bluuebunny/crossref_metadata_2025 huggingface dataset:
Do Radiographic Joint Damage and Disease Activity Influence Functional Disability Through Different Mechanisms? Direct and Indirect Effects of Disease Activity in Established Rheumatoid Arthritis
Authors: Nair Sandhya C. , Bijlsma Johannes W.J. , van der Werf Jacobien H. , van der Veen Maaike J. , Linn-Rasker Suzanne P. , Vreugdenhil Simone , Lafeber Floris P.J.G. , Welsing Paco M.J.
Published: July 2013

Objective.

To explore the relationship between rheumatoid arthritis (RA) disease activity and functional disability over time, considering indirect (predictive) and direct (concurrent) associations as well as the influence of radiographic joint damage and treatment strategy.

Methods.

Functional disability [Health Assessment Questionnaire (HAQ)], disease activity [28-joint Disease Activity Score (DAS28)], and radiographic joint damage [Sharp/van der Heijde score (SHS)] were measured in 4 consecutive randomized controlled trials with increasingly intensive (tight control) treatment strategies. Average followup time for the 3 cohorts was 97, 53, and 50 months, respectively. Next to current DAS28, the previous DAS28 was used to study the predictive effect of a change in DAS28 on progression of functional disability (HAQ). Finally, it was investigated whether SHS mediated the predictive effect of DAS28.

Results.

In patients treated with intensive treatment strategies, the progression of HAQ over time was statistically significantly less (p < 0.0001). The predictive influence of DAS28 on HAQ progression increased over the duration of the disease. SHS was not found to influence HAQ progression and did not mediate the predictive effect of DAS28. In the less intensively treated patients, the direct effect of disease activity decreased with disease duration, and contrarily, SHS did influence HAQ progression, but was not found to (fully) mediate the predictive effect of DAS28.

Conclusion.

In patients with RA treated with modern treatment strategies, there is less functional decline over time. Further, disease activity does predict functional decline but joint damage does not. This might indicate that factors associated with cumulative disease activity but not visible on radiographs can influence functional decline in patients with RA. This further underlines the importance of disease activity as a treatment target in early RA and in established RA.
Vitamin D Deficiency, Interleukin 17, and Vascular Function in Rheumatoid Arthritis
Authors: Ranganathan Prabha , Khalatbari Shokoufeh , Yalavarthi Srilakshmi , Marder Wendy , Brook Robert , Kaplan Mariana J.
Published: July 2013

Objective.

Vitamin D deficiency is associated with increased cardiovascular (CV) disease risk in the general population. We examined the association between vitamin D deficiency and CV risk in rheumatoid arthritis (RA).

Methods.

We measured large artery compliance by pulse wave velocity and microvascular function by the reactive hyperemia index in patients with stable RA (n = 87). We quantified CV risk factors, serum 25-hydroxyvitamin D [25(OH)D], and interleukin 17 (IL-17), and RA disease activity by Disease Activity Score of 28 joints. We used linear regression to test associations between serum 25(OH)D and CV risk factors.

Results.

The mean serum 25(OH)D level in the cohort was 27.1 ± SD 13.6 ng/ml. Fifty-nine patients (68%) were vitamin D-insufficient (25(OH)D < 30 ng/ml; mean 20.2 ± 5.9 ng/ml) and of these, 25 (29%) were vitamin D-deficient (25(OH)D < 20 ng/ml; mean 14.4 ± 3.4 ng/ml). In the whole cohort and the vitamin D-insufficient group, serum 25(OH)D was inversely associated with IL-17 (log IL-17; β = −0.83, p = 0.04; β = −0.63, p = 0.004, respectively) by univariate analysis, which persisted after adjustment for season, and in multivariate analysis after adjustment for confounders (log IL-17; β = −0.74, p = 0.04; β = −0.53, p = 0.02). In vitamin D-deficient patients, serum 25(OH)D was positively associated with microvascular function by univariate and multivariate analysis after adjustment for confounders (β = 2.1, p = 0.04; β = 2.7, p = 0.04).

Conclusion.

Vitamin D deficiency in RA may affect Th17 responses and microvascular function. Maintaining normal serum vitamin D levels may protect against IL-17-mediated inflammation and vascular dysfunction in RA.
Attack Rate of Chlamydia-induced Reactive Arthritis and Effect of the CCR5-Delta-32 Mutation: A Prospective Analysis
Authors: Carter John D. , Rehman Aasim , Guthrie Jason P. , Gerard Herve C. , Stanich Jessica , Hudson Alan P.
Published: July 2013

Objective.

Factors that predispose patients to Chlamydia-induced reactive arthritis (CiReA) are poorly defined. Data indirectly suggest chemokine receptor-5 (CCR5)-delta-32 mutation might play a role in CiReA. We investigated the attack rate of CiReA and we hypothesized that the CCR5-delta-32 allele may modulate disease susceptibility.

Methods.

Patients who tested positive for Chlamydia trachomatis after either (1) symptoms of an acute venereal disease or (2) sexual contact with an individual known to be positive for the same organism were followed in a prospective fashion. All patients were contacted at Week 6 after their acute infection and queried for symptoms of CiReA. Patients who had new-onset symptoms suggestive of CiReA were followed at Weeks 12, 26, and 52. All subjects were tested for CCR5-delta-32 mutation.

Results.

A total of 365 study participants were enrolled, with average age 24.4 years, 201 men (55%) and 164 women (45%). We followed up with 149 patients (41%) at Week 6. Twelve of 149 participants (8.1%) had symptoms suggestive of CiReA at Week 6. None of these 12 patients was positive for the CCR5-delta-32 mutation. Of the 12 patients that had symptoms at Week 6, we were able to follow up with 7 through Week 52. All 7 had complete resolution of their symptoms by Week 26. Overall, 25/365 (6.8%) subjects were positive for the CCR5-delta-32 mutation.

Conclusion.

The attack rate of CiReA in our study was higher than previously reported, but the CCR5-delta-32 mutation does not seem to play a role in CiReA disease susceptibility.
A Questionnaire Using the Modified 2010 American College of Rheumatology Criteria for Fibromyalgia: Specificity and Sensitivity in Clinical Practice
Authors: Ferrari Robert , Russell Anthony S.
Published: July 2013

Objective.

To determine the specificity and sensitivity of the Modified 2010 American College of Rheumatology (ACR) Diagnostic Criteria for Fibromyalgia (given as a self-administered questionnaire) in clinical practice.

Methods.

A cohort of patients with widespread pain, referred by primary care physicians to rheumatologists, completed the questionnaire for the Modified ACR 2010 criteria. Prior to completion of the questionnaire, patients were diagnosed by at least 1 rheumatologist as either having fibromyalgia (FM) or not having FM, using the rheumatologist’s clinical assessment as the gold standard for diagnosis of FM. The Modified ACR 2010 criteria were then applied to determine whether a diagnosis of FM was satisfied by the criteria. Sensitivity and specificity were determined, using the rheumatologist’s clinical assessment as the gold standard. A score ≥ 12 on the Modified ACR 2010 criteria questionnaire was also tested as the criterion to satisfy a diagnosis of FM, and subsequently to determine sensitivity and specificity. We examined the effect of using a cutoff score ≥ 13, as previous research indicated that this may be a more useful cutoff value.

Results.

A total of 451 subjects completed the questionnaire: 174 with an a priori diagnosis of FM by a rheumatologist and 277 with widespread pain who did not have an a priori clinical diagnosis of FM by a rheumatologist. The Modified ACR 2010 criteria were satisfied by 90.2% of patients with an a priori diagnosis of FM, and by 10.5% of subjects who had widespread pain, but were not diagnosed with FM when previously assessed by a rheumatologist. Thus, sensitivity and specificity are 90.2% and 89.5%, respectively, using the Modified ACR 2010 criteria. A score ≥ 12 on the Modified ACR 2010 criteria was observed in 97.4% of patients with an a priori diagnosis of FM, and 14.8% of subjects who had widespread pain, but were not diagnosed with FM when previously assessed by a rheumatologist. Thus, the sensitivity and specificity are 97.4% and 85.2%, respectively, using a cutoff score ≥ 12. Using a score of ≥ 13, however, the sensitivity was 93.1% and the specificity was 91.7%.

Conclusion.

The Modified ACR 2010 criteria questionnaire can be used in primary care as a tool to assist physicians in the diagnosis of FM with high specificity and sensitivity. Calculating the total score on a Modified ACR 2010 criteria questionnaire, and setting the value of ≥ 13 as the cutoff for a diagnosis of FM appears to be the most effective approach. The Modified ACR 2010 criteria may reduce the need for rheumatology referral simply for the diagnosis of FM.
Démocratiser les tiers-lieux
Authors: Burret Antoine
Published: July 2013

Les nouvelles technologies ont été mises à la disposition du public dans des espaces publics de statuts divers où des individus passionnés ont partagé leurs connaissances sans poser de conditions préalables avec ceux que cela intéressait. Ont émergé ainsi de nouveaux lieux d’apprentissage et de travail en commun. Cette dynamique est étudiée ici dans le cas exemplaire du Comptoir numérique à Saint-Étienne. Il reste à banaliser le vocabulaire de ces expérimentations pour les rendre complètement accessibles.
Modèles coopératifs émergents
Authors: Nghiem Thanh
Published: July 2013

Les pratiques coopératives qui émergent sur Internet ou dans les lieux qui cherchent à démocratiser les nouvelles technologies vont-ils pouvoir transformer nos modes de vie ? Le partage et le recyclage qui étaient des pratiques de proximité ancestrales redeviennent désirables face à la crise climatique et écologique. Le logiciel libre a ouvert la voie d’une éthique open source et de transmission des innovations qui s’étend au monde matériel.
Séduction et dépendance marchande
Authors: Pharo Patrick
Published: July 2013

Cet article est consacré au rôle des plaisirs et récompenses dans l’expérience des dépendances addictives ou pratiques – la dépendance marchande constituant un cas intermédiaire. Le texte donne quelques exemples des affinités électives entre une motivation naturelle à consommer et user des plaisirs et l’extension du profit marchand à la vie privée et affective. Il montre aussi comment la gloire du marché, issue de quelques élites, peut alimenter les rêves ordinaires de belle vie. Contrairement cependant à la thèse pessimiste d’une corruption marchande généralisée du regard de soi-même sur soi-même, le texte conclut en faveur d’une autonomie des sources morales de grandissement interne et d’auto-sublimation.
Prospective Contralateral Eye Study to Compare 80- and 120-
μ
m Flap LASIK Using the VisuMax Femtosecond Laser
Authors: Lim Dong Hui , Keum Ji Eun , Ju Won-Kyung , Lee Jeong-Hye , Chung Tae-Young , Chung Eui-Sang
Published: July 2013

PURPOSE:

To compare visual outcomes and flap stability of LASIK with ultrathin 80- and 120-
μ
m flaps created with a VisuMax femtosecond laser (Carl Zeiss Meditec, Jena, Germany) for moderate to high myopia and to evaluate the effect of corneal flap thickness on outcomes.

METHODS:

In a prospective contralateral eye study, 36 consecutive patients (72 eyes) underwent bilateral LASIK for myopia ranging from −2.00 to −10.00 diopters using the VisuMax femtosecond laser and MEL-80 excimer laser (Carl Zeiss Meditec). One eye of each patient was randomized to have the 80-
μ
m flap and the other to the 120-
μ
m flap created with 200-kHz VisuMax femtosecond laser. Preoperative and postoperative tests included visual acuity, manifest refraction, contrast sensitivity, and flap thickness measured by anterior segment optical coherence tomography. Main outcomes and complications were checked at postoperative 1 week and 1, 3, and 6 months.

RESULTS:

There were no differences in visual outcome, residual refractive error, or contrast sensitivity between groups during follow-up, except for better uncorrected visual acuity at postoperative 1 day in the 120-
μ
m group. Mean standard deviations of measured flap thickness during follow-up ranged from 3.16 to 3.80
μ
m in both groups. Opaque bubble layer, a unique complication in femtosecond LASIK, was more frequent in the 80-
μ
m group (7 of 36: 19%) than in the 120-
μ
m flap group (3 of 36: 8%) without a statistically significant difference (
P
= .301) and was related to thicker central cornea and steeper keratometric value, although it did not influence clinical results. Comparison of the intended versus achieved correction showed no significant differences between groups.

CONCLUSIONS:

LASIK using the VisuMax femtosecond laser supplied good clinical results and flap reproducibility in both the 80- and 120-
μ
m flap groups. Patients with relatively thin cornea may benefit from 80-
μ
m flap LASIK.

[
J Refract Surg.
2013;29(7):462–468.]
Implications and Management of Suction Loss During Refractive Lenticule Extraction (ReLEx)
Authors: Sharma Ratnesh , Vaddavalli Pravin Krishna
Published: July 2013

PURPOSE:

To describe a case in which the ReLEx procedure was abandoned following suction loss on two occasions due to an uncooperative patient.

METHODS:

Case report with anterior segment optical coherence tomography and aberrometry changes before and after surgery.

RESULTS:

Lamellar haze was present but diminished in the early postoperative period. The patient successfully underwent a femtosecond LASIK procedure in the same eye 2 months later.

CONCLUSIONS:

This case demonstrates the possibility of performing femtosecond LASIK after failed ReLEx, with good visual outcomes.

[
J Refract Surg.
2013;29(7):502–503.]
Origen, vías de penetración y expansión de cruces y cruceros en la Península Ibérica
Authors: Plaza Beltrán Marta
Published: July 2013

¿Cómo nacen las cruces monumentales que nosotros conocemos? El artículo que nos ocupa pretende dar a conocer el origen de las cruces de piedra que vemos distribuidas por toda la geografía española, consideradas todas ellas elementos artísticos con una fuerte carga simbólica, social y cultural.
La doctrina cristiana, utilizó primero el signo de la cruz para la consagración de lugares o elementos pertenecientes a antiguos cultos paganos y más tarde, de forma material, la situó en estos puntos (sobre dólmenes, menhires, miliarios; en los caminos, puentes, fuentes o montes), con o sin pedestal, construida de madera o de piedra, con diferentes formas y características.
Cadena de oro para atraer a los herejes. Argumentos de persuasión y estrategias de supervivencia en Fray Juan de Villagarcía, o.p., discípulo de Fray Bartolomé de Carranza
Authors: Moreno Doris
Published: July 2013

En este artículo se aborda, en primer lugar, el perfil biográfico del dominico fray Juan de Villagarcía, su papel en la recatolización de Inglaterra y sus problemas con el Santo Oficio, paralelos al proceso de su maestro, el arzobispo de Toledo Carranza. Se analizará también su manuscrito: Diálogo o Cadena de oro para atraer a los herejes, escrito entre 1560 y 1563, estableciendo similitudes y distancias respecto al pensamiento de Carranza.
La intervención musical en las exequias reales de la catedral de Cuenca (1598-1621)
Authors: De la Fuente Charfolé José Luis
Published: July 2013

El artículo discute la unicidad musical en el oficio de difuntos a partir de un primer acercamiento a los actos exequiales que tuvieron lugar en la catedral de Cuenca entre 1598 y 1621, relacionados con los óbitos de Felipe II, Margarita de Austria y Felipe III: ceremonias de acusada magnificencia, reiteradas en las principales capitales españolas. Tras el análisis de su organización el artículo incluye la transcripción de cinco documentos asociados que contienen datos inéditos de interés histórico y artístico.
De la iglesia a la plantación: tras la huella de los betlemitas en La Habana (1704-1842)
Authors: Camacho Domínguez Adriam
Published: July 2013

La orden de Nuestra Señora de Belén ocupó una importante posición económica y social durante el período colonial en La Habana, esta posibilidad le permitió establecer redes y alianzas con diversos sectores sociales y grupos de élite. Estos compromisos crearon complejas relaciones entre la orden religiosa y la realidad socio-económica de su tiempo, involucrándola en la administración de ingenios azucareros, haciendas ganaderas y el contrabando de esclavos para cumplir con sus compromisos benéficos.
El cristiano Joan Maragall: tres artículos sobre la semana trágica
Authors: Raguer i Suñer Hilari
Published: July 2013

Entre el 19 y el 25 de julio de 1909 estalló en Barcelona un movimiento popular de protesta contra la movilización de reservistas enviados a Marruecos. La subversión revistió un carácter marcadamente anticlerical, con muchos incendios de iglesias y conventos y tres sacerdotes asesinados. Joan Maragall escribió tres artículos disintiendo de la dura represión del gobierno, respaldado por la opinión general. En un primer artículo Maragall acusaba a la burguesía catalana de falta de amor a los pobres. En el segundo pedía que no se aplicaran más penas de muerte, pero no se lo publicaron. En el tercero y más famoso explicaba su experiencia de una misa celebrada en una iglesia quemada por los revolucionarios, en la que vio lo que debería ser la Iglesia, libre de la protección del estado y de los ricos, y la misa en la lengua del pueblo. Este artículo causó gran escándalo entre la burguesía de Barcelona.

[ct] Entre el 19 i el 25 juliol 1909 va esclatar a Barcelona un moviment popular de protesta contra la mobilització de reservistes enviats al Marroc. La subversió revestí un caràcter marcadament anticlerical, amb molts incendis d’esglésies i convents i tres sacerdots assassinats. Joan Maragall va escriure tres articles dissentint de la dura repressió del govern, recolzat per l’opinió general. En un primer article Maragall acusava a la burgesia catalana de manca d’amor als pobres. En el segon demanava que no s’aplicaran més penes de mort, però no l’hi van publicar. En el tercer i més famós explicava la seva experiència d’una missa celebrada en una església cremada pels revolucionaris, en la qual va veure el que hauria de ser l’Església, lliure de la protecció de l’estat i dels rics, i la missa en la llengua del poble. Aquest article va causar gran escàndol entre la burgesia de Barcelona.
Mayo del 68 y los católicos catalanes
Authors: Martínez Hoyos Francisco
Published: July 2013

En 1968, la Iglesia catalana vivía en plena crisis postconciliar. Los sectores más progresistas se sentían decepcionados porque no se habían producido los cambios que esperaban tras el Vaticano II. Los acontecimientos parisinos inciden sobre este contexto eclesial, marcado por la división y el influjo del marxismo. El artículo se centra en las reacciones de Alfonso Carlos Comín, El Ciervo y el clero representado por la revista Correspondència.
Antigen-Free Adjuvant Assists Late Effector CD4 T Cells To Transit to Memory in Lymphopenic Hosts
Authors: Guloglu F. Betul , Ellis Jason S. , Wan Xiaoxiao , Dhakal Mermagya , Hoeman Christine M. , Cascio Jason A. , Zaghouani Habib
Published: July 2013

The events controlling the transition of T cells from effector to memory remain largely undefined. Many models have been put forth to account for the origin of memory precursors, but for CD4 T cells initial studies reported that memory T cells derive from IFN-γ–nonproducing effectors, whereas others suggested that memory emanates from highly activated IFN-γ–producing effectors. In this study, using cell proliferation, expression of activation markers, and production of IFN-γ as a measure of activation, we defined two types of effector CD4 T cells and investigated memory generation. The moderately activated early effectors readily transit to memory, whereas the highly activated late effectors, regardless of their IFN-γ production, develop minimal memory. Boosting with Ag-free adjuvant, however, rescues late effectors from cell death and sustains both survival and IFN-γ cytokine responses in lymphopenic hosts. The adjuvant-mediated memory transition of late effectors involves the function of TLRs, most notably TLR9. These findings uncover the mechanism by which late effector CD4 T cells are driven to transit to memory and suggest that timely boosts with adjuvant may enhance vaccine efficacy.
IL-16 Induces Intestinal Inflammation via PepT1 Upregulation in a Pufferfish Model: New Insights into the Molecular Mechanism of Inflammatory Bowel Disease
Authors: Wang Ping , Lu Yi-qi , Wen Yi , Yu Dai-yong , Ge Liang , Dong Wei-ren , Xiang Li-xin , Shao Jian-zhong
Published: July 2013

Inflammatory bowel disease (IBD) has long been a worldwide health care problem with a persistently increasing incidence. Although its clinical features have been well described, its etiology and pathogenesis remain unclear. IL-16 is a chemoattractant cytokine with various effects on cellular activities and diseases. However, the involvement of IL-16 in IBD remains poorly understood. In this study, to our knowledge we report for the first time the mechanism by which IL-16 induces intestinal inflammation by upregulating the expression of oligopeptide transporter member 1 (PepT1) in a Tetraodon nigroviridis fish model. The dextran sodium sulfate–induced colitis model in this species revealed that IL-16 levels significantly increase accompanied by elevations in PepT1 in the colon. Moreover, the signs of colitis were dramatically attenuated by IL-16 depletion using anti–IL-16 Abs. In vivo IL-16 administration induced remarkable intestinal inflammation with typical ulcerative colitis–like features, including histologic damage, inflammatory cell infiltration, increased myeloperoxidase activity, and proinflammatory cytokines expression, which corresponded with significant PepT1 upregulation in the colon. The IL-16–induced PepT1 expression and its upregulated fMLF transport were also demonstrated in vitro. To our knowledge, our study provides the first evidence of the connection between IL-16 and PepT1, which provides new insights into the molecular mechanism underlying IBD development. Additionally, this study suggests that fish species are an attractive model for studying IBD. By providing a better understanding of IL-16 biology from fish to mammals, this study should aid the development of IL-16–based therapies for IBD.
Tumor-Derived Lactate Modifies Antitumor Immune Response: Effect on Myeloid-Derived Suppressor Cells and NK Cells
Authors: Husain Zaheed , Huang Yannu , Seth Pankaj , Sukhatme Vikas P.
Published: July 2013

In this study, we explore the hypothesis that enhanced production of lactate by tumor cells, because of high glycolytic activity, results in inhibition of host immune response to tumor cells. Lactate dehydrogenase-A (LDH-A), responsible for conversion of pyruvate to lactate, is highly expressed in tumor cells. Lentiviral vector–mediated LDH-A short hairpin RNA knockdown Pan02 pancreatic cancer cells injected in C57BL/6 mice developed smaller tumors than mice injected with Pan02 cells. A decrease occurred in the frequency of myeloid-derived suppressor cells (MDSCs) in the spleens of mice carrying LDH-A–depleted tumors. NK cells from LDH-A–depleted tumors had improved cytolytic function. Exogenous lactate increased the frequency of MDSCs generated from mouse bone marrow cells with GM-CSF and IL-6 in vitro. Lactate pretreatment of NK cells in vitro inhibited cytolytic function of both human and mouse NK cells. This reduction of NK cytotoxic activity was accompanied by lower expression of perforin and granzyme in NK cells. The expression of NKp46 was decreased in lactate-treated NK cells. These studies strongly suggest that tumor-derived lactate inhibits NK cell function via direct inhibition of cytolytic function as well as indirectly by increasing the numbers of MDSCs that inhibit NK cytotoxicity. Depletion of glucose levels using a ketogenic diet to lower lactate production by glycolytic tumors resulted in smaller tumors, decreased MDSC frequency, and improved antitumor immune response. These studies provide evidence for an immunosuppressive role of tumor-derived lactate in inhibiting innate immune response against developing tumors via regulation of MDSC and NK cell activity.
Differential Impact of Age and Cytomegalovirus Infection on the γδ T Cell Compartment
Authors: Roux Antoine , Mourin Gisèle , Larsen Martin , Fastenackels Solène , Urrutia Alejandra , Gorochov Guy , Autran Brigitte , Donner Catherine , Sidi Daniel , Sibony-Prat Joyce , Marchant Arnaud , Stern Marc , Sauce Delphine , Appay Victor
Published: July 2013

γδ T cells represent a subset of unconventional T lymphocytes that are known for their reactivity against different pathogens and considered as intermediate mediators between adaptive and innate immunity. We provide in this paper further insights underlying the changes that affect the γδ T cell compartment with advanced age in humans. We show that both aging and CMV infection impact independently on the γδ T cell compartment. Most γδ T cells are significantly affected by age and present a decreased frequency in the elderly. The decline of the γδ T cell pool appears to be independent from the activity of the thymus, arguing in favor of an extrathymic site of γδ T cell production in humans. Of note, CMV infection, which is directly associated with the activation of the pool of Vδ2− γδ T cells, promotes nonetheless the inflation of this compartment throughout life. CMV seropositivity accentuates further the accumulation of highly differentiated lymphocytes in Vδ2− γδ T cell subsets with time, in contrast to Vδ2+ γδ T cells, which maintain a less differentiated phenotype. This is similar to the effect of CMV on αβ T cells and suggests that γδ T cells may vary in differentiation phenotype according to distinct stimuli or pathogens.
Adipocytes Modulate the Phenotype of Human Macrophages through Secreted Lipids
Authors: Klein-Wieringa Inge R. , Andersen Stefan N. , Kwekkeboom Joanneke C. , Giera Martin , de Lange-Brokaar Badelog J. E. , van Osch Gerjo J. V. M. , Zuurmond Anne-Marie , Stojanovic-Susulic Vedrana , Nelissen Rob G. H. H. , Pijl Hanno , Huizinga Tom W. J. , Kloppenburg Margreet , Toes René E’. M. , Ioan-Facsinay Andreea
Published: July 2013

Previous studies have shown accumulation and an enhanced proinflammatory profile of macrophages in adipose tissue of obese mice, indicating the presence of an interaction between adipocytes and macrophages in this tissue. However, the consequences of this interaction in humans are yet incompletely understood. In this study, we explored the modulating effects of adipocytes on the phenotype of macrophages in humans and studied the possible molecular pathways involved. Adipocyte-conditioned media (ACM) treatment of macrophages for 48 h strongly reduced the LPS-induced IL-12p40 secretion by macrophages, whereas the production of TNF-α and other cytokines remained largely unaffected. This effect was independent of the source of adipocytes. Interestingly, the level of inhibition correlated directly with body mass index (BMI) of the adipocyte donor. Because adipocytes release many different cytokines, adipokines, and lipids, we have separated the protein and lipid fractions of ACM, to obtain insight into the molecular nature of the soluble mediators underlying the observed effect. These experiments revealed that the inhibitory effect resided predominantly in the lipid fraction. Further studies revealed that PGE2 and linoleic and oleic acid were potent inhibitors of IL-12p40 secretion. Interestingly, concentrations of these ACM-derived lipids increased with increase in BMI of the adipocyte donor, suggesting that they could mediate the BMI-dependent effects of ACM. To our knowledge, these results provide first evidence that obesity-related changes in adipose tissue macrophage phenotype could be mediated by adipocyte-derived lipids in humans. Intriguingly, these changes appear to be different from those in murine obesity.
The Encephalitogenic, Human Myelin Oligodendrocyte Glycoprotein–Induced Antibody Repertoire Is Directed toward Multiple Epitopes in C57BL/6-Immunized Mice
Authors: Bansal Pankaj , Khan Tarique , Bussmeyer Uta , Challa Dilip K. , Swiercz Rafal , Velmurugan Ramraj , Ober Raimund J. , Ward E. Sally
Published: July 2013

Although Abs specific for myelin oligodendrocyte glycoprotein (MOG) have been detected in patients with multiple sclerosis (MS), their contribution to pathogenesis remains poorly understood. Immunization of C57BL/6 mice with recombinant human MOG (hMOG) results in experimental autoimmune encephalomyelitis involving MOG-specific, demyelinating Abs. This model is therefore informative for understanding anti-MOG humoral responses in MS. In the current study, we have characterized the hMOG-specific Ab repertoire in immunized C57BL/6 mice using both in vitro and in vivo approaches. We demonstrate that hMOG-specific mAbs are not focused on one specific region of MOG, but instead target multiple epitopes. Encephalitogenicity of the mAbs, assessed by the ability of the mAbs to exacerbate experimental autoimmune encephalomyelitis in mice, correlates with the activity of the mAbs in binding to CNS tissue sections, but not with other in vitro assays. The targeting of different MOG epitopes by encephalitogenic Abs has implications for disease pathogenesis, because it could result in MOG cross linking on oligodendrocytes and/or immune complex formation. These studies reveal several novel features concerning pathogenic, humoral responses that may have relevance to human MS.
A Protective Hsp70–TLR4 Pathway in Lethal Oxidant Lung Injury
Authors: Zhang Yi , Zhang Xuchen , Shan Peiying , Hunt Clayton R. , Pandita Tej K. , Lee Patty J.
Published: July 2013

Administering high levels of inspired oxygen, or hyperoxia, is commonly used as a life-sustaining measure in critically ill patients. However, prolonged exposures can exacerbate respiratory failure. Our previous study showed that TLR4 confers protection against hyperoxia-induced lung injury and mortality. Hsp70 has potent cytoprotective properties and has been described as a TLR4 ligand in cell lines. We sought to elucidate the relationship between TLR4 and Hsp70 in hyperoxia-induced lung injury in vitro and in vivo and to define the signaling mechanisms involved. Wild-type, TLR4−/−, and Trif−/− (a TLR4 adapter protein) murine lung endothelial cells (MLECs) were exposed to hyperoxia. We found markedly elevated levels of intracellular and secreted Hsp70 from wild-type mice lungs and MLECs after hyperoxia. We confirmed that Hsp70 and TLR4 coimmunoprecipitate in lung tissue and MLECs. Hsp70-mediated NF-κB activation appears to depend upon TLR4. In the absence of TLR4, Hsp70 loses its protective effects in endothelial cells. Furthermore, these protective properties of Hsp70 are TLR4 adapter Trif dependent and MyD88 independent. Hsp70-deficient mice have increased mortality during hyperoxia, and lung-targeted adenoviral delivery of Hsp70 effectively rescues both Hsp70-deficient and wild-type mice. To our knowledge, our studies are the first to define an Hsp70–TLR4–Trif cytoprotective axis in the lung and endothelial cells. This pathway is a potential therapeutic target against a range of oxidant-induced lung injuries.
Corticosteroids Block Autophagy Protein Recruitment in Aspergillus fumigatus Phagosomes via Targeting Dectin-1/Syk Kinase Signaling
Authors: Kyrmizi Irene , Gresnigt Mark S. , Akoumianaki Tonia , Samonis George , Sidiropoulos Prodromos , Boumpas Dimitrios , Netea Mihai G. , van de Veerdonk Frank L. , Kontoyiannis Dimitrios P. , Chamilos Georgios
Published: July 2013

Aspergillus fumigatus is the predominant airborne fungal pathogen in immunocompromised patients. Genetic defects in NADPH oxidase (chronic granulomatous disease [CGD]) and corticosteroid-induced immunosupression lead to impaired killing of A. fumigatus and unique susceptibility to invasive aspergillosis via incompletely characterized mechanisms. Recent studies link TLR activation with phagosome maturation via the engagement of autophagy proteins. In this study, we found that infection of human monocytes with A. fumigatus spores triggered selective recruitment of the autophagy protein LC3 II in phagosomes upon fungal cell wall swelling. This response was induced by surface exposure of immunostimulatory β-glucans and was mediated by activation of the Dectin-1 receptor. LC3 II recruitment in A. fumigatus phagosomes required spleen tyrosine kinase (Syk) kinase–dependent production of reactive oxygen species and was nearly absent in monocytes of patients with CGD. This pathway was important for control of intracellular fungal growth, as silencing of Atg5 resulted in impaired phagosome maturation and killing of A. fumigatus. In vivo and ex vivo administration of corticosteroids blocked LC3 II recruitment in A. fumigatus phagosomes via rapid inhibition of phosphorylation of Src and Syk kinases and downstream production of reactive oxygen species. Our studies link Dectin-1/Syk kinase signaling with autophagy-dependent maturation of A. fumigatus phagosomes and uncover a potential mechanism for development of invasive aspergillosis in the setting of CGD and corticosteroid-induced immunosupression.
Ficolin-1–PTX3 Complex Formation Promotes Clearance of Altered Self-Cells and Modulates IL-8 Production
Authors: Ma Ying Jie , Doni Andrea , Romani Luigina , Jürgensen Henrik Jessen , Behrendt Niels , Mantovani Alberto , Garred Peter
Published: July 2013

The long pentraxin 3 (PTX3) has been shown to be important in maintaining internal tissue homeostasis and in protecting against fungal Aspergillus fumigatus infection. However, the molecular mechanisms of how these functions are elicited are poorly delineated. Ficolin-1 is a soluble pattern recognition molecule that interacts with PTX3. We hypothesized that heterocomplexes between ficolin-1 and PTX3 might mediate the signals necessary for sequestration of altered self-cells and A. fumigatus. We were able to show that ficolin-1 interacts with PTX3 via its fibrinogen-like domain. The interaction was affected in a pH- and divalent cation–sensitive manner. The primary binding site for ficolin-1 on PTX3 was located in the N-terminal domain portion of PTX3. Ficolin-1 and PTX3 heterocomplex formation occurred on dying host cells, but not on A. fumigatus. The heterocomplex formation was a prerequisite for enhancement of phagocytosis by human monocyte–derived macrophages and downregulation of IL-8 production during phagocytosis. On A. fumigatus, PTX3 exposed the C-terminal portion of the molecule, probably resulting in steric hindrance of ficolin-1 interaction with PTX3. These results demonstrate that ficolin-1 and PTX3 heterocomplex formation acts as a noninflammatory “find me and eat me” signal to sequester altered-host cells. The fact that the ficolin-1–PTX3 complex formation did not occur on A. fumigatus shows that PTX3 uses different molecular effector mechanisms, depending on which domains it exposes during ligand interaction.
Deficiency of Phospholipase A2 Receptor Exacerbates Ovalbumin-Induced Lung Inflammation
Authors: Tamaru Shun , Mishina Hideto , Watanabe Yosuke , Watanabe Kazuhiro , Fujioka Daisuke , Takahashi Soichiro , Suzuki Koji , Nakamura Takamitsu , Obata Jun-ei , Kawabata Kenichi , Yokota Yasunori , Murakami Makoto , Hanasaki Kohji , Kugiyama Kiyotaka
Published: July 2013

Secretory phospholipase A2 (sPLA2) plays a critical role in the genesis of lung inflammation through proinflammatory eicosanoids. A previous in vitro experiment showed a possible role of cell surface receptor for sPLA2 (PLA2R) in the clearance of extracellular sPLA2. PLA2R and groups IB and X sPLA2 are expressed in the lung. This study examined a pathogenic role of PLA2R in airway inflammation using PLA2R-deficient (PLA2R−/−) mice. Airway inflammation was induced by immunosensitization with OVA. Compared with wild-type (PLA2R+/+) mice, PLA2R−/− mice had a significantly greater infiltration of inflammatory cells around the airways, higher levels of groups IB and X sPLA2, eicosanoids, and Th2 cytokines, and higher numbers of eosinophils and neutrophils in bronchoalveolar lavage fluid after OVA treatment. In PLA2R−/− mice, intratracheally instilled [125I]-labeled sPLA2-IB was cleared much more slowly from bronchoalveolar lavage fluid compared with PLA2R+/+ mice. The degradation of the instilled [125I]-labeled sPLA2-IB, as assessed by trichloroacetic acid-soluble radioactivity in bronchoalveolar lavage fluid after instillation, was lower in PLA2R−/− mice than in PLA2R+/+ mice. In conclusion, PLA2R deficiency increased sPLA2-IB and -X levels in the lung through their impaired clearance from the lung, leading to exaggeration of lung inflammation induced by OVA treatment in a murine model.
Dendritic Cells Regulate High-Speed Interstitial T Cell Migration in the Lymph Node via LFA-1/ICAM-1
Authors: Katakai Tomoya , Habiro Katsuyoshi , Kinashi Tatsuo
Published: July 2013

T lymphocytes vigorously migrate within the paracortex of lymph nodes (LNs) in search of cognate Ags that are presented by dendritic cells (DCs). However, the mechanisms that support T cells to exert the highest motility in a densely packed LN microenvironment are not fully understood. Two-photon microscopy using LN tissue slices revealed that LFA-1 and ICAM-1 were required for high-velocity migration (>10 μm/min) with relatively straight movement. Importantly, ICAM-1 expressed by myeloid lineages, most likely DCs, but not stromal cells or lymphocytes, was sufficient to support the high-velocity migration. Visualizing DCs in the LN from CD11c-EYFP mice showed that T cells traveled over thin dendrites and the body of DCs. Interestingly, DCs supported T cell motility in vitro in chemokine- and ICAM-1–dependent manners. Moreover, an acute lymphopenic environment in the LN significantly increased LFA-1 dependency for T cell migration, indicating that lymphocyte density modulates the use of LFA-1. Therefore, our results indicate that LFA-1/ICAM-1–dependent interactions between T cells and DCs play a crucial role not only in supporting firm arrest during Ag recognition but also in facilitating the Ag scanning processes.
Automated Identification of Fiducial Points on 3D Torso Images
Authors: Kawale Manas M. , Reece Gregory P. , Crosby Melissa A. , Beahm Elisabeth K. , Fingeret Michelle C. , Markey Mia K. , Merchant Fatima A.
Published: July 2013

Breast reconstruction is an important part of the breast cancer treatment process for many women. Recently, 2D and 3D images have been used by plastic surgeons for evaluating surgical outcomes. Distances between different fiducial points are frequently used as quantitative measures for characterizing breast morphology. Fiducial points can be directly marked on subjects for direct anthropometry, or can be manually marked on images. This paper introduces novel algorithms to automate the identification of fiducial points in 3D images. Automating the process will make measurements of breast morphology more reliable, reducing the inter- and intra-observer bias. Algorithms to identify three fiducial points, the nipples, sternal notch, and umbilicus, are described. The algorithms used for localization of these fiducial points are formulated using a combination of surface curvature and 2D color information. Comparison of the 3D coordinates of automatically detected fiducial points and those identified manually, and geodesic distances between the fiducial points are used to validate algorithm performance. The algorithms reliably identified the location of all three of the fiducial points. We dedicate this article to our late colleague and friend, Dr. Elisabeth K. Beahm. Elisabeth was both a talented plastic surgeon and physician-scientist; we deeply miss her insight and her fellowship.
Assouad–Nagata Dimension of Wreath Products of Groups
Authors: Brodskiy N. , Dydak J. , Lang U.
Published: July 2013

Consider the wreath product H ≀ G, where H ≠ 1 is finite and G is finitely generated. We show that the Assouad–Nagata dimension dimAN(H ≀ G) of H ≀ G depends on the growth of G as follows: if the growth of G is not bounded by a linear function, then dimAN(H ≀ G) = ∞; otherwise dimAN(H ≀ G) = dimAN(G) ≤ 1.
On the $\mathrm{SL}(2,\mathbb C)$ quantum $6j$-symbols and their relation to the hyperbolic volume
Authors: Costantino Francesco , Murakami Jun
Published: July 2013

We generalize the colored Alexander invariant of knots to an invariant of graphs and we construct a face model for this invariant by using the corresponding

6j

-symbols, which come from the non-integral representations of the quantum group

{\mathcal U}_q(\mathrm{sl}_2)

. We call it the

\mathrm{SL}(2, \mathbb C)

-quantum

6j

-
symbols
, and show their relation to the hyperbolic volume of a truncated tetrahedron.
Free-Ranging Chickens in Households in a Periurban Shantytown in Peru—Attitudes and Practices 10 Years after a Community-Based Intervention Project
Authors: Martinez Leonardo , Collazo Gisela , Cabrera Lilia , Bernabe-Ortiz Antonio , Ramos-Peña Yasnina , Oberhelman Richard
Published: July 2013

Free-ranging chickens are often found in periurban communities in developing countries, and their feces can pose a significant public health sanitation problem. Corralling chickens raised in these periurban areas in chicken coops has been proposed previously as an intervention to address this problem. Aims of this study were to revisit households in a corralling intervention study conducted in 2000–2001 to compare poultry-raising practices and investigate current attitudes regarding the impact of raising chickens in a periurban environment. Sociobehavioral questionnaires were given sequentially to all study participants; 30 families (58%) ceased raising poultry of any kind, whereas 42 (81%) do not raise chickens in their home. This finding indicates a significant reduction in poultry-raising in our study population since 2000–2001, possibly because of acculturation and/or change in socioeconomic status. However, attitudes about corral use for raising poultry were overwhelmingly positive, and the most common reason cited was cleanliness of the home.
Blood Glucose as a Predictor of Mortality in Children Admitted to the Hospital with Febrile Illness in Tanzania
Authors: Nadjm Behzad , Mtove George , Amos Ben , Hildenwall Helena , Najjuka Anne , Mtei Frank , Todd Jim , Reyburn Hugh
Published: July 2013

Data from a prospective study of 3,319 children ages 2 months to 5 years admitted with febrile illness to a Tanzanian district hospital were analyzed to determine the relationship of blood glucose and mortality. Hypoglycemia (blood sugar < 2.5 mmol/L and < 45 mg/dL) was found in 105 of 3,319 (3.2%) children at admission, and low-normal blood glucose (2.5–5 mmol/L and 45–90 mg/dL) was found in 773 of 3,319 (23.3%) children. Mortality was inversely related to admission blood sugar; compared with children with an admission blood glucose of > 5 mmol/L, the adjusted odds of dying were 3.3 (95% confidence interval = 2.1–5.2) and 9.8 (95% confidence interval = 5.1–19.0) among children with admission blood glucose 2.5–5 and < 2.5 mmol/L, respectively. Receiver operating characteristic (ROC) analysis suggested an optimal cutoff for admission blood sugar of < 5 mmol/L in predicting mortality (sensitivity = 57.7%, specificity = 75.2%). A cutoff for admission blood glucose of < 5 mmol/L represents a simple and clinically useful predictor of mortality in children admitted with severe febrile illness to hospital in resource-poor settings.
Sequence Analyses of 2012 West Nile Virus Isolates from Texas Fail to Associate Viral Genetic Factors with Outbreak Magnitude
Authors: Duggal Nisha K. , D'Anton Mary , Xiang Jeannie , Seiferth Robyn , Day Joanne , Nasci Roger , Brault Aaron C.
Published: July 2013

In 2012, Texas experienced the largest outbreak of human West Nile encephalitis (WNE) since the introduction of West Nile virus (WNV) in 2002. Despite the large number of WNV infections, data indicated the rate of reported WNE among human cases was no higher than in previous years. To determine whether the increase in WNV human cases could have been caused by viral genetic changes, the complete genomes of 17 isolates made from mosquito pools in Dallas and Montgomery Counties in 2012 were sequenced. The 2012 Texas isolates were found to be composed of two distinct clades, both circulating in Dallas and Montgomery Counties despite a 5-fold higher disease incidence in the former. Although minor genetic differences existed between Dallas and Montgomery WNV populations, there was weak support for population subdivision or adaptive changes. On the basis of these data, alternative explanations for increased WNV disease incidence in 2012 are proposed.
Antioxidant Activity of Pandanus amaryllifolius Leaf and Root Extract and its Application in Topical Emulsion
Authors: Jimtaisong Ampa , Krisdaphong Panvipa
Published: July 2013

Purpose: To develop Thai pandan (Pandanus amaryllifolius) as an antioxidant ingredient for topical emulsion.Methods: Dried leaf and root of P. amaryllifolius (Pandanceae) were extracted separately by maceration with either ethanol or propylene glycol. Antioxidant capacity was investigated by 2,2-diphenyl-1-picry hydrazyl radical (DPPH) and linoleic acid peroxidation method. The total phenoliccontent was measured by Folin-Ciocalteau assay. Oil-in-water topical emulsions containing the individual extracts were prepared and tested for stability.Results: Propylene glycol extract exhibited higher DPPH activity and total phenolic content than the ethanol extract while the DPPH activity of the leaf extract was higher than that of the root. The 50 % inhibition concentration (IC50) value of leaf and root extracts was 0.810 and 2.340 mg/ml, respectively. Although the antioxidant activity of the crude extracts was lower than that of standard vitamin C and butylated hydroxytoluene (BHT), the ethanol/propylene glycol solution extract (ethanol was reduced to50 % extract volume) showed higher inhibition (90.1 %) of linoleic acid peroxidation than 200 ppm of vitamin C (57.1 %) and BHT (71.1 %). An oil-in-water emulsion containing 3 % of the ethanol and propylene glycol extract showed creamy texture with medium viscosity and demonstrated good stability under accelerated aging test.Conclusion: The results indicate a potential for the development of P. amaryllifolius leaf extract as an antioxidant ingredient in topically applied formulations.Keywords: Pandanus amaryllifolius, Extraction, Antioxidant, Emulsion, Stability.