An Industry Proposal for a Cell and Gene Therapy Safety Data Sheet.

Introduction: A safety data sheet (SDS) is an established hazard communication tool for chemicals, for which no comparable document exists in the biotherapeutics industry. As the cell and gene therapy (CGT) field expands, industry leaders have identified a growing need to address this gap in communication of the unique occupational health and safety risks posed by CGT materials and products. Methods: Following the sections of a traditional chemical SDS, information was modified by industry subject matter experts, relevant to CGT biological materials. This guide was developed based on assumptions of a maximum biosafety level 2, and any chemical components present in the material were excluded from the hazard classification. Results: The guide contains necessary information to conduct a workplace risk assessment and communicate the unique workplace hazards posed by potential exposures to the material. The target audience is intended to be entities handling and producing these materials, plus collaborators, contractors, or operations sites receiving and handling the CGT material. An example of a CGT SDS is provided in Table 1. Discussion: The CGT SDS provides industry with a best practice to address an existing gap in hazard communication for CGT. We expect that, as the field evolves, so may the contents. The CGT SDS can be used as a reference for other biological modalities in the field. Conclusions: This initial CGT SDS communicates workplace hazards and assesses the unique risks posed by these biological materials and can assist in creating exposure control plans specific to the workplace hazards.

Steel slag as a potential adsorbent for efficient removal of Fe(II) from simulated acid mine drainage: adsorption performance and mechanism.

Acid mine drainage is an extraordinarily acidic and highly heavy metal ion-contaminated leachate, seriously threatening the environment. In this work, an industrial solid waste of steel slag is the adsorbent to remediate the simulated acid mine drainage containing a large amount of Fe(II) ions. Due to the excellent physicochemical properties and structures, steel slag exhibited remarkable Fe(II) removal performance. Its maximum removal efficiency was up to 100%. The initial pH, the dosage and particle size of steel slag, and initial concentration of heavy metal ions on Fe(II) removal efficiency were determined. The pseudo-second-order model and Freundlich isotherm model well described the adsorption behavior of steel slag, implying that the adsorption of Fe(II) by steel slag was mainly multilayer chemisorption. The thermodynamic study demonstrated that the adsorption process was endothermic and spontaneous; the enthalpy change was calculated to equal 91.21 kJ/mol. Mechanism study showed that the entire removal process of Fe(II) by steel slag was completed by electrostatic adsorption, chemical precipitation, and surface complexation in cooperation, and the chemical precipitation was the dominant mechanism. Meaningfully, this study provides a valuable strategy and path for engineering applications of AMD remediation by steel slag, which is prospective as an ideal candidate for Fe(II) ions elimination, inspiring the future development of "Treating the wastes with wastes."

Synergistic removal of dust using the wet flue gas desulfurization systems.

Coal is still a major energy source, mostly used in power plants. However, the coal combustion emits harmful SO2 and fly ash. Wet flue gas desulfurization (WFGD) technology is extensively used to control SO2 emissions in power plants. However, only limited studies have investigated the synergistic dust removal by the WFGD system. Spray scrubbers and sieve-tray spray scrubbers are often used in WFGD systems to improve the SO2 removal efficiency. In this study, the synergistic dust removal of WFGD systems for a spray scrubber and a sieve-tray spray scrubber was investigated using the experimental and modelling approaches, respectively. For the spray scrubber, the influence of parameters, including dust particle diameters and inlet concentrations of dust particles, and the flow rates of flue gas and slurry of limestone/gypsum on the dust removal efficiency, was investigated. For the sieve-tray spray scrubber, the influence of parameters such as the pore diameter and porosity of sieve trays on the dust removal efficiency was examined. The study found that the dust removal efficiency in the sieve-tray spray scrubber was approximately 1.1-10.6% higher than that of the spray scrubber for the same experimental conditions. Based on the parameters investigated and geometric parameters of a scrubber, a novel droplets swarm model for dust removal efficiency was developed from the single droplet model. The enhanced dust removal efficiency of sieve tray was expressed by introducing a strength coefficient to an inertial collision model. The dust removal efficiency model for the sieve-tray spray scrubber was developed by combining the droplets swarm model for the spray scrubber with the modified inertial collision model for the sieve tray. The results simulated using both models are consistent with the experimental data obtained.

In vitro effect of adenosine on the mRNA expression of Kir 2.1 and Kir 4.1 channels in rat retinal Müller cells at elevated hydrostatic pressure.

The aim of this study was to investigate the expression of Kir 2.1 and Kir 4.1 channels at an elevated hydrostatic pressure in vitro, and to determine whether adenosine may modulate the mRNA expression of Kir 2.1 and Kir 4.1 channels in retinal Müller cells at an elevated hydrostatic pressure in vitro. Müller cells treated with 1 µM adenosine at 40 mmHg/24 h, and mRNA expression of Kir 2.1 and Kir 4.1 channels were examined using real-time PCR. Müller cells significantly increased the mRNA expression of Kir 2.1 and Kir 4.1 channels at 40 mmHg/24 h. When further treated with 1 µM adenosine at 40 mmHg/24 h, the mRNA expression of the Kir 2.1 channels decreased, while the mRNA expression of the Kir 4.1 channels continued to increase. When the pressure was elevated, Müller cells were still able to take up K(+) and mediate the potassium concentration of the retina. Adenosine upregulated the expression of the Kir 4.1 channels, but weakly affected the expression of the Kir 2.1 channels.

Effect of A(2A) receptor antagonist (SCH 442416) on the mRNA expression of glutamate aspartate transporter and glutamine synthetase in rat retinal Müller cells under hypoxic conditions in vitro.

The purpose of the present study was to investigate the effect of the A(2A) receptor antagonist (SCH 442416) on the mRNA expression of glutamate aspartate transporter (GLAST) and glutamine synthetase (GS) in rat retinal Müller cells under hypoxic conditions in vitro. Immunofluorescent staining of GS and GFAP was used for the identification of Müller cells. The GLAST and GS mRNA expression of Müller cells treated with 0.1, 1 and 10 µM SCH 442416 under hypoxic conditions was examined by real-time PCR. Müller cells increased the mRNA expression of GLAST under hypoxic conditions; those treated with 0.1 µM SCH 442416 showed a further significant increase in the mRNA expression of GLAST in vitro. Although the mRNA expression of GS was decreased under hypoxic conditions, the mRNA expression was increased when Müller cells were treated with 0.1 µM SCH 442416. A(2A) receptor antagonist increased the GLAST and GS expression of Müller cells and accelerated the clearance of extracellular glutamate under hypoxic conditions in vitro.

Topical anesthesia versus regional anesthesia for cataract surgery: a meta-analysis of randomized controlled trials.

PURPOSE: To examine possible differences in the clinical outcomes of topical anesthesia (TA) and regional anesthesia including retrobulbar anesthesia (RBA) and peribulbar anesthesia (PBA) in phacoemulsification. DESIGN: Systematic review and meta-analysis. PARTICIPANTS: Patients from previously published randomized controlled trials (RCTs) of phacoemulsification under TA and RBA/PBA reporting clinical outcomes. METHODS: A comprehensive literature search was performed according to the Cochrane Collaboration method to identify RCTs that compare TA and RBA/PBA in phacoemulsification. MAIN OUTCOME MEASURES: Primary outcome parameters investigated were pain score during and after surgery, intraoperative difficulties and inadvertent ocular movement, intraoperative necessity to administer additional anesthesia, and patient preference. Secondary outcome parameters investigated were postoperative visual acuity, anesthesia-related complications, intraoperative complications, and severe local or systemic complications. RESULTS: Fifteen studies were identified and analyzed to compare TA (1084 eyes) with RBA/PBA (1121 eyes) in phacoemulsification. Data synthesis showed that intraoperative and postoperative pain perception was significantly higher in the TA group (P < 0.05). The TA group showed more frequent inadvertent ocular movement (P < 0.05) and a greater intraoperative need for supplementary anesthesia (P = 0.03). There was no statistically significant difference between the 2 groups in intraoperative difficulties as assessed by the surgeons (P > 0.05). Patients significantly preferred TA (P < 0.00001). The RBA/PBA group had more frequent anesthesia-related complications, such as chemosis, periorbital hematoma, and subconjunctival hemorrhage (P < 0.05). There was no statistically significant difference in surgery-related complications (P > 0.05). CONCLUSIONS: Compared with RBA/PBA, TA does not provide the same excellent pain relief in cataract surgery; however, it achieves similar surgical outcomes. Topical anesthesia reduces injection-related complications and alleviates patients' fear of injection. The choice of TA is not suitable for patients with a higher initial blood pressure or greater pain perception.

Microchip-based macroporous silica sol-gel monolith for efficient isolation of DNA from clinical samples.

Effective microchip extraction of deoxyribonucleic acid (DNA) from crude biological matrixes has been demonstrated using silica beads or hybrid phases composed of beads and sol-gel. However, the use of monolithic sol-gels alone for extraction of human genomic DNA has been more difficult to define. Here we describe, for the first time, the successful use of monolithic tetramethyl orthosilicate-based sol-gels for effective micro-solid-phase extraction (muSPE) of DNA in a glass microchip format. A functional monolithic silica phase with micrometer-scale pores in the silica matrix resulted from addition of poly(ethylene glycol), a poragen, to the precursor mixture. This allowed a monolithic sol-gel bed to be established in a microchip channel that provided large surface area for DNA extraction with little flow-induced back pressure. DNA extraction efficiencies for simple systems (lambda-phage DNA) were approximately 85%, while efficiencies for the reproducible extraction of human genomic DNA from complex biological matrixes (human blood) were approximately 70%. Blockage of the sol-gel pores by components in the lysed blood was observed in repeat extraction on a single device as a decrease in the extraction efficiency. The developed muSPE protocol was further evaluated to show applicability to clinical samples and bacterial cultures, through extraction of PCR-amplifiable DNA.

Metal complex-substituted polysiloxanes as novel coatings for capillary electrophoresis and capillary electrochromatography.

Two novel polysiloxane-based polymers, which contain metal complexes, have been prepared. To prepare the Co(TACN)3+(2) (TACN= 1,4,7-triazacyclononane) based polymers, an orthoamide derivative of TACN was added to bromobutane-substituted methylpolysiloxane and hydrolyzed with base. Co(II) was then coordinated to the TACN, followed by cobalt oxidation to make polymer A or followed by N-octyl TACN coordination and cobalt oxidation to make polymer B. In both materials, TACN forms thermodynamically and kinetically stable Co(TACN)3+(2) complexes in which the six coordination sites of the Co(III) are occupied by nitrogens from the TACN. The polymers were coated on fused-silica capillary columns and spherical silica particles, which were used for capillary electrophoresis and capillary electrochromatography, respectively. The open and packed columns showed strong and pH-independent reversed electroosmotic flow.

Performance of metal complex substituted polysiloxanes in capillary electrophoresis and capillary electrochromatography.

Two novel polysiloxanes containing the metal complex, Co(TACN)(3+)2 (TACN= 1,4,7-triazacyclononane) were used as coatings for capillary electrophoresis (CE) and capillary electrochromatography (CEC). Through crosslinking and covalent bonding, the positively charged polymers were bonded to silica supports. In both CE and CEC, these coatings exhibited strong, pH-independent, and anodic electroosmotic flow (EOF), and had excellent long-term stability. Successful separations of aromatic acids were achieved in CE. In CEC, separation of alkylbenzenes (7 min) and basic compounds (20 min) was achieved with higher resolving power than conventional octadecyl silica packings. These polymers represent a new class of coatings for CE and CEC that generate pH-independent EOF.