Multi-Analysis Characterisation of a Vernacular House in Doha (Qatar): Petrography and Petrophysics of its Construction Materials

This study characterises the original construction materials (building stones and mortars) of a collapsed two-storey colonnaded structure in the Ismail Mandani house, located in the old city centre of Doha (Qatar). Results were drawn based on interpretation and integration of historical, in situ observations and analytical data. The mortars and stones were characterised following a multidisciplinary approach, combining macroscopic observation with petrographic microscopy, mineralogical analysis (X-ray diffraction) and elemental analysis (handheld X-ray fluorescence) of samples. Moreover, hydric properties, ultrasonic pulse velocity and colour of representative samples of the house were studied. The results revealed the use of two types of stones and three different types of gypsum mortars. The original construction materials came from nearby coastal stones. Gypsum of the most used mortar had a calcination temperature between 120 and 160 ◦C and its colour was produced by lumps with higher Fe content. The materials’ effective porosity and water absorption were high, and their ultrasonic pulse velocity was low. These petrophysical results indicated they had low quality for construction purposes. The composition and colour of the original construction materials were quantified, which will allow the reproduction of their aesthetic characteristics and improvement of their quality in future reconstruction works

Draft genome sequence and biofilm production of a carbapenemase-producing Klebsiella pneumoniae (KpR405) sequence type 405 strain isolated in Italy

Rapid identification and characterization of multidrug-resistant Klebsiella pneumoniae strains is essential to diagnose severe infections in patients. In clinical routine practice, K. pneumoniae is frequently identified and characterized for outbreak investigation. Pulsed-field gel electrophoresis or multilocus sequence typing could be used, but, unfortunately, these methods are time-consuming, laborious, expensive, and do not provide any information about the presence of resistance and virulence genes. In recent years, the decreasing cost of next-generation sequencing and its easy use have led to it being considered a useful method, not only for outbreak surveillance but also for rapid identification and evaluation, in a single step, of virulence factors and resistance genes. Carbapenem-resistant strains of K. pneumoniae have become endemic in Italy, and in these strains the ability to form biofilms, communities of bacteria fixed in an extracellular matrix, can defend the pathogen from the host immune response as well as from antibiotics, improving its persistence in epithelial tissues and on medical device surfaces

Spontaneous immunogenicity of ribosomal P0 protein in patients with benign and malignant breast lesions and delay of mammary tumor growth in P0-vaccinated mice

A common carboxyl-terminal epitope (C-22 P0) of the ribosomal P proteins (P0, P1 and P2) was shown to elicit autoantibodies in systemic lupus erythematosus (SLE) and in head and neck cancer patients. In this report we provide evidence for the in vivo immunogenicity of the P0 protein in breast cancer patients. Using recombinant P proteins, we demonstrated that sera from breast carcinoma patients (8/75) displayed significant reactivity to P0 protein when compared with healthy donor sera (0/45). Four out of the eight sera showed simultaneous reactivity to all P proteins. Breast benign tumor (3/17) and mammary hyperplasia (3/17) patient sera also showed significant reactivity to P proteins, thus suggesting that the occurrence of P protein autoantibodies might reveal mammary cell cycle dysregulation. Patient sera reacting with all P proteins recognized C-22 P0. Anti-P0 autoantibodies did not correlate with prognostic parameters of breast carcinomas. High level expression of C-22 P0 was found in mammary carcinomas compared with normal adjacent epithelium and benign lesions. To determine the antitumor activity of P0 as an immunogen, BALB-neuT transgenic mice displaying age-related breast cancer progression were vaccinated using xenogeneic P0 at the stage of mammary atypical hyperplasia. P0 vaccination significantly delayed the onset of mouse mammary tumors that overexpressed C-22 P0. Sera from P0 vaccinated mice recognized C-22 P0. Evidence for immunity to the P0 protein, its overexpression in carcinomas and its peculiar surface localization on cancer cells, along with its antitumor activity as an immunogen might be relevant for the use of P0 protein in monitoring cancer progression and in planning immunotherapeutic strategies

Comparison of established and emerging biodosimetry assays

Rapid biodosimetry tools are required to assist with triage in the case of a large-scale radiation incident. Here, we aimed to determine the dose-assessment accuracy of the well-established dicentric chromosome assay (DCA) and cytokinesis-block micronucleus assay (CBMN) in comparison to the emerging γ-H2AX foci and gene expression assays for triage mode biodosimetry and radiation injury assessment. Coded blood samples exposed to 10 X-ray doses (240 kVp, 1 Gy/min) of up to 6.4 Gy were sent to participants for dose estimation. Report times were documented for each laboratory and assay. The mean absolute difference (MAD) of estimated doses relative to the true doses was calculated. We also merged doses into binary dose categories of clinical relevance and examined accuracy, sensitivity and specificity of the assays. Dose estimates were reported by the first laboratories within 0.3-0.4 days of receipt of samples for the γ-H2AX and gene expression assays compared to 2.4 and 4 days for the DCA and CBMN assays, respectively. Irrespective of the assay we found a 2.5-4-fold variation of interlaboratory accuracy per assay and lowest MAD values for the DCA assay (0.16 Gy) followed by CBMN (0.34 Gy), gene expression (0.34 Gy) and γ-H2AX (0.45 Gy) foci assay. Binary categories of dose estimates could be discriminated with equal efficiency for all assays, but at doses ≥1.5 Gy a 10% decrease in efficiency was observed for the foci assay, which was still comparable to the CBMN assay. In conclusion, the DCA has been confirmed as the gold standard biodosimetry method, but in situations where speed and throughput are more important than ultimate accuracy, the emerging rapid molecular assays have the potential to become useful triage tools

A longitudinal study on perceived health in cardiovascular patients. The role of conscientiousness, subjective wellbeing and cardiac self-efficacy

Cardiovascular disease (CVD) is the world’s most prevalent chronic disease and the leading chronic cause of morbidity. There are several psychosocial factors associated with quality of life during CVD. Our main objectives were to analyze the roles of conscientiousness, subjective wellbeing and self-efficacy beliefs. The sample comprised 514 patients (mean age 63.57 years) who were assessed twice over a nine-month interval. At Time 1, participants answered a questionnaire assessing conscientiousness, perceived subjective wellbeing (positive and negative affect, life satisfaction), cardiac self-efficacy and health-related quality of life (HRQoL). The same variables (except for conscientiousness) were re-assessed at Time 2. Results showed that conscientiousness had a positive relation with subjective wellbeing, cardiac self-efficacy, and HRQoL at Time 1. Moreover, cardiac self-efficacy at Time 1 had a positive longitudinal effect on HRQoL at Time 2, while controlling for autoregressive effects. Mediation analyses indicated that the relationship between conscientiousness and HRQoL was mediated by positive affect and cardiac self-efficacy. These results suggest the usefulness of psychosocial interventions aimed at promoting positive affect and self-efficacy beliefs among CVD patients

Gene-specific inhibition of breast carcinoma in BALB-neuT mice by active immunization with rat Neu or human ErbB receptors

Employing the transgenic BALB-neuT mouse tumor model, we explored the in vivo biologic relevance of immunocompetent epitopes shared among the four ErbB receptors. The outcome of neu-mediated tumorigenesis was compared following vaccination with isogeneic normal rat ErbB2/Neu (LTR-Neu) or xenogeneic human ErbB receptors (LTR-EGFR, LTR-ErbB2, LTR-ErbB3 and LTR-ErbB4), each recombinantly expressed in an NIH3T3 murine cell background. Vaccination using rat LTR-Neu at the stage of atypical hyperplasia potently inhibited neu-mediated mammary tumorigenesis. Moreover, all human ErbB receptors specifically interfered with tumor development in BALB-neuT mice. Relative increase in tumor-free survival and reduction in tumor incidence corresponded to structural similarity shared with the etiologic neu oncogene, as rat orthologue LTR-Neu proved most effective followed by the human homologue LTR-ErbB2 and the other three human ErbB receptors. Vaccination resulted in high titer specific serum antibodies, whose tumor-inhibitory effect correlated with cross-reactivity to purified rat Neu extracellular domain in vitro. Furthermore, a T cell response specific for peptide epitopes of rat Neu was elicited in spleen cells of mice immunized with LTR-Neu and was remotely detectable for discrete peptides upon vaccination with LTR-ErbB2 and LTR-EGFR. The most pronounced tumor inhibition by LTR-Neu vaccination was associated with leukocyte infiltrate and tumor necrosis in vivo, while immune sera specifically induced cytotoxicity and apoptosis of BALB-neuT tumor cells in vitro. Our findings indicated that targeted inhibition of neu oncogene-mediated mammary carcinogenesis is conditional upon the immunization schedule and discrete immunogenic epitopes shared to a variable extent by different ErbB receptors

β-Secretase1 biological markers for Alzheimer's disease: state-of-art of validation and qualification

β-Secretase1 (BACE1) protein concentrations and rates of enzyme activity, analyzed in human bodily fluids, are promising candidate biological markers for guidance in clinical trials investigating BACE1 inhibitors to halt or delay the dysregulation of the amyloid-β pathway in Alzheimer’s disease (AD). A robust body of evidence demonstrates an association between cerebrospinal fluid/blood BACE1 biomarkers and core pathophysiological mechanisms of AD, such as brain protein misfolding and aggregration, neurodegeneration, and synaptic dysfunction. In pharmacological trials, BACE1 candidate biomarkers may be applied to a wide set of contexts of use (CoU), including proof of mechanism, dose-finding, response and toxicity dose estimation. For clinical CoU, BACE1 biomarkers show good performance for prognosis and disease prediction. The roadmap toward validation and qualification of BACE1 biomarkers requires standardized pre-analytical and analytical protocols to reduce inter-site variance that may have contributed to inconsistent results. BACE1 biomarker-drug co-development programs, including biomarker-guided outcomes and endpoints, may support the identification of sub-populations with a higher probability to benefit from BACE1 inhibitors with a reduced risk of adverse effects, in line with the evolving precision medicine paradigm

Impacts of citrus pulp addition and wilting on elephant grass silage quality.

The objective of this work was to evaluate the use of citrus pulp addition and wilting on fermentative characteristics, chemical composition as well as gas and effluent losses of elephant grass silage. The elephant grass (70 growth days) was collected manually; one portion was immediately chopped and another one was allowed to wilt in the sun for a period of 6 h and subsequently chopped for the production of silage. Experimental PVC silos (10 cm diameter x 30 cm height) were used and sand bags were placed at the bottom of the silos. Citrus pulp (80 g kg-1 of MN) was added at the beginning of ensilage. The ensiled material was manually compressed to provide a specific mass of approximately 600 kg m-3 of silage. After 60 days, the silos were opened; gas and effluent losses were calculated and we determined pH, dry matter (DM), crude protein(CP), neutral detergent fibre (NDF), lignin, ammonia nitrogen, ash and in vitro dry matter digestibility (IVDMD). We added 0 or 80 g kg-1 of citrus pulp to wilted and un-wilted elephant grass. We used a completely randomised design with a 2 x 2 factorial arrangement (wilted or un-wilted) x (with or without citrus pulp), totalling treatments with five repetitions. Average values were compared using the F test with a probability of 5%. The addition of citrus pulp resulted in reduced levels of NDF, lignin, ash, N-NH3 and pH and in increased values of DM and IVDMD of silages. Wilting increased the DM, NDF and lignin values and reduced the concentrations of CP, IVDMD and N-NH3. Based on our results, citrus pulp addition improves the chemical composition of elephant grass silage and increases its in vitro dry matter digestibility