Abstract We studied the induction of antigen-specific IgA memory B cells (BM ) in volunteers who received live attenuated Shigella flexneri 2a vaccines. Subjects ingested a single oral dose of 107 , ...108 or 109 CFU of S. flexneri 2a with deletions in guaBA (CVD 1204) or in guaBA , set and sen (CVD 1208). Antigen-specific serum and stool antibody responses to LPS and Ipa B were measured on days 0, 7, 14, 28 and 42. IgA BM cells specific to LPS, Ipa B and total IgA were assessed on days 0 and 28. We show the induction of significant LPS-specific IgA BM cells in anti-LPS IgA seroresponders. Positive correlations were found between anti-LPS IgA BM cells and anti-LPS IgA in serum and stool; IgA BM cell responses to IpaB were also observed. These BM cell responses are likely play an important role in modulating the magnitude and longevity of the humoral response.
Abstract We evaluated the safety, reactogenicity and immunogenicity of escalating doses of a new Francisella tularensis Live Vaccine Strain (LVS) lot by scarification (SCAR) or subcutaneously (SQ) in ...humans. Subjects ( N = 10/group) received one dose of LVS via SCAR at 105 ,107 or 109 cfu/ml or SQ at 102 , 103 ,104 or 105 cfu/ml; 14 subjects received placebo. All doses/routes were well tolerated. When compared to placebo, vaccination with 107 SCAR and 109 SCAR resulted in significantly higher serologic response frequencies, as measured by ELISA for IgG, IgM, IgA and microagglutination; whereas vaccination with 105 SCAR, 107 SCAR 109 SCAR and 105 SQ elicited a significantly higher interferon-γ response frequency.
The aim of this study was to evaluate the effect of replacing corn grain for sugar cane molasses (MO) or glucose syrup (GS) in the starter concentrate on performance and metabolism of dairy calves. ...Thirty-six individually housed Holstein male calves were blocked according to weight and date of birth and assigned to one of the starter feed treatments, during an 8 week study: i) starter containing 65% corn with no MO or GS (0MO); ii) starter containing 60% corn and 5% MO (5MO); iii) starter containing 55% corn and 10% MO (10MO); and iv) starter containing 60% corn and 5% GS (5GS). Animals received 4 L of milk replacer daily (20 crude protein, 16 ether extract, 12.5% solids), divided in two meals (0700 and 1700 h). Starter and water were provided ad libitum. Starter intake and fecal score were monitored daily until animals were eight weeks old. Body weight and measurements (withers height, hip width and heart girth) were measured weekly before the morning feeding. From the second week of age, blood samples were collected weekly, 2 h after the morning feeding, for glucose, β-hydroxybutyrate and lactate determination. Ruminal fluid was collected at 4, 6, and 8 weeks of age using an oro-ruminal probe and a suction pump for determination of pH and short-chain fatty acids (SCFA). At the end of the eighth week, animals were harvested to evaluate development of the proximal digestive tract. The composition of the starter did not affect (p>0.05) concentrate intake, weight gain, fecal score, blood parameters, and rumen development. However, treatment 5MO showed higher (p<0.05) total concentration of SCFAs, acetate and propionate than 0MO, and these treatments did not differ from 10MO and 5GS (p>0.05). Thus, it can be concluded that the replacement of corn by 5% or 10% sugar cane molasses or 5% GS on starter concentrate did not impact performance, however it has some positive effects on rumen fermentation which may be beneficial for calves with a developing rumen.
Purpose
The value of FDG PET-derived parameters in predicting overall survival (OS), local relapse-free survival (LRFS) and distant relapse-free survival (DRFS) in treated patients with malignant ...pleural mesothelioma (MPM) was evaluated.
Methods
This retrospective evaluation included 55 MPM patients treated between March 2006 and February 2015 with FDG PET/CT-guided salvage helical tomotherapy (HTT) after previous surgery plus chemotherapy. Univariate Cox regression analysis was performed to assess the impact of the following FDG PET-derived parameters: biological target volume (BTV), mean and maximum standardized uptake values (SUV
mean/max
), metabolic tumour volume (MTV) and total lesion glycolysis (TLG), measured using different uptake thresholds (40%, 50% and 60%). Logistic regression was then performed to identify the best FDG PET-derived parameters for selecting patients with poorer survival.
Results
The median OS was 9.1 months (range 0.0 – 69.6 months) after the end of HTT; 54/55 patients were dead at the last follow-up. BTV and TLG40, TLG50 and TLG60 were the most significant predictors of OS (
p
< 0.005). The median OS was 4.8 months in patients with MTV60 >5 cm
3
and TLG40 >334.4, compared with 13.8 months and 16.1 months in patients with smaller values, respectively. The median LRFS and DRFS were 6.2 months (range 1.2 – 39.4 months) and 6.5 months (0.0 – 66.4 months), respectively. TLG40, TLG50 and TLG60 were significantly correlated with LRFS (
p
< 0.015). Median DRFS was 6.4 months in patients with MTV40 >39.6 cm
3
and 6.2 months in patients with TLG40 >334.4, compared with 17 months and 18.8 months in patients with smaller values. BTV, TLG40 and MTV40 were also found to be good predictors in patients with poor OS/LRFS/DRFS (median survival times less than the median values).
Conclusion
FDG PET-derived parameters effectively discriminated patients with a poor prognosis and may be helpful in the selection of MPM patients for salvage HTT.
Safe and effective immunization of newborns and infants can significantly reduce childhood mortality, yet conventional vaccines have been largely unsuccessful in stimulating the neonatal immune ...system. We explored the capacity of a novel mucosal antigen delivery system consisting of non-living, non-genetically modified Lactococcus lactis particles, designated as Gram-positive enhancer matrix (GEM), to induce immune responses in the neonatal setting. Yersinia pestis LcrV, used as model protective antigen, was displayed on the GEM particles. Newborn mice immunized intranasally with GEM-LcrV developed LcrV-specific antibodies, Th1-type cell-mediated immunity, and were protected against lethal Y. pestis (plague) infection. The GEM particles activated and enhanced the maturation of neonatal dendritic cells (DCs) both in vivo and in vitro. These DCs showed increased capacities for secretion of proinflammatory and Th1-cell polarizing cytokines, antigen presentation and stimulation of CD4(+) and CD8(+) T cells. These data show that mucosal immunization with L. lactis GEM particles carrying vaccine antigens represents a promising approach to prevent infectious diseases early in life.
Carbon dioxide (CO2) enrichment in controlled environmental conditions has proved to enhance the growth and production of a wide variety of crops. Previous studies suggested that the use of this ...horticulture practice in greenhouses may represent a useful opportunity for the capture and utilization of industrial CO2 emissions. The symbiosis among industrial installations and horticulture facilities may in fact allow to reduce the overall amounts of CO2 released in the atmosphere, by reusing the direct production of carbon dioxide into crop enrichment processes. The present study provides a quantitative analysis of the economic benefits related to the use of CO2 emissions generated by an industrial activity into a nearby greenhouse facility. The analysis takes into account the savings related to the reuse of carbon emissions from the industrial process, and the additional revenues due to the increase of the yield of products from the horticulture activity. Since the results of the enrichment process strictly depend on the specific crop, the analysis was conducted by comparing three different cultivations, viz. tomatoes, cucumbers and strawberries. The outcomes showed that, for the considered case study, the total benefits related to the implementation of the symbiosis network could reach up to 8.1 € per square meter of cultivated soil per each production cycle, and would also allow to capture up to the 21% of the overall carbon dioxide emissions produced by the industrial process.
Previous clinical studies have demonstrated the feasibility of using edible transgenic plants to deliver protective antigens as new oral vaccines. Transgenic corn is particularly attractive for this ...purpose since the recombinant antigen is stable and homogeneous, and corn can be formulated in several edible forms without destroying the cloned antigen. Transgenic corn expressing 1
mg of LT-B of
Escherichia coli without buffer was fed to adult volunteers in three doses, each consisting of 2.1
g of plant material. Seven (78%) of nine volunteers developed rises in both serum IgG anti-LT and numbers of specific antibody secreting cells after vaccination. Four (44%) of nine volunteers also developed stool IgA. Transgenic plants represent a new vector for oral vaccine antigens.
Abstract Aims To report 5 year outcome and late toxicity in prostate cancer patients treated with image-guided tomotherapy with a moderate hypofractionated simultaneous integrated boost approach. ...Materials and methods In total, 211 prostate cancer patients, 78 low risk, 53 intermediate risk and 80 high risk were treated between 2005 and 2011. Intermediate- and high-risk patients received 51.8 Gy to pelvic lymph nodes and concomitant simultaneous integrated boost to prostate up to 74.2 Gy/28 fractions, whereas low-risk patients were treated to the prostate only with 71.4 Gy/28 fractions. Daily megavoltage computed tomography (MVCT) image guidance was applied. Androgen deprivation was prescribed for a median duration of 6 months for low-risk patients (for downsizing), 12 months for intermediate-risk and 36 months for high-risk patients. The 5 year biochemical relapse-free survival (bRFS), cancer-specific survival (CSS), overall survival and late gastrointestinal and genitourinary CTCAE.v3 toxicity were assessed. The effect of several clinical variables on both outcome and gastrointestinal/genitourinary toxicity was tested by uni- and multivariate Cox regression analyses. Results After a median follow-up of 5 years, the late toxicity actuarial incidence was: genitourinary ≥ grade 2: 20.2%; genitourinary ≥ grade 3: 5.9%; gastrointestinal ≥ grade 2: 17%; gastrointestinal ≥ grade 3: 6.3% with lower prevalence at the last follow-up visit (≥ grade 3: genitourinary: 1.9%; gastrointestinal: 1.9%). Major predictors of ≥ grade 3 genitourinary and gastrointestinal late toxicity were genitourinary acute toxicity ≥ grade 2 (hazard ratio: 4.9) and previous surgery (hazard ratio: 3.4). The overall 5 year bRFS was 93.7% (low risk: 94.6%; intermediate risk: 96.2%; high risk: 91.1%), overall survival and CSS were 88.6% (low risk: 90.5%; intermediate risk: 87.4%; high risk: 87%) and 97.5% (low risk: 98.7%; intermediate risk: 95%; high risk: 94.3%), respectively. Risk classes and androgen deprivation were not significantly correlated with either bRFS, overall survival or CSS. Twelve patients experienced a biochemical relapse but none experienced clinically proven local and/or pelvic recurrence. Conclusion A satisfactory 5 year outcome with an acceptable toxicity profile was observed. The combination of image-guided radiotherapy–intensity-modulated radiotherapy, high equivalent 2 Gy dose (EQD2) with a moderate hypofractionated approach and extensive prophylactic lymph node irradiation also leads to very good outcome in high-risk patients.
PDF
