RNA uridyl transferases TUT4/7 differentially regulate miRNA variants depending on the cancer cell type.

The human terminal uridyl transferases TUT4 and TUT7 (TUT4/7) catalyze the additions of uridines at the 3' end of RNAs, including the precursors of the tumor suppressor miRNA let-7 upon recruitment by the oncoprotein LIN28A. As a consequence, let-7 family miRNAs are down-regulated. Disruption of this TUT4/7 activity inhibits tumorigenesis. Hence, targeting TUT4/7 could be a potential anticancer therapy. In this study, we investigate TUT4/7-mediated RNA regulation in two cancer cell lines by establishing catalytic knockout models. Upon TUT4/7 mutation, we observe a significant reduction in miRNA uridylation, which results in defects in cancer cell properties such as cell proliferation and migration. With the loss of TUT4/7-mediated miRNA uridylation, the uridylated miRNA variants are replaced by adenylated isomiRs. Changes in miRNA modification profiles are accompanied by deregulation of expression levels in specific cases. Unlike let-7s, most miRNAs do not depend on LIN28A for TUT4/7-mediated regulation. Additionally, we identify TUT4/7-regulated cell-type-specific miRNA clusters and deregulation in their corresponding mRNA targets. Expression levels of miR-200c-3p and miR-141-3p are regulated by TUT4/7 in a cancer cell-type-specific manner. Subsequently, BCL2, which is a well-established target of miR-200c is up-regulated. Therefore, TUT4/7 loss causes deregulation of miRNA-mRNA networks in a cell-type-specific manner. Understanding of the underlying biology of such cell-type-specific deregulation will be an important aspect of targeting TUT4/7 for potential cancer therapies.

Assessing benzene and toluene adsorption with peat depth: Implications on their fate and transport.

After a hydrocarbon spill in a peatland, dissolution of water-soluble compounds including benzene and toluene introduces a dissolved-phase plume to the peatland groundwater system, while the adsorption of these solutes onto the peat matrix restrains their distribution velocity. The adsorption of benzene and toluene and its dependency on peat depth, thus degree of decomposition, are investigated. The batch adsorption experiments revealed that benzene and toluene adsorption isotherms in peat are linear, with adsorption coefficients ranging from 16.2 to 48.7 L/kg and 31.6-48.7 L/kg, respectively. In a vertical peat profile benzene adsorption decreased with depth, while toluene adsorption increased. Considering toluene adsorption onto cellulose is significantly less than toluene adsorption onto humic substance, the increase in toluene adsorption was attributed to decreasing cellulose and increasing humic substances with depth. Negligible competition for adsorption was observed between benzene and toluene at the measured concentrations. The retardation factors of benzene and toluene ranged respectively from 3.5 to 10.7 and from 5.4 to 17.7, both increasing with depth. Higher retardation in deeper peat coupled with lower hydraulic conductivity will lead to a weaker solute velocity in deeper peat, thus preferential migration of these dissolved-phase contaminants in shallow layers. The results can help predict the behavior of dissolved hydrocarbons in peatlands after a hydrocarbon spill.

Cysteine synthases CYSL-1 and CYSL-2 mediate C. elegans heritable adaptation to P. vranovensis infection.

Parental exposure to pathogens can prime offspring immunity in diverse organisms. The mechanisms by which this heritable priming occurs are largely unknown. Here we report that the soil bacteria Pseudomonas vranovensis is a natural pathogen of the nematode Caenorhabditis elegans and that parental exposure of animals to P. vranovensis promotes offspring resistance to infection. Furthermore, we demonstrate a multigenerational enhancement of progeny survival when three consecutive generations of animals are exposed to P. vranovensis. By investigating the mechanisms by which animals heritably adapt to P. vranovensis infection, we found that parental infection by P. vranovensis results in increased expression of the cysteine synthases cysl-1 and cysl-2 and the regulator of hypoxia inducible factor rhy-1 in progeny, and that these three genes are required for adaptation to P. vranovensis. These observations establish a CYSL-1, CYSL-2, and RHY-1 dependent mechanism by which animals heritably adapt to infection.

The Challenges of Redo Aortic Coarctation Repair in Adults.

PURPOSE OF REVIEW: Aortic coarctation is a common congenital abnormality causing significant morbidity and mortality if not corrected. Re-coarctation or restenosis of the aorta following treatment is a relatively common long-term problem and the optimal therapy has not been elucidated. In this review, we identify the challenges associated with and the optimal management for recurrent aortic coarctation and the most appropriate therapy for different patient cohorts. RECENT FINDINGS: Open surgery provides a durable long-term aortic repair, however, given the complex nature of the procedure, has a somewhat higher rate of serious complications. Endovascular repair, although less invasive and relatively safe, has limitations in treated complex anatomy and is more likely to require repeat intervention. Open surgical repair is more appropriate for infants that have not been intervened on and endovascular therapy should be reserved for older children and adults and those that require repeat intervention.

Needs-based quality of life in adults dependent on home parenteral nutrition.

BACKGROUND & AIMS: Home parenteral nutrition (HPN) provides life sustaining treatment for people with chronic intestinal failure. Individuals may require HPN for months or years and are dependent on regular intravenous infusions, usually 12-14 h overnight between 1 and 7 days each week. This regime can have adverse impact on the life of people dependent on the treatment. The aim of this study was to establish mean values for the Parenteral Nutrition Impact Questionnaire (PNIQ) and to determine the effect of disease, frequency of infusions per week and patient characteristics on quality of life of patients fed HPN. METHOD: The PNIQ was distributed to patients across nine UK HPN clinics. Data were analysed using linear regression, with PNIQ score as the dependent variable and potential confounders as independent variables. Unadjusted and adjusted models are presented. Higher PNIQ scores reflect poorer quality of life. RESULTS: Completed questionnaires were received from 466 people dependent on HPN. Mean PNIQ score was 11.04 (SD 5.79). A higher PNIQ score (effect size 0.52, CI 0.184 to 0.853) was recorded in those dependent on a higher frequency of HPN infusions per week. Respondents with cancer had a similar mean PNIQ score to those with inflammatory bowel disease (mean 10.82, SD 6.00 versus 11.04, SD 5.91). Those with surgical complications reported a poorer QoL (effect size 3.03, CI 0.642 to 5.418) and those with severe gastro-intestinal dysmotility reported a better QoL (effect size -3.03, CI -5.593 to -0.468), compared to other disease states. CONCLUSIONS: This large cohort study of quality of life in chronic intestinal failure demonstrates that HPN impacts individuals differently depending on their underlying disease. Furthermore, since the number of HPN infusions required per week is inversely related to an individual's needs-based quality of life, therapies that reduce PN burden should lead to an improvement in QoL.

Evaluating Imaging Biomarkers of Acquired Resistance to Targeted EGFR Therapy in Xenograft Models of Human Head and Neck Squamous Cell Carcinoma.

Background: Overexpression of EGFR is a negative prognostic factor in head and neck squamous cell carcinoma (HNSCC). Patients with HNSCC who respond to EGFR-targeted tyrosine kinase inhibitors (TKIs) eventually develop acquired resistance. Strategies to identify HNSCC patients likely to benefit from EGFR-targeted therapies, together with biomarkers of treatment response, would have clinical value. Methods: Functional MRI and 18F-FDG PET were used to visualize and quantify imaging biomarkers associated with drug response within size-matched EGFR TKI-resistant CAL 27 (CALR) and sensitive (CALS) HNSCC xenografts in vivo, and pathological correlates sought. Results: Intrinsic susceptibility, oxygen-enhanced and dynamic contrast-enhanced MRI revealed significantly slower baseline R2∗ , lower hyperoxia-induced ΔR2∗ and volume transfer constant Ktrans in the CALR tumors which were associated with significantly lower Hoechst 33342 uptake and greater pimonidazole-adduct formation. There was no difference in oxygen-induced ΔR1 or water diffusivity between the CALR and CALS xenografts. PET revealed significantly higher relative uptake of 18F-FDG in the CALR cohort, which was associated with significantly greater Glut-1 expression. Conclusions: CALR xenografts established from HNSCC cells resistant to EGFR TKIs are more hypoxic, poorly perfused and glycolytic than sensitive CALS tumors. MRI combined with PET can be used to non-invasively assess HNSCC response/resistance to EGFR inhibition.

The distribution and migration of sodium from a reclaimed upland to a constructed fen peatland in a post-mined oil sands landscape.

Post-mine landscape reclamation of the Athabasca Oil Sands Region requires the use of tailings sand, an abundant mine-waste material that often contains large amounts of sodium (Na+). Due to the mobility of Na+ in groundwater and its effects on vegetation, water quality is a concern when incorporating mine waste materials, especially when attempting to construct groundwater-fed peatlands. This research is the first published account of Na+ redistribution in groundwater from a constructed tailings sand upland to an adjacent constructed fen peat deposit (Nikanotee Fen). A permeable petroleum coke layer underlying the fen, extending partway into the upland, was important in directing flow and Na+ beneath the peat, as designed. Initially, Na+ concentration was highest in the tailings sand (average of 232mgL-1) and lowest in fen peat (96mgL-1). Precipitation-driven recharge to the upland controlled the mass flux of Na from upland to fen, which ranged from 2 to 13tons Na+ per year. The mass flux was highest in the driest summer, in part from dry-period flowpaths that direct groundwater with higher concentrations of Na+ into the coke layer, and in part because of the high evapotranspiration loss from the fen in dry periods, which induces upward water flow. With the estimated flux rates of 336mmyr-1, the Na+ arrival time to the fen surface was estimated to be between 4 and 11years. Over the four-year study, average Na+ concentrations within the fen rooting zone increased from 87 to 200mgL-1, and in the tailings sand decreased to 196mgL-1. The planting of more salt-tolerant vegetation in the fen is recommended, given the potential for Na+ accumulation. This study shows reclamation designs can use layered flow system to control the rate, pattern, and timing of solute interactions with surface soil systems.

Solute pools in Nikanotee Fen watershed in the Athabasca oil sands region.

Overburden and tailings materials from oil sands production were used as construction materials as part of a novel attempt to create a self-sustaining, peat accumulating fen-upland ecosystem. To evaluate the potential for elemental release from the construction materials, total elemental concentrations in the tailings sand, petroleum coke and peat used to construct a fen ecosystem were determined using microwave-assisted acid digestions and compared to a leaching experiment conducted under environmentally-relevant conditions. A comparison of solid phase to aqueous Na, Ca, S and Mg concentrations showed they were highly leachable in the materials. Given that the concentrations of these elements can affect plant community structure, it is important to understand their leachability and mobility as they migrate between materials used to construct the system. To that end, a mass balance of aqueous Na, Ca, S and Mg was conducted based on leaching experiments and materials analysis coupled with existing data from the constructed system. The data indicate that there is a large pool of leachable Na, Ca, S and Mg in the system, estimated at 27 t of Na, 14 t of Ca, 37.3 t of S and 8.8 t of Mg. Since recharge mainly drives the fen-upland system water regime, and discharge in the fen, evapo-accumulation of these solutes on the surface may occur.

Exercise therapy for chronic fatigue syndrome.

BACKGROUND: Chronic fatigue syndrome (CFS) is characterised by persistent, medically unexplained fatigue, as well as symptoms such as musculoskeletal pain, sleep disturbance, headaches and impaired concentration and short-term memory. CFS presents as a common, debilitating and serious health problem. Treatment may include physical interventions, such as exercise therapy, which was last reviewed in 2004. OBJECTIVES: The objective of this review was to determine the effects of exercise therapy (ET) for patients with CFS as compared with any other intervention or control.• Exercise therapy versus 'passive control' (e.g. treatment as usual, waiting-list control, relaxation, flexibility).• Exercise therapy versus other active treatment (e.g. cognitive-behavioural therapy (CBT), cognitive treatment, supportive therapy, pacing, pharmacological therapy such as antidepressants).• Exercise therapy in combination with other specified treatment strategies versus other specified treatment strategies (e.g. exercise combined with pharmacological treatment vs pharmacological treatment alone). SEARCH METHODS: We searched The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), the Cochrane Central Register of Controlled Trials (CENTRAL) and SPORTDiscus up to May 2014 using a comprehensive list of free-text terms for CFS and exercise. We located unpublished or ongoing trials through the World Health Organization (WHO) International Clinical Trials Registry Platform (to May 2014). We screened reference lists of retrieved articles and contacted experts in the field for additional studies SELECTION CRITERIA: Randomised controlled trials involving adults with a primary diagnosis of CFS who were able to participate in exercise therapy. Studies had to compare exercise therapy with passive control, psychological therapies, adaptive pacing therapy or pharmacological therapy. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, risk of bias assessments and data extraction. We combined continuous measures of outcomes using mean differences (MDs) and standardised mean differences (SMDs). We combined serious adverse reactions and drop-outs using risk ratios (RRs). We calculated an overall effect size with 95% confidence intervals (CIs) for each outcome. MAIN RESULTS: We have included eight randomised controlled studies and have reported data from 1518 participants in this review. Three studies diagnosed individuals with CFS using the 1994 criteria of the Centers for Disease Control and Prevention (CDC); five used the Oxford criteria. Exercise therapy lasted from 12 to 26 weeks. Seven studies used variations of aerobic exercise therapy such as walking, swimming, cycling or dancing provided at mixed levels in terms of intensity of the aerobic exercise from very low to quite rigorous, whilst one study used anaerobic exercise. Control groups consisted of passive control (eight studies; e.g. treatment as usual, relaxation, flexibility) or CBT (two studies), cognitive therapy (one study), supportive listening (one study), pacing (one study), pharmacological treatment (one study) and combination treatment (one study). Risk of bias varied across studies, but within each study, little variation was found in the risk of bias across our primary and secondary outcome measures.Investigators compared exercise therapy with 'passive' control in eight trials, which enrolled 971 participants. Seven studies consistently showed a reduction in fatigue following exercise therapy at end of treatment, even though the fatigue scales used different scoring systems: an 11-item scale with a scoring system of 0 to 11 points (MD -6.06, 95% CI -6.95 to -5.17; one study, 148 participants; low-quality evidence); the same 11-item scale with a scoring system of 0 to 33 points (MD -2.82, 95% CI -4.07 to -1.57; three studies, 540 participants; moderate-quality evidence); and a 14-item scale with a scoring system of 0 to 42 points (MD -6.80, 95% CI -10.31 to -3.28; three studies, 152 participants; moderate-quality evidence). Serious adverse reactions were rare in both groups (RR 0.99, 95% CI 0.14 to 6.97; one study, 319 participants; moderate-quality evidence), but sparse data made it impossible for review authors to draw conclusions. Study authors reported a positive effect of exercise therapy at end of treatment with respect to sleep (MD -1.49, 95% CI -2.95 to -0.02; two studies, 323 participants), physical functioning (MD 13.10, 95% CI 1.98 to 24.22; five studies, 725 participants) and self-perceived changes in overall health (RR 1.83, 95% CI 1.39 to 2.40; four studies, 489 participants). It was not possible for review authors to draw conclusions regarding the remaining outcomes.Investigators compared exercise therapy with CBT in two trials (351 participants). One trial (298 participants) reported little or no difference in fatigue at end of treatment between the two groups using an 11-item scale with a scoring system of 0 to 33 points (MD 0.20, 95% CI -1.49 to 1.89). Both studies measured differences in fatigue at follow-up, but neither found differences between the two groups using an 11-item fatigue scale with a scoring system of 0 to 33 points (MD 0.30, 95% CI -1.45 to 2.05) and a nine-item Fatigue Severity Scale with a scoring system of 1 to 7 points (MD 0.40, 95% CI -0.34 to 1.14). Serious adverse reactions were rare in both groups (RR 0.67, 95% CI 0.11 to 3.96). We observed little or no difference in physical functioning, depression, anxiety and sleep, and we were not able to draw any conclusions with regard to pain, self-perceived changes in overall health, use of health service resources and drop-out rate.With regard to other comparisons, one study (320 participants) suggested a general benefit of exercise over adaptive pacing, and another study (183 participants) a benefit of exercise over supportive listening. The available evidence was too sparse to draw conclusions about the effect of pharmaceutical interventions. AUTHORS' CONCLUSIONS: Patients with CFS may generally benefit and feel less fatigued following exercise therapy, and no evidence suggests that exercise therapy may worsen outcomes. A positive effect with respect to sleep, physical function and self-perceived general health has been observed, but no conclusions for the outcomes of pain, quality of life, anxiety, depression, drop-out rate and health service resources were possible. The effectiveness of exercise therapy seems greater than that of pacing but similar to that of CBT. Randomised trials with low risk of bias are needed to investigate the type, duration and intensity of the most beneficial exercise intervention.

Intracardiac Extension of Intravenous Leiomyomatosis.

Intravenous leiomyomatosis with intracardiac extension is a rare condition characterized by extensive growth of a benign uterine mass that extends into the venous system through uterine channels and then into the cardiac chambers. A variety of presentations exist; cure relies on complete surgical resection. Extensive abdominal dissection, cardiopulmonary bypass (with or without circulatory arrest), and removal of the intracaval component are required. However, because of the rarity and variety of presentation, exact preferred management has not been well defined. A specific case, followed by a comprehensive literature review, helps delineate the specific decision making necessary for mass removal.

Detailed analysis of research and practice in the life of a pediatric surgeon in East Central Europe in the 20th century - an example of prof. Zofia Umiastowska-Sawicka

Professor Zofia Umiastowska Sawicka laid the foundations for modern pediatric surgery in Poland, first in Bialystok, and subsequently in Kielce. She was a student of Prof. Jan Kossakowski from Warsaw Medical University to be counted among his most talented and skilled disciples. Professor Umiastowska became the head of the first Department of Pediatric Surgery in Bialystok, which was later incorporated into the Medical Academy of Bialystok. In 1977 she moved to Kielce to run the Department of Pediatric Surgery until her retirement in 1991. In these locations she was the one who trained generations of pediatric surgeons with special emphasis on surgical management of exstrophy of the bladder, vaginal labial adhesion (synechia), injuries of the male urethra, liver and hepatic ligament. During her professional lifetime she focused on congenital diaphragmatic hernia, Meckel's diverticulum, and some aspects of pediatric oncology as well. Every school she attended enriched her with the best of knowledge and skills that made her a perfect teacher for others. However, the Warsaw Medical University essentially played the main role at the core of her surgical training: here she was taught and she learnt how to be pediatric surgeon for good of public health of the society in concord with the motto of the Warsaw Medical University: Saluti publicae.

Exercise therapy for chronic fatigue syndrome.

BACKGROUND: Chronic fatigue syndrome (CFS) is characterised by persistent, medically unexplained fatigue, as well as symptoms such as musculoskeletal pain, sleep disturbance, headaches and impaired concentration and short-term memory. CFS presents as a common, debilitating and serious health problem. Treatment may include physical interventions, such as exercise therapy, which was last reviewed in 2004. OBJECTIVES: The objective of this review was to determine the effects of exercise therapy (ET) for patients with CFS as compared with any other intervention or control.• Exercise therapy versus 'passive control' (e.g. treatment as usual, waiting-list control, relaxation, flexibility).• Exercise therapy versus other active treatment (e.g. cognitive-behavioural therapy (CBT), cognitive treatment, supportive therapy, pacing, pharmacological therapy such as antidepressants).• Exercise therapy in combination with other specified treatment strategies versus other specified treatment strategies (e.g. exercise combined with pharmacological treatment vs pharmacological treatment alone). SEARCH METHODS: We searched The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), the Cochrane Central Register of Controlled Trials (CENTRAL) and SPORTDiscus up to May 2014 using a comprehensive list of free-text terms for CFS and exercise. We located unpublished or ongoing trials through the World Health Organization (WHO) International Clinical Trials Registry Platform (to May 2014). We screened reference lists of retrieved articles and contacted experts in the field for additional studies SELECTION CRITERIA: Randomised controlled trials involving adults with a primary diagnosis of CFS who were able to participate in exercise therapy. Studies had to compare exercise therapy with passive control, psychological therapies, adaptive pacing therapy or pharmacological therapy. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, risk of bias assessments and data extraction. We combined continuous measures of outcomes using mean differences (MDs) and standardised mean differences (SMDs). We combined serious adverse reactions and drop-outs using risk ratios (RRs). We calculated an overall effect size with 95% confidence intervals (CIs) for each outcome. MAIN RESULTS: We have included eight randomised controlled studies and have reported data from 1518 participants in this review. Three studies diagnosed individuals with CFS using the 1994 criteria of the Centers for Disease Control and Prevention (CDC); five used the Oxford criteria. Exercise therapy lasted from 12 to 26 weeks. Seven studies used variations of aerobic exercise therapy such as walking, swimming, cycling or dancing provided at mixed levels in terms of intensity of the aerobic exercise from very low to quite rigorous, whilst one study used anaerobic exercise. Control groups consisted of passive control (eight studies; e.g. treatment as usual, relaxation, flexibility) or CBT (two studies), cognitive therapy (one study), supportive listening (one study), pacing (one study), pharmacological treatment (one study) and combination treatment (one study). Risk of bias varied across studies, but within each study, little variation was found in the risk of bias across our primary and secondary outcome measures.Investigators compared exercise therapy with 'passive' control in eight trials, which enrolled 971 participants. Seven studies consistently showed a reduction in fatigue following exercise therapy at end of treatment, even though the fatigue scales used different scoring systems: an 11-item scale with a scoring system of 0 to 11 points (MD -6.06, 95% CI -6.95 to -5.17; one study, 148 participants; low-quality evidence); the same 11-item scale with a scoring system of 0 to 33 points (MD -2.82, 95% CI -4.07 to -1.57; three studies, 540 participants; moderate-quality evidence); and a 14-item scale with a scoring system of 0 to 42 points (MD -6.80, 95% CI -10.31 to -3.28; three studies, 152 participants; moderate-quality evidence). Serious adverse reactions were rare in both groups (RR 0.99, 95% CI 0.14 to 6.97; one study, 319 participants; moderate-quality evidence), but sparse data made it impossible for review authors to draw conclusions. Study authors reported a positive effect of exercise therapy at end of treatment with respect to sleep (MD -1.49, 95% CI -2.95 to -0.02; two studies, 323 participants), physical functioning (MD 13.10, 95% CI 1.98 to 24.22; five studies, 725 participants) and self-perceived changes in overall health (RR 1.83, 95% CI 1.39 to 2.40; four studies, 489 participants). It was not possible for review authors to draw conclusions regarding the remaining outcomes.Investigators compared exercise therapy with CBT in two trials (351 participants). One trial (298 participants) reported little or no difference in fatigue at end of treatment between the two groups using an 11-item scale with a scoring system of 0 to 33 points (MD 0.20, 95% CI -1.49 to 1.89). Both studies measured differences in fatigue at follow-up, but neither found differences between the two groups using an 11-item fatigue scale with a scoring system of 0 to 33 points (MD 0.30, 95% CI -1.45 to 2.05) and a nine-item Fatigue Severity Scale with a scoring system of 1 to 7 points (MD 0.40, 95% CI -0.34 to 1.14). Serious adverse reactions were rare in both groups (RR 0.67, 95% CI 0.11 to 3.96). We observed little or no difference in physical functioning, depression, anxiety and sleep, and we were not able to draw any conclusions with regard to pain, self-perceived changes in overall health, use of health service resources and drop-out rate.With regard to other comparisons, one study (320 participants) suggested a general benefit of exercise over adaptive pacing, and another study (183 participants) a benefit of exercise over supportive listening. The available evidence was too sparse to draw conclusions about the effect of pharmaceutical interventions. AUTHORS' CONCLUSIONS: Patients with CFS may generally benefit and feel less fatigued following exercise therapy, and no evidence suggests that exercise therapy may worsen outcomes. A positive effect with respect to sleep, physical function and self-perceived general health has been observed, but no conclusions for the outcomes of pain, quality of life, anxiety, depression, drop-out rate and health service resources were possible. The effectiveness of exercise therapy seems greater than that of pacing but similar to that of CBT. Randomised trials with low risk of bias are needed to investigate the type, duration and intensity of the most beneficial exercise intervention.

Resuscitative endovascular balloon occlusion of the aorta (REBOA) in the pre-hospital setting: An additional resuscitation option for uncontrolled catastrophic haemorrhage.

This report describes the first use of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) in the pre-hospital setting to control catastrophic haemorrhage. The patient, who had fallen 15 meters, suffered catastrophic internal haemorrhage associated with a pelvic fracture. He was treated by London's Air Ambulance's Physician-Paramedic team. This included insertion of a REBOA balloon catheter at the scene to control likely fatal exsanguination. The patient survived transfer to hospital, emergency angio-embolization and subsequent surgery. He was discharged neurologically normal after 52 days and went on to make a full recovery. The poor prognosis in catastrophic torso haemorrhage and novel endovascular methods of haemorrhage control are discussed. Also the challenges of Pre-Hospital REBOA are discussed together with the training and governance required for a safe system.

Exercise therapy for chronic fatigue syndrome.

BACKGROUND: Chronic fatigue syndrome (CFS) is characterised by persistent, medically unexplained fatigue, as well as symptoms such as musculoskeletal pain, sleep disturbance, headaches and impaired concentration and short-term memory. CFS presents as a common, debilitating and serious health problem. Treatment may include physical interventions, such as exercise therapy, which was last reviewed in 2004. OBJECTIVES: The objective of this review was to determine the effects of exercise therapy (ET) for patients with CFS as compared with any other intervention or control.• Exercise therapy versus 'passive control' (e.g. treatment as usual, waiting-list control, relaxation, flexibility).• Exercise therapy versus other active treatment (e.g. cognitive-behavioural therapy (CBT), cognitive treatment, supportive therapy, pacing, pharmacological therapy such as antidepressants).• Exercise therapy in combination with other specified treatment strategies versus other specified treatment strategies (e.g. exercise combined with pharmacological treatment vs pharmacological treatment alone). SEARCH METHODS: We searched The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), the Cochrane Central Register of Controlled Trials (CENTRAL) and SPORTDiscus up to May 2014 using a comprehensive list of free-text terms for CFS and exercise. We located unpublished or ongoing trials through the World Health Organization (WHO) International Clinical Trials Registry Platform (to May 2014). We screened reference lists of retrieved articles and contacted experts in the field for additional studies SELECTION CRITERIA: Randomised controlled trials involving adults with a primary diagnosis of CFS who were able to participate in exercise therapy. Studies had to compare exercise therapy with passive control, psychological therapies, adaptive pacing therapy or pharmacological therapy. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, risk of bias assessments and data extraction. We combined continuous measures of outcomes using mean differences (MDs) and standardised mean differences (SMDs). We combined serious adverse reactions and drop-outs using risk ratios (RRs). We calculated an overall effect size with 95% confidence intervals (CIs) for each outcome. MAIN RESULTS: We have included eight randomised controlled studies and have reported data from 1518 participants in this review. Three studies diagnosed individuals with CFS using the 1994 criteria of the Centers for Disease Control and Prevention (CDC); five used the Oxford criteria. Exercise therapy lasted from 12 to 26 weeks. Seven studies used variations of aerobic exercise therapy such as walking, swimming, cycling or dancing provided at mixed levels in terms of intensity of the aerobic exercise from very low to quite rigorous, whilst one study used anaerobic exercise. Control groups consisted of passive control (eight studies; e.g. treatment as usual, relaxation, flexibility) or CBT (two studies), cognitive therapy (one study), supportive listening (one study), pacing (one study), pharmacological treatment (one study) and combination treatment (one study). Risk of bias varied across studies, but within each study, little variation was found in the risk of bias across our primary and secondary outcome measures.Investigators compared exercise therapy with 'passive' control in eight trials, which enrolled 971 participants. Seven studies consistently showed a reduction in fatigue following exercise therapy at end of treatment, even though the fatigue scales used different scoring systems: an 11-item scale with a scoring system of 0 to 11 points (MD -6.06, 95% CI -6.95 to -5.17; one study, 148 participants; low-quality evidence); the same 11-item scale with a scoring system of 0 to 33 points (MD -2.82, 95% CI -4.07 to -1.57; three studies, 540 participants; moderate-quality evidence); and a 14-item scale with a scoring system of 0 to 42 points (MD -6.80, 95% CI -10.31 to -3.28; three studies, 152 participants; moderate-quality evidence). Serious adverse reactions were rare in both groups (RR 0.99, 95% CI 0.14 to 6.97; one study, 319 participants; moderate-quality evidence), but sparse data made it impossible for review authors to draw conclusions. Study authors reported a positive effect of exercise therapy at end of treatment with respect to sleep (MD -1.49, 95% CI -2.95 to -0.02; two studies, 323 participants), physical functioning (MD 13.10, 95% CI 1.98 to 24.22; five studies, 725 participants) and self-perceived changes in overall health (RR 1.83, 95% CI 1.39 to 2.40; four studies, 489 participants). It was not possible for review authors to draw conclusions regarding the remaining outcomes.Investigators compared exercise therapy with CBT in two trials (351 participants). One trial (298 participants) reported little or no difference in fatigue at end of treatment between the two groups using an 11-item scale with a scoring system of 0 to 33 points (MD 0.20, 95% CI -1.49 to 1.89). Both studies measured differences in fatigue at follow-up, but neither found differences between the two groups using an 11-item fatigue scale with a scoring system of 0 to 33 points (MD 0.30, 95% CI -1.45 to 2.05) and a nine-item Fatigue Severity Scale with a scoring system of 1 to 7 points (MD 0.40, 95% CI -0.34 to 1.14). Serious adverse reactions were rare in both groups (RR 0.67, 95% CI 0.11 to 3.96). We observed little or no difference in physical functioning, depression, anxiety and sleep, and we were not able to draw any conclusions with regard to pain, self-perceived changes in overall health, use of health service resources and drop-out rate.With regard to other comparisons, one study (320 participants) suggested a general benefit of exercise over adaptive pacing, and another study (183 participants) a benefit of exercise over supportive listening. The available evidence was too sparse to draw conclusions about the effect of pharmaceutical interventions. AUTHORS' CONCLUSIONS: Patients with CFS may generally benefit and feel less fatigued following exercise therapy, and no evidence suggests that exercise therapy may worsen outcomes. A positive effect with respect to sleep, physical function and self-perceived general health has been observed, but no conclusions for the outcomes of pain, quality of life, anxiety, depression, drop-out rate and health service resources were possible. The effectiveness of exercise therapy seems greater than that of pacing but similar to that of CBT. Randomised trials with low risk of bias are needed to investigate the type, duration and intensity of the most beneficial exercise intervention.

Exercise therapy for chronic fatigue syndrome.

BACKGROUND: Chronic fatigue syndrome (CFS) is characterised by persistent, medically unexplained fatigue, as well as symptoms such as musculoskeletal pain, sleep disturbance, headaches and impaired concentration and short-term memory. CFS presents as a common, debilitating and serious health problem. Treatment may include physical interventions, such as exercise therapy, which was last reviewed in 2004. OBJECTIVES: The objective of this review was to determine the effects of exercise therapy (ET) for patients with CFS as compared with any other intervention or control.• Exercise therapy versus 'passive control' (e.g. treatment as usual, waiting-list control, relaxation, flexibility).• Exercise therapy versus other active treatment (e.g. cognitive-behavioural therapy (CBT), cognitive treatment, supportive therapy, pacing, pharmacological therapy such as antidepressants).• Exercise therapy in combination with other specified treatment strategies versus other specified treatment strategies (e.g. exercise combined with pharmacological treatment vs pharmacological treatment alone). SEARCH METHODS: We searched The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), the Cochrane Central Register of Controlled Trials (CENTRAL) and SPORTDiscus up to May 2014 using a comprehensive list of free-text terms for CFS and exercise. We located unpublished or ongoing trials through the World Health Organization (WHO) International Clinical Trials Registry Platform (to May 2014). We screened reference lists of retrieved articles and contacted experts in the field for additional studies SELECTION CRITERIA: Randomised controlled trials involving adults with a primary diagnosis of CFS who were able to participate in exercise therapy. Studies had to compare exercise therapy with passive control, psychological therapies, adaptive pacing therapy or pharmacological therapy. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, risk of bias assessments and data extraction. We combined continuous measures of outcomes using mean differences (MDs) and standardised mean differences (SMDs). We combined serious adverse reactions and drop-outs using risk ratios (RRs). We calculated an overall effect size with 95% confidence intervals (CIs) for each outcome. MAIN RESULTS: We have included eight randomised controlled studies and have reported data from 1518 participants in this review. Three studies diagnosed individuals with CFS using the 1994 criteria of the Centers for Disease Control and Prevention (CDC); five used the Oxford criteria. Exercise therapy lasted from 12 to 26 weeks. Seven studies used variations of aerobic exercise therapy such as walking, swimming, cycling or dancing provided at mixed levels in terms of intensity of the aerobic exercise from very low to quite rigorous, whilst one study used anaerobic exercise. Control groups consisted of passive control (eight studies; e.g. treatment as usual, relaxation, flexibility) or CBT (two studies), cognitive therapy (one study), supportive listening (one study), pacing (one study), pharmacological treatment (one study) and combination treatment (one study). Risk of bias varied across studies, but within each study, little variation was found in the risk of bias across our primary and secondary outcome measures.Investigators compared exercise therapy with 'passive' control in eight trials, which enrolled 971 participants. Seven studies consistently showed a reduction in fatigue following exercise therapy at end of treatment, even though the fatigue scales used different scoring systems: an 11-item scale with a scoring system of 0 to 11 points (MD -6.06, 95% CI -6.95 to -5.17; one study, 148 participants; low-quality evidence); the same 11-item scale with a scoring system of 0 to 33 points (MD -2.82, 95% CI -4.07 to -1.57; three studies, 540 participants; moderate-quality evidence); and a 14-item scale with a scoring system of 0 to 42 points (MD -6.80, 95% CI -10.31 to -3.28; three studies, 152 participants; moderate-quality evidence). Serious adverse reactions were rare in both groups (RR 0.99, 95% CI 0.14 to 6.97; one study, 319 participants; moderate-quality evidence), but sparse data made it impossible for review authors to draw conclusions. Study authors reported a positive effect of exercise therapy at end of treatment with respect to sleep (MD -1.49, 95% CI -2.95 to -0.02; two studies, 323 participants), physical functioning (MD 13.10, 95% CI 1.98 to 24.22; five studies, 725 participants) and self-perceived changes in overall health (RR 1.83, 95% CI 1.39 to 2.40; four studies, 489 participants). It was not possible for review authors to draw conclusions regarding the remaining outcomes.Investigators compared exercise therapy with CBT in two trials (351 participants). One trial (298 participants) reported little or no difference in fatigue at end of treatment between the two groups using an 11-item scale with a scoring system of 0 to 33 points (MD 0.20, 95% CI -1.49 to 1.89). Both studies measured differences in fatigue at follow-up, but neither found differences between the two groups using an 11-item fatigue scale with a scoring system of 0 to 33 points (MD 0.30, 95% CI -1.45 to 2.05) and a nine-item Fatigue Severity Scale with a scoring system of 1 to 7 points (MD 0.40, 95% CI -0.34 to 1.14). Serious adverse reactions were rare in both groups (RR 0.67, 95% CI 0.11 to 3.96). We observed little or no difference in physical functioning, depression, anxiety and sleep, and we were not able to draw any conclusions with regard to pain, self-perceived changes in overall health, use of health service resources and drop-out rate.With regard to other comparisons, one study (320 participants) suggested a general benefit of exercise over adaptive pacing, and another study (183 participants) a benefit of exercise over supportive listening. The available evidence was too sparse to draw conclusions about the effect of pharmaceutical interventions. AUTHORS' CONCLUSIONS: Patients with CFS may generally benefit and feel less fatigued following exercise therapy, and no evidence suggests that exercise therapy may worsen outcomes. A positive effect with respect to sleep, physical function and self-perceived general health has been observed, but no conclusions for the outcomes of pain, quality of life, anxiety, depression, drop-out rate and health service resources were possible. The effectiveness of exercise therapy seems greater than that of pacing but similar to that of CBT. Randomised trials with low risk of bias are needed to investigate the type, duration and intensity of the most beneficial exercise intervention.

An abridged version of the Cochrane review of exercise therapy for chronic fatigue syndrome.

BACKGROUND: Chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME) is estimated to affect between 2 in 1000 and 2 in 100 adults depending on how diagnostic criteria are applied. Patients with CFS have long-lasting fatigue in addition to symptoms including muscle pain, concentration and sleep problems. These symptoms cause significant disability and distress to the people affected. This review is an update of a previous Cochrane review (2004) that showed that exercise therapy was a promising treatment for adults with CFS. AIM: The aim of this systematic review was to determine the effects of exercise therapy for patients with CFS. DESIGN: Systematic review. SETTING: Health care settings. POPULATION: Participants over 18 years with a primary diagnosis of CFS, able to attend an outpatient clinic for exercise therapy, were included. METHODS: We searched electronic databases, including SPORTDiscus, up to May 2014 using a comprehensive list of free-text terms for CFS and exercise. Randomized clinical trials from all health care settings with participants over 18 years with a primary diagnosis of CFS, able to attend an outpatient clinic for exercise therapy, were included. We have included 8 randomized clinical studies that reported data from 1518 participants. Seven studies used aerobic exercise such as walking, swimming, or cycling and one study used non-aerobic exercise. The exercise therapies lasted between 12 and 26 weeks. Meta-analysis was done when appropriate. RESULTS: Exercise therapy was more effective at reducing fatigue than "passive" treatments or no treatment at end of treatment. Exercise therapy also had a positive effect on people's daily physical functioning, sleep quality and self-rated overall health. Nearly twice as many patients reported improvement self-rated overall health after exercise therapy (40 per 100) compared to standard treatment (22 per 100). The evidence was too sparse and/or of too low quality to conclude if exercise therapy has an effect on pain, quality of life, anxiety or depression. Exercise therapy was not found to worsen symptoms for people with CFS, while serious side effects were rare in all exercise and comparison groups. CONCLUSIONS: Patiens with CFS may generally benefit from and feel less fatigued following exercise therapy, and no evidence suggests that exercise therapy may worsen outcomes. CLINICAL REHABILITATION IMPACT: Exercise therapy should be considered.

Intraoperative Epiaortic Ultrasound for Traumatic Pseudoaneurysm of the Ascending Aorta.

Epiaortic ultrasound is an imaging modality that is commonly used to evaluate the ascending aorta for atheroma and other mural lesions during elective cardiac surgery. Its use in contained aortic rupture has not been established. We present a case of thoracic trauma with contained pseudoaneurysm of the ascending aorta. At operation, the precise location of the aortic tear could not be identified by visual inspection, manual palpation, or transesophageal echocardiography. Epiaortic ultrasound was employed and the aortic defect was identified and successfully repaired. This intraoperative imaging modality may play an increasing role in the identification of aortic pathology when visual inspection and other intraoperative imaging is insufficient.

A genome-wide survey of DNA methylation in hexaploid wheat.

BACKGROUND: DNA methylation is an important mechanism of epigenetic gene expression control that can be passed between generations. Here, we use sodium bisulfite treatment and targeted gene enrichment to study genome-wide methylation across the three sub-genomes of allohexaploid wheat. RESULTS: While the majority of methylation is conserved across all three genomes we demonstrate that differential methylation exists between the sub-genomes in approximately equal proportions. We correlate sub-genome-specific promoter methylation with decreased expression levels and show that altered growing temperature has a small effect on methylation state, identifying a small but functionally relevant set of methylated genes. Finally, we demonstrate long-term methylation maintenance using a comparison between the D sub-genome of hexaploid wheat and its progenitor Aegilops tauschii. CONCLUSIONS: We show that tri-genome methylation is highly conserved with the diploid wheat progenitor while sub-genome-specific methylation shows more variation.