المؤلفون: Hammamieh, R, Chakraborty, N, Gautam, A, Muhie, S, Yang, R, Donohue, D, Kumar, R, Daigle, BJ, Zhang, Y, Amara, DA, Miller, S-A, Srinivasan, S, Flory, J, Yehuda, R, Petzold, L, Wolkowitz, OM, Mellon, SH, Hood, L, Doyle, FJ, Marmar, C, Jett, M

المصدر: Translational psychiatry. 7(7)

مصطلحات موضوعية: Humans, Stress Disorders, Post-Traumatic, DNA Methylation, Epigenesis, Genetic, CpG Islands, Adult, Middle Aged, Veterans, Male, Promoter Regions, Genetic, Young Adult, Afghan Campaign 2001-, Veterans Health, Iraq War, 2003-2011, Stress Disorders, Post-Traumatic, Epigenesis, Genetic, Promoter Regions, Iraq War, 2003-2011, Brain Disorders, Anxiety Disorders, Genetics, Human Genome, Mental Health, Post-Traumatic Stress Disorder, 2.1 Biological and endogenous factors, Psychology, Clinical Sciences, Public Health and Health Services

الوصف: Emerging knowledge suggests that post-traumatic stress disorder (PTSD) pathophysiology is linked to the patients' epigenetic changes, but comprehensive studies examining genome-wide methylation have not been performed. In this study, we examined genome-wide DNA methylation in peripheral whole blood in combat veterans with and without PTSD to ascertain differentially methylated probes. Discovery was initially made in a training sample comprising 48 male Operation Enduring Freedom (OEF)/Operation Iraqi Freedom (OIF) veterans with PTSD and 51 age/ethnicity/gender-matched combat-exposed PTSD-negative controls. Agilent whole-genome array detected ~5600 differentially methylated CpG islands (CpGI) annotated to ~2800 differently methylated genes (DMGs). The majority (84.5%) of these CpGIs were hypermethylated in the PTSD cases. Functional analysis was performed using the DMGs encoding the promoter-bound CpGIs to identify networks related to PTSD. The identified networks were further validated by an independent test set comprising 31 PTSD+/29 PTSD- veterans. Targeted bisulfite sequencing was also used to confirm the methylation status of 20 DMGs shown to be highly perturbed in the training set. To improve the statistical power and mitigate the assay bias and batch effects, a union set combining both training and test set was assayed using a different platform from Illumina. The pathways curated from this analysis confirmed 65% of the pool of pathways mined from training and test sets. The results highlight the importance of assay methodology and use of independent samples for discovery and validation of differentially methylated genes mined from whole blood. Nonetheless, the current study demonstrates that several important epigenetically altered networks may distinguish combat-exposed veterans with and without PTSD.

الوصول الحر: https://escholarship.org/uc/item/6mf0q60xTest

المؤلفون: Mazuski, C, Abel, JH, Chen, SP, Hermanstyne, TO, Jones, JR, Simon, T, Doyle, FJ, Herzog, ED

المصدر: Neuron , 99 (3) pp. 555-563. (2018)

مصطلحات موضوعية: vasoactive intestinal peptide, suprachiasmatic nucleus, neuropeptide, Period gene, multielectrode array, optogenetic, channelrhodopsin, daily oscillation

الوصف: The mammalian suprachiasmatic nucleus (SCN) functions as a master circadian pacemaker, integrating environmental input to align physiological and behavioral rhythms to local time cues. Approximately 10% of SCN neurons express vasoactive intestinal polypeptide (VIP); however, it is unknown how firing activity of VIP neurons releases VIP to entrain circadian rhythms. To identify physiologically relevant firing patterns, we optically tagged VIP neurons and characterized spontaneous firing over 3 days. VIP neurons had circadian rhythms in firing rate and exhibited two classes of instantaneous firing activity. We next tested whether physiologically relevant firing affected circadian rhythms through VIP release. We found that VIP neuron stimulation with high, but not low, frequencies shifted gene expression rhythms in vitro through VIP signaling. In vivo, high-frequency VIP neuron activation rapidly entrained circadian locomotor rhythms. Thus, increases in VIP neuronal firing frequency release VIP and entrain molecular and behavioral circadian rhythms.

وصف الملف: text

العلاقة: https://discovery.ucl.ac.uk/id/eprint/10059353/1/Mazuski_Entrainment%20of%20Circadian%20Rhythms%20Depends%20on%20Firing%20Rates%20and%20Neuropeptide%20Release%20of%20VIP%20SCN%20Neurons_AAM.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10059353Test/

الإتاحة: https://discovery.ucl.ac.uk/id/eprint/10059353/1/Mazuski_Entrainment%20of%20Circadian%20Rhythms%20Depends%20on%20Firing%20Rates%20and%20Neuropeptide%20Release%20of%20VIP%20SCN%20Neurons_AAM.pdfTest
https://discovery.ucl.ac.uk/id/eprint/10059353Test/

المؤلفون: Brown SA, Kovatchev BP, Raghinaru D, Lum JW, Buckingham BA, Kudva YC, Laffel LM, Levy CJ, Pinsker JE, Wadwa RP, Dassau E, Doyle FJ, Anderson SM, Church MM, Dadlani V, Ekhlaspour L, Forlenza GP, Isganaitis E, Lam DW, Kollman C, Beck RW, Trial Research Group. iDCL

المساهمون: University of Virginia [Charlottesville], Department of Molecular Medicine [Tampa], University of South Florida [Tampa] (USF), Stanford School of Medicine [Stanford], Stanford Medicine, Stanford University-Stanford University, Mayo Clinic [Rochester], Harvard Medical School [Boston] (HMS), Université de Lorraine (UL)

المصدر: New England Journal of Medicine
New England Journal of Medicine, Massachusetts Medical Society, 2019, 381 (18), pp.1707-1717. ⟨10.1056/NEJMoa1907863⟩

مصطلحات موضوعية: Adult, Blood Glucose, Male, Pancreas, Artificial, Pediatrics, medicine.medical_specialty, Adolescent, Insulin delivery, 030204 cardiovascular system & hematology, law.invention, Young Adult, 03 medical and health sciences, Insulin Infusion Systems, 0302 clinical medicine, Randomized controlled trial, law, Diabetes mellitus, Multicenter trial, medicine, Humans, Hypoglycemic Agents, Insulin, MESH: Diabetes Mellitus, Type 1/drug therapy, Hypoglycemic Agents/administration & dosage, Insulin/administration & dosage, Pancreas, Artificial/adverse effects, In patient, 030212 general & internal medicine, Aged, Glycemic, Glycated Hemoglobin, Type 1 diabetes, business.industry, Equipment Design, General Medicine, Middle Aged, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, medicine.disease, 3. Good health, Diabetes Mellitus, Type 1, Multicenter study, Female, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology

الوصف: Closed-loop systems that automate insulin delivery may improve glycemic outcomes in patients with type 1 diabetes.In this 6-month randomized, multicenter trial, patients with type 1 diabetes were assigned in a 2:1 ratio to receive treatment with a closed-loop system (closed-loop group) or a sensor-augmented pump (control group). The primary outcome was the percentage of time that the blood glucose level was within the target range of 70 to 180 mg per deciliter (3.9 to 10.0 mmol per liter), as measured by continuous glucose monitoring.A total of 168 patients underwent randomization; 112 were assigned to the closed-loop group, and 56 were assigned to the control group. The age range of the patients was 14 to 71 years, and the glycated hemoglobin level ranged from 5.4 to 10.6%. All 168 patients completed the trial. The mean (±SD) percentage of time that the glucose level was within the target range increased in the closed-loop group from 61±17% at baseline to 71±12% during the 6 months and remained unchanged at 59±14% in the control group (mean adjusted difference, 11 percentage points; 95% confidence interval [CI], 9 to 14; P0.001). The results with regard to the main secondary outcomes (percentage of time that the glucose level was180 mg per deciliter, mean glucose level, glycated hemoglobin level, and percentage of time that the glucose level was70 mg per deciliter or54 mg per deciliter [3.0 mmol per liter]) all met the prespecified hierarchical criterion for significance, favoring the closed-loop system. The mean difference (closed loop minus control) in the percentage of time that the blood glucose level was lower than 70 mg per deciliter was -0.88 percentage points (95% CI, -1.19 to -0.57; P0.001). The mean adjusted difference in glycated hemoglobin level after 6 months was -0.33 percentage points (95% CI, -0.53 to -0.13; P = 0.001). In the closed-loop group, the median percentage of time that the system was in closed-loop mode was 90% over 6 months. No serious hypoglycemic events occurred in either group; one episode of diabetic ketoacidosis occurred in the closed-loop group.In this 6-month trial involving patients with type 1 diabetes, the use of a closed-loop system was associated with a greater percentage of time spent in a target glycemic range than the use of a sensor-augmented insulin pump. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases; iDCL ClinicalTrials.gov number, NCT03563313.).

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::84267546ab801b96b04bdc2b2278ee67Test
https://doi.org/10.1530/ey.17.10.13Test

المؤلفون: Renard E, Magni L, Toffanin C, Patek S, Hughes C, Place J, Farret A, Vedovato M, Dassau E, Zisser H, Doyle FJ, Kovatchev B, De Nicolao G, Breton M, BRUTTOMESSO, DANIELA, DALLA MAN, CHIARA, DEL FAVERO, SIMONE, MARAN, ALBERTO, AVOGARO, ANGELO, COBELLI, CLAUDIO

المساهمون: Renard, E, Bruttomesso, Daniela, Magni, L, DALLA MAN, Chiara, DEL FAVERO, Simone, Toffanin, C, Patek, S, Hughes, C, Place, J, Farret, A, Maran, Alberto, Vedovato, M, Dassau, E, Zisser, H, Doyle, Fj, Kovatchev, B, De Nicolao, G, Avogaro, Angelo, Breton, M, Cobelli, Claudio

العلاقة: ispartofbook:Abstracts from American Diabetes Association 71nd Scientific Sessions; American Diabetes Association 71nd Scientific Sessions; volume:60 suppl1; firstpage:155-OR; journal:DIABETES; http://hdl.handle.net/11577/2531181Test

الإتاحة: http://hdl.handle.net/11577/2531181Test

المؤلفون: Chase HP, Doyle FJ 3rd, Zisser H, Renard E, Nimri R, Buckingham BA, Maahs DM, Anderson S, Magni L, Lum J, Calhoun P, Kollman C, Beck RW, Control to Range Study Group, COBELLI, CLAUDIO

المساهمون: Chase, Hp, Doyle FJ, 3rd, Zisser, H, Renard, E, Nimri, R, Cobelli, Claudio, Buckingham, Ba, Maahs, Dm, Anderson, S, Magni, L, Lum, J, Calhoun, P, Kollman, C, Beck, Rw, Control to Range Study, Group

الوصف: Background: This study evaluated meal bolus insulin delivery strategies and associated postprandial glucose control while using an artificial pancreas (AP) system. Subjects and Methods: This study was a multicenter trial in 53 patients, 12-65 years of age, with type 1 diabetes for at least 1 year and use of continuous subcutaneous insulin infusion for at least 6 months. Four different insulin bolus strategies were assessed: standard bolus delivered with meal (n=51), standard bolus delivered 15 min prior to meal (n=40), over-bolus of 30% delivered with meal (n=40), and bolus purposely omitted (n=46). Meal carbohydrate (CHO) intake was 1 g of CHO/kg of body weight up to a maximum of 100 g for the first three strategies or up to a maximum of 50 g for strategy 4. Results: Only three of 177 meals (two with over-bolus and one with standard bolus 15 min prior to meal) had postprandial blood glucose values of <60 mg/dL. Postprandial hyperglycemia (blood glucose level >180 mg/dL) was prolonged for all four bolus strategies but was shorter for the over-bolus (41% of the 4-h period) than the two standard bolus strategies (73% for each). Mean postprandial blood glucose level was 15.9 mg/dL higher for the standard bolus with meal compared with the prebolus (baseline-adjusted, P=0.07 for treatment effect over the 4-h period). Conclusions: The AP handled the four bolus situations safely, but at the expense of having elevated postprandial glucose levels in most subjects. This was most likely secondary to suboptimal performance of the algorithm.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/25188375; info:eu-repo/semantics/altIdentifier/wos/WOS:000342561100003; volume:16; firstpage:613; lastpage:622; numberofpages:10; journal:DIABETES TECHNOLOGY & THERAPEUTICS; http://hdl.handle.net/11577/3032572Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84907531638

الإتاحة: https://doi.org/10.1089/dia.2014.0050Test
http://hdl.handle.net/11577/3032572Test

المؤلفون: Zisser H, Renard E, Kovatchev B, Nimri R, Magni L, Buckingham BA, Chase HP, Doyle FJ 3rd, Lum J, Calhoun P, Kollman C, Dassau E, Farret A, Place J, Breton M, Anderson SM, Filippi A, Scotton R, Phillip M, Atlas E, Muller I, Miller S, Toffanin C, Raimondo DM, De Nicolao G, Beck RW, Control to Range Study Group, COBELLI, CLAUDIO, AVOGARO, ANGELO, DALLA MAN, CHIARA, DEL FAVERO, SIMONE, BRUTTOMESSO, DANIELA

المساهمون: Zisser, H, Renard, E, Kovatchev, B, Cobelli, Claudio, Avogaro, Angelo, Nimri, R, Magni, L, Buckingham, Ba, Chase, Hp, Doyle FJ, 3rd, Lum, J, Calhoun, P, Kollman, C, Dassau, E, Farret, A, Place, J, Breton, M, Anderson, Sm, DALLA MAN, Chiara, DEL FAVERO, Simone, Bruttomesso, Daniela, Filippi, A, Scotton, R, Phillip, M, Atlas, E, Muller, I, Miller, S, Toffanin, C, Raimondo, Dm, De Nicolao, G, Beck, Rw, Control to Range Study, Group

وصف الملف: STAMPA

العلاقة: info:eu-repo/semantics/altIdentifier/wos/WOS:000342561100002; volume:16; firstpage:613; lastpage:622; numberofpages:10; journal:DIABETES TECHNOLOGY & THERAPEUTICS; http://hdl.handle.net/11577/3156537Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84907485182

الإتاحة: https://doi.org/10.1089/dia.2014.0066Test
http://hdl.handle.net/11577/3156537Test

المؤلفون: Maahs, DM, Buckingham, BA, Castle, JR, Cinar, A, Damiano, ER, Dassau, E, DeVries, JH, Doyle, FJ, Griffen, SC, Haidar, A, Heinemann, L, Hovorka, R, Jones, TW, Kollman, C, Kovatchev, B, Levy, BL, Nimri, R, O'Neal, DN, Philip, M, Renard, E, Russell, SJ, Weinzimer, SA, Zisser, H, Lum, JW

الوصف: Research on and commercial development of the artificial pancreas (AP) continue to progress rapidly, and the AP promises to become a part of clinical care. In this report, members of the JDRF Artificial Pancreas Project Consortium in collaboration with the wider AP community 1) advocate for the use of continuous glucose monitoring glucose metrics as outcome measures in AP trials, in addition to HbA1c, and 2) identify a short set of basic, easily interpreted outcome measures to be reported in AP studies whenever feasible. Consensus on a broader range of measures remains challenging; therefore, reporting of additional metrics is encouraged as appropriate for individual AP studies or study groups. Greater consistency in reporting of basic outcome measures may facilitate the interpretation of study results by investigators, regulatory bodies, health care providers, payers, and patients themselves, thereby accelerating the widespread adoption of AP technology to improve the lives of people with type 1 diabetes.

العلاقة: pii: 39/7/1175; Maahs, D. M., Buckingham, B. A., Castle, J. R., Cinar, A., Damiano, E. R., Dassau, E., DeVries, J. H., Doyle, F. J., Griffen, S. C., Haidar, A., Heinemann, L., Hovorka, R., Jones, T. W., Kollman, C., Kovatchev, B., Levy, B. L., Nimri, R., O'Neal, D. N., Philip, M. ,. Lum, J. W. (2016). Outcome Measures for Artificial Pancreas Clinical Trials: A Consensus Report. DIABETES CARE, 39 (7), pp.1175-1179. https://doi.org/10.2337/dc15-2716Test.; http://hdl.handle.net/11343/269301Test

الإتاحة: https://doi.org/10.2337/dc15-2716Test
http://hdl.handle.net/11343/269301Test

المؤلفون: Herrero P, Palerm CC, Dassau E, Zisser H, Jovanovič L, Vehí J, Doyle FJ, DALLA MAN, CHIARA, COBELLI, CLAUDIO

المساهمون: Herrero, P, Palerm, Cc, Dassau, E, Zisser, H, Jovanovič, L, DALLA MAN, Chiara, Cobelli, Claudio, Vehí, J, Doyle, Fj

العلاقة: Diabetes Technology Meeting; firstpage:A174; http://hdl.handle.net/11577/2531013Test

الإتاحة: http://hdl.handle.net/11577/2531013Test

المؤلفون: Breton M, Farret A, Anderson S, Magni L, Patek S, Place J, Demartini S, Toffanin C, Hughes Karvetski C, Dassau E, Zisser H, Doyle FJ 3rd, De Nicolao G, Renard E, Kovatchev B, on behalf of The International Artificial Pancreas Study Group, BRUTTOMESSO, DANIELA, DALLA MAN, CHIARA, DEL FAVERO, SIMONE, AVOGARO, ANGELO, COBELLI, CLAUDIO

المساهمون: Breton, M, Farret, A, Bruttomesso, Daniela, Anderson, S, Magni, L, Patek, S, DALLA MAN, Chiara, Place, J, Demartini, S, DEL FAVERO, Simone, Toffanin, C, Hughes Karvetski, C, Dassau, E, Zisser, H, Doyle FJ, 3rd, De Nicolao, G, Avogaro, Angelo, Cobelli, Claudio, Renard, E, Kovatchev, B, on behalf of The International Artificial Pancreas Study, Group

الوصف: Integrated closed-loop control (CLC), combining continuous glucose monitoring (CGM) with insulin pump (continuous subcutaneous insulin infusion [CSII]), known as artificial pancreas, can help optimize glycemic control in diabetes. We present a fundamental modular concept for CLC design, illustrated by clinical studies involving 11 adolescents and 27 adults at the Universities of Virginia, Padova, and Montpellier. We tested two modular CLC constructs: standard control to range (sCTR), designed to augment pump plus CGM by preventing extreme glucose excursions; and enhanced control to range (eCTR), designed to truly optimize control within near normoglycemia of 3.9-10 mmol/L. The CLC system was fully integrated using automated data transfer CGM→algorithm→CSII. All studies used randomized crossover design comparing CSII versus CLC during identical 22-h hospitalizations including meals, overnight rest, and 30-min exercise. sCTR increased significantly the time in near normoglycemia from 61 to 74%, simultaneously reducing hypoglycemia 2.7-fold. eCTR improved mean blood glucose from 7.73 to 6.68 mmol/L without increasing hypoglycemia, achieved 97% in near normoglycemia and 77% in tight glycemic control, and reduced variability overnight. In conclusion, sCTR and eCTR represent sequential steps toward automated CLC, preventing extremes (sCTR) and further optimizing control (eCTR). This approach inspires compelling new concepts: modular assembly, sequential deployment, testing, and clinical acceptance of custom-built CLC systems tailored to individual patient needs.

وصف الملف: STAMPA

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/22688340; info:eu-repo/semantics/altIdentifier/wos/WOS:000308254100009; volume:61; firstpage:2230; lastpage:2237; journal:DIABETES; http://hdl.handle.net/11577/2502889Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84865453569

الإتاحة: https://doi.org/10.2337/db11-1445Test
http://hdl.handle.net/11577/2502889Test

المؤلفون: Breton MD, Patek SD, Demartini S, Farret A, Brown S, Hughes CS, Place J, Magni L, Dassau E, Zisser H, Doyle FJ, Anderson SM, Kovatchev BP, Renard E., DALLA MAN, CHIARA, COBELLI, CLAUDIO

المساهمون: Breton, Md, Patek, Sd, Demartini, S, Farret, A, Brown, S, Hughes, C, Place, J, DALLA MAN, Chiara, Magni, L, Dassau, E, Zisser, H, Cobelli, Claudio, Doyle, Fj, Anderson, Sm, Kovatchev, Bp, Renard, E.

العلاقة: volume:60 suppl1; firstpage:151-OR; journal:DIABETES; http://hdl.handle.net/11577/2531172Test

الإتاحة: http://hdl.handle.net/11577/2531172Test