Efficient capture of recombinant SARS-CoV-2 receptor-binding domain (RBD) with citrate-coated magnetic iron oxide nanoparticles.

Several vaccines against COVID-19 use a recombinant SARS-CoV-2 receptor-binding domain (RBD) as antigen, making the purification of this protein a key step in their production. In this work, citrate-coated magnetic iron oxide nanoparticles were evaluated as nano adsorbents in the first step (capture) of the purification of recombinant RBD. The nanoparticles were isolated through coprecipitation and subsequently coated with sodium citrate. The citrate-coated nanoparticles exhibited a diameter of 10 ± 2 nm, a hydrodynamic diameter of 160 ± 3 nm, and contained 1.9 wt% of citrate. The presence of citrate on the nanoparticles' surface was confirmed through FT-IR spectra and thermogravimetric analysis. The crystallite size (10.1 nm) and the lattice parameter (8.3646 Å) were determined by X-ray diffraction. In parallel, RBD-containing supernatant extracted from cell culture was exchanged through ultrafiltration and diafiltration into the adsorption buffer. The magnetic capture was then optimized using different concentrations of nanoparticles in the purified supernatant, and we found 40 mg mL-1 to be optimal. The ideal amount of nanoparticles was assessed by varying the RBD concentration in the supernatant (between 0.113 mg mL-1 and 0.98 mg mL-1), which resulted in good capture yields (between 83 ± 5% and 94 ± 4%). The improvement of RBD purity after desorption was demonstrated by SDS-PAGE and RP-HPLC. Furthermore, the magnetic capture was scaled up 100 times, and the desorption was subjected to chromatographic purifications. The obtained products recognized anti-RBD antibodies and bound the ACE2 receptor, proving their functionality after the developed procedure.

Leveling Up the Access to Radiation Therapy in Latin America: Economic Analysis of Investment, Equity, and Inclusion Opportunities Up to 2030.

PURPOSE: Latin America faces a shortage in radiation therapy (RT) units and qualified personnel for timely and high-quality treatment of patients with cancer. Investing in equitable and inclusive access to RT over the next decade would prevent thousands of deaths. Measuring the investment gap and payoff is necessary for stakeholder discussions and capacity planning efforts. METHODS AND MATERIALS: Data were collected from the International Atomic Energy Agency's Directory of Radiotherapy Centers, industry stakeholders, and individual surveys sent to national scientific societies. Nationwide data on available devices and personnel were compiled. The 10 most common cancers in 2020 with RT indication and their respective incidence rates were considered for gap calculations. The gross 2-year financial return on investment was calculated based on an average monthly salary across Latin America. A 10-year cost projection was calculated according to the estimated population dynamics for the period until 2030. RESULTS: Eleven countries were included in the study, accounting for 557,213,447 people in 2020 and 561 RT facilities. Approximately 1,065,684 new cancer cases were diagnosed, and a mean density of 768,469 (standard deviation ±392,778) people per available unit was found. By projecting the currently available treatment fractions to determine those required in 2030, it was found that 62.3% and 130.8% increases in external beam RT and brachytherapy units are needed from the baseline, respectively. An overall regional investment of approximately United States (US) $349,650,480 in 2020 would have covered the existing demand. An investment of US $872,889,949 will be necessary by 2030, with the expectation of a 2-year posttreatment gross return on investment of more than US $2.1 billion from patients treated in 2030 only. CONCLUSIONS: Investment in RT services is lagging in Latin America in terms of the population's needs. An accelerated outlay could save additional lives during the next decade, create a self-sustaining system, and reduce region-wide inequities in cancer care access. Cash flow analyses are warranted to tailor precise national-level intervention strategies.

Longitudinal Remote SBRT/SRS Training in Latin America: A Prospective Cohort Study.

Background: Continuing medical education in stereotactic technology are scarcely accessible in developing countries. We report the results of upscaling a longitudinal telehealth training course on stereotactic body radiation therapy (SBRT) and stereotactic radiosurgery (SRS), after successfully developing a pilot course in Latin America. Methods: Longitudinal training on SBRT and SRS was provided to radiation oncology practitioners in Peru and Colombia at no cost. The program included sixteen weekly 1-hour live conferencing sessions with interactive didactics and a cloud-based platform for case-based learning. Participant-reported confidence was measured in 16 SBRT/SRS practical domains, based on a 1-to-5 Likert scale. Pre- and post-curriculum exams were required for participation credit. Knowledge-baseline, pre- and post-curriculum surveys, overall and single professional-group confidence changes, and exam results were assessed. Results: One hundred and seventy-three radiotherapy professionals participated. An average of 56 (SD ±18) attendees per session were registered. Fifty (29.7%) participants completed the pre- and post-curriculum surveys, of which 30% were radiation oncologists (RO), 26% radiation therapists (RTT), 20% residents, 18% medical physicists and 6% neurosurgeons. Significant improvements were found across all 16 domains with overall mean +0.55 (SD ±0.17, p<0.001) Likert-scale points. Significant improvements in individual competences were most common among medical physicists, RTT and residents. Pre- and post-curriculum exams yielded a mean 16.15/30 (53.8 ± 20.3%) and 23.6/30 (78.7 ± 19.3%) correct answers (p<0.001). Conclusion: Longitudinal telehealth training is an effective method for improving confidence and knowledge on SBRT/SRS amongst professionals. Remote continuing medical education should be widely adopted in lower-middle income countries.

Long-Term Outcomes of an International Cooperative Study of Intraoperative Radiotherapy Upfront Boost With Low Energy X-Rays in Breast Cancer.

Purpose: The purpose of this study was to assess the effectivity of upfront kilovoltage intraoperative radiotherapy (IORT) as a boost in high-risk early-stage breast cancer patients from an international pooled cohort. Materials/Methods: Patients from four centers in three different countries were retrospectively screened. Those with a minimum 1-year follow-up were included. Cumulative local (LR), regional (RR), and distant metastasis rates (DM) were analyzed. Additionally, the estimated overall survival (OS) was assessed. The Cox regression analysis was performed to identify failure predicting factors. Results: A total of 653 patients from centers in Peru, Spain, and Germany were included. The median follow-up was 55 (12-180) months, and age was 58 (27-86) years. Clinical tumor (T) staging was T1 65.85%, T2 30.17%, and T3 3.98%. Positive margins were found in 7.9% and in-situ component in 20.06%. The median IORT dose was 20 (6-20). The median time from IORT to EBRT was 74.5 (13-364) days. An overall 3.4% (n = 22) of patients developed local recurrence at some point during follow-up. The 12-, 60-, and 120-month cumulative LR were 0.3%, 2.3%, and 7.9%, respectively. After multivariate analysis, only age <50 remained to be a significant prognostic factor for local recurrence (HR 0.19, 95% CI 0.08-0.47; p < 0.05). The 10-year estimated OS was 81.2%. Conclusion: Upfront boost with IORT yields similar local control outcomes to those EBRT-based reports. Results from prospective trials, regarding toxicity, cosmesis, and effectivity are awaited to confirm these findings.

Cognitive Impairment Is a Common Comorbidity in Deceased COVID-19 Patients: A Hospital-Based Retrospective Cohort Study.

We analyzed the frequency of cognitive impairment (CI) in deceased COVID-19 patients at a tertiary hospital in Spain. Among the 477 adult cases who died after admission from March 1 to March 31, 2020, 281 had confirmed COVID-19. CI (21.1% dementia and 8.9% mild cognitive impairment) was a common comorbidity. Subjects with CI were older, tended to live in nursing homes, had shorter time from symptom onset to death, and were rarely admitted to the ICU, receiving palliative care more often. CI is a frequent comorbidity in deceased COVID-19 subjects and is associated with differences in care.