BLOOD COMPONENTS: A novel approach to pathogen reduction in platelet concentrates using short‐wave ultraviolet light

BACKGROUND: Transfusion of platelet concentrates (PCs) is the basic treatment for severe platelet disorders. PCs carry the risk of pathogen transmission, especially bacteria. Pathogen reduction (PR) by addition of photochemical reagents and irradiation with visible or ultraviolet (UV) light can significantly reduce this risk. We present a novel approach for PR in PCs employing UVC light alone. STUDY DESIGN AND METHODS: UVC PR was evaluated by bacteria and virus infectivity assays. PC quality was investigated by measuring pH, lactate, glucose, hypotonic shock response, platelet aggregation, CD62P expression, and annexin V binding as in vitro parameters. The impact of UVC PR on the platelet proteome was assessed by differential in‐gel electrophoresis and compared with changes caused by UVB and gamma‐irradiation, respectively. RESULTS: Vigorous agitation of loosely placed PCs generated thin fluid layers that allow penetration of UVC light for inactivation of the six bacteria and six of the seven virus species tested. HIV‐1 was only moderately inactivated. UVC light at the dose used (0.4 J/cm²) had a minor impact on in vitro parameters and on storage stability of treated PCs. Proteome analysis revealed a common set of 92 (out of 793) protein spots being affected by all three types of irradiation. Specific alterations were most pronounced for gamma‐irradiation (45 spots), followed by UVB (11 spots) and UVC (2 spots). CONCLUSION: UVC irradiation is a potential new method for pathogen reduction in PCs. The data obtained until now justify further development of this process.     

Sterilization of platelet concentrates at production scale by irradiation with short-wave ultraviolet light

BACKGROUND: Bacterial contamination of platelet concentrates (PCs) is recognized as a serious threat to transfusion safety. We developed a simple method for sterilization of PCs with short-wave ultraviolet light (UVC). The effects of treatment on the sterility of contaminated PCs and in vitro platelet (PLT) variables were evaluated.
STUDY DESIGN AND METHODS: Plasma-reduced PCs were prepared from pools of five buffy coats. Irradiation with UVC (wavelength, 254 nm) under vigorous agitation was from both sides of the irradiation bags. Kinetics of the inactivation of Bacillus cereus , Propionibacterium acnes , and Staphylococcus epidermidis were determined. PCs spiked with approximately 10 to 100 colony-forming units (CFUs)/mL of 10 bacteria species (n = 12/species) were irradiated with UVC doses between 0.25 and 0.4 J/cm² and tested for sterility by a commercially available bacterial detection system (BacT/ALERT, bioMérieux) after storage at 22°C for 3 or 6 days. The influence of a dose of 0.3 J/cm² on PLT variables was investigated on Days 1, 4, and 6 after irradiation.
RESULTS: At 0.3 J/cm² all bacteria species tested were inactivated by more than 4 log. At this dose the influence of UVC on in vitro PLT variables was marginal; the storage stability for up to 6 days after treatment was maintained. PCs spiked with approximately 10 to 100 CFUs/mL were reproducibly sterilized in the dose range tested. In individual experiments with the spore former B. cereus , PCs were, however, unsterile after treatment.
CONCLUSION: Irradiation at UVC doses not detrimental to in vitro PLT variables sterilizes PCs contaminated with a wide range of different bacteria species.     

UVC Irradiation for Pathogen Reduction of Platelet Concentrates and Plasma

Besides the current efforts devoted to microbial risk reduction, pathogen inactivation technologies promise reduction of the residual risk of known and emerging infectious agents. A novel pathogen reduction process for platelets, the THERAFLEX UV-Platelets system, has been developed and is under clinical evaluation for its efficacy and safety. In addition, proof of principle has been shown for UVC treatment of plasma units. The pathogen reduction process is based on application of UVC light of a specific wavelength (254 nm) combined with intense agitation of the blood units to ensure a uniform treatment of all blood compartments. Due to the different absorption characteristics of nucleic acids and proteins, UVC irradiation mainly affects the nucleic acid of pathogens and leukocytes while proteins are largely preserved. UVC treatment significantly reduces the infectivity of platelet units contaminated by disease-causing viruses and bacteria. In addition, it inactivates residual white blood cells in the blood components while preserving platelet function and coagulation factors. Since no photoactive compound needs to be added to the blood units, photoreagent-related adverse events are excluded. Because of its simple and rapid procedure without the need to change the established blood component preparation procedures, UVC-based pathogen inactivation could easily be implemented in existing blood banking procedures.     

Significantly enhanced dielectric constant and energy storage properties in polyimide/reduced BaTiO3 composite films with excellent thermal stability

In this work, reduced BaTiO₃ (rBT) particles with a large number of defects sintered in a reducing atmosphere (95N₂/5H₂) were introduced into polyimide (PI) matrix without using any modifier or surfactant components. The rBT/PI composite films fabricated by an in situ polymerization method showed significantly enhanced dielectric constant and energy storage density. The dielectric constant of the rBT/PI composite with 30 wt% rBT reached up to 31.6, while maintaining lower loss (tg δ = 0.031@1000 kHz) compared to pure PI (ε_r = 4.1). Its energy storage density (9.7 J cm⁻³ at 2628 kV cm⁻¹) was enhanced by more than 400% over that of pure PI (1.9 J cm⁻³ at 3251 kV cm⁻¹), and was greater than the energy density of the best commercial biaxially-oriented-polypropylenes (BOPP) (1.2 J cm⁻³ at 6400 kV cm⁻¹). The energy storage efficiency was around 90% due to the linear dielectric performance of rBT/PI composite films. The improved dielectric constant and energy storage density could be attributed to the combined effect of the interface interaction between two phases and the surface defects of rBT induced by the reducing atmosphere. Therefore, rBT/PI composite films with high dielectric constant, energy storage density and storage efficiency may have potential applications in the preparation of embedded capacitors.

The semiconductor properties of reduced barium titanate, with a high energy density of 9.7 J cm⁻³.     

Characteristics of the THERAFLEX UV-Platelets pathogen inactivation system - an update

Considerable progress has been made in the last decade in producing purer, safer, leucocyte and plasma reduced platelet concentrates (PC) with an extended shelf life. The development of different pathogen inactivation technologies (PIT) has made a substantial contribution to this trend. Preceding platelet PIT (INTERCEPT Blood System/Cerus Corporation, Concord, CA, USA; MIRASOL/Caridian BCT, Lakewood, CO, USA) are based on adding a photosensitive compound to PC. The mixture is then activated by UV light in the UVB and/or UVA spectral regions. A novel procedure, THERAFLEX UV-Platelets (MacoPharma, Mouvaux, France), was recently developed that uses short-wave ultraviolet light (UVC), without addition of any photoactive agent. This technology has proven to be highly effective in sterilising bacteria (the major cause of morbidity/mortality after platelet transfusion) as well as inactivating other transfusion transmitted DNA/RNA containing pathogens and residual leucocytes. Any PIT reflects a balance between the efficacy of pathogen inactivation and preservation of platelet quality and function. A broad spectrum of in vitro tests have become available for the assessment of platelet storage lesion (PSL), aiming to better predict clinical outcome and untoward effects of platelet therapy. Recent paired studies on the release of platelet-derived cytokines, as new platelet performance indicators, revealed a parallel increase in both THERAFLEX UV-treated and control PC throughout storage, supporting the notion that the bioavailability of platelet function is not grossly affected by UVC treatment. This is corroborated by some newer technologies for proteomic analysis, showing that the THERAFLEX UV-Platelets system results in limited disruption of integrin-regulating extracellular disulfide bonds and minimal protein alterations when compared to UVB and gamma irradiation. Moreover, standard in vitro parameters reflecting activation, metabolic activity and function of platelets are useful indicators of the overall performance of processing and storage and may be used as surrogate markers of platelet quality in vivo. However, there is some doubt as to what degree each marker alone or in combination reflects the true clinical outcome of transfused platelets. Therefore, an appropriate clinical programme has been initiated. The preclinical evaluation demonstrated tolerability and immunological safety of THERAFLEX UV-Platelets using an animal model. Additionally, the system has successfully completed two autologous Phase I trials on recovery and survival. Preliminary results suggest that the recovery and survival rates are consistent with other pathogen reduced platelet products that are licensed and in use. The method is currently under evaluation for safety and tolerability of UVC-treated platelets in healthy volunteers. Presently the THERAFLEX UV-Platelets system is the simplest and purest PIT easily adaptable to the existing blood bank setting. In the future, extension of the application range of the THERAFLEX UV-Platelets system is expected, in order to make this new technology compatible with a broad spectrum of collection and processing platforms, and with other blood products.     

Two pathogen reduction technologies—methylene blue plus light and shortwave ultraviolet light—effectively inactivate hepatitis C virus in blood products

BACKGROUND: Contamination of blood products with hepatitis C virus (HCV) can cause infections resulting in acute and chronic liver diseases. Pathogen reduction methods such as photodynamic treatment with methylene blue (MB) plus visible light as well as irradiation with shortwave ultraviolet (UVC) light were developed to inactivate viruses and other pathogens in plasma and platelet concentrates (PCs), respectively. So far, their inactivation capacities for HCV have only been tested in inactivation studies using model viruses for HCV. Recently, a HCV infection system for the propagation of infectious HCV in cell culture was developed. STUDY DESIGN AND METHODS: Inactivation studies were performed with cell culture–derived HCV and bovine viral diarrhea virus (BVDV), a model for HCV. Plasma units or PCs were spiked with high titers of cell culture–grown viruses. After treatment of the blood units with MB plus light (Theraflex MB‐Plasma system, MacoPharma) or UVC (Theraflex UV‐Platelets system, MacoPharma), residual viral infectivity was assessed using sensitive cell culture systems. RESULTS: HCV was sensitive to inactivation by both pathogen reduction procedures. HCV in plasma was efficiently inactivated by MB plus light below the detection limit already by 1/12 of the full light dose. HCV in PCs was inactivated by UVC irradiation with a reduction factor of more than 5 log. BVDV was less sensitive to the two pathogen reduction methods. CONCLUSIONS: Functional assays with human HCV offer an efficient tool to directly assess the inactivation capacity of pathogen reduction procedures. Pathogen reduction technologies such as MB plus light treatment and UVC irradiation have the potential to significantly reduce transfusion‐transmitted HCV infections.     

Differential sensitivities of viruses in red cell suspensions to methylene blue photosensitization

Background : Previous studies explored the feasibility of using the photosensitizer methylene blue (MB) as a virucidal agent in red cell suspensions. Under treatment conditions (5 μM [5 μmol/L] MB, 3.4 × 10(4) J/m²) that resulted in more than 6 log₁₀ inactivation of vesicular stomatitis virus (VSV) or of the enveloped bacteriophage φ6, red cell membrane alterations were observed. Increased red cell ion permeability and the binding of plasma proteins to the red cell surface were the most sensitive indicators, which varied in a dose-dependent fashion. Study Design and Methods : Inactivation of three additional extracellular viruses and intracellular human immunodeficiency virus type 1 (HIV-1) was assessed after MB phototreatment of red cell suspensions. Potassium leakage and IgG binding also were characterized in MB-treated red cell suspensions that were exposed to low-fluence light (6 × 10³ J/m²). Results : Different viruses exhibit a wide range of sensitivities to MB photoinactivation. For example, phototreatment conditions (5 μM [5 μmol/L] MB, 3.4 × 10⁴ J/m²) that inactivated more than 6 log₁₀ of VSV did not inactivate the nonenveloped picornavirus, encephalomyocarditis virus. In contrast, lower fluences (6 × 10³ J/m²) inactivated approximately 5 log₁₀ or more of Sindbis virus and approximately 4log₁₀ of extracellular HIV-1. These less stringent phototreatment conditions (5 μM [5 μmol/L] 6 × 10³ J/m²) caused lower rates of red cell potassium leakage (reduction by 6- fold) and little or no binding of plasma proteins to the red cell surface, compared to values observed previously with higher fluences. However, neither 6 × 10³ nor 4.1 × 10⁴ J per m² fluences resulted in any inactivation of intracellular HIV as represented by changes in the amount of p24 antigen produced during co-culture of actively infected H9 cells. Conclusion : MB-based protocols would require the use of high-efficiency (> 6log₁₀) white cell-reduction filters or additional inactivation steps to deplete or inactivate intracellular virus.     

Storage of single donor platelet concentrates: Paired comparison of storage as single or double concentrates

Modern cell separators allow the collection of two plateletpheresis concentrates (PCs) at one session. This study evaluates the quality of PCs stored as double concentrates in standard storage containers of two manufacturers. We collected 20 PCs that contained 4.5 × 10¹¹ platelets in 375 ml plasma (10 using the COBE Spectra and 10 using the Fresenius AS.TEC 204 with 500 ml bags) that were split into one unit of 3.0 × 10¹¹ platelets in 250 ml (3.0‐PC) and one of 1.5 × 10¹¹ platelets in 125 ml (1.5‐PC). Storage of one 3.0‐PC per bag of a two‐bag system corresponded to storage conditions for double PCs and storage of one 1.5‐PC per bag to storage conditions of single PCs. Cell counts, blood gas analysis, glucose and lactate levels, platelet aggregation, and activation and plasma levels of β‐ thromboglobulin (β‐TG) and complement factor 3a (C3a) were measured before storage and again on days 3 and 5. COBE 3.0‐PCs demonstrated less pH rise, lactate production, CD 62P expression and β‐TG plasma levels, and better aggregability after storage than COBE 1.5‐PCs. Fresenius 1.5‐PCs had similar platelet quality to COBE 3.0‐PCs. Fresenius 3.0‐PCs showed a fall of pH (day 5: 6.22 ± 0.56), the highest amount of anaerobic glycolysis compared to all other storage conditions investigated, high CD 62P‐ expression and β‐TG plasma levels, and impaired aggregability on days 3 and 5. The highest C3a levels were found in COBE 1.5‐PCs. 3.0 × 10¹¹ platelets in 250 ml plasma should be stored either in one bag of the COBE system or in two 500 ml bags of the Fresenius system. The COBE two‐bag system allows the storage of two PCs without loss of platelet quality. Two PCs should not be stored in the Fresenius C4L 500 ml storage containers. J. Clin. Apheresis. 16:148‐154, 2000. © 2001 Wiley‐Liss, Inc.     

Inactivation of pathogens in single units of therapeutic fresh plasma by irradiation with ultraviolet light

BACKGROUND: Ultraviolet (UV) light, especially UVC, is germicidal but its ability to penetrate layers of protein containing solutions is poor. This hampers its use to inactivate pathogens in therapeutic fresh plasma (FP).
STUDY DESIGN AND METHODS: FP units were spiked with lipid-enveloped or nonenveloped viruses. Others were used without spiking. The units were transferred into UV-transparent bags and irradiated with UVB or UVC light from both sides. The bags either were clamped between quartz plates or remained loose. In addition they were agitated at different speeds. Before and after irradiation virus titers or plasma variables were measured.
RESULTS: Virus inactivation by UV irradiation was marginal when the FP units were not agitated or when the irradiation bags were fixed between quartz plates. It was strongly enhanced when they remained unfixed and were intensively agitated during treatment. At 100 rpm and UVC doses of approximately 1 J/cm², with the exception of human immunodeficiency virus Type 1, all viruses used were effectively inactivated. UVB up to 2.5 J/cm² was less effective. At 1 J/cm² UVC or 2.5 J/cm² UVB the activities of the clotting factors tested in general were reduced by approximately 10% to 20% compared to untreated plasma. More sensitive was clotting factor XI whose activity was lowered by approximately 23 and 29%, respectively. No further reductions were determined after storage of UVC-treated FP for 3 months at 30°C or less.
CONCLUSIONS: Pathogen inactivation of FP by UV light becomes effective when the unfixed irradiation bags are strongly agitated. The decrease in some clotting factor activities could be acceptable.     

Longitudinal analysis of annual national hemovigilance data to assess pathogen reduced platelet transfusion trends during conversion to routine universal clinical use and 7-day storage

Background

France converted to universal pathogen reduced (PR; amotosalen/UVA) platelets in 2017 and extended platelet component (PC) shelf-life from 5- to 7-days in 2018 and 2019. Annual national hemovigilance (HV) reports characterized longitudinal PC utilization and safety over 11 years, including several years prior to PR adoption as the national standard of care.

Methods

Data were extracted from published annual HV reports. Apheresis and pooled buffy coat [BC] PC use was compared. Transfusion reactions (TRs) were stratified by type, severity, and causality. Trends were assessed for three periods: Baseline (2010–14; ~7% PR), Period 1 ([P1] 2015–17; 8%–21% PR), and Period 2 ([P2] 2018–20; 100% PR).

Results

PC use increased by 19.1% between 2010 and 2020. Pooled BC PC production increased from 38.8% to 68.2% of total PCs. Annual changes in PCs issued averaged 2.4% per year at baseline, −0.02% (P1) and 2.8% (P2). The increase in P2 coincided with a reduction in the target platelet dose and extension to 7-day storage. Allergic reactions, alloimmunization, febrile non-hemolytic TRs, immunologic incompatibility, and ineffective transfusions accounted for >90% of TRs. Overall, TR incidence per 100,000 PCs issued declined from 527.9 (2010) to 345.7 (2020). Severe TR rates declined 34.8% between P1-P2. Forty-six transfusion-transmitted bacterial infections (TTBI) were associated with conventional PCs during baseline and P1. No TTBI were associated with amotosalen/UVA PCs. Infections with Hepatitis E (HEV) a non-enveloped virus resistant to PR, were reported in all periods.

Discussion

Longitudinal HV analysis demonstrated stable PC utilization trends with reduced patient risk during conversion to universal 7-day amotosalen/UVA PCs.     

Quality of platelet concentrates irradiated with UVB light: effect of UV dose and dose rate on glycocalicin release and correlation with other markers of the platelet storage lesion

Summary. The amount of membrane-associated glycoprotein Ib in platelet concentrates (PCs) irradiated with a high dose of UVB light has been shown to be significantly reduced after 48 h storage. We recently corroborated this finding when we noted an increase in the supernatant levels of glycocalicin (GC, a major segment of glycoprotein Ib) in UVB-treated PCs during storage. The aim of the present study was to determine whether GC release was related to both the UV dose and the rate of dose delivery. Plateletpheresis concentrates obtained from five donors were pooled and split into five equal parts. Four of these were treated with 7500 and 15000 mJ/cm² UVB using two prototype UV sources with differing rates of dose delivery; namely, Baxter (BAT) and British Aerospace (BAC) cabinets, with the latter having the slower rate of delivery. On days 1 and 5 of storage, GC levels in the supernatants of PCs were determined by ELISA. Moreover, the following parameters were also assessed: platelet and WBC count; hypotonic shock response (HSR) and platelet aggregation response to ADP, ADP +collagen, ADP + arachidonic acid and ristocetin; pH; supernatant levels of lactate, glucose, von Willebrand factor (vWf) and β-thrornboglobulin (βTG). The results revealed an association of GC release with UVB dose using both UV sources, although this was more apparent in the BAC system, in which glycocalicin release at day 5 of storage was as follows (μg/ml, mean ± SD): 4·8±0·3 and 9·5±3·6 at 7500 and 15000 mJ/cm² respectively. Moreover, at 15000 mJ/cm², PCs treated in the BAC system exhibited significantly higher levels of GC than those treated in the BAT system: 9·5±3·6 and 4·8± 3·6 respectively at day 5 of storage (P= 0·05). This differential GC increase in the BAC was coupled with a decrease in HSR and a significant increase in lactate and βTG levels compared with the BAT system. In contrast to the GC results, vWf supernatant levels in PCs treated with UVB were decreased relative to non-treated PCs of the same origin. Moreover, GC release correlated significantly with various standard tests of platelet function indicating its importance as a quality indicator for the investigation of the platelet storage lesion. Our results show that UVB not only increases GC release in a dose/rate-dependent manner but that it may also affect the quality of irradiated PCs and their shelf life.     

Riboflavin and ultraviolet light reduce the infectivity of Babesia microti in whole blood

BACKGROUND: Babesia microti is the parasite most frequently transmitted by blood transfusion in the United States. Previous work demonstrated the efficacy of riboflavin (RB) and ultraviolet (UV) light to inactivate B. microti in apheresis plasma and platelet units. In this study we investigated the effectiveness of RB and UV light to reduce the levels of B. microti in whole blood (WB). STUDY DESIGN AND METHODS: WB units were spiked with B. microti‐infected hamster blood. Spearman‐Karber methods were used to calculate infectivity of each sample in terms of hamster infectious dose 50% (HID₅₀) value. After RB addition, the units were illuminated with 80 J/mL_RBC UV light. Two samples were collected: one before illumination and one after illumination. The samples were serially diluted and dilutions injected into a group of five naive hamsters. Four weeks postinoculation (PI), blood was collected from the animals and evaluated by microscopic observation. RESULTS: One pilot study showed a good dose response in the animals and demonstrated that sample infectivity could be calculated in terms of an HID₅₀. Three additional replicates were performed in the same manner as the pilot study, but with fewer dilutions. Infectivity values were consistent between the experiments and were used to calculate log reduction. The posttreatment reduction of B. microti for all the experiments was more than 5 log. CONCLUSIONS: The data collected indicate that use of RB and UV is able to decrease the parasite load in WB units thus reducing the risk of transfusion‐transmitted B. microti from blood components containing B. microti‐infected RBCs.     

Psoralen photochemical inactivation of Orientia tsutsugamushi in platelet concentrates

BACKGROUND: The risk of transfusion transmission of disease has been reduced by the combination of predonation questions and improved transfusion-transmitted disease assays, but the risk is still present. This study was conducted to determine if psoralen photochemistry could inactivate an obligate intracellular bacterium, with documented potential for transfusion, in PCs to further improve safety. STUDY DESIGN AND METHODS: PCs were inoculated with MNCs infected with Orientia tsutsugamushi. The concentrates were treated with amounts ranging from 0.86 to 138 micromol per L of 4'-(aminomethyl)-4,5',8-trimethylpsoralen hydrochloride (AMT) combined with a constant long-wave UVA light (320-400 nm) exposure of 5 J per cm(2). The effects of photochemical treatment were analyzed by using a mouse infectivity assay along with in vitro testing by PCR, indirect fluorescence antibody, direct fluorescence antibody, and Giemsa staining. RESULTS: AMT, at 0.86 micromol per L or more, combined with UVA light of 5 J per cm(2), inactivated O. tsutsugamushi that contaminated PCs. The PCs that did not receive the combined treatment caused infection. CONCLUSIONS: The psoralen AMT, in conjunction with UVA light exposure, effectively abolished the infectivity of PCs deliberately contaminated with the scrub typhus organism O. tsutsugamushi, as tested in a mouse infectivity assay.     

Treatment of electrochemical plating wastewater by heterogeneous photocatalysis: the simultaneous removal of 6:2 fluorotelomer sulfonate and hexavalent chromium

6:2 fluorotelomer sulfonate (6:2 FtS) is being widely used as a mist suppressant in the chromate (Cr(vi)) plating process. As a result, it is often present alongside Cr(vi) in the chromate plating wastewater (CPW). While the removal of Cr(vi) from CPW has been studied for decades, little attention has been paid to the treatment of 6:2 FtS. In this study, the removal of Cr(vi) and 6:2 FtS by Ga₂O₃, In₂O₃, and TiO₂ photocatalysts was investigated. In the Ga₂O₃/UVC system, over 95% of Cr(vi) was reduced into Cr(iii) after only 5 min. Simultaneously, 6:2 FtS was degraded into F⁻ and several perfluorocarboxylates. The predominant reactive species responsible for the degradation of 6:2 FtS in the Ga₂O₃ system were identified to be h_VB⁺ and O₂˙⁻. In addition, it was observed that the presence of Cr(vi) helped accelerate the degradation of 6:2 FtS. This synergy between Cr(vi) and 6:2 FtS was attributable to the scavenging of e_CB⁻ by Cr(vi), which retarded the recombination of e_CB⁻ and h_VB⁺. The In₂O₃/UVC system was also capable of removing Cr(vi) and 6:2 FtS, although at significantly slower rates. In contrast, poor removal of 6:2 FtS was achieved with the TiO₂/UVC system, because Cr(iii) adsorbed on TiO₂ and inhibited its reactivity. Based on the results of this study, it is proposed that CPW can be treated by a treatment train that consists of an oxidation–reduction step driven by Ga₂O₃/UVC, followed by a neutralization step that converts dissolved Cr(iii) into Cr(OH)_3(S).

6:2 fluorotelomer sulfonate (6:2 FtS) and chromate (Cr(vi)) in chromate plating wastewaters can be simultaneously removed by photocatalysis.     

Study on photovoltaic stability and performance by incorporating tetrabutyl phosphonium iodide into the active layer of a perovskite type photovoltaic cell

A simple synthesis of an ionic liquid is carried out using a trialkylphosphine and an alkyl halide. The results showed that the quality of perovskite crystals is enhanced by the incorporation of B₄PI, when the percentage is 1.5% the PCE of champion PSCs MA_98.5(B₄PI)_1.5PbI₃ increases significantly from 15.5%, with a V_OC of 0.957 mV, J_SC of 23.6 mA cm⁻², and an FF of 68.4%. Stability tests show that excess B₄PI by 20% has a protective effect against humidity, MA₈₀(B₄PI)₂₀PbI₃ was more stable towards humidity, losing only 20% efficiency for 200 h.

Schematic representation of the solar cell configuration with alkylphosphonium modified perovskite layer.     

Inactivation of parvovirus B19 in coagulation factor concentrates by UVC radiation: assessment by an in vitro infectivity assay using CFU-E derived from peripheral blood CD34+ cells

BACKGROUND: Nonenveloped and thermostable viruses such as parvovirus B19 (B19) can be transmitted to patients who are receiving plasma-derived coagulation factor concentrates treated by the S/D method for inactivating enveloped viruses. Therefore, it is important to develop and validate new methods for the inactivation of nonenveloped viruses. STUDY DESIGN AND METHODS: Suspensions of B19 in coagulation factor concentrates (FVIII) were irradiated with UVC light. B19 infectivity was determined by an indirect immunofluorescence assay using CFU-E, as a host cell, derived from peripheral blood CD34+ cells. The effects of catechins on B19 infectivity and on FVIII activity after UVC illumination were also examined. RESULTS: The indirect immunofluorescence assay estimated the B19 infectivity of samples containing virus copies of 10(5) to 10(11) per 10 microL to be a median tissue culture-infectious dose of 10(0.3) to 10(5.4) per 10 microL. B19 was inactivated by 3 log at 750 J per m(2) of UVC radiation and was undetectable after 1000 or 2000 J per m(2) of irradiation. However, FVIII activity decreased to 55 to 60 percent of pretreatment activity after 2000 J per m(2) of UVC radiation. This was inhibited in the presence of rutin or catechins. Epigallocatechin gallate could maintain FVIII activity at almost 100 percent of pretreatment activity after 2000 J per m(2) of UVC radiation, while B19 infectivity was decreased to undetectable levels, which resulted in >3.9 log inactivation. CONCLUSION: UVC radiation in the presence of catechins, especially epigallocatechin gallate, appears to be an effective method of increasing the viral safety of FVIII concentrates without the loss of coagulation activity.     

Low-level laser therapy for osteonecrotic lesions: effects on osteoblasts treated with zoledronic acid

Purpose

Clinical studies have shown that low-level laser therapy (LLLT) can improve local tissue healing of bisphosphonate-induced osteonecrosis of the jaw. However, the effects of laser irradiation on bisphosphonate-treated osteoblasts have not been completely elucidated.

Methods

Human osteoblasts were cultured in plain culture medium (DMEM). After 48 h, plain DMEM was replaced by DMEM with no fetal bovine serum, for a 24-h incubation followed by addition of zoledronic acid (5 μM) for additional 48 h. Cells were subjected to LLLT (InGaAsP; 780?±?3 nm; 0.025 W) at 0.5, 1.5, 3, 5, and 7 J/cm², three times every 24 h. Cell viability, total protein production, alkaline phosphatase activity (ALP), mineral nodule formation, gene expression of collagen type I and ALP, and cell morphology were evaluated.

Results

LLLT at 0.5 J/cm² increased cell viability of cultured osteoblasts. ALP activity and gene expression, in addition to mineral nodule formation and Col-I gene expression, were not increased by LLLT. LLLT applied to ZA-treated cells increased Col-I expression at 0.5, 1.5, and 3 J/cm² but did not improve any other cell activity assessed.

Conclusion

LLLT showed limited effects on bisphosphonate-treated osteoblasts.     

Charge balance control of quantum dot light emitting diodes with atomic layer deposited aluminum oxide interlayers

We developed a 1.0 nm thick aluminum oxide (Al₂O₃) interlayer as an electron blocking layer to reduce leakage current and suppress exciton quenching induced by charge imbalance in inverted quantum dot light emitting diodes (QLEDs). The Al₂O₃ interlayer was deposited by an atomic layer deposition (ALD) process that allows precise thickness control. The Al₂O₃ interlayer lowers the mobility of electrons and reduces Auger recombination which causes the degradation of device performance. A maximum current efficiency of 51.2 cd A⁻¹ and an external quantum efficiency (EQE) of 12.2% were achieved in the inverted QLEDs with the Al₂O₃ interlayer. The Al₂O₃ interlayer increased device efficiency by 1.1 times, increased device lifetime by 6 times, and contributed to reducing efficiency roll-off from 38.6% to 19.6% at a current density up to 150 mA cm⁻². The improvement of device performance by the Al₂O₃ interlayer is attributed to the reduction of electron injection and exciton quenching induced by zinc oxide (ZnO) nanoparticles (NPs). This work demonstrates that the Al₂O₃ interlayer is a promising solution for charge control in QLEDs and that the ALD process is a reliable approach for atomic scale thickness control for QLEDs.

We developed a 1.0 nm thick aluminum oxide (Al₂O₃) interlayer as an electron blocking layer to reduce leakage current and suppress exciton quenching induced by charge imbalance in inverted quantum dot light emitting diodes (QLEDs).     

β-Blockers bearing hydroxyethylamine and hydroxyethylene as potential SARS-CoV-2 Mpro inhibitors: rational based design,in silico,in vitro,and SAR studies for lead optimization

The global COVID-19 pandemic became more threatening especially after the introduction of the second and third waves with the current large expectations for a fourth one as well. This urged scientists to rapidly develop a new effective therapy to combat SARS-CoV-2. Based on the structures of β-adrenergic blockers having the same hydroxyethylamine and hydroxyethylene moieties present in the HIV-1 protease inhibitors which were found previously to inhibit the replication of SARS-CoV, we suggested that they may decrease the SARS-CoV-2 entry into the host cell through their ability to decrease the activity of RAAS and ACE2 as well. Herein, molecular docking of twenty FDA-approved β-blockers was performed targeting SARS-CoV-2 Mpro. Results showed promising inhibitory activities especially for Carvedilol (CAR) and Nebivolol (NEB) members. Moreover, these two drugs together with Bisoprolol (BIS) as an example from the lower active ones were subjected to molecular dynamics simulations at 100 ns. Great stability across the whole 100 ns timeframe was observed for the top docked ligands, CAR and NEB, over BIS. Conformational analysis of the examined drugs and hydrogen bond investigation with the pocket''s crucial residues confirm the great affinity and confinement of CAR and NEB within the Mpro binding site. Moreover, the binding-free energy analysis and residue-wise contribution analysis highlight the nature of ligand–protein interaction and provide guidance for lead development and optimization. Furthermore, the examined three drugs were tested for their in vitro inhibitory activities towards SARS-CoV-2. It is worth mentioning that NEB achieved the most potential anti-SARS-CoV-2 activity with an IC₅₀ value of 0.030 μg ml⁻¹. Besides, CAR was found to have a promising inhibitory activity with an IC₅₀ of 0.350 μg ml⁻¹. Also, the IC₅₀ value of BIS was found to be as low as 15.917 μg ml⁻¹. Finally, the SARS-CoV-2 Mpro assay was performed to evaluate and confirm the inhibitory effects of the tested compounds (BIS, CAR, and NEB) towards the SARS-CoV-2 Mpro enzyme. The obtained results showed very promising SARS-CoV-2 Mpro inhibitory activities of BIS, CAR, and NEB (IC₅₀ = 118.50, 204.60, and 60.20 μg ml⁻¹, respectively) compared to lopinavir (IC₅₀ = 73.68 μg ml⁻¹) as a reference standard.

Hydroxyethylamine and hydroxyethylene moieties of β-blockers exert potential SARS-CoV-2 inhibitory effects: rational-based design and in silico, in vitro, and SAR Studies.     

Factors associated with household transmission of SARS-CoV-2 omicron variant to health care workers: A retrospective cohort study

Aim

The aim of this study was to determine the risk factors for household transmission of the omicron variant of SARS-CoV-2.

Background

The household infection rate has been reported to be higher for the omicron variant than for non-omicron variants of SARS-CoV-2. Determination of the risk factors for household transmission of the omicron variant is therefore important.

Design

A Retrospective Cohort Study was conducted.

Methods

When family members of health care workers (HCWs) were found to be infected with SARS-CoV-2, the HCWs had to receive two nucleic acid amplification tests for SARS-CoV-2: immediately after and 5 to 10 days after the onset of COVID-19 in the family members. Risk factors of household transmission were analysed by comparing cases (HCWs infected with SARS-CoV-2) and controls (HCWs not infected with SARS-CoV-2) using multivariable analysis.

Results

Unvaccinated status (OR: 3.97), age of index cases (≤6 years) (OR: 1.94) and staying at home with index cases (OR: 10.18) were risk factors for household transmission.

Conclusion

If there is a strong desire to avoid household infection, family members infected with SARS-CoV-2 should live separately during the period of viral shedding.