bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of Incident Seizure in Systemic Lupus Erythematosus
Authors: Huang XiangYang , Magder Laurence S. , Petri Michelle
Published: January 2016

Objective.

The risk factors for incident seizures in systemic lupus erythematosus (SLE) were prospectively determined in a cohort study.

Methods.

A total of 2203 patients with SLE followed longitudinally in the Hopkins Lupus Cohort were analyzed. Demographic variables, clinical manifestations, laboratory tests, and SLE disease activity were recorded at each quarterly visit. Adjusted estimates of association of risk factors for onset of seizure were derived using pooled logistic regression. We examined incident seizures in 3 ways: at the time of diagnosis, more than 45 days after the diagnosis of SLE, and after cohort entry.

Results.

Of 2203 patients with no history of seizure prior to SLE diagnosis, 157 (7.13%) had the first seizure occurrence at the time of (37 patients, 1.68%) or after diagnosis (120 patients, 5.45%) of SLE. The risk of seizure occurring around the time of SLE diagnosis was higher in patients with a history of malar rash (p = 0.002), proteinuria (p = 0.004), and psychosis (p < 0.001). Multivariable analysis of the first seizure occurring after the diagnosis of SLE showed that history of low C3 (p = 0.0078), psychosis (p < 0.0001), cranial or peripheral neuropathy (p = 0.0043), anti-Sm antibody (p = 0.0551), renal involvement (p = 0.0177), and current corticosteroid dose (p < 0.0001) were independently associated with a higher incidence of seizure. Disease activity was not predictive after adjusting for corticosteroids.

Conclusion.

Risk of seizure after diagnosis of SLE is increased in those patients with prior psychosis, neuropathy, proteinuria, anti-Sm, low C3, and use of corticosteroids.
A Prospective Study Investigating Prediagnostic Leukocyte Telomere Length and Risk of Developing Rheumatoid Arthritis in Women
Authors: Prescott Jennifer , Karlson Elizabeth W. , Orr Esther H. , Zee Robert Y.L. , De Vivo Immaculata , Costenbader Karen H.
Published: January 2016

Objective.

To prospectively examine the association between leukocyte telomere length (LTL) and subsequent rheumatoid arthritis (RA) development in women.

Methods.

Using a case-control design nested within the prospective Nurses’ Health Study (NHS), NHS II (NHSII), and Women’s Health Study (WHS), each validated case of RA with a prediagnostic blood sample was matched to 3 controls by cohort, age, menopausal status, postmenopausal hormone therapy, and blood collection covariates. We measured telomere length in genomic DNA extracted from stored buffy coat samples using quantitative PCR. We used unconditional logistic regression to determine OR and 95% CI, and random-effects metaanalysis to combine study results.

Results.

In total, we analyzed 296 incident RA cases and 827 matched controls. Mean age of diagnosis among women who developed RA was 60.5 in NHS/NHSII and 61.3 in WHS. Metaanalysis demonstrated that longer prediagnostic LTL was associated with increased RA risk when women in the longest versus shortest LTL tertile were compared (OR 1.51, 95% CI 1.03–2.23, pheterogeneity = 0.27). However, statistically significant between-study heterogeneity was observed for the intermediate tertile category (pheterogeneity = 0.008). We did not observe heterogeneity by menopausal status, inflammatory cytokine levels, age at diagnosis, age at blood collection, body mass index, seropositivity, or HLA-DRβ1 shared epitope status.

Conclusion.

Our results do not support an involvement for short LTL preceding RA development.
Examining the Minimal Important Difference of Patient-reported Outcome Measures for Individuals with Knee Osteoarthritis: A Model Using the Knee Injury and Osteoarthritis Outcome Score
Authors: Mills Kathryn A.G. , Naylor Justine M. , Eyles Jillian P. , Roos Ewa M. , Hunter David J.
Published: January 2016

Objective.

To examine the influence of different analytical methods, baseline covariates, followup periods, and anchor questions when establishing a minimal important difference (MID) for individuals with knee osteoarthritis (OA). Second, to propose MID for improving and worsening on the Knee injury and Osteoarthritis Outcome Score (KOOS).

Methods.

Retrospective analysis of prospectively collected data from 272 patients with knee OA undergoing a multidisciplinary nonsurgical management strategy. The magnitude and rate of change as well as the influence of baseline covariates were examined for 5 KOOS subscales over 52 weeks. The MID for improving and worsening were investigated using 4 anchor-based methods.

Results.

Waitlisted for joint replacement and exhibiting unilateral/bilateral symptoms influenced change in KOOS over time. Generally, low correlations between anchors and KOOS change scores limited calculations of MID; thus, they were only proposed for the pain, activities of daily living, and quality of life subscales. The method used to calculate the MID influenced the cutpoint; however, the type of anchor question only influenced the MID when analyzed with a particular mean change method. Depending on patient and clinical characteristics, the subscale, and the analytical approach used, the MID for KOOS improvement ranged from an absolute change of −1.5 to 20.6 points and worsening ranged from −19.17 to 8.5 points.

Conclusion.

MID vary with patient and clinical characteristics, KOOS subscale, and analytical approach. Provided the anchor question is relevant to the patient-reported outcome and baseline status is considered, the anchor does not appear to influence the MID for improvement or worsening when using some anchor-based methods.
Incremental Costs for Psoriasis and Psoriatic Arthritis in a Population-based Cohort in Southern Sweden: Is It All Psoriasis-attributable Morbidity?
Authors: Löfvendahl Sofia , Petersson Ingemar F. , Theander Elke , Svensson Åke , Zhou Caddie , Steen Carlsson Katarina
Published: January 2016

Objective.

To estimate incremental costs for patients with psoriasis/psoriatic arthritis (PsO/PsA) compared to population-based referents free from PsO/PsA and estimate costs attributable specifically to PsO/PsA.

Methods.

Patients were identified by International Classification of Diseases, 10th ed., codes for PsO/PsA using information from 1998 to 2007 in the Skåne Healthcare Register, covering healthcare use for the population of the Skåne region of Sweden. For each patient, 3 population-based referents were selected. Data were retrieved from Swedish registers on healthcare, drugs, and productivity loss. The human capital method was used to value productivity losses. Mean annual costs for 2008 to 2011 were assessed from a societal perspective.

Results.

We identified 15,283 patients fulfilling the inclusion criteria for PsO [n = 12,562, 50% women, mean age (SD) 52 (21) yrs] or PsA [n = 2721, 56% women, mean age 54 (16) yrs] and included 45,849 referents. Mean annual cost per patient with PsO/PsA was 55% higher compared to referents: €10,500 vs €6700. The cost was 97% higher for PsA compared to PsO. Costs due to productivity losses represented the largest share of total costs, ranging from 52% for PsO to 60% for PsA. Biological drug costs represented 10% of the costs for PsA and 1.6% for PsO. The proportion of cost identified as attributable to PsO/PsA problems was greatest among the patients with PsA (drug costs 71% and healthcare costs 31%).

Conclusion.

Annual mean incremental societal cost per patient was highest for PsA, mainly because of productivity losses and biological treatment. A minor fraction of the costs were identified as attributable to PsO/PsA specifically, indicating an increased morbidity in these patients that needs to be further investigated.
Monocytic Angiotensin and Endothelin Receptor Imbalance Modulate Secretion of the Profibrotic Chemokine Ligand 18
Authors: Rademacher Judith , Kill Angela , Mattat Kathrin , Dragun Duska , Siegert Elise , Günther Jeannine , Riemekasten Gabriela
Published: January 2016

Objective.

To assess monocytic expression and ratio of angiotensin and endothelin receptors in systemic sclerosis (SSc) and their functional relevance.

Methods.

Receptor expression was measured by flow cytometry. Chemokine ligand 18 (CCL18) concentration in supernatants of peripheral blood mononuclear cells stimulated with immunoglobulin G was measured by ELISA.

Results.

Monocytes of patients with SSc presented an increased angiotensin II Type 1 receptor (AT1R)/AT2R ratio compared with those of healthy donors. Patients with lung fibrosis and patients with high modified Rodnan skin score showed a reduced endothelin 1 Type A receptor (ETAR)/ETBR ratio. High AT1R/AT2R, but low ETAR/ETBR ratios corresponded to higher CCL18 secretion.

Conclusion.

Altered angiotensin and endothelin receptor ratios observed in SSc influence autoantibody-mediated effects such as secretion of profibrotic CCL18.
Venous and Arterial Thrombotic Events in Systemic Lupus Erythematosus
Authors: Hinojosa-Azaola Andrea , Romero-Diaz Juanita , Vargas-Ruiz Angel Gabriel , Nuñez-Alvarez Carlos A. , Cicero-Casarrubias Alba , Ocampo-Torres Mario C. , Sanchez-Guerrero Jorge
Published: January 2016

Objective.

The incidence of thrombosis in patients with systemic lupus erythematosus (SLE) is 25 to 50-fold higher than in the general population; we aimed to define the characteristics of venous thrombotic events (VTE) and arterial thrombotic events (ATE) to identify the patients at highest risk.

Methods.

The study included 219 patients with recent-onset SLE. At baseline, standardized medical history and laboratory tests were done. Followup visits occurred quarterly, and information about damage accrual, comorbidities, and cardiovascular risk factors was updated annually. Main outcome was development of TE after SLE diagnosis.

Results.

Thirty-five patients (16%) developed TE (27 VTE, 8 ATE) during 5.21 years of followup; incidence rate 31/1000 patient-years. Most events (57%) developed within the first year of diagnosis, and 69% were not associated with lupus anticoagulant (LAC), determined with 1 method. VTE developed earlier than ATE (2.0 vs 57.5 mos, p = 0.02). In the multivariate analysis, variables preceding VTE included cutaneous vasculitis, nephrotic syndrome, dose of prednisone, and LAC in combination with anti-RNP/Sm antibodies (p < 0.03). Patients with ATE were older (median age 44 vs 29 yrs, p = 0.04), smokers, and had hypertension, diabetes mellitus, dyslipidemia, at least 2 traditional risk factors, nephrotic syndrome, chronic damage, and a higher cumulative dose of prednisone (p < 0.05). LAC in combination with anti-RNP/Sm antibodies was associated with VTE and improved the accuracy for predicting it.

Conclusion.

Our study suggests that in SLE, VTE and ATE have different risk factors. Understanding these differences is helpful for identifying patients at highest risk. The use of LAC plus anti-RNP/Sm for predicting VTE deserves further study.
The Framingham Score and the Systematic Coronary Risk Evaluation at Low Cutoff Values Are Useful Surrogate Markers of High-risk Subclinical Atherosclerosis in Patients with Rheumatoid Arthritis
Authors: Dessein Patrick H. , Corrales Alfonso , Lopez-Mejias Raquel , Solomon Ahmed , Woodiwiss Angela J. , Llorca Javier , Norton Gavin R. , Genre Fernanda , Blanco Ricardo , Pina Trinitario , Gonzalez-Juanatey Carlos , Tsang Linda , Gonzalez-Gay Miguel A.
Published: January 2016

Objective.

We determined the performance of the Framingham score and the Systematic COronary Risk Evaluation (SCORE) in assessing high-risk atherosclerosis in patients with rheumatoid arthritis (RA).

Methods.

We assembled 330 cases without established cardiovascular disease (CVD), diabetes, and moderate or severe chronic kidney disease among 451 consecutive Spanish patients who underwent CVD risk screening and carotid ultrasound-determined plaque assessment. The findings were validated in 90 black and 97 white African patients.

Results.

When sensitivity for the Framingham score was set at 80% in receiver-operator curve analysis [area under the curve (AUC) = 0.799], the corresponding cutoff value and specificity were 7.3% and 63%, respectively. At a specificity of 80%, the cutoff value and sensitivity were 10.8% and 65%, respectively. When sensitivity for SCORE (AUC = 0.747) was set at 80%, the cutoff value and specificity were 0.5% and 58%, respectively. At a specificity of 80%, the cutoff value and sensitivity were 1.5% and 50%, respectively. Upon applying a cutoff value of 7.3% for the Framingham and 0.5% for SCORE in African white patients with RA, the corresponding sensitivities and specificities were 67% and 72%, and 67% and 55%, respectively. CVD risk equations did not discriminate between black African patients with and without plaque (AUC = 0.544 and 0.549 for Framingham score and SCORE, respectively).

Conclusion.

The Framingham score and SCORE at markedly low cutoff values of 7.3% to 10.8% and 0.5% to 1.5%, respectively, can usefully estimate plaque presence in RA. Effective population-specific CVD risk assessment strategies are needed in black African patients with RA.
Development of System-level Performance Measures for Evaluation of Models of Care for Inflammatory Arthritis in Canada
Authors: Barber Claire E.H. , Marshall Deborah A. , Mosher Dianne P. , Akhavan Pooneh , Tucker Lori , Houghton Kristin , Batthish Michelle , Levy Deborah M. , Schmeling Heinrike , Ellsworth Janet , Tibollo Heidi , Grant Sean , Khodyakov Dmitry , Lacaille Diane ,   The Arthritis Alliance of Canada Performance Measurement Development Panel
Published: January 2016

Objective.

To develop system-level performance measures for evaluating the care of patients with inflammatory arthritis (IA), including rheumatoid arthritis (RA), psoriatic arthritis, ankylosing spondylitis, and juvenile idiopathic arthritis.

Methods.

This study involved several methodological phases. Over multiple rounds, various participants were asked to help define a set of candidate measurement themes. A systematic search was conducted of existing guidelines and measures. A set of 6 performance measures was defined and presented to 50 people, including patients with IA, rheumatologists, allied health professionals, and researchers using a 3-round, online, modified Delphi process. Participants rated the validity, feasibility, relevance, and likelihood of use of the measures. Measures with median ratings ≥ 7 for validity and relevance were included in the final set.

Results.

Six performance measures were developed evaluating the following aspects of care, with each measure being applied separately for each type of IA except where specified: waiting times for rheumatology consultation for patients with new onset IA, percentage of patients with IA seen by a rheumatologist, percentage of patients with IA seen in yearly followup by a rheumatologist, percentage of patients with RA treated with a disease-modifying antirheumatic drug (DMARD), time to DMARD therapy in RA, and number of rheumatologists per capita.

Conclusion.

The first set of system-level performance measures for IA care in Canada has been developed with broad input. The measures focus on timely access to care and initiation of appropriate treatment for patients with IA, and are likely to be of interest to other arthritis care systems internationally.
Improved Function and Reduced Pain after Swimming and Cycling Training in Patients with Osteoarthritis
Authors: Alkatan Mohammed , Baker Jeffrey R. , Machin Daniel R. , Park Wonil , Akkari Amanda S. , Pasha Evan P. , Tanaka Hirofumi
Published: January 2016

Objective.

Arthritis and its associated joint pain act as significant barriers for adults attempting to perform land-based physical activity. Swimming can be an ideal form of exercise for patients with arthritis. Yet there is no information on the efficacy of regular swimming exercise involving patients with arthritis. The effect of a swimming exercise intervention on joint pain, stiffness, and physical function was evaluated in patients with osteoarthritis (OA).

Methods.

Using a randomized study design, 48 sedentary middle-aged and older adults with OA underwent 3 months of either swimming or cycling exercise training. Supervised exercise training was performed for 45 min/day, 3 days/week at 60–70% heart rate reserve for 12 weeks. The Western Ontario and McMaster Universities Arthritis Index was used to measure joint pain, stiffness, and physical limitation.

Results.

After the exercise interventions, there were significant reductions in joint pain, stiffness, and physical limitation accompanied by increases in quality of life in both groups (all p < 0.05). Functional capacity as assessed by maximal handgrip strength, isokinetic knee extension and flexion power (15–30% increases), and the distance covered in the 6-min walk test increased (all p < 0.05) in both exercise groups. No differences were observed in the magnitude of improvements between swimming and cycling training.

Conclusion.

Regular swimming exercise reduced joint pain and stiffness associated with OA and improved muscle strength and functional capacity in middle-aged and older adults with OA. Additionally, the benefits of swimming exercise were similar to the more frequently prescribed land-based cycling training. Trial registration: clinicaltrials.govNCT01836380.
Un artifice rhétorique au temps des guerres de religion
Authors: Daussy Hugues
Published: January 2016

Pendant les guerres de religion, les théoriciens huguenots se sont efforcés de rallier les catholiques modérés à leur cause politique. Afin d’y parvenir, ils ont développé une stratégie rhétorique fondée sur l’usage d’une supercherie littéraire qui consistait à faire passer l’auteur réformé d’un texte polémique pour un auteur catholique. À travers quelques exemples, cet article analyse les mécanismes de ce procédé et tente d’évaluer son efficacité.
Éloquence de la chaire et éloquence du barreau : une rivalité dans la seconde moitié du xvii e siècle ?
Authors: Simiz Stefano
Published: January 2016

Le xvii e siècle, déjà considéré comme un petit âge d’or de l’éloquence sacrée, connaît également le développement de l’éloquence juridique. C’est le moment où un débat se développe sur la valeur respective de l’une et de l’autre et, surtout, de l’une (barreau) par rapport à l’autre (chaire). Pour y parvenir, des lieux d’apprentissage commun existent, telle l’Académie des orateurs de Richesource à Paris. C’est à l’occasion d’une séance publique de l’académie qu’une question est posée : est-ce que l’éloquence de la chaire est plus difficile que celle du barreau ? L’analyse des argumentaires affrontés dévoile un espace de réflexion situé entre rivalité et complémentarité de ces deux grands genres éloquents.
Théophile Raynaud et le choix de la théologie comme rhétorique en soi
Authors: Gay Jean-Pascal
Published: January 2016

Ce texte explore le devenir de stratégies argumentatives fondées sur la revendication d’une autorité et d’un positionnement disciplinaire théologien dans le monde catholique à partir du xvii e siècle. Il le fait autour du cas du jésuite Théophile Raynaud qui peut-être plus que d’autres théologiens de son temps apparaît comme un exemple radical de telles stratégies argumentatives. Il apparaît alors non seulement qu’une telle stratégie est obsolète mais que cette obsolescence est bien le produit d’évolutions politiques, culturelles et religieuses conjointes.
Une performance oratoire et au-delà
Authors: Beaurepaire Pierre-Yves
Published: January 2016

Il y a clairement un paradoxe du discours maçonnique. Omniprésent dans la vie d’une loge maçonnique comme d’une Grande Loge, il est dès le xviii e siècle copié, recopié, imprimé, parfois publié dans la presse périodique maçonnique ou profane. Il constitue l’un des principaux matériaux à disposition de l’historien pour étudier la sociabilité des frères. Pourtant, le corpus des discours maçonniques a été peu étudié pour lui-même jusqu’ici.
La Chalotais et le Compte rendu des Constitutions des jésuites (1761)
Authors: Lemaître Alain J.
Published: January 2016

Les critiques que La Chalotais formule violemment contre les jésuites, au parlement de Bretagne, ne sont pour lui que des prétextes. Dans ses réquisitoires, c’est l’ensemble du clergé qui est attaqué. Dans ces remontrances, c’est la place de la religion qui est posée dans l’État, juste admise par réalisme politique. Dans ce flot de critiques d’une violence peu commune sous sa plume, c’est le rôle du parlement et des parlementaires qui importe et qui est mis en valeur, entre le roi et l’opinion publique.
Des usages de l’histoire politique dans l’homilétique protestante du xviii e siècle
Authors: Borello Céline
Published: January 2016

Lorsqu’il prêche, le pasteur protestant peut être amené à user de motifs rhétoriques qui ne relèvent pas uniquement de la sphère théologique. Le propos est ici de comprendre comment l’histoire politique, c’est-à-dire le passé profane des États, les relations nouées entre pays, peuvent se retrouver dans l’homilétique d’Ancien Régime et plus particulièrement dans celle de la seconde moitié du xviii e siècle.
Lost in translation : une mission britannique auprès des Druzes à la fin du xix e siècle
Authors: Foliard Daniel
Published: January 2016

La Palestine and Lebanon Nurses mission to the Druses fut créée à Baakline en 1883. Elle est un témoignage du regain évangélique qui caractérisa une partie du protestantisme britannique à la fin du xix e siècle. L’étude des modes d’évangélisation et des soutiens de cette mission installée dans la montagne druze démontre à la fois les spécificités des missions britanniques dans le contexte du Mont Liban de la fin au tournant du siècle et le rapport plus qu’ambigu que les populations locales entretinrent avec cette institution.
Les consultations avant l’adoption
Authors: de Monléon Jean-Vital
Published: January 2016

Pratique aujourd’hui en décroissance, l’adoption internationale concerne fréquemment des enfants atteints de problèmes de santé plus ou moins lourds. D’où l’émergence d’une forte demande de conseils médicaux, chez les parents candidats à l’adoption, à l’origine des récentes « consultations pédiatriques avant adoption ». Un exercice particulièrement délicat, exigeant du praticien la mise en œuvre de repères éthiques à la fois clairs et solides.
Renoncer à être traître
Authors: Terrier Marie-Claire
Published: January 2016

Résumé La fin de l’analyse permet d’aborder l’au-delà de la castration et ouvre ainsi à chacun qui s’y risque la possibilité de s’inscrire dans l’un ou dans l’autre sexe sans trahir ce que son analyse lui a permis de conclure. On questionnera, à partir du mythe celte de la Déesse blanche, ce qui reste au sujet de sa préhistoire : son sinthome, issu de la mise en fonction par la femme de mère de sa jouissance féminine en deçà de sa jouissance phallique. Quelle est la place de la poésie pour que le sujet ne s’égare pas ?
Tentatives de feindre l’impossible et « faire désirer »
Authors: Tigirlas Luminitza Claudepierre
Published: January 2016

Résumé L’oscillation entre l’âmoureuse et les étendues psychiques où se cultive le désir de désir de l’insatisfaction ne trouve pas de repos chez certains sujets et conduit à l’impossible logique du faire désirer. Peut-on le feindre par la fiction lyrique ? La poétesse russe Marina Tsvetaïeva – l’Aimante par son nom de sinthome –, les analysantes de Lacan et la dite Aurore s’emploient chacune dans son style aux tentatives de faire désirer via l’écriture.
Du bien-dire et du réel dans la psychanalyse
Authors: Chatelard Daniela
Published: January 2016

Résumé Pour toucher au réel dans la psychanalyse, nous partirons de la notion de lalangue, en passant par la réinterprétation analytique à partir d’une reprise en considération du terme de Bedeutung. Ensuite, nous passerons à l’au-delà de l’Œdipe pour arriver à ce qui échapperait à l’interprétation, c’est-à-dire à l’ininterprétable, enfin, à l’acte. Pour autant, nous ferons aussi un bref détour par le père réel, celui qui a fonction d’exception de l’universel de la fonction phallique.
Le sexe incertain… et le corps ?
Authors: Mahé Lucie , Ramos Carlos
Published: January 2016

Résumé L’approche du corps à partir des trois registres de J. Lacan permet de saisir la question de la subjectivation sexuelle. Cette sexuation se caractérise par le malentendu produit à partir du constat organique. Le corps sera capté dans le miroir et interrogé par la jouissance et le langage, par la lalangue. L’objet indéterminé de la pulsion et le sexe incertain amènent à articuler le choix du sexe et son objet : le corps s’y prend. Entre être et avoir, le sujet pourra se reconnaître d’un sexe ou de l’autre, là où se joue une perte nécessaire liée à la privation.
La clinique infantile : choix du sexe, choix de jouissance
Authors: Pelegrí Matilde
Published: January 2016

Résumé Le choix du sexe ne dépend ni de l’anatomie ni d’un déterminisme social. C’est une énigme pour chaque sujet et c’est le résultat d’un long processus singulier. En nous appuyant sur les élaborations de Freud concernant l’Œdipe et sur les formules de la sexuation de Lacan, nous aborderons quatre cas cliniques qui nous montrent les avatars de ce choix au-delà des identifications et comment, en tant que psychanalyste, nous devons accompagner ces sujets, enfants et adolescents.
Alpha
Authors: Bruno Pierre
Published: January 2016

Résumé Il s’agit de souligner la distinction entre mode de production capitaliste et discours capitaliste et d’indiquer le statut foncièrement illégal de l’argent.
Discours capitaliste et répétition
Authors: Papatheodorou Panos
Published: January 2016

Résumé Comment le discours capitaliste opère-t-il sur la subjectivité de notre époque ? La répétition est le lieu privilégié où le discours capitaliste prend son effet, effaçant toute tentative du sujet de se repérer dans l’acte de répétition de son symptôme.
Symptôme et sinthome, 4 e partie. Le symptôme dans la seconde topique (Freud, 1920-1939)
Authors: Guillen Fabienne
Published: January 2016

Résumé La seconde topique marque un tournant majeur dans la conception que se fait Freud de l’appareil psychique et de son fonctionnement qui retentit sur son idée du symptôme. Sa remise à l’honneur du concept de défense diversifie les modes de négation du sujet confronté à la castration et précise les diverses modalités de formation des symptômes. Enfin, toute analyse se heurte à l’impossible éradication du symptôme qui vient s’échouer sur le roc de la castration.
Chances de vie et risques de mort de notre planète : le combat contre l’hydre bancaire mondiale
Authors: Morin François
Published: January 2016

Résumé Notre planète s’est transformée brutalement depuis deux décennies avec notamment la globalisation des marchés monétaires et financiers. Il en résulte des instabilités, des crises et nombre de pathologies toujours plus graves. Au cœur de ce processus mortifère se niche l’hydre des plus grandes banques mondiales dont l’action doit être considérée comme dévastatrice.
The Boy’s Froissart de Lanier ou la réappropriation d’une mémoire européenne à destination des garçons en Amérique
Authors: Victorin Patricia
Published: January 2016

Pourquoi Sidney Clopton Lanier juge-t-il bon, peu après la guerre de Sécession, d’écrire un livre à destination d’un jeune lectorat masculin américain dans lequel il adapte les Chroniques de Froissart, chroniqueur du xive siècle qui a relaté en son temps la guerre de Cent Ans ? Nous tenterons de comprendre les liens que Lanier tisse entre l’Europe et l’Amérique, et de cerner tout particulièrement le rôle fondateur que jouent Caxton et Lord Berners qui ont permis de faire connaître Froissart aux Anglais. L’objet principal de cette contribution est de retisser le fil ou lignage qui mène de Froissart à Sidney Clopton Lanier, de l’Europe au Vieux Sud, en passant par deux figures emblématiques des xve et xvie siècles anglais, Caxton et Lord Berners qui permettent d’enraciner le jeune lecteur américain dans le terreau d’ancêtres prestigieux.
Inter-disciplinarité et trans-nationalisme
Authors: Miller Anne-Hélène
Published: January 2016

Cet article s’intéresse à l’état de la recherche et l’enseignement du français médiéval dans le contexte actuel des orientations transnationales au sein des programmes interdisciplinaires d'études médiévales en Amérique du nord. Souvent influencés par la recherche en postcolonial medievalism ou medieval multiculturalism, à l’instar des programmes sur les espaces méditerranéen ou francophone au Moyen Âge, ceux-ci visent à se libérer des filiations identitaires nationales afin de repenser les délimitations territoriales, linguistiques, religieuses, voire périodiques, et décentrer le discours plus traditionnel sur le Moyen Âge latin occidental. Nous évaluons dans quelle mesure les études de français médiéval, surtout d’un point de vue théorique, ont pu servir de moteur en ce domaine et jouent aujourd’hui encore un rôle déterminant, et nous faisons le bilan des défis auxquels elles se trouvent confrontées en raison de ces nouvelles orientations.
« French belongs to no one, French belongs to everyone ». Sur l’attractivité de la littérature médiévale aux États-Unis
Authors: Uhlig Marion
Published: January 2016

À l’heure où les offres de poste comme les Masters spécialisés en langue et littérature françaises du Moyen Âge se font de plus en plus rares dans les universités américaines, il paraît urgent de réfléchir aux moyens de stimuler l’intérêt des étudiants pour cette discipline afin d’en assurer la relève outremer. Mais comment accroître l’attractivité de la littérature médiévale en français, là où rien ne prédispose les étudiants à s’y intéresser tant elle paraît éloignée de leur héritage culturel ? Le présent témoignage revient sur les solutions, toutes potentielles, que mes collègues et moi avons envisagées durant mon séjour comme professeur adjoint de littérature française médiévale à l’université du Wisconsin-Madison entre 2013 et 2015. Elles invitent d’une part à questionner le choix des langues dans lesquelles les textes sont lus et enseignés, à savoir le français moderne dans les deux cas ou, respectivement, l’ancien français et l’anglais, et d’autre part à tirer parti du formidable engouement des chercheurs et des étudiants pour les Global Studies et pour la littérature de la francophonie avec lesquelles la littérature médiévale en français entre aisément en dialogue.
C1q Modulates the Response to TLR7 Stimulation by Pristane-Primed Macrophages: Implications for Pristane-Induced Lupus
Authors: Carlucci Francesco , Ishaque Attia , Ling Guang Sheng , Szajna Marta , Sandison Ann , Donatien Philippe , Cook H. Terence , Botto Marina
Published: January 2016

The complement component C1q is known to play a controversial role in the pathogenesis of systemic lupus erythematosus, but the underlying mechanisms remain poorly understood. Intraperitoneal injection of pristane induces a lupus-like syndrome whose pathogenesis implicates the secretion of type I IFN by CD11b+ Ly6Chigh inflammatory monocytes in a TLR7-dependent fashion. C1q was also shown to influence the secretion of IFN-α. In this study, we explored whether C1q deficiency could affect pristane-induced lupus. Surprisingly, C1qa−/− mice developed lower titers of circulating Abs and milder arthritis compared with the controls. In keeping with the clinical scores, 2 wk after pristane injection the peritoneal recruitment of CD11b+ Ly6Chigh inflammatory monocytes in C1qa−/− mice was impaired. Furthermore, C1q-deficient pristane-primed resident peritoneal macrophages secreted significantly less CCL3, CCL2, CXCL1, and IL-6 when stimulated in vitro with TLR7 ligand. Replenishing C1q in vivo during the pristane-priming phase rectified this defect. Conversely, pristane-primed macrophages from C3-deficient mice did not show impaired cytokine production. These findings demonstrate that C1q deficiency impairs the TLR7-dependent chemokine production by pristane-primed peritoneal macrophages and suggest that C1q, and not C3, is involved in the handling of pristane by phagocytic cells, which is required to trigger disease in this model.
Ecdysone Titer Determined by 3DE-3β-Reductase Enhances the Immune Response in the Silkworm
Authors: Sun Wei , Shen Yi-Hong , Zhou Liang-Xiao , Zhang Ze
Published: January 2016

Although recent studies have demonstrated that 20-hydroxyecdysone (20E), one of the two most important hormones for development, could promote the insect innate immune response, how insects regulate 20E titer to affect the immunity after suffering pathogen attack remains unknown. In this study, to our knowledge, we first found that 20E titer was significantly elevated after bacterial infection in the domesticated silkworm, Bombyx mori. Furthermore, the elevated 20E enhanced the silkworm innate immune system against invading bacteria via ecdysone receptor. During immune response, the expression of the silkworm 3-dehydroecdysone-3β-reductase (3DE-3β-reductase) that converts 3DE released from prothoracic glands into ecdysone was induced. RNA interference experiments suggested that 3DE-3β-reductase is essential to upregulate the 20E titer after bacterial infection. The rescue experiments showed that injection with the recombinant 3DE-3β-reductase protein can significantly elevate the 20E concentration and modulate the expressions of the silkworm immune-related genes. Taken together, 20E titer determined by 3DE-3β-reductase enhances the silkworm defense against the bacterial infection. Thus, our findings reveal an important role of the 20E synthesis pathway from 3DE in enhancing the silkworm immune response and have profound implications for the understanding of interaction mechanisms between insect hormone and immunity.
Fatty Acid Amide Hydrolase Regulates Peripheral B Cell Receptor Revision, Polyreactivity, and B1 Cells in Lupus
Authors: Pathak Simanta , Kumar Kirthi Raman , Kanta Hasna , Carr-Johnson Ferdicia , Han Jie , Bashmakov Anna , Faure Lionel , Ding Huihua , Vanarsa Kamala , Khan Shaheen , Li Quan-Zhen , Chapman Kent , Wakeland Edward K. , Mohan Chandra
Published: January 2016

C57BL/6 mice bearing the Sle2z lupus-susceptibility congenic interval on chromosome 4 display high titers of polyclonal autoantibodies with generalized B cell hyperactivity, hallmarks of systemic lupus erythematosus. In B6.Sle2zHELIg.sHEL BCR-transgenic mice, Sle2z did not breach central tolerance, but it led to heightened expression of endogenous Ig H and L chains in splenic B cells, upregulation of RAG, and serological polyreactivity, suggestive of excessive receptor revision. Fatty acid amide hydrolase (FAAH), a gene in the minimal subcongenic interval generated through recombinant mapping, was found to be upregulated in Sle2z B cells by microarray analysis, Western blot, and functional assays. Pharmacological inhibition of FAAH reversed the increase in receptor revision, RAG expression, and polyreactive autoantibodies in lupus-prone mice. These studies indicate that increased peripheral BCR revision, or selective peripheral expansion of BCR-revised B cells, may lead to systemic autoimmunity and that FAAH is a lupus-susceptibility gene that might regulate this process.
A Novel Factor H–Fc Chimeric Immunotherapeutic Molecule against Neisseria gonorrhoeae
Authors: Shaughnessy Jutamas , Gulati Sunita , Agarwal Sarika , Unemo Magnus , Ohnishi Makoto , Su Xia-Hong , Monks Brian G. , Visintin Alberto , Madico Guillermo , Lewis Lisa A. , Golenbock Douglas T. , Reed George W. , Rice Peter A. , Ram Sanjay
Published: January 2016

Neisseria gonorrhoeae, the causative agent of the sexually transmitted infection gonorrhea, has developed resistance to almost every conventional antibiotic. There is an urgent need to develop novel therapies against gonorrhea. Many pathogens, including N. gonorrhoeae, bind the complement inhibitor factor H (FH) to evade complement-dependent killing. Sialylation of gonococcal lipooligosaccharide, as occurs in vivo, augments binding of human FH through its domains 18–20 (FH18–20). We explored the use of fusing FH18–20 with IgG Fc (FH18–20/Fc) to create a novel anti-infective immunotherapeutic. FH18–20 also binds to select host glycosaminoglycans to limit unwanted complement activation on host cells. To identify mutation(s) in FH18–20 that eliminated complement activation on host cells, yet maintained binding to N. gonorrhoeae, we created four mutations in domains 19 or 20 described in atypical hemolytic uremic syndrome that prevented binding of mutated fH to human erythrocytes. One of the mutant proteins (D to G at position 1119 in domain 19; FHD1119G/Fc) facilitated complement-dependent killing of gonococci similar to unmodified FH18–20/Fc but, unlike FH18–20/Fc, did not lyse human erythrocytes. FHD1119G/Fc bound to all (100%) of 15 sialylated clinical N. gonorrhoeae isolates tested (including three contemporary ceftriaxone-resistant strains), mediated complement-dependent killing of 10 of 15 (67%) strains, and enhanced C3 deposition (≥10-fold above baseline levels) on each of the five isolates not directly killed by complement. FHD1119G/Fc facilitated opsonophagocytic killing of a serum-resistant strain by human polymorphonuclear neutrophils. FHD1119G/Fc administered intravaginally significantly reduced the duration and burden of gonococcal infection in the mouse vaginal colonization model. FHD1119G/Fc represents a novel immunotherapeutic against multidrug-resistant N. gonorrhoeae.
Potential Role of the Formation of Tunneling Nanotubes in HIV-1 Spread in Macrophages
Authors: Hashimoto Michihiro , Bhuyan Farzana , Hiyoshi Masateru , Noyori Osamu , Nasser Hesham , Miyazaki Mitsue , Saito Tamio , Kondoh Yasumitsu , Osada Hiroyuki , Kimura Shunsuke , Hase Koji , Ohno Hiroshi , Suzu Shinya
Published: January 2016

Tunneling nanotubes (TNTs), the long membrane extensions connecting distant cells, have emerged as a novel form of cell-to-cell communication. However, it is not fully understood how and to what extent TNTs contribute to intercellular spread of pathogens including HIV-1. In this study, we show that HIV-1 promotes TNT formation per se via its protein Nef and a cellular protein M-Sec, which appears to mediate approximately half of viral spread among monocyte-derived macrophages (MDMs). A small compound that inhibits M-Sec–induced TNT formation reduced HIV-1 production by almost half in MDMs. Such inhibition was not observed with Nef-deficient mutant HIV-1 that fails to promote TNT formation and replicates less efficiently than the wild-type HIV-1 in MDMs. The TNT inhibitor–sensitive/Nef-promoting viral production was also observed in a T cell line ectopically expressing M-Sec, but not in another M-Sec− T cell line. Our results suggest the importance of TNTs in HIV-1 spread among MDMs and might answer the long-standing question how Nef promotes HIV-1 production in a cell type–specific manner.
Pro- and Anti-Inflammatory Role of ChemR23 Signaling in Pollutant-Induced Inflammatory Lung Responses
Authors: Provoost Sharen , De Grove Katrien C. , Fraser Graeme L. , Lannoy Vincent J. , Tournoy Kurt G. , Brusselle Guy G. , Maes Tania , Joos Guy F.
Published: January 2016

Inhalation of traffic-related particulate matter (e.g., diesel exhaust particles [DEPs]) is associated with acute inflammatory responses in the lung, and it promotes the development and aggravation of allergic airway diseases. We previously demonstrated that exposure to DEP was associated with increased recruitment and maturation of monocytes and conventional dendritic cells (DCs), resulting in TH2 polarization. Monocytes and immature DCs express the G-protein coupled receptor chemR23, which binds the chemoattractant chemerin. Using chemR23 knockout (KO) and corresponding wild-type (WT) mice, we determined the role of chemR23 signaling in response to acute exposure to DEPs and in response to DEP-enhanced house dust mite (HDM)-induced allergic airway inflammation. Exposure to DEP alone, as well as combined exposure to DEP plus HDM, elevated the levels of chemerin in the bronchoalveolar lavage fluid of WT mice. In response to acute exposure to DEPs, monocytes and monocyte-derived DCs accumulated in the lungs of WT mice, but this response was significantly attenuated in chemR23 KO mice. Concomitant exposure to DEP plus HDM resulted in allergic airway inflammation with increased eosinophilia, goblet cell metaplasia, and TH2 cytokine production in WT mice, which was further enhanced in chemR23 KO mice. In conclusion, we demonstrated an opposing role for chemR23 signaling depending on the context of DEP-induced inflammation. The chemR23 axis showed proinflammatory properties in a model of DEP-induced acute lung inflammation, in contrast to anti-inflammatory effects in a model of DEP-enhanced allergic airway inflammation.
Depletion of CD8+ T Cells Exacerbates CD4+ T Cell–Induced Monocyte-to-Fibroblast Transition in Renal Fibrosis
Authors: Dong Yanjun , Yang Min , Zhang Jing , Peng Xiaogang , Cheng Jizhong , Cui Taigeng , Du Jie
Published: January 2016

Bone marrow–derived monocyte-to-fibroblast transition is a key step in renal fibrosis pathogenesis, which is regulated by the inflammatory microenvironment. However, the mechanism by which the inflammatory microenvironment regulates this transition is not fully understood. In this study, we examined how the CD8+ T cell/IFN-γ microenvironment regulates the monocyte-to-fibroblast transition in renal fibrosis. Genetic ablation of CD8 promoted a monocyte-to-fibroblast transition and increased renal interstitial fibrosis, whereas reconstitution of CD8 knockout (KO) mice with CD8+ T cells decreased fibrosis. However, depletion of CD4+ T cells in CD8 KO mice also reduced fibrosis. To elucidate the role of CD4+ T cells in mediating CD8-regulated monocyte-to-fibroblast transition, CD4+ T cells were isolated from obstructed kidneys of CD8 KO or wild-type mice. CD4+ T cells isolated from CD8 KO obstructed kidney expressed more IL-4 and GATA3 and less IFN-γ and T-bet and showed increased monocyte-to-fibroblast transition in vitro compared with those isolated from wild-type obstructed kidney. To examine the role of IFN-γ–expressing CD8+ T cells, we reconstituted CD8 KO mice with CD8+ T cells isolated from IFN-γ KO mice. The IFN-γ KO CD8+ cells had no effect on IL-4, GATA3, IFN-γ, and T-bet mRNA expression in obstructed kidneys or renal fibrosis. Taken together, our findings identify the axis of CD8+ T cells and IFN-γ–CD4+ T cells as an important microenvironment for the monocyte-to-fibroblast transition, which negatively regulates renal fibrosis.
Swift and Strong NK Cell Responses Protect 129 Mice against High-Dose Influenza Virus Infection
Authors: Zhou Kai , Wang Jing , Li An , Zhao Wenming , Wang Dongfang , Zhang Wei , Yan Jinghua , Gao George Fu , Liu Wenjun , Fang Min
Published: January 2016

It is generally unclear what roles NK cells play during influenza virus infection with regard to different host genetic backgrounds. In this study, we show that in six inbred mouse strains, NK cells play an important protective role only in 129 mice during high-dose influenza A H1N1 virus infection. Swift and strong NK cell responses efficiently control early pulmonary viral replication in 129 mice, providing survival privilege. In addition, we identified that early activation of TLRs and RIG-I signaling in 129 mice resulted in quick production of type 1 IFNs and inflammatory cytokines, which are important reasons for the swift kinetics of NK cell responses post influenza virus infection. Thus, under different microenvironments, NK cells play differential roles against viral infections. The kinetics and magnitude of NK cell responses correlate with the distinct roles that NK cells play against influenza virus infections. Thus, our works further our understandings about the complex role of NK cells during influenza virus infection.
p52 Overexpression Increases Epithelial Apoptosis, Enhances Lung Injury, and Reduces Survival after Lipopolysaccharide Treatment
Authors: Saxon Jamie A. , Cheng Dong-Sheng , Han Wei , Polosukhin Vasiliy V. , McLoed Allyson G. , Richmond Bradley W. , Gleaves Linda A. , Tanjore Harikrishna , Sherrill Taylor P. , Barham Whitney , Yull Fiona E. , Blackwell Timothy S.
Published: January 2016

Although numerous studies have demonstrated a critical role for canonical NF-κB signaling in inflammation and disease, the function of the noncanonical NF-κB pathway remains ill-defined. In lung tissue from patients with acute respiratory distress syndrome, we identified increased expression of the noncanonical pathway component p100/p52. To investigate the effects of p52 expression in vivo, we generated a novel transgenic mouse model with inducible expression of p52 in Clara cell secretory protein–expressing airway epithelial cells. Although p52 overexpression alone did not cause significant inflammation, p52 overexpression caused increased lung inflammation, injury, and mortality following intratracheal delivery of Escherichia coli LPS. No differences in cytokine/chemokine expression were measured between p52-overexpressing mice and controls, but increased apoptosis of Clara cell secretory protein–positive airway epithelial cells was observed in transgenic mice after LPS stimulation. In vitro studies in lung epithelial cells showed that p52 overexpression reduced cell survival and increased the expression of several proapoptotic genes during cellular stress. Collectively, these studies demonstrate a novel role for p52 in cell survival/apoptosis of airway epithelial cells and implicate noncanonical NF-κB signaling in the pathogenesis of acute respiratory distress syndrome.
NK Cell–Specific Gata3 Ablation Identifies the Maturation Program Required for Bone Marrow Exit and Control of Proliferation
Authors: Ali Alaa Kassim , Oh Jun Seok , Vivier Eric , Busslinger Meinrad , Lee Seung-Hwan
Published: January 2016

NK cells are innate lymphocytes capable of eliciting an innate immune response to pathogens. NK cells develop and become mature in the bone marrow (BM) before they migrate out to peripheral organs. Although the developmental program leading to mature NK cells has been studied in the context of several transcription factors, the stage-specific role of GATA3 in NK cell development has been incompletely understood. Using NKp46-Cre-Gata3fl/fl mice in which Gata3 deficiency was induced as early as the immature stage of NK cell differentiation, we demonstrated that GATA3 is required for the NK cell maturation beyond the CD27 single-positive stage and is indispensable for the maintenance of liver-resident NK cells. The frequencies of NK cells from NKp46-Cre-Gata3fl/fl mice were found higher in the BM but lower in peripheral organs compared with control littermates, indicating that GATA3 controls the maturation program required for BM egress. Despite the defect in maturation, upon murine CMV infection, NK cells from NKp46-Cre-Gata3fl/fl mice expanded vigorously, achieving NK cell frequencies surpassing those in controls and therefore provided comparable protection. The heightened proliferation of NK cells from NKp46-Cre-Gata3fl/fl mice was cell intrinsic and associated with enhanced upregulation of CD25 expression. Taken together, our results demonstrate that GATA3 is a critical regulator for NK cell terminal maturation and egress out of the BM and that immature NK cells present in the periphery of NKp46-Cre-Gata3fl/fl mice can rapidly expand and provide a reservoir of NK cells capable of mounting an efficient cytotoxic response upon virus infection.