Effects of Randomized Controlled Infancy-Onset Dietary Intervention on Leukocyte Telomere Length—The Special Turku Coronary Risk Factor Intervention Project (STRIP)

Reduced telomere length (TL) is a biological marker of aging. A high inter-individual variation in TL exists already in childhood, which is partly explained by genetics, but also by lifestyle factors. We examined the influence of a 20-year dietary/lifestyle intervention on TL attrition from childhood to early adulthood. The study comprised participants of the longitudinal randomized Special Turku Coronary Risk Factor Intervention Project (STRIP) conducted between 1990 and 2011. Healthy 7-month-old children were randomized to the intervention group (n = 540) receiving dietary counseling mainly focused on dietary fat quality and to the control group (n = 522). Leukocyte TL was measured using the Southern blot method from whole blood samples collected twice: at a mean age of 7.5 and 19.8 years (n = 232; intervention n = 108, control n = 124). Yearly TL attrition rate was calculated. The participants of the intervention group had slower yearly TL attrition rate compared to the controls (intervention: mean = −7.5 bp/year, SD = 24.4 vs. control: mean = −15.0 bp/year, SD = 30.3; age, sex and baseline TL adjusted β = 0.007, SE = 0.004, p = 0.040). The result became stronger after additional adjustments for dietary fat quality and fiber intake, serum lipid and insulin concentrations, systolic blood pressure, physical activity and smoking (β = 0.013, SE = 0.005, p = 0.009). A long-term intervention focused mainly on dietary fat quality may affect the yearly TL attrition rate in healthy children/adolescents

Effects of Randomized Controlled Infancy-Onset Dietary Intervention on Leukocyte Telomere Length—The Special Turku Coronary Risk Factor Intervention Project (STRIP)

Reduced telomere length (TL) is a biological marker of aging. A high inter-individual variation in TL exists already in childhood, which is partly explained by genetics, but also by lifestyle factors. We examined the influence of a 20-year dietary/lifestyle intervention on TL attrition from childhood to early adulthood. The study comprised participants of the longitudinal randomized Special Turku Coronary Risk Factor Intervention Project (STRIP) conducted between 1990 and 2011. Healthy 7-month-old children were randomized to the intervention group (n = 540) receiving dietary counseling mainly focused on dietary fat quality and to the control group (n = 522). Leukocyte TL was measured using the Southern blot method from whole blood samples collected twice: at a mean age of 7.5 and 19.8 years (n = 232; intervention n = 108, control n = 124). Yearly TL attrition rate was calculated. The participants of the intervention group had slower yearly TL attrition rate compared to the controls (intervention: mean = −7.5 bp/year, SD = 24.4 vs. control: mean = −15.0 bp/year, SD = 30.3; age, sex and baseline TL adjusted β = 0.007, SE = 0.004, p = 0.040). The result became stronger after additional adjustments for dietary fat quality and fiber intake, serum lipid and insulin concentrations, systolic blood pressure, physical activity and smoking (β = 0.013, SE = 0.005, p = 0.009). A long-term intervention focused mainly on dietary fat quality may affect the yearly TL attrition rate in healthy children/adolescents

Effects of Randomized Controlled Infancy-Onset Dietary Intervention on Leukocyte Telomere Length - The Special Turku Coronary Risk Factor Intervention Project (STRIP)

Reduced telomere length (TL) is a biological marker of aging. A high inter-individual variation in TL exists already in childhood, which is partly explained by genetics, but also by lifestyle factors. We examined the influence of a 20-year dietary/lifestyle intervention on TL attrition from childhood to early adulthood. The study comprised participants of the longitudinal randomized Special Turku Coronary Risk Factor Intervention Project (STRIP) conducted between 1990 and 2011. Healthy 7-month-old children were randomized to the intervention group (n = 540) receiving dietary counseling mainly focused on dietary fat quality and to the control group (n = 522). Leukocyte TL was measured using the Southern blot method from whole blood samples collected twice: at a mean age of 7.5 and 19.8 years (n = 232; intervention n = 108, control n = 124). Yearly TL attrition rate was calculated. The participants of the intervention group had slower yearly TL attrition rate compared to the controls (intervention: mean = -7.5 bp/year, SD = 24.4 vs. control: mean = -15.0 bp/year, SD = 30.3; age, sex and baseline TL adjusted beta = 0.007, SE = 0.004, p = 0.040). The result became stronger after additional adjustments for dietary fat quality and fiber intake, serum lipid and insulin concentrations, systolic blood pressure, physical activity and smoking (beta = 0.013, SE = 0.005, p = 0.009). A long-term intervention focused mainly on dietary fat quality may affect the yearly TL attrition rate in healthy children/adolescents

Person-centred care in interventions to limit weight gain in pregnant women with obesity - a systematic review

Background Person-centred care, asserting that individuals are partners in their care, has been associated with care satisfaction but the value of using it to support women with obesity during pregnancy is unknown. Excessive gestational weight gain is associated with increased risks for both mother and baby and weight gain therefore is an important intervention target. The aims of this review was to 1) explore to what extent and in what manner interventions assessing weight in pregnant women with obesity use person-centred care and 2) assess if interventions including aspects of person-centred care are more effective at limiting weight gain than interventions not employing person-centred care. Methods Ten databases were systematically searched in January 2014. Studies had to report an intervention offered to pregnant women with obesity and measure gestational weight gain to be included. All included studies were independently double coded to identify to what extent they included three defined aspects of person-centred care: 1) “initiate a partnership” including identifying the person’s circumstances and motivation; 2) “working the partnership” through sharing the decision-making regarding the planned action and 3) “safeguarding the partnership through documentation” of care preferences. Information on gestational weight gain, study quality and characteristics were also extracted. Results Ten studies were included in the review, of which five were randomised controlled trials (RCT), and the remaining observational studies. Four interventions included aspects of person-centred care; two observational studies included both “initiating the partnership”, and “working the partnership”. One observational study included “initiating the partnership” and one RCT included “working the partnership”. No interventions included “safeguarding the partnership through documentation”. Whilst all studies with person-centred care aspects showed promising findings regarding limiting gestational weight gain, so did the interventions not including person-centred care aspects. Conclusions The use of an identified person-centred care approach is presently limited in interventions targeting gestational weight gain in pregnant women with obesity. Hence to what extent person-centred care may improve health outcomes and care satisfaction in this population is currently unknown and more research is needed. That said, our findings suggest that use of routines incorporating person-centredness are feasible to include within these interventions

The dUTPase Enzyme Is Essential in Mycobacterium smegmatis

Thymidine biosynthesis is essential in all cells. Inhibitors of the enzymes involved in this pathway (e.g. methotrexate) are thus frequently used as cytostatics. Due to its pivotal role in mycobacterial thymidylate synthesis dUTPase, which hydrolyzes dUTP into the dTTP precursor dUMP, has been suggested as a target for new antitubercular agents. All mycobacterial genomes encode dUTPase with a mycobacteria-specific surface loop absent in the human dUTPase. Using Mycobacterium smegmatis as a fast growing model for Mycobacterium tuberculosis, we demonstrate that dUTPase knock-out results in lethality that can be reverted by complementation with wild-type dUTPase. Interestingly, a mutant dUTPase gene lacking the genus-specific loop was unable to complement the knock-out phenotype. We also show that deletion of the mycobacteria-specific loop has no major effect on dUTPase enzymatic properties in vitro and thus a yet to be identified loop-specific function seems to be essential within the bacterial cell context. In addition, here we demonstrated that Mycobacterium tuberculosis dUTPase is fully functional in Mycobacterium smegmatis as it rescues the lethal knock-out phenotype. Our results indicate the potential of dUTPase as a target for antitubercular drugs and identify a genus-specific surface loop on the enzyme as a selective target

Metabolism during anaesthesia and recovery in colic and healthy horses: a microdialysis study

<p>Abstract</p> <p>Background</p> <p>Muscle metabolism in horses has been studied mainly by analysis of substances in blood or plasma and muscle biopsy specimens. By using microdialysis, real-time monitoring of the metabolic events in local tissue with a minimum of trauma is possible. There is limited information about muscle metabolism in the early recovery period after anaesthesia in horses and especially in the colic horse. The aims were to evaluate the microdialysis technique as a complement to plasma analysis and to study the concentration changes in lactate, pyruvate, glucose, glycerol, and urea during anaesthesia and in the recovery period in colic horses undergoing abdominal surgery and in healthy horses not subjected to surgery.</p> <p>Methods</p> <p>Ten healthy university-owned horses given anaesthesia alone and ten client-owned colic horses subjected to emergency abdominal surgery were anaesthetised for a mean (range) of 230 min (193–273) and 208 min (145–300) respectively. Venous blood samples were taken before anaesthesia. Venous blood sampling and microdialysis in the gluteal muscle were performed during anaesthesia and until 24 h after anaesthesia. Temporal changes and differences between groups were analysed with an ANOVA for repeated measures followed by Tukey Post Hoc test or Planned Comparisons.</p> <p>Results</p> <p>Lactate, glucose and urea, in both dialysate and plasma, were higher in the colic horses than in the healthy horses for several hours after recovery to standing. In the colic horses, lactate, glucose, and urea in dialysate, and lactate in plasma increased during the attempts to stand. The lactate-to-pyruvate ratio was initially high in sampled colic horses but decreased over time. In the colic horses, dialysate glycerol concentrations varied considerably whereas in the healthy horses, dialysate glycerol was elevated during anaesthesia but decreased after standing. In both groups, lactate concentration was higher in dialysate than in plasma. The correspondence between dialysate and plasma concentrations of glucose, urea and glycerol varied.</p> <p>Conclusion</p> <p>Microdialysis proved to be suitable in the clinical setting for monitoring of the metabolic events during anaesthesia and recovery. It was possible with this technique to show greater muscle metabolic alterations in the colic horses compared to the healthy horses in response to regaining the standing position.</p

Skin Electroporation: Effects on Transgene Expression, DNA Persistence and Local Tissue Environment

BACKGROUND: Electrical pulses have been used to enhance uptake of molecules into living cells for decades. This technique, often referred to as electroporation, has become an increasingly popular method to enhance in vivo DNA delivery for both gene therapy applications as well as for delivery of vaccines against both infectious diseases and cancer. In vivo electrovaccination (gene delivery followed by electroporation) is currently being investigated in several clinical trials, including DNA delivery to healthy volunteers. However, the mode of action at molecular level is not yet fully understood. METHODOLOGY/PRINCIPAL FINDINGS: This study investigates intradermal DNA electrovaccination in detail and describes the effects on expression of the vaccine antigen, plasmid persistence and the local tissue environment. Gene profiling of the vaccination site showed that the combination of DNA and electroporation induced a significant up-regulation of pro-inflammatory genes. In vivo imaging of luciferase activity after electrovaccination demonstrated a rapid onset (minutes) and a long duration (months) of transgene expression. However, when the more immunogenic prostate specific antigen (PSA) was co-administered, PSA-specific T cells were induced and concurrently the luciferase expression became undetectable. Electroporation did not affect the long-term persistence of the PSA-expressing plasmid. CONCLUSIONS/SIGNIFICANCE: This study provides important insights to how DNA delivery by intradermal electrovaccination affects the local immunological responses of the skin, transgene expression and clearance of the plasmid. As the described vaccination approach is currently being evaluated in clinical trials, the data provided will be of high significance

Report on the sixth blind test of organic crystal structure prediction methods.

The sixth blind test of organic crystal structure prediction (CSP) methods has been held, with five target systems: a small nearly rigid molecule, a polymorphic former drug candidate, a chloride salt hydrate, a co-crystal and a bulky flexible molecule. This blind test has seen substantial growth in the number of participants, with the broad range of prediction methods giving a unique insight into the state of the art in the field. Significant progress has been seen in treating flexible molecules, usage of hierarchical approaches to ranking structures, the application of density-functional approximations, and the establishment of new workflows and `best practices' for performing CSP calculations. All of the targets, apart from a single potentially disordered Z' = 2 polymorph of the drug candidate, were predicted by at least one submission. Despite many remaining challenges, it is clear that CSP methods are becoming more applicable to a wider range of real systems, including salts, hydrates and larger flexible molecules. The results also highlight the potential for CSP calculations to complement and augment experimental studies of organic solid forms.The organisers and participants are very grateful to the crystallographers who supplied the candidate structures: Dr. Peter Horton (XXII), Dr. Brian Samas (XXIII), Prof. Bruce Foxman (XXIV), and Prof. Kraig Wheeler (XXV and XXVI). We are also grateful to Dr. Emma Sharp and colleagues at Johnson Matthey (Pharmorphix) for the polymorph screening of XXVI, as well as numerous colleagues at the CCDC for assistance in organising the blind test. Submission 2: We acknowledge Dr. Oliver Korb for numerous useful discussions. Submission 3: The Day group acknowledge the use of the IRIDIS High Performance Computing Facility, and associated support services at the University of Southampton, in the completion of this work. We acknowledge funding from the EPSRC (grants EP/J01110X/1 and EP/K018132/1) and the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC through grant agreements n. 307358 (ERC-stG- 2012-ANGLE) and n. 321156 (ERC-AG-PE5-ROBOT). Submission 4: I am grateful to Mikhail Kuzminskii for calculations of molecular structures on Gaussian 98 program in the Institute of Organic Chemistry RAS. The Russian Foundation for Basic Research is acknowledged for financial support (14-03-01091). Submission 5: Toine Schreurs provided computer facilities and assistance. I am grateful to Matthew Habgood at AWE company for providing a travel grant. Submission 6: We would like to acknowledge support of this work by GlaxoSmithKline, Merck, and Vertex. Submission 7: The research was financially supported by the VIDI Research Program 700.10.427, which is financed by The Netherlands Organisation for Scientific Research (NWO), and the European Research Council (ERC-2010-StG, grant agreement n. 259510-KISMOL). We acknowledge the support of the Foundation for Fundamental Research on Matter (FOM). Supercomputer facilities were provided by the National Computing Facilities Foundation (NCF). Submission 8: Computer resources were provided by the Center for High Performance Computing at the University of Utah and the Extreme Science and Engineering Discovery Environment (XSEDE), supported by NSF grant number ACI-1053575. MBF and GIP acknowledge the support from the University of Buenos Aires and the Argentinian Research Council. Submission 9: We thank Dr. Bouke van Eijck for his valuable advice on our predicted structure of XXV. We thank the promotion office for TUT programs on advanced simulation engineering (ADSIM), the leading program for training brain information architects (BRAIN), and the information and media center (IMC) at Toyohashi University of Technology for the use of the TUT supercomputer systems and application software. We also thank the ACCMS at Kyoto University for the use of their supercomputer. In addition, we wish to thank financial supports from Conflex Corp. and Ministry of Education, Culture, Sports, Science and Technology. Submission 12: We thank Leslie Leiserowitz from the Weizmann Institute of Science and Geoffrey Hutchinson from the University of Pittsburgh for helpful discussions. We thank Adam Scovel at the Argonne Leadership Computing Facility (ALCF) for technical support. Work at Tulane University was funded by the Louisiana Board of Regents Award # LEQSF(2014-17)-RD-A-10 “Toward Crystal Engineering from First Principles”, by the NSF award # EPS-1003897 “The Louisiana Alliance for Simulation-Guided Materials Applications (LA-SiGMA)”, and by the Tulane Committee on Research Summer Fellowship. Work at the Technical University of Munich was supported by the Solar Technologies Go Hybrid initiative of the State of Bavaria, Germany. Computer time was provided by the Argonne Leadership Computing Facility (ALCF), which is supported by the Office of Science of the U.S. Department of Energy under contract DE-AC02-06CH11357. Submission 13: This work would not have been possible without funding from Khalifa University’s College of Engineering. I would like to acknowledge Prof. Robert Bennell and Prof. Bayan Sharif for supporting me in acquiring the resources needed to carry out this research. Dr. Louise Price is thanked for her guidance on the use of DMACRYS and NEIGHCRYS during the course of this research. She is also thanked for useful discussions and numerous e-mail exchanges concerning the blind test. Prof. Sarah Price is acknowledged for her support and guidance over many years and for providing access to DMACRYS and NEIGHCRYS. Submission 15: The work was supported by the United Kingdom’s Engineering and Physical Sciences Research Council (EPSRC) (EP/J003840/1, EP/J014958/1) and was made possible through access to computational resources and support from the High Performance Computing Cluster at Imperial College London. We are grateful to Professor Sarah L. Price for supplying the DMACRYS code for use within CrystalOptimizer, and to her and her research group for support with DMACRYS and feedback on CrystalPredictor and CrystalOptimizer. Submission 16: R. J. N. acknowledges financial support from the Engineering and Physical Sciences Research Council (EPSRC) of the U.K. [EP/J017639/1]. R. J. N. and C. J. P. acknowledge use of the Archer facilities of the U.K.’s national high-performance computing service (for which access was obtained via the UKCP consortium [EP/K014560/1]). C. J. P. also acknowledges a Leadership Fellowship Grant [EP/K013688/1]. B. M. acknowledges Robinson College, Cambridge, and the Cambridge Philosophical Society for a Henslow Research Fellowship. Submission 17: The work at the University of Delaware was supported by the Army Research Office under Grant W911NF-13-1- 0387 and by the National Science Foundation Grant CHE-1152899. The work at the University of Silesia was supported by the Polish National Science Centre Grant No. DEC-2012/05/B/ST4/00086. Submission 18: We would like to thank Constantinos Pantelides, Claire Adjiman and Isaac Sugden of Imperial College for their support of our use of CrystalPredictor and CrystalOptimizer in this and Submission 19. The CSP work of the group is supported by EPSRC, though grant ESPRC EP/K039229/1, and Eli Lilly. The PhD students support: RKH by a joint UCL Max-Planck Society Magdeburg Impact studentship, REW by a UCL Impact studentship; LI by the Cambridge Crystallographic Data Centre and the M3S Centre for Doctoral Training (EPSRC EP/G036675/1). Submission 19: The potential generation work at the University of Delaware was supported by the Army Research Office under Grant W911NF-13-1-0387 and by the National Science Foundation Grant CHE-1152899. Submission 20: The work at New York University was supported, in part, by the U.S. Army Research Laboratory and the U.S. Army Research Office under contract/grant number W911NF-13-1-0387 (MET and LV) and, in part, by the Materials Research Science and Engineering Center (MRSEC) program of the National Science Foundation under Award Number DMR-1420073 (MET and ES). The work at the University of Delaware was supported by the U.S. Army Research Laboratory and the U.S. Army Research Office under contract/grant number W911NF-13-1- 0387 and by the National Science Foundation Grant CHE-1152899. Submission 21: We thank the National Science Foundation (DMR-1231586), the Government of Russian Federation (Grant No. 14.A12.31.0003), the Foreign Talents Introduction and Academic Exchange Program (No. B08040) and the Russian Science Foundation, project no. 14-43-00052, base organization Photochemistry Center of the Russian Academy of Sciences. Calculations were performed on the Rurik supercomputer at Moscow Institute of Physics and Technology. Submission 22: The computational results presented have been achieved in part using the Vienna Scientific Cluster (VSC). Submission 24: The potential generation work at the University of Delaware was supported by the Army Research Office under Grant W911NF-13-1-0387 and by the National Science Foundation Grant CHE-1152899. Submission 25: J.H. and A.T. acknowledge the support from the Deutsche Forschungsgemeinschaft under the program DFG-SPP 1807. H-Y.K., R.A.D., and R.C. acknowledge support from the Department of Energy (DOE) under Grant Nos. DE-SC0008626. This research used resources of the Argonne Leadership Computing Facility at Argonne National Laboratory, which is supported by the Office of Science of the U.S. Department of Energy under Contract No. DE-AC02-06CH11357. This research used resources of the National Energy Research Scientific Computing Center, which is supported by the Office of Science of the U.S. Department of Energy under Contract No. DEAC02-05CH11231. Additional computational resources were provided by the Terascale Infrastructure for Groundbreaking Research in Science and Engineering (TIGRESS) High Performance Computing Center and Visualization Laboratory at Princeton University.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1107/S2052520616007447