Clinical Manifestations Associated with Overweight/Obesity in Puerto Ricans with Fibromyalgia Syndrome

Objective. To determine the clinical manifestations associated with overweight/obesity in Hispanics from Puerto Rico with fibromyalgia syndrome (FMS). Methods. A cross-sectional study was performed in 144 patients with FMS (per American College of Rheumatology (ACR) classification criteria). Sociodemographic features, FMS-related symptoms, tender points (per ACR criteria), comorbidities, and FMS treatment were examined. BMI was calculated and patients were grouped into two categories: BMI ≤ 24.9 kg/m2 (nonoverweight/obese) and BMI ≥ 25 kg/m2 (overweight/obese). Bivariate and multivariate analyses were used to evaluate differences between the study groups. Results. The mean (standard deviation (SD)) age of patients was 50.2 (9.9) years; 95.1% were females and 75.7% were overweight/obese. In the bivariate analysis, overweight/obese patients were more likely to have self-reported memory impairment, anxiety, shortness of breath, and urinary frequency than nonoverweight/obese patients. In addition, the tender point count was higher in the overweight/obese group. In the logistic regression analyses, self-reported memory impairment and urinary frequency differences remained significant after adjusting for confounding variables. Conclusion. In this population of Puerto Ricans with FMS, overweight/obese patients experienced more FMS-related manifestations than nonoverweight/obese individuals. However, prospective studies are needed to confirm these associations and to elucidate if weight reduction interventions could favorably impact the severity of FMS

Time to Renal Disease and End-Stage Renal Disease in PROFILE: A Multiethnic Lupus Cohort

BACKGROUND: Renal involvement is a serious manifestation of systemic lupus erythematosus (SLE); it may portend a poor prognosis as it may lead to end-stage renal disease (ESRD). The purpose of this study was to determine the factors predicting the development of renal involvement and its progression to ESRD in a multi-ethnic SLE cohort (PROFILE). METHODS AND FINDINGS: PROFILE includes SLE patients from five different United States institutions. We examined at baseline the socioeconomic–demographic, clinical, and genetic variables associated with the development of renal involvement and its progression to ESRD by univariable and multivariable Cox proportional hazards regression analyses. Analyses of onset of renal involvement included only patients with renal involvement after SLE diagnosis (n = 229). Analyses of ESRD included all patients, regardless of whether renal involvement occurred before, at, or after SLE diagnosis (34 of 438 patients). In addition, we performed a multivariable logistic regression analysis of the variables associated with the development of renal involvement at any time during the course of SLE. In the time-dependent multivariable analysis, patients developing renal involvement were more likely to have more American College of Rheumatology criteria for SLE, and to be younger, hypertensive, and of African-American or Hispanic (from Texas) ethnicity. Alternative regression models were consistent with these results. In addition to greater accrued disease damage (renal damage excluded), younger age, and Hispanic ethnicity (from Texas), homozygosity for the valine allele of FcγRIIIa (FCGR3A*GG) was a significant predictor of ESRD. Results from the multivariable logistic regression model that included all cases of renal involvement were consistent with those from the Cox model. CONCLUSIONS: Fcγ receptor genotype is a risk factor for progression of renal disease to ESRD. Since the frequency distribution of FCGR3A alleles does not vary significantly among the ethnic groups studied, the additional factors underlying the ethnic disparities in renal disease progression remain to be elucidated

Genetic association of CD247 (CD3ζ) with SLE in a large-scale multiethnic study

A classic T-cell phenotype in systemic lupus erythematosus (SLE) is the downregulation and replacement of the CD3ζ chain that alters T-cell receptor signaling. However, genetic associations with SLE in the human CD247 locus that encodes CD3ζ are not well established and require replication in independent cohorts. Our aim was therefore to examine, localize and validate CD247-SLE association in a large multiethnic population. We typed 44 contiguous CD247 single-nucleotide polymorphisms (SNPs) in 8922 SLE patients and 8077 controls from four ethnically distinct populations. The strongest associations were found in the Asian population (11 SNPs in intron 1, 4.99 × 10(-4) < P < 4.15 × 10(-2)), where we further identified a five-marker haplotype (rs12141731-rs2949655-rs16859085-rs12144621-rs858554; G-G-A-G-A; P(hap) = 2.12 × 10(-5)) that exceeded the most associated single SNP rs858554 (minor allele frequency in controls = 13%; P = 4.99 × 10(-4), odds ratio = 1.32) in significance. Imputation and subsequent association analysis showed evidence of association (P < 0.05) at 27 additional SNPs within intron 1. Cross-ethnic meta-analysis, assuming an additive genetic model adjusted for population proportions, showed five SNPs with significant P-values (1.40 × 10(-3) < P< 3.97 × 10(-2)), with one (rs704848) remaining significant after Bonferroni correction (P(meta) = 2.66 × 10(-2)). Our study independently confirms and extends the association of SLE with CD247, which is shared by various autoimmune disorders and supports a common T-cell-mediated mechanism.National Institutes of Health grants: (UL1RR025741, K24AR002138, P602AR30692, P01AR49084, UL1TR000165, P01AI083194, RO1AR43814, P60AR053308, UL1TR000004, AR43727, R21AI070304, RO1AR057172, UL1RR025014, R01AR051545-03, UL1RR029882, P60AR062755, P30AR53483, U19AI082714, P30GM103510, U01AI101934, AI063274, AR056360, AI083194, R37AI024717, P01083194, P01AR049084, PR094002); Northwestern University Feinberg School of Medicine; University of Alabama Birmingham; National Institute of Arthritis and Musculoskeletal and Skin Diseases; University of California Los Angeles; University of California San Francisco; Hopkins University; University of Colorado School of Medicine; University of Southern California; Seattle Children's Research Institute Arthritis Foundation; Medical University of South Carolina; Oklahoma Medical Research Foundation; Cincinnati Children's Hospital Medical Center; US Departments of Defense grant: (PR094002); Veterans Affairs; Alliance for Lupus Research; Kirkland Scholar Award; Korea Healthcare technology R & D project: (A121983); Ministry for Health and Welfare; Republic of Korea; Swedish Research Council; Instituto de Salud Carlos III grant: (PS09/00129); European Union FEDER funds; Fundação para a Ciência e Tecnologia fellowships: (SFRH/BPD/29354/2006, SFRH/BPD/34648/2007)

Synergy of extreme drought and shrub invasion reduce ecosystem functioning and resilience in water-limited climates

Extreme drought events and plant invasions are major drivers of global change that can critically affect ecosystem functioning and alter ecosystem-atmosphere exchange. Invaders are expanding worldwide and extreme drought events are projected to increase in frequency and intensity. However, very little is known on how these drivers may interact to affect the functioning and resilience of ecosystems to extreme events. Using a manipulative shrub removal experiment and the co-occurrence of an extreme drought event (2011/2012) in a Mediterranean woodland, we show that native shrub invasion and extreme drought synergistically reduced ecosystem transpiration and the resilience of key-stone oak tree species. Ecosystem transpiration was dominated by the water use of the invasive shrub Cistus ladanifer, which further increased after the extreme drought event. Meanwhile, the transpiration of key-stone tree species decreased, indicating a competitive advantage in favour of the invader. Our results suggest that in Mediterranean-type climates the invasion of water spending species and projected recurrent extreme drought events may synergistically cause critical drought tolerance thresholds of key-stone tree species to be surpassed, corroborating observed higher tree mortality in the invaded ecosystems. Ultimately, this may shift seasonally water limited ecosystems into less desirable alternative states dominated by water spending invasive shrubs

Emerging Hyalomma lusitanicum: From identification to vectorial role and integrated control

In the Mediterranean basin, the tick species Hyalomma lusitanicum Koch stands out among other species of the Hyalomma genus due to its wide distribution, and there is great concern about its potential role as a vector and/or reservoir and its continuous expansion to new areas because of climate warming and human and other animal movements. This review aims to consolidate all the information on H. lusitanicum, including taxonomy and evolution, morphological and molecular identification, life cycle, sampling methods, rearing under laboratory conditions, ecology, hosts, geographical distribution, seasonality, vector role and control methods. The availability of adequate data is extremely relevant to the development of appropriate control strategies in areas where this tick is currently distributed as well as in new areas where it could become established in the near future.This work was partially supported by the COST Action CA21170 “Prevention, anticipation and mitigation of tick-borne disease risk applying the DAMA protocol (PRAGMATICK)”.Peer reviewe

The Role of Genetic Variation Near Interferon-Kappa in Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by increased type I interferons (IFNs) and multiorgan inflammation frequently targeting the skin. IFN-kappa is a type I IFN expressed in skin. A pooled genome-wide scan implicated the IFNK locus in SLE susceptibility. We studied IFNK single nucleotide polymorphisms (SNPs) in 3982 SLE cases and 4275 controls, composed of European (EA), African-American (AA), and Asian ancestry. rs12553951C was associated with SLE in EA males (odds ratio = 1.93, P = 2.5 × 10−4), but not females. Suggestive associations with skin phenotypes in EA and AA females were found, and these were also sex-specific. IFNK SNPs were associated with increased serum type I IFN in EA and AA SLE patients. Our data suggest a sex-dependent association between IFNK SNPs and SLE and skin phenotypes. The serum IFN association suggests that IFNK variants could influence type I IFN producing plasmacytoid dendritic cells in affected skin

Preferential binding to elk-1 by sle-associated il10 risk allele upregulates il10 expression

Immunoregulatory cytokine interleukin-10 (IL-10) is elevated in sera from patients with systemic lupus erythematosus (SLE) correlating with disease activity. The established association of IL10 with SLE and other autoimmune diseases led us to fine map causal variant(s) and to explore underlying mechanisms. We assessed 19 tag SNPs, covering the IL10 gene cluster including IL19, IL20 and IL24, for association with SLE in 15,533 case and control subjects from four ancestries. The previously reported IL10 variant, rs3024505 located at 1 kb downstream of IL10, exhibited the strongest association signal and was confirmed for association with SLE in European American (EA) (P = 2.7×10−8, OR = 1.30), but not in non-EA ancestries. SNP imputation conducted in EA dataset identified three additional SLE-associated SNPs tagged by rs3024505 (rs3122605, rs3024493 and rs3024495 located at 9.2 kb upstream, intron 3 and 4 of IL10, respectively), and SLE-risk alleles of these SNPs were dose-dependently associated with elevated levels of IL10 mRNA in PBMCs and circulating IL-10 protein in SLE patients and controls. Using nuclear extracts of peripheral blood cells from SLE patients for electrophoretic mobility shift assays, we identified specific binding of transcription factor Elk-1 to oligodeoxynucleotides containing the risk (G) allele of rs3122605, suggesting rs3122605 as the most likely causal variant regulating IL10 expression. Elk-1 is known to be activated by phosphorylation and nuclear localization to induce transcription. Of interest, phosphorylated Elk-1 (p-Elk-1) detected only in nuclear extracts of SLE PBMCs appeared to increase with disease activity. Co-expression levels of p-Elk-1 and IL-10 were elevated in SLE T, B cells and monocytes, associated with increased disease activity in SLE B cells, and were best downregulated by ERK inhibitor. Taken together, our data suggest that preferential binding of activated Elk-1 to the IL10 rs3122605-G allele upregulates IL10 expression and confers increased risk for SLE in European Americans

Early, transient depletion of plasmacytoid dendritic cells ameliorates autoimmunity in a lupus model

Plasmacytoid dendritic cells (pDCs) have long been implicated in the pathogenesis of lupus. However, this conclusion has been largely based on a correlative link between the copious production of IFN-α/β by pDCs and the IFN-α/β “signature” often seen in human lupus patients. The specific contribution of pDCs to disease in vivo has not been investigated in detail. For this reason, we generated a strain of BXSB lupus-prone mice in which pDCs can be selectively depleted in vivo. Early, transient ablation of pDCs before disease initiation resulted in reduced splenomegaly and lymphadenopathy, impaired expansion and activation of T and B cells, reduced antibodies against nuclear autoantigens and improved kidney pathology. Amelioration of pathology coincided with decreased transcription of IFN-α/β–induced genes in tissues. PDC depletion had an immediate impact on the activation of immune cells, and importantly, the beneficial effects on pathology were sustained even though pDCs later recovered, indicating an early pDC contribution to disease. Together, our findings demonstrate a critical function for pDCs during the IFN-α/β–dependent initiation of autoimmune lupus and point to pDCs as an attractive therapeutic target for the treatment of SLE

Biomechanical study of autograft anatomic reconstruction in lateral ankle instability

Introduction: The purpose of this work is perform a biomechanical comparison of anatomic reconstruction of the anterior talofibular ligament (ATFL) with the intact ATFL. Materials and methods: We studied 18 fresh cadaveric ankles with intact ATFL. Each specimen was clinically assessed with the anterior drawer (AD) and varus tilt (VT) tests and the angular movement in the three spatial planes (axial, coronal and sagittal) was measured with an arthrometer using a sensor located in the talus. Results: Statistically significant differences were found in the axial plane, between the intact ATFL versus the sectioned ATFL for AD test with p = 0.012, and for VT test with p = 0.013. Regarding the coronal plane, we also observed a statistically significant difference for VT test with p = 0.016. In the sagittal plane, there are no statistically significant differences in both maneuvers. No statistically significant differences were found when comparing the biomechanics of anatomic ligament reconstruction versus the intact ATFL. Conclusion: Autograft anatomic reconstruction of the ATFL showed biomechanical properties similar to those of the native ATFL, at the zero moment in a cadaveric model.publishersversionpublishe