Human Female Genital Tract Infection by the Obligate Intracellular Bacterium Chlamydia trachomatis Elicits Robust Type 2 Immunity

While Chlamydia trachomatis infections are frequently asymptomatic, mechanisms that regulate host response to this intracellular Gram-negative bacterium remain undefined. This investigation thus used peripheral blood mononuclear cells and endometrial tissue from women with or without Chlamydia genital tract infection to better define this response. Initial genome-wide microarray analysis revealed highly elevated expression of matrix metalloproteinase 10 and other molecules characteristic of Type 2 immunity (e.g., fibrosis and wound repair) in Chlamydia-infected tissue. This result was corroborated in flow cytometry and immunohistochemistry studies that showed extant upper genital tract Chlamydia infection was associated with increased co-expression of CD200 receptor and CD206 (markers of alternative macrophage activation) by endometrial macrophages as well as increased expression of GATA-3 (the transcription factor regulating TH2 differentiation) by endometrial CD4+ T cells. Also among women with genital tract Chlamydia infection, peripheral CD3+ CD4+ and CD3+ CD4- cells that proliferated in response to ex vivo stimulation with inactivated chlamydial antigen secreted significantly more interleukin (IL)-4 than tumor necrosis factor, interferon-γ, or IL-17; findings that repeated in T cells isolated from these same women 1 and 4 months after infection had been eradicated. Our results thus newly reveal that genital infection by an obligate intracellular bacterium induces polarization towards Type 2 immunity, including Chlamydia-specific TH2 development. Based on these findings, we now speculate that Type 2 immunity was selected by evolution as the host response to C. trachomatis in the human female genital tract to control infection and minimize immunopathological damage to vital reproductive structures. © 2013 Vicetti Miguel et al

Presence of Antibodies Against Coxiella burnetii and Risk of Spontaneous Abortion: A Nested Case-Control Study

BACKGROUND AND AIMS: Q fever is a bacterial zoonosis caused by infection with Coxiella burnetii. It is well established that Q fever causes fetal loss in small ruminants. The suspicion has been raised that pregnant women may also experience adverse pregnancy outcome when the infection is acquired or reactivated during pregnancy. The purpose of this study was to assess the potential association between serologic markers of infection with C. burnetii and spontaneous abortion. METHODS: A nested case-control study within the Danish National Birth Cohort, a cohort of 100,418 pregnancies recruited from 1996-2002. Women were recruited in first trimester of pregnancy and followed prospectively. Median gestational age at enrolment was 8 weeks (25 and 75 percentiles: 7 weeks; 10 weeks). During pregnancy, a blood sample was collected at gestational week 6-12 and stored in a bio bank. For this study, a case sample of 218 pregnancies was drawn randomly among the pregnancies in the cohort which ended with a miscarriage before 22 gestational weeks, and a reference group of 482 pregnancies was selected in a random fashion among all pregnancies in the cohort. From these pregnancies, serum samples were screened for antibodies against C. burnetii in a commercial enzyme-linked immunosorbent assay (ELISA). Samples that proved IgG or IgM antibody positive were subsequently confirmatory tested by an immunofluorescence (IFA) test. RESULTS: Among cases, 11 (5%) were C. burnetii positive in ELISA of which one was confirmed in the IFA assay compared to 29 (6%) ELISA positive and 3 IFA confirmed in the random sample. CONCLUSIONS: We found no evidence of a higher prevalence of C. burnetii antibodies in serum samples from women who later miscarried and the present study does not indicate a major association between Q fever infection and spontaneous abortion in humans. Very early first trimester abortions were, however, not included in the study

Communication, advice exchange and job satisfaction of nursing staff: a social network analyses of 35 long-term care units

Background: The behaviour of individuals is affected by the social networks in which they are embedded. Networks are also important for the diffusion of information and the influence of employees in organisations. Yet, at the moment little is known about the social networks of nursing staff in healthcare settings. This is the first study that investigates informal communication and advice networks of nursing staff in long-term care. We examine the structure of the networks, how they are related to the size of units and characteristics of nursing staff, and their relationship with job satisfaction. Methods: We collected social network data of 380 nursing staff of 35 units in group projects and psychogeriatric units in nursing homes and residential homes in the Netherlands. Communication and advice networks were analyzed in a social network application (UCINET), focusing on the number of contacts (density) between nursing staff on the units. We then studied the correlation between the density of networks, size of the units and characteristics of nursing staff. We used multilevel analyses to investigate the relationship between social networks and job satisfaction of nursing staff, taking characteristics of units and nursing staff into account. Results: Both communication and advice networks were negatively related to the number of residents and the number of nursing staff of the units. Communication and advice networks were more dense when more staff worked part-time. Furthermore, density of communication networks was positively related to the age of nursing staff of the units. Multilevel analyses showed that job satisfaction differed significantly between individual staff members and units and was influenced by the number of nursing staff of the units. However, this relationship disappeared when density of communication networks was added to the model. Conclusions: Overall, communication and advice networks of nursing staff in long-term care are relatively dense. This fits with the high level of cooperation that is needed to provide good care to residents. Social networks are more dense in small units and are also shaped by characteristics of staff members. The results furthermore show that communication networks are important for staff's job satisfaction. (aut. ref.

Autoimmune and autoinflammatory mechanisms in uveitis

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders

Logics of knowledge and action: critical analysis and challenges

International audienceWe overview the most prominent logics of knowledge and action that were proposed and studied in the multiagent systems literature. We classify them according to these two dimensions, knowledge and action, and moreover introduce a distinction between individual knowledge and group knowledge, and between a nonstrategic an a strategic interpretation of action operators. For each of the logics in our classification we highlight problematic properties. They indicate weaknesses in the design of these logics and call into question their suitability to represent knowledge and reason about it. This leads to a list of research challenges

Measurement of the branching fraction and CP content for the decay B(0) -> D(*+)D(*-)

This is the pre-print version of the Article. The official published version can be accessed from the links below. Copyright @ 2002 APS.We report a measurement of the branching fraction of the decay B0→D*+D*- and of the CP-odd component of its final state using the BABAR detector. With data corresponding to an integrated luminosity of 20.4  fb-1 collected at the Υ(4S) resonance during 1999–2000, we have reconstructed 38 candidate signal events in the mode B0→D*+D*- with an estimated background of 6.2±0.5 events. From these events, we determine the branching fraction to be B(B0→D*+D*-)=[8.3±1.6(stat)±1.2(syst)]×10-4. The measured CP-odd fraction of the final state is 0.22±0.18(stat)±0.03(syst).This work is supported by DOE and NSF (USA), NSERC (Canada), IHEP (China), CEA and CNRS-IN2P3 (France), BMBF (Germany), INFN (Italy), NFR (Norway), MIST (Russia), and PPARC (United Kingdom). Individuals have received support from the A.P. Sloan Foundation, Research Corporation, and Alexander von Humboldt Foundation

Measurement of D-s(+) and D-s(*+) production in B meson decays and from continuum e(+)e(-) annihilation at √s=10.6 GeV

This is the pre-print version of the Article. The official published version can be accessed from the links below. Copyright @ 2002 APSNew measurements of Ds+ and Ds*+ meson production rates from B decays and from qq̅ continuum events near the Υ(4S) resonance are presented. Using 20.8 fb-1 of data on the Υ(4S) resonance and 2.6 fb-1 off-resonance, we find the inclusive branching fractions B(B⃗Ds+X)=(10.93±0.19±0.58±2.73)% and B(B⃗Ds*+X)=(7.9±0.8±0.7±2.0)%, where the first error is statistical, the second is systematic, and the third is due to the Ds+→φπ+ branching fraction uncertainty. The production cross sections σ(e+e-→Ds+X)×B(Ds+→φπ+)=7.55±0.20±0.34pb and σ(e+e-→Ds*±X)×B(Ds+→φπ+)=5.8±0.7±0.5pb are measured at center-of-mass energies about 40 MeV below the Υ(4S) mass. The branching fractions ΣB(B⃗Ds(*)+D(*))=(5.07±0.14±0.30±1.27)% and ΣB(B⃗Ds*+D(*))=(4.1±0.2±0.4±1.0)% are determined from the Ds(*)+ momentum spectra. The mass difference m(Ds+)-m(D+)=98.4±0.1±0.3MeV/c2 is also measured.This work was supported by DOE and NSF (USA), NSERC (Canada), IHEP (China), CEA and CNRS-IN2P3 (France), BMBF (Germany), INFN (Italy), NFR (Norway), MIST (Russia), and PPARC (United Kingdom). Individuals have received support from the Swiss NSF, A. P. Sloan Foundation, Research Corporation, and Alexander von Humboldt Foundation

The influence of sentinel lymph node tumour burden on additional lymph node involvement and disease-free survival in cutaneous melanoma – a retrospective analysis of 392 cases

Twenty per cent of sentinel lymph node (SLN)-positive melanoma patients have positive non-SLN lymph nodes in completion lymph node dissection (CLND). We investigated SLN tumour load, non-sentinel positivity and disease-free survival (DFS) to assess whether certain patients could be spared CLND. Sentinel lymph node biopsy was performed on 392 patients between 1999 and 2005. Median observation period was 38.8 months. Sentinel lymph node tumour load did not predict non-SLN positivity: 30.8% of patients with SLN macrometastases (⩾2 mm) and 16.4% with micrometastases (⩽2 mm) had non-SLN positivity (P=0.09). Tumour recurrences after positive SLNs were more than twice as frequent for SLN macrometastases (51.3%) than for micrometastases (24.6%) (P=0.005). For patients with SLN micrometastases, the DFS analysis was worse (P=0.003) when comparing those with positive non-SLNs (60% recurrences) to those without (17.6% recurrences). This difference did not translate into significant differences in DFS: patients with SLN micrometastasis, either with (P=0.022) or without additional positive non-SLNs (P<0.0001), fared worse than patients with tumour-free SLNs. The 2-mm cutoff for SLN tumour load accurately predicts differences in DFS. Non-SLN positivity in CLND, however, cannot be predicted. Therefore, contrary to other studies, no recommendations concerning discontinuation of CLND based on SLN tumour load can be deduced

Efficacy of interventions to increase the uptake of chlamydia screening in primary care: a systematic review

<p>Abstract</p> <p>Background</p> <p>As most genital chlamydia infections are asymptomatic, screening is the main way to detect and cases for treatment. We undertook a systematic review of studies assessing the efficacy of interventions for increasing the uptake of chlamydia screening in primary care.</p> <p>Methods</p> <p>We reviewed studies which compared chlamydia screening in the presence and the absence of an intervention. The primary endpoints were screening rate or total tests.</p> <p>Results</p> <p>We identified 16 intervention strategies; 11 were randomised controlled trials and five observational studies, 10 targeted females only, five both males and females, and one males only. Of the 15 interventions among females, six were associated with significant increases in screening rates at the 0.05 level including a multifaceted quality improvement program that involved provision of a urine jar to patients at registration (44% in intervention clinics vs. 16% in the control clinic); linking screening to routine Pap smears (6.9% vs. 4.5%), computer alerts for doctors (12.2% vs. 10.6%); education workshops for clinic staff; internet-based continuing medical education (15.5% vs. 12.4%); and free sexual health consultations (16.8% vs. 13.2%). Of the six interventions targeting males, two found significant increases including the multifaceted quality improvement program in which urine jars were provided to patients at registration (45% vs. 15%); and the offering by doctors of a test to all presenting young male clients, prior to consultation (29 vs. 4%).</p> <p>Conclusions</p> <p>Interventions that promoted the universal offer of a chlamydia test in young people had the greatest impact on increasing screening in primary care.</p