COVID-19 outcomes among hospitalized men with or without exposure to alpha-1-adrenergic receptor blocking agents -
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+Importance: Alpha-1-adrenergic receptor antagonists (α1-blockers) can abrogate pro-inflammatory cytokines and may improve outcomes among patients with respiratory infections. Repurposing readily available drugs such as α1-blockers could augment the medical response to the COVID-19 pandemic. Objective: To evaluate the association between α1-blocker exposure and COVID-19 mortality Design: Real-world evidence study Setting: Patient level data with 32,355 records tested for SARS-CoV-2 at the Mount Sinai Health System including 8,442 laboratory-confirmed cases extracted from five member hospitals in the New York City metropolitan area. Participants: 2,627 men aged 45 or older admitted with COVID-19 between February 24 and May 31, 2020 Exposures: α1-blocker use as an outpatient or while admitted for COVID-19 Main Outcomes and Measures: In-hospital mortality Results: Men exposed to α1-blockers (N=436) were older (median age 73 vs. 64 years, P<0.001) and more likely to have comorbidities than unexposed men (N=2,191). Overall, 758 (28.9%) patients died in hospital, 1,589 (60.5%) were discharged, and 280 (10.7%) were still hospitalized as of May 31, 2020. Outpatient exposure to α1-blockers was not associated with COVID-19 hospital outcomes, though there was a trend towards significance (OR 0.749, 95% CI 0.527-1.064; P=0.106). Conversely, inpatient use of α1-blockers was independently associated with improved in-hospital mortality in both multivariable logistic (OR 0.633, 95% CI 0.434-0.921; P=0.017) and Cox regression analyses (HR 0.721, 95% CI 0.572-0.908; P=0.006) adjusting for patient demographics, comorbidities, and baseline vitals and labs. Age-stratified analyses suggested greater benefit from inpatient α1-blocker use among younger age groups: Age 45-65 OR 0.384, 95% CI 0.164-0.896 (P=0.027); Age 55-75 OR 0.511, 95% CI 0.297-0.880 (P=0.015); Age 65-89 OR 0.810, 95% CI 0.509-1.289 (P=0.374). Conclusions and Relevance: Inpatient α1-blocker use was independently associated with improved COVID-19 mortality among hospitalized men. Clinical trials to assess the therapeutic value of α1-blockers in COVID-19 are warranted.
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Program and patient characteristics for the United States Expanded Access Program to COVID-19 convalescent plasma -
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+Background The United States (US) Expanded Access Program (EAP) to COVID-19 convalescent plasma was initiated in response to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease-2019 (COVID-19). While randomized clinical trials were in various stages of development and enrollment, there was an urgent need for widespread access to potential therapeutic agents particularly for vulnerable racial and ethnic minority populations who were disproportionately affected by the pandemic. The objective of this study is to report on the demographic, geographic, and chronological access to COVID 19 convalescent plasma in the US via the EAP. Methods and findings Mayo Clinic served as the central IRB for all participating facilities and any US physician could participate as local physician-principal investigator. Registration occurred through the EAP central website. Blood banks rapidly developed logistics to provide convalescent plasma to hospitalized patients with COVID-19. Demographic and clinical characteristics of all enrolled patients in the EAP were summarized. Temporal trends in access to COVID-19 convalescent plasma were investigated by comparing daily and weekly changes in EAP enrollment in response to changes in infection rate on a state level. Geographical analyses on access to convalescent plasma included assessing EAP enrollment in all national hospital referral regions as well as assessing enrollment in metropolitan and less populated areas which did not have access to COVID-19 clinical trials. From April 3 to August 23, 2020, 105,717 hospitalized patients with severe or life-threatening COVID-19 were enrolled in the EAP. A majority of patients were older than 60 years of age (57.8%), male (58.4%), and overweight or obese (83.8%). There was substantial inclusion of minorities and underserved populations, including 46.4% of patients with a race other than White, and 37.2% of patients were of Hispanic ethnicity. Severe or life-threatening COVID-19 was present in 61.8% of patients and 18.9% of patients were mechanically ventilated at time of convalescent plasma infusion. Chronologically and geographically, increases in enrollment in the EAP closely followed confirmed infections across all 50 states. Nearly all national hospital referral regions enrolled patients in the EAP, including both in metropolitan and less populated areas. Conclusions The EAP successfully provided widespread access to COVID-19 convalescent plasma in all 50 states, including for underserved racial and ethnic minority populations. The efficient study design of the EAP may serve as an example framework for future efforts when broad access to a treatment is needed in response to a dynamic disease affecting demographic groups and areas historically underrepresented in clinical studies.
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Spike protein antibodies mediate the apparent correlation between SARS-CoV-2 nucleocapsid antibodies and neutralization test results -
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+Objectives SARS-CoV-2 infection induces the formation of different antibodies. However, not all of which might prevent the virus from entering the cell, although their concentrations correlate with the titers of viral neutralization tests (NTs). Antibodies against the viral nucleocapsid (NC), e.g., can be classified as such. We aimed to prove the hypothesis that the apparent correlation between NC-antibody levels and NT-titers is mediated by simultaneously occurring antibodies against viral spike-protein components. Methods We included 64 individuals with previous SARS-CoV-2 infection (>14d after symptom onset). SARS-CoV-2 antibodies against the NC (Roche total antibody ECLIA, Abbott IgG CMIA) and spike-protein (Technozym RBD ELISA, DiaSorin S1/S2 CLIA) were measured, and neutralization tests were performed. The effect of spike-protein antibodies on the correlation between NC-antibodies and NT-titers was evaluated by partial correlation and mediation analyses. Results Both tested assays assessing antibodies against the NC correlated significantly with NT titers: Abbott ρ=0.742, P<0.0001; Roche ρ=0.365, P<0.01. However, when controlling the rank correlations for the presence of RBD or S1/S2 antibodies, correlation coefficients dropped to ρ=0.318/ρ=0.329 (P<0.05/P<0.01) , respectively for Abbott and vanished for Roche. As a result, only a maximum of 11% of NT titer variability could be explained by NC-antibody levels. Conclusions Our data suggest that the apparent correlation between NC antibodies and NT titers is strongly mediated by co-occurring RBD antibody concentrations. To avoid falsely implied causal relationships, all correlation analyses of non-spike-associated antibody assays and neutralization assays should include a partial correlation analysis to exclude a possible mediator effect of spike-associated antibodies.
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An Update on Novel Approaches for Diagnosis and Treatment of SARS-CoV-2 Infection -
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+The ongoing pandemic of coronavirus disease 2019 (COVID-19) has made serious public health and economic crisis worldwide which united global efforts to develop rapid, precise, and cost-efficient diagnostics, vaccines, and therapeutics. Numerous multi-disciplinary studies and techniques have been designed to investigate and develop various approaches to help frontline health workers, policymakers, and populations to overcome the disease. While these techniques have been reviewed within individual disciplines, it is now timely to provide a cross-disciplinary overview of novel diagnostic and therapeutic approaches summarizing complementary efforts across multiple fields of research and technology. Accordingly, we reviewed and summarized various advanced novel approaches used for diagnosis and treatment of COVID-19 to help researchers across diverse disciplines on their prioritization of resources for research and development and to give them a better picture of the latest techniques. These include artificial intelligence, nano-based, CRISPR-based, and mass spectrometry technologies as well as neutralizing factors and traditional medicines. We also reviewed new approaches for vaccine development and developed a dashboard to provide frequent updates on the current and future approved vaccines.
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Invasive airway “Intubation” in COVID-19 patients: statistics, causes and recommendations -
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+Background: Severe COVID-19 disease could induce acute respiratory distress which is characterized by tachypnea, hypoxia, and dyspnea. Intubation and mechanical ventilation are a strategic treatment of COVID-19 distress or hypoxia. Methods: We searched PubMed, Embase, and Scopus databases through April 1, 2021, to identify relevant randomized control trials, observational studies, and case series. Results: 24 studies were included in this review. Studies were conducted in the USA, China, Spain, South Korea, Italy, Iran, and Brazil. Most patients were intubated in the intensive care unit. Rapid sequence induction was mostly used for intubation. ROX index might be utilized for the predictor of the necessity of intubation in COVID-19 patients. According to the previous studies the rate of intubation reported 5 to 88%. It was revealed that 1.4 - 44.5% of patients might be extubated. Yet obesity and age (elderly) are the only risk factors of delayed or difficult extubation. Discussion and conclusion: Acute respiratory distress in COVID-19 patients could require endotracheal intubation and mechanical ventilation. Severe respiratory distress, loss of consciousness, and hypoxia were the most important reasons for intubation. Also, increased levels of ferritin, d-dimer, and lipase in common with hypoxia are correlated with intubation and ICU admission Mortality following intubation is reported to be 15 to 36%. Awake-prone positioning in comparison to high-flow nasal oxygen therapy did not reduce the risk of intubation and mechanical ventilation. There was no association between intubation timing and mortality of infected patients. noninvasive ventilation may have survival benefits. Keywords: Intubation, COVID-19, critical care, respiratory disease, infectious disease, hypoxia, airway management.
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Incidence of Long-term Post-acute Sequelae of SARS-CoV-2 Infection Related to Pain and Other Symptoms: A Living Systematic Review and Meta-analysis -
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+Importance: Persistent symptoms are reported in patients who survive the initial stage of COVID-19, often referred to as ″long COVID″ or ″post-acute sequelae of SARS-CoV-2 infection″ (PASC); however, evidence on incidence is still lacking, and symptoms relevant to pain are yet to be assessed. Objective: To determine long-term symptoms in COVID-19 survivors after infection. Data Sources: A literature search was performed using the electronic databases PubMed, EMBASE, Scopus, and CHINAL and preprint servers MedRχiv and BioRχiv through January 15, 2021. Study Selection: Eligible studies were those reporting patients with a confirmed diagnosis of SARS-CoV-2 and who showed any symptoms persisting beyond the acute phase. Data Extraction and Synthesis: Incidence rate of symptoms were pooled using inverse variance methods with a DerSimonian-Laird random-effects model. Main Outcomes and Measures: The primary outcome was pain-related symptoms such as headache or myalgia. Secondary outcomes were symptoms relevant to pain (depression or muscle weakness) and symptoms frequently reported (anosmia and dyspnea). Heterogeneity among studies and publication bias for each symptom were estimated. The source of heterogeneity was explored using meta-regression, with follow-up period, age and sex as covariates. Results: In total, 35 studies including 18,711 patients were eligible. Eight pain-related symptoms and 26 other symptoms were identified. The highest pooled incidence among pain-related symptoms was chest pain (17%, 95% CI, 12%-25%), followed by headache (16%, 95% CI, 9%-27%), arthralgia (13%, 95% CI, 7%-24%), neuralgia (12%, 95% CI, 3%-38%) and abdominal pain (11%, 95% CI, 7%-16%). The highest pooled incidence among other symptoms was fatigue (45%, 95% CI, 32%-59%), followed by insomnia (26%, 95% CI, 9%-57%), dyspnea (25%, 95% CI, 15%-38%), weakness (25%, 95% CI, 8%-56%) and anosmia (19%, 95% CI, 13%-27%). Substantial heterogeneity was identified (I2, 50-100%). Meta-regression analyses partially accounted for the source of heterogeneity, and yet, 53% of the symptoms remained unexplained. Conclusions and Relevance: The current meta-analysis may provide a complete picture of incidence in PASC. It remains unclear, however, whether post-COVID symptoms progress or regress over time or to what extent PASC are associated with age or sex.
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Development of a tool to prioritize the monitoring of COVID-19 patients by public health teams -
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+Background: In the context of the COVID-19 pandemic, public health teams have struggled to conduct monitoring for confirmed or suspicious COVID-19 patients. However, monitoring these patients is critical to improving the chances of survival, and therefore, a prioritization strategy for these patients is warranted. This study developed a monitoring algorithm for COVID-19 patients for the Colombian Ministry of Health and Social Protection (MOH). Methods: This work included 1) a literature review, 2) consultations with MOH and National Institute of Health officials, and 3) data analysis of all positive COVID-19 cases and their outcomes. We used clinical and socioeconomic variables to develop a set of risk categories to identify severe cases of COVID-19. Results: This tool provided four different risk categories for COVID-19 patients. As soon as the time of diagnosis, this tool can identify 91% of all severe and fatal COVID-19 cases within the first two risk categories. Conclusion: This tool is a low-cost strategy to prioritize patients at higher risk of experiencing severe COVID-19. This tool was developed so public health teams can focus their scarce monitoring resources on individuals at higher mortality risk. This tool can be easily adapted to the context of other lower and middle-income countries. Policymakers would benefit from this low-cost strategy to reduce COVID-19 mortality, particularly during outbreaks.
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Accuracy of antigen and nucleic acid amplification testing on saliva and naopharyngeal samples for detection of SARS-CoV-2 in ambulatory care -
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+Background: Nasopharyngeal sampling for nucleic acid amplification testing (NAAT) is the current standard diagnostic test for of coronavirus disease 2019 (COVID-19). However, the NAAT technique is lengthy and nasopharyngeal sampling requires trained personnel. Saliva NAAT represents an interesting alternative but diagnostic performances vary widely between studies. Objective: To assess the diagnostic accuracy of a nasopharyngeal point-of-care antigen (Ag) test and of saliva NAAT for detection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), as compared to nasopharyngeal NAAT. Design: Prospective participant enrollment from 19 October through 18 December 2020. Setting: Two community COVID-19 screening centers in Paris, France. Participants: 1452 ambulatory children and adults referred for SARS-CoV-2 testing. Interventions: NAAT on a saliva sample (performed with three different protocols for pre-processing, amplification and detection of SARS-CoV-2) and Ag testing on a nasopharyngeal sample. Measurements: Performance of saliva NAAT and nasopharyngeal Ag testing. Results: Overall, 129/1443 (9%) participants tested positive on nasopharyngeal NAAT (102/564 [18%] in symptomatic and 27/879 [3%] in asymptomatic participants). Sensitivity was of 94% (95% CI, 86% to 98%), 23% (CI, 14% to 35%), 94% (CI, 88% to 97%) and 96% (CI, 91% to 99%) for the nasopharyngeal Ag test and the three different protocols of saliva NAAT, respectively. Estimates of specificity were above 95% for all methods. Diagnostic accuracy was similar in symptomatic and asymptomatic individuals. Limitations: Few children (n=122, 8%) were included. Conclusion: In the ambulatory setting, diagnostic accuracy of nasopharyngeal Ag testing and of saliva NAAT seems similar to that of nasopharyngeal NAAT, subject to strict compliance with specific pre-processing and amplification protocols. Registration number: NCT04578509 Funding Sources: French Ministry of Health and the Assistance Publique-Hopitaux de Paris Foundation.
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Emergence of multiple SARS-CoV-2 antibody escape variants in an immunocompromised host undergoing convalescent plasma treatment -
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+SARS-CoV-2 Variants of Concerns (VOC), e.g., B.1.351 (20H/501Y.V2) and P1 (20J/501Y.V3), harboring N-terminal domain (NTD) or the receptor-binding domain (RBD) (e.g., E484K) mutations, exhibit reduced in vitro susceptibility to convalescent serum, commercial antibody cocktails, and vaccine neutralization, and have been associated with reinfection. The accumulation of these mutations could be the consequence of intra-host viral evolution due to prolonged infection in immunocompromised hosts. In this study, we document the microevolution of SARS-CoV-2 recovered from sequential tracheal aspirates from an immunosuppressed patient on tacrolimus, steroids and convalescent plasma therapy, and identify the emergence of multiple NTD and RBD mutations associated with reduced antibody neutralization as early as three weeks after infection. SARS-CoV-2 genomes from the first swab (Day 0) and three tracheal aspirates (Day 7, 21 and 27) were compared at the sequence level. We identified five different S protein mutations at the NTD or RBD regions from the second tracheal aspirate sample (21 Day). The S:Q493R substitution and S:243-244LA deletion had ~70% frequency, while ORF1a:A138T, S:141-144LGVY deletion, S:E484K and S:Q493K substitutions demonstrated ~30%, ~30%, ~20% and ~10% mutation frequency, respectively. However, the third tracheal aspirate sample collected one week later (Day 27) was predominated by the haplotype of ORF1a:A138T, S:141-144LGVY deletion and S:E484K (> 95% mutation frequency). Notably, S protein deletions (141-144LGVY and 243-244LA deletions in NTD region) and substitutions (Q493K/R and E484K in the RBD region) previously showed reduced susceptibly to monoclonal antibody or convalescent plasma. The observation supports the hypothesis that VOCs can independently arise and that immunocompromised patients on convalescent plasma therapy are potential breeding grounds for immune-escape mutants.
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Estimation of real-infection and immunity against SARS-CoV-2 in Indian populations -
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+Infection born by Coronavirus SARS-CoV-2 has swept the world within a time of a few months. It has created a devastating effect on humanity with social and economic depression. Europe and America were the hardest hit continents. India has also lost lives, making the country fourth most deadly worldwide. However, the infection and death rate per million and the case fatality ratio in India were substantially lower than in many developed nations. Several factors have been proposed including genetics. One of the important facts is that a large chunk of Indian population is asymptomatic to the SARS-CoV-2 infection. Thus, the real infection in India is much higher than the reported number of cases. Therefore, the majority of people are already immune in the country. To understand the dynamics of real infection as well as the level of immunity against SARS-CoV-2, we have performed antibody testing (serosurveillance) in the urban region of fourteen Indian districts encompassing six states. In our survey, the seroprevalence frequency varied between 0.01-0.48, suggesting high variability of viral transmission between states. We also found out that the cases reported by the government were several fold lower than the real incidence of infection. This discrepancy is mainly driven by the higher number of asymptomatic cases. Overall, we suggest that with the high level of immunity developed against SARS-CoV-2 in the majority of the districts, the case fatality rate of second wave in India will be minor than first wave.
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Resilient SARS-CoV-2 diagnostics workflows including viral heat inactivation -
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+There is a worldwide need for reagents to perform SARS-CoV-2 detection. Some laboratories have implemented kit-free protocols, but many others do not have the capacity to develop these and/or perform manual processing. We provide multiple workflows for SARS-CoV-2 nucleic acid detection in clinical samples by comparing several commercially available RNA extraction methods: QIAamp Viral RNA Mini Kit (QIAgen), RNAdvance Blood/Viral (Beckman) and Mag-Bind Viral DNA/RNA 96 Kit (Omega Bio-tek). We also compared One-step RT-qPCR reagents: TaqMan Fast Virus 1-Step Master Mix (FastVirus, ThermoFisher Scientific), qPCRBIO Probe 1-Step Go Lo-ROX (PCR Biosystems) and Luna® Universal Probe One-Step RT-qPCR Kit (Luna, NEB). We used primer-probes that detect viral N (EUA CDC) and RdRP (PHE guidelines). All RNA extraction methods provided similar results. FastVirus and Luna proved most sensitive. N detection was more reliable than that of RdRP, particularly in samples with low viral titres. Importantly, we demonstrate that treatment of nasopharyngeal swabs with 70 degrees for 10 or 30 min, or 90 degrees for 10 or 30 min (both original variant and B 1.1.7) inactivates SARS-CoV-2 employing plaque assays, and that it has minimal impact on the sensitivity of the qPCR in clinical samples. These findings make SARS-CoV-2 testing portable to settings that do not have CL-3 facilities. In summary, we provide several testing pipelines that can be easily implemented in other laboratories and have made all our protocols and SOPs freely available at https://osf.io/uebvj/.
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Parallel pandemics illustrate the need for One Health solutions -
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+African Swine Fever (ASF) was reported in domestic pigs in China in 2018. This highly contagious viral infection with no effective vaccine reached pandemic proportions by 2019, substantially impacting protein availability in the same region where the COVID-19 pandemic subsequently emerged. We discuss the genesis, spread, and wide-reaching impacts of an epidemic in a vital livestock species, noting parallels and potential contributions to ignition of COVID-19. We speculate about follow-on impacts of these pandemics on global public health infrastructure and suggest intervention strategies using a cost: benefit approach for low-risk, massive-impact events. We note that substantive changes in how the world reacts to potential threats will be required to overcome catastrophes driven by climate change, food insecurity, lack of surveillance infrastructure and other gaps. We note that a One Health approach creating collaborative processes connecting expertise in human, animal, and environmental health is essential for combating future global health crises.
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Living in Uncertain Times: Pre-existing Mental Health Symptoms, Intolerance of Uncertainty and Perceived COVID-19 Threat as Predictors of Psychological Distress During the Pandemic -
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+Amidst the ongoing COVID-19 pandemic, people are facing heightened uncertainty about the future and increasing rates of psychological distress. Intolerance of uncertainty (IU) and perceived COVID-19 threat may be contributing to mental health problems. This study investigated changes in mental health problems prior to and during the first two pandemic waves in the U.S., and the extent to which IU and perceived COVID-19 threat predicted these problems. MTurk participants (n=192; 50% women) were recruited from a pre-pandemic study in December 2019/January 2020 for a follow-up study on COVID-19 experiences, across five timepoints between April and August 2020. IU, perceived COVID-19 threat, and mental health problems (i.e., worry, COVID-19 fear, and trauma symptoms) were assessed. On average, mental health problems were not elevated, relative to pre-pandemic levels, and remained stable across time. Heightened IU and perceived COVID-19 threat were associated with more mental health problems. Surprisingly, objective measures of COVID-19 threat (e.g., state case rates) showed no associations with IU, and were slightly negatively correlated with psychological distress and perceived threat. Pre-existing mental health symptoms, IU and perceived COVID-19 threat may foster vulnerability to mental health problems during the pandemic, more so than objective threat levels.
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Risk and protective factors of college students’ psychological well-being during the COVID-19 pandemic: emotional stability, mental health, and household resources -
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+Colleges and universities have increasingly worried in recent decades about college students’ wellbeing, with the COVID-19 pandemic aggravating these concerns. Our study provides empirical evidence of changes to undergraduate emotional sentiments and psychological wellbeing from before to after the onset of the pandemic. In addition, we explore whether certain risk factors (i.e., prior mental health impairments, trait emotional stability) and protective factors (i.e., subjective socioeconomic status, parental education, household resources) predicted students’ emotions and their intra-individual changes due to the pandemic onset. We compared experience sampling method data from 120 students from before and after the pandemic onset, examining intra-individual trajectories. There was only little change in students’ emotions. Prior mental health impairment and trait emotional stability predicted students’ emotions, averaged across time points, but not emotion changes. Few associations with emotions were found for subjective socioeconomic status and parental education, but study-related household-resources predicted levels and changes in emotions.
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The demographic and geographic impact of the COVID pandemic in Bulgaria and Eastern Europe in 2020 -
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+Background: The COVID-19 pandemic followed a unique trajectory in Eastern Europe compared to other heavily affected regions, with most countries there only experiencing a major surge of cases and deaths towards the end of 2020 after a relatively uneventful first half of the year. However, the consequences of that surge have not received as much attention as the situation in Western countries. Bulgaria, even though it has been one of the most heavily affected countries, has been one of those neglected cases. Methods: We use mortality and mobility data from Eurostat, official governmental and other sources to examine the development and impact of the COVID-19 pandemic in Bulgaria and other European countries. Results: We find a very high level of excess mortality in Eastern European countries measured by several metrics including excess mortality rate (EMR), P-scores and potential years of life lost. By the last metric Eastern Europe emerges as the hardest hit region by the pandemic in Europe in 2020. With a record EMR at ~0.25% and a strikingly large and mostly unique to it mortality rate in the working age demographics, Bulgaria emerges as one of the most affected countries in Eastern Europe. The high excess mortality in Bulgaria correlates with insufficient intensity of testing and with delayed imposition of lockdown measures. We also find major geographic and demographic disparities within the country, with considerably lower mortality observed in major cities relative to more remote areas (likely due to disparities in the availability of medical resources). Analysis of the course of the epidemic revealed that individual mobility measures were predictive of the eventual decline in cases and deaths. However, while mobility declined as a result of the imposition of a lockdown, it already trended downwards before such measures were introduced, which resulted in a reduction of deaths independent of the effect of restrictions. Conclusions: Large excess mortality and high numbers of potential years of life lost are observed as a result of the COVID pandemic in Bulgaria, as well as in several other countries in Eastern Europe. Significant delays in the imposition of stringent mobility-reducing measures combined with a lack of medical resources likely caused a substantial loss of life, including in the working age population.
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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
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Study of DS-5670a (COVID-19 Vaccine) in Japanese Healthy Adults and Elderly Subjects - Condition: Covid19 Interventions: Biological: DS-5670a; Biological: Placebo Sponsor: Daiichi Sankyo Co., Ltd. Recruiting
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Efficacy, Immunogenicity and Safety of Inactivated ERUCOV-VAC Compared With Placebo in COVID-19 - Condition: COVID-19 Interventions: Biological: ERUCOV-VAC 3 µg/0.5 ml Vaccine; Biological: ERUCOV-VAC 6 µg/0.5 ml Vaccine; Other: Placebo Sponsors: Health Institutes of Turkey; Erciyes University Scientific Research Projects Coordination Recruiting
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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
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Viral Clearance, PK and Tolerability of Ensovibep in COVID-19 Patients - Condition: Covid19 Intervention: Drug: ensovibep Sponsor: Molecular Partners AG Recruiting
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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
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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
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A Dose Finding, Efficacy and Safety Study of Ensovibep (MP0420) in Ambulatory Adult Patients With Symptomatic COVID-19 - Condition: COVID-19 Interventions: Drug: ensovibep; Drug: Placebo Sponsors: Molecular Partners AG; Novartis Pharmaceuticals; Iqvia Pty Ltd; Datamap; SYNLAB Analytics & Services Switzerland AG; Q2 Solutions Not yet recruiting
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Vitamin D, Omega-3, and Combination Vitamins B, C and Zinc Supplementation for the Treatment and Prevention of COVID-19 - Condition: Covid19 Interventions: Dietary Supplement: Vitamin D; Dietary Supplement: Omega DHA / EPA; Dietary Supplement: Vitamin C, Vitamin B complex and Zinc Acetate Sponsors: Hospital de la Soledad; Microclinic International Recruiting
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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 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
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Cetirizine and Famotidine for COVID-19 - Condition: Covid19 Interventions: Drug: Cetirizine and Famotidine; Drug: Placebo Sponsor: Emory University Not yet recruiting
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TCB008 in Patients With COVID-19 - Condition: Covid19 Intervention: Drug: TCB008 Sponsor: TC Biopharm Not yet recruiting
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Dual MRI for Cardiopulmonary COVID-19 Long Haulers - Condition: Covid19 Intervention: Drug: Hyperpolarized 129Xenon gas Sponsor: Bastiaan Driehuys Not yet recruiting
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From PubMed
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Antiviralis es gyulladasellenes kezelesi lehetosegek COVID-19-ben - Összefoglaló. Az új típusú koronavírus-fertőzés (COVID-19) nagy terhet ró az egészségügyi ellátórendszerre és a társadalomra. A betegségnek három nagy szakasza van, melyek alapvetően meghatározzák a kezelést. Az I-IIA fázisban az antivirális, míg a IIB-III. fázisban a gyulladásgátló kezelés áll előtérben, melyhez intenzív terápiás, szupportív kezelés csatlakozik. A jelen ajánlás kizárólag a gyógyszeres kezelésre vonatkozik, és a rendelkezésre álló bizonyítékok alapján foglalja össze a terápiás…
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Coronavirus genomic nsp14-ExoN, structure, role, mechanism, and potential application as a drug target - The recent coronavirus disease 2019 (COVID-19), causing a global pandemic with devastating effects on healthcare and social-economic systems, has no special antiviral therapies available for human coronaviruses (CoVs). The severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) possesses a non-structural protein (nsp14), with amino terminal domain coding for a proofreading exoribonuclease (ExoN) that is required for high-fidelity replication. The ability of CoVs during genome replication…
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Silencing of SARS-CoV-2 with modified siRNA-peptide dendrimer formulation - CONCLUSIONS: Thus, we developed a therapeutic strategy for COVID-19 based on inhalation of a modified siRNA-peptide dendrimer formulation. The developed medication is intended for inhalation treatmentof COVID-19 patients.
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GCG inhibits SARS-CoV-2 replication by disrupting the liquid phase condensation of its nucleocapsid protein - Lack of detailed knowledge of SARS-CoV-2 infection has been hampering the development of treatments for coronavirus disease 2019 (COVID-19). Here, we report that RNA triggers the liquid-liquid phase separation (LLPS) of the SARS-CoV-2 nucleocapsid protein, N. By analyzing all 29 proteins of SARS-CoV-2, we find that only N is predicted as an LLPS protein. We further confirm the LLPS of N during SARS-CoV-2 infection. Among the 100,849 genome variants of SARS-CoV-2 in the GISAID database, we…
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Identification of COVID-19 subtypes based on immunogenomic profiling - Although previous studies have shown that the host immune response is crucial in determining clinical outcomes in COVID-19 patients, the association between host immune signatures and COVID-19 patient outcomes remains unclear. Based on the enrichment levels of 11 immune signatures (eight immune-inciting and three immune-inhibiting signatures) in leukocytes of 100 COVID-19 patients, we identified three COVID-19 subtypes: Im-C1, Im-C2, and Im-C3, by clustering analysis. Im-C1 had the lowest…
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TOP1 inhibition therapy protects against SARS-CoV-2-induced lethal inflammation - The ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently affecting millions of lives worldwide. Large retrospective studies indicate that an elevated level of inflammatory cytokines and pro-inflammatory factors are associated with both increased disease severity and mortality. Here, using multidimensional epigenetic, transcriptional, in vitro, and in vivo analyses, we report that topoisomerase 1 (TOP1) inhibition suppresses lethal inflammation…
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Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination - CONCLUSIONS: Vaccination with ChAdOx1 nCov-19 can result in the rare development of immune thrombotic thrombocytopenia mediated by platelet-activating antibodies against PF4, which clinically mimics autoimmune heparin-induced thrombocytopenia. (Funded by the German Research Foundation.).
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Involvement of the complement cascade in severe forms of COVID-19 - The complement system is an essential component of the innate immune system. Its excessive activation during COVID-19 contributes to cytokine storm, disease-specific endothelial inflammation (endotheliitis) and thrombosis that comes with the disease. Targeted therapies of complement inhibition in COVID-19, in particular blocking the C5a-C5aR1 axis have to be taken into account in the establishment of potential biomarkers and development of therapeutic strategies in the most severe forms of the…
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Ultraviolet A Radiation and COVID-19 Deaths in the USA with replication studies in England and Italy - CONCLUSIONS: Our analysis suggests that higher ambient UVA exposure is associated with lower COVID-19 specific mortality. Further research on the mechanism may indicate novel treatments. Optimised UVA exposure may have population health benefits.
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Interferon-lambda3 Exacerbates the Inflammatory Response to Microbial Ligands: Implications for SARS-CoV-2 Pathogenesis - INTRODUCTION: Interferon lambdas (IFN-λs) are antiviral cytokines that restrict pathogen infection and dissemination at barrier surfaces. Controlled expression of IFN-λs efficiently eliminates acute infections by activating a suite of interferon stimulated genes that inhibit viral propagation and activate local immune cells. Excessive or prolonged production of IFN-λs can however mediate tissue inflammation and disrupt epithelial barriers in both viral and non-viral disease. The mechanism by…
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MUC1-C influences cell survival in lung adenocarcinoma Calu-3 cells after SARS-CoV-2 infection - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces coronavirus disease 2019 (COVID-19) and may increase the risk of adverse outcomes in lung cancer patients. In this study, we investigated the expression and function of mucin 1 (MUC1) after SARS-CoV-2 infection in the lung epithelial cancer cell line Calu-3. MUC1 is a major constituent of the mucus layer in the respiratory tract and contributes to pathogen defense. SARS-CoV-2 infection induced MUC1 C-terminal subunit (MUC1-C)…
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The green tea catechin epigallocatechin gallate inhibits SARS-CoV-2 infection - The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has caused a pandemic with tens of millions of cases and more than a million deaths. The infection causes COVID-19, a disease of the respiratory system of divergent severity. No treatment exists. Epigallocatechin-3-gallate (EGCG), the major component of green tea, has several beneficial properties, including antiviral activities. Therefore, we examined whether EGCG has antiviral activity against SARS-CoV-2. EGCG blocked…
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C-Phycocyanin-derived Phycocyanobilin as a Potential Nutraceutical Approach for Major Neurodegenerative Disorders and COVID-19-induced Damage to the Nervous System - The edible cyanobacterium Spirulina platensis and its chief biliprotein C-Phycocyanin have shown protective activity in animal models of diverse human health diseases, often reflecting antioxidant and anti-inflammatory effects. The beneficial effects of C-Phycocyanin seem likely to be primarily attributable to its covalently attached chromophore Phycocyanobilin (PCB). Within cells, biliverdin is generated from free heme and it is subsequently reduced to bilirubin. Although bilirubin can function…
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ATP energy-independently controls protein homeostasis with unique structure and diverse mechanisms - Proteins function in the crowded cellular environments with high salt concentrations, thus facing tremendous challenges of misfolding/aggregation which represents a pathological hallmark of aging and an increasing spectrum of human diseases. Recently, intrinsically disordered regions (IDRs) were recognized to drive liquid-liquid phase separation (LLPS), a common principle for organizing cellular membraneless organelles (MLOs). ATP, the universal energy currency for all living cells, mysteriously…
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ORF10-Cullin-2-ZYG11B complex is not required for SARS-CoV-2 infection - In order to understand the transmission and virulence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is necessary to understand the functions of each of the gene products encoded in the viral genome. One feature of the SARS-CoV-2 genome that is not present in related, common coronaviruses is ORF10, a putative 38-amino acid protein-coding gene. Proteomic studies found that ORF10 binds to an E3 ubiquitin ligase containing Cullin-2, Rbx1, Elongin B, Elongin C, and ZYG11B…
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From Patent Search
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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
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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
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Peptides and their use in diagnosis of SARS-CoV-2 infection - - link
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A PROCESS FOR SUCCESSFUL MANAGEMENT OF COVID 19 POSITIVE PATIENTS - - link
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IN SILICO SCREENING OF ANTIMYCOBACTERIAL NATURAL COMPOUNDS WITH THE POTENTIAL TO DIRECTLY INHIBIT SARS COV 2 - IN SILICO SCREENING OF ANTIMYCOBACTERIAL NATURAL COMPOUNDS WITH THE POTENTIAL TO DIRECTLY INHIBIT SARS COV 2Insilico screening of antimycobacterial natural compounds with the potential to directly inhibit SARS COV2 relates to the composition for treating SARS-COV-2 comprising the composition is about 0.1 – 99% and other pharmaceutically acceptable excipients. The composition also treats treating SARS, Ebola, Hepatitis-B and Hepatitis–C comprising the composition is about 0.1 – 99% and other pharmaceutically acceptable excipients. - link
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Aronia-Mundspray -
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+Anordnung zum Versprühen einer Substanz in die menschliche Mundhöhle und/oder in den Rachen oder zum Trinken, dadurch gekennzeichnet, dass die Anordnung eine Flasche mit einer Substanz aufweist, die wenigstens Aroniasaft und eine Alkoholkomponente aufweist und einen Sprühkopf besitzt.
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INTERFASE ANTIBACTERIANA Y VIRICIDA PARA VENTILACION MECANICA NO INVASIVA - - link
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一种用于检测新型冠状病毒COVID-19的引物组及试剂盒 - 本发明涉及生物技术领域，特别是涉及一种用于检测冠状病毒的引物组及试剂盒，所述引物组包括以下中的一对或多对：外侧引物对：所述外侧引物对包括如SEQ ID NO:1所示的上游引物F3和如SEQ ID NO:2所示的下游引物B3；内侧引物对：所述内侧引物对包括如SEQ ID NO:3所示的上游引物FIP和如SEQ ID NO:4所示的下游引物BIP；环引物对：所述环引物对包括如SEQ ID NO:5所示的上游引物LF和如SEQ ID NO:6所示的下游引物LB。试剂盒包括所述引物组。本发明在一个管中整合了RT‑LAMP和CRISPR，能依据两次颜色变化检测病毒和各种靶标核酸。 - link
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新冠病毒中和性抗体检测试剂盒 - 本发明提供一种新冠病毒中和性抗体检测试剂盒。所述试剂盒基于BAS‑HTRF技术，主要包含：生物素标记的hACE2、新冠病毒棘突蛋白RBD‑Tag1、能量供体Streptavidin‑Eu cryptate、能量受体MAb Anti‑Tag1‑d2和新冠病毒中和性抗体。本发明将BAS和HTRF两种技术相结合，用于筛选新型冠状病毒中和性抗体，3小时内即可实现筛选，且操作简单，无需经过多次洗板过程。BAS和HTRF联用大大提升了反应灵敏度，且两种体系都能最大限度地减少非特异的干扰，适用于血清样品的检测。该方法可实现高通量检测，对解决大批量样品的新冠病毒中和性抗体的检测具有重要意义。 - link
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Infektionsschutzmaske -
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Infektionsschutzmaske (1) zum Schutz vor Übertragung von Infektionskrankheiten mit einer Außen - und einer Innenseite (2,3) sowie Haltemitteln (5) zum Befestigen der Infektionsschutzmaske (1) am Kopf eines Maskenträgers, dadurch gekennzeichnet, dass an der Infektionsschutzmaske (1) mindestens eine Testoberfläche (6) zum Nachweis von Auslösern einer Infektionskrankheit derart angeordnet ist, dass diese bei korrekt angelegter Infektionsschutzmaske (1) mit der Ausatemluft des Maskenträgers unmittelbar in Kontakt gelangt.
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+ 11 April, 2021
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+Daily-Dose
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Why It’s So Hard for America to End Its Wars - Is there any way for Biden to achieve peace with honor in Iraq, Syria, and Afghanistan? - link
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Vladimir Putin Has a Message: “Hey, Joe, Are You Listening?” - The Biden Administration can’t escape the Russia problem. - link
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How Can We Continue to Keep Schools Relatively Safe from the Coronavirus? - Experts warn that any vaccine mandate for educators could backfire. - link
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The Long Trip Home - After a young athlete died, there was no question that he would be buried in his home town. How his parents would transport the casket nearly nine thousand miles during a pandemic was less clear. - link
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A Cautionary Tale of Workplace Harassment in the Cuomo Administration - As Albany decides what due process for Andrew Cuomo should look like, women in his administration who faced retaliation in 2017 have waited years for a resolution. - link
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From Vox
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Michigan’s governor emphasizes voluntary efforts to curb the most severe coronavirus outbreak in the US -
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+Covid-19 cases are surging in Michigan, the latest epicenter of the virus in the US. | Getty Images
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+Gov. Gretchen Whitmer’s actions fly in the face of mandatory restrictions she instituted last year.
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+Michigan Gov. Gretchen Whitmer is declining to order state-wide lockdowns in response to her state experiencing the most severe Covid-19 outbreak in the country, opting instead to recommend that people take “personal responsibility” and “voluntarily” take a break from spaces where transmission is more likely.
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+The decision to refrain from instituting mandatory restrictions is a striking development for a Democratic governor who last year garnered national attention for swiftly instituting and standing by social distancing laws even in the face of militant right-wing protests and a kidnapping attempt against her. This time around, even as her state is experiencing a full-blown crisis, she’s taking a softer approach in what may be a political calculation about her reelection prospects next year.
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+But Whitmer has taken a decidedly incremental approach on reinstating distancing rules as her state is overwhelmed by new cases. At a press conference on Friday, she took a position that indicated a reluctance to reinstate full-blown lockdowns.
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+“We all have to step up our game for the next two weeks to bring down rising cases,” she said. “And that’s why I’m calling on high schools to voluntarily go remote for two weeks past spring break, I’m calling on youth sports to voluntarily suspend games and practices for two weeks, and I’m strongly encouraging all Michiganders to avoid dining indoors and avoid gathering with friends indoors for two weeks.”
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+“Policy alone won’t change the tide. We need everyone to step up and to take personal responsibility,” she said.
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+Whitmer emphasized that she wasn’t making restrictions mandatory, but didn’t rule out future restrictions.
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+Her actions in this situation stand in contrast to her use of state of emergency executive orders and stay-at-home orders last spring to bring down the rate of cases in her state — a response that was popular but also elicited vociferous push-back from conservative activists and the state’s Republican-controlled legislature.
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+Whitmer might be worried about pushback
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+A growing number of public health officials and experts are calling on Whitmer to take more aggressive action, and it is possible that she will do so at some point in the future. But for now, there are a few factors that could be playing a role in her resistance to issuing mandated actions.
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+One is the issue of efficacy. A great deal of polling data shows that fatigue with Covid-19 restrictions is a very real phenomenon, and that even many months ago people were reporting a decline in compliance with rules. Whitmer might be concerned that with the spread of the vaccine, better weather, the relaxation of restrictions in other states, and growing optimism, it could be difficult to achieve compliance with mandatory restrictions. There could be a concern that making rules required will make people resentful while not significantly improving health outcomes.
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+Another factor is political calculation. She may fear backlash and disapproval at a time when people are sick of restrictions, something of concern to her as she approaches reelection next year — in a state where Republicans control the legislature and have wasted no opportunities to paint her past Covid-19 restrictions as tyrannical.
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+Political observers believe Whitmer’s management of the pandemic will play a pivotal role in determining her reelection — and the reality is that perception of the virus is different now than it was a year ago.
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+But some public health experts say that trying to take what seems like a moderate position on social distancing during a crisis-level surge is a dangerous mistake.
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+“What it looks like happened is she tried to be fair and meet us in the middle,” Debra Furr-Holden, a Michigan State University epidemiologist whom Whitmer appointed to a coronavirus task force, told the New York Times. “And what I think we’ve learned — and I hope other states will get the message — is that there really isn’t a lot of middle ground here. We just have to tighten up and hold tight.”
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Northern Ireland is experiencing some of the worst violence it’s seen in 8 years. Here’s why. -
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+A protester throwing a rock at a police vehicle in Belfast, Northern Ireland, on April 8, 2021. | Paul Faith/AFP/Getty Images
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+Brexit and suspicions of favoritism are fueling a conflict that has been simmering for years despite peace accords.
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+The night of violence marked the eighthstraight day of demonstrations and unrest in five towns and cities across Northern Ireland — a trend that has some experts worried about the possibility that the region could be seeing a sustained resurgence of sectarian violence. Saturday, April 10, is the 23rd anniversary of the 1998 Good Friday peace agreement that ended 30 years of such conflict, known as “the Troubles,” but unrest and violence has flared up from time to time ever since.
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+Over the past week, a double-decker bus has been hijacked and set on fire; masked youths have hurled homemade gas bombs at police; rival gangs have thrown bricks and fireworks at each other. So far there have been no deaths reported, but at least 74 police officers have been injured, and observers say that the period of turbulence marks the worst sectarian violence Northern Ireland has seen in eight years.
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+Most of the rioters are young people — some as young as 12, the Police Service of Northern Ireland told CNN. The violence has been concentrated in “unionist” communities, but conflict has also taken place in areas dividing unionist communities from “nationalist” neighborhoods. During the Troubles, unionists were largely Protestant and identified with loyalty to the United Kingdom, and nationalists were mostly Catholics, identified as Irish, and sought a united Ireland.
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+While conflict between the groups formally ended with the Good Friday Agreement in 1998, tensions and violence that hark back to the Troubles still resurface, and are often tied to concerns that one group holds undue influence or power over national affairs. The current set of clashes has become high-profile enough that the Biden administration released a brief statement expressing concern about rising violence.
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+Experts say that there is not one clear explanation for the recent clashes, but that there are a few different factors — which may be feeding off of each other. Brexit, and the sense in unionist communities that London is neglecting Northern Ireland by the terms of the agreement are one factor. Another issue is a recent decision by authorities to avoid prosecuting nationalist politicians for flouting Covid-19 protocols.
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+What is clear is that political observers see violence escalating at a worrying pace. “I think it’s very serious. It’s easy to see how things can escalate and hard to see how things can calm down,” Katy Hayward, a professor of political sociology at Queen’s University, Belfast, told the New York Times.
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+There are multiple factors driving the unrest in Northern Ireland
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+Conflict and violence between unionists and nationalists dates back decades. But the most recent spate of violence seems to be, at least in part, a response to a specific flashpoint in the relationship between the two communities.
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+A great deal of the initial violence came after state prosecutors decided last month they would not charge the leaders of nationalist party Sinn Fein for breaking Covid-19 regulations in June by attending the funeral for Bobby Storey. Storey was a former top member of the Irish Republican Army, the paramilitary group that waged a violent campaign against the British and for a reunified Ireland during the Troubles.
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+Many unionists perceived the decision to not prosecute the members of the party as a sign of political favoritism, given that unionists were told to cancel their traditional Twelfth of July parades last summer, and the loaded symbolism surrounding the funeral. The decision sparked outrage and protests.
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+“This is happening because of the PSNI [Police Service of Northern Ireland] and the judiciary system’s appeasement of republicans,” said Ian Edwards, a resident of the Shankill Road, a Protestant community, referring to the nationalists who favor a united Ireland.
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+Experts say another major factor fueling the anger and protests is the way that many in Northern Ireland feel betrayed by the terms of Brexit — the United Kingdom’s departure from the European Union — which was completed at the beginning of this year. In this scenario, unionists feel blindsided by the British government, which they believe has left them in a lurch, as the New York Times reports:
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+Under an agreement in a protocol struck by [British Prime Minister Boris] Johnson, Northern Ireland was given a special economic status that leaves it straddling the United Kingdom and the European Union trade systems.
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+Despite the deal he signed up to, Mr. Johnson promised that there would be no new “border in the Irish Sea,” and, glossing over the looming difficulties, his government did little to prepare opinion in Northern Ireland for the changes.
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+Yet on Jan. 1, when the post-Brexit trade rules came into force, businesses faced new paperwork and some British companies stopped moving goods to Northern Ireland, causing some shortages on supermarket shelves. Amid rising tensions, checks on goods were halted temporarily after threats were made against customs staff.
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+In other words, Northern Ireland unionists feel they’ve been misled about the terms of Brexit and the economic impact it would have on them.
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+Another complicating factor is that the period around the Easter holiday often features “increased communal conflict,” Politico notes, because of Irish Republican Army commemorations among nationalists in Northern Ireland on the one side and unionist parades on the other.
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+There’s a complex array of factors that could explain what’s contributing to the current chaos — and given that swirl, it could evolve further in the future.
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Supreme Court rules against California’s Covid-19 restrictions on grounds of religious liberty -
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+The US Supreme Court is seen from Capitol Hill in Washington, DC, in February 2021. | Salwan Georges/The Washington Post/Getty Images
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+The court rules that Bible study groups should be able to gather in private homes if commercial spaces are open.
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+The Supreme Court blocked California’s Covid-19 restrictions on religious gatherings in private homes in a late-night order on Friday, saying that the law infringes on constitutionally protectedreligious rights in a 5-4 vote.
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+The decision, in which Chief Justice John Roberts voted with the three dissenting liberal justices, marks the fifth time that the Supreme Court has sided with religious adherents protesting California’s laws designed to slow the spread of the coronavirus. And it underscores how Justice Amy Coney Barrett’s replacement of the late Justice Ruth Bader Ginsburg in November has tilted the high court toward overruling state Covid-19 restrictions on religious services.
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+The unsigned majority opinion argued that California’s law — which limits both religious and non-religious gatherings in homes to no more than three households — treats religious gatherings unfairly in light of allowances for gatherings in commercial spaces. “California treats some comparable secular activities more favorably than at-home religious exercise, permitting hair salons, retail stores, personal care services, movie theaters, private suites at sporting events and concerts and indoor restaurants,” the opinion said.
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+But in her dissent, Justice Elena Kagan, joined by Justices Sonia Sotomayor and Stephen Breyer, wrote that the majority opinion was making the wrong comparison between unlike activities: “The First Amendment requires that a state treat religious conduct as well as the state treats comparable secular conduct. Sometimes finding the right secular analogue may raise hard questions. But not today.”
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+The courts split on how California’s law treats commercial spaces differently than private homes
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+In her dissent, Kagan explained that California’s law doesn’t single out religious gatherings but simply treats all at-home gatherings differently than commercial spaces.
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+“California limits religious gatherings in homes to three households. If the state also limits all secular gatherings in homes to three households, it has complied with the First Amendment. And the state does exactly that: It has adopted a blanket restriction on at-home gatherings of all kinds, religious and secular alike,” she wrote.
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+The reason for the restrictions on households that don’t apply to commercial spaces, she wrote, is that gatherings in private homes are considered categorically riskier because of the more intimate way people gather in them.
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+That argument was in line with the majority opinion from the 9th Circuit Court of Appeals that the Supreme Court ultimately rejected.
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+In that opinion, judges Milan Smith Jr. and Bridget Bade wrote that it made sense for California law to treat commercial and non-commercial spaces differently: “The state reasonably concluded that when people gather in social settings, their interactions are likely to be longer than they would be in a commercial setting; that participants in a social gathering are more likely to be involved in prolonged conversations; that private houses are typically smaller and less ventilated than commercial establishments; and that social distancing and mask-wearing are less likely in private settings and enforcement is more difficult.”
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+The case that prompted the decision was brought by two Santa Clara County residents who said that Covid-19 restrictions violated their free speech rights by preventing their Bible study and prayer sessions with eight to 12 individuals.
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+Barrett has shifted the Supreme Court’s outlook on religious services
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+The Supreme Court’s decision in their favor is a reminder of how Barrett’s arrival has shifted the ideological makeup of the court, and its outlook on clashes between states and advocates for minimizing Covid-19 state restrictions on religious gatherings.
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+As legal analyst Adam Liptak notes at the New York Times, before Ginsburg’s death last year, the Supreme Court allowed California and Nevada to restrict religious service attendance, and Roberts, the chief justice, was siding with what was then a liberal contingent made up of four justices.
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+But that pattern shifted after Barrett’s arrival last fall, and the Supreme Court blocked New York’s restrictions on religious services.
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+Conservative activists rankled by Covid-19 restrictions hailed Friday’s Supreme Court ruling as a victory for the right and for freedom to worship.
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+That the state of California thinks it should be able to regulate who can pray together inside private homes is almost as appalling as the desire of all the brainwashed Fauci worshipping sheep for more arbitrary authoritarian COVID rules to keep them “safe” https://t.co/55fy62CyHc
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+Meanwhile, commentators on the left have said the issue at hand is not religious liberty but rather an emerging culture war over the status of religion in American life. In a New Republic piece about the trend of the new conservative majority’s rulings on Covid-19 and religion, Katherine Stewart writes that the Supreme Court’s recent legal interventions are designed to “validate a false underlying narrative of religious persecution” in America.
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From The Hindu: Sports
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IPL 2021 | Made small changes in my technique, minimized mistakes, says Prithvi - The 21-year-old on Saturday blasted his way to a 38-ball 72-run innings as Delhi Capitals chased down a winning target of 189 against CSK with more than an over to spare
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IPL 2021 | Big-hitters galore: RR, Punjab Kings aim for winning start to IPL campaign - Rajasthan Royals could opt to open with the highly-rated Yashasvi Jaiswal and Buttler
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IPL 2021 | Shikhar Dhawan impressed by Rishabh Pant’s calmness on captaincy debut, says he’s only going to get better - “The best thing about Rishabh Pant is that he stays calm. His presence of mind is quite there, which is very very good,” says Shikhar Dhawan
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Hockey: Harmanpreet’s brilliance, Sreejesh’s grit fetches India bonus point in shootout win over Argentina - The result meant India consolidated their fifth position in the FIH Hockey Pro League standings with 12 points from seven matches.
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IPL 2021 | Dhoni fined for slow over rate in CSK’s opener - Three-time champions CSK witnessed a poor start to its IPL 14 campaign.
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From The Hindu: National News
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COVID-19 wreaking havoc on Indian lives due to Modi govt’s policies: Congress - The Congress also alleged that every section of the society was troubled due to the policies of the government.
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Protest organised against sale of public sector units - ‘Immediately allocate captive mines to steel plant’
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Coronavirus | Remdesivir shortage in Nagpur; Gadkari dials Sun Pharma chief - Mr. Gadkari also appealed to the people of Nagpur to follow all COVID-19 prevention protocols
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West Bengal Assembly polls | Cooch Behar incident result of conspiracy hatched by BJP to intimidate voters, says Mamata - Mamata Banerjee said the saffron party has always deceived common people.
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Coronavirus | Over 200 Delhi jail inmates vaccinated, no adverse events reported - Earlier, the Delhi Prisons Department had set up a COVID-19 vaccination centre inside Tihar Jail to vaccinate the inmates
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From BBC: Europe
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Prince Philip: World leaders and royals send heartfelt sympathy - Australia’s PM attends a commemorative service in Sydney, as tributes pour in from around the world.
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Giorgos Karaivaz: Veteran crime journalist shot dead in Greece - Giorgos Karaivaz was shot with a silenced weapon by two men on a moped outside his home in Athens.
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Covid: Over 100 Paris restaurant diners fined for violating rules - More than 100 diners at a Paris restaurant are fined and the manager arrested for violating Covid restrictions.
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Save our wine! Big freeze spells disaster for French vineyards - Vineyards in some areas are reporting extensive damage and the government is declaring a disaster.
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Nikolai Glushkov: Putin critic ‘strangled in London home by third party’ - Former Aeroflot director and Russian exile Nikolai Glushkov was unlawfully killed, a coroner rules.
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From Ars Technica
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More lightning in the Arctic is bad news for the planet - Lightning strikes in the far north could double by 2100. - link
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Voyagers explores complexities of coming of age in space - Director Neil Burger discusses how his film delves into the core of human nature - link
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Lego has a new 2,354-piece NASA Space Shuttle set, and it’s awesome - The toymaker has had space shuttle sets in the past, but none as detailed as this. - link
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Court rules grocery store’s inaccessible website isn’t an ADA violation - The Winn-Dixie website isn’t accessible for blind users with screen readers. - link
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Diablo II Resurrected impressions: Unholy cow, man - Blizzard Classic follows WarCraft III’s utter failure with an udder success. - link
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From Jokes Subreddit
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What’s the difference between a Pakistani elementary school and an Al-qaeda outpost? -
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Three expectant mothers are sitting in the doctor’s office, knitting… [warning: offensive!] -
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+[I once killed a party with this joke. You have been warned!]
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+Three expectant mothers are sitting in the doctor’s office, knitting.
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+The first mother puts down her knitting, picks up her handbag, pulls out a bottle of pills, takes one, then resumes knitting. She sees the other two mothers looking at her, so she says, “Vitamins. Good for mummy-” She pats her stomach. “-and good for little baby.”
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+The second mother puts down her knitting, picks up her handbag, pulls out a bottle of pills, takes one, then resumes knitting. She sees the other two mothers looking at her, so she says, “Essential minerals. Good for mummy-” She pats her stomach. “-and good for little baby.”
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+The third mother puts down her knitting, picks up her handbag, pulls out a bottle of pills, takes one, then resumes knitting. She sees the other two mothers looking at her, so she says, “Thalidomide.” She shrugs. “I can’t knit sleeves.”
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+A woman asked an Army General when the last time he had made love to a woman. The general replied “1956, ma’am.” The woman, in disbelief said “1956?! That long? Come with me and let me make your night better.” The woman and general went back to her apartment and made passionate love for over an hour. Afterwards, the woman cuddled up to the general and said “Well, you sure haven’t forgotten anything since 1956…” The general looked at her, confused, and replied “I sure hope not, it’s only 2130 now.”
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A Saudi Prince wants to buy a bull, so he goes to see a famous Russian bovine breeder. -
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+The Russian tells him, “I have many good animal. Here is Swedish bull, is born black color, but color turns white when grows.”
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+“Over there is American bull. Color when born is red, but become dark brown when full grown.”
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+“And here, Turkish bull. They is born dark brown, but grow up to be light brown color.”
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+The prince says, “I rather like the Turkish bulls. Fine specimens indeed.”
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+“Excellent choice, your majesty. But Turkish bull is special. They is bred for royalty, like you. But if you have royal blood, you must be bonding with bull calf when young, before they change color. Or they will reject you,” the Russian explains.
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+“Well”, the prince says, “I’m looking for a strong, adult bull. I’m not particularly interested in buying a calf. I rather like this big, beige bull over here.”
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+The prince attempts to pet the large Turkish bull. It sniffs his hand, shakes its head in disgust, turns around and kicks the prince with its hind legs.
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+The prince goes flying across the room and lands in a pile of hay.
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+“Where did you get such a horrible beast?! Why did it kick me!?” He sputters.
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+“I told you. From Turkey.” The Russian explains. “Is tan bull, can’t stand a noble.”
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