Exogenous interleukin-2 can rescue in-vitro T cell activation and proliferation in patients with a novel capping protein regulator and myosin 1 linker 2 mutation.

Capping protein regulator and myosin 1 linker 2 (CARMIL2) deficiency is characterized by impaired T cell activation, which is attributed to defective CD28-mediated co-signaling. Herein, we aimed to analyze the effect of exogenous interleukin (IL)-2 on in-vitro T cell activation and proliferation in a family with CARMIL2 deficiency. This study included four children (one male and three females; aged 2·5-10 years at presentation). The patients presented with inflammatory bowel disease and recurrent viral infections. Genetic analysis revealed a novel homozygous 25-base pairs deletion in CARMIL2. Immunoblotting demonstrated the absence of CARMIL2 protein in all four patients and confirmed the diagnosis of CARMIL2 deficiency. T cells were activated in-vitro with the addition of IL-2 in different concentrations. CD25 and interferon (IFN)-γ levels were measured after 48 h and 5 days of activation. CD25 surface expression on activated CD8+ and CD4+ T cells was significantly diminished in all patients compared to healthy controls. Additionally, CD8+ T cells from all patients demonstrated significantly reduced IFN-γ production. When cells derived from CARMIL2-deficient patients were treated with IL-2, CD25 and IFN-γ production increased in a dose-dependent manner. T cell proliferation, as measured by Cell Trace Violet, was impaired in one patient and it was also rescued with IL-2. In conclusion, we found that IL-2 rescued T cell activation and proliferation in CARMIL2-deficient patients. Thus, IL-2 should be further studied as a potential therapeutic modality for these patients.

Effect of in situ exopolysaccharide production on physicochemical, rheological, sensory, and microstructural properties of the yogurt drink ayran: an optimization study based on fermentation kinetics.

Exopolysaccharide (EPS)-producing starter cultures are preferred for the manufacture of fermented milk products to improve rheological and technological properties. However, no clear correlation exists between EPS production and the rheological and technological properties of fermented milk products such as the yogurt drink ayran. In this study, 4 different strain conditions (EPS- and EPS+ Streptococcus thermophilus strains) were tested as a function of incubation temperature (32, 37, or 42°C) and time (2, 3, or 4 h) to determine the effect of culture type and in situ EPS production on physicochemical, rheological, sensory, and microstructural properties of ayran. Furthermore, we assessed the effect of fermentation conditions on amounts of EPS production by different EPS-producing strains during ayran production. A multifactorial design of response surface methodology was used to model linear, interaction, and quadratic effects of these variables on steady shear rheological properties of ayran samples and in situ EPS production levels. The physicochemical and microbiological characteristics of ayran samples altered depending on incubation conditions and strain selection. Steady shear tests showed that ayran samples inoculated with EPS+ strains exhibited pseudoplastic flow behavior. Production of ayran with EPS- strain (control sample) resulted in the lowest apparent viscosity values (η50), whereas those produced with the combination of 2 EPS+ strains yielded ayran with notably increased η50 values. We concluded that incubation time was the variable with the greatest effect on η50, consistency coefficient (K), and flow behavior index (n) values. In situ EPS production was also affected by these conditions during ayran fermentation in which strain-specific metabolism conditions were found to be the most important factor for EPS production. In addition, these findings correlated the amount of in situ EPS produced with the rheological properties of ayran. Scanning electron microscopy images of the samples showed differences in structural features, revealing a prominent network strand structure in the ayran samples inoculated with the admixture of 2 EPS-producing strains incubated at 37°C for 3 h. These results provide useful information for large-scale production of ayran by the dairy industry.

A week-by-week analysis of the low-risk criteria for serious bacterial infection in febrile neonates.

OBJECTIVE: To examine the reliability of "low-risk" criteria (LRC) to exclude serious bacterial infection (SBI) in febrile neonates (< or =28 days), according to age in weeks. DESIGN: Epidemiological and clinical data and final diagnosis of all febrile neonates presenting to the emergency room from June 1997 to May 2006 were reviewed. Neonates who fulfilled specific LRC for the presence of SBI were classified as LRC+. The prevalence of SBI and the percentage of LRC+ neonates who had SBI were calculated for each of the first 4 weeks of life. RESULTS: A total of 449 neonates were evaluated. Eighty-seven (19.4%) neonates had an SBI. The prevalence of SBI among infants 3-7, 8-14, 15-21 and 22-28 days of age was 21.6%, 26.1%, 17.9% and 12.1%, respectively (p = 0.007 for linear trend after second week of life). Of the 226 LRC+ neonates, 14 (6.2%) had an SBI, including one case of bacteraemia and meningitis and 13 cases of urinary tract infection (UTI). The negative predictive value (NPV) of the LRC for SBI was 93.8% (95% CI 90.1% to 96.4%). The prevalence of SBI among LRC+ infants 3-7, 8-14, 15-21 and 22-28 days of age was similar, with rates of 15%, 6.3%, 3.0% and 6.7%, respectively. CONCLUSION: LRC are not sufficiently reliable to exclude the presence of SBI, including bacteraemia and meningitis in febrile neonates of all ages. All febrile neonates should therefore be hospitalised, undergo a full "sepsis evaluation" and receive empirical intravenous antibiotic therapy.