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Abstract Background: Therapeutic plasmapheresis (TP) is an extracorporeal therapy that allows the removal of pathogens from plasma. The role of TP in immuno-mediated diseases and toxic conditions has been of interest for decades. Summary: We reviewed the recent literature on the application and the optimal choice of TP technique ranging from plasma exchange, double filtration plasmapheresis, rheopheresis, immunoadsorptions, plasma adsorption perfusion and lipidoapheresis. In addition, we report our experience in the application of TP for various diseases ranging in different medical specialties, following the American Society for Apheresis (ASFA) recommendations. Key Messages: Overall patients receiving TP showed an improvement in clinical and laboratory parameters. Our review and single-center experience suggest a benefit of the application of TP in multiple clinical disciplines.

This study aimed to explore microbial aerosol distribution characteristics in the dental clinic during ultrasonic scaling and evaluate the effects of three different interventions on aerosol distribution and protective effects. For twenty minutes, ultrasonic scaling was carried out in a standardized operatory room. A blank control group and three intervention groups were created: high-volume evacuator (HVE), plasma purification (PP), and fenestrated ventilation (VT). The mass concentration of PM1.0, PM2.5, and PM10.0 aerosol particles was tracked in real time, and colony counts were calculated using air deposition. After ultrasonic scaling, there was a significant increase in aerosol dispersion of various particle sizes and distribution within a 1.5-m radius of the core area ( P  < 0.05). The number of colonies in each group varied over time at 0.5 and 1.0 m from the patient’s head, but there was no significant difference at 1.5 m ( P  > 0.05). The PP group demonstrated the greatest decrease in aerosol mass concentration difference. The VT group initially had the lowest aerosol mass concentration difference, but with a slight decrease. The aerosol mass concentration difference between the HVE groups grew with distance. Traditional ultrasonic scaling poses a risk of aerosol contamination during and after treatment. The operatory room’s air can be efficiently purified by plasma purification, which maintains lower levels of aerosol particle size than other groups. Microbial aerosols created by ultrasonic scaling can be quickly reduced by ventilation. At close range, the high-volume evacuator can lower the risk of infection while the benefit diminishes as the distance increases. Trial registration: This study was registered on the website of China Clinical Trial Registration Center (ChiCTR2400090751) (12/10/2024).

Complement factor H (FH) is a major regulator of the complement alternative pathway, its mutations predispose to an uncontrolled activation in the kidney and on blood cells and to secondary C3 deficiency. Plasma exchange has been used to correct for FH deficiency and although the therapeutic potential of purified FH has been suggested by experiments in animal models, a clinical approved FH concentrate is not yet available. We aimed to develop a purification process of FH from a waste fraction rather than whole plasma allowing a more efficient and ethical use of blood and plasma donations. Waste fractions from industrial plasma fractionation (pooled human plasma) were analyzed for FH content by ELISA. FH was purified from unused fraction III and its decay acceleration, cofactor, and C3 binding capacity were characterized Biodistribution was assessed by high-resolution dynamic PET imaging. Finally, the efficacy of the purified FH preparation was tested in the mouse model of C3 glomerulopathy (Cfh-/- mice). Our purification method resulted in a high yield of highly purified (92,07%), pathogen-safe FH. FH concentrate is intact and fully functional as demonstrated by functional assays. The biodistribution revealed lower renal and liver clearance of human FH in Cfh-/- mice than in wt mice. Treatment of Cfh-/- mice documented its efficacy in limiting C3 activation and promoting the clearance of C3 glomerular deposits. We developed an efficient and economical system for purifying intact and functional FH, starting from waste material of industrial plasma fractionation. The FH concentrate could therefore constitute possible treatments options of patients with C3 glomerulopathy, particularly for those with FH deficiency, but also for patients with other diseases associated with alternative pathway activation.

Background: Hyperlipidemia hypercholesterolemia [cholesterol >5.18 mmol/L) or hypertriglyceridemia [triglycerides >2.3 mmol/L], mixed hyperlipidemia [cholesterol >5.18 mmol/L and triglycerides >2.3 mmol/L], and high low-density lipoproteinemia [low-density lipoprotein (LDL) >3.4 mmol/L] is a strong risk factor for arteriosclerosis and cardiovascular disease (CVD). Therapy with lipid-lowering drugs often results in many side effects. Our study aimed to investigate the potential effects of non-drug therapy with double-filtration plasmapheresis (DFPP) on lipid metabolism-, endoplasmic reticulum (ER) stress-, and apoptosis-related proteins in peripheral blood mononuclear cells (PBMCs) before and after lipid clearance in patients with hyperlipidemia. Methods: Thirty-five hyperlipidemia patients were selected. Proteins related to lipid metabolism [CD36, proprotein convertase subtilisin/kexin type 9 (PCSK9), and LDL receptor], ER stress [glucose-regulated protein 78 (Grp78), C/EBP homologous protein (CHOP), activating transcription factor 4 (ATF4), and eukaryotic initiation factor 2α (EIF2α)], and apoptosis [B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (BAX), and cysteinyl aspartate specific proteinase-3 (Caspase-3)] were assayed by Western blot, reactive oxygen species (ROS) were measured by flow cytometry (FCM), and ELISA detected serum inflammatory [interleukin (IL)-1β, IL-6, and tumor necrosis factor α (TNF-α)] factors. Results: Compared with their pre-DFPP values, the values of most lipid metabolic parameters, such as cholesterol, triglycerides, LDL, lipoprotein a [Lp(a)], and small dense LDL (sdLDL) cholesterol, were reduced after DFPP. DFPP was associated with the downregulation of proteins related to lipid metabolism, ER stress, and apoptosis, resulting in decreased ROS and serum inflammatory factor release. Conclusion: DFPP has lipid-lowering activity and can also regulate lipid metabolism-, ER stress-, and apoptosis-related proteins in PBMCs and reduce the levels of inflammatory factors in patients with hyperlipidemia ( ClinicalTrials.gov number: NCT03491956).

Background The activity and purity of Fibrin Sealant Grifols are described in this article. This fibrin sealant contains two components (fibrinogen and thrombin) that mimic the final stages of clotting. Fibrin sealants are primarily used as an adjunct to hemostasis for mild to moderate surgical bleeding in adults when standard surgical techniques are ineffective or impractical. Objective The aim of these studies was to assess the biochemical and functional characteristics of Fibrin Sealant Grifols. Methods Total protein, plasma protein impurities, and molecular forms were analyzed for both components. Clottable fibrinogen and thrombin activity were also measured. Both components were analyzed by SDS-PAGE and Western blot. The fibrin sealant clot was functionally characterized. Results The components had minimal contamination by other plasma proteins and no aggregates or degradation products. The fibrinogen component was almost completely clottable fibrinogen. The thrombin component contains albumin. The fibrinogen component formed a fibrin polymer and clots with tensile strength similar to literature values. The application device applied the components in a 1:1 volume ratio. Clotting time was ∼ 5 s when applied with the drip tip and nearly instantaneous when applied with the airless spray apparatus. Conclusion This fibrin sealant was shown to contain highly purified fibrinogen and thrombin delivered in a 1:1 volume ratio. These properties contribute to the clinical safety and efficacy of this product for many applications.

IntroductionThere is controversy regarding the importance of air-transmitted infections for surgical site infections (SSIs) after orthopaedic surgery. Research has been hindered by both the inability in blinding the exposure, and by the need for recruiting large enough cohorts. The aim of this study is to investigate whether using a new form of air purifier using plasma air purification (PAP) in operating rooms (ORs) lowers the SSI rate or not.Methods and analysisMulticentre, double-blind, cluster-randomised, placebo-controlled trial conducted at seven hospitals in 2017–2022. All patients that undergo orthopaedic surgery for minimum 30 min are included. Intervention group: patients operated in OR with PAP devices turned on. Control group: patients operated in OR with PAP devices turned off. Randomisation: each OR will be randomised in periods of 4 weeks, 6 weeks or 8 weeks to either have the devices on or off. Primary outcome: any SSI postoperatively defined as a composite endpoint of any of the following: use of isoxazolylpenicillin, clindamycin or rifampicin for 2 days or more, International Classification of Diseases codes or Nordic Medico-Statistical Committee codes indicating postoperative infection. In a second step, we will perform a chart review on those patients with positive indicators of SSI to further validate the outcome. Secondary outcomes are described in the Methods section. Power: we assume an SSI rate of 2%, an SSI reduction rate of 25% and we need approximately 45 000 patients to attain a power of 80% at a significance level of 0.05.Ethics and disseminationThe study is approved by the Swedish Ethical Review Authority. The interim analysis results from the study will be presented only to the researchers involved unless the study thereafter is interrupted for whatever reason. Publication in a medical journal will be presented after inclusion of the last patient.Trial registration numberNCT02695368.

Seminal fluid proteins transferred from males to females during copulation are required for full fertility and can exert dramatic effects on female physiology and behavior. In Drosophila melanogaster, the seminal protein sex peptide (SP) affects mated females by increasing egg production and decreasing receptivity to courtship. These behavioral changes persist for several days because SP binds to sperm that are stored in the female. SP is then gradually released, allowing it to interact with its female-expressed receptor. The binding of SP to sperm requires five additional seminal proteins, which act together in a network. Hundreds of uncharacterized male and female proteins have been identified in this species, but individually screening each protein for network function would present a logistical challenge. To prioritize the screening of these proteins for involvement in the SP network, we used a comparative genomic method to identify candidate proteins whose evolutionary rates across the Drosophila phylogeny co-vary with those of the SP network proteins. Subsequent functional testing of 18 co-varying candidates by RNA interference identified three male seminal proteins and three female reproductive tract proteins that are each required for the long-term persistence of SP responses in females. Molecular genetic analysis showed the three new male proteins are required for the transfer of other network proteins to females and for SP to become bound to sperm that are stored in mated females. The three female proteins, in contrast, act downstream of SP binding and sperm storage. These findings expand the number of seminal proteins required for SP's actions in the female and show that multiple female proteins are necessary for the SP response. Furthermore, our functional analyses demonstrate that evolutionary rate covariation is a valuable predictive tool for identifying candidate members of interacting protein networks.

The dopamine transporter is a member of the neurotransmitter:sodium symporters (NSSs), which are responsible for termination of neurotransmission through Na + -driven reuptake of neurotransmitter from the extracellular space. Experimental evidence elucidating the coordinated conformational rearrangements related to the transport mechanism has so far been limited. Here we probe the global Na + - and dopamine-induced conformational dynamics of the wild-type Drosophila melanogaster dopamine transporter using hydrogen-deuterium exchange mass spectrometry. We identify Na + - and dopamine-induced changes in specific regions of the transporter, suggesting their involvement in protein conformational transitions. Furthermore, we detect ligand-dependent slow cooperative fluctuations of helical stretches in several domains of the transporter, which could be a molecular mechanism that assists in the transporter function. Our results provide a framework for understanding the molecular mechanism underlying the function of NSSs by revealing detailed insight into the state-dependent conformational changes associated with the alternating access model of the dopamine transporter. The dopamine transporter is responsible for termination of neurotransmission through Na + -driven reuptake of neurotransmitter from the extracellular space. Here authors use hydrogen-deuterium exchange mass spectrometry to monitor Na + - and dopamine-induced conformational dynamics of the dopamine transporter.

The serotonin transporter (SERT), a member of the neurotransmitter:sodium symporter family, is responsible for termination of serotonergic signaling by re-uptake of serotonin (5-HT) into the presynaptic neuron. Its key role in synaptic transmission makes it a major drug target, e.g. for the treatment of depression, anxiety and post-traumatic stress. Here, we apply hydrogen-deuterium exchange mass spectrometry to probe the conformational dynamics of human SERT in the absence and presence of known substrates and targeted drugs. Our results reveal significant changes in dynamics in regions TM1, EL3, EL4, and TM12 upon binding co-transported ions (Na + /K + ) and ligand-mediated changes in TM1, EL3 and EL4 upon binding 5-HT, the drugs S-citalopram, cocaine and ibogaine. Our results provide a comprehensive direct view of the conformational response of SERT upon binding both biologically relevant substrate/ions and ligands of pharmaceutical interest, thus advancing our understanding of the structure-function relationship in SERT. The serotonin transporter (SERT) is responsible for re-uptake of serotonin into the presynaptic neuron and plays a key role in synaptic transmission. Here, the authors use hydrogen-deuterium exchange mass spectrometry to probe the conformational dynamics of human SERT in the absence and presence of known substrates and targeted drugs.

Although understanding of the olfactory system has progressed at the level of downstream receptor signaling and the wiring of olfactory neurons, the system remains poorly understood at the molecular level of the receptors and their interaction with and recognition of odorant ligands. The structure and functional mechanisms of these receptors still remain a tantalizing enigma, because numerous previous attempts at the large-scale production of functional olfactory receptors (ORs) have not been successful to date. To investigate the elusive biochemistry and molecular mechanisms of olfaction, we have developed a mammalian expression system for the large-scale production and purification of a functional OR protein in milligram quantities. Here, we report the study of human OR 17-4 (hOR17-4) purified from a HEK293S tetracydine-inducible system. Scale-up of production yield was achieved through suspension culture in a bioreactor, which enabled the preparation of > 10 mg of monomeric hOR17-4 receptor after immunoaffinity and size exclusion chromatography, with expression yields reaching 3 mg/L of culture medium. Several key post-translational modifications were identified using MS, and CD spectroscopy showed the receptor to be ≈ 50% a-helix, similar to other recently determined G protein-coupled receptor structures. Detergent-solubilized hOR17-4 specifically bound its known activating odorants lilial and f loralozone in vitro, as measured by surface plasmon resonance. The hOR17-4 also recognized specific odorants in heterologous cells as determined by calcium ion mobilization. Our system is feasible for the production of large quantities of OR necessary for structural and functional analyses and research into OR biosensor devices.