A Customizable Platform to Integrate CAR and Conditional Expression of Immunotherapeutics in T Cells.

The potential of chimeric antigen receptor (CAR)-based immunotherapy as a promising therapeutic approach is often hindered by the presence of highly immunosuppressive tumor microenvironments (TME). Combination therapies with either co-administration or built-in expression of additional TME-modulating therapeutic molecules to potentiate the functions of CAR-T cells can cause systemic toxicities due to the lack of control over the delivery of biologics. Here, we present a proof-of-concept engineered platform in human Jurkat T cells that combines CAR with a therapeutic gene circuit capable of sensing ß-galactosidase (a reported cancer-associated signal) and subsequently activate the production of customized therapeutic gene products. We have demonstrated the integration of the chemically induced proximity (CIP) and associated signal sensing technologies with CAR in this study. A ß-galactosidase-activatable prodrug was designed by conjugating a galactose moiety with a CIP inducer abscisic acid (ABA). We showed that Jurkat T cells engineered with CAR and the ABA-inducible genetic circuits can respond to recombinant ß-galactosidase to drive the production and secretion of various immunotherapeutics including an anti-cancer agent, an immunomodulatory cytokine, and immune checkpoint inhibitors. Our design is highly modular and could be adapted to sense different cancer-related signals to locally produce antitumor therapeutics that can potentially boost CAR-T efficacy and persistence.

Implementation of an Immunoassay Based on the MVA-T7pol-Expression System for Rapid Identification of Immunogenic SARS-CoV-2 Antigens: A Proof-of-Concept Study.

The emergence of hitherto unknown viral pathogens presents a great challenge for researchers to develop effective therapeutics and vaccines within a short time to avoid an uncontrolled global spread, as seen during the coronavirus disease 2019 (COVID-19) pandemic. Therefore, rapid and simple methods to identify immunogenic antigens as potential therapeutical targets are urgently needed for a better pandemic preparedness. To address this problem, we chose the well-characterized Modified Vaccinia virus Ankara (MVA)-T7pol expression system to establish a workflow to identify immunogens when a new pathogen emerges, generate candidate vaccines, and test their immunogenicity in an animal model. By using this system, we detected severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) nucleoprotein (N)-, and spike (S)-specific antibodies in COVID-19 patient sera, which is in line with the current literature and our observations from previous immunogenicity studies. Furthermore, we detected antibodies directed against the SARS-CoV-2-membrane (M) and -ORF3a proteins in COVID-19 patient sera and aimed to generate recombinant MVA candidate vaccines expressing either the M or ORF3a protein. When testing our candidate vaccines in a prime-boost immunization regimen in humanized HLA-A2.1-/HLA-DR1-transgenic H-2 class I-/class II-knockout mice, we were able to demonstrate M- and ORF3a-specific cellular and humoral immune responses. Hence, the established workflow using the MVA-T7pol expression system represents a rapid and efficient tool to identify potential immunogenic antigens and provides a basis for future development of candidate vaccines.

Targeting Parallel Topology of G-Quadruplex Structures by Indole- Fused Quindoline Scaffolds.

Preferential stabilization of G-quadruplex (G4) structures using small-molecule ligands has emerged as an effective approach to develop anticancer drugs. Herein, we report the synthesis of three indole-fused quindoline derivatives with varying lengths of side chains (InqEt1, InqEt2, and InqPr2) as selective ligands for promoter G4 structures. The ligands stabilize the parallel topology of c-MYC and c-KIT1 promoter G4 DNAs over telomeric and duplex DNAs, as evident from the circular dichroism melting and polymerase stop-assay experiments. The lead ligand, InqPr2, downregulates the gene expression of c-MYC and c-KIT in HeLa and HepG2 cells, respectively, leading to apoptotic cell death. Molecular modeling and dynamics studies support the 2:1 binding stoichiometry revealed from the Job plot analysis and show the ligand's structural features that enable the preferential binding to the parallel G4 structures over other topologies. Our studies show that indole-fused quindoline derivatives can be harnessed as new molecular scaffolds for selective targeting of parallel G4 topologies.

Bisindolylmaleimide Ligands Stabilize c-MYC G-Quadruplex DNA Structure and Downregulate Gene Expression.

G-Quadruplex (G4) structures play a pivotal role in diverse biological functions, including essential processes, such as telomere maintenance and gene regulation. G4 structures formed in functional regions of genomes are actively pursued toward therapeutics and are targeted by small-molecule ligands that alter their structure and/or stability. Herein, we report the synthesis of bisindolylmaleimide-based (BIM) ligands, which preferentially stabilize parallel G4 structures of c-MYC and c-KIT oncogenes over the telomeric h-RAS1 G4 and duplex DNAs. The preferential stabilization of parallel G4s with BIM ligands is further validated by the DNA polymerase stop assay, where stop products were only observed for templates containing the c-MYC G4 sequence. Nuclear magnetic resonance (NMR) titration studies indicate that the lead ligand BIM-Pr1 forms a 2:1 complex with c-MYC G4 DNA with a KD of 38 ± 5 µM. The BIM ligand stacks at the 5' and 3' quartets, with molecular modeling and dynamics studies supporting the proposed binding mode. The ligand is cytotoxic to HeLa cells and downregulates c-MYC gene expression. Collectively, the results present bisindolylmaleimide scaffolds as novel and powerful G4 targeting agents.

Comparative evaluation of ADVIA Centaur® XP chemiluminescence system for screening of HBV, HCV, HIV and syphilis in Indian blood donors.

BACKGROUND: The introduction of chemiluminescent immunoassay (CLIA) in blood donor screening has led to a gradual replacement of enzyme-linked-immunosorbent assay (ELISA) as the former offers automation, higher sensitivity and lower turn-around-time. However, only a few CLIA platforms are used for blood donor screening in India. The present study evaluated one such newer platform viz., Adiva Centaur XP CLIA for screening of HBV, HCV, HIV and syphilis. MATERIAL AND METHODS: Prospective comparative study wherein 4843 whole blood donors were screened for HBsAg, Anti-HCV, HIV Ag-Ab and Anti-treponemal antibodies in both Advia Centaur XP and Architect i2000SR platforms. Additional tests were performed in samples which were reactive in only one of the platforms. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy, false positive rate and false negative rate of both the platforms were compared. Kappa coefficient was calculated to determine the agreement between the testing platforms. RESULTS: The sensitivity of Advia Centaur platform for HBV, HCV, HIV and syphilis detection were 94.9 %, 100 %, 100 % and 100 % respectively as compared to 96.6 %, 100 %, 100 % and 100 % in Architect i2000SR platform. The specificity of both the platforms were 99.8-99.9 % for all the four tests. The agreement between the two platforms was almost perfect for HBV, HCV and syphilis testing; and fair for HIV testing. CONCLUSION: The Advia Centaur CLIA platform was found to be comparable with the Architect CLIA platform for blood donor screening. Unexpected finding was the occurrence of HBV false negatives in both the platforms, possibly due to HBsAg mutations.

Preliminary assessment of heavy metals in surface water and sediment in Nakuvadra-Rakiraki River, Fiji using indexical and chemometric approaches.

River water and sediment embody environmental characteristics that give valuable environmental management information. However, indexical and chemometric appraisal of heavy metals (HMs) in river water and sediment is very scarce in Island countries including Fiji. In this research, forty-five sediment and fifteen water samples from the Nakuvadra-Rakiraki River, Fiji were analyzed for appraising spatial distribution, pollution, and source identification of selected heavy metals (HMs) using the coupling tools of self-organizing map (SOM), compositional data analysis (CDA), and sediment and water quality indices. The mean concentration of HMs increased in the order of Cd < Co < Pb < Cu < Zn < Ni < Cr < Mn < Fe for sediment and Cd < Pb < Cu < Ni < Zn < Co < Cr < Fe < Mn for water, respectively. The outcomes of the enrichment factor, geo-accumulation index and contamination factor index varied spatially and most of the sediment samples were polluted by Pb, Mn, and Cu. The potential ecological risk recognized Cd, and Pb as ecological and public health risks to the surrounding communities. Based on SOM and CDA, three potential sources (e.g., point, nonpoint and lithological sources) of HMs for sediment and two sources (e.g., geogenic and human-induced sources) of HMs for water were identified. The spatial patterns of EWQI values revealed that the northern and northeast zones of the studied area possess a high degree of water pollution. The entropy weight indicated Ni and Cd as the main pollutants degrading the water quality. This study gives a baseline dataset for combined eco-environmental measures for the river's water and sediment pollution as well as contributes to an inclusive appraisal of HMs contamination in global rivers.

Water resources pollution associated with risks of heavy metals from Vatukoula Goldmine region, Fiji.

Although mining is essential for human economic development, is amongst the most polluting anthropogenic sources that influence seriously in water resources. Thus, understanding the presence and concentration of heavy metals in water and sediment in the vicinity of mines is important for the sustainability of the ecosystem. In this work, a multidisciplinary approach was developed to characterize the contamination level, source apportionment, co-existence, and degree of ecological and human health risks of HMs on water resources in the Vatukoula Goldmine region (VGR), Fiji. The outcomes suggested significant contamination by Cd (range: 0.01-0.95 g/L), Pb (range: 0.03-0.53 g/L), and Mn (range: 0.01-3.66 g/L) in water samples surpassed the level set by Fiji and international laws, whereas higher concentration of Cd (range: 2.60-23.16 mg/kg), Pb (range: 28.50-200.90 mg/kg) and Zn (range: 36.50-196.66 mg/kg) were detected in sediment samples. Lead demonstrated a strong significant co-existence network with other metals (e.g., Mn, Ni). Source apportionment recognized four source patterns (Cd, Pb, Ni, and Mn) for water and (Cr, Cd-Pb, Mn, and Zn) for sediment which was further confirmed by principal component analysis. The mine inputs source mainly contributed to Cd (66.07%) for water, while mineral processing mostly contributed to Zn (76.10%) for sediment. High non-carcinogenic (>1) and carcinogenic (>10-4) health risks, particularly in children, are related to the elevated Cd, Pb and Cr contents from the VGR. Uncertainty analysis demonstrates that the 90th quantile of Cd led to higher carcinogenic risk. Pollution indices disclosed a moderate to extremely contamination status mainly along the Toko dam which poses high ecological risks identified by index calculation. However, sediment quality indicators based on probable effect levels showed that there was a 75% of likelihood that the concentrations of Cd and Pb adjacent to the VGR have a severe toxic impact on aquatic lives.

Merkel cell polyomavirus oncoproteins induce microRNAs that suppress multiple autophagy genes.

Viruses can inhibit host autophagy through multiple mechanisms, and evasion of autophagy plays an important role in immune suppression and viral oncogenesis. Merkel cell polyomavirus (MCPyV) T-antigens are expressed and involved in the pathogenesis of a large proportion of Merkel cell carcinoma (MCC). Yet, how MCPyV induces tumorigenesis is not fully understood. Herein, we show that MCPyV T-antigens induce miR-375, miR-30a-3p and miR-30a-5p expressions, which target multiple key genes involved in autophagy, including ATG7, SQSTM1 (p62) and BECN1. In MCC tumors, low expression of ATG7 and p62 are associated with MCPyV-positive tumors. Ectopic expression of MCPyV small T-antigen and truncated large T-antigen (LT), but not the wild-type LT, resulted in autophagy suppression, suggesting the importance of autophagy evasion in MCPyV-mediated tumorigenesis. Torin-1 treatment induced cell death, which was attenuated by autophagy inhibitor, but not pan-caspase inhibitor, suggesting a potential role of autophagy in promoting cell death in MCC. Conceptually, our study shows that MCPyV oncoproteins suppress autophagy to protect cancer cells from cell death, which contribute to a better understanding of MCPyV-mediated tumorigenesis and potential MCC treatment.

Uranyl tris nitrato as a luminescent probe for trace water detection in acetonitrile.

Uranyl tris nitrato i.e. [UO2 (NO3 )3 ]- was formed by adding tetramethylammonium nitrate to uranyl nitrate in acetonitrile medium. The luminescence features of this complex in acetonitrile are very sensitive to water content, which could lead to the use of it as a luminescent probe for water present in acetonitrile. The luminescence intensity ratio of 507 to 467 nm peak of uranyl tris nitrato showed a linear response in the range 0-5% (v/v) water content in acetonitrile. The present method was applied for three synthetic samples of acetonitrile for water detection and the results obtained were compared using Karl Fischer titration. There was a good agreement in the values obtained by both the methods.

Estrone-Based Derivatives Stabilize the c-MYC and c-KIT G-Quadruplex DNA Structures.

G-rich sequences are present across the genome and can fold to form dynamic secondary structures, namely, G-quadruplexes (G4). These structures play a pivotal role in regulating numerous biological processes including replication, transcription, and translation. Therefore, targeting these structures using molecular scaffolds is an attractive approach to modulating their functions. Herein, we report the synthesis of three estrone-based derivatives (Est-1, Est-2, and Est-3) with a nonplanar core and a cationic alkyl side chain as G4 stabilizers. CD melting and polymerase stop assay results indicate that these ligands preferentially stabilize parallel c-MYC and c-KIT1 G4s over the other G4s and duplex DNAs. The ligand Est-3 shows cytotoxicity against cancer cell lines and effectively downregulates the c-KIT gene in HepG2 cell lines. Molecular modeling and dynamics studies showed that the ligand prefers stacking over the 5'-quartet of c-MYC G4 using the aromatic ring of the ligand. Overall, the findings of this study demonstrate that even G4 ligands can accommodate nonplanar scaffolds, which opens up new avenues for ligand design.

Solanum tuberosum tuber-driven starch-mediated green-hydrothermal synthesis of cerium oxide nanoparticles for efficient photocatalysis and antimicrobial activities.

In this study, we are reporting for the first time the utilization of Solanum tuberosum tuber-driven, starch-mediated, green-hydrothermally synthesized cerium oxide nanoparticles (G-CeO2 NPs) for the antibacterial activity and photodegradation of cationic (methylene blue, MB) and anionic (methyl orange, MO) dyes separately and in combination, aimed at environmental remediation. The XRD analysis confirms the fluorite structure of G-CeO2 NPs, displaying an average crystallite size of 9.6 nm. Further, XPS confirms the existence of 24% of Ce3+ oxidation states within G-CeO2 NPs. Morphological studies through FE-SEM and TEM reveal that starch-driven OH- ion production leads to a high percentage of active crystal facets, favoring the formation of Ce3+-rich CeO2 NPs. Photocatalytic experiments conducted under UV-A illumination demonstrate the superior degradation performance of G-CeO2 NPs, with MB degradation reaching 93.4% and MO degradation at 77.2% within 90 min. This outstanding catalytic activity is attributed to the mesoporous structure (pore diameter of 5.63 nm) with a narrow band gap, a large surface area (103.38 m2g-1), and reduced charge recombination, as validated by BET, UV-visible, and electrochemical investigations. The identification of photogenerated intermediates is achieved through LCMS, while the mineralization is monitored via total organic carbon analysis. Moreover, the scavenging experiments point towards the involvement of reactive oxygen species in organic oxidation, demonstrating efficiency over five consecutive trials. Additionally, G-CeO2 NPs exhibit potent antibacterial activity against both gram-positive and gram-negative bacteria. This study presents an innovative, and efficient approach to environmental remediation, shedding light on the potential of G-CeO2 NPs in addressing environmental pollution challenges.

Single MVA-SARS-2-ST/N Vaccination Rapidly Protects K18-hACE2 Mice against a Lethal SARS-CoV-2 Challenge Infection.

The sudden emergence of SARS-CoV-2 demonstrates the need for new vaccines that rapidly protect in the case of an emergency. In this study, we developed a recombinant MVA vaccine co-expressing SARS-CoV-2 prefusion-stabilized spike protein (ST) and SARS-CoV-2 nucleoprotein (N, MVA-SARS-2-ST/N) as an approach to further improve vaccine-induced immunogenicity and efficacy. Single MVA-SARS-2-ST/N vaccination in K18-hACE2 mice induced robust protection against lethal respiratory SARS-CoV-2 challenge infection 28 days later. The protective outcome of MVA-SARS-2-ST/N vaccination correlated with the activation of SARS-CoV-2-neutralizing antibodies (nABs) and substantial amounts of SARS-CoV-2-specific T cells especially in the lung of MVA-SARS-2-ST/N-vaccinated mice. Emergency vaccination with MVA-SARS-2-ST/N just 2 days before lethal SARS-CoV-2 challenge infection resulted in a delayed onset of clinical disease outcome in these mice and increased titers of nAB or SARS-CoV-2-specific T cells in the spleen and lung. These data highlight the potential of a multivalent COVID-19 vaccine co-expressing S- and N-protein, which further contributes to the development of rapidly protective vaccination strategies against emerging pathogens.

Transmural invasion of hepatic flexure of colon causing cholecystocolic fistula by aggressive gallbladder carcinoma.

Spontaneous enterobiliary fistulae are a complication of biliary disease or a disease of adjacent structures. Cholecystocolic fistulae are rare in relation to gallbladder carcinoma (GBC). Previous reports have presented images showing subtle findings suggestive of cholecystocolic fistula. We report the unusual spread and rare images of a case of cholecystocolicfistula,to highlight the aggressive nature of GBC and findings of gross transmural invasion of the colonic wall. The images acquired in all three planes define the anatomical and pathological extent conclusively. There are a higher number of GBC cases across the geographic belt of North India compared to the West. In this case, the patient's pathology was extensive and unresectable, and therefore palliative and supportive care wasadvised.

Management of Non-union Distal Femur Fractures With Augmentation Nail Plate Construct.

Background and objective A non-union distal femur fracture is a challenging fracture to treat. Common treatment modalities for non-union distal femur fractures include dual plating, intramedullary nails, ilizarov, and hybrid fixators. Despite the availability of a wide armamentarium of constructs, the clinical and functional outcome of these modalities is often complicated by significant morbidity, joint stiffness, and delayed union. The augmentation of the intramedullary nail with a locking plate results in a robust architecture, improving the likelihood of union. The use of this nail plate construct improves biomechanical stability and restores limb alignment, which enables early rehabilitation and weight bearing and lowers the likelihood of fixation failure. Methodology A prospective study was conducted at the Government Institute of Medical Science, Greater Noida, from January 2021 to January 2022 on 10 patients with non-union of the distal femur. All the patients were operated on with nail plate construct. The minimum follow-up period was 12 months. Results A total of 10 patients with a mean age of 55 years were included. Six were earlier treated with an intramedullary nail and four with extramedullary implants. All patients were managed with implant removal and fixation with nail plate construct and bone grafting. The average duration of the union was 10.3 months. The International Knee Documentation Committee (IKDC) score improved from 30.6 preoperatively to 67.3 postoperatively. Only one patient developed a superficial infection, which was managed by wound debridement and targeted antibiotic therapy. Conclusion In our experience, this relatively novel technique of combining nail plate constructs offers encouraging outcomes in the management of non-union of distal femur fractures, especially in elderly and osteopenic patients.

Distribution, sources, and pollution levels of toxic metal(loid)s in an urban river (Ichamati), Bangladesh using SOM and PMF modeling with GIS tool.

Indexical assessment coupled with a self-organizing map (SOM) and positive matrix factorization (PMF) modeling of toxic metal(loid)s in sediment and water of the aquatic environment provides valuable information from the environmental management perspective. However, in northwest Bangladesh, indexical and modeling assessments of toxic metal(loid)s in surface water and sediment are still rare. Toxic metal(loid)s were measured in sediment and surface water from an urban polluted river (Ichamati) in northwest Bangladesh using an atomic absorption spectrophotometer to assess distribution, pollution levels, sources, and potential environmental risks to the aquatic environment. The mean concentrations (mg/kg) of metal(loid)s in water are as follows: Fe (871) > Mn (382) > Cr (72.4) > Zn (34.2) > Co (20.8) > Pb (17.6) > Ni (16.7) > Ag (14.9) > As (9.0) > Cu (5.63) > Cd (2.65), while in sediment, the concentration follows the order, Fe (18,725) > Mn (551) > Zn (213) > Cu (47.6) > Cr (30.2) > Ni (24.2) > Pb (23.8) > Co (9.61) > As (8.23) > Cd (0.80) > Ag (0.60). All metal concentrations were within standard guideline values except for Cr and Pb for water and Cd, Zn, Cu, Pb, and As for sediment. The outcomes of eco-environmental indices, including contamination and enrichment factors and geo-accumulation index, differed spatially, indicating that most of the sediment sites were moderately to highly polluted by Cd, Zn, and As. Cd and Zn content can trigger ecological risks. The positive matrix factorization (PMF) model recognized three probable sources of sediment, i.e., natural source (49.39%), industrial pollution (19.72%), and agricultural source (30.92%), and three possible sources of water, i.e., geogenic source (45.41%), industrial pollution (22.88%), and industrial point source (31.72%), respectively. SOM analysis identified four spatial patterns, e.g., Fe-Mn-Ag, Cd-Cu, Cr-Pb-As-Ni, and Zn-Co in water and three patterns, e.g., Mn-Co-Ni-Cr, Cd-Cu-Pb-Zn, and As-Fe-Ag in sediment. The spatial distribution of entropy water quality index values shows that the southwestern area possesses "poor" quality water. Overall, the levels of metal(loid) pollution in the investigated river surpassed a critical threshold, which might have serious consequences for the river's aquatic biota and human health in the long run.

Enhanced luminescence of tris(carboxylato)uranyl(VI) complexes and energy transfer to Eu(III): a combined spectroscopic and theoretical investigation.

Complex formation between uranyl and carboxylate ligands (benzoate, nicotinate and isonicotinate) has been studied extensively by absorption and luminescence spectroscopy in acetonitrile medium. Experimental data had indicated the existence of stable and enhanced luminescent tris(carboxylato) uranyl(VI) complexes i.e. [UO2(L)3]- with D3h symmetry. The high luminescence of these complexes was due to the sensitization of the Oyl → U ligand to metal charge transfer (LMCT) emission by extremely intense equatorial (carboxylate ligands) LMCT bands. The variation in the experimentally observed parameters such as intensity of equatorial LMCT bands, luminescence lifetimes, quantum yields and structural parameters among tris(carboxylato) uranyl(VI) complexes are affirmed by quantum chemical calculations using density functional theory and the computational results are found to be in good agreement with experimental findings. Interestingly, in a very dilute mixture of [UO2(L)3]- and Eu(III), energy transfer from uranyl to Eu(III) is observed and it leads to the detection of europium at trace levels. This is an intriguing observation as none of the previous studies have reported such a low level of detection limit of Eu(III) by means of energy transfer from any metal.

Method to Eliminate Fluoride Interference in the Spectrophotometric Estimation of Zirconium: Application to U-Zr Alloys.

In the estimation of Zr using the ultraviolet-visible (UV-Vis) spectrophotometric technique, fluoride interference is a decade-old unsolved problem. The process of repeated fuming with strong acids is often used to remove fluoride from the solution in order to estimate Zr using spectrophotometry analysis. For the first time, in this work, a simple use of AlCl3 is reported as a suppressing reagent to eliminate the interference of fluoride in the estimation of Zr. Xylenol orange in HCl medium is used as a complexing reagent. Linearity in the datum acquired from absorbance at 551 nm (λmax) is achieved over the concentration range 0.25-4.5 µg mL-1 of Zr with a molar absorptivity of 35030 L·mol-1·cm-1 and Sandell's sensitivity of 0.003 µg·cm-2. Zr is quantified in the variety of U-Zr alloys and various water samples using spectrophotometric detection with a classical univariate calibration with suppressing of fluoride interference through AlCl3. Results from this novel analytical method herein developed for the first time are compared with those achieved from gravimetric analysis.

Unraveling the coordination approach of Eu(III) in cyphos nitrate ionic liquid - a comprehensive luminescence spectroscopy study.

In consideration of the mounting attention drawn by the ionic liquid cyphos 101 (trihexyl(tetradecyl)phosphonium chloride: [P66614][Cl]) in the recovery of rare earth metals and other valuable species from their waste matrices, an effort was made using luminescence spectroscopy to study the detailed liquid-liquid extraction and coordination behavior of Eu(III) using the nitrate form of cyphos 101 (cyphos nitrate: [P66614][NO3]) in its undiluted form. Eu(III) complexation with [P66614][NO3] at each stage of the extraction process was investigated using the luminescence spectroscopy technique. Various extraction parameters such as aqueous phase acidity, concentrations of ionic liquid extractant and initial Eu(III) ion, extraction time, experimental temperature, etc. were tuned to discover their impact on the complexation process. The uniqueness of the nitrate ion in ionic liquid was explored by comparing the emission patterns of Eu(III) with [P66614]-based ionic liquids containing different anions. In addition, the affirmative effect of increasing the initial aqueous phase nitrate ion concentration in the coordination process was underscored by comparing the emission patterns in the chloride medium. The luminescence results of the Eu(III)- [P66614][NO3] complex were compared both in unirradiated and irradiated ionic liquid phases. Asymmetry ratio (AR) and lifetime data under each experimental condition were ascertained, thereby revealing the precise nature of complex formation and strength of the metal-solvate species (metal-ligand complex formation) formed. The stripping of the loaded Eu(III) from the [P66614][NO3] phase was established and the results were presented in the form of the emission patterns of Eu(III) in both phases.

A Cross-Sectional Study of the Impact of the COVID-19 Pandemic on Previously Diagnosed Patients With Fibromyalgia.

Introduction Coronavirus disease 2019 (COVID-19) was a one-of-its-kind pandemic due to its high infectivity and mortality rate. Prolonged lockdown periods imposed during the pandemic saved many lives but, on the other hand, had a huge psychological and clinical impact on patients suffering from chronic medical illnesses. Aims This study aimed to find the impact of the COVID-19 pandemic on patients with previously diagnosed fibromyalgia. Methods A prospective observational study including the cohort of previously diagnosed cases of fibromyalgia as per American College of Rheumatology (ACR) 2010 criteria where the patients were evaluated by an online survey for socio-demographic profile, subjective improvement, and objective improvement in quality of life by the Fibromyalgia Impact Questionnaire-Revised (FIQR). Pre and post-COVID-19 scores were analyzed. The statistical procedure used included the chi-square test. Results A total of 78 subjects were recruited for the study, with a female preponderance (75%) and mean (SD) age of 37.2 (9.2) years. The duration of symptoms was nine to 12 months followed by more than 12 months at the time of the first consultation for the majority of subjects. Sixty-five percent (65%) of subjects had no improvement or deterioration on FIQR. Statistical analysis This included mean, standard deviation, proportions, percentages, and the chi-square test. Conclusion COVID-19 had a significant negative impact on patients with fibromyalgia even on continued pharmacological treatment. However, there was no statistically significant data on the comparison of the overall mean score of FIQR and each domain individually with the continuation of treatment and improvement of symptoms.

Assessment of dengue virus inactivation in random donor platelets using amotosalen and ultraviolet A illumination.

OBJECTIVES: The study objective was evaluation of amotosalen and ultraviolet A (UVA) illumination-based inactivation of dengue virus (DENV) in blood platelets. MATERIALS AND METHODS: Whole blood was collected from healthy donors and platelet concentrates were prepared at a tertiary care hospital in Gurugram, India. Platelet units collected from five blood group matched individuals were pooled and spiked with DENV. The spiked platelet units were subjected to amotosalen treatment followed by UVA illumination, to evaluate the efficiency of this method for viral inactivation. The treated platelet units were evaluated for the presence of infectious DENV. Amotosalen levels were quantified in the treated samples using high-performance liquid chromatography. RESULTS: The presence of replicating DENV was not observed in spiked platelet units treated with amotosalen and UVA illumination, whereas untreated units contained actively replicating DENV. Amotosalen levels were found to be in the permissible range after photochemical inactivation. CONCLUSIONS: Amotosalen/UVA pathogen inactivation treatment showed efficient inactivation of DENV in platelet components. Therefore, it seems to be a promising method for mitigating the risk of dengue transmission through transfusion of potentially contaminated platelet components in dengue-endemic countries such as India.