No Substitute for the Real Thing? Physical and Digital Cultural Participation in Denmark during the COVID-19 Pandemic: A Research Note -
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+In this research note, we analyze the impact of the COVID-19 pandemic on cultural participation. We use rich survey data from Denmark to construct pooled time-series cross-sectional data for each month of the years 2019-2021 and report three findings. First, participation in physical cultural activities (e.g., attending a concert or a museum) plummeted during two lockdowns and did not return to its pre-pandemic level by the end of 2021. Second, participation in digital activities (e.g., reading a digital book or following a museum on social media) did not change much during the pandemic. Overall, we find little evidence of substitution from physical to digital cultural participation during the COVID-19 lockdown in Denmark. Third, socioeconomic gradients in cultural participation decreased during the pandemic for physical cultural participation, but did not change for digital cultural participation. We end by discussing what we can learn from our results about how social disruptions affect patterns of cultural participation and inequality.
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Stratification in Parents’ Selection of Developmentally Appropriate Books for Children: Register-based Evidence from Danish Public Libraries -
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+This paper studies socioeconomic gradients in selecting developmentally appropriate children’s books from public libraries. I draw on research on developmental gradients in parental inputs to hypothesize that families with high socioeconomic status (SES) are more likely to select books that match children’s developmental stage in order to best improve children’s learning environments. In contrast to previous survey-based research, I use behavioral data on the actual books families have selected from libraries. Based on Danish registry data that cover all books borrowed from public libraries in 2020, I find that highly educated families are more likely to use libraries and borrow more books when they use libraries, but they do not select a larger share of developmentally appropriate books; in fact, they select a slightly lower share. In contrast, I find only a weak positive income gradient for the amount of books borrowed and the share of developmentally appropriate books. The supplementary analyses show that results are robust across families with children of different ages and to account for nonrandom selection into the sample of library users, socioeconomic differences in children’s reading skills, and the impact of library lockdowns due to Covid-19. I conclude that stratification in library book selection is more prominent concerning the voraciousness with which highly educated parents provide reading inputs (more books) than how discriminating they are in terms of selecting developmentally appropriate books.
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No Utilitarians in a Pandemic? Shifts in Moral Reasoning during the COVID-19 Global Health Crisis -
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+The COVID-19 pandemic poses many real-world moral dilemmas, which can pit the needs and rights of the many against the needs and rights of the few. We investigated the influence of this contemporary global crisis on moral judgments in older adults, who are at greatest personal risk from the pandemic. We hypothesized that during this pandemic, individuals would give fewer utilitarian responses to hypothetical dilemmas, accompanied by higher levels of confidence and emotion elicitation. Our pre-registered analysis (https://osf.io/g2wtp) involved two waves of data collection, before (2014) and during (2020) the COVID-19 pandemic, regarding three categories of moral dilemmas (personal rights, agent-centered permissions, and special obligations). While utilitarian responses considered across all categories of dilemma did not differ, participants during the 2020 wave gave fewer utilitarian responses to dilemmas involving personal rights; that is, they were less willing to violate the personal rights of others to produce the best overall outcomes.
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The global and specific cardiovascular burden of spike-based Covid-19 1 Vaccination -
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+Aims: The aim of this investigation was to determine whether the global and cardiovascular 10 burden associated with spike-based Covid-19 vaccination has continued to increase. 11 Methods and results: An updated analysis of spontaneously reported individual cases with 12 ADRs and their fatal outcomes associated with Covid-19 vaccines, as well as adverse 13 cardiovascular events caused by the spike-inducing vaccine Tozinameran, was performed. 14 Data were retrieved from the EudraVigilance web reports of the European Medicines Agency 15 (EMA). All evaluated adverse events correspond to the search terms of the EudraVigilance 16 based on clinical characterisation. 17 The total number of individual cases (n=2256506; i.e. 2338/day) with adverse effects that were 18 fatal in 2.3% (n=51740; i.e. 54 deaths/day), as well as the wide range of reports of 19 cardiovascular adverse effects, have revealed the unusual magnitude and specificity of these 20 events. 21 Tachycardia, arrhythmia, atrial fibrillation/flatter, bradyarrhythmia and impaired stimulus 22 formation and conduction (n=57438 combined) dominated the cardiovascular side effect profile 23 of Tozinameran, followed by blood pressure increase (n=25907), myo-/pericarditis (n=23775), 24 heart failure, cardiomyopathy, cardiac flatter/fibrillation, cardiac arrest, circulatory collaps 25 (n=16778 combined) and coronary artery disease/myocardial infarction (n=9912). The 26 importance of acute cardiovascular reactions is underlined by the fact that deaths caused by 27 them accounted for at least one third (35%) of all deaths associated with Tozinameran’s side 28 effects 29 Based on individual assessment, ARBs are currently recommended in the treatment of spike-30 induced symptoms. 31 Conclusions: The spectrum of side effects of spike-based Covid-19 vaccines is more extensive 32 and severe than is generally known, Adverse cardiovascular events convincingly reflect the 33 mode of spike action, namely down-regulating of the cardiovascular protective enzyme ACE2 34 resulting in increasing Ang II concentrations. A fundamental re-evaluation of the benefit-risk 35 assessment of these novel vaccines is mandatory. Health professionals should be educated about 36 the consequences of spike-induced ACE2 downregulation, the resulting symptoms and 37 therapeutic options.
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Suspected Cardiovascular Side Effects of two Covid-19 Vaccines -
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+Fatalities or cardiovascular side effects of vaccines were rather uncommon in the past. So far, numerous reports of side effects and deaths associated with Covid-19 vaccination have been accepted behind the background of the pandemic situation and the priority vaccinated elderly population at the beginning of the vaqccination campaign. Cardiac and heart circulatory disturbances resp. cardiovascular side effects associated with the application of Covid-19 vaccines have not been recognized up to now with the exception of thrombotic/embolic side effects and cases of myo-/pericarditis. But the mechanism of action suggests that downregulation of ACE2 by non-neutralised spike proteins may have cardiovascular effects. The objective of this analysis was to determine the total number of reported adverse events and fatalities and to record suspected important cardiovascular adverse events up to the cut-off date in European countries. Therefore, a current review/analysis of spontaneously reported fatalities as well as of adverse events after application of Covid-19 vaccines has been performed. Data were retrieved from the EudraVigilance web reports of the European Medicines Agency (EMA), partly also from the safety reports of the German PEI. Covid-19 vaccine-associated suspected side effects and related deaths are alarming. Surprisingly, numerous cardiovascular reactions were reported, many of which were life-threatening. Cardiac and heart circulatory caused fatalities alone accounted for about 33% of all ComirnatyR vaccine-related deaths. The second most important side effects were vascular thrombotic/embolic side effects, often also associated with serious consequences. Based on their quality and quantity, these side effects seem to be characteristic for spike-producing vaccines and do not appear to be substance-specific. Further investigations are needed to clarify the approximately 3.5 times more frequent cases of sinus vein thrombosis and the some different frequent cases of thrombotic/embolic events after VaxzevriaR. The hypothesis could be confirmed. Because of their importance and their sometimes life-threatening consequences, cardiovascular side effects need to be better communicated. Limitations of the investigation result from the individual reporting and recording procedure, the lack of detailed individual information and the lack of an appropriate comparison population.
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CD4+ and CD8+ T cells are required to prevent SARS-CoV-2 persistence in the nasal compartment -
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+SARS-CoV-2 is the causative agent of COVID-19 and continues to pose a significant public health threat throughout the world. Following SARS-CoV-2 infection, virus-specific CD4+ and CD8+ T cells are rapidly generated to form effector and memory cells and persist in the blood for several months. However, the contribution of T cells in controlling SARS-CoV-2 infection within the respiratory tract are not well understood. Using C57BL/6 mice infected with a naturally occurring SARS-CoV-2 variant (B.1.351), we evaluated the role of T cells in the upper and lower respiratory tract. Following infection, SARS-CoV-2-specific CD4+ and CD8+ T cells are recruited to the respiratory tract and a vast proportion secrete the cytotoxic molecule Granzyme B. Using antibodies to deplete T cells prior to infection, we found that CD4+ and CD8+ T cells play distinct roles in the upper and lower respiratory tract. In the lungs, T cells play a minimal role in viral control with viral clearance occurring in the absence of both CD4+ and CD8+ T cells through 28 days post-infection. In the nasal compartment, depletion of both CD4+ and CD8+ T cells, but not individually, results in persistent and culturable virus replicating in the nasal compartment through 28 days post-infection. Using in situ hybridization, we found that SARS-CoV-2 infection persisted in the nasal epithelial layer of tandem CD4+ and CD8+ T cell-depleted mice. Sequence analysis of virus isolates from persistently infected mice revealed mutations spanning across the genome, including a deletion in ORF6. Overall, our findings highlight the importance of T cells in controlling virus replication within the respiratory tract during SARS-CoV-2 infection.
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Adaptive advantage of deletion repair in the N terminal domain of the SARS-CoV-2 spike protein in variants of concern -
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+Mutations within the N-terminal domain (NTD) of the spike (S) protein play a pivotal role in the emergence of successful SARS-CoV-2 viral lineages. This study investigates the influence of novel combinations of NTD lineage-defining mutations found in the Alpha, Delta, and Omicron variants on viral success. We performed comparative genomics of more than 10 million public SARS-CoV-2 samples to decipher the transmission success of different NTD markers. Additionally, we characterized the viral phenotype of such markers in a surrogate in vitro system. We found that viruses bearing repaired deletions SDeltaH69/V70 and SDeltaY144 in Alpha background were associated with increased transmission rates. After the emergence of the Omicron BA.1 lineage, Alpha viruses harbouring both repaired deletions still showed increased transmission compared to their BA.1 counterparts. Remarkably, Alpha viruses with the SDeltaH69/V70 repair displayed the highest emergence rate, while those in BA.1 exhibited the lowest. Moreover, repaired deletions were more frequently observed among older individuals infected with Alpha, but not with BA.1. In vitro biological characterization of Omicron BA.1 spike deletion repair patterns revealed substantial differences with Alpha. In BA.1, SDeltaV143/Y145 repair enhanced fusogenicity and susceptibility to neutralization by vaccinated individuals' sera. In contrast, the SDeltaH69/V70 repair did not significantly alter these traits but reduced viral infectivity. Simultaneous repair of both deletions led to lower fusogenicity. These findings highlight the intricate genotype-phenotype landscape of the spike NTD in SARS-CoV-2, which impacts viral biology, transmission efficiency, and susceptibility to neutralization. Overall, this study advances our comprehension of SARS-CoV-2 evolution, carrying implications for public health and future research.
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In COVID-19 health messaging, loss framing increases anxiety with little-to-no concomitant benefits: Experimental evidence from 84 countries -
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+The COVID-19 pandemic (and its aftermath) highlights a critical need to communicate health information effectively to the global public. Given that subtle differences in information framing can have meaningful effects on behavior, behavioral science research highlights a pressing question: Is it more effective to frame COVID-19 health messages in terms of potential losses (e.g., “If you do not practice these steps, you can endanger yourself and others”) or potential gains (e.g., “If you practice these steps, you can protect yourself and others”)? Collecting data in 48 languages from 15,929 participants in 84 countries, we experimentally tested the effects of message framing on COVID-19-related judgments, intentions, and feelings. Loss- (vs. gain-) framed messages increased self-reported anxiety among participants cross-nationally with little-to-no impact on policy attitudes, behavioral intentions, or information seeking relevant to pandemic risks. These results were consistent across 84 countries, three variations of the message framing wording, and 560 data processing and analytic choices. Thus, results provide an empirical answer to a global communication question and highlight the emotional toll of loss-framed messages. Critically, this work demonstrates the importance of considering unintended affective consequences when evaluating nudge-style interventions.
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A Global Experiment on Motivating Social Distancing during the COVID-19 Pandemic -
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+Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e. a controlling message) compared to no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly-internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared to the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly-internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing: Controlled motivation was associated with more defiance and less long-term behavioral intentions to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges.
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A global test of brief reappraisal interventions on emotions during the COVID-19 pandemic -
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+The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion regulation strategy which modifies how one thinks about a situation. Participants from 87 countries/regions (N = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vs. both control conditions) had consistent effects in reducing negative emotions and increasing positive emotions across different measures. Reconstrual and repurposing had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world to build resilience during the pandemic and beyond.
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Correlates of Health-Protective Behavior During the Initial Days of the COVID-19 Outbreak in Norway -
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+The coronavirus outbreak manifested in Norway in March 2020. It was met with a combination of mandatory changes (closing of public institutions) and recommended changes (hygiene behavior, physical distancing). It has been emphasized that health-protective behavior such as increased hygiene or physical distancing are able to slow the spread of infections and flatten the curve. Drawing on previous health-psychological studies during the outbreak of various pandemics, we investigated psychological and demographic factors predicting the adoption and engagement in health-protective behavior and changes in such behavior, attitudes, and emotions over time. We recruited a non-representative sample of Norwegians (n = 8676) during a 15-day period (March 12–26 2020) at the beginning of the COVID-19 outbreak in Norway. Employing both traditional methods and exploratory machine learning, we replicated earlier findings that engagement in health-protective behavior is associated with specific demographic characteristics. Further, we observed that increased media exposure, perceiving measures as effective, and perceiving the outbreak as serious positively was related to engagement in health-protective behavior. We also found indications that hygiene and physical distancing behaviors were related to somewhat different psychological and demographic factors. Over the sampling period, reported engagement in physical distancing increased, while experienced concern or fear declined. Contrary to previous studies, we found no or only small positive predictions by confidence in authorities, knowledge about the outbreak, and perceived individual risk, while all of those variables were rather high. These findings provide guidance for health communications or interventions targeting the adoption of health-protective behaviors in order to diminish the spread of COVID-19.
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Evaluation of the cross reactivity of neutralising antibody response in vaccinated human and convalescent hamster sera against SARS-CoV-2 variants up to and including JN.1 using an authentic virus neutralisation assay -
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+New vaccines, therapeutics and immunity elicited by natural infection create evolutionary pressure on SARS-CoV-2 to evolve and adapt to evade vaccine-induced and infection-elicited immunity. Vaccine and therapeutics developers thus find themselves in an “arms race” with the virus. The ongoing assessment of emerging SARS-CoV-2 variants remains essential as the global community transitions from an emergency response to a long-term management plan. Here, we describe how an authentic virus neutralisation assay using low passage clinical virus isolates has been employed to monitor resistance of emerging virus variants to neutralising antibodies from humans and experimentally infected hamsters. Sera and plasma from people who received three doses of a vaccine as well as those who received a bivalent booster were assessed against SARS-CoV-2 variants, up to and including JN.1. Contemporary or recent virus variants showed substantial resistance to neutralisation by antibodies from those who had received three doses of an ancestral vaccine but were still effectively neutralised by antibodies from individuals who had received a bivalent booster (ancestral/BA.1). In our recent studies, however, the JN.1 VOI was found to be significantly more resistant to neutralisation by antibodies from those who had received the ancestral/BA.1 bivalent boost. Convalescent sera from hamsters that had been experimentally infected with one of seven virus variants (ancestral, BA.1, BA.4, BA.5.2.1, XBB.1.5, XBB.1.16, XBB.2.3) were also tested here. The recent contemporary variant, BA.2.86, was effectively neutralised by sera from hamsters infected with XBB.1.5 and XBB.1.16 but it was not neutralised by sera from those infected with BA.5.2.1. These data support the recommendations given by the WHO that a new vaccine was required and should consist of an XBB sub-lineage antigen.
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Comparing frequency of booster vaccination to prevent severe COVID-19 by risk group in the United States -
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+There is a public health need to understand how different frequencies of COVID-19 booster vaccines may mitigate the risk of severe COVID-19, while accounting for waning of protection and differential risk by age and immune status. By analyzing United States COVID-19 surveillance and seroprevalence data in a microsimulation model, here we show that more frequent COVID-19 booster vaccination (every 6-12 months) in older age groups and the immunocompromised population would effectively reduce the burden of severe COVID-19, while frequent boosters in the younger population may only provide modest benefit against severe disease. In persons 75+ years, the model estimated that annual boosters would reduce absolute annual risk of severe COVID-19 by 199 (uncertainty interval: 188-229) cases per 100,000 persons, compared to a one-time booster dose. In contrast, for persons 18-49 years, the model estimated that annual boosters would reduce this risk by 14 (11-19) cases per 100,000 persons. Those with prior infection had lower benefit of more frequent boosting, and immunocompromised persons had larger benefit. Scenarios with emerging variants with immune evasion increased the benefit of more frequent variant-targeted boosters. This study underscores the benefit of considering key risk factors to inform frequency of COVID-19 booster vaccines in public health guidance and ensuring at least annual boosters in high-risk populations.
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Migraine inhibitor olcegepant reduces weight loss and IL-6 release in SARS-CoV-2 infected older mice with neurological signs -
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+COVID-19 can result in neurological symptoms such as fever, headache, dizziness, and nausea. However, neurological signs of SARS-CoV-2 infection have been hardly assessed in mouse models. Here, we infected two commonly used wildtype mice lines (C57BL/6 and 129S) with mouse-adapted SARS-CoV-2 and demonstrated neurological signs including motion-related dizziness. We then evaluated whether the Calcitonin Gene-Related Peptide (CGRP) receptor antagonist, olcegepant, used in migraine treatment could mitigate acute neuroinflammatory and neurological responses to SARS-COV-2 infection. We infected wildtype C57BL/6J and 129/SvEv mice, and a 129 CGRP-null mouse line with a mouse-adapted SARS-CoV-2 virus, and evaluated the effect of CGRP receptor antagonism on the outcome of that infection. First, we determined that CGRP receptor antagonism provided protection from permanent weight loss in older (>12 m) C57BL/6J and 129 SvEv mice. We also observed acute fever and motion-induced dizziness in all older mice, regardless of treatment. However, in both wildtype mouse lines, CGRP antagonism reduced acute interleukin 6 (IL-6) levels by half, with virtually no IL-6 release in mice lacking CGRP. These findings suggest that migraine inhibitors such as those blocking CGRP signaling protect against acute IL-6 release and subsequent inflammatory events after SARS-CoV-2 infection, which may have repercussions for related pandemic and/or endemic coronaviruses.
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SOX9-regulated matrix proteins predict poor outcomes in patients with COVID-19 and pulmonary fibrosis -
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+Pulmonary fibrosis is an increasing and major cause of death worldwide. Understanding the cellular and molecular mechanisms underlying the pathophysiology of lung fibrosis may lead to urgently needed diagnostic and prognostic strategies for the disease. SOX9 is a core transcription factor that has been associated with fibrotic disease, however its role and regulation in acute lung injury and/or fibrosis have not been fully defined. In this study we apply a hypothesis based approach to uncover unique SOX9-protein signatures associated with both acute lung injury and fibrotic progression. Using in vivo models of lung injury in the presence or absence of SOX9, our study shows SOX9 is essential to the damage associated response of alveolar epithelial cells from an early time-point in lung injury. In parallel, as disease progresses, SOX9 is responsible for regulating tissue damaging ECM production from pro-fibrotic fibroblasts. In determining the in vivo role of SOX9 we identified secreted ECM components downstream of SOX9 as markers of acute lung injury and fibrosis. To underscore the translational potential of our SOX9-regulated markers, we analysed serum samples from acute COVID19, post COVID19 and idiopathic pulmonary fibrosis (IPF) patient cohorts. Our hypothesis driven SOX9-panels showed significant capability in all cohorts at identifying patients who had poor disease outcomes. This study shows that SOX9 is functionally critical to disease in acute lung injury and pulmonary fibrosis and its regulated pathways have diagnostic, prognostic and therapeutic potential in both COVID19 and IPF disease.
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Long-COVID [11C]CPPC Study - Conditions: COVID Long-Haul Interventions: Drug: [11C]CPPC Injection; Drug: [11C]CPPC Injection Sponsors: Johns Hopkins University; Radiological Society of North America Not yet recruiting
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Thrombohemorrhagic Complications of COVID-19 - Conditions: COVID-19 (Coronavirus Disease 2019) Interventions: Diagnostic Test: Prevention algorithm Sponsors: Volgograd State Medical University Active, not recruiting
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Combined Use of Immunoglobulin and Pulse Steroid Therapies in Severe Covid-19 Patients - Conditions: Pulse Steroid and Immunoglobulins Drugs in Covid 19 Patients Interventions: Drug: pulse steroid and nanogam Sponsors: Konya City Hospital Completed
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Beneficial Effects of Natural Products on Management of Xerostomia - Conditions: Xerostomia; Diabetes Mellitus; Hypertension; Post COVID-19 Condition Interventions: Other: (Manuka honey-green tea- ginger) Sponsors: British University In Egypt Completed
Diet and Fasting for Long COVID - Conditions: Long Covid19; Long COVID Interventions: Other: Low sugar diet and 10-12 hour eating window; Other: Low sugar diet, 8 hour eating window and fasting Sponsors: Pacific Northwest University of Health Sciences Recruiting
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The Effectiveness of a Health Promotion Program for Older People With Post-Covid-19 Sarcopenia - Conditions: Post COVID-19 Condition Interventions: Other: Protein powder and Resistance exercise Sponsors: Mahidol University; National Health Security Office, Thailand Not yet recruiting
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Chronic-disease Self-management Program in Patients Living With Long-COVID in Puerto Rico - Conditions: Long Covid19 Interventions: Other: “Tomando control de su salud” (Spanish Chronic Disease Self-Management) Sponsors: University of Puerto Rico; National Institutes of Health (NIH) Recruiting
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Treatment of Persistent Post-Covid-19 Smell and Taste Disorders - Conditions: Post-covid-19 Persistent Smell and Taste Disorders Interventions: Drug: Cerebrolysin; Other: olfactory and gustatory trainings Sponsors: Sherifa Ahmed Hamed Completed
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A Study to Evealuate Safety and Immunogenicity of TI-0010 SARS-CoV-2 Vaccine in Healthy Adults - Conditions: COVID-19; COVID-19 Immunisation Interventions: Biological: TI-0010; Biological: Placebo Sponsors: National Drug Clinical Trial Institute of the Second Affiliated Hospital of Bengbu Medical College; Therorna Recruiting
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Sodium Citrate in Smell Retraining for People With Post-COVID-19 Olfactory Dysfunction - Conditions: Long Haul COVID-19; Post-Acute COVID-19 Syndrome; Anosmia; Olfaction Disorders Interventions: Drug: Sodium Citrate; Drug: Normal Saline; Other: Olfactory Training Kit - “The Olfactory Kit, by AdvancedRx” Sponsors: University of North Carolina, Chapel Hill Recruiting
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From PubMed
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Excess phosphate promotes SARS‑CoV‑2 N protein‑induced NLRP3 inflammasome activation via the SCAP‑SREBP2 signaling pathway - Hyperphosphatemia or severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection can promote cardiovascular adverse events in patients with chronic kidney disease. Hyperphosphatemia is associated with elevated inflammation and sterol regulatory element binding protein 2 (SREBP2) activation, but the underlying mechanisms in SARS‑CoV‑2 that are related to cardiovascular disease remain unclear. The present study aimed to elucidate the role of excess inorganic phosphate (PI) in SARS‑CoV‑2…
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Quercetin inhibits SARS-CoV-2 infection and prevents syncytium formation by cells co-expressing the viral spike protein and human ACE2 - CONCLUSION: These findings suggest that at low 3-digit micromolar concentrations of quercetin could impair SARS-CoV-2 infection of human cells partly by blocking the fusion process that promotes its propagation.
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The temporal association of CapZ with early endosomes regulates endosomal trafficking and viral entry into host cells - CONCLUSIONS: These results indicate that the temporal association of CapZ with EEs facilitates early-to-late endosome transition (physiologically) and the release of the viral genome from endocytic vesicles (pathologically).
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Drug repurposing platform for deciphering the druggable SARS-CoV-2 interactome - The coronavirus disease 2019 (COVID-19) pandemic has heavily challenged the global healthcare system. Despite the vaccination programs, the new virus variants are circulating. Further research is required for understanding of the biology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and for discovery of therapeutic agents against the virus. Here, we took advantage of drug repurposing to identify if existing drugs could inhibit SARS-CoV-2 infection. We established an…
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Mechanistic Understanding of the Modes of Ca2+ Ion Binding to the SARS-CoV-1 Fusion Peptide and Their Role in the Dynamics of Host Membrane Penetration - The SARS-CoV-1 spike glycoprotein contains a fusion peptide (FP) segment that mediates the fusion of the viral and host cell membranes. Calcium ions are thought to position the FP optimally for membrane insertion by interacting with negatively charged residues in this segment (E801, D802, D812, E821, D825, and D830); however, which residues bind to calcium and in what combinations supportive of membrane insertion are unknown. Using biological assays and molecular dynamics studies, we have…
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Pharmacokinetics of recombinant human annexin A5 (SY-005) in patients with severe COVID-19 - Objective: Annexin A5 is a phosphatidylserine binding protein with anti-inflammatory, anticoagulant and anti-apoptotic properties. Preclinical studies have shown that annexin A5 inhibits pro-inflammatory responses and improves organ function and survival in rodent models of sepsis. This clinical trial aimed to evaluate the pharmacokinetic (PK) properties of the recombinant human annexin A5 (SY-005) in severe COVID-19. Methods: This was a pilot randomized, double-blind, placebo-controlled trial….
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Biosurfactant potential and antiviral activity of multistrain probiotics - The COVID-19 caused by the SARS-CoV-2 has become a great threat to humans. However, there is no recommendation for an effective and safe drug to treat the disease. The strategy developed in this study is to utilize biosurfactant potential activity of Lactobacillus spp. and Rhodopseudomonas palustris probiotics to prevent the virus from entering human body. The outer membrane of the virus is comprising of phospholipid compounds. Biosurfactants, are known to have detergent-like properties (able to…
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Online Group Supervision as Pedagogy: A Qualitative Inquiry of Student Mental Health Nurses’ Discourses and Participation - This study explored online group clinical supervision participation, as a component of pre-registration education following mental health nursing students’ clinical placements. Clinical supervision has historically been valued as a supportive strategy by healthcare professionals to develop practice and competence and prevent burnout. As many student nurses do not have access to clinical supervision via practice areas as a standardised process, their experiences of engaging in or benefitting from…
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CRL4B E3 ligase recruited by PRPF19 inhibits SARS-CoV-2 infection by targeting ORF6 for ubiquitin-dependent degradation - The accessory protein ORF6 of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a key interferon (IFN) antagonist that strongly suppresses the production of primary IFN as well as the expression of IFN-stimulated genes. However, how host cells respond to ORF6 remains largely unknown. Our research of ORF6-binding proteins by pulldown revealed that E3 ligase components such as Cullin 4B (CUL4B), DDB1, and RBX1 are potential ORF6-interacting proteins. Further study found that the…
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Identification of amentoflavone as a potent SARS-CoV-2 Mpro inhibitor: a combination of computational studies and in vitro biological evaluation - Small-molecule inhibitors of SARS-CoV-2 M^(pro) that block the active site pocket of the viral main protease have been considered potential therapeutics for the development of drugs against SARS-CoV-2. Here, we report the identification of amentoflavone (a biflavonoid) through docking-based virtual screening of a library comprised of 231 compounds consisting of flavonoids and isoflavonoids. The docking results were further substantiated through extensive analysis of the data obtained from…
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Molecular dynamics simulation study on the binding mechanism between carbon nanotubes and RNA-dependent RNA polymerase - Carbon nanotubes (CNTs) have potential prospects in disease treatment, so it is of great significance to study CNTs as the possible inhibitors of RNA-dependent RNA polymerase (RdRp). Through the way of using the RdRp of SARS-COV-2 as a model, five armchair single-walled carbon nanotubes (SWCNTs) (namely Dn, which stands for CNTs (n, m = n), n = 3-7) and RdRp have been selected to study the interactions by means of molecular docking and molecular dynamics simulation. After five SWCNT-RdRp complex…
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A novel film spray containing curcumin inhibits SARS-CoV-2 and influenza virus infection and enhances mucosal immunity - CONCLUSION: Film spray containing curcumin possesses multiple actions against SARS-CoV-2 infection by inhibiting ACE-2 binding in target cells and enhancing mucosal innate immunity. The film spray can also inhibit influenza virus infection. Therefore, the curcumin film spray may be effective in preventing the viral infection of both SARS-CoV-2 and influenza.
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A basally active cGAS-STING pathway limits SARS-CoV-2 replication in a subset of ACE2 positive airway cell models - Host factors that define the cellular tropism of SARS-CoV-2 beyond the cognate ACE2 receptor are poorly defined. From a screen of human airway derived cell lines that express varying levels of ACE2/TMPRSS2, we found a subset that express comparably high endogenous levels of ACE2 but surprisingly did not support SARS-CoV-2 replication. Here we report that this resistance is mediated by a basally active cGAS-STING pathway culminating in interferon (IFN)-mediated restriction of SARS-CoV-2…
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Innate Immune Activation and Mitochondrial ROS Invoke Persistent Cardiac Conduction System Dysfunction after COVID-19 - CONCLUSIONS: The findings indicate that long term dysfunction and immune cell remodeling of the CCS is induced by COVID-19, arising indirectly from oxidative stress and excessive activation of cardiac innate immune responses during infection, with implications for long COVID Syndrome.
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Impact of leisure satisfaction on perceived risk of infectious disease during the COVID-19 pandemic: evidence from new worker classes - CONCLUSION: This study verified the risk factors that inhibit leisure satisfaction among new worker classes that emerged during the COVID-19 pandemic. Furthermore, the psychological health of people suffering pandemic-related financial constraints was affected, as they experienced a lower quality of life owing to reduced leisure activities and satisfaction.
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From Patent Search
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How the Hindu Right Triumphed in India - A razed mosque, a new temple, and the rise of Narendra Modi. - link
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Sofia Coppola’s Path to Filming Gilded Adolescence - There are few Hollywood families in which one famous director has spawned another. Coppola says, “It’s not easy for anyone in this business, even though it looks easy for me.” - link
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How to Eat a Tire in a Year, by David Sedaris - Walking and talking with my friend Dawn. - link
The Woman Who Spent Five Hundred Days in a Cave - Beatriz Flamini liked to be alone so much that she decided to live underground—and pursue a world record. The experience was gruelling and surreal. - link
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From Vox
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A controversial execution in Alabama renews the fight over capital punishment -
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+Anti-death penalty activists place signs along the road heading to Holman Correctional Facility in Atmore, Alabama, ahead of the scheduled execution of Kenneth Eugene Smith, on January 25, 2024. | Kim Chandler/AP
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+
+The state is using a new untested method that’s prompted backlash.
+
+
+A controversial Alabama execution taking place on Thursday has reignited scrutiny of the death penalty and highlighted the enduring nature of the practice despite attempts to end it.
+
+
+Physicians and human rights experts have condemned the execution — which relies on an untested method known as nitrogen hypoxia — because there are concerns it could be painful and inhumane. Alabama is planning to use this method on an inmate named Kenneth Smith, after the state botched his first scheduled execution in 2022 when it couldn’t find an accessible vein for a lethal injection. Smith was sentenced to the death penalty after he was convicted of capital murder in 1988.
+
+
+Using nitrogen hypoxia, the state will place a mask over Smith’s head that contains nitrogen instead of oxygen, an action that will eventually suffocate him.
+
+
+Though a slim majority of Americans still back executions — Gallup’s November 2023 polling found a new low of 53 percent to be in favor of executing convicted murders — support has been declining for three decades, since a peak in 1994. Medical and ethical questions have also led critics to call for the abolition of the death penalty. And Gallup found that, for the first time, more people now feel the death penalty is unfairly applied than those who believe it’s fairly applied.
+
+
+These stances have gained steam in recent years, with some pharmaceutical companies refusing to supply lethal drugs and equipment to conduct executions. Corporations like Pfizer and Johnson & Johnson are among those that block the sale of drugs and medical supplies for this purpose. Politically, the idea has begun to take hold as well. As part of his presidential policy platform in 2020, President Joe Biden said he’d work to abolish the federal death penalty, a proposal he’s been scrutinized for failing to follow through on. More than 20 states have also abolished the death penalty.
+
+
+States like Texas, Florida, and Alabama have held out against this pressure, arguing that the death penalty is a fitting punishment and deterrent against violent crime. These states’ insistence on using the death penalty in an environment where there are fewer avenues for killing people has also led them to embrace more extreme measures, like firing squads and nitrogen hypoxia.
+
+
+Alabama’s decision to pursue an untested method only adds to longstanding concerns that have been raised about the death penalty, while underscoring how committed some states are to keeping it.
+
+
+The ongoing fight over the death penalty, briefly explained
+
+
+Critiques regarding the use of capital punishment have increased in the last decade as opponents have emphasized the racial disparities in its application, identified worries about how humane it is, and cited cases when innocent people have been convicted. Among the chief problems that have been raised are that people of color are much more likely to be sentenced to executions than white defendants and evidence that it does little to deter violent crime.
+
+
+Ethical concerns are also a major part of the equation. Smith’s attorneys have argued, for instance, that the state may not be able to conduct his execution without concerning side effects that draw out the killing. There are also worries that Smith could choke during the process if he vomits while it’s taking place. And as UN human rights officials have warned, nitrogen hypoxia could “amount to torture or other cruel, inhuman or degrading treatment.”
+
+
+Lawyers for the state of Alabama, meanwhile, have defended the practice and said that it will be painless, that Smith will be unconscious within seconds. Similar methods have also been used in assisted suicides in Europe. In recent weeks, Smith’s counsel put in a last-ditch plea to block the execution on the grounds that it violates his constitutional protections against “cruel and unusual punishment,” but the Supreme Court declined to do so.
+
+
+“I think the various practical problems of the death penalty have generated a public opinion movement against it,” says Frank Baumgartner, a political science professor at the University of North Carolina at Chapel Hill who has specialized in the study of capital punishment. “It started with innocence but has spread to botched executions, cost overruns, time delays, [and] lack of deterrence value.”
+
+
+Democrats, in particular, have embraced efforts to roll back or get rid of the death penalty entirely. In the Gallup survey, just 32 percent of Democrats said the death penalty should be applied to someone who committed murder while 81 percent of Republicans said the same.
+
+
+Actions by Republican-led states, like Alabama, have underscored the contrast between the two parties. Those who favor the continued application of capital punishment argue that it deters violent crimes, that it’s fitting retribution for crimes like murder, and that it brings justice to the families of victims. The case for the death penalty is also often made in conjunction with other “law and order” rhetoric during times when violent crime rates are high.
+
+
+The use of the death penalty overall, however, has been on the decline. Although 27 states still allow the death penalty, 14 of those have not conducted any executions in the past 10 years, according to CNN. Executions have dwindled since 1999, which marked a recent high when nearly 100 people were killed. In 2023, 24 people were executed across five states.
+
+
+These declines are due to political backlash toward capital punishment, changes in the law that have raised the legal bar for such sentences, declines in crime in recent decades, and better representation for capital defendants.
+
+
+“I think anytime a state engages in a highly controversial act concerning the death penalty, it adds one more pebble on top of a pebble mountain of opposition,” says Deborah Denno, a Fordham University law professor who has specialized in the study of capital punishment. “That said, the death penalty is deeply rooted in the US — it’s part of our identity — and it’s going to take a massive number of pebbles to change that fact.”
+
+
Why Trump fears a Biden-GOP immigration deal -
+
+
+
+Former US President Donald Trump talks to reporters while visiting the polling site at Londonderry High School on January 23, 2024, in New Hampshire. | Chip Somodevilla/Getty
+
+
+
+“He doesn’t want us to solve the border problem because he wants to blame Biden for it.”
+
+
+For years, Republicans have professed fury over a crisis at the US-Mexico border. For months, many in the GOP have insisted they could only support further aid to Ukraine if it was paired with tougher border security measures to address that crisis.
+
+
+So President Joe Biden accepted their conditions, giving up Democrats’ longtime demands on immigration and conceding much of what the right wanted — and as recently as Monday, a bipartisan deal seemed near.
+
+
+But now, Republicans may be backing out. Not because of the substance of the deal, but because it might hurt Donald Trump’s chances of retaking the White House.
+
+
+That’s what Senate Minority Leader Mitch McConnell told Republican senators in a closed-door meeting, according to Jake Sherman of Punchbowl News, saying “the politics” had put them “in a quandary.”
+
+
+“When we started this, the border united us and Ukraine divided us,” McConnell said, per Sherman. But, he went on, “The politics on this have changed.” The issue is that “the nominee” — Trump — wants to campaign on immigration. “We don’t want to do anything to undermine him.”
+
+
+Some pro-deal senators pushed back on how these remarks were reported Thursday, claiming McConnell wasn’t affirmatively declaring the talks dead or separating the two issues. Sen. Mitt Romney (R-UT) said instead that McConnell was “ambiguous” about a path forward.
+
+
+But it’s clear what McConnell was alluding to: that Trump wants there to be chaos at the border while Biden is president, because he thinks such chaos will help defeat the incumbent. Trump does not want congressional Republicans making a deal with Biden to address the actual substantive problem because that would make Biden look good.
+
+
+Romney confirmed that interpretation. “The border is a very important issue for Donald Trump,” he told reporters Thursday. “And the fact that he would communicate to Republican senators and congresspeople that he doesn’t want us to solve the border problem because he wants to blame Biden for it is really appalling.”
+
+
+If Republicans do kill the deal, it would make all their protestations about how much they supposedly care about this issue look hollow, and the GOP would come off looking tremendously cynical. They claim to believe the migrant surge of the past few years is destroying the country, but they’d be happy to let it continue unaddressed for another year if it means they win an election.
+
+
+Why Republicans thought a difficult immigration deal was the key to passing Ukraine aid
+
+
+ Alex Wong/Getty
+
+US Senate Minority Leader Mitch McConnell (R-KY) and then-Speaker of the House Kevin McCarthy (R-CA) speak to reporters after meeting with President Joe Biden and fellow congressional leaders at the White House on May 16, 2023.
+
+
+
+The reason the immigration talks got as far as they did was because of an entirely different issue: Ukraine aid.
+
+
+The national security establishment in both parties strongly supports further aid to Ukraine, believing that without it, the country’s resistance to Russia’s invasion might collapse. Many GOP senators, including McConnell, share that view, as did former speaker Kevin McCarthy and some House Republicans. But the MAGA right is strongly against further Ukraine aid. And with Republicans in control of the House, they’ve exerted pressure on their chamber’s leaders not to bring a “clean” Ukraine bill to a vote.
+
+
+So, last year, various Republicans gradually glommed on to the idea of linking Ukraine aid to something they thought Trump supporters (and really all Republicans) wanted: border security.
+
+
+To McConnell and the faction of Republicans truly trying to pass Ukraine aid, the theory was that forcing Biden into major border security concessions would be a “win” for the right and help make the bill more palatable for Republicans fearing backlash from the base (like new speaker Mike Johnson).
+
+
+GOP leaders argued to their senators that this was the best chance they’d ever have to get Democrats to accept tough border measures — because, they said, Democrats would surely never agree to a deal with President Trump if he wins. And Republican senators, even anti-MAGA and pro-Ukraine ones like Mitt Romney, presented a united front in negotiations, saying Ukraine aid simply couldn’t pass unless Biden played ball on immigration.
+
+
+Biden did play ball. And this was a big deal. The longtime reason for congressional gridlock on immigration was that Democrats insisted tougher border measures be paired with an agreement to legalize the status of unauthorized immigrants already living here. But in these talks, Democrats dropped that demand. The bill would be full of restrictionist measures and have nothing on legalization.
+
+
+As I wrote in December, Biden made this shift in part to try to get the Ukraine aid and in part because he and other Democrats had concluded that the border status quo was unacceptable — that it was both a substantive mess and a political liability for their party.
+
+
+The talks have been lengthy and difficult, and have at times provoked outrage from both the left and the right. But NBC News reported, citing a source, that as recently as Monday the major policy sticking points had been “largely resolved,” suggesting a deal could be finalized relatively soon.
+
+
+But it all might fall apart — due to Trump’s campaign needs
+
+
+ Anna Moneymaker/Getty
+
+US Speaker of the House Mike Johnson (R-LA) on January 19, 2024.
+
+
+
+The prospects for the Senate deal have always been questionable in the House. Johnson has spoken of linking Ukraine aid to border security in a way that has surface similarities to Senate Republicans’ strategy. But he’s also said he’d demand far more than it seemed plausible for Republicans to get from Biden, and he hasn’t sounded thrilled with the emerging Senate framework.
+
+
+In his few months since becoming speaker, Johnson has floundered about trying to please the right wing in the House. But now he has another problem: Trump.
+
+
+Last week, Johnson appeared on Fox News, and host Laura Ingraham opened her interview by saying, “The president [Trump] actually just got off the phone with me right before the show, and he said he has spoken to you about this deal, and that he is against it, and he urged you to be against this deal.” She added, “President Trump was extremely adamant about that.”
+
+
+Trump has publicly condemned the potential deal, writing last week on Truth Social, “I do not think we should do a Border Deal, at all, unless we get EVERYTHING needed to shut down the INVASION of Millions & Millions of people, many from parts unknown, into our once great, but soon to be great again, Country!”
+
+
+When Republicans in the House and Senate have publicly criticized the deal, they have tended to say it simply wouldn’t be tough enough. Sen. Ted Cruz (R-TX) called it a “stinking pile-of-crap bill” and claimed it wouldn’t actually solve the border crisis. And it is unclear how much it would change the fundamental situation, since border arrivals are driven to a significant extent by factors outside of the US’s control.
+
+
+But McConnell’s comments on “the politics” seem to reveal what he thinks is driving Trump’s recalcitrance. Indeed, Trump’s biggest fear might be that the bill will work, because then he’ll have a harder time attacking Biden. And in truth, he wouldn’t be wrong in that political analysis. A bipartisan border security deal would indeed make Biden look good — that’s one reason he’s been so eager for that deal.
+
+
+Such blatant hackery, though, reveals the selfishness that’s always been core to who Trump is — he’s happy to throw the country under the bus for his own personal gain, as most famously demonstrated in his attempt to shred democracy rather than admit defeat in the 2020 election.
+
+
+“The reality is that we have a crisis at the border,” Romney told CNN Thursday. And Trump, he said, was telling Republicans not to do anything about it, saying instead, “Hey, save that problem. Don’t solve it. Let me take credit for solving it later.”
+
+
Why would anyone be against life-saving malaria bednets? -
+
+
+
+A young boy rolls up a mosquito net covering bedding at a refugee camp in 2023 in South Sudan. | Luke Dray/Getty Images
+
+
+
+The no good, very bad case against malaria bednets, explained.
+
+
+Marc Andreessen, the billionaire venture capitalist and early web browser developer, thinks we’re giving too many insecticidal bednets to people exposed to malaria, tweeting, “Mosquito nets are a triple threat — dangerous to people, dangerous to fish, and dangerous to fishing ecosystems and the communities they feed.”
+
+
+
+
+
+That mosquito nets are dangerous to people would be news to basically any public health professional who’s ever studied them. A systematic review by the Cochrane Collaboration, probably the most respected reviewer of evidence on medical issues, found that across five different randomized studies, insecticide-treated nets reduce child mortality from all causes by 17 percent, and save 5.6 lives for every 1,000 children protected by nets. That implies that the 282 million nets distributed in 2022 alone saved about 1.58 million lives. In one year.
+
+
+So … what the hell is Andreessen even talking about?
+
+
+To understand why someone who has historically been more interested in crypto art than global health is suddenly tweeting about malaria, you have to know a little bit about Andreessen’s grudges. Andreessen’s VC firm, Andreessen Horowitz (a16z), has invested in a lot in AI companies lately, and he has aligned himself with a faction known as “effective accelerationists,” who favor aggressive progress in AI with minimal regulation or guardrails.
+
+
+The effective accelerationists, or e/acc, define themselves in large part by their opposition to effective altruists, the social movement that began by focusing on cost-effective global health interventions and has more recently advocated for tough regulations to prevent AI from going awry (Future Perfect, the section running this article, is broadly inspired by EA ideas). Effective altruists have long been identified with anti-malarial bednets, a prime example of the very cheap, very effective global health causes they favor.
+
+
+So, largely to stick it to the people who want AI regulation, Andreessen has committed himself to attacking one of the best methods of preventing malaria. If that doesn’t make sense to you, don’t worry; you’re not the one acting ridiculous.
+
+
+But it’s worth taking the critique here at least marginally seriously. Do bednets have serious downsides, related to misuse for fishing, that their advocates are simply ignoring?
+
+
+In a word: no. In multiple words: The finding that bednets save lives is not affected, at all, by the minority of people who use bednets to fish, rather than to protect themselves from malaria. Some of these people use nets that are several years old with insecticide that’s worn off, and are no longer effective at killing mosquitos. There is little research on what fishing with these nets actually does to fish or people — but also little reason to think the magnitudes of these effects are remotely near the number of lives saved by nets.
+
+
+Bednets and fishing nets
+
+
+Andreessen’s objection is rooted in something that’s been true of bednets for decades: sometimes, people use them as fishing nets instead.
+
+
+This has occasionally popped up as an objection to bednet programs, notably in a 2015 New York Times article. One related argument is that the diversion of nets toward fishing means they’re not as effective an anti-malaria program as they initially appear.
+
+
+That’s simply a misunderstanding of how the research on bednets works. The scientists who study these programs, and the charities that operate them, are well aware that some share of people who get the nets don’t use them for their intended purpose.
+
+
+The Against Malaria Foundation, for instance, a charity that funds net distribution in poor countries, conducts extensive “post-distribution monitoring,” sending surveyors into villages that get the nets and having them count up the nets they find hanging in people’s houses, compared to the number previously distributed. When conducted six to 11 months after distribution, they find that about 68 percent of nets are hanging up as they’re supposed to; the percent gradually falls over the years, and by the third year the nets have lost much of their effectiveness.
+
+
+So does this mean that bednets are only 68 percent as effective as previously estimated? No. Studies of bednet programs do not assume full takeup, because that would be a dumb thing to assume. Instead, they evaluate programs where some villages or households randomly get free bednets, and compare outcomes (like mortality or malaria cases) between the treated people who got the nets and untreated people who didn’t.
+
+
+For instance, take a 2003 paper evaluating a randomized trial of net distribution in Kenya (this was one of the papers included in the Cochrane review). The researchers’ own surveys show that about 66 percent of nets were used as intended. The researchers did not exclude the one-third of households not using the nets from the study. Instead, they simply compared death rates and other metrics in the villages randomized to receive nets to those metrics in villages randomized to not get them. That comparison already bakes in the fact that a third of households who received the nets weren’t using them.
+
+
+So estimates like “bednets reduce child mortality by 17 percent” are already assuming that not everybody is using the nets as intended. This just isn’t a problem for the impact estimates.
+
+
+But is it a problem for fisheries? Andreessen cites one recent article to make this case. It’s not clear to me he actually read it.
+
+
+The authors start by acknowledging that bednets have saved millions of lives, and even that the use of nets for fishing makes sense for many people. It’s a free way to get food you need to survive in regions often reliant on subsistence farming. Moreover, the authors note that “The worldwide collapse of tropical inland freshwater fisheries is well documented and occurred before the scale-up of ITNs.” At worst, you can accuse nets of making an existing problem worse.
+
+
+The bigger question the authors raise is that insecticides are toxic. That’s, of course, the point: They’re meant to kill mosquitoes. The question, then, is whether they are toxic to fish or humans when used for fishing. The authors’ conclusion is maybe, but we have no research indicating one way or another. “To our knowledge there is currently a complete lack of data to assess the potential risks associated with pyrethroid insecticide leaching from ITNs,” the authors conclude. They are not sure if the amount leaching from nets is enough to be toxic to fish; they’re not fully sure that the insecticide leaches into the water at all, though they suspect it does. Even less clear is how these insecticides might affect humans who then eat fish that might be exposed to them.
+
+
+I asked the study’s lead author, David Larsen, chair of the department of public health at Syracuse’s Falk College of Sport & Human Dynamics and an expert on malaria and mosquito-borne illnesses, for his reaction to Andreessen citing his work. He found the idea that one should stop using bednets because of the issues the paper raises ridiculous:
+
+
+
+Andreessen is missing a lot of the nuance. In another study we discussed with traditional leaders the damage they thought ITNs [insecticide-treated nets] were doing to the fisheries. Although the traditional leaders attributed fishery decline to ITN fishing, they were adamant that the ITNs must continue. Malaria is a scourge, and controlling malaria should be the priority. In 2015 ITNs were estimated to have saved more than 10 million lives — likely 20-25 million at this point.
+
+
+… ITNs are perhaps the most impactful medical intervention of this century. Is there another intervention that has saved so many lives? Maybe the COVID-19 vaccine. ITNs are hugely effective at reducing malaria transmission, and malaria is one of the most impactful pathogens on humanity. My thought is that local communities should decide for themselves through their processes. They should know the potential risk that ITN fishing poses, but they also experience the real risk of malaria transmission.
+
+
+
+He notes that the fish toxicity issue is real and worth investigating further; a colleague, the University of Florida’s Joe Bisesi, is investigating this and, preliminarily, the insecticide does seem to harm fish. Just because an intervention like bednets is effective at its primary purpose doesn’t mean it doesn’t have unintended consequences, and it’s worth investigating those fully.
+
+
+But, as Larsen says, people like him, me, and Andreessen aren’t the people affected here. The people affected, in rural Africa and other malarial regions, overwhelmingly want bednets as a tool to help them survive.
+
+
+Put your money where your mouth is
+
+
+Luckily for Andreessen and like-minded folks, people genuinely worried about fisheries and insecticidal toxicity in Africa have other options. They can support the Malaria Consortium, for instance, which instead of bednets offers seasonal chemoprevention, an approach in which people in malarial regions get preventive medicines meant to reduce their risk of infections. If you’ve traveled to a malarial region, you may have gotten these drugs yourself from a travel medicine clinic; I did before a trip to Burma. There are no fishing-related concerns with chemoprevention, and it also saves lives very cost-effectively.
+
+
+One could also fund work on malaria vaccines. The R21 vaccine, recently approved by the World Health Organization, is 75 percent effective against infection, and stakeholders like the vaccine distribution group GAVI and the Global Fund to Fight AIDS, Tuberculosis and Malaria are currently working out a plan to fund a mass rollout. Bednet skeptics could easily donate to those groups, or fund advocacy to get governments like the US to increase their commitments to the Global Fund and GAVI to ensure the vaccination effort is adequately funded.
+
+
+The broader point Andreessen was trying to make by attacking bednets, in his words, was that, “It is very, very hard to intervene in other people’s lives — particularly from a distance — and not make things worse.” It is indeed really hard, and requires a lot of research — but luckily people have done that research, and even if for whatever reason bednets don’t clear the bar for you, there are plenty of effective interventions against malaria and other diseases that don’t raise any issues around fishing.
+
+
+The question, then, is whether that moves you to support these causes, or if attacking bednets is just an excuse for one’s own inaction. I don’t know Andreessen’s own donation history; maybe he’s been giving to the Malaria Consortium this whole time. If so, god bless. If not, he should consider taking his own arguments a bit more seriously.
+
+
+
From The Hindu: Sports
+
+
AUS vs WI | West Indies pacemen ruin Australia’s day in gripping pink-ball test - The eighth-ranked tourists antagonised the world test champions with the bat for 18 overs after resuming from 266-8 overnight.
+
Exuma shines -
+
Australian Open 2024 | Jannik Sinner ends Novak Djokovic Grand Slam history bid - Sinner thus ended the Serbian’s astonishing 33-match winning run at Melbourne Park to reach his first major final.
+
Jurgen Klopp announces he will step down as Liverpool manager at end of season - He made the shock announcement on Friday that he will resign at the end of the season, saying he is “running out of energy.”
+
IND vs ENG | Jadeja, Rahul make classy fifties as India pushes England to corner - Despite that lead, slight disappointment in the Indian camp is that none of their frontline batters did not score a hundred.
+
+
From The Hindu: National News
+
+
KCR wants party MPs to fight for Telangana’s rights -
+
NEP 2020 will be implemented in all programmes soon at Univ of Hyderabad: VC Prof BJ Rao -
+
Here are the big stories from Karnataka today - Welcome to the Karnataka Today newsletter, your guide from The Hindu on the major news stories to follow today. Curated and written by Nalme Nachiyar.
+
Military rule hurts Myanmar’s economy, nation scores zero in civil liberty index | Data - Myanmar shares the joint last rank with Syria and North Korea in the civil liberty index
+
Padma awards for four people from France underscore strength of its ties with India: Officials - Charlotte Chopin, Kiran Vyas, Pierre Sylvain Filliozat and Fred Negrit received the honour.
+
+
From BBC: Europe
+
+
France set to tighten immigration law after court scraps some measures - The Macron government is to push through the long-running law, despite many measures being struck out.
+
Identical twins separated and sold at birth reunited by TikTok - Thousands of people in Georgia have found out they were stolen from their parents at birth and sold.
+
Jurgen Klopp to step down as Liverpool manager at end of season - Liverpool manager Jurgen Klopp is to step down from the role at the end of the season, saying he is “running out of energy”.
+
Gustav Klimt portrait found after almost 100 years - The Portrait of Fraulein Lieser’ - last seen in public in 1925 - has been discovered in Vienna.
+
Igor Girkin shot down a passenger jet, then insulted Putin. Which one put him in jail? - Igor Girkin escaped justice for downing flight MH17 but goes to jail after criticising Russia’s leader.
+
+
From Ars Technica
+
+
LIGO goes to space: ESA to proceed with LISA gravitational wave detector - A gravitational wave detector in space will be sensitive to unexplored phenomena. - link
+
Resident Evil Kart’s fixed camera angles make for a charmingly frustrating classic - “WELCOME TO THE WORST THING I HAVE EVER CREATED!” - link
+
Apple announces sweeping EU App Store policy changes—including sideloading - Most of these changes only apply to Europe. - link
+
X can’t stop spread of explicit, fake AI Taylor Swift images - Will Swifties’ war on AI fakes spark a deepfake porn reckoning? - link
+
Microsoft cancels Blizzard survival game, lays off 1,900 - Job cuts hit Xbox, ZeniMax businesses, too, reports say. - link
+
+
From Jokes Subreddit
+
+
A milkman is dying in the hospital -
+
+
+He’s surrounded by his two sons, his daughter, his wife, and a nurse. He turns to his family and says:
+
+
+“Peter, my eldest, I leave you the villas in Beverly Hills. Samantha, my beautiful daughter, to you I give the apartments in Los Angeles Plaza. Charlie, my youngest son, I see a long and bright future in you, so I leave the city center offices to you. And my dear wife, the three residential towers in downtown are all yours.”
+
+
+The nurse hears all of this and is impressed at the man’s sizeable fortune. She turns to the wife and says, “Ma’am, your husband must be very rich to be bequeathing so many properties. You all are so lucky.”
+
+
+The wife retorts, “Rich? Lucky? Are you kidding me? He’s a milkman. He’s giving us his routes.”
+
+
+/cdn.vox-cdn.com/uploads/chorus_asset/file/25248171/GettyImages_1490759676.jpg)
Alex Wong/Getty
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Anna Moneymaker/Getty
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