A new design equation for prediction of ultimate bearing capacity of shallow foundation on granular soils

A major concern in design of structures is to provide precise estimations of ultimate bearing capacity of soil beneath their foundations. Direct determination of the bearing capacity of foundations requires performing expensive and time consuming laboratory tests. To cope with this issue, several numerical models have been presented by researchers. This paper presents the development of a new design equation for the prediction of the ultimate bearing capacity of shallow foundations on granular soils using linear genetic programming (LGP) methodology. The ultimate bearing capacity is formulated in terms of width of footing, footing geometry, depth of footing, unit weight of sand, and angle of shearing resistance. The LGP-based design equation is established using the results of several load tests on real sized foundations presented in the literature. Validity of the model is verified using a part of laboratory data that are not involved in the calibration process. The statistical measures of coefficient of determination, root mean squared error and mean absolute error are used to evaluate the performance of the model. Sensitivity and parametric analyses are conducted and discussed. The proposed model accurately characterizes the ultimate bearing capacity resulting in a very good prediction performance. The LGP model reaches a better prediction performance than the well-known prediction equations for the bearing capacity of shallow foundations

Development of a bivalent protein-based vaccine candidate against invasive pneumococcal diseases based on novel pneumococcal surface protein A in combination with pneumococcal histidine triad protein D

Extensive efforts have been made toward improving effective strategies for pneumococcal vaccination, focusing on evaluating the potential of multivalent protein-based vaccines and overcoming the limitations of pneumococcal polysaccharide-based vaccines. In this study, we investigated the protective potential of mice co-immunization with the pneumococcal PhtD and novel rPspA proteins against pneumococcal sepsis infection. The formulations of each antigen alone or in combination were administered intraperitoneally with alum adjuvant into BALB/c mice three times at 14-day intervals. The production of antigen-specific IgG, IgG1 and IgG2a subclasses, and IL-4 and IFN-γ cytokines, were analyzed. Two in vitro complement- and opsonophagocytic-mediated killing activities of raised antibodies on day 42 were also assessed. Finally, the protection against an intraperitoneal challenge with 106 CFU/mouse of multi-drug resistance of Streptococcus pneumoniae ATCC49619 was investigated. Our findings showed a significant increase in the anti-PhtD and anti-rPspA sera IgG levels in the immunized group with the PhtD+rPspA formulation compared to each alone. Moreover, the results demonstrated a synergistic effect with a 6.7- and 1.3- fold increase in anti-PhtD and anti-rPspA IgG1, as well as a 5.59- and 1.08- fold increase in anti-PhtD and anti-rPspA IgG2a, respectively. Co-administration of rPspA+PhtD elicited a mixture of Th-2 and Th-1 immune responses, more towards Th-2. In addition, the highest complement-mediated killing activity was observed in the sera of the immunized group with PhtD+rPspA at 1/16 dilution, and the opsonophagocytic activity was increased from 74% to 86.3%. Finally, the survival rates showed that mice receiving the rPspA+PhtD formulation survived significantly longer (100%) than those receiving protein alone or PBS and exhibited the strongest clearance with a 2 log10 decrease in bacterial load in the blood 24h after challenge compared to the control group. In conclusion, the rPspA+PhtD formulation can be considered a promising bivalent serotype-independent vaccine candidate for protection against invasive pneumococcal infection in the future

Distribution of Gens for Five Protein Antigens among Streptococcus Pneumoniae Isolates Recovered from Healthy Children in Ardabil, Iran

Background & objectives: Streptococcus pneumoniae is  one of the major causes of vaccine - preventable diseases worldwide. Current pneumococcal vaccines consist of serotype specific capsular polysaccharide antigen and do not offer full clinical protection against pneumococcal diseases. Due to such limitations, a new generation of protein-based pneumococcal vaccines is being developed. The objective of this study was to determine the distribution of gens encoding five protein antigens including pneumococcal histidine triad D and E (phtD, phtE), rlr- regulated gene A (rrgA), Autolysin (lytA) and Pneumococcal surface protein C (pcpC) among pneumococcal isolates collected from nasopharyngeal specimens in healthy children. Methods: A total of 43 pneumococcal isolates were collected from nasopharyngeal specimens of healthy children attending the kindergartens in Ardabil province. The strains were identified using optochin susceptibility and bile solubility testes and further confirmed by amplification of capsular polysaccharide A gene (cpsA). PCR was used for screening the presence of pcpC, phtD, phtE, rrgA and lytA genes. Results: 81.4 % of isolates were found to contain at least one of the tested genes. lytA, pcpC, phtE, phtD and rrgA were detected in 70, 60, 39.5, 35 and 25.5 percent of isolates, respectively. The results showed that the genes were not distributed consistently among the isolates and for obtaining a full coverage pneumococcal vaccine, multiple choices of these antigens should be included

Comparison of survival in patients with end-stage renal disease receiving hemodialysis versus peritoneal dialysis

Although the life expectancy of patients with end-stage renal disease (ESRD) has improved in recent years, it is still far below that of the general population. In this retrospective study, we compared the survival of patients with ESRD receiving hemodialysis (HD) versus those on peritoneal dialysis (PD). The study was conducted on patients referred to the HD and PD centers of the Emam Khomini Hospital and the Aboozar Children′s Hospital from January 2007 to May 2012 in Ahvaz, Iran. All ESRD patients on maintenance HD or PD for more than two months were included in the study. The survival was estimated by the Kaplan-Meier method and the differences between HD and PD patients were tested by the log-rank test. Overall, 239 patients, 148 patients on HD (61.92%) and 91 patients on continuous ambulatory PD (CAPD) (38.55%) with mean age of 54.1 ± 17 years were enrolled in the study. Regardless of the causes of ESRD and type of renal replacement therapy (RRT), one-, two- and three-year survival of patients was 65%, 51% and 35%, respectively. There was no significant difference between type of RRT in one- (P-value = 0.737), two- (P-value = 0.534) and three- (P-value = 0.867) year survival. There was also no significant difference between diabetic and non-diabetic patients under HD and CAPD in the one-, two- and three-year survival. Although the three-year survival of diabetic patients under CAPD was lower than that of non-diabetic patients (13% vs. 34%), it was not statistically significant (P-value = 0.50). According to the results of the current study, there is no survival advantage of PD during the first years of initiation of dialysis, and the one-, two- and three-year survival of HD and PD patients is also similar

In-silico design and evaluation of an epitope-based serotype-independent promising vaccine candidate for highly cross-reactive regions of pneumococcal surface protein A

Abstract Background The pathogenicity of pneumococcus with high morbidity, mortality, and multi-drug resistance patterns has been increasing. The limited coverage of the licensed polysaccharide-based vaccines and the replacement of the non-vaccine serotypes are the main reasons for producing a successful serotype-independent vaccine. Pneumococcal surface protein A (PspA) is an extremely important virulence factor and an interesting candidate for conserved protein-based pneumococcal vaccine classified into two prominent families containing five clades. PspA family-elicited immunity is clade-dependent, and the level of the PspA cross-reactivity is restricted to the same family. Methods To cover and overcome the clade-dependent immunity of the PspAs in this study, we designed and tested a PspA1-5c+p vaccine candidate composed of the highest immunodominant coverage of B- and T-cell epitope truncated domain of each clade focusing on two cross-reactive B and C regions of the PspAs. The antigenicity, toxicity, physicochemical properties, 3D structure prediction, stability and flexibility of the designed protein using molecular dynamic (MD) simulation, molecular docking of the construct withHLADRB1*(01:01) and human lactoferrin N-lop, and immune simulation were assessed using immunoinformatics tools. In the experimental section, after intraperitoneal immunization of the mice with Alum adjuvanted recombinant PspA1-5c+p, we evaluated the immune response, cross-reactivity, and functionality of the Anti-PspA1-5c+p antibody using ELISA, Opsonophagocytic killing activity, and serum bactericidal assay. Results For the first time, this work suggested a novel PspA-based vaccine candidate using immunoinformatics tools. The designed PspA1-5c+p protein is predicted to be highly antigenic, non-toxic, soluble, stable with low flexibility in MD simulation, and able to stimulate both humoral and cellular immune responses. The designed protein also could interact strongly with HLADRB1*(01:01) and human lactoferrin N-lop in the docking study. Our immunoinformatics predictions were validated using experimental data. Results showed that the anti-PspA1-5c+p IgG not only had a high titer with strong and same cross-reactivity coverage against all pneumococcal serotypes used but also had high and effective bioactivity for pneumococcal clearance using complement system and phagocytic cells. Conclusion Our findings elucidated the potential application of the PspA1-5c+p vaccine candidate as a serotype-independent pneumococcal vaccine with a strong cross-reactivity feature. Further in-vitro and in-vivo investigations against other PspA clades should be performed to confirm the full protection of the PspA1-5c+p vaccine candidate

Immunization with 3-oxododecanoyl-L-homoserine lactone-r-PcrV conjugate enhances survival of mice against lethal burn infections caused by Pseudomonas aeruginosa

Quorum Sensing and type III secretion system play an important role in the virulence of Pseudomonas (P.) aeruginosa in burn wound infections. We aimed to explore the feasibility of using 3-oxo-C12-HSL-r-PcrV conjugate as a candidate vaccine against P. aeruginosa caused infections. 3-oxo-C12-HSL-r-PcrV conjugate was prepared and used for immunization of mice (10 μg, subcutaneous, three times, at 2-week intervals). Mice were divided into five groups: I: PcrV; II: 3-oxo-C12-HSL-r-PcrV (10 μg); III: 3-oxo-C12-HSL-r-PcrV (20 μg); IV: 3-oxo-C12-HSL; and V: PBS receiving groups.  After each shot of immunization, total and isotype antibody responses against corresponding antigen were measured to determine the immunization efficacy. One month after the last immunization, all groups were burned and challenged subeschar with P. aeruginosa PAO1. Survival rate and bacterial quantity in the skin and internal organs (liver and spleen) were evaluated 25-hr after burn infection. Immunization with 3-oxo-C12-HSL-r-PcrV significantly increased total IgG and specific subclass antibodies (IgG1, IgG2a, IgG2b, and IgM) in the serum of the groups II and III compared to the control group (p<0.001). While all the control mice (PBS injected group) died within 2 days after bacterial challenge, 64% of the group I, 78% of group II, and 86% of group III, survived within 14 days after challenge. Interestingly, bacterial burden in the liver and spleen of 3-oxo-C12-HSL-r-PcrV injected group (III) was significantly lower than the control group (p<0.001).  The present study proposed two-component vaccine to inhibit Pseudomonas infections in burned mouse.

Rapid detection of MDR–Mycobacterium tuberculosis using modified PCR-SSCP from clinical Specimens

Objective: To design a rapid test to detect the rifampin (RIF) and isoniazid (INH) resistant mutant based on polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique that analyzes the katG, rpoB genes. Methods: Biochemical test as well as IS6110 targeting PCR revealed 103 clinical samples were tuberculosis. To determine the susceptibility of isolates to anti TB drugs, the proportional method was used. Mutations presented within the amplified products of the katG, rpoB genes were evaluated by SSCP. Results: Using proportional method, 12 (11.6%) and 9 (8.7%) isolates were resistant respectively to INH and RIF and 9 (8.7%) isolates showed resistance to both drug (multi-drug resistant tuberculosis). Three (2.9%) multi-drug resistant tuberculosis and two INH resistant isolates were detected by the PCR-SSCP and sequencing. The sensitivity and specificity of PCR-SSCP for multi-drug resistant isolates were 33% and 100%, respectively. Conclusions: Complete agreement between SSCP and sequencing can indicate that resistance-associated mutations have occurred in other genes except our considered genes