Lactobacillus gasseri suppresses Th17 pro-inflammatory response and attenuates allergen-induced airway inflammation in a mouse model of allergic asthma

Probiotics are normal inhabitants of the gastrointestinal tract of man and are widely considered to exert a number of beneficial effects in many diseases. But the mechanism by which they modulate the immune system is poorly understood. The present study was planned to explore the anti-allergic effect of Lactobacillus gasseri on a mouse model of allergic asthma. Dermatophoides pteronyssinus (Der p) sensitised and challenged BALB/c mice were orally administered via oral administration with three different doses of L. gasseri (low, 1 × 10(6) colony-forming units (CFU); medium, 2 × 10(6) CFU; high, 4 × 10(6) CFU), in 700 μl of PBS daily, starting from 2 weeks before Der p sensitisation for 4 weeks. After the allergen challenge, airway responsiveness to methacholine, influx of inflammatory cells to the lung, and cytokine levels in bronchoalveolar lavage (BAL) fluids and splenocytes culture were assessed. Our results showed that oral administration of a high dose of L. gasseri (4 × 10(6) CFU) decreased airway responsiveness to methacholine, attenuated the influx of inflammatory cells to the airways and reduced the levels of TNF-α, thymus and activation-regulated chemokine (TARC) and IL-17A in BAL fluids of Der p-sensitised and -challenged mice. Moreover, L. gasseri decreased IL-17A production in transforming growth factor-α and IL-6 stimulated splenocytes and cell numbers of IL-17 producing alveolar macrophages in L. gasseri-treated mice as compared to non-treated, Der p-sensitised and -challenged mice. In conclusion, oral administration with L. gasseri can attenuate major characteristics of allergen-induced airway inflammation and IL-17 pro-inflammatory immune response in a mouse model of allergic asthma, which may have clinical implication in the preventive or therapeutic potential in allergic asthma.     

Early Treg suppression by a listeriolysin-O-expressing E. coli vaccine in heterologous prime–boost vaccination against cancer

Studies have shown that an enhanced CD8+ T cell response and better tumor protection can be achieved by heterologous prime–boost vaccination in mice. Such heterologous vaccination can be more immunogenic than the homologous setting. We previously demonstrated that a listeriolysin-O (LLO)-expressing E. coli vaccine can enhance CD8-cytotoxic T cell (CTL) responses by reducing regulatory T cell (Treg)-directed suppression. In the present study, we assessed the combination of this approach with plasmid DNA vaccination, in a prime–boost immunization strategy. E. coli-LLO bacteria expressing ovalbumin (OVA) and plasmid pcDNA-encoding OVA were used to vaccinate naive or B16-OVA tumor-bearing C57B6 mice. The anticancer activity was measured in a tumor prevention or therapeutic model. Higher OVA-specific CD8+ T cell responses and greater tumor inhibition were seen in the bacterial-prime/plasmid–boost setting than with the homologous and reversed sequences. This tumor protection effect from heterologous prime–boost remained in the therapeutic model. When examining the Treg effect during the prime–boost immunization, we found that only early Treg-suppression/depletion could lead to better antigen-specific CTL and tumor response. Our studies offer the first evidence that a listeriolysin-O E. coli vaccine can induce an enhanced antitumor effect in conjunction with DNA in a heterologous prime–boost protocol, and suggest that early Treg inhibition is crucial to a successful immunization against cancer.     

The clinical application of 4D 18F-FDG PET/CT on gross tumor volume delineation for radiotherapy planning in esophageal squamous cell cancer

A combination of four-dimensional computed tomography with ¹⁸F-fluorodeoxyglucose positron emission tomography (4D CT-FDG PET) was used to delineate gross tumor volume (GTV) in esophageal cancer (EC). Eighteen patients with EC were prospectively enrolled. Using 4D images taken during the respiratory cycle, the average CT image phase was fused with the average FDG PET phase in order to analyze the optimal standardized uptake values (SUV) or threshold. PET-based GTV (GTV_PET) was determined with eight different threshold methods using the auto-contouring function on the PET workstation. The difference in volume ratio (VR) and conformality index (CI) between GTV_PET and CT-based GTV (GTV_CT) was investigated. The image sets via automatic co-registrations of 4D CT-FDG PET were available for 12 patients with 13 GTV_CT values. The decision coefficient (R²) of tumor length difference at the threshold levels of SUV 2.5, SUV 20% and SUV 25% were 0.79, 0.65 and 0.54, respectively. The mean volume of GTV_CT was 29.41 ± 19.14 ml. The mean VR ranged from 0.30 to 1.48. The optimal VR of 0.98, close to 1, was at SUV 20% or SUV 2.5. The mean CI ranged from 0.28 to 0.58. The best CI was at SUV 20% (0.58) or SUV 2.5 (0.57). The auto-contouring function of the SUV threshold has the potential to assist in contouring the GTV. The SUV threshold setting of SUV 20% or SUV 2.5 achieves the optimal correlation of tumor length, VR, and CI using 4D-PET/CT images.     

Interactive effects of family socioeconomic status and body mass index on depression in school-aged children

Depression is an important health problem in children and the onset of depression is occurring at a younger age than previously suggested. The associations of being overweight and low socioeconomic status in childhood depression have been well documented; nevertheless few studies have addressed the combined effects of socioeconomic status and body weight, with depression in school-age children. We intended to examine if the relationship between socioeconomic status and childhood depression could be modified by abnormal body weight. A cross-sectional study was performed with a total of 559 subjects from 29 elementary schools in Taiwan. A depression scale was used to determine the depression status. Children receiving governmental monetary assistance for after-school class were categorized as being in the lower socioeconomic group. Data for depression-related demographic characteristics, family and school variables were collected. Children in the lower socioeconomic status group have a higher prevalence of depression (23.5%) than those in higher socioeconomic status groups(16.4%). Being overweight demonstrates the opposite effect on depression risk in the different socioeconomic groups. In lower socioeconomic families, the risk of depression in overweight children is three times higher than that for normal weight children; whereas in higher socioeconomic families, overweight children have a lower risk for depression than normal weight children. We concluded that a qualitative interactive effect existed between being overweight and socioeconomic status with childhood depression. More attention should be paid to overweight children from lower socioeconomic status families to prevent depression in school-age children.     

Factors affecting metacognition of undergraduate nursing students in a blended learning environment

This paper is a report of a study to examine the influence of demographic, learning involvement and learning performance variables on metacognition of undergraduate nursing students in a blended learning environment. A cross‐sectional, correlational survey design was adopted. Ninety‐nine students invited to participate in the study were enrolled in a professional nursing ethics course at a public nursing college. The blended learning intervention is basically an assimilation of classroom learning and online learning. Simple linear regression showed significant associations between frequency of online dialogues, the Case Analysis Attitude Scale scores, the Case Analysis Self Evaluation Scale scores, the Blended Learning Satisfaction Scale scores, and Metacognition Scale scores. Multiple linear regression indicated that frequency of online dialogues, the Case Analysis Self Evaluation Scale and the Blended Learning Satisfaction Scale were significant independent predictors of metacognition. Overall, the model accounted for almost half of the variance in metacognition. The blended learning module developed in this study proved successful in the end as a catalyst for the exercising of metacognitive abilities by the sample of nursing students. Learners are able to develop metacognitive ability in comprehension, argumentation, reasoning and various forms of higher order thinking through the blended learning process.     

Survival of gastric cancer with concomitant liver metastases

BACKGROUND/AIMS: Prognosis of gastric cancer with concomitant liver metastasis is poor. Gastrectomy and chemotherapy had been reported to be beneficial to this group of patients. Whether all the patients can benefit from that treatment modality and whether the clinical characteristics can give some information about survival have not been evaluated. METHODOLOGY: Eighty-three gastric cancer patients with concomitant liver metastases who had received treatment in the past 10 years were retrospectively studied with special reference to different extent of liver metastases. Clinical characteristics (peritoneal tumor dissemination, tumor markers, clinicopathological factors), treatment modalities (gastrectomy or chemotherapy) and survival were analyzed for their possible relationship with the extent of liver metastases. RESULTS: There were 33 patients with liver metastases limited to one lobe and 50 patients had metastases in both lobes. The clinicopathological characteristics show no difference between uni- and bilobar liver metastases except higher percentage of concomitant peritoneal dissemination in patients with bilobar disease. More unilobar involvement patients underwent gastrectomy (70% vs. 48%, p=0.018). Higher frequency of abnormal CEA level in bilobar metastases (38% vs. 60%, p=0.045). Median survival of unilobar metastasis is 7.8 months and 4.3 months for the bilobar involvement (p=0.001). Gastrectomy might prolong the survival in patients with unilobar metastasis (p=0.005), but not in patients with bilobar diseases (p=0.074). Chemotherapy could prolong the survival in patients without gastrectomy, but not the survival after gastrectomy. CONCLUSIONS: The clinicopathological characteristics and tumor markers have no role in predicting the survival among patients with liver metastases. Both gastrectomy and chemotherapy for the patients without gastrectomy could prolong survival, but chemotherapy could not prolong the survival after gastrectomy, the benefit of resection and chemotherapy are probably caused by selection bias.     

A protein that preferentially binds Drosophila satellite DNA.

Using a nitrocellulose filter binding assay, we have detected and partially purified a protein from embryos of Drosophila melanogaster that preferentially binds to a highly repeated satellite DNA of the same species. Formation of the satellite DNA-protein complex requires physiological conditions of salt and temperature, but once formed, the complex is stable in high salt (1 M NaCl) or at low temperature. Optimal formation of the specific complex also requires the satellite DNA to be in a supertwisted conformation. The protein interacts with a limited region within the 359-base-pair repeated sequence of the satellite DNA.