Exercise combined with Acceptance and Commitment Therapy for chronic pain: One-year follow-up from a randomized controlled trial.

BACKGROUND: Acceptance and Commitment Therapy (ACT) is a type of Cognitive Behavioural Therapy, which has demonstrated positive outcomes in individuals with chronic pain. The purpose of this study was to compare the effect of an 8-week programme combining Exercise with Acceptance and Commitment Therapy (ExACT) with a standalone supervised exercise programme at 1-year follow-up. METHODS: One hundred and seventy-five people with chronic pain were randomly assigned to ExACT or supervised exercise only. The primary outcome was pain interference measured with the Brief Pain Inventory-Interference Scale. Secondary and treatment process outcomes included pain severity, depression, anxiety, pain catastrophizing, pain self-efficacy, fear avoidance, pain acceptance, committed action, healthcare utilization, patient satisfaction, and global impression of change. Estimates of treatment effects at 1-year follow-up were based on intention-to-treat analyses, implemented using a linear mixed-effects model. RESULTS: Eighty-three participants (47.4%) returned the outcome measures at 1-year follow-up. No significant difference was observed between the groups for the primary outcome, pain interference. There was a statistically significant difference between the groups, in favour of ExACT for pain catastrophizing. Within group improvements that were observed within both groups at earlier timepoints were maintained at 1-year follow-up for many of the secondary and treatment process outcomes. ExACT group participants reported higher levels of satisfaction with treatment and global perceived change. CONCLUSIONS: The study results showed no significant difference between the two groups for the primary outcome pain interference at 1-year follow-up. Future research could investigate factors that may predict and optimize outcomes from these types of intervention for people living with chronic pain. SIGNIFICANCE: Few previous randomized controlled trials investigating ACT for chronic pain have included long-term follow-up. This study found that Exercise combined with ACT was not superior to supervised exercise alone for reducing pain interference at 1-year follow-up. Further research is necessary to identify key processes of therapeutic change and to explore how interventions may be modified to enhance clinical outcomes for people with chronic pain.

Using methylcholanthrene-induced fibrosarcomas to study tumor immunology.

Mouse models of cancer are essential in furthering our understanding both of the mechanisms that drive tumor development and the immune response that develops in parallel, and also in providing a platform for testing novel anti-cancer therapies. The majority of solid tumor models available rely on the injection of existing cancer cell lines into naïve hosts which, while providing quick and reproducible model systems, typically lack the development of a tumor microenvironment that recapitulates those seen in human cancers. Administration of the carcinogen 3-methylcholanthrene (MCA), allows tumors to develop in situ, forming a tumor microenvironment with an established stroma and vasculature. This article provides a detailed set of protocols for the administration of MCA into mice and the subsequent monitoring of tumors. Protocols are also provided for some of the routinely used downstream applications that can be used for MCA tumors.

Pain sensitization in people with knee osteoarthritis: a systematic review and meta-analysis.

OBJECTIVE: Emerging evidence suggests that pain sensitization plays an important role in pain associated with knee osteoarthritis (OA). This systematic review and meta-analysis examined the evidence for pain sensitization in people with knee OA and the relationship between pain sensitization and symptom severity. METHODS: A search of electronic databases and reference lists was carried out. All full text observational studies published between 2000 and 2014 with the aim of investigating pain sensitization in humans with knee OA using quantitative sensory testing (QST) measures of hyperalgesia and central hyperexcitability were eligible for inclusion. Meta-analysis of data was carried out using a random effects model, which included results comparing knee OA participants to controls, and results comparing high symptom severity to low symptom severity. RESULTS: Fifteen studies were identified following screening and quality appraisal. For the meta-analysis, pressure pain threshold (PPT) and heat pain threshold (HPT) means and standard deviations were pooled using random effects models. The point estimate was large for differences in PPTs between knee OA participants and controls [-0.85; confidence interval (CI): -1.1 to -0.6], and moderate for PPT differences between knee OA participants with high symptom severity vs those with low symptom severity (0.51; CI: -0.73 to -0.30). A small point estimate was found for differences in HPTs between knee OA participants and controls (-0.42; CI: -0.87 to 0.02). CONCLUSION: Evidence from this systematic review and meta-analysis suggests that pain sensitization is present in people with knee OA and may be associated with knee OA symptom severity.

Development of a phenotypic assay for characterisation of ethanologenic yeast strain sensitivity to inhibitors released from lignocellulosic feedstocks.

Inhibitors released by the breakdown of plant cell walls prevent efficient conversion of sugar into ethanol. The aim of this study was to develop a fast and reliable inhibitor sensitivity assay for ethanologenic yeast strains. The assay comprised bespoke 96-well plates containing inhibitors in isolation or combination in a format that was compatible with the Phenotypic Microarray Omnilog reader (Biolog, hayward, CA, USA). A redox reporter within the assay permits analysis of inhibitor sensitivity in aerobic and/or anaerobic conditions. Results from the assay were verified using growth on spot plates and tolerance assays in which maintenance of viability was assessed. The assay allows for individual and synergistic effects of inhibitors to be determined. It was observed that the presence of both acetic and formic acid significantly inhibited the yeast strains assessed, although this impact could be partially mitigated by buffering to neutral pH. Scheffersomyces stipitis, Candida spp., and Pichia guilliermondii demonstrated increased sensitivity to short chain weak acids at concentrations typically present in lignocellulosic hydrolysates. S. cerevisiae exhibited robustness to short chain weak acids at these concentrations. However, S. stipitis, Candida spp., and P. guilliermondii displayed increased tolerance to HMF when compared to that observed for S. cerevisiae. The results demonstrate that the phenotypic microarray assay developed in the current study is a valuable tool that can be used to identify yeast strains with desirable resistance to inhibitory compounds found in lignocellulosic hydrolysates.

Orthopaedic triage at a physiotherapist-led 'Musculoskeletal Assessment Clinic': a seven-month service evaluation of outcomes.

BACKGROUND: A number of clinical specialist physiotherapist (CSP)-led musculoskeletal triage clinics have been established in the Republic of Ireland as a means of managing patients referred for an outpatient orthopaedic consultation. AIMS: The purpose of this study was to evaluate the outcomes of a recently established 'Musculoskeletal Assessment Clinic' (MAC) in St Vincent's University Hospital (SVUH) Dublin. We identified the (a) number of patients independently managed by the CSPs and (b) conversion rate to orthopaedic intervention as a useful measure of this. METHODS: University College Dublin Research Ethics Committee granted ethical exemption and the Clinical Audit Department of SVUH approved the study. A retrospective service evaluation was carried out on all orthopaedic patients who attended the MAC between January and July 2012. Data were analysed using SPSS v20 using descriptive statistics. RESULTS: Seven-hundred and fourteen patients attended the MAC, 54 % of whom were female; mean age 50 years (range 12-89). The majority of patients were diagnosed with low back pain (35 %) and knee osteoarthritis (16 %). The majority of patients who attended the MAC (76 %) were independently managed by the CSPs without need for orthopaedic consultation; from a valid sample (n = 110), 80 patients required orthopaedic intervention, a conversion rate of 73 %. The most common interventions were arthroplasty (22 %) and arthroscopy (16 %). CONCLUSIONS: The findings of this service evaluation indicate that a significant number of patients referred for an orthopaedic consultation may be managed independently by a CSP and that onward referrals for orthopaedic consultation were highly appropriate.

Highly prevalent colorectal cancer-infiltrating LAP⁺ Foxp3⁻ T cells exhibit more potent immunosuppressive activity than Foxp3⁺ regulatory T cells.

Although elevated CD4⁺Foxp3⁺ regulatory T cell (Treg) frequencies within tumors are well documented, the functional and phenotypic characteristics of CD4⁺Foxp3⁺ and CD4⁺Foxp3⁻ T cell subsets from matched blood, healthy colon, and colorectal cancer require in-depth investigation. Flow cytometry revealed that the majority of intratumoral CD4⁺Foxp3⁺ T cells (Tregs) were Helios⁺ and expressed higher levels of cytotoxic T-lymphocyte antigen 4 (CTLA-4) and CD39 than Tregs from colon and blood. Moreover, ∼30% of intratumoral CD4⁺Foxp3⁻ T cells expressed markers associated with regulatory functions, including latency-associated peptide (LAP), lymphocyte activation gene-3 (LAG-3), and CD25. This unique population of cells produced interleukin-10 (IL-10) and transforming growth factor-ß (TGF-ß), and was ∼50-fold more suppressive than Foxp3⁺ Tregs. Thus, intratumoral Tregs are diverse, posing multiple obstacles to immunotherapeutic intervention in colorectal malignancies.

Evaluation of ITS PCR and RFLP for Differentiation and Identification of Brewing Yeast and Brewery 'Wild' Yeast Contaminants.

A reference library of ITS PCR/RFLP profiles was collated and augmented to evaluate its potential for routine identification of domestic brewing yeast and known 'wild' yeast contaminants associated with wort, beer and brewing processes. This library contains information on band sizes generated by restriction digestion of the ribosomal RNA-encoding DNA (rDNA) internal transcribed spacer (ITS) region consisting of the 5.8 rRNA gene and two flanking regions (ITS1 and ITS2) with the endonucleases CfoI, HaeIII, HinfI and includes strains from 39 non-Saccharomyces yeast species as well as for brewing and non-brewing strains of Saccharomyces. The efficacy of the technique was assessed by isolation of 59 wild yeasts from industrial fermentation vessels and conditioning tanks and by matching their ITS amplicon sizes and RFLP profiles with those of the constructed library. Five separate, non-introduced yeast taxa were putatively identified. These included Pichia species, which were associated with conditioning tanks and Saccharomyces species isolated from fermentation vessels. Strains of the lager yeast S. pastorianus could be reliably identified as belonging to either the Saaz or Frohberg hybrid group by restriction digestion of the ITS amplicon with the enzyme HaeIII. Frohberg group strains could be further sub-grouped depending on restriction profiles generated with HinfI.

Copper and calcium uptake in colored hair.

During hair coloring a number of disulfide bonds in cystine are oxidized (1) to create cysteic acid, forming binding sites for metal ions such as Ca(2+ )and Cu(2+ )from tap water (2). The increased uptake of these metals can have a detrimental impact on fiber properties-for example, reducing shine and causing a poor wet and dry feel (3). In addition, the increased uptake of copper can also contribute to further fiber damage during subsequent coloring due to its ability to take part in metal-induced radical chemistry (4). It is important to know where in the fibers these metals are located in order to either effectively remove these metals or control their chemistry. Nanoscale secondary ion mass spectrometry (NanoSIMS) has been used to locate the calcium and copper within hair that has been treated with a colorant and washed multiple times in tap water containing these ions. Untreated hair is used as a baseline standard material. Images with up to 50-nm spatial resolution of the preferential locations of calcium uptake were obtained, showing a high concentration of calcium in the cuticle region of colored hair, specifically in the sulfur-rich regions (A-layer and exocuticle).

Petite mutation in aged and oxidatively stressed ale and lager brewing yeast.

AIMS: To determine the role of oxidative stress and chronological ageing on the propensity of brewing yeast strains to form respiratory deficient 'petites'. METHODS AND RESULTS: Four industrial yeast strains (two ale and two lager strains) were exposed to oxidative stress in the form of H(2)O(2) (5 mmol l(-1)) for two hours. Cell viability and occurrence of petites were determined by the slide culture and TTC-overlay techniques, respectively. Increases in petite frequency were observed but only in those strains sensitive to oxidative stress. Chronological ageing under aerobic conditions led to an increase in petites in strains sensitive to oxidative stress. No such increase was observed under anaerobic conditions. CONCLUSION: Ageing may contribute to mitochondrial DNA damage and increase the propensity of brewing yeast cells to become respiratory deficient. Tolerant strains may be less likely to generate petites as a result of serial re-pitching. SIGNIFICANCE AND IMPACT OF THE STUDY: Continuous re-use of brewing yeast is associated with an increase in the frequency of petites within brewery yeast slurries, a phenomenon resulting in reduced fermentative capacity. The cause of petite generation during brewery handling is unknown. We show that endogenous oxidative stress has the potential to generate petites within brewing yeast populations.

Paracetamol overdose as a result of dental pain requiring medical treatment - two case reports.

Two cases of unintentional paracetamol overdose are presented. Over a one month period these patients presented to an Accident and Emergency (A&E) department with symptoms of paracetamol toxicity, following the ingestion of large quantities of analgesia for the self treatment of dental pain. In one case the patient had no access to a dentist. Both patients required admission under the care of the medical on-call team and required anti-toxicity treatment to prevent permanent liver injury. Subsequent referrals were made to the oral and maxillofacial surgery team who provided emergency dental treatment and advice on further dental care. This paper highlights the significant signs and symptoms of paracetamol overdose about which dental practitioners should be aware. It also describes the management principles required to prevent potentially life threatening liver damage. Discussion is also made of the potential impact on patients struggling to cope with pulpal pain without access to a general dental practitioner.

Credible investigation of air accidents.

Within the United Kingdom the Air Accidents Investigation Branch (AAIB) has been used as a model for the other transport modes accident investigation bodies. Government Ministers considered that the AAIB's approach had established the trust of the public and the aviation industry in its ability to conduct independent and objective investigations. The paper will examine the factors that are involved in establishing this trust. They include: the investigation framework; the actual and perceived independence of the accident investigating body; the aviation industry's safety culture; the qualities of the investigators and the quality of their liaison with bereaved families those directly affected by the accidents they investigate.

The impact of catalase expression on the replicative lifespan of Saccharomyces cerevisiae.

The role of catalase on Saccharomyces cerevisiae replicative lifespan was investigated using a wild-type haploid laboratory yeast W303a, a catalase A mutant, a catalase T mutant and an acatalasaemic mutant. Lifespan analysis was performed in two different environmental conditions. Under repressing conditions, on glucose media, catalase T activity, but not catalase A activity was necessary to assure longevity. However, under derepressing conditions, on ethanol media, both catalases were required for longevity assurance. Although catalase activity and carbon source influence yeast lifespan, the relationship between oxidative defence and replicative senescence is complex.

Issues in life support and human factors in crew rescue from the ISS.

The design and development of crew emergency response systems, particularly to provide an unplanned emergency return to Earth, requires an understanding of crew performance challenges in space. The combined effects of psychological and physiological adaptation during long-duration missions will have a significant effect on crew performance in the unpredictable and potentially life-threatening conditions of an emergency return to Earth. It is therefore important that the systems to be developed for emergency egress address these challenges through an integrated program to produce optimum productivity and safety in times of utmost stress. Fundamental to the success of the CRV is the Environmental Control and Life Support System (ECLSS), which provides the necessary conditions for the crew to survive their return mission in a shirtsleeve environment. This article will discuss the many issues in the design of an ECLSS system for CRV and place it in the context of the human performance challenges of the mission.

Human factors and life support issues in crew rescue from the International Space Station (ISS).

The design and development of crew emergency response systems, particularly to provide an unplanned emergency return to earth, requires an understanding of crew performance challenges in space. The combined effects of psychological and physiological adaptation during long duration missions will have a significant effect on crew performance in the unpredictable and potentially life threatening conditions of an emergency return to earth. It is therefore important that the systems to be developed for emergency egress address these challenges through an integrated program to produce optimum productivity and safety in times of utmost stress. Fundamental to the success of the CRV is the Environmental Control and Life Support System (ECLSS), which provides the necessary conditions for the crew to survive their return mission in a shirt-sleeve environment. This paper will discuss the many issues in the design of an ECLSS system for CRV and place it in the context of the human performance challenges of the mission.

The impact of media composition and petite mutation on the longevity of a polyploid brewing yeast strain.

Ageing in Saccharomyces cerevisiae is a finite phenomenon, determined by replicative, rather than chronological lifespan. Yeast physiological condition is known to influence industrial fermentation performance, however, until recently cellular senescence has not been considered as a brewing yeast stress factor. A polyploid lager yeast (BB11) and a brewery isolate, exhibiting petite mutation were analysed for longevity. It was observed that mitochondrial deficiency induced a reduction in lifespan. In addition, replicative capacity was perceived to be dependent on environmental conditions.

Sentinel lymphadenectomy for staging patients with intermediate-level melanoma.

Sentinel lymph node dissection (SLND) as originally described by D.L. Morton et al. (Surg Oncol Clin North Am 1992;1:247-59), is currently being used at most tertiary institutions for staging patients with intermediate-level melanomas. Identification and subsequent surgical resection of occult metastasis before the development of clinical disease may improve survival in these patients. This study is a retrospective review of patients with intermediate melanomas treated by the senior author (P.S.D.). Isosulfan blue dye and a radioactive technetium-labeled dye were used to identify the sentinel node. Sentinel nodes were evaluated by routine hematoxylin and eosin staining, immunohistochemical staining for S-100 and HMB-45, and later in the study with multipanel reverse transcriptase-polymerase chain reaction analysis. All patients were followed closely. Fifty-seven patients with primary melanoma were evaluated between December 1995 and June 1998. Thirty-two patients underwent SLND; two patients underwent SLND on two separate drainage basins, for a total of 34 procedures. The median age was 49 years (range, 19-77). There were 11 females and 21 males. The locations of the primary melanoma were: head and neck, seven; extremity, 8; and trunk, 18; 1 patient had a dual primary melanoma at presentation. Clark's levels of invasion among the patients were level III, 5; and level IV, 27; median Breslow thickness was 1.4 mm (range, 0.45-3.8 mm). A sentinel node was not identified in four procedures (11.1%). Twenty-two nodes (73%) were negative by all methods, and eight (27%) were positive by at least one method. All positive patients underwent complete lymphadenectomy, and routine hematoxylin and eosin stains identified no additional positive nodes. Median follow-up was 21 months (6-36 months). Two patients developed recurrent disease. The other 30 patients remain disease free at last follow-up. SLND is a low-morbidity technique that accurately stages patients with intermediate-level melanoma. Early intervention with complete therapeutic lymphadenectomy and possible interferon therapy may improve the survival of patients with stage III melanoma. A complete discussion of the technique for SLND and an update of this data is presented.

Isoproterenol inhibits bacterial lipopolysaccharide-stimulated release of tumor necrosis factor-alpha from human heart tissue.

Recent evidence suggests that inflammatory cytokines, particularly tumor necrosis factor alpha (TNF-alpha), may play a role in heart disease. Elevated plasma levels of the cytokine have been reported in congestive heart failure and severe angina and after myocardial infarction. The exact role of TNF-alpha in heart disease and how production is stimulated and regulated in the heart are current areas of investigation. Regarding regulation of production, isoproterenol elevates cyclic AMP and inhibits TNF-alpha release in macrophages. Therefore we hypothesized that stimulation of beta-adrenergic receptors of the sympathetic nervous system would inhibit release of the cytokine from heart tissue. With Institutional Review Board approval and patient consent atrial tissue was obtained during preparation for cardiac bypass. The tissue was divided into segments, placed in culture medium, and incubated for various times in the presence or absence of lipopolysaccharide (LPS) (20 microg/mL) and/or isoproterenol (1 microM). The medium was removed and analyzed for biologically active TNF-alpha by the L929 cell cytotoxicity assay. Tissue samples were weighed and TNF-alpha release was expressed as pg TNF-alpha/mg tissue. Initially, to determine the time course of release, measurements were made at 2, 5, 10, 15, 30, 60, 120, 180, and 360 minutes after the addition of LPS. Elevated TNF-alpha levels in the culture medium were reliably detected at 360 minutes after exposure to LPS. In atrial tissue obtained from seven patients TNF-alpha released into the culture medium at 360 minutes was 6 +/- 3 pg/mg tissue. In the presence of LPS, levels of the cytokine in the culture medium increased to 604 +/- 233 pg/mg tissue (P < 0.05 vs LPS alone). When isoproterenol and LPS were simultaneously added to the culture medium release of TNF-alpha was reduced by 87 per cent to 82 +/- 40 pg/mg tissue (P < 0.05 vs LPS alone). Our results show that activation of the beta-adrenergic receptor inhibits myocardial production of TNF-alpha. This finding suggests that the sympathetic nervous system inhibits production of the cytokine and that impaired sympathetic function in heart failure may play a role in the elevated levels of TNF-alpha.

Effect of Cu,Zn superoxide dismutase disruption mutation on replicative senescence in Saccharomyces cerevisiae.

The role of oxidative damage in determining the replicative lifespan of Saccharomyces cerevisiae was investigated using a wild-type haploid laboratory yeast and a Cu,Zn superoxide dismutase (sod1) mutant derivative on glucose, ethanol, glycerol and galactose media. SOD1 expression was necessary to ensure longevity on all carbon sources tested. Whilst carbon source and SOD1 gene expression do influence yeast lifespan, the relationship between the two factors is complex.

Influence of ascending versus descending balloon counterpulsation on bypass graft blood flow.

BACKGROUND: Mechanical circulatory assistance is frequently needed in postcardiotomy patients to support the failing heart. A balloon catheter called SupraCor (ABIOMED Cardiovascular, Inc, Danvers, MA) has been developed and is similar to the existing intraaortic balloon pump with the exception of placement in the ascending versus the descending thoracic aorta. This investigation compared the effects of SupraCor versus standard intraaortic balloon pump on internal mammary artery and venous conduit bypass graft blood flow. METHODS: Porcine total heart bypass was used to anastomose a jugular vein from the ascending aorta to a subsequently ligated left anterior descending coronary artery. The left internal mammary artery was then anastomosed to the jugular vein so each conduit perfused the same coronary vascular bed. An additional right heart bypass preparation allowed precise control of cardiac output and blood pressure, which were maintained constant throughout mechanical circulatory assistance. Electromagnetic flow probes measured flow through each bypass graft and the other conduit was atraumatically occluded. RESULTS: The SupraCor caused a significant increase in both internal mammary artery (+70% from 35 +/- mL/min to 56 +/- 9 mL/min; p = 0.04) and venous bypass graft blood flow (+49% from 66 +/- 12 mL/min to 95 +/- 15 mL/min; p = 0.02) when compared with controls. The intraaortic balloon pump failed to alter internal mammary artery or venous bypass graft flow. CONCLUSIONS: The results demonstrate that counterpulsation with an ascending aortic balloon significantly increases coronary bypass graft flow in both internal mammary artery and venous conduits. In contrast, counterpulsation with a descending aortic balloon did not alter coronary bypass graft flow.