Enhancing antibody responses by multivalent antigen display on thymus-independent DNA origami scaffolds -
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+Multivalent antigen display is a well-established principle to enhance humoral immunity. Protein based virus-like particles (VLPs) are commonly used to spatially organize antigens. However, protein-based VLPs are limited in their ability to control valency on fixed scaffold geometries and are thymus-dependent antigens that elicit neutralizing B cell memory themselves, which can distract immune responses. Here, we investigated DNA origami as an alternative material for multivalent antigen display in vivo, applied to the receptor binding domain (RBD) of SARS-CoV-2 that is the primary antigenic target of neutralizing antibody responses. Icosahedral DNA-VLPs elicited neutralizing antibodies to SARS-CoV-2 in a valency-dependent manner following sequential immunization in mice, quantified by pseudo- and live-virus neutralization assays. Further, induction of B cell memory against the RBD required T cell help, but the immune sera did not contain boosted, class-switched antibodies against the DNA scaffold. This contrasted with protein-based VLP display of the RBD that elicited B cell memory against both the target antigen and the scaffold. Thus, DNA-based VLPs enhance target antigen immunogenicity without generating off-target, scaffold-directed immune memory, thereby offering a potentially important alternative material for particulate vaccine design.
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What drives preventative health behaviors several months into a pandemic: A replication and extension -
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+There is continued interest in understanding what leads people to do CDC-recommended COVID-19 prevention behaviors. We tested whether fear and COVID-19 worry would replicate as the primary drivers of six CDC recommend prevention behaviors. We recruited 741 adult participants during the second major peak of the COVID-19 pandemic in the United States (early 2021). Participants completed a 10-day daily diary. Mixed effects models identified the strongest predictors of each individual prevention behavior. At the between-person level, COVID-19 worry, COVID-19 perceived susceptibility, fear, and positive emotions all had positive zero-order associations with the prevention behaviors. However, with all predictors in the same model together, only COVID-19 worry remained significant. At the within-person level, only fear related to assessing oneself for COVID-19 on the same day, but not the next day. Findings replicated worry about yourself or a loved one getting COVID-19 as the strongest predictor of prevention behaviors.
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Effective Leadership Strategies in Managing the COVID-19 Pandemic -
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+The COVID-19 pandemic has posed unprecedented challenges to governments, organizations, and communities worldwide. Effective leadership has played a critical role in managing the crisis and mitigating its impact. This paper examines the various leadership approaches and strategies employed by leaders across the globe in response to the COVID-19 pandemic. It explores the key attributes and actions demonstrated by effective leaders during this crisis and identifies best practices for future leaders facing similar challenges. The findings highlight the importance of proactive decision-making, clear communication, empathy, and collaboration in effective COVID-19 leadership.
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Detecting episodic evolution through Bayesian inference of molecular clock models -
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+Molecular evolutionary rate variation is a key aspect of the evolution of many organisms that can be modelled using molecular clock models. For example, fixed local clocks revealed the role of episodic evolution in the emergence of SARS-CoV-2 variants of concern. Like all statistical models, however, the reliability of such inferences is contingent on an assessment of statistical evidence. We present a novel Bayesian phylogenetic approach for detecting episodic evolution. It consists of computing Bayes factors, as the ratio of posterior and prior odds of evolutionary rate increases, effectively quantifying support for the effect size. We conducted an extensive simulation study to illustrate the power of this method and benchmarked it to formal model comparison of a range of molecular clock models using (log) marginal likelihood estimation, and to inference under a random local clock model. Quantifying support for the effect size has higher sensitivity than formal model testing and is straight-forward to compute, because it only needs samples from the posterior and prior distribution. However formal model testing has the advantage of accommodating a wide range molecular clock models. In contrast, the random local clock had low power for detecting episodic evolution. In an empirical analysis of a data set of SARS-CoV-2 genomes, we find 'very strong' evidence for episodic evolution. Our results provide guidelines and practical methods for Bayesian detection of episodic evolution, as well as avenues for further research into this phenomenon.
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Health promoting properties and functions of medicinal and culinary mushrooms for the COVID-19 era. An appraisal: does the “anti” mantra stack up? -
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+Many mushroom species are consumed as food, while significant numbers are also utilised medicinally. Mushrooms are rich in nutrients and bioactive compounds. A growing body of in vitro, in vivo, and human research has revealed their therapeutic potentials. Some of the most notable benefits include such properties as anti-pathogenic, antioxidant, anti-inflammatory, immunomodulatory, gut microbiota enhancement, and angiotensin-converting enzyme 2 specificity. The use of medicinal mushrooms (MMs) as extracts in nutraceuticals and other health products are burgeoning. COVID-19 presents an opportunity to consider how, and if, specific MM compounds might be utilised therapeutically to mitigate associated risk factors, reduce disease severity, and support recovery. As vaccines become a mainstay, MMs may have the potential as an adjunct therapy to enhance immunity. In the context of COVID-19, this review explores current research about MMs to identify the key properties claimed to confer health benefits. Considered also are barriers or limitations that may impact general recommendations on MMs as therapy. It is contended that the extraction method used to isolate bioactive compounds must be a primary consideration for efficacious targeting of physiological endpoints. Mushrooms commonly available for culinary use and obtainable as a dietary supplement for medicinal purposes are included in this review. Specific properties related to these mushrooms have been considered due to their potential mediating effects on human exposure to the SARS CoV-2 virus and the ensuing COVID-19 disease processes.
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The public health impact of Paxlovid COVID-19 treatment in the United States -
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+The antiviral drug Paxlovid has been shown to rapidly reduce viral load. Coupled with vaccination, timely administration of safe and effective antivirals could provide a path towards managing COVID-19 without restrictive non-pharmaceutical measures. Here, we estimate the population-level impacts of expanding treatment with Paxlovid in the US using a multi-scale mathematical model of SARS-CoV-2 transmission that incorporates the within-host viral load dynamics of the Omicron variant. We find that, under a low transmission scenario (Re~1.2) treating 20% of symptomatic cases with Paxlovid would be life and cost saving, leading to an estimated 0.26 (95% CrI:0.03, 0.59) million hospitalizations averted, 30.61 (95% CrI:1.69, 71.15) thousand deaths averted, and US$52.16 (95% CrI:2.62, 122.63) billion reduction in the US. Rapid and broad use of the antiviral Paxlovid could substantially reduce COVID-19 morbidity and mortality, while averting socioeconomic hardship.
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Association of Long COVID with housing insecurity in the United States, 2022-2023 -
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+Objectives. To assess the association of Long COVID with housing insecurity in the United States. Methods. To compare the prevalence of 3 binary indicators of housing insecurity between people with Long COVID (symptoms > 3 months) and COVID-19 survivors who don9t report long-term symptoms, we used survey-weighted regression models on 203,807 responses from the Household Pulse Survey, a representative survey of US households collected September 2022 - April 2023. Among people with Long COVID, we assessed whether functional impairment, current COVID-19 related symptoms, and symptom impact on day-to-day life were associated with a higher prevalence of housing insecurity. Results. During the study period, 54,446 (27.2%) respondents with COVID-19 experienced symptoms lasting 3 months or longer, representing an estimated 27 million US adults. People with Long COVID were nearly twice as likely to experience significant difficulty with household expenses (Prevalence ratio [PR] 1.85, 95% CI 1.74-1.96), be behind on housing payments (PR 1.76, 95% CI 1.57-1.99), and face likely eviction or foreclosure (PR 2.12, 95% CI 1.58-2.86). Functional limitation and current symptoms which impact day-to-day life were associated with higher prevalence of housing insecurity. Conclusions. Compared with COVID-19 survivors who don9t experience long-term symptoms, people with Long COVID are more likely to report indicators housing insecurity, particularly those with functional limitations and long-term COVID-19 related symptoms impacting day-to-day life. Policies are needed to support people living with chronic illnesses following SARS-CoV-2 infection.
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BUILDING RESILIENCE AGAINST HOAX: IMPROVING INTERNET MEDIA LITERACY IN THE ERA OF THE PANDEMIC COVID-19 -
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+In facing the Covid-19 pandemic, the importance of enhancing internet media literacy has become crucial in building resilience against misinformation. The dissemination of false information is increasingly worrisome, despite intensive social campaigns addressing hoaxes. This research aims to enhance internet media literacy in the era of the Covid-19 pandemic. This study adopts a literature research or library research methodology. The data collection method involves two sources: primary data and secondary data. Primary data is obtained from reliable journals, articles, and readings that support this research. Meanwhile, secondary data is obtained from relevant books that pertain to the main issues addressed in the research. The findings of this study include the high prevalence of misinformation, the increase in internet media literacy, and the model for combating hoaxes.
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Dysregulated Platelet Function and Thrombosis in Patients with Post-Acute Sequelae of COVID-19 -
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+Objective: Post-acute sequelae of COVID-19 (PASC, also referred as Long-COVID) sometimes follows COVID-19, a disease caused by SARS-CoV-2. While SARS-CoV-2 is well-known to promote a prothrombotic state, and especially to activate platelets acutely, less is known about the thrombosis risk in PASC. Approach and Results: PASC patients and age-matched healthy controls were enrolled in the study on average 15 months after documented SARS-CoV-2 infection. Platelet activation was evaluated by Light Transmission Aggregometry (LTA) and flow cytometry in response to platelet surface receptor agonists. Thrombosis in platelet-deplete plasma was evaluated by Factor Xa activity. A microfluidics system assessed thrombosis in whole blood under venous shear stress conditions. While only a mild increase in platelet aggregation in PASC patients through the thromboxane receptor was observed platelet activation through the glycoprotein VI (GPVI) receptor was markedly decreased in PASC patients compared to age- and sex-matched healthy controls. Thrombosis under venous shear conditions as well as Factor Xa activity were reduced in PASC patients. Plasma from PASC patients was an extremely potent activator of washed, healthy platelets - a phenomenon not observed using age- and sex-matched platelets from healthy individuals. Conclusions: PASC patients demonstrate dysregulated responses in platelets and coagulation in plasma, likely caused by a circulating plasma-derived molecule that promotes thrombosis. A hitherto undescribed protective response appears to exists in PASC patients to counterbalance ongoing thrombosis that is common to SARS-CoV-2 infection.
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SARS-CoV-2 variants of concern exhibit differential gastro-intestinal tropism and pathogenesis in the Syrian golden hamster model. -
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+The Coronavirus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has taken its toll on worldwide public health infrastructure. SARS-CoV-2 is reported to exhibit wide tissue tropism, contributing to its severe pathogenicity that often culminates in multiple-organ failure. The onslaught of this disease has intensified due to the emergence of variants of concern (VOC), such as Delta and Omicron. These variants have been linked to gastrointestinal (GI) symptoms, suggesting a potential fecal-oral route of viral transmission. Here we compared the broad tissue tropism of ancestral Hong-Kong SARS-CoV-2 (SARS-CoV-2 HK) against Delta and Omicron VOCs in aa hamster model by analyzing tissue samples collected from the upper and lower respiratory system and the GI tract. We observed an overall increase in vRNA load and pro-inflammatory cytokines, especially in GI tracts of animals infected with Delta virus, indicating selective virus tropism and pathology in these tissues. However, no apparent spike in Delta viral load was observed in the large intestine and fecal matter. Overall, our research investigates the wide range of tissues that various SARS-CoV-2 strains can infect in hamsters and presents evidence supporting the increased preference of Delta VOCs for infecting the GI tract.
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Tracking national opinion about wastewater monitoring as a standard complement of public health tools in the United States -
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+National opinion on a wide variety of public health topics can change over time or have highly contextual nuisances. As the COVID-19 pandemic has progressed, we aimed to see how public perceptions have changed regarding the acceptance of using wastewater for community health monitoring in the metropolitan United States. This study is an annual update of prior inquiry into knowledge of wastewater-based epidemiology, privacy concerns surrounding the collection of wastewater samples and the use of data acquired along with privacy awareness from an online survey administered in the winter of 2023. We found public support for monitoring of toxins (90.8%), disease (90.6%), terror (86.8%), gun residue (59.8%), alcohol (49%), illicit drugs (70.5%), and prescription medications (68.6%) remained high. Most respondents supported monitoring of the entire city (77.6%). This longitudinal research has shown year-upon-year only slight increases in public support of wastewater monitoring for public health protection and continues to show an absence of significant nationwide privacy concerns as long as catchment population sizes ensure fully anonymous households. This support is conditional and is probably best understood through the lens of the COVID-19 pandemic where the value proposition of public protection was popularized. The survey also consistently showed the public would support expansion of wastewater monitoring as a standard complement of public health tools into other areas of public health protection.
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Anti SARS-CoV-2 Antibody Kinetics up to 6 months of follow-up: Result from a Nation-wide Population-based, Age Stratified Sero-Epidemiological Prospective Cohort Study in India -
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+Repeated serological testing tells about the change in the overall infection in a community. This study aimed to evaluate changes in antibody prevalence and kinetics in a closed cohort over six months in different sub-populations in India. The study included 10,000 participants from rural and urban areas in five states and measured SARS-CoV-2 antibodies in serum in three follow-up rounds. The overall seroprevalence increased from 73.9% in round one to 90.7% in round two and 92.9% in round three. Among seropositive rural participants in round one, 98.2% remained positive in round two, and this percentage remained stable in urban and tribal areas in round three. The results showed high antibody prevalence that increased over time and was not different based on area, age group, or sex. Vaccinated individuals had higher antibody prevalence, and nearly all participants had antibody positivity for up to six months.
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Effective vaccination strategies to control COVID-19 outbreak: A modeling study -
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+OBJECTIVES Three years following the start of the COVID-19 pandemic, the World Health Organization (WHO) declared COVID-19 a global health emergency of international concern. As immunity levels in the population acquired through past infections and vaccinations have been decreasing, booster vaccinations have become necessary to control new outbreaks. This study aimed to determine the most suitable vaccination strategy to control the COVID-19 surge. METHODS A mathematical model was developed to simultaneously consider the immunity levels induced by vaccines and infections, and employed to analyze the possibility of future resurgence and control using vaccines and antivirals. RESULTS As of May 11, 2023, a peak in resurgence is predicted to occur around mid-October of the same year if the current epidemic trend continues without additional vaccinations. In the best scenario, the peak number of severely hospitalized patients can be reduced by 43% (480) compared to the scenario without vaccine intervention (849). Depending on the outbreak trends and vaccination strategies, the best timing for vaccination in terms of minimizing the said peak varies from May to August 2023. CONCLUSIONS Our results indicate that if the epidemic continues, the best timing for vaccinations must be earlier than specified by the current plan in Korea. Further monitoring of outbreak trends is crucial for determining the optimal timing of vaccinations to manage future surges.
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HPV Vaccination in immunosuppressed patients with established skin warts and non-melanoma skin cancer: A single-institutional cohort study -
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+Background: cSCC (cutaneous squameous cell carcinom) and its precursors are a major cause of morbidity especially in immunosuppressed patients and are frequently associated with human papilloma virus (HPV) infections. Objective: The purpose of this study is to investigate the therapeutically potential of alpha-HPV vaccination for immunosuppressed patients with established cSCC and its precursors. Methods: In this retrospective study, all patients who received Gardasil-9, a nonavalent HPV vaccine, as secondary prophylaxis were examined. Dermatologic interventions in both the pre- and post-vaccination periods were analyzed with zero-inflated poisson regression and a proportional intensity model for repeated events with consideration of the clinically relevant cofactors. Results: The hazard ratio for major dermatologic interventions was 0.27 (CI 0.14-0.51, p <0.001) between pre- and post Gardasil-9 intervention. Gardasil-9 vaccination showed good efficacy in reducing major dermatologic interventions even after correction of relevant cofactors and national COVID-19 case loads during the observational period. Limitation: The retrospective study design and the rather low number of patients may influence study results. Furthermore, analysis of HPV types and data collection on vaccine-specific HPV antibody measurements was not possible. Conclusion: Alpha-HPV vaccination may potentially cause a significant decrease in dermatologic interventions in immunosuppressed patients with high skin tumor burden.
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Viral clearance as a surrogate of clinical efficacy for COVID-19 therapies in outpatients: A systematic review and meta-analysis -
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+Background Surrogates of antiviral efficacy are needed for COVID-19. We investigated the relationship between the virological effect of treatment and clinical efficacy as measured by progression to severe disease in unvaccinated outpatients treated for mild to moderate COVID-19. Methods We searched PubMed, Scopus and medRxiv from inception to 27th September 2022, for randomised controlled trials (RCTs) which tested potential treatments for COVID-19 in non-hospitalized patients. We included studies that reported both clinical and virological outcomes. Clinical outcomes were the rate of disease progression (generally hospitalization or death within 28 days of commencing treatment) and virological outcomes were viral load (viral RNA copies in upper respiratory tract swabs) within the first 7 days of treatment. Studies were excluded if they did not report on the outcome of a primary randomised controlled trial, or if results were reported in a more complete form in another publication. Risk of Bias assessment was performed using the RoB 2.0 tool. We used generalised linear models with random effects to assess the association between outcomes and account for study heterogeneity. Findings We identified 1372 unique studies of which 14 (with a total of 9257 participants) met inclusion criteria. Larger virological treatment effects at both day 3 and day 5 were associated with decreased odds of progression to hospitalisation or death in unvaccinated ambulatory subjects. The odds ratio (OR) for each extra two-fold reduction in viral load in treated compared to control subjects was 0.54 on both days 3 and 5 post treatment (day 3 95% CI 0.38 to 0.74, day 5 95%CI 0.41 to 0.72). There was no relationship between the odds of hospitalisation or death and virological treatment effect at day 7 (OR 0.91, 95%CI 0.74 to 1.13). Interpretation Despite the aggregation of studies with differing designs, and evidence of risk of bias in some virological outcomes, this review provides evidence that treatment-induced acceleration of viral clearance within the first 5 days after treatment is a surrogate of clinical efficacy to prevent hospitalisation with COVID-19. This work supports the use of viral clearance as an early phase clinical trial endpoint of therapeutic efficacy. Funding The authors were supported by the Australian Government Department of Health, Medical Research Future Fund, National Health and Medical Research Council and the University of New South Wales.
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Influence of Manual Diaphragm Release on Pulmonary Functions in Women With COVID-19 - Condition: COVID-19 Pneumonia Interventions: Other: manual therapy; Other: breathing exercise and prone position alone Sponsor: Cairo University Completed
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Safety Study of COVID19 Vaccine on the Market - Condition: COVID-19 Intervention: Biological: Recombinant new coronavirus vaccine (CHO cell) Sponsors: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.; Hunan Provincial Center for Disease Control and Prevention; Guizhou Center for Disease Control and Prevention; Hainan Center for Disease Control & Prevention Recruiting
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Community-engaged Optimization of COVID-19 Rapid Evaluation And TEsting Experiences - Conditions: COVID-19; COVID-19 Pandemic Interventions: Behavioral: COVID-19 walk-up, on-site testing strategy; Behavioral: Community Health Worker (CHW) leading testing navigation and general preventive care reminders; Behavioral: No-cost self-testing kit vending machines Sponsors: University of California, San Diego; San Ysidro Health Center Not yet recruiting
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Study Evaluating SHEN26 Capsule in Patients With Mild to Moderate COVID-19 - Condition: COVID-19 Interventions: Drug: SHEN26 capsule; Drug: SHEN26 placebo Sponsor: Shenzhen Kexing Pharmaceutical Co., Ltd. Recruiting
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ACTIV-6: COVID-19 Study of Repurposed Medications - Arm F (Montelukast) - Condition: Covid19 Interventions: Other: Placebo; Drug: Montelukast Sponsors: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center Recruiting
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ACTIV-6: COVID-19 Study of Repurposed Medications - Arm B (Fluvoxamine) - Condition: Covid19 Interventions: Drug: Fluvoxamine; Other: Placebo Sponsors: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center Completed
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ACTIV-6: COVID-19 Study of Repurposed Medications - Arm D (Ivermectin 600) - Condition: Covid19 Interventions: Drug: Ivermectin; Other: Placebo Sponsors: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center Completed
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ACTIV-6: COVID-19 Study of Repurposed Medications - Arm E (Fluvoxamine 100) - Condition: Covid19 Interventions: Drug: Fluvoxamine; Other: Placebo Sponsors: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center Completed
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A Study to Investigate the Safety, Immunogenicity of a Bivalent mRNA Vaccine RQ3025 as a Booster Dose in Healthy Adults - Condition: COVID-19 Interventions: Biological: RQ3013; Biological: RQ3025 Sponsors: Affiliated Hospital of Yunnan University; Yunnan University; Kunming Medical University Recruiting
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Pycnogenol® in Post-COVID-19 Condition - Conditions: Post COVID-19 Condition; Long COVID Interventions: Drug: Pycnogenol®; Drug: Placebo Sponsor: University of Zurich Recruiting
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Efficacy of Bailing Capsule on Pulmonary Fibrosis After COVID-19 - Conditions: Pulmonary Fibrosis; COVID-19 Pneumonia Intervention: Drug: Bailing capsule Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University Not yet recruiting
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To Evaluate the Immunogenicity and Safety of Sequential Booster Immunization of Recombinant Novel Coronavirus Vaccine (CHO Cells) for SARS-CoV-2 - Condition: COVID-19 Intervention: Biological: Recombinant Novel Coronavirus vaccine (CHO Cells) Sponsor: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd. Completed
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A Study to Evaluate the Safety and Efficacy of COVID-19 Convalescent Plasma (CCP) Transfusion to Prevent COVID-19 in Adult Recipients Following Hematopoietic Stem Cell Transplantation - Conditions: COVID-19; Hematopoietic Stem Cell Transplantation Intervention: Biological: COVID Convalescent Plasma Sponsor: Institute of Hematology & Blood Diseases Hospital Recruiting
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Immunogenicity and Safety Study of SARS-CoV-2 DNA Vaccine (ICCOV) - Condition: COVID-19 Intervention: Biological: SARS-CoV-2 DNA Vaccine (ICCOV) Sponsors: Immuno Cure 3 Limited; The University of Hong Kong Recruiting
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Cupping Therapy on Immune System in Post Covid -19 - Condition: Covid-19 Patients Interventions: Combination Product: Cupping therapy with convential medical treatment; Drug: Convential medical treatment Sponsor: Cairo University Completed
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From PubMed
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Targeting the cGAS-STING pathway as an inflammatory crossroad in coronavirus disease 2019 (COVID-19) - Context and objective: The emerging pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has imposed significant mortality and morbidity on the world. An appropriate immune response is necessary to inhibit SARS-CoV-2 spread throughout the body.Results: During the early stages of infection, the pathway of stimulators of interferon genes (STING), known as the cGAS-STING pathway, has a significant role in the induction of the…
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Losartan in hospitalized patients with COVID-19 in North America: An individual participant data meta-analysis - CONCLUSIONS: In this IPD meta-analysis of hospitalized COVID-19 patients, we found no convincing evidence for the benefit of losartan versus control treatment, but a higher rate of hypotension adverse events with losartan.
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2’,3’ cyclic-nucleotide 3’-phosphodiesterase (CNP) inhibits SARS-CoV-2 virion assembly by blocking infection-induced mitochondria depolarization - The COVID-19 pandemic has claimed over 6.5 million lives worldwide and continues to have lasting impacts on the world’s healthcare and economic systems. Several approved and emergency authorized therapeutics that inhibit early stages of the virus replication cycle have been developed however, effective late-stage therapeutical targets have yet to be identified. To that end, our lab identified 2’,3’ cyclic-nucleotide 3’-phosphodiesterase (CNP) as a late-stage inhibitor of SARS-CoV-2 replication….
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An evolutionarily conserved strategy for ribosome binding and inhibition by β-coronavirus non-structural protein 1 - An important pathogenicity factor of SARS-CoV-2 and related coronaviruses is Nsp1, which suppresses host gene expression and stunts antiviral signaling. SARS-CoV-2 Nsp1 binds the ribosome to inhibit translation through mRNA displacement and induces degradation of host mRNAs through an unknown mechanism. Here we show that Nsp1-dependent host shutoff is conserved in diverse coronaviruses, but only Nsp1 from β-CoV inhibits translation through ribosome binding. The C-terminal domain of all β-CoV…
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Green and rapid and instrumental one-pot method for the synthesis of imidazolines having potential anti-SARS-CoV-2 main protease activity - The Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) is responsible for ongoing epidemics in humans and some other mammals and has been declared a public health emergency of international concern. In this project, several small non-peptide molecules were synthesized to inhibit the major proteinase (M^(pro)) of SARS-CoV-2 using rational strategies of drug design and medicinal chemistry. M^(pro) is a key enzyme of coronaviruses and plays an essential role in mediating viral replication…
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Pharmacokinetic analysis of vilobelimab, anaphylatoxin C5a and antidrug antibodies in PANAMO: a phase 3 study in critically ill, invasively mechanically ventilated COVID-19 patients - CONCLUSIONS: This analysis shows that vilobelimab efficiently inhibits C5a in critically ill COVID-19 patients. There was no evidence of immunogenicity associated with vilobelimab treatment. Trial registration ClinicalTrials.gov, NCT04333420. Registered 3 April 2020, https://clinicaltrials.gov/ct2/show/NCT04333420.
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Covalent-reversible peptide-based protease inhibitors. Design, synthesis, and clinical success stories - Dysregulated human peptidases are implicated in a large variety of diseases such as cancer, hypertension, and neurodegeneration. Viral proteases for their part are crucial for the pathogens’ maturation and assembly. Several decades of research were devoted to exploring these precious therapeutic targets, often addressing them with synthetic substrate-based inhibitors to elucidate their biological roles and develop medications. The rational design of peptide-based inhibitors offered a rapid…
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Hybrid immunity in older adults is associated with reduced SARS-CoV-2 infections following BNT162b2 COVID-19 immunisation - CONCLUSIONS: Hybrid immunity in older adults was associated with considerably higher antibody titres, neutralisation and inhibition capacity. Instances of high anti-RBD titre with lower inhibition suggests antibody quantity and quality as independent potential correlates of protection, highlighting added value of measuring inhibition over antibody titre alone to inform vaccine strategy.
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Multivalent bicyclic peptides are an effective antiviral modality that can potently inhibit SARS-CoV-2 - COVID-19 has stimulated the rapid development of new antibody and small molecule therapeutics to inhibit SARS-CoV-2 infection. Here we describe a third antiviral modality that combines the drug-like advantages of both. Bicycles are entropically constrained peptides stabilized by a central chemical scaffold into a bi-cyclic structure. Rapid screening of diverse bacteriophage libraries against SARS-CoV-2 Spike yielded unique Bicycle binders across the entire protein. Exploiting Bicycles’ inherent…
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Tocilizumab for the treatment of COVID-19 - INTRODUCTION: Since the beginning of the COVID-19 pandemic, the repurposing of medicines has been pursued to find interventions effective in preventing fatal outcome of the disease. One of these drugs was tocilizumab, an interleukin-6 inhibiting monoclonal antibody, previously used to treat several immune-related disorders.
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Preventative and therapeutic potential of animal milk components against COVID-19: A comprehensive review - The global pandemic of COVID-19 is considered one of the most catastrophic events on earth. During the pandemic, food ingredients may play crucial roles in preventing infectious diseases and sustaining people’s general health and well-being. Animal milk acts as a super food since it has the capacity to minimize the occurrence of viral infections due to inherent antiviral properties of its ingredients. SARS-CoV-2 virus infection can be prevented by immune-enhancing and antiviral properties of…
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COVID-19 PCR: frequency of internal control inhibition in clinical practice - CONCLUSIONS: This study showed a low percentage of inhibition using RNase P as an internal control in COVID-19 PCRs using the CDC protocol, thus proving the effectiveness of this protocol for identification of SARS-CoV-2 in clinical samples. Re-extraction was efficacious for samples that showed little or no fluorescence for the RNase P gene.
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A suitable drug structure for interaction with SARS-CoV-2 main protease between boceprevir, masitinib and rupintrivir; a molecular dynamics study - In recent years, more than 200 countries of the world have faced a health crisis due to the epidemiological disease of COVID-19 caused by the SARS-CoV-2 virus. It had a huge impact on the world economy and the global health sector. Researchers are studying the design and discovery of drugs that can inhibit SARS-CoV-2. The main protease of SARS-CoV-2 is an attractive target for the study of antiviral drugs against coronavirus diseases. According to the docking results, binding energy for…
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Combining virtual screening with cis-/trans-cleavage enzymatic assays effectively reveals broad-spectrum inhibitors that target the main proteases of SARS-CoV-2 and MERS-CoV - The main protease (M^(pro)) of SARS-CoV-2 is essential for viral replication, which suggests that the M^(pro) is a critical target in the development of small molecules to treat COVID-19. This study used an in-silico prediction approach to investigate the complex structure of SARS-CoV-2 M^(pro) in compounds from the United States National Cancer Institute (NCI) database, then validate potential inhibitory compounds against the SARS-CoV-2 M^(pro) in cis- and trans-cleavage proteolytic assays….
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Structure-Based Drug Design of RdRp Inhibitors against SARS-CoV-2 - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide pandemic since 2019, spreading rapidly and posing a significant threat to human health and life. With over 6 billion confirmed cases of the virus, the need for effective therapeutic drugs has become more urgent than ever before. RNA-dependent RNA polymerase (RdRp) is crucial in viral replication and transcription, catalysing viral RNA synthesis and serving as a promising therapeutic target for developing…
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From Patent Search
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“I Am the Only One”: Trump’s Messianic 2024 Message - Under threat of prison, the master of fear and anger takes another dark political turn. - link
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Ukraine’s Counter-Offensive, and What Comes After - Zelensky has mounted a major effort to take back territory seized by the Russians. But he’ll have to do more than prevail on the battlefield. - link
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Is Donald Trump Scared? - At the former President’s arraignment in Miami on Tuesday, it was impossible to say whether his fate was more likely to be a return to the White House—or prison. - link
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What Justice John Paul Stevens’s Papers Reveal About Affirmative Action - Twenty years ago, Justice Sandra Day O’Connor wrote, in a draft opinion, that white applicants could not be favored over Asian Americans. Why did she delete those lines—and why did Justice Clarence Thomas adopt them in his own opinion? - link
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Why Isn’t Joe Biden Getting More Credit for a Big Drop in Inflation? - Throughout the past year, the rate at which prices are rising has fallen dramatically, but public perceptions are lagging, perhaps because many prices are still a lot higher than they were in 2020. - link
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From Vox
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In Lorrie Moore’s new book, a man and his dead ex-girlfriend go on a road trip -
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+I Am Homeless If This Is Not My Home by Lorrie Moore. | Knopf
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+I Am Homeless If This Is Not My Home is weird, funny, gross, and tender.
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+I Am Homeless If This Is Not My Home, the latest novel from beloved short-story writer Lorrie Moore, resists analysis. This is a novel made out of air, unstructured, unskeletoned. There’s a central storyline, sort of, but summarizing that doesn’t quite get at what the experience of reading this weird, funny, tender, and occasionally gross book is like.
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+Here goes: Finn is a high school history teacher visiting his dying brother in hospice care. We can see immediately that Finn is not entirely well himself. He’s been put on leave from his job for reasons he is cagey about. He has developed the habit of seeing how the comments he leaves in the New York Times opinion section play to the commentariat, and then judging his sanity for the day by their reception. He can’t stop talking about his ex-girlfriend, Lily, who left him for another man one year before. “I feel sorry for you, man,” his dying brother tells him.
+
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+Before Finn has done much for his brother besides getting the TV in his room tuned to the World Series, he gets a text. Lily, a therapeutic clown who struggles with depression, is in trouble. (Lily “wore floppy shoes, the laces of which she had once used to strangle herself,” Moore informs us.)
+
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+At once Finn drops everything, leaves his brother’s bedside, and drives from the Bronx toward Lily in Illinois. But by the time Finn makes it to his hometown, Lily has already died by suicide. She’s buried in a green cemetery in an unmarked grave.
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+“I was hoping you’d get here soon,” Lily says when Finn arrives at the cemetery. She emerges shrouded and in her clown shoes, wiping dirt off her face, not “deeply dead” but “death-adjacent.” The worms have just begun to start on her.
+
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+Lily and Finn agree that they hate the green cemetery. So Finn loads Lily’s slowly decaying corpse into his car to drive her to a body farm in Tennessee, where they will donate Lily’s body to forensic science. What ensues is part Lolita, part American Gods, with a dash of Borges for good measure.
+
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+In between chapters, we read letters written by a Reconstruction-era innkeeper named Libby to her own long-dead sister. Libby has a new guest she finds suspicious, a classical actor with secessionist sympathies. In the present, Finn, who harbors a weakness for old-fashioned conspiracy theories (“ones that put groups and systems back into the situations where individuals were taking the rap”), entertains doubts about what really happened to John Wilkes Booth.
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+Libby’s letters are gripping — Moore can really write a 19th-century pastiche! — but don’t expect the Booth stuff to become a mystery or the key to the plot. There isn’t a plot. This is the kind of book where not all that much happens, but all of it seems to matter.
+
+
+The engine of this novel comes from Lily’s rotting flesh, which provides a ticking clock of sorts: The more her body falls apart, the vaguer her presence in Finn’s life becomes. Lily’s body is also where Moore indulges in her most extravagant language, lavishing us with metaphor. Lily’s skin “resembled the gray-green yolk of an overcooked egg,” her eyes “gold as chicken fat,” lips with “the shimmer and slip of fish skin.”
+
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+Finn loves Lily’s corpse ardently. He cradles “the sweet dense rot of her” in his arms and gently washes her failing skin in rest-stop bathrooms. When they have sex in the car, he notes that “her shifting organs and her stoop would be of use in this particular situation.” To love in this novel is to love the body that will rot away and decay, the mind that may sometimes long for rot.
+
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+Moore’s short stories frequently deal with death and illness and hospitals. The stories are shaggy, like this novel, but compact; the constraints of the medium grant them shape and form, as though Moore has poured her lovely sentences like water into the vessel of the short story. In I Am Homeless If This Is Not My Home, she seems to have poured her sentences out onto the ground, where they spread and stretch and sink into the soil. This is a strange and beautiful book, and when you try to catch it in your hands, it dissolves.
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The hottest new perk in tech is freedom -
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+Small tech companies are way more likely to let employees work remotely than big ones. | Getty Images/Westend61
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+How small tech companies are using remote work to compete with the big guys.
+
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+It used to be that Big Tech companies like Google, Meta, and Apple led the way when it came to workplace advantages. On top of great pay, they offered freebies like gourmet meals, massages, and on-site laundry. Then, when the pandemic made the office a physical danger, those same companies were among the first to offer the ultimate perk: the ability to work where you wish.
+
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+But, as their stock prices have suffered, Big Tech has not only dialed back on many on-site perks, they’ve also called workers back to the office. Facing hard times, they’ve retrenched into what they knew before the pandemic, typically asking workers to come into the office three days a week. Google is even factoring office attendance into performance reviews.
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+Smaller tech companies have since picked up the mantle of remote work. They are much more likely than their larger peers to allow people to work fully remotely, with 81 percent of those with fewer than 5,000 employees either allowing remote work or only having remote options, according to new data from Scoop Technologies, a software firm that builds tech to help hybrid teams coordinate and also tracks the office policies at major companies. Meanwhile, just 26 percent of companies with more than 25,000 employees are fully flexible.
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+Tech has the greatest variation in fully remote policy by company size than any other industry. This suggests that remote work is completely possible in the tech industry, but different-sized companies have settled on different policies based on how they think it benefits them or not. And their reasons for doing so might depend, in part, on how they want to portray themselves to the outside world.
+
+
+Why the so-called “flexibility divide” among tech companies?
+
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+Tech companies with fewer employees are using remote work as a way to pull in more talent in what had been a notoriously difficult hiring environment and to signify that they, unlike Big Tech, are where progress is happening. People in the tech industry, especially, are more likely to be lured by remote work, according to Gartner, which has found that better work-life balance and greater flexibility were the top benefits tech employees would choose over 10 percent higher compensation.
+
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+That’s a big deal for smaller tech companies, which haven’t always been able to compete with the Googles of the world in terms of salary. Airbnb, which employs more than 6,000 people, has used its work-from-anywhere policy to attract not only more applicants — its career page saw twice the traffic last year as it had the year before — but also more diverse ones, with 21 percent of new hires being under-represented minorities.
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+“We want to hire the best talent we can all around the world,” Dave Stephenson, Airbnb’s CFO and head of employee experience, told Vox. “If we narrow that definition of getting the best talent around the world to being 50 miles around San Francisco, that’s going to put us at a disadvantage.”
+
+
+At the same time, Airbnb has cut its office footprint by half, slowed attrition, and marked its first full year of profitability. The company pays to fly in its far-off employees — about 20 percent of its workforce — to be together from time to time. But this only happens if the company’s “ground control” team has deemed that there’s an important project that requires them to be in person.
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+“If they’re satisfied with their ability to balance their personal lives with their work lives, I think we get more effective performance out of people,” Stephenson said.
+
+
+The situation is similar at Yelp, which also lets its 5,000 workers choose where they work and notched its sixth straight quarter of record revenue last quarter while also rolling out products like AI-powered search. The company says that remote work hadn’t hurt sales goals or engineering productivity but had caused a huge spike in its talent pipeline.
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+“I think we saw pretty early on during the pandemic that, wow, this is actually working,” said Carmen Whitney Orr, Yelp’s chief people officer, who joined the company remotely last year. “Happy employees are productive employees and that means happy customers.”
+
+
+The ability to work remotely is most common among the smallest tech companies.
+
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+“If you can demonstrate that you’re able to create a team that is just as productive, if not more, by being remote, then there’s really no reason to not do it,” said Zuhayeer Musa, co-founder of tech compensation comparison platform Levels.fyi, which has nine workers. Levels.fyi was founded as a remote company in 2017, which Musa says makes it easier to continue working remotely.
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+In turn, remote work has meant the company has had better access to talent than it would if it demanded office attendance.
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+“If you require someone to move to a certain location, you are inherently limiting the talent pool that you’re going to be working with,” he said.
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+ Getty Images/Westend61
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+
+That could be what Big Tech is doing.
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+
+Amid economic uncertainty, flagging stock prices, and years without major innovation, larger tech companies are using their calls back to the office to signify to shareholders that they are grown-up and responsible corporations. Gone are the days of ping-pong-playing engineers and squandered profits. Here are the days of penny-pinching and strict oversight, probably in an office environment.
+
+
+In other words, what were once considered the most innovative and forward-thinking companies are behaving a lot more like their stodgy non-tech corporate counterparts.
+
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+When it comes to allowing fully remote work, policies at big tech companies are closest to their non-tech peers, like Citigroup and Starbucks. Like their non-tech counterparts, many tech companies have quickly shifted to a structured hybrid model, where workers have to come in a set number of days per week. The share of large tech companies that are doing hybrid (65 percent) is nearly the same as large companies overall (60 percent), as is the number of days per week they want people in (2.5 on average), according to Scoop.
+
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+“Bigger companies, more complex companies, are more likely to be looking for more professional types of management,” said Kathy Harrigan, a professor of corporate management at Columbia University’s business school. “Investors expect that.”
+
+
+And professionalism to them means butts in chairs. Harrigan says in-person work is necessary to coordinate the complicated, varied businesses these tech conglomerates now operate. The move to AI has only made in-person coordination more of a necessity, she said.
+
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+“They’re working with a more complex kind of product. It means a lot more coordination from a lot of different points of view, where previously these workers were permitted to work in silos,” Harrigan said.
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+One could argue that companies like Google, Meta, and Apple all ran very complex businesses during the pandemic, when they recorded record profits while their workers toiled from home.
+
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+“In the face of volatility and uncertainty, it is human nature to want to revert back to something that is a known quantity,” said Caitlin Duffy, a research director at Gartner, about the push to return to the office. “And so there might be some psychological things happening that may be overriding the evidence in front of them.”
+
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+The evidence, she says, shows that offering flexibility in where people work makes them happier and, by extension, more productive and innovative. Accounts to the contrary were “unfounded.” What’s worse, Duffy said, is that arbitrarily calling people back to the office might actually hurt workers’ productivity and innovation by driving fatigue and burnout.
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+Whether their back-to-office plans ultimately end up harming these companies remains to be seen. Big Tech companies, of course, might be able to sit back on their brand names and giant salaries to attract talent. But to some extent, with their flexible remote policies, small tech companies are expressing their ability to innovate and grow, just like the big guys used to do.
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+
The decline of American playtime — and how to resurrect it -
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+Experts say kids’ freedom to play has been declining since the 1980s. | Jorm Sangsorn via Getty Images/iStockphoto
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+The world can be terrifying. But we should still give kids the freedom to explore it.
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+About 30 years ago, something happened to the way kids play.
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+While American children had once commonly enjoyed the freedom to run around outside with minimal adult interference, they began to spend more time indoors where their parents could watch them. When they did go outside, they were more often accompanied by a grown-up; unstructured roughhousing and roleplaying were replaced by supervised play dates or carefully shepherded trips to the park. Kids began to spend more time in organized activities, like dance or sports, and less time in the kind of disorganized milling-about familiar to generations past.
+
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+The reasons for this shift were many: fears of kidnapping, stoked by a series of highly publicized cases; an increase in the length of the school year; parental anxieties about children’s futures in a time of growing income inequality and economic insecurity. The result was a 25 percent drop in children’s unstructured playtime between 1981 and 1997, setting in motion a pattern of less freedom and more adult surveillance that historians and child psychologists believe continues to this day. “All kinds of independent activities that used to be part of normal childhood have gradually been diminishing,” said Peter Gray, a psychology professor at Boston College who studies play.
+
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+The decline in kids’ unstructured time is bad for fun as structured activities like classes and sports in which adults are evaluating and judging kids’ performance can be more like work than play, Gray said. It’s bad for learning, because children need playtime to develop motor and social skills. And it could be hurting kids’ health — in a commentary earlier this year in the Journal of Pediatrics, Gray and his co-authors argue that the decline in play and independence could be one reason children and teens have reported skyrocketing levels of anxiety, depression, and sadness in recent years.
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+In a time when parents can be arrested for letting children play unsupervised, and threats to children, both real and perceived, seem only to multiply, giving a kid the freedom to roam can seem impossible. Still, experts say there are ways families can grant children more autonomy, as well as structural changes that can make schools, communities, and the country as a whole more friendly to children’s freedom. After all, “if you take away play from children, they’re going to be depressed,” Gray said. “What is life for anybody without play?”
+
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+How kids lost the freedom to play
+
+
+A lot of experts trace the decline of play back to a spate of high-profile kidnappings. It started with Etan Patz, a 6-year-old New York City boy who disappeared in 1979 on the way to the bus stop, argues Paul Renfro, a history professor at Florida State University and the author of Stranger Danger: Family Values, Childhood, and the American Carceral State. His case was soon followed by the disappearances of Adam Walsh, Kevin Collins, and two Iowa paperboys — Johnny Gosch and Eugene Martin — who vanished during their routes (then, as now, the victims whose stories made the biggest headlines were white).
+
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+The crimes weren’t connected, nor were they indicative of a wider increase in child abductions. But they received enormous media attention, with the boys’ stories, photographs, and interviews with their grieving parents featured on newscasts across the country. Some of the boys’ images also appeared on the backs of milk cartons as part of a campaign launched by the nonprofit National Child Safety Council in 1984. The campaign only lasted a few years, but it had an outsize cultural impact, inspiring the bestselling young adult novel The Face on the Milk Carton and creating a climate in which families were “surrounded by reminders of missing children,” Renfro said.
+
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+The fear was such that 72 percent of parents feared their children getting abducted, according to one 1991 study — in another study, conducted in 1987, 44 percent of children said it was likely or highly likely that they would be kidnapped at some point. Newscasters claimed that 50,000 children were abducted every year.
+
+
+The real figure was closer to 100, Renfro said, and children have always been more likely to be kidnapped by family members or other adults they know than by strangers. Still, “stranger danger” gripped the American unconscious and didn’t let go.
+
+
+At the same time, commentators across the political spectrum were pushing the idea that “the American family” — really the white nuclear family with two parents and 2.5 children, living in the suburbs — was at risk, Renfro said. In addition to kidnappers, supposed dangers included women entering the workforce, a decline in the prosperity that white families had enjoyed in the wake of World War II, and a burgeoning gay rights movement. “The narrative of the family under threat and, by extension, the child under threat really takes hold and is really appealing to people in this particular moment,” Renfro said. (That narrative continues to this day, and fears of stranger danger can be seen in QAnon conspiracy theories about child trafficking, Renfro said, and in anti-LGBTQ rhetoric about “grooming.”)
+
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+These anxieties collided with another worry: that American schoolchildren were falling behind the rest of the world academically. In the second half of the 20th century, the length of the school year increased by five weeks, Gray said. Kids began getting homework as early as kindergarten, and recess and lunch got shorter. To compensate for the lack of exercise in school, parents began putting their children in more sports and other organized extracurricular activities. Meanwhile, the growing wealth gap increased middle-class parents’ fear for their children’s economic futures, as well as the pressure to go to college in order to find a good job. “Children began to be pressured, even early on, to build the kind of resume that would ultimately get them into a fancy college,” Gray said.
+
+
+The result of all of this was a shift in how Americans thought and talked about childhood. Prior to the 1980s, parenting advice had often emphasized the importance of independence, Gray said — allowing children to walk to school on their own, play unsupervised, and hold part-time jobs when they were old enough. Starting in that decade, however, conventional wisdom began to shift toward the idea that children should be watched all the time.
+
+The last 20 years or so have also seen a rise in parents’ access to “technology that allows us to know or to think we’re supposed to know exactly what our kids are doing,” said Lynn Lyons, a therapist who specializes in anxiety disorders. That includes everything from cellphones (which a majority of kids now have by age 12) to AirTags (which some parents use to track children) to parent portals at schools and day cares (which can send notifications about something as small as a baby’s dirty diaper).
+
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+The effect of smartphones themselves on children’s play is complex. While many blame screen time for a decline in active play, some research suggests that smartphones can enrich kids’ outdoor experiences by, for example, allowing them to listen to music or stay in touch with friends. For parents, however, the constant stream of information can be the opposite of reassuring, and lead them to further monitor and restrict their kids’ movements. “Access to more information about everything that’s going on doesn’t make you feel better,” Lyons said. “It actually makes you more anxious.”
+
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+Meanwhile, Black parents in particular have also had to contend with the risk of police brutality and other racist violence. In interviews with researchers, Black moms of sons have expressed “a baseline of concern every time their child walked out the door,” said J. Richelle Joe, a professor of counselor education at the University of Central Florida. “The concern was, will people who engage with my son see him as a threat, and will he potentially be harmed or even killed just for existing?”
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+As a Black mom living in majority-white Orange County, California, Trina Greene Brown says she didn’t let her son play outside on his own. “Some people will call that helicopter parenting,” said Brown, the founder and executive director of the nonprofit Parenting for Liberation. “I would say it’s not helicopter parenting; it’s because Black people have often lived in helicopter environments where our children and ourselves and our bodies have been under heavy surveillance.”
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+Kids of color and low-income kids also face disproportionate structural barriers to spending time outside, from a lack of green space to levels of neighborhood crime. All these factors and more contribute to an environment in which, whether it’s for their sheer physical safety or out of concern for their economic future, kids are losing out on opportunities for free and independent play.
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+Playing is fun. It’s also necessary.
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+Such play, though, has a host of benefits, experts say. Free play helps develop kids’ executive functioning abilities, a set of skills that includes planning and self-control, Lyons said. It’s also important for building friendships. One study, conducted in Switzerland in the 1990s, compared children who played unsupervised in their neighborhoods to children who spent more time playing in parks with their parents looking on. The free-playing kids had more than twice as many friends as the park visitors, and had better social and motor skills — they also spent more time outside overall.
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+Play can also be a way for kids to develop a sense of autonomy, which in turn helps them feel good about themselves. Regardless of age, “people are happier and mentally healthier when they feel that they are in charge of their own lives,” Gray said. “When people feel that they’re not in charge, that other people are making their decisions for them, they don’t feel so good.”
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+Indeed, the presence of grown-ups seems to diminish the psychological benefits of kids’ activities, experts say. “The more that play for kids is organized and directed by adults, the less opportunities that kids have to develop some really important skills that we know are preventive for anxiety — and, because anxiety is so closely linked to depression, to depression as well,” Lyons said.
+
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+These and other mental health problems have been on the rise among kids and teens for decades — one in 11 American children today has an anxiety disorder, and a report released by the Centers for Disease Control and Prevention earlier this year found that almost three in five teenage girls experienced persistent sadness in 2021, the highest level in 10 years. Experts and armchair commentators alike have floated explanations for this phenomenon from the advent of social media to climate change and economic insecurity, but Gray and others believe the drop in play — and in other measures of freedom like walking to school and holding part-time jobs — could be to blame. “What children need is freedom to be children,” Gray said, “to play and explore and interact with other kids.”
+
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+Adults can give kids back their playtime, but it will take work
+
+
+Reintroducing unstructured play into children’s lives, however, is easier said than done. Just sending kids out to play until the streetlights come on is no longer a social norm. Families can face anything from social opprobrium to prosecution for letting kids play unsupervised, and the consequences are especially severe for parents of color and low-income parents, who are already subject to a disproportionate degree of surveillance around their childrearing choices.
+
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+Moreover, the events of the last few years, from the pandemic to wildfires to formula shortages and more, have contributed to a climate of intense anxiety among today’s parents — many of whom grew up in the milk-carton era and were anxious children and teenagers themselves. “Anxiety seeks certainty,” Lyons said. “The more that we restrict, the more that we don’t let our kids move into the world, the better we feel in terms of our own anxiety.”
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+However, there are ways parents can give their kids more freedom, even in a society that doesn’t make it easy. It starts with adults recognizing and coping with their anxieties, as much as they can. “I encourage parents to do their own work, engage in their own counseling to unpack whatever concerns that they might have, whatever fears that they’re holding on to,” Joe said. In addition to working with a therapist, if possible, it’s helpful to reach out to other parents for support and commiseration. “Then parents themselves feel less isolated with their concerns,” Joe said.
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+Parents can also take steps to avoid passing their anxieties to their children. They can limit what Lyons calls “safety chatter”: “the constant stream of be careful, get down, watch out” that can serve as the soundtrack to a playground trip or scooter ride. They can also work on letting kids take reasonable risks, whether that’s climbing a tree or just stepping into a situation that might be a bit uncomfortable at first. “We want kids to be pushed a little bit,” Lyons said. “We want to offer them things that feel challenging.”
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+Grown-ups can also resist the pull of tracking apps and other technologies that let parents keep tabs on kids at all times. “I work with parents that have baby monitors in their kids’ bedrooms, and their kids are 12 years old,” Lyons said. “We’ve got this idea right now that the closer we keep our kids, the more information we have, the more we direct, the more that we control, the better off our kids will be. And the research is showing the opposite.”
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+Parents can also band together to make their neighborhoods more hospitable for children’s play. One strategy would be for neighboring parents to agree to send their kids outdoors at certain times of the week, with one adult on hand just for safety, Gray said.
+
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+But it can’t be just on individual parents to reverse a trend that took a whole society to create — especially since not all families have access to outdoor space, trees to climb, or affordable therapy options. Schools, too, can encourage freedom and exploration for kids by bringing back recess in places where it’s been curtailed, Gray said. Districts in Connecticut, New York, and elsewhere have also adopted what they call play clubs, an hour before or after school in which kids of all ages play together with minimal interference from teachers and “no rules except don’t hurt anybody,” Gray said. “Schools can play a big role, if schools can see themselves as places for play.”
+
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+Colorado, Nevada, and other states have also passed reasonable independence laws, spearheaded by Let Grow, a nonprofit co-founded by Gray. The laws protect parents from being prosecuted for letting their children do unsupervised activities like walking to school or playing outside.
+
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+If giving kids and parents more freedom is one side of the solution, though, another side is making society as a whole safer for kids to roam free. While stranger kidnappings may not be a common danger for kids, others, like shootings, car crashes, and family violence, all deserve attention, Renfro said. “If we’re serious about protecting kids, these are all matters that need to be discussed rather than shrugged away or ignored in favor of more sensational or salacious issues.”
+
+
+Dismantling systemic racism in law enforcement, schools, and everywhere it exists is also an inextricable part of the conversation around children’s autonomy, Joe said. As long as Black parents have to worry about their children being harmed while playing in a park or walking home, “then Black families are still going to have the challenge of trying to encourage their children to be autonomous and independent within a context that’s not always so safe for them.”
+
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+White Americans also need to address the racist biases within themselves and their families that lead to Black children being perceived as less innocent or more adult than their age, and their play or simple existence being perceived as threatening. “As a Black parent who’s raising a child in a predominantly white community, I really need white folks to check their misunderstanding and adultification of Black children,” Brown, the Parenting for Liberation founder, said. “For me, it’s about, how do we think about the responsibility as a collective and not put the onus only on Black people to make sure that Black children are safe?”
+
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+Finally, there are ways of thinking about kids’ independence and autonomy within a larger context of their connections with others. “Whereas we often prioritize this kind of individualistic development where I take on the world,” Joe said, “that’s not what’s valued for many people in many communities.”
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+Indeed, a more collectivist approach, one embraced by many cultures both within the US and around the world, teaches children that “your existence in the world is intricately connected to other people,” Joe said. “That allows for the development of empathy, because we recognize we’re not out there living on our own.”
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+A collectivist view of children’s play might acknowledge that we all have a role in creating communities that are not just safe but joyful, that provide children with opportunities to grow and explore without fear. Most communities in the US don’t look like that right now, but Gray and others believe they can be built, if we have the will and the wherewithal to build them.
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+
From The Hindu: Sports
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Satwiksairaj hails doubles coach Boe, terms Indonesia triumph ‘one of the biggest achievements’ - BADMINTON | The champion says that he and doubles partner Chirag want to earn that kind of reputation of being invincible, instil that kind of fear and respect that opponents concede a few easy points
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Paris Olympics 2024 headquarters searched as part of corruption investigations - The National Financial Prosecutor’s Office said the Paris 2024 headquarters were raided amid a preliminary investigation into contracts made by the Summer Games Organising Committee
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Chelsea signs Christopher Nkunku from Leipzig on 6-year deal - Chelsea has signed France forward Christopher Nkunku from Leipzig on six-year contract
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Daily Quiz | On Leander Paes - Leander Paes, one of India’s greatest sportspersons, turned 50 on June 17. A quiz on the life and career of this phenomenal tennis player
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The Ashes 2023 | Rain delays start of final day to post-lunch - The Test won’t start before 1:10 p.m. at the earliest; Australia needs 174 more runs and England seven more wickets to win
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From The Hindu: National News
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TS received 15 mm rain as against normal of 83 mm so far this month - Nearly the entire State has reported a large deficient rainfall so far, according to the data collated by the Telangana State Development Planning Society
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Special dental care services for differently abled - NIPMR aims at providing inclusive dental care services for individuals with mental, physical disabilities, catering specifically to the needs of differently abled children.
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Three-day international pharma expo to begin in Hyderabad on July 5 - IPHEX will help showcase capabilities of Indian pharma industry and build confidence among stakeholders globally, says Pharmexcil DG Ravi Uday Bhaskar
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Zero tolerance on spurious medicines, 71 firms issued notices: Mandaviya on cough syrup row - From June 1, a test has been made mandatory for cough syrups before they are exported
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Congress, BJP spar over participation of government officials in RSS event in Madhya Pradesh - While Congress demanded that such officials be kept away from preparations for the Assembly polls due this year-end, a State BJP leader said this only shows the Congress’ “hatred” for the RSS
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From BBC: Europe
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Paris 2024 Olympics: French police raid organisers’ headquarters - French officials say the searches are part of two earlier preliminary corruption investigations.
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Russia renews drone and missile attacks on Ukraine - A wave of air attacks is reported on Kyiv and other cities - but no-one is injured, officials say.
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Andrew Tate charged with rape and human trafficking - Andrew Tate and his brother charged in Romania over human trafficking and sexual exploitation.
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Airbus experiments with more control for the autopilot - Airbus has been testing new automated technology that it says has the potential to improve flight safety.
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Two international matches abandoned after alleged racist abuse - Two international matches, New Zealand v Qatar and Republic of Ireland U21 v Kuwait U22, are abandoned on Monday following allegations of racial abuse.
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From Ars Technica
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50 Years of Text Games parses the rich history of a foundational genre - Zork and MUD? Sure. But also Universal Paperclips, AI Dungeon and Lifeline. - link
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Review: The Flash isn’t a terrible film—just a forgettable one - There’s nothing here we haven’t seen many, many times before—and frankly done better. - link
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Even galaxies recycle - A quasar ejected the remains of stars, but another galaxy sucked them back in. - link
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Parker Solar Probe images the launch of the solar wind - This discovery is literally the hottest thing in a while. - link
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The sleeper hits of Summer Game Fest 2023 - Games about time travel, foam spraying guns, and… space hospitals? - link
The Maid asked the master’s wife for a pay raise!! -
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+The wife was very upset about this, and decided to talk to her about the raise. She asked “Now Maria, why do you want a pay increase?” Maria: “Well, Señora, there are tree reasons why I wanna increaze.” “The first is that I iron better than you.” Wife: “Who said you iron better than me?” Maria: “Jor huzban he say so.” Wife: “Oh yeah?” Maria: “The second reason eez that I am a better cook than you.” Wife: “Nonsense, who said you were a better cook than me ?” Maria: “Jor hozban did.” Wife, increasingly agitated: “Oh he did, did he?” Maria: “The third reason is that I am better at sex than you Wife: (Really boiling now and gritting her teeth): “And did my husband say that as well?” Maria: “No Señora….the gardener did. Wife: “So, how much do you think would be fair ??”
+
An infinite number of mathematicians walk into a bar… -
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+An infinite number of mathematicians walk into a bar. The first mathematician orders a beer. The second orders half a beer.
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+“I don’t serve half-beers,” the bartender replies.
+
+
+“Excuse me?” asks the second mathematician.
+
+
+“What kind of bar serves half-beers?” The bartender remarks. “That’s ridiculous.”
+
+
+“Oh c’mon,” says mathematician #1, “do you know how hard it is to collect an infinite number of us? Just play along!”
+
+
+“No, you see, there are very strict laws on how I can serve drinks. I couldn’t serve you half a beer even if I wanted to.”
+
+
+“But that’s not a problem,” chimes in a third mathematician, “at the end of the joke, you serve us a whole number of beers. You see, when you take the sum of a continuously halving function–”
+
+
+“I know how limits work,” interjects the bartender.
+
+
+“Oh, alright then. I didn’t want to assume a bartender would be familiar with such advanced mathematics.”
+
+
+“Are you kidding me?” replies the bartender. “You learn limits in, like, 9th grade! What kind of mathematician thinks limits are advanced mathematics?”
+
+
+“HE’S ON TO US!” mathematician #1 screeches.
+
+
+Simultaneously, every mathematician opens their mouth and out pours a cloud of multicolored mosquitoes. Each mathematician is bellowing insects of a different shade.
+
+
+The mosquitoes form into a singular, polychromatic swarm. “FOOLS!” it booms in unison. “I WILL INFECT EVERY BEING ON THIS PATHETIC PLANET WITH MALARIA!”
+
+
+The bartender stands fearless against the technicolor horde. “But wait!” he interrupts, thinking fast, “if you do that, politicians will use the catastrophe as an excuse to implement free healthcare. Think of how much that will hurt the taxpayers!”
+
+
+The mosquitoes fall silent for a brief moment. “My God, you’re right. We didn’t think about the economy! Very well, we will not attack this dimension. FOR THE TAXPAYERS!”
+
+
+And with that, they vanish.
+
+
+A nearby barfly stumbles over to the bartender. “How did you know that that would work?” he slurs.
+
+
+“It’s simple, really,” the bartender says. “I saw that the vectors formed a gradient, and therefore must be conservative.”
+
+
+/cdn.vox-cdn.com/uploads/chorus_asset/file/24731078/GettyImages_748326823.jpg)
Getty Images/Westend61
+
+![[link]](https://i.redd.it/1j5nee06kx5b1.png){kind=link}