The Situation During the COVID-19 Pandemic: A Snapshot in Germany -
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+During government-implemented restrictions in the wake of the COVID-19 pandemic, people’s everyday lives changed profoundly. However, there is to date little research chronicling how people perceived their changed everyday lives and which consequences this had. In a two-wave study, we examined the psychological characteristics of people’s situations and their correlates during shutdown in a large German sample (NT1 = 1,353; NT2 = 446). First, we compared characteristics during government-issued restrictions with retrospective accounts from before and with a follow-up assessment 6 to 7 months later when many restrictions had been lifted. We found that mean levels were lower and variances were higher for most characteristics during the shutdown. Second, the experience of certain situation characteristics was associated in meaningful and theoretically expected ways with people’s traits, appraisals of the COVID-19 crisis, and subjective well-being. Lastly, situation characteristics often substantially explained the associations of traits with appraisals and well-being. Our findings highlight the importance of considering perceived situations as these contribute to people’s functioning during crises.
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Who is impacted? Personality predicts individual differences in psychological consequences of the COVID-19 pandemic in Germany -
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+The COVID-19 pandemic has led to changes in people’s private and public lives that are unprecedented in modern history. However, little is known about the differential psychological consequences of restrictions that have been imposed to fight the pandemic. In a large and diverse German sample (N = 1,320), we examined how individual differences in psychological consequences of the pandemic (perceived restrictiveness of government-supported measures; global pandemic-related appraisals; subjective well-being) were associated with a broad set of faceted personality traits (Big Five, Honesty-Humility, Dark Triad). Facets of Extraversion, Neuroticism, and Openness were among the strongest and most important predictors of psychological outcomes, even after controlling for basic socio-demographic variables (gender, age). These findings suggest that psychological consequences of the pandemic depend on personality and thus add to the growing literature on the importance of considering individual differences in crisis situations.
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Isogenic iPSC-derived proximal and distal lung-on-chip models: Tissue- and virus-specific immune responses in human lungs -
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+Micro-physiological systems (MPS) are set to play a vital role in preclinical studies, particularly in the context of future viral pandemics. Nonetheless, the development of MPS is often impeded by the scarcity of reliable cell sources, especially when seeking various organs or tissues from a single patient for comparative analysis of the host immune response. Herein, we developed human airway-on-chip and alveolus-on-chip models using induced pluripotent stem cell (iPSC)-derived isogenic lung progenitor cells. Both models demonstrated the replication of two different respiratory viruses, namely SARS-CoV-2 and Influenza, as well as related cellular damage and innate immune responses-on-chip. Our findings reveal distinct immune responses to SARS-CoV-2 in the proximal and distal lung-on-chip models. The airway chips exhibited a robust interferon (IFN)-dependent immune response, whereas the alveolus chips exhibited dysregulated IFN activation but a significantly upregulated chemokine pathway. In contrast, Influenza virus infection induced a more pronounced immune response and cellular damage in both chip models compared to SARS-CoV-2. Thus, iPSC-derived lung-on-chip models may aid in quickly gaining insights into viral pathology and screening potential drugs for future pandemics.
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REPORT : Study on ‘Institutionalizing Science Advice to Governments -
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+The provision of appropriate science advice to governments is of national, regional, and global importance. However, many countries, especially in the developing world, lack effective framework to provide science advice to governments, which was laid bare during the COVID-19 pandemic. Hence, there is an urgent need to describe and analyse the structures and processes providing science advice to governments with a view to strengthening science advice. Science advice requires synthesizing and brokering valid, relevant, and reliable scientific evidence in respect of different policies. The National Academy of Sciences of Sri Lanka conducted a study on the status and processes of institutionalizing Science Advice to Governments in the Australasian region. The aims of the study were to a) propose and facilitate the development and strengthening of systematic science advice in member countries and its institutionalization b) Improve awareness among partners on a range of laws and regulations that exist legitimizing institutions and the processes used for government science advice c) develop capacities of participating academies in providing science advice d) enable academies to play a role and be part of the science advice process The methodology included administration of a structured questionnaire to gather data for the Situation Analysis with respect to science advice in partner countries. The questionnaire responses were categorized under several headings identified as the ‘Colombo Framework’: Selection of advisors, organizational structures to provide advice, the process followed to collate and synthesize advice, the process of communication, and evaluation of the process and impact of advice. The results showed a diversity of responses indicating a range of structures and processes: • The structures and types of advisors included, chief science advisor or advisors, a science advisory office or agency, science advisory boards, science advisory councils and ad-hoc arrangements during emergencies or crises, such as task forces. • Selection of advisors varied from appointments by an executive authority to nominations by science organizations or selection processes based on academic credentials. • The initial framing of questions requiring science advice were by policymakers, parliament committee or the President and advisory council. • Collation and synthesizing evidence: The methods used included systematic reviews, meta-analyses, through surveys, consultative meetings, expert opinion, foresight tools and workshops and/meetings of the experts where the evidence was reviewed. • The process of communicating science advice included reports issued by the science advisors, or advice directed to the Presidential Office, to Cabinet office, or submitted through Secretary of the Ministry of Science and Technology to the Head of State, or reports to the relevant minister and presidential secretariat. • The impact of science advice on policy was rarely evaluated. • Case Studies for individual countries supplemented the situation analysis for that country. • A SWOT analyses was compiled based on each country responses to reflect the totality of responses and for guidance in drafting a framework for Roadmaps for each country. As part of the project a three-day workshop was held in Colombo, Sri Lanka on ‘Institutionalizing Science Advice to Governments’ 6-8 July 2023. A descriptive ‘Colombo Declaration’ was released calling on governments to partner with scientists and demonstrate stronger commitment in strengthening action to institutionalize science advice to governments. The concluding session described future actions of developing Roadmaps and Case Studies by each partner country. The contextualized roadmaps will be developed through an iterative process and ‘work in progress’ submitted by most partner agencies were included in the report. The key outcomes of the Project were the following: 1. Documentation of Science Advice Systems in countries with situation analysis, reinforced with case studies and SWOT analyses and a framework for contextualized roadmaps that could form the foundation for further activities with support from the IAP and AASSA. 2. Developed and disseminated the ‘Colombo Declaration’ calling on governments to institutionalize science advice 3. Availability of validated questionnaire and framework (‘Colombo framework’) to replicate similar studies elsewhere. 4. Development of a process for promotion of institutionalization of science advice to governments that could be replicated in other countries or regions. 5. Promoted awareness among public, public administrators and policymakers and younger generation of scientists to be part of this transformative process, particularly to ensure continuity of efforts. 6. Contextualized Roadmaps design process has been initiated that is meant to trigger further discussions.
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DEFEN-CE: Social Dialogue in Defence of Vulnerable Groups in Post-COVID-19 Labour Markets. Report on Serbia -
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+The aim of this country report is to provide answers to the following DEFEN-CE research questions: 1. What public policy and social dialogue measures targeting the selected vulnerable groups were implemented to employment and social protection during the COVID-19 pandemic 2020-2022? 2. To what extent and how did social dialogue play a role in the implementation of social and employment rights of selected vulnerable groups in the COVID-19 pandemic between 2020 and 2022? 3. What lessons and opportunities does the COVID-19 pandemic yield for strengthening social dialogue in the studied countries? In order to answer these questions we used a mixed-method approach, combining qualitative and quantitative techniques. We started with the collection of the most relevant labour market data, especially regarding vulnerable groups. Then, by using the desk research we were able to synthesize the existing knowledge on public policies and social dialogue in the COVID-19 crisis. Finally, we conducted 10 semi-structured interviews to explore in-depth the role of social partners in the defence of the vulnerable groups.
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Gaining Biological Insights through Supervised Data Visualization -
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+Dimensionality reduction-based data visualization is pivotal in comprehending complex biological data. The most common methods, such as PHATE, t-SNE, and UMAP, are unsupervised and therefore reflect the dominant structure in the data, which may be independent of expert-provided labels. Here we introduce a supervised data visualization method called RF-PHATE, which integrates expert knowledge for further exploration of the data. RF-PHATE leverages random forests to capture intricate feature-label relationships. Extracting information from the forest, RF-PHATE generates low-dimensional visualizations that highlight relevant data relationships while disregarding extraneous features. This approach scales to large datasets and applies to classification and regression. We illustrate RF-PHATE's prowess through three case studies. In a multiple sclerosis study using longitudinal clinical and imaging data, RF-PHATE unveils a sub-group of patients with non-benign relapsing-remitting Multiple Sclerosis, demonstrating its aptitude for time-series data. In the context of Raman spectral data, RF-PHATE effectively showcases the impact of antioxidants on diesel exhaust-exposed lung cells, highlighting its proficiency in noisy environments. Furthermore, RF-PHATE aligns established geometric structures with COVID-19 patient outcomes, enriching interpretability in a hierarchical manner.
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scSniper: Single-cell Deep Neural Network-based Identification of Prominent Biomarkers -
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+Discovering disease biomarkers at the single-cell level is crucial for advancing our understanding of diseases and improving diagnostic accuracy. However, current computational methods often have limitations, such as a reliance on prior knowledge, constraints to unimodal data, and the use of conventional statistical tests for feature selection. To address these issues, we introduce scSniper, a novel approach that employs a specialized deep neural network framework tailored for robust single-cell multi-omic biomarker detection. A standout feature of scSniper is the mimetic attention block, enhancing alignment across multi-modal data types. Moreover, scSniper utilizes sensitivity analysis based on a deep neural network for feature selection and uncovers intricate gene regulatory networks without requiring prior knowledge. Comprehensive evaluations on real-world datasets, including COVID-19 CITE-Seq and LUAD scRNA-Seq, demonstrate scSniper's exceptional ability to identify critical biomarkers consistently outperforming traditional methods like MAST, Wilcox, and DESeq2.The scSniper tool and related experimental codes are publicly accessible at https://github.com/mcgilldinglab/scSniper.
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Enhanced surface accessibility of SARS-CoV-2 Omicron spike protein due to an altered glycosylation profile -
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+SARS-CoV-2 spike (S) proteins undergo extensive glycosylation, aiding proper folding, enhancing stability, and evading host immune surveillance. In this study, we used mass spectrometric analysis to elucidate the N-glycosylation characteristics and disulfide bonding of recombinant spike proteins derived from the SARS-CoV-2 Omicron variant (B.1.1.529) in comparison with the D614G spike variant. Furthermore, we conducted microsecond-long molecular dynamics simulations on spike proteins to resolve how the different N-glycans impact spike conformational sampling in the two variants. Our findings reveal that the Omicron spike protein maintains an overall resemblance to the D614G spike variant in terms of site-specific glycan processing and disulfide bond formation. Nonetheless, alterations in glycans were observed at certain N-glycosylation sites. These changes, in synergy with mutations within the Omicron spike protein, result in increased surface accessibility of the macromolecule, including ectodomain, receptor-binding domain, and N-terminal domain. These insights contribute to our understanding of the interplay between structure and function, thereby advancing effective vaccination and therapeutic strategies.
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Assembly reactions of SARS-CoV-2 nucleocapsid protein with nucleic acid -
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+The viral genome of SARS-CoV-2 is packaged by the nucleocapsid (N-)protein into ribonucleoprotein particles (RNPs), 38+/-10 of which are contained in each virion. Their architecture has remained unclear due to the pleomorphism of RNPs, the high flexibility of N-protein intrinsically disordered regions, and highly multivalent interactions between viral RNA and N-protein binding sites in both N-terminal (NTD) and C-terminal domain (CTD). Here we explore critical interaction motifs of RNPs by applying a combination of biophysical techniques to mutant proteins binding different nucleic acids in an in vitro assay for RNP formation, and by examining mutant proteins in a viral assembly assay. We find that nucleic acid-bound N-protein dimers oligomerize via a recently described protein-protein interface presented by a transient helix in its long disordered linker region between NTD and CTD. The resulting hexameric complexes are stabilized by multi-valent protein-nucleic acid interactions that establish crosslinks between dimeric subunits. Assemblies are stabilized by the dimeric CTD of N-protein offering more than one binding site for stem-loop RNA. Our study suggests a model for RNP assembly where N-protein scaffolding at high density on viral RNA is followed by cooperative multimerization through protein-protein interactions in the disordered linker.
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Predicting Antibody and ACE2 Affinity forSARS-CoV-2 BA.2.86 with In Silico ProteinModeling and Docking -
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+The emergence of the Omicron sublineage of SARS-CoV-2 virus BA.2.86 (nicknamed "Pirola") has raised concerns about its potential impact on public health and personal health as it has many mutations with respect to previous variants. We conducted an in silico analysis of neutralizing antibody binding to BA.2.86. Selected antibodies came from patients who were vaccinated and/or infected. We predicted binding affinity between BA.2.86 and antibodies. We also predicted the binding affinity between the same antibodies and several previous SARS-CoV2 variants (Wuhan and Omicron descendants BA.1, BA.2, and XBB.1.5). Additionally, we examined binding affinity between BA.2.86 and human angiotensin converting enzyme 2 (ACE2) receptor, a cell surface protein crucial for viral entry. We found no statistically significant difference in binding affinity between BA.2.86 and other variants, indicating a similar immune response. These findings contradict media reports of BA.2.86's high immune evasion potential based on its mutations. We discuss the implications of our findings and highlight the need for modeling and docking studies to go above and beyond mutation and basic serological neutralization analysis. Future research in this area will benefit from increased structural analyses of memory B-cell derived antibodies and should emphasize the importance of choosing appropriate samples for in silico studies to assess protection provided by vaccination and infection. This research contributes to understanding the BA.2.86 variant's potential impact on public health. Moreover, we introduce new methodologies for predictive medicine in ongoing efforts to combat the evolving SARS-CoV-2 pandemic and prepare for other hazards.
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Development of attenuated coxsackievirus B3 vectored intranasal pre-emptive pan-coronavirus vaccine -
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+SARS-CoV-2 has the ability to evade immunity, resulting in breakthrough infections even after vaccination. Similarly, zoonotic coronaviruses pose a risk of spillover to humans. There is an urgent need to develop a pre-emptive pan-coronavirus vaccine that can induce systemic and mucosal immunity. Here, we employed a combination of immune-informatics approaches to identify shared immunodominant linear B- and T-cell epitopes from SARS-CoV-2 variants of concern (VOCs) and variants of interest (VOIs), as well as zoonotic coronaviruses. Epitope-guided vaccine were designed and the attenuated coxsackievirus B3 vectored intranasal vaccines rCVB3-EPI and rCVB3-RBD-trimer were constructed. The immunogenicity of these candidate vaccines was evaluated using Balb/c mice. The results demonstrated effective immune responses, including the production of SARS-CoV-2-specific IgG and sIgA antibodies, as well as T cell-mediated responses. However, further verification is required to assess cross-reactivity with various variants. Our intranasal pre-emptive pan-coronavirus vaccine design framework offers an appealing candidate for future vaccine development.
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Building energy use in COVID-19 lockdowns: did much change? -
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+The UK national lockdowns introduced to prevent the spread of COVID-19 had huge impacts on daily lives, as people were largely confined to their homes. It could be expected that residential energy use would drastically increase while non-residential decreased, however the picture is not so clear. In this paper three complementary datasets on different scales are used to explore changes in building energy use during two national lockdowns (spring 2020 and winter 2021): the complete building stock of Great Britain, a sample of ~1000 residential buildings, and a sample of ~24,000 residential boilers. Energy signature analysis was used for the building data to estimate the changes in energy consumption for space heating and otherwise, with the boiler data able to separate space and water heating and explore changes in these. In the 2020 lockdown residential energy consumption for water heating and appliances increased, with decreased use for heating, resulting in a reduction in total energy use during the heating season. In the 2021 lockdown total energy consumption changed little, however a decrease in the use of gas space heating was observed. These residential changes counteracted any non-domestic changes, resulting in little difference in national energy consumption.
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Tertiary folds of the SL5 RNA from the 5’ proximal region of SARS-CoV-2 and related coronaviruses -
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+Coronavirus genomes sequester their start codons within stem-loop 5 (SL5), a structured, 5' genomic RNA element. In most alpha- and betacoronaviruses, the secondary structure of SL5 is predicted to contain a four-way junction of helical stems, some of which are capped with UUYYGU hexaloops. Here, using cryogenic electron microscopy (cryo-EM) and computational modeling with biochemically-determined secondary structures, we present three-dimensional structures of SL5 from six coronaviruses. The SL5 domain of betacoronavirus SARS-CoV-2, resolved at 4.7 [A] resolution, exhibits a T-shaped structure, with its UUYYGU hexaloops at opposing ends of a coaxial stack, the T's "bar." Further analysis of SL5 domains from SARS-CoV-1 and MERS (7.1 and 6.4-6.9 [A] resolution, respectively) indicate that the junction geometry and inter-hexaloop distances are conserved features across the studied human-infecting betacoronaviruses. The MERS SL5 domain displays an additional tertiary interaction, which is also observed in the non-human-infecting betacoronavirus BtCoV-HKU5 (5.9-8.0 [A] resolution). SL5s from human-infecting alphacoronaviruses, HCoV-229E and HCoV-NL63 (6.5 and 8.4-9.0 [A] resolution, respectively), exhibit the same coaxial stacks, including the UUYYGU-capped bar, but with a phylogenetically distinct crossing angle, an X-shape. As such, all herein studied SL5 domains fold into stable tertiary structures with cross-genus similarities, with implications for potential protein-binding modes and future therapeutic targets.
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Transmission dynamics of MERS-CoV in a transgenic human DPP4 mouse model -
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+Since 2002, three novel coronavirus outbreaks have occurred: severe acute respiratory syndrome coronavirus (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2. A better understanding of the transmission potential of coronaviruses will result in adequate infection control precautions and an early halt of transmission within the human population. Experiments on the stability of coronaviruses in the environment, as well as transmission models, are thus pertinent. Here, we show that transgenic mice expressing human DPP4 can be infected with MERS-CoV via the aerosol route. Exposure to 5x106 TCID50 and 5x104 TCID50 MERS-CoV per cage via fomites resulted in transmission in 15 out of 20 and 11 out of 18 animals, respectively. Exposure of sentinel mice to donor mice one day post inoculation with 105 TCID50 MERS-CoV resulted in transmission in 1 out of 38 mice via direct contact and 4 out of 54 mice via airborne contact. Exposure to donor mice inoculated with 104 TCID50 MERS-CoV resulted in transmission in 0 out of 20 pairs via direct contact and 0 out of 5 pairs via the airborne route. Our model shows limited transmission of MERS-CoV via the fomite, direct contact, and airborne routes. The hDPP4 mouse model will allow assessment of the ongoing evolution of MERS-CoV in the context of acquiring enhanced human-to-human transmission kinetics and will inform the development of other transmission models.
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SARS-CoV-2 monoclonal antibody treatment followed by vaccination shifts human memory B cell epitope recognition suggesting antibody feedback -
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+Therapeutic anti-SARS-CoV-2 monoclonal antibodies (mAbs) have been extensively studied in humans, but the impact on immune memory of mAb treatment during an ongoing immune response has remained unclear. Here, we evaluated the effect of infusion of the anti-SARS-CoV-2 spike receptor binding domain (RBD) mAb bamlanivimab on memory B cells (MBCs) in SARS-CoV-2-infected individuals. Bamlanivimab treatment skewed the repertoire of memory B cells targeting Spike towards non-RBD epitopes. Furthermore, the relative affinity of RBD memory B cells was weaker in mAb-treated individuals compared to placebo-treated individuals over time. Subsequently, after mRNA COVID-19 vaccination, memory B cell differences persisted and mapped to a specific defect in recognition of the class II RBD site, the same RBD epitope recognized by bamlanivimab. These findings indicate a substantial role of antibody feedback in regulating human memory B cell responses, both to infection and vaccination. These data indicate that mAb administration can promote alterations in the epitopes recognized by the B cell repertoire, and the single administration of mAb can continue to determine the fate of B cells in response to additional antigen exposures months later.
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Collection of Additional Biological Samples From Potentially COVID-19 Patients for Monitoring of Biological Parameters Carried Out as Part of the Routine - Conditions: SARS CoV 2 Infection Interventions: Diagnostic Test: RIPH2 Sponsors: CerbaXpert Not yet recruiting
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Mitigating Mental and Social Health Outcomes of COVID-19: A Counseling Approach - Conditions: Social Determinants of Health; Mental Health Issue; COVID-19 Interventions: Behavioral: Individual counseling; Behavioral: Group counseling; Other: Resources Sponsors: Idaho State University Not yet recruiting
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Promoting Engagement and COVID-19 Testing for Health - Conditions: COVID-19 Interventions: Behavioral: COVID-19 Test Reporting; Behavioral: Personalized Nudges via Text Messaging; Behavioral: Non-personalized Nudges via Text Messaging Sponsors: Emory University; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Morehouse School of Medicine; Georgia Institute of Technology Not yet recruiting
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Development and Qualification of Methods for Analyzing the Mucosal Immune Response to COVID-19 - Conditions: Certain Disorders Involving the Immune Mechanism Interventions: Biological: Sampling; Biological: PCR (polymerase chain reaction) SARS-CoV-2 Sponsors: University Hospital, Tours Not yet recruiting
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Water-based Activity to Enhance Recovery in Long COVID - Conditions: Long COVID Interventions: Behavioral: WATER+CT; Behavioral: Usual Care Sponsors: VA Office of Research and Development Not yet recruiting
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Performance Evaluation of the Lucira COVID-19 & Flu Test - Conditions: COVID-19; Influenza Interventions: Device: Lucira COVID-19 & Flu Test Sponsors: Lucira Health Inc Completed
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Efficacy of Two Therapeutic Exercise Modalities for Patients With Persistent COVID - Conditions: Persistent COVID-19 Interventions: Other: exercise programe Sponsors: Facultat de ciencies de la Salut Universitat Ramon Llull Recruiting
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Robotic Assisted Hand Rehabilitation Outcomes in Adults After COVID-19 - Conditions: Robotic Exoskeleton; Post-acute Covid-19 Syndrome; Rehabilitation Outcome; Physical And Rehabilitation Medicine Interventions: Device: Training with a Robotic Hand Exoskeleton Sponsors: University of Valladolid; Centro Hospitalario Padre Benito Menni Completed
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Cognitive Rehabilitation in Post-COVID-19 Syndrome - Conditions: Post-COVID-19 Syndrome Interventions: Behavioral: CO-OP Procedures; Behavioral: Inactive Control Group Sponsors: University of Missouri-Columbia; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Not yet recruiting
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Safety and Immunogenicity of BNT162b2 Coadministered With SIIV in Adults 18 Through 64 Years of Age - Conditions: SARS-CoV-2 Infection; COVID-19 Interventions: Biological: BNT162b2; Other: Placebo; Biological: Seasonal Inactivated Influenza Vaccine Sponsors: Pfizer Completed
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Clinical Evaluation of the Panbio™ COVID-19/Flu A&B Panel - Conditions: COVID-19; Influenza A; Influenza B Interventions: Diagnostic Test: Panbio™ Sponsors: Abbott Rapid Dx Recruiting
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A Multicenter, Adaptive, Randomized, doublE-blinded, Placebo-controlled Study in Participants With Long COVID-19: The REVIVE Trial - Conditions: Long COVID-19 Syndrome; Chronic Fatigue Syndrome Interventions: Drug: Fluvoxamine Maleate 100 MG; Drug: Placebo; Drug: Metformin Extended Release Oral Tablet Sponsors: Cardresearch Recruiting
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Connecting Friends and Health Workers to Boost COVID-19 Vaccination in Latino Communities - Conditions: COVID-19; Vaccine Interventions: Behavioral: REDES; Behavioral: Control Sponsors: Johns Hopkins University; National Institute on Minority Health and Health Disparities (NIMHD); Rutgers University Recruiting
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Influence of Hypoxic, Normobaric and Hypobaric Training on the Immunometabolism of Post-covid-19 Athletes - Conditions: Normobaric Hypoxia; Hypoventilation; Normoxia Interventions: Other: Repeated sprint Sponsors: Faculdade de Motricidade Humana; University of Sao Paulo; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. Not yet recruiting
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The Safety and Tolerability of A8G6 COVID-19 Neutralization Antibody Combined With Nasal Spray - Conditions: SARS-CoV-2; Prevention Interventions: Biological: A8G6 SARS-CoV-2 Neutralization Antibody combination nasal spray; Other: A8G6 SARS-CoV-2 Neutralization Antibody nasal excipient Sponsors: The Second Affiliated Hospital of Chongqing Medical University Recruiting
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From PubMed
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Predictions based on inflammatory cytokine profiling of Egyptian COVID-19 with 2 potential therapeutic effects of certain marine-derived compounds - CONCLUSION: The investigated inflammatory biomarkers in Egyptian COVID-19 patients showed a strong correlation between IL6, TNF-α, NF-κB, CRB, DHL, and ferritin as COVID-19 biomarkers and determined the severity of the infection. Also, the oxidative /antioxidant showed good biomarkers for infection recovery and progression of the patients.
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Circularized Nanodiscs for Multivalent Mosaic Display of SARS-CoV-2 Spike Protein Antigens - The emergence of vaccine-evading SARS-CoV-2 variants urges the need for vaccines that elicit broadly neutralizing antibodies (bnAbs). Here, we assess covalently circularized nanodiscs decorated with recombinant SARS-CoV-2 spike glycoproteins from several variants for eliciting bnAbs with vaccination. Cobalt porphyrin-phospholipid (CoPoP) was incorporated into the nanodisc to allow for anchoring and functional orientation of spike trimers on the nanodisc surface through their His-tag….
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Comparative Immune Response after Vaccination with SOBERANA® 02 and SOBERANA® plus Heterologous Scheme and Natural Infection in Young Children - (1) Background: In children, SARS-CoV-2 infection is mostly accompanied by mild COVID-19 symptoms. However, multisystem inflammatory syndrome (MIS-C) and long-term sequelae are often severe complications. Therefore, the protection of the pediatric population against SARS-CoV-2 with effective vaccines is particularly important. Here, we compare the humoral and cellular immune responses elicited in children (n = 15, aged 5-11 years) vaccinated with the RBD-based vaccines SOBERANA^(®) 02 and…
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Screening Drugs for Broad-Spectrum, Host-Directed Antiviral Activity: Lessons from the Development of Probenecid for COVID-19 - In the early stages of drug discovery, researchers develop assays that are compatible with high throughput screening (HTS) and structure activity relationship (SAR) measurements. These assays are designed to evaluate the effectiveness of new and known molecular entities, typically targeting specific features within the virus. Drugs that inhibit virus replication by inhibiting a host gene or pathway are often missed because the goal is to identify active antiviral agents against known viral…
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Covalent Inhibitors from Saudi Medicinal Plants Target RNA-Dependent RNA Polymerase (RdRp) of SARS-CoV-2 - COVID-19, a disease caused by SARS-CoV-2, has caused a huge loss of human life, and the number of deaths is still continuing. Despite the lack of repurposed drugs and vaccines, the search for potential small molecules to inhibit SARS-CoV-2 is in demand. Hence, we relied on the drug-like characters of ten phytochemicals (compounds 1-10) that were previously isolated and purified by our research team from Saudi medicinal plants. We computationally evaluated the inhibition of RNA-dependent RNA…
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Chemoprophylactic Assessment of Combined Intranasal SARS-CoV-2 Polymerase and Exonuclease Inhibition in Syrian Golden Hamsters - Pibrentasvir (PIB) has been demonstrated to block exonuclease activity of the SARS-CoV-2 polymerase, protecting favipiravir (FVP) and remdesivir (RDV) from post-incorporation excision and eliciting antiviral synergy in vitro. The present study investigated the chemoprophylactic efficacy of PIB, FVP, RDV, FVP with PIB, or RDV with PIB dosed intranasally twice a day, using a Syrian golden hamster contact transmission model. Compared to the saline control, viral RNA levels were significantly lower…
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SARS-CoV-2 Papain-like Protease Negatively Regulates the NLRP3 Inflammasome Pathway and Pyroptosis by Reducing the Oligomerization and Ubiquitination of ASC - The interaction of viruses with hosts is complex, especially so with the antiviral immune systems of hosts, and the underlying mechanisms remain perplexing. Infection with SARS-CoV-2 may result in cytokine syndrome in the later stages, reflecting the activation of the antiviral immune response. However, viruses also encode molecules to negatively regulate the antiviral immune systems of hosts to achieve immune evasion and benefit viral replication during the early stage of infection. It has been…
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Potent Antiviral Activity of Vitamin B12 against Severe Acute Respiratory Syndrome Coronavirus 2, Middle East Respiratory Syndrome Coronavirus, and Human Coronavirus 229E - Repurposing vitamins as antiviral supporting agents is a rapid approach used to control emerging viral infections. Although there is considerable evidence supporting the use of vitamin supplementation in viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the specific role of each vitamin in defending against coronaviruses remains unclear. Antiviral activities of available vitamins on the infectivity and replication of human coronaviruses, namely,…
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Development and Evaluation of a Self-Nanoemulsifying Drug Delivery System for Sinapic Acid with Improved Antiviral Efficacy against SARS-CoV-2 - This study aimed to develop a self-nanoemulsifying drug delivery system (SNE) for sinapic acid (SA) to improve its solubility and antiviral activity. Optimal components for the SA-SNE formulation were selected, including Labrafil as the oil, Cremophor EL as the surfactant, and Transcutol as the co-surfactant. The formulation was optimized using surface response design, and the optimized SA-SNE formulation exhibited a small globule size of 83.6 nm, high solubility up to 127.1 ± 3.3, and a 100%…
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Effect of a Total Extract and Saponins from Astragalus glycyphyllos L. on Human Coronavirus Replication In Vitro - Members of the family Coronaviridae cause diseases in mammals, birds, and wildlife (bats), some of which may be transmissible to humans or specific to humans. In the human population, they can cause a wide range of diseases, mainly affecting the respiratory and digestive systems. In the scientific databases, there are huge numbers of research articles about the antiviral, antifungal, antibacterial, antiviral, and anthelmintic activities of medicinal herbs and crops with different ethnobotanical…
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Kaempferol: A Review of Current Evidence of Its Antiviral Potential - Kaempferol and its derivatives are flavonoids found in various plants, and a considerable number of these have been used in various medical applications worldwide. Kaempferol and its compounds have well-known antioxidant, anti-inflammatory and antimicrobial properties among other health benefits. However, the antiviral properties of kaempferol are notable, and there is a significant number of experimental studies on this topic. Kaempferol compounds were effective against DNA viruses such as…
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Unwinding the SARS-CoV-2 Ribosomal Frameshifting Pseudoknot with LNA and G-Clamp-Modified Phosphorothioate Oligonucleotides Inhibits Viral Replication - Ribosomal frameshifting (RFS) at the slippery site of SARS-CoV-2 RNA is essential for the biosynthesis of the viral replication machinery. It requires the formation of a pseudoknot (PK) structure near the slippery site and can be inhibited by PK-disrupting oligonucleotide-based antivirals. We obtained and compared three types of such antiviral candidates, namely locked nucleic acids (LNA), LNA-DNA gapmers, and G-clamp-containing phosphorothioates (CPSs) complementary to PK stems. Using optical…
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Herbal Compounds Dauricine and Isoliensinine Impede SARS-CoV-2 Viral Entry - Targeting viral entry has been the focal point for the last 3 years due to the continued threat posed by SARS-CoV-2. SARS-CoV-2’s entry is highly dependent on the interaction between the virus’s Spike protein and host receptors. The virus’s Spike protein is a key modulator of viral entry, allowing sequential cleavage of ACE2 at the S1/S2 and S2 sites, resulting in the amalgamation of membranes and subsequent entry of the virus. A Polybasic insertion (PRRAR) conveniently located at the S1/S2 site…
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Evaluation of A-ring hydroxymethylene-amino- triterpenoids as inhibitors of SARS-CoV-2 spike pseudovirus and influenza H1N1 - A set of triterpene A-ring hydroxymethylene-amino-derivatives was synthesized and their antiviral activity was studied. The synthesized compounds were tested for their potential inhibition of SARS-CoV-2 pseudovirus in BHK-21-hACE2 cells and influenza A/PuertoRico/8/34 (H1N1) virus in MDCK cell culture. Compounds 6, 8 and 19 showed significant anti-SARS-CoV-2 pseudovirus activity with EC(50) value of 3.20-11.13 µM, which is comparable to the positive control amodiaquine (EC(50) 3.17 µM). Among…
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Applications of peptide-functionalized or unfunctionalized selenium nanoparticles for the passivation of SARS-CoV-2 variants and the respiratory syncytial virus (RSV) - The SARS-CoV-2 Omicron subvariants BA.4, BA. 5 and XBB are currently causing a COVID resurgence due to their increased spreading and infectivity. These latest subvariants have been shown to be somewhat resistant to the most common vaccines even with the third dose. Moreover, it has been well documented that when patients stop taking some commercial therapies (such as Paxlovid), COVID from these variants may return and may even be more contagious. Herein, we tested unfunctionalized and…
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From Patent Search
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+Daily-Dose
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One Family’s Perilous Escape from Gaza City - When Israel invaded Kamal Al-Mashharawi’s neighborhood, he crowded into a basement with his extended family. “The world is closing in on us,” he wrote on WhatsApp. - link
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The Free-Market Fundamentalism of Argentina’s Javier Milei - The President-elect, a right-wing populist with authoritarian instincts, has been compared to Donald Trump, but his radical views on the economy set him apart. - link
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The Next Power Plant Is on the Roof and in the Basement - A Department of Energy report promotes a new system that could remake the energy grid. - link
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The Death of a Relic Hunter - Bill Erquitt was an unforgettable character among Georgia’s many Civil War enthusiasts. After he died, his secrets came to light. - link
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Should People Have the Right to Say Awful Things Without Facing Legal Consequences? - Those who want to curtail freedom of speech do not log the debits and credits of censorship, nor do they care about the balance of norms—they act when they have power. - link
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From Vox
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The US doesn’t have universal health care — but these states (almost) do -
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+Getty Images/iStockphoto
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+Ten states have uninsured rates below 5 percent. What are they doing right?
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+Universal health care remains an unrealized dream for the United States. But in some parts of the country, the dream has drawn closer to a reality in the 13 years since the Affordable Care Act passed.
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+Overall, the number of uninsured Americans has fallen from 46.5 million in 2010, the year President Barack Obama signed his signature health care law, to about 26 million today. The US health system still has plenty of flaws — beyond the 8 percent of the population who are uninsured, far higher than in peer countries, many of the people who technically have health insurance still find it difficult to cover their share of their medical bills. Nevertheless, more people enjoy some financial protection against health care expenses than in any previous period in US history.
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+The country is inching toward universal coverage. If everybody who qualified for either the ACA’s financial assistance or its Medicaid expansion were successfully enrolled in the program, we would get closer still: More than half of the uninsured are technically eligible for government health care aid.
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+Particularly in the last few years, it has been the states, using the tools made available by them by the ACA, that have been chipping away most aggressively at the number of uninsured.
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+Today, 10 states have an uninsured rate below 5 percent — not quite universal coverage, but getting close. Other states may be hovering around the national average, but that still represents a dramatic improvement from the pre-ACA reality: In New Mexico, for instance, 23 percent of its population was uninsured in 2010; now just 8 percent is.
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+Their success indicates that, even without another major federal health care reform effort, it is possible to reduce the number of uninsured in the United States. If states are more aggressive about using all of the tools available to them under the ACA, the country could continue to bring down the number of uninsured people within its borders.
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+The law gave states discretion to build upon its basic structure. Many received approval from the federal government to create programs that lower premiums; some also offer state subsidies in addition to the federal assistance to reduce the cost of coverage, including for people who are not eligible for federal aid, such as undocumented immigrants. A few states are even offering new state-run health plans that will compete with private offerings.
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+I asked several leading health care experts which states stood out to them as having fully weaponized the ACA to reduce the number of uninsured. There was not a single answer.
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+“I don’t think any state has taken advantage of everything,” said Larry Levitt, executive vice president at the KFF health policy think tank. “No state has put all the pieces together to the full extent available under the ACA.”
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+But a few stood out for the steps they have taken over the last decade to strive toward universal health care.
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+Massachusetts (and New Mexico): Streamlined enrollment and state subsidies
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+Massachusetts has the lowest uninsured rate of any state: Just 2.4 percent of the population lacks coverage. It had a head start: The law provided the model for the ACA itself, with its system of government subsidies for private plans sold on a public marketplace that existed prior to 2010.
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+But experts say it still deserves credit for the steps it has taken since the Massachusetts model was applied to the rest of the country. Matt Fiedler, a senior fellow with the Brookings Schaeffer Initiative on Health Policy, said two policies stood above any others in expanding coverage: integrating the enrollment process for both Medicaid and ACA marketplace plans and offering state-based assistance on top of the law’s federal subsidies.
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+Massachusetts was among the first states to do both.
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+“The former can do a lot to reduce the risk that people lose their coverage when incomes change,” Fiedler told me, “while the latter directly improves affordability and thereby promotes take-up.”
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+Integrated enrollment means that, for the consumer, they can be directed to either the ACA’s marketplace (where they can use government subsidies to buy private coverage) or to the state Medicaid program through one portal. They enter their information and the state tells them which program they should enroll in. Without that integration, people might have to first apply to Medicaid and then, if they don’t qualify, separately seek out marketplace coverage. The more steps that a person must take to successfully enroll in a health plan, the more likely it is people will fall through the cracks.
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+The state assistance, meanwhile, both reduces premiums for people and makes it easier for them to afford more generous coverage, with lower out-of-pocket costs when they actually use medical services. Nine states including Massachusetts now have state assistance, with interest picking up in the past few years.
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+New Mexico, for example, only recently converted to a state-based ACA marketplace and started offering additional aid in 2023. Having already seen some dramatic improvements, it remains to be seen how much more progress the state can make toward universal coverage with that policy in place.
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+Minnesota and New York: The Basic Health Plan states
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+The basic structure of the ACA was this: Medicaid expansion for people living in or near poverty and marketplace plans for people with incomes above that. But the law included an option for states to more seamlessly integrate those two populations — and so far, the two states that have taken advantage of it, Minnesota and New York, are also among those states with the lowest uninsured rates. Just 4.3 percent of Minnesotans and 4.9 percent of New Yorkers lack coverage today.
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+They have both created Basic Health Plans, the product of one of the more obscure provisions of the health care law. This is a state-regulated health insurance plan meant to cover people up to 200 percent of the federal poverty level (about $29,000 for an individual or $50,000 for a family of three). Those are people who may not technically qualify for Medicaid under the ACA but who can still struggle to afford their monthly premiums and out-of-pocket obligations with a marketplace plan.
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+In both states, the Basic Health Plans offered insurance options with lower premiums and reduced cost-sharing responsibilities than the marketplace coverage that they would otherwise have been left with. In New York, for example, people between 100 percent and 150 percent of the federal poverty level pay no premiums at all, while people between 150 percent and 200 percent pay just $20 per month.
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+There is good evidence that the approach has increased coverage: In New York, for example, enrollment among people below 200 percent of the poverty level increased by 42 percent when the state adopted its BHP in 2016, compared to what it had been the year before when those people were relegated to conventional marketplace coverage.
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+State interest in Basic Health Plans has been limited so far, but Minnesota and New York provide a model others could follow. Fiedler said part of the basic plans’ success in those states has been using Medicaid managed-care companies to administer the plan: Those insurers already pay providers lower rates than marketplace plans do and the savings give the states money to reduce premiums and cost-sharing.
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+Colorado and Washington: Public options and assistance for the undocumented
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+These states have been inventive in myriad ways. They are both early adopters of a public option, a government health plan that competes with private plans on the marketplace, a policy also being tested in Nevada.
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+There is another policy that unites them, one that addresses a sizable part of the remaining uninsured nationwide: They both provide some state subsidies to undocumented immigrants.
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+Most uninsured Americans are already technically eligible for some kind of government assistance, whether Medicaid or marketplace subsidies. But there is a large chunk of people who are not: About 29 percent of the US’s uninsured are ineligible for government aid, among them the people who are in the country undocumented. Those people bear the full cost of their medical bills and may avoid care for that reason (among others, of course).
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+Starting this year, Washington is allowing undocumented people with incomes that would make them eligible for Medicaid expansion to enroll in that program, and making state subsidies available to people with higher incomes no matter their immigration status. Colorado has set aside a small pool of money annually to provide state aid to about 11,000 undocumented people. (After that threshold is hit, those folks can still enroll in a health plan but they must pay the full price.)
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+Interest has been robust: Last year, Colorado hit the enrollment limit after about a month. This year, enrollment capped out in just two days, suggesting the state may need to put more money behind the effort.
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+It is difficult to imagine insurance subsidies for undocumented people nationwide any time soon, given the fraught national politics of immigration. But states are finding ways to make inroads on their own: California has made undocumented people eligible for Medicaid.
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+Through these and other means, they are helping the US inch toward universal health care.
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+
How Myanmar’s resistance could topple its military government — for good -
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+Thomas De Cian/NurPhoto via Getty Images
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+A surprise offensive on October 27 stunned the junta. A revolution could build a new Myanmar.
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+A coalition of ethnic armed militias in Myanmar have launched what could be the best possible chance to overthrow the military government that has controlled the country since a 2021 coup ousted the democratically elected National League for Democracy (NLD).
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+If successful, this could be the groundwork for a more normalized democracy for a country that has historically been dominated by military juntas and dictators. Engagement from civil society has been high and is a key factor that can turn military victories into long term successes. Still, nothing is guaranteed and the fight is likely to be difficult.
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+On October 27, the Three Brotherhood Alliance, a coalition of three ethnic armed groups launched a well-coordination offensive in the eastern Shan state, the largest of Myanmar’s seven states by land area. The surprise attack successfully captured several government military installations by the Chinese border and has also inspired other armed groups to launch their own successful campaigns against the repressive Tatmadaw or State Administration Council, as the junta is called in Myanmar.
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+Myanmar has been under military rule for much of its history as an independent nation; as in many other Southeast Asian nations, democratic movements have struggled to gain traction against powerful and entrenched military interests. After a decade of democratic reforms driven by a series of popular uprisings against the military government Myanmar seemed to break from the past; in 2015 and 2020, the country held free elections, which the NLD won handily. But the Tatmadaw seized power in 2021, igniting nearly three years of brutal civil conflict in which the government has killed thousands of civilians.
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+Though the Three Brotherhood Alliance and similar ethnic armed groups have not taken over the whole country and the Tatmadaw still has far more firepower than any of the armed groups, the October 27 offensive and ensuing military successes have kindled a cautious hope that the military dictatorship could be toppled.
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+So far the revolutionary forces have successfully cut off about 40 percent of the Tatmadaw’s land access to China, taken over military installations, major border crossings, several towns, and transit routes — as well as forcing government troops to defect en masse.
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+Though there is likely still a long, brutal war to be fought to dislodge the Tatmadaw from power, revolutionary forces — both armed groups and civil society resistance — are also tentatively working toward a new kind of democratic, grassroots governance model in hopes of preventing violent military governments in the future.
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+The anti-government offensive is just beginning, but its success is galvanizing
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+Armed ethnic groups are nothing new in Myanmar — it’s a highly ethnically diverse nation, but the majority Bamar group has always enjoyed a privileged position in society, including in the military and the government. Meanwhile smaller ethnic groups, such as the Shan, Karen, and Rakhine groups, have historically faced serious discrimination, both under British colonial rule and under military dictatorships.
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+After the 2021 coup, ethnic militias like the Arakan Army, the Myanmar National Democratic Alliance Army and the Ta’ang National Liberation Army which make up the Three Brotherhood Alliance have been leading the charge against the Tatmadaw. In many cases they have also allied with People’s Defense Forces groups (PDFs), militia groups formed or supported by the shadow National Unity Government (NUG).
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+The October 27 offensive — which the Three Brotherhood Alliance calls “Operation 1027” — likely took months of planning and has shown impressive coordination between the alliance, other ethnic armed organizations, and PDFs. That’s a new dimension in the ongoing fight against military leadership, experts told Vox.
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+“This level of cooperation is not exactly unprecedented, but I think the scale of the operation and what they’ve managed to pull off in the last month — I’ve never really seen anything to this extent,” David Mathieson, an independent analyst based in Thailand, told Vox. “I think it shows a combination of long-term cooperation between the three main groups,” or the Three Brotherhood Alliance, which have been collaborating in some fashion since 2009, and more recent collaboration with other ethnic armed organizations such as the Bamar People’s Liberation Army, Mathieson said.
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+“Our primary objectives in launching this operation are multi-faceted and driven by the collective desire to safeguard the lives of civilians, assert our right to self-defense, maintain control over our territory and respond resolutely to ongoing artillery attacks and air strikes” perpetuated by the military government against civilians, the alliance said in a statement announcing Operation 1027. The statement also said the alliance is “dedicated to eradicating the oppressive military dictatorship, a shared aspiration of the entire Myanmar population.”
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+That goal, to remove the Tatmadaw from power, has been the galvanizing force in the month-long uprising, uniting disparate groups with competing priorities toward a common goal. The Tatmadaw has, over the years, engaged in what Lucas Myers, Senior Associate for Southeast Asia at the Wilson Center, called a “divide and rule” strategy, with the military junta giving special concessions to certain groups, thereby encouraging competition between the different armed actors.
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+But since 2021, the government’s brutal attacks against not only ethnic minorities but also Bamar civilians has encouraged a tentative trust and cooperation between various armed groups, as well as between those groups and the NUG.
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+Another major aspect of the resistance’s success is the military’s weakness. Morale is low, and defections are high, meaning that even though the military has superior artillery and air dominance, it just doesn’t have the manpower to mount an effective defense in any of the areas that the resistance has taken over, nor does it have the strategy to put together an offensive of its own.
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+“They’re essentially adopting a reprisal strategy — they’ve been just bombing civilian targets and striking the EAOs heavily,” Myers said. “It’s essentially a punishment strategy.” The government does have air superiority and can attack with fighter jets and attack helicopters, since the resistance forces don’t yet have effective anti-aircraft capabilities, Myers said. “But at the same time, I think the military is stretched to the point that they have limited capability, and they can’t strike everything all at once. Their pilots are overstretched, reportedly — that’s a high tempo.”
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+Myanmar can’t go back to the days of Aung San Suu Kyi
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+More than just a military sea change, the 1027 and subsequent offensives are part of a potential political revolution and demonstrate a desire to break with the old, hierarchical, and exclusive governance structures — both under the Tatmadaw and the short-lived democratic transition.
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+“The military maintained significant sway, even during the democratization period — they had 30 percent of the seats in parliament guaranteed to them, which essentially gave them a veto over anything constitutional, they maintained control over several key ministries,” Myers said. “It was very much not a democratic system.”
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+There’s also a “sea change,” as Myers said, in the opinions of the Bamar majority about the need to incorporate ethnic minority voices into the larger government, particularly after the failure of Suu Kyi’s government and its defense of the horrific massacre and mass displacement of the majority-Muslim Rohingya ethnic minority in 2017. The NUG has adopted the idea of an intersectional revolution and the need to incorporate minorities into a future democratic federal state — but in order for that to happen, the NUG must actually commit to bringing those ethnic minority actors into any future government.
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+Ethnic armed groups and their related political and civil society organizations are also demanding more autonomy over local affairs, which Mathieson and Myers both said would be critical for a political future. Over Myanmar’s post-colonial history and particularly since the 1962 military coup, the government has centralized power in the Bamar heartland and within the Bamar ethnic group, leading to autocratic governance.
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+“A lot of these groups are like, ‘Look, it’s not as if we’re going to go to the NUG with our hats in our hands and basically say, [autonomy] is what we want,’” Mathieson said. Rather, that autonomy and a federalized governance system are going to be requirements for most of these groups. “A lot of these groups are like, ‘Look, we’re building our form of federalism from the ground up, we’re seeing the local perspective, and what you — the NUG — and your largely Western supporters are trying to do is build a top-down federalism.’”
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+Some of the ethnic armed groups, like the Kachin Independence Army (KIA) and the Karen National Union (KNU), have broader community investments, as Htet Min Lwin and Thiha Wint Aung wrote for The Diplomat on Friday. Since the 2021 coup, the KIA and KNU have been involved in political activities like “training young protesters and providing sanctuary to displaced members of parliament to getting involved in various consultative councils.”
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+Civil society groups and public support have also been a crucial part of the successful military operation — as the Lwin and Aung point out, medical professionals with the Civil Disobedience Movement have been caring for the wounded and coordinating other logistical activities. Widespread civil society engagement is a sign that the revolution has legitimacy among the people of Myanmar and that they, too, are committed to the end of military rule and a potential democratic future.
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+But that future is far off — though the military’s advantage is waning, there is still likely a long and bloody fight ahead before the revolutionary forces gain control of the country. And even if that happens, the political work of building an inclusive democratic state from one that has been exploited and oppressed for decades will be its own struggle.
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Mary Kay Letourneau, the grim inspiration for May December, explained -
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+Mary Kay Letourneau and Vili Fualaau during a photo shoot at her beachfront home April 27, 2006, in Normandy Park, | Ron Wurzer/Getty Images
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+We still don’t know how to talk about Mary Kay Letourneau and Vili Fualaau.
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+In many ways, the country isn’t ready to revisit and reassess the story of Mary Kay Letourneau and her sexual-abuse-victim-turned-husband Vili Fualaau. In 1997, Letourneau, a beloved 35-year-old Seattle-area schoolteacher, shocked the nation when she was revealed to be pregnant by Fualaau, her then-13-year-oldstudent with whom she’d been having sex for nearly a year. The story fueled tabloid media for months, with Letourneau pleading guilty to two counts of secondary rape but insisting on reuniting with Fualaau — and giving birth to two of his children before he turned 15.
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+Perhaps because it was difficult to look at too closely, however, the story of Letourneau and Fualaau fell out of the media spotlight just when it became really layered: after their 2005 wedding. Despite the circumstances of their relationship and the 22-year age gap between them, the couple stayed married for nearly 15 years. They divorced in 2019, with sources claiming the relationship had “run its course.” Letourneau died a year later, of cancer.
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+The Letourneau-Fualaau saga now regains the media spotlight thanks to Todd Haynes’s star-studded drama May December, arriving to Netflix on December 1. In this fictionalized version of the story, an actress (Natalie Portman) cast in a film about analogues Grace and Joe (Julianne Moore and Charles Melton) shadows the couple to witness their superficially happy relationship, only to realize things aren’t as they seem.
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+What society wasn’t ready to confront at the time of the scandal — and what seems shockingly clear to us today — is that Letourneau meets the definition of a pedophile: someone whose preferred sexual object is a child. She spent years grooming her target, then strengthened her ties to him through the legitimacy afforded her by motherhood and marriage. The way we talk about predatory behavior has evolved tremendously since then, but the way we understand what happened to Vili Fualaau hasn’t necessarily evolved with it.
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+While the film doesn’t purport to tell the real story — Grace and Joe were pet shop coworkers, not teacher and student, for one thing — what actually happened between Letourneau and Fualaau is something we’ve turned away from for too long.
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+The unsettling relationship between Mary Kay Letourneau and Vili Fualaau
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+Letourneau came from a large family — one of seven children born to white, wealthy, privileged, extremely conservative parents. Her father, an Orange County politician named John Schmitz, was notorious for his antisemitic, homophobic, and misogynist public remarks; he was banned from the notably extremist John Birch Society for being too extremist.
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+Letourneau’s father was embroiled in a sex scandal with a student. In the late ’70s or early ’80s, Schmitz, who was then in his 50s, was teaching government at Santa Ana College when he began sleeping with one of his students, then in her 40s. The two had a multi-year affair that resulted in the birth of two children. In 1982, the affair came to light after a bizarre incident in which one of Schmitz’s two children by his student was taken to the hospital because hair had become tightly wrapped around his penis — so tightly it was almost severed. The resulting investigation forced his mother to confess who the boy’s father was, a revelation that severely damaged Schmitz’s political career.
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+Letourneau, who never professed her father’s politics, grew up pretty and popular. She married her college sweetheart, Steve Letourneau, after she became pregnant, and the two moved to the middle-class Seattle suburb of Normandy Park. As a teacher, Letourneau was described as having “boundless energy,” a fact later attributed in part to her diagnosis of bipolar disorder. She seemed to balance huge bursts of creativity with extreme recklessness. She gained a reputation as an “exceptionally gifted” teacher and loving mother who was devoted to her four children by husband Steve.
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+Because Fualaau, a Samoan American, was a minor, his identity was withheld for most of the ’90s, which meant the narrative of their relationship was entirely dominated by Letourneau’s version of it — and she portrayed them as star-crossed soul mates who just couldn’t help themselves. She ascribed impossible traits to Fualaau when she met him in second grade, gushing to the Seattle Times that she somehow recognized in the child a mutual “respect, an insight, a spirit, an understanding between us that grew over time.”
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+Letourneau described lavishing Fualaau with attention, giving him special focus as a teacher, taking him on trips, and showering him with gifts. By the time Fualaau entered her class again as a sixth grader, “He was my best friend. We just walked together in the same rhythm.” Letourneau gave a similar narrative to Oprah, insisting that Fualaau had “called” to her and that he was “the love of my life.”
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+Today, most people would probably find this narrative horrifying, the frank confession of a pedophile who spent years grooming their target. The gifts and attention she heaped on him would doubtless raise numerous red flags as signs of a predator. But in 1997, these actions went largely unremarked upon, while Letourneau’s attorney, David Gehrke, defended her in terms that read as jaw-dropping in 2023:
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+“This was a child she took an interest in, not unlike one of us might have taken an interest in one of our teachers,” he said. “She did a horrible thing … but we all make mistakes. She’s a very good person who did a very bad thing.”
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+The idea that Letourneau did something understandable and that Fualaau was actually a lucky kid was bandied about throughout the media of the time. Outlets gleefully reported Fualaau’s claim that he “bet a friend $20” that he would have sex with Letourneau, allegedly long before they started sleeping together. The double standard that applied to Fualaau as a male victim is striking, even in the small details. For example, when Steve Letourneau learned about the abuse by discovering his wife’s letters to Fualaau (the tipping point that ultimately led a relative to notify authorities), his instinct was not to confront her about whether she had been sexually assaulting a student, but to go to Fualaau’s house and confront him, demanding whether he was sleeping with her — as if Fualaau were merely the other man in an illicit affair.
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+Equally telling was the repeated insistence of Fualaau’s mother, Soona Vili, that her son was mature beyond his years — “an old soul trapped in a young body,” she told the Seattle Times. In court in August 1997, just two months after Letourneau gave birth to her son’s child, Vili said in a prepared statement, “I don’t feel that this is a crime. My son does not feel victimized.” She urged the court to be lenient in sentencing, and initially the court agreed: Although the standard sentence for two counts of second-degree rape was between five and seven years, the judge originally suspended most of Letourneau’s 89-month sentence, instead ordering her to serve just six months and receive treatment for sexual offenders. Vili took custody of Letourneau’s newborn daughter during her brief prison stint.
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+A key condition of Letourneau’s parole, however, was that she eschew all contact with Fualaau. Letourneau, still claiming to be “in love” with her victim, violated this term immediately. A month after her release — after serving just three months of her original six-month order — police discovered Letourneau and Fualaau together in Letourneau’s parked car. Police found over $6,000 in cash in the car and noted that Letourneau appeared to be planning to flee the country with him. Instead, she was sent back to jail to serve out the remainder of her seven-year sentence — now six weeks pregnant with her second child by Fualaau.
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+While serving out the remainder of her prison sentence for this offense, Letourneau appeared on the cover of People in 1998 under the headline, “Their bizarre story of obsessive love: Pregnant again after trysting with her former pupil, Mary Kay Letourneau, 36, is back in prison — and still defiant.” The accompanying photo showed Letourneau holding her first child in her arms while fixing the camera with a pleading expression. The profile questioned if Letourneau’s psychological issues could be blamed on her conservative father. For all it portrayed her as unwieldy and obsessive, it also balanced every caution with a quote like a friend’s insistence that the pair were “drawn together like magnets.”
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+The friend’s prediction that the couple would likely marry as soon as Letourneau was released proved accurate: In 2005, they did just that, bringing what NBC called her “notorious seduction” to a relatively happy ending.
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+But was it? And was that really the end?
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+What happened to Mary Kay Letourneau and Vili Fualaau after they left the spotlight
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+In a 1997 Seattle Times interview, Fualaau, then 14, gave a quote that many people point to in order to justify his agency in the relationship:
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+The boy expressed frustration at being treated like a child. He said he realized that people were trying to protect him but that, as a result, he had not been given a voice in all that’s happened.
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+“I want people to stop seeing me as a victim,” he said. “My life is going to be fine. Mary didn’t harm me in any way. Who are they to say I’m too young to know anything when they don’t even know me?”
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+Fualaau, even while under the cover of anonymity, stuck doggedly to Letourneau’s narrative that they were in love. In 2002, Soona Vili sued the school district over what she was now calling Letourneau’s “abuse” of her son, and reportedly said she regretted allowing Fualaau to “sell his story to the media” — but still spoke of having forgiven Letourneau and trying her best to move forward. She and Fualaau raised the couple’s two children together until Letourneau’s release from prison and their subsequent marriage.
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+But even at the time, not everyone had such a positive outlook. Sex offender therapist Florence Wolfe flatly called Letourneau’s behavior “exploitation,” telling the Seattle Times in 1997, “The proclamation of love — it is a rationalization. Did she care about his welfare, about what could happen to him by becoming a father at 13? … That’s not love — that’s a big emotional party.”
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+“The great disparity in age, position, and developmental level between the teacher and student make any true form of consensual relationship impossible,” wrote a reader named John Baker in a perceptive and perhaps prescient letter to the editor of the Brattleboro Reformer. “Children invariably suffer the same kinds of side effects regardless of sex. In boys it can become more damaging due to an often more difficult time in accessing the emotional centers to resolve issues.”
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+Although the couple were married for well over a decade, they first began to separate two years before their actual divorce in 2019, at Fualaau’s behest. Still, when Letourneu entered her final battle with cancer just months later, Fualaau reportedly returned to help care for her until she died in July 2020. From the outside, even in the latter years of the marriage and beyond, family and friends seemed to be supportive of them. In September, the couple’s younger daughter described Letourneau to People as “an amazing mother” as she prepared for motherhood herself. Another family friend, speaking to People in 2017, described their relationship as “deep,” forged through the fire of a media scandal, adding, “I give them a lot of credit. They will always have a bond.”
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+But a closer look at the situation raises some questions. A 2006 profile of the family in People after a full year of marriage found 22-year-old Fualaau struggling with alcoholism, driving under the influence, and depression, as well as with integrating himself into a family where he was only one year older than Letourneau’s oldest son. “I feel like I don’t really have a place except that I’m their mother’s husband,” he told the outlet. “I get so frustrated.” On their 10th anniversary, even as he celebrated their marriage, he reportedly told Barbara Walters that he believed “the system had failed him” as a child.
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+As heartbreaking as this statement is in retrospect, Fualaau seems to be moving on with his life; last year, at age 39, he welcomed his third child into the world.
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+Still, even after Fualaau and Letourneu separated, he continued to grieve her loss. In a 2020 interview with Dr. Oz, he described her as his “best friend,” and said that he felt she was “the only one who actually cared” given everything that had happened between them.
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+“Is everything going to be okay?” Dr. Oz asked.
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Satwik and Chirag go down fighting to world No 1 Liang-Wang in China Masters final - The Indian pair, gold medallists at the Hangzhou Asian Games, made their way back into the contest by taking the second game and take the final to the decider.
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New wrestling selection policy has its pros and cons: Olympic medallist Yogeshwar -
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Compensate if India refuse to travel to Pakistan for CT 2025, sign hosting rights: PCB urges ICC - Zaka Ashraf said the PCB officials had told ICC that if India refuses to play in Pakistan on security grounds, the global body should appoint an independent security agency.
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Mumbai Indians have struck gold: Ashwin on Pandya’s potential return to his old franchise - Hardik Pandya began his Indian Premier League career with MI in 2015 and was a part of the side until 2021. He won four titles with Mumbai Indians.
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From The Hindu: National News
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Real estate sector in Vizianagaram has a bright future, says Deputy Speaker - 80 stalls have been set up in the CREDAI’s property show in Vizianagaram
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Will obtain exemption from NEET with people’s support; will oppose NExT too, says Stalin - NEET campaign has emerged into a people’s movement, says the Chief Minister
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‘Modi gaari’ guarantee means the corrupt will be sent to jail, says PM Modi - Two ‘ailments’ like BRS and Congress Party can be treated by the BJP alone and cautioned the people not to choose between them.
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On 15th anniversary of 26/11 attack, Moshe’s grandfather thanks Indians for treating his family’s pain as their own -
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National Tiger Conservation Authority recommends shifting temple fair outside Bandipur - The NTCA has recommended phasing out the Beladakuppe temple fair rituals to outside the core area of tiger reserve to reduce disturbance to wildlife, habitat loss, and spread of diseases.
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From BBC: Europe
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Ukraine war: Fierce row erupts over 2024 election - Some right-wing US politicians want Ukraine to vote as scheduled next year. Ukrainians don’t.
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Ukraine war: Kyiv hit by biggest drone attack since war began - Thousands of homes are without power after Russia bombarded the capital over six hours.
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Italy rallies to condemn violence against women draw huge crowds - Crowds gathered in major cities after the killing of a student sent shockwaves across the country.
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What Geert Wilders’ victory means for Dutch society - After his Dutch election win. will the anti-Islam populist leader be able to effect any of his ideas?
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Mikhail Kasyanov: Russia labels ex-PM and Putin critic ‘foreign agent’ - A critic of the war in Ukraine, Mikhail Kasyanov was PM during President Putin’s first term.
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From Ars Technica
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Black Friday 2023: The latest tech deals on Apple, Lenovo, Dyson, Vitamix, and more - The best savings on tech from laptops to headphones, TVs, Herman Miller chairs, and more. - link
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Do the Black Friday e-bike deals change the price/performance equation? - Some of the bikes we’ve looked at over the last couple of years are now on sale. - link
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The Ars guide to time travel in the movies - We picked 20 time-travel movies and rated them by scientific logic and entertainment value. - link
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Porsche’s third-gen Panamera plug-in hybrid pairs V8 with a big battery - We also test out the optional—and slightly odd—active ride system. - link
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These newest vacuums from 2023 clean up well, and they’re on sale - The best vacuums from Dyson, Roborock, and iRobot are on sale for Black Friday - link
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From Jokes Subreddit
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An Englishman, Frenchman and Turk -
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+Were all in a train cabin. Feeling a little warm, the Frenchman opened the window and a little fly came buzzing in.
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+Wanting to impress the other two, the Frenchman takes out his sword and in one swoop sliced the fly in half. Feeling proud of himself, closes the window and hands out his business card to the other two in the cabin, reading “Best swordsman in France”.
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+The Englishman, not wanting to be outdone by the Frenchman opens the window, and another fly comes buzzing in. The Englishman then takes out his bow and arrow and pins the fly to the wall. Feeling proud, he hands out his business card to the other two, saying “Best archer in England” and closes the window.
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+The Turk, feeling a little jealous proceeds to open the window and a little fly comes in. The Turk proceeds to take out a little knife and cuts the fly. The fly falls to the ground, and after a minute he wakes up and flies off. The Englishman and Frenchman start laughing, that the Turk failed to kill the fly. After a minute, the Turk handed them his business card, it read
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A woman, cranky because her husband was late coming home again, decided to leave a note -
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+A woman, cranky because her husband was late coming home again, decided to leave a note, saying, “I’ve had enough and have left you. Don’t bother coming after me.” Then she hid under the bed to see his reaction.
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+After a short while, the husband comes home and she could hear him in the kitchen before he comes into the bedroom.
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+She could see him walk towards the dresser and pick up the note.
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+After a few minutes, he wrote something on it before picking up the phone and calling someone.
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+“She’s finally gone…yeah I know, about bloody time, I’m coming to see you, put on that sexy French nightie. I love you…can’t wait to see you…we’ll do all the naughty things you like.”
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+He hung up, grabbed his keys and left.
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+She heard the car drive off as she came out from under the bed.
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+Seething with rage and with tears in her eyes she grabbed the note to see what he wrote…
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+“I can see your feet. We’re outta bread: be back in five minutes.”
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A nun woke up one morning feeling great, she got out of bed and decided to go to the kitchen for some breakfast. On her way over there she runs into sister Jane and she says, “Hi sister Jane,” by which sister Jane says, "I see you got off on the wrong side of the bed sister. -
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+She did not understand what sister Jane meant by that so she ignored it and went on. She was passing by the garden when she ran into sister Roberta and she says, “Good morning sister Roberta I am having a great day. Sister Roberta says,”I see you got off on the wrong side of the bed." The nun was wondering why everybody she met kept saying that when she felt great so she decides to go and see mother superior. She asks mother superior, “Everybody keeps telling me that I got off on the wrong side of the bed when I feel great and mother superior says,”That is because you have brother Johns shoes on."
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It was November 25th and the Indians on the reservation asked their new chief if it was going to be a cold winter. -
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+Raised in the ways of the modern world, the chief had never been taught the old secrets and had no way of knowing whether the winter would be cold or mild.
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+To be on the safe side, he advised the tribe to collect wood and be prepared for a cold winter. A few days later, as a practical afterthought, he called the National Weather Service and asked whether they were forecasting a cold winter. The meteorologist replied that, indeed, he thought the winter would be quite cold.
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+The chief advised the tribe to stock even more wood.
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+A couple of days later, the chief checked in again with the Weather Service. “Does it still look like a cold winter?” asked the chief.
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+“It sure does,” replied the meteorologist. “It looks like a very cold winter.” The chief advised the tribe to gather up every scrap of wood they could find.
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+A couple of days later, the chief called the Weather Service again and asked how the winter was looking at that point. The meteorologist said, “We’re now forecasting that it will be one of the coldest winters on record!” “Really?” said the chief. “How can you be so sure?”
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+The meteorologist replied, “The Indians are collecting wood like crazy!”
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