Salmonella Paratyphi A Outer Membrane Vesicles Displaying Vi Polysaccharide as a Multivalent Vaccine against Enteric Fever.

Typhoid and paratyphoid fevers have a high incidence worldwide and coexist in many geographical areas, especially in low-middle-income countries (LMIC) in South and Southeast Asia. There is extensive consensus on the urgent need for better and affordable vaccines against systemic Salmonella infections. Generalized modules for membrane antigens (GMMA), outer membrane exosomes shed by Salmonella bacteria genetically manipulated to increase blebbing, resemble the bacterial surface where protective antigens are displayed in their native environment. Here, we engineered S Paratyphi A using the pDC5-viaB plasmid to generate GMMA displaying the heterologous S Typhi Vi antigen together with the homologous O:2 O antigen. The presence of both Vi and O:2 was confirmed by flow cytometry on bacterial cells, and their amount was quantified on the resulting vesicles through a panel of analytical methods. When tested in mice, such GMMA induced a strong antibody response against both Vi and O:2, and these antibodies were functional in a serum bactericidal assay. Our approach yielded a bivalent vaccine candidate able to induce immune responses against different Salmonella serovars, which could benefit LMIC residents and travelers.BactiVac catalyst Grant in collaboration with GSK

Organization of plastid genomes in the freshwater red algal order Batrachospermales (Rhodophyta)

Little is known about genome organization in members of the order Batrachospermales, and the infra-ordinal relationship remains unresolved. Plastid (cp) genomes of seven members of the freshwater red algal order Batrachospermales were sequenced, with the following aims: (i) to describe the characteristics of cp genomes and compare these with other red algal groups; (ii) to infer the phylogenetic relationships among these members to better understand the infra-ordinal classification. Cp genomes of Batrachospermales are large, with several cases of gene loss, they are gene-dense (high gene content for the genome size and short intergenic regions) and have highly conserved gene order. Phylogenetic analyses based on concatenated nucleotide genome data roughly supports the current taxonomic system for the order. Comparative analyses confirm data for members of the class Florideophyceae that cp genomes in Batrachospermales is highly conserved, with little variation in gene composition. However, relevant new features were revealed in our study: genome sizes in members of Batrachospermales are close to the lowest values reported for Florideophyceae; differences in cp genome size within the order are large in comparison with other orders (Ceramiales, Gelidiales, Gracilariales, Hildenbrandiales, and Nemaliales); and members of Batrachospermales have the lowest number of protein-coding genes among the Florideophyceae. In terms of gene loss, apcF, which encodes the allophycocyanin beta subunit, is absent in all sequenced taxa of Batrachospermales. We reinforce that the interordinal relationships between the freshwater orders Batrachospermales and Thoreales within the Nemaliophycidae is not well resolved due to limited taxon sampling

Gas Analysis and Monitoring Systems for the RPC Detector of CMS at LHC

The Resistive Plate Chambers (RPC) detector of the CMS experiment at the LHC proton collider (CERN, Switzerland) will employ an online gas analysis and monitoring system of the freon-based gas mixture used. We give an overview of the CMS RPC gas system, describe the project parameters and first results on gas-chromatograph analysis. Finally, we report on preliminary results for a set of monitor RPC.Comment: 9 pages, 8 figures. Presented by Stefano Bianco (Laboratori Nazionali di Frascati dell'INFN) at the IEEE NSS, San Diego (USA), October 200

Secondary malignancies after high-dose chemotherapy in germ cell tumor patients: A 34-year retrospective study of the European Society for Blood and Marrow Transplantation (EBMT)

We aimed to assess the incidence and risk factors of secondary malignancy (SM) in the young adult patients who received high-dose chemotherapy (HDCT) for germ cell tumors (GCT). The EBMT database was interrogated. Criteria for patient selection included adult male GCT and HDCT administered in any line of therapy. Cumulative incidence methods were used to estimate the time-to-SM diagnosis. Univariable Fine and Gray proportional hazard regression evaluated risk factors of SM occurrence. From 1981 to 2015, 9153 autografts were identified. Among 5295 patients, 59 cases of SM, developed after a median follow-up of 3.8 years, were registered. Of these patients, 23 (39%) developed hematologic SM, 34 (57.6%) solid SM (two patients had uncoded SM). Twenty-year cumulative incidence of solid versus hematologic SM was 4.17% (95% CI: 1.78-6.57) versus 1.37% (95% CI: 0.47-2.27). Median overall survival after SM was significantly shorter for patients who developed hematologic SM versus solid SM (8.6 versus 34.4 months, p = 0.003). Age older than 40 years at the time of HDCT was significantly associated with hematologic, but not solid, SM development (p = 0.004 versus p = 0.234). SM occurrence post-HDCT showed different patterns of incidence and mortality in GCT. These data may be important to optimize patient selection, counseling and follow-up after HDCT

The CMS RPC gas gain monitoring system: an overview and preliminary results

The status of the CMS RPC Gas Gain Monitoring (GGM) system developed at the Frascati Laboratory of INFN (Istituto Nazionale di Fisica Nucleare) is reported on. The GGM system is a cosmic ray telescope based on small RPC detectors operated with the same gas mixture used by the CMS RPC system. The GGM gain and efficiency are continuously monitored on-line, thus providing a fast and accurate determination of any shift in working point conditions. The construction details and the first result of GGM commissioning are described.Comment: 8 pages, 9 figures, uses lnfprepCMS.sty, presented by L. Benussi at RPC07, Mumbai, INDIA 200

Predictors of CD34+ cell mobilization and collection in adult men with germ cell tumors: implications for the salvage treatment strategy

BACKGROUND: High-dose chemotherapy with tandem or triple carboplatin and etoposide course is currently the first curative choice for relapsing GCT. The collection of an adequate amount of hematopoietic (CD34(+)) stem cells is a priority. PATIENTS AND METHODS: We analyzed data of patients who underwent HDCT at 2 referral institutions. Chemotherapy followed by myeloid growth factors was applied in all cases. Uni- and multivariable models were used to evaluate the association between 2 prespecified variables and mobilization parameters. Analyses included only the first mobilizing course of chemotherapy and mobilization failures. RESULTS: A total of 116 consecutive patients underwent a mobilization attempt from December 1995 to November 2012. Mobilizing regimens included cyclophosphamide (CTX) 7 gr/m(2) (n = 39), cisplatin, etoposide, and ifosfamide (PEI) (n = 42), paclitaxel, cisplatin, and gemcitabine (TPG) (n = 11), and mixed regimens (n = 24). Thirty-seven percent were treated in first-line, 50% (n = 58) in second-line, 9.5% (n = 11) and 3.4% (n = 4) in third- and fourth-line settings, respectively. Six patients did not undergo HDCT because they were poor mobilizers, 2 in first- and second-line (1.9%), and 4 beyond the second-line (26.7%). In the multivariable model, third-line or later setting was associated with a lower CD34(+) cell peak/μL (P = .028) and a lower total CD34(+)/kg collected (P = .008). The latter was also influenced by the type of mobilizing regimen (P < .001). CONCLUSION: A decline in significant mobilization parameters was found, primarily depending on the pretreatment load. Results lend support to the role of CD34(+) cell mobilization in the therapeutic algorithm of relapsing GCT, for whom multiple HDCT courses are still an option, and potentially a cure

Combination of baseline LDH, performance status and age as integrated algorithm to identify solid tumor patients with higher probability of response to anti PD-1 and PD-l1 monoclonal antibodies

Predictive biomarkers of response to immune-checkpoint inhibitors (ICIs) are an urgent clinical need. The aim of this study is to identify manageable parameters to use in clinical practice to select patients with higher probability of response to ICIs. Two-hundred-and-seventy-one consecutive metastatic solid tumor patients, treated from 2013 until 2017 with anti-Programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) ICIs, were evaluated for baseline lactate dehydrogenase (LDH) serum level, performance status (PS), age, neutrophil-lymphocyte ratio, type of immunotherapy, number of metastatic sites, histology, and sex. A training and validation set were used to build and test models, respectively. The variables\u2019 effects were assessed through odds ratio estimates (OR) and area under the receive operating characteristic curves (AUC), from univariate and multivariate logistic regression models. A final multivariate model with LDH, age and PS showed significant ORs and an AUC of 0.771. Results were statistically validated and used to devise an Excel algorithm to calculate the patient\u2019s response probabilities. We implemented an interactive Excel algorithm based on three variables (baseline LDH serum level, age and PS) which is able to provide a higher performance in response prediction to ICIs compared with LDH alone. This tool could be used in a real-life setting to identify ICIs in responding patients

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Down syndrome-recent progress and future prospects

Down syndrome (DS) is caused by trisomy of chromosome 21 (Hsa21) and is associated with a number of deleterious phenotypes, including learning disability, heart defects, early-onset Alzheimer's disease and childhood leukaemia. Individuals with DS are affected by these phenotypes to a variable extent; understanding the cause of this variation is a key challenge. Here, we review recent research progress in DS, both in patients and relevant animal models. In particular, we highlight exciting advances in therapy to improve cognitive function in people with DS and the significant developments in understanding the gene content of Hsa21. Moreover, we discuss future research directions in light of new technologies. In particular, the use of chromosome engineering to generate new trisomic mouse models and large-scale studies of genotype-phenotype relationships in patients are likely to significantly contribute to the future understanding of DS