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Yousef Fazaeli1,2, Mostafa M Amini1, Hamed Ashourion3, Homayoun Heydari2, Abbas Majdabadi2, Amir Reza Jalilian2, Shamsozoha Abolmaali2,31Department of Chemistry, Faculty of Sciences, Shahid Beheshti University, Evin, Tehran, 2Agricultural, Medical and Industrial Research School, Moazzen Boulevard, Rajaee Shahr, Karaj, 3Department of Biotechnology, Faculty of New Technologies and Engineering, Shahid Beheshti University, Evin, Tehran, IranAbstract: The goal of this research was to investigate the potential of newly synthesized gold complex trichloro(2,4,6-trimethylpyridine)Au(III) as an anticancer agent. The gold(III) complex was synthesized and grafted on nanoporous silica, MCM-41, to produce AuCl3@PF-MCM-41 (AuCl3 grafted on pyridine-functionalized MCM-41). The toxicity of trichloro(2,4,6-trimethylpyridine)Au(III) and AuCl3@PF-MCM-41 in Saccharomyces cerevisiae (as a model system) was studied. The gold(III) complex showed a mid cytotoxic effect on yeast viability. Using the drug delivery system, nanoporous MCM-41, the gold(III) complex became a strong inhibitor for growth of yeast cells at a very low concentration. Furthermore, the animal tests revealed a high uptake of AuCl3@PF-MCM-41 in tumor cells. The stability of the compound was confirmed in human serum.Keywords: trichloro(2,4,6-trimethylpyridine)Au(III), MCM-41, Au(III), Saccharomyces cerevisiae, anticancer agent

In this article, a critical path identification method is proposed for ternary logic circuits. The considered structure for the ternary circuits is based on 2:1 multiplexers. Sensitization conditions for the employed ternary multiplexers are introduced. Moreover, static timing analysis and dynamic programming are utilized in the identification of true and false paths of the circuit for obtaining more realistic results in a reasonable time. An event-driven simulation engine is also developed for confirming the sensitization state of the identified paths. Some ternary arithmetic logic circuits are designed to depict the effectiveness of the proposed identification method. Simulation results show the correctness and efficiency of the proposed method. [ABSTRACT FROM AUTHOR]

Area reduction of a circuit is a promising solution for decreasing the power consumption and the chip cost. Timing constraints should be preserved after a delay increase of resized circuit gates to guarantee proper circuit operation. Sensitization of paths should also be considered in timing analysis of circuit to prevent pessimistic resizing of circuit gates. In this work, a greedy area reduction algorithm is proposed which is pathbased and benefits well from viability analysis as the sensitization method. A proper metric based on viability conditions is presented to guide the algorithm towards selecting useful circuit nodes to be resized with acceptable performance and area reduction results. Instead of using gate slacks in resizing the candidate gates, all circuit gates are down-sized first and then the sizes of circuit gates that violate the circuit timing constraint are increased. This approach leads to considerable improvement in the complexity and performance of the proposed method. Results show that area improvement of about 88% is achievable. Comparison to a pessimistic method also reveals that on average 14.2% growth in area improvement is obtained by the presented method. [ABSTRACT FROM AUTHOR]

Accurate delay calculation of circuit gates is very important in timing analysis of digital circuits. Waveform shapes on the input ports of logic gates should be considered, in the characterization phase of delay calculation, to obtain accurate gate delay values. Glitches and their temporal effect on circuit gate delays should be taken into account for this purpose. However, the explosive number of combinations of waveform shapes, which can be applied to the input ports of logic gates, causes existing lookup-based methods to have huge space requirements. In this article, instead of considering all possible combinations of waveform shapes in the characterization phase of delay calculation process, the least number of combinations, which are dominant in determining the waveform shape of gate output, is presented. Multivariate Polynomial Regression (MPR) method is used to further reduce the required memory space. Exploration of the possible MPR analyses is performed to find the best regression case with proper memory space reduction and precision. Attained results show a 1.013E6 times reduction in storage space required for storing parameters utilized in extraction of output waveform characteristics in comparison to a state of the artwork, accompanied by acceptable precision. [ABSTRACT FROM AUTHOR]

Melanoma is an especially fatal neoplasm resistant to traditional treatment. The advancement of novel therapeutical approaches has gained attention in recent years by shedding light on the molecular mechanisms of melanoma tumorigenesis and their powerful interplay with the immune system. The presence of many mutations in melanoma cells results in the production of a varied array of antigens. These antigens can be recognized by the immune system, thereby enabling it to distinguish between tumors and healthy cells. In the context of peptide cancer vaccines, generally, they are designed based on tumor antigens that stimulate immunity through antigen-presenting cells (APCs). As naked peptides often have low potential in eliciting a desirable immune reaction, immunization with such compounds usually necessitates adjuvants and nanocarriers. Actually, nanoparticles (NPs) can provide a robust immune response to peptide-based melanoma vaccines. They improve the directing of peptide vaccines to APCs and induce the secretion of cytokines to get maximum immune response. This review provides an overview of the current knowledge of the utilization of nanotechnology in peptide vaccines emphasizing melanoma, as well as highlights the significance of physicochemical properties in determining the fate of these nanovaccines in vivo, including their drainage to lymph nodes, cellular uptake, and influence on immune responses., (Copyright © 2024. Published by Elsevier B.V.)

In medical settings, interprofessional education (IPE) plays an important role by bringing students from multiple disciplines together to learn how to collaborate effectively and coordinate safe patient care. Yet developing effective IPE is complex, considering that stakeholders from different schools and programs are involved, each with varying curriculum requirements and interests. Given its critical importance and inherent complexity, innovative approaches to address these challenges are needed to effectively develop and sustain effective IPE programs. Systems engineering (SE) combines a lifecycle perspective with established interdisciplinary processes to develop and sustain large complex systems. The need for SE approaches to manage healthcare complexity has been recognized, but the application of SE to IPE programs has been limited. We believe that there is a significant opportunity for IPE programs to benefit from the application of SE. The common themes running through SE and IPE led us to ask if SE can be used to address IPE complexity and achieve desired IPE outcomes. We believe that SE could facilitate further development and sustainability of a recently developed healthcare curriculum. We also propose to use SE to accelerate and manage future IPE curriculum development, while better understanding the states of vital IPE-related components. We discuss a framework that considers transitions of key IPE elements. We believe that use of interdisciplinary SE processes and holistic perspectives and methods such as system thinking will improve the management of system challenges while addressing IPE's inherent complexity and leading to better patient outcomes and more effective interprofessional collaboration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ferreira, Phelps, Abolmaali, Reed and Greilich.)

High-dose methotrexate (MTX) chemotherapeutic applications confront drug specificity and pharmacokinetic challenges, which can be overcome by utilizing targeted drug delivery systems. In the present study, biotin-PEG conjugated nanogels of carboxymethyl polyethyleneimine (Biotin-PEG-CMPEI) were developed for active targeted delivery of MTX in triple negative breast cancer (TNBC). TEM and DLS analyses revealed uniform, discrete, and spherical particles with a mean hydrodynamic diameter of about 100 nm and ζ-potential of + 15 mV (pH = 7.4). Biotin-PEG-CMPEI nanogels exhibited a zero-order MTX release kinetics at pH = 7.5 and a swelling-controlled release at pH = 5.5. In 4 T1 cells treated with the MTX-loaded Biotin-PEG-CMPEI, the IC 50 was reduced by about 10 folds compared to the free drug, while the unloaded nanogels showed no significant toxicity. In the model mice, the group treated with the MTX-loaded Biotin-PEG-CMPEI had a lower tumor volume and mortality rate animal model when compared to free drug. Additionally, histopathological analyses showed that the group treated with the MTX-loaded nanogels had less lung metastasis and glomerular damage caused by MTX. Overall, the MTX-loaded Biotin-PEG-CMPEI targeted directly against overexpressed biotin receptors in TNBC have been shown to improve the MTX safety and therapeutic efficacy., (Copyright © 2022 Elsevier B.V. All rights reserved.)

It is becoming evident that holistic perspectives toward cancer are crucial in deciphering the overwhelming complexity of tumors. Single-layer analysis of genome-wide data has greatly contributed to our understanding of cellular systems and their perturbations. However, fundamental gaps in our knowledge persist and hamper the design of effective interventions. It is becoming more apparent than ever, that cancer should not only be viewed as a disease of the genome but as a disease of the cellular system. Integrative multilayer approaches are emerging as vigorous assets in our endeavors to achieve systemic views on cancer biology. Herein, we provide a comprehensive review of the approaches, methods and technologies that can serve to achieve systemic perspectives of cancer. We start with genome-wide single-layer approaches of omics analyses of cellular systems and move on to multilayer integrative approaches in which in-depth descriptions of proteogenomics and network-based data analysis are provided. Proteogenomics is a remarkable example of how the integration of multiple levels of information can reduce our blind spots and increase the accuracy and reliability of our interpretations and network-based data analysis is a major approach for data interpretation and a robust scaffold for data integration and modeling. Overall, this review aims to increase cross-field awareness of the approaches and challenges regarding the omics-based study of cancer and to facilitate the necessary shift toward holistic approaches., (© The Author(s) 2021. Published by Oxford University Press.)

Background: To obtain endolysin with impact(s) on gram-negative bacteria as well as gram-positive bacteria, N-acetylmuramyl L-alanine-amidase (MurNAc-LAA) from a Bacillus subtilis -hosted Siphoviridae phage (SPP1 phage, Subtilis Phage Pavia 1) was exogenously expressed in Escherichia coli (E. coli) ., Methods: The sequences of MurNAc-LAA genes encoding peptidoglycan hydrolases were obtained from the Virus-Host database. The sequence of MurNAc-LAA was optimized by GenScript software to generate MurNAc-LAA-MMI (LysM2) for optimal expression in E. coli . Furthermore, the structure and function of LysM2 was evaluated in silico . The optimized gene was synthesized, subcloned in the pET28a, and expressed in E. coli BL21(DE3). The antibacterial effects of the protein on the peptidoglycan substrates were studied., Results: LysM2 , on 816 bp gene encoding a 33 kDa protein was confirmed as specific SPP1 phage enzyme. The enzyme is composed of 271 amino acids, with a half-life of 10 hr in E. coli . In silico analyses showed 34.2% alpha-helix in the secondary structure, hydrophobic N-terminal, and lysine-rich C-terminal, and no antigenic properties in LysM2 protein. This optimized endolysin revealed impacts against Proteus (sp) by turbidity, and an antibacterial activity against Klebsiella pneumoniae, Salmonella typhimurium , and Proteus vulgaris in agar diffusion assays., Conclusion: Taken together, our results confirmed that LysM2 is an inhibiting agent for gram-negative bacteria., Competing Interests: Conflict of Interest The authors declare that they have no competing interest., (Copyright© 2022 Avicenna Research Institute.)

Background: Silibinin (SBN), a major active constituent of milk thistle seeds, exhibits numerous pharmacological activities. However, its oral bioavailability is low due to poor water solubility. This study aimed to develop a new synthetic approach for tuning the pore characteristics of mesoporous silica nanoparticles (MSNs) intended for the oral delivery of SBN. In addition, the effects of the pore diameter of MSNs on the loading capacity and the release profile of SBN were investigated., Methods: The present study was performed at Shiraz University of Medical Sciences, Shiraz, Iran, in 2019. This synthesis method shares the features of the simultaneous free-radical polymerization of methyl methacrylate and the sol-gel reaction of the silica precursor at the n-heptane/water interface. SBN was loaded onto MSNs, the in vitro release was determined, and the radical scavenging activities were compared between various pH values using the analysis of variance., Results: According to the Brunauer-Emmett-Teller protocol, the pore sizes were well-tuned in the range of 2 to 7 nm with a large specific surface area (600-1200 m 2 /g). Dynamic light scattering results showed that different volume ratios of n-heptane/water resulted in different sizes, ranging from 25 to 100 nm. Interestingly, high SBN loading (13% w/w) and the sustained release of the total drug over 12 hours were achieved in the phosphate buffer (pH=6.8). Moreover, the antioxidant activity of SBN was well preserved in acidic gastric pH., Conclusion: Well-tuned pores of MSNs provided a proper substrate, and thus, enhanced SBN loading and oral dissolution and preserved its antioxidant activity. Nevertheless, further in vitro and in vivo investigations are needed., (Copyright: © Iranian Journal of Medical Sciences.)

Starting February 2020, COVID-19 was confirmed in 11,946 people worldwide, with a mortality rate of almost 2%. A significant number of epidemic diseases consisting of human Coronavirus display patterns. In this study, with the benefit of data analytic, we develop regression models and a Susceptible-Infected-Recovered (SIR) model for the contagion to compare the performance of models to predict the number of cases. First, we implement a good understanding of data and perform Exploratory Data Analysis (EDA). Then, we derive parameters of the model from the available data corresponding to the top 4 regions based on the history of infections and the most infected people as of the end of August 2020. Then models are compared, and we recommend further research., Competing Interests: Conflict of interest: The authors report no conflict of interest., (© 2021 the Author(s), licensee AIMS Press.)

Fmoc-dipeptides are a class of short aromatic peptides featuring eminent supramolecular self-assembly, which is due to the aromaticity of the Fmoc group, which improves the association of peptide building blocks. This study aimed to introduce a new dipeptide hydrogel scaffold, Fmoc-phenylalanine-valine (Fmoc-FV), for 3D culture of various cells. Peptide hydrogel scaffolds were prepared by the pH-titration method in various concentrations and temperatures, and characterized by spectroscopic methods, including circular dichroism, attenuated total reflection FT-IR and fluorimetry. Mechanical behaviors such as thixotropy and temperature-sensitivity were investigated by oscillatory rheology. The Fmoc-FV hydrogels were then applied in 3D-culture of WJ-MSCs (mesenchymal stem cells), HUVECs (normal endothelial cells), and MDA-MB231 (tumor cell line) by live-dead fluorescence microscopy and Alamar blue viability assay experiments. The results confirmed that the β-sheet structure is principally interlocked by π-π stacking of the Fmoc groups and entangled nanofibrous morphologies as revealed by FE-SEM. Fmoc-FV self-assembly in physiologic conditions resulted in a thermo-sensitive and shear-thinning hydrogel. Notably, the Fmoc-FV hydrogel exhibited cell type-dependent biological activity, so higher cell proliferation was attained in HUVEC or MDA-MB231 cells than WJ-MSCs, indicating a possible need for incorporating cell-adhesion ligands in the Fmoc-FV hydrogel matrix. Therefore, the structural and biological properties of the Fmoc-dipeptide hydrogels are inter-related and can affect their applications in 3D cell culture and regenerative medicine.

Plant defensins are a group of small disulfide-rich cationic peptides that exhibit a broad spectrum of antimicrobial activities. In the present study, an antibacterial plant defensin peptide was successfully identified and characterized from the transcriptome of the oat (Avena sativa L.), and called AsDef1. The complete nucleotide sequence of AsDef1 was determined (321 bp) and found to contain an open reading frame (ORF) encoding a peptide of 77 aa with a putative 22 aa signal peptide sequence that addresses the mature defensin to the apoplast. Further in silico analyses revealed that the structure of the identified defensin (AsDef1) consists of the Knot1 functional domain with eight conserved cysteine residues and four disulfide bonds. The highest expression of AsDef1 was observed in the developing seeds of the A. sativa plant. AsDef1 also showed antibacterial activity against both Gram-positive and Gram-negative bacteria. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values ranged from 0.15625 μM to 0.625 μM. In this study, we identified and characterized an antibacterial defensin from A. sativa for the first time. The findings of the present study offer insights that can be used in producing pathogen-resistant transgenic plants and in developing potential antibacterial agents in the future using AsDef1 from A. sativa., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background and Objectives: The great potential of bacteriophage for removing pathogen bacteria via targeting the cell wall is highly concerned. With a priority for overcoming drug-resistance, we screened against endolysins targeting Gram-negative bacteria to introduce a new antibacterial agent. This study was aimed to identify endolysins from the lysogenic phage of the Siphoviridea family in Bacillus subtilis., Materials and Methods: The Bacillus subtilis strain DDBCC46 was isolated from a preliminary antibacterial screening program. The endolysin (s) was extracted, concentrated with ammonium sulfate saturation, and their activity evaluated against the indicator bacteria. The phage particles were extracted from the bacteria using the minimum inhibition concentration of mitomycin C, followed by testing the phage inhibitory effect on the growth of indicator bacteria. The NCBI, Virus-Host DB, and EXPASY databases were used to obtain and confirm the sequences of the genes encoding PG hydrolases in Siphoviridea phages hosted in B. subtilis., Results: An 816 bp gene encoding an endolysin enzyme, was approved in the B. subtilis DDBCC 46, with specific primers of Bacillus phage SPP1. The purified-endolysin indicated antibacterial activity against Klebsiella pneumoniae, Salmonella typhimurium , Proteus (sp), and Escherichia coli . SDS-PAGE profiling followed by silica gel purification, led to introduce Lys46 30 as a therapeutic product and food preservative., Conclusion: lys46 30 showed antibacterial effects on the common Gram-negative pathogens in clinics and food industries; E. coli, P. aeruginosa and Salmonella (sp)., (Copyright© 2020 The Authors.)

Background: Recently, using antibacterial peptides has been considered as a strategy to manage the worldwide antibiotic-resistance crisis. Screening of Dasht-Desert Bacterial Culture Collection (DDBCC) for bacteriocin or bacteriocin-like producer was aimed in this study to introduce native antibacterial agent(s)., Methods: In this study, 170 isolates were examined by the cross-streak method against G+ and G- indicators. Isolates with antimicrobial activity were compared using turbidity and well diffusion tests. The candidate isolate, DDBCC70, was molecularly and biochemically characterized. Then, the production of an antibacterial agent was physicochemically optimized. The supernatant was saturated ammonium sulfate. SDS-PAGE and Thin-Layer Chromatography (TLC) analyses, cytotoxicity, and hemagglutination tests were performed., Results: First, 23 isolates were detected with antimicrobial activity against at least three of the indicator strains. DDBCC70 was distinguished with the broad-spectrum of antibacterial effects of the Cell-Free Supernatants (CFSs). The black pigments on BHI and a 98% similarity in 16S rDNA and similarity in biochemical tests confirmed the strain of DDBCC70 as Bacillus atrophaeus (B. atrophaeus) . The highest amount of the antibacterial agent, Bac70, was obtained from the modified brain heart infusion medium. It was revealed that 70% ammonium sulfate-saturated Bac70 was 3.8 and 1.6 times more effective on Pseudomonas aeuroginosa (P. aeuroginosa) and Klebsiella pneumoniae (K. pneumoniae) . Bac70, a >25 kDa protein and a safe compound for blood cells, neither agglutinated human erythrocyte nor lysed sheep blood. The purified bacteriocin-like molecule destroyed biofilms from P. aeruginosa and Staphylococcus aureus (S. aureus) . Moreover, the fraction of Bac70 from the TLC plate showed higher inhibitory effects against K. pneumoniae ., Conclusion: Based on the above-mentioned features, Bac70 is a potential alternative therapeutic agent in pharmaceutical, food preservative and biotech-related industries., Competing Interests: Conflict of Interest The authors have no competing interest., (Copyright© 2020 Avicenna Research Institute.)

Drug-resistant Gram-positive pathogens have been a rising risk in hospitals and food industries from the last decades. Here in, the potential of endolysin production in Dasht Desert Bacterial Culture Collection (DDBCC), against indicator bacteria, was investigated. DDBCC was screened against autoclaved-indicator bacteria; Streptococcus faecalis, Streptococcus pyogenes, Bacillus sp, Bacillus subtilis and Staphylococcus aureus as the substrates for the endolysin enzymes. The endolysins were produced in BHI medium followed by ammonium sulfate purification. Peptidoglycan hydrolytic activity was tested by zymogram method. Lysogenic bacteria were induced by 0.1 μg/ml mitomycin C for bacteriophages extraction. The lysogenic bacteria inhibited S. pyogenes, S. faecalis, Bacillus sp. and B. subtilis. The strain DDBCC10 was selected for further experiments on its higher and specific activity against the cell wall of S. faecalis. The highest activity for the endolysin was obtained at 50-60% ammonium sulfate saturation as 8 U/ml. Lys10, a 22 kDa enzyme, digested the cell wall of S. faecalis in 15 min while the whole phage from DDBCC10 could form plaque on S. faecalis and S. pyogenes. In a Transmission Electron Microscopy assay (TEM), the phage was distinguished as a member of Siphoviridae. Here; Lys10 is introduced as a new biocontrol agent against S. faecalis for therapeutics, disinfection, and food preservatives purposes at a much lower expense than recombinant endolysins., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: As radiologic assessment is a key part in evaluating patients visited in emergency department, this survey was conducted to measure emergency medicine residents' competency in choosing appropriate diagnostic imaging in different clinical scenarios., Methods: All emergency medicine residents enrolled in an academic emergency medicine discipline in the three medical universities of Tehran, Iran were recruited. A questionnaire was designed consisting of 10 clinically common scenarios selected from the American College of Radiology appropriateness criteria. Each resident completed the survey separately with answers only given after all residents participated., Results: 196 residents completed the survey (95% of all residents). The results were stratified by post-graduate year and university. The average number of correct answers was 6.2. First, second and third year residents scored the average of 6.1, 5.8 and 6.5, respectively (P=0.04). The average score of residents from different universities did not differ significantly., Conclusion: According to the low average score, it is recommended that attentive educational perfections are needed to help residents order more appropriate diagnostic images, which may also be helpful for other healthcare providers. However, it seems that our emergency medicine academic curriculum is relatively efficient to enhance residents' skills in choosing proper imaging., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

A class of double hydrophilic copolymers comprising ionic and nonionic water-soluble blocks, which are also called block ionomers, represent an interesting type of polymer assembly forming stable, homogeneous core-corona dispersions. They exhibit the solution behavior of normal polyelectrolytes, whereas assembly into micelle, vesicle or disk morphology happens by an external stimulus (pH, temperature or ionic strength) or complex formation with metal ions, ionic surfactants, polyelectrolytes, etc. Temperature, pH, redox or salt sensitivity affords a unique opportunity to control the triggered release of payloads accommodated through electrostatic interaction, coordination or chemical conjugation. Moreover, the non-ionic block provides the surface passivation, prolongation of the blood circulation and tumor accumulation, supporting targeted delivery of chemotherapeutic agents based on pathophysiology of tumor microenvironment. Potentiation of antitumor activity, sensitization of the resistant tumors, increased tolerated dose and translation into clinical practice are among their most intriguing characteristics. Their high functionality has been suggested for co-delivery of multiple agents for reversal of chemo-resistance as well as simultaneous therapy and diagnostics. Nevertheless, some stability concerns may be raised due to the polymer disassembly beyond a critical concentration of pH, salt and polyion concentration that can be modulated by introducing crosslinks between the polymer chains (Nano-networks)., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: The study aimed to illustrate application of polycation Stealth nanogels for sustained delivery of methotrexate (MTX) in collagen induced arthritis (CIA) model in C57Bl/6 mice., Methods: Nanogel synthesis involves metal ion coordinated self-assembly of PEGylated poly ethyleneimine (L-histidine substituted), chemical crosslinking and subsequent removal of the coordinated metal. The nanogels were characterized by TEM and DLS-zeta potential. Comparative efficacy and pharmacokinetics of the i.v. administred MTX-loaded nanogels were investigated in the CIA model. Inflammation site passive accumulation of the fluorophore-labeled nanogels was tested using in-vivo imaging of mice paw received unilateral injection of lipopolysaccharide., Results: Uniform nanogels (sizes ~40 nm by TEM) were loaded with MTX (entrapment efficiency = 62% and drug loading = 54% at the MTX feeding ratio of 0.3 relative to total molar concentration of the polymer amines). The nanogels exhibited neutral surface charge and an acceptable biocompatibility in terms of albumin aggregation, hemolysis, erythrocyte aggregation and cytotoxicity. Single dose pharmacokinetics of the MTX-loaded nanogels, unlike free drug, showed a sustained plasma profile. When arthritis established as confirmed by histopathology, a remarkable decline of paw swelling and clinical scores was observed. Fluorescence intensity of the nanogels was enhanced about 2.7 folds at the inflamed than control normal ankle., Conclusion: Sustained delivery of MTX and preferential accumulation of the nanogels in inflamed paw might explain the superior clinical outcome of the MTX-loaded nanogels.

Single-walled carbon nanotubes (SWNTs) are among the promising nano-devices for delivery of therapeutic agents. Yet the drastic hydrophobic natures of SWNTs make their handling and hence application difficult. Several researches have been conducted to make them more hydrophilic and water dispersible and less toxic. Among the different approaches, dispersion methods exploit different reagents such as surfactants and block copolymers. The question is whether these so called dispersed SWNTs are stable enough and suitable for biomedical applications. Herein we aimed to functionalize SWNT surface by dioleoylphosphatidylethanolamine-polyethylene glycol (PL-PEG) and sodium deoxycholate (SDC) micelles and compare their efficacy in SWNT stabilization for biomedical application such as delivery of doxorubicin. Shortening and water dispersion of SWNTs were carried out by ultrasonication in aqueous solutions at different concentrations of SDC or PL-PEG micelle and assessed by UV-Vis-NIR spectroscopy. The stability of SWNT dispersions were assessed over the time and in the presence of salt by macroscopic observation and UV-Vis-NIR spectroscopy. Doxorubicin loading and release were carried out under different pH conditions. SWNT dispersions were stable in water for at least several weeks at room temperature, but SDC prepared dispersions were prone to agglomeration in the presence of salt and doxorubicin. The critical PL-PEG concentration for stability in physiologic conditions was about 5 times its critical micelle concentration. Doxorubicin loading was pH dependent and its release was triggered in acidic condition of tumor medium.

Purpose: To compare central corneal thickness (CCT) in subjects with controlled primary congenital glaucoma (PCG) and nonglaucomatous subjects and to investigate the correlation between CCT and intraocular pressure (IOP) in the study population., Materials and Methods: Twenty-three consecutive PCG cases with controlled IOP and no clinical evidence of corneal edema comprised the Study Group. There was an interval of at least 2 months between last intraocular surgery and inclusion in the study. Twenty-one subjects with strabismus or lacrimal drainage insufficiency who did not have glaucoma or any history of intraocular surgery or ocular trauma comprised the control group. The Control Group was age and sex-matched. Data from ultrasonic pachymetry and applanation tonometry were analyzed for differences between groups. Correlation of the study parameters was investigated. A P-value less than 0.05 was statistically significant., Results: Data from both eyes of subjects in the Study Group and Control Group were included in the original analysis. Mean CCT was statistically significantly higher in the Study Group compared to the Control Group (589.42 ± 53.44 μm vs. 556.14 ± 30.51 μm, respectively; P=0.001). There was a significant correlation between CCT and IOP (r=0.63; P<0.0001). Similar statistically significant outcomes were observed when only one eye per subject was used in a reanalysis of the data for the Study and Control Groups., Conclusion: Patients with PCG who had controlled IOP have statistically significantly thicker corneas than nonglaucomatous age and sex-matched subjects The thicker cornea could significantly alter IOP measurement with applanation tonometry. Pachymetry should be considered an essential part of the evaluation for PCG.

Background: Selective IgA deficiency (SIGAD) is the most common primary antibody deficiency, characterized by significant decreased serum levels of IgA in the presence of normal IgG and IgM. Despite several investigations into the nature of the disease, the exact pathophysiology of SIGAD is still unknown., Methods: In this study, switched memory B cells (CD19+/CD27+/IgD- cell population) of 28 patients with SIGAD and 28 matched healthy controls were investigated using flow cytometry., Results: The percentage of switched memory B cells in all healthy controls was more than 0.4%. In SIGAD patients, who were classified as group I, the percentage of switched memory B cells was less than 0.4% (0.34 ± 0.06) in 7 patients (25%). The remaining 21 patients were designated as group II (1.74 ± 0.12%). The mean concentration of IgG in group I was significantly lower than in group II (1,014 ± 278 vs. 1,388 ± 406 mg/dl, p = 0.028). Comparison of clinical features between the 2 groups revealed that episodes of pneumonia during the course of disease were significantly higher in group I than in group II (p = 0.002). Autoimmune diseases in group I (57.1%) were also significantly higher (p = 0.01) than in group II (23.8%). The prevalence of bronchiectasis was 57% in group I, while only 1 patient (4.7%) in group II developed bronchiectasis (p = 0.006). Specific antibody deficiency in group I was documented in 5 patients and in group II in 4 patients (p = 0.01)., Conclusions: The classification of SIGAD patients by assessment of switched memory B cells could help physicians with the clinical prognosis for these patients, whereas the patients with reduced switched memory B cells are prone to severe phenotypes., (Copyright © 2011 S. Karger AG, Basel.)

Objective: There are some controversial studies on effects of anti-epileptic drugs (AEDs) on serum IgG subclasses; however, the role of these medications is still unclear. The aim of this study was evaluation the effects of anti-epileptic drugs on serum concentration of IgG and its subclasses, Methods: Serum IgG and IgG subclasses of 61 newly diagnosed epileptic patients were measured at the beginning of monotherapy with carbamazepine, sodium valproate, and phenobarbital, and 6 months later. Measurement of IgG and its subclasses was performed using nephlometry and ELISA techniques, respectively., Findings: Reduction of at least one IgG subclass was found in 6 patients 6 months after treatment with AEDs. Among 27 patients receiving carbamazepine, decrease in at least one serum IgG subclass level was found in 5 patients. Among 20 patients using sodium valproate, only one patient showed decrease in IgG2 subclass. None of the 14 patients using phenobarbital revealed significant decrease in IgG subclasses. No infection was seen in the patients with reduction of subclasses., Conclusion: Although in our study, children with selective IgG subclass deficiency were asymptomatic, assessment of serum immunoglobulin levels could be recommended at starting the administration of AEDs and in serial intervals afterward in epileptic patients.

Epilepsy is one of the most frequent neurological disorders. Despite the advances and improvements in treatment of seizure disorders, immunologic alterations related to anticonvulsant drugs have been described. The aim of this paper is to assess the effect of some antiepileptic drugs on serum immunoglobulin levels in epileptic patients. Seventy-one patients with epilepsy were included in the study. Participants were divided into three groups based on their treatment with carbamazepine (n=33), sodium valproate (n=22) or phenobarbital (n=16) as monotherapy. Three samples were taken from each patient and serum immunoglobulin levels were measured before treatment, 3 months and 6 months after therapy. Overall, eleven patients out of 71 (15.5%) had a decrease in at least one serum immunoglobulin level (more than 2SD below age-matched control). In the patients receiving carbamazepine, 8 patients (24.2%) showed significant decline in at least one immunoglobulin (3 cases in IgA and 5 cases in IgG). In the group of treated with sodium valproate, 2 patients showed significant decrease in serum IgA level. Results of the last group indicated a significant reduction in serum IgG concentration only in one patient. No patient at all showed significant decrease in serum IgM level. This study suggests that anti-epileptic drugs could reduce serum immunoglobulins, especially IgA and IgG; among them carbamazepine effect is of more concern.

The aim of this study was to increase the sensitivity of Saccharomyces cerevisiae towards trichothecene toxins, in particular to deoxynivalenol (DON), in order to improve the utility of this yeast as a bioassay indicator organism. We report the construction of a strain with inactivated genes (PDR5, PDR10, PDR15) encoding ABC transporter proteins with specificity for the trichothecene deoxynivalenol, with inactivated AYT1 (encoding a trichothecene-3-O-acetyltransferase), and inactivated UBI4 and UBP6 genes. Inactivation of the stress inducible polyubiquitin gene UBI4 or the ubiquitin protease UBP6 increased DON sensitivity, the inactivation of both genes had a synergistic effect. The resulting pdr5 pdr10 pdr15 ayt1 ubp6 ubi4 mutant strain showed 50% growth inhibition at a DON concentration of 5 mg/l under optimal conditions. The development of a simple two step assay for microbial DON degradation in 96 well microtiter format and its testing with the DON detoxifying bacterium BBSH 797 is reported.

Plant pathogenic fungi of the genus Fusarium can cause severe diseases on small grain cereals and maize. The contamination of harvested grain with Fusarium mycotoxins is a threat to human and animal health. In wheat production of the toxin deoxynivalenol (DON), which inhibits eukaryotic protein biosynthesis, is a virulence factor of Fusarium, and resistance against DON is considered to be part of Fusarium resistance. Previously, single amino acid changes in RPL3 (ribosomal protein L3) conferring DON resistance have been described in yeast. The goal of this work was to characterize the RPL3 gene family from wheat and to investigate the potential role of naturally existing RPL3 alleles in DON resistance by comparing Fusarium-resistant and susceptible cultivars. The gene family consists of three homoeologous alleles of both RPL3A and RPL3B, which are located on chromosomes 4A (RPL3-B2), 4B (RPL3-B1), 4D (RPL3-B3), 5A (RPL3-A3), 5B (RPL3-A2) and 5D (RPL3-A1). Alternative splicing was detected in the TaRPL3-A2 gene. Sequence comparison revealed no amino acid differences between cultivars differing in Fusarium resistance. While using developed SNP markers we nevertheless found that one of the genes, namely, TaRPL3-A3 mapped close to a Fusarium resistance QTL (Qfhs.ifa-5A). The potential role of the RPL3 gene family in DON resistance of wheat is discussed.