Total IgE and eotaxin (CCL11) contents in tears of patients suffering from seasonal allergic conjunctivitis.

BACKGROUND: To prospectively investigate patients with seasonal allergic conjunctivitis (SAC) during the pollen season and test associations between tears total IgE, eotaxin concentrations, and SAC severity. METHODS: Enrolled patients presented ocular symptoms and clinical signs of SAC at the time of presentation. Ocular itching, hyperaemia, chemosis, eyelid swelling, and tearing were scored, and the sum of these scores was defined as the clinical score. Conjunctival papillae were separately graded. We measured eotaxin concentration in tears by an enzyme-linked immunosorbent assay (ELISA) and total tear IgE by Lacrytest strip. RESULTS: Among thirty patients (30 eyes), 11 showed neither tear IgE nor tear eotaxin, while 15 out of 19 patients with positive IgE values presented a positive amount of eotaxin in their tears (Fisher's test: p < 0.001). The mean eotaxin concentration was 641 ± 154 (SEM) pg/ml. In patients with no amount of tear IgE, we observed a lower conjunctival papilla grade than in patients whose tears contained some amount of IgE (trend test: p = 0.032). In the 15 patients whose tear eotaxin concentration was null, tear IgE concentration was 5.3 ± 3.5 arbitrary units; in the other 15 patients whose eotaxin was positive, IgE reached 21 ± 4.3 arbitrary U (Mann-Whitney: p < 0.001). We measured 127 ± 47 pg/ml eotaxin in patients with no history of SAC but newly diagnosed as suffering from SAC, and 852 ± 218 pg/ml eotaxin in patients with a known SAC (p = 0.008). In contrast, tear IgE concentrations of both groups did not differ statistically significantly (p = 0.947). CONCLUSIONS: If IgE and eotaxin secreted in tears are major contributors in SAC pathogenesis, they however act at different steps of the process.

The use of classification and regression trees to predict the likelihood of seasonal influenza.

Background Individual signs and symptoms are of limited value for the diagnosis of influenza. Objective To develop a decision tree for the diagnosis of influenza based on a classification and regression tree (CART) analysis. Methods Data from two previous similar cohort studies were assembled into a single dataset. The data were randomly divided into a development set (70%) and a validation set (30%). We used CART analysis to develop three models that maximize the number of patients who do not require diagnostic testing prior to treatment decisions. The validation set was used to evaluate overfitting of the model to the training set. Results Model 1 has seven terminal nodes based on temperature, the onset of symptoms and the presence of chills, cough and myalgia. Model 2 was a simpler tree with only two splits based on temperature and the presence of chills. Model 3 was developed with temperature as a dichotomous variable (≥38°C) and had only two splits based on the presence of fever and myalgia. The area under the receiver operating characteristic curves (AUROCC) for the development and validation sets, respectively, were 0.82 and 0.80 for Model 1, 0.75 and 0.76 for Model 2 and 0.76 and 0.77 for Model 3. Model 2 classified 67% of patients in the validation group into a high- or low-risk group compared with only 38% for Model 1 and 54% for Model 3. Conclusions A simple decision tree (Model 2) classified two-thirds of patients as low or high risk and had an AUROCC of 0.76. After further validation in an independent population, this CART model could support clinical decision making regarding influenza, with low-risk patients requiring no further evaluation for influenza and high-risk patients being candidates for empiric symptomatic or drug therapy.

The changing preference of T and B cells for partners as T-dependent antibody responses develop.

Recirculating virgin CD4+ T cells spend their life migrating between the T zones of secondary lymphoid tissues where they screen the surface of interdigitating dendritic cells. T-cell priming starts when processed peptides or superantigen associated with class II MHC molecules are recognised. Those primed T cells that remain within the lymphoid tissue move to the outer T zone, where they interact with B cells that have taken up and processed antigen. Cognate interaction between these cells initiates immunoglobulin (Ig) class switch-recombination and proliferation of both B and T cells; much of this growth occurs outside the T zones B cells migrate to follicles, where they form germinal centres, and to extrafollicular sites of B-cell growth, where they differentiate into mainly short-lived plasma cells. T cells do not move to the extrafollicular foci, but to the follicles; there they proliferate and are subsequently involved in the selection of B cells that have mutated their Ig variable-region genes. During primary antibody responses T-cell proliferation in follicles produces many times the peak number of T cells found in that site: a substantial proportion of the CD4+ memory T-cell pool may originate from growth in follicles.

Impact of anti-T cell therapy in the immunogenicity of seasonal influenza vaccine in kidney transplants recipients

1. Mise en perspective de l'étude La grippe est une cause importante de morbidité et de mortalité après la transplantation d'organe. Bien que la principale stratégie de prévention de la grippe après la transplantation d'organes soit l'administration du vaccin antigrippal annuel, l'immunogénicité de ce vaccin chez les greffés d'organe n'est pas optimale. Nous avons effectué une étude prospective pour évaluer l'influence de la thérapie d'induction sur l'immunogénicité du vaccin de la grippe. 2. Méthodes Nous avons comparé la réponse au vaccin de la grippe chez deux groupes de greffés rénaux en fonction de la thérapie d'induction reçu (thymoglobulin vs basiliximab). Le taux des anticorps ont étés mesurés par inhibition de l'hémagglutination (HI). La réponse au vaccin (taux de séroconversion) a été définie comme l'augmentation > 4 fois du taux d'anticorps (immunoglobulines) et ceci a été notre outcome primaire. 3. Résultats Soixante transplantés rénaux ont été inclus dans l'étude (thymoglobuline=22, basiliximab=38). Les patients dans le group traité par thymoglobuline étaient plus âgés (p=0.16), avaient des valeurs de créatinine plus élevés (p=0.16) et avaient étés transplanté auparavant (p=0.02). Aucune différence n'a été mise en évidence au niveau de taux des immunoglobulines pour les 3 souches virales entre les 2 groupes (p=0.69 pour H INI, p=0.56 pour H3N2, p=0.7 pour Influenza Β). Le taux de séroconversion à au moins une souche virale a été de 68 % pour le groupe thymoglobuline et de 73% pour le groupe basiliximab (p=0.77). 4. Conclusion Aucune différence significative n'a été démontré dans l'immunogénicité du vaccin de la grippe dans les transplantés rénaux ayant reçu soit du thymoglobuline soit du basiliximab comme traitement d'induction.

Low-dose intradermal versus intramuscular trivalent inactivated seasonal influenza vaccine in lung transplant recipients.

BACKGROUND: In this study we compared the immunogenicity of influenza vaccine administered intradermally to the standard intramuscular vaccination in lung transplant recipients. METHODS: Patients were randomized to receive the trivalent inactivated seasonal 2008-9 influenza vaccine containing either 6 μg (intradermal) or 15 μg (intramuscular) of hemagglutinin per viral strain. Immunogenicity was assessed by measurement of geometric mean titer of antibodies using the hemagglutination-inhibition (HI) assay. Vaccine response was defined as a 4-fold or higher increase of antibody titers to at least one vaccine antigen. RESULTS: Eighty-five patients received either the intradermal (n = 41) or intramuscular (n = 44) vaccine. Vaccine response was seen in 6 of 41 patients (14.6%) in the intradermal vs 8 of 43 (18.6%) in the intramuscular group (p = 0.77). Seroprotection (HI ≥1:32) was 39% for H1N1, 83% for H3N2 and 29% for B strain in the intradermal group vs 28% for H1N1, 98% for H3N2 and 58% for B strain in the intramuscular group (p = 0.36 for H1N1, p = 0.02 for H3N2, p < 0.01 for B). Mild adverse events were seen in 44% of patients in the intradermal group and 34% in the intramuscular group (p = 0.38). CONCLUSIONS: Immunogenicity of the 2008-9 influenza vaccine given intradermally or intramuscularly was overall poor in lung transplant recipients. Novel strategies for influenza vaccination in this population are needed.

Controls on ostracod valve geochemistry, Part 1: Variations of environmental parameters in ostracod (micro-)habitats

The variations of environmental conditions (T°, pH, δ13CDIC, [DIC], δ18O, Mg/Ca, and Sr/Ca) of ostracod habitats were examined to determine the controls of environmental parameters on the chemical and isotopic composition of ostracod valves. Results of a one-year monitoring of environmental parameters at five sites, with depths of between 2 and 70 m, in Lake Geneva indicate that in littoral to sub-littoral zones (2, 5, and 13 m), the chemical composition of bottom water varies seasonally in concert with changes in temperature and photosynthetic activity. An increase of temperature and photosynthetic activity leads to an increase in δ13C values of DIC and to precipitation of authigenic calcite, which results in a concomitant increase of Mg/Ca and Sr/Ca ratios of water. In deeper sites (33 and 70 m), the composition of bottom water remains constant throughout the year and isotopic values and trace element contents are similar to those of deep water within the lake. The chemical composition of interstitial pore water also does not reflect seasonal variations but is controlled by calcite dissolution, aerobic respiration, anaerobic respiration with reduction of sulphate and/or nitrate, and methanogenesis that may occur in the sediment pores. Relative influence of each of these factors on the pore water geochemistry depends on sediment thickness and texture, oxygen content in bottom as well as pore water. Variations of chemical compositions of the ostracod valves of this study vary according to the specific ecology of the ostracod species analysed, that is its life-cycle and its (micro-)habitat. Littoral species have compositions that are related to the seasonal variations of temperature, δ13C values of DIC, and of Mg/Ca and Sr/Ca ratios of water. In contrast, the compositions of profundal species are largely controlled by variations of pore fluids along sediment depth profiles according to the specific depth preference of the species. The control on the geochemistry of sub-littoral species is a combination of controls for the littoral and profundal species as well as the specific ecology of the species.

In kittiwakes food availability partially explains the seasonal decline in immunocompetence

1. The immune system plays an important role in fitness, and interindividual variation in immunocompetence is due to several factors including food supply. 2. Seasonal variation in food resources may therefore explain why immunocompetence in bird nestlings usually declines throughout the breeding season, with chicks born early in the season receiving more food than chicks born later, and thereby possibly developing a more potent immune system. Although there are studies supporting this hypothesis, none has been experimental. 3. We performed an experiment in the kittiwake Rissa tridactyla by manipulating the food supply of pairs that were left to produce a first brood, and of pairs that were induced to produce a late replacement brood. 4. If food supply mediates, at least partially, seasonal variations in chick immunocompetence, non-food-supplemented chicks would show a stronger seasonal decline in immunocompetence than food-supplemented chicks. 5. Food supplementation improved humoral immunocompetence (the production of immunoglobulins Y), but not T-cell immunocompetence (phytohaemagglutinin, PHA response). T-cell immunocompetence of food-supplemented and non-food-supplemented chicks decreased through the season but to a similar extent, whereas the humoral immunocompetence of non-food-supplemented chicks decreased more strongly than that of food-supplemented chicks. 6. Our results suggest that the seasonal decline in humoral immunocompetence can be explained, at least partly, by variations in food supply throughout the breeding season.

Seasonal fluctuations of bacterial community diversity in agricultural soil and experimental validation by laboratory disturbance experiments.

Natural fluctuations in soil microbial communities are poorly documented because of the inherent difficulty to perform a simultaneous analysis of the relative abundances of multiple populations over a long time period. Yet, it is important to understand the magnitudes of community composition variability as a function of natural influences (e.g., temperature, plant growth, or rainfall) because this forms the reference or baseline against which external disturbances (e.g., anthropogenic emissions) can be judged. Second, definition of baseline fluctuations in complex microbial communities may help to understand at which point the systems become unbalanced and cannot return to their original composition. In this paper, we examined the seasonal fluctuations in the bacterial community of an agricultural soil used for regular plant crop production by using terminal restriction fragment length polymorphism profiling (T-RFLP) of the amplified 16S ribosomal ribonucleic acid (rRNA) gene diversity. Cluster and statistical analysis of T-RFLP data showed that soil bacterial communities fluctuated very little during the seasons (similarity indices between 0.835 and 0.997) with insignificant variations in 16S rRNA gene richness and diversity indices. Despite overall insignificant fluctuations, between 8 and 30% of all terminal restriction fragments changed their relative intensity in a significant manner among consecutive time samples. To determine the magnitude of community variations induced by external factors, soil samples were subjected to either inoculation with a pure bacterial culture, addition of the herbicide mecoprop, or addition of nutrients. All treatments resulted in statistically measurable changes of T-RFLP profiles of the communities. Addition of nutrients or bacteria plus mecoprop resulted in bacteria composition, which did not return to the original profile within 14 days. We propose that at less than 70% similarity in T-RFLP, the bacterial communities risk to drift apart to inherently different states.

Prophylaxis with resin in wood ants

Animals may use plant compounds to defend themselves against parasites. Wood ants, Formica paralugubris, incorporate pieces of solidified conifer resin into their nests. This behaviour inhibits the growth of bacteria and fungi in nest material and protects the ants against some detrimental microorganisms. Here, we studied the resin-collecting behaviour of ants under field and laboratory conditions. First, we focused on an important assumption of the self-medication hypothesis, which is that the animals deliberately choose the active plant material. In field cafeteria tests, the ants indeed showed a strong preference for resin over twigs and stones, which are building materials commonly encountered in their environment. We detected seasonal variation in the choice of ants: the preference for resin over twigs was more pronounced in spring than in summer, whereas in autumn the ants collected twigs and resin at equal rates. Second, we found almost similar seasonal patterns when comparing the collecting rates of pieces of wood that had been impregnated with turpentine (a distillate of oleoresin) and untreated pieces of wood, which reveals that the preference for resin is based on odour cues. Third, we tested whether the collection of resin is prophylactic or therapeutic. We found that the relative collection rate of resin versus stones did not depend on an experimental infection with the entomopathogenic fungus Metarhizium anisopliae in laboratory colonies. Together, these results show that the ants deliberately choose the resin and suggest that resin collection is prophylactic rather than therapeutic.

Oseltamivir in seasonal, avian H5N1 and pandemic 2009 A/H1N1 influenza: pharmacokinetic and pharmacodynamic characteristics.

Oseltamivir is the ester-type prodrug of the neuraminidase inhibitor oseltamivir carboxylate. It has been shown to be an effective treatment for both seasonal influenza and the recent pandemic 2009 A/H1N1 influenza, reducing both the duration and severity of the illness. It is also effective when used preventively. This review aims to describe the current knowledge of the pharmacokinetic and pharmacodynamic characteristics of this agent, and to address the issue of possible therapeutic drug monitoring. According to the currently available literature, the pharmacokinetics of oseltamivir carboxylate after oral administration of oseltamivir are characterized by mean ± SD bioavailability of 79 ± 12%, apparent clearance of 25.3 ± 7.0 L/h, an elimination half-life of 7.4 ± 2.5 hours and an apparent terminal volume of distribution of 267 ± 122 L. A maximum plasma concentration of 342 ± 83 μg/L, a time to reach the maximum plasma concentration of 4.2 ± 1.1 hours, a trough plasma concentration of 168 ± 32 μg/L and an area under the plasma concentration-time curve from 0 to 24 hours of 6110 ± 1330 μg · h/L for a 75 mg twice-daily regimen were derived from literature data. The apparent clearance is highly correlated with renal function, hence the dosage needs to be adjusted in proportion to the glomerular filtration rate. Interpatient variability is moderate (28% in apparent clearance and 46% in the apparent central volume of distribution); there is no indication of significant erratic or limited absorption in given patient subgroups. The in vitro pharmacodynamics of oseltamivir carboxylate reveal wide variation in the concentration producing 50% inhibition of influenza A and B strains (range 0.17-44 μg/L). A formal correlation between systemic exposure to oseltamivir carboxylate and clinical antiviral activity or tolerance in influenza patients has not yet been demonstrated; thus no formal therapeutic or toxic range can be proposed. The pharmacokinetic parameters of oseltamivir carboxylate after oseltamivir administration (bioavailability, apparent clearance and the volume of distribution) are fairly predictable in healthy subjects, with little interpatient variability outside the effect of renal function in all patients and bodyweight in children. Thus oseltamivir carboxylate exposure can probably be controlled with sufficient accuracy by thorough dosage adjustment according to patient characteristics. However, there is a lack of clinical study data on naturally infected patients. In addition, the therapeutic margin of oseltamivir carboxylate is poorly defined. The usefulness of systematic therapeutic drug monitoring in patients therefore appears to be questionable; however, studies are still needed to extend the knowledge to particular subgroups of patients or dosage regimens.

Mg/Ca and Sr/Ca ratios of ostracod valves from living species of Lake Geneva

The Mg/Ca and Sr/Ca ratios of living ostracods belonging to 15 different species and sampled monthly over a one year-cycle at five sites (2, 5, 13, 33, and 70 m water depths) in western Lake Geneva (Switzerland) are compared to the oxygen and carbon isotope compositions measured on the same samples as well as to the temperature and chemical composition of the water (δ18OH2O, δ13CDIC, Mg/CaH2O, and Sr/CaH2O) at the time of ostracod calcification. The results indicate that trace element incorporation varied at the species level, mainly because of the ecological and biological differences between the different species (life-cycle, (micro-)habitat preference, biomineralisation processes) and the control thereof on trace element incorporation of the ostracods. In littoral zones, the Mg/Ca and Sr/Ca of ostracod valves increase as temperature and Mg/Ca and Sr/Ca of water increase during spring and summer, hence reflecting mainly seasonal variations. However, given that for Lake Geneva the Mg/Ca and Sr/Ca of water also vary with temperature, it is not possible to distinguish the effects of temperature from those of changes in chemical composition of water on the trace element content in ostracod valves. Results support that both water temperature and water Mg/Ca and Sr/Ca ratios control the final trace element content of Cyprididae valves. In contrast, the trace element content of species living in deeper zones of the basin is influenced by variations in the chemical composition of the pore water for the infaunal species. Trace element content measured for these specimens cannot, therefore, be used to reconstruct the compositions of the water lake bottom. In addition, incorporation of Mg and Sr into the shell differs from one family, sub-family, or even species to the other. This suggests that the distinctive Mg and Sr partition coefcients for the analysed taxa result from different valve calcification strategies that may be phylogenetic.

Impact of Anti-T-Cell Therapy in the Immunogenicity of Seasonal Influenza Vaccine in Kidney Transplant Recipients.

BACKGROUND: The influence of anti-T-cell therapy in the immunogenicity of the influenza vaccine in kidney transplant recipients remains unclear. METHODS: During the 2010 to 2011 influenza season, we evaluated the immune response to the inactivated trivalent influenza vaccine in kidney transplant recipients having received Thymoglobulin or basiliximab as induction therapy. A hemagglutination inhibition assay was used to assess the immunogenicity of the vaccine. The primary outcome was geometric mean titers of hemagglutination inhibition after influenza vaccination. RESULTS: Sixty patients (Thymoglobulin n=22 and basiliximab n=38) were included. Patients in the Thymoglobulin group were older (P=0.16), showed higher creatinine levels (P=0.16) and had more frequently received a previous transplant (P=0.02). There were no significant differences in geometric mean titers for any of the three viral strains between groups (P=0.69 for H1N1, P=0.56 for H3N2, and P=0.7 for B strain). Seroconversion to at least one viral strain was seen in 15 (68%) of 22 patients in the Thymoglobulin group and 28 (73%) of 38 in the basiliximab group (P=0.77). In patients vaccinated during the first year after receiving anti-T-cell therapy (n=25), there was a trend toward lower vaccine responses in the Thymoglobulin group. Patients who received Thymoglobulin showed lower CD4 cell counts and lower levels of IgM, at an average of 16.2 months after transplantation. A multivariate analysis showed that only the absence of mycophenolate was associated with a better vaccine response (odds ratio=9.47; 95% confidence interval, 1.03-86.9; P=0.047). CONCLUSION: No significant differences were seen in immunogenicity of the influenza vaccine in kidney transplant recipients having received either Thymoglobulin or basiliximab.

Preference, specificity and cheating in the arbuscular mycorrhizal symbiosis.

Arbuscular mycorrhizal symbioses are mutualistic interactions between fungi and most plants. There is considerable interest in this symbiosis because of the strong nutritional benefits conferred to plants and its influence on plant diversity. Until recently, the symbiosis was assumed to be unspecific. However, two studies have now revealed that although it can be largely unspecific with the fungal community composition changing seasonally, in certain ecosystems it can also be highly specific and might potentially allow plants to cheat the arbuscular mycorrhizal network that connects plants below ground.

Support for Seasonal Influenza Vaccination Requirements among US Healthcare Personnel.

Objective. To measure support for seasonal influenza vaccination requirements among US healthcare personnel (HCP) and its associations with attitudes regarding influenza and influenza vaccination and self-reported coverage by existing vaccination requirements. Design. Between June 1 and June 30, 2010, we surveyed a sample of US HCP ([Formula: see text]) recruited using an existing probability-based online research panel of participants representing the US general population as a sampling frame. Setting. General community. Participants. Eligible HCP who (1) reported having worked as medical doctors, health technologists, healthcare support staff, or other health practitioners or who (2) reported having worked in hospitals, ambulatory care facilities, long-term care facilities, or other health-related settings. Methods. We analyzed support for seasonal influenza vaccination requirements for HCP using proportion estimation and multivariable probit models. Results. A total of 57.4% (95% confidence interval, 53.3%-61.5%) of US HCP agreed that HCP should be required to be vaccinated for seasonal influenza. Support for mandatory vaccination was statistically significantly higher among HCP who were subject to employer-based influenza vaccination requirements, who considered influenza to be a serious disease, and who agreed that influenza vaccine was safe and effective. Conclusions. A majority of HCP support influenza vaccination requirements. Moreover, providing HCP with information about the safety of influenza vaccination and communicating that immunization of HCP is a patient safety issue may be important for generating staff support for influenza vaccination requirements.