Genome-wide association study reveals different T cell distributions in peripheral blood of healthy individuals at high genetic risk of type 1 diabetes and long COVID -
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+The immune system plays a crucial role in many human diseases. In this context, genome-wide association studies (GWAS) offer valuable insights to elucidate the role of immunity in health and disease. The present multi-omics study aimed to identify genetic determinants of immune cell type distributions in the blood of healthy individuals and to assess whether the distributions of these cells may play a role for autoimmune and COVID-19 disease risk. To this end, the frequencies of different immune cells in 483 healthy individuals from the Berlin Aging Study II were quantified using flow cytometry, and GWAS was performed for 92 immune cell phenotypes. Additionally, we performed linear regression analyses of immune cell distributions using polygenic risk scores (PRS) based on prior GWAS for five autoimmune diseases as well as for COVID-19 infection and post-COVID syndrome (“long COVID”). We validated seven previously described immune loci and identified 13 novel loci showing genome-wide significant (α=5.00E-8) association with different immune cell phenotypes. The most significant novel signal was conferred by the SLC52A3 locus, encoding for a riboflavin transporter protein, which was associated with naïve CD57+ CD8+ T cells (p=4.13E-17) and colocalized with SLC52A3 expression. Several novel loci contained immunologically plausible candidate genes, e.g., variants near TBATA and B3GAT1 representing genes associated with T cell phenotypes. The PRS of type 1 diabetes were significantly associated with CD8+ T cells at different differentiation states (p≤7.02E-4), and PRS of long COVID were associated with early-differentiated CD4+ T cells (p≤1.54E-4). In conclusion, our extensive immune cell GWAS analyses highlight several novel genetic loci of likely relevance for immune system function. Furthermore, our PRS analyses point to a shared genetic basis between immune cell distributions in healthy adults and T1D (CD8+ T cells) as well as long COVID (CD4+ T cells).
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Implementation of Smart Triage combined with a quality improvement program for children presenting to facilities in Kenya and Uganda: An interrupted time series analysis. -
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+PLOS DH (298/300 word limit) Sepsis occurs predominantly in low-middle-income countries. Sub-optimal triage contributes to poor early case recognition and outcomes from sepsis. We evaluated the impact of Smart Triage using improved time to intravenous antimicrobial administration in a multisite interventional study. Smart Triage was implemented (with control sites) in Kenya (February 2021-December 2022) and Uganda (April 2020-April 2022). Children presenting to the outpatient departments with an acute illness were enrolled. A controlled interrupted time series was used to assess the effect on time from arrival at the facility to intravenous antimicrobial administration. Secondary analyses included antimicrobial use, admission rates and mortality (NCT04304235). During the baseline period, the time to antimicrobials decreased significantly in Kenya (132 and 58 minutes) at control and intervention sites, but less in Uganda (3 minutes) at the intervention site. Then, during the implementation period in Kenya, the time to IVA at the intervention site decreased by 98 min (57%, 95% CI 81-114) but increased by 49 min (21%, 95% CI: 23-76) at the control site. In Uganda, the time to IVA initially decreased but was not sustained, and there was no significant difference between intervention and control sites. At the intervention sites, there was a significant reduction in IVA utilization of 47% (Kenya) and 33% (Uganda), a reduction in admission rates of 47% (Kenya) and 33% (Uganda) and a 25% (Kenya) and 75% (Uganda) reduction in mortality rates compared to the baseline period. We showed significant improvements in time to intravenous antibiotics in Kenya but not Uganda, likely due to COVID-19, a short study period and resource constraints. The reduced antimicrobial use and admission and mortality rates are remarkable and welcome benefits but should be interpreted cautiously as these were secondary outcomes. This study underlines the difficulty of implementing technologies and sustaining quality improvement in resource-poor health systems.
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Physicians experiences with telemedicine during the COVID-19 pandemic in India -
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+Purpose: Digital health is an important factor in Indias healthcare system. Inclusive policy measures, a fertile technological landscape, and relevant infrastructural development with unprecedented levels of telemedicine adoption catalysed by the recent COVID-19 pandemic have thrown open new possibilities and opportunities for clinicians, end-users, and other stakeholders. Nevertheless, there are still several challenges to properly integrating and scaling telemedicine use in India. This studys objective was to understand the views of practising physicians in India on the use of telemedicine and the challenges experienced during the accelerated rollout during the first wave of the COVID-19 pandemic. Methods: We acquired data through an anonymous, cross-sectional, internet-based survey of physicians (n=444) across India on the COVID-19 frontline. These responses were subjected to qualitative data analysis (via inductive coding and thematic analyses) and descriptive statistics, as appropriate. Results: Most responses (n=51) were categorised under a code indicating that telemedicine-led healthcare delivery compromised treatment quality. The second largest proportion of responses (n=22) suggested that Accessibility, quality and maturity of software and hardware infrastructure was a considerable challenge. Conclusions: Despite the considerable uptake, perceived benefits, and the foreseen positive role of telemedicine in India, several challenges of telemedicine use (viz., technical, user experience-based integration, and non-user-based integration challenges) have been identified. These must be addressed through suggested relevant opportunities to realise telemedicines potential and help inform the future design of effective telemedicine policy and practice in India.
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Factors associated with knowledge, attitudes, and behaviors regarding antiviral medications for COVID-19 among US adults -
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+Background: Little is known about public perceptions of antivirals for the treatment of mild-to-moderate COVID-19 in the United States (US). Our objective was to explore adult perceptions toward COVID-19 antivirals with the goal of improving outreach communications about antivirals for COVID-19. Methods: During July 2022, potential respondents 18 years and older were randomly sampled from a national opt-in, non-representative, cross-sectional internet panel, with oversampling of African Americans, Hispanics, and adults 65 years and older. Respondents were asked about sociodemographic factors, and knowledge, attitudes, and perceptions regarding COVID-19 antivirals. Results were weighted to represent the non-institutionalized US adult population. Results: Among 1,155 respondents, 51% were female, 60% were 18-49 years, 21% were 50-64 years, and 19% were 65 years or older. Compared to those aged 18-49 years and 50-64 years, a greater proportion of adults 65 years and older were knowledgeable about COVID-19 antivirals and would take them if they tested positive or their doctor recommended them. Adults 65 years and over and those reporting immunosuppression or disability had the highest rates of willingness to take antivirals. For all groups, the proportion of people willing to take antivirals increased by >20% if recommended by their doctor. Respondents in the 50-64 and 65+ groups who were sure they would take COVID-19 antivirals were more likely to be fully vaccinated and less likely to be living in isolation. Conclusion: Groups that are less likely to have been vaccinated, those living in isolation, and those not sure about whether they would take an antiviral or not may be at risk for not receiving treatment to prevent severe COVID-19 outcomes. However, trust in doctor recommendations may be enough to overcome individual patient concerns about COVID-19 antivirals. Targeted initiatives to educate those at risk for severe COVID-19 outcomes about the effectiveness of antivirals, including those who are unvaccinated given their increased risk of severe disease, may be needed to further lower this population9s risk of severe COVID-19.
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SARS-COV-2 induces blood-brain barrier and choroid plexus barrier impairments and vascular inflammation in mice -
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+The coronavirus disease of 2019 (COVID-19) pandemic that has led to more than 700 million confirmed cases and near 7 million deaths. Although Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) virus mainly infects the respiratory system, neurological complications are widely reported in both acute infection and long-COVID cases. Despite the success of vaccines and antiviral treatments, neuroinvasiveness of SARS-CoV-2 remains as an important question, which is also centered on the mystery whether the virus is capable of breaching the barriers into the central nervous system. By studying the K18-hACE2 infection model, we observed clear evidence of microvascular damage and breakdown of the blood-brain barrier (BBB). Mechanistically, SARS-CoV-2 infection caused pericyte damage, tight junction loss, endothelial activation and vascular inflammation, which together drive microvascular injury and BBB impairment. In addition, the blood-cerebrospinal fluid barrier at the choroid plexus was also impaired after infection. Therefore, cerebrovascular and choroid plexus dysfunctions are important aspects of COVID-19 and may contribute to the neurological complications both acutely and in long COVID.
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Unfolded Von Willebrand Factor Binds Protein S and Reduces Anticoagulant Activity -
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+Protein S (PS), the critical plasma cofactor for the anticoagulants tissue factor (TF) pathway inhibitor (TFPI) and activated protein C (APC), circulates in two functionally distinct pools: free (anticoagulant) or bound to complement component 4b-binding protein (C4BP) (anti-inflammatory). Acquired free PS deficiency is detected in several viral infections, but its cause is unclear. Here, we identified a shear-dependent interaction between PS and von Willebrand Factor (VWF) by mass spectrometry. Consistently, plasma PS and VWF comigrated in both native and agarose gel electrophoresis. The PS/VWF interaction was blocked by TFPI but not APC, suggesting an interaction with the C-terminal sex hormone binding globulin (SHBG) region of PS. Microfluidic systems, mimicking arterial laminar flow or disrupted turbulent flow, demonstrated that PS stably binds VWF as VWF unfolds under turbulent flow. PS/VWF complexes also localized to platelet thrombi under laminar arterial flow. In thrombin generation-based assays, shearing plasma decreased PS activity, an effect not seen in the absence of VWF. Finally, free PS deficiency in COVID-19 patients, measured using an antibody that binds near the C4BP binding site in SHBG, correlated with changes in VWF, but not C4BP, and with thrombin generation. Our data suggest that PS binds to a shear-exposed site on VWF, thus sequestering free PS and decreasing its anticoagulant activity, which would account for the increased thrombin generation potential. As many viral infections present with free PS deficiency, elevated circulating VWF, and increased vascular shear, we propose that the PS/VWF interaction reported here is a likely contributor to virus-associated thrombotic risk.
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Distinct evolution of SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 lineages combining increased fitness and antibody evasion -
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+The unceasing circulation of SARS-CoV-2 leads to the continuous emergence of novel viral sublineages. Here, we isolated and characterized XBB.1, XBB.1.5, XBB.1.9.1, XBB.1.16.1, EG.5.1.1, EG.5.1.3, XBF, BA.2.86.1 and JN.1 variants, representing >80% of circulating variants in January 2024. The XBB subvariants carry few but recurrent mutations in the spike, whereas BA.2.86.1 and JN.1 harbor >30 additional changes. These variants replicated in IGROV-1 but no longer in Vero E6 and were not markedly fusogenic. They potently infected nasal epithelial cells, with EG.5.1.3 exhibiting the highest fitness. Antivirals remained active. Neutralizing antibody (NAb) responses from vaccinees and BA.1/BA.2-infected individuals were markedly lower compared to BA.1, without major differences between variants. An XBB breakthrough infection enhanced NAb responses against both XBB and BA.2.86 variants. JN.1 displayed lower affinity to ACE2 and higher immune evasion properties compared to BA.2.86.1. Thus, while distinct, the evolutionary trajectory of these variants combines increased fitness and antibody evasion.
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Forecasting dominance of SARS-CoV-2 lineages by anomaly detection using deep AutoEncoders -
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+The coronavirus disease of 2019 (COVID-19) pandemic is characterized by sequential emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and lineages outcompeting previously circulating ones because of, among other factors, increased transmissibility and immune escape. We devised an unsupervised deep learning AutoEncoder for viral genomes anomaly detection to predict future dominant lineages (FDLs), i.e., lineages or sublineages comprising >= 10% of viral sequences added to the GISAID database on a given week. The algorithm was trained and validated by assembling global and country specific data sets from 16,187,950 Spike protein sequences sampled between December 24th, 2019, and November 8th, 2023. The AutoEncoder flags low frequency FDLs (0.01% - 3%), with median lead times of 4-16 weeks. Over time, positive predictive values oscillate, decreasing linearly with the number of unique sequences per data set, showing average performance up to 30 times better than baseline approaches. The B.1.617.2 vaccine reference strain was flagged as FDL when its frequency was only 0.01%, more than one year earlier of being considered for an updated COVID-19 vaccine. Our AutoEncoder, applicable in principle to any pathogen, also pinpoints specific mutations potentially linked to increased fitness, and may provide significant insights for the optimization of public health pre-emptive intervention strategies.
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The Importance of Cause-of-Death Certification for the COVID-19 Burden Assessment: the Case of Central Europe -
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+Background: In Central Europe, the increase in mortality during the COVID-19 pandemic exceeded the number of deaths registered due to coronavirus disease. Miscertification of COVID-19 has been suggested as one of the possible explanations. Analysis of all mentions from death certificates allows us to identify cases where COVID-19 was reported as a contributing rather than the underlying cause of death (UCoD). Methods: Analysis of 187,000 death certificates with a COVID-19 mention from Austria, Bavaria, Czechia, Lithuania and Poland, 2020–2021. Cause of Death Association Indicators (CDAIs) and Contributing CDAIs were calculated to identify and measure the strength of associations between COVID-19, reported as UCoD or not, and all other medical mentions. Results: Death certificates reporting COVID-19 included on average more medical information than other death certificates. In 171,600 deaths with COVID-19 as the UCoD, ten groups of comorbidities and ten types of complications revealed significant and strong association with COVID-19. Further 15,700 deaths were certified with COVID-19 only as a contributing condition, of which almost 20% were assigned to typical coronavirus complications, such as cerebral infarction, Acute Myocardial Infarction, renal failure. In Austria, Bavaria, Czechia and Lithuania the reported scale of COVID-19 mortality would have been 18-27% higher had COVID-19 been coded as the UCoD in all the cases. Conclusions: Complete death certificate information allows us to assess the scale of COVID-19 miscertification and the burden of COVID-19. Deaths registered with a coronavirus comorbidity were equivalent to the total estimated excess mortality in Austria and Czech Republic, and a large proportion of in Lithuania and Bavaria.
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+Immunization with mosaic-8b [60-mer nanoparticles presenting 8 SARS-like betacoronavirus (sarbecovirus) receptor-binding domains (RBDs)] elicits more broadly cross-reactive antibodies than homotypic SARS-CoV-2 RBD-only nanoparticles and protects against sarbecoviruses. To investigate original antigenic sin (OAS) effects on mosaic-8b efficacy, we evaluated effects of prior COVID-19 vaccinations in non-human primates and mice on sarbecovirus response breadths elicited by mosaic-8b, admix-8b (8 homotypics), and homotypic SARS-CoV-2, finding greatest cross-reactivity for mosaic-8b. As demonstrated by molecular fate-mapping in which antibodies derived from specific cohorts of B cells are differentially detected, B cells primed by WA1 spike mRNA-LNP dominated antibody responses after RBD-nanoparticle boosting. While mosaic-8b and homotypic-nanoparticles boosted cross-reactive antibodies, de novo antibodies were predominantly induced with mosaic-8b boosting, and these were specific for variant RBDs with increased identity to RBDs on mosaic-8b. These results inform OAS mechanisms and support using mosaic-8b to protect COVID-19 vaccinated/infected humans against as-yet-unknown SARS-CoV-2 variants and animal sarbecoviruses with human spillover potential.
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Use of substances to cope predicts PTSD symptom persistence: Investigating patterns of interactions between PTSD symptoms and its maintaining mechanisms -
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+Objective. Post-traumatic stress disorder (PTSD) remains a growing public health challenge across the globe and is associated with negative and persistent long-term consequences. The last decades of research identified different mechanisms associated with the development and persistence of PTSD, including maladaptive coping strategies, cognitive and experiential avoidance, positive, and negative metacognitions. Despite these advances, little is known about how these different processes interact with specific PTSD symptoms, and how they influence each other over time at the within-person level. Method. Leveraging a large (N > 1,800) longitudinal dataset representative of the Norwegian population during the COVID-19 pandemic, this pre-registered study investigated these symptom-process interactions over an eight-month period. Results. Our panel graphical vector autoregressive (GVAR) network model revealed the dominating role of substance use to cope in predicting higher levels of PTSD symptoms over time and increases in PTSD symptomatology within more proximal time-windows (i.e., within six weeks). Threat monitoring was associated with increased suicidal ideation, while threat monitoring itself was increasing upon decreased avoidance behavior, greater presence of negative metacognitions, and higher use of substances to cope. Conclusions. Our findings speak to the importance of attending to different coping strategies, particularly the use of substances as a coping behavior in efforts to prevent PTSD chronicity upon symptom onset. We outline future directions for research efforts to better understand the complex interactions and temporal pathways leading up to the development and maintenance of PTSD symptomatology.
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Predicting COVID-19 booster immunogenicity against future SARS-CoV-2 variants and the benefits of vaccine updates -
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+The ongoing evolution of the SARS-CoV-2 virus has led to a move to update vaccine antigens in 2022 and 2023. These updated antigens were chosen and approved based on in vitro neutralisation titres against recent SARS-CoV-2 variants. However, unavoidable delays in viral manufacture and distribution meant that the updated booster vaccine was no longer well matched to the circulating SARS-CoV-2 variant by the time of its deployment. Understanding whether the updating of booster vaccine antigens improves immune responses to subsequent SARS-CoV-2 circulating variants is a major priority in justifying future vaccine updates. Here we analyse all available data on the immunogenicity of variant containing SARS-CoV-2 vaccines and their ability to neutralise later circulating SARS-CoV-2 variants. We find that updated booster antigens give a 1.4-fold [95%CI 1.07-1.82] greater increase in neutralising antibody levels when compared with a historical vaccine immunogen. We then use this to predict the relative protection that can be expected from an updated vaccine even when the circulating variant has evolved away from the updated vaccine immunogen. These findings help inform the roll out of future booster vaccination programs.
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Can longitudinal electronic health record data identify patients at higher risk of developing long COVID? -
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+With hundreds of millions of COVID-19 infections to date, a considerable portion of the population has developed or will develop long COVID. Understanding the prevalence, risk factors, and healthcare costs of long COVID can be of significant societal importance. To investigate the utility of large-scale electronic health record (EHR) data in identifying and predicting long COVID, we analyzed data from the National COVID Cohort Collaborative (N3C), a longitudinal EHR data repository from 65 sites in the US with over 8 million COVID-19 patients. We characterized the prevalence of long COVID using a few different types of definition to illustrate their relative strengths and weaknesses. Then we developed a machine learning model to predict the risk of developing long COVID using demographic factors and comorbidity in the EHR. The risk factors for long COVID include patient age; sex; smoking status; and comorbidities characterized by the Charlson Comorbidity Index.
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Mechanistic models of humoral kinetics following COVID-19 vaccination -
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+Introduction: Future COVID-19 vaccine programmes need to take into account the variable responses elicited by different vaccines and their waning protection over time. Existing descriptions of antibody response to COVID-19 vaccination convey limited information about the mechanisms of antibody production and maintenance. Methods: We describe the antibody dynamics elicited by COVID-19 vaccination with two biologically-motivated mathematical models of antibody production by plasma cells and subsequent decay. We fit the models using Markov Chain Monte Carlo to seroprevalence data from 14,602 uninfected individuals collected via the primary care network in England between May 2020 and September 2022. We ensure our models are structurally and practically identifiable when using anti- body data alone. We analyse the effect of age, vaccine type, number of doses, and the interval between doses on antibody production and longevity of response. Results: We find evidence that individuals over 35 years of age who received a second dose of ChAdOx1-S generate a persistent antibody response suggestive of long-lived plasma cell induction, while individuals that receive two doses of BNT162b2, or one dose of either vaccine do not. We also find that plasamblast productive capacity, the likely driver of short-term antibody responses, is greater in younger people than older people (≤ 4.5 fold change in point estimates), people vaccinated with two doses than people vaccinated with one dose (≤ 12 fold change), and people vaccinated with BNT162b2 than people vaccinated with ChAdOx1-S (≤ 440 fold change). The effect of age on antibody dynamics is more pronounced in people vaccinated with BNT162b2 than people vaccinated with ChAdOx1-S. We find the half-life of an antibody to be between 23 - 106 days. Conclusion: Routinely-collected seroprevalence data are a valuable source of information for characterising within-host mechanisms of antibody production and persistence. Extended sampling and linking seroprevalence data to outcomes would allow for powerful conclusions about how humoral kinetics protect against disease.
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Dimensionality reduction distills complex evolutionary relationships in seasonal influenza and SARS-CoV-2 -
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+Public health researchers and practitioners commonly infer phylogenies from viral genome sequences to understand transmission dynamics and identify clusters of genetically-related samples. However, viruses that reassort or recombine violate phylogenetic assumptions and require more sophisticated methods. Even when phylogenies are appropriate, they can be unnecessary or difficult to interpret without specialty knowledge. For example, pairwise distances between sequences can be enough to identify clusters of related samples or assign new samples to existing phylogenetic clusters. In this work, we tested whether dimensionality reduction methods could capture known genetic groups within two human pathogenic viruses that cause substantial human morbidity and mortality and frequently reassort or recombine, respectively: seasonal influenza A/H3N2 and SARS-CoV-2. We applied principal component analysis (PCA), multidimensional scaling (MDS), t-distributed stochastic neighbor embedding (t-SNE), and uniform manifold approximation and projection (UMAP) to sequences with well-defined phylogenetic clades and either reassortment (H3N2) or recombination (SARS-CoV-2). For each low-dimensional embedding of sequences, we calculated the correlation between pairwise genetic and Euclidean distances in the embedding and applied a hierarchical clustering method to identify clusters in the embedding. We measured the accuracy of clusters compared to previously defined phylogenetic clades, reassortment clusters, or recombinant lineages. We found that MDS maintained the strongest correlation between pairwise genetic and Euclidean distances between sequences and best captured the intermediate placement of recombinant lineages between parental lineages. Clusters from t-SNE most accurately recapitulated known phylogenetic clades and recombinant lineages. Both MDS and t-SNE accurately identified reassortment groups. We show that simple statistical methods without a biological model can accurately represent known genetic relationships for relevant human pathogenic viruses. Our open source implementation of these methods for analysis of viral genome sequences can be easily applied when phylogenetic methods are either unnecessary or inappropriate.
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Investigating the Effectiveness of Vimida - Conditions: Long COVID; Post COVID-19 Condition Interventions: Behavioral: vimida Sponsors: Gaia AG; Medical School Hamburg; Institut Long-Covid Rostock Not yet recruiting
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Effects of Physiotherapy Via Video Calls on Cardiopulmonary Functions, Physical Function, Cognitive Function, Activity Daily Livings, and Quality of Life in Patients With COVID-19 - Conditions: COVID-19; Long COVID-19; Cardiopulmonary Function; Physical Function Interventions: Behavioral: Exercise training Sponsors: Chulabhorn Hospital Enrolling by invitation
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Acute Cardiovascular Responses to a Single Exercise Session in Patients With Post-COVID-19 Syndrome - Conditions: Post-Acute COVID-19 Syndrome Interventions: Behavioral: Exercise session; Behavioral: Control session Sponsors: University of Nove de Julho Not yet recruiting
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Reducing Respiratory Virus Transmission in Bangladeshi Classrooms - Conditions: SARS-CoV2 Infection; Influenza Viral Infections; Respiratory Viral Infection Interventions: Device: Box Fan; Device: UV Germicidal Irradiation Lamp Unit; Device: Combined: Box Fan and UV Germicidal Irradiation Lamp Units Sponsors: Stanford University; Centers for Disease Control and Prevention; International Centre for Diarrhoeal Disease Research, Bangladesh Not yet recruiting
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SMILE: Clinical Trial to Evaluate Mindfulness as Intervention for Racial and Ethnic Populations During COVID-19 - Conditions: Anxiety; COVID-19 Pandemic Interventions: Behavioral: Mindfulness Sponsors: University of North Carolina, Chapel Hill; National Institute on Minority Health and Health Disparities (NIMHD); RTI International Not yet recruiting
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A Study to Learn About a Combined COVID-19 and Influenza Shot in Healthy Adults - Conditions: Influenza, Human; SARS-CoV-2 Infection; COVID-19 Interventions: Biological: BNT162b2 (Omi XBB.1.5)/RIV; Biological: BNT162b2 (Omi XBB.1.5); Biological: RIV; Other: Normal saline placebo Sponsors: Pfizer Recruiting
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The Effects of Nutritional Intervention on Health Parameters in Participants With Type 2 Diabetes Mellitus - Conditions: Diabetes Mellitus Type 2; Diabetes Mellitus Type 2 in Obese; Diabetes; Diabetes Mellitus Non-insulin-dependent; Hypertension; Type 2 Diabetes Mellitus Interventions: Behavioral: Nutritional Intervention Sponsors: Sao Jose do Rio Preto Medical School; Fundação de Amparo à Pesquisa do Estado de São Paulo Completed
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The Impact of the Covid-19 Pandemic on Orthopedic Trauma Management - Conditions: Trauma; COVID-19 Pandemic Interventions: Other: epidemyolojical Sponsors: Bakirkoy Dr. Sadi Konuk Research and Training Hospital Completed
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Open-label, Multi-centre, Non-Inferiority Study of Safety and Immunogenicity of BIMERVAX for the Prevention of COVID-19 in Adolescents From 12 Years to Less Than 18 Years of Age. - Conditions: SARS CoV 2 Infection Interventions: Biological: BIMERVAX Sponsors: Hipra Scientific, S.L.U; Veristat, Inc.; VHIR; Asphalion Recruiting
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A Study of Amantadine for Cognitive Dysfunction in Patients With Long-Covid - Conditions: Long COVID; Post-Acute COVID-19 Syndrome Interventions: Drug: Amantadine; Other: Physical, Occupational, Speech Therapy; Other: Provider Counseling; Other: Medications for symptoms management Sponsors: University of Texas Southwestern Medical Center Not yet recruiting
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Study on the Effect of Incentive Spirometer-based Respiratory Training on the Long COVID-19 - Conditions: COVID-19 Pandemic; Diabetes; Hypertension; Cardiac Disease; Long COVID Interventions: Behavioral: Incentive Spirometer respiratory training Sponsors: National Taipei University of Nursing and Health Sciences; Tri-Service General Hospital Not yet recruiting
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Balance Acceptance and Commitment Therapy for Long COVID - Conditions: Post-COVID-19 Syndrome; Long COVID Interventions: Behavioral: Balance Acceptance and Commitment Therapy Sponsors: King’s College London Not yet recruiting
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Predict + Protect Study: Exploring the Effectiveness of a Predictive Health Education Intervention on the Adoption of Protective Behaviors Related to ILI - Conditions: Influenza; Influenza A; Influenza B; COVID-19; Respiratory Syncytial Virus (RSV) Interventions: Behavioral: ILI Predictive Alerts, Reactive Content, and Proactive Content; Behavioral: ILI Predictive Alerts, Reactive Content; Behavioral: Proactive Content; Behavioral: No Intervention Sponsors: Evidation Health; Biomedical Advanced Research and Development Authority Not yet recruiting
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From PubMed
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Influenza vaccination during the 2021/22 season: A data-linkage test-negative case-control study of effectiveness against influenza requiring emergency care in England and serological analysis of primary care patients - We present England 2021/22 end-of-season adjusted vaccine effectiveness (aVE) against laboratory confirmed influenza related emergency care use in children aged 1-17 and in adults aged 50+, and serological findings in vaccinated vs unvaccinated adults by hemagglutination inhibition assay. Influenza vaccination has been routinely offered to all children aged 2-10 years and adults aged 65 years + in England. In 2021/22, the offer was extended to children to age 15 years, and adults aged 50-64…
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Evaluation of molecular mechanisms of riboflavin anti-COVID-19 action reveals anti-inflammatory efficacy rather than antiviral activity - CONCLUSIONS: It is concluded that riboflavin reveals anti-inflammatory rather than antiviral activity for SARS-CoV-2 infection.
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An enhanced broad-spectrum peptide inhibits Omicron variants in vivo - The continual emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) poses a major challenge to vaccines and antiviral therapeutics due to their extensive evasion of immunity. Aiming to develop potent and broad-spectrum anticoronavirus inhibitors, we generated A1-(GGGGS)7-HR2m (A1L35HR2m) by introducing an angiotensin-converting enzyme 2 (ACE2)-derived peptide A1 to the N terminus of the viral HR2-derived peptide HR2m through a long flexible linker,…
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Mesenchymal stromal cells (MSCs) as a therapeutic agent of inflammatory disease and infectious COVID-19 virus: live or dead mesenchymal? - The COVID-19 infection is a worldwide disease that causes numerous immune-inflammatory disorders, tissue damage, and lung dysfunction. COVID-19 vaccines, including those from Pfizer, AstraZeneca, and Sinopharm, are available globally as effective interventions for combating the disease. The severity of COVID-19 can be most effectively reduced by mesenchymal stromal cells (MSCs) because they possess anti-inflammatory activity and can reverse lung dysfunction. MSCs can be harvested from various…
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Genetic justification of COVID-19 patient outcomes using DERGA, a novel data ensemble refinement greedy algorithm - Complement inhibition has shown promise in various disorders, including COVID-19. A prediction tool including complement genetic variants is vital. This study aims to identify crucial complement-related variants and determine an optimal pattern for accurate disease outcome prediction. Genetic data from 204 COVID-19 patients hospitalized between April 2020 and April 2021 at three referral centres were analysed using an artificial intelligence-based algorithm to predict disease outcome (ICU vs….
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Milk Antiviral Proteins and Derived Peptides against Zoonoses - Milk is renowned for its nutritional richness but also serves as a remarkable reservoir of bioactive compounds, particularly milk proteins and their derived peptides. Recent studies have showcased several robust antiviral activities of these proteins, evidencing promising potential within zoonotic viral diseases. While several publications focus on milk’s bioactivities, antiviral peptides remain largely neglected in reviews. This knowledge is critical for identifying novel research directions…
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The Inhibition of Serine Proteases by Serpins Is Augmented by Negatively Charged Heparin: A Concise Review of Some Clinically Relevant Interactions - Serine proteases are members of a large family of hydrolytic enzymes in which a particular serine residue in the active site performs an essential role as a nucleophile, which is required for their proteolytic cleavage function. The array of functions performed by serine proteases is vast and includes, among others, the following: (i) the ability to fight infections; (ii) the activation of blood coagulation or blood clot lysis systems; (iii) the activation of digestive enzymes; and (iv)…
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A Narrative Review: The Role of NETs in Acute Respiratory Distress Syndrome/Acute Lung Injury - Nowadays, acute respiratory distress syndrome (ARDS) still has a high mortality rate, and the alleviation and treatment of ARDS remains a major research focus. There are various causes of ARDS, among which pneumonia and non-pulmonary sepsis are the most common. Trauma and blood transfusion can also cause ARDS. In ARDS, the aggregation and infiltration of neutrophils in the lungs have a great influence on the development of the disease. Neutrophils regulate inflammatory responses through various…
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Unveiling the Antiviral Properties of Panduratin A through SARS-CoV-2 Infection Modeling in Cardiomyocytes - Establishing a drug-screening platform is critical for the discovery of potential antiviral agents against SARS-CoV-2. In this study, we developed a platform based on human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) to investigate SARS-CoV-2 infectivity, with the aim of evaluating potential antiviral agents for anti-SARS-CoV-2 activity and cardiotoxicity. Cultured myocytes of iPSC-CMs and immortalized human cardiomyocyte cell line (AC-16) were primarily characterized for the…
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Ligand-Based Design of Selective Peptidomimetic uPA and TMPRSS2 Inhibitors with Arg Bioisosteres - Trypsin-like serine proteases are involved in many important physiological processes like blood coagulation and remodeling of the extracellular matrix. On the other hand, they are also associated with pathological conditions. The urokinase-pwlasminogen activator (uPA), which is involved in tissue remodeling, can increase the metastatic behavior of various cancer types when overexpressed and dysregulated. Another member of this protease class that received attention during the SARS-CoV 2 pandemic…
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Phytochemical Elucidation and Effect of Maesa indica (Roxb.) Sweet on Alleviation of Potassium Dichromate-Induced Pulmonary Damage in Rats - Maesa indica (Roxb.) Sweet is one of the well-known traditionally-used Indian plants. This plant is rich in secondary metabolites like phenolic acids, flavonoids, alkaloids, glycosides, saponins, and carbohydrates. It contains numerous therapeutically active compounds like palmitic acid, chrysophanol, glyceryl palmitate, stigmasterol, β-sitosterol, dodecane, maesaquinone, quercetin 3-rhaminoside, rutin, chlorogenic acid, catechin, quercetin, nitrendipine, 2,3-dihydroxypropyl…
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SARS-CoV-2 Nsp1 cooperates with initiation factors EIF1 and 1A to selectively enhance translation of viral RNA - A better mechanistic understanding of virus-host dependencies can help reveal vulnerabilities and identify opportunities for therapeutic intervention. Of particular interest are essential interactions that enable production of viral proteins, as those could target an early step in the virus lifecycle. Here, we use subcellular proteomics, ribosome profiling analyses and reporter assays to detect changes in protein synthesis dynamics during SARS-CoV-2 (CoV2) infection. We identify specific…
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Application of a Biomimetic Nanoparticle-Based Mock Virus to Determine SARS-CoV-2 Neutralizing Antibody Levels in Blood Samples Using a Lateral Flow Assay - The presence of neutralizing antibodies against SARS-CoV-2 in blood, acquired through previous infection or vaccination, is known to prevent the (re)occurrence of outbreaks unless the virus mutates. Therefore, the measurement of neutralizing antibodies constitutes an indispensable tool in assessing an individual’s and a population’s immunity against SARS-CoV-2. For this reason, we have developed an innovative lateral flow assay (LFA) capable of detecting blood-derived neutralizing antibodies…
+
Kidney organoids reveal redundancy in viral entry pathways during ACE2-dependent SARS-CoV-2 infection - With a high incidence of acute kidney injury among hospitalized COVID-19 patients, considerable attention has been focussed on whether SARS-CoV-2 specifically targets kidney cells to directly impact renal function, or whether renal damage is primarily an indirect outcome. To date, several studies have utilized kidney organoids to understand the pathogenesis of COVID-19, revealing the ability for SARS-CoV-2 to predominantly infect cells of the proximal tubule (PT), with reduced infectivity…
+
Role of PCSK9 inhibition during the inflammatory stage of SARS-COV-2: an updated review - The potential role of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition in the management of COVID-19 and other medical conditions has emerged as an intriguing area of research. PCSK9 is primarily known for its impact on cholesterol metabolism, but recent studies have unveiled its involvement in various physiological processes, including inflammation, immune regulation, and thrombosis. In this abstract, the authors review the rationale and potential implications of PCSK9…
+
+
From Patent Search
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+
+
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+ 12 February, 2024
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+Daily-Dose
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+
Trying to Keep His Family Safe in Rafah - As Israel’s military campaign turns to what has become Gaza’s home for displaced civilians, a Palestinian aid worker describes his long journey to the city, and how he talks to his kids about air strikes. - link
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Is the Media Prepared for an Extinction-Level Event? - Ads are scarce, search and social traffic is dying, and readers are burned out. The future will require fundamentally rethinking the press’s relationship to its audience. - link
+
The Friendship Challenge - How envy destroyed the perfect connection between two teen-age girls. - link
+
The Art World Before and After Thelma Golden, by Calvin Tomkins - When Golden was a young curator in the nineties, her shows, centering Black artists, were unprecedented. Today, those artists are the stars of the art market. - link
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A Teen’s Fatal Plunge Into the London Underworld - After Zac Brettler mysteriously plummeted into the Thames, his grieving parents were shocked to learn that he’d been posing as an oligarch’s son. Would the police help them solve the puzzle of his death? - link
+
+
From Vox
+
+
Yes, Democrats, it’s Biden or bust -
+
+
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+President Biden is seen here responding to Special Counsel Robert Hur’s report on his mishandling of classified documents. | Samuel Corum/Sipa/Bloomberg via Getty Images
+
+
+
+Even if voters or the establishment wanted to, there really isn’t a viable process to replace Biden as the nominee.
+
+But after last week’s special counsel report on Biden’s handling of classified documents highlighted lapses in Biden’s memory during questioning, a familiar question has taken hold: Is Biden really the best option Democrats have in 2024?
+
+
+This malaise isn’t limited to Biden; this presidential cycle there’s widespread dissatisfaction that two old men are all but guaranteed to be the major parties’ presidential nominees.
+
+
+On the Republican side, that’s come across through a contested primary that despite still delivering Donald Trump resounding victory after resounding victory, has shown a small but fierce opposition to Trump among a subset of GOP voters.
+
+
+Meanwhile, in the press and on the Democratic side, there’s an unwillingness by a subset of people (progressives, young people, and some politicians) to accept that Biden’s nomination is really happening. Now the past week has left normies and politicos alike wondering: What would it take for someone to replace Biden at this point? Is there a feasible process? Is it too late?
+
+
+It would be a historic effort to even try — no sitting president has lost his party’s nomination to a primary challenger in the modern political era.
+
+
+Replacing Biden as the Democratic nominee at this point would be a herculean, if not impossible, task. It would take overcoming two kinds of obstacles: real-world, practical challenges, and the more hypothetical but still important political challenges that exist for any potential Biden replacement.
+
+
+The practical problems are daunting
+
+
+Let’s start with the real-world challenges.
+
+
+The Democratic presidential nominee is chosen in August at the Democratic National Convention in Chicago, where a candidate needs to win the support of 1,969 of the 3,936 Democratic delegates. Those delegates are assigned proportionally based on the vote totals in a state’s primary (for any candidate who wins more than 15 percent of votes), and are then “pledged” or “bound” to that candidate in the first round of voting at the Democratic convention. Under this system, another candidate would need to win more delegates than Biden.
+
+
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+Those 2024 primaries are well underway, and Biden has won every contest and every delegate so far. His support has been nearly uniform: In South Carolina, he won about 96 percent of the vote and in Nevada, he won about 90 percent of the vote. Those states collectively only have 91 delegates — or 2 percent of the total available — but his primary challengers have either dropped out or face nearly impossible odds of beating him in any of the upcoming March contests, when more than 2,000 delegates will be up for grabs.
+
+
+And in those upcoming contests, before even rallying a base of support or raising money, a Democratic challenger would need to have registered with states to appear on the primary ballot. As the former political pollster Adam Carlson has pointed out, those filing deadlines have passed in 44 states. So it’s literally too late for a primary challenger who isn’t already out there (ahem, Dean Phillips) to make it onto ballots.
+
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+Even if someone could magically mount a successful challenge and notch some delegates, any that Biden has won will be bound to support him at the first DNC floor vote, according to party rules. Only Biden can make the decision to direct his delegates to vote for someone else, but they are pledged to vote for him unless he drops out beforehand.
+
+
+And this is where the practical and political challenges merge: Biden is the only one who can decide if he wants to drop out before the floor vote. And there are plenty of reasons that wouldn’t happen.
+
+
+The political challenges are very risky
+
+
+Politically, it’s incredibly risky for anyone else to jump into the contest. The vast majority of the Democratic establishment has already united around Biden — endorsing him, stumping for him, and leading the party’s operations because of Biden.
+
+
+This is also where it’s important to dispel the notion that anyone could force Biden to drop out.
+
+
+The DNC is not some omnipotent, shadowy operation that has the power, influence, or ability to crown a different party leader. Who do you think chose the DNC chair and vice-chairs? There just isn’t a council of decision-makers who can tell Biden to drop out or choose to ditch him.
+
+
+And that speaks to a bigger issue with how our political parties are thought of. The power of party elites is often overstated — and the primaries so far show the influence of voters. As unpopular as Biden might seem to some folks, he still won handily in the 2020 primary, and when given options to protest-vote in New Hampshire or select “none of these candidates” in Nevada this year, Democrats have still sided with Biden.
+
+
+So only Biden could make the decision to drop out. He doesn’t want to (not least because he sees himself as key to stopping Trump’s reelection.) And even if he did choose to, the only option that would not risk massive dissension among the Democratic base would be to choose his vice president, Kamala Harris. The vice president has her own political drawbacks: She polls worse than Biden against Trump, hasn’t run a successful national campaign before, and, unfortunately, faces different voter prejudices because she is a woman of color.
+
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+Other Democratic stars, like Govs. Gavin Newsom of California, Gretchen Whitmer of Michigan, Josh Shapiro of Pennsylvania, and Secretary Pete Buttigieg, are also loyal Biden Democrats, poll worse than Biden, or are biding their time. And to bypass Harris for one of them also opens up potential ire from Black voters, without whom Democrats can’t win.
+
+
+Should a different, other Democrat emerge, with the vocal support of, I don’t know, Barack Obama and a core of Biden-critical strategists and politicians, and should first lady Jill Biden and other Biden confidantes approach Biden and convince him to drop out, we’d likely head toward a brokered convention with multiple rounds of voting. That also opens up the chance for even more chaos and disunity among Democrats. Does that seem worth it to anyone in Democratic politics right now?
+
+
+The simple answer is no. It’s too late.
+
+
+If you’re a Democrat, or want to beat Donald Trump, it looks like it’s Biden or bust.
+
A European grocery chain is boycotting high prices. Could it happen in the US? -
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+
+
+European grocery chain Carrefour has delisted PepsiCo products from thousands of stores, citing price hikes. | Mustafa Yalcin/Anadolu via Getty Images
+
+
+
+Inflation is cooling, but food companies keep raising prices.
+
+
+In 2022, grocery prices rose more than they had in over four decades, since the “great inflation” of the 1970s. The hair-raising climb has finally stopped, but the pain remains: We’re still paying 25 percent more for groceries than we did in 2019. A pound of ground beef in December 2019 was $3.86 — in December 2023 it was $5.21. A 16-ounce bag of potato chips went from $4.53 to $6.40. The price of a 12-ounce can of soda rose almost 64 percent. Consumer prices tend to go only one way — up.
+
+
+Despite a falling inflation rate and low unemployment, Americans have a dismal outlook on the economy; food prices being stuck stubbornly high is almost certainly a big reason why. A majority of people, according to a recent YouGov survey, now blame inflation on big corporations seeking maximum profits.
+
+
+Food companies were quick to pass along their rising input costs to consumers, says Lindsay Owens, executive director of the progressive economic advocacy group Groundwork Collaborative. Now those costs have come down, but “they are not quick to pass along their savings,” she says.
+
+
+Not only that, but companies haven’t stopped raising prices, partly because demand hasn’t plummeted. PepsiCo, which makes not just beverages (Pepsi, Gatorade, Aquafina) but beloved snacks (Doritos, Cheetos) as well as packaged foods (Quaker Oats), raised prices seven quarters in a row, and by 11 percent just between July and September of last year, according to AP. It plans to make more “modest” hikes in 2024. There’s been anger and pushback from both consumers and lawmakers, and even the president — yet food prices keep trickling higher, even if at a slower pace.
+
+
+But is another world possible?
+
+
+In January, a major European grocery chain called Carrefour said it would drop some of Pepsi’s products from over 9,000 store shelves in Poland, Belgium, France, Italy, and Spain, citing “unacceptable price increases,” displaying signs in stores to explain the absence. Across the pond, apparently, it’s not just consumers that try to boycott food brands — powerful grocery retailers get in on the game too. PepsiCo, for its part, is insisting that it pulled out of Carrefour, not the other way around, because it couldn’t agree on a new contract. A PepsiCo spokesperson told the Wall Street Journal that it couldn’t “sustain customer relationships which are no longer profitable.” Neither Carrefour nor PepsiCo responded to a request for comment for this article.
+
+
+It’s a kind of corporate beef that may feel novel to those in the US, where grocery retailers and food companies have been raising prices with no end in sight for the last few years. In theory, the biggest supermarkets in the nation — Walmart, Kroger, Costco, and Publix — could send a similar volley putting the blame on food conglomerates. Why there hasn’t been a public brouhaha between these factions here highlights the dire state of market concentration in the grocery industry, where a sprinkling of companies pull almost all of the strings.
+
+
+Has a US grocery chain ever said “no way” to a brand over price?
+
+
+It’s not quite accurate to call what Carrefour is doing a “boycott.” Not all PepsiCo products are gone from all their 14,000-plus stores, and the industry term for when a store no longer sells a product is “delisting.” It happens from time to time, for a variety of reasons — but usually the impetus for it isn’t so public.
+
+
+We know Walmart isn’t happy with its price-hiking suppliers, with some food brands reportedly getting pushback from the largest grocery chain in the nation. But the company hasn’t publicly made any threats or taken any action so far. In 2022, CEO Doug McMillon said mildly that the company has been asking suppliers to “help us not have to pass something on to a customer,” that “something” being costs. Mostly, the company line has been that they’re working together with food brands to negotiate prices.
+
+
+Often we just don’t know why a store stops carrying a brand. It could be that they didn’t sell well enough, or there was another more appealing brand that deserved the shelf space, or an item was hard to get consistently in stock, or its competitors were offering it for a lot cheaper than the store was willing to. What’s notable in Carrefour’s case is that it has not only delisted products from a huge, well-known company, but has also made explicit why it’s doing so: It’s PepsiCo’s fault. It’s a good PR move for Carrefour, and it also handily explains why some sought-after products are suddenly unavailable.
+
+
+It’s also not the first time that Carrefour, headquartered in France, has been publicly aggressive about food companies’ price hikes. Late last year, it started adding labels next to products such as Lipton ice tea showing that their package size had shrunk but their price didn’t decrease — a practice coined as #shrinkflation.
+
+
+Why we haven’t seen a grocer vs. food giant face-off in the US
+
+Owens, whose organization just released a report on how to bring down high grocery prices, called the #shrinkflation labels Carrefour rolled out last year an interesting strategic move. “The [price] negotiations are coming up, and they’re basically driving down the volume of sales in certain companies — sort of saber rattling.”
+
+
+While President Biden recently called for food companies and grocery stores to end “price gouging” and “greedflation,” the US hasn’t gone after food corporations directly to lower prices. It has beefed up antitrust enforcement and has spent money on bolstering competition in concentrated food industries like meatpacking in the hope of keeping prices lower in the long term. But the fruits of these efforts will take a while to grow; the discontent over food prices isn’t going away.
+
+
+“In principle, nothing stops companies such as Walmart or Target responding in a similar way to Carrefour,” Isabella Weber, an economist at the University of Massachusetts Amherst, told Vox in an email. “But this would require major political pressure. Retailers will not act on their own, but with the right mix of sticks and carrots they might be mobilized as strategic allies in the fight against the cost of living crisis.”
+
+
+Walmart versus everyone else
+
+
+One reason we might not have seen a Carrefour-like campaign play out here is that there’s an even greater power imbalance in the grocery business than in Europe. Neil Saunders, managing director of retail at the consulting firm GlobalData, notes that the European grocery market overall is more competitive than America’s. No single major player wallops all others in market share: In France, the largest grocery chain, E. Leclerc, commands about 24 percent of the market, according to consulting firm Kantar. The next biggest — Carrefour — has about 19 percent. In the US, Walmart possesses about a quarter of the grocery store market (not including Sam’s Club, which it also owns), while its closest competitor, Costco, has just 7 percent.
+
+
+“I think that the brands are just so much keener to stay on the shelves of grocers like Walmart,” Saunders says. Walmart is the source of about 20 percent of sales for big suppliers like General Mills. The supermarket king may not see a reason to drag disputes out into the daylight. They regularly demand — and get — cheaper prices from their suppliers than smaller competitors can. Those suppliers then make up their losses by charging more to other smaller grocers.
+
+
+Food company executives have overtly recognized that “capitalism is a little more unfettered in the US and in Europe,” says Elizabeth Pancotti, a strategic adviser at Groundwork and one of the authors of its recent grocery price report. The negotiation approach is different, too — nicer. “They’re like, ‘Look how much volume we can give you if you cut a dollar off the price you’re charging us,’” Pancotti continues. Owning 25 percent of the US grocery market is also a lot bigger than having a quarter of the French market.
+
+
+Price disagreements between grocery stores and the suppliers that fill their shelves happen from time to time. Retailers want to gain customers who will stuff their shopping carts, so they would prefer the cost of goods not to rise too much — especially if you’re a value chain like Walmart or Costco. In 2017, Walmart reduced their Campbell Soup orders, reportedly over a dispute on discounts and shelf space. Campbell’s sales dipped as a result. It’s not clear how the standoff was resolved, but it’s worth noting that, at the time, Walmart made up 20 percent of the company’s yearly sales.
+
+
+At the same time, grocers, even ones as mighty as Walmart, have less leverage when it comes to kicking out the likes of Pepsi. The company makes too many popular snacks and beverages; people tend to have strong feelings about Pepsi versus Coke, and no store-brand substitute will do. PepsiCo’s CEO even boasted in an earnings call that people “are willing to pay more” for their brand. On the other hand, people are much more likely to buy the cheapest trash bag or household cleaning product, so it’s harder to push prices up there.
+
+
+It’s a lose-lose for the consumer — for now
+
+
+It might be refreshing to see a giant grocery chain attack out-of-control food inflation, but the reality is that meaningful pro-consumer change is unlikely to arise from giant retailers taking a stand on our behalf when the messy root is market concentration.
+
+
+There’s an incentive for grocers to offer a lower sticker price than competitors, but they — just like food companies — are eager to improve profit margins where they can. One of the most notorious industry practices is something called a “slotting fee,” which is a price that a store charges suppliers to get shelf real estate. Nielsen says slotting fees for new products can cost between $250 to $1,000 per item, and the most expensive slots are areas like the checkout counter, where it’s easy for a customer to impulsively throw a candy bar onto the conveyor belt.
+
+
+Pancotti calls it a “pay-to-play and a pay-to-stay model,” and says that slotting fees are “ripe for regulation.”
+
+
+Slotting fees are one more cost that ultimately gets passed on to the consumer. These fees have the added effect of widening the price gap between other brands and stores’ private labels, which grocery giants have been leaning into in recent years. Walmart’s cheaper private label is great for your bank account, but it means giving even more market share to the industry heavyweight — which, in the end, can counterintuitively drive up prices. A dominant retailer like Walmart doesn’t need to keep prices roughly the same (and it hasn’t) — it just has to be cheaper than the other guys that are marking up groceries, and small, independent grocers can’t compete. Pancotti notes that there’s already a federal law, called the Robinson-Patman Act, that outlaws suppliers from giving special discounts to just some of their buyers — like, say, Walmart. But enforcement of the law has fallen to the wayside since the 1980s. Slowly, the small grocers will either fail or try to merge to survive.
+
+
+The way to discipline continued price hikes is to dismantle food monopolies — but that doesn’t happen in the blink of an eye, especially when so much money is arrayed against it. Whether the Kroger-Albertsons merger, which would make it the second biggest supermarket chain in the US, will be blocked by the government is still up in the air. A quicker balm to high grocery prices would be to increase food stamp benefits and increase eligibility for them, say Pancotti and Owens of Groundwork, putting more money for food into people’s hands.
+
+
+As grocery prices remain sky-high and continue to creep higher, some retailers want a hard stop, says Saunders. But food brands don’t see a reason to stop. “We’re seeing more of these skirmishes emerge now,” he says. It remains unlikely that grocery retailers will suddenly band together to publicly call out their suppliers. Vox reached out to the four biggest supermarkets in the US, who together make up almost half of the entire market, asking whether they were considering doing something similar to what Carrefour has done. None responded.
+
+
Did El Salvador just vote to end democracy? -
+
+
+
+Marvin Recinos/AFP via Getty Images
+
+
+
+On February 4, as El Salvador held presidential elections, current president Nayib Bukele showed up at a polling place accompanied by speakers blasting “It’s the End of the World as We Know It (And I Feel Fine)” by R.E.M.
+
+
+The song choice was deliberate — Bukele was once again trolling critics who claim he’s steering the country toward autocracy. For a while, his Twitter bio read “The World’s Coolest Dictator.”
+
+
+Since being elected president in 2019, Bukele has made international headlines for what some have described as a millennial persona, eschewing ties and suits in favor of jeans and sunglasses and taking a selfie during his first speech to the United Nations General Assembly. He has famously sold El Salvador as a cryptocurrency paradise, making it the first country in the world to adopt Bitcoin as legal tender.
+
+
+But Bukele’s detractors say he has used the presidency to push El Salvador away from democracy, packing the nation’s judiciary with judges sympathetic to his policies and reshaping electoral law to ensure his political party holds a majority in the legislature.
+
+
+During his nearly five years in office, Bukele has declared an ongoing state of emergency, using the threat of gang violence to curtail civil liberties. He very publicly stormed the legislature with the aid of the military to demand funding for his policy priorities. And the fact that Bukele ran for reelection at all was unprecedented and probably illegal: El Salvador’s constitution explicitly bars reelection to consecutive presidential terms. Still, he has claimed victory in the vote and few are disputing that he won the presidency, though 60 seats in Congress are being disputed by El Salvador’s electoral body.
+
+
+Silvia Viñas is the co-host of a new podcast about Bukele, Bukele: El señor de Los Sueños. She says that if you define a democracy only as the people being able to vote, El Salvador has that.
+
+
+However, democracy is about much more. If Bukele controls everything without checks to his authority, Silvia asks, is the country’s government still a democracy? What follows is an adapted transcript of her conversation with Sean Rameswaram, co-host of Vox’s Today, Explained podcast, edited for length and clarity.
+
+
+
+
+
+Sean Rameswaram
+
+
+[Bukele is] the youngest president in the history of El Salvador when he’s elected in 2019. A millennial president. What’s he like when he gets into office? Is it all avocado toast and Instagram or what?
+
+
+Silvia Viñas
+
+
+He sells this image of the young, hip millennial president who is different from the other presidents in Latin America. He was 37 — as you say he looked very different from other presidents. He didn’t wear suits. He wore leather jackets, he used social media to conduct state business, to fire government employees or to ask them to take care of an issue. When he went to the UN, he took a selfie.
+
+
+When he took office, the Congress did their job of being a counterweight and performing checks and balances, as they should in a democracy, because he doesn’t have a majority there. And so he started a fight with lawmakers because he wanted them to help finance his plan to reduce violent killings and to fight the gangs.
+
+
+So Congress asked for more details about how he’s going to spend the money. And Bukele got tired of legislators delaying everything, so he called for an extraordinary session for Sunday, February 9th, 2020.
+
+
+So some legislators go, but they don’t have enough people to actually carry out a session to vote on the loan. Meanwhile, Bukele advertised on social media for people to go march to Congress. They use government buses driven by military personnel to bring people to this gathering. And inside, while the legislators are waiting for the session to start, armed military personnel show up inside the building.
+
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+Legislators feared that this was a coup, with military entering the Congress.
+
+
+Sean Rameswaram
+
+
+It sounds like January 6th if it worked.
+
+
+Silvia Viñas
+
+
+Yes, and so Bukele asked the crowd, will you let me enter Congress? And of course, they say “Yes!”
+
+
+So he entered the room where the legislators are waiting, with the military already inside. He sat in the chair where the president of the Congress would sit during a session. And he said, “Let’s say a prayer.”
+
+
+He puts his hands on his head and he prayed in silence. And then he just got up and left. It was like a show of force, showing what he’s capable of doing. It was a fear tactic, showing that he could instigate a coup.
+
+
+Sean Rameswaram
+
+
+Does he find a way to consolidate power after that?
+
+
+Silvia Viñas
+
+
+Yeah, he consolidates power the following year when his party and allied parties win a majority in Congress. So within a few months after winning that election, he was able to gain legislative power and then judicial power. After that it’s like, okay, he can do anything he wants. He controls everything.
+
+
+Sean Rameswaram
+
+
+It’s my understanding that one of the reasons people back Bukele is because he’s taking a stand against the gangs and gang violence in El Salvador. How does he, as president, oppose the gangs?
+
+
+Silvia Viñas
+
+
+You might remember the images of prisoners in Salvadoran jails with shaved heads, without a shirt, with their hands behind their back, all sitting very close to one another in lines? Those images went around the world.
+
+
+That was a reaction from President Bukele, because in April 2020 there was a surge in violence and 76 homicides in four days. His response was to crack down on gang members in jails, and he authorized security officers to use lethal force on inmates and suspects. He mixed members of rival gangs in the same cells. He was trying to show that he was treating the gang members terribly because they’ve done so much damage to our society. But then another big wave of violence happens, and there are 87 murders in three days.
+
+
+So Bukele requested that Congress declare a state of emergency. And this state of emergency has been renewed 22 times, every 30 days. We’re almost at a two-year mark under a state of emergency in the name of fighting the gangs.
+
+
+Sean Rameswaram
+
+
+And what does the state of emergency get him in terms of power?
+
+
+Silvia Viñas
+
+
+It suspends basic rights, like right to defense or the presumption of innocence. More military on the streets and more military resources. The government so far has imprisoned over 75,000 people — that’s more than 1 percent of the population.
+
+
+El Salvador is the country with the highest incarceration rate in the world. There are thousands of reports of arbitrary arrests, of abuse, of torture. But again, this is possibly his most celebrated measure and the one that has ultimately made him one of the most popular politicians in the Americas.
+
+
+Sean Rameswaram
+
+
+Bukele seems to have consolidated so much power while in office. But he is still restricted by a constitutional term limit. How does he get past that?
+
+
+Silvia Viñas
+
+
+The Salvadoran constitution is very clear that reelection is prohibited. Basically, you can be president as many times as you win in El Salvador, but just not consecutively. So in September 2021, the Constitutional chamber, which is controlled by pro-Bukele magistrates, issued a resolution that says that only the people can decide whether the president should continue, ignoring the articles of the Constitution.
+
+
+The chamber basically interprets one article of the constitution to say the only requirement is that he step down from the position of president six months before the beginning of the new presidential term. So he stepped down from office before December 1st of 2023, and the new period will begin in June.
+
+
+Sean Rameswaram
+
+
+What do people think he’s going to do now that he has this historic second term?
+
+
+Silvia Viñas
+
+
+When he announced that he was running, he said we have shown that this is the only correct path for El Salvador. We can expect the state of emergency to continue. There’s no indication that Bukele plans to dial back his policies.
+
+
+There’s a concern that several experts mentioned concerning his popularity while so many people have been arrested. As his popularity decreases, there’s a concern that he will use the military even more, become more ironfisted, and implement more of these policies to maintain his power.
+
World marathon record holder Kelvin Kiptum dies in road accident - The crash happened on a road between the towns of Eldoret and Kaptagat in western Kenya
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Party begins as Ivory Coast rallies to beat Nigeria 2-1 and win Africa Cup of Nations - Sébastien Haller scored late to lead host nation Ivory Coast to a remarkable Africa Cup of Nations title with a 2-1 victory over Nigeria in the final on February 11, 2024.
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Morning Digest | India welcomes release of eight Navy veterans jailed in Qatar; Nitish Kumar Government to face floor test today, and more - Here is a select list of stories to start the day
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Sevilla claim 1-0 home win over Atletico - Real Madrid top the standings with 61 points, five ahead of second-placed Girona
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Rybakina cruises past Kasatkina to claim Abu Dhabi title - Both players will now head to Doha for the Qatar Open, with Kasatkina set to face Anastasia Pavlyuchenkova in her opener on Monday while Rybakina has a bye into the second round
+
+
From The Hindu: National News
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AP PolyCET-2024 to be held on April 27 - All the 87 government polytechnic colleges in the State will provide free coaching in English and Telugu for the entrance test, preparation books will be distributed free of charge to the students, says official
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Congress leader Chinta Mohan demands imposition of President’s rule in Andhra Pradesh - Centre should intervene in the voter list irregularities and ensure peaceful elections in the State, he says
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Telangana CM slams KCR for skipping Assembly debate on Krishna waters - Revanth wonders whether BRS is in support of or opposing handing over of projects to the Centre
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Nitish Kumar-led NDA govt wins trust vote in Bihar Assembly - A total of 129 members of the Bihar Assembly voted in favour of Nitish Kumar’s government
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Telangana Govt bans hookah parlours with immediate effect - Legislative assembly unanimously passed a bill to this effect
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From BBC: Europe
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Inside Ukraine’s struggle to find new men to fight - Two years into the war, there is no flood of volunteer fighters as energy and enthusiasm fades.
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Conservative ex-PM Stubb elected Finland president - His victory comes amid rising tensions between Finland, the newest Nato member, and neighbouring Russia.
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Faisal Islam: Russia’s war economy cannot last but has bought time - Western nations must now weigh up the risks of diverting some seized assets to Ukraine.
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Seven ‘burned alive’ as Russia hits Kharkiv oil depot - Three children are among the dead as one street turns “into a hellish melted mass”, Ukraine’s police say.
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The Ukrainians ‘disappearing’ in Russia’s prisons - Finding Ukrainian civilians in Russian captivity is hard - and there is no formal way to secure their release.
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From Ars Technica
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Building durable basketball players from the ground up (way up) - Can new scientific insights help the newest crop of NBA stars stay healthy? - link
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Fake grass, real injuries? Dissecting the NFL’s artificial turf debate - Artificial turf has its advantages, but the NFLPA wants it banished from the NFL. - link
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Canada declares Flipper Zero public enemy No. 1 in car-theft crackdown - How do you ban a device built with open source hardware and software anyway? - link
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A sleuthing enthusiast says he found the US military’s X-37B spaceplane - Officials didn’t disclose details about the X-37B’s orbit after its December launch. - link
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Big Pharma spends billions more on executives and stockholders than on R&D - Senate report points to greed and “patent thickets” as key reasons for high prices. - link
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From Jokes Subreddit
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A 70 year old man goes into a brothel. He picks out a young pretty woman, …. -
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+… they go up to her room, strip down and climb into bed. The old man performs like a teenager, the prostitute is amazed at how energetic and agile he is, she tells him if he can do it like that again, she’ll give him one for free. He says “Yeah, I can, but I need to take a 20 minute nap, and while I’m asleep, I need you to hold my old pecker.” She agrees, he wakes up 20 minutes later and goes at it again, just as vigorously as before. The girl is amazed at the old man’s stamina, and repeats her freebie offer, the old man tells her that once again, he’ll need a 20 minute nap and she’ll have to hold his dick while he’s asleep. She does as he asks, he wakes up 20 minutes later and he goes at it again, with even more enthusiasm than previously. The hooker catches her breath, and needing to satisfy her curiosity, asks the old man “I can understand why you need the nap, but why do you need me to hold your dick while you’re sleeping?” The old man replies “Oh, that’s just so you don’t steal my wallet.”
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A guy took his blonde girlfriend to the Super Bowl. -
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+They had great seats right behind the Chiefs’ bench. After the game, he asked her how she liked it.
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+“Oh, I really liked it,” she replied, “especially the tight pants and all the big muscles, but I just couldn’t understand why they were killing each other over 25 cents.”
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+Confused, her boyfriend asked, “What do you mean?”
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+She said “Well, they flipped a coin, one team got it and then for the rest of the game, all they kept screaming was ‘Get the quarter back! Get the quarter back!’ I’m like, hello? It’s only 25 cents!”
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