Evaluation of the ability of Streptococcus agalactiae strains isolated from genital and neonatal specimens to bind to human fibrinogen and correlation with characteristics of the fbsA and fbsB genes

The ability of 111 Streptococcus agalactiae strains to bind to human fibrinogen was quantified. We correlated the percentages of bacteria that bound to immobilized fibrinogen with fibrinogen-binding (fbs) gene characteristics of strains and with clinical origin, serotypes, and phylogenetic positions of strains. Percentages varied from 0.4 to 29.9%. Fifty-five strains (49.5%) had the fbsB gene sensu stricto described by Gutekunst et al. (Infect. Immun., 72:3495-3504, 2004), allowing adhesion to human fibrinogen, and all of the other strains had an fgag variant gene. Ninety strains (81.1%) had a fbsA gene and 55 of them also had the fbsB gene. The other 21 strains (18.9%) had a truncated form of fbsA without the fbsB gene sensu stricto. The numbers of 48-nucleotide repeat sequences (rs) in the fbsA gene varied from 2 to 26. The population of strains with the highest ability to bind to human fibrinogen significantly more frequently had the fbsB gene sensu stricto and 4 to 7 rs in the fbsA gene (P < 0.05). However, the single strain that carried the highest number of rs (26 rs) in the fbsA gene showed high fibrinogen-binding activity (24.3%). Strains exhibiting significantly higher levels of binding to human fibrinogen belonged to a phylogenetic group of strains associated with neonatal meningitis, currently known as the ST-17 clone, that is mostly composed of serotype III strains. These findings indicate that S. agalactiae strains possess a wide variety of fbs gene content that markedly influences the ability of strains to bind to human fibrinogen. Variations in the configuration and the expression of the Fbs proteins may therefore partly explain the variability of virulence in S. agalactiae species.     

Recirculating CD4 memory T cells mount rapid secondary responses without major contributions from follicular CD4 effectors and B cells

For weeks after primary immunization with thymus-dependent antigens the responding lymph nodes contain effector CD4 T cells in T zones and germinal centers as well as recirculating memory T cells. Conversely, remote nodes, not exposed to antigen, only receive recirculating memory cells. We assessed whether lymph nodes with follicular effector CD4 T cells in addition to recirculating memory CD4 T cells mount a more rapid secondary response than nodes that only contain recirculating memory cells. Also, the extent to which T cell frequency governs accelerated CD4 T cell recall responses was tested. For this, secondary antibody responses to a superantigen, where the frequency of responding T cells is not increased at the time of challenge, were compared with those to conventional protein antigens. With both types of antigens similar accelerated responses were elicited in the node draining the site of primary immunization and in the contralateral node, not previously exposed to antigen. Thus recirculating memory cells are fully capable of mounting accelerated secondary responses, without the assistance of CD4 effector T cells, and accelerated memory responses are not solely dependent on higher T cell frequencies. Accelerated memory CD4 T cell responses were also seen in B cell-deficient mice.     

CD83 expression on dendritic cells and T cells: correlation with effective immune responses

Human CD83 is a marker molecule for mature dendritic cells (DC) and is also expressed on activated B and T cells. Although CD83 has been implicated in immune responses, its function on DC and T cells remains unclear. In this study, we wanted to assess the role of CD83 expressed on DC and T cells in the immune response. Down-regulation of CD83 expression on human DC through RNA interference (RNAi) results in a less potent induction of allogeneic T cell proliferation, reduced IFN-gamma secretion by established T cells and decreased capacity in the priming of functional tumor antigen-specific CD8+ T lymphocytes. In addition, CD83 mRNA-electroporated DC are stronger T cell stimulators. However, CD83 overexpression on Melan-A/MART-1-specific tumor-infiltrating lymphocytes (TIL) circumvents the need for CD83 expression on DC. Co-culture of immature DC with TIL or K562 cells overexpressing CD83 results in the production of enhanced levels of pro-inflammatory cytokines, whereas this production is less pronounced or even absent in co-cultures with non-modified TIL or K562 cells. In conclusion, we demonstrate that CD83 expression on T cells and DC modulates the immune response by activating DC and by delivering costimulatory signals for the stimulation of naive and memory T cells, respectively.     

Ethnic differences in all-cause and cardiovascular mortality by physical activity levels among older adults in the US

Aims: This study sought to determine whether the association between varying levels of physical activity (PA) and all-cause and cardiovascular mortality differ by race/ethnicity in older adults.

Methods: The sample comprised 2520 women and 2398 men drawn from National Health and Nutrition Examination Survey III (1988–1994) aged?≥?60 years. We used the metabolic equivalent (MET) of self-reported PA levels to define activity groups (inactive: those who did not report any PA; active: those who reported 3–6 METs for ≥5 times/week or >6 METs, ≥3 times/week; insufficiently active: those meeting neither criteria). Racial/Ethnic differences were modeled using proportional hazard regression (HR) adjusting for age, education, smoking, diabetes, and hypertension.

Results: Among those classified as inactive, Non-Hispanic Blacks (NHB) (HR: 0.72, 95% CI: 0.58–0.90) and Mexican Americans (HR: 0.59, 95%CI: 0.45–0.78) had a lower risk of all-cause mortality when compared to non-Hispanic Whites (NHW). Among those classified as insufficiently active, Mexican Americans (HR: 0.63, 95% CI: 0.51–0.77), but not NHB (HR: 0.81, (95% CI: 0.64–1.02) had a lower risk of all-cause mortality when compared to NHWs Similar results were observed for cardiovascular mortality.

Conclusion: Overall, PA in the elderly (either insufficient or active) is associated with a lower all-cause mortality across all race/ethnic groups as compared to NHW. Further investigation, including studies with larger sample, is needed to address the health consequences of varying degrees of PA in ethnically diverse populations.     

Using case management in a universal health coverage system to improve quality of life of frequent Emergency Department users: a randomized controlled trial

Purpose

Frequent Emergency Department users are likely to experience poor quality of life (QOL). Case management interventions are efficient in responding to the complex needs of this population, but their effects on QOL have not been tested yet. Therefore, the aim of our study was to examine to what extent a case management intervention improved frequent Emergency Department users’ QOL in a universal health coverage system.

Methods

Data were part of a randomized controlled trial designed to improve frequent Emergency Department users’ QOL at the Lausanne University Hospital, Switzerland. A total of 250 frequent Emergency Department users (≥?5 attendances during the previous 12 months) were randomly assigned to the control (n?=?125) or the intervention group (n?=?125). The latter benefited from case management intervention. QOL was evaluated using the WHOQOL-BREF at baseline, two, five and a half, nine, and twelve months later. It included four dimensions: physical health, psychological health, social relationship, and environment. Linear mixed-effects models were used to analyze the change in the patients’ QOL over time.

Results

Patients’ QOL improved significantly (p?<?0.001) in both groups for all dimensions after two months. However, environment QOL dimension improved significantly more in the intervention group after 12 months.

Conclusions

Environment QOL dimension was the most responsive dimension for short-term interventions. This may have been due to case management’s assistance in obtaining income entitlements, health insurance coverage, stable housing, or finding general health care practitioners. Case management in general should be developed to enhance frequent users’ QOL.Trial registration: http://www.clinicaltrials.gov, Unique identifier: NCT01934322

     

Antibody-functionalized polymer nanoparticle leading to memory recovery in Alzheimer's disease-like transgenic mouse model

Alzheimer's disease (AD) is a neurodegenerative disorder related, in part, to the accumulation of amyloid-β peptide (Aβ) and especially the Aβ peptide 1-42 (Aβ_1-42). The aim of this study was to design nanocarriers able to: (i) interact with the Aβ_1-42 in the blood and promote its elimination through the “sink effect” and (ii) correct the memory defect observed in AD-like transgenic mice. To do so, biodegradable, PEGylated nanoparticles were surface-functionalized with an antibody directed against Aβ_1-42. Treatment of AD-like transgenic mice with anti-Aβ_1-42-functionalized nanoparticles led to: (i) complete correction of the memory defect; (ii) significant reduction of the Aβ soluble peptide and its oligomer level in the brain and (iii) significant increase of the Aβ levels in plasma. This study represents the first example of Aβ_1-42 monoclonal antibody-decorated nanoparticle-based therapy against AD leading to complete correction of the memory defect in an experimental model of AD.     

Use of a case-mix approach to study the trends in the incidence of second primary cancers

Purpose

To analyze trends in second primary cancer (SPC) incidence by using a case-mix approach to standardize on first cancer site distribution.