Inflammatory Stratification in Primary Sjögren’s Syndrome Reveals Novel Immune Cell Alterations in Patients’ Minor Salivary Glands

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Blockade of lymphotoxin-beta receptor signaling reduces aspects of Sjögren's syndrome in salivary glands of non-obese diabetic mice

Introduction The lymphotoxin-beta receptor (LTβR) pathway is important in the development and maintenance of lymphoid structures. Blocking this pathway has proven beneficial in murine models of autoimmune diseases such as diabetes and rheumatoid arthritis. The aim of this study was to determine the effects of LTβR pathway blockade on Sjögren syndrome (SS)-like salivary gland disease in non-obese diabetic (NOD) mice. Methods The course of SS-like disease was followed in NOD mice that were given lymphotoxin-beta receptor-immunoglobulin fusion protein (LTβR-Ig) starting at 9 weeks of age. Treatment was given as a single weekly dose for 3, 7, or 10 weeks. Age-matched NOD mice treated with mouse monoclonal IgG1, or not treated at all, were used as controls. The severity of inflammation, cellular composition, and lymphoid neogenesis in the submandibular glands were determined by immunohistochemistry. Mandibular lymph nodes were also studied. Saliva flow rates were measured, and saliva was analyzed by a multiplex cytokine assay. The salivary glands were analyzed for CXCL13, CCL19, and CCL21 gene expression by quantitative polymerase chain reaction. Results Treatment with LTβR-Ig prevented the increase in size and number of focal infiltrates normally observed in this SS-like disease. Compared with the controls, the submandibular glands of LTβR-Ig-treated mice had fewer and smaller T- and B-cell zones and fewer high endothelial venules per given salivary gland area. Follicular dendritic cell networks were lost in LTβR-Ig-treated mice. CCL19 expression was also dramatically inhibited in the salivary gland infiltrates. Draining lymph nodes showed more gradual changes after LTβR-Ig treatment. Saliva flow was partially restored in mice treated with 10 LTβR-Ig weekly injections, and the saliva cytokine profile of these mice resembled that of mice in the pre-disease state. Conclusions Our findings show that blocking the LTβR pathway results in ablation of the lymphoid organization in the NOD salivary glands and thus an improvement in salivary gland function

Identification and characterisation of novel SNP markers in Atlantic cod: Evidence for directional selection

<p>Abstract</p> <p>Background</p> <p>The Atlantic cod (<it>Gadus morhua</it>) is a groundfish of great economic value in fisheries and an emerging species in aquaculture. Genetic markers are needed to identify wild stocks in order to ensure sustainable management, and for marker-assisted selection and pedigree determination in aquaculture. Here, we report on the development and evaluation of a large number of Single Nucleotide Polymorphism (SNP) markers from the alignment of Expressed Sequence Tag (EST) sequences in Atlantic cod. We also present basic population parameters of the SNPs in samples of North-East Arctic cod and Norwegian coastal cod obtained from three different localities, and test for SNPs that may have been targeted by natural selection.</p> <p>Results</p> <p>A total of 17,056 EST sequences were used to find 724 putative SNPs, from which 318 segregating SNPs were isolated. The SNPs were tested on Atlantic cod from four different sites, comprising both North-East Arctic cod (NEAC) and Norwegian coastal cod (NCC). The average heterozygosity of the SNPs was 0.25 and the average minor allele frequency was 0.18. <it>F</it>_{<it>ST </it>}values were highly variable, with the majority of SNPs displaying very little differentiation while others had <it>F</it>_{<it>ST </it>}values as high as 0.83. The <it>F</it>_{<it>ST </it>}values of 29 SNPs were found to be larger than expected under a strictly neutral model, suggesting that these loci are, or have been, influenced by natural selection. For the majority of these outlier SNPs, allele frequencies in a northern sample of NCC were intermediate between allele frequencies in a southern sample of NCC and a sample of NEAC, indicating a cline in allele frequencies similar to that found at the Pantophysin I locus.</p> <p>Conclusion</p> <p>The SNP markers presented here are powerful tools for future genetics work related to management and aquaculture. In particular, some SNPs exhibiting high levels of population divergence have potential to significantly enhance studies on the population structure of Atlantic cod.</p

Distribution and determinants of patient satisfaction in oncology with a focus on health related quality of life

<p>Abstract</p> <p>Background</p> <p>Cancer patients usually undergo extensive and debilitating treatments, which make quality of life (QoL) and patient satisfaction important health care assessment measures. However, very few studies have evaluated the relationship between QoL and patient satisfaction in oncology. We investigated the clinical, demographic and QoL factors associated with patient satisfaction in a large heterogeneous sample of cancer patients.</p> <p>Methods</p> <p>A cohort of 538 cancer patients treated at Cancer Treatment Centers of America^®(CTCA) was assessed. A patient satisfaction questionnaire developed in-house by CTCA was used. It covered the following dimensions of patient satisfaction: hospital operations and services, physicians and staff, and patient endorsements for themselves and others. QoL was assessed using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30). The clinical, demographic and QoL factors were evaluated for predictive significance using univariate and multivariate logistic regression.</p> <p>Results</p> <p>The mean age of our patient population was 54.1 years (SD = 10.5, range 17-86), with a slight preponderance of females (57.2%). Breast cancer (n = 124) and lung cancer (n = 101) were the most frequent cancer types. 481 (89.4%) patients were "very satisfied" with their overall experience. Age and several QoL function and symptom scales were predictive of overall patient satisfaction upon univariate analysis. In the multivariate modeling, only those with a score above the median on the fatigue measure (i.e. worse fatigue) had reduced odds of 0.28 of being very satisfied (p = 0.03).</p> <p>Conclusion</p> <p>Patient fatigue, as reported by the QoL fatigue scale, was an independent significant predictor of overall patient satisfaction. This finding argues for special attention and programs for cancer patients who report higher levels of fatigue given that fatigue is the most frequently reported symptom in cancer patients.</p

Are one or two simple questions sufficient to detect depression in cancer and palliative care? A Bayesian meta-analysis

The purpose of this study is to examine the value of one or two simple verbal questions in the detection of depression in cancer settings. This study is a systematic literature search of abstract and full text databases to January 2008. Key authors were contacted for unpublished studies. Seventeen analyses were found. Of these, 13 were conducted in late stage palliative settings. (1) Single depression question: across nine studies, the prevalence of depression was 16%. A single ‘depression' question enabled the detection of depression in 160 out of 223 true cases, a sensitivity of 72%, and correctly reassured 964 out of 1166 non-depressed cancer sufferers, a specificity of 83%. The positive predictive value (PPV) was 44% and the negative predictive value (NPV) 94%. (2) Single interest question: there were only three studies examining the ‘loss-of-interest' question, with a combined prevalence of 14%. This question allowed the detection of 60 out of 72 cases (sensitivity 83%) and excluded 394 from 459 non-depressed cases (specificity of 86%). The PPV was 48% and the NPV 97%. (3) Two questions (low mood and low interest): five studies examined two questions with a combined prevalence of 17%. The two-question combination facilitated a diagnosis of depression in 138 of 151 true cases (sensitivity 91%) and gave correct reassurance to 645 of 749 non-cases (specificity 86%). The PPV was 57% and the NPV 98%. Simple verbal methods perform well at excluding depression in the non-depressed but perform poorly at confirming depression. The ‘two question' method is significantly more accurate than either single question but clinicians should not rely on these simple questions alone and should be prepared to assess the patient more thoroughly