Prion removal capacity of plasma protein manufacturing processes

BACKGROUND The variant Creutzfeldt-Jakob disease incidence peaked a decade ago and has since declined. Based on epidemiologic evidence, the causative agent, pathogenic prion, has not constituted a tangible contamination threat to large-scale manufacturing of human plasma-derived proteins. Nonetheless, manufacturers have studied the prion removal capabilities of various manufacturing steps to better understand product safety. Collectively analyzing the results could reveal experimental reproducibility and detect trends and mechanisms driving prion removal. STUDY DESIGN AND METHODS Plasma Protein Therapeutics Association member companies collected more than 200 prion removal studies on plasma protein manufacturing steps, including precipitation, adsorption, chromatography, and filtration, as well as combined steps. The studies used a range of model spiking agents and bench-scale process replicas. The results were grouped based on key manufacturing variables to identify factors impacting removal. The log reduction values of a group are presented for comparison. RESULTS Overall prion removal capacities evaluated by independent groups were in good agreement. The removal capacity evaluated using biochemical assays was consistent with prion infectivity removal measured by animal bioassays. Similar reduction values were observed for a given step using various spiking agents, except highly purified prion protein in some circumstances. Comparison between combined and single-step studies revealed complementary or overlapping removal mechanisms. Steps with high removal capacities represent the conditions where the physiochemical differences between prions and therapeutic proteins are most significant. CONCLUSION The results support the intrinsic ability of certain plasma protein manufacturing steps to remove prions in case of an unlikely contamination, providing a safeguard to products.

Uranium mining industry views on ICRP statement on radon

In 2009, the International Commission on Radiological Protection issued a statement on radon which stated that the dose conversion factor for radon progeny would likely double, and the calculation of risk from radon should move to a dosimetric approach, rather than the longstanding epidemiological approach. Through the World Nuclear Association, whose members represent over 90% of the world's uranium production, industry has been examining this issue with a goal of offering expertise and knowledge to assist with the practical implementation of these evolutionary changes to evaluating the risk from radon progeny. Industry supports the continuing use of the most current epidemiological data as a basis for risk calculation, but believes that further examination of these results is needed to better understand the level of conservatism in the potential epidemiological-based risk models. With regard to adoption of the dosimetric approach, industry believes that further work is needed before this is a practical option. In particular, this work should include a clear demonstration of the validation of the dosimetric model which includes how smoking is handled, the establishment of a practical measurement protocol, and the collection of relevant data for modern workplaces. Industry is actively working to address the latter two items.

PVR recurrence and the timing of silicon oil removal

BACKGROUND: Following vitrectomy for PVR-associated retinal detachment, placement of an encircling band, filling with silicone oil (SO) and successful retinal reattachment, a recurrence of PVR can develop. Retinal redetachment after SO removal is usually due to secondary or residual PVR. We wanted to ascertain whether the anatomical and functional outcomes of surgery in patients with a reattached retina and recurrent PVR can be improved by delaying the removal of SO. PATIENTS AND METHODS: 112 consecutive patients with PVR-associated retinal detachment who had undergone vitrectomy with SO filling, were monitored for at least 6 months after SO removal. Prior to SO removal, the retina posterior to the encircling band had to be completely reattached. Patients who developed PVR after SO filling were divided into two groups according to the duration of SO retention: 12 - 18 months (group 2: n = 48); > 18 months (group 3: n = 21). Individuals without PVR recurrence after SO filling and in whom the SO was consequently removed within 4 - 12 months served as control (group 1: n = 43). Anatomical success, intraocular pressure (IOP) and best-corrected visual acuity (BCVA) served as the primary clinical outcome parameters. RESULTS: Six months after SO removal, the anatomical success rates (86.3 %, 88.8 % and 84.6 %, in groups 1, 2 and 3, respectively; log rank = 0.794) and the BCVAs (p = 0.861) were comparable in the three groups. Mean IOP (p = 0.766), and the frequency of complications such as PVR recurrence (p = 0.936), bullous keratopathy (p = 0.981) and macular pucker (p = 0.943) were likewise similar. Patients in whom SO was retained for more than 18 months had the highest IOPs and required the heaviest dosage with anti-glaucoma drugs. CONCLUSIONS: In patients who develop a recurrence of PVR after vitrectomy and SO filling the surgeon can observe and treat retinal changes for up to 18 months without impairing the anatomical and functional outcomes. The retention of SO for more than 18 months does not improve the anatomical outcome. However, it can impair the functional outcome by precipitating the development of a persisting secondary glaucoma.

[Complications during and after surgical removal of mandibular third molars. Impact of patient related and anatomical factors]

The estimation of possible intra- and postoperative complications for surgical removal of third molars in the mandible poses a frequent dilemma in oral surgery. In the present study, the influence of the patient's age and gender, a reduced mouth opening, and the anatomical position of the tooth in the mandible on intra- and postoperative complications were evaluated. In a total of 120 surgically removed third molars, 9.2% intraoperative complications occurred, mainly bleeding. Factors influencing the risk for intraoperative complications were a male patient, a reduced mouth opening, and distally angulated teeth. Postoperative complications were encountered in 6.7%, mainly dry sockets. For this group, a female gender, a higher age, and distally angulated teeth were identified as risk parameters. As most of the patient- and anatomy-related factors are set parameters when evaluating possible risk factors for third molar surgery, only the timepoint of surgery can be influenced by the surgeon. Regarding the increase in intra- and postoperative complications for third molar removal in higher age groups, the prophylactic third molar surgery between the age of 18 and 25 seems justified.

Effect of transcutaneous electrical muscle stimulation and passive cycling movements on blood pressure and removal of urea and phosphate during hemodialysis

BACKGROUND: Intradialytic exercise has been described to improve blood pressure stability and dialysis efficacy. However, comorbid conditions in the dialysis population often preclude the widespread use of active intradialytic exercise. Therefore, we investigated the effect of intradialytic transcutaneous muscle stimulation (TEMS) and passive cycling movements (PCMs) on blood pressure and dialysis efficacy in patients. STUDY DESIGN: Prospective, controlled, randomized, crossover investigation. SETTING ; PARTICIPANTS: Ten patients were randomly allocated to TEMS, PCMs, or no intervention (NI) for 9 consecutive dialysis sessions. INTERVENTION: Participants were studied with NI, PCMs using a motor-driven ergometer, and bilateral TEMS of the leg musculature. Individual dialysis prescriptions were unchanged during the investigation. OUTCOMES ; MEASUREMENTS: The effect of TEMS and PCMs on blood pressure and dialysis efficacy in patients was assessed. RESULTS: Mean blood pressure increased from 121/64 +/- 21/15 mm Hg with NI to 132/69 +/- 21/15 mm Hg (P < 0.001) during sessions with PCMs and 125/66 +/- 22/16 mm Hg (P < 0.05) during sessions with TEMS. Urea and phosphate removal during dialysis were significantly (P < 0.001) greater with TEMS (19.4 +/- 3.7 g/dialysis and 1,197 +/- 265 mg/dialysis) or PCMs (20.1 +/- 3.4 g/dialysis and 1,172 +/- 315 mg/dialysis) than with NI (15.1 +/- 3.9 g/dialysis and 895 +/- 202 mg/dialysis). Body weight, ultrafiltration, Kt/V, and increases in hemoglobin and albumin levels during dialysis did not differ among the NI, PCMs, and TEMS groups. LIMITATIONS: The study design does not allow extension of the findings to prolonged treatment. CONCLUSION: Future studies during longer observation periods will have to prove the persistence of these acute findings. Both TEMS and PCMs deserve future investigations in dialysis patients because they increase intradialytic blood pressure and facilitate urea and phosphate removal when applied short term.

Electrospun chitosan nanofibers for virus removal

Electrospinning uses electrostatic forces to create nanofibers that are far smaller than conventional fiber spinning process. Nanofibers made with chitosan were created and techniques to control fibers diameter and were well developed. However, the adsorption of porcine parvovirus (PPV) was low. PPV is a small, nonenveloped virus that is difficult to remove due to its size, 18-26 nm in diameter, and its chemical stability. To improve virus adsorption, we functionalized the nanofibers with a quaternized amine, forming N-[(2-hydroxy-3-trimethylammonium) propyl] chitosan chloride (HTCC). This was blended with additives to increase the ability to form HTCC nanofibers. The additives changed the viscosity and conductivity of the electrospinning solution. We have successfully synthesized and functionalized HTCC nanofibers that absorb PPV. HTCC blend with graphene have the ability to remove a minimum of 99% of PPV present in solution.

Hydrogeochemical controls on uranium in aquifers of the Jacobsville Sandstone

The occurrence of elevated uranium (U) in sandstone aquifers was investigated in the Upper Peninsula of Michigan, focusing on aquifers of the Jacobsville Sandstone. The hydrogeochemical controls on groundwater U concentrations were characterized using a combination of water sampling and spectral gamma-ray logging of sandstone cliffs and residential water wells. 235U/238U isotope ratios were consistent with naturally occurring U. Approximately 25% of the 270 wells tested had U concentrations above the U.S. Environmental Protection Agency Maximum Contaminant Level (MCL) of 30 μg/L, with elevated U generally occurring in localized clusters. Water wells were logged to determine whether groundwater U anomalies could be explained by the heterogeneous distribution of U in the sandstone. Not all wells with relative U enrichment in the sandstone produced water with U above the MCL, indicating that the effect of U enrichment in the sandstone may be modified by other hydrogeochemical factors. Well water had high redox, indicating U is in its highly soluble (VI) valence. Equilibrium modeling indicated that aqueous U is complexed with carbonates. In general, wells with elevated U concentrations had low 235U/238U activity ratios. However, in some areas U concentrations and 235U/238U activity ratios were simultaneously high, possibly indicating differences in rock-water interactions. Limited groundwater age dating suggested that residence time may also help explain variations in well water U concentrations. Low levels of U enrichment (4 to 30 ppm) in the Jacobsville sandstone may make wells in its oxidized aquifers at risk for U concentrations above the MCL. On average, U concentrations were highest in heavy mineral and clay layers and rip up conglomerates. Uranium concentrations above 4 ppm also occurred in siltstones, sandstones and conglomerates. Uranium enrichment was likely controlled by deposition processes, sorption to clays, and groundwater flow, which was controlled by permeability variations in the sandstone. Low levels of U enrichment were found at deltaic, lacustrine and alluvial fan deposits and were not isolated to specific depositional environments.

Fluidic oscillator design for water removal enhancement in a PEM fuel cell

This research initiative was triggered by the problems of water management of Polymer Electrolyte Membrane Fuel Cell (PEMFC). In low temperature fuel cells such as PEMFC, some of the water produced after the chemical reaction remains in its liquid state. Excess water produced by the fuel cell must be removed from the system to avoid flooding of the gas diffusion layers (GDL). The GDL is responsible for the transport of reactant gas to the active sites and remove the water produced from the sites. If the GDL is flooded, the supply gas will not be able to reach the reactive sites and the fuel cell fails. The choice of water removal method in this research is to exert a variable asymmetrical force on a liquid droplet. As the drop of liquid is subjected to an external vibrational force in the form of periodic wave, it will begin to oscillate. A fluidic oscillator is capable to produce a pulsating flow using simple balance of momentum fluxes between three impinging jets. By connecting the outputs of the oscillator to the gas channels of a fuel cell, a flow pulsation can be imposed on a water droplet formed within the gas channel during fuel cell operation. The lowest frequency produced by this design is approximately 202 Hz when a 20 inches feed-back port length was used and a supply pressure of 5 psig was introduced. This information was found by setting up a fluidic network with appropriate data acquisition. The components include a fluidic amplifier, valves and fittings, flow meters, a pressure gage, NI-DAQ system, Siglab®, Matlab software and four PCB microphones. The operating environment of the water droplet was reviewed, speed of the sound pressure which travels down the square channel was precisely estimated, and measurement devices were carefully selected. Applicable alternative measurement devices and its application to pressure wave measurement was considered. Methods for experimental setup and possible approaches were recommended, with some discussion of potential problems with implementation of this technique. Some computational fluid dynamic was also performed as an approach to oscillator design.