1,078 results on '"M. Costantini"'
Search Results
52. Nephrometry scores predicting value of Trifecta achievement in a multicenter analysis (ROSULA database) of Robotic Partial Nephrectomy for totally endophytic 'deep' renal masses
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G. Tuderti, R. Autorino, R. Mastroianni, A. Mari, U. Carbonara, L. Misuraca, U. Anceschi, A. Brassetti, M. Ferriero, A. Bove, M. Costantini, F. Porpiglia, J. Kaouk, C. Lau, I. Derweesh, K.H. Rha, R. Schiavina, A. Mottrie, M. Gallucci, and G. Simone more...
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Urology - Published
- 2022
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53. Age of First Exposure to Collision Sports Does Not Affect Patient Reported Outcomes in Women and Men Community Rugby Players
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Katherine J, Hunzinger, Jaclyn B, Caccese, Katelyn M, Costantini, C Buz, Swanik, and Thomas A, Buckley
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Adult ,Male ,Adolescent ,Age Factors ,Football ,Middle Aged ,Young Adult ,Athletic Injuries ,Quality of Life ,Humans ,Female ,Patient Reported Outcome Measures ,Brain Concussion ,Aged - Abstract
This study aimed to determine the relationship between age of first exposure (AFE) to repetitive head impacts through contact/collision sports and patient-reported outcomes in community rugby players.We recruited community rugby players older than 18 yr with at least 1 yr of contact rugby participation to complete an online survey. Participants completed the Brief Symptom Inventory-18 (BSI-18), Short-Form Health Survey 12 (SF-12), and Satisfaction with Life Scale (SWLS) via Qualtrics. We used generalized linear models to examine the association between AFE (continuous) and patient-reported outcomes by sex, while controlling for cumulative years contact/collision sport history, age, and concussion history (yes/no). In addition, we used Mann-Whitney U tests to compare patient-reported outcomes between AFE12 and AFE ≥12.A total of 1037 rugby players (31.6 ± 11.3 yr (range, 18-74 yr), 59.1% men) participated in this study. Whether analyzed continuously or dichotomously at age 12 yr, younger AFE was not associated with worse patient-reported outcomes for either men or women. Positive concussion history was a significant predictor of worse BSI-18 subscores, SF-12 subscores, and SWLS in women and worse BSI-18 subscores in men. Cumulative contact/collision sport history was a significant predictor of better BSI-18 Depression and SF-12 (Mental Component Summary) subscores in men only. In men and women, older age was a significant predictor of better BSI-18 Depression, Anxiety, and GSI subscores; better SWLS (in men only); and better SF-12 Mental Component Summary, but worse SF-12 (Physical Component Summary).Younger AFE to contact/collision sport is not associated with worse patient-reported outcomes in early adult rugby players. Concussion history was predictive of worse patient-reported outcomes. more...
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- 2021
54. Diagnosed concussion is associated with increased risk for lower extremity injury in community rugby players
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Thomas A. Buckley, Katelyn M. Costantini, Katherine J. Hunzinger, and C. Buz Swanik
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Adult ,Male ,medicine.medical_specialty ,Football ,Physical Therapy, Sports Therapy and Rehabilitation ,Logistic regression ,Odds ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Sex Factors ,Risk Factors ,Surveys and Questionnaires ,Concussion ,Injury prevention ,medicine ,Humans ,Orthopedics and Sports Medicine ,030212 general & internal medicine ,Brain Concussion ,Retrospective Studies ,business.industry ,Incidence (epidemiology) ,LOWER EXTREMITY INJURY ,030229 sport sciences ,Odds ratio ,medicine.disease ,Lower Extremity ,Athletic Injuries ,Musculoskeletal injury ,Physical therapy ,Female ,business - Abstract
To determine (1) the association between lifetime diagnosed concussion and lower extremity musculoskeletal injury (LE-MSI) among community rugby union players and (2) the sex specific risk of LE-MSI given concussion history among males and females.Retrospective survey.1037 (59.0% male, (612/1037), age: 31.6 ± 11.3 years) rugby players (10.1 ± 8.1 years played) completed an online survey to ascertain injury history. A chi-squared test of association was performed between concussion and LE-MSI; significant outcomes were followed-up with an odds ratio. A binary logistic regression with any LE-MSI (yes/no) as the outcome and concussion (yes/no) and sex (male/female) as predictors was performed to determine if there was a sex by concussion interaction.There was an overall significant association between concussion and any LE-MSI(χ(1) = 13.055, p 0.001, OR = 2.30 [95%CI: 1.45, 3.65]). Both male (OR = 2.21) and females (OR = 2.49) had significant associations for concussion and LE-MSI, but there were no differences between sex for risk of LE-MSI (RCommunity rugby players with a history of concussion are2× more likely to also experience an LE-MSI than those without a history of concussion. There were no differences in the odds of LE-MSI between males and females with a history of diagnosed concussion. In line with current World Rugby injury prevention programs, future research should aim to reduce LE-MSI incidence to maximize player safety and wellness through targeted injury prevention and teams should utilize a conservative return to play protocols following concussion. more...
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- 2020
55. Concussion history is associated with increased lower-extremity injury incidence in Reserve Officers' Training Corps cadets
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Katelyn M. Costantini, Thomas A. Buckley, Kara N. Radzak, Charles Buz Swanik, and Katherine J. Hunzinger
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medicine.medical_specialty ,Active duty ,biology ,Sports medicine ,Athletes ,business.industry ,Poison control ,030229 sport sciences ,General Medicine ,biology.organism_classification ,medicine.disease ,Occupational safety and health ,03 medical and health sciences ,0302 clinical medicine ,Injury prevention ,Concussion ,Musculoskeletal injury ,medicine ,Physical therapy ,business ,030217 neurology & neurosurgery - Abstract
IntroductionConcussions have been associated with an increased risk of lower-extremity musculoskeletal injury (LE-MSI) in athletes and US Army soldiers, creating an added economic, physical and social burden. Yet, there is a paucity of evidence on this relationship among Reserve Officers’ Training Corps (ROTC) cadets, a group which engages in activities with high-injury risk and will subsequently commission as active duty officers. This study aimed to examine the association between concussions and LE-MSI in ROTC cadets.Methods125 (83 were male) Army and Air Force ROTC cadets (19.8±2.0 years) from two large state universities’ Army and Air Force ROTC programmes participated in this study. Cadets completed a reliable injury history questionnaire to ascertain the following variables of interest: (1) any concussion history, (2) reported concussions, (3) undiagnosed concussions, and (4) potentially unrecognised concussion history and LE-MSI history (eg, ankle sprain, knee sprain or muscle strain). Data were analysed using a χ2test for association and binary logistic regression to determine ORs.ResultsCadets with any concussion history (n=42) had a significantly (p=0.035) higher association with LE-MSI (OR 2.47, 95% CI 1.05 to 5.83) than those without. Cadets who had a reported concussion (n=33) had a significantly (p=0.026) higher association with LE-MSI (OR 2.95, 95% CI 1.11 to 7.84) compared to cadets without.ConclusionsROTC cadets with a history of diagnosed concussion were more likely to have suffered an LE-MSI than cadets without a concussion history. ROTC cadre should be aware of this relationship and incorporate injury prevention protocols. more...
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- 2020
56. Bikes and bodies: ghost bike memorials as performances of mourning, warning, and protest
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Nicole M. Costantini
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History ,Literature and Literary Theory ,Visual Arts and Performing Arts ,Communication ,Social change ,Performative utterance ,Visual arts - Abstract
In this article, I explore the performative nature of ghost bike memorials across the United States. Ghost bikes, flat-white painted immobile bicycles, are installed roadside to mark the location o... more...
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- 2019
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57. Sentinel node biopsy versus elective neck dissection in early-stage oral cancer: a systematic review
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F M, Crocetta, C, Botti, C, Pernice, D, Murri, A, Castellucci, M, Menichetti, M, Costantini, F, Venturelli, M C, Bassi, and A, Ghidini
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Sentinel Lymph Node Biopsy ,Carcinoma, Squamous Cell ,Quality of Life ,Humans ,Neck Dissection ,Mouth Neoplasms ,Neoplasm Recurrence, Local - Abstract
To provide a summary of the evidence on the comparative effectiveness of two surgical treatment strategies, sentinel node biopsy (SNB) and elective neck dissection (END), in patients with T1-T2 oral cancer and clinically negative (cN0) neck, in terms of overall survival (OS), disease-free survival (DFS) and neck recurrence rates (NRRs).A systematic review was performed by including studies published up to April 2019. Meta-analysis was performed to compare NRRs between SNB and END. A narrative summary of the results was generated for OS, DFS and morbidity outcomes. The certainty of evidence was assessed according to the GRADE methodology.No randomized studies were retrieved. Five observational studies were included in the comparative effectiveness analysis and four observational studies were included in the comparative morbidity analysis. The pooled risk ratio showed no differences in NRRs between SNB and END (10.5% vs 11.6%; pooled RR 1.09; 95% CI 0.67-1.76). No differences in OS or DFS between the two treatments were found. SNB appears to be associated with a lower rate of postoperative complications and lower shoulder dysfunction than END. Conversely, the results of the quality of life (QoL) questionnaires are not sufficient to advocate a particular strategy.Our review highlights the lack of well conducted and randomized studies comparing SNB to END, leading to poor clinical evidence. Although our findings suggest no significant differences in OS, DFS and NRR between the two strategies, the certainty of our evidence is too low to make it useful for clinical decision making. more...
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- 2020
58. OC.11.3 LAPAROSCOPIC HELLER DOR IS AN EFFECTIVE TREATMENT FOR ESOPHAGEAL-GASTRIC JUNCTION OUTFLOW OBSTRUCTION
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R. Salvador, L. Provenzano, G. Nezi, G. Capovilla, L. Nicoletti, E.S. Pierobon, L. Moletta, M. Valmasoni, S. Merigliano, and M. Costantini
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Hepatology ,Gastroenterology - Published
- 2022
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59. T.01.10 THE LAPAROSCOPIC HELLER-DOR IS AN EFFECTIVE LONG-TERM TREATMENT FOR END-STAGE ACHALASIA
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G. Nezi, F. Forattini, F. Riccio, A. Vittori, L. Provenzano, G. Capovilla, L. Nicoletti, L. Moletta, E.S. Pierobon, G. Zanchettin, M. Valmasoni, S. Merigliano, M. Costantini, and R. Salvador
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Hepatology ,Gastroenterology - Published
- 2022
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60. Accesibilidad a ventanas ecocardiográficas transtorácicas intraoperatorias en cirugía abdominal bajo anestesia general
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Martín Carpinella and Mauro M. Costantini
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lcsh:RD78.3-87.3 ,transthoracic echocardiography ,Anesthesiology and Pain Medicine ,lcsh:Anesthesiology ,lcsh:R ,lcsh:Medicine ,Accessibility ,general anesthesia - Published
- 2018
61. Trans-arterial ICG delivery before purely off-clamp robot-assisted partial nephrectomy for totally endophytic renal tumors: mid-term outcomes
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A. Brassetti, U. Anceschi, A. Bove, M. Ferriero, L. Misuraca, R. Mastroianni, M. Costantini, and G. Simone
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Urology - Published
- 2021
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62. Long term oncologic outcomes of partial nephrectomy for cystic renal tumors: a propensity score matched-pair comparison of cystic versus clear cell carcinoma from a single center experience
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M. Ferriero, R. Mastroianni, G. Tuderti, M. Costantini, U. Anceschi, L. Misuraca, A. Brassetti, S. Guaglianone, A.M. Bove, M. Gallucci, and G. Simone
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Urology - Published
- 2021
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63. O89 TWENTY-FIVE YEARS OF LAPAROSCOPIC TREATMENT FOR ESOPHAGEAL ACHALASIA: OUR EXPERIENCE ON 1001 LAPAROSCOPIC HELLER-DOR OPERATIONS
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R Salvador, G Capovilla, L Provenzano, L Moletta, E Pierobon, L Nicoletti, G Nezi, M Valmasoni, S Merigliano, and M Costantini
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Gastroenterology ,General Medicine - Abstract
Background In the last decade of the past century, primary Laparoscopic Heller-Dor (LHD) for Achalasia progressively became the procedure of choice in the new millennium. The aim of this study was to assess the long-term outcome of LHD to treat Achalasia at a single high-volume institution during the past 25 years. Methods 1000 patients underwent LHD from 1992-2017 by 6 staff surgeons alternatively. Patients who had already been treated with surgical or endoscopic myotomy were ruled out. Symptoms were collected and scored using a detailed questionnaire; barium-swallow, endoscopy, manometry were performed, before and after surgery while, 24-hour pH monitoring were performed 6 months after surgery. Results LHD was the primary treatment for 1000 patients (M:F=536:464); the median age was 46 (IQR 36-54), 183 (18.3%) had a history of endoscopic treatments (pneumatic dilation or botox injections, or both). The surgical procedure was completed laparoscopically in all but 7 patients (0.7%) and there was one perioperative death for heart attack. There were 25 perforations (2.5%): 22 were recognized and repaired during the operation, 3 were detected by postoperative contrast swallow. The outcome was positive in 902 patients (90.2%). In patients who had a previous treatment the failures were 25/183 (13.7%) while in the primary treatment group the failures were 73/817 (8.9%) (p=0.055). All the 98 patients whose LHD failed subsequently underwent one or more endoscopic pneumatic dilations, which ameliorated their recurrent symptoms in all but 11 patients (10 of whom required reoperation). The overall success rate of the combination of LHD and endoscopic dilations (where necessary) was 98.4%. At univariate analysis, manometric pattern (p=0.001), sigmoid megaesophagus (p=0.003) and a chest pain score (p=0.002) were the only factors predictive of a positive final results. At multivariate analysis, these three factors were independently associated to good outcome. Postoperative 24-hour pH-monitoring was abnormal in 50/590 patients (8.5%) Two patients developed an esophageal cancer during the follow-up time. Conclusions In a university tertiary referral center LHD can durably relieve achalasia symptoms. Preoperative manometric pattern, a presence of a sigmoid esophagus and the chest pain score represent the strongest predictor of outcome. more...
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- 2019
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64. Experimental data demonstrating the effects of silver nanoparticles on basement membrane gene and protein expression in cultured colon, mammary and bronchial epithelia
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Lindsey M. Costantini, Denise K. Reaves, Jeffrey R. Enders, Jodie M. Fleming, Susan Yeyeodu, and Megan E. Martin
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Basement membrane ,Integrin ,TGF-Beta ,Epithelial cells ,lcsh:Computer applications to medicine. Medical informatics ,Focal adhesion ,Extracellular matrix ,03 medical and health sciences ,0302 clinical medicine ,Biochemistry, Genetics and Molecular Biology ,Gene expression ,medicine ,Extracellular ,lcsh:Science (General) ,030304 developmental biology ,Intracellular signalling pathway analysis ,0303 health sciences ,Multidisciplinary ,biology ,Chemistry ,Cell adhesion molecule ,Epithelium ,3. Good health ,Cell biology ,medicine.anatomical_structure ,biology.protein ,lcsh:R858-859.7 ,Silver nanoparticles ,030217 neurology & neurosurgery ,lcsh:Q1-390 - Abstract
This data article is related to the research article entitled “Silver nanoparticles alter epithelial basement membrane integrity, cell adhesion molecule expression and TGF-beta secretion”, available in the journal Nanomedicine: Nanotechnology, Biology, and Medicine [1]. This Data in Brief consists of data that describe changes in the expression of basement membrane (BM)-associated genes and proteins in three non-transformed epithelial cell lines following acute (6 h) and chronic (24 h plus 7-day chase) exposure to silver nanoparticles (AgNPs). Human BEAS2B (lung), MCF10AI (breast), and CCD-18Co (colon) cultured epithelia were analyzed for protein expression by LC-MS/MS and for gene expression by pathway-focused QRT-PCR arrays of 168 focal adhesion, integrin, and extracellular matrix (ECM) genes known to be localized to the plasma membrane, the BM/ECM, or secreted into the extracellular space. Ingenuity pathway analysis (IPA) of combined gene and protein expression datasets was then used to predict canonical pathways affected by AgNP exposure. Keywords: Silver nanoparticles, Epithelial cells, Basement membrane, Extracellular matrix, TGF-Beta, Intracellular signalling pathway analysis more...
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- 2019
65. Age Of First Exposure Does Not Affect Quality Of Life Outcomes In Community Rugby Players
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Katelyn M. Costantini, Katherine J. Hunzinger, C. Buz Swanik, Jaclyn B Caccese, and Thomas A. Buckley
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Gerontology ,Quality of life (healthcare) ,Physical Therapy, Sports Therapy and Rehabilitation ,Orthopedics and Sports Medicine ,Affect (psychology) ,Psychology - Published
- 2021
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66. Purely off-clamp robot-assisted partial nephrectomy for totally endophytic renal tumors: Surgical technique and mid-term outcomes of a single center series
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G. Tuderti, R. Mastroianni, U. Anceschi, S. D’Annunzio, L. Misuraca, M. Ferriero, A. Bove, A. Brassetti, M. Costantini, S. Guaglianone, M. Gallucci, and G. Simone
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Urology - Published
- 2021
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67. Age of First Exposure to Collision Sports Does Not Affect Quality of Life Outcomes in Community Rugby Players
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Katelyn M. Costantini, Thomas A. Buckley, Katie Hunzinger, and Charles Buz Swanik
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Computer-assisted web interviewing ,Affect (psychology) ,medicine.disease ,Quality of life ,Mann–Whitney U test ,medicine ,Anxiety ,Neurology (clinical) ,medicine.symptom ,Psychology ,Somatization ,Depression (differential diagnoses) ,Clinical psychology ,Cohort study - Abstract
ObjectiveTo determine the relationship between exposure to repetitive head impacts (RHI) through collision sports prior to the age of 12 and quality of life measures in community rugby players.BackgroundIt is suggested that RHI incurred before age 12 may be associated with later life neurologic impairments. However, research on age of first exposure (AFE) to collision sports and psychological outcomes has not be explored in rugby, a sport which participants often continue in community settings beyond college.Design/MethodsIndividuals over 18 years old who currently or previously played contact rugby completed an online questionnaire. To assess quality of life and psychological status, participants completed the Brief-Symptoms Inventory 18 (BSI-18), Short Form 12 (SF-12), and Satisfaction with Life Survey (SWLS). Participants were dichotomized into AFE to collision sports (12); AFE to rugby was not used since most participated in other collision sports prior to rugby. Data were not normally distributed; therefore, a Mann-Whitney U test was performed to compare outcomes between AFE groups.Results1,037 rugby players (31.6 + 11.3 years, 59.1% male) participated in this study. There were no significant differences between AFE 12 groups on all outcomes: BSI-18 Somatization (U = 97,286, p = 0.307), BSI-18 Depression (U = 100,267, p = 0.778), BSI-18 Anxiety (U = 98,851, p = 0.531), SF-12 Physical (U = 94,413, p = 0.241), SF-12 Mental (U = 96,517, p = 0.512), SWLS (U = 98,866, p = 0.537). Mean scores for all outcomes were: BSI-18 Somatization (2.33 + 2.99), BSI-18 Depression (4.20 + 4.91), BSI-18 Anxiety (3.32 + 3.75), SF-12 Physical (52.40 + 7.25), SF-12 Mental (46.20 + 11.45), SWLS (24.86 + 6.31).ConclusionsConsistent with recent cohort studies, there was no observed difference on three common measures of psychological well-being and quality of life in rugby players based upon AFE to collision sports. However, later life potential consequences of RHI in rugby players remains to be elucidated. more...
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- 2020
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68. No Sex Differences in Risk for Lower-Extremity Musculoskeletal Injury in Concussed Amateur Rugby Players
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Katie Hunzinger, Katelyn M. Costantini, Thomas A. Buckley, and Charles Buz Swanik
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education.field_of_study ,medicine.medical_specialty ,biology ,business.industry ,Athletes ,Population ,Odds ratio ,medicine.disease ,biology.organism_classification ,Logistic regression ,Test (assessment) ,Concussion ,Musculoskeletal injury ,Physical therapy ,Medicine ,Neurology (clinical) ,business ,education ,Amateur - Abstract
ObjectiveTo examine sex differences between concussion and lower-extremity musculoskeletal injury (LE-MSI) in community male and female rugby players.BackgroundThere is an ∼2x elevated risk of post-concussion subsequent MSI in high school through professional athletes. However, the effect of sex on risk is inconsistent and sparse, and rugby provides an ideal population as it’s the only collision sport with the same rules for both sexes.Design/Methods1,037 rugby players (31.6 + 11.3 years, 59.1% male), with at least one year of rugby playing experience, participated in this study, completing an online injury history questionnaire to ascertain concussion (yes/no) and LE-MSI (yes/no) history. A chi-squared test was performed to determine the association between concussion and any LE-MSI; significant findings were followed up with a post hoc odds ratio test. A binary logistic regression with any LE-MSI (yes/no) as the outcome and concussion (yes/no) and sex (male/female) as predictors was performed to determine if there was a sex by concussion interaction.ResultsThere was a significant association between concussion and any LE-MSI for all groups (Overall: ?(1) =13.06, p < 0.001, OR = 2.30 [95% CI: 1.45–3.65]; Males: ?(1) =7.43 p = 0.006, OR = 2.21 [95% CI: 1.24–3.96]; and Females: ?(1) = 5.78, p = 0.016, OR = 2.48 [95% CI: 1.16–5.31]). However, there were no differences for risk of LE-MSI between males and females (p = 0.99, R2 = 0.024).ConclusionsBoth male and female community rugby players had a 2x greater risk of LE-MSI, given a history of concussion compared to those without a history of concussion, which aligns with previous studies focused on collegiate athletes. However, there was no difference in risk of LE-MSI between sexes, contrary to smaller, but more controlled studies. Future research should investigate the potential physiological mechanisms for increased risk of LE-MSI. more...
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- 2020
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69. Raman investigation of ion irradiated TiC and ZrC
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S. Pellegrino, Lionel Thomé, E. Jouanny, P. Trocellier, Sandrine Miro, J-M. Costantini, CEA-Direction des Energies (ex-Direction de l'Energie Nucléaire) (CEA-DES (ex-DEN)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre de Sciences Nucléaires et de Sciences de la Matière (CSNSM), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), CEA-Direction de l'Energie Nucléaire (CEA-DEN), and Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Sud - Paris 11 (UP11) more...
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010302 applied physics ,[PHYS]Physics [physics] ,Nuclear and High Energy Physics ,Materials science ,Analytical chemistry ,02 engineering and technology ,021001 nanoscience & nanotechnology ,01 natural sciences ,Crystallographic defect ,Fluence ,Carbide ,Ion ,symbols.namesake ,0103 physical sciences ,symbols ,Irradiation ,Dislocation ,0210 nano-technology ,Raman spectroscopy ,Instrumentation ,Stoichiometry - Abstract
International audience; Single crystals of transition metal carbides from group IV, TiC 1-x and ZrC 1-x , have been irradiated at room temperature (RT) with 1.2 MeV gold ions for various fluences in the range 2 × 10 14 –3 × 10 16 ions/cm 2 and polycrystals for fluences between 2 × 10 13 and 4 × 10 15 ions/cm 2 . The irradiated samples were characterized by micro Raman spectroscopy. For this purpose, the evolution of main parameters of Raman spectra for both types of samples (band positions, shifts, and intensities, and optical over acoustical band area ratios) versus ion fluence are reported, and discussed. All acoustic and optical bands increase and broaden with fluence. Yet no amorphization is achieved under the highest fluence for both carbides. From the lowest fluence up to 10 15 ions/cm 2 , point defects like interstitials and vacancies are created. The increasing number of carbon vacancies involves a local variation in stoichiometry accompanied by carbon release. For fluence above 10 15 ions/cm 2 , extended defects like dislocation loops appear, as seen by TEM observations. more...
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- 2019
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70. Large-scale, cross-flow based isolation of highly pure and endocytosis-competent extracellular vesicles
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Jack D. Griffith, Dirk P. Dittmer, Blossom Damania, Carolina Caro-Vegas, Justin T. Landis, Lindsey M. Costantini, and Ryan P. McNamara
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0301 basic medicine ,Histology ,Chemistry ,lcsh:Cytology ,Size-exclusion chromatography ,Industrial scale ,Isolation procedures ,Cell Biology ,Tangential flow ,Extracellular vesicles ,Endocytosis ,03 medical and health sciences ,030104 developmental biology ,cross-flow ,Biophysics ,industrial scale ,Cell culture supernatant ,capto core ,tangential flow ,lcsh:QH573-671 ,Research Article - Abstract
Isolation of extracellular vesicles (EVs) from cell culture supernatant or plasma can be accomplished in a variety of ways. Common measures to quantify relative success are: concentration of the EVs, purity from non-EVs associated protein, size homogeneity and functionality of the final product. Here, we present an industrial-scale workflow for isolating highly pure and functional EVs using cross-flow based filtration coupled with high-molecular weight Capto Core size exclusion. Through this combination, EVs loss is kept to a minimum. It outperforms other isolation procedures based on a number of biochemical and biophysical assays. Moreover, EVs isolated through this method can be further concentrated down or directly immunopurified to obtain discreet populations of EVs. From our results, we propose that cross-flow/Capto Core isolation is a robust method of purifying highly concentrated, homogenous, and functionally active EVs from industrial-scale input volumes with few contaminants relative to other methods. more...
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- 2018
71. Cardiomyopathy Mutations in Metavinculin Disrupt Regulation of Vinculin-Induced F-Actin Assemblies
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Sharon L. Campbell, Lin Mei, Jack D. Griffith, Laura Yen, Nikolay V. Dokholyan, Andrey Krokhotin, Hyunna T. Lee, Muzaddid Sarker, Lindsey M. Costantini, Gregory M. Alushin, and Santiago Reyes
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Gene isoform ,Models, Molecular ,Conformational change ,Mutant ,Cardiomyopathy ,macromolecular substances ,Article ,03 medical and health sciences ,0302 clinical medicine ,Protein Domains ,Structural Biology ,medicine ,Animals ,Humans ,Point Mutation ,Protein Interaction Maps ,Cytoskeleton ,Molecular Biology ,Actin ,030304 developmental biology ,0303 health sciences ,biology ,Chemistry ,Point mutation ,Vinculin ,medicine.disease ,Actins ,Cell biology ,biology.protein ,Cardiomyopathies ,Chickens ,030217 neurology & neurosurgery ,Protein Binding - Abstract
Debilitating heart conditions, notably dilated and hypertrophic cardiomyopathies (CM), are associated with point mutations in metavinculin, a larger isoform of the essential cytoskeletal protein vinculin. Metavinculin is co-expressed with vinculin at sub-stoichiometric ratios in cardiac tissues. Cardiomyopathy mutations in the metavinculin tail domain (MVt) occur within the extra 68-residue insert that differentiates it from the vinculin tail domain (Vt). Vt binds actin filaments (F-actin) and promotes vinculin dimerization to bundle F-actin into thick fibers. While MVt binds to F-actin in a similar manner to Vt, MVt is incapable of F-actin bundling and inhibits Vt-mediated F-actin bundling. We performed F-actin co-sedimentation and negative-stain EM experiments to dissect the coordinated roles of metavinculin and vinculin in actin fiber assembly and the effects of three known metavinculin CM mutations. These CM mutants were found to weakly induce the formation of disordered F-actin assemblies. Notably, they fail to inhibit Vt mediated F-actin bundling, and instead promote formation of large assemblies embedded with linear bundles. Computational models of MVt bound to F-actin suggest that MVt undergoes a conformational change licensing the formation of a protruding sub-domain incorporating the insert, which sterically prevents dimerization and bundling of F-actin by Vt. Sub-domain formation is destabilized by CM mutations, disrupting this inhibitory mechanism. These findings provide new mechanistic insights into the ability of metavinculin to tune actin organization by vinculin and suggest that dysregulation of this process by CM mutants could underlie their malfunction in disease. more...
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- 2018
72. U.S. Navy Physical Readiness Test Modality Pilot Study
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Rebecca S. Weller, Andrew J. Ordille, Valerie M. Costantini, John J. Fraser, Douglas M. Jones, Trevor B. Viboch, Jay H. Heaney, Melissa D. Laird, Katherine M. Wilson, Aaron J. Wolf, Heath Clifford, and Dale A. Hirsch more...
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medicine.medical_specialty ,Modality (human–computer interaction) ,medicine ,U s navy ,Physical Therapy, Sports Therapy and Rehabilitation ,Orthopedics and Sports Medicine ,Medical physics ,Psychology ,Test (assessment) - Published
- 2019
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73. Nef Secretion into Extracellular Vesicles or Exosomes Is Conserved across Human and Simian Immunodeficiency Viruses
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Ryan P. McNamara, Lindsey M. Costantini, T. Alix Myers, Blake Schouest, Nicholas J. Maness, Jack D. Griffith, Blossom A. Damania, Andrew G. MacLean, Dirk P. Dittmer, and Vincent R. Racaniello
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0301 basic medicine ,Endosome ,viruses ,Cell ,exosomes ,Biology ,medicine.disease_cause ,Microbiology ,Gene Products, nef ,03 medical and health sciences ,0302 clinical medicine ,Virology ,medicine ,Animals ,Humans ,Secretion ,Cells, Cultured ,Immunodeficiency ,Nef ,HIV ,virus diseases ,Lipid bilayer fusion ,Simian immunodeficiency virus ,medicine.disease ,QR1-502 ,Microvesicles ,3. Good health ,Protein Transport ,030104 developmental biology ,medicine.anatomical_structure ,SIV ,Viral replication ,030220 oncology & carcinogenesis ,HIV-1 ,Macaca ,Simian Immunodeficiency Virus ,extracellular vesicles ,microvesicles ,Research Article - Abstract
Extracellular vesicles (EVs) or exosomes have been implicated in the pathophysiology of infections and cancer. The negative regulatory factor (Nef) encoded by simian immunodeficiency virus (SIV) and human immunodeficiency virus (HIV) plays a critical role in the progression to AIDS and impairs endosomal trafficking. Whether HIV-1 Nef can be loaded into EVs has been the subject of controversy, and nothing is known about the connection between SIV Nef and EVs. We find that both SIV and HIV-1 Nef proteins are present in affinity-purified EVs derived from cultured cells, as well as in EVs from SIV-infected macaques. Nef-positive EVs were functional, i.e., capable of membrane fusion and depositing their content into recipient cells. The EVs were able to transfer Nef into recipient cells. This suggests that Nef readily enters the exosome biogenesis pathway, whereas HIV virions are assembled at the plasma membrane. It suggests a novel mechanism by which lentiviruses can influence uninfected and uninfectable, i.e., CD4-negative, cells., IMPORTANCE Extracellular vesicles (EVs) transfer biologically active materials from one cell to another, either within the adjacent microenvironment or further removed. EVs also package viral RNAs, microRNAs, and proteins, which contributes to the pathophysiology of infection. In this report, we show that both human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) incorporate the virus-encoded Nef protein into EVs, including EVs circulating in the blood of SIV-infected macaques and that this presents a novel mechanism of Nef transfer to naive and even otherwise non-infectable cells. Nef is dispensable for viral replication but essential for AIDS progression in vivo. Demonstrating that Nef incorporation into EVs is conserved across species implicates EVs as novel mediators of the pathophysiology of HIV. It could help explain the biological effects that HIV has on CD4-negative cells and EVs could become biomarkers of disease progression. more...
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- 2018
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74. Engineering and exploitation of a fluorescent HIV-1 gp120 for live cell CD4 binding assays
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Harris Goldstein, Betsy C. Herold, Feng Guo, Steven C. Kennedy, Susan C. Irvin, Lindsey M. Costantini, and Erik L. Snapp
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CD4-Positive T-Lymphocytes ,Recombinant Fusion Proteins ,viruses ,Green Fluorescent Proteins ,HIV Infections ,HIV Envelope Protein gp120 ,Article ,Green fluorescent protein ,Diffusion ,Envelope ,Viral entry ,Virology ,Inhibitory antibody ,Humans ,Neutralizing antibody ,chemistry.chemical_classification ,biology ,Ligand binding assay ,virus diseases ,Fluorescent protein ,Molecular biology ,Fusion protein ,CD4 ,Superfolder GFP ,3. Good health ,Cell biology ,gp120 ,chemistry ,Cell Tracking ,HIV-1 ,FRAP ,biology.protein ,Receptors, Virus ,Laser scanning cytometry ,Antibody ,Genetic Engineering ,Glycoprotein ,Intracellular - Abstract
The HIV-1 envelope glycoprotein, gp120, binds the host cell receptor, CD4, in the initial step of HIV viral entry and infection. This process is an appealing target for the development of inhibitory drugs and neutralizing antibodies. To study gp120 binding and intracellular trafficking, we engineered a fluorescent fusion of the humanized gp120 JRFL HIV-1 variant and GFP. Gp120-sfGFP is glycosylated with human sugars, robustly expressed, and secreted from cultured human cells. Protein dynamics, quality control, and trafficking can be visualized in live cells. The fusion protein can be readily modified with different gp120 variants or fluorescent proteins. Finally, secreted gp120-sfGFP enables a sensitive and easy binding assay that can quantitatively screen potential inhibitors of gp120-CD4 binding on live cells via fluorescence imaging or laser scanning cytometry. This adaptable research tool should aid in studies of gp120 cell biology and the development of novel anti-HIV drugs. more...
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- 2015
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75. Hyaluronan: an overview
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F, Abbruzzese, F, Basoli, M, Costantini, S M, Giannitelli, M, Gori, P, Mozetic, A, Rainer, and M, Trombetta
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Drug Delivery Systems ,Tissue Engineering ,Osteoarthritis ,Humans ,Ophthalmologic Surgical Procedures ,Hyaluronic Acid ,Surgery, Plastic - Abstract
Hyaluronic acid (HA) is a polyanionic natural polymer occurring as a linear polysaccharide composed of glucuronic acid and N-acetylglucosamine repeats. Hyaluronic acid has a wide range of applications with its excellent physicochemical properties such as biodegradability, biocompatibility, non-toxicity, non-immunogenicity and serves as an excellent tool in biomedical applications such as osteoarthritis surgery, ocular surgery, plastic surgery, tissue engineering and drug delivery. This work provides an overview on hyaluronic acid, its chemistry and biochemistry and its medical applications. more...
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- 2017
76. Kaposi’s Sarcoma-Associated Herpesvirus Increases PD-L1 and Proinflammatory Cytokine Expression in Human Monocytes
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Kurtis M. Host, Sarah R. Jacobs, John A. West, Zhigang Zhang, Lindsey M. Costantini, Charles M. Stopford, Dirk P. Dittmer, Blossom Damania, and Michael J. Imperiale
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Gene Expression Regulation, Viral ,PD-L1 ,0301 basic medicine ,Chemokine ,T cell ,viruses ,medicine.disease_cause ,Microbiology ,B7-H1 Antigen ,Monocytes ,Viral Proteins ,03 medical and health sciences ,Immune system ,Kaposi’s sarcoma-associated herpesvirus ,Virology ,PD-1 ,Humans ,Medicine ,Kaposi's sarcoma-associated herpesvirus ,innate immunity ,Innate immune system ,biology ,business.industry ,virus diseases ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,human herpesvirus ,Immunity, Innate ,QR1-502 ,Up-Regulation ,Virus Latency ,3. Good health ,030104 developmental biology ,medicine.anatomical_structure ,Lytic cycle ,Herpesvirus 8, Human ,Host-Pathogen Interactions ,biology.protein ,Cancer research ,Cytokines ,Primary effusion lymphoma ,business ,Research Article - Abstract
Kaposi’s sarcoma-associated herpesvirus (KSHV) is associated with the human malignancy Kaposi’s sarcoma and the lymphoproliferative disorders primary effusion lymphoma and multicentric Castleman’s disease. KSHV establishes lytic infection of monocytes in vivo, which may represent an important cellular reservoir during KS disease progression. KS tumors consist of latently infected endothelial cells; however, lytic phase gene products are important for KS onset. Early KS lesion progression is driven by proinflammatory cytokines supplied by immune cell infiltrates including T cells and monocytes. KSHV-infected monocytes may supply the lytic viral products and the inflammatory milieu conducive to KS tumor progression. To establish successful infection, KSHV extensively modulates the host immune system. KSHV antigens activate both innate and adaptive immune responses including KSHV-specific T cells, but lifelong infection is still established. Programmed death ligand 1 (PD-L1) is a prosurvival cell surface protein that suppresses T-cell-mediated killing. PD-L1 is variably present on various tumor cells and is a targetable marker for cancer treatment. We show that KSHV infection of human monocytes increases PD-L1 expression and transcription in a dose-dependent manner. We also saw evidence of lytic gene expression in the KSHV-infected monocytes. Intact KSHV is needed for full PD-L1 response in human monocytes. KSHV induces a general proinflammatory cytokine milieu including interleukins 1α, 1β, and 6, which have been implicated in early KS lesion progression. KSHV-mediated PD-L1 increase may represent a novel mechanism of KSHV-mediated immune modulation to allow for virus survival and eventually malignant progression., IMPORTANCE KSHV is the etiologic agent of Kaposi’s sarcoma and the lymphoproliferative disorders primary effusion lymphoma and multicentric Castleman’s disease. Programmed death ligand 1 (PD-L1) is an immunosuppressive cell surface marker that inhibits T cell activation. We report that KSHV infection of primary human monocytes upregulates PD-L1 transcription and protein expression. Analysis of the cytokine and chemokine milieu following KSHV infection of monocytes revealed that KSHV induces interleukins 1α, 1β, and 6, all of which have been implicated in KS development. Our work has identified another potential immune evasion strategy for KSHV and a potential target for immunotherapy of KSHV-derived disease. more...
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- 2017
77. Distinct Binding Modes of Vinculin Isoforms Underlie Their Functional Differences
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Muzaddid Sarker, Sharon L. Campbell, Ernesto Alva Sevilla, Andrey Krokhotin, Jack D. Griffith, Lindsey M. Costantini, and Nikolay V. Dokholyan
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Models, Molecular ,Gene isoform ,Motility ,macromolecular substances ,Filamentous actin ,Article ,Protein Structure, Secondary ,03 medical and health sciences ,Transduction (genetics) ,Protein Domains ,Structural Biology ,Animals ,Molecular Biology ,Actin ,030304 developmental biology ,0303 health sciences ,Binding Sites ,biology ,Chemistry ,Point mutation ,C-terminus ,Cryoelectron Microscopy ,030302 biochemistry & molecular biology ,Vinculin ,Actins ,Cell biology ,Alternative Splicing ,Mutation ,biology.protein ,Protein Binding - Abstract
Vinculin and its splice isoform metavinculin play key roles in regulating cellular morphology, motility, and force transduction. Vinculin is distinct from metavinculin in its ability to bundle filamentous actin (F-actin). To elucidate the molecular basis for these differences, we employed computational and experimental approaches. Results from these analyses suggest that the C terminus of both vinculin and metavinculin form stable interactions with the F-actin surface. However, the metavinculin tail (MVt) domain contains a 68 amino acid insert, with helix 1 (H1) sequestered into a globular subdomain, which protrudes from the F-actin surface and prevents actin bundling by sterically occluding actin filaments. Consistent with our model, deletion and selective point mutations within the MVt H1 disrupt this protruding structure, and facilitate actin bundling similar to vinculin tail (Vt) domain. more...
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- 2019
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78. Silver nanoparticles alter epithelial basement membrane integrity, cell adhesion molecule expression, and TGF-β1 secretion
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Jodie M. Fleming, Susan Yeyeodu, Lindsey M. Costantini, Terrance J. Kavanagh, Breanna Jeffcoat, Diane Botta, Denise K. Reaves, Megan E. Martin, and Jeffrey R. Enders
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Silver ,Integrin ,Biomedical Engineering ,Metal Nanoparticles ,Pharmaceutical Science ,Medicine (miscellaneous) ,Bioengineering ,02 engineering and technology ,Basement Membrane ,Article ,Transforming Growth Factor beta1 ,Extracellular matrix ,Focal adhesion ,03 medical and health sciences ,Cell Line, Tumor ,medicine ,Humans ,Epithelial Physiology ,General Materials Science ,Cell adhesion ,030304 developmental biology ,Basement membrane ,0303 health sciences ,biology ,Chemistry ,Cell adhesion molecule ,CD44 ,021001 nanoscience & nanotechnology ,Cell biology ,medicine.anatomical_structure ,Gene Expression Regulation ,biology.protein ,Molecular Medicine ,0210 nano-technology ,Cell Adhesion Molecules - Abstract
Silver nanoparticles (AgNPs) are widely used in consumer and pharmaceutical products due to their antipathogenic properties. However, safety concerns have been raised due to their bioactive properties. While reports have demonstrated AgNPs can embed within the extracellular matrix, their effects on basement membrane (BM) production, integrin engagement, and tissue-integrity are not well-defined. This study analyzed the effects of AgNPs on BM production, composition and integrin/focal adhesion interactions in representative lung, esophageal, breast and colorectal epithelia models. A multidisciplinary approach including focused proteomics, QPCR arrays, pathway analyses, and immune-based, structural and functional assays was used to identify molecular and physiological changes in cell adhesions and the BM induced by acute and chronic AgNP exposure. Dysregulated targets included CD44 and transforming growth factor-beta, two proteins frequently altered during pathogenesis. Results indicate AgNP exposure interferes with BM and cell adhesion dynamics, and provide insight into the mechanisms of AgNP-induced disruption of epithelial physiology. more...
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- 2019
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79. Preliminary Concussion and Lower Extremity Injury Risk Among R.O.T.C. Cadets
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C. Buz Swanik, Kelsey Bryk, Thomas A. Buckley, Katelyn M. Costantini, and Katie Hunzinger
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medicine.medical_specialty ,Active duty ,biology ,Athletes ,business.industry ,Incidence (epidemiology) ,LOWER EXTREMITY INJURY ,biology.organism_classification ,medicine.disease ,Concussion ,Cohort ,medicine ,Cadet ,Musculoskeletal injury ,Physical therapy ,Neurology (clinical) ,business - Abstract
ObjectiveTo examine the association between concussions and lower extremity musculoskeletal injury (LE-MSI) rates in Reserve Officer Training Corps (ROTC) cadets.BackgroundConcussions have been associated with an increased risk for LE-MSI among high school, collegiate, and professional athletes as well as U.S. Army Soldiers. However, there is a paucity evidence on this relationship among U.S. Army ROTC cadets, future U.S. Army Officers, and a group similar to student-athletes in regards to physical activity levels.Design/MethodsA modified reliable injury questionnaire (ICC = 0.92) was used to identify the total number of reported concussions, intentionally unreported concussions, and potentially unrecognized concussions (e.g., memory loss not diagnosed as a concussion) as well as LE-MSI (e.g., muscle strains, ACL rupture) a cadet had suffered. A chi-square analysis was performed to identify the association between concussion and LE-MSI and any concussive injury and LE-MSI.Results47 cadets (19.9 ± 1.3 years) were recruited from one Army ROTC program. There was not a significant association between reported concussions and LE-MSI (Χ(1) = 3.122, p = 0.077). There was not a significant association between any concussive injury (reported, unreported, or potentially unrecognized) and LE-MSI (Χ(1) = 3.590, p = 0.058). The reported concussion history was 38.3% (18/47), any concussive history was 46.8% (22/47), and 68.1% (32/47) reported history of LE-MSI.ConclusionsPreliminary results showed that there was no statistically significant association between concussion and LE-MSI among ROTC cadets at this university. Future research is warranted on a larger cohort of cadets to determine if this relationship exists since cadets will soon commission, potentially risking injury while serving on active duty, causing limited duty days, reduced Department of Defense readiness, and increased healthcare costs. Cadets showed a high incidence of concussion and LE-MSK injury, and future research should target reducing these injuries among ROTC cadets prior to commissioning. more...
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- 2019
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80. Prognostic Impact of Diabetes and Prediabetes on Survival Outcomes in Patients With Chronic Heart Failure: A Post-Hoc Analysis of the GISSI-HF (Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca-Heart Failure) Trial
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Marco Dauriz, Giovanni Targher, Pier Luigi Temporelli, Donata Lucci, Lucio Gonzini, Gian Luigi Nicolosi, Roberto Marchioli, Gianni Tognoni, Roberto Latini, Franco Cosmi, Luigi Tavazzi, Aldo Pietro Maggioni, Simona Barlera, Maria Grazia Franzosi, Aldo P. Maggioni, Maurizio Porcu, Salim Yusuf, Fulvio Camerini, Jay N. Cohn, Adriano Decarli, Bertram Pitt, Peter Sleight, Philip A. Poole‐Wilson, Enrico Geraci, Marino Scherillo, Gianna Fabbri, Barbara Bartolomei, Daniele Bertoli, Franco Cobelli, Claudio Fresco, Antonietta Ledda, Giacomo Levantesi, Cristina Opasich, Franco Rusconi, Gianfranco Sinagra, Fabio Turazza, Alberto Volpi, Martina Ceseri, Gianluca Alongi, Antonio Atzori, Filippo Bambi, Desiree Bastarolo, Francesca Bianchini, Iacopo Cangioli, Vittoriana Canu, Concetta Caporusso, Gabriele Cenni, Laura Cintelli, Michele Cocchio, Alessia Confente, Eva Fenicia, Giorgio Friso, Marco Gianfriddo, Gianluca Grilli, Beatrice Lazzaro, Giuseppe Lonardo, Alessia Luise, Rachele Nota, Mariaelena Orlando, Rosaria Petrolo, Chiara Pierattini, Valeria Pierota, Alessandro Provenzani, Velia Quartuccio, Anna Ragno, Chiara Serio, Alvise Spolaor, Arianna Tafi, Elisa Tellaroli, Stefano Ghio, Elisa Ghizzardi, Serge Masson, Lella Crociati, Maria Teresa La Rovere, Ugo Corrà, Andrea Finzi, Marco Gorini, Valentina Milani, Giampietro Orsini, Elisa Bianchini, Silvia Cabiddu, Ilaria Cangioli, Laura Cipressa, Maria Lucia Cipressa, Giuseppina Di Bitetto, Barbara Ferri, Luisa Galbiati, Andrea Lorimer, Carla Pera, Paola Priami, Antonella Vasamì, T. Moccetti, M.G. Rossi, E. Pasotti, F. Vaghi, P. Roncarolo, M.T. Zunino, F. Matta, E. Actis Perinetto, F. Gaita, G. Azzaro, M. Zanetta, A.M. Paino, U. Parravicini, D. Vegis, R. Conte, P. Ferraro, A. De Bernardi, S. Morelloni, M. Fagnani, P. Greco Lucchina, L. Montagna, E. Bellone, D. Sappè, F. Ferraro, M. Delucchi, S.G. Reynaud, M. Dore, A. La Brocca, N. Massobrio, L. Bo, R. Trinchero, M. Imazio, G. Brocchi, A. Nejrotti, L. Rissone, S. Gabasio, C. Zocchi, S. Randazzo, A. Crenna, P. Giannuzzi, E. Bonanomi, A. Mezzani, M. De Marchi, G. Begliuomini, C.A. Gianonatti, A. Gavazzi, A. Grosu, L. Dei Cas, S. Nodari, P. Garyfallidis, A. Bertoletti, C. Bonifazi, S. Arisi, F. Mascaro, M. Fraccarollo, S. Dell'Orto, M. Sfolcini, F. Bortolini, D. Raccagni, A. Turelli, M. Santarone, E. Miglierina, L. Sormani, R. Jemoli, F. Tettamanti, S. Pirelli, C. Bianchi, S. Verde, M. Mariani, V. Ziacchi, A. Ferrazza, A. Russo, M. Bortolotti, G.F. Pasini, A. Volpi, K.N. Jones, D. Cuzzucrea, G. Gullace, C. Carbone, A. Granata, S. De Servi, G. Del Rosso, C. Inserra, E. Renaldini, C. Zappa, M. Moretti, R. Zanini, M. Ferrari, E. Moroni, A. Cei, C. Lissi, E. Dovico, C. Fiorentini, P. Palermo, B. Brusoni, M. Negrini, J. Heyman, G.B. Danzi, A. Finzi, M. Frigerio, F. Turazza, L. Beretta, A. Sachero, F. Casazza, L. Squadroni, F. Lombardi, L. Marano, A. Margonato, G. Fragasso, O.C. Febo, E. Aiolfi, F. Olmetti, A. Grieco, V. Antonazzo, G. Specchia, A. Mortara, F. Robustelli, M.G. Songini, C. Schweiger, A. Frisinghelli, M. Palvarini, C. Campana, L. Scelsi, N. Ajmone Marsan, F. Cobelli, A. Gualco, C. Opasich, S. De Feo, R. Mazzucco, M.A. Iannone, T. Diaco, D. Zaniboni, G. Milanesi, D. Nassiacos, S. Meloni, P. Giani, T. Nicoli, C. Malinverni, A. Gusmini, L. Pozzoni, G. Bisiani, P. Margaroli, A. Schizzarotto, A. Daverio, G. Occhi, N. Partesana, P. Bandini, M.G. Rosella, S. Giustiniani, G. Cucchi, R. Pedretti, R. Raimondo, R. Vaninetti, A. Fedele, I. Ghezzi, E. Rezzonico, J.A. Salerno Uriarte, F. Morandi, F. Salvucci, C. Valenti, G. Graziano, M. Romanò, C. Cimminiello, I. Mangone, M. Lombardo, P. Quorso, G. Marinoni, M. Breghi, M. Erckert, A. Dienstl, G. Mirante Marini, C. Stefenelli, G. Cioffi, E. Buczkowska, A. Bonanome, F. Bazzanini, L. Parissenti, C. Serafini, G. Catania, L. Tarantini, G. Rigatelli, S. Boni, A. Pasini, E. Masini, A.A. Zampiero, M. Zanchetta, L. Franceschetto, P. Delise, C. Marcon, A. Sacchetta, L. Borgese, L. Artusi, P. Casolino, F. Corbara, A. Banzato, M. Barbiero, M.P. Aldegheri, R. Bazzucco, G. Crivellenti, A. Raviele, C. Zanella, P. Pascotto, P. Sarto, S. Milan, E. Barbieri, P. Girardi, W. Dalla Villa, J. Dalle Mule, M.L. Di Sipio, R. Cazzin, D. Milan, P. Zonzin, M. Carraro, R. Rossi, E. Carbonieri, I. Rossi, P. Stritoni, P. Meneghetti, G. Risica, P.L. Tenderini, C. Vassanelli, L. Zanolla, G. Perini, G. Brighetti, R. Chiozza, G. Giuliano, R. Gortan, R. Cesanelli, G.L. Nicolosi, R. Piazza, L. Mos, O. Vriz, D. Pavan, G. Pascottini, E. Alberti, M. Werren, L. Solinas, G. Sinagra, F. Longaro, P. Fioretti, M.C. Albanese, D. Miani, R. Gianrossi, A. Pende, P. Rubartelli, O. Magaia, S. Domenicucci, D. Caruso, A.S. Faraguti, L. Magliani, F. Miccoli, G. Guglielmino, D. Bertoli, A. Cantarelli, S. Orlandi, A. Vallebona, A. Pozzati, G. Brega, L.G. Pancaldi, R. Vandelli, S. Urbinati, M.G. Poci, M. Zoli, G.M. Costa, U. Guiducci, G. Zobbi, F. Tartagni, A. Tisselli, A. Gentili, P. Pieri, E. Cagnetta, S. Bendinelli, A. Barbieri, R. Conti, R. Ferrari, F. Merlini, A. Fucili, P. Moruzzi, E. Buia, M. Galvani, D. Ferrini, G. Baggioni, P. Yiannacopulu, G. Canè, A. Bonfiglioli, R. Zandomeneghi, L. Brugioni, A. Giannini, R. Di Ruvo, M. Giuliani, L. Rusconi, P. Del Corso, G. Piovaccari, F. Bologna, P. Venturi, F. Melandri, E. Bagni, L. Bolognese, R. Perticucci, A. Zuppiroli, M. Nannini, N. Consoli, P. Petrone, C. Pipitò, L. Colombi, D. Bernardi, P.R. Mariani, R. Testa, F. Mazzinghi, F. Cosmi, D. Cosmi, A. Zipoli, A. Cecchi, G. Castelli, M. Ciaccheri, F. Mori, F. Pieri, P. Valoti, D. Chiarantini, G.M. Santoro, C. Minneci, F. Marchi, M. Milli, G. Zambaldi, A.A. Brandinelli Geri, M. Cipriani, M. Alessandri, S. Severi, S. Stefanelli, A. Comella, R. Poddighe, A. Digiorgio, M. Carluccio, S. Berti, A. Rizza, V. Bonatti, V. Molendi, A. Brancato, N. D'Aprile, G. Giappichini, S. Del Vecchio, G. Mantini, F. De Tommasi, G. Meucci, M. Cordoni, S. Bechi, L. Barsotti, P. Baldini, M. Romei, G. Scopelliti, G. Lauri, F. Pestelli, F. Furiozzi, M. Cocchieri, D. Severini, F. Patriarchi, P. Chiocchi, M. Buccolieri, S. Martinelli, A. Wee, F. Angelici, M. Bernardinangeli, G. Proietti, B. Biscottini, R. Panciarola, L. Marinacci, G.P. Perna, D. Gabrielli, A. Moraca, L. Moretti, L. Partemi, G. Gregori, R. Amici, G. Patteri, P. Capone, E. Savini, G.L. Morgagni, L. Paccaloni, F. Pezzuoli, S. Carincola, S. Papi, S. De Crescentini, P. Gerardi, P. Midi, E. Gallenzi, G. Pajes, C. Mancone, V. Di Spirito, M. Di Gennaro, S. Calcagno, S. Toscano, S. Antonicoli, F. Carta, G. Giorgi, F. Comito, E. Daniele, O. Ciarla, P.G. Gelfo, A. Acquaviva, D. Testa, G. Testa, F.A. Pagliaro, F. Russo, F. Vetta, I. Marchese, G. Di Sciascio, A. D'Ambrosio, F. Leggio, D. Del Sindaco, A. Lacchè, A. Avallone, M.P. Risa, P. Azzolini, E. Baldo, E. Giovannini, G. Pulignano, C. Tondo, E. Picchio, E. ani, P. Tanzi, F. Pozzar, F. Farnetti, M. Azzarito, M. Santini, A. Varveri, G. Ferraiuolo, C. Valtorta, A. Gaspardone, G. Barbato, V. Ceci, N. Aspromonte, F. Bellocci, C. Colizzi, F. Fedele, F.I. Perez, A. Galati, A. Rossetti, A. Mainella, D. etta, C. Matteucci, G. Busi, A. De Angelis, G. Farina, A. Granatelli, F. Leone, F. Frasca, R. Di Giovambattista, G. Castellani, G. Massaro, G. Mastrogiuseppe, A. Vacri, F. De Sanctis, M. Cioli, S. Di Luzio, C. Napoletano, L.L. Piccioni, G. De Simone, A. Ottaviano, V. Mazza, C. Spedaliere, D. Staniscia, E. Calgione, G. De Marco, T. Chiacchio, T. Di Napoli, S. Romanzi, G. Salvatore, P. Golino, A. Palermo, F. Mascia, A. Vetrano, A. Vinciguerra, L. Caliendo, R. Longobardi, G. De Caro, R. Di Nola, F. Piemonte, D. Prinzi, P. De Rosa, V. De Rosa, F. Riello, V. Capuano, G. Vecchio, M. Landi, S. Amato, M. Garofalo, M. D'Avino, P. Sensale, O. Maiolica, R. Santoro, P. Caso, D. Miceli, N. Maurea, U. Bianchi, C. Crispo, M. Chiariello, P. Perrone Filardi, L. Russo, N. Capuano, G. Ungaro, G. Vergara, F. Scafuro, G. D'Angelo, C. Campaniello, P. Bottiglieri, A. Volpe, R. Battista, L. De Risi, G. Cardillo, G. Sibilio, A.P. Marino, F. Silvestri, P. Predotti, A. Iervoglini, C. De Matteis, P. Sarnicola, M.M. Matarazzo, S. Baldi, V. Iuliano, C. Astarita, P. Cuccaro, A. Liguori, G. Liguori, G. Gregorio, L. Petraglia, G. Antonelli, G. Amodio, I. De Luca, D. Traversa, G. Franchini, M.L. Lenti, D. Cavallari, C. D'Agostino, G. Scalera, C.M. Altamura, M. Russo, A.R. Mascolo, G. Pettinati, S.A. Ciricugno, D. Scrutinio, A. Passantino, D. Mastrangelo, A. Di Masi, R. De Carne, M. Cannone, F. Dibiase, M. Pensato, F. Loliva, F. Trapani, I. Panettieri, L. Leone, M. Di Biase, M. Carrone, V. Gallone, F. Cocco, M. Costantini, C. Tritto, F. Cavalieri, L. Stella, F. Magliari, M. Callerame, A. De Giorgi, L. Pellegrino, M. Correra, V. Portulano, G.L. Nisi, G. Grassi, E. Cristallo, D. De Laura, C. Salerno, R. Fanelli, M. Villella, S. Pede, A. Renna, E. De Lorenzi, L. Urso, V. Lenti, A. Peluso, N. Baldi, G. Polimeni, P. Palma, R. Lauletta, E. Tagliamonte, T. Cirillo, B. Silvestri, G. Centonze, B. D'Alessandro, L. Truncellito, D. Mecca, M.A. Petruzzi, R.O.M. Coviello, A. Lopizzo, M. telli, S. Barbuzzi, S. Gubelli, G. Germinario, N. Cosentino, A. Mingrone, R. Vico, G. Borrello, M.L. Mazza, R. Cimino, D. Galasso, F. Cassadonte, U. Talarico, F. Perticone, S. Cassano, F. Catapano, S. Calemme, E. Feraco, C. Cloro, G. Misuraca, R. Caporale, L. Vigna, V. Spagnuolo, F. De Rosa, G. Spadafora, G. Zampaglione, R. Russo, F.A. Schipani, A.F. Ferragina, D. Stranieri, G. Musca, C. Carpino, P. Bencardino, F. Raimondo, D. Musacchio, G. Pulitanò, A. Ruggeri, A. Provenzano, S. Salituri, M. Musolino, S. Calandruccio, A. Marrari, E. Tripodi, R. Scali, L. Anastasio, A. Arone, P. Aragona, L. Donnangelo, M.G.A. Comito, F. Bilotta, I. Vaccaro, R. Rametta, V. Ventura, A. Bonvegna, A. Alì, C. Cinnirella, M. Raineri, F. Pompeo, N. Cascio Ingurgio, V. Carini, R. Coco, G. Giunta, G. Leonardi, V. Randazzo, V. Di Blasi, C. Tamburino, G. Russo, S. Mangiameli, R. Cardillo, D. Castelli, V. Inserra, A. Arena, M.M. Gulizia, S. Raciti, G. Rapisarda, R. Romano, P. Prestifilippo, G.B. Braschi, G. Ledda, R. Terrazzino, M. De Caro, G. Scilabra, B. agnino, R. Grassi, G. Di Tano, G.F. Scimone, L. Vasquez, C. Coppolino, A. Casale, M. Castelli, G. D'Urso, E. D'Antonio, L. Lo Presti, E. Badalamenti, P. Conti, N. Sanfilippo, V. Cirrincione, M.T. Cinà, G. Cusimano, A. Taormina, P. Giuliano, A. Bajardi, V. Mandalà, A. Canonico, G. Geraci, F.P. Sabella, F. Enia, A.M. Floresta, I. Lo Cascio, D. Gumina, A. Cavallaro, G. Piccione, R. Ferrante, M. Blandino, M.S. Iudicello, E. Mossuti, G. Romano, L. Lombardo, P. Monastra, D. Di Vincenzo, M. Porcu, P. Orrù, F. Muscas, G. Giardina, M. Corda, G. Locci, A. Podda, M. Ledda, P. Siddi, C. Lai, G. Pili, G. Mercuro, G. Mureddu, A. Ganau, G. Meloni, G. Poddighe, G. Sanna, Dauriz, Marco, Targher, Giovanni, Temporelli, Pier Luigi, Lucci, Donata, Gonzini, Lucio, Nicolosi, Gian Luigi, Marchioli, Roberto, Tognoni, Gianni, Latini, Roberto, Cosmi, Franco, Tavazzi, Luigi, Maggioni, Aldo Pietro, on behalf of the GISSI-HF, Investigator, Margonato, Alberto, Moccetti, T., Rossi, M. G., Pasotti, E., Vaghi, F., Roncarolo, P., Zunino, M. T., Matta, F., Actis Perinetto, E., Gaita, F., Azzaro, G., Zanetta, M., Paino, A. M., Parravicini, U., Vegis, D., Conte, R., Ferraro, P., De Bernardi, A., Morelloni, S., Fagnani, M., Greco Lucchina, P., Montagna, L., Bellone, E., Sappè, D., Ferraro, F., Delucchi, M., Reynaud, S. G., Dore, M., La Brocca, A., Massobrio, N., Bo, L., Trinchero, R., Imazio, M., Brocchi, G., Nejrotti, A., Rissone, L., Gabasio, S., Zocchi, C., Randazzo, S., Crenna, A., Giannuzzi, P., Bonanomi, E., Mezzani, A., De Marchi, M., Begliuomini, G., Gianonatti, C. A., Gavazzi, A., Grosu, A., Dei Cas, L., Nodari, S., Garyfallidis, P., Bertoletti, A., Bonifazi, C., Arisi, S., Mascaro, F., Fraccarollo, M., Dell'Orto, S., Sfolcini, M., Bortolini, F., Raccagni, D., Turelli, A., Santarone, M., Miglierina, E., Sormani, L., Jemoli, R., Tettamanti, F., Pirelli, S., Bianchi, C., Verde, S., Mariani, M., Ziacchi, V., Ferrazza, A., Russo, A., Bortolotti, M., Pasini, G. F., Volpi, A., Jones, K. N., Cuzzucrea, D., Gullace, G., Carbone, C., Granata, A., De Servi, S., Del Rosso, G., Inserra, C., Renaldini, E., Zappa, C., Moretti, M., Zanini, R., Ferrari, M., Moroni, E., Cei, A., Lissi, C., Dovico, E., Fiorentini, C., Palermo, P., Brusoni, B., Negrini, M., Heyman, J., Danzi, G. B., Finzi, A., Frigerio, M., Turazza, F., Beretta, L., Sachero, A., Casazza, F., Squadroni, L., Lombardi, F., Marano, L., Margonato, A., Fragasso, G., Febo, O. C., Aiolfi, E., Olmetti, F., Grieco, A., Antonazzo, V., Specchia, G., Mortara, A., Robustelli, F., Songini, M. G., Schweiger, C., Frisinghelli, A., Palvarini, M., Campana, C., Scelsi, L., Ajmone Marsan, N., Cobelli, F., Gualco, A., Opasich, C., De Feo, S., Mazzucco, R., Iannone, M. A., Diaco, T., Zaniboni, D., Milanesi, G., Nassiacos, D., Meloni, S., Giani, P., Nicoli, T., Malinverni, C., Gusmini, A., Pozzoni, L., Bisiani, G., Margaroli, P., Schizzarotto, A., Daverio, A., Occhi, G., Partesana, N., Bandini, P., Rosella, M. G., Giustiniani, S., Cucchi, G., Pedretti, R., Raimondo, R., Vaninetti, R., Fedele, A., Ghezzi, I., Rezzonico, E., Salerno Uriarte, J. A., Morandi, F., Salvucci, F., Valenti, C., Graziano, G., Romanò, M., Cimminiello, C., Mangone, I., Lombardo, M., Quorso, P., Marinoni, G., Breghi, M., Erckert, M., Dienstl, A., Mirante Marini, G., Stefenelli, C., Cioffi, G., Buczkowska, E., Bonanome, A., Bazzanini, F., Parissenti, L., Serafini, C., Catania, G., Tarantini, L., Rigatelli, G., Boni, S., Pasini, A., Masini, E., Zampiero, A. A., Zanchetta, M., Franceschetto, L., Delise, P., Marcon, C., Sacchetta, A., Borgese, L., Artusi, L., Casolino, P., Corbara, F., Banzato, A., Barbiero, M., Aldegheri, M. P., Bazzucco, R., Crivellenti, G., Raviele, A., Zanella, C., Pascotto, P., Sarto, P., Milan, S., Barbieri, E., Girardi, P., Dalla Villa, W., Dalle Mule, J., Di Sipio, M. L., Cazzin, R., Milan, D., Zonzin, P., Carraro, M., Rossi, R., Carbonieri, E., Rossi, I., Stritoni, P., Meneghetti, P., Risica, G., Tenderini, P. L., Vassanelli, C., Zanolla, L., Perini, G., Brighetti, G., Chiozza, R., Giuliano, G., Baldin, M. G., Gortan, R., Cesanelli, R., Nicolosi, G. L., Piazza, R., Mos, L., Vriz, O., Pavan, D., Pascottini, G., Alberti, E., Werren, M., Solinas, L., Sinagra, G., Longaro, F., Fioretti, P., Albanese, M. C., Miani, D., Gianrossi, R., Pende, A., Rubartelli, P., Magaia, O., Domenicucci, S., Caruso, D., Faraguti, A. S., Magliani, L., Miccoli, F., Guglielmino, G., Bertoli, D., Cantarelli, A., Orlandi, S., Vallebona, A., Pozzati, A., Brega, G., Pancaldi, L. G., Vandelli, R., Urbinati, S., Poci, M. G., Zoli, M., Costa, G. M., Guiducci, U., Zobbi, G., Tartagni, F., Tisselli, A., Gentili, A., Pieri, P., Cagnetta, E., Bendinelli, S., Barbieri, A., Conti, R., Ferrari, R., Merlini, F., Fucili, A., Moruzzi, P., Buia, E., Galvani, M., Ferrini, D., Baggioni, G., Yiannacopulu, P., Canè, G., Bonfiglioli, A., Zandomeneghi, R., Brugioni, L., Giannini, A., Di Ruvo, R., Giuliani, M., Rusconi, L., Del Corso, P., Piovaccari, G., Bologna, F., Venturi, P., Melandri, F., Bagni, E., Bolognese, L., Perticucci, R., Zuppiroli, A., Nannini, M., Consoli, N., Petrone, P., Pipitò, C., Colombi, L., Bernardi, D., Mariani, P. R., Testa, R., Mazzinghi, F., Cosmi, F., Cosmi, D., Zipoli, A., Cecchi, A., Castelli, G., Ciaccheri, M., Mori, F., Pieri, F., Valoti, P., Chiarantini, D., Santoro, G. M., Minneci, C., Marchi, F., Milli, M., Zambaldi, G., Brandinelli Geri, A. A., Cipriani, M., Alessandri, M., Severi, S., Stefanelli, S., Comella, A., Poddighe, R., Digiorgio, A., Carluccio, M., Berti, S., Rizza, A., Bonatti, V., Molendi, V., Brancato, A., D'Aprile, N., Giappichini, G., Del Vecchio, S., Mantini, G., De Tommasi, F., Meucci, G., Cordoni, M., Bechi, S., Barsotti, L., Baldini, P., Romei, M., Scopelliti, G., Lauri, G., Pestelli, F., Furiozzi, F., Cocchieri, M., Severini, D., Patriarchi, F., Chiocchi, P., Buccolieri, M., Martinelli, S., Wee, A., Angelici, F., Bernardinangeli, M., Proietti, G., Biscottini, B., Panciarola, R., Marinacci, L., Perna, G. P., Gabrielli, D., Moraca, A., Moretti, L., Partemi, L., Gregori, G., Amici, R., Patteri, G., Capone, P., Savini, E., Morgagni, G. L., Paccaloni, L., Pezzuoli, F., Carincola, S., Papi, S., De Crescentini, S., Gerardi, P., Midi, P., Gallenzi, E., Pajes, G., Mancone, C., Di Spirito, V., Di Gennaro, M., Calcagno, S., Toscano, S., Antonicoli, S., Carta, F., Giorgi, G., Comito, F., Daniele, E., Ciarla, O., Gelfo, P. G., Acquaviva, A., Testa, D., Testa, G., Pagliaro, F. A., Russo, F., Vetta, F., Marchese, I., Di Sciascio, G., D'Ambrosio, A., Leggio, F., Del Sindaco, D., Lacchè, A., Avallone, A., Risa, M. P., Azzolini, P., Baldo, E., Giovannini, E., Pulignano, G., Tondo, C., Picchio, E., Biffani, E., Tanzi, P., Pozzar, F., Farnetti, F., Azzarito, M., Santini, M., Varveri, A., Ferraiuolo, G., Valtorta, C., Gaspardone, A., Barbato, G., Ceci, V., Aspromonte, N., Bellocci, F., Colizzi, C., Fedele, F., Perez, F. I., Galati, A., Rossetti, A., Mainella, A., Ciuffetta, D., Matteucci, C., Busi, G., De Angelis, A., Farina, G., Granatelli, A., Leone, F., Frasca, F., Di Giovambattista, R., Castellani, G., Massaro, G., Mastrogiuseppe, G., Vacri, A., De Sanctis, F., Cioli, M., Di Luzio, S., Napoletano, C., Piccioni, L. L., De Simone, G., Ottaviano, A., Mazza, V., Spedaliere, C., Staniscia, D., Calgione, E., De Marco, G., Chiacchio, T., Di Napoli, T., Romanzi, S., Salvatore, G., Golino, P., Palermo, A., Mascia, F., Vetrano, A., Vinciguerra, A., Caliendo, L., Longobardi, R., De Caro, G., Di Nola, R., Piemonte, F., Prinzi, D., De Rosa, P., De Rosa, V., Riello, F., Capuano, V., Vecchio, G., Landi, M., Amato, S., Garofalo, M., D'Avino, M., Sensale, P., Maiolica, O., Santoro, R., Caso, P., Miceli, D., Maurea, N., Bianchi, U., Crispo, C., Chiariello, M., Perrone Filardi, P., Russo, L., Capuano, N., Ungaro, G., Vergara, G., Scafuro, F., D'Angelo, G., Campaniello, C., Bottiglieri, P., Volpe, A., Battista, R., De Risi, L., Cardillo, G., Sibilio, G., Marino, A. P., Silvestri, F., Predotti, P., Iervoglini, A., De Matteis, C., Sarnicola, P., Matarazzo, M. M., Baldi, S., Iuliano, V., Astarita, C., Cuccaro, P., Liguori, A., Liguori, G., Gregorio, G., Petraglia, L., Antonelli, G., Amodio, G., De Luca, I., Traversa, D., Franchini, G., Lenti, M. L., Cavallari, D., D'Agostino, C., Scalera, G., Altamura, C. M., Russo, M., Mascolo, A. R., Pettinati, G., Ciricugno, S. A., Scrutinio, D., Passantino, A., Mastrangelo, D., Di Masi, A., De Carne, R., Cannone, M., Dibiase, F., Pensato, M., Loliva, F., Trapani, F., Panettieri, I., Leone, L., Di Biase, M., Carrone, M., Gallone, V., Cocco, F., Costantini, M., Tritto, C., Cavalieri, F., Stella, L., Magliari, F., Callerame, M., De Giorgi, A., Pellegrino, L., Correra, M., Portulano, V., Nisi, G. L., Grassi, G., Cristallo, E., De Laura, D., Salerno, C., Fanelli, R., Villella, M., Pede, S., Renna, A., De Lorenzi, E., Urso, L., Lenti, V., Peluso, A., Baldi, N., Polimeni, G., Palma, P., Lauletta, R., Tagliamonte, E., Cirillo, T., Silvestri, B., Centonze, G., D'Alessandro, B., Truncellito, L., Mecca, D., Petruzzi, M. A., Coviello, R. O. M., Lopizzo, A., Chiaffitelli, M., Barbuzzi, S., Gubelli, S., Germinario, G., Cosentino, N., Mingrone, A., Vico, R., Borrello, G., Mazza, M. L., Cimino, R., Galasso, D., Cassadonte, F., Talarico, U., Perticone, F., Cassano, S., Catapano, F., Calemme, S., Feraco, E., Cloro, C., Misuraca, G., Caporale, R., Vigna, L., Spagnuolo, V., De Rosa, F., Spadafora, G., Zampaglione, G., Russo, R., Schipani, F. A., Ferragina, A. F., Stranieri, D., Musca, G., Carpino, C., Bencardino, P., Raimondo, F., Musacchio, D., Pulitanò, G., Ruggeri, A., Provenzano, A., Salituri, S., Musolino, M., Calandruccio, S., Marrari, A., Tripodi, E., Scali, R., Anastasio, L., Arone, A., Aragona, P., Donnangelo, L., Comito, M. G. A., Bilotta, F., Vaccaro, I., Rametta, R., Ventura, V., Bonvegna, A., Alì, A., Cinnirella, C., Raineri, M., Pompeo, F., Cascio Ingurgio, N., Carini, V., Coco, R., Giunta, G., Leonardi, G., Randazzo, V., Di Blasi, V., Tamburino, C., Russo, G., Mangiameli, S., Cardillo, R., Castelli, D., Inserra, V., Arena, A., Gulizia, M. M., Raciti, S., Rapisarda, G., Romano, R., Prestifilippo, P., Braschi, G. B., Ledda, G., Terrazzino, R., De Caro, M., Scilabra, G., Graffagnino, B., Grassi, R., Di Tano, G., Scimone, G. F., Vasquez, L., Coppolino, C., Casale, A., Castelli, M., D'Urso, G., D'Antonio, E., Lo Presti, L., Badalamenti, E., Conti, P., Sanfilippo, N., Cirrincione, V., Cinà, M. T., Cusimano, G., Taormina, A., Giuliano, P., Bajardi, A., Mandalà, V., Canonico, A., Geraci, G., Sabella, F. P., Enia, F., Floresta, A. M., Lo Cascio, I., Gumina, D., Cavallaro, A., Piccione, G., Ferrante, R., Blandino, M., Iudicello, M. S., Mossuti, E., Romano, G., Lombardo, L., Monastra, P., Di Vincenzo, D., Porcu, M., Orrù, P., Muscas, F., Giardina, G., Corda, M., Locci, G., Podda, A., Ledda, M., Siddi, P., Lai, C., Pili, G., Mercuro, G., Mureddu, G., Ganau, A., Meloni, G., Poddighe, G., Sanna, G., Barlera, Simona, Franzosi, Maria Grazia, Porcu, Maurizio, Yusuf, Salim, Camerini, Fulvio, Cohn, Jay N., Decarli, Adriano, Pitt, Bertram, Sleight, Peter, Poole-Wilson, Philip A., Geraci, Enrico, Scherillo, Marino, Fabbri, Gianna, Bartolomei, Barbara, Bertoli, Daniele, Cobelli, Franco, Fresco, Claudio, Ledda, Antonietta, Levantesi, Giacomo, Opasich, Cristina, Rusconi, Franco, Sinagra, Gianfranco, Turazza, Fabio, Volpi, Alberto, Ceseri, Martina, Alongi, Gianluca, Atzori, Antonio, Bambi, Filippo, Bastarolo, Desiree, Bianchini, Francesca, Cangioli, Iacopo, Canu, Vittoriana, Caporusso, Concetta, Cenni, Gabriele, Cintelli, Laura, Cocchio, Michele, Confente, Alessia, Fenicia, Eva, Friso, Giorgio, Gianfriddo, Marco, Grilli, Gianluca, Lazzaro, Beatrice, Lonardo, Giuseppe, Luise, Alessia, Nota, Rachele, Orlando, Mariaelena, Petrolo, Rosaria, Pierattini, Chiara, Pierota, Valeria, Provenzani, Alessandro, Quartuccio, Velia, Ragno, Anna, Serio, Chiara, Spolaor, Alvise, Tafi, Arianna, Tellaroli, Elisa, Ghio, Stefano, Ghizzardi, Elisa, Masson, Serge, Crociati, Lella, La Rovere, Maria Teresa, Corrà, Ugo, Di Giulio, Paola, Finzi, Andrea, Gorini, Marco, Milani, Valentina, Orsini, Giampietro, Bianchini, Elisa, Cabiddu, Silvia, Cangioli, Ilaria, Cipressa, Laura, Cipressa, Maria Lucia, Di Bitetto, Giuseppina, Ferri, Barbara, Galbiati, Luisa, Lorimer, Andrea, Pera, Carla, Priami, Paola, and Vasamì, Antonella more...
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Blood Glucose ,Male ,Glycated Hemoglobin A ,heart failure ,Kaplan-Meier Estimate ,prediabetes ,030204 cardiovascular system & hematology ,time factors ,Settore MED/11 ,cause of death ,0302 clinical medicine ,Glycemic control ,prediabetic state ,Cause of Death ,italy ,middle aged ,Prevalence ,80 and over ,double-blind method ,blood glucose ,risk factors ,030212 general & internal medicine ,Prediabetes ,Rosuvastatin Calcium ,humans ,rosuvastatin calcium ,Cause of death ,Original Research ,Metabolic Syndrome ,Aged, 80 and over ,adult ,Chronic heart failure ,Diabetes mellitus ,Heart failure ,Mortality ,Cardiology and Cardiovascular Medicine ,Hazard ratio ,chronic heart failure ,diabetes mellitus ,glycemic control ,mortality ,Treatment Outcome ,Adolescent ,Biomarkers ,Chronic Disease ,Diabetes Mellitus ,Fatty Acids, Omega-3 ,Double-Blind Method ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Hospitalization ,Heart Failure ,Italy ,Prediabetic State ,Risk Assessment ,Proportional Hazards Models ,Risk Factors ,Time Factors ,risk assessment ,Middle Aged ,kaplan-meier estimate ,aged ,female ,Prediabete ,young adult ,Female ,omega-3 ,Human ,hospitalization ,Adult ,medicine.medical_specialty ,Diabetes mellitu ,proportional hazards models ,Time Factor ,hydroxymethylglutaryl-coa reductase inhibitors ,prevalence ,fatty acids ,03 medical and health sciences ,Young Adult ,male ,Internal medicine ,Post-hoc analysis ,glycated hemoglobin a ,medicine ,Intensive care medicine ,Aged ,Glycated Hemoglobin ,Proportional hazards model ,business.industry ,Risk Factor ,biomarkers ,Biomarker ,medicine.disease ,Clinical trial ,adolescent ,Proportional Hazards Model ,treatment outcome ,aged, 80 and over ,chronic disease ,fatty acids, omega-3 ,cardiology and cardiovascular medicine ,Hydroxymethylglutaryl-CoA Reductase Inhibitor ,business - Abstract
Background The independent prognostic impact of diabetes mellitus ( DM ) and prediabetes mellitus (pre‐ DM ) on survival outcomes in patients with chronic heart failure has been investigated in observational registries and randomized, clinical trials, but the results have been often inconclusive or conflicting. We examined the independent prognostic impact of DM and pre‐ DM on survival outcomes in the GISSI ‐HF (Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca‐Heart Failure) trial. Methods and Results We assessed the risk of all‐cause death and the composite of all‐cause death or cardiovascular hospitalization over a median follow‐up period of 3.9 years among the 6935 chronic heart failure participants of the GISSI ‐ HF trial, who were stratified by presence of DM (n=2852), pre‐ DM (n=2013), and non‐ DM (n=2070) at baseline. Compared with non‐ DM patients, those with DM had remarkably higher incidence rates of all‐cause death (34.5% versus 24.6%) and the composite end point (63.6% versus 54.7%). Conversely, both event rates were similar between non‐ DM patients and those with pre‐ DM . Cox regression analysis showed that DM , but not pre‐ DM , was associated with an increased risk of all‐cause death (adjusted hazard ratio, 1.43; 95% CI , 1.28–1.60) and of the composite end point (adjusted hazard ratio, 1.23; 95% CI , 1.13–1.32), independently of established risk factors. In the DM subgroup, higher hemoglobin A1c was also independently associated with increased risk of both study outcomes (all‐cause death: adjusted hazard ratio, 1.21; 95% CI , 1.02–1.43; and composite end point: adjusted hazard ratio, 1.14; 95% CI , 1.01–1.29, respectively). Conclusions Presence of DM was independently associated with poor long‐term survival outcomes in patients with chronic heart failure. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00336336. more...
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- 2017
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81. Cysteineless non-glycosylated monomeric blue fluorescent protein, secBFP2, for studies in the eukaryotic secretory pathway
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Lindsey M. Costantini, Vladislav V. Verkhusha, Erik L. Snapp, Matías Jaureguiberry-Bravo, and Oksana M. Subach
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Protein Folding ,Glycosylation ,Molecular Sequence Data ,Biophysics ,Biology ,Endoplasmic Reticulum ,Protein Engineering ,Biochemistry ,Article ,chemistry.chemical_compound ,N-linked glycosylation ,Cell Line, Tumor ,Humans ,Amino Acid Sequence ,Cysteine ,Molecular Biology ,Secretory pathway ,Secretory Pathway ,Endoplasmic reticulum ,Cell Biology ,Protein engineering ,Luminescent Proteins ,Eukaryotic Cells ,Secretory protein ,Amino Acid Substitution ,chemistry ,Mutagenesis ,Cytoplasm ,Protein folding ,Protein Processing, Post-Translational - Abstract
Fluorescent protein (FP) technologies suitable for use within the eukaryotic secretory pathway are essential for live cell and protein dynamic studies. Localization of FPs within the endoplasmic reticulum (ER) lumen has potentially significant consequences for FP function. All FPs are resident cytoplasmic proteins and have rarely been evolved for the chemically distinct environment of the ER lumen. In contrast to the cytoplasm, the ER lumen is oxidizing and the site where secretory proteins are post-translationally modified by disulfide bond formation and N-glycosylation on select asparagine residues. Cysteine residues and N-linked glycosylation consensus sequences were identified within many commonly utilized FPs. Here, we report mTagBFP is post-translationally modified when localized to the ER lumen. Our findings suggest these modifications can grossly affect the sensitivity and reliability of FP tools within the secretory pathway. To optimize tools for studying events in this important intracellular environment, we modified mTagBFP by mutating its cysteines and consensus N-glycosylation sites. We report successful creation of a secretory pathway-optimized blue FP, secBFP2. more...
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- 2013
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82. Assessing the Tendency of Fluorescent Proteins to Oligomerize Under Physiologic Conditions
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Matteo Fossati, Lindsey M. Costantini, Erik L. Snapp, and Maura Francolini
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animal structures ,Endoplasmic reticulum ,Cell Biology ,Biology ,Biochemistry ,Fluorescence ,Green fluorescent protein ,Cell biology ,Cytosol ,Membrane ,Membrane protein ,Structural Biology ,Cytoplasm ,Genetics ,Signal transduction ,Molecular Biology - Abstract
Several fluorescent proteins (FPs) are prone to forming low-affinity oligomers. This undesirable tendency is exacerbated when FPs are confined to membranes or when fused to naturally oligomeric proteins. Oligomerization of FPs limits their suitability for creating fusions with proteins of interest. Unfortunately, no standardized method evaluates the biologically relevant oligomeric state of FPs. Here, we describe a quantitative visual assay for assessing whether FPs are sufficiently monomeric under physiologic conditions. Membrane-associated FP-fusion proteins, by virtue of their constrained planar geometry, achieve high effective concentrations. We exploited this propensity to develop an assay to measure FP tendencies to oligomerize in cells. FPs were fused on the cytoplasmic end of an endoplasmic reticulum (ER) signal-anchor membrane protein (CytERM) and expressed in cells. Cells were scored based on the ability of CytERM to homo-oligomerize with proteins on apposing membranes and restructure the ER from a tubular network into organized smooth ER (OSER) whorl structures. The ratio of nuclear envelope and OSER structures mean fluorescent intensities for cells expressing enhanced green fluorescent protein (EGFP) or monomeric green fluorescent protein (mGFP) CytERM established standards for comparison of uncharacterized FPs. We tested three FPs and identified two as sufficiently monomeric, while a third previously reported as monomeric was found to strongly oligomerize. more...
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- 2012
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83. Alcohol Disrupts Endoplasmic Reticulum Function and Protein Secretion in Hepatocytes
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Ana M. Vacaru, Lindsey M. Costantini, Orkhontuya Tsedensodnom, Natalia Nieto, Kirsten C. Sadler, Erik L. Snapp, Deanna L. Howarth, and Elisabetta Mormone
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Endoplasmic reticulum ,Medicine (miscellaneous) ,Biology ,Toxicology ,biology.organism_classification ,Molecular biology ,Cell biology ,Psychiatry and Mental health ,Secretory protein ,medicine.anatomical_structure ,Apoptosis ,Hepatocyte ,medicine ,biology.protein ,Unfolded protein response ,Ethanol metabolism ,Zebrafish ,Alcohol dehydrogenase - Abstract
Background: Many alcoholic patients have serum protein deficiency that contributes to their systemic problems. The unfolded protein response (UPR) is induced in response to disequilibrium in the protein folding capability of the endoplasmic reticulum (ER) and is implicated in hepatocyte lipid accumulation and apoptosis, which are associated with alcoholic liver disease (ALD). We investigated whether alcohol affects ER structure, function, and UPR activation in hepatocytes in vitro and in vivo. Methods: HepG2 cells expressing human cytochrome P450 2E1 and mouse alcohol dehydrogenase (VL-17A) were treated for up to 48 hours with 50 and 100 mM ethanol. Zebrafish larvae at 4 days postfertilization were exposed to 350 mM ethanol for 32 hours. ER morphology was visualized by fluorescence in cells and transmission electron microscopy in zebrafish. UPR target gene activation was assessed using quantitative PCR, in situ hybridization, and Western blotting. Mobility of the major ER chaperone, BIP, was monitored in cells by fluorescence recovery after photobleaching (FRAP). Results: VL-17A cells metabolized alcohol yet only had slight activation of some UPR target genes following ethanol treatment. However, ER fragmentation, crowding, and accumulation of unfolded proteins as detected by immunofluorescence and FRAP demonstrate that alcohol induced some ER dysfunction despite the lack of UPR activation. Zebrafish treated with alcohol, however, showed modest ER dilation, and several UPR targets were significantly induced. Conclusions: Ethanol metabolism directly impairs ER structure and function in hepatocytes. Zebrafish are a novel in vivo system for studying ALD. more...
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- 2011
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84. Extracellular vesicles from Kaposi Sarcoma-associated herpesvirus lymphoma induce long-term endothelial cell reprogramming
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Anthony B. Eason, Aubrey Bailey, Blossom Damania, Kurtis M. Host, Jie Xiong, Justin T. Landis, Avery Cheves, Rachele Bigi, Zhe Ma, Lindsey M. Costantini, Ryan P. McNamara, Pauline E. Chugh, Dirk P. Dittmer, and Jack D. Griffith more...
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MAPK/ERK pathway ,Lymphoma ,Physiology ,viruses ,Pathology and Laboratory Medicine ,medicine.disease_cause ,Biochemistry ,Epithelium ,Hematologic Cancers and Related Disorders ,Spectrum Analysis Techniques ,Animal Cells ,Cell Movement ,Immune Physiology ,Tumor Virus ,Virus latency ,Medicine and Health Sciences ,Biology (General) ,Post-Translational Modification ,Phosphorylation ,Innate Immune System ,0303 health sciences ,030302 biochemistry & molecular biology ,Cell migration ,Hematology ,Kaposi's Sarcoma-Associated Herpesvirus ,Flow Cytometry ,Cellular Reprogramming ,Virus Latency ,Cell biology ,Nucleic acids ,Cell Motility ,Cell Transformation, Neoplastic ,Oncology ,Spectrophotometry ,Medical Microbiology ,Viral Pathogens ,Viruses ,Herpesvirus 8, Human ,Host-Pathogen Interactions ,Cytokines ,Lymphomas ,Cytophotometry ,Pathogens ,Cellular Types ,Anatomy ,Signal transduction ,Research Article ,Signal Transduction ,Herpesviruses ,QH301-705.5 ,Immunology ,Cell Migration ,Biology ,Research and Analysis Methods ,Microbiology ,Extracellular Vesicles ,Viral Proteins ,03 medical and health sciences ,Virology ,Human Umbilical Vein Endothelial Cells ,Genetics ,Extracellular ,medicine ,Humans ,Kaposi's sarcoma-associated herpesvirus ,Non-coding RNA ,Microbial Pathogens ,Sarcoma, Kaposi ,Molecular Biology ,Cell Proliferation ,030304 developmental biology ,Natural antisense transcripts ,Biology and life sciences ,Organisms ,Cancers and Neoplasms ,Endothelial Cells ,Proteins ,Epithelial Cells ,Cell Biology ,RC581-607 ,Molecular Development ,medicine.disease ,Microvesicles ,Gene regulation ,MicroRNAs ,Biological Tissue ,Immune System ,RNA ,Parasitology ,Gene expression ,Immunologic diseases. Allergy ,DNA viruses ,Transcriptome ,Developmental Biology - Abstract
Extracellular signaling is a mechanism that higher eukaryotes have evolved to facilitate organismal homeostasis. Recent years have seen an emerging interest in the role of secreted microvesicles, termed extracellular vesicles (EV) or exosomes in this signaling network. EV contents can be modified by the cell in response to stimuli, allowing them to relay information to neighboring cells, influencing their physiology. Here we show that the tumor virus Kaposi’s Sarcoma-associated herpesvirus (KSHV) hijacks this signaling pathway to induce cell proliferation, migration, and transcriptome reprogramming in cells not infected with the virus. KSHV-EV activates the canonical MEK/ERK pathway, while not alerting innate immune regulators, allowing the virus to exert these changes without cellular pathogen recognition. Collectively, we propose that KSHV establishes a niche favorable for viral spread and cell transformation through cell-derived vesicles, all while avoiding detection., Author summary The role of extracellular vesicles (EV) has received considerable attention in recent years. The contents of these cell-derived vesicles have been shown to be modulated upon challenge by a virus or neoplastic transformation, and can influence the behavior of recipient cells. Here we demonstrate that purified EV from an AIDS-associated, virus-driven lymphoma induces unique cellular signaling, motility, and gene expression reprogramming in recipient endothelial cells. This was accomplished without activation of innate immune activation, even after prolonged exposure to these EV. Collectively our results point toward a model in which tumor-derived EV condition neighboring cell physiology, while avoiding detection by immune regulators. more...
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- 2019
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85. Andrology (Male Fertility, Spermatogenesis)
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Y. Matsumoto, S. Goto, H. Hashimoto, S. Kokeguchi, M. Shiotani, H. Okada, P. Cohen - Bacrie, A. Hazout, S. Belloc, J. De Mouzon, Y. Menezo, M. Dumont, A. M. Junca, M. Cohen-Bacrie, S. Alvarez, F. Olivennes, N. Prisant, M. Weltin, W. Geissler, C. Clussmann, T. Strowitzki, W. Eggert-Kruse, Y. Endou, Y. Fjii, H. Motoyama, F. Q. Quintana, Z. L. Zaloa Larreategui, I. P. Iratxe Penalba, S. O. Sara Ortega, M. M. Monica Martin, G. Q. Guillermo Quea, J. S. Jose Serna, M. G. Showell, J. Brown, A. Yazdani, M. T. Stankiewicz, R. J. Hart, C. Zumoffen, M. J. Munuce, A. Caille, S. Ghersevich, A. M. Lendinez, B. Perez-Nevot, A. R. Palomares, A. Serrano Garballo, A. Rodriguez, A. Reche, A. Mayor-Olea, M. Ruiz-Galdon, A. Reyes-Engel, J. Mendiola, N. Jorgensen, A. M. Andersson, A. M. Calafat, J. B. Redmon, E. Z. Drobnis, C. Wang, A. Sparks, S. W. Thurston, F. Liu, S. H. Swan, A. C. Tarasconi, B. V. Tarasconi, D. V. Tarasconi, E. M. V. Silva, Y. Fujii, I. Crha, J. Pribyl, P. Skladal, J. Zakova, P. Ventruba, M. Pohanka, G. De La Fuente, A. Pacheco, J. A. G. Velasco, A. Requena, A. Pacheco Castro, M. San Celestino Carchenilla, R. Salvanes, A. Arnanz, C. Balmori, A. Pellicer, J. A. Garcia-Velasco, T. Ishikawa, M. Fujisawa, S. Kranz, K. Hersemeyer, A. Hentrich, H. R. Tinneberg, L. Konrad, L. Simon, D. Lutton, J. McManus, S. E. M. Lewis, S. Rubio, P. Simon Sanjurjo, S. Lewis, J. Buzzi, A. Valcarcel, E. Lombardi, R. Oses, V. Rawe, E. Young, A. Magendzo, S. Lizama, G. Duque, A. Mackenna, A. Monqaut, C. Zavaleta, G. Lopez, R. Lafuente, M. Brassesco, R. Condorelli, S. La Vignera, S. La Rosa, N. Barone, E. Vicari, S. Bellanca, R. D'Agata, A. E. Calogero, M. Enciso, M. Iglesias, I. Galan, A. Gosalvez, J. Gosalvez, M. Curaba, J. Poels, A. Van Langendonckt, J. Donnez, C. Wyns, M. Garcez, M. Salvador, E. B. Pasqualotto, D. P. A. F. Braga, E. Borges, F. F. Pasqualotto, T. Aoki, R. C. S. Figueira, L. G. L. Maldonado, A. Iaconelli, R. Frassini, J. Mandelli, A. S. Setti, S. S. Cortezzi, M. Di Mauro, N. Burrello, J. Kashir, C. Jones, C. Young, M. Ruas, P. Grasa, K. Rietdorf, E. Heytens, B. Heindryckx, S. Y. Yoon, R. A. Fissore, C. M. Deane, D. Nikiforaki, S. T. Tee, P. de Sutter, J. Parrington, K. Coward, L. Visser, G. H. Westerveld, S. K. M. van Daalen, F. van der Veen, M. P. Lombardi, S. Repping, S. Cubillos, S. Sanchez, J. Pedraza, G. Charria, H. Aparicio, A. Gongora, F. Caldino, S. Cuneo, J. P. Ou, W. E. Zhao, Y. F. Liu, Y. W. Xu, C. Q. Zhou, N. Al-Asmar Pinar, V. Peinado, J. Gruhn, M. Susiarjo, M. Gil-Salom, J. M. Martinez-Jabaloyas, J. Remohi, C. Rubio, T. Hassold, N. Al-Asmar, L. Rodrigo, T. J. Hassold, M. Bungum, N. Forsell, A. Giwercman, I. Amiri, N. Sheikh, R. Najafi, M. Godarzi, M. Farimani, H. Makukh, M. Tyrkus, D. Zastavna, A. Nakonechnuy, S. S. Khayat, L. V. Schileiko, L. F. Kurilo, S. Garcia-Herrero, N. Garrido, J. A. Martinez-Conejero, L. Romany, M. Meseguer, B. Dorphin, M. Lefevre, C. Gout, P. Oger, C. Yazbeck, N. Rougier, S. De Stefani, V. Scala, S. Benedetti, M. C. Tagliamonte, E. Zavagnini, S. Palini, C. Bulletti, F. Canestrari, N. Subiran, F. M. Pinto, M. L. Candenas, E. Agirregoitia, J. Irazusta, E. M. Cha, J. H. Lee, I. H. Park, K. H. Lee, M. H. Kim, M. S. Jensen, C. Rebordosa, A. M. Thulstrup, G. Toft, H. T. Sorensen, J. P. Bonde, T. B. Henriksen, J. Olsen, L. Bosco, M. Speciale, M. Manno, N. Amireh, M. C. Roccheri, E. Cittadini, P. Wu, Y. M. Lee, H. W. Chen, C. R. Tzeng, J. Llacer, J. Ten, B. Lledo, A. Rodriguez-Arnedo, R. Morales, R. Bernabeu, A. Garcia-Peiro, J. Martinez-Heredia, M. Oliver-Bonet, J. Ribas, C. Abad, M. J. Amengual, J. Navarro, J. Benet, C. Moutou, N. Gardes, J. C. Nicod, N. Becker, M. P. Bailly, I. Galland, O. Pirello, C. Rongieres, C. Wittemer, S. Viville, W. Elmahaishi, B. Smith, A. Doshi, P. Serhal, J. C. Harper, C. Rennemeier, U. Kammerer, J. Dietl, P. Staib, K. Elgmati, M. Nomikos, M. Theodoridou, B. Calver, K. Swann, F. A. Lai, I. Georgiou, L. Lazaros, N. Xita, A. Kaponis, N. Plachouras, E. Hatzi, K. Zikopoulos, F. Ferfouri, P. Clement, D. Molina Gomes, M. Albert, M. Bailly, R. Wainer, J. Selva, F. Vialard, T. Takisawa, K. Usui, T. Kyoya, Y. Shibuya, H. Hattori, Y. Sato, M. Ota, K. Kyono, P. C. Chiu, K. K. Lam, C. L. Lee, M. K. Chung, V. W. Huang, W. S. O, F. Tang, P. C. Ho, W. S. Yeung, C. H. Kim, J. Y. Lee, S. H. Kim, C. S. Suh, Y. K. Shin, Y. J. Kang, J. H. Jung, C. Y. Cha, E. S. Hwang, T. Mukaida, M. Nagaba, K. Takahashi, D. Elkaffash, M. Sedrak, I. Huhtaniemi, T. Abdel-Al, D. Younan, N. G. Cassuto, D. Bouret, I. Hammoud, Y. Barak, S. Seshadri, M. Bates, G. Vince, D. I. Jones, M. Ben Khalifa, D. Montjean, P. Cohen-Bacrie, F. X. Aubriot, M. Cohen, E. Boudjema, M. C. Magli, A. Crippa, B. Baccetti, A. P. Ferraretti, L. Gianaroli, T. Singer, Q. V. Neri, J. C. Hu, R. Maggiulli, Z. Kollman, E. Rauch, P. N. Schlegel, Z. Rosenwaks, G. D. Palermo, B. Zorn, B. Skrbinc, E. Matos, B. Golob, M. Pfeifer, J. Osredkar, E. Sabanegh, R. K. Sharma, A. Thiyagarajan, A. Agarwal, G. Robin, F. Boitrelle, F. Marcelli, C. Marchetti, V. Mitchell, D. Dewailly, J. M. Rigot, N. Rives, A. Perdrix, A. Travers, J. P. Milazzo, N. Mousset-Simeon, B. Mace, A. Jakab, Z. Molnar, M. Benyo, I. Levai, Z. Kassai, A. Ihan, A. Kopitar, M. Kolbezen, D. Vaamonde, M. E. Da Silva-Grigoletto, J. M. Garcia-Manso, R. Vaamonde-Lemos, S. C. Oehninger, G. Walis, D. Monahan, E. Ermolovich, E. Fadlon, A. Abu Elhija, M. Abu Elhija, E. Lunenfeld, M. Huleihel, M. Costantini-Ferrando, J. C. Y. Hu, J. G. Alvarez, E. Velilla, M. Lopez-Teijon, C. Lopez-Fernandez, H. G. Tempest, F. Sun, E. Ko, P. Turek, R. H. Martin, M. T. Zomeno-Abellan, A. Ramirez, A. Gutierrez-Adan, J. C. Martinez, J. Landeras, J. Ballesta, M. Aviles, M. Ganaiem, S. Binder, A. Meinhardt, L. Sousa, A. Grangeia, F. Carvalho, M. Sousa, A. Barros, C. Sifer, N. Sermondade, E. Hafhouf, C. Poncelet, B. Benzacken, R. Levy, J. P. Wolf, L. Crisol, F. Aspichueta, M. L. Hernandez, A. Exposito, R. Matorras, M. B. Ruiz-Larrea, J. I. Ruiz-Sanz, S. Jallad, F. Atig, H. Ben Amor, A. L. I. Saad, A. Kerkeni, M. Ajina, A. L. I. Othmane, I. Koscinski, L. Ladureau, F. Scarselli, V. Casciani, M. Lobascio, M. G. Minasi, P. Rubino, A. Colasante, L. Arizzi, K. Litwicka, E. Iammarrone, S. Ferrero, C. Mencacci, G. Franco, D. Zavaglia, Z. P. Nagy, E. Greco, S. Ohgi, M. Takahashi, C. Kishi, K. Suga, A. Yanaihara, L. W. Chamley, A. Wagner, and A. N. Shelling more...
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Andrology ,Reproductive Medicine ,Phospholipase C ,Point mutation ,Rehabilitation ,Obstetrics and Gynecology ,Identification (biology) ,Biology ,Sperm ,Gene ,Molecular biology - Published
- 2010
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86. Going Viral with Fluorescent Proteins
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Erik L. Snapp and Lindsey M. Costantini
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Models, Molecular ,Viral protein ,Extramural ,Immunology ,Optical Imaging ,Computational biology ,Biology ,medicine.disease_cause ,Bioinformatics ,Microbiology ,Luminescent Proteins ,Cellular Microenvironment ,Insect Science ,Virology ,medicine ,Fluorescent protein ,Viral Fusion Proteins ,Cellular localization ,Gems - Abstract
Many longstanding questions about dynamics of virus-cell interactions can be answered by combining fluorescence imaging techniques with fluorescent protein (FP) tagging strategies. Successfully creating a FP fusion with a cellular or viral protein of interest first requires selecting the appropriate FP. However, while viral architecture and cellular localization often dictate the suitability of a FP, a FP's chemical and physical properties must also be considered. Here, we discuss the challenges of and offer suggestions for identifying the optimal FPs for studying the cell biology of viruses. more...
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- 2015
87. A palette of fluorescent proteins optimized for diverse cellular environments
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Mikhail Baloban, Megan A. Rizzo, Lindsey M. Costantini, Feng Guo, Erik L. Snapp, Michele L. Markwardt, and Vladislav V. Verkhusha
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Green Fluorescent Proteins ,General Physics and Astronomy ,Biology ,Article ,General Biochemistry, Genetics and Molecular Biology ,Madin Darby Canine Kidney Cells ,Green fluorescent protein ,03 medical and health sciences ,Dogs ,0302 clinical medicine ,Bacterial Proteins ,Live cell imaging ,Cell Line, Tumor ,Organelle ,Animals ,Humans ,Secretory pathway ,Cellular compartment ,Fluorescent Dyes ,030304 developmental biology ,0303 health sciences ,Multidisciplinary ,Staining and Labeling ,Cell Membrane ,Optical Imaging ,Biological membrane ,General Chemistry ,Protein subcellular localization prediction ,Transmembrane protein ,Cell biology ,Luminescent Proteins ,Microscopy, Fluorescence ,030217 neurology & neurosurgery ,HeLa Cells - Abstract
To perform quantitative live cell imaging, investigators require fluorescent reporters that accurately report protein localization and levels, while minimally perturbing the cell. Yet, within the biochemically distinct environments of cellular organelles, popular fluorescent proteins (FPs), including EGFP, can be unreliable for quantitative imaging, resulting in the underestimation of protein levels and incorrect localization. Specifically, within the secretory pathway, significant populations of FPs misfold and fail to fluoresce due to non-native disulphide bond formation. Furthermore, transmembrane FP-fusion constructs can disrupt organelle architecture due to oligomerizing tendencies of numerous common FPs. Here, we describe a powerful set of bright and inert FPs optimized for use in multiple cellular compartments, especially oxidizing environments and biological membranes. Also, we provide new insights into the use of red FPs in the secretory pathway. Our monomeric ‘oxFPs’ finally resolve long-standing, underappreciated and important problems of cell biology and should be useful for a number of applications. Quantitative live cell imaging of protein trafficking suffers from misfolding and inappropriate disulphide bond formation of fluorescent proteins in the secretory pathway. Here, the authors present an optimized collection of fluorescent proteins suitable for use in oxidizing subcellular compartments. more...
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- 2015
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88. Defects induced by electron irradiation in hollandite ceramics, specific radioactive cesium-host wasteforms: a 57Fe Mössbauer study
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Daniel Caurant, N. Nguyen, F. Studer, J.-M. Costantini, A. Ducouret, Didier Gourier, and V. Aubin
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Nuclear and High Energy Physics ,Radiochemistry ,Analytical chemistry ,chemistry.chemical_element ,Electron ,Condensed Matter Physics ,Atomic and Molecular Physics, and Optics ,Ion ,chemistry ,Hollandite ,Caesium ,visual_art ,Mössbauer spectroscopy ,Electron beam processing ,visual_art.visual_art_medium ,Ceramic ,Irradiation ,Physical and Theoretical Chemistry - Abstract
Several single phase hollandite ceramics having Ba2+ xCs+ y(C = Al,Fe)3+ 2x+y Ti4+ 8−2x−y O16 composition have been synthesized and irradiated under external electron beams simulating the β-irradiation of radioactive cesium. These samples have been characterized by 57Fe transmission Mossbauer spectroscopy. Mossbauer results show that the irradiation modifies the local arrangements of Ba cations around Fe3+ ions by atomic displacement of Ba ions. more...
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- 2006
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89. High-pressure phase behavior of systems with ionic liquids: Part V. The binary system carbon dioxide+1-butyl-3-methylimidazolium tetrafluoroborate
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Roger A. Sheldon, A. Shariati Sarabi, M. Costantini, Geert-Jan Witkamp, J. van Spronsen, Maaike C. Kroon, Cor J. Peters, and Chemical Engineering and Chemistry
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chemistry.chemical_classification ,Tetrafluoroborate ,Chromatography ,General Chemical Engineering ,Analytical chemistry ,General Chemistry ,Atmospheric temperature range ,Supercritical fluid ,chemistry.chemical_compound ,chemistry ,Phase (matter) ,Carbon dioxide ,Ionic liquid ,Binary system ,Alkyl - Abstract
The phase behavior of the binary system consisting of the supercritical fluid carbon dioxide (CO2) and the ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim][BF4]) was studied experimentally. A synthetic method was used to measure its phase behavior. Bubble-point pressures of the system CO2 + [bmim][BF4] are reported for carbon dioxide concentrations ranging from (10.22 to 60.17) mole % and within a temperature range of (278.47 to 368.22) K. The CO2 + [bmim][BF4] binary system has a two-phase liquid-vapor region extending up to very high pressures. Most likely, the type of fluid-phase behavior is type III according to the classification of Scott and Van Konynenburg. The experimental results obtained were compared with the available phase behavior data of the binary system CO2 + 1-hexyl-3-methylimidazolium tetrafluoroborate ([hmim][BF4]) to investigate the effect of the length of the alkyl group on the phase behavior of this type of system. A larger alkyl group leads to lower bubble-point pressures and, therefore, to higher solubilities of carbon dioxide in the imidazolium-based ionic liquid more...
- Published
- 2005
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90. Neonatal and juvenile sandbar sharks in the northern Adriatic Sea
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M. Costantini and M. Affronte
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geography ,Sandbar shark ,geography.geographical_feature_category ,biology ,Shoal ,Aquatic Science ,biology.organism_classification ,Chondrichthyes ,Population density ,Fishery ,Geographic distribution ,Mediterranean sea ,Carcharhinus ,Juvenile ,Ecology, Evolution, Behavior and Systematics - Abstract
The occurrence of neonatal sandbar sharks Carcharhinus plumbeus in the Adriatic Sea is reported; however, nursery areas still need to be identified.
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- 2003
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91. APLASIA CUTIS CONGENITA OF THE SCALP, THE SKULL, AND THE DURA
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Diego Ribuffo, N. D. Houseman, P. Gullo, G. I. Taylor, and M. Costantini
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Male ,medicine.medical_specialty ,Dura mater ,Surgical Flaps ,Aplasia cutis congenita ,Encephalocele ,Scalp flap ,Ectodermal Dysplasia ,medicine ,Humans ,Dura ,Scalp ,business.industry ,Skull ,Infant, Newborn ,Infant ,General Medicine ,Anatomy ,Newborn ,medicine.disease ,Surgery ,medicine.anatomical_structure ,Full thickness ,Temporal artery ,Dura Mater ,medicine.symptom ,business - Abstract
A newborn baby boy presented with a full thickness defect of the scalp, skull, and dura measuring 6 x 7 cm caused by aplasia cutis congenita. Full thickness loss is extremely rare and to our knowledge this case is the twenty-first reported. It has an established mortality of up to 55%. An encephalocele forced us to do an emergency operation with a single large scalp flap based on the supratrochlear and superficial temporal arteries. After revision the child is now 9 months old and progressing well. There are several ways to treat these rare and delicate cases. more...
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- 2003
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92. Robot assisted radical nephrectomy and inferior vena cava thrombectomy: Surgical technique, perioperative and mid-term oncologic outcomes
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G. Simone, S. Guaglianone, F. Minisola, M. Ferriero, G. Tuderti, L. Misuraca, G. Vallati, G. Pizzi, M. Costantini, and M. Gallucci
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Urology - Published
- 2018
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93. OC.09.5 THE NATURAL HISTORY OF ACHALASIA: EVIDENCE OF A CONTINUUM – 'THE EVOLUTIVE PATTERN THEORY'
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G. Capovilla, R. Salvador, G. Voltarel, E. Savarino, E. Pesenti, A. Perazzolo, L. Nicoletti, A. Costantini, S. Merigliano, and M. Costantini
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Hepatology ,Gastroenterology - Published
- 2018
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94. The effectiveness and cost-effectiveness of inpatient specialist palliative care in acute hospitals for adults with advanced illness and their caregivers
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Daveson BA, Smith M, Yi D, McCrone P, Grande G, Todd C, Gysels M, Costantini M, Murtagh FE, Higginson IJ, Evans CJ.
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specialist palliative care ,Caregivers ,education ,cost-effectiveness ,effectieveness - Abstract
This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the effectiveness and cost-effectiveness of inpatient specialist palliative care in acute hospitals for adults with advanced illness and their unpaid caregivers. more...
- Published
- 2015
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95. Shorter myotomy on the gastric site (≤2.5 cm) provides adequate relief of dysphagia in achalasia patients
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R, Salvador, V, Caruso, M, Costantini, P, Parise, L, Nicoletti, F, Cavallin, L, Zanatta, R, Bardini, E, Ancona, and G, Zaninotto
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Adult ,Male ,dysphagia ,Manometry ,myotomy ,Fundoplication ,achalasia ,Heller–Dor ,Deglutition Disorders ,Esophageal Achalasia ,Esophagus ,Female ,Gastric Fundus ,Humans ,Laparoscopy ,Middle Aged ,Postoperative Complications ,Postoperative Period ,Severity of Illness Index ,Treatment Outcome - Abstract
The right length of the myotomy on the gastric side for esophageal achalasia is still a debated issue. We aimed to investigate the final outcome after classic myotomy (CM) as compared with a longer myotomy on the gastric side (LM) in two cohorts of achalasia patients. Forty-four achalasia patients who underwent laparoscopic Heller-Dor were considered; patients with a sigmoid-shaped esophagus were excluded. Symptoms were scored using a detailed questionnaire for dysphagia, regurgitation, and chest pain. Barium swallow, endoscopy, and esophageal manometry were performed before and 6 months after the surgical treatment; 24-hour pH-monitoring was also performed 6 months after the procedure. CM was defined as a gastric myotomy length in the range of 1.5-2.0 cm, while LM was 2.5-3 cm in length. The surgical treatment (CM or LM) was adopted in two consecutive cohorts. Treatment failure was defined as a postoperative symptom score10th percentile of the preoperative score (i.e.8). Of the 44 patients representing the study population, 20 had CM and 24 had LM. The patients' demographic and clinical parameters (age, sex, symptom score, duration of symptoms, esophageal diameter, and manometric pattern) were similar in the two groups. The median follow up was 24 months (interquartile range 12-39). One patient in each group was classified as a treatment failure. After the treatment, there was a significant decrease in both groups' symptom score, and resting and residual pressure (P0.01), with no statistically significant differences between the two groups in terms of postoperative symptom score, resting and residual pressure, or total and abdominal lower esophageal sphincter length and esophageal diameter. Extending the length of the myotomy on the gastric side does not seem to change the final outcome of the laparoscopic Heller-Dor procedure. more...
- Published
- 2015
96. Ageing and thermal recovery of paramagnetic centers induced by electron irradiation in yttria-stabilized zirconia
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J.-M. Costantini and François Beuneu
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Nuclear and High Energy Physics ,Radiation ,Materials science ,Radiochemistry ,Analytical chemistry ,Electron ,Condensed Matter Physics ,Fluence ,law.invention ,Paramagnetism ,law ,Electron beam processing ,General Materials Science ,Orthorhombic crystal system ,Irradiation ,Electron paramagnetic resonance ,Yttria-stabilized zirconia - Abstract
We have used electron spin resonance spectroscopy to study the defects induced in yttria-stabilized zirconia (YSZ) single crystals by 2.5-MeV electron irradiations. Two paramagnetic centers are produced: the first one with an axial symmetry is similar to the trigonal Zr 3+ electron center (T center) found after X-ray irradiation or thermochemical reduction, whereas the second one is a new oxygen hole center with an axial symmetry different from the orthorhombic O - center induced by X-ray irradiation. At a fluence around 10 18 e/cm , both centers are bleached out near 600 K, like the corresponding X-ray induced defects. At a fluence around 10 19 e/cm 2 , defects are much more stable, since complete thermal bleaching occurs near 1000 K. Accordingly, ageing of as-irradiated samples shows that high-dose defects at more stable than the low-dose ones. more...
- Published
- 2002
- Full Text
- View/download PDF
97. Selected Commentary to 'Pneumatic dilation versus laparoscopic Heller's myotomy for idiopathic achalasia'
- Author
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M. Costantini and Giovanni Zaninotto
- Subjects
Myotomy ,medicine.medical_specialty ,Pneumatic dilation ,business.industry ,medicine.medical_treatment ,medicine ,Surgery ,Idiopathic achalasia ,Vascular surgery ,business ,Cardiac surgery ,Abdominal surgery - Published
- 2011
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- View/download PDF
98. Self-trapped exciton luminescence induced in alpha quartz by swift heavy ion irradiations
- Author
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B. Gervais, F. Brisard, Emmanuel Balanzat, G. Biotteau, and J. M. Costantini
- Subjects
Swift heavy ion ,Photoluminescence ,Chemistry ,Exciton ,General Physics and Astronomy ,Stopping power (particle radiation) ,Atomic physics ,Spectroscopy ,Luminescence ,Fluence ,Ion - Abstract
Natural quartz single crystals (α-SiO2) have been exposed to pulsed heavy ion beams (12C, 19F, 32S) with energies of 1 MeV amu−1 in the electronic slowing down regime. The simultaneous recording of the ion fluence and emitted photons with time-resolved spectroscopy experiments allowed the measurement of the “blue luminescence” time decay at 85 K as a function of the fluence at the various electronic stopping power, Se=(−dE/dx)e, of the ions. For all ions, regardless of fluence, the spectra are similar and have two broad bands centered at 1.60 and 2.75 eV with full widths at half maximum around 0.30 and 0.75 eV, respectively. Single-exponential time decay curves are found regardless of Se increasing from 1.4 keV nm−1 (12 MeV 12C) to 5.2 keV nm−1 (32 MeV 32S) across the amorphous track-formation threshold at 2.5±0.5 keV nm−1. At low damaged fractions (⩽22%), the decay-time constant ranges between 1.0 and 1.6 ms. The luminescence intensities at zero delay time approximately decrease in an exponential fashion... more...
- Published
- 2000
- Full Text
- View/download PDF
99. The possible influences of B2A2 and B3A2 BCR/ABL protein structure on thrombopoiesis in chronic myeloid leukaemia
- Author
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Roberto Perego, M Costantini, Enrica Morra, Cristina Bianchi, G Cornacchini, E Pungolino, L Gargantini, and E Rovida
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Male ,Cancer Research ,Molecular Sequence Data ,Fusion Proteins, bcr-abl ,Biology ,Philadelphia chromosome ,Polymerase Chain Reaction ,Exon ,Megakaryocyte ,Antigens, CD ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,hemic and lymphatic diseases ,medicine ,Humans ,RNA, Messenger ,Thrombopoiesis ,BRCA2 Protein ,Membrane Glycoproteins ,ABL ,Base Sequence ,breakpoint cluster region ,CD24 Antigen ,Middle Aged ,medicine.disease ,Antigens, Differentiation ,Neoplasm Proteins ,Leukemia ,medicine.anatomical_structure ,Oncology ,Cancer research ,Female ,Bone marrow ,Megakaryocytes ,Cell Division ,Transcription Factors - Abstract
The Philadelphia chromosome, t(9;22)(q34;q11) gives rise more frequently, in chronic myeloid leukaemia (CML), to two BCR/ABL chimeric transcripts differing only by the absence of 75 nucleotides and defined as b2a2 and b3a2 types, encoding two 210-kDa tyrosine kinase proteins differing only by the absence of 25 amino acids coded by the b3 exon. In the present study the two transcripts, detected by RT-PCR in 88 consecutive unselected CML patients, were correlated with haematological findings at diagnosis and with the megakaryocyte size and frequency by morphometric evaluation of 45 bone marrow biopsies. The secondary structure prediction and hydrophobicity of the b2a2 and b3a2 type BCR/ABL protein were also obtained. The prediction results for the b3 exon amino acids using GOR IV and NnPredict methods showed a short beta strand corresponding to the hydrophobic portion of the peptide. Significantly higher values were found in the platelet count of patients carrying b3a2 transcripts. The megakaryocyte size and frequency in bone marrow biopsies did not show significant differences between the two groups of patients. Stratifying the patients on the basis of white blood cell (WBC) count below or above 100x10(9)/l we still had, in both groups, a significant difference in the platelet count between the b2a2 and b3a2 patients. The possible relationships between the structure of b2a2 and b3a2 types of BCR/ABL fused protein and thrombopoiesis are discussed. more...
- Published
- 2000
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100. Amorphization and recrystallization of yttrium iron garnet under swift heavy ion beams
- Author
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J. M. Desvignes, M. Toulemonde, and J.-M. Costantini
- Subjects
Materials science ,Silicon ,Condensed matter physics ,Doping ,Yttrium iron garnet ,General Physics and Astronomy ,chemistry.chemical_element ,Mineralogy ,Recrystallization (metallurgy) ,Conductivity ,Amorphous solid ,Ion ,chemistry.chemical_compound ,Swift heavy ion ,chemistry - Abstract
The room-temperature dc conductivity is used to monitor the damage and structural modifications induced by swift heavy ion irradiations in yttrium iron garnet (Y3Fe5O12 or YIG) epitaxial layers doped with calcium (CaYIG) or silicon (SiYIG), with a variable conductivity due to a variable degree of compensation, and amorphous YIG layers. Irradiations are performed with heavy ions in the 0.8–6 MeV amu−1 energy range, in the electronic slowing down regime, with an electronic stopping power ranging between 7 and 41 MeV μm−1 above the amorphous track formation threshold (4.5 MeV μm−1) in this low-ion velocity range. A conductivity decrease versus ion fluence is found in the case of the high-conductivity uncompensated epilayers whereas an increase occurs for the low-conductivity compensated ones, either p-type (CaYIG) or n-type (SiYIG). These results are discussed by considering the competing effects of disorder on the carrier density and mobility in the case of compensated and uncompensated semiconductors. In b... more...
- Published
- 2000
- Full Text
- View/download PDF
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