295 results on '"Roberts, Rl"'
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2. Perinatal Steroid Treatments Alter Alloparental and Affiliative Behavior in Prairie Voles
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Carter Cs, Gustafson Ea, Zullo A, and Roberts Rl
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medicine.medical_specialty ,medicine.drug_class ,Sexual Behavior, Animal ,Behavioral Neuroscience ,chemistry.chemical_compound ,Endocrinology ,Corticosterone ,Internal medicine ,medicine ,Animals ,Microtus ,Alloparenting ,Testosterone ,Sex Characteristics ,biology ,Arvicolinae ,Endocrine and Autonomic Systems ,biology.organism_classification ,Androgen ,chemistry ,Maternal Exposure ,Female ,Steroids ,Psychology ,Sex characteristics ,Hormone - Abstract
This experiment was designed to examine the hypothesis that perinatal manipulation of gonadal or adrenal steroids can alter the subsequent expression of juvenile parental (alloparenting) and affiliative behavior in prairie voles (Microtus ochrogaster). Corticosterone (PRECORT), testosterone (PRE-TP), or oil injections (PRESES) were given on Prenatal Days 12-20 or on Postnatal Days 1-6 (CORT6, TP6, or SES6, respectively). Alloparenting was reduced significantly in females in the CORT6 group and in males in the TP6 group. Sibling affiliative preferences were increased significantly in PRE-TP females and stranger preferences were increased in TP6 and CORT6 females. The results suggest timing is a critical factor determining whether hormones have a facilitative or inhibitory effect on alloparental and affiliative behavior in prairie voles. In this species, corticosterone and testosterone have similar organizational effects on affiliative behavior in females. Alloparental behavior is inhibited by postnatal corticosterone administration in females and by postnatal testosterone administration in males, whereas prenatal steroid administration had no significant effect on alloparenting in either gender. more...
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- 1996
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3. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease
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Jostins, Luke, Ripke, Stephan, Weersma, Rinse K., Duerr, Richard H., Mcgovern, Dermot P., Hui, Ken Y., Lee, James C., Philip Schumm, L., Sharma, Yashoda, Anderson, Carl A., Essers, Jonah, Mitrovic, Mitja, Ning, Kaida, Cleynen, Isabelle, Theatre, Emilie, Spain, Sarah L., Raychaudhuri, Soumya, Goyette, Philippe, Wei, Zhi, Abraham, Clara, Achkar, Jean Paul, Ahmad, Tariq, Amininejad, Leila, Ananthakrishnan, Ashwin N., Andersen, Vibeke, Andrews, Jane M., Baidoo, Leonard, Balschun, Tobias, Bampton, Peter A., Bitton, Alain, Boucher, Gabrielle, Brand, Stephan, Büning, Carsten, Cohain, Ariella, Cichon, Sven, D'Amato, Mauro, De Jong, Dirk, Devaney, Kathy L., Dubinsky, Marla, Edwards, Cathryn, Ellinghaus, David, Ferguson, Lynnette R., Franchimont, Denis, Fransen, Karin, Gearry, Richard, Georges, Michel, Gieger, Christian, Glas, Jürgen, Haritunians, Talin, Hart, Ailsa, Hawkey, Chris, Hedl, Matija, Xinli, Hu, Karlsen, Tom H., Kupcinskas, Limas, Kugathasan, Subra, Latiano, Anna, Laukens, Debby, Lawrance, Ian C., Lees, Charlie W., Louis, Edouard, Mahy, Gillian, Mansfield, John, Morgan, Angharad R., Mowat, Craig, Newman, William, Palmieri, Orazio, Ponsioen, Cyriel Y., Potocnik, Uros, Prescott, Natalie J., Regueiro, Miguel, Rotter, Jerome I., Russell, Richard K., Sanderson, Jeremy D., Sans, Miquel, Satsangi, Jack, Schreiber, Stefan, Simms, Lisa A., Sventoraityte, Jurgita, Targan, Stephan R., Taylor, Kent D., Tremelling, Mark, Verspaget, Hein W., De Vos, Martine, Wijmenga, Cisca, Wilson, David C., Winkelmann, Juliane, Xavier, Ramnik J., Zeissig, Sebastian, Zhang, Bin, Zhang, Clarence K., Zhao, Hongyu, Silverberg, Mark S., Annese, Vito, Hakonarson, Hakon, Brant, Steven R., Radford Smith, Graham, Mathew, Christopher G., Rioux, John D., Schadt, Eric E., Daly, Mark J., Franke, Andre, Parkes, Miles, Vermeire, Severine, Barrett, Jeffrey C., Cho, Judy H., Barclay, M, Peyrin Biroulet, L, Chamaillard, M, Colombel, Jf, Cottone, M, Croft, A, D'Incà, R, Halfvarson J, Hanigan K, Henderson, P, Hugot, Jp, Karban, A, Kennedy, Na, Khan, Ma, Lémann, M, Levine, A, Massey, D, Milla, M, Montgomery, Gw, Ng, Sm, Oikonomou, I, Peeters, H, Proctor, Dd, Rahier, Jf, Roberts, R, Rutgeerts, P, Seibold, F, Stronati, Laura, Taylor, Km, Törkvist, L, Ublick, K, Van Limbergen, J, Van Gossum, A, Vatn, Mh, Zhang, H, Zhang, W, Andrews, Jm, Bampton, Pa, Florin, Th, Gearry, R, Krishnaprasad, K, Lawrance, Ic, Mahy, G, Radford Smith, G, Roberts, Rl, Simms, La, Amininijad, L, Cleynen, I, Dewit, O, Franchimont, D, Georges, M, Laukens, D, Theatre, E, Vermeire, S, Aumais, G, Baidoo, L, Barrie AM 3rd, Beck, K, Bernard, Ej, Binion, Dg, Bitton, A, Brant, Sr, Cho, Jh, Cohen, A, Croitoru, K, Daly, Mj, Datta, Lw, Deslandres, C, Duerr, Rh, Dutridge, D, Ferguson, J, Fultz, J, Goyette, P, Greenberg, Gr, Haritunians, T, Jobin, G, Katz, S, Lahaie, Rg, Mcgovern, Dp, Nelson, L, Ning, K, Paré, P, Regueiro, Md, Rioux, Jd, Ruggiero, E, Schumm, L, Schwartz, M, Scott, R, Sharma, Y, Silverberg, Ms, Spears, D, Steinhart, A, Stempak, Jm, Swoger, Jm, Tsagarelis, C, Zhang, C, Zhao, H, Aerts, J, Ahmad, T, Arbury, H, Attwood, A, Auton, A, Ball, Sg, Balmforth, Aj, Barnes, C, Barrett, Jc, Barroso, I, Barton, A, Bennett, Aj, Bhaskar, S, Blaszczyk, K, Bowes, J, Brand, Oj, Braund, Ps, Bredin, F, Breen, G, Brown, Mj, Bruce, In, Bull, J, Burren, Os, Burton, J, Byrnes, J, Caesar, S, Cardin, N, Clee, Cm, Coffey, Aj, Connell, Jm, Conrad, Df, Cooper, Jd, Dominiczak, Af, Downes, K, Drummond, He, Dudakia, D, Dunham, A, Ebbs, B, Eccles, D, Edkins, S, Edwards, C, Elliot, A, Emery, P, Evans, Dm, Evans, G, Eyre, S, Farmer, A, Ferrier, In, Flynn, E, Forbes, A, Forty, L, Franklyn, Ja, Frayling, Tm, Freathy, Rm, Giannoulatou, E, Gibbs, P, Gilbert, P, Gordon Smith, K, Gray, E, Green, E, Groves, Cj, Grozeva, D, Gwilliam, R, Hall, A, Hammond, N, Hardy, M, Harrison, P, Hassanali, N, Hebaishi, H, Hines, S, Hinks, A, Hitman, Ga, Hocking, L, Holmes, C, Howard, E, Howard, P, Howson, Jm, Hughes, D, Hunt, S, Isaacs, Jd, Jain, M, Jewell, Dp, Johnson, T, Jolley, Jd, Jones, Ir, Jones, La, Kirov, G, Langford, Cf, Lango Allen, H, Lathrop, Gm, Lee, J, Lee, Kl, Lees, C, Lewis, K, Lindgren, Cm, Maisuria Armer, M, Maller, J, Mansfield, J, Marchini, Jl, Martin, P, Massey, Dc, Mcardle, Wl, Mcguffin, P, Mclay, Ke, Mcvean, G, Mentzer, A, Mimmack, Ml, Morgan, Ae, Morris, Ap, Mowat, C, Munroe, Pb, Myers, S, Newman, W, Nimmo, Er, O'Donovan, Mc, Onipinla, A, Ovington, Nr, Owen, Mj, Palin, K, Palotie, A, Parnell, K, Pearson, R, Pernet, D, Perry, Jr, Phillips, A, Plagnol, V, Prescott, Nj, Prokopenko, I, Quail, Ma, Rafelt, S, Rayner, Nw, Reid, Dm, Renwick, A, Ring, Sm, Robertson, N, Robson, S, Russell, E, St Clair, D, Sambrook, Jg, Sanderson, Jd, Sawcer, Sj, Schuilenburg, H, Scott, Ce, Seal, S, Shaw Hawkins, S, Shields, Bm, Simmonds, Mj, Smyth, Dj, Somaskantharajah, E, Spanova, K, Steer, S, Stephens, J, Stevens, He, Stirrups, K, Stone, Ma, Strachan, Dp, Su, Z, Symmons, Dp, Thompson, Jr, Thomson, W, Tobin, Md, Travers, Me, Turnbull, C, Vukcevic, D, Wain, Lv, Walker, M, Walker, Nm, Wallace, C, Warren Perry, M, Watkins, Na, Webster, J, Weedon, Mn, Wilson, Ag, Woodburn, M, Wordsworth, Bp, Yau, C, Young, Ah, Zeggini, E, Brown, Ma, Burton, Pr, Caulfield, Mj, Compston, A, Farrall, M, Gough, Sc, Hall, As, Hattersley, At, Hill, Av, Mathew, Cg, Pembrey, M, Satsangi, J, Stratton, Mr, Worthington, J, Hurles, Me, Duncanson, A, Ouwehand, Wh, Parkes, M, Rahman, N, Todd, Ja, Samani, Nj, Kwiatkowski, Dp, Mccarthy, Mi, Craddock, N, Deloukas, P, Donnelly, P, Blackwell, Jm, Bramon, E, Casas, Jp, Corvin, A, Jankowski, J, Markus, Hs, Palmer, Cn, Plomin, R, Rautanen, A, Trembath, Rc, Viswanathan, Ac, Wood, Nw, Spencer, Cc, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Pirinen, M, Strange, A, Blackburn, H, Bumpstead, Sj, Dronov, S, Gillman, M, Jayakumar, A, Mccann, Ot, Liddle, J, Potter, Sc, Ravindrarajah, R, Ricketts, M, Waller, M, Weston, P, Widaa, S, Whittaker, P., AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and Hepatology, and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI) more...
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Genome-wide association study ,Disease ,SUSCEPTIBILITY ,Inflammatory bowel disease ,NUMBER ,0302 clinical medicine ,Crohn Disease ,NETWORK ,Genetics ,0303 health sciences ,Multidisciplinary ,Genomics ,Ulcerative colitis ,3. Good health ,Colitis, Ulcerative ,Genetic Predisposition to Disease ,Genome, Human ,Haplotypes ,Humans ,Inflammatory Bowel Diseases ,Mycobacterium ,Mycobacterium Infections ,Mycobacterium tuberculosis ,Phenotype ,Polymorphism, Single Nucleotide ,Reproducibility of Results ,Genome-Wide Association Study ,Host-Pathogen Interactions ,IRGM ,Medical genetics ,030211 gastroenterology & hepatology ,EXPRESSION ,medicine.medical_specialty ,Immunology ,Biology ,Molecular gastro-enterology and hepatology Pathogenesis and modulation of inflammation [IGMD 2] ,TUBERCULOSIS ,03 medical and health sciences ,Medical research ,medicine ,Allele ,METAANALYSIS ,030304 developmental biology ,HYPER-IGE SYNDROME ,MUTATIONS ,medicine.disease ,RISK LOCI ,Genetic architecture ,digestive system diseases - Abstract
Crohn's disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, with rising prevalence in other populations(1). Genome-wide association studies and subsequent meta-analyses of these two diseases(2,3) as separate phenotypes have implicated previously unsuspected mechanisms, such as autophagy(4), in their pathogenesis and showed that some IBD loci are shared with other inflammatory diseases(5). Here we expand on the knowledge of relevant pathways by undertaking a meta-analysis of Crohn's disease and ulcerative colitis genome-wide association scans, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci, that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional (consistently favouring one allele over the course of human history) and balancing (favouring the retention of both alleles within populations) selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe considerable overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD. more...
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- 2012
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4. Faecal S100A12 Concentrations Correlate with Mucosal Inflammation More Strongly Than Clinical Symptom Scores in Crohn and #8217;s Disease Patients and #8211; Results of the Novel Biomarkers in Inflammatory Bowel Disease (NBIBD) Project
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Hooper Em, Ashcroft Al, Yeo J, Roberts Rl, Hoskin Ts, Gearry Rb, Day As, and Falvey Jf
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Crohn's disease ,medicine.medical_specialty ,education.field_of_study ,medicine.diagnostic_test ,business.industry ,Population ,Colonoscopy ,Inflammation ,Gold standard (test) ,medicine.disease ,Gastroenterology ,Inflammatory bowel disease ,Internal medicine ,Genetics ,medicine ,Biomarker (medicine) ,Animal Science and Zoology ,medicine.symptom ,Calprotectin ,education ,business - Abstract
Background Inflammatory bowel disease (IBD) lead to significant morbidity amongst the New Zealand population. The gold standard for assessing inflammation is colonoscopy but this is invasive and costly. Clinical assessment is subjective and may not reflect mucosal inflammation. The faecal biomarker, S100A12 has been shown to correlate with inflammation in paediatric patients. We aimed to correlate S100A12 concentration and symptom scores with mucosal appearances in IBD patients. Methods Patients with known/possible IBD provided faecal samples prior to colonoscopy. Concentrations of S100A12 and calprotectin were measured using validated ELISA methods. The endoscopic appearances were scored using the Simple Endoscopic Score for CD (SES) and the Rachmilewitz score for UC. Clinical symptom scores were calculated using the Harvey Bradshaw Index (HBI) for CD and the Simple Clinical Colitis Activity Index (SCCAI) for UC. Results 44 CD, 39 UC and 19 controls have currently been assessed. Using mucosal scores 10 CD and 9 UC patients had inactive disease. For CD, the HBI did not significantly correlate with SES (r=0.178, p=0.247). For UC, the SCCAI did correlate with the Rachmilewitz Index (r=0.529, p=0.001). S100A12 concentrations correlated significantly with SES (r=0.56, p=0.001) for CD, and the Rachmilewitz index (r=0.439, p=0.007) for UC. Concentrations of S100A12 were significantly correlated with calprotectin (r=0.798, p more...
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- 2012
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5. A Prospective Evaluation of S100A12 in IBD Patients in the Novel Biomarkers in Inflammatory Bowel Disease (NBIBD) Project
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Roberts Rl, Falvey Jf, Yeo J, Day As, Ashcroft Al, Hoskin Ts, Gearry Rb, and Hooper Em
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medicine.medical_specialty ,business.industry ,Internal medicine ,Genetics ,medicine ,Animal Science and Zoology ,medicine.disease ,business ,Gastroenterology ,Inflammatory bowel disease ,Prospective evaluation - Published
- 2012
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6. Gastrointestinal: Mycobacterium avium paratuberculosis and Crohn's disease
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Gearry, RB, primary, Aitken, JM, additional, Roberts, RL, additional, Ismail, S, additional, Keenan, J, additional, and Barclay, ML, additional
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- 2005
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7. Characterization of the p67phox gene: genomic organization and restriction fragment length polymorphism analysis for prenatal diagnosis in chronic granulomatous disease
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Kenney, RT, primary, Malech, HL, additional, Epstein, ND, additional, Roberts, RL, additional, and Leto, TL, additional
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- 1993
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8. Vitamin D receptor polymorphisms in colorectal cancer in New Zealand: an association study.
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Bentley RW, Keown DA, Gearry RB, Cameron VA, Keenan J, Roberts RL, and Day AS
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- 2012
9. HALF-DAY MEETING. MANAGEMENT GROUP. PORTS IN DEVELOPING COUNTRIES.
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LETHBRIDGE, JR, VEAL, DG, ROBERTS, RL, and GIFFORD, EWH
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- 1989
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10. N-acetylcysteine enhances antibody-dependent cellular cytotoxicity in neutrophils and mononuclear cells from healthy adults and human immunodeficiency virus-infected patients.
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Roberts RL, Aroda VR, Ank BJ, Roberts, R L, Aroda, V R, and Ank, B J
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Patients with AIDS have decreased levels of the intracellular antioxidant, glutathione, in their circulating lymphocytes and plasma. N-acetylcysteine (NAC) increases intracellular stores of glutathione and has direct antioxidant properties. In this study, the effects of glutathione and NAC on the cytotoxicity of neutrophils and mononuclear cells were tested using cells from healthy controls and human immunodeficiency virus (HIV)-infected patients. NAC (1 and 5 mM) enhanced the antibody-dependent cellular cytotoxicity (ADCC) of neutrophils from healthy adult controls and HIV-infected adults and children. The antineoplastic drug, 1,3 bis(2-chloroethyl)-1-nitrosourea (BCNU), which depletes intracellular glutathione, inhibited the ADCC of neutrophils; the addition of NAC partially reversed this inhibition. Similar effects of BCNU and NAC were seen when the cytotoxicity of mononuclear cells was tested using CEM tumor cells bearing the HIV gp120 antigen as targets. Thus, NAC enhances various forms of cytotoxicity and may be beneficial to AIDS patients whose defects in leukocyte cytotoxicity may be due to glutathione depletion. [ABSTRACT FROM AUTHOR] more...
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- 1995
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11. Phosphorylation of the oxidase-related 48K phosphoprotein family in the unusual autosomal cytochrome-negative and X-linked cytochrome-positive types of chronic granulomatous disease
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Okamura, N, Malawista, SE, Roberts, RL, Rosen, H, Ochs, HD, Babior, BM, and Curnutte, JT
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Activation of 32P-loaded neutrophils with phorbol myristate acetate causes the labeling of a family of three 48K proteins that focus near neutral pH. The relationship between these phosphoproteins and the activation of the respiratory burst has been supported by the previous finding that phosphorylation was defective in the two most common types of chronic granulomatous disease (CGD): X-linked cytochrome-negative (X/-) and autosomal cytochrome-positive (A/+). In this report, these studies have now been extended to the rare A/- and X/+ forms of the disease. In all three patients with A/- CGD examined, the two most acidic 48K proteins failed to undergo enhanced phosphorylation in response to phorbol stimulation, a finding similar to that seen in X/- patients. In contrast, neutrophils from two patients with X/+ CGD appeared to phosphorylate the neutral 48K proteins in a normal fashion. It thus appears that the different phosphorylation patterns seen in chronic granulomatous disease are a reflection of the genetic heterogeneity of this disorder. These findings lend further support to the conclusion that the 48K phosphoprotein family is related to the respiratory burst, although not necessarily in a straightforward manner. more...
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- 1988
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12. Rapid method for isolation of normal human peripheral blood eosinophils on discontinuous Percoll gradients and comparison with neutrophils
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Roberts, RL and Gallin, JI
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Previous studies on human eosinophils often have used cells from patients with hypereosinophilia syndrome or parasitosis owing to the difficulty in isolating pure populations of eosinophils from normal individuals. In the present study, human eosinophils were isolated with a purity of 97%, with 70% recovery from normal individuals with blood eosinophil counts of less than 3%. Human eosinophils are denser than neutrophils, but the range of densities of the two cell types overlap, making purification of eosinophils by density-gradient centrifugation difficult. However, if neutrophils were exposed to the chemotactic peptide (f-Met-Leu-Phe), which did not stimulate eosinophils, the neutrophils' density decreased, shifting them away from the density of eosinophils. Whole normal blood anticoagulated with EDTA was incubated at 37 degrees C for 15 minutes with 10(-6) mol/L f-Met-Leu-Phe and then layered over a discontinuous Percoll gradient (65% and 75% in diluted phosphate-buffered saline) and centrifuged at 400 g for 25 minutes at 22 degrees C. The cell layer between the 65% and 75% Percoll was collected and washed, and hypotonic lysis was used to remove erythrocytes. This cell layer contained 97.3 +/- 0.7% eosinophils (N = 8) with a yield of 4.9 X 10(4) eosinophils per milliliter of whole blood, or 70% of the total eosinophil count. The isolated eosinophils were in a quiescent state but responded to Escherichia coli endotoxin- activated serum with shape change and chemotaxis, membrane depolarization, and reduced nitroblue tetrazolium (96.0 +/- 1.0%), when stimulated with phorbol myristate acetate. In phagocytic assays, 89.3 +/- 1.3% of the eosinophils ingested Candida albicans v 96.0% +/- 1.0% of neutrophils. In contrast, the eosinophils did not respond chemotactically, alter membrane potential, or reduce nitroblue tetrazolium when treated with f-Met-Leu-Phe, and studies with f-Met-Leu- [3H]Phe showed that normal eosinophils lacked expression of receptors for f-Met-Leu-Phe. In control studies, normal eosinophils that were not exposed to f-Met-Leu-Phe during purification also failed to respond to f-Met-Leu-Phe, indicating intrinsic differences between normal eosinophils and neutrophils. Thus, exposure of whole blood to f-Met-Leu- Phe, followed by separation on Percoll is a simple method for rapid isolation of normal human eosinophils. more...
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- 1985
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13. Granulocyte- and granulocyte-macrophage colony-stimulating factors enhance neutrophil cytotoxicity toward HIV-infected cells
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Baldwin, GC, Fuller, ND, Roberts, RL, Ho, DD, and Golde, DW
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Although the control of retroviral disease in animal systems often involves antibody-dependent cell-mediated cytotoxicity (ADCC), the role of cytotoxic function in human retroviral disorders is uncertain. The ability of the neutrophil to kill HIV-infected targets directed by antiviral antibody was examined. Neutrophils from patients with AIDS killed HIV-infected MOLT-3A cells in a manner equivalent to neutrophils obtained from normal volunteers. Both granulocyte- and granulocyte- macrophage colony-stimulating factors (G-CSF and GM-CSF) markedly augmented the cytotoxic function. Studies done with fractionated human antisera revealed that ADCC to HIV-infected cells was mediated only by antibody to the env glycoprotein. ADCC in this system was not dependent on oxidative metabolism because neutrophils from patients with chronic granulomatous disease (CGD) were capable of CSF-augmented cytotoxicity. Although ADCC can be mediated by various classes of lymphocytes and mononuclear phagocytes, such cells may be infected by HIV. Because the neutrophil apparently is not productively infected by the virus, it is an ideal cell to focus on with regard to cytotoxic function in AIDS patients. The findings regarding neutrophil ADCC in AIDS are clinically relevant because the availability of CSFs now permits therapeutic regulation of neutrophils in AIDS patients, and presumably natural antibody may be useful in targeting HIV-infected cells for neutrophil cytotoxicity in vivo. more...
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- 1989
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14. Genotype markers predict time to first resection in Crohn's disease patients
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Simms, La, James Doecke, Huang, N., Zhao, Zz, Kristine, Fu, Roberts, Rl, Barclay, Ml, Montgomery, Gw, Lawrance, Ic, Gearry, Rb, and Radford-Smith, Gl
15. HALF-DAY MEETING. MANAGEMENT GROUP. PORTS IN DEVELOPING COUNTRIES.
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LETHBRIDGE, JR, primary, VEAL, DG, additional, ROBERTS, RL, additional, and GIFFORD, EWH, additional
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- 1989
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16. Lack of association between HLA-G 14 bp insertion/deletion polymorphism and response to long-term therapy with methotrexate response in rheumatoid arthritis.
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Stamp LK, O'Donnell JL, Chapman PT, Barclay ML, Kennedy MA, Frampton CM, and Roberts RL
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- 2009
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17. Comment: Breast-feeding during maternal use of azathioprine.
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Gardiner SJ, Gearry RB, Roberts RL, Zhang M, Barclay ML, Begg EJ, Gardiner, Sharon J, Gearry, Richard B, Roberts, Rebecca L, Zhang, Mei, Barclay, Murray L, and Begg, Evan J
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- 2007
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18. Endosome Fusion and Tubule Formation in Cells Overexpressing GFP-Rab5 Fusion Proteins
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Roberts, RL, Barbieri, MA, and Stahl, PD
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Previous studies have demonstrated that GTPgS and rab5:Q79L, a constitutively active rab5 mutant, stimulate endosome fusion in in vitroassays [Cell Reg. 1:113-124 (1989)]. Additionally, electron microscopy has shown that under these conditions, endosomes form incompletely fused couplets [Cell Reg. 1:113-124 (1989); Arch. Biochem. Biophys. 326:64-72 (1996)]. CHO and BHK cells that overexpress rab5:Q79L develop ‘giant’ cytoplasmic vesicles that exhibit many characteristics of early endosomes including immunoreactivity for rab 5 and transferrin receptor (data not shown). The formation of these vesicles has been analyzed by time-lapse video microscopy which shows the enlarged endosomes arise primarily by fusion of smaller vesicles. These endosome fusion events occur by two distinct mechanisms that differ in temporal and spatial characteristics of the membrane merger process and we refer to these processes as “explosive” versus “bridge” fusion. “Explosive” fusion is a rapid process in which the initial opening that forms between contacting vesicles expands rapidly and permits an abrupt, complete coalescence of membranes (Fig. 1). more...
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- 1997
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19. Comparative performances of machine learning methods for classifying Crohn Disease patients using genome-wide genotyping data
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Romagnoni, A., Jegou, S., Van Steen, K., Wainrib, G., Hugot, J. -P., Peyrin-Biroulet, L., Chamaillard, M., Colombel, J. -F., Cottone, M., D'Amato, M., D'Inca, R., Halfvarson, J., Henderson, P., Karban, A., Kennedy, N. A., Khan, M. A., Lemann, M., Levine, A., Massey, D., Milla, M., S. M. E., Ng, Oikonomou, I., Peeters, H., Proctor, D. D., Rahier, J. -F., Rutgeerts, P., Seibold, F., Stronati, L., Taylor, K. M., Torkvist, L., Ublick, K., Van Limbergen, J., Van Gossum, A., Vatn, M. H., Zhang, H., Zhang, W., Andrews, J. M., Bampton, P. A., Barclay, M., Florin, T. H., Gearry, R., Krishnaprasad, K., Lawrance, I. C., Mahy, G., Montgomery, G. W., Radford-Smith, G., Roberts, R. L., Simms, L. A., Hanigan, K., Croft, A., Amininijad, L., Cleynen, I., Dewit, O., Franchimont, D., Georges, M., Laukens, D., Theatre, E., Vermeire, S., Aumais, G., Baidoo, L., Barrie, A. M., Beck, K., Bernard, E. -J., Binion, D. G., Bitton, A., Brant, S. R., Cho, J. H., Cohen, A., Croitoru, K., Daly, M. J., Datta, L. W., Deslandres, C., Duerr, R. H., Dutridge, D., Ferguson, J., Fultz, J., Goyette, P., Greenberg, G. R., Haritunians, T., Jobin, G., Katz, S., Lahaie, R. G., Mcgovern, D. P., Nelson, L., S. M., Ng, Ning, K., Pare, P., Regueiro, M. D., Rioux, J. D., Ruggiero, E., Schumm, L. P., Schwartz, M., Scott, R., Sharma, Y., Silverberg, M. S., Spears, D., Steinhart, A. H., Stempak, J. M., Swoger, J. M., Tsagarelis, C., Zhang, C., Zhao, H., Aerts, J., Ahmad, T., Arbury, H., Attwood, A., Auton, A., Ball, S. G., Balmforth, A. J., Barnes, C., Barrett, J. C., Barroso, I., Barton, A., Bennett, A. J., Bhaskar, S., Blaszczyk, K., Bowes, J., Brand, O. J., Braund, P. S., Bredin, F., Breen, G., Brown, M. J., Bruce, I. N., Bull, J., Burren, O. S., Burton, J., Byrnes, J., Caesar, S., Cardin, N., Clee, C. M., Coffey, A. J., MC Connell, J., Conrad, D. F., Cooper, J. D., Dominiczak, A. F., Downes, K., Drummond, H. E., Dudakia, D., Dunham, A., Ebbs, B., Eccles, D., Edkins, S., Edwards, C., Elliot, A., Emery, P., Evans, D. M., Evans, G., Eyre, S., Farmer, A., Ferrier, I. N., Flynn, E., Forbes, A., Forty, L., Franklyn, J. A., Frayling, T. M., Freathy, R. M., Giannoulatou, E., Gibbs, P., Gilbert, P., Gordon-Smith, K., Gray, E., Green, E., Groves, C. J., Grozeva, D., Gwilliam, R., Hall, A., Hammond, N., Hardy, M., Harrison, P., Hassanali, N., Hebaishi, H., Hines, S., Hinks, A., Hitman, G. A., Hocking, L., Holmes, C., Howard, E., Howard, P., Howson, J. M. M., Hughes, D., Hunt, S., Isaacs, J. D., Jain, M., Jewell, D. P., Johnson, T., Jolley, J. D., Jones, I. R., Jones, L. A., Kirov, G., Langford, C. F., Lango-Allen, H., Lathrop, G. M., Lee, J., Lee, K. L., Lees, C., Lewis, K., Lindgren, C. M., Maisuria-Armer, M., Maller, J., Mansfield, J., Marchini, J. L., Martin, P., Massey, D. C., Mcardle, W. L., Mcguffin, P., Mclay, K. E., Mcvean, G., Mentzer, A., Mimmack, M. L., Morgan, A. E., Morris, A. P., Mowat, C., Munroe, P. B., Myers, S., Newman, W., Nimmo, E. R., O'Donovan, M. C., Onipinla, A., Ovington, N. R., Owen, M. J., Palin, K., Palotie, A., Parnell, K., Pearson, R., Pernet, D., Perry, J. R., Phillips, A., Plagnol, V., Prescott, N. J., Prokopenko, I., Quail, M. A., Rafelt, S., Rayner, N. W., Reid, D. M., Renwick, A., Ring, S. M., Robertson, N., Robson, S., Russell, E., Clair, D. S., Sambrook, J. G., Sanderson, J. D., Sawcer, S. J., Schuilenburg, H., Scott, C. E., Seal, S., Shaw-Hawkins, S., Shields, B. M., Simmonds, M. J., Smyth, D. J., Somaskantharajah, E., Spanova, K., Steer, S., Stephens, J., Stevens, H. E., Stirrups, K., Stone, M. A., Strachan, D. P., Su, Z., Symmons, D. P. M., Thompson, J. R., Thomson, W., Tobin, M. D., Travers, M. E., Turnbull, C., Vukcevic, D., Wain, L. V., Walker, M., Walker, N. M., Wallace, C., Warren-Perry, M., Watkins, N. A., Webster, J., Weedon, M. N., Wilson, A. G., Woodburn, M., Wordsworth, B. P., Yau, C., Young, A. H., Zeggini, E., Brown, M. A., Burton, P. R., Caulfield, M. J., Compston, A., Farrall, M., Gough, S. C. L., Hall, A. S., Hattersley, A. T., Hill, A. V. S., Mathew, C. G., Pembrey, M., Satsangi, J., Stratton, M. R., Worthington, J., Hurles, M. E., Duncanson, A., Ouwehand, W. H., Parkes, M., Rahman, N., Todd, J. A., Samani, N. J., Kwiatkowski, D. P., Mccarthy, M. I., Craddock, N., Deloukas, P., Donnelly, P., Blackwell, J. M., Bramon, E., Casas, J. P., Corvin, A., Jankowski, J., Markus, H. S., Palmer, C. N., Plomin, R., Rautanen, A., Trembath, R. C., Viswanathan, A. C., Wood, N. W., Spencer, C. C. A., Band, G., Bellenguez, C., Freeman, C., Hellenthal, G., Pirinen, M., Strange, A., Blackburn, H., Bumpstead, S. J., Dronov, S., Gillman, M., Jayakumar, A., Mccann, O. T., Liddle, J., Potter, S. C., Ravindrarajah, R., Ricketts, M., Waller, M., Weston, P., Widaa, S., Whittaker, P., Romagnoni, A., Jegou, S., Van Steen, K., Wainrib, G., Hugot, J. -P., Peyrin-Biroulet, L., Chamaillard, M., Colombel, J. -F., Cottone, M., D'Amato, M., D'Inca, R., Halfvarson, J., Henderson, P., Karban, A., Kennedy, N. A., Khan, M. A., Lemann, M., Levine, A., Massey, D., Milla, M., Ng, S. M. E., Oikonomou, I., Peeters, H., Proctor, D. D., Rahier, J. -F., Rutgeerts, P., Seibold, F., Stronati, L., Taylor, K. M., Torkvist, L., Ublick, K., Van Limbergen, J., Van Gossum, A., Vatn, M. H., Zhang, H., Zhang, W., Andrews, J. M., Bampton, P. A., Barclay, M., Florin, T. H., Gearry, R., Krishnaprasad, K., Lawrance, I. C., Mahy, G., Montgomery, G. W., Radford-Smith, G., Roberts, R. L., Simms, L. A., Hanigan, K., Croft, A., Amininijad, L., Cleynen, I., Dewit, O., Franchimont, D., Georges, M., Laukens, D., Theatre, E., Vermeire, S., Aumais, G., Baidoo, L., Barrie, A. M., Beck, K., Bernard, E. -J., Binion, D. G., Bitton, A., Brant, S. R., Cho, J. H., Cohen, A., Croitoru, K., Daly, M. J., Datta, L. W., Deslandres, C., Duerr, R. H., Dutridge, D., Ferguson, J., Fultz, J., Goyette, P., Greenberg, G. R., Haritunians, T., Jobin, G., Katz, S., Lahaie, R. G., Mcgovern, D. P., Nelson, L., Ng, S. M., Ning, K., Pare, P., Regueiro, M. D., Rioux, J. D., Ruggiero, E., Schumm, L. P., Schwartz, M., Scott, R., Sharma, Y., Silverberg, M. S., Spears, D., Steinhart, A. H., Stempak, J. M., Swoger, J. M., Tsagarelis, C., Zhang, C., Zhao, H., Aerts, J., Ahmad, T., Arbury, H., Attwood, A., Auton, A., Ball, S. G., Balmforth, A. J., Barnes, C., Barrett, J. C., Barroso, I., Barton, A., Bennett, A. J., Bhaskar, S., Blaszczyk, K., Bowes, J., Brand, O. J., Braund, P. S., Bredin, F., Breen, G., Brown, M. J., Bruce, I. N., Bull, J., Burren, O. S., Burton, J., Byrnes, J., Caesar, S., Cardin, N., Clee, C. M., Coffey, A. J., MC Connell, J., Conrad, D. F., Cooper, J. D., Dominiczak, A. F., Downes, K., Drummond, H. E., Dudakia, D., Dunham, A., Ebbs, B., Eccles, D., Edkins, S., Edwards, C., Elliot, A., Emery, P., Evans, D. M., Evans, G., Eyre, S., Farmer, A., Ferrier, I. N., Flynn, E., Forbes, A., Forty, L., Franklyn, J. A., Frayling, T. M., Freathy, R. M., Giannoulatou, E., Gibbs, P., Gilbert, P., Gordon-Smith, K., Gray, E., Green, E., Groves, C. J., Grozeva, D., Gwilliam, R., Hall, A., Hammond, N., Hardy, M., Harrison, P., Hassanali, N., Hebaishi, H., Hines, S., Hinks, A., Hitman, G. A., Hocking, L., Holmes, C., Howard, E., Howard, P., Howson, J. M. M., Hughes, D., Hunt, S., Isaacs, J. D., Jain, M., Jewell, D. P., Johnson, T., Jolley, J. D., Jones, I. R., Jones, L. A., Kirov, G., Langford, C. F., Lango-Allen, H., Lathrop, G. M., Lee, J., Lee, K. L., Lees, C., Lewis, K., Lindgren, C. M., Maisuria-Armer, M., Maller, J., Mansfield, J., Marchini, J. L., Martin, P., Massey, D. C., Mcardle, W. L., Mcguffin, P., Mclay, K. E., Mcvean, G., Mentzer, A., Mimmack, M. L., Morgan, A. E., Morris, A. P., Mowat, C., Munroe, P. B., Myers, S., Newman, W., Nimmo, E. R., O'Donovan, M. C., Onipinla, A., Ovington, N. R., Owen, M. J., Palin, K., Palotie, A., Parnell, K., Pearson, R., Pernet, D., Perry, J. R., Phillips, A., Plagnol, V., Prescott, N. J., Prokopenko, I., Quail, M. A., Rafelt, S., Rayner, N. W., Reid, D. M., Renwick, A., Ring, S. M., Robertson, N., Robson, S., Russell, E., Clair, D. S., Sambrook, J. G., Sanderson, J. D., Sawcer, S. J., Schuilenburg, H., Scott, C. E., Seal, S., Shaw-Hawkins, S., Shields, B. M., Simmonds, M. J., Smyth, D. J., Somaskantharajah, E., Spanova, K., Steer, S., Stephens, J., Stevens, H. E., Stirrups, K., Stone, M. A., Strachan, D. P., Su, Z., Symmons, D. P. M., Thompson, J. R., Thomson, W., Tobin, M. D., Travers, M. E., Turnbull, C., Vukcevic, D., Wain, L. V., Walker, M., Walker, N. M., Wallace, C., Warren-Perry, M., Watkins, N. A., Webster, J., Weedon, M. N., Wilson, A. G., Woodburn, M., Wordsworth, B. P., Yau, C., Young, A. H., Zeggini, E., Brown, M. A., Burton, P. R., Caulfield, M. J., Compston, A., Farrall, M., Gough, S. C. L., Hall, A. S., Hattersley, A. T., Hill, A. V. S., Mathew, C. G., Pembrey, M., Satsangi, J., Stratton, M. R., Worthington, J., Hurles, M. E., Duncanson, A., Ouwehand, W. H., Parkes, M., Rahman, N., Todd, J. A., Samani, N. J., Kwiatkowski, D. P., Mccarthy, M. I., Craddock, N., Deloukas, P., Donnelly, P., Blackwell, J. M., Bramon, E., Casas, J. P., Corvin, A., Jankowski, J., Markus, H. S., Palmer, C. N., Plomin, R., Rautanen, A., Trembath, R. C., Viswanathan, A. C., Wood, N. W., Spencer, C. C. A., Band, G., Bellenguez, C., Freeman, C., Hellenthal, G., Pirinen, M., Strange, A., Blackburn, H., Bumpstead, S. J., Dronov, S., Gillman, M., Jayakumar, A., Mccann, O. T., Liddle, J., Potter, S. C., Ravindrarajah, R., Ricketts, M., Waller, M., Weston, P., Widaa, S., Whittaker, P., Daly, Mark J. [0000-0002-0949-8752], Apollo - University of Cambridge Repository, Hugot, Jean-Pierre [0000-0002-8446-6056], UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - (MGD) Service de gastro-entérologie, Romagnoni, A, Jegou, S, VAN STEEN, Kristel, Wainrib, G, Hugot, JP, Peyrin-Biroulet, L, Chamaillard, M, Colombel, JF, Cottone, M, D'Amato, M, D'Inca, R, Halfvarson, J, Henderson, P, Karban, A, Kennedy, NA, Khan, MA, Lemann, M, Levine, A, Massey, D, Milla, M, Ng, SME, Oikonomou, I, Peeters, H, Proctor, DD, Rahier, JF, Rutgeerts, P, Seibold, F, Stronati, L, Taylor, KM, Torkvist, L, Ublick, K, Van Limbergen, J, Van Gossum, A, Vatn, MH, Zhang, H, Zhang, W, Andrews, JM, Bampton, PA, Barclay, M, Florin, TH, Gearry, R, Krishnaprasad, K, Lawrance, IC, Mahy, G, Montgomery, GW, Radford-Smith, G, Roberts, RL, Simms, LA, Hanigan, K, Croft, A, Amininijad, L, Cleynen, I, Dewit, O, Franchimont, D, Georges, M, Laukens, D, Theatre, E, Vermeire, S, Aumais, G, Baidoo, L, Barrie, AM, Beck, K, Bernard, EJ, Binion, DG, Bitton, A, Brant, SR, Cho, JH, Cohen, A, Croitoru, K, Daly, MJ, Datta, LW, Deslandres, C, Duerr, RH, Dutridge, D, Ferguson, J, Fultz, J, Goyette, P, Greenberg, GR, Haritunians, T, Jobin, G, Katz, S, Lahaie, RG, McGovern, DP, Nelson, L, Ng, SM, Ning, K, Pare, P, Regueiro, MD, Rioux, JD, Ruggiero, E, Schumm, LP, Schwartz, M, Scott, R, Sharma, Y, Silverberg, MS, Spears, D, Steinhart, AH, Stempak, JM, Swoger, JM, Tsagarelis, C, Zhang, C, Zhao, HY, AERTS, Jan, Ahmad, T, Arbury, H, Attwood, A, Auton, A, Ball, SG, Balmforth, AJ, Barnes, C, Barrett, JC, Barroso, I, Barton, A, Bennett, AJ, Bhaskar, S, Blaszczyk, K, Bowes, J, Brand, OJ, Braund, PS, Bredin, F, Breen, G, Brown, MJ, Bruce, IN, Bull, J, Burren, OS, Burton, J, Byrnes, J, Caesar, S, Cardin, N, Clee, CM, Coffey, AJ, Mc Connell, J, Conrad, DF, Cooper, JD, Dominiczak, AF, Downes, K, Drummond, HE, Dudakia, D, Dunham, A, Ebbs, B, Eccles, D, Edkins, S, Edwards, C, Elliot, A, Emery, P, Evans, DM, Evans, G, Eyre, S, Farmer, A, Ferrier, IN, Flynn, E, Forbes, A, Forty, L, Franklyn, JA, Frayling, TM, Freathy, RM, Giannoulatou, E, Gibbs, P, Gilbert, P, Gordon-Smith, K, Gray, E, Green, E, Groves, CJ, Grozeva, D, Gwilliam, R, Hall, A, Hammond, N, Hardy, M, Harrison, P, Hassanali, N, Hebaishi, H, Hines, S, Hinks, A, Hitman, GA, Hocking, L, Holmes, C, Howard, E, Howard, P, Howson, JMM, Hughes, D, Hunt, S, Isaacs, JD, Jain, M, Jewell, DP, Johnson, T, Jolley, JD, Jones, IR, Jones, LA, Kirov, G, Langford, CF, Lango-Allen, H, Lathrop, GM, Lee, J, Lee, KL, Lees, C, Lewis, K, Lindgren, CM, Maisuria-Armer, M, Maller, J, Mansfield, J, Marchini, JL, Martin, P, Massey, DCO, McArdle, WL, McGuffin, P, McLay, KE, McVean, G, Mentzer, A, Mimmack, ML, Morgan, AE, Morris, AP, Mowat, C, Munroe, PB, Myers, S, Newman, W, Nimmo, ER, O'Donovan, MC, Onipinla, A, Ovington, NR, Owen, MJ, Palin, K, Palotie, A, Parnell, K, Pearson, R, Pernet, D, Perry, JRB, Phillips, A, Plagnol, V, Prescott, NJ, Prokopenko, I, Quail, MA, Rafelt, S, Rayner, NW, Reid, DM, Renwick, A, Ring, SM, Robertson, N, Robson, S, Russell, E, St Clair, D, Sambrook, JG, Sanderson, JD, Sawcer, SJ, Schuilenburg, H, Scott, CE, Seal, S, Shaw-Hawkins, S, Shields, BM, Simmonds, MJ, Smyth, DJ, Somaskantharajah, E, Spanova, K, Steer, S, Stephens, J, Stevens, HE, Stirrups, K, Stone, MA, Strachan, DP, Su, Z, Symmons, DPM, Thompson, JR, Thomson, W, Tobin, MD, Travers, ME, Turnbull, C, Vukcevic, D, Wain, LV, Walker, M, Walker, NM, Wallace, C, Warren-Perry, M, Watkins, NA, Webster, J, Weedon, MN, Wilson, AG, Woodburn, M, Wordsworth, BP, Yau, C, Young, AH, Zeggini, E, Brown, MA, Burton, PR, Caulfield, MJ, Compston, A, Farrall, M, Gough, SCL, Hall, AS, Hattersley, AT, Hill, AVS, Mathew, CG, Pembrey, M, Satsangi, J, Stratton, MR, Worthington, J, Hurles, ME, Duncanson, A, Ouwehand, WH, Parkes, M, Rahman, N, Todd, JA, Samani, NJ, Kwiatkowski, DP, McCarthy, MI, Craddock, N, Deloukas, P, Donnelly, P, Blackwell, JM, Bramon, E, Casas, JP, Corvin, A, Jankowski, J, Markus, HS, Palmer, CNA, Plomin, R, Rautanen, A, Trembath, RC, Viswanathan, AC, Wood, NW, Spencer, CCA, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Pirinen, M, Strange, A, Blackburn, H, Bumpstead, SJ, Dronov, S, Gillman, M, Jayakumar, A, McCann, OT, Liddle, J, Potter, SC, Ravindrarajah, R, Ricketts, M, Waller, M, Weston, P, Widaa, S, Whittaker, P, and Kwiatkowski, D more...
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Male ,692/4020/1503/257/1402 ,Genotype ,Genotyping Techniques ,LOCI ,45/43 ,lcsh:Medicine ,Polymorphism, Single Nucleotide ,Crohn's disease, genetics, genome wide association ,Article ,Deep Learning ,Crohn Disease ,INDEL Mutation ,Genetics research ,Humans ,genetics ,Genetic Predisposition to Disease ,129 ,lcsh:Science ,Alleles ,Science & Technology ,genome wide association ,RISK PREDICTION ,45 ,Models, Genetic ,lcsh:R ,Decision Trees ,692/308/2056 ,ASSOCIATION ,Multidisciplinary Sciences ,Crohn's disease ,Logistic Models ,Nonlinear Dynamics ,ROC Curve ,Area Under Curve ,Science & Technology - Other Topics ,lcsh:Q ,Female ,Neural Networks, Computer ,INFLAMMATORY-BOWEL-DISEASE ,Genome-Wide Association Study - Abstract
Crohn Disease (CD) is a complex genetic disorder for which more than 140 genes have been identified using genome wide association studies (GWAS). However, the genetic architecture of the trait remains largely unknown. The recent development of machine learning (ML) approaches incited us to apply them to classify healthy and diseased people according to their genomic information. The Immunochip dataset containing 18,227 CD patients and 34,050 healthy controls enrolled and genotyped by the international Inflammatory Bowel Disease genetic consortium (IIBDGC) has been re-analyzed using a set of ML methods: penalized logistic regression (LR), gradient boosted trees (GBT) and artificial neural networks (NN). The main score used to compare the methods was the Area Under the ROC Curve (AUC) statistics. The impact of quality control (QC), imputing and coding methods on LR results showed that QC methods and imputation of missing genotypes may artificially increase the scores. At the opposite, neither the patient/control ratio nor marker preselection or coding strategies significantly affected the results. LR methods, including Lasso, Ridge and ElasticNet provided similar results with a maximum AUC of 0.80. GBT methods like XGBoost, LightGBM and CatBoost, together with dense NN with one or more hidden layers, provided similar AUC values, suggesting limited epistatic effects in the genetic architecture of the trait. ML methods detected near all the genetic variants previously identified by GWAS among the best predictors plus additional predictors with lower effects. The robustness and complementarity of the different methods are also studied. Compared to LR, non-linear models such as GBT or NN may provide robust complementary approaches to identify and classify genetic markers. Tis work was supported by Fondation pour la Recherche Médical (ref DEI20151234405) and Investissements d’Avenir programme ANR-11-IDEX-0005-02, Sorbonne Paris Cite, Laboratoire d’excellence INFLAMEX. Te authors thank the students that participated to the wisdom of the crowd exercise. more...
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- 2019
20. Osteocyte Sptbn1 Deficiency Alters Cell Survival and Mechanotransduction Following Formation of Plasma Membrane Disruptions (PMD) from Mechanical Loading.
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Hagan ML, Tuladhar A, Yu K, Alhamad DW, Bensreti H, Dorn J, Piedra VM, Cantu N, Stokes EG, Blumenthal D, Roberts RL, Balayan V, Bass SM, Dickerson T, Cartelle AL, Montesinos-Cartagena M, Awad ME, Castro AA, Garland T Jr, Cooley MA, Johnson M, Hamrick MW, McNeil PL, and McGee-Lawrence ME more...
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- Animals, Mice, Cell Membrane metabolism, Cell Survival physiology, Mice, Knockout, Osteocytes metabolism, Stress, Mechanical, Mechanotransduction, Cellular physiology, Spectrin metabolism, Spectrin deficiency
- Abstract
We and others have shown that application of high-level mechanical loading promotes the formation of transient plasma membrane disruptions (PMD) which initiate mechanotransduction. We hypothesized that increasing osteocyte cell membrane fragility, by disrupting the cytoskeleton-associated protein β2-spectrin (Sptbn1), could alter osteocytic responses and bone adaptation to loading in a PMD-related fashion. In MLO-Y4 cells, treatment with the spectrin-disrupting agent diamide or knockdown of Sptbn1 via siRNA increased the number of PMD formed by fluid shear stress. Primary osteocytes from an osteocyte-targeted DMP1-Cre Sptbn1 conditional knockout (CKO) model mimicked trends seen with diamide and siRNA treatment and suggested the creation of larger PMD, which repaired more slowly, for a given level of stimulus. Post-wounding cell survival was impaired in all three models, and calcium signaling responses from the wounded osteocyte were mildly altered in Sptbn1 CKO cultures. Although Sptbn1 CKO mice did not demonstrate an altered skeletal phenotype as compared to WT littermates under baseline conditions, they showed a blunted increase in cortical thickness when subjected to an osteogenic tibial loading protocol as well as evidence of increased osteocyte death (increased lacunar vacancy) in the loaded limb after 2 weeks of loading. The impaired post-wounding cell viability and impaired bone adaptation seen with Sptbn1 disruption support the existence of an important role for Sptbn1, and PMD formation, in osteocyte mechanotransduction and bone adaptation to mechanical loading., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.) more...
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- 2024
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21. Enablers and Barriers for End-of-Life Symptom Management Medications in Long-Term Care Homes: A Qualitative Study.
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Roberts RL, Milani C, Webber C, Bush SH, Boese K, Simon JE, Downar J, Arya A, Tanuseputro P, and Isenberg SR
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- Humans, Ontario, Male, Female, Middle Aged, Interviews as Topic, Caregivers psychology, Aged, Adult, Qualitative Research, Terminal Care, Long-Term Care, Nursing Homes
- Abstract
Objectives: Long-term care (LTC) homes provide personal and medical care 24/7 to individuals unable to live at home due to illness or disability and are often the final place of care and death for their residents. Therefore, LTC homes are tasked with providing quality end-of-life care, often requiring injectable symptom management medications to relieve distressing symptoms (eg, pain). In this study, we aimed to understand the enablers and barriers to prescribing and administering end-of-life symptom management medications in LTC homes., Design: Qualitative study., Setting and Participants: From February 2021 to December 2022, we conducted virtual semi-structured interviews with health care providers (physicians and nurses) who worked in Ontario LTC homes and family caregivers of residents who died in LTC., Methods: We analyzed interview transcripts using thematic analysis., Results: We identified 4 themes related to factors that may impact the prescribing and administering of medications for end-of-life symptom management: (1) identifying the end-of-life period and symptoms, (2) communication among health care providers and between health care providers and family caregivers, (3) health care provider competency with end-of-life medications, and (4) resources for LTC staff to support medication prescribing and administrating., Conclusions and Implications: In LTC, there are distinct challenges in the prescribing and administrating of end-of-life symptom management medications. Our findings can be used to inform interventions aimed at improving end-of-life care for LTC residents. However, these interventions require buy-in and investment from the provincial government and the LTC sector., Competing Interests: Disclosures The authors declare no conflicts of interest., (Copyright © 2024 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.) more...
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- 2024
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22. Corrigendum: Measuring the Use of End-of-Life Symptom Relief Medications in Long-Term Care Homes-a Qualitative Study.
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Roberts RL, Milani C, Webber C, Bush SH, Boese K, Simon JE, Downar J, Arya A, Tanuseputro P, and Isenberg SR
- Abstract
[This corrects the article DOI: 10.5770/cgj.27.712.]., (© 2024 Author(s).)
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- 2024
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23. Changes in End-of-Life Symptom Management Prescribing among Long-Term Care Residents during COVID-19.
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Fremont D, Roberts RL, Webber C, Clarke AE, Milani C, Isenberg SR, Bush SH, Kobewka D, Turcotte L, Howard M, Boese K, Arya A, Robert B, Sinnarajah A, Simon JE, Lau J, Qureshi D, Downar J, and Tanuseputro P more...
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- Humans, Ontario epidemiology, Female, Male, Retrospective Studies, Aged, Aged, 80 and over, Pandemics, Practice Patterns, Physicians' statistics & numerical data, COVID-19 epidemiology, Terminal Care, Long-Term Care, Nursing Homes, SARS-CoV-2
- Abstract
Objective: To examine changes in the prescribing of end-of-life symptom management medications in long-term care (LTC) homes during the COVID-19 pandemic., Design: Retrospective cohort study using routinely collected health administrative data in Ontario, Canada., Setting and Participants: We included all individuals who died in LTC homes between January 1, 2017, and March 31, 2021. We separated the study into 2 periods: before COVID-19 (January 1, 2017, to March 17, 2020) and during COVID-19 (March 18, 2020, to March 31, 2021)., Methods: For each LTC home, we measured the percentage of residents who died before and during COVID-19 who had a subcutaneous symptom management medication prescription in their last 14 days of life. We grouped LTC homes into quintiles based on their mean prescribing rates before COVID-19, and examined changes in prescribing during COVID-19 and COVID-19 outcomes across quintiles., Results: We captured 75,438 LTC residents who died in Ontario's 626 LTC homes during the entire study period, with 19,522 (25.9%) dying during COVID-19. The mean prescribing rate during COVID-19 ranged from 46.9% to 79.4% between the lowest and highest prescribing quintiles. During COVID-19, the mean prescribing rate in the lowest prescribing quintile increased by 9.6% compared to before COVID-19. Compared to LTC homes in the highest prescribing quintile, homes in the lowest prescribing quintile experienced the highest proportion of COVID-19 outbreaks (73.4% vs 50.0%), the largest mean outbreak intensity (0.27 vs 0.09 cases/bed), the highest mean total days with a COVID-19 outbreak (72.7 vs 24.2 days), and the greatest proportion of decedents who were transferred and died outside of LTC (22.1% vs 8.6%)., Conclusions and Implications: LTC homes in Ontario had wide variations in the prescribing rates of end-of-life symptom management medications before and during COVID-19. Homes in the lower prescribing quintiles had more COVID-19 cases per bed and days spent in an outbreak., Competing Interests: Disclosure The authors declare no conflicts of interest., (Copyright © 2024 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.) more...
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- 2024
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24. A Personalized and Interactive Web-Based Advance Care Planning Intervention for Older Adults (Koda Health): Pilot Feasibility Study.
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Roberts RL, Cherry KD, Mohan DP, Statler T, Kirkendall E, Moses A, McCraw J, Brown Iii AE, Fofanova TY, and Gabbard J
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- Humans, Pilot Projects, Male, Female, Middle Aged, Aged, North Carolina, Internet-Based Intervention, Internet, Surveys and Questionnaires, Advance Care Planning, Feasibility Studies
- Abstract
Background: Advance care planning (ACP) is a process that involves patients expressing their personal goals, values, and future medical care preferences. Digital applications may help facilitate this process, though their use in older adults has not been adequately studied., Objective: This pilot study aimed to evaluate the reach, adoption, and usability of Koda Health, a web-based patient-facing ACP platform, among older adults., Methods: Older adults (aged 50 years and older) who had an active Epic MyChart account at an academic health care system in North Carolina were recruited to participate. A total of 2850 electronic invitations were sent through MyChart accounts with an embedded hyperlink to the Koda platform. Participants who agreed to participate were asked to complete pre- and posttest surveys before and after navigating through the Koda Health platform. Primary outcomes were reach, adoption, and System Usability Scale (SUS) scores. Exploratory outcomes included ACP knowledge and readiness., Results: A total of 161 participants enrolled in the study and created an account on the platform (age: mean 63, SD 9.3 years), with 80% (129/161) of these participants going on to complete all steps of the intervention, thereby generating an advance directive. Participants reported minimal difficulty in using the Koda platform, with an overall SUS score of 76.2. Additionally, knowledge of ACP (eg, mean increase from 3.2 to 4.2 on 5-point scale; P<.001) and readiness (eg, mean increase from 2.6 to 3.2 on readiness to discuss ACP with health care provider; P<.001) significantly increased from before to after the intervention., Conclusions: This study demonstrated that the Koda Health platform is feasible, had above-average usability, and improved ACP documentation of preferences in older adults. Our findings indicate that web-based health tools like Koda may help older individuals learn about and feel more comfortable with ACP while potentially facilitating greater engagement in care planning., (© R Lynae Roberts, Katelin D Cherry, Desh P Mohan, Tiffany Statler, Eric Kirkendall, Adam Moses, Jennifer McCraw, Andrew E Brown III, Tatiana Y Fofanova, Jennifer Gabbard. Originally published in JMIR Aging (https://aging.jmir.org).) more...
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- 2024
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25. Mindfulness-Based Interventions for Perioperative Pain Management and Opioid Risk Reduction Following Surgery: A Stepped Care Approach.
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Roberts RL, Hanley AW, and Garland EL
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- Humans, Analgesics, Opioid therapeutic use, Pain Management, Pain, Postoperative prevention & control, Pain, Postoperative drug therapy, Mindfulness methods, Chronic Pain drug therapy, Opioid-Related Disorders prevention & control
- Abstract
Surgical procedures often improve health and function but can sometimes also result in iatrogenic effects, including chronic pain and opioid misuse. Due to the known risks of opioids and the physical, emotional, and financial suffering that often accompanies chronic pain, there has been a call for greater use of complementary non-pharmacological treatments like mindfulness-based interventions. Mindfulness can be broadly described as an attentional state involving moment-by-moment meta-awareness of thoughts, emotions, and body sensations. An expanding number of randomized clinical trials have found strong evidence for the value of mindfulness techniques in alleviating clinical symptomology relevant to surgical contexts. The purpose of this review is to examine the empirical evidence for the perioperative use of mindfulness interventions. We present a mindfulness-based stepped care approach that first involves brief mindfulness to treat preoperative pain and anxiety and prevent development of postoperative chronic pain or opioid misuse. More extensive mindfulness-based interventions are then provided to patients who continue to experience high pain levels or prolonged opioid use after surgery. Finally, we review psychophysiological mechanisms of action that may be integral to the analgesic and opioid sparing effects of mindfulness., Competing Interests: Declaration Of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Eric Garland, PhD, LCSW is the Director of the Center on Mindfulness and Integrative Health Intervention Development. The Center provides Mindfulness-Oriented Recovery Enhancement (MORE), mindfulness-based therapy, and cognitive-behavioral therapy in the context of research trials for no cost to research participants; however, Dr. Garland has received honoraria and payment for delivering seminars, lectures, and teaching engagements (related to training clinicians in MORE and mindfulness) sponsored by institutions of higher education, government agencies, academic teaching hospitals, and medical centers. Dr. Garland also receives royalties from the sale of books related to MORE. The other authors declare that they have no competing interests. more...
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- 2024
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26. Palliative End-of-Life Medication Prescribing Rates in Long-Term Care: A Retrospective Cohort Study.
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Tanuseputro P, Roberts RL, Milani C, Clarke AE, Webber C, Isenberg SR, Kobewka D, Turcotte L, Bush SH, Boese K, Arya A, Robert B, Sinnarajah A, Simon JE, Howard M, Lau J, Qureshi D, Fremont D, and Downar J more...
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- Humans, Retrospective Studies, Death, Ontario, Long-Term Care, Terminal Care
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Background: Medications are often needed to manage distressing end-of-life symptoms (eg, pain, agitation)., Objectives: In this study, we describe the variation in prescribing rates of symptom relief medications at the end of life among long-term care (LTC) decedents. We evaluate the extent these medications are prescribed in LTC homes and whether prescribing rates of end-of-life symptom management can be used as an indicator of quality end-of-life care., Design: Retrospective cohort study using administrative health data., Setting and Participants: LTC decedents in all 626 publicly funded LTC homes in Ontario, Canada, between January 1, 2017, and March 17, 2020., Methods: For each LTC home, we measured the percent of decedents who received 1+ prescription(s) for a subcutaneous end-of-life symptom management medication ("end-of-life medication") in their last 14 days of life. We then ranked LTC homes into quintiles based on prescribing rates., Results: We identified 55,916 LTC residents who died in LTC. On average, two-thirds of decedents (64.7%) in LTC homes were prescribed at least 1 subcutaneous end-of-life medication in the last 2 weeks of life. Opioids were the most common prescribed medication (overall average prescribing rate of 62.7%). LTC homes in the lowest prescribing quintile had a mean of 37.3% of decedents prescribed an end-of-life medication, and the highest quintile mean was 82.5%. In addition, across these quintiles, the lowest prescribing quintile had a high average (30.3%) of LTC residents transferred out of LTC in the 14 days compared with the highest prescribing quintile (12.7%)., Conclusions and Implications: Across Ontario's LTC homes, there are large differences in prescribing rates for subcutaneous end-of-life symptom relief medications. Although future work may elucidate why the variability exists, this study provides evidence that administrative data can provide valuable insight into the systemic delivery of end-of-life care., Competing Interests: Disclosure The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.) more...
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- 2024
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27. Measuring the Use of End-of-Life Symptom Relief Medications in Long-Term Care Homes-a Qualitative Study.
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Roberts RL, Milani C, Webber C, Bush SH, Boese K, Simon JE, Downar J, Arya A, Tanuseputro P, and Isenberg SR
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Background: At the end of life, individuals may experience physical symptoms such as pain, and guidelines recommend medications to manage these symptoms. Yet, little is known about the symptom management long-term care (LTC) residents receive at the end of life. Our research team developed a metric-whether residents receive one or more prescriptions for an end-of-life symptom management medication in their last two weeks-to explore end-of-life care for LTC residents. This qualitative study aimed to inform the refinement of the end-of-life prescribing metric, including the acceptability and applicability to assess the quality of a resident's symptom management at end-of-life., Methods: We conducted 14 semi-structured interviews with Ontario health-care providers (physicians and nurses) who work in LTC homes and family caregivers of residents who died in LTC. Interviews were conducted virtually between February 2021 and December 2022, and were analyzed using thematic analysis., Results: We identified three major themes relating to perceptions of the metric: 1) appropriateness, 2) health-care provider applicability, and 3) caregiver applicability. Participants noted that the metric may be appropriate to assess end-of-life care, but noted important nuances. Regarding applicability, health-care providers found value in the metric and that it could inform their practice. Conversely, caregivers found limited value in the metric., Conclusion: The proposed metric captures a very specific aspect of end-of-life care-whether end-of-life medications were prescribed or not. Participants deemed that the metric may reflect whether LTC homes have processes to manage a resident's end-of-life symptoms with medication. However, participants thought the metric could not provide a complete picture of end-of-life care and its quality., Competing Interests: CONFLICT OF INTEREST DISCLOSURES: We have read and understood the Canadian Geriatrics Journal’s policy on conflicts of interest disclosure and declare there are none. Three of the authors of this paper had prior professional or personal relationships with four participants. To mitigate bias, interviewers did not interview participants with whom they had relationships. Additionally, nine authors helped develop the indicator. The indicator was used in the quantitative phase of the overarching research program., (© 2024 Author(s).) more...
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- 2024
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28. Deployment of a Digital Advance Care Planning Platform at an Accountable Care Organization.
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Roberts RL, Mohan DP, Cherry KD, Sanky S, Huffman TR, Lukasko C, Comito A, Hashemi D, Menn ZK, Fofanova TY, and Andrieni JD
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- Humans, Retrospective Studies, Quality of Life, Accountable Care Organizations, Advance Care Planning
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Background: Advance care planning (ACP), a process of sharing one's values and preferences for future medical treatments, can improve quality of life, reduce loved ones' anxiety, and decrease unwanted medical utilization and costs. Despite benefits to patients and health care systems, ACP uptake often remains low, due partially to lack of knowledge and difficulty initiating discussions. Digital tools may help reduce these barriers to entry., Methods: We retrospectively examined data from pilot deployment of Koda Health patient-facing ACP among Houston Methodist Coordinated Care patients, for quality improvement (QI) purposes. Patients referred by nurse navigators could access Koda's digital platform, complete ACP, and share the legal documentation generated. Analyzed measures include usage rates and ACP-related decisions within the platform., Results: Of eligible patients (n = 203), 52.7% voluntarily completed their plan. Engagement and completion rates were similar across demographics. Patients indicated majority preference (66.4%) toward spending the last days of life at home. Most patients indicated wanting no life-support intervention if quality of life became unacceptable (51 to 71% across 4 treatments). Life-support decisions were similar between demographic categories, excepting CPR and dialysis, wherein a greater portion of Black patients than White patients preferred at least trial intervention, rather than none., Conclusions: As an observational QI analysis, limitations include bounded geographical reach and lack of data on ACP impacts to subsequent health care utilization, which future studies will address. Findings suggest that digital health tools like Koda can effectively facilitate equitable ACP access and may help support health systems and providers in offering comprehensive ACP., Competing Interests: Conflict of interest: DM, RLR, KC, TF, SS, TH, CL, AC, and DH were each affiliated with Koda Health at the time of work on this project. ZM and JDA have no conflicts of interest to report., (© Copyright by the American Board of Family Medicine.) more...
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- 2024
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29. Association between non-medical cannabis legalization and emergency department visits for cannabis-induced psychosis.
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Myran DT, Pugliese M, Roberts RL, Solmi M, Perlman CM, Fiedorowicz J, Tanuseputro P, and Anderson KK
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- Male, Adolescent, Humans, Female, Emergency Room Visits, Emergency Service, Hospital, Cannabis adverse effects, Marijuana Abuse complications, Psychotic Disorders, Methamphetamine, Cocaine
- Abstract
A major public health concern of cannabis legalization is that it may result in an increase in psychotic disorders. We examined changes in emergency department (ED) visits for cannabis-induced psychosis following the legalization and subsequent commercialization (removal of restrictions on retail stores and product types) of non-medical cannabis in Ontario, Canada (population of 14.3 million). We used health administrative data containing the cause of all ED visits to examine changes over three periods; 1) pre-legalization (January 2014-September 2018); 2) legalization with restrictions (October 2018 - February 2020); and 3) commercialization (March 2020 - September 2021). We considered subgroups stratified by age and sex and examined cocaine- and methamphetamine-induced psychosis ED visits as controls. During our study, there were 6300 ED visits for cannabis-induced psychosis. The restricted legalization period was not associated with changes in rates of ED visits for cannabis-induced psychosis relative to pre-legalization. The commercialization period was associated with an immediate increase in rates of ED visits for cannabis-induced psychosis (IRR 1.30, 95% CI 1.02-1.66) and no gradual monthly change; immediate increases were seen only for youth above (IRR 1.63, 1.27-2.08, ages 19-24) but not below (IRR 0.73 95%CI 0.42-1.28 ages, 15-18) the legal age of purchase, and similar for men and women. Commercialization was not associated with changes in rates of ED visits for cocaine- or methamphetamine-induced psychosis. This suggests that legalization with store and product restrictions does not increase ED visits for cannabis-induced psychosis. In contrast, cannabis commercialization may increase cannabis-induced psychosis presentations highlighting the importance of preventive measures in regions considering legalization., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.) more...
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- 2023
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30. Needle decompression of tension pneumoperitoneum as a resuscitative measure prior to induction of general anaesthesia.
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Bickerton M, Dawson S, Sharma M, and Roberts RL
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- 2023
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31. The Mindful Reappraisal of Pain Scale (MRPS): Validation of a New Measure of Psychological Mechanisms of Mindfulness-Based Analgesia.
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Garland EL, Roberts RL, Hanley AW, Zeidan F, and Keefe FJ
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Objectives: Mindfulness is theorized to decrease the affective amplification of chronic pain by facilitating a shift from emotionally-laden, catastrophic pain appraisals of nociceptive input to reappraising chronic pain as an innocuous sensory signal that does not signify harm. Understanding of these hypothetical psychological mechanisms of mindfulness-based analgesia has been limited by a lack of direct measures. We conducted a series of psychometric and experimental studies to develop and validate the Mindful Reappraisal of Pain Sensations Scale (MPRS)., Methods: After item generation, we conducted exploratory and confirmatory factor analyses of the MRPS in samples of opioid-treated chronic pain patients both before (n=450; n=90) and after (n=222) participating in Mindfulness-Oriented Recovery Enhancement (MORE). We then examined the convergent and divergent validity of the MRPS. Finally, in data from a randomized clinical trial (n=250), the MRPS was tested as a mediator of the effects of MORE on reducing chronic pain severity., Results: Exploratory and confirmatory factor analyses demonstrated the single-factor structure of the MRPS. The MRPS also evidenced convergent and divergent validity. Mindfulness training through MORE significantly increased MRPS scores relative to supportive psychotherapy ( F
4,425.03 = 16.15, p < .001). Changes in MRPS scores statistically mediated the effect of MORE on reducing chronic pain severity through 9-month follow-up., Conclusions: Taken together, these studies demonstrate that the MRPS is a psychometrically sound and valid measure of novel analgesic mechanisms of mindfulness including attentional disengagement from affective pain appraisals and interoceptive exposure to pain sensations., Competing Interests: ELG is the Director of the Center on Mindfulness and Integrative Health Intervention Development. The Center provides Mindfulness-Oriented Recovery Enhancement (MORE), mindfulness-based therapy, and cognitive behavioral therapy in the context of research trials for no cost to research participants; however, Dr. Garland has received honoraria and payment for delivering seminars, lectures, and teaching engagements (related to training clinicians in mindfulness) sponsored by institutions of higher education, government agencies, academic teaching hospitals, and medical centers. Dr. Garland also receives royalties from the sale of books related to MORE. Dr. Garland has also been a consultant and licensor to BehaVR, LLC. No other authors have any related conflicts of interest to disclose. more...- Published
- 2023
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32. Characterization of Problematic Alcohol Use Among Physicians: A Systematic Review.
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Wilson J, Tanuseputro P, Myran DT, Dhaliwal S, Hussain J, Tang P, Noor S, Roberts RL, Solmi M, and Sood MM
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- Male, Female, Humans, Alcohol Drinking epidemiology, Surveys and Questionnaires, Alcoholism, Physicians, Medicine
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Importance: Problematic alcohol use in physicians poses a serious concern to physicians' health and their ability to provide care. Understanding the extent and characteristics of physicians with problematic alcohol use will help inform interventions., Objective: To estimate the extent of problematic alcohol use in physicians and how it differs by physician sex, age, medical specialty, and career stage (eg, residency vs practicing physician)., Evidence Review: Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020-compliant systematic review, searching Medline, Embase, and PsychInfo from January 2006 to March 2020. Search terms included Medical Subject Headings terms and keywords related to physicians as the population and problematic alcohol use as the primary outcome. The quality of studies was assessed using the Newcastle-Ottawa Scale. We included articles where problematic alcohol use was measured by a validated tool (ie, Alcohol Use Disorders Identification Test [AUDIT], AUDIT Version C [AUDIT-C], or CAGE [Cut down, Annoyed, Guilty, and Eye-opener] questionnaire) in practicing physicians (ie, residents, fellows, or staff physicians)., Findings: Thirty-one studies involving 51 680 participants in 17 countries published between January 2006 and March 2020 were included. All study designs were cross-sectional, self-reported surveys. Problematic alcohol use varied widely regardless of measurement method (0 to 34% with AUDIT; 9% to 35% with AUDIT-C; 4% to 22% with CAGE). Reported problematic alcohol use increased over time from 16.3% in 2006 to 2010 to 26.8% in 2017 to 2020. The extent of problematic use by sex was examined in 19 studies, by age in 12 studies, by specialty in 7 studies, and by career stage in 5 studies. Seven of 19 studies (37%) identified that problematic alcohol use was more common in males than females. Based on the wide heterogeneity of methods for included studies, limited conclusions can be made on how problematic alcohol use varies based on physician age, sex, specialty, and career stage., Conclusions and Relevance: Studies about problematic alcohol use in physicians demonstrate a high degree of heterogeneity in terms of methods of measurement, definitions for problematic alcohol use, and cohorts assessed. Most studies are primarily self-reported, precluding the ability to determine the true prevalence among the profession. Few studies provide relevant comparisons to aid in identifying key risk groups for targeted interventions. more...
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- 2022
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33. Association between opioid use disorder and blunted heart rate variability among opioid-treated chronic pain patients.
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Roberts RL and Garland EL
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- Humans, Female, Male, Analgesics, Opioid therapeutic use, Heart Rate physiology, Cross-Sectional Studies, Chronic Pain drug therapy, Opioid-Related Disorders
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Given the severity of the ongoing opioid epidemic, it is essential to understand the mechanisms of risk for development and maintenance of opioid use disorder (OUD). The aim of the current large-scale psychophysiological investigation was to test whether patients with OUD had lower resting-state high-frequency heart rate variability (HF-HRV) than those without OUD, controlling for sociodemographic and clinical confounds. Additionally, we tested whether HF-HRV was associated with opioid craving in this population. Participants in this cross-sectional study were 490 chronic pain patients (50.4% female) treated with long-term opioid therapy. OUD diagnosis was determined by psychiatric interview. HF-HRV was measured at resting baseline. We computed the association between OUD and resting-state HF-HRV, controlling for age, gender, race, pain severity, emotional distress and opioid dose. Opioid craving was measured with visual analogue scales to assess whether HF-HRV was associated with craving. Results showed that resting HF-HRV was significantly lower for patients with OUD than for those without OUD (p < 0.001, d = 0.36), indicating deficits in autonomic flexibility. OUD diagnosis (p = 0.002) and OUD severity (p = 0.03) were associated with lower HF-HRV in regression models accounting for a range of confounders. Additionally, lower HF-HRV was significantly (but weakly) correlated with heightened opioid craving (r = -0.166, p < 0.001). Overall, findings suggest that resting-state HF-HRV may serve as a valid biomarker of addiction among people on long-term opioid therapy., (© 2022 Society for the Study of Addiction.) more...
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- 2022
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34. Willingness and Accessibility of a Hypnosis Intervention for Anxiety Among a Low Socioeconomic Status Population.
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Rhodes JR, Biggs ML, Griggs J, Roberts RL, and Elkins GR
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- Adult, Anxiety Disorders, Female, Humans, Male, Social Class, Surveys and Questionnaires, Anxiety therapy, Hypnosis methods
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Objective: This survey study aimed to investigate the willingness and accessibility of a hypnosis intervention for anxiety among low socioeconomic status patients in a primary care setting. Methods: Participants were asked to complete a one-page survey during a scheduled office visit with their primary care provider. Survey questions included participants' interest in hypnosis as a treatment for anxiety, how many sessions they would be willing/able to attend, how they would prefer access to a recorded hypnosis intervention, and items relating to anxiety, including the Generalized Anxiety Disorder-7 measure. Results: Two hundred participants (71.5% female) completed the survey with a mean age of 43.16 (standard deviation = 15.78). Over half (54.6%) of the survey participants reported that they experience anxiety, and 74% of the participants indicated that they would be interested in hypnosis if it were recommended by their provider for anxiety. Discussion: Given the high prevalence of anxiety among survey participants, there exists a clear need for effective and accessible treatment options. These results demonstrate the willingness of individuals to use hypnosis for anxiety and to engage in remote hypnosis interventions. more...
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- 2022
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35. The Glucocorticoid Receptor in Osterix-Expressing Cells Regulates Bone Mass, Bone Marrow Adipose Tissue, and Systemic Metabolism in Female Mice During Aging.
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Pierce JL, Sharma AK, Roberts RL, Yu K, Irsik DL, Choudhary V, Dorn JS, Bensreti H, Benson RD Jr, Kaiser H, Khayrullin A, Davis C, Wehrle CJ, Johnson MH, Bollag WB, Hamrick MW, Shi X, Isales CM, and McGee-Lawrence ME more...
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- Adipose Tissue metabolism, Aging, Animals, Female, Glucocorticoids pharmacology, Mice, Mice, Inbred C57BL, Osteoblasts metabolism, Bone Marrow metabolism, Receptors, Glucocorticoid metabolism
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Hallmarks of aging-associated osteoporosis include bone loss, bone marrow adipose tissue (BMAT) expansion, and impaired osteoblast function. Endogenous glucocorticoid levels increase with age, and elevated glucocorticoid signaling, associated with chronic stress and dysregulated metabolism, can have a deleterious effect on bone mass. Canonical glucocorticoid signaling through the glucocorticoid receptor (GR) was recently investigated as a mediator of osteoporosis during the stress of chronic caloric restriction. To address the role of the GR in an aging-associated osteoporotic phenotype, the current study utilized female GR conditional knockout (GR-CKO; GR
fl/fl :Osx-Cre+) mice and control littermates on the C57BL/6 background aged to 21 months and studied in comparison to young (3- and 6-month-old) mice. GR deficiency in Osx-expressing cells led to low bone mass and BMAT accumulation that persisted with aging. Surprisingly, however, GR-CKO mice also exhibited alterations in muscle mass (reduced % lean mass and soleus fiber size), accompanied by reduced voluntary physical activity, and also exhibited higher whole-body metabolic rate and elevated blood pressure. Moreover, increased lipid storage was observed in GR-CKO osteoblastic cultures in a glucocorticoid-dependent fashion despite genetic deletion of the GR, and could be reversed via pharmacological inhibition of the mineralocorticoid receptor (MR). These findings provide evidence of a role for the GR (and possibly the MR) in facilitating healthy bone maintenance with aging in females. The effects of GR-deficient bone on whole-body physiology also demonstrate the importance of bone as an endocrine organ and suggest evidence for compensatory mechanisms that facilitate glucocorticoid signaling in the absence of osteoblastic GR function; these represent new avenues of research that may improve understanding of glucocorticoid signaling in bone toward the development of novel osteogenic agents. © 2021 American Society for Bone and Mineral Research (ASBMR)., (© 2021 American Society for Bone and Mineral Research (ASBMR).) more...- Published
- 2022
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36. Hypnotizability Norms may not be Representative of the General Population: Potential Sample and Self-Selection Bias Considerations.
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Peter B and Roberts RL
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- Adult, Child, Humans, Selection Bias, Students, Universities, Hypnosis methods
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The analysis of the methods sections of 66 normalization tests of hypnotizability scales reveals that out of 33,338 subjects, 58.57% were college and university students, and the majority of these were students of psychology. Of all subjects, 7.45% were younger school children, 27.63% were patients treated with hypnosis, and out of these, 85.26% were patients of 1 single therapist. Only 0.51% were trainees of dental or nursing schools, 0.13% were prisoners, and 5.71% were other adults. These figures suggest a sample-selection bias. As 83.08% of these subjects were told beforehand that they were to undergo a hypnosis study, a self-selection bias is also implied in the data. It can be presumed that those interested in hypnosis participated, whereas others who had no interest in hypnosis may have refrained. It is concluded that some of the published norms of hypnotizability tests may not be adequately representative of the general population. Many hypnosis studies, whether clinical or experimental, which are based on hypnotizability, may be afflicted by these biases. more...
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- 2022
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37. Mindful Lawyering: a Pilot Study on Mindfulness Training for Law Students.
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Rosky CJ, Roberts RL, Hanley AW, and Garland EL
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Objectives: Many US law schools are now offering elective courses in mindfulness training to alleviate disproportionately high levels of anxiety, depression, stress, and disordered alcohol use among law students. To date, empirical evidence on the effectiveness of these courses has been lacking. The aim of this pilot study was to explore the feasibility and impact of a 13-week mindfulness course, "Mindful Lawyering," specifically tailored to law students. The primary hypothesis was that mindfulness training would be significantly correlated with improvements in well-being and mindfulness., Methods: The design was a non-randomized, quasi-experimental study involving 64 law students. The mindfulness group was 31 students taking Mindful Lawyering; the comparison group was 33 students taking other law school courses. Outcome measures were the Depression, Anxiety, and Stress Scale; the Positive and Negative Affect Scale; the Alcohol Use Disorders Identification Test; and the Five Facet Mindfulness Questionnaire., Results: Results provide promising evidence to support the hypothesis. The mindfulness group showed significantly greater improvement on measures of stress ( p < .001, d = 1.15), anxiety ( p < .001, d = . 90), depression ( p = .012, d = .66), negative affect ( p = .002, d = .81), disordered alcohol use ( p = .011, d = .67), and mindfulness ( p < .001, d = 1.32) from pre to post relative to the comparison group. The course was well accepted and feasible for law students., Conclusions: Findings from the current study suggest that mindfulness training may occasion improvements in the well-being of law students. More research is needed to replicate these findings in larger, randomized samples of law students., Supplementary Information: The online version contains supplementary material available at 10.1007/s12671-022-01965-w., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s) 2022.) more...
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- 2022
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38. Mindfulness-Oriented Recovery Enhancement for Addictive Behavior, Psychiatric Distress, and Chronic Pain: A Multilevel Meta-Analysis of Randomized Controlled Trials.
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Parisi A, Roberts RL, Hanley AW, and Garland EL
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Objectives: Mindfulness-Oriented Recovery Enhancement (MORE) is an integrative intervention designed to ameliorate addiction, chronic pain, and psychiatric symptoms. Although multiple randomized controlled trials (RCTs) have examined the clinical efficacy of MORE, no study has quantitatively synthesized this body of research. Thus, we conducted a meta-analysis of RCTs examining the effects of MORE on addictive behaviors, craving, opioid dose, pain, and psychiatric symptoms., Methods: Relevant manuscripts were identified through comprehensive searches of four bibliographic databases. Two- and three-level random-effects models were used to generate synthesized effect size estimates, and meta-regressions were performed to examine whether study and sample characteristics influenced the magnitude of aggregate effect sizes., Results: Our search identified 16 manuscripts reporting data from eight RCTs ( N = 816). Moderate to small effects in favor of MORE were observed for addictive behaviors (SMC = - .54, p = .007), craving (SMC = - .42, p = .010), opioid dose (MC = - 17.95, p < .001), chronic pain (SMC = - .60, p < .001), and psychiatric symptoms (SMC = - .34, p < .001). MORE's effects on psychiatric symptoms and craving were not moderated by participant race, gender, age, or income., Conclusions: Study findings provide empirical evidence of MORE's efficacy for a wide diversity of individuals, and as such, MORE should now be disseminated broadly throughout the healthcare system., Supplementary Information: The online version contains supplementary material available at 10.1007/s12671-022-01964-x., Competing Interests: Competing InterestsEric Garland, PhD, LCSW, is the Director of the Center on Mindfulness and Integrative Health Intervention Development. The Center provides Mindfulness-Oriented Recovery Enhancement (MORE), mindfulness-based therapy, and cognitive behavioral therapy in the context of research trials for no cost to research participants; however, Dr. Garland has received honoraria and payment for delivering seminars, lectures, and teaching engagements (related to training clinicians in MORE and mindfulness) sponsored by institutions of higher education, government agencies, academic teaching hospitals, and medical centers. Dr. Garland also receives royalties from the sale of books related to MORE. Dr. Garland is also a consultant and licensor to BehaVR, LLC., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.) more...
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- 2022
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39. Effect of Hypnosis on Anxiety: Results from a Randomized Controlled Trial with Women in Postmenopause.
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Roberts RL, Rhodes JR, and Elkins GR
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- Anxiety therapy, Anxiety Disorders, Female, Hot Flashes, Humans, Hypnosis, Postmenopause
- Abstract
Anxiety is common, yet often under-treated, among women in postmenopause. This study examined the effect of a hypnotic intervention designed to reduce hot flashes, on anxiety levels of postmenopausal women. Anxiety was assessed using the State-Trait Anxiety Inventory, the Hospital Anxiety and Depression Scale-Anxiety subscale, and a visual analog scale. Additionally, hypnotizability was tested as a moderator of anxiety reductions. Significant reductions in anxiety were found from baseline to endpoint and follow-up and hypnosis was superior to the control condition. Additionally, ratings of Current Anxiety decreased from pre-session to post-session at each weekly visit and the pre-session scores reduced continuously. Hypnotizability was found to moderate anxiety reductions, but regardless of hypnotizability level participants, on average, experienced significant symptom improvement from baseline scores. These data provide initial support for the use of hypnosis to reduce symptoms of anxiety among postmenopausal women.Trial registration: This study was registered at ClinicalTrials.gov on February 11, 2011 under Identifier number NCT01293695 ( https://clinicaltrials.gov/ct2/show/NCT01293695?term=Elkins&cond=hot+flashes&draw=2&rank=2 )., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.) more...
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- 2021
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40. Mindfulness-oriented recovery enhancement improves negative emotion regulation among opioid-treated chronic pain patients by increasing interoceptive awareness.
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Roberts RL, Ledermann K, and Garland EL
- Abstract
Objective: Long-term opioid therapy presents health risks for people with chronic pain. Some chronic pain patients escalate their opioid dose to regulate negative emotions. Therefore, emotion regulatory strategies like reappraisal are key treatment targets for this population. Mindfulness has been shown to enhance reappraisal, but the mechanisms of action are unknown. This study was a secondary analysis of data from a randomized, controlled trial of Mindfulness-Oriented Recovery Enhancement (MORE) to test a specific postulate of the Mindfulness-to-Meaning Theory: that mindfulness-based interventions promote reappraisal, via interoceptive self-regulation, as a means of decreasing emotional distress., Methods: Ninety-five patients with opioid-treated chronic pain (age = 56.8 ± 11.7, 66% female) were randomized to 8 weeks of MORE or Support Group (SG) psychotherapy. An interoceptive awareness latent variable was constructed from the Multidimensional Assessment of Interoceptive Awareness (MAIA). Next, interoceptive self-regulation was assessed as a mediator of the effect of MORE on post-treatment reappraisal, and then reappraisal was examined as a mediator of change in distress through 3-month follow-up., Results: MORE participants had greater improvements in interoceptive awareness than the SG as measured by the interoceptive awareness latent variable (β = 0.310, p = 0.008) and by the self-regulation MAIA subscale (β = 0.335, p = 0.001). The effect of MORE on treatment-induced increases in reappraisal was mediated by increased interoceptive self-regulation (indirect effect: β = 0.110, p = 0.030). In turn, decreases in distress through 3-month follow-up were mediated by increases in reappraisal (indirect: β = -0.136, p = 0.031)., Conclusion: MORE facilitated reappraisal of distress by enhancing interoceptive self-regulation, supporting a central mechanistic causal pathway specified by the Mindfulness-to-Meaning Theory., (Copyright © 2021. Published by Elsevier Inc.) more...
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- 2021
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41. The Senolytic Drug Navitoclax (ABT-263) Causes Trabecular Bone Loss and Impaired Osteoprogenitor Function in Aged Mice.
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Sharma AK, Roberts RL, Benson RD Jr, Pierce JL, Yu K, Hamrick MW, and McGee-Lawrence ME
- Abstract
Senescence is a cellular defense mechanism that helps cells prevent acquired damage, but chronic senescence, as in aging, can contribute to the development of age-related tissue dysfunction and disease. Previous studies clearly show that removal of senescent cells can help prevent tissue dysfunction and extend healthspan during aging. Senescence increases with age in the skeletal system, and selective depletion of senescent cells or inhibition of their senescence-associated secretory phenotype (SASP) has been reported to maintain or improve bone mass in aged mice. This suggests that promoting the selective removal of senescent cells, via the use of senolytic agents, can be beneficial in the treatment of aging-related bone loss and osteoporosis. Navitoclax (also known as ABT-263) is a chemotherapeutic drug reported to effectively clear senescent hematopoietic stem cells, muscle stem cells, and mesenchymal stromal cells in previous studies, but its in vivo effects on bone mass had not yet been reported. Therefore, the purpose of this study was to assess the effects of short-term navitoclax treatment on bone mass and osteoprogenitor function in old mice. Aged (24 month old) male and female mice were treated with navitoclax (50 mg/kg body mass daily) for 2 weeks. Surprisingly, despite decreasing senescent cell burden, navitoclax treatment decreased trabecular bone volume fraction in aged female and male mice (-60.1% females, -45.6% males), and BMSC-derived osteoblasts from the navitoclax treated mice were impaired in their ability to produce a mineralized matrix (-88% females, -83% males). Moreover, in vitro administration of navitoclax decreased BMSC colony formation and calcified matrix production by aged BMSC-derived osteoblasts, similar to effects seen with the primary BMSC from the animals treated in vivo . Navitoclax also significantly increased metrics of cytotoxicity in both male and female osteogenic cultures (+1.0 to +11.3 fold). Taken together, these results suggest a potentially harmful effect of navitoclax on skeletal-lineage cells that should be explored further to definitively assess navitoclax's potential (or risk) as a therapeutic agent for combatting age-related musculoskeletal dysfunction and bone loss., (Copyright © 2020 Sharma, Roberts, Benson, Pierce, Yu, Hamrick and McGee-Lawrence.) more...
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- 2020
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42. Kynurenine suppresses osteoblastic cell energetics in vitro and osteoblast numbers in vivo.
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Pierce JL, Roberts RL, Yu K, Kendall RK, Kaiser H, Davis C, Johnson MH, Hill WD, Isales CM, Bollag WB, Hamrick MW, and McGee-Lawrence ME
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- Aging metabolism, Animals, Bone Density, Bone and Bones metabolism, Female, Histone Deacetylases, Male, Mice, Osteoporosis metabolism, Sex Characteristics, Tryptophan, Cell Differentiation drug effects, Kynurenine metabolism, Osteoblasts metabolism
- Abstract
Aging is a progressive process associated with declining tissue function over time. Kynurenine, an oxidized metabolite of the essential amino acid tryptophan that increases in abundance with age, drives cellular processes of aging and dysfunction in many tissues, and recent work has focused on understanding the pathways involved in the harmful effects of kynurenine on bone. In this study, we sought to investigate the effects of controlled kynurenine administration on osteoblast bioenergetics, in vivo osteoblast abundance, and marrow fat accumulation. Additionally, as an extension of earlier studies with dietary administration of kynurenine, we investigated the effects of kynurenine on Hdac3 and NCoR1 expression and enzymatic deacetylase activity as potential mechanistic contributors to the effects of kynurenine on osteoblasts. Kynurenine administration suppressed cellular metabolism in osteoblasts at least in part through impaired mitochondrial respiration, and suppressed osteoblastic numbers in vivo with no concurrent effects on marrow adiposity. Deleterious effects of kynurenine treatment on osteoblasts were more pronounced in female models as compared to males. However, kynurenine treatment did not inhibit Hdac3's enzymatic deacetylase activity nor its repression of downstream glucocorticoid signaling. As such, future work will be necessary to determine the mechanisms by which increased kynurenine contributes to aging bone bioenergetics. The current study provides novel further support for the idea that kynurenine contributes to impaired osteoblastic function, and suggests that impaired matrix production by kynurenine-affected osteoblasts is attributed in part to impaired osteoblastic bioenergetics. As circulating kynurenine levels in increase with age, and human bone density inversely correlates with the serum kynurenine to tryptophan ratio, these mechanisms may have important relevance in the etiology and pathogenesis of osteoporosis in humans., (Copyright © 2019 Elsevier Inc. All rights reserved.) more...
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- 2020
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43. Zebrafish dscaml1 Deficiency Impairs Retinal Patterning and Oculomotor Function.
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Ma M, Ramirez AD, Wang T, Roberts RL, Harmon KE, Schoppik D, Sharma A, Kuang C, Goei SL, Gagnon JA, Zimmerman S, Tsai SQ, Reyon D, Joung JK, Aksay ERF, Schier AF, and Pan YA
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- Adaptation, Ocular genetics, Adaptation, Ocular physiology, Amacrine Cells physiology, Animals, Animals, Genetically Modified, Calcium Signaling, Cell Adhesion Molecules physiology, Eye Movements genetics, Fixation, Ocular genetics, Fixation, Ocular physiology, Larva, Locomotion, Muscle Fatigue, Mutation, Oculomotor Muscles growth & development, Oculomotor Muscles physiopathology, Retina growth & development, Retina ultrastructure, Saccades genetics, Saccades physiology, Zebrafish growth & development, Zebrafish Proteins physiology, Eye Movements physiology
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Down syndrome cell adhesion molecules ( dscam and dscaml1 ) are essential regulators of neural circuit assembly, but their roles in vertebrate neural circuit function are still mostly unexplored. We investigated the functional consequences of dscaml1 deficiency in the larval zebrafish (sexually undifferentiated) oculomotor system, where behavior, circuit function, and neuronal activity can be precisely quantified. Genetic perturbation of dscaml1 resulted in deficits in retinal patterning and light adaptation, consistent with its known roles in mammals. Oculomotor analyses revealed specific deficits related to the dscaml1 mutation, including severe fatigue during gaze stabilization, reduced saccade amplitude and velocity in the light, greater disconjugacy, and impaired fixation. Two-photon calcium imaging of abducens neurons in control and dscaml1 mutant animals confirmed deficits in saccade-command signals (indicative of an impairment in the saccadic premotor pathway), whereas abducens activation by the pretectum-vestibular pathway was not affected. Together, we show that loss of dscaml1 resulted in impairments in specific oculomotor circuits, providing a new animal model to investigate the development of oculomotor premotor pathways and their associated human ocular disorders. SIGNIFICANCE STATEMENT Dscaml1 is a neural developmental gene with unknown behavioral significance. Using the zebrafish model, this study shows that dscaml1 mutants have a host of oculomotor (eye movement) deficits. Notably, the oculomotor phenotypes in dscaml1 mutants are reminiscent of human ocular motor apraxia, a neurodevelopmental disorder characterized by reduced saccade amplitude and gaze stabilization deficits. Population-level recording of neuronal activity further revealed potential subcircuit-specific requirements for dscaml1 during oculomotor behavior. These findings underscore the importance of dscaml1 in the development of visuomotor function and characterize a new model to investigate potential circuit deficits underlying human oculomotor disorders., (Copyright © 2020 the authors.) more...
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- 2020
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44. Decreased pericellular matrix production and selection for enhanced cell membrane repair may impair osteocyte responses to mechanical loading in the aging skeleton.
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Hagan ML, Yu K, Zhu J, Vinson BN, Roberts RL, Montesinos Cartagena M, Johnson MH, Wang L, Isales CM, Hamrick MW, McNeil PL, and McGee-Lawrence ME
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- Aging, Animals, Female, Humans, Male, Mice, Cell Membrane metabolism, Mechanotransduction, Cellular physiology, Osteocytes metabolism
- Abstract
Transient plasma membrane disruptions (PMD) occur in osteocytes with in vitro and in vivo loading, initiating mechanotransduction. The goal here was to determine whether osteocyte PMD formation or repair is affected by aging. Osteocytes from old (24 months) mice developed fewer PMD (-76% females, -54% males) from fluid shear than young (3 months) mice, and old mice developed fewer osteocyte PMD (-51%) during treadmill running. This was due at least in part to decreased pericellular matrix production, as studies revealed that pericellular matrix is integral to formation of osteocyte PMD, and aged osteocytes produced less pericellular matrix (-55%). Surprisingly, osteocyte PMD repair rate was faster (+25% females, +26% males) in osteocytes from old mice, and calcium wave propagation to adjacent nonwounded osteocytes was blunted, consistent with impaired mechanotransduction downstream of PMD in osteocytes with fast PMD repair in previous studies. Inducing PMD via fluid flow in young osteocytes in the presence of oxidative stress decreased postwounding cell survival and promoted accelerated PMD repair in surviving cells, suggesting selective loss of slower-repairing osteocytes. Therefore, as oxidative stress increases during aging, slower-repairing osteocytes may be unable to successfully repair PMD, leading to slower-repairing osteocyte death in favor of faster-repairing osteocyte survival. Since PMD are an important initiator of mechanotransduction, age-related decreases in pericellular matrix and loss of slower-repairing osteocytes may impair the ability of bone to properly respond to mechanical loading with bone formation. These data suggest that PMD formation and repair mechanisms represent new targets for improving bone mechanosensitivity with aging., (© 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.) more...
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- 2020
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45. Rapid eye movement sleep mediates age-related decline in prospective memory consolidation.
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Scullin MK, Gao C, Fillmore P, Roberts RL, Pruett N, and Bliwise DL
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- Adolescent, Adult, Aged, Aged, 80 and over, Aging, Cognition physiology, Female, Humans, Male, Mental Recall physiology, Middle Aged, Polysomnography, Young Adult, Memory Consolidation physiology, Memory, Episodic, Sleep, REM physiology
- Abstract
Study Objectives: Prospective memory, or remembering to execute future intentions, accounts for half of everyday forgetting in older adults. Sleep intervals benefit prospective memory consolidation in young adults, but it is unknown whether age-related changes in slow wave activity, sleep spindles, and/or rapid eye movement (REM) sleep mediate hypothesized effects of aging on prospective memory consolidation., Methods: After an adaptation night, 76 adults aged 18-84 completed two experimental nights of in-laboratory polysomnography recording. In the evening, participants encoded and practiced a prospective memory task and were tested the next morning. On a counterbalanced night, they encoded and practiced a control task, and were tested the following morning., Results: Increasing age predicted worse prospective memory consolidation (r = -.34), even when controlling for encoding, speed, and control-task performance (all ps < .05). Frontal delta power, slow oscillations, and spindle density were not related to prospective memory consolidation. REM sleep duration, however, explained significant variance in prospective memory consolidation when controlling for age (∆R2 = .10). Bootstrapping mediation showed that less REM sleep significantly mediated the aging effect on prospective memory consolidation [b = -.0016, SE = 0.0009 (95% confidence interval [CI] = -0.0042 to -0.0004)]. REM sleep continued to mediate 24.29% of the total effect of age on prospective memory after controlling for numerous demographic, cognitive, mental health, and sleep variables., Conclusion: Age-related variance in REM sleep is informative to how prospective memory consolidation changes with increasing age. Future work should consider how both REM sleep and slow wave activity contribute, perhaps in a sequential or dynamic manner, to preserving cognitive functioning with increasing age., (© Sleep Research Society 2019. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.) more...
- Published
- 2019
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46. ABCG2 rs2231142 (Q141K) and oxypurinol concentrations in people with gout receiving allopurinol.
- Author
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Stamp LK, Wallace M, Roberts RL, Frampton C, Miner JN, Merriman TR, and Dalbeth N
- Subjects
- ATP Binding Cassette Transporter, Subfamily G, Member 2, Humans, Neoplasm Proteins, Organic Anion Transporters, Oxypurinol, Xanthine Dehydrogenase, Allopurinol, Gout
- Published
- 2018
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47. Nonsynonymous Polymorphism in Guanine Monophosphate Synthetase Is a Risk Factor for Unfavorable Thiopurine Metabolite Ratios in Patients With Inflammatory Bowel Disease.
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Roberts RL, Wallace MC, Seinen ML, van Bodegraven AA, Krishnaprasad K, Jones GT, van Rij AM, Baird A, Lawrance IC, Prosser R, Bampton P, Grafton R, Simms LA, Studd C, Bell SJ, Kennedy MA, Halliwell J, Gearry RB, Radford-Smith G, Andrews JM, McHugh PC, and Barclay ML more...
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- Adult, Cohort Studies, Female, Guanine Nucleotides blood, Humans, Inflammatory Bowel Diseases blood, Inflammatory Bowel Diseases drug therapy, Male, Mercaptopurine analogs & derivatives, Mercaptopurine blood, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, Thionucleotides blood, Young Adult, Azathioprine therapeutic use, Carbon-Nitrogen Ligases with Glutamine as Amide-N-Donor genetics, Inflammatory Bowel Diseases enzymology
- Abstract
Background: Up to 20% of patients with inflammatory bowel disease (IBD) who are refractory to thiopurine therapy preferentially produce 6-methylmercaptopurine (6-MMP) at the expense of 6-thioguanine nucleotides (6-TGN), resulting in a high 6-MMP:6-TGN ratio (>20). The objective of this study was to evaluate whether genetic variability in guanine monophosphate synthetase (GMPS) contributes to preferential 6-MMP metabolizer phenotype., Methods: Exome sequencing was performed in a cohort of IBD patients with 6-MMP:6-TGN ratios of >100 to identify nonsynonymous single nucleotide polymorphisms (nsSNPs). In vitro assays were performed to measure GMPS activity associated with these nsSNPs. Frequency of the nsSNPs was measured in a cohort of 530 Caucasian IBD patients., Results: Two nsSNPs in GMPS (rs747629729, rs61750370) were detected in 11 patients with very high 6-MMP:6-TGN ratios. The 2 nsSNPs were predicted to be damaging by in silico analysis. In vitro assays demonstrated that both nsSNPs resulted in a significant reduction in GMPS activity (P < 0.05). The SNP rs61750370 was significantly associated with 6-MMP:6-TGN ratios ≥100 (odds ratio, 5.64; 95% confidence interval, 1.01-25.12; P < 0.031) in a subset of 264 Caucasian IBD patients., Conclusions: The GMPS SNP rs61750370 may be a reliable risk factor for extreme 6MMP preferential metabolism. more...
- Published
- 2018
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48. Mindful Self-Hypnosis for Self-Care: An Integrative Model and Illustrative Case Example.
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Elkins GR, Roberts RL, and Simicich L
- Subjects
- Adult, Humans, Hypnosis methods, Mindfulness methods, Models, Psychological, Self Care methods
- Abstract
The combination of mindfulness and self-hypnosis could provide a tool that is easily implemented by individuals who want to care for their well-being in times of high stress. Each discipline has been shown to be effective in relieving stress, and integration could further facilitate change while creating a tool that is highly accessible. There are many similarities between the two practices, such as focusing of attention and the emphasis on mind-body connection. However, important distinctions in psychological (e.g., self-monitoring) and neural (e.g., functional connectivity) elements are noted. A theory of how integrated mindful self-hypnosis may create change is presented. An illustrative case example of mindful self-hypnosis practice and a self-hypnosis transcript are provided. more...
- Published
- 2018
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49. Association of Crohn's disease-related chromosome 1q32 with ankylosing spondylitis is independent of bowel symptoms and faecal calprotectin.
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Roberts RL, Wallace MC, Harrison AA, White D, Dalbeth N, Stamp LK, Ching D, Highton J, Merriman TR, Robinson PC, Brown MA, and Stebbings SM
- Abstract
Background: Genome-wide association studies have identified a plethora of risk genes for both Crohn's disease (CD) and ankylosing spondylitis (AS). A subset of genes found to be risk factors for CD have also been found to be risk factors for AS. The objective of our study was to assess whether CD risk genes were associated with non-invasive clinical markers of gut inflammation in patients with AS, indicating a potential subset of patients with clinical as well as genetic overlap., Methods: A total of 308 Caucasian patients who fulfilled the modified New York Criteria for AS, were assessed for bowel symptoms using the Dudley Inflammatory Bowel Symptom Questionnaire (DISQ). Of these patients, 157 also had faecal calprotectin measured. All AS patients and 568 healthy controls were genotyped for 10 CD risk loci using predesigned single nucleotide polymorphism (SNP) genotyping assays. Chi-square analysis was used to test for association between genotype and DISQ score and faecal calprotectin level., Results: The minor allele of two SNPs, one in chromosome region 1q32 SNP (rs11584383), and one in the gene coding for IL23R (rs11209026) conferred protection against AS. Only the association of 1q32 remained significant after Bonferroni correction for multiple testing. Stratification by DISQ score and faecal calprotectin did not influence the association of 1q32 with AS., Conclusion: In patients with AS, the association of the CD 1q32 SNP was independent of non-invasive markers of bowel inflammation. Other CD related SNPs were not found have a significant association with AS., Competing Interests: The authors declare that they have no competing interests. more...
- Published
- 2018
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50. Urethral Steinstrasse following Laser Lithotripsy of Prostatic Urethral Calculi.
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Den J, Kerr PS, Dafashy TJ, Kosarek CD, Roberts RL, and Sreshta JN
- Abstract
Symptomatic prostatic calculi are rare occurrences with several management options, the most popular of which is currently transurethral laser lithotripsy. This is a generally well-tolerated procedure with minimal complications. To date, no reported episodes of steinstrasse at the urethral level following prostatic calculi lithotripsy have been documented to our knowledge. We report a unique case of acute urinary retention secondary to obstructive calculi fragments following a transurethral laser lithotripsy of large prostatic calculi, further complicated by stricture at the fossa navicularis. more...
- Published
- 2018
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