'I feel like I am being stabbed by a thousand tiny men’: The challenges of communicating endometriosis pain

Endometriosis, as a widespread gynecological condition, affects an estimated 1 in 10 women and yet has a worldwide average diagnosis length of 7.5 years. Causing incapacitating pain, among other associated manifestations, the condition severely impacts on women’s lives. This article uses online survey data to investigate how pre-diagnosis endometriosis pain is conceptualized and articulated in order to explore communication challenges reported in early consultations that can potentially be seen to play a role in diagnosis delay. The findings of this study indicate that women feel that they do not have the appropriate tools to describe their pain and, in many instances, feel dismissed therefore prolonging diagnosis. The article finds that the majority of the pain descriptors identified use elaborate metaphorical scenarios to convey the intensity of the pain and concludes with some reflections on the issue of metaphorical language in endometriosis pain communication practices while calling for interdisciplinary work in order to devise appropriate tools for endometriosis pain communication

Innate Immune Function in Placenta and Cord Blood of Hepatitis C – Seropositive Mother-Infant Dyads

Vertical transmission accounts for the majority of pediatric cases of hepatitis C viral (HCV) infection. In contrast to the adult population who develop persistent viremia in ∼80% of cases following exposure, the rate of mother-to-child transmission (2–6%) is strikingly low. Protection from vertical transmission likely requires the coordination of multiple components of the immune system. Placenta and decidua provide a direct connection between mother and infant. We hypothesized that innate immune responses would differ across the three compartments (decidua, placenta and cord blood) and that hepatitis C exposure would modify innate immunity in these tissues. The study was comprised of HCV-infected and healthy control mother and infant pairs from whom cord blood, placenta and decidua were collected with isolation of mononuclear cells. Multiparameter flow cytometry was performed to assess the phenotype, intracellular cytokine production and cytotoxicity of the cells. In keeping with a model where the maternal-fetal interface provides antiviral protection, we found a gradient in proportional frequencies of NKT and γδ-T cells being higher in placenta than cord blood. Cytotoxicity of NK and NKT cells was enhanced in placenta and placental NKT cytotoxicity was further increased by HCV infection. HCV exposure had multiple effects on innate cells including a decrease in activation markers (CD69, TRAIL and NKp44) on NK cells and a decrease in plasmacytoid dendritic cells in both placenta and cord blood of exposed infants. In summary, the placenta represents an active innate immunological organ that provides antiviral protection against HCV transmission in the majority of cases; the increased incidence in preterm labor previously described in HCV-seropositive mothers may be related to enhanced cytotoxicity of NKT cells

Hepatitis C Virus (HCV) Evades NKG2D-Dependent NK Cell Responses through NS5A-Mediated Imbalance of Inflammatory Cytokines

Understanding how hepatitis C virus (HCV) induces and circumvents the host's natural killer (NK) cell-mediated immunity is of critical importance in efforts to design effective therapeutics. We report here the decreased expression of the NKG2D activating receptor as a novel strategy adopted by HCV to evade NK-cell mediated responses. We show that chronic HCV infection is associated with expression of ligands for NKG2D, the MHC class I-related Chain (MIC) molecules, on hepatocytes. However, NKG2D expression is downmodulated on circulating NK cells, and consequently NK cell-mediated cytotoxic capacity and interferon-γ production are impaired. Using an endotoxin-free recombinant NS5A protein, we show that NS5A stimulation of monocytes through Toll-like Receptor 4 (TLR4) promotes p38- and PI3 kinase-dependent IL-10 production, while inhibiting IL-12 production. In turn, IL-10 triggers secretion of TGFβ which downmodulates NKG2D expression on NK cells, leading to their impaired effector functions. Moreover, culture supernatants of HCV JFH1 replicating Huh-7.5.1 cells reproduce the effect of recombinant NS5A on NKG2D downmodulation. Exogenous IL-15 can antagonize the TGFβ effect and restore normal NKG2D expression on NK cells. We conclude that NKG2D-dependent NK cell functions are modulated during chronic HCV infection, and demonstrate that this alteration can be prevented by exogenous IL-15, which could represent a meaningful adjuvant for therapeutic intervention

Arginine Metabolism by Macrophages Promotes Cardiac and Muscle Fibrosis in mdx Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is the most common, lethal disease of childhood. One of 3500 new-born males suffers from this universally-lethal disease. Other than the use of corticosteroids, little is available to affect the relentless progress of the disease, leading many families to use dietary supplements in hopes of reducing the progression or severity of muscle wasting. Arginine is commonly used as a dietary supplement and its use has been reported to have beneficial effects following short-term administration to mdx mice, a genetic model of DMD. However, the long-term effects of arginine supplementation are unknown. This lack of knowledge about the long-term effects of increased arginine metabolism is important because elevated arginine metabolism can increase tissue fibrosis, and increased fibrosis of skeletal muscles and the heart is an important and potentially life-threatening feature of DMD.We use both genetic and nutritional manipulations to test whether changes in arginase metabolism promote fibrosis and increase pathology in mdx mice. Our findings show that fibrotic lesions in mdx muscle are enriched with arginase-2-expressing macrophages and that muscle macrophages stimulated with cytokines that activate the M2 phenotype show elevated arginase activity and expression. We generated a line of arginase-2-null mutant mdx mice and found that the mutation reduced fibrosis in muscles of 18-month-old mdx mice, and reduced kyphosis that is attributable to muscle fibrosis. We also observed that dietary supplementation with arginine for 17-months increased mdx muscle fibrosis. In contrast, arginine-2 mutation did not reduce cardiac fibrosis or affect cardiac function assessed by echocardiography, although 17-months of dietary supplementation with arginine increased cardiac fibrosis. Long-term arginine treatments did not decrease matrix metalloproteinase-2 or -9 or increase the expression of utrophin, which have been reported as beneficial effects of short-term treatments.Our findings demonstrate that arginine metabolism by arginase promotes fibrosis of muscle in muscular dystrophy and contributes to kyphosis. Our findings also show that long-term, dietary supplementation with arginine exacerbates fibrosis of dystrophic heart and muscles. Thus, commonly-practiced dietary supplementation with arginine by DMD patients has potential risk for increasing pathology when performed for long periods, despite reports of benefits acquired with short-term supplementation

Production of Coturnix quail immunoglobulins Y (IgYs) against Vibrio parahaemolyticus and Vibrio vulnificus

This research article published by Springer Nature Switzerland AG., 2011Production of chicken immunoglobulins Y (IgYs) and their applications in prophylactic, therapeutic, detection of microbial contaminants and as a diagnostic tool has been widely studied with limited information from other avians. This study produced Coturnix quail (Coturnix coturnix japonica) egg yolk IgYs against Vibrio parahaemolyticus and Vibrio vulnificus. Formalin inactivated (FIVP, FIVV, mixed FI-VP/VV) and heat inactivated (HIVP, HIVV, mixed HI-VP/VV) Vibrio immunogens (109 CFU/mL) were intramuscularly immunized into quail through thigh muscles. Egg yolk IgY was purified by water dilution-ammonium sulfate precipitation method and the activity was determined by enzyme-linked immunosorbent assay (ELISA). Formalin inactivated immunogens induced high humoral immune response for both V. parahaemolyticus and V. vulnificus over heat inactivated immunogens. However, IgYs resulted from HIVP and FIVV immunogens, showed high specificity to V. parahaemolyticus and V. vulnificus respectively. Detection limits of the indirect ELISA using the produced IgYs were 105 CFU/mL for V. parahaemolyticus and 106 CFU/mL for V. vulnificus. The developed antibodies showed high binding affinity to their corresponding immunogens, very little cross reactivity to Staphylococcus aureus and not other bacteria strains (p<0.05), a phenomenon which was also observed in Western blot

Sensor Fusion Using Entropic measures of Dependence

As opposed to standard methods of association which rely on measures of central dispersion, entropic measures quantify multivalued relations. This distinction is especially important when high fidelity models of the sensed phenomena do not exist. The properties of entropic measures are shown to fit within the Bayesian framework of hierarchical sensor fusion. A method of estimating probabilistic structure for categorical and continuous valued measurements that is unbiased for finite data collections is presented. Additionally, a branch and bound method for optimal sensor suite selection suitable for either target refinement or anomaly detection is described. Finally, the methodology is applied against a known data set used in a standard data mining competition that features both sparse categorical and  ontinuous valued descriptors of a target. Excellent quantitative and computational results against this data set support the conclusion that the proposed methodology is promising for general purpose low level data fusion

Sensor Fusion Using Entropic measures of Dependence

As opposed to standard methods of association which rely on measures of central dispersion, entropic measures quantify multivalued relations. This distinction is especially important when high fidelity models of the sensed phenomena do not exist. The properties of entropic measures are shown to fit within the Bayesian framework of hierarchical sensor fusion. A method of estimating probabilistic structure for categorical and continuous valued measurements that is unbiased for finite data collections is presented. Additionally, a branch and bound method for optimal sensor suite selection suitable for either target refinement or anomaly detection is described. Finally, the methodology is applied against a known data set used in a standard data mining competition that features both sparse categorical and  ontinuous valued descriptors of a target. Excellent quantitative and computational results against this data set support the conclusion that the proposed methodology is promising for general purpose low level data fusion.Contrario a los métodos estándar de asociación que ligan medidas de dispersión central, las medidas de entropía cuantifican relaciones multivaluadas. Esta distinción es especialmente importante cuando no existen modelos de alta fidelidad de los fenómenos detectados. Se muestra que las propiedades de las medidas de entropía calzan en la marco Bayesiano de sensores jerárquicos de fusión. Se presenta un método de estimación de la estructura probabilística para medidas categóricas y continuas, el cual es insesgado para colecciones finitas de datos. Adicionalmente, se describe un método de ramificación y acotamiento de selección óptima del sensor apropiado tanto para refinamiento del objetivo como para detección de anomalías. Finalmente, la metodología es aplicada sobre un conjunto conocido de datos usados en una competencia estándar de minería de datos, que caracteriza tanto descriptores ralos categóricos como continuos de un objetivo. Excelentes resultados cuantitativos y computacionales con estos datos apoyan la conclusión de que la metodología propuesta es promisoria para propósitos generales con datos bajos niveles de fusión