BACKGROUND: Transarterial radio-embolization (TARE) became a routine procedure for non-resectable liver tumor mainly hepatocellular carcinoma (HCC). Personalized dosimetry to the index lesion increased tumor response rate. However, there is no requirement to measure the precise activity injected during TARE. We measured 90Y-glass microspheres residue (90Y-Res) in the application system after TARE and assessed its potential impact on the tumor absorbed dose (AD) previously planned with 99mTc MAA SPECT/CT.
METHODS: We measured 90Y-Res using PET/CT in all patients that underwent TARE using 90Y-glass-microspheres for non-resectable liver tumors over one year.
RESULTS: 90Y-Res was measured in 34 patients (HCC n = 22) with 61 injections, 93.1 ± 94.6 MBq [2-437] that was 4.8 ± 3.5% [0.2-13.7] in comparison to the activity measured in the sealed TheraSphere™ vial (ρ = 0.697; p < 0.001).
CONCLUSIONS: We reported an average of 5% 90Y-Res using PET/CT after TARE with the strongest association to the activity in the TheraSphere™ vial. Therefore, when a high 90Y-Res is suspected on the survey meter, a 90Y-PET/CT scan of 90Y-Res might be useful as a first step to estimate if the target lesion received the recommended AD, especially in HCC patients with borderline tumor dosimetry on the pre-treatment 99mTc-MAA SPECT/CT.

Lycorma delicatula White (Hemiptera: Fulgoridae), spotted lanternfly, is a univoltine, phloem-feeding, polyphagous and invasive insect in the United States. Although a primary host for this species is Ailanthus altissima (Mill.) Swingle, tree of heaven, L. delicatula also feeds on many other plant species, including cultivated grapevines. As this species continues to spread, it is important to develop effective management tools. Here, we evaluated the residual efficacy of 4 insecticides commonly used in tree fruit management programs: dinotefuran, bifenthrin, carbaryl, and thiamethoxam. First, all mobile life stages (early instars, late instars, and adults) of L. delicatula were exposed for 1 h to dry insecticide residues (18 h old) applied to glass or A. altissima bark surfaces. While some mortality was detected immediately following the 1 h exposure period, 100% mortality occurred within 24 h for all materials and life stages exposed on both glass and bark surfaces. To evaluate longer residual activity of these materials, groups of adult L. delicatula were introduced into cages containing A. altissima trees treated with the same individual insecticides and exposed 6 h to residues that were 18 h or 7 days old. Paired, untreated A. altissima served as controls. In these bioassays, 48 h mortality for 18 h old residue reached 95% for thiamethoxam and 100% for bifenthrin and dinotefuran. Seven-day-old bifenthrin and dinotefuran residues again yielded 100% mortality, while thiamethoxam resulted in 58% mortality, and carbaryl yielded only 13.3% and was not significantly different from the control. These results clearly document the efficacy of specific insecticide applications as management tools against L. delicatula.

Southern stem rot of peanut, caused by Athelia rolfsii, is an important fungal disease that impacts peanut production worldwide. Foliar-applied fungicides are used to manage the disease, and several fungicides have been recently registered for southern stem rot control in peanuts. This study compared fungicidal, residual, and potential systemic activity of current fungicides against A. rolfsii using a laboratory bioassay. Peanut plants grown in the field were treated with eight fungicides approximately 90 days after planting, and plants were collected for the laboratory bioassay weekly for 5 weeks following application. Peanut plants were separated into the newest fully mature leaf present at sample collection, the second newest fully mature leaf present at the time of fungicide application, the upper stem, and the crown tissues. Each plant tissue was inoculated with A. rolfsii then incubated at 30°C for 2 days. Lesion length was measured, and percent inhibition of fungal growth by each fungicide relative to the control was calculated. All fungicides provided the greatest inhibition of A. rolfsii on leaf tissues that were present at the time of fungicide application, followed by the newly grown leaf and upper stem. Little inhibition occurred on the crown. Fungal inhibition decreased at similar rates over time for all fungicides tested. Succinate dehydrogenase inhibitors provided less basipetal protection of upper stems than quinone outside inhibitor or demethylation inhibitor fungicides. Properties of the fungicides characterized in this study, including several newly registered products, are useful for developing fungicide application recommendations to maximize their efficacy in controlling both foliar and soilborne peanut diseases.

BACKGROUND: Injectable radioactive iodine (I-131) frequently is used to treat hyperthyroidism in cats. In human medicine, residual activity after injection of radionuclides has been reported, and the actual quantity administered is recorded after administration.
OBJECTIVE: Our aim was to evaluate actual administered dose variability after administration of preprepared I-131 single unit doses for the treatment of hyperthyroidism in cats.
METHODS: Twenty-seven cats with hyperthyroidism treated with I-131 between April 2017 and March 2019.
METHODS: Retrospective observational study of cats treated with preprepared single unit I-131 doses. For each dose, the measured activity before administration and residual activity were recorded. The measured dose and the actual dose administered were compared to the prescribed dose.
RESULTS: Measured activity before administration ranged from 88.4% to 103.3% of the prescribed dose. Mean residual activity was 5.2 ± 3.0 MBq (ranging from 1.5% to 15% of the prescribed dose). The actual dose administered (measured activity - residual activity) ranged from 79.1% to 100.2% of the prescribed dose. Seventeen of 28 (60.7%) of the actual administered doses differed between 10% and 20% of the prescribed dose. One administered dose had a >20% difference compared to the prescribed dose (79.10% of the prescribed dose).
CONCLUSIONS: Our study identified variability in the residual and actual administered activity of I-131 as compared to the prescribed dose, which should be taken into consideration when treating cats with (predrawn) I-131.

Atrial fibrillation (AF) ablation with minimally interrupted direct oral anticoagulants (DOACs) may raise a concern about their remaining activity. We tested the residual activity of four different DOACs and its impact on intraprocedural heparinization in patients undergoing AF ablation.
We measured the anti-factor Χa activity for rivaroxaban, apixaban, and edoxaban, and serum DOAC concentration for rivaroxaban, apixaban, and dabigatran, 24 hours after the last intake in patients undergoing AF ablation treated with standard or reduced doses of DOACs. The heparin requirement during the procedure was also measured.
We enrolled 34 patients with rivaroxaban, 35 with apixaban, 32 with edoxaban, and 31 with dabigatran, and among them, 30 were treated with reduced doses. The anti-factor Χa activity was the highest in the apixaban group among the patients with standard doses. The DOAC concentration was paradoxically lower in patients with standard doses than in those with reduced doses among the patients with rivaroxaban (34.3 ± 19.8 vs 56.6 ± 7.7 ng/mL; P = .01) and dabigatran (12.6 ± 10.6 vs 23.4 ± 14.7 ng/mL; P = .03). The total heparin requirement per body surface area had significant correlations with the anti-factor Χa activity (r = -.36) and DOAC concentration (r = -.32). Two different multiple linear regression models (adjusted R2  = 0.56 and 0.6, respectively) revealed that the anti-factor Χa activity (β = -.28; P = .002) and DOAC concentration (β = -.38; P < .001) were independent determinants of the total heparin requirement.
Factors determining residual DOAC activity may include its type and dose regimen, and it may influence the heparin requirement during AF ablation.

OBJECTIVE: After yttrium-90 (90Y) radioembolization, residual activity and its consequences for dosimetric calculations are often not reported. The manufacturer for glass microspheres prescribes standard residual activity measurements by a survey meter, but the validity lacks evidence. This study aims to verify the accuracy of the survey meter approach for measuring residual activity of glass microspheres after treatment with glass microspheres.
METHODS: To validate the accuracy of the survey meter approach, the measured residual activity of glass microspheres by survey meter was compared with measurements by PET. A sample of these waste containers was also measured by dose calibrator to confirm the accuracy of the PET.
RESULTS: Twenty-four waste containers from glass microsphere treatments were prospectively scanned with 90Y-PET/CT. Bland-Altman plots showed substantial disagreement in residual activity measured by survey meter versus the residual activity measured by PET and dose calibrator, whereas the correlation between PET and dose calibrator was excellent (ρ = 0.99).
CONCLUSIONS: This study found a significant disagreement between the residual activities measured by the survey meter, compared to measurements by PET and dose calibrator. If relatively high amounts of residual activity are encountered using the exposure rate measurement with a survey meter, additional quantification should be considered using either PET/CT or a dose calibrator measurement.

BACKGROUND: Accurate determination of the efficacy of antimicrobial agents requires neutralization of residual antimicrobial activity in the samples before microbiological assessment of the number of surviving bacteria. Sodium polyanethol sulfonate (SPS) is a known neutralizer for the antimicrobial activity of aminoglycosides and polymyxins. In this study, we evaluated the ability of SPS to neutralize residual antimicrobial activity of antimicrobial peptides [SAAP-148 and pexiganan; 1% (wt/v) in PBS], antibiotics [mupirocin (Bactroban) and fusidic acid (Fucidin) in ointments; 2% (wt/wt))] and disinfectants [2% (wt/wt) silver sulfadiazine cream (SSD) and 0.5% (v/v) chlorhexidine in 70% alcohol].
METHODS: Homogenates of human skin models that had been exposed to various antimicrobial agents for 1 h were pipetted on top of Methicillin-resistant Staphylococcus aureus (MRSA) on agar plates to determine whether the antimicrobial agents display residual activity. To determine the optimal concentration of SPS for neutralization, antimicrobial agents were mixed with PBS or increasing doses of SPS in PBS (0.05-1% wt/v) and then 105 colony forming units (CFU)/mL MRSA were added. After 30 min incubation, the number of viable bacteria was assessed. Next, the in vitro efficacy of SAAP-148 against various gram-positive and gram-negative bacteria was determined using PBS or 0.05% (wt/v) SPS immediately after 30 min incubation of the mixture. Additionally, ex vivo excision wound models were inoculated with 105 CFU MRSA for 1 h and exposed to SAAP-148, pexiganan, chlorhexidine or PBS for 1 h. Subsequently, samples were homogenized in PBS or 0.05% (wt/v) SPS and the number of viable bacteria was assessed.
RESULTS: All tested antimicrobials displayed residual activity in tissue samples, resulting in a lower recovery of surviving bacteria on agar. SPS concentrations at ≥0.05% (wt/v) were able to neutralize the antimicrobial activity of SAAP-148, pexiganan and chlorhexidine, but not of SSD, Bactroban and Fucidin. Finally, SPS-neutralization in in vitro and ex vivo efficacy tests of SAAP-148, pexiganan and chlorhexidine against gram-positive and gram-negative bacteria resulted in significantly higher numbers of CFU compared to control samples without SPS-neutralization.
CONCLUSIONS: SPS was successfully used to neutralize residual activity of SAAP-148, pexiganan and chlorhexidine and this prevented an overestimation of their efficacy.

BACKGROUND: Atrial fibrillation (AF) ablation with minimally interrupted direct oral anticoagulants (DOACs) predominates, possibly raising concern about their remaining activity during the procedure. We aimed to examine residual activities of 4 different DOACs.
METHODS: The serum DOAC concentration and anti-factor Χa activity were measured 3 and 24 h after the last intake in patients undergoing AF ablation who were treated with rivaroxaban, apixaban, edoxaban, or dabigatran.
RESULTS: The reduction in the apixaban concentration between the 2 blood sampling time points (N = 32, mean ± SD, -67.7 ± 14.8% [231.6 ± 93.1 to 71.9 ± 31.8 ng/mL]) was smaller than that for rivaroxaban (N = 28, -83.6 ± 10.9% [234.2 ± 96.6 to 34.3 ± 19.8 ng/mL]; P < 0.001) and dabigatran (N = 20, -90.7 ± 7.3% [135.3 ± 68.3 to 12.6 ± 10.6 ng/mL]; P < 0.001), with its greatest value measured 24 h after the last intake in the apixaban group. The decrease in the anti-factor Χa activity was also smaller in the patients with apixaban (-73.8 ± 12.7%) than with rivaroxaban (-87.9 ± 7.9%; P < 0.001) and edoxaban (N = 22, -81.9 ± 15.2%; P = 0.049), and its remaining activity 24 h after the last dose was the highest in the apixaban group. A serum DOAC concentration measured 24 h after the last dose of >30 ng/mL was seen in 41 (51.3%) patients with rivaroxaban, apixaban, or dabigatran, and it was independently associated with apixaban versus rivaroxaban (odds ratio 5.0; P = 0.01) and apixaban versus dabigatran (odds ratio 74.0; P < 0.001).
CONCLUSIONS: The pattern of drug elimination from blood may vary depending on DOACs, and their residual activity may not be negligible even 24 h after the last intake.

One of the important physicochemical features of the proteins specifically multi-subunit types is their stability at high temperatures. The kinetics of the dissociation and denaturation of proteins possessing at least two subunits has certain challenges because the overall mechanism of dissociation can include hidden reversible and/or irreversible steps (conformational lock). There are numerous proteins related to diseases which are in equilibrium with oligomer forms. This equilibrium plays an important role in holding the activity levels of these proteins in vitro and in vivo. The stability of proteins is an essential milestone to study conformational changes of the proteins in the living cell. This concept is of great importance when proteins are used in biomedicine fields. The quaternary structure of multi-subunit proteins includes properties that affect function and kinetics of denaturation. The kinetics of denaturation may include some hidden stages of conformational transitions in the protein and steps of reversible dissociation of the oligomer. The transforming factors affect different areas especially active centers in the clefts of each subunit. The distinctive agent among all, is the temperature which sequentially destructs independent inter-subunit contact sites. Recent experimental data regarding dissociative mechanism for irreversible thermal denaturation of multi-subunit proteins have been summarized in the present paper.

Phenylketonuria (PKU), caused by phenylalanine hydroxylase (PAH) gene variants, is a common autosomal inherited metabolic disease. So far, 1111 PAH variants have been revealed. The residual activity of the PAH variants is the key determinant of the metabolic phenotype and BH4 responsiveness in PKU patients. In this study, the spectrum of PAH variants in 1083 Chinese PKU patients was analyzed. Then 20 variants (p.L52F, p.R86P, p.L128P, p.L142P, p.D163N, p.C203G, p.E214G, p.F260L, p.M276T, p.L311R, p.P314A, p.L364F, p.Q375H, p.F382I, p.A395S, p.V412D, p.E108*, p.C203*, p.C284* and p.E353*) were expressed in COS-7 cells. The residual activities and protein expression levels were detected by isotope-dilution liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) and Western blotting, respectively. We compared the results of the phenotypic prediction based on APV and PAH activity respectively, and further explored the relationship between residual activity and phenotype in PKU patients. We reported 9 newly discovered PAH variants for the first time, thereby expanding the spectrum of PAH variants. Among the 20 variants in our assay, 8 variants showed mild impaired residual activities (48-92%) and approximately normal protein expression levels compared to the wild-type PAH. In contrast, 9 variants showed severely impaired residual activities (0-34%) and reduced protein expression. However, three variants (p.L52F, p.F260L and p.P314A) showed impaired residual activities (5%, 32% and 29%), although the proteins were well expressed. We assigned APV scores for 14 variants, in which the results of the phenotypic prediction were consistent for 12/14 (86%) variants based on APV and residual activity respectively, and the residual activity correctly predicted 17/22 (77%) of the patients. Our study helped to further understand the genotype-phenotype correlation in PKU patients.