In vitro infection of human dendritic cells by Aspergillus fumigatus conidia triggers the secretion of chemokines for neutrophil and Th1 lymphocyte recruitment.

Given the role played by chemokines in the selective homing of immune cells, we sought to characterize the profile of chemokines produced by human dendritic cells (DC) following in vitro Aspergillus fumigatus infection and their ability to recruit cells involved in the antifungal defense. At the onset of A. fumigatus infection, DC released elevated amounts of CXCL8 that promote the migration of polymorphonuclear cells (PMN). Moreover, soluble factors released from A. fumigatus-infected DC increased also the surface expression of two activation markers, CD11b and CD18, on PMN. A. fumigatus infection resulted also in CCL3, CCL4, CXCL10 and CCL20 productions that induce the migration of effector memory Th1 cells. Moreover, the late expression of CCL19 suggests that A. fumigatus-infected DC could be implicated in the migration of CCR7+ naïve T cells and mature DC in lymph nodes. Together these results suggested the involvement of human DC in the regulation of innate and adaptive immunity against A. fumigatus through the recruitment of cells active in the fungal destruction.

Risk factors of latent tuberculosis infection among asylum-seekers recently arrived in Switzerland : A pilot study in Vaud county

Background: Asylum seekers may have a higher rate of latenttuberculosis infection (LTBI) than resident populations in Westerncountries. LTBI can be detected by an Interferon Gamma ReleaseAssay (IGRA). Screening asylum seekers at highest risk for LTBI orfuture tuberculosis by IGRA could be considered. The aims of this pilotstudy were to assess the prevalence and the risk factors of LTBI amonga group of asylum seekers recently arrived in Switzerland.Methods: A prospective cross-sectional study was performed amongadult asylum seekers, staying in two migrant centers of the Vaud county,Switzerland, after a first screening for active tuberculosis at the border.The participants were offered IGRA screening using T-SPOT.TB andwere questioned about risk factors associated with LTBI. Migrants with apositive test had a chest radiograph and a medical examination. Thosewith active tuberculosis were excluded and were treated. The migrantswith LTBI received a preventive treatment, if indicated. The risk factorswere analyzed by univariate and multivariate logistical regression.Results: Among 788 migrants recently arrived, 639 were adults, 393agreed to be screened (61.50%) and 98 of them had a positive T-SPOT.TB (24.93%) of which 5 (5.1%) had an active tuberculosis (previouslynot detected at the border), and 2 had already been treated for activetuberculosis. In univariate analysis, the major risk factors associatedwith LTBI were country of origin and travel conditions. Compared withmigrants from Balkanic countries, migrants from Africa had an OR forLTBI of 3.68, migrants from Asia an OR of 4.3 and migrants fromFormer Soviet Union an OR of 4.5. Migrants who crossed severalborders before arriving in Switzerland had an OR of LTBI of 2.49compared with migrants who came directly from the home country.Age, cough and prior exposure to tuberculosis had a non-significantinfluence on the rate of test positivity. In multivariate analysis, thecombination of country of origin, travel conditions, age, cough andexposure to tuberculosis resulted in a score with optimal predictivevalue (Roc = 81%).Conclusions: Asylum seekers recently arrived in Vaud county had ahigh prevalence of LTBI and active tuberculosis. The major risk factorswere country of origin and travel conditions. Selecting for screening byIGRA the asylum seekers with the highest risk factors seems possible.

Prevalence of the metabolic syndrome in the Seychelles according to different definitions, contribution of components, and agreement between different definitions

Background: The metabolic syndrome (MS) represents a cluster of metabolic disorders that predicts diabetes and cardiovascular disease. Several definitions exist and further descriptive and prospective data are needed to compare these definitions and their significance in different populations. Objective: We examined, in a country of the African region, i) the prevalence of MS according to three major definitions (ATP, IDF, WHO); ii) the contribution of individual MS components; and iii) the agreement between the three considered definitions. We also examined the prevalence among diabetics and non-diabetics. Methods: We conducted an examination survey in a sample representative of the general population aged 25-64 of the Seychelles (Indian Ocean, African region), attended by 1255 persons (participation rate of 80.2%). Results: The prevalence of MS was similar with either definition of MS in men (24%-25%) but differed in women (WHO: 25%, ATP: 32%; IDF: 35%). Upon exclusion of diabetic persons, the prevalence was 5-10% lower for all three MS definitions: most diabetic persons had MS although a substantial proportion of diabetic men aged 45-64 did not have MS. The following components were found most often among persons with MS: 90% had high blood pressure (HBP) and 78% had obesity (ATP); 95% had obesity and 84% had HBP (WHO), and 89% had HBP and 75% had impaired glucose regulation (IDF) -not considering impaired glucose regulation and obesity that are compulsory components of the WHO and IDF definitions, respectively. Among persons with MS based on either of the three definitions (37% of total population), less than 80% met both ATP and IDF criteria, 67% both WHO and IDF criteria, 54% both WHO and ATP criteria and only 37% met all three definitions. Conclusions. We found a fairly high prevalence of MS in an African population. However, because there was only poor agreement between the 3 MS definitions, the fairly similar proportions of MS based on ATP, IDF or WHO definitions identified, to a substantial extent, different subjects as having MS.

Epidemiology of Chagas disease in non endemic countries: the role of international migration

Human infection with the protozoa Trypanosoma cruzi extends through North, Central, and South America, affecting 21 countries. Most human infections in the Western Hemisphere occur through contact with infected bloodsucking insects of the triatomine species. As T. cruzi can be detected in the blood of untreated infected individuals, decades after infection took place; the infection can be also transmitted through blood transfusion and organ transplant, which is considered the second most common mode of transmission for T. cruzi. The third mode of transmission is congenital infection. Economic hardship, political problems, or both, have spurred migration from Chagas endemic countries to developed countries. The main destination of this immigration is Australia, Canada, Spain, and the United States. In fact, human infection through blood or organ transplantation, as well as confirmed or potential cases of congenital infections has been described in Spain and in the United States. Estimates reported here indicates that in Australia in 2005-2006, 1067 of the 65,255 Latin American immigrants (16 per 1000) may be infected with T. cruzi, and in Canada, in 2001, 1218 of the 131,135 immigrants (9 per 1000) whose country of origin was identified may have been also infected. In Spain, a magnet for Latin American immigrants since the 2000, 5125 of 241,866 legal immigrants in 2003 (25 per 1000), could be infected. In the United States, 56,028 to 357,205 of the 7,20 million, legal immigrants (8 to 50 per 1000), depending on the scenario, from the period 1981-2005 may be infected with T. cruzi. On the other hand, 33,193 to 336,097 of the estimated 5,6 million undocumented immigrants in 2000 (6 to 59 per 1000) could be infected. Non endemic countries receiving immigrants from the endemic ones should develop policies to protect organ recipients from T. cruzi infection, prevent tainting the blood supply with T. cruzi, and implement secondary prevention of congenital Chagas disease.

Preserving memories on-line : the exhibition 'Memories of our childhood' and the Catalan Immigration History Museum

Gràcies a la introducció d'Internet, les institucions de la memòria poden anar ara un pas endavant i proporcionar narratives i documentació en línia. La present comunicació intenta descobrir com poden ser utilitzades les memòries en línia basant-se en dues experiències: una exposició de nens de la guerra i un portal d'immigració.

The depuration dynamics of oysters (Crassostrea gigas) artificially contaminated with hepatitis A virus and human adenovirus

Within the country of Brazil, Santa Catarina is a major shellfish producer. Detection of viral contamination is an important step to ensure production quality and consumer safety during this process. In this study, we used a depuration system and ultraviolet (UV) disinfection to eliminate viral pathogens from artificially infected oysters and analysed the results. Specifically, the oysters were contaminated with hepatitis A virus (HAV) or human adenovirus type 5 (HAdV5). After viral infection, the oysters were placed into a depuration tank and harvested after 48, 72 and 96 h. After sampling, various oyster tissues were dissected and homogenised and the viruses were eluted with alkaline conditions and precipitated with polyethylene glycol. The oyster samples were evaluated by cell culture methods, as well as polymerase chain reaction (PCR) and quantitative-PCR. Moreover, at the end of the depuration period, the disinfected seawater was collected and analysed by PCR. The molecular assays showed that the HAdV5 genome was present in all of the depuration time samples, while the HAV genome was undetectable after 72 h of depuration. However, viral viability tests (integrated cell culture-PCR and immunofluorescence assay) indicated that both viruses were inactivated with 96 h of seawater recirculation. In conclusion, after 96 h of UV treatment, the depuration system studied in this work purified oysters that were artificially contaminated with HAdV5 and HAV.

Indirect effects of peri-and postnatal choline treatment on place-learning abilities in rat.

This work was aimed at analyzing the effects of perinatal choline supplementation on the development of spatial abilities and upon adult performance. Choline supplementation (3.5 g/L in 0.02 M saccharin solution in tap water) was maintained for two weeks before birth and for up to four weeks postnatally. Additional supplementation was maintained from the fifth to the tenth week postnatally. Spatial-learning capacities were studied at the ages of 26, 65, or 80 days in a circular swimming pool (Morris place-navigation task) and at the age of 7 months in a homing arena. Treatment effects were found in both juvenile and adult rats, and thus persisted for several months after the cessation of the supplementation. The choline supplementation improved the performance in the water maze in a very selective manner. The most consistent effect was a reduction in the latency to reach a cued platform at a fixed position in space, whereas the improvement was limited when the platform was invisible and had to be located relative to distant cues only. However, after removal of the goal cue, the treated rats showed a better retention of the training position than did the control rats. A similar effect was observed in a dry-land task conducted in the homing arena. The choline supplementation thus induced a significant improvement of spatial memory. But since this effect was only evident following training with a salient cue, it might be regarded as an indirect effect promoted by an optimal combination of cue guidance with a place strategy.

Association of socioeconomic status with overall and cause specific mortality in the republic of seychelles : results from a cohort study in the african region

BACKGROUND: Low socioeconomic status (SES) is consistently associated with higher mortality in high income countries. Only few studies have assessed this association in low and middle income countries, mainly because of sparse reliable mortality data. This study explores SES differences in overall and cause-specific mortality in the Seychelles, a rapidly developing small island state in the African region. METHODS: All deaths have been medically certified over more than two decades. SES and other lifestyle-related risk factors were assessed in a total of 3246 participants from three independent population-based surveys conducted in 1989, 1994 and 2004. Vital status was ascertained using linkage with vital statistics. Occupational position was the indicator of SES used in this study and was assessed with the same questions in the three surveys. RESULTS: During a mean follow-up of 15.0 years (range 0-23 years), 523 participants died (overall mortality rate 10.8 per 1000 person-years). The main causes of death were cardiovascular disease (CVD) (219 deaths) and cancer (142 deaths). Participants in the low SES group had a higher mortality risk for overall (HR = 1.80; 95% CI: 1.24-2.62), CVD (HR = 1.95; 1.04-3.65) and non-cancer/non-CVD (HR = 2.14; 1.10-4.16) mortality compared to participants in the high SES group. Cancer mortality also tended to be patterned by SES (HR = 1.44; 0.76-2.75). Major lifestyle-related risk factors (smoking, heavy drinking, obesity, diabetes, hypertension, hypercholesterolemia) explained a small proportion of the associations between low SES and all-cause, CVD, and non-cancer/non-CVD mortality. CONCLUSIONS: In this population-based study assessing social inequalities in mortality in a country of the African region, low SES (as measured by occupational position) was strongly associated with overall, CVD and non-cancer/non-CVD mortality. Our findings support the view that the burden of non-communicable diseases may disproportionally affect people with low SES in low and middle income countries.

Results from a multicentre international registry of familial Mediterranean fever: impact of environment on the expression of a monogenic disease in children.

BACKGROUND AND AIM: Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by mutations of the MEFV gene. We analyse the impact of ethnic, environmental and genetic factors on the severity of disease presentation in a large international registry. METHODS: Demographic, genetic and clinical data from validated paediatric FMF patients enrolled in the Eurofever registry were analysed. Three subgroups were considered: (i) patients living in the eastern Mediterranean countries; (ii) patients with an eastern Mediterranean ancestry living in western Europe; (iii) Caucasian patients living in western European countries. A score for disease severity at presentation was elaborated. RESULTS: Since November 2009, 346 FMF paediatric patients were enrolled in the Eurofever registry. The genetic and demographic features (ethnicity, age of onset, age at diagnosis) were similar among eastern Mediterranean patients whether they lived in their countries or western European countries. European patients had a lower frequency of the high penetrance M694V mutation and a significant delay of diagnosis (p<0.002). Patients living in eastern Mediterranean countries had a higher frequency of fever episodes/year and more frequent arthritis, pericarditis, chest pain, abdominal pain and vomiting compared to the other two groups. Multivariate analysis showed that the variables independently associated with severity of disease presentation were country of residence, presence of M694V mutation and positive family history. CONCLUSIONS: Eastern Mediterranean FMF patients have a milder disease phenotype once they migrate to Europe, reflecting the effect of environment on the expression of a monogenic disease.

Modulation of TCR avidity of primary HIV-1-specific CD8 T-cell responses by early and potent antiviral therapy responses

Background: CD8 T-cells play a critical role in antiviral immunity. However, mechanisms of virus control and immune correlates of protection are still not fully understood. Among other factors, TCR avidity (antigen sensitivity) is thought to play a critical role. Whereas there is a large consensus that high TCR avidity T-cell responses are correlated to higher efficacy against cancer and acute viral infections, it may be not the case in chronic persistent viral infections. Methods: TCR avidity (measured by the effect concentration 50% [EC50]) of HIV-1-specific CD8 T-cell responses directed against optimal epitopes was investigated in different cohorts of HIV-1- infected subjects (n¼114) including early acute and chronic (progressive and non-progressive) HIV-1-infection. Overall, TCR avidity was investigated in 245 HIV-1-specific CD8 T-cell responses. The relationships between TCR avidity, T-cell differentiation and functional profile including cytokine secretion, proliferation and cytotoxic potential (determined by polychromatic flow cytometry) were analyzed. Results: HIV-1-specific CD8 T-cell responses from patients with acute infection had significantly lower TCR avidity as compared to patients with chronic (progressive or non-progressive) HIVinfection (P¼0.03 and 0.003, respectively). These differences remained significant when the analyses were restricted to common epitopes (same epitopes restricted by the same class I HLA). Interestingly, some patients treated during acute infection underwent spontaneous treatment interruption. Re-exposure to high viral load induced two major effects: a) the increase in TCR avidity of pre-existing high avidity (EC50<0.01) T-cell responses (P<0.02) and b) the generation of new T-cell responses with higher TCR avidity as compared to the average pre-existing T-cell responses. Conclusion: These results suggest that high TCR avidity T-cell responses are selected during the course of HIV-1 infection and that one of the potential driving mechanisms is continuous exposure to HIV-1 antigens. These results advance our understanding of the relationship between TCR avidity and Ag exposure of antiviral memory CD8 T-cells.

Counties of Iowa, 1923

Iowa Poem also called "99 Counties" And "Our Home is in Iowa", from the Annals of Iowa, Volume 13, no. 8, pg. 619, under counties of Iowa.

Epidemiology of inflammatory bowel disease: Is there a shift towards onset at a younger age?

OBJECTIVES: Increasing numbers of paediatric and adolescent patients with Crohn disease (CD) and ulcerative colitis (UC) are reported. To determine whether this observation is a consequence of a shift towards onset at a younger age, we analysed retrospective data from patients enrolled in the Swiss IBD Cohort Study (SIBDCS). PATIENTS AND METHODS: The SIBDCS is a disease-based cohort in Switzerland, which collects retrospective and prospective data on a large sample of patients with inflammatory bowel disease (IBD). Patients, diagnosed from 1980, were stratified according to diagnosis of CD and UC. Age at disease onset (age at first symptoms and age at diagnosis) was analysed in relation to calendar year of disease onset. Data were extracted from physician and patient questionnaires. Linear regressions of age at disease onset by calendar year of disease onset adjusted by sex, country of birth, and education were performed. RESULTS: Adjusted regression coefficients for CD and UC were significantly positive, that is, age at disease onset has increased with time. Male sex was associated with an increase in age at disease onset, and birth in Switzerland with a decrease. These associations were statistically significant. CONCLUSIONS: The results from the SIBDCS do not support the hypothesis that disease onset of both CD and UC occur today at a younger age. On the contrary, our results show that there is a significant trend for age at disease onset occurring at an older age today as compared with recent decades. We conclude that the observation of increasing numbers of paediatric and adolescent patients with IBD is not caused by a trend towards disease onset at a younger age, but that this may rather be a consequence of the overall increasing incidence of these conditions.

Therapeutic PD-1 pathway blockade augments with other modalities of immunotherapy T-cell function to prevent immune decline in ovarian cancer.

The tumor microenvironment mediates induction of the immunosuppressive programmed cell death-1 (PD-1) pathway, and targeted interventions against this pathway can help restore antitumor immunity. To gain insight into these responses, we studied the interaction between PD-1 expressed on T cells and its ligands (PD-1:PD-L1, PD-1:PD-L2, and PD-L1:B7.1), expressed on other cells in the tumor microenvironment, using a syngeneic orthotopic mouse model of epithelial ovarian cancer (ID8). Exhaustion of tumor-infiltrating lymphocytes (TIL) correlated with expression of PD-1 ligands by tumor cells and tumor-derived myeloid cells, including tumor-associated macrophages (TAM), dendritic cells, and myeloid-derived suppressor cells (MDSC). When combined with GVAX or FVAX vaccination (consisting of irradiated ID8 cells expressing granulocyte macrophage colony-stimulating factor or FLT3 ligand) and costimulation by agonistic α-4-1BB or TLR 9 ligand, antibody-mediated blockade of PD-1 or PD-L1 triggered rejection of ID8 tumors in 75% of tumor-bearing mice. This therapeutic effect was associated with increased proliferation and function of tumor antigen-specific effector CD8(+) T cells, inhibition of suppressive regulatory T cells (Treg) and MDSC, upregulation of effector T-cell signaling molecules, and generation of T memory precursor cells. Overall, PD-1/PD-L1 blockade enhanced the amplitude of tumor immunity by reprogramming suppressive and stimulatory signals that yielded more powerful cancer control.

Phenotypic heterogeneity of antigen-specific CD4 T cells under different conditions of antigen persistence and antigen load.

The factors responsible for the phenotypic heterogeneity of memory CD4 T cells are unclear. In the present study, we have identified a third population of memory CD4 T cells characterized as CD45RA(+)CCR7(-) that, based on its replication history and the homeostatic proliferative capacity, was at an advanced stage of differentiation. Three different phenotypic patterns of memory CD4 T cell responses were delineated under different conditions of antigen (Ag) persistence and load using CD45RA and CCR7 as markers of memory T cells. Mono-phenotypic CD45RA(-)CCR7(+) or CD45RA(-)CCR7(-) CD4 T cell responses were associated with conditions of Ag clearance (tetanus toxoid-specific CD4 T cell response) or Ag persistence and high load (chronic HIV-1 and primary CMV infections), respectively. Multi-phenotypic CD45RA(-)CCR7(+), CD45RA(-)CCR7(-) and CD45RA(+)CCR7(-) CD4 T cell responses were associated with protracted Ag exposure and low load (chronic CMV, EBV and HSV infections and HIV-1 infection in long-term nonprogressors). The mono-phenotypic CD45RA(-)CCR7(+) response was typical of central memory (T(CM)) IL-2-secreting CD4 T cells, the mono-phenotypic CD45RA(-)CCR7(-) response of effector memory (T(EM)) IFN-gamma-secreting CD4 T cells and the multi-phenotypic response of both IL-2- and IFN-gamma-secreting cells. The present results indicate that the heterogeneity of different Ag-specific CD4 T cell responses is regulated by Ag exposure and Ag load.

Making sense of AMPA receptor trafficking by modeling molecular mechanisms of synaptic plasticity.

Synaptic plasticity involves a complex molecular machinery with various protein interactions but it is not yet clear how its components give rise to the different aspects of synaptic plasticity. Here we ask whether it is possible to mathematically model synaptic plasticity by making use of known substances only. We present a model of a multistable biochemical reaction system and use it to simulate the plasticity of synaptic transmission in long-term potentiation (LTP) or long-term depression (LTD) after repeated excitation of the synapse. According to our model, we can distinguish between two phases: first, a "viscosity" phase after the first excitation, the effects of which like the activation of NMDA receptors and CaMKII fade out in the absence of further excitations. Second, a "plasticity" phase actuated by an identical subsequent excitation that follows after a short time interval and causes the temporarily altered concentrations of AMPA subunits in the postsynaptic membrane to be stabilized. We show that positive feedback is the crucial element in the core chemical reaction, i.e. the activation of the short-tail AMPA subunit by NEM-sensitive factor, which allows generating multiple stable equilibria. Three stable equilibria are related to LTP, LTD and a third unfixed state called ACTIVE. Our mathematical approach shows that modeling synaptic multistability is possible by making use of known substances like NMDA and AMPA receptors, NEM-sensitive factor, glutamate, CaMKII and brain-derived neurotrophic factor. Furthermore, we could show that the heteromeric combination of short- and long-tail AMPA receptor subunits fulfills the function of a memory tag.