Comparing infusion-related reactions of the first full dose (600 mg) biosimilar ocrelizumab administration with the standard divided protocol in multiple sclerosis patients: a randomized controlled trial study.

BACKGROUND: Ocrelizumab is a humanized antiCD20, thought to be a highly effective disease-modifying therapy (DMT). Its most frequent adverse effects are infusion-related reactions (IRRs). To reduce these reactions, the first dose of ocrelizumab is administered as two 300 mg infusions separated by two weeks. However, in the phase II trial of ocrelizumab, severe IRRs were not significantly different between two doses of 600 mg dose (two separate 300 mg doses) and 2000 mg dose (two separate 1000 mg doses). We compared the IRRs in undivided full (one 600 mg) and divided (two 300 mg) doses of ocrelizumab which is the standard protocol. METHODS: MS patients (relapsing or primary progressive MS) who are selected to receive ocrelizumab by neurologist or MS fellowship were enrolled in an open-label randomized controlled trial. Iranian biosimilar of the drug (Xacrel® by Cinnagen, approved by the Iranian Food and Drug Administration in 2021) was used. The participants received the first dose of ocrelizumab as either one 600 mg dose in one session or two 300 mg doses in two weeks apart. IRRs during or in the first 24 h after infusion were recorded. RESULTS: Of 332 participants, 150 received two 300 mg doses, and 182 received one 600 mg dose (by random selection). Life-threatening adverse effects were not observed in both groups. Overnight admission or permanent drug discontinuation was not needed. Temporary drug discontinuation was significantly higher in the one 600 mg dose group (p-value < 0.001). During the infusions, malaise (p-value: 0.003), skin reactions (p-value: 0.04), throat swelling (p-value: 0.03), and dyspnea (p-value: 0.01) were significantly increased in the intervention group. However, in the first 24 h, there was no significant difference between two different treatment protocols (one 600 mg dose or two 300 mg doses) in the onset of IRRS (p-value: 0.12). CONCLUSION: These findings suggest one 600 mg dose of ocrelizumab administration for the first dose is relatively safe. With some protocol modifications, it could lead to fewer patient referrals, saving time and cost and improvement the access for patients.

Smart green CQD@SiO2 hybrid coated optical fiber manifesting dual versatile absorptive and MIP features towards epinephrine detection.

For the first time, in this study, a novel optical fiber biosensor is proposed and developed via coating only one smart functional layer of silica-supported carbon dots realizing the concepts of both lossy mode resonance (LMR) and molecularly imprinted polymer (MIP) for epinephrine detection. The carbon quantum dots (CQDs) are prepared using a green synthesis method and then treated with a molecularly imprinted polymer (MIP) strategy. Under ultrasonic irradiation, a SiO2 shell was stabilized on the surface of the CQDs to graft and to provide the LMR/MIP functional layer onto the curved optical fiber surface. Accurate structural and morphological characterization confirmed the carbon quantum dot agents and also the SiO2 supporting shells on the optical fiber, while spectroscopic analysis confirms the formation of the imprinted polymer and desirable absorbance characteristics. The experimental and numerical sensing studies revealed that the proposed sensing probe allows the rapid adsorption/desorption of epinephrine to the sensing films and highly permeable coating for studying the influence of effective parameters. Under the optimal experimental conditions, the sensitivity of the proposed LMR-based optical fiber sensor is reported to be 0.37 nm µM-1 with a correlation coefficient of 0.99. So, sensitive detection of epinephrine at a low concentration can be guaranteed with a 0.72 mM LOD.

Antibacterial activity and mechanism of action of chitosan nanofibers against toxigenic Clostridioides (Clostridium) difficile Isolates.

BACKGROUND: Clostridioides difficile a Gram-positive, obliged anaerobic, rod-shaped spore-former bacterium, causes a wide spectrum of diseases, ranging from mild, self-limiting diarrhoea to serious diarrhea. Chitosan, a natural polysaccharide, is largely known for its activity against a wide range of microorganisms. Chitosan, in the form of nanofibrils (nanofibrilated chitosan), consists of separated fibers which can be suspended easily in aqueous media. STUDY DESIGN: This paper, for the first time, aims to evaluate the antimicrobial activity of chitosan nanofibers against C. difficile isolates. METHODS: Chitosan nanofibers were characterized through scanning electron microscopy and atomic force microscopy. Minimum inhibitory concentration and minimum bactericidal concentration of chitosan nanofibers against toxigenic C. difficile isolates (with resistance gene: ermB, tetM and tetW) was determined by the standard broth microdilution method. RESULTS: The Miniumum Inhibitory Concentration of chitosan nanofibers for two toxigenic isolates with resistance genes ermB, tetM and tetW, two toxigenic isolates ermB+ tetM+ and the standard strain ATCC 700057 was similar and equal to 0.25 mg/mL. The minimum bactericidal concentration for all isolates was 0.5 mg/mL. CONCLUSIONS: The results demonstrated that chitosan nanofibers exhibit potent antimicrobial activities against multiple toxigenic C. difficile isolates, and the antibacterial effect of chitosan nanofibers against C. difficile isolates with ermB, tetM and tetW resistance genes indicates that interfering with the synthesis of proteins is not the mechanism of action of chitosan nanofibers.

Natural Source-Based Graphene as Sensitising Agents for Air Quality Monitoring.

Natural carbon powder has been used as a precursor to prepare two main types of sensitising agents of nitrogen-doped carbon nanoparticles (N-CNPs) and nitrogen-doped graphene quantum dots coupled to nanosheets (N-GQDs-NSs) by using simple treatments of chemical oxidation and centrifugation separation. Characterization based on FTIR, XPS, XRD, Raman spectroscopy, FE-SEM, HR-TEM, AFM, UV-Vis and FL, revealed successful doping carbon nanoparticle with nitrogen with an average plane dimension of 50 nm and relatively smooth surface. The versatility of the prepared samples as sensitising agents was developed and established by exploiting its ability for detection of volatile organic compounds via simple optical fibre based sensing configuration. The comparative experimental studies on the proposed sensor performance indicate fast response achieved at a few tens of seconds and excellent repeatability in exposure to the methanol vapour. The low limit of detection of 4.3, 4.9 and 10.5 ppm was obtained in exposure to the methanol, ethanol and propanol vapours, respectively, in the atmosphere condition. This study gives insights into the chemical/physical mechanism of an enhanced economic optical fibre based gas sensor and illustrates it for diverse sensing applications, especially for chemical vapour remote detection and future air quality monitoring.

Fast food consumption and overweight/obesity prevalence in students and its association with general and abdominal obesity.

Nowadays, the prevalence of both fast food consumption and overweight/obesity has been increased. This study aimed to estimate the prevalence of fast food consumption and to assess its association with abdominal and general obesity. In an analytical cross-sectional study, 300 students were selected randomly from two largest universities in Qom, center of Iran, studying in medical and basic sciences fields in 2015. Data collection was conducted by a modified version of NELSON's fast food questionnaire and anthropometric measures including Waist-Hip Ratio (WHR) and Body Mass Index (BMI). Chi-square, independent t-test, and multivariate logistic regression were used for statistical analysis. According to our results, 72.4% (67.4% in females vs 80.7% in males) had at least one type of fast food consumption in the recent month including sandwich 44.4%, pizza 39.7%, and fried chicken 13.8%, The obesity prevalence based on BMI and WHR was 21.3% (95% CI: 19.4, 23.2%) and 33.2% (95% CI: 0.7, 35.7), respectively. Fast food consumption was related to abdominal obesity as WHR (OR: 1.46, 95% CI: 1.11, 2.26), but was not related to general obesity as BMI (OR: 0.97, 95% CI: 0.63, 1.52). The prevalence of fast food consumption and obesity/overweight in Iranian student is high. Fast food consumption was associated with abdominal obesity based WHR, but did not related to general obesity based on BMI.

Characterization of virulence factors, antimicrobial resistance patterns and biofilm formation of Pseudomonas aeruginosa and Staphylococcus spp. strains isolated from corneal infection.

INTRODUCTION: Infectious keratitis is a serious ocular infection that can lead to severe visual impairment and blindness. Bacterial pathogens are responsible for nearly half of infectious keratitis cases. This study was performed to determine the virulence factors, antimicrobial resistance patterns, and biofilm formation ability of Pseudomonas aeruginosa and Staphylococcus spp. strains isolated from corneal infections. METHODS: A total of 56 corneal scraping samples were collected over 8 months. P. aeruginosa and staphylococcal strains were identified by phenotypic and genotypic methods. Determination of multidrug resistance was performed according to its definition of multidrug resistance (MDR). Detection of antimicrobial resistance genes and determinants of virulence were also performed using standard procedures. Biofilm formation ability of the isolates was determined by colorimetric microtitration plate assay and Modified Congo red agar (MCRA). RESULTS: In the present study, P. aeruginosa, MSSA, MRSA, MS-CoNS and MR-CoNS strains were isolated from corneal infections. Multidrug resistance was observed in 42.9% and 57.1% of P. aeruginosa and Staphylococcus spp., respectively. The most frequent virulence genes among P. aeruginosa strains were exoA and exoS (100%) followed by exoU (71.4%) and lasB (28.6%). All the P. aeruginosa isolates were biofilm producers and carried the algD gene (100%). All staphylococcal strains were negative for pvl gene amplification. Biofilm formation was also observed in 4 (57.1%) isolates. Both icaA and icaD genes were detected in the biofilm producers. CONCLUSION: Our results indicated that P. aeruginosa and Staphylococcus spp. were the most prevalent bacterial agents that cause corneal infections. However, their virulence traits and biofilm formation ability were noteworthy.

Reducing Radiation Doses in Female Breast and Lung during CT Examinations of Thorax: A new Technique in two Scanners.

BACKGROUND: Chest CT is a commonly used examination for the diagnosis of lung diseases, but a breast within the scanned field is nearly never the organ of interest. OBJECTIVE: The purpose of this study is to compare the female breast and lung doses using split and standard protocols in chest CT scanning. MATERIALS AND METHODS: The sliced chest and breast female phantoms were used. CT exams were performed using a single-slice (SS)- and a 16 multi-slice (MS)- CT scanner at 100 kVp and 120 kVp. Two different protocols, including standard and split protocols, were selected for scanning. The breast and lung doses were measured using thermo-luminescence dosimeters which were inserted into different layers of the chest and breast phantoms. The differences in breast and lung radiation doses in two protocols were studied in two scanners, analyzed by SPSS software and compared by t-test. RESULTS: Breast dose by split scanning technique reduced 11% and 31% in SS- and MS- CT. Also, the radiation dose of lung tissue in this method decreased 18% and 54% in SS- and MS- CT, respectively. Moreover, there was a significant difference (p< 0.0001) in the breast and lung radiation doses between standard and split scanning protocols. CONCLUSION: The application of a split scan technique instead of standard protocol has a considerable potential to reduce breast and lung doses in SS- and MS- CT scanners. If split scanning protocol is associated with an optimum kV and MSCT, the maximum dose decline will be provided.

Biochemical characterization and stability assessment of Rhizopus oryzae lipase covalently immobilized on amino-functionalized magnetic nanoparticles.

Amino-functionalized magnetic nanoparticles (Fe3O4) have been investigated as a support for covalent immobilization of lipase. The nanoparticles were prepared by chemical coprecipitation method and subsequently were coated with 3-aminopropyltriethoxysilane (APTES) via silanization reaction. With glutaraldehyde, as the coupling agent, the lipase from Rhizopus oryzae was successfully immobilized onto the amino-functionalized magnetic nanoparticles. The synthesized support was characterized by transmission electron microscopy and Fourier transform infrared spectroscopy. The results showed that the load of immobilized protein could reach as high as 7mg protein g-1 support. The optimum pH for maximal catalytic activity of the immobilized enzyme was 8.0 at 40°C. The Km values were found as 0.66 and 0.57mgmL-1 for the free and immobilized enzymes, respectively. The Vmax values for the free and immobilized enzymes were calculated as 0.14 and 0.47µmolmg-1min-1, in turn, when p-nitrophenyl butyrate (pNPB) was used as the substrate. A quick separation of lipase from the reaction mixture was achieved when a magnetically active support was applied. In comparison to the free enzyme, the immobilized enzyme was thermally stable and was reusable for 10 cycles while retaining 64% of its initial activity.

Molecular epidemiology and characteristics of 16 cases with Stenotrophomonas maltophilia bacteraemia in pediatric Intensive Care Units.

BACKGROUND: Recently, Stenotrophomonas maltophilia has increasingly been reported as an important nosocomial opportunistic pathogen. Limited therapeutic options of S. maltophilia infections demand early identification and knowledge about the probable risk factors for controlling its spread. STUDY DESIGN: The present study aimed to investigate the risk factors and trend of antibiotic susceptibility, along with genetic analysis in bacteraemia cases at pediatric intensive care units (PICUs). METHODS: A total of 16 S. maltophilia isolates were obtained, during 4 months from August to November 2015, from blood cultures of patients admitted to PICUs at Nemazee teaching hospital, Shiraz, Iran. S. maltophilia isolates were identified by conventional tests and confirmed by specific PCR primers. Minimum inhibitory concentrations (MICs) were determined by the MIC strip test as described by the Clinical and Laboratory Standards Institute's (CLSI) recommendation. The genetic relatedness among the isolates was assessed by ERIC-PCR. RESULTS: All isolates of S. maltophilia were susceptible to ciprofloxacin, co-trimoxazole and colistin, and only 1 (6.2%) isolate was resistant against ceftazidime. The MIC50/MIC90 of ciprofloxacin, trimethoprim/sulfamethoxazole, colistin and ceftazidime was 0.25/0.38 mg/mL, 0.125/0.19 mg/mL, 0.25/0.38 mg/mL, and 2/4 mg/mL, respectively. Genotypic analysis of ERIC-PCR results revealed two distinct types of pattern. Interestingly, the only ceftazidime resistant isolate showed different patterns with other isolates. CONCLUSIONS: Our findings indicated the importance of routine surveillance in infection control, since early detection of pathogens prevented the spread of nosocomial infections and granted effectiveness to care practices. Moreover, the results suggest that the routine drug of choice for S. maltophilia was mostly active against clinical isolates in our region.

Role of glycogen synthase kinase following myocardial infarction and ischemia-reperfusion.

Glycogen synthase kinase-3 beta (GSK3ß) is principally is a glycogen synthase phosphorylating enzyme that is well known for its role in muscle metabolism. GSK3ß is a serine/threonine protein Kinase, which is responsible for several essential roles in mammalian cells. This enzyme is implicated in the pathophysiology of many conditions involved in homeostasis and cellular immigration. GSK3ß is involved in several pathways leading to neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Increasing evidence has shown the potential importance of GSK3ß in ischemic heart disease and ischemia-reperfusion pathologies. Reperfusion injury may occur in tissues after prolonged ischemia following reperfusion. Reperfusion injury can be life threatening. Reperfusion injury occurs due to a change in ionic homeostasis, excess free radical production, mitochondrial damage and cell death. There are however clear, cardiac-protective signals; although the molecular pathophysiology is not clearly understood. In normal physiology, GSK3ß has a critical role in the cytoprotective pathway. However, it`s controversial role in ischemia and ischemia-reperfusion is a topic of current interest. In this review, we have opted to focus on GSK3ß interactions with mitochondria in ischemic heart disease and expand on the therapeutic interventions.

Characterization of virulence genes, serogroups and antimicrobial susceptibility of Shiga toxin producing Escherichia coli isolated from bovine mastitic milk in Tehran, Iran.

Clinical mastitis caused by Enterobacteriaceae accounts for significant economic loss in dairy herds. One of the important pathogens that causes mastitis is Shiga toxinproducing Escherichia coli (STEC). Moreover, mastitis caused by STEC can be considered as a source of transmission of STEC strains to humans through unpasteurized milk. The aim of the current study was to determine of the prevalence, the identification of serogroups, the molecular characterization of virulence factors, and the antibiotic resistance properties of STEC isolates from bovine mastitic milk in dairy cattle in Tehran. A total of 325 milk samples from dairy cattle with clinical signs of mastitis were collected. All E. coli isolates (n: 87, 26.7%) were subjected to multiplex PCR for the detection of stx1, stx2, eaeA, and ehly genes and serogroups. Antibiotic susceptibility testing was carried out by the disc diffusion method for all the STEC isolates. Eighty-seven (26.8%) E. coli and 9 (2.8%) STEC strains were isolated from the bovine mastitic milk samples. Shiga-like toxin genes (stx1 and stx2 or one of them), eaeA and ehly were detected in 100%, 66.6%, and 33.3% of STEC isolates, respectively. O26 (22.2%) and O111 (22.2%) were the most commonly detected STEC serogroups. Other serogroups included O145, O121, O128, O157 and O113. High resistance rate to ampicillin and tetracycline (100%) was observed, followed by trimethoprim/sulfamethoxazole (66.6%) and chloramphenicol (55.5%). STEC isolates were found in bovine mastitic milk in Tehran and most of the STEC isolates in our study were non-O157 strains.

Efficient Immobilization of Porcine Pancreatic α-Amylase on Amino-Functionalized Magnetite Nanoparticles: Characterization and Stability Evaluation of the Immobilized Enzyme.

The potential of the modified magnetic nanoparticles for covalent immobilization of porcine pancreatic α-amylase has been investigated. The synthesis and immobilization processes were simple and fast. The co-precipitation method was used for synthesis of magnetic iron oxide (Fe3O4) nanoparticles (NPs) which were subsequently coated with silica through sol-gel reaction. The amino-functionalized NPs were prepared by treating silica-coated NPs with 3-aminopropyltriethoxysilane followed by covalent immobilization of α-amylase by glutaraldehyde. The optimum enzyme concentration and incubation time for immobilization reaction were 150 mg and 4 h, respectively. Upon this immobilization, the α-amylase retained more than 50 % of its initial specific activity. The optimum pH for maximal catalytic activity of the immobilized enzyme was 6.5 at 45 °C. The kinetic studies on the immobilized enzyme and its free counterpart revealed an acceptable change of Km and Vmax. The Km values were found as 4 and 2.5 mM for free and immobilized enzymes, respectively. The Vmax values for the free and immobilized enzymes were calculated as 1.75 and 1.03 µmol mg-1 min-1, in order, when starch was used as the substrate. A quick separation of immobilized amylase from reaction mixture was achieved when a magnetically active support was applied. In comparison to the free enzyme, the immobilized enzyme was thermally stable and was reusable for 9 cycles while retaining 68 % of its initial activity.

Colonization Rate and Risk Factors of Vancomycin-Resistant Enterococci among Patients Received Hematopoietic Stem Cell Transplantation in Shiraz, Southern Iran.

BACKGROUND: Infections caused by antimicrobial-resistant bacteria are associated with increased mortality and health care costs. Enterococci have been recognized as a clinically important pathogen in hospitalized patients. Vancomycin-resistant enterococci (VRE) infections cause significant morbidity and mortality among patients undergoing transplantation. OBJECTIVE: To identify epidemiology of VRE colonization and related risk factors among patients with hematological malignancies after hematopoietic stem cell transplantation (HSCT). METHODS: This cross-sectional study was performed on 42 patients who underwent bone-marrow transplantation between July 2013 and March 2014. A stool sample was taken from each patient 3-5 days after transplantation and cultured on appropriate media. Suspected colonies of enterococci were detected to species level by their culture characteristics, biochemical reactions and molecular features. VRE were confirmed via phenotypic and genotypic methods. RESULTS: VRE were detected in 14 (33%) of studied samples. 10 (71%) of the detected VRE isolates were identified as high level vancomycin-resistant E. faecium with minimum inhibitory concentration (MIC) of ≥256 µg/mL of vancomycin; 3 isolates were E. galinarum and 1 was E. casseliflavus with an MIC of 8-16 µg/mL. VanA was dominant phenotype and all VRE isolates with high-level of vancomycin resistance had vanA gene. VRE isolation was mostly observed in patients with acute lymphoblastic leukemia (ALL) than other diseases. Moreover, antibiotic prophylaxis and hospitalization were independent risk factors for acquisition of VRE after transplantation. CONCLUSION: We found high level of vancomycin-resistance in E. faecium isolates obtained from HSCT patients. The vancomycin-resistant isolates of E.faecium had vanA and/or simultaneously vanB genes.

Quantitative Tomography of Organic Photovoltaic Blends at the Nanoscale.

The success of semiconducting organic materials has enabled green technologies for electronics, lighting, and photovoltaics. However, when blended together, these materials have also raised novel fundamental questions with respect to electronic, optical, and thermodynamic properties. This is particularly important for organic photovoltaic cells based on the bulk heterojunction. Here, the distribution of nanoscale domains plays a crucial role depending on the specific device structure. Hence, correlation of the aforementioned properties requires 3D nanoscale imaging of materials domains, which are embedded in a multilayer device. Such visualization has so far been elusive due to lack of contrast, insufficient signal, or resolution limits. In this Letter, we introduce spectral scanning transmission electron tomography for reconstruction of entire volume plasmon spectra from rod-shaped specimens. We provide 3D structural correlations and compositional mapping at a resolution of approximately 7 nm within advanced organic photovoltaic tandem cells. Novel insights that are obtained from quantitative 3D analyses reveal that efficiency loss upon thermal annealing can be attributed to subtle, fundamental blend properties. These results are invaluable in guiding the design and optimization of future devices in plastic electronics applications and provide an empirical basis for modeling and simulation of organic solar cells.

Nafion/lead nitroprusside nanoparticles modified carbon ceramic electrode as a novel amperometric sensor for L-cysteine.

This work describes the electrochemical and electrocatalytic properties of carbon ceramic electrode (CCE) modified with lead nitroprusside (PbNP) nanoparticles as a new electrocatalyst material. The structure of deposited film on the CCE was characterized by energy dispersive X-ray (EDX), Fourier transform infrared (FTIR), and scanning electron microscopy (SEM). The cyclic voltammogram (CV) of the PbNP modified CCE showed two well-defined redox couples due to [Fe(CN)5NO](3-)/[Fe(CN)5NO](2-) and Pb(IV)/Pb(II) redox reactions. The modified electrode showed electrocatalytic activity toward the oxidation of L-cysteine and was used as an amperometric sensor. Also, to reduce the fouling effect of L-cysteine and its oxidation products on the modified electrode, a thin film of Nafion was coated on the electrode surface. The sensor response was linearly changed with L-cysteine concentration in the range of 1 x 10(-6) to 6.72 x 10(-5)mol L(-1) with a detection limit (signal/noise ratio [S/N]=3) of 0.46 microM. The sensor sensitivity was 0.17 microA (microM)(-1), and some important advantages such as simple preparation, fast response, good stability, interference-free signals, antifouling properties, and reproducibility of the sensor for amperometric determination of L-cysteine were achieved.

The incidence and risk factors of delayed graft function in 689 consecutive living unrelated donor renal transplantation.

Due to the severe shortage of deceased donor kidneys, the number of renal transplantation from living-related and living-unrelated donors has increased worldwide. The incidence and risk factors of delayed graft function after deceased donor renal transplantation have been extensively studied. In this analysis, the incidence and predictors of delayed graft function was investigated in 689 living-unrelated kidney recipients. In 53 recipients, dialysis was needed within the first week after renal transplantation (7.7%). The risk factors for delayed graft function upon univariate analysis models were: female gender of kidney donor (P=.027), renal allograft with multiple arteries (P=.005) and previous transplantation (P<.005). Upon multivariate analysis, the only risk factor for development of delayed graft function was retransplantation (P=.001).

Specificity of signaling by STAT1 depends on SH2 and C-terminal domains that regulate Ser727 phosphorylation, differentially affecting specific target gene expression.

Complete activation of signal transducer and activator of transcription 1 (STAT1) requires phosphorylation at both Y701 and a conserved PMS(727)P sequence. S727 phosphorylation of STAT1 in interferon-gamma (IFN-gamma)-treated mouse fibroblasts occurred without a need for p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinases 1 and 2 or c-Jun kinases, and required both an intact SH2 domain and phosphorylation of Y701. In contrast, UV irradiation-induced STAT1 phosphorylation on S727 required p38MAPK, but no SH2 domain- phosphotyrosine interactions. Mutation of S727 differentially affected IFN-gamma target genes, at the level of both basal and induced expression. Particularly strong effects were noted for the GBP1 and TAP1 genes. The PMS(727)P motif of STAT3 was phosphorylated by stimuli and signaling pathways different from those for STAT1 S727. Transfer of the STAT3 C-terminus to STAT1 changed the stimulus and pathway specificity of STAT1 S727 phosphorylation to that of STAT3. Our data suggest that STAT C-termini contribute to the specificity of cellular responses by linking individual STATs to different serine kinase pathways and through an intrinsically different requirement for serine phosphorylation at different target gene promoters.