activity of the biceps femoris (BF) and medial hamstrings (MH) was measured during all isokinetic contractions. Repeated measures mixed model (Fixed factors = time [pre- and post- repeat sprint] and leg [dominant and non-dominant], random factor = participants) design was fitted with the restricted maximal likelihood method. Repeat sprint running resulted in significant declines in eccentric, and concentric, knee flexor strength (eccentric = 25 ± 34 Nm, 15% p<0.001; concentric 11 Nm± 22 Nm, 10% p = 0.001). Eccentric BF myoelectrical activity was significantly reduced (10%; p= 0.033). Concentric BF and all MH myoelectrical activity were not altered. The declines in maximal eccentric torque were associated with the change in eccentric biceps femoris myoelectrical activity (p = 0.013). Following repeat sprint running there were preferential declines in the myoelectrical activity of the BF, which explained declines in eccentric knee flexor strength.

Clinical skin examination outcomes after a video-based behavioral intervention analysis from a randomized clinical trial

Importance Older men are at risk of dying of melanoma. Objective To assess attendance at and clinical outcomes of clinical skin examinations (CSEs) in older men exposed to a video-based behavioral intervention. Design, Setting, and Participants This was a behavioral randomized clinical trial of a video-based intervention in men aged at least 50 years. Between June 1 and August 31, 2008, men were recruited, completed baseline telephone interviews, and were than randomized to receive either a video-based intervention (n = 469) or brochures only (n = 461; overall response rate, 37.1%) and were again interviewed 7 months later (n = 870; 93.5% retention). Interventions Video on skin self-examination and skin awareness and written informational materials. The control group received written materials only. Main Outcomes and Measures Participants who reported a CSE were asked for the type of CSE (skin spot, partial body, or whole body), who initiated it, whether the physician noted any suspicious lesions, and, if so, how lesions were managed. Physicians completed a case report form that included the type of CSE, who initiated it, the number of suspicious lesions detected, how lesions were managed (excision, nonsurgical treatment, monitoring, or referral), and pathology reports after lesion excision or biopsy. Results Overall, 540 of 870 men (62.1%) self-reported a CSE since receiving intervention materials, and 321 of 540 (59.4%) consented for their physician to provide medical information (received for 266 of 321 [82.9%]). Attendance of any CSE was similar between groups (intervention group, 246 of 436 [56.4%]; control group, 229 of 434 [52.8%]), but men in the intervention group were more likely to self-report a whole-body CSE (154 of 436 [35.3%] vs 118 of 434 [27.2%] for control group; P = .01). Two melanomas, 29 squamous cell carcinomas, and 38 basal cell carcinomas were diagnosed, with a higher proportion of malignant lesions in the intervention group (60.0% vs 40.0% for controls; P = .03). Baseline attitudes, behaviors, and skin cancer history were associated with higher odds of CSE and skin cancer diagnosis. Conclusions and Relevance A video-based intervention may increase whole-body CSE and skin cancer diagnosis in older men. Trial Registration: anzctr.org.au Identifier: ACTRN12608000384358

Evaluation of canine bone marrow-derived mesenchymal stem cells after long-term cryopreservation

Autologous bone marrow-derived mesenchymal stem cell (BMSCs)-based therapies show great potential in regenerative medicine. However, long-term storage and preservation of BMSCs for clinical use is still a great clinical challenge. The present study aimed to analyze the effect of long-term cryopreservation on the regenerative ability of BMSCs. After cryopreservation of BMSCs from beagle dogs for three years, cell viability, and quantitative analysis of alkaline phosphatase (ALP) activity, surface adherence, and mineralized nodule formation were analyzed. BMSCs in cell-scaffold complex were then implanted into nude mice. There was no significant difference in cell viability and ALP activity between osteogenic differentiation and non-osteogenic differentiation of BMSCs, and BMSCs in cell-scaffold complex retained osteogenic differentiation ability in vivo. These results indicate that long-term cryopreserved BMSCs maintain their have capacity to contribute to regeneration.

Carbonic anhydrase IX expression and outcome after radiotherapy for muscle-invasive bladder cancer

Aims: Carbonic anhydrase IX (CA IX) expression has been described as an endogenous marker of hypoxia in solid neoplasms. Furthermore, CA IX expression has been associated with an aggressive phenotype and resistance to radiotherapy. We assessed the prognostic significance of CA IX expression in patients with muscle-invasive bladder cancer treated with radiotherapy. Materials and methods: A standard immunohistochemistry technique was used to show CA IX expression in 110 muscle-invasive bladder tumours treated with radiotherapy. Clinicopathological data were obtained from medical case notes. Results: CA IX immunostaining was detected in 89 (∼81%) patients. Staining was predominantly membranous, with areas of concurrent cytoplasmic and nuclear staining and was abundant in luminal and perinecrotic areas. No significant correlation was shown between the overall CA IX status and the initial response to radiotherapy, 5-year bladder cancer-specific survival or the time to local recurrence. Conclusions: The distribution of CA IX expression in paraffin-embedded tissue sections seen in this series is consistent with previous studies in bladder cancer, but does not provide significant prognostic information with respect to the response to radiotherapy at 3 months and disease-specific survival after radical radiotherapy. © 2007 The Royal College of Radiologists.