Profiling antibody epitopes induced by mRNA-1273 vaccination and boosters.

Background: Characterizing the antibody epitope profiles of messenger RNA (mRNA)-based vaccines against SARS-CoV-2 can aid in elucidating the mechanisms underlying the antibody-mediated immune responses elicited by these vaccines. Methods: This study investigated the distinct antibody epitopes toward the SARS-CoV-2 spike (S) protein targeted after a two-dose primary series of mRNA-1273 followed by a booster dose of mRNA-1273 or a variant-updated vaccine among serum samples from clinical trial adult participants. Results: Multiple S-specific epitopes were targeted after primary vaccination; while signal decreased over time, a booster dose after >6 months largely revived waning antibody signals. Epitope identity also changed after booster vaccination in some subjects, with four new S-specific epitopes detected with stronger signals after boosting than with primary vaccination. Notably, the strength of antibody responses after booster vaccination differed by the exact vaccine formulation, with variant-updated mRNA-1273.211 and mRNA-1273.617.2 booster formulations inducing significantly stronger S-specific signals than a mRNA-1273 booster. Conclusion: Overall, these results identify key S-specific epitopes targeted by antibodies induced by mRNA-1273 primary and variant-updated booster vaccination.

Advances in remote and cloud-based simulation through web conferencing platforms.

INTRODUCTION: Simulation-based learning has become an essential element in entry-level perfusion education. While the use of simulation has been demonstrated to improve patient outcomes, few institutions possess the budgetary resources to build and maintain a high-fidelity simulation environment. This project aims to identify novel uses of web conferencing platforms to support in-person, remote, and virtual simulation exercises. METHODS: The Zoom Virtual Meeting platform (Zoom Video Communications, Inc.) was incorporated into the perfusion simulation curriculum at the Medical University of South Carolina CVP Program. Among the observed benefits of incorporating meeting platform software included high-definition audio/visual outputs and recording capabilities, 3-D remote simulation, remote simulation proctoring, and classroom-based learning. Additional Zoom features included remote controlled screen access and sharing, annotations, and break-out rooms and activities. CONCLUSION: The combination of high-fidelity simulation with virtual and remote features may enhance the learning experience in healthcare education. Future developments in technology and software, simulation education, and instructions through virtual/remote learning may provide a pathway for the future of cardiovascular perfusion education.

Plasmodium infection is associated with cross-reactive antibodies to carbohydrate epitopes on the SARS-CoV-2 Spike protein.

Sero-surveillance can monitor and project disease burden and risk. However, SARS-CoV-2 antibody test results can produce false positive results, limiting their efficacy as a sero-surveillance tool. False positive SARS-CoV-2 antibody results are associated with malaria exposure, and understanding this association is essential to interpret sero-surveillance results from malaria-endemic countries. Here, pre-pandemic samples from eight malaria endemic and non-endemic countries and four continents were tested by ELISA to measure SARS-CoV-2 Spike S1 subunit reactivity. Individuals with acute malaria infection generated substantial SARS-CoV-2 reactivity. Cross-reactivity was not associated with reactivity to other human coronaviruses or other SARS-CoV-2 proteins, as measured by peptide and protein arrays. ELISAs with deglycosylated and desialated Spike S1 subunits revealed that cross-reactive antibodies target sialic acid on N-linked glycans of the Spike protein. The functional activity of cross-reactive antibodies measured by neutralization assays showed that cross-reactive antibodies did not neutralize SARS-CoV-2 in vitro. Since routine use of glycosylated or sialated assays could result in false positive SARS-CoV-2 antibody results in malaria endemic regions, which could overestimate exposure and population-level immunity, we explored methods to increase specificity by reducing cross-reactivity. Overestimating population-level exposure to SARS-CoV-2 could lead to underestimates of risk of continued COVID-19 transmission in sub-Saharan Africa.

Swap Up Your Meal: A Mass Media Nutrition Education Campaign for Oklahoma Teens.

To address a statewide need for obesity prevention, the Oklahoma Tobacco Settlement Endowment Trust launched Swap Up in 2021, a mass media nutrition education effort for teens, ages 13-18. Swap Up utilizes the SAVI messaging approach, an audience-centric message development framework that recognizes barriers to healthy living and offers realistic solutions. Five months into the campaign, an online survey was conducted (n = 200) to assess short-term program goals related to campaign delivery, engagement, and relevance. A secondary, long-term goal related to documenting and understanding self-reported changes in past month nutrition-related behaviors was also explored. A majority of participants (72%) reported aided awareness of the campaign brand logo/advertisements, and awareness (83%) of at least one main message. Nearly half (44%) of the participants reported at least one engagement with digital media. Main message recognition, perceived relevance, and self-reported nutritional behaviors were consistently highest among those reporting both campaign awareness and digital engagement. Ultimately, Swap Up reached and delivered nutrition education messages to Oklahoma teens within the first year of launch, as intended, and was associated with self-reported changes in recent behavior. This study provides evidence that SAVI offers a promising approach for nutrition education, and underscores why digital and social media engagement strategies are critical for mass media teen behavior change campaigns. Campaign implementation and evaluation are ongoing.

Examining Vaccine Sentiment on Twitter and Local Vaccine Deployment during the COVID-19 Pandemic.

Understanding local public attitudes toward receiving vaccines is vital to successful vaccine campaigns. Social media platforms may help uncover vaccine sentiments during infectious disease outbreaks at the local level, and whether offline local events support vaccine-promotion efforts. Communication Infrastructure Theory (CIT) served as a guiding framework for this case study of the San Diego region examining local public sentiment toward vaccines expressed on Twitter during the COVID-19 pandemic. We performed a sentiment analysis (including positivity and subjectivity) of 187,349 tweets gathered from May 2020 to March 2021, and examined how sentiment corresponded with local vaccine deployment. The months of November and December (52.9%) 2020 saw a majority of tweets expressing positive sentiment and coincided with announcements of offline local events signaling San Diego's imminent deployment of COVID-19 vaccines. Across all months, tweets remained mostly objective (never falling below 63%). In terms of CIT, considering multiple levels of the Story Telling Network in online spaces, and examining sentiment about vaccines on Twitter may help scholars to explore the Communication Action Context, as well as cultivate positive community attitudes to improve the Field of Health Action regarding vaccines. Real-time analysis of local tweets during development and deployment of new vaccines may help monitor local public responses and guide promotion of immunizations in communities.

High-resolution epitope mapping and characterization of SARS-CoV-2 antibodies in large cohorts of subjects with COVID-19.

As Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to spread, characterization of its antibody epitopes, emerging strains, related coronaviruses, and even the human proteome in naturally infected patients can guide the development of effective vaccines and therapies. Since traditional epitope identification tools are dependent upon pre-defined peptide sequences, they are not readily adaptable to diverse viral proteomes. The Serum Epitope Repertoire Analysis (SERA) platform leverages a high diversity random bacterial display library to identify proteome-independent epitope binding specificities which are then analyzed in the context of organisms of interest. When evaluating immune response in the context of SARS-CoV-2, we identify dominant epitope regions and motifs which demonstrate potential to classify mild from severe disease and relate to neutralization activity. We highlight SARS-CoV-2 epitopes that are cross-reactive with other coronaviruses and demonstrate decreased epitope signal for mutant SARS-CoV-2 strains. Collectively, the evolution of SARS-CoV-2 mutants towards reduced antibody response highlight the importance of data-driven development of the vaccines and therapies to treat COVID-19.

Plasmodium infection induces cross-reactive antibodies to carbohydrate epitopes on the SARS-CoV-2 Spike protein.

Individuals with acute malaria infection generated high levels of antibodies that cross-react with the SARS-CoV-2 Spike protein. Cross-reactive antibodies specifically recognized the sialic acid moiety on N-linked glycans of the Spike protein and do not neutralize in vitro SARS-CoV-2. Sero-surveillance is critical for monitoring and projecting disease burden and risk during the pandemic; however, routine use of Spike protein-based assays may overestimate SARS-CoV-2 exposure and population-level immunity in malaria-endemic countries.

Effect of inpatient electroencephalography on clinical decision making.

CONTEXT: Routine inpatient electroencephalography (EEG) is commonly used as a diagnostic and therapeutic decision-making tool in the care of patients with a wide spectrum of conditions. Previous investigations on EEG use have focused on current guidelines or specific clinical presentations. OBJECTIVE: To assess the effect of EEGs on clinical diagnosis and management of disease in adult inpatients in a community hospital. METHODS: Medical records of adult patients who underwent EEG between October 2008 and June 2009 in a single general community hospital were retrospectively reviewed. Data were collected for comorbidities, diagnoses, and management. Findings from EEGs were classified as normal, abnormal, or uninterpretable and according to whether they resulted in a change in diagnosis or management, supported clinical decision making and resulted in no change in diagnosis or management, or did not contribute to diagnosis or management. RESULTS: A total of 200 medical records were reviewed; 110 (55%) were for male patients and 90 (45%) were for female patients, with a mean (range) age of 60 (18-96) years. The most common pre-EEG diagnoses were altered mental status (52 [26%]) and seizure (48 [24%]). Of all EEGs, 115 (57.5%) had findings that were normal, 83 (41.5%) had findings that were abnormal, and 2 (1%) had findings that were uninterpretable. No EEGs had findings that resulted in a change in diagnosis or management, 8 EEGs (4%) had findings that supported clinical decision making and resulted in no change in diagnosis or management, and 192 EEGs (96%) had findings that did not contribute to diagnosis or management. CONCLUSION: In this study, inpatient EEGs rarely contributed to clinical decision making and in no case resulted in a change in diagnosis or management. These findings warrant future research on the effectiveness of inpatient EEGs for a wide breadth of clinical inpatient diagnoses.

Percutaneous vesicoamniotic shunting versus conservative management for fetal lower urinary tract obstruction (PLUTO): a randomised trial.

BACKGROUND: Fetal lower urinary tract obstruction (LUTO) is associated with high perinatal and long-term childhood mortality and morbidity. We aimed to assess the effectiveness of vesicoamniotic shunting for treatment of LUTO. METHODS: In a randomised trial in the UK, Ireland, and the Netherlands, women whose pregnancies with a male fetus were complicated by isolated LUTO were randomly assigned by a central telephone and web-based randomisation service to receive either the intervention (placement of vesicoamniotic shunt) or conservative management. Allocation could not be masked from clinicians or participants because of the invasive nature of the intervention. Diagnosis was by prenatal ultrasound. The primary outcome was survival of the baby to 28 days postnatally. All primary analyses were done on an intention-to-treat basis, but these results were compared with those of an as-treated analysis to investigate the effect of a fairly large proportion of crossovers. We used Bayesian methods to estimate the posterior probability distribution of the effectiveness of vesicoamniotic shunting at 28 days. The study is registered with the ISRCTN Register, number ISRCTN53328556. FINDINGS: 31 women with singleton pregnancies complicated by LUTO were included in the trial and main analysis, with 16 allocated to the vesicoamniotic shunt group and 15 to the conservative management group. The study closed early because of poor recruitment. There were 12 livebirths in each group. In the vesicoamniotic shunt group one intrauterine death occurred and three pregnancies were terminated. In the conservative management group one intrauterine death occurred and two pregnancies were terminated. Of the 16 pregnancies randomly assigned to vesicoamniotic shunting, eight neonates survived to 28 days, compared with four from the 15 pregnancies assigned to conservative management (intention-to-treat relative risk [RR] 1·88, 95% CI 0·71-4·96; p=0·27). Analysis based on treatment received showed a larger effect (3·20, 1·06-9·62; p=0·03). All 12 deaths were caused by pulmonary hypoplasia in the early neonatal period. Sensitivity analysis in which non-treatment-related terminations of pregnancy were excluded made some slight changes to point estimates only. Bayesian analysis in which the trial data were combined with elicited priors from experts suggested an 86% probability that vesicoamniotic shunting increased survival at 28 days and a 25% probability that it had a large, clinically important effect (defined as a relative increase of 55% or more in the proportion of neonates who survived). There was substantial short-term and long-term morbidity in both groups, including poor renal function-only two babies (both in the shunt group) survived to 2 years with normal renal function. Seven complications occurred in six fetuses from the shunt group, including spontaneous ruptured membranes, shunt blockage, and dislodgement. These complications resulted in four pregnancy losses. INTERPRETATION: Survival seemed to be higher in the fetuses receiving vesicoamniotic shunting, but the size and direction of the effect remained uncertain, such that benefit could not be conclusively proven. Our results suggest that the chance of newborn babies surviving with normal renal function is very low irrespective of whether or not vesicoamniotic shunting is done. FUNDING: UK National Institute of Health Research, Wellbeing of Women, Hannah Eliza Guy Charity (Birmingham Children's Hospital Charity).

Intra-dance variation among waggle runs and the design of efficient protocols for honey bee dance decoding.

Noise is universal in information transfer. In animal communication, this presents a challenge not only for intended signal receivers, but also to biologists studying the system. In honey bees, a forager communicates to nestmates the location of an important resource via the waggle dance. This vibrational signal is composed of repeating units (waggle runs) that are then averaged by nestmates to derive a single vector. Manual dance decoding is a powerful tool for studying bee foraging ecology, although the process is time-consuming: a forager may repeat the waggle run 1- >100 times within a dance. It is impractical to decode all of these to obtain the vector; however, intra-dance waggle runs vary, so it is important to decode enough to obtain a good average. Here we examine the variation among waggle runs made by foraging bees to devise a method of dance decoding. The first and last waggle runs within a dance are significantly more variable than the middle run. There was no trend in variation for the middle waggle runs. We recommend that any four consecutive waggle runs, not including the first and last runs, may be decoded, and we show that this methodology is suitable by demonstrating the goodness-of-fit between the decoded vectors from our subsamples with the vectors from the entire dances.

Ecological studies of the bio-inoculant Trichoderma hamatum LU592 in the root system of Pinus radiata.

The plant health- and growth-promoting biological inoculant (bio-inoculant) Trichoderma hamatum LU592 was transformed with the constitutively expressed green fluorescent protein (gfp) and hygromycin B resistance (hph) genes to specifically monitor the isolate in the root system of Pinus radiata within a strong indigenous Trichoderma population. A modified dilution plating technique was developed to allow the determination of the mycelia proportion of total propagule levels. LU592 was shown to colonize the rhizosphere most effectively when 10(5)  spores per pot were applied compared with inoculum concentrations of 10(3) and 10(7)  spores per pot. LU592 extended its zone of activity beyond the rhizosphere to at least 1 cm away from the root surface. A positive relationship was shown between P. radiata root maturation and the spatial and temporal proliferation of LU592 in the root system. A steep increase in mycelia levels and proportion of penetrated root segments was observed after 12 weeks. This study reinforces the value of genetic markers for use in ecological studies of filamentous fungi. However, despite isolate-specific recovery of the introduced isolate, it was shown that total propagule counts do not always correlate with the amount of viable mycelium present in the root system. Therefore, it is proposed that the differentiation of mycelia from spores and root penetration is used as more accurate measures of fungal activity.

Maintaining functionality in later years: a review of nutrition and physical activity interventions in postmenopausal women.

Independence and quality of life of postmenopausal women are influenced by functional status. Nutrition and physical activity impact functional changes through changes in body composition. The article presents a narrative review of the literature to identify interventions that improve the functionality of community-dwelling postmenopausal women. The authors used the Evidence Analysis Approach developed by the American Dietetic Association to appraise current research. Strong evidence does exist that interventions that incorporate both physical activity and nutrition can improve physical function of older women. However, research focusing on functional status and quality of life, in addition to nutrition and exercise, is extremely limited.

Dysfunctional transforming growth factor-beta receptor II accelerates prostate tumorigenesis in the TRAMP mouse model.

The contribution of a dysfunctional transforming growth factor-beta type II receptor (TGF beta RII) to prostate cancer initiation and progression was investigated in an in vivo mouse model. Transgenic mice harboring the dominant-negative mutant TGF-beta type II receptor (DNTGF beta RII) in mouse epithelial cell were crossed with the TRAMP prostate cancer transgenic mouse to characterize the in vivo consequences of inactivated TGF-beta signaling on prostate tumor initiation and progression. Histopathologic diagnosis of prostate specimens from the TRAMP+/DNTGF beta RII double transgenic mice revealed the appearance of early malignant changes and subsequently highly aggressive prostate tumors at a younger age, compared with littermates TRAMP+/Wt TGF beta RII mice. Immunohistochemical and Western blotting analysis revealed significantly increased proliferative and apoptotic activities, as well as vascularity and macrophage infiltration that correlated with an elevated vascular endothelial growth factor and MCP-1 protein levels in prostates from TRAMP+/DNTGF beta RII+ mice. An epithelial-mesenchymal transition (EMT) effect was also detected in prostates of TRAMP+/DNTGF beta RII mice, as documented by the loss of epithelial markers (E-cadherin and beta-catenin) and up-regulation of mesenchymal markers (N-cadherin) and EMT-transcription factor Snail. A significant increase in the androgen receptor mRNA and protein levels was associated with the early onset of prostate tumorigenesis in TRAMP+/DNTGF beta RII mice. Our results indicate that in vivo disruption of TGF-beta signaling accelerates the pathologic malignant changes in the prostate by altering the kinetics of prostate growth and inducing EMT. The study also suggests that a dysfunctional TGF beta RII augments androgen receptor expression and promotes inflammation in early stage tumor growth, thus conferring a significant contribution by TGF-beta to prostate cancer progression.

Targeting TGF-beta in prostate cancer: therapeutic possibilities during tumor progression.

BACKGROUND: TGF-beta regulates prostate growth by inhibiting epithelial cell proliferation and inducing apoptosis through eliciting a dynamic signaling pathway. In metastatic prostate cancer, however, TGF-beta serves as a tumor promoter. TGF-beta engages Smad-dependent and Smad-independent mechanisms to exert its action. During prostate tumorigenesis, prostate cells exhibit loss or mutation of TGF-beta transmembrane receptors. Increased production of TGF-beta causes immunosuppression, extracellular matrix degradation, epithelia to mesenchymal transition and angiogenesis that promotes tumor cell invasion and metastasis. OBJECTIVE: The molecular basis for effective therapeutic targeting of TGF-beta must be directed towards the double-edge-sword nature of the cytokine: inhibiting the TGF-beta tumor promoter capabilities in advanced metastatic prostate cancer, although retaining the growth-inhibitory abilities exhibited in early stages of prostate tumorigenesis. RESULTS/CONCLUSION: The current understanding of the therapeutic possibilities of targeting TGF-beta signaling during prostate tumor progression is built on preclinical studies. Studies targeting TGF-beta signaling pathway for the treatment of several human malignancies include the use of neutralizing antibodies, antisense oligonucelotides and small molecule inhibitors of kinase activity of the receptor complex. This review focuses on exploiting the therapeutic potential of targeting TGF-beta signaling in the context of its contribution to prostate cancer initiation and progression to metastasis.

Irreversible global DNA hypomethylation as a key step in hepatocarcinogenesis induced by dietary methyl deficiency.

Dietary methyl group deprivation is now well recognized as a model of hepatocarcinogenesis in rodents. In the present study, we examined the effects of feeding a methyl-deficient diet followed by a methyl-adequate diet on the extent of methylation of liver DNA and on the formation and evolution of altered hepatic foci. Male F344 rats were fed a methyl-deficient diet for 9, 18, 24, and 36 weeks, followed by re-feeding a methyl-adequate diet for a total of 54 weeks. Similar to previous findings, the methyl-deficient diet resulted in decreased levels of S-adenosylmethionine (SAM), SAM/SAH ratios, and global DNA hypomethylation. Feeding the methyl-adequate diet restored the liver SAM levels and SAM/SAH ratios to control levels in all experimental groups. In contrast, re-feeding the complete diet restored DNA methylation to normal level only in the group that had been fed the methyl-deficient diet for 9 weeks; in animals exposed to methyl deprivation longer, the methyl-adequate diet failed to reverse the hypomethylation of DNA. Liver tissue of rats exposed to methyl deficiency for 9, 18, 24, or 36 weeks was characterized by the persistent presence of placental isoform of glutathione-S-transferase (GSTpi)-positive lesions despite re-feeding the methyl-adequate diet. The persistence of altered hepatic foci in liver after withdrawal of methyl-deficient diet serves as an indication of the carcinogenic potential of a methyl-deficient diet. Substitution of the methyl-deficient diet with complete diet failed to prevent the expansion of initiated foci and restore DNA methylation in animals exposed to deficiency for 18, 24, or 36 weeks. The association between DNA hypomethylation and expansion of foci suggests that stable DNA hypomethylation is a promoting factor for clonal expansion of initiated cells. These results provide an experimental evidence and a mechanistic basis by which epigenetic alterations may contribute to the initiation and promotion steps of carcinogenesis.