Role of Nutrition in Alcoholic Liver Disease: Summary of the Symposium at the ESBRA 2017 Congress.

The symposium, "Role of Nutrition in Alcoholic Liver Disease", was held at the European Society for Biomedical Research on Alcoholism Congress on 9 October 2017 in Crete, Greece. The goal of the symposium was to highlight recent advances and developments in the field of alcohol and nutrition. The symposium was focused on experimental and clinical aspects in relation to the role of different types of dietary nutrients and malnutrition in the pathogenesis of alcoholic liver disease (ALD). The following is a summary of key research presented at this session. The speakers discussed the role of dietary fats and carbohydrates in the development and progression of alcohol-induced multi-organ pathology in animal models of ALD, analyzed novel nutrition-related therapeutics (specifically, betaine and zinc) in the treatment of ALD, and addressed clinical relevance of malnutrition and nutrition support in ALD. This summary of the symposium will benefit junior and senior faculty currently investigating alcohol-induced organ pathology as well as undergraduate, graduate, and post-graduate students and fellows

Recreational soccer is an effective health-promoting activity for untrained men

Copyright BMJ publishing GroupTo examine the effects of regular participation in recreational soccer on health profile, 36 healthy untrained Danish men aged 20-43 years were randomised into a soccer group (SO; n=13), a running group (RU; n=12) and a control group (CO; n=11). Training was performed for 1 h two or three times per week for 12 weeks; at an average heart rate of 82% (SEM 2%) and 82% (1%) of HRmax for SO and RU, respectively. During the 12 week period, maximal oxygen uptake increased (p < 0.05) by 13% (3%) and 8% (3%) in SO and RU, respectively. In SO, systolic and diastolic blood pressure were reduced (p < 0.05) from 130 (2) to 122 (2) mm Hg and from 77 (2) to 72 (2) mm Hg, respectively, after 12 weeks, with similar decreases observed for RU. After the 12 weeks of training, fat mass was 3.0% (2.7 (0.6) kg) and 1.8% (1.8 (0.4) kg) lower (p < 0.05) for SO and RU, respectively. Only SO had an increase in lean body mass (1.7 (0.4) kg, p < 0.05), an increase in lower extremity bone mass (41 (8) g, p < 0.05), a decrease in LDL-cholesterol (2.7 (0.2) to 2.3 (0.2) mmol/l; p < 0.05) and an increase (p < 0.05) in fat oxidation during running at 9.5 km/h. The number of capillaries per muscle fibre was 23% (4%) and 16% (7%) higher (p < 0.05) in SO and RU, respectively, after 12 weeks. No changes in any of the measured variables were observed for CO. In conclusion, participation in regular recreational soccer training, organised as small-sided drills, has significant beneficial effects on health profile and physical capacity for untrained men, and in some aspects it is superior to frequent moderate-intensity running

Could it be advantageous to tune the temperature controller during radiofrequency ablation? A feasibility study using theoretical models

Purpose: To assess whether tailoring the Kp and Ki values of a proportional-integral (PI) controller during radiofrequency (RF) cardiac ablation could be advantageous from the point of view of the dynamic behaviour of the controller, in particular, whether control action could be speeded up and larger lesions obtained. Methods: Theoretical models were built and solved by the finite element method. RF cardiac ablations were simulated with temperature controlled at 55 degrees C. Specific PI controllers were implemented with Kp and Ki parameters adapted to cases with different tissue values (specific heat, thermal conductivity and electrical conductivity) electrode-tissue contact characteristics (insertion depth, cooling effect of circulating blood) and electrode characteristics (size, location and arrangement of the temperature sensor in the electrode). Results: The lesion dimensions and T(max) remained almost unchanged when the specific PI controller was used instead of one tuned for the standard case: T(max) varied less than 1.9 degrees C, lesion width less than 0.2 mm, and lesion depth less than 0.3 mm. As expected, we did observe a direct logical relationship between the response time of each controller and the transient value of electrode temperature. Conclusion: The results suggest that a PI controller designed for a standard case (such as that described in this study), could offer benefits under different tissue conditions, electrode-tissue contact, and electrode characteristics.This work received financial support from the Spanish 'Plan Nacional de I+D+I del Ministerio de Ciencia e Innovacion' Grant no. TEC2008-01369/TEC and FEDER Project MTM2010-14909. The translation of this paper was funded by the Universitat Politecnica de Valencia, Spain. The authors alone are responsible for the content and writing of the paperAlba Martínez, J.; Trujillo Guillen, M.; Blasco Giménez, RM.; Berjano Zanón, E. (2011). Could it be advantageous to tune the temperature controller during radiofrequency ablation? A feasibility study using theoretical models. International Journal of Hyperthermia. 27(6):539-548. https://doi.org/10.3109/02656736.2011.586665S539548276Gaita, F., Caponi, D., Pianelli, M., Scaglione, M., Toso, E., Cesarani, F., … Leclercq, J. F. (2010). Radiofrequency Catheter Ablation of Atrial Fibrillation: A Cause of Silent Thromboembolism? Circulation, 122(17), 1667-1673. doi:10.1161/circulationaha.110.937953Anfinsen, O.-G., Aass, H., Kongsgaard, E., Foerster, A., Scott, H., & Amlie, J. P. (1999). Journal of Interventional Cardiac Electrophysiology, 3(4), 343-351. doi:10.1023/a:1009840004782PETERSEN, H. H., CHEN, X., PIETERSEN, A., SVENDSEN, J. H., & HAUNSO, S. (2000). Tissue Temperatures and Lesion Size During Irrigated Tip Catheter Radiofrequency Ablation: An In Vitro Comparison of Temperature-Controlled Irrigated Tip Ablation, Power-Controlled Irrigated Tip Ablation, and Standard Temperature-Controlled Ablation. Pacing and Clinical Electrophysiology, 23(1), 8-17. doi:10.1111/j.1540-8159.2000.tb00644.xTungjitkusolmun, S., Woo, E. J., Cao, H., Tsai, J. Z., Vorperian, V. R., & Webster, J. G. (2000). Thermal—electrical finite element modelling for radio frequency cardiac ablation: Effects of changes in myocardial properties. Medical & Biological Engineering & Computing, 38(5), 562-568. doi:10.1007/bf02345754Lai, Y.-C., Choy, Y. B., Haemmerich, D., Vorperian, V. R., & Webster, J. G. (2004). Lesion Size Estimator of Cardiac Radiofrequency Ablation at Different Common Locations With Different Tip Temperatures. IEEE Transactions on Biomedical Engineering, 51(10), 1859-1864. doi:10.1109/tbme.2004.831529Jain, M. K., & Wolf, P. D. (1999). Temperature-controlled and constant-power radio-frequency ablation: what affects lesion growth? IEEE Transactions on Biomedical Engineering, 46(12), 1405-1412. doi:10.1109/10.804568Panescu, D., Whayne, J. G., Fleischman, S. D., Mirotznik, M. S., Swanson, D. K., & Webster, J. G. (1995). Three-dimensional finite element analysis of current density and temperature distributions during radio-frequency ablation. IEEE Transactions on Biomedical Engineering, 42(9), 879-890. doi:10.1109/10.412649Hong Cao, Vorperian, V. R., Tungjitkusolmun, S., Jan-Zern Tsai, Haemmerich, D., Young Bin Choy, & Webster, J. G. (2001). Flow effect on lesion formation in RF cardiac catheter ablation. IEEE Transactions on Biomedical Engineering, 48(4), 425-433. doi:10.1109/10.915708Tungjitkusolmun, S., Vorperian, V. R., Bhavaraju, N., Cao, H., Tsai, J.-Z., & Webster, J. G. (2001). Guidelines for predicting lesion size at common endocardial locations during radio-frequency ablation. IEEE Transactions on Biomedical Engineering, 48(2), 194-201. doi:10.1109/10.909640Schutt, D., Berjano, E. J., & Haemmerich, D. (2009). Effect of electrode thermal conductivity in cardiac radiofrequency catheter ablation: A computational modeling study. International Journal of Hyperthermia, 25(2), 99-107. doi:10.1080/02656730802563051Langberg, J. J., Calkins, H., el-Atassi, R., Borganelli, M., Leon, A., Kalbfleisch, S. J., & Morady, F. (1992). Temperature monitoring during radiofrequency catheter ablation of accessory pathways. Circulation, 86(5), 1469-1474. doi:10.1161/01.cir.86.5.1469Calkins, H., Prystowsky, E., Carlson, M., Klein, L. S., Saul, J. P., & Gillette, P. (1994). Temperature monitoring during radiofrequency catheter ablation procedures using closed loop control. Atakr Multicenter Investigators Group. Circulation, 90(3), 1279-1286. doi:10.1161/01.cir.90.3.1279Lennox CD, Temperature controlled RF coagulation. Patent number: 5.122.137 Hudson NHEdwards SD, Stern RA, Electrode and associated system using thermally insulated temperature sensing elements. Patent number: US Patent 5,456,682Panescu D, Fleischman SD, Whayne JG, Swanson DK, (EP Technology. Effects of temperature sensor placement on performance of temperature-controlled ablation. IEEE 17th Annual Conference, Engineering in Medicine and Biology Society, Montreal, Canada (1995)BLOUIN, L. T., MARCUS, F. I., & LAMPE, L. (1991). Assessment of Effects of a Radiofrequency Energy Field and Thermistor Location in an Electrode Catheter on the Accuracy of Temperature Measurement. Pacing and Clinical Electrophysiology, 14(5), 807-813. doi:10.1111/j.1540-8159.1991.tb04111.xBerjano, E. J. (2006). BioMedical Engineering OnLine, 5(1), 24. doi:10.1186/1475-925x-5-24Bhavaraju, N. C., Cao, H., Yuan, D. Y., Valvano, J. W., & Webster, J. G. (2001). Measurement of directional thermal properties of biomaterials. IEEE Transactions on Biomedical Engineering, 48(2), 261-267. doi:10.1109/10.909647Hong Cao, Tungjitkusolmun, S., Young Bin Choy, Jang-Zern Tsai, Vorperian, V. R., & Webster, J. G. (2002). Using electrical impedance to predict catheter-endocardial contact during RF cardiac ablation. IEEE Transactions on Biomedical Engineering, 49(3), 247-253. doi:10.1109/10.983459PETERSEN, H. H., & SVENDSEN, J. H. (2003). Can Lesion Size During Radiofrequency Ablation Be Predicted By the Temperature Rise to a Low Power Test Pulse in Vitro? Pacing and Clinical Electrophysiology, 26(8), 1653-1659. doi:10.1046/j.1460-9592.2003.t01-1-00248.xLANGBERG, J. J., LEE, M. A., CHIN, M. C., & ROSENQVIST, M. (1990). Radiofrequency Catheter Ablation: The Effect of Electrode Size on Lesion Volume In Vivo. Pacing and Clinical Electrophysiology, 13(10), 1242-1248. doi:10.1111/j.1540-8159.1990.tb02022.

Circulating gluten-specific FOXP3⁺CD39⁺ regulatory T cells have impaired suppressive function in patients with celiac disease

Background Celiac disease is a chronic immune-mediated inflammatory disorder of the gut triggered by dietary gluten. Although the effector T-cell response in patients with celiac disease has been well characterized, the role of regulatory T (Treg) cells in the loss of tolerance to gluten remains poorly understood. Objective We sought to define whether patients with celiac disease have a dysfunction or lack of gluten-specific forkhead box protein 3 (FOXP3)+ Treg cells. Methods Treated patients with celiac disease underwent oral wheat challenge to stimulate recirculation of gluten-specific T cells. Peripheral blood was collected before and after challenge. To comprehensively measure the gluten-specific CD4+ T-cell response, we paired traditional IFN-γ ELISpot with an assay to detect antigen-specific CD4+ T cells that does not rely on tetramers, antigen-stimulated cytokine production, or proliferation but rather on antigen-induced coexpression of CD25 and OX40 (CD134). Results Numbers of circulating gluten-specific Treg cells and effector T cells both increased significantly after oral wheat challenge, peaking at day 6. Surprisingly, we found that approximately 80% of the ex vivo circulating gluten-specific CD4+ T cells were FOXP3+CD39+ Treg cells, which reside within the pool of memory CD4+CD25+CD127lowCD45RO+ Treg cells. Although we observed normal suppressive function in peripheral polyclonal Treg cells from patients with celiac disease, after a short in vitro expansion, the gluten-specific FOXP3+CD39+ Treg cells exhibited significantly reduced suppressive function compared with polyclonal Treg cells. Conclusion This study provides the first estimation of FOXP3+CD39+ Treg cell frequency within circulating gluten-specific CD4+ T cells after oral gluten challenge of patients with celiac disease. FOXP3+CD39+ Treg cells comprised a major proportion of all circulating gluten-specific CD4+ T cells but had impaired suppressive function, indicating that Treg cell dysfunction might be a key contributor to disease pathogenesis

HFrEF subphenotypes based on 4210 repeatedly measured circulating proteins are driven by different biological mechanisms

BACKGROUND: HFrEF is a heterogenous condition with high mortality. We used serial assessments of 4210 circulating proteins to identify distinct novel protein-based HFrEF subphenotypes and to investigate underlying dynamic biological mechanisms. Herewith we aimed to gain pathophysiological insights and fuel opportunities for personalised treatment. METHODS: In 382 patients, we performed trimonthly blood sampling during a median follow-up of 2.1 [IQR:1.1–2.6] years. We selected all baseline samples and two samples closest to the primary endpoint (PEP; composite of cardiovascular mortality, HF hospitalization, LVAD implantation, and heart transplantation) or censoring, and applied an aptamer-based multiplex proteomic approach. Using unsupervised machine learning methods, we derived clusters from 4210 repeatedly measured proteomic biomarkers. Sets of proteins that drove cluster allocation were analysed via an enrichment analysis. Differences in clinical characteristics and PEP occurrence were evaluated. FINDINGS: We identified four subphenotypes with different protein profiles, prognosis and clinical characteristics, including age (median [IQR] for subphenotypes 1–4, respectively:70 [64, 76], 68 [60, 79], 57 [47, 65], 59 [56, 66]years), EF (30 [26, 36], 26 [20, 38], 26 [22, 32], 33 [28, 37]%), and chronic renal failure (45%, 65%, 36%, 37%). Subphenotype allocation was driven by subsets of proteins associated with various biological functions, such as oxidative stress, inflammation and extracellular matrix organisation. Clinical characteristics of the subphenotypes were aligned with these associations. Subphenotypes 2 and 3 had the worst prognosis compared to subphenotype 1 (adjHR (95%CI):3.43 (1.76–6.69), and 2.88 (1.37–6.03), respectively). INTERPRETATION: Four circulating-protein based subphenotypes are present in HFrEF, which are driven by varying combinations of protein subsets, and have different clinical characteristics and prognosis. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01851538 https://clinicaltrials.gov/ct2/show/NCT01851538. Funding: EU/ EFPIA IMI2JU BigData@Heart grant n° 116074, Jaap Schouten Foundation and Noordwest Academie

Services just for men? Insights from a national study of the well men services pilots.

Men continue to have a lower life expectancy in most countries compared to women. Explanations of this gendered health inequality tend to focus on male risk taking, unhealthy lifestyle choices and resistance to seeking help from health services. In the period 2005-2008 the Scottish Government funded a nationwide community health promotion programme aimed at improving men's health, called Well Men Service Pilots (henceforth WMS)

Incidence and trends of low back pain hospitalisation during military service – An analysis of 387,070 Finnish young males

<p>Abstract</p> <p>Background</p> <p>There is evidence that low back pain (LBP) during young adulthood and military service predicts LBP later in life. The purpose of this study was to investigate the incidence and trends of LBP hospitalisation among Finnish military conscripts.</p> <p>Methods</p> <p>All male conscripts performing their compulsory military service during 1990–2002 were included in the study population. Altogether 387,070 military conscripts were followed throughout their six-to-twelve-month service period. Data on LBP hospitalisations were obtained from the National Hospital Discharge Register.</p> <p>Results</p> <p>Altogether 7,240 LBP hospitalisations were identified among 5,061 (1.3%) male conscripts during the study period. The event-based incidence of LBP hospitalisation was 27.0 (95% confidence interval (CI): 25.7–28.2). In most cases, the diagnosis was unspecified LBP (<it>n </it>= 5,141, 71%) followed by lumbar disc disorders (<it>n </it>= 2,069, 29%). Hospitalisation incidence due to unspecified LBP was 19.1 per 1,000 person-years (95% CI: 18.3 to 20.4), and 7.8 per 1,000 person-years (95% CI: 6.7 to 8.3) due to lumbar disc disorders. The incidence of unspecified LBP remained unaltered, while hospitalisation due to lumbar disc disorders declined from 1993 onwards.</p> <p>Conclusion</p> <p>Although conscripts accepted into military training pass physician-performed examinations as healthy, young adults, LBP hospitalisation causes significant morbidity during military service.</p

Quality Control-Driven Image Segmentation Towards Reliable Automatic Image Analysis in Large-Scale Cardiovascular Magnetic Resonance Aortic Cine Imaging

“The final authenticated version is available online at https://doi.org/10.1007/978-3-030-32245-8_83.”© 2019, Springer Nature Switzerland AG. Recent progress in fully-automated image segmentation has enabled efficient extraction of clinical parameters in large-scale clinical imaging studies, reducing laborious manual processing. However, the current state-of-the-art automatic image segmentation may still fail, especially when it comes to atypical cases. Visual inspection of segmentation quality is often required, thus diminishing the improvements in efficiency. This drives an increasing need to enhance the overall data processing pipeline with robust automatic quality scoring, especially for clinical applications. We present a novel quality control-driven (QCD) framework to provide reliable segmentation using a set of different neural networks. In contrast to the prior segmentation and quality scoring methods, the proposed framework automatically selects the optimal segmentation on-the-fly from the multiple candidate segmentations available, directly utilizing the inherent Dice similarity coefficient (DSC) predictions. We trained and evaluated the framework on a large-scale cardiovascular magnetic resonance aortic cine image sequences from the UK Biobank Study. The framework achieved segmentation accuracy of mean DSC at 0.966, mean prediction error of DSC within 0.015, and mean error in estimating lumen area ≤17.6 mm2 for both ascending aorta and proximal descending aorta. This novel QCD framework successfully integrates the automatic image segmentation along with detection of critical errors on a per-case basis, paving the way towards reliable fully-automatic extraction of clinical parameters for large-scale imaging studies

EGF functionalized polymer-coated gold nanoparticles promote EGF photostability and EGFR internalization for photothermal therapy

The application of functionalized nanocarriers on photothermal therapy for cancer ablation has wide interest. The success of this application depends on the therapeutic efficiency and biocompatibility of the system, but also on the stability and biorecognition of the conjugated protein. This study aims at investigating the hypothesis that EGF functionalized polymer -coated gold nanoparticles promote EGF photostability and EGFR internalization, making these conjugated particles suitable for photothermal therapy. The conjugated gold nanoparticles (100-200 nm) showed a plasmon absorption band located within the near infrared range (650-900 nm), optimal for photothermal therapy applications. The effects of temperature, of polymer-coated gold nanoparticles and of UVB light (295nm) on the fluorescence properties of EGF have been investigated with steady-state and time-resolved fluorescence spectroscopy. The fluorescence properties of EGF, including the formation of Trp and Tyr photoproducts, is modulated by temperature and by the intensity of the excitation light. The presence of polymeric-coated gold nanoparticles reduced or even avoided the formation of Trp and Tyr photoproducts when EGF is exposed to UVB light, protecting this way the structure and function of EGF. Cytotoxicity studies of conjugated nanoparticles carried out in normal-like human keratinocytes showed small, concentration dependent decreases in cell viability (0-25%). Moreover, conjugated nanoparticles could activate and induce the internalization of overexpressed Epidermal Growth Factor Receptor in human lung carcinoma cells. In conclusion, the gold nanoparticles conjugated with Epidermal Growth Factor and coated with biopolymers developed in this work, show a potential application for near infrared photothermal therapy, which may efficiently destroy solid tumours, reducing the damage of the healthy tissue.Support was provided by: Fundacao para a Ciencia e Tecnologia (FCT) for the financial support under the project reference PTDC/BBB-BMC/0611/2012 [https://www.fct.pt/apoios/projectos)]. The work at CBMA was supported by the strategic programme UID/BIA/04050/2013 (POCI-01-0145-FEDER-007569) funded by national funds through the FCT I.P. and by the ERDF through the COMPETE2020 - Programa Operacional Competitividade e Internacionalizacao (POCI) [https://www.fct.pt/apoios/projectos]; European Commission through the project H2020-644242-SAPHELY (https://saphely.eu/project.php) and the project H2020-634013-2-PHOCNOSIS [http://cordis.europa.eu/project/rcn/193268_en.html].The authors would like to thank Fundacao para a Ciencia e Tecnologia (FCT) for the financial support under the project reference PTDC/BBB-BMC/0611/2012. The work at CBMA was supported by the strategic programme UID/BIA/04050/2013 (POCI-01-0145-FEDER-007569) funded by national funds through the FCT I.P. and by the ERDF through the COMPETE2020 - Programa Operacional Competitividade e Internacionalizacao (POCI). The authors acknowledge the funding from the European Commission through the project H2020-644242-SAPHELY and the project H2020-634013-2-PHOCNOSIS. Finally, the authors would also like to thank the master student Joao Lopes from Universidade Lusofona (Portugal) for the help with in vitro cytotoxic assays. Isabel Correia acknowledges FCT for Investigator FCT contract.info:eu-repo/semantics/publishedVersio

Innate immune responses and antioxidant/oxidant imbalance are major determinants of human Chagas disease.

We investigated the pathological and diagnostic role of selected markers of inflammation, oxidant/antioxidant status, and cellular injury in human Chagas disease. METHODS: Seropositive/chagasic subjects characterized as clinically-symptomatic or clinically-asymptomatic (n = 116), seronegative/cardiac subjects (n = 102), and seronegative/healthy subjects (n = 45) were analyzed for peripheral blood biomarkers. RESULTS: Seropositive/chagasic subjects exhibited an increase in sera or plasma levels of myeloperoxidase (MPO, 2.8-fold), advanced oxidation protein products (AOPP, 56%), nitrite (5.7-fold), lipid peroxides (LPO, 12-17-fold) and malondialdehyde (MDA, 4-6-fold); and a decline in superoxide dismutase (SOD, 52%) and glutathione (GSH, 75%) contents. Correlation analysis identified a significant (p0.95). The MPO (r = 0.664) and LPO (r = 0.841) levels were also correlated with clinical disease state in chagasic subjects (p<0.001). Seronegative/cardiac subjects exhibited up to 77% decline in SOD, 3-5-fold increase in LPO and glutamate pyruvate transaminase (GPT) levels, and statistically insignificant change in MPO, AOPP, MDA, GPX, GSH, and creatine kinase (CK) levels. CONCLUSIONS: The interlinked effects of innate immune responses and antioxidant/oxidant imbalance are major determinants of human Chagas disease. The MPO, LPO and nitrite are excellent biomarkers for diagnosing seropositive/chagasic subjects, and MPO and LPO levels have potential utility in identifying clinical severity of Chagas diseaseFil: Dhiman, Monisha. University Of Texas Medical Branch. Department Of Microbiology & Immunology And Pathology; United State of America;Fil: Coronado, Yun A.. University Of Texas Medical Branch. Department Of Microbiology & Immunology And Pathology; United State of America;Fil: Vallejo, Cecilia K.. University Of Texas Medical Branch. Department Of Microbiology & Immunology And Pathology; United State of America;Fil: Petersen, John R.. University of Texas Medical Branch. Department of Pathology; United States of America;Fil: Ejilemele, Adetoum. University of Texas Medical Branch. Department of Pathology; United States of America;Fil: Nuñez, Sonia. Hospital Público de Gestión Descentralizada San Bernardo (HPGDSA); Argentina;Fil: Zago, María Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Salta. Instituto de Patologia Experimental; Argentina;Fil: Spratt, Heidi. Departments of Biochemistry and Molecular Biology and Preventive Medicine and Community Health. University of Texas Medical Branch; United States of America;Fil: Garg, Nisha Jain. University of Texas Medical Branch. Department of Pathology; United States of America