Determination of the Effects of Prenatal Remdesivir Exposure on Placenta Morphology, Placental IgG Transfer, and Fetal Growth in a Humanized Mouse Model

Remdesivir (RDV) is an antiviral medication used most recently for the treatment of COVID-19. Although no adverse effects were observed on perinatal parameters in reproductive and development toxicology studies at doses up to four-fold clinical area under the curve (AUC) exposures, some researchers have reported that therapeutic levels of RDV may impair early embryogenesis, as observed by in vitro studies. In addition, the influence of prenatal RDV exposure on maternal IgG transfer in the placenta is still unknown. Administration of RDV in pregnant humanized mouse model (Tg32), which expresses the human Fc gamma receptor and transporter (FCGRT) gene, was used to further evaluate potential effects on IgG transfer and concurrent perinatal endpoints. Animals were dosed daily from gestational days (GDs) 10- 14 with 25 mg/kg RDV (GS-5734) via intravenous injection (n=3-5 per group). Concurrent vehicle control animals were dosed intravenously with 12% sulfobutyl ether- beta-cyclodextrin in water (pH3.5;NaOH/HCl). All animals were administered 2 mg/kg human IgG via intravenous injection on GD 14. Placentae and fetuses were collected from dams on GD 14, 15, 16, and 18 and evaluated using histopathology and qPCR for inflammation markers. No abnormal morphologies (necrosis/apoptosis) of placentae were observed between the concurrent control and RDVdosed groups. Additionally, no differences in maternal body weights were observed. There were no statistically significant differences in placenta weights. There were no statistically significant changes in pregnancy parameters (implantation sites and dead fetuses/litter) and fetal weights between the RDV-dosed group and concurrent controls at GD 14, 15, 16, and 18. No changes were observed in transcript levels of inflammation markers in the RDV-dosed group when compared to the concurrent control group. There was a slightly lower ratio of fetal IgG level to maternal IgG levels in the RDV-dosed group;however, no statistically significant differences were observed between the RDV-dosed group and concurrent controls on GD 14, 15, 16, and 18. Our results suggest that a daily dose of 25 mg/kg RDV on GDs 10-14 in humanized mice did not cause adverse effects on placenta and fetal development. (Funded by the Perinatal Health Center of Excellence: E0300201.).

CourseExpo: An Immersive Collaborative Learning Ecosystem

Inspired by the need for remote learning technologies due to the Covid-19 pandemic and the isolated sense of lonely learners, we reimagined a remote classroom that fosters collaboration, builds community and yet without the constraints of the physical world. This paper presents a collaborative learning ecosystem that resembles a traditional city square where avatars of learners and facilitators wander, commingle, discover, and learn together. Buildings in the city square are learning modules which include typical knowledge units, assessment booths, or custom collaborative sketching studios. Our attempted prototype at realizing this conceptualization demonstrated initial success and we offer recommendations for future work. © 2022 Owner/Author.

Contemporary Practice in Telemedicine through Telecommunication Technology during COVID-19 Pandemic in Taiwan - A Single Center Experience

Background: To evaluate the feasibility, baseline characteristics, and satisfaction of patients receiving telemedicine care during the coronavirus 2019 (COVID-19) pandemic in Taiwan. Methods: We retrospectively analyzed patients during the COVID-19 pandemic between May 2021 and December 2021 in a tertiary medical center in northern Taiwan. Information on the distribution of physician divisions, patients' clinical characteristics, and patterns of prescription use in telemedicine care was analyzed. Data were extracted from both the ordinary outpatient department (OPD) and nursing home systems. Results: A total of 6587 patients (55.8% female, mean age: 57.3 +/- 25.8 years) included in our telemedicine care conducted during the pandemic COVID-19 epidemic. Those who were older, female, and patients of Internal Medicine and Family Medicine utilized telemedicine more frequently than ordinary OPD, with a high refill prescription rate (82.6%) and low mail-back prescription use (35.9%). Patients of Family Medicine comprised the majority (40.3%) of nursing home telemedicine, with lower refill pre-scription use (37.3%). Overall satisfaction was high regarding telemedicine care, physicians profession-alism, and medical problem solving (98.3% and 97.7%, respectively). Conclusion: Older age, female sex, and potentially more health conditions were associated with higher willingness to access telemedicine. We identified medical divisional and disease-based differences in prescription patterns. Copyright (c) 2022, Taiwan Society of Geriatric Emergency & Critical Care Medicine.

Managing advanced prostate cancer in the Asia Pacific region: "Real-world" application of Advanced Prostate Cancer Consensus Conference 2019 statements.

AIM: The second Asia-Pacific Advanced Prostate Cancer Consensus Conference (APAC APCCC 2020) gathered insights into the real-world application in the Asia-Pacific (APAC) region of consensus statements from the 3rd Advanced Prostate Cancer Consensus Conference (APCCC 2019). METHODS: The 4-h our virtual meeting in October 2020 brought together 26 experts from 14 APAC countries to discuss APCCC 2019 recommendations. Presentations were prerecorded and viewed prior to the meeting. A postmeeting survey gathered views on current practice. RESULTS: The meeting and survey highlighted several developments since APAC APCCC 2018. Increased access and use in the region of PSMA PET/CT imaging is providing additional diagnostic and staging information for advanced prostate cancer and influencing local and systemic therapy choices. Awareness of oligometastatic disease, although not clearly defined, is increasing. Novel androgen receptor pathway antagonists are expanding treatment options. Cost and access to contemporary treatments and technologies continue to be a significant factor influencing therapeutic decisions in the region. With treatment options increasing, multidisciplinary treatment planning, shared decision making, and informed choice remain critical. A discussion on the COVID-19 pandemic highlighted challenges for diagnosis, treatment, and clinical trials and new service delivery models that will continue beyond the pandemic. CONCLUSION: APAC-specific prostate cancer research and data are important to ensure that treatment guidelines and recommendations reflect local populations and resources. Facilitated approaches to collaboration across the region such as that achieved through APAC APCCC meetings continue to be a valuable mechanism to ensure the relevance of consensus guidelines within the region.

Binding signatures and cross-reactivity in the SARS-CoV-2 immune response

Background: Mounting evidence indicates that antibodies generated during SARS-CoV-2 infection are correlates of protection. Antibodies targeting Spike (S) on the viral surface have been shown to neutralize the virus. However, the full repertoire of neutralizing and non-neutralizing antibodies against SARSCoV-2, as well as cross-reactivity between SARS-CoV-2 and other circulating (CoVs), remains unclear. We sought to profile the complete repertoire of linear CoV epitopes targeted by the humoral immune response in patients with and without COVID-19 from Seattle, WA. Methods: To map the linear epitope profiles in patients, we developed a comprehensive pan-CoV phage display library composed of 39 amino acid peptides covering the complete genomes of SARS-CoV-2 and the six other CoVs known to infect humans. Using samples from patients with confirmed COVID-19 and with no known SARS-CoV-2 exposure, we immunoprecipitated antibodies against CoV peptides, deep sequenced the co-immunoprecipitated phage, and applied a customized computational pipeline to define SARS-CoV-2 and crossreactive epitopes. Results: The dominant immune responses to SARS-CoV-2 were targeted to regions spanning S, Nucleocapsid (N), and ORF1ab. We identified 17 epitopes within S that were present in two or more individuals, spanning both the S1 and S2 subunits, with some detected in > 75% of individuals. The most commonly mapped S epitope (S- residues 1121-1159) was a region just upstream of the second heptad repeat. We identified nine epitopes within N that were reactive in at least two individuals, four of which were present in at least 35% of patients. The two most prominent N epitopes were derived from the RNA binding domain (N residues 141-179 and 161-199). Epitopes isolated from ORF1ab were the most variable across patients. Of the 46 unique ORF1ab epitopes we identified, only five were present in two or more individuals, suggesting that ORF1ab responses are individual-specific. We also found a high degree of variation in the total number of epitopes targeted by individuals (ranging from 2 to 25). Finally, we identified four unique cross-reactive sequences that were bound by antibodies in SARS-CoV-2 unexposed individuals. Conclusion: Our study comprehensively defined the linear epitope profiles of a population of COVID-19 and SARS-CoV-2 unexposed patients. Epitope maps and functional characterization of SARS-CoV-2 antibodies will be critical for the development of a broad repertoire of COVID-19 treatments and vaccine strategies.