Jet injection potentiates naked mRNA SARS-CoV-2 vaccine in mice and non-human primates by adding physical stress to the skin -
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+Naked mRNA-based vaccines may reduce the reactogenicity associated with delivery carriers, but their effectiveness has been suboptimal against infectious diseases. Herein, we aimed to enhance their efficacy by using a pyro-drive liquid jet injector that precisely controls pressure to widely disperse mRNA solution in the skin. The jet injection boosted naked mRNA delivery efficiency in the mouse skin. Mechanistic analyses indicate that dendritic cells, upon uptake of antigen mRNA in the skin, migrate to the draining lymph nodes for antigen presentation. Additionally, the jet injector activated innate immune responses in the skin, presumably by inducing physical stress, thus serving as a physical adjuvant. From a safety perspective, our approach, utilizing naked mRNA, restricted mRNA distribution solely to the injection site, preventing systemic pro-inflammatory reactions following vaccination. Ultimately, the jet injection of naked mRNA encoding SARS-CoV-2 spike protein elicited robust humoral and cellular immunity, providing protection against SARS-CoV-2 infection in mice. Furthermore, our approach induced plasma activity of neutralizing SARS-CoV-2 in non-human primates, comparable to that observed in mice, with no detectable systemic reactogenicity.
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COVID-19 is Feminine: Grammatical Gender Influences Future Danger Perceptions and Precautionary Behavior -
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+Gendered languages assign masculine and feminine grammatical gender to all nouns, including nonhuman entities. In French, Italian, and Spanish, the name of the disease resulting from the virus (COVID-19) is grammatically feminine, whereas the virus that causes the disease (coronavirus) is masculine. In this research, we test whether the grammatical gender mark matters. In a series of experiments with French and Spanish speakers, we find that grammatical gender affects virus-related judgments consistent with gender stereotypes: feminine- (vs. masculine-) marked terms for the virus decrease perceptions of future danger of the virus and reduce intentions to take precautionary behavioral measures to mitigate contraction and spread of the virus (e.g., avoiding restaurants, movies, travel). Secondary data analyses of online search behavior for France, Spain, and Italy further demonstrate this negative relation between the anticipated threat (daily new cases and deaths, search for masks) and usage of the feminine- (vs. masculine-) marked terms for the coronavirus. These effects occur even though the grammatical gender assignment is semantically arbitrary.
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Chlorpheniramine Maleate Displays Multiple Modes of Antiviral Action Against SARS-CoV- 2: A Mechanistic Study -
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+Chlorpheniramine Maleate (CPM) has been identified as a potential antiviral compound against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). In this study, we investigated the in vitro effects of CPM on key stages of the SARS-CoV-2 replication cycle, including viral adsorption, replication inhibition, and virucidal activity. Our findings demonstrate that CPM exhibits antiviral properties by interfering with viral adsorption, replication, and directly inactivating the virus. Molecular docking analysis revealed interactions between CPM and essential viral proteins, such as the main protease receptor, spike protein receptor, and RNA polymerase. CPM's interactions were primarily hydrophobic in nature, with an additional hydrogen bond formation in the RNA polymerase active site. These results suggest that CPM has the potential to serve as a multitarget antiviral agent against SARS-CoV-2 and potentially other respiratory viruses. Further investigations are warranted to explore its clinical implications and assess its efficacy in vivo.
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Age-Associated Weaker Immunity to Coronaviruses is Characteristic of Children that Develop Multisystem Inflammatory Syndrome following SARS-CoV-2 Infection -
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+We analyzed the antibody and cytokine responses of twenty-three patients with multisystem inflammatory syndrome of children (MIS-C) that appeared with a three-to-six-week delay following a mild or asymptomatic SARS-CoV-2 infection. These responses were compared to healthy convalescent pediatric COVID-19 patients approximately twenty-eight days after the onset of symptoms. Both groups had strong IgG responses to SARS-CoV-2 spike (S) and nucleocapsid (N) proteins, but the MIS-C patients had weaker antibody responses to certain epitopes in the SARS-CoV-2 S and N proteins and to the S and N proteins of endemic human coronaviruses (HCoV) compared to pediatric convalescent COVID patients. HCoV antibody reactivity was correlated with age. In contrast, MIS-C patients had elevated serum levels of several proinflammatory cytokines compared to convalescent COVID patients, including interleukins IL-6, IL-8, IL-18 and chemokines CCL2, CCL8, CXCL5, CXCL9 and CXCL10 as well as tumor necrosis factor alpha and interferon gamma. Moreover, many cytokine responses of MIS-C patients were positively correlated with antibody responses to the SARS-CoV-2 S, N, membrane and ORF3a proteins while pediatric convalescent COVID patient cytokine responses were more often negatively correlated with antibody responses to the S, N and ORF3a proteins of SARS-CoV-2.
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Heterogeneous SARS-CoV-2 kinetics due to variable timing and intensity of immune responses -
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+The viral kinetics of documented SARS-CoV-2 infections exhibit a high degree of inter-individual variability. We identified six distinct viral shedding patterns, which differed according to peak viral load, duration, expansion rate and clearance rate, by clustering data from 810 infections in the National Basketball Association cohort. Omicron variant infections in previously vaccinated individuals generally led to lower cumulative shedding levels of SARS-CoV-2 than other scenarios. We then developed a mechanistic mathematical model that recapitulated 1510 observed viral trajectories, including viral rebound and cases of reinfection. Lower peak viral loads were explained by a more rapid and sustained transition of susceptible cells to a refractory state during infection, as well as an earlier and more potent late, cytolytic immune response. Our results suggest that viral elimination occurs more rapidly during omicron infection, following vaccination, and following re-infection due to enhanced innate and acquired immune responses. Because viral load has been linked with COVID-19 severity and transmission risk, our model provides a framework for understanding the wide range of observed SARS-CoV-2 infection outcomes.
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Risk factors for SARS-Cov-2 infection at a United Kingdom electricity-generating company: a test-negative design case-control study -
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+Objectives Identify workplace risk factors for SARS-Cov-2 infection, using data collected by a United Kingdom electricity-generating company. Methods Using a test-negative design case-control study we estimated the odds ratios (OR) of infection by job category, site, test reason, sex, vaccination status, vulnerability, site outage, and site COVID-19 weekly risk rating, adjusting for age, test date and test type. Results From an original 80,077 COVID-19 tests, there were 70,646 included in the final analysis. Most exclusions were due to being visitor tests (5,030) or tests after an individual first tested positive (2,968). Women were less likely to test positive than men (OR=0.71; 95% confidence interval=0.58-0.86). Test reason was strongly associated with positivity and although not a cause of infection itself, due to differing test regimes by area it was a strong confounder for other variables. Compared to routine tests, tests due to symptoms were highest risk (94.99; 78.29-115.24), followed by close contacts (16.73; 13.80-20.29) and looser work contacts 2.66 (1.99-3.56). After adjustment, we found little difference in risk by job category, but some differences by site with three sites showing substantially lower risks, and one site showing higher risks in the final model. Conclusions Infection risk was not associated with job category. Vulnerable individuals were at slightly lower risk, tests during outages were higher risk, vaccination showed no evidence of an effect on testing positive, and site COVID-19 risk rating did not show an ordered trend in positivity rates.
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Predictive Systems Biology Modeling: Unraveling Host Metabolic Disruptions and Potential Drug Targets in Acute Viral Infections -
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+Background: Host response is critical to the onset, progression, and outcome of viral infections. Since viruses hijack the host cellular metabolism for their replications, we hypothesized that restoring host cell metabolism can efficiently reduce viral production. Results: Here, we present a viral-host Metabolic Modeling (vhMM) method to systematically evaluate the disturbances in host metabolism in viral infection and computationally identify targets for modulation by integrating genome-wide precision metabolic modeling and cheminformatics. We applied vhMM to SARS-CoV-2 infections and identified consistent changes in host metabolism and gene and endogenous metabolite targets between the original SARS-COV-2 and different variants (Alpha, Delta, and Omicron). Among six compounds predicted for repurposing, methotrexate, cinnamaldehyde, and deferiprone were tested in vitro and effective in inhibiting viral production with IC50 less than 4uM. Further, an analysis of real-world patient data showed that cinnamon usage significantly reduced the SARS-CoV-2 infection rate with an odds ratio of 0.65 [95%CI: 0.55~0.75]. Conclusions: These results demonstrated that vhMM is an efficient method for predicting targets and drugs for viral infections.
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Deep metric learning for few-shot X-ray image classification -
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+Deep learning models have proven the potential to aid professionals with medical image analysis, including many image classification tasks. However, the scarcity of data in medical imaging poses a significant challenge, as the limited availability of diverse and comprehensive datasets hinders the development and evaluation of accurate and robust imaging algorithms and models. Few-shot learning approaches have emerged as a potential solution to address this issue. In this research, we propose to deploy the Generalized Metric Learning Model for Few-Shot X-ray Image Classification. The model comprises a feature extractor to embed images into a lower-dimensional space and a distance-based classifier for label assignment based on the relative distance of these embeddings. We extensively evaluate the model using various pre-trained convolutional neural networks (CNNs) and vision transformers (ViTs) as feature extractors. We also assess the performance of the commonly used distance-based classifiers in several few-shot settings. Finally, we analyze the potential to adapt the feature encoders to the medical domain with both supervised and self-supervised frameworks. Our model achieves 0.689 AUROC in 2-way 5-shot COVID-19 recognition task when combined with REMEDIS (Robust and Efficient Medical Imaging with Self-supervision) domain-adapted model as feature extractor, and 0.802 AUROC in 2-way 5-shot tuberculosis recognition task with domain-adapted DenseNet-121 model. Moreover, the simplicity and flexibility of our approach allows for easy improvement in the feature, either by incorporating other few-shot methods or new, powerful architectures into the pipeline.
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The role and influence of perceived experts in an anti-vaccine misinformation community -
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+The role of perceived experts (i.e., medical professionals and biomedical scientists) as potential anti-vaccine influencers has not been characterized systematically. We describe the prevalence and importance of anti-vaccine perceived experts by constructing a coengagement network based on a Twitter data set containing over 4.2 million posts from April 2021. The coengagement network primarily broke into two large communities that differed in their stance toward COVID-19 vaccines, and misinformation was predominantly shared by the anti-vaccine community. Perceived experts had a sizable presence within the anti-vaccine community and shared academic sources at higher rates compared to others in that community. Perceived experts occupied important network positions as central anti-vaccine nodes and bridges between the anti- and pro-vaccine communities. Perceived experts received significantly more engagements than other individuals within the anti- and pro-vaccine communities and there was no significant difference in the influence boost for perceived experts between the two communities. Interventions designed to reduce the impact of perceived experts in spreading anti-vaccine misinformation may be warranted.
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Family Separation and COVID-19: The Impact of International Border Restrictions on Refugees in Australia -
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+COVID-19 resulted in global restrictions on migration, with pronounced consequences in Australia, where the resettlement of refugees was significantly curtailed from March 2020. This research, comprising a third phase in an ongoing study, seeks to understand the broader implications of these restrictions on family separation and reunion among resettled refugees in Australia. Employing a mixed-method approach of surveys and family interviews conducted in late 2021, we explore various themes the pandemic’s effects on family reunion, concerns about family still `at home’, maintaining social connections, post-migration difficulties and financial hardships. The findings reveal a negative impact of COVID-19 on refugees’ ability to reunite with families, with evidence pointing differences between gender, visa category, and language group/ethnicity. The research underscores the need for innovative approaches in resettlement to address the negative impacts of family separation and for governments to expedite family reunion pathways to alleviate isolation and uncertainty among resettled refugees.
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A short sequence in the tail of SARS-CoV-2 envelope protein controls accessibility of its PDZ Binding Motif to the cytoplasm. -
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+The carboxy terminal tail of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) envelope protein (E) contains a PDZ-binding motif (PBM) which is crucial for coronavirus pathogenicity. During SARS-CoV-2 infection, the viral E protein is expressed within the Golgi apparatus membrane of host cells with its PBM facing the cytoplasm. In this work we study the molecular mechanisms controlling the presentation of the PBM to host PDZ (PSD-95/Dlg/ZO-1) domain-containing proteins. We show that at the level of the Golgi apparatus, the PDZ-binding motif of the E protein is not detected by E C-terminal specific antibodies neither by PDZ domain-containing protein binding partner. Four alanine substitutions upstream of the PBM in the central region of the E protein tail is sufficient to generate immunodetection by anti-E antibodies and trigger robust recruitment of the PDZ domain-containing protein into the Golgi organelle. Overall, this work suggests that the presentation of the PBM to the cytoplasm is under conformational regulation mediated by the central region of the E protein tail and that PBM presentation probably does not occur at the surface of Golgi cisternae but likely at post-Golgi stages of the viral cycle.
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A low molecular weight dextran sulphate, ILB®, for the treatment of amyotrophic lateral sclerosis (ALS): an open-label, single-arm, single-centre, phase II trial -
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+Background Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig9s disease, is a rare neurological disease and is the most common motor neurone disease. It is a fatal disease with specific loss of motor neurons in the spinal cord, brain stem, and motor cortex leading to progressive paralysis and usually death within five years of diagnosis. There remains no cure for ALS, and management is focused on a combination of neuroprotective medication, respiratory support, and management be multidisciplinary clinics. Patients and Methods This prospective, single-arm, open-label phase II clinical trial of sustained weekly administration of 2 mg/kg ILB® (a low-molecular weight dextran sulphate) was conducted in a single UK hospital. Eligible patients were at least 18 years and had a definite diagnosis of ALS according to El Escorial Criteria. The co-primary outcomes were safety, tolerability, and quantity of ILB® administered. All evaluable patients were analysed in a modified intention-to-treat analysis. EudraCT number. 2018-000668-28 Findings Between 18-Apr-2019 and 27-Mar-2020, 11 patients were recruited and treated for up to 38 weeks. There were no treatment terminations or withdrawals. One serious adverse event was reported, which was not related to ILB® and resolved without sequalae. 270 mild/moderate adverse events were reported with no intolerable events occurring during the trial. The total number of ILB® treatments administered per patient ranged from 4 to 38, with a cumulative dose ranging from 745 to 6668 mg. As a result of the COVID-19 pandemic and the high-risk status of study participants, recruitment and treatment was suspended early in Mar-2020. At the long-term follow-up, three patients had died after the trial was halted, between 53 and 62 weeks after their final ILB® injection. Interpretation Long-term weekly ILB® injections of 2 mg/kg was well tolerated and had an acceptable safety profile in patients with ALS.
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Impact of the COVID-19 Pandemic on Same-day Discharge Adoption Following Percutaneous Coronary Intervention for Stable CAD: A National Time Series Analysis -
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+Abstract Background: Elective percutaneous coronary intervention (PCI) historically required hospitalization post procedure. Same day discharge (SDD) has emerged as a safe and cost efficient option, although the impact of the coronavirus disease of 2019 (COVID-19) pandemic on rates of SDD and associated care episode costs remains uncertain. Methods: A national sample of consecutive patients undergoing elective PCI at 42 hospitals (Ascension, St.Louis, MO) between May 2019 to April 2021 were identified using internal registry data and administrative claims data. Rates of SDD before and after the COVID-19 pandemic (March 2020) were compared using multivariable logistic regression adjusted for patient and procedural characteristics. Additionally, an interrupted time series model was used to determine the effect of the pandemic and policy on SDD rates before and after pandemic declaration. Lastly, we estimated total costs per PCI episode in pre and post pandemic periods. Results: In total, 12,740 interventions were performed within 42 Ascension facilities that met study eligibility criteria (5955 PCI prior to the pandemic and 6785 after). Demographic data were similar between both populations although higher rates of dyslipidemia, prior myocardial infarction, and heart failure history were noted in the post pandemic group. Pandemic declaration was associated with a higher likelihood of SDD (OR 2.09, CI 1.93-2.25, p < 0.001). From pre-pandemic to post-pandemic, mean SDD rose from 34% to 45% (p< 0.001) with an accelerated monthly SDD adoption rate after the pandemic (0.1% per month vs 1.0% per month, p=0.02). Total costs per episode were $679.52 (95% CI $476.12 ? $882.92, p < 0.001) higher in the post-pandemic period, driven by increased material costs. SDD was associated with a $2137.05 (95% CI $1925.03 - $2349.07, p < 0.001) reduction in costs relative to non-SDD episodes throughout the study period. Conclusion: Among a large national risk-adjusted sample of consecutive patients, the COVID-19 pandemic accelerated adoption of SDD. As a care strategy, SDD was associated with reduced episode costs during elective PCI in the post-pandemic period .
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Estimating seroprevalence of SARS-CoV-2 infection after highly contagious Omicron outbreak: A cross sectional study in a university setting -
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+Abstract Objective: This study aimed to investigate the seroprevalence of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) antibodies among individuals aged 18 years and older Design: Prospective cohort study. Settings: Population-based study was conducted within the Arizona State University (ASU) community. Participants: The study recruited 1,397 adult participants that volunteered over a period of three days (March 1-March 3 of 2022). Primary outcome measures: Seroprevalence was conducted in the community to assess the presence of SARS-CoV-2-specific antibodies resulting from previous exposure to SARS-CoV-2 and/or vaccination. Results: The seroprevalence of anti-receptor binding domain (RBD) antibodies was found to be 96.3% using a semi-quantitative chemiluminescent immunoassay and 98% using an electrochemiluminescent immunoassay. For anti-nucleocapsid (NC) antibodies, the seroprevalence was 39.1% by an ELISA assay and 41.4% by an electrochemiluminescent immunoassay. Individuals that experienced breakthrough infections exhibited the highest levels of anti-RBD antibodies. Additionally, saliva samples showed promise as a potential diagnostic biofluid for measuring antibody levels, as they exhibited a strong correlation with the data obtained from serum samples. Conclusion: Accurate estimation of population-based serosurveillance for SARS-CoV-2 will monitor the trend of infection in the community and delineate the geographical spread of the infection. Cumulative incidence of SARS-CoV-2 infection during and after outbreaks is crucial for informing the development of effective risk mitigation protocols within the community. Protocols may include measures such as encouraging booster shots, extending mask mandates, or transitioning to online classes. Serosurveys repeated at regular intervals can also guide containment measures in communities and prompt respond to future outbreaks. Strengths and limitations of this study: * We simultaneously investigated active infection and seroprevalence for the university population. * Our study was strengthened by having the participants self-report data independently validated with diagnostic tests. * Saliva samples could be a potential diagnostic biofluid for measuring antibody levels. * Our study was performed within the university setting therefore it only reflects the COVID-19 situation within that community. * The number of breakthrough infections and the longitudinal samples were small, thus requiring confirmation.
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The impact of COVID-19 Pandemic on Domestic Gender Based Violence Against Female HIV and Tuberculosis Patients in Timor-Leste: A Qualitative Study -
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+Abstract: Context: Globally, there is still widespread of violence against women and girls. Timor-Leste reports high prevalence of GBV with 30% women have experienced intimate partner (IPV) or non-partner sexual violence. Several studies reported about the increase of domestic violence gender-based violence (D-GBV) against girls and women worldwide during the COVID-19 pandemic. Aims: To understand whether women living with these two diseases experienced D- GBV during the lockdowns in Timor-Leste. Methods and Material: The study was a qualitative phenomenology design, utilizing purposive sampling technic. Was conducted in eight municipalities from early October 2022 to end of February 2023. It considered eight independent variables to identified the occurrence of D-GBV. Subject 42 in-depth interviews: 19 HIV, 23 TB participants, and 3 FGDs. Data analysis with NVIVO version 12.1. Results: The D- GBV were widely reported from all municipalities. Psychological, socio-economic, verbal, and physical violence were mostly reported. The COVID-19 pandemic exacerbated D- GBV, and impeded participants to apply coping mechanisms in dealing with the violence. Stigma and discrimination were prevalent. The main causes of the violence were economic factors, jealousy, denial, cultural issues, and failure to perform household work. The participants reported using various coping mechanisms to deal with D- GBV: seeking external support or avoidance and staying, facing the perpetrator at home. Conclusions: The triple vulnerabilities (weaknesses of system to combat D-GBV, stigma, discrimination against female TB and HIV patients. It is recommended to train clinician working on D-GBV subject.
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THE EFFECT OF ARGININE AND GLUTAMINE ON COVID-19 PATIENTS OUTCOME: A RANDOMIZED CLINICAL TRIAL - Condition: COVID-19 Intervention: Dietary Supplement: Neomune Sponsors: Universitas Sriwijaya; M. Djamil General Hospital Completed
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Study of Obeldesivir in Children and Adolescents With COVID-19 - Condition: COVID-19 Intervention: Drug: Obeldesivir Sponsor: Gilead Sciences Not yet recruiting
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KAND567 Versus Placebo in Subjects Hospitalized With COVID-19 - Condition: Covid19 Interventions: Drug: KAND567; Drug: Microcrystalline cellulose Sponsor: Kancera AB Terminated
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Aerobic Training for Rehabilitation of Patients With Post Covid-19 Syndrome - Conditions: Post-COVID-19 Syndrome; Long-COVID-19 Syndrome Intervention: Behavioral: Aerobic Exercise Training Sponsors: University of Witten/Herdecke; Verein und Institut für Rehabilitationsforschung Norderney Completed
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A Pilot Clinical Evaluation of Astepro® Nasal Spray for Management of Early SARS-CoV-2 Infection - Condition: COVID-19 Interventions: Drug: Experimental: Primary Cohort; Other: Placebo Comparator: Primary Cohort - Placebo Sponsor: University of Chicago Active, not recruiting
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Digital Health Literacy on COVID-19 for All: Co-creation and Evaluation of Interventions for Ethnic Minorities and Chinese People With Chronic Illnesses in Hong Kong - Conditions: Digital Health Literacy; COVID-19 Intervention: Behavioral: Digital health literacy intervention Sponsor: The Hong Kong Polytechnic University Not yet recruiting
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COVID-19 Vaccination Hesitancy in Adults With Sickle Cell Disease - Conditions: Sickle Cell Disease; COVID-19 Vaccine; Vaccine Hesitancy Intervention: Behavioral: SCD-specific COVID-19 vaccination information (SCVI) video Sponsors: Duke University; American Society of Hematology Not yet recruiting
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Leveraging Community Health Workers to Combat COVID-19 and Mental Health Misinformation in Haiti, Malawi, and Rwanda - Conditions: Mental Health; COVID-19; Misinformation Interventions: Behavioral: Card-Sorting Activity (Pre-intervention design); Behavioral: SMS Crafting (Pre-intervention design); Behavioral: SMS Messaging Sponsors: Harvard Medical School (HMS and HSDM); Partners in Health Active, not recruiting
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Effect of Pulmonary Rehabilitation Among Post-COVID-19 Patients in a Tertiary Care Hospital in Bangladesh - Condition: Pulmonary Pathology Intervention: Behavioral: Pulmonary Rehabilitation Sponsor: Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh Active, not recruiting
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A Study to Learn About New COVD-19 RNA Vaccine Candidates for New Varients in Healthy Individuals - Conditions: SARS-CoV-2 Infection; COVID-19 Intervention: Biological: BNT162b2 (Omi XBB.1.5) Sponsors: BioNTech SE; Pfizer Not yet recruiting
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Randomized, Double-blind, Placebo-controlled Trial of the Efficacy and Safety of Tianeptine in the Treatment of Covid Fog Symptoms in Patients After COVID-19. - Condition: Nervous System Diseases Interventions: Drug: Tianeptine; Drug: Placebo Sponsors: Military Institute od Medicine National Research Institute; ABM Industries Recruiting
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Effects of Cognitive-behavioral Therapy for Insomnia in Nurses With Post Covid-19 Condition - Condition: Cognitive Behavioral Therapy Intervention: Behavioral: cognitive behavioral therapy Sponsor: Tri-Service General Hospital Not yet recruiting
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The Effectiveness of Natural Resources for Reducing Stress - Conditions: Distress, Emotional; COVID-19 Interventions: Combination Product: Balneotherapy plus complex; Combination Product: Combined nature resources treatment; Other: Nature therapy procedure Sponsors: Klaipėda University; Research Council of Lithuania Active, not recruiting
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Study of LAU-7b for the Treatment of Long COVID in Adults - Condition: Long COVID Interventions: Drug: LAU-7b for 3 cycles; Drug: LAU-7b for 1 cycle, then placebo; Other: Placebo for 3 cycles Sponsor: Laurent Pharmaceuticals Inc. Not yet recruiting
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Complementary and Integrative Medicine as an Online Intervention in Patients With Post-covid Syndrome After COVID-19 - Condition: Post-COVID Syndrome Interventions: Behavioral: Complementary and Integrative Medicine online intervention, routine care and book; Behavioral: Routine care and book Sponsor: Charite University, Berlin, Germany Not yet recruiting
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From PubMed
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Pathophysiology and clinical management of coronavirus disease (COVID-19): a mini-review - An unprecedented global pandemic caused by a novel coronavirus named SARS-CoV-2 has created a severe healthcare threat and become one of the biggest challenges to human health and the global economy. As of July 2023, over 767 million confirmed cases of COVID-19 have been diagnosed, including more than 6.95 million deaths. The S protein of this novel coronavirus binds to the ACE2 receptor to enter the host cells with the help of another transmembrane protease TMPRSS2. Infected subjects that can…
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Proton pump inhibitors in critically ill mechanically ventilated patients with COVID-19: protocol for a substudy of the Re-EValuating the Inhibition of Stress Erosions (REVISE) Trial - BACKGROUND: Critically ill patients commonly receive proton pump inhibitors (PPIs) to prevent gastrointestinal (GI) bleeding from stress-induced ulceration. Despite widespread use in the intensive care unit (ICU), observational data suggest that PPIs may be associated with adverse outcomes in patients with COVID-19 infection. This preplanned study is nested within a large randomized trial evaluating pantoprazole versus placebo in invasively ventilated patients. The 3 objectives are as follows:…
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Development of ELISA-Based Assay for Detection of SARS-CoV-2 Neutralizing Antibody - Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulates the plasma B cells to secrete specific antibodies against the viral antigen. However, not all antibodies can prevent the virus from entering the cells. The subpopulation of antibodies which blocks the entry of the virus into host cells is termed neutralizing antibodies (NAbs). The gold standard test for the detection of NAbs is the viral plaque reduction and neutralization test; however, various other methods…
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The natural tannins oligomeric proanthocyanidins and punicalagin are potent inhibitors of infection by SARS-CoV-2 - The Coronavirus Disease 2019 (COVID-19) pandemic continues to infect people worldwide. While the vaccinated population has been increasing, the rising breakthrough infection persists in the vaccinated population. For living with the virus, the dietary guidelines to prevent virus infection are worthy of and timely to develop further. Tannic acid has been demonstrated to be an effective inhibitor of coronavirus and is under clinical trial. Here we found that two other members of the tannins…
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The hope and hype of ellagic acid and urolithins as ligands of SARS-CoV-2 Nsp5 and inhibitors of viral replication - Non-structural protein 5 (Nsp5) is a cysteine protease that plays a key role in SARS-CoV-2 replication, suppressing host protein synthesis and promoting immune evasion. The investigation of natural products as a potential strategy for Nsp5 inhibition is gaining attention as a means of developing antiviral agents. In this work, we have investigated the physicochemical properties and structure-activity relationships of ellagic acid and its gut metabolites, urolithins A-D, as ligands of Nsp5….
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Customizably designed multibodies neutralize SARS-CoV-2 in a variant-insensitive manner - The COVID-19 pandemic evolves constantly, requiring adaptable solutions to combat emerging SARS-CoV-2 variants. To address this, we created a pentameric scaffold based on a mammalian protein, which can be customized with up to 10 protein binding modules. This molecular scaffold spans roughly 20 nm and can simultaneously neutralize SARS-CoV-2 Spike proteins from one or multiple viral particles. Using only two different modules targeting the Spike’s RBD domain, this construct outcompetes human…
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Drug-induced phospholipidosis is not correlated with the inhibition of SARS-CoV-2 - inhibition of SARS-CoV-2 is cell line-specific - Recently, Tummino et al. reported that 34 compounds, including Chloroquine and Fluoxetine, inhibit SARS-CoV-2 replication by inducing phospholipidosis, although Chloroquine failed to suppress viral replication in Calu-3 cells and patients. In contrast, Fluoxetine represses viral replication in human precision-cut lung slices (PCLS) and Calu-3 cells. Thus, it is unlikely that these compounds have similar mechanisms of action. Here, we analysed a subset of these compounds in the viral replication…
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Investigation of the Host Kinome Response to Coronavirus Infection Reveals PI3K/mTOR Inhibitors as Betacoronavirus Antivirals - Host kinases play essential roles in the host cell cycle, innate immune signaling, the stress response to viral infection, and inflammation. Previous work has demonstrated that coronaviruses specifically target kinase cascades to subvert host cell responses to infection and rely upon host kinase activity to phosphorylate viral proteins to enhance replication. Given the number of kinase inhibitors that are already FDA approved to treat cancers, fibrosis, and other human disease, they represent an…
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Azvudine and mortality in patients with coronavirus disease 2019: A retrospective cohort study - CONCLUSION: Our results reveal that in patients with COVID-19, FNC administration was associated with a significantly reduced 28-day mortality.
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Hexamethylene Amiloride Binds the SARS-CoV-2 Envelope Protein at the Protein-Lipid Interface - The SARS-CoV-2 envelope (E) protein forms a five-helix bundle in lipid bilayers whose cation-conducting activity is associated with the inflammatory response and respiratory distress symptoms of COVID-19. E channel activity is inhibited by the drug 5-(N,N-hexamethylene) amiloride (HMA). However, the binding site of HMA in E has not been determined. Here we use solid-state NMR to measure distances between HMA and the E transmembrane domain (ETM) in lipid bilayers. ^(13) C, ^(15) N-labeled HMA is…
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Effectiveness of Bivalent Omicron-Containing Booster Vaccines against SARS-CoV-2 Omicron Variant among Individuals with and without Prior SARS-CoV-2 Infection - In this study, we evaluated the effectiveness of the bivalent mRNA COVID-19 vaccines against the Omicron variant in individuals with or without prior SARS-CoV-2 infection history. We assessed the SARS-CoV-2-specific neutralizing antibody in serum samples by surrogate virus neutralizing assay (sVNT) and determined the serum’s neutralizing capacity against the Omicron BA.5 by a plaque reduction neutralizing test (PRNT50). The results of the sVNT assay demonstrate a higher percentage of inhibition…
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Evaluation of Nafamostat as Chemoprophylaxis for SARS-CoV-2 Infection in Hamsters - The successful development of a chemoprophylaxis against SARS-CoV-2 could provide a tool for infection prevention that is implementable alongside vaccination programmes. Nafamostat is a serine protease inhibitor that inhibits SARS-CoV-2 entry in vitro, but it has not been characterised for chemoprophylaxis in animal models. Clinically, nafamostat is limited to intravenous delivery and has an extremely short plasma half-life. This study sought to determine whether intranasal dosing of nafamostat…
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Interchangeability of the Assays Used to Assess the Activity of Anti-SARS-CoV-2 Monoclonal Antibodies - The recent global COVID-19 pandemic caused by SARS-CoV-2 lasted for over three years. A key measure in combatting this pandemic involved the measurement of the monoclonal antibody (mAb)-mediated inhibition of binding between the spike receptor-binding domain (RBD) and hACE2 receptor. Potency assessments of therapeutic anti-SARS-CoV-2 mAbs typically include binding or cell-based neutralization assays. We assessed the inhibitory activity of five anti-SARS-CoV-2 mAbs using ELISA, surface plasmon…
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Phenothiazines Inhibit SARS-CoV-2 Entry through Targeting Spike Protein - Novel coronavirus disease 2019 (COVID-19), a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has brought an unprecedented public health crisis and continues to threaten humanity due to the persistent emergence of new variants. Therefore, developing more effective and broad-spectrum therapeutic and prophylactic drugs against infection by SARS-CoV-2 and its variants, as well as future emerging CoVs, is urgently needed. In this study, we screened several…
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Clinical Utility of SARS-CoV-2 Antibody Titer Multiplied by Binding Avidity of Receptor-Binding Domain (RBD) in Monitoring Protective Immunity and Clinical Severity - Conventional serum antibody titer, which expresses antibody level, does not provide antigen binding avidity of the variable region of the antibody, which is essential for the defense response to infection. Here, we quantified anti-SARS-CoV-2 antibody binding avidity to the receptor-binding domain (RBD) by competitive binding-inhibition activity (IC50) between SARS-CoV-2 S1 antigen immobilized on the DCP microarray and various RBD doses added to serum and expressed as 1/IC50 nM. The binding…
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From Patent Search
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+ 30 August, 2023
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+Daily-Dose
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The Case for Negotiating with Russia - Samuel Charap is asking Ukraine and its allies to consider how much worse the war could get. - link
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How a Man in Prison Stole Millions from Billionaires - With smuggled cell phones and a handful of accomplices, Arthur Lee Cofield, Jr., took money from large bank accounts and bought houses, cars, clothes, and gold. - link
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The Trump Mug Shot’s Art-Historical Lineage - Assessing the forty-fifth President’s Georgia photo op in the context of Da Vinci, Warhol, and a rogues’ gallery of accused criminals. - link
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Trump’s 2020 Trial Is Set to Dominate the 2024 Primary Season - Jury selection could begin a day before Super Tuesday. - link
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“Braiding Sweetgrass,” and a Lesson in Extreme Heat - Parul Sehgal visits Robin Wall Kimmerer, who set out to bridge the gap between Western science and Indigenous teaching. Plus, Dhruv Khullar looks at extreme heat and the body. - link
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From Vox
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Why Hurricane Idalia is so dangerous, explained in 7 maps -
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+Hurricane Idalia is expected to make landfall on the west coast of Florida on Wednesday morning. | National Hurricane Center
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+Several factors put Idalia on track to rival damage from previous deadly hurricanes.
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+Hurricane Idalia made landfall in Florida on Wednesday morning as a dangerous category 3 storm with wind speeds of 125 miles per hour. Meteorologists are projecting severe impacts along Florida’s Gulf Coast: storm surges of up to 16 feet, several inches of rainfall, and possibly tornadoes. The National Hurricane Center is warning Idalia will bring “catastrophic impacts” and “destructive life-threatening winds.”
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+The potential impacts from Idalia are certainly frightening, but they’re not all that surprising. This region of the world has all the ingredients for a powerful, dangerous, expensive, and destructive hurricane, from extremely warm ocean temperatures that fuel tropical storms to growing coastal populations that are vulnerable to storm surges. And unfortunately, some of these ingredients are becoming more potent as average temperatures rise.
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+Here’s what could turn Idalia into one of the year’s most dangerous storms.
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+Idalia churned over unusually warm ocean water on its path to Florida
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+If there’s one thing a hurricane needs to grow, it’s warm ocean water. And this summer, the Gulf of Mexico and the broader Caribbean have been extremely and anomalously warm. In late July, a buoy off the coast of Florida registered 101.1 degrees Fahrenheit, which is about as warm as the water in a hot tub.
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+As Hurricane Idalia moved north from Cuba toward Florida’s Big Bend region — where the Pan Handle meets the peninsula — it passed over water that’s still unusually hot. Check out the chart below, which shows sea-surface temperature anomalies, measured in Celsius. Darker red indicates regions that are warmer than average.
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+ Climate Change Institute/University of Maine
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+Water in the path of the storm was roughly 1 to 3.5 degrees Fahrenheit warmer than average temperatures this time of year. That provided fuel for Idalia to go through what’s called rapid intensification, which is when a storm’s wind speeds increase by roughly 35 mph or more in less than 24 hours.
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+The chart below shows, more simply, how hot the Atlantic is as of a few days ago. Waters around Tampa, just south of the storm’s center of impact, are currently in the high 80s, according to the National Oceanic and Atmospheric Administration (NOAA).
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+ Climate Change Institute/University of Maine
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+One complicating factor: The world is in an El Niño year, a climate phenomenon that refers to the warm phase of the Pacific Ocean’s temperature cycle.
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+On the one hand, El Niño tends to raise global temperatures. On the other, it usually increases wind shear in the North Atlantic, which can prevent hurricanes from forming. While these forces usually counteract each other to an extent, resulting in an average hurricane season, this year has been so hot that the scales have been nudged in favor of more storms. Earlier this month, forecasters updated their outlook to “an above-normal level of activity” for hurricanes.
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+The hurricane is pushing a huge amount of water inland
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+When a hurricane rams the coast, it usually pushes water inland, causing what’s known as storm surge. It’s often the deadliest part of tropical storms.
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+That’s a major concern with Idalia. Even a few feet of storm surge can sweep away vehicles, yet current forecasts show parts of the Gulf Coast getting surge as high as 16 feet above ground level. This torrent of water can knock out critical infrastructure, inundate roads, spread disease, and cause injuries. And in low-lying areas like Florida’s Gulf Coast, that water can linger for days.
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+Worsening the threat, the forecasted landfall of Idalia lines up with Tampa Bay’s highest tides of the month, meaning even more water could surge inland.
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+The Florida Forgotten Coast and Big Bend are some of the most surge-prone areas in the world. The terrain is essentially flat inland a long way from the coast. The NHC’s storm surge maps for a category 4 hurricane show the potential for 6-9+ feet of surge 10 miles inland. #Idaliapic.twitter.com/eroXuswtfD
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+Idalia is striking an area still recovering from another storm
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+Hurricane Ian, which struck Florida last year, became the deadliest storm in the state since 1935, killing at least 149 people. It landed on Florida’s Gulf Coast at Category 4 strength and drove a storm surge as high as 18 feet; the surge alone was blamed for 41 deaths. The storm also dumped more than 25 inches of rain in some areas, only adding to the flooding.
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+Hurricane Ian was remarkably destructive too, damaging more than 52,000 structures. The storm’s price tag ultimately amounted to an estimated $109 billion, making it the costliest hurricane in Florida history.
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+NOAA
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+Hurricane Ian drenched parts of Florida with more than 26 inches of rain.
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+The damage displaced a number of residents who have still not returned home, and many Floridians are still waiting for insurance payouts. Some areas, meanwhile, are still clearing debris, while others are filled with buildings waiting to be demolished.
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+Now Idalia is threatening a similar region. Although the eye of the storm will make landfall north of where Ian struck, the zone of impact will at least partially overlap with Ian’s, compounding the impacts of the prior storm.
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+National Hurricane Center
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+Hurricane Idalia is heading for the same region struck by Hurricane Ian.
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+Florida’s population is highest in its most vulnerable areas
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+More than three-quarters of people in Florida live along the coast. Coastal regions also have some of the fastest growth rates in the state. Between 2010 and 2020, the Tampa-St. Petersburg area grew by more than 365,000 people, according to the Florida Department of Transportation.
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+Wikimedia Commons
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+Some of Florida’s most densely populated regions are along its coastline.
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+This means that as Idalia makes landfall, more people and property will be in the path of destruction.
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+Update, August 30, 7:50 am ET: This story was originally published on August 29 and has been updated with new information about Hurricane Idalia’s location and strength.
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America’s unique, enduring gun problem, explained -
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+A man views rifles for sale in Carpentersville, Illinois. | John J. Kim/Chicago Tribune/Tribune News Service/Getty Images
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+The factors that lead to tragedies like the UNC-Chapel Hill shooting are deeply ingrained in US politics, culture, and law.
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+A grad student accused of shooting and killing a faculty member at the University of North Carolina at Chapel Hill on August 28 has been arrested and charged with first-degree murder and possessing a gun on an education property.
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+The faculty member was the grad student’s adviser, Zijie Yan, an associate professor in the department of Applied Physical Sciences. It’s not yet clear what the shooter’s motivation may have been. Police are still searching for the weapon used in the attack and have not determined whether it was obtained legally.
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+It’s one of dozens of school shootings this year alone, and comes just after another high-profile shooting in Jacksonville, Florida, where the shooter appeared to first try to target Edward Waters University, a historically Black university, before opening fire at Black victims in a Dollar General store instead.
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+This kind of violence is unique to the US and should not be normalized.
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+No other high-income country has suffered such a high death toll from gun violence. Every day, 120 Americans die at the end of a gun, including suicides and homicides, an average of 43,375 per year. According to the latest available analysis of data from 2015 to 2019,the US gun homicide rate was 26 times that of other high-income countries; its gun suicide rate was nearly 12 times higher. Mass shootings, defined as attacks in which at least four people are injured or killed excluding the shooter, have been on the rise since 2015, peaking at 686 incidents in 2021. There have been 476 mass shootings in the US in 2023 as of late August, and at the current pace, the US is set to eclipse the 2021 record this year.
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+Despite that sheer carnage, however, the political debate over how to ensure that guns don’t fall into the hands of people who may hurt themselves and others — such as the UNC shooter — has long proved intractable. Last year,Congress reached a deal on limited gun reforms for the first time in nearly 30 yearsin the wake of a shooting at an elementary school in Uvalde, Texas — the deadliest school shooting since 2012.
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+But those narrow reforms clearly haven’t stopped America’s gun violence epidemic. The US’s expansive view of civilian gun ownership has been so ingrained in politics, in culture, and in the law since the nation’s founding that there’s no telling how many more people will die before federal lawmakers take further action. In that absence, many red states have loosened their gun laws over the last few years, rather than making it harder to obtain a gun.
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+“America is unique in that guns have always been present, there is wide civilian ownership, and the government hasn’t claimed more of a monopoly on them,” said David Yamane, a professor at Wake Forest University who studies American gun culture.
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+The US has a lot of guns, and more guns mean more gun deaths
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+It’s hard to estimate the number of privately owned guns in America since there is no countrywide database where people register whether they own guns, there is a thriving black market for them in the absence of strong federal gun trafficking laws, and people can manufacture their own guns with DIY kits or 3D printers. The gun lobby has also vehemently opposed federal legislation to track gun sales and establish a national handgun registry.
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+One estimate from the Small Arms Survey, a Swiss-based research project, found that there were approximately 390 million guns in circulation in the US in 2018, or about 120.5 firearms per 100 residents. That number has likely climbed in the years since, given that one in five households purchased a gun during the pandemic, though the 2018 estimate remains the most recent available. There has also been a significant increase in the number of guns manufactured and imported in the years since. But even without accounting for that increase, US gun ownership is still well above any other country: Yemen, which has the world’s second-highest level of gun ownership, has only 52.8 guns per 100 residents; in Iceland, it’s 31.7.
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+ Scott Olson/Getty Images
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+A makeshift memorial set up for the victims of the Club Q nightclub shooting in Colorado Springs that happened on November 19, 2022.
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+American guns are concentrated in a tiny minority of households: just 3 percent own about half the nation’s guns, according to a 2016 Harvard and Northeastern University study. They’re called “super owners” who have an average of 17 guns each. Gallup, using a different methodology, found that45 percent of Americans lived in a household with guns in 2022.
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+Researchers have found a clear link between gun ownership in the US and gun violence, and some argue that it’s causal. One 2013 Boston University-led study, for instance, found that for each percentage point increase in gun ownership at the household level, the state firearm homicide rate increased by 0.9 percent. And states with weaker gun laws have higher rates of gun-related homicides and suicides, according to a study by the gun control advocacy group Everytown for Gun Safety.
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+The link between gun deaths and gun ownership is much stronger than the link thatgun rights advocates often seek to drawbetween violence and mental health issues. If it were possible to cure all schizophrenia, bipolar, and depressive disorders, violent crime in the US would fall by only 4 percent, according to a study from Duke University professor Jeffrey Swanson, who examines policies to reduce gun violence.
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+There’s still a pervasive idea, pushed by gun manufacturers and gun rights organizations like the National Rifle Association, that further arming America is the answer to preventing gun violence — the “good guy with a gun” theory. But there have been relatively few instances in which police or armed bystanders have been able to successfully stop an active attack.
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+According to a database maintained by Advanced Law Enforcement Rapid Response Training Center at Texas State University, there were 520 active attacks — defined as when one or more people are “actively killing or attempting to kill multiple unrelated people in a public space,” including but not limited to shootings — between 2000 and 2022. In many of those cases, police were unable to stop the attacker, either because the attack had already ended by the time they arrived or because the attacker surrendered or committed suicide. Only in 160 cases were police able to successfully intervene by shooting or otherwise subduing the attacker.
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+Another 2021 study from Hamline University and Metropolitan State University found that the rate of deaths in 133 mass school shootings between 1980 and 2019 was 2.83 times greater in cases where there was an armed guard present. The researchers argue the results suggest the presence of an armed guard increased shooters’ aggression and that because many school shooters have been found to be suicidal, “an armed officer may be an incentive rather than a deterrent.”
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+“The idea that the solution to mass shootings is that we need more guns in the hands of more people in more places so that we’ll be able to protect ourselves — there’s no evidence that that’s true,” Swanson said.
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+The prevalence of the self-defense narrative is part of what sets apart the gun rights movement in the US from similar movements in places like Canada and Australia, according to Robert Spitzer, a professor at SUNY Cortland who studies the politics of gun control.
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+Self-defense has become by far the most prominent reason for gun ownership in the US today, eclipsing hunting, recreation, or owning guns because they’re antiques, heirlooms, or work-related. That’s also reflected in ballooning handgun sales, since the primary purpose of those guns isn’t recreational, but self-defense.
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+American gun culture “brings together the hunting-sporting tradition with the militia-frontier tradition, but in modern times the hunting element has been eclipsed by a heavily politicized notion that gun carrying is an expression of freedom, individuality, hostility to government, and personal self-protection,” Spitzer said.
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+ Chandan Khanna/AFP via Getty Images
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+People gather at Sacred Heart Catholic Church to pray for the victims of the mass shooting at Robb Elementary School in Uvalde, Texas, on May 25, 2022.
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+That culture of gun ownership in the US has made it all the more difficult to explore serious policy solutions to gun violence after mass shootings. In high-income countries lacking that culture, mass shootings have historically galvanized public support behind gun control measures that would seem extreme by US standards.
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+Canada banned military-style assault weapons two weeks after a 2020 mass shooting in Nova Scotia. In 2019, less than a month after the Christchurch massacre, New Zealand lawmakers passed a gun buyback scheme, as well as restrictions on AR-15s and other semiautomatic weapons, and they later established a firearms registry. The 1996 Port Arthur massacre in Australia spurred the government to buy back 650,000 firearms within a year, and murders and suicides plummeted as a result.
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+By contrast, nearly a decade went by after the 2012 school shooting at Sandy Hook Elementary School in Newtown, Connecticut, before Congress passed a new gun control law. The Bipartisan Safer Communities Act, the law passed in June 2022, was relatively limited:It incentivized states to pass red flag laws, enhanced background checks for gun buyers under 21, and closed the “boyfriend loophole,” which allowed some people with domestic violence convictions to purchase guns. But it did not ban any types of weapons, and certain studies suggest that even truly universal background checks may have limited effects on gun violence.
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+At the same time, many states have sought to expand gun ownership in recent years. At least 27 states have now passed laws allowing residents to carry a handgun without a permit and allow school staff and teachers to carry guns on campus.
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+“Other countries look at this problem and say, ‘People walking around in the community with handguns is just way too dangerous, so we’re going to broadly limit legal access to that and make exceptions on the margins for people who might have a good reason to have a gun,’” Swanson said. “Here we do just the opposite: We say that, because of the way that the Supreme Court interpreted the Second Amendment, everybody has the right to a gun for personal protection, and then we tried to make exceptions for really dangerous people, but we can’t figure out who they are.”
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+While the majority of Americans support more gun control restrictions, including universal background checks, a vocal Republican minority unequivocally opposes such laws — and is willing to put pressure on GOP lawmakers to do the same. Alongside the NRA, and a well-funded gun lobby, this contingent of voters sees gun control as a deciding issue, and one that could warrant a primary challenge for a lawmaker who votes for it.
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+The gun lobby has the advantage of enthusiasm. “Despite being outnumbered, Americans who oppose gun control are more likely to contact public officials about it and to base their votes on it,” Barnard College’s Matthew Lacombe explained in 2020. “As a result, many politicians believe that supporting gun regulation is more likely to lose them votes than to gain them votes.”
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+ Sarah Reingewirtz/MediaNews Group/Los Angeles Daily News via Getty Images
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+Mourners honor the victims of the January 27, 2023, Monterey Park, California, mass shooting.
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+The Supreme Court has made it impossible to cure America’s gun violence epidemic
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+In 2008, the Supreme Court effectively wrote NRA CEO Wayne LaPierre’s “good guy with a gun” theory into the Constitution. The Court’s 5-4 decision inDistrict of Columbia v. Heller (2008) was the first Supreme Court decision in American history to hold that the Second Amendment protects an individual right to possess a firearm. But it also went much further than that.
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+Heller held that one of the primary purposes of the Second Amendment is to protect the right of individuals — good guys with a gun, in LaPierre’s framework — to use firearms to stop bad guys with guns. As Justice Antonin Scalia wrote in Heller, an “inherent right of self-defense has been central to the Second Amendment right.”
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+We don’t need to guess why the Second Amendment protects a right to firearms because it is right there in the Constitution. The Second Amendment’s purpose is to preserve “a well-regulated Militia,” not to allow individuals to use their weapons for personal self-defense.
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+For many years, the Supreme Court took the first 13 words of the Second Amendment seriously. As the Court said inUnited States v. Miller(1939), the “obvious purpose” of the Second Amendment was to “render possible the effectiveness” of militias. And thus the amendment must be “interpreted and applied with that end in view.” Heller abandoned that approach.
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+Heller also reached another important policy conclusion. Handguns, according to Scalia, are “overwhelmingly chosen” by gun owners who wish to carry a firearm for self-defense. For this reason, he wrote, handguns enjoy a kind of super-legal status. Lawmakers are not allowed to ban what Scalia described as “the most preferred firearm in the nation to ‘keep’ and use for protection of one’s home and family.”
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+This declaration regarding handguns matters because this easily concealed weapon is responsible for far more deaths than any other weapon in the United States — and it isn’t close. In 2021, for example, a total of 14,616 people were murdered in the US, according to the FBI. Of these murder victims, at least 5,992 — just over 40 percent — were killed by handguns.
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+ Allison Dinner/AFP via Getty Images
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+A woman holds a photo of Nevaeh Bravo, who was killed in the mass shooting at Robb Elementary School, during a vigil for the victims in Uvalde, Texas, on May 25, 2022.
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+Last year, the Supreme Court made it even harder for federal and state lawmakers to combat gun violence. In its decision inNew York State Rifle & Pistol Association v. Bruen, it massively expands the scope of the Second Amendment, abandons more than a decade of case law governing which gun laws are permitted by the Constitution, and replaces this case law with a new legal framework that, as Justice Stephen Breyer writes in dissent, “imposes a task on the lower courts that judges cannot easily accomplish.”
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+Bruen has since allowed handguns — which are responsible for the overwhelming majority of gun murders in the United States — to proliferate on many American streets. That’s because Bruen strikes the types of laws that limit who can legally carry handguns in public, holding that “the Second and Fourteenth Amendments protect an individual’s right to carry a handgun for self-defense outside the home.” Amid a flurry of activity in the courts over the last year, more than a dozen state and federal gun control laws have been invalidated in whole or in part as a result.
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+Under this new legal regime, the future of firearm regulation looks grim for anyone who believes that the government should help protect us from gun violence.
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+Update, August 29, 5:30 pm ET: This story was originally published on May 26, 2022, and has been updated multiple times, most recently with details from the August 28 shooting at UNC Chapel Hill.
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Did Israel’s national security minister just admit to apartheid policies? -
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+A Palestinian woman stands near an Israeli army checkpoint on October 13, 2021, near Bait A’wa village on the outskirts of the West Bank city of Hebron. | Hazem Bader/AFP via Getty Images
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+With “Sorry, Mohammad,” Ben-Gvir goes viral.
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+The State of Israel has occupied the Palestinian territory of the West Bank, Gaza, and East Jerusalem since the 1967 war. The Palestinians living in those territories quite simply do not have the same rights as Israeli settlers there. For instance, it’s rare for the Israeli state to grant Palestinians building permits even as settlements expand.
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+Israeli leaders rarely articulate in clear terms that separate legal systems rule over Israeli settlers and Palestinians in the same area. To do so would be to recognize the split realities, which Palestinian, Israeli, and international human rights groups have documented as apartheid. But Israeli politicians have preferred to obscure this reality.
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+That is, until an incendiary settler-politician serving in the extreme-right Israel government caused a stir in Israel last week when he described the situation almost exactly as human rights groups have — not accidentally, as a slip of the tongue, but very much on purpose.
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+“My right, the right of my wife and my children to move around Judea and Samaria” — the biblical names for the West Bank — “is more important than freedom of movement for the Arabs,” National Security Minister Itamar Ben-Gvir told Israel’s version of Meet the Press. “My right to life comes before freedom of movement.”
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+“Sorry, Mohammad, but that’s the reality,” Ben-Gvir paused to say, turning to a member of the TV panel, journalist Mohammad Magadli, who is a Palestinian citizen of Israel.
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+Ben-Gvir justified the intensive security regime at a time of a growing grassroots Palestinian movement willing to violently resist the Israeli state, and as settler violence against Palestinians has spiked.
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+That clip quickly traveled around the internet. Ben-Gvir’s disparaging aside — “Sorry, Mohammad” — became a meme. One Israeli editor wrote that “Sorry, Mohammad,” would be a “fitting name for the Israeli national anthem.” The prominent Israeli human rights organization B’Tselem started posting violent videos and photos of the Israeli occupation captioned with the words “Sorry, Mohammad.” Some accounts began posting historical photos of racism and discrimination — from the Jim Crow years, apartheid-era South Africa and Nazi Germany — with those words. (Some posts appear to have been removed or deleted for violating social media terms of service.)
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+Because Ben-Gvir’s tone may have seemed provocative, but what he stated on TV is actually just the policy of the State of Israel.
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+The controversy over Ben-Gvir’s remarks, briefly explained
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+Ben-Gvir’s statement caused a backlash. The US State Department spokesperson condemned his remarks. And two days later, Netanyahu’s office weighed in on the social media platform X, formerly known as Twitter, to undo the damage.
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+“Israel allows maximum freedom of movement in Judea and Samaria for both Israelis and Palestinians,” the statement said. “Unfortunately, Palestinian terrorists take advantage of this freedom of movement to murder Israeli women, children and families by ambushing them at certain points on different routes.”
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+ Emmanuel Dunand/AFP via Getty Images
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+Two Palestinian women approach a checkpoint to cross into the Israeli-controlled Shuhada Street in the divided town of Hebron, in the Israeli-occupied West Bank, on January 13, 2020.
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+“This is what Minister Ben-Gvir meant when he said ‘the right to life precedes freedom of movement’,” the prime minister’s office went on to explain.
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+New grassroots Palestinian militant groups and individual acts of terrorism have increased this year. But it has also been an exceedingly deadly year for Palestinians in the West Bank. Under Netanyahu’s government, settlers have been emboldened, leading to more settler violence, the further annexation of Palestinian land, and settlement expansion. That encroachment has in turn fueled violent Palestinian resistance. This dynamic creates situations like one earlier this summer, when an Israeli military raid in Jenin killed 12 Palestinians, seemingly leading to a retaliatory Palestinian shooting of four Israelis near a settlement, which then led to more settler violence against Palestinians, all within three days.
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+Netanyahu, then, was not so much condemning Ben-Gvir’s policy stance as his tone.
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+Israeli attorney Daniel Seidemann pointed out that Netanyahu’s team posted on X on Friday evening after sunset, that is during the Jewish sabbath when Ben-Gvir and his colleagues from the Jewish Power Party would likely be offline. “He posted it only in English, not in Hebrew, so as not to anger his base,” Seidemann explained.
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+And when Ben-Gvir got online after sunset on Saturday, he stood by his comments. “Not only do I not regret my words, I am saying them yet again,” he said, with an Israeli flag behind him and Netanyahu’s official portrait sitting on the bookshelf.
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+Itamar Ben Gvir does not apologize for his Jewish Supremacist comments when he said that Jews rights are more important than Arabs’ rights. In fact he doubles down and repeats exactly what he said last night. Ben Gvir is a prize to BDS. pic.twitter.com/xEYTs6M4aB
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+Amichai Eliyahu, Israel’s minister of heritage and a member of Ben-Gvir’s party, added another example to the genre on Sunday.
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+“As soon as someone threatens my rights to live, I slightly reduce his civil rights,” he said in a TV segment.
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+“Limit just a tiny bit?” TV anchor Attila Somfalvi responded. “It’s called apartheid, I think, in the dictionary.”
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+What Ben-Gvir’s comments really reveal
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+Ben-Gvir is not only any ordinary provocateur shaped by the racist ideology of the late Rabbi Meir Kahane. He is not just a lawyer who has represented Jewish terrorists who have killed Palestinians. He is a powerful minister in Israel’s far-right government.
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+Now he has laid plain what Palestinians endure every day. They lack rights so that settlers like Ben-Gvir can move freely through the occupied West Bank. Palestinians and Israeli settlers travel on separate roads in the territory; they are subject to different legal systems. “The elevation of Jewish rights to move (and most civil and human rights) over Palestinian freedom of movement (and other rights) is as old as the state itself,” Dahlia Scheindlin notes in the Israeli newspaper Haaretz.
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+Netanyahu has advanced a controversial overhaul of the Israeli judiciary that, among other issues, would enable policies of further annexation of Palestinian land. The ethno-nationalist partners in the governing coalition support such bureaucratic measures. In particular, the government’s recent moves of “transferring many powers overseeing the West Bank from military to civilian leaders—in contravention of international law,” as Israeli lawyer Michael Sfard notes, openly advance “a policy of unilateral annexation.”
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+In 2017, Bezalel Smotrich, now Netanyahu’s finance minister, published a radical manifesto entitled “Israel’s Decisive Plan” that advocates the expulsion of Palestinians who seek an independent state. His self-described “pragmatic document” also detailed how to further advance the settlements and illegal outposts, what he calls “Victory Through Settlement.”
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+For Palestinians, none of these comments come as a surprise. This is the reality of the occupied territories. But it’s somehow clarifying for Ben-Gvir to say them aloud — and shows that Netanyahu’s most extreme coalition partners are operating from a place of comfort.
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From The Hindu: Sports
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TNCA President’s XI goes down without a fight -
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A lot depends on nutrition and strength for athletes, says Dr. Aashish Contractor -
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U.S. Open | Alcaraz gets easy start to title defence, Medvedev advances - Seven-time Grand Slam winner Venus Williams lost 6-1 6-1 to Belgian qualifier Greet Minnen in her 100th U.S. Open match
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Bangladesh wicketkeeper-batter Litton Das ruled out of entire Asia Cup due to illness - Das could not recover from a viral fever, and he did not travel to Sri Lanka whom Bangladesh face in their opening match on Thursday; Anamul Haque Bijoy named as replacement
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Buttler welcomes ‘superstar’ Stokes back into England ODI fold - Stokes played a pivotal role in England’s 2019 World Cup triumph, scoring an unbeaten 84 in the final against New Zealand
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From The Hindu: National News
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RJD MP Manoj Jha says DU cancelled his lecture planned for Sept 4 - Mr. Jha received an e-mail from Delhi University on August 30 informing that the lecture has been cancelled due to “unavoidable circumstances”
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Reprieve for actors Shane Nigam, Sreenath Bhasi - The two agree not to create problems at shooting locations
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Here are the big stories from Karnataka today - Welcome to the Karnataka Today newsletter, your guide from The Hindu on the major news stories to follow today. Curated by Nalme Nachiyar.
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Baseless allegations: Pralhad Joshi flays Rahul over his claim about China usurped India’s land - He said “whatever land that China has grabbed was during the tenure of Jawaharlal Nehru”.
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Former Karnataka chief minister H.D. Kumaraswamy hospitalised - The JD(S) leader arrived at Apollo Specialty Hospital in Jayanagar around 3:40 am on August 30, complaining of weakness and discomfort in limbs.
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From BBC: Europe
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Russia’s kamikaze drones raining down on Ukraine’s east - The BBC’s Quentin Sommerville witnesses Russia’s increasingly sophisticated drone attacks.
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Ukraine war: Wave of drone strikes hits several Russian regions - Moscow says military planes were damaged in strikes on an airport and vows Ukraine will “not go unpunished”.
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Nagorno-Karabakh: ‘People are fainting queuing up for bread’ - Azerbaijan’s nine-month blockade of disputed territory Nagorno-Karabakh takes its toll on residents.
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Brexit: EU-derived equal pay protections to be brought back - Women will keep the right to the same pay as men doing similar jobs in what Labour says is a government U-turn.
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Prigozhin buried in private funeral - Wagner chief’s press service - The mercenary group boss, who led June’s aborted armed rebellion, was killed in a plane crash last week.
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From Ars Technica
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Fairphone 5 sets a new standard with 8-10 years of Android support - The Fairphone 5 will keep on trucking until at least 2031. - link
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The 10 drugs up for Medicare price negotiation have seen steep price hikes - Much of the drugs’ costs are due to repeated price hikes over the years. - link
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After Musk’s mass layoffs, X says it’s expanding safety and election teams - X, née Twitter, greenlights wider range of political advertising. - link
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Google’s $30-per-month “Duet” AI will craft awkward emails, images for you - Google’s new kitchen-sink AI branding is everything to everyone in every Workspace app. - link
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iFixit tears down a McDonald’s ice cream machine, demands DMCA exemption for it - Public Knowledge and iFixit want the right to repair commercial kitchen gear. - link
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From Jokes Subreddit
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A guy goes into a store and tells the clerk, “I’d like some Polish sausage.” The clerk looks at him and says, “Are you Polish?” -
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+The guy, clearly offended, says, ““Well, yes I am. But let me ask you something. If I had asked for Italian sausage would you ask me if I was Italian? Or if I had asked for German bratwurst, would you ask me if I was German? Or if I asked for a kosher hot dog would you ask me if I was Jewish? Or if I had asked for a taco would you ask if I was Mexican? Would ya, huh? Would ya?”
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+The clerk says, “Well, no.”
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+With deep self-righteous ndignation, the guy says, “Well, all right then, why did you ask me if I’m Polish just because I ask for Polish sausage?”
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+The clerk replies, “Because this is Home Depot.”
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A man seeks cover in a cabin from the winter storm. -
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Very NSFW!
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Allright, so this is a story from Norway.
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It is a dark night in the winter. A small cabin is barely visible through the snow drift. A lone man, the cabin owner, sits in front of the fireplace. What little light there is comes from the fireplace and a few dim candles.
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Suddenly there is a knock on the door. In enters a man half frozen to death by the cold and the wind.
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In tradition with the local rules of the mountain, the guest is offered dry clothes and a hot meal.
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Hours pass, and bedtime is approaching. The cabin owner has to guard the fire, so the guest is offered his bed in the bedroom. With strict instructions not to bother his wife, who’s resting in a different bed in the same room.
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Next morning, the two are having breakfast. Suddenly, the cabin owner stares sternly at the guest. “You did bother my wife, didn’t you?” asks the cabin owner. The guest responds with “No! No! Absolutely not!”. For a brief moment the cabin owner settles down, before he again cries out “Yes! Yes! You did bother my wife!”. “Allright, Yes! Yes, I did” admits the guest. “But, how can you tell?” he asks the cabin owner. A few dead quiet seconds pass, then the cabin owner responds “Well, she’s been dead for 6 weeks, and you have larvae in your beard”.
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Note: In the mountainous parts of Norway, without road access or passable paths for horses, anyone who died during the winter was laid to rest in the crawl space beneath the cabin. When the snow thawed, the body was brought to the parish church, so it could be buried in consecrated ground. This story, or folk tale, is based on this practise.
A man is sitting at a bar at closing time, complaining to his friend. -
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+How is it I always get in trouble with my wife for staying at the bar so late and you never get in trouble with your wife? When I come home from a night out, I do everything so quietly. I turn off my car and coast into the driveway. I sneak in the basement door. I take off my clothes in the basement and tiptoe into the bedroom. I get in bed very slowly and quietly. My wife always wakes up and yells at me and won’t talk to me the next day.
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+His friend looks at him and says you’re doing it all wrong. Before I leave the bar, I always buy a shot and pour it on myself even if I haven’t been drinking. I screech into the driveway and come in through the front door, closing it loudly. I strip right next to the bed and climb in. Then I pat my wife on the butt and say, “How ‘bout it babe?” She always pretends she’s asleep.
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+He knows his wife don’t like it when he drinks, so he sneaks his way to the bathroom so he can piss. When he opens the bathroom door, the light automatically turns on. He finds it odd, since he didn’t buy any automated lights or something like that. He thinks that maybe his wife had installed the lights while he was in the bar, but it would be improbable for him to not see that she bought them. He thinks that maybe he entered the wrong house, but quickly looks outside the bathroom to see that this wasn’t the case. He thinks that maybe he was getting crazy, but thinking about this gave him goosebumps. In the end, he concludes that he is too drunk to think anything, so he piss and goes to sleep. He enters his room, lay in the bed with his wife, and tries to sleep, but the mistery of how his bathroom had an automatic light was too much for him, so he wakes up his wife to ask her. After explaining what happened, his wife, who had a sleepy and confused face at first, puts on a really angry face and start yelling at him: “YOU DRUNK BASTARD, DID YOU PISS IN THE FRIDGE AGAIN?”
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+and then the Greeks improved it by removing the sheep and adding lubrication.
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+The Romans perfected it by discovering that you could have it with women too, then the French ruined it by adding misogynistic condescension, and the British made it worse by adding shame; after that, the Americans made it terrible by making it a commodity.
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+And finally the fucking furries ruin it by putting the sheep back in!
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Climate Change Institute/University of Maine
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Climate Change Institute/University of Maine
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National Hurricane Center
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Scott Olson/Getty Images
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Chandan Khanna/AFP via Getty Images
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