tbuckley/cabot-search huggingface dataset:
Teaching global health ethics using simulation: interprofessional training
Authors: M Shoeb, T Logar, M H Glass, J D Harrison, T P Brock, S James-Ryan, S Barajas, P V Le
Journal: The Lancet Global Health (2014)

BackgroundMany ethical dilemmas in global health fieldwork stem from cultural differences and limited resources, and trainees frequently report feeling ill-equipped to deal with such issues. A literature review shows a need for predeparture training that would enable participants to develop a strategy for recognising and resolving such problems.MethodsAfter reviewing global health ethics education and predeparture training resources, we organised multidisciplinary focus groups with global-health experts at our institution. These sessions identified key ethical issues that our training should address: scope of practice, informed consent, privacy or confidentiality, professional ethics, harm and benefit, and corruption. We then developed four scenarios focusing on these ethical issues. Each scenario was followed by a debriefing session led by a faculty facilitator. We piloted the simulation training with a multidisciplinary cohort (n=27) of postgraduate trainees. All participants completed prestimulation and postsimulation evaluations that assessed their exposure to the scenarios' ethical issues and ability to deal with these ethical dilemmas and identify resources for help.FindingsThe results showed a significant knowledge gain in the above domains. Paired t-tests were used to compare participants' agreement scores with the statement "I have a strategy to deal with this ethical issue," which significantly increased (p<0·05) postsimulation for the following ethical issues: scope of practice, privacy, harm, and corruption.InterpretationOur preliminary results show that the simulation sessions accomplish our training's objectives. Further, our institution's ethics faculty expressed a keen interest in integrating these exercises into the mainstream ethics curriculum.FundingThe Haile T Debas Academy of Medical Educators Innovations Funding Grant.
Calorie Restriction and Matched Weight Loss From Exercise: Independent and Additive Effects on Glucoregulation and the Incretin System in Overweight Women and Men
Authors: Edward P. Weiss, Stewart G. Albert, Dominic N. Reeds, Kathleen S. Kress, Uthayashanker R. Ezekiel, Jennifer L. McDaniel, Bruce W. Patterson, Samuel Klein, Dennis T. Villareal
Journal: Diabetes Care (2015)

It is not known whether calorie restriction (CR) has additive benefits to those from exercise (EX)-induced weight loss. We hypothesized that weight loss from CR and EX (CREX) improves insulin sensitivity more than matched weight loss induced by EX or CR alone and that the incretin system may be involved in adaptations to CR.Sedentary, overweight men and women (n = 52, 45-65 years of age) were randomized to undergo 6-8% weight loss by using CR, EX, or CREX. Glucose, insulin, C-peptide, insulin sensitivity, and incretin hormones (glucagon-like peptide 1 [GLP-1] and glucose-dependent insulinotropic polypeptide [GIP]) were measured during frequently sampled oral glucose tolerance tests (FSOGTTs). Incretin effects on insulin secretion were measured by comparing insulin secretion rates from the FSOGTTs to those from a glycemia-matched glucose infusion.Despite similar weight losses in all groups, insulin sensitivity index values increased twofold more in the CREX group (2.09 ± 0.35 μM/kg/pM × 100) than in the CR (0.89 ± 0.39 μM/kg/pM × 100) and EX (1.04 ± 0.39 μM/kg/pM × 100) groups. Postprandial GLP-1 concentrations decreased only in the CR group (P = 0.04); GIP concentrations decreased in all groups. Incretin effects on insulin secretion were unchanged.CR and EX have additive beneficial effects on glucoregulation. Furthermore, the adaptations to CR may involve reductions in postprandial GLP-1 concentrations. These findings underscore the importance of promoting both CR and EX for optimal health. However, because data from participants who withdrew from the study and from those who did not adhere to the intervention were excluded, the results may be limited to individuals who are capable of adhering to a healthy lifestyle intervention.
Regulation of Cardiomyocyte Proliferation and Myocardial Growth During Development by FOXO Transcription Factors
Authors: Heather J. Evans-Anderson, Christina M. Alfieri, Katherine E. Yutzey
Journal: Circulation Research (2008)

Cardiomyocytes actively proliferate during embryogenesis and withdraw from the cell cycle during neonatal stages. FOXO (Forkhead O) transcription factors are a direct target of phosphatidylinositol-3 kinase/AKT signaling in skeletal and smooth muscle and regulate expression of the Cip/Kip family of cyclin kinase inhibitors in other cell types; however, the interaction of phosphatidylinositol-3 kinase/AKT signaling, FOXO transcription factors, and cyclin kinase inhibitor expression has not been reported for the developing heart. Here, we show that FOXO1 and FOXO3 are expressed in the developing myocardium concomitant with increased cyclin kinase inhibitor expression from embryonic to neonatal stages. Cell culture studies show that embryonic cardiomyocytes are responsive to insulin-like growth factor 1 stimulation, which results in the induction of the phosphatidylinositol-3 kinase/AKT pathway, cytoplasmic localization of FOXO proteins, and increased myocyte proliferation. Likewise, adenoviral-mediated expression of AKT promotes cardiomyocyte proliferation and cytoplasmic localization of FOXO. In contrast, increased expression of FOXO1 negatively affects myocyte proliferation. In vivo myocyte-specific transgenic expression of FOXO1 during heart development causes embryonic lethality at embryonic day 10.5 because of severe myocardial defects that coincide with premature activation of p21 cip1 , p27 kip1 , and p57 kip2 and decreased myocyte proliferation. Transgenic expression of dominant negative FOXO1 in cardiomyocytes does not obviously affect heart development at embryonic day 10.5, but results in abnormal morphology of the myocardium by embryonic day 18.5 along with decreased cyclin kinase inhibitor expression and increased myocyte proliferation. These data support FOXO transcription factors as negative regulators of cardiomyocyte proliferation and promoters of neonatal cell cycle withdrawal during heart development.
Disparities in A1C Levels Between Hispanic and Non-Hispanic White Adults With Diabetes
Authors: Julienne K. Kirk, Leah V. Passmore, Ronny A. Bell, K.M. Venkat Narayan, Ralph B. D'Agostino, Thomas A. Arcury, Sara A. Quandt
Journal: Diabetes Care (2008)

OBJECTIVE—Hispanics have higher rates of diabetes and diabetes-related complications than do non-Hispanic whites. A meta-analysis was conducted to estimate the difference between the mean values of A1C for these two groups. RESEARCH DESIGN AND METHODS—We executed a PubMed search of articles published from 1993 through July 2007. Data sources included PubMed, Web of Science, Cumulative Index to Nursing and Allied Health, the Cochrane Library, Combined Health Information Database, and Education Resources Information Center. Data on sample size, age, sex, A1C, geographical location, and study design were extracted. Cross-sectional data and baseline data from clinical trials and cohort studies for Hispanics and non-Hispanic whites with diabetes were included. Studies were excluded if they included individuals &amp;lt;18 years of age or patients with pre-diabetes or gestational diabetes. RESULTS—A total of 495 studies were reviewed, of which 73 contained data on A1C for Hispanics and non-Hispanic whites, and 11 met the inclusion criteria. Meta-analysis revealed a statistically significant mean difference (P &amp;lt; 0.0001) of −0.46 (95% CI −0.63 to −0.33), correlating to an ∼0.5% higher A1C for Hispanics. Grouping studies by design (cross-sectional or cohort), method of data collection for A1C (chart review or blood sampling), and care type (managed or nonmanaged) yielded similar results. CONCLUSIONS—In this meta-analysis, A1C was ∼0.5% higher in Hispanic patients with diabetes than in non-Hispanic patients. Understanding the reasons for this disparity should be a focus for future research.
Reviews and Notes: Hematology: Blood Transfusion in Clinical Medicine
Authors: Lawrence Tim Goodnough
Journal: Annals of Internal Medicine (1993)

Literature of Medicine1 December 1993Reviews and Notes: Hematology: Blood Transfusion in Clinical MedicineLawrence Tim Goodnough, MDLawrence Tim Goodnough, MDWashington University Medical Center, St. Louis, MO 63110.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-119-11-199312010-00032 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Blood Transfusion in Clinical MedicineP. L. Mollison, C. P. Engelfriet, and Marcela Contreras; eds. 1015 pages. Oxford, England: Blackwell; 1993. $129.95.The ninth edition of this textbook continues to reinforce its deserved place as a standard reference work in the field of blood banking. The encyclopedic detail and extensive references provide current information in most areas of blood banking. The book is especially strong in the serologic aspects of blood transfusion. The field of transfusion medicine is changing greatly, however, and one wonders if a text on clinical blood transfusion should not also address the clinical aspects of transfusion medicine in ... Author, Article, and Disclosure InformationAffiliations: Washington University Medical Center, St. Louis, MO 63110. Previousarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 December 1993Volume 119, Issue 11Page: 1154KeywordsBlood banksBlood cellsBlood transfusionHealth care quality assessmentHematology and oncologyHematopoietic growth factorsPatientsStem cell transplantationTransfusion medicine Issue Published: 1 December 1993 Copyright & PermissionsCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Domestication Relaxed Selective Constraints on the Yak Mitochondrial Genome
Authors: Zhaofeng Wang, Takahiro Yonezawa, Bin Liu, Tao Ma, Xin Shen, Jianping Su, Songchang Guo, Masami Hasegawa, Jianquan Liu
Journal: Molecular Biology and Evolution (2010)

Wild yaks roaming in the high-altitude Qinghai–Tibetan plateau have to maintain high metabolic efficiency. However, domestic yaks do not require such high efficiency because of their limited activity. Hence, domestication may have caused the relaxation of selective constraints on the yak mitochondrial genome because mitochondrial mutations are extremely sensitive to energy-related selective pressures. We have tested this hypothesis by analyzing the mitochondrial genomes of 51 domestic yaks and 21 wild yaks. The results show that the ratio of nonsynonymous/synonymous substitutions in mitochondrial protein-coding genes is significantly higher in domestic yak lineages than those of wild yaks. This genetic difference suggests that the relaxation of selective constraints following the domestication in addition to bottlenecks has allowed faster accumulation of nonsilent substitutions in the yak mitochondrial genome, despite its short domestication history.
Amino-terminal truncation of CXCR3 agonists impairs receptor signaling and lymphocyte chemotaxis, while preserving antiangiogenic properties
Authors: Paul Proost, Evemie Schutyser, Patricia Menten, Sofie Struyf, Anja Wuyts, Ghislain Opdenakker, Michel Detheux, Marc Parmentier, Christine Durinx, Anne-Marie Lambeir, Johan Neyts, Sandra Liekens, Prabhat C. Maudgal, Alfons Billiau, Jo Van Damme
Journal: Blood (2001)
Estrogen promotes Leydig cell engulfment by macrophages in male infertility
Authors: Wanpeng Yu, Han Zheng, Wei Lin, Astushi Tajima, Yong Zhang, Xiaoyan Zhang, Hongwen Zhang, Jihua Wu, Daishu Han, Nafis A. Rahman, Kenneth S. Korach, George Fu Gao, Ituro Inoue, Xiangdong Li
Journal: Journal of Clinical Investigation (2014)

Male infertility accounts for almost half of infertility cases worldwide. A subset of infertile men exhibit reduced testosterone and enhanced levels of estradiol (E2), though it is unclear how increased E2 promotes deterioration of male fertility. Here, we utilized a transgenic mouse strain that overexpresses human CYP19, which encodes aromatase (AROM+ mice), and mice with knockout of Esr1, encoding estrogen receptor α (ERαKO mice), to analyze interactions between viable Leydig cells (LCs) and testicular macrophages that may lead to male infertility. In AROM+ males, enhanced E2 promoted LC hyperplasia and macrophage activation via ERα signaling. E2 stimulated LCs to produce growth arrest–specific 6 (GAS6), which mediates phagocytosis of apoptotic cells by bridging cells with surface exposed phosphatidylserine (PS) to macrophage receptors, including the tyrosine kinases TYRO3, AXL, and MER. Overproduction of E2 increased apoptosis-independent extrusion of PS on LCs, which in turn promoted engulfment by E2/ERα-activated macrophages that was mediated by AXL-GAS6-PS interaction. We further confirmed E2-dependant engulfment of LCs by real-time 3D imaging. Furthermore, evaluation of molecular markers in the testes of patients with nonobstructive azoospermia (NOA) revealed enhanced expression of CYP19, GAS6, and AXL, which suggests that the AROM+ mouse model reflects human infertility. Together, these results suggest that GAS6 has a potential as a clinical biomarker and therapeutic target for male infertility.
The Combination of Circulating Ang1 and Tie2 Levels Predicts Progression-Free Survival Advantage in Bevacizumab-Treated Patients with Ovarian Cancer
Authors: Alison Backen, Andrew G. Renehan, Andrew R. Clamp, Carlo Berzuini, Cong Zhou, Amit Oza, Selina Bannoo, Stefan J. Scherer, Rosamonde E. Banks, Caroline Dive, Gordon C. Jayson
Journal: Clinical Cancer Research (2014)

Randomized ovarian cancer trials, including ICON7, have reported improved progression-free survival (PFS) when bevacizumab was added to conventional cytotoxic therapy. The improvement was modest prompting the search for predictive biomarkers for bevacizumab.
Efficacy and Optimization of Palivizumab Injection Regimens Against Respiratory Syncytial Virus Infection
Authors: Alexander Gutfraind, Alison P. Galvani, Lauren Ancel Meyers
Journal: JAMA Pediatrics (2015)

<h3>Importance</h3> Infection with the respiratory syncytial virus (RSV) is the leading cause of hospitalizations in children, accounting for more than 90 000 hospitalizations every year in the United States. For children who are at risk for severe RSV infections, the American Academy of Pediatrics recommends immunoprophylaxis with a series of up to 5 injections of the antibody palivizumab administered monthly, beginning on November 1 of each year. However, many practitioners initiate injections at the onset of RSV season as indicated by local surveillance. <h3>Objectives</h3> To evaluate the effectiveness of current regimens for palivizumab injections across different cities and to design an optimized regimen. <h3>Design, Setting, and Participants</h3> We performed a mathematical modeling study of the risk for hospitalization due to RSV infection. The model accounted for the pharmacokinetics of the antibody, the timing of the injections, and seasonal patterns of RSV, including geographic and year-to-year variability. We used the model to estimate the efficacy of current regimens, including the American Academy of Pediatrics recommendation, and to design a more effective injection regimen, the optimized fixed start (OFS), which uses city-specific initiation dates. Participants were the approximately 700 000 individuals who had specimens tested for RSV by National Respiratory and Enteric Virus Surveillance System laboratories in 18 US cities from July 1, 1994, through June 30, 2011 (a total of 725 741 tests). <h3>Interventions</h3> Different palivizumab injection regimens. <h3>Main Outcomes and Measures</h3> The primary outcome measure was reduction in hospitalizations due to RSV infections. The secondary measures were cost (number of palivizumab doses) and duration of protection (in days). <h3>Results</h3> The American Academy of Pediatrics–recommended 5-injection regimen is expected to reduce hospitalization risk by a median of 2.7% (range, −2.2% to 6.1%) compared with the conventional regimen based on RSV surveillance. The 5-injection OFS regimen is expected to further reduce risk by a median of 6.8% (range, 4.9% to 14.8%), and the 4-injection OFS regimen is expected to achieve efficacy comparable to that of the conventional 5-injection regimen while reducing costs by 20%. <h3>Conclusions and Relevance</h3> Modified palivizumab regimens can improve protection for children at risk for severe outcomes of RSV infection and thereby lower rates of hospitalization due to RSV.
APPLICATION OF APPROPRIATENESS CRITERIA TO STRESS SINGLE-PHOTON EMISSION COMPUTED TOMOGRAPHY SESTAMIBI STUDIES: A COMPARISON OF THE 2009 REVISED APPROPRIATENESS CRITERIA TO THE 2005 ORIGINAL CRITERIA
Authors: Damita J. Carryer, J. Wells Askew, David O. Hodge, Todd D. Miller, Raymond J. Gibbons
Journal: Journal of the American College of Cardiology (2010)
gammadelta T cell subsets in patients with arthritis and chronic neutropenia
Authors: I Bank
Journal: Annals of the Rheumatic Diseases (2002)

An abnormal distribution of subsets of gammadelta T cells, which are a component of the inflammatory infiltrate in arthritic synovium, has been demonstrated in the peripheral blood (PB) of patients with arthritis and neutropenia.To evaluate whether the clinical manifestations of patients with arthritis and neutropenia are related to the specific gammadelta T cell subset predominant in the PB.Flow cytometry of PB lymphocytes in six consecutive patients with chronic neutropenia and arthritis was performed. Variable (V) gamma and delta gene families were analysed by polymerase chain reaction. cDNA was subjected to direct automated sequencing of T cell receptor (TCR) genes.Three patients had non-deforming and non-erosive rheumatoid factor (RF)(+) polyarticular rheumatoid arthritis, RF(+) oligoarticular arthritis, or RF(-) non-deforming oligoarticular psoriatic arthritis with persistent expansions of Vgamma1(+)/Vdelta2(+), Vgamma2(+)/Vdelta2(+), or Vgamma1(+)/Vdelta (undetermined (2- 1-)) T cells, respectively. The other three patients, without persistent expansion of gammadelta T cells, had either non-deforming and non-erosive oligo- or polyarthritis with a balanced distribution of several Vdelta and Vgamma genes, or severe erosive RF(+) arthritis with deficiency of all but Vgamma1(+)/Vdelta1(+) T cells.gammadelta T cell lymphoproliferations in chronic neutropenia and arthritis use different Vgamma and Vdelta gene families, often forming T cell receptor (TCR) structures that are infrequent in normal adult PB. Arthritis with Vgamma1(+)/Vdelta2(+), Vgamma2(+)/Vdelta2(+), or Vgamma1(+)/Vdelta2(-)/Vdelta1(-) gammadelta T cells in the PB is non-deforming and non-erosive, suggesting a protective effect of these cells, as opposed to a more pathogenic contribution of Vgamma1(+)/Vdelta1(+) cells.
BMA says referral schemes are used to restrict access to hospitals
Authors: Rebecca Coombes
Journal: BMJ (2006)

Referral management schemes are being used to ration treatment and delay access to secondary care, the BMA warned this week. The schemes are set up by primary care trusts to vet individual GPs' decisions to refer a patient for hospital treatment.

In extreme cases, trusts are using clerks to judge whether a GP is appropriately referring a patient. In other cases, the schemes are being used as holding centres, to impose a delay on making referrals, the BMA has claimed.

The schemes, which have …
THE RELATION OF BLOOD CHOLESTEROL AND THE SIZE OF PROSTATIC AND VESICULAR TRANSPLANTS IN THE ANTERIOR CHAMBER OF THE EYE
Authors: Robert A. Moore, J. J. Smith
Journal: The Journal of Experimental Medicine (1937)

In male rabbits, injections of the female sex hormone result in marked increase in the size of ocular transplants of the prostate and seminal vesicles and a correlated elevation of the blood cholesterol. Other hormones, which cause an increase in the size of the transplants, do not show this correlation. The ingestion of cholesterol with conspicuous increase of the blood cholesterol, has no effect on the size of the transplants.
Glucocorticoids induce senescence in primary human tenocytes by inhibition of sirtuin 1 and activation of the p53/p21 pathway: in vivo and in vitro evidence
Authors: Raewyn C Poulsen, Anna C Watts, Richard J Murphy, Sarah J Snelling, Andrew J Carr, Philippa A Hulley
Journal: Annals of the Rheumatic Diseases (2013)

Cellular senescence is an irreversible side effect of some pharmaceuticals which can contribute to tissue degeneration.To determine whether pharmaceutical glucocorticoids induce senescence in tenocytes.Features of senescence (β-galactosidase activity at pH 6 (SA-β-gal) and active mammalian/mechanistic target of rapamycin (mTOR) in cell cycle arrest) as well as the activity of the two main pathways leading to cell senescence were examined in glucocorticoid-treated primary human tenocytes. Evidence of senescence-inducing pathway induction in vivo was obtained using immunohistochemistry on tendon biopsy specimens taken before and 7 weeks after subacromial Depo-Medrone injection.Dexamethasone treatment of tenocytes resulted in an increased percentage of SA-βgal-positive cells. Levels of phosphorylated p70S6K did not decrease with glucocorticoid treatment indicating mTOR remained active. Increased levels of acetylated p53 as well as increased RNA levels of its pro-senescence effector p21 were evident in dexamethasone-treated tenocytes. Levels of the p53 deacetylase sirtuin 1 were lower in dexamethasone-treated cells compared with controls. Knockdown of p53 or inhibition of p53 activity prevented dexamethasone-induced senescence. Activation of sirtuin 1 either by exogenous overexpression or by treatment with resveratrol or low glucose prevented dexamethasone-induced senescence. Immunohistochemical analysis of tendon biopsies taken before and after glucocorticoid injection revealed a significant increase in the percentage of p53-positive cells (p=0.03). The percentage of p21-positive cells also tended to be higher post-injection (p=0.06) suggesting glucocorticoids activate the p53/p21 senescence-inducing pathway in vivo as well as in vitro.As cell senescence is irreversible in vivo, glucocorticoid-induced senescence may result in long-term degenerative changes in tendon tissue.