diff --git a/archive-covid-19/17 April, 2021.html b/archive-covid-19/17 April, 2021.html new file mode 100644 index 0000000..25c66db --- /dev/null +++ b/archive-covid-19/17 April, 2021.html @@ -0,0 +1,208 @@ + +
+ + + ++Background. The US Food and Drug Administration authorized Convalescent Plasma (CCP) therapy for hospitalized COVID-19 patients with via the Expanded Access Program (EAP) and the Emergency Use Authorization (EUA), leading to its use in some 500,000 patients during the first year of the pandemic. Methods. We tracked the number of CCP units dispensed to hospitals by blood banking organizations and correlated that usage with hospital admission and mortality data over the course of the year. Results. CCP usage per admission peaked in Fall 2020, with > 40% of inpatients estimated to have received CCP between late September and early November 2020. However, after randomized controlled trials failed to show a reduction in mortality, usage/admissions declined steadily to a nadir of < 10% in March 2021. We found a strong inverse correlation (Pearsons correlation coefficient of -0.52 with P = 0.002) between CCP usage/hospital admission and deaths occurring two weeks after admission, and this finding was robust to examination of deaths taking place one, two or three weeks after admission. Changes in the number of hospital admissions, prevalence of variants, and age of patients could not explain these findings. The retreat from CCP usage might have resulted in as many as 29,000 excess deaths from mid-November 2020 to February 2021. Conclusions. A strong inverse correlation between CCP use and mortality per admission in the USA provides population level evidence consistent the notion that CCP reduces mortality in COVID-19 and suggests that the recent decline in usage could have resulted in excess deaths. +
++Purpose: To report on the impact of the COVID-19 outbreak on eating habits and sedentary behavior among adolescents with multiple chronic conditions (n=347) from a tertiary, referral hospital vs. healthy peers. Methods: This observational study was conducted in Sao Paulo (Brazil) between July and October 2020, period in which a set of social distancing measures to contain the pandemic. Results: The main findings of this study were that adolescents with chronic conditions showed important changes in eating habits (e.g., less often consumption of convenience foods and more often eating in front of television than before quarantine). Also, 86.8% of adolescents with chronic conditions reported increasing screen time during pandemic. No major differences were observed between patients and controls. Conclusions: Adolescents with chronic conditions exposed to pandemic showed substantial changes in lifestyle, stressing the need for specific care to mitigate poor eating habits and excessive sedentary behavior in this group. +
++The number of new daily SARS-CoV-2 infections experienced an abrupt increase during the last quarter of 2020 in almost every European country. The phenomenological explanation offered was a new mutation of the virus, first identified in the UK. We use publicly available data in combination with a time-delayed controlled SIR model, which captures the effects of preventive measures and concomitant social response on the spreading of the virus. The model, which has a unique transmission rate, enables us to reproduce the waves of infection occurred in the UK. This suggests that the new SARS-CoV-2 UK variant is as transmissible as previous strains. Our findings reveal that the sudden surge in cases was in fact related to the relaxation of preventive measures and social awareness. We also simulate the combined effects of restrictions and vaccination campaigns in 2021, demonstrating that lockdown policies are not fully effective to flatten the curve; fully effective mitigation can only be achieved via a vigorous vaccination campaign. As a matter of fact, incorporating recent data about vaccine efficacy, our simulations advocate that the UK might have overcome the worse of the CoVid-19 pandemic, provided that the vaccination campaign maintains a rate of approximately 140k jabs per day. +
++Background: Little is known about the comparative kinetics of SARS-CoV-RNA load in the lower respiratory tract and in blood compartment in patients admitted to the intensive care unit, and how these relate to biomarkers of COVID-19 severity. Methods: Seventy-three consecutive critically ill COVID-19 patients (median age, 65 years) were recruited. Serial lower respiratory tract (n=165) and plasma (n=340) specimens were collected. RT-PCR and lateral flow immunochromatography assay were used for SARS-CoV-2 RNA quantitation and N protein detection in plasma, respectively. Serum levels of inflammatory and tissue-damage biomarkers in paired specimens were analyzed. Results: SARS-CoV-RNA was detected in the lower respiratory tract of most patients (92%). Viral RNAemia and N-antigenemia were documented in 35.6% and 40.1% of patients, respectively. Viral RNAemia and N-antigenemia cleared at a faster rate than SARS-CoV-2 RNA in tracheal aspirates (TA). SARS-CoV-2 RNA load was higher (P<0.001) in TA than in plasma, and correlated significantly (Rho, 0.41; P<0.001). A modest correlation was found between SARS-CoV-2 RNA load in TA and plasma and levels of ferritin and lactose dehydrogenase (Rho≤0.3; P≤0.008) in paired serum specimens. Neither the dynamics of SARS-CoV-2 RNA load in TA and plasma, nor N-antigenemia detection rate differed between surviving and deceased patients. Yet, a trend towards a higher mortality was seen in patients with viral RNAemia (OR; 2.82; 95% CI, 0.94-8.47; P=0.06). +
++Serological testing for anti-SARS-CoV-2 antibodies is used to detect ongoing or past SARS-CoV-2 infections. To study the kinetics of anti-SARS-CoV-2 antibodies and to assess the diagnostic performances of eight serological assays, we used 129 serum samples collected on known days post symptom onset (dpso) from 42 patients with PCR-confirmed COVID-19 and 54 serum samples from healthy blood donors, and children infected with seasonal coronaviruses. The sera were analyzed for the presence of IgG, IgM and IgA antibodies using indirect immunofluorescence testing (IIFT) based on SARS-CoV-2-infected cells. They were further tested for antibodies against the S1 domain of the SARS-CoV-2 spike protein (IgG, IgA) and against the viral nucleocapsid protein (IgG, IgM) using ELISA. The assay specificities were 94.4%-100%. The sensitivities varied largely between assays, reflecting their respective purposes. The sensitivities of IgA and IgM assays were highest between 11 and 20 dpso, whereas the sensitivities of IgG assays peaked between 20 and 60 dpso. IIFT showed highest sensitivities due to the use of the whole SARS-CoV-2 as substrate and provided information whether or not the individual has been infected with SARS-CoV-2. ELISAs provided further information about both the prevalence and concentration of specific antibodies against selected antigens of SARS-CoV-2. +
++Background: Acute respiratory distress syndrome (ARDS) in COVID-19 has been associated with dysregulated immune responses leading to catastrophic inflammation. The activation pathways remain to be fully elucidated. We investigated the ability of circulating to induce dysregulated immune responses. Materials & Methods: Calprotectin and high mobility group box 1 (HMGB1) were associated with ARDS in 60 COVID-19 patients. In a second cohort of 40 COVID-19 patients calprotectin at hospital admission was associated with serum levels of soluble urokinase plasminogen activator receptor (suPAR). A COVID-19 animal model was developed by intravenous injection of plasma from healthy volunteers or patients with COVID-19 ARDS into C57/BL6 mice once daily for 3 consecutive days. In separate experiments, mice were treated with a) the IL-1 receptor antagonist Anakinra or vehicle and b) Flo1-2a anti-murine anti-IL-1α monoclonal antibody or the specific anti-human IL-1α antibody XB2001, or isotype controls. Mice were sacrificed on day 4. Cytokines and myeloperoxidase (MPO) in tissues were measured. Results: Calprotectin, but not HMGB1, was elevated ARDS. Higher suPAR readouts indicated higher calprotectin levels. CHallenge of mice with COVID-19 plasma led to inflammatory reactions in murine lung and intestines as evidenced by increased levels of TNFα, IL-6, IFNγ and MPO. Anakinra treatment brought these levels down. Similar decrease was found in mice treated with Flo1-2a but not with XB2001. Conclusion: Circulating alarmins, specifically calprotectin, of critically ill COVID-19 patients induces tissue-specific inflammatory responses through an IL-1α mediated mechanism. This could be attenuated through inhibition of IL-1 receptor or specific inhibition of IL-1α. +
++The infectiousness and presymptomatic transmission of SARS-CoV-2 hinder pandemic control efforts worldwide. Therefore, the frequency of testing, accessibility, and immediate results are critical for reopening societies until an effective vaccine becomes available for a substantial proportion of the population. The loss of sense of smell is among the earliest, most discriminant, and prevalent symptoms of COVID-19, with 75-98% prevalence when clinical olfactory tests are used. Frequent screening for olfactory dysfunction could substantially reduce viral spread. However, olfactory dysfunction is generally self-reported, which is problematic as partial olfactory impairment is broadly unrecognized. To address this limitation, we developed a rapid psychophysical olfactory test (KOR) deployed on a web platform for automated reporting and traceability based on a low-cost (about USD 0.50/test), six-odor olfactory identification kit. Based on test results, we defined an anosmia score -a classifier for olfactory impairment-, and a Bayesian Network (BN) model that incorporates other symptoms for detecting COVID-19. We trained and validated the BN model on two samples: suspected COVID-19 cases in five healthcare centers (n=926; 32% COVID-19 prevalence) and healthy (asymptomatic) mining workers (n=1,365; 1.1% COVID-19 prevalence). All participants had COVID-19 assessment by RT-PCR assay. Using the BN model, we predicted COVID-19 status with 76% accuracy (AUC=0.79 [0.75-0.82]) in the healthcare sample and 84% accuracy (AUC=0.71 [0.63-0.79]) among miners. The KOR test and BN model enabled the detection of COVID-19 cases that otherwise appeared asymptomatic. Our results confirmed that olfactory dysfunction is the most discriminant symptom to predict COVID-19 status when based on olfactory function measurements. Overall, this work highlights the potential for low-cost, frequent, accessible, routine testing for COVID-19 surveillance to aid society9s reopening. +
++Between December 2020-March 2021 we measured anti-SARS-CoV-2 IgG titers post-vaccination with the BNT162b2 vaccine among 725 Israeli hospital workers. Previously infected individuals who received one dose had higher IgG titres than fully vaccinated, never-infected workers. Post-vaccination infection did not increase IgG titres. Individuals infected post-dose one should receive the second. +
++Background The ongoing coronavirus disease 2019 (COVID-19) pandemic has resulted in implementation of public health measures worldwide to mitigate disease spread, including; travel restrictions, lockdowns, messaging on handwashing, use of face coverings and physical distancing. As the pandemic progresses, exceptional decreases in seasonal respiratory viruses are increasingly reported. We aimed to evaluate the impact of the pandemic on circulation of influenza, respiratory syncytial virus and other seasonal respiratory viruses in Canada. Methods Epidemiologic data were obtained from the Canadian Respiratory Virus Detection Surveillance System. Weekly data from the week ending 30th August 2014 until the week ending the 13th February 2021 were analysed. We compared trends in laboratory detection and test volumes during the 2020/2021 influenza season with baseline pre-pandemic seasons from 2014 to 2019. Findings We observed a dramatically lower percentage of tests positive for all seasonal respiratory viruses during 2020-2021 compared to baseline. For influenza A and B the percent positive decreased to 0.0017 and 0.0061 times that of baseline respectively and for RSV, the percent positive dropped to 0.0145 times that of baseline. Ongoing detection of enterovirus/rhinovirus occurred, with regional variation in the epidemic patterns and intensity. Interpretation We report an effective absence of the annual seasonal epidemic of most seasonal respiratory viruses in 2020/2021. This dramatic decrease is likely related to implementation of multi-layered public health measures during the pandemic. The impact of such measures may have relevance for public health practice in mitigating seasonal respiratory virus epidemics and for informing responses to future respiratory virus pandemics. +
++Vaccine-induced neutralizing antibodies are key in combating the COVID-19 pandemic. However, delays of boost immunization due to limited availability of vaccines may leave individuals vulnerable to infection and disease for prolonged periods. The emergence of SARS-CoV-2 variants of concern (VOC), B.1.1.7 (United Kingdom), B.1.351 (South Africa) and P.1 (Brazil), may reinforce this issue with the latter two being able to evade control by antibodies. We assessed humoral and T cell responses against SARS-CoV-2 WT and VOC and endemic human coronaviruses (hCoV) that were induced after single and double vaccination with BNT162b2. Despite readily detectable IgG against the receptor-binding domain (RBD) of the SARS-CoV-2 S protein at day 14 after a single vaccination, inhibition of SARS-CoV-2 S-driven host cell entry was weak and particularly low for the B.1.351 variant. Frequencies of SARS-CoV-2 specific T cells were low in many vaccinees after application of a single dose and influenced by immunity against endemic hCoV. The second vaccination significantly boosted T cell frequencies reactive for WT, B.1.1.7 and B.1.351 variants. These results call into question whether neutralizing antibodies significantly contribute to protection against COVID-19 upon single vaccination and suggest that cellular immunity is central for the early defenses against COVID-19. +
++The SARS-CoV-2 pandemic has been raging for over a year, creating global detrimental impact. The BNT162b2 mRNA vaccine has demonstrated high protection levels, yet apprehension exists that several variants of concerns (VOCs) can surmount the immune defenses generated by the vaccines. Neutralization assays have revealed some reduction in neutralization of VOCs B.1.1.7 and B.1.351, but the relevance of these assays in real life remains unclear. Here, we performed a case-control study that examined whether BNT162b2 vaccinees with documented SARS-CoV-2 infection were more likely to become infected with B.1.1.7 or B.1.351 compared with unvaccinated individuals. Vaccinees infected at least a week after the second dose were disproportionally infected with B.1.351 (odds ratio of 8:1). Those infected between two weeks after the first dose and one week after the second dose, were disproportionally infected by B.1.1.7 (odds ratio of 26:10), suggesting reduced vaccine effectiveness against both VOCs under different dosage/timing conditions. Nevertheless, the B.1.351 incidence in Israel to-date remains low and vaccine effectiveness remains high against B.1.1.7, among those fully vaccinated. These results overall suggest that vaccine breakthrough infection is more frequent with both VOCs, yet a combination of mass-vaccination with two doses coupled with non-pharmaceutical interventions control and contain their spread. +
++SARS-CoV-2 has spread rapidly across the globe, with most nations failing to prevent or substantially delay its introduction. While many countries have imposed some limitations on trans-border passenger traffic, the effect of these measures on the spread of COVID-19 strains remains unclear. Here, we report an analysis of whole-genome sequencing of 3206 SARS-CoV-2 samples from 78 regions of Russia covering the period between March and November 2020. We describe recurring imports of multiple COVID-19 strains throughout this period, giving rise to 457 uniquely Russian transmission lineages, as well as repeated cross-border transmissions of local circulating variants out of Russia. +
++Background Most individuals with COVID-19 will recover without sequelae, but some will develop long-term multi-system impairments. The definition, duration, prevalence and symptoms associated with long COVID, however, have not been established. Methods Public Health England (PHE) initiated longitudinal surveillance of clinical and non-clinical healthcare workers for monthly assessment and blood sampling for SARS-CoV-2 antibodies in March 2020. Eight months after enrolment, participants completed an online questionnaire including 72 symptoms in the preceding month. Symptomatic mild-to-moderate cases with confirmed COVID-19 were compared with asymptomatic, seronegative controls. Multivariable logistic regression was used to identify independent symptoms associated with long COVID. Findings All 2,147 participants were contacted and 1,671 (77.8%) completed the questionnaire, including 140 (8.4%) cases and 1,160 controls. At a median of 7.5 (IQR 7.1-7.8) months after infection, 20 cases (14.3%) had ongoing (4/140, 2.9%) or episodic (16/140, 11.4%) symptoms. We identified three clusters of symptoms associated with long COVID, those affecting the sensory (ageusia, anosmia, loss of appetite and blurred vision), neurological (forgetfulness, short-term memory loss and confusion/brain fog) and cardiorespiratory (chest tightness/pain, unusual fatigue, breathlessness after minimal exertion/at rest, palpitations) systems. The sensory cluster had the highest association with being a case (aOR 5.25, 95% CI 3.45-8.01). Dermatological, gynaecological, gastrointestinal or mental health symptoms were not significantly different between cases and controls. Interpretation Most persistent symptoms reported following mild COVID-19 were equally common in cases and controls. While all three clusters identified had a strong association with cases, the sensory cluster had the highest specificity and strength of association, and therefore, most likely to be characteristic of long COVID. +
+Clinical Study in the Treatment of Patients With Moderate Course of COVID-19 - Condition: COVID-19
Interventions: Drug: COVID-globulin; Drug: Placebo
Sponsor: Microgen
Not yet recruiting
Rehabilitation for Patients With Persistent Symptoms Post COVID-19 - Condition: Covid19
Intervention: Other: Concentrated rehabilitation for patients with persistent symptoms post COVID-19
Sponsors: Western Norway University of Applied Sciences; Helse-Bergen HF
Recruiting
A Nurse-Community Health Worker-Family Partnership Model: Addressing Uptake of COVID-19 Testing and Control Measures - Condition: COVID-19
Intervention: Behavioral: Nurse-Community-Family Partnership Intervention
Sponsor: New York University
Not yet recruiting
Efficacy and Safety of Three Different Doses of an Anti SARS-CoV-2 Hyperimmune Equine Serum in COVID-19 Patients - Condition: Covid19
Interventions: Biological: Anti SARS-CoV-2 equine hyperimmune serum; Biological: placebo
Sponsors: Caja Costarricense de Seguro Social; Universidad de Costa Rica; Ministry of Health Costa Rica
Not yet recruiting
Viral Clearance, PK and Tolerability of Ensovibep in COVID-19 Patients - Condition: Covid19
Intervention: Drug: ensovibep
Sponsor: Molecular Partners AG
Recruiting
A Clinical Study Evaluating Inhaled Aviptadil on COVID-19 - Condition: Covid19
Interventions: Drug: Inhaled Aviptadil; Drug: Placebo
Sponsors: Centurion Pharma; Klinar CRO
Recruiting
ACTIV-3b: Therapeutics for Severely Ill Inpatients With COVID-19 - Condition: Covid19
Interventions: Biological: Remdesivir; Drug: Remdesivir placebo; Biological: VIP; Drug: VIP Placebo; Drug: Corticosteroid
Sponsors: National Institute of Allergy and Infectious Diseases (NIAID); International Network for Strategic Initiatives in Global HIV Trials (INSIGHT); University of Copenhagen; Medical Research Council; Kirby Institute; Washington D.C. Veterans Affairs Medical Center; AIDS Clinical Trials Group; National Heart, Lung, and Blood Institute (NHLBI); US Department of Veterans Affairs; Prevention and Early Treatment of Acute Lung Injury (PETAL); Cardiothoracic Surgical Trials Network (CTSN); NeuroRx, Inc.
Not yet recruiting
The Effects of a Multi-factorial Rehabilitation Program for Healthcare Workers Suffering From Post-COVID-19 Fatigue Syndrome - Condition: COVID-19
Intervention: Other: Exercise
Sponsor: Medical University of Vienna
Recruiting
Safety and Immunogenicity of the Inactivated Koçak-19 Inaktif Adjuvanlı COVID-19 Vaccine Compared to Placebo - Condition: COVID-19 Vaccine
Interventions: Biological: Koçak-19 Inaktif Adjuvanlı COVID-19 Vaccine 4 µg/0.5 ml Vaccine; Biological: Koçak-19 Inaktif Adjuvanlı COVID-19 Vaccine 6 µg/0.5 ml Vaccine; Biological: Placebo
Sponsor: Kocak Farma
Recruiting
Study on Sequential Immunization of Recombinant COVID-19 Vaccine (Ad5 Vector) and RBD-based Protein Subunit Vaccine - Condition: COVID-19
Interventions: Biological: recombinant Ad5 vectored COVID-19 vaccine; Biological: RBD-based protein subunit vaccine (ZF2001) against COVID-19; Biological: trivalent split influenza vaccine
Sponsor: Jiangsu Province Centers for Disease Control and Prevention
Recruiting
Total-Body Parametric 18F-FDG PET of COVID-19 - Condition: Covid19
Intervention: Device: uEXPLORER/mCT
Sponsor: University of California, Davis
Recruiting
Cetirizine and Famotidine for COVID-19 - Condition: Covid19
Interventions: Drug: Cetirizine and Famotidine; Drug: Placebo
Sponsor: Emory University
Not yet recruiting
TCB008 in Patients With COVID-19 - Condition: Covid19
Intervention: Drug: TCB008
Sponsor: TC Biopharm
Not yet recruiting
Omega-3 Oil Use in COVID-19 Patients in Qatar - Condition: COVID-19
Intervention: Drug: Omega 3 fatty acid
Sponsor: Hamad Medical Corporation
Recruiting
COVID-19 Supplemental Vaccine Boost to Enhance T Cell Protection in Those Who Have Already Received EUA S-Based Vaccines - Condition: Covid19
Intervention: Biological: hAd5-S-Fusion+N-ETSD vaccine
Sponsor: ImmunityBio, Inc.
Recruiting
Novel inhibitors of the main protease enzyme of SARS-CoV-2 identified via molecular dynamics simulation-guided in vitro assay - For the COVID-19 pandemic caused by SARS-CoV-2, there are currently no effective drugs or vaccines to treat this coronavirus infection. In this study, we focus on the main protease enzyme of SARS-CoV-2, 3CL^(pro), which is critical for viral replication. We employ explicit solvent molecular dynamics simulations of about 150 compounds docked into 3CL^(pro)’s binding site and that had emerged as good main protease ligands from our previous in silico screening of over 1.2 million compounds. By…
Induction of Exaggerated Cytokine Production in Human Peripheral Blood Mononuclear Cells by a Recombinant SARS-CoV-2 Spike Glycoprotein S1 and Its Inhibition by Dexamethasone - An understanding of the pathological inflammatory mechanisms involved in SARS-CoV-2 virus infection is necessary in order to discover new molecular pharmacological targets for SARS-CoV-2 cytokine storm. In this study, the effects of a recombinant SARS-CoV-2 spike glycoprotein S1 was investigated in human peripheral blood mononuclear cells (PBMCs). Stimulation of PBMCs with spike glycoprotein S1 (100 ng/mL) resulted in significant elevation in the production of TNFα, IL-6, IL-1β and IL-8….
Polysulfates block SARS-CoV-2 uptake via electrostatic interactions - Here we report that negatively charged polysulfates can bind to the spike protein of SARS-CoV-2 via electrostatic interactions. Using a plaque reduction assay, we compare inhibition of SARS-CoV-2 by heparin, pentosan sulfate, linear polyglycerol sulfate (LPGS) and hyperbranched polyglycerol sulfate (HPGS). Highly sulfated LPGS is the optimal inhibitor, with a half-maximal inhibitory concentration (IC 50 ) of 67 μg/mL (approx. 1.6 μM). This synthetic polysulfate exhibits more than 60-fold higher…
Wuhan to World: The COVID-19 Pandemic - COVID-19 is a Severe Acute Respiratory Syndrome (SARS), caused by SARS-CoV-2, a novel virus which belongs to the family Coronaviridae. It was first reported in December 2019 in the Wuhan city of China and soon after, the virus and hence the disease got spread to the entire world. As of February 26, 2021, SARS-CoV-2 has infected ~112.20 million people and caused ~2.49 million deaths across the globe. Although the case fatality rate among SARS-CoV-2 patient is lower (~2.15%) than its earlier…
Development of flexible electrochemical impedance spectroscopy-based biosensing platform for rapid screening of SARS-CoV-2 inhibitors - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the cells through the binding of its spike protein (S-protein) to the cell surface-expressing angiotensin-converting enzyme 2 (ACE2). Thus, inhibition of S-protein-ACE2 binding may impede SARS-CoV-2 cell entry and attenuate the progression of Coronavirus disease 2019 (COVID-19). In this study, an electrochemical impedance spectroscopy-based biosensing platform consisting of a recombinant ACE2-coated palladium nano-thin-film…
SARS-CoV-2 mutations acquired in mink reduce antibody-mediated neutralization - Transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from humans to farmed mink has been observed in Europe and the US. In the infected animals, viral variants arose that harbored mutations in the spike (S) protein, the target of neutralizing antibodies, and these variants were transmitted back to humans. This raised concerns that mink might become a constant source of human infection with SARS-CoV-2 variants associated with an increased threat to human health and…
Synergistic Inhibition of SARS-CoV-2 Replication Using Disulfiram/Ebselen and Remdesivir - The SARS-CoV-2 replication and transcription complex (RTC) comprising nonstructural protein (nsp) 2-16 plays crucial roles in viral replication, reducing the efficacy of broad-spectrum nucleoside analog drugs such as remdesivir and evading innate immune responses. Most studies target a specific viral component of the RTC such as the main protease or the RNA-dependent RNA polymerase. In contrast, our strategy is to target multiple conserved domains of the RTC to prevent SARS-CoV-2 genome…
Intriguing Antiviral Modified Nucleosides: A Retrospective View into the Future Treatment of COVID-19 - Great pioneers of nucleic acid chemistry had elucidated nucleic acid functions and structures and developed various antiviral modified nucleoside drugs. It is possible in theory that antiviral modified nucleosides prevent viral replication by inhibiting viral polymerases. However, biological phenomena far exceed our predictions at times. We describe the characteristics of the approved antiviral modified nucleosides from an organic chemistry perspective. Also, based on our experiences and…
Angiotensin Receptor Blockers for COVID-19: Pathophysiological and Pharmacological Considerations About Ongoing and Future Prospective Clinical Trials - COVID-19 pandemic demands a swift response to find therapeutic tools that effectively reduce morbidity and mortality. Despite initial fears, evidence from retrospective observational studies supports the inhibition of the renin-angiotensin system as an emerging pathway to delay or moderate angiotensin II-driven lung inflammation. This has triggered several prospective clinical trials. In this commentary we provide an overview and analysis of current ongoing clinical trials aimed at evaluating…
Epstein-Barr virus lytic replication induces ACE2 expression and enhances SARS CoV-2 pseudotyped virus entry in epithelial cells - Understanding factors that affect the infectivity of SARS CoV-2 is central to combatting COVID-19. The virus surface spike protein of SARS CoV-2 mediates viral entry into cells by binding to the ACE2 receptor on epithelial cells and promoting fusion. We find that Epstein-Barr virus (EBV) induces ACE2 expression when it enters the lytic replicative cycle in epithelial cells. By using VSV particles pseudotyped with the SARS CoV-2 spike protein, we show that lytic EBV replication enhances…
C5aR inhibition of non-immune cells suppresses inflammation and maintains epithelial integrity in SARS-CoV-2-infected primary human airway epithelia - CONCLUSION: Crucially, we illustrate here for the first time, that targeting the anaphylotoxin receptors C3aR and C5aR in non-immune respiratory cells can prevent intrinsic lung inflammation and tissue damage. This opens up the exciting possibility in the treatment of COVID-19.
Hypoxic and pharmacological activation of HIF inhibits SARS-CoV-2 infection of lung epithelial cells - COVID-19, caused by the novel coronavirus SARS-CoV-2, is a global health issue with more than 2 million fatalities to date. Viral replication is shaped by the cellular microenvironment, and one important factor to consider is oxygen tension, in which hypoxia inducible factor (HIF) regulates transcriptional responses to hypoxia. SARS-CoV-2 primarily infects cells of the respiratory tract, entering via its spike glycoprotein binding to angiotensin-converting enzyme 2 (ACE2). We demonstrate that…
Vaccine-induced immune thrombotic thrombocytopenia (VITT): targeting pathomechanisms with Bruton tyrosine kinase inhibitors - A series of cases with rare thromboembolic incidents including cerebral sinus vein thrombosis (some of them fatal) and concomitant thrombocytopenia occurring shortly after vaccination with the COVID-19 vaccine AZD1222 (Vaxzevria) has caused significant concern and led to its temporary suspension in many countries. Immediate laboratory efforts in four of these patients have identified a tentative pathomechanism underlying this syndrome termed vaccine-induced prothrombotic immune thrombocytopenia…
Mendelian randomisation identifies alternative splicing of the FAS death receptor as a mediator of severe COVID-19 - Severe COVID-19 is characterised by immunopathology and epithelial injury. Proteomic studies have identified circulating proteins that are biomarkers of severe COVID-19, but cannot distinguish correlation from causation. To address this, we performed Mendelian randomisation (MR) to identify proteins that mediate severe COVID-19. Using protein quantitative trait loci (pQTL) data from the SCALLOP consortium, involving meta-analysis of up to 26,494 individuals, and COVID-19 genome-wide association…
Structural basis for broad sarbecovirus neutralization by a human monoclonal antibody - The recent emergence of SARS-CoV-2 variants of concern (VOC) and the recurrent spillovers of coronaviruses in the human population highlight the need for broadly neutralizing antibodies that are not affected by the ongoing antigenic drift and that can prevent or treat future zoonotic infections. Here, we describe a human monoclonal antibody (mAb), designated S2×259, recognizing a highly conserved cryptic receptor-binding domain (RBD) epitope and cross-reacting with spikes from all sarbecovirus…
Compositions and methods for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection - - link
5-(4-TERT-BUTOXY PHENYL)-3-(4N-OCTYLOXYPHENYL)-4,5-DIHYDROISOXAZOLE MOLECULE (C-I): A PROMISING DRUG FOR SARS-COV-2 (TARGET I) AND BLOOD CANCER (TARGET II) - The present invention relates to a method ofmolecular docking of crystalline compound (C-I) with SARS-COV 2 proteins and its repurposing with proteins of blood cancer, comprising the steps of ; employing an algorithmto carry molecular docking calculations of the crystalized compound (C-I); studying the compound computationally to understand the effect of binding groups with the atoms of the amino acids on at least four target proteins of SARS-COV 2; downloading the structure of the proteins; removing water molecules, co enzymes and inhibitors attached to the enzymes; drawing the structure using Chem Sketch software; converting the mol file into a PDB file; using crystalized compound (C-I) for comparative and drug repurposing with two other mutated proteins; docking compound into the groove of the proteins; saving format of docked molecules retrieved; and filtering and docking the best docked results. - link
AQUEOUS ZINC OXIDE NANOSPRAY COMPOSITIONS - Disclosed herein is aqueous zinc oxide nano spray compositions comprising zinc oxide nanoparticles and a synthetic surfactant for controlling the spread of Covid-19 virus. - link
一种肝素类药物组合物、喷鼻剂及其制备方法及应用 - 本发明公开了一种肝素类药物组合物、喷鼻剂及其制备方法及应用。该肝素类药物组合物包括肝素钠和阿比朵尔。本发明中的肝素类药物组合物首次采用肝素钠和阿比朵尔联合使用,普通肝素钠联合1μM/L以上的阿比朵尔病毒抑制效率显著高于单独普通肝素钠或单独阿比多尔组(p<0.05)。 - link
USING CLINICAL ONTOLOGIES TO BUILD KNOWLEDGE BASED CLINICAL DECISION SUPPORT SYSTEM FOR NOVEL CORONAVIRUS (COVID-19) WITH THE ADOPTION OF TELECONFERENCING FOR THE PRIMARY HEALTH CENTRES/SATELLITE CLINICS OF ROYAL OMAN POLICE IN SULTANATE OF OMAN - - link
抗SARS-COV-2中和抗体 - 本公开提供了针对SARS‑COV‑2的新颖中和抗体和其抗原结合片段。还提供了包括其的药物组合物和试剂盒以及其用途。 - link
Peptides and their use in diagnosis of SARS-CoV-2 infection - - link
Method and compositions for treating coronavirus infection - A method of treating viral infection, such as viral infection caused by a virus of the Coronaviridae family, is provided. A composition having at least oleandrin is used to treat viral infection. - link
**一种4-肟-5-(2-甲基丙酰基)尿苷的制备方法** - 本发明公开了一种4‑肟‑5
‑(2‑甲基丙酰基)尿苷的制备方法,包括:S1:在酸存在条件下,使得化合物1和2,2‑二甲氧基丙烷在有机溶剂中反应得到化合物2;S2:在碱存在条件下,使得化合物2在有机溶剂中反应得到化合物3;S3:在羟胺水溶液存在条件下使化合物3在有机溶剂中反应得到化合物4;S4:在酸存在条件下使化合物4在有机溶剂中反应得到化合物I。本发明制备得到的结晶性能良好的固体,且制备条件简单,转化率以及原子经济性好。 - link
一种COVID-19假病毒及其制备方法和用途 - 本发明涉及生物技术领域,特别是涉及一种COVID‑19假病毒及其制备方法和用途本发明,所述COVID‑19假病毒由外壳蛋白质粒与辅助质粒经病毒包装而成,所述外壳蛋白质粒包括表达COVID‑19 S蛋白的质粒、表达COVID‑19 M蛋白的质粒和表达COVID‑19 E蛋白的质粒。本发明的COVID‑19假病毒采用三质粒系统包装,以S/M/E蛋白替代表达VSV‑G蛋白,比仅含有S蛋白的假病毒感染能力更强、灵敏度更高。而且,COVID‑19假病毒携带两种荧光报告基团,不同的荧光报告基团可应用于不同的场景,使得COVID‑19假病毒应用时更简便。 - link
Leaving Afghanistan, and the Lessons of America’s Longest War - It is the Afghan people, of course, who have paid the highest price for America’s failed ambitions. - link
What Will It Take to Pandemic-Proof America? - When the next virus strikes, we’ll look back on this moment as an opportunity that we either seized or squandered. - link
How We Fell in Love in Lockdown - The artist Philippa Found compiled hundreds of written accounts of love in the time of COVID-19 for a project called “Lockdown Love Stories.” - link
Andrew Cuomo, Matt Gaetz, and the New “Never Resign” School of Politics - In recent years, many politicians have seemed to realize that remaining in office is often the best path out of a scandal—for their own sake if no one else’s. - link
How the Pandemic Changed Europe - The historian Adam Tooze discusses the vaccine rollout and shifting politics in the E.U. - link
+The Court’s new majority could make it much easier for big spenders to influence American politics in secret. +
++The Supreme Court will hear a major case on April 26 that could fundamentally alter the Court’s approach to laws requiring political organizations to disclose their donors — a change that could make it much easier for big spenders to hide the ways they seek to influence policy and elections. +
++That case is Americans for Prosperity Foundation v. Rodriquez. But to fully understand it, it’s important to keep in mind the Supreme Court’s decision in Citizens United v. FEC (2010). +
++Citizens United is best known for its anti-canonical holding that corporations may spend unlimited money to influence elections. While five of the justices who heard Citizens United voted to dismantle much of the nation’s campaign finance laws, eight justices also voted that the government has fairly broad authority to require advocacy groups to disclose major funders of their political activity. +
++Disclosure requirements should be upheld, Justice Anthony Kennedy wrote for the Court, so long as there is “a ‘substantial relation’ between the disclosure requirement and a ‘sufficiently important’ governmental interest.” +
++A lot has changed since Citizens United tucked this pro-disclosure ruling into its broader ruling against campaign finance limits, however. Four of the eight justices who supported disclosure rules have since left the Court, and three of them were replaced by judges who are significantly more conservative than the person they replaced. +
++Which brings us to Americans for Prosperity Foundation. The plaintiffs in the case — which include a conservative advocacy group closely associated with the billionaire Koch brothers, and the Thomas More Law Center, a conservative law firm that claims it was formed to promote “America’s Judeo-Christian heritage” — seek to undercut pro-disclosure decisions such as Citizens United. And, with six Republican appointees on the Supreme Court, they have a very good chance of prevailing. +
++The specific issue in Americans for Prosperity is fairly far afield of the foundational questions about money in politics that animated Citizens United. The plaintiffs challenge a California regulation that requires charities that wish to raise tax-deductible funds in California to disclose their largest contributors to the state attorney general’s office. State regulations require the attorney general to keep this information confidential from the public, but the attorney general’s office may use it to investigate allegations of fraud by nonprofits. +
++The Americans for Prosperity plaintiffs claim that this disclosure regulation is unconstitutional, and they rely largely on doctrines created to prevent civil rights organizations from having to disclose their donors to Jim Crow government officials in the 1950s and ’60s. +
++There are difficult questions underlying Americans for Prosperity. If you are inclined to be unsympathetic to a Koch-aligned group that wants to keep its donors secret, imagine a very similar case where Texas required Planned Parenthood to disclose its donors to the state attorney general’s office. Would you have confidence that no one in that office would leak the names of those donors to Tucker Carlson? +
++But the Court has also spent the past 60 years striking a careful balance between the public’s interest in requiring charities and advocacy groups to disclose where they get their money, and the groups’ interest in making sure that their donors are not harassed, intimidated, or attacked by people who loathe a particular group and what it stands for. +
++Americans for Prosperity gives the Court’s very conservative majority an opportunity to rework this balance. And those justices could allow political groups to operate with far more secrecy, allowing wealthy donors to shape American politics in the shadows. +
++In the mid-1950s, an Alabama court ordered the NAACP, which was then the preeminent organization fighting segregation in the Jim Crow South, to turn over a full list of its members to the state attorney general — and then imposed a $100,000 fine on the NAACP if it did not comply. +
++Had the NAACP complied, it could have placed those members in grave danger. State officials could have turned over the list of members to the Ku Klux Klan. Or they may have disclosed them to racist employers who could have fired the NAACP’s members and blacklisted them from obtaining future employment. +
++The Alabama court’s order, in other words, was a fairly transparent effort to shut down the NAACP’s operations in Alabama, either by terrorizing the organization’s members or by imposing crippling fines on the NAACP. The $100,000 fine imposed by the state court was roughly the equivalent of a $1 million fine in today’s dollars. +
++Ultimately, however, this scheme did not succeed. In NAACP v. Alabama ex rel. Patterson (1958), a unanimous Supreme Court ruled that Alabama could not force the NAACP to disclose its members, given the obvious danger to those members if their names were disclosed. +
++“We think that the production order, in the respects here drawn in question, must be regarded as entailing the likelihood of a substantial restraint upon the exercise by petitioner’s members of their right to freedom of association,” Justice John Marshall Harlan wrote for his Court. He added that the NAACP had made “an uncontroverted showing” that “revelation of the identity of its rank-and-file members has exposed these members to economic reprisal, loss of employment, threat of physical coercion, and other manifestations of public hostility.” +
++NAACP was an extreme case, and the plaintiffs in Americans for Prosperity do not allege anything that even vaguely resembles the kind of abuse and intimidation that NAACP members faced in the Jim Crow South. As a lower court that upheld California’s disclosure law explained, an executive with the Americans for Prosperity Foundation “described two individuals who, she believed, stopped supporting the Foundation in light of actual or feared retaliation by the IRS,” and another donor who “did business with the Government” said that he and his associates “did not feel like they could take on the risk of continuing to give to us.” +
++Similarly, the Thomas More Law Center “introduced a letter from a contributor who chose to make a $25 contribution anonymously out of fear that ISIS would break into the Law Center’s office, obtain a list of contributors and target them.” +
++Unlike the NAACP in the 1950s, in other words, the Americans for Prosperity plaintiffs largely raise speculative fears that, by disclosing their major donors to one government agency, that information may somehow — in violation of California state regulations — wind up in the hands of another agency, which might target those donors. (Or, in the case of the law center, that the donor information might wind up being discovered by a terrorist organization located on the other side of the globe, which will then target American donors to the law center.) +
++That said, the plaintiffs do have some basis to fear that some of their donor information might accidentally be disclosed to the public. An expert witness hired by Americans for Prosperity was able to hack the state’s website and uncover confidential donor information — although this security hole has since been plugged — and clerical workers in the California attorney general’s office once accidentally made a small fraction of the office’s confidential records public. +
++The plaintiffs fear that, had their donor information become widely available to the public through a similar error, then those donors might be harassed or their businesses might be boycotted. +
++The core question in Americans for Prosperity is whether this fear that an inadvertent disclosure might happen and that such a disclosure might lead to consequences for donors is sufficient reason to invoke constitutional protections intended to shield organizations like the NAACP in the Jim Crow era. +
++Under current precedents, the Supreme Court uses two sorting mechanisms to help it identify which disclosure laws should be struck down. +
++The first is a balancing test described in Citizens United. Under that test, a disclosure law should be upheld if there is “a ‘substantial relation’ between the disclosure requirement and a ‘sufficiently important’ governmental interest.” Thus, Alabama’s attempt to obtain the NAACP’s members list was invalid, because the only “interest” that Alabama sought to advance when it sought this list was undermining the NAACP. +
++By contrast, a federal appeals court upheld California’s disclosure rule because, by obtaining information about major donors to nonprofit organizations, the state advanced its important interest in determining “whether a charity is actually engaged in a charitable purpose, or is instead violating California law by engaging in self-dealing, improper loans, or other unfair business practices.” +
++As California explains in its brief to the Supreme Court, the state’s disclosure rule “helps state regulators detect whether a charity is misusing charitable assets, such as by diverting funds for a donor’s personal enrichment.” A businessman might, for example, make a tax-deductible “donation” to a nonprofit organization, which immediately turns around and hires that businessman’s company as a “consultant” — thus allowing the businessman to take a fraudulent tax deduction without actually contributing anything to charity. +
++The second mechanism that the Court uses to sort through challenges to disclosure laws is that it ordinarily requires such challenges to be brought on an “as applied” basis, a mechanism that allows courts to pay special attention to the specific facts of an individual case. +
++Courts distinguish between “facial” challenges, which allege that a law is invalid in all circumstances and must cease to operate altogether, and “as applied” challenges, which allege that the law is only unconstitutional when applied to a particular plaintiff. Thus, if a plaintiff prevails in a facial challenge, the challenged law can no longer be enforced against anyone. But if a plaintiff prevails in an as-applied challenge, the government may still be able to enforce the challenged law against other parties. +
++As-applied challenges are the preferred mechanism to challenge a disclosure law because such a challenge typically hinges on the particular impact of that law on a particular plaintiff. In Americans for Prosperity, for example, the plaintiffs allege that they engage in unpopular political work that makes their donors unusually vulnerable to harassment and intimidation. But the same cannot be said about most nonprofits — it is highly unlikely, for example, that donors to the March of Dimes would be harassed if their donations became public knowledge. +
++Thus, when a party challenges a particular disclosure law, courts will often ask whether that individual party should be exempted from the law, rather than striking down the law on its face. In Citizens United, for example, the Court explained that a facial challenge to certain campaign finance disclosure laws was inappropriate, but “as-applied challenges would be available if a group could show a ‘reasonable probability’ that disclosure of its contributors’ names ‘will subject them to threats, harassment, or reprisals from either Government officials or private parties.’” +
++Nevertheless, the plaintiffs in Americans for Prosperity bring a facial challenge to California’s disclosure law. They also claim that the balancing test described in Citizens United should be abandoned in favor of something much more skeptical of disclosure laws. +
++Though there are some important differences between the argument in the Americans for Prosperity Foundation’s brief and the Thomas More Law Center’s brief, both argue that Citizens United’s relatively permissive rule governing disclosure laws should be, in the words of the former brief, “confined to election regulation.” Thus, while the government may be able to require advocacy groups to disclose their donors when those groups attempt to influence an election, disclosure laws enacted in any other context would be treated as more suspect. +
++Most disclosure laws, the plaintiffs claim, must be “narrowly tailored” to serve the purpose of that law. Thus, they argue, the California law should fall because the state could use less intrusive methods to investigate fraudulent nonprofits, such as only subpoenaing records from charities that are under investigation. +
++The state, for its part, argues that relying on subpoenas is not enough, in part because subpoenas tip off a fraudulent organization that it is under investigation. But there’s also a much more fundamental problem with the plaintiffs’ attempts to draw a line between election-related disclosure laws and laws that do not touch on elections — the border between “issue” advocacy and election-related advocacy is notoriously porous. +
++Before Citizens United opened the floodgates to unlimited corporate sending on elections, for example, lawmakers struggled to draw a sensible line between “issue” ads — ads intended to inform voters about a policy-related matter — and “electioneering communications,” which sought to influence an election. If an advocacy group runs an ad saying “tell Congressman Smith that he was wrong to vote for Obamacare,” for example, is that ad merely educating voters about a policy matter, or does it seek to undermine Smith’s reelection bid? What if the ad also praises Smith’s opponent for opposing Obamacare? What if the ad runs a week before the election? +
++The plaintiffs’ proposed rule could very easily allow advocacy groups to evade disclosure rules that apply to election ads and similar communications with voters, so long as those communications superficially appear to focus on “issues.” +
++Ultimately, cases like Americans for Prosperity come down to a question of values. Should donors who wish to spend gobs of money influencing public policy be allowed to do so anonymously? And if we think that the answer to this question typically should be no, at what point should we give special protections to donors who face harassment, boycotts, or worse? +
++In Doe v. Reed (2010), a case about whether the public should be allowed to learn who signed a petition seeking to call a referendum on a state law, Justice Antonin Scalia offered a bracing answer to these questions: +
++++Requiring people to stand up in public for their political acts fosters civic courage, without which democracy is doomed. For my part, I do not look forward to a society which, thanks to the Supreme Court, campaigns anonymously . . . and even exercises the direct democracy of initiative and referendum hidden from public scrutiny and protected from the accountability of criticism. This does not resemble the Home of the Brave. +
+
+“Harsh criticism, short of unlawful action,” Scalia added, “is a price our people have traditionally been willing to pay for self-governance.” +
++There do have to be some limits on the government’s power to require advocacy groups to disclose their donors — NAACP presents a particularly stark example of why. And if either of the plaintiffs in Americans for Prosperity has evidence that their donors face a serious risk of illegal reprisals, then they should be allowed to bring an as-applied challenge to disclosure laws that endanger those donors. +
++But the Americans for Prosperity plaintiffs ask for much more. They ask for a fundamental shift in how the Court approaches disclosure laws. And, while they concede that there may still be campaign disclosure laws in the elections context, it’s far from clear that the Court will draw a sensible line between issue-related advocacy and election advocacy. +
++The views that Scalia expressed in Doe represent a confident conservatism — a conservatism that believes it can win the hearts and minds of the nation through open debate. But that brand of conservatism has been replaced by something far more insecure, and far more fearful of a frequently overblown “cancel culture” that is ready to pounce on anyone brazen enough to express a conservative viewpoint. +
++Americans for Prosperity will be an early sign of just how far this new, far more insecure conservatism has penetrated into the Supreme Court. +
+The law limits the cost of broadband access to $15 a month for needy families. +
++At the beginning of the pandemic, Gov. Andrew Cuomo tapped former Google CEO Eric Schmidt to help him pivot New York to the digital age. +
++A year later, Cuomo and Schmidt have unveiled the first major change to state policy: A new law signed Friday to expand internet access to low-income New Yorkers. +
++Cuomo took the recommendation from Schmidt’s reform commission, Reimagine New York, and signed a bill that requires internet providers like Verizon to offer lower-income families basic broadband access for no more than $15 a month, a cap that Cuomo says is the first of its kind in the nation. High-speed plans will be capped at $20 a month. +
++About 7 million New Yorkers who currently qualify for government assistance will now have access to cheaper internet — a high-speed plan typically costs an average of more than $50 a month, Cuomo said — making it easier for them to attend online classes, communicate with family, and work from home. Americans who lack broadband access are disproportionately low-income and people of color. +
++“The internet is no longer optional,” Schmidt said on Friday, seated alongside Cuomo. “It’s essential to education. Think of the generation that we could be creating that are not learning because we didn’t give them the right access — and they’re the ones most at risk that need it most of all.” +
++The law is the most significant accomplishment to date from the Schmidt-led commission. The former Google CEO said from the beginning that the group would have three priorities: expanding broadband access, building out more capabilities for virtual medical appointments, and improving remote learning. +
++Schmidt is a billionaire philanthropist who splits his time among technical issues like artificial intelligence, political issues like Democratic campaigns, and the intersection of those tech and policy interests — such as ways to bridge the gap between Silicon Valley’s engineering talent and the American military. +
++Some New York progressives were upset when Schmidt — along with another major tech philanthropist, Bill Gates — were chosen to help guide New York’s post-coronavirus recovery, fearing it would expand the private sector’s influence. A longtime political ally of Cuomo, Schmidt praised the “extraordinary” coronavirus leadership of the New York governor, who is managing several crises, including an FBI investigation over whether he covered up the total number of Covid-19 deaths at nursing homes. Cuomo is also facing unrelated sexual harassment allegations. +
++In addition to the new state law, Schmidt’s philanthropic group, Schmidt Futures, is also helping to finance internet access for the next school year for up to 50,000 New York families that cannot afford the reduced $15-a-month rate. Hundreds of thousands of New Yorkers “apparently had no internet access at all,” Schmidt said. +
++Schmidt portrayed the commission as epitomizing the best of philanthropy and how it can collaborate with the public sector during a crisis. +
++“This is when New York does its best — a combination of private actors and the public doing the right thing for the benefit of all the citizens,” Schmidt said. “Governor, send us more challenges.” +
+As his own party moves ahead on the issue, the president remains opposed to legalization. +
++This month, something unusual happened: Senate Majority Leader Chuck Schumer took a stand against President Joe Biden. +
++The New York Democrat, typically a strong Biden ally, has transformed into one of the Senate’s biggest advocates for marijuana legalization, which Biden continues to oppose. But Schumer said he’ll move forward with his legalization bill anyway. +
++“I want to make my arguments to him, as many other advocates will,” Schumer said. “But at some point we’re going to move forward, period.” +
++Schumer is likely worried, at least in part, about a primary challenge from the left in the future — something Rep. Alexandria Ocasio-Cortez (D-NY) has openly discussed. +
++But there’s a bigger issue here for Biden. Increasingly, the president is out of step with not just his party but the country and perhaps even most Republicans on marijuana legalization. +
++Marijuana legalization is extremely popular. Gallup and the Pew Research Center, two of the country’s leading polling organizations, have consistently found at least two-thirds of Americans back legalization. +
++Support is so high that, at this point, a majority of Republicans — who are generally more skeptical of drug policy reforms — may support it. Pew found 55 percent of Republicans back legalization. Gallup found a slim majority of Republicans supported it in 2017, 2018, and 2019. That reversed in 2020, but the difference between support and opposition among Republicans was still within the sampling margin of error. And, at any rate, a solid minority of 48 percent were behind it. +
++Support among Democrats, meanwhile, is in the high 70s and 80s across polls. +
++Maybe Biden doesn’t entirely trust the polls — after 2016 and 2020, many of us don’t. But there’s real-world evidence legalization is very popular, too. +
++For one, 17 states have now legalized marijuana, most recently New Mexico. Among the 15 states where marijuana legalization has been put in front of voters since 2012 (when Colorado and Washington state first legalized), it’s won in 13. +
++Even more impressive is marijuana’s recent record in Republican states. Since 2012, marijuana legalization has come up for a vote in four states that former President Donald Trump won by double digits in 2020. It’s won in three of those states (Alaska, Montana, and South Dakota), and lost in one (North Dakota). Weed is 3-1 in deep-red states. +
++So what could explain Biden’s opposition? Based on his public remarks, he seems genuinely conservative on the issue — arguing only for decriminalization (in which the threat of jail or prison time is removed for possession, but sales remain illegal), and calling for “more scientific investigations” into the issue, particularly whether pot is a “gateway drug.” +
++Biden, after all, not just supported but spearheaded many of the country’s current drug war policies. During the 1980s and ’90s, he backed and helped write bill after bill that toughened federal criminal penalties against all sorts of drugs. Biden has since admitted to going too far in at least some respects, but this is where he built his early political career. +
++Of course, the failure of these policies to stop major drug problems — the country is currently mired in its deadliest drug overdose crisis ever in the opioid epidemic — and these policies’ punitive nature are reasons the public has shifted toward backing marijuana legalization. And the real-life evidence of legalization suggests it works fine, even leading governors in legalization states to regularly flip to supporting it. +
++But Biden is not convinced, even as his party moves ahead without him. With a veto pen in hand, it could make the president the biggest barrier to legalization. +
We need to build a bunch of pacers for T20 World Cup and other series, says Waqar - The T20 World Cup is scheduled to be held in India in October-November.
Chahar feels “good” answering “that critic”, earns praise from national head coach Shastri - After an indifferent last season, Chahar is satisfied as he looked in fine rhythm with Dhoni bowling him out within the first 10 overs.
Indian Premier League 2021 | Delhi Capitals hold edge over Punjab Kings as Nortje set to replace Tom Curran - Both teams are coming into the ‘Norther Derby’ of IPL after enduring defeats in their previous games
IPL 2021 | Kolkata looks to overcome middle-order muddle, return to winning ways against Bangalore - Against the star-studded RCB who are yet to fire in unison this season, KKR’s bowling would once again look to make an impact.
Stokes to undergo surgery on Monday: ECB - The England all-rounder will be out for up to 12 weeks
Virus surges will continue periodically, says IIPH Director - Only way to reduce risk is permanent change in people’s behaviour and adequate vaccination
Savadi isolates himself after gunman tests positive - Laxman Savadi, Deputy Chief Minister and Transport Minister, has isolated himself following his gunman and some of his associates testing positive for
Plea for resumption of day train in Nilambur route - The Nilambur-Mysore Railway Action Council has demanded resumption of train services between Nilambur and Shoranur during the day.Action council leade
Coronavirus | India’s largest COVID-19 facility in south Delhi to be revived as cases go through roof - The management at the spiritual organisation’s centre in Chattarpur confirmed that the facility will be restarted soon
Coronavirus | Shiv Sena blames Centre, EC for second wave of COVID-19 in India - From West Bengal, BJP workers are going back to their homes in different parts of the country with COVID-19, the Shiv Sena said
Russia retaliates for US diplomatic expulsions - Moscow expels 10 diplomats and blacklists eight US officials after the US imposed sanctions.
France Mia kidnapping: Four men held over abduction of girl aged 8 - Mia was taken from her grandmother’s home as part of a plot ordered by her mother, prosecutors say.
Brexit: UK-EU talks on Northern Ireland ‘to intensify’ - The chief negotiators on both sides have held talks about the post-Brexit arrangements for NI.
On the front line in eastern Ukraine - The BBC’s Jonah Fisher reports from the front line between soldiers and separatists.
Afghanistan war: US spies doubt reports of Russian ‘bounties’ for troops - US spies have “low to moderate confidence” that Russia offered cash for American deaths, officials say.
At 38.5% vaccinated, US may be running low on people eager for a shot - Some worry the country can’t keep up the current pace of vaccination. - link
DC’s Rorschach: A detective walks into a world shaped by squids and superheroes - During COVID-19, Rorschach has been something to look forward to each month. - link
NASA selects SpaceX as its sole provider for a lunar lander - “We looked at what’s the best value to the government.” - link
21.5-inch iMac supply dwindles amid chip shortages, possible refresh - A new iMac landing next week is a real possibility. - link
Backdoored developer tool that stole credentials escaped notice for 3 months - AWS credentials and private repository tokens could allow self-perpetuating attacks. - link
+The priest is in jail now. +
+ submitted by /u/kappi17
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+Pierre, zee French fighter pilot is with his amour. +
++“Oh, Pierre, I want you to kiss me”, she exclaims. +
++And so he tilts her chin up and leans in, but just before he plants a kiss on her lips, he pours a little red wine on them, and then goes in for the kiss. +
++“Oh, Pierre, mon dieu, that was so arousing and erotic, but tell me, why before you kissed me, did you pour red wine on my lip?” +
++“I am Pierre, zee French fighter pilot, and when i taste the red meat, i have the red wine.” +
++“Oh Pierre, that is so romantic, kiss me again, but lower this time!” and so he carefully unbuttons her blouse and lowers his head. But before he begins, he pours a little bit of white wine on her breast, and then, ravagement. +
++“Oh, Pierre, Pierre”, she squealed, “again, so erotic, so arousing, so magnifique! but tell me, why this time, at my breast, the white wine?” +
++“I am Pierre, zee French fighter pilot, and when I have the white meat, I pair it with the white wine.” +
++“Oh Pierre, Pierre, so romantic, so sensual, kiss me lower, kiss me lower!” +
++And so he gets down on his knne and lifts her bustle, pushing aside her bloomers and lowers his head. Just before he engages, however, he pours a little bit of cognac onto her pubic hair and sets it alight. +
++“PIERRE, PIERRE, WHY HAVE YOU DONE THIS?” she cried, batting out the flames. +
++“I am Pierre, zee french fighter pilot, and when i go down, i go down in flames.” +
++Edit: I’m an old duffer that does not know how to format properly. +
++Edit: holy guacamole guys! Thank you so much, if for nothing else, a thoroughly entertaining comments section. It’s not about fish though. +
++Edit: spelling. +
+ submitted by /u/dotsandloops1929
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+Every now and then the train passes through a tunnel, during which time the compartment is plunged into complete darkness. On one such occasion, a ringing slap is heard and as the train passes back into daylight, the Frenchman is rubbing his sore, red cheek. +
++The brunette thinks “I bet that dirty Frenchman fondled the blonde and she struck the pervert.” +
++The blonde thinks “I bet that filthy Frenchman was looking to grope me in the dark, mistook the dowdy brunette for me and she slapped the beast.” +
++The Frenchman thinks “I bet that perfidious Englishman touched up the blonde in the dark and she slapped me by mistake.” +
++The Englishman thinks “I can’t wait for another tunnel so I can slap that French twat again.” +
+ submitted by /u/kingheet
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+‘’Dong, Ding Dong’’ +
+ submitted by /u/PokeBattle_Fan
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+The stepdad denies her so she begs and begs and begs until finally the stepdad says, “fine, I’ll let you borrow the car if you drop on your knees and suck my dick.” +
++Disgusted, she turns around and goes back to her room. +
++30 mins later, she comes back to ask again because she really needs to borrow his car. +
++He says “Ok, but you still have to suck my dick!” She agrees, “fine but you better not tell anyone!” +
++She drops to her knees and puts his dick in her mouth but instantly pops up on her feet. “Ew! Your dick taste like shit!” +
++The father then remembers, “oh that’s right, your brother has the car tonight!” +
+ submitted by /u/jeffreypooh
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