Eosinophil and T Cell Markers Predict Functional Decline in COPD Patients

BACKGROUND. The major marker utilized to monitor COPD patients is forced expiratory volume in one second (FEV1). However, asingle measurement of FEV1 cannot reliably predict subsequent decline. Recent studies indicate that T lymphocytes and eosinophils are important determinants of disease stability in COPD. We therefore measured cytokine levels in the lung lavage fluid and plasma of COPD patients in order to determine if the levels of T cell or eosinophil related cytokines were predictive of the future course of the disease. METHODS. Baseline lung lavage and plasma samples were collected from COPD subjects with moderately severe airway obstruction and emphysematous changes on chest CT. The study participants were former smokers who had not had a disease exacerbation within the past six months or used steroids within the past two months. Those subjects who demonstrated stable disease over the following six months (ΔFEV1 % predicted = 4.7 ± 7.2; N = 34) were retrospectively compared with study participants who experienced a rapid decline in lung function (ΔFEV1 % predicted = -16.0 ± 6.0; N = 16) during the same time period and with normal controls (N = 11). Plasma and lung lavage cytokines were measured from clinical samples using the Luminex multiplex kit which enabled the simultaneous measurement of several T cell and eosinophil related cytokines. RESULTS AND DISCUSSION. Stable COPD participants had significantly higher plasma IL-2 levels compared to participants with rapidly progressive COPD (p = 0.04). In contrast, plasma eotaxin-1 levels were significantly lower in stable COPD subjects compared to normal controls (p < 0.03). In addition, lung lavage eotaxin-1 levels were significantly higher in rapidly progressive COPD participants compared to both normal controls (p < 0.02) and stable COPD participants (p < 0.05). CONCLUSION. These findings indicate that IL-2 and eotaxin-1 levels may be important markers of disease stability in advanced emphysema patients. Prospective studies will need to confirm whether measuring IL-2 or eotaxin-1 can identify patients at risk for rapid disease progression.National Heart, Lung, and Blood Institute (NO1-HR-96140, NO1-HR-96141-001, NO1-HR-96144, NO1-HR-96143; NO1-HR-96145; NO1-HR-96142, R01HL086936-03); The Flight Attendant Medical Research Institute; the Jo-Ann F. LeBuhn Center for Chest Diseas

The role of childhood social position in adult type 2 diabetes: Evidence from the English Longitudinal Study of Ageing

Copyright @ 2014 Pikhartova et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.This article has been made available through the Brunel Open Access Publishing Fund.Background: Socioeconomic circumstances in childhood and early adulthood may influence the later onset of chronic disease, although such research is limited for type 2 diabetes and its risk factors at the different stages of life. The main aim of the present study is to examine the role of childhood social position and later inflammatory markers and health behaviours in developing type 2 diabetes at older ages using a pathway analytic approach. Methods. Data on childhood and adult life circumstances of 2,994 men and 4,021 women from English Longitudinal Study of Ageing (ELSA) were used to evaluate their association with diabetes at age 50 years and more. The cases of diabetes were based on having increased blood levels of glycated haemoglobin and/or self-reported medication for diabetes and/or being diagnosed with type 2 diabetes. Father's job when ELSA participants were aged 14 years was used as the measure of childhood social position. Current social characteristics, health behaviours and inflammatory biomarkers were used as potential mediators in the statistical analysis to assess direct and indirect effects of childhood circumstances on diabetes in later life. Results: 12.6 per cent of participants were classified as having diabetes. A disadvantaged social position in childhood, as measured by father's manual occupation, was associated at conventional levels of statistical significance with an increased risk of type 2 diabetes in adulthood, both directly and indirectly through inflammation, adulthood social position and a risk score constructed from adult health behaviours including tobacco smoking and limited physical activity. The direct effect of childhood social position was reduced by mediation analysis (standardised coefficient decreased from 0.089 to 0.043) but remained statistically significant (p = 0.035). All three indirect pathways made a statistically significantly contribution to the overall effect of childhood social position on adulthood type 2 diabetes. Conclusions: Childhood social position influences adult diabetes directly and indirectly through inflammatory markers, adulthood social position and adult health behaviours. © 2014Pikhartova et al.; licensee BioMed Central Ltd.Economic and Social Research Council-funded International Centre for Life Course Studies in Society and Health (RES-596-28-0001)

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Modelling ranging behaviour of female orang-utans: a case study in Tuanan, Central Kalimantan, Indonesia

Quantification of the spatial needs of individuals and populations is vitally important for management and conservation. Geographic information systems (GIS) have recently become important analytical tools in wildlife biology, improving our ability to understand animal movement patterns, especially when very large data sets are collected. This study aims at combining the field of GIS with primatology to model and analyse space-use patterns of wild orang-utans. Home ranges of female orang-utans in the Tuanan Mawas forest reserve in Central Kalimantan, Indonesia were modelled with kernel density estimation methods. Kernel results were compared with minimum convex polygon estimates, and were found to perform better, because they were less sensitive to sample size and produced more reliable estimates. Furthermore, daily travel paths were calculated from 970 complete follow days. Annual ranges for the resident females were approximately 200 ha and remained stable over several years; total home range size was estimated to be 275 ha. On average, each female shared a third of her home range with each neighbouring female. Orang-utan females in Tuanan built their night nest on average 414 m away from the morning nest, whereas average daily travel path length was 777 m. A significant effect of fruit availability on day path length was found. Sexually active females covered longer distances per day and may also temporarily expand their ranges

Pulmonary valve endocarditis caused by right ventricular outflow obstruction in association with sinus of valsalva aneurysm: a case report

<p>Abstract</p> <p>Background</p> <p>Right-sided infective endocarditis is uncommon. This is primarily seen in patients with intravenous drug use, pacemaker or central venous lines, or congenital heart disease. The vast majority of cases involve the tricuspid valve. Isolated pulmonary valve endocarditis is extremely rare. We report the first case of a pulmonary valve nonbacterial thrombotic endocarditis caused by right ventricular outlflow tract (RVOT) obstruction in association with a large sinus of Valsalva aneurysm.</p> <p>Case presentation</p> <p>A 60-year-old man with a six-week history of fever, initially treated as pneumonia and sinusitis with levofloxacin, was admitted to the hospital with a new onset of a heart murmur. An echocardiogram showed thickening of the pulmonary valve suggestive of valve vegetation. A dilated aortic root and sinus of Valsalva aneurysm measuring at least 6.4 cm were also identified. The patient was empirically treated for infective endocarditis with vancomycin and gentamycin for 28 days. Four months later, the patient underwent resection of a large aortic root aneurysm and exploration of the pulmonary valve. During the surgery, vegetation of the pulmonary valve was confirmed. Microscopic pathological examination revealed fibrinous debris with acute inflammation and organizing fibrosis with chronic inflammation, compatible with a vegetation. Special stains were negative for bacteria and fungi.</p> <p>Conclusion</p> <p>This is the first case report of a pulmonary valve nonbacterial endocarditis caused by RVOT obstruction in association with a sinus of Valsalva aneurysm. We speculate that jets created by the RVOT obstruction and large sinus of Valsalva aneurysm hitting against endothelium of the pulmonary valve is the etiology of this rare nonbacterial thrombotic endocarditis.</p

Poly I:C enhances cycloheximide-induced apoptosis of tumor cells through TLR3 pathway

<p>Abstract</p> <p>Background</p> <p>Toll-like receptor 3 (TLR3) is a critical component of the innate immune response to dsRNA viruses, which was considered to be mainly expressed in immune cells and some endothelial cells. In this study, we investigated the expression and proapoptotic activity of TLR3 in human and murine tumor cell lines.</p> <p>Methods</p> <p>RT-PCR and FACS analysis were used to detect expression of TLR3 in various human and murine tumor cell lines. All tumor cell lines were cultured with poly I:C, CHX, or both for 12 h, 24 h, 72 h, and then the cell viability was analyzed with CellTiter 96^®AQueous One Solution, the apoptosis was measured by FACS with Annexin V and PI staining. Production of Type I IFN in poly I:C/CHX mediated apoptosis were detected through western blotting. TLR3 antibodies and IFN-β antibodies were used in Blockade and Neutralization Assay.</p> <p>Results</p> <p>We show that TLR3 are widely expressed on human and murine tumor cell lines, and activation of TLR3 signaling in cancerous cells by poly I:C made Hela cells (human cervical cancer) and MCA38 cells (murine colon cancer) become dose-dependently sensitive to protein synthesis inhibitor cycloheximide (CHX)-induced apoptosis. Blockade of TLR3 recognition with anti-TLR3 antibody greatly attenuated the proapoptotic effects of poly I:C on tumor cells cultured with CHX. IFN-β production was induced after poly I:C/CHX treatment and neutralization of IFN-β slightly reduced poly I:C/CHX -induced apoptosis.</p> <p>Conclusion</p> <p>Our study demonstrated the proapoptotic activity of TLR3 expressed by various tumor cells, which may open a new range of clinical applications for TLR3 agonists as an adjuvant of certain cancer chemotherapy.</p

Self-reported use of complementary and alternative medicine (CAM) products in topical treatment of diabetic foot disorders by diabetic patients in Jeddah, Western Saudi Arabia

<p>Abstract</p> <p>Background</p> <p>There is little published on current Saudi diabetic patients' practices when they are exposed to foot disorders such as open wound, ulcer, and skin cracks. These factors are usually influenced by local culture and communities beliefs. The aim of the current study was to identify the pattern of patients' use of CAM products in dealing with diabetic foot disorders topically in a group of diabetic patients.</p> <p>Findings</p> <p>A Cross-sectional descriptive study of a representative cohort of diabetic patients living in Jeddah, Saudi Arabia was designed. A pre-designed questionnaire to identify local diabetics' practices in dealing topically with foot disorders including open wound, chronic ulcer, and skin cracks was designed. Questionnaire was administered by a group of trained nutrition female students to diabetics face to face living in their neighborhood. A total of 1634 Saudi diabetics were interviewed. Foot disorders occurred in approximately two thirds of the respondents 1006 (61.6%). Out of the 1006 patients who had foot disorders, 653 reported trying some sort of treatment as 307 patients (47.1%) used conventional topical medical treatment alone, 142 (21.7%) used CAM products alone, and 204 (31.2%) used both treatments. The most commonly used CAM product by the patients was Honey (56.6%) followed by Commiphora Molmol (Myrrh) in (37.4%) and Nigellia Sativa (Black seed) in (35.1%). The least to be used was Lawsonia inermis (Henna) in (12.1%). Ten common natural preparations used topically to treat diabetic foot disorders were also identified.</p> <p>Conclusions</p> <p>The use of CAM products in topical treatment of diabetic foot disorders is fairly common among Saudi diabetic patients. Honey headed the list as a solo topical preparation or in combination with other herbs namely black seeds and myrrh. The efficacy of the most common products needs further research.</p

Coexpression of VEGF-C and COX-2 and its association with lymphangiogenesis in human breast cancer

<p>Abstract</p> <p>Background</p> <p>Lymphangiogenesis has become a new research frontier in tumor metastasis since the discovery of reliable lymphatic markers that have allowed observation and isolation of lymphatic endothelium. Cyclooxygenase-2 (COX-2) has been reported to be involved in the critical steps in carcinogenesis. However, possible role of COX-2 in lymphangiogenesis and lymphatic metastasis is still poorly understood. In present study, we aimed to investigate the relationship between vascular endothelial growth factor-C (VEGF-C) and COX-2 in human breast cancer, and correlations with lymphangiogenesis and prognosis.</p> <p>Methods</p> <p>Tissue samples of primary tumors from 70 patients undergoing intentionally curative surgical resections for breast cancer were immunohistochemically examined for VEGF-C, COX-2, and D2-40 expressions. The association between COX-2 and VEGF-C expressions and clinicopathological parameters as well as prognosis were analysised. To demonstrate the presence of proliferating lymphatic endothelial cells, 10 random cases with high LVD counts were selected for D2-40/Ki-67 double immunostaining.</p> <p>Results</p> <p>A significant correlation was found between the expression of VEGF-C and COX-2 (<it>r </it>= 0.529, <it>P </it>< 0.001), and both elevated VEGF-C expression and elevated COX-2 expression were associated with higher lymph vessel density (LVD), lymph node metastasis and D2-40 positive lymphatic invasion (LVI) as well as worse disease free survival (DFS) and overall survival (OS) in a univariate analysis. In the double immunostain for the lymph vessel marker D2-40 and the proliferation marker Ki-67, the results confirmed Ki-67-positive nuclei in a proportion of lymph vessel endothelial cells.</p> <p>Conclusion</p> <p>There is indeed lymphangiogenesis in breast cancer, the most compelling evidence being the presence of proliferating lymphatic endothelial cells. VEGF-C and COX-2 are coexpressed and significantly associated with lymphangiogenesis and prognosis in invasive breast cancer. Suggesting COX-2 may up-regulate VEGF-C expression and thus promote lymph node metastasis via lymphangiogenesis pathway in human breast cancer.</p

Genetic Analysis of HIV-1 Subtypes in Nairobi, Kenya

Background: Genetic analysis of a viral infection helps in following its spread in a given population, in tracking the routes of infection and, where applicable, in vaccine design. Additionally, sequence analysis of the viral genome provides information about patterns of genetic divergence that may have occurred during viral evolution. Objective: In this study we have analyzed the subtypes of Human Immunodeficiency Virus -1 (HIV-1) circulating in a diverse sample population of Nairobi, Kenya. Methodology: 69 blood samples were collected from a diverse subject population attending the Aga Khan University Hospital in Nairobi, Kenya. Total DNA was extracted from peripheral blood mononuclear cells (PBMCs), and used in a Polymerase Chain Reaction (PCR) to amplify the HIV gag gene. The PCR amplimers were partially sequenced, and alignment and phylogenetic analysis of these sequences was performed using the Los Alamos HIV Database. Results: Blood samples from 69 HIV-1 infected subjects from varying ethnic backgrounds were analyzed. Sequence alignment and phylogenetic analysis showed 39 isolates to be subtype A, 13 subtype D, 7 subtype C, 3 subtype AD and CRF01_AE, 2 subtype G and 1 subtype AC and 1 AG. Deeper phylogenetic analysis revealed HIV subtype A sequences to be highly divergent as compared to subtypes D and C. Conclusion: Our analysis indicates that HIV-1 subtypes in the Nairobi province of Kenya are dominated by a genetically diverse clade A. Additionally, the prevalence of highly divergent, complex subtypes, intersubtypes, and the recombinant forms indicates viral mixing in Kenyan population, possibly as a result of dual infections