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+ + + ++This study aimed to evaluate the link between microbial translocation markers and systemic inflammation at the earliest time-point after hospitalization and at the last 72 h of hospitalization in survivors and non-survivors COVID-19 patients. Sixty-six SARS-CoV-2 RT-PCR+ infected patients and nine non-COVID-19 pneumonia controls were admitted in this study. Blood samples were collected at hospital admission (T1) (Controls and COVID-19+ patients) and 0-72 h before hospital discharge (T2, alive or dead) to analyze systemic cytokines and chemokines, LPS concentrations, and soluble CD14 (sCD14) levels. THP-1 human monocytic cell line was incubated with plasma from survivors and non-survivors COVID-19 patients and their phenotype, activation status, TLR4, and chemokine receptors were analyzed by flow cytometry. COVID-19 patients presented higher IL-6, IFN-γ, TNF-α, TGF-β1, CCL2/MCP-1, CCL4/MIP-1β, and CCL5/RANTES levels than controls. Moreover, LPS and sCD14 were higher at hospital admission in SARS-CoV-2-infected patients. Non-survivors COVID-19 patients had increased LPS levels concomitant with higher IL-6, TNF-α, CCL2/MCP-1, and CCL5/RANTES levels at T2. Increased expression of CD16 and CCR5 were identified in THP-1 cells incubated with the plasma of survivor patients obtained at T2. The incubation of THP-1 with T2 plasma of non-survivors COVID-19 leads to higher TLR4, CCR2, CCR5, CCR7, and CD69 expression. In conclusion, increased microbial translocation during hospitalization coexist with the inflammatory condition of SARS-CoV-2 infection and could lead to higher monocyte activation in non-survivors COVID-19 patients. +
++Background: The SARS-CoV-2 Alpha variant B.1.1.7 became prevalent in the United States (US). We aimed to evaluate the impact of vaccination scale-up and potential reduction in the vaccination effectiveness on the COVID-19 epidemic and social restoration in the US. Methods: We extended a published compartmental model and calibrated the model to the latest US COVID-19 data. We estimated the vaccine effectiveness against B.1.1.7 and evaluated the impact of a potential reduction in vaccine effectiveness on future epidemics. We projected the epidemic trends under different levels of social restoration. Results: We estimated the overall existing vaccine effectiveness against B.1.1.7 to be 88.5% (95%CI: 87.4-89.5%) and vaccination coverage would reach 70% by the end of August, 2021. With this vaccine effectiveness and coverage, we anticipated 498,972 (109,998-885,947) cumulative infections and 15,443 (3,828-27,057) deaths nationwide over the next 12 months, of which 95.0% infections and 93.3% deaths were caused by B.1.1.7. Complete social restoration at 70% vaccination coverage would only slightly increase cumulative infections and deaths to 511,159 (110,578-911,740) and 15,739 (3,841-27,638), respectively. However, if the vaccine effectiveness were reduced to 75%, 50% or 25% due to new SARS-CoV-2 variants, we predicted 667,075 (130,682-1,203,468), 1.7m (0.2-3.2m), 19.0m (5.3-32.7m) new infections and 19,249 (4,281-34,217), 42,265 (5,081-79,448), 426,860 (117,229-736,490) cumulative deaths to occur over the next 12 months. Further, social restoration at a lower vaccination coverage would lead to even greater future outbreaks. Conclusion: Current COVID-19 vaccines remain effective against the B.1.1.7 variant, and 70% vaccination coverage would be sufficient to restore social activities to a pre-pandemic level. Further reduction in vaccine effectiveness against SARS-CoV-2 variants would result in a potential surge of the epidemic in the future. +
++Background Despite impressive improvements in institutional births and a fall in maternal mortality, satisfaction of women with birthing experience in public health institutions is low (68%). Birth Companion is an important part of the Labour room Quality Improvement (LaQshya) programme introduced by the Government of India in 2017. Despite mandates, implementation of the concept has been unsatisfactory (9%), even though the importance of Birth Companion has increased due to enhanced risk posed by COVID-19. Little is known about awareness among health care providers on Birth Companions, perceived barriers or their suggestions. Methods We canvassed a 15-question instrument using ordinal scales on 151 health care providers comprising consultants, post graduates, residents, and nurses (response rate 69%) in the department of Obstetrics & Gynecology, Lok Nayak Hospital, Delhi, India to gauge their awareness and opinions about Birth Companions. Results Most health care providers across all categories were aware of the concept (93%), World Health Organization recommendation (83%) and Government instructions for its hospitals (68%) that every woman should be accompanied by a Birth Companion of her choice during labour. Birth Companions of choice suggested by them were the mother (70%), husband (69%). sister (46%) or nurse (43%). Most health care providers agreed that a Birth Companion should wear clean clothes (95%), be free from any communicable disease (91%), stay with the pregnant woman throughout the process of labour (74%) and should have herself gone though labour (42%). Almost all providers (95%) agreed that the presence of a Birth Companion during labour will be beneficial, as they would provide emotional support (99%), boost the confidence of the woman (98%), provide comfort measures like massage (95%), early initiation of breastfeeding (93%), reduce post-partum depression (91%), humanize labour (83%), reduce need for analgesia (70%) and increase spontaneous vaginal births (69%). Yet support for its introduction in their hospital was low (59%). Staff nurses had reservations (62%) with only 40% of those who believed Birth Companion to be beneficial approving of its introduction in their hospital. Over-crowding in labour room and privacy concerns for other women were identified as key barriers. Conclusion Even though most health care providers were aware of and convinced of multiple benefits of Birth Companion during labour, lack of adequate infrastructure in the labour room prevented them from supporting its introduction. Government should provide adequate funding to upgrade labour rooms in a way that provides privacy to the delivering women and frame guidelines and train Birth Companions to perform their role appropriately. Keywords: Birth Companion, Delivery, Respectful Maternity Care, Privacy, Health Care Providers, COVID-19 +
++Introduction: COVID-19 pandemic is grappling the world with the surge of infection time and again. Clinicians are trying to justify the ethics of public health care. Asymptomatic COVID-19 cases are going undocumented and most of them practice self-isolation. Studies have revealed significant radiological changes among RT-PCR positive asymptomatic COVID-19 cases. Objective: The aim of this cross-sectional study is to characterized chest CT findings of asymptomatic RT-PCR-positive patients in one of the COVID designated hospitals in Nepal. Results: Out of 43, 26 (60.5%) participants had positive Chest CT scan findings consistent with COVID pneumonia. 65% had bilateral and 77% had multifocal lesions. The ground-glass opacities (92%), mixed (ground-glass opacities and consolidation) pattern (30.7%), and consolidation only (34.6%) were common chest CT findings. The median CT score was 3.5 (Interquartile range; 2-6). Conclusion: The majority of the RT-PCR positive asymptomatic patient present with CT scan changes of lungs which are important to determine clinical status, prognosis, and long-term sequel in those cohorts. +
++Background: The scope of vaccination rollout and the mRNA SARS-CoV-2 vaccine effectiveness (VE) in the United States (US), and specifically among US Veterans, has not been fully assessed. Methods: Vaccination histories were obtained from medical records to determine if patients were unvaccinated, partially vaccinated (first dose of mRNA SARS-CoV-2 vaccine), or fully vaccinated (two doses) at time of SARS-CoV-2 test. First, coverage with any COVID-19 vaccination by March 7, 2021 was described for all Veterans enrolled in Veterans Health Administration (VHA). Second, to evaluate VE, a matched test negative case-control evaluation was conducted utilizing SARS-CoV-2 positive (cases [n=16,690]) and SARS-CoV-2 negative (controls [n=61,610]) tests from Veterans aged ≥18 years old who routinely sought care at a VHA facility and were tested for SARS-CoV-2 from December 14, 2020 through March 14, 2021. VE was calculated from odds ratios (ORs) with 95% confidence intervals (CI). Results: By March 7, 2021, among 6,170,750 Veterans, 1,547,045 (23%) received at least one COVID-19 vaccination. mRNA SARS-CoV-2 VE against infection was 94% (95% confidence interval [CI] 92-95) and 58% (95%CI 54-62) for full and partial vaccination (vs. no vaccination), respectively. VE was similar for subpopulations. VE against COVID-19-related hospitalization and death for full vs. no vaccination was 89% (95%CI 81-93) and 98.5% (95%CI 86.6-99.9), respectively. Conclusions: The efficient and equitable distribution of effective vaccines against SARS-CoV-2 infections, hospitalization and mortality helped the VHA to reduce COVID-19 disease burden and health inequalities among Veterans. +
++Global healthcare systems are challenged by the COVID-19 pandemic. There is a need to optimize allocation of treatment and resources in intensive care, as clinically established risk assessments such as SOFA and APACHE II scores show only limited performance for predicting the survival of severely ill COVID-19 patients. Comprehensively capturing the host physiology, we speculated that proteomics in combination with new data-driven analysis strategies could produce a new generation of prognostic discriminators. We studied two independent cohorts of patients with severe COVID-19 who required intensive care and invasive mechanical ventilation. SOFA score, Charlson comorbidity index and APACHE II score were poor predictors of survival. Plasma proteomics instead identified 14 proteins that showed concentration trajectories different between survivors and non-survivors. A proteomic predictor trained on single samples obtained at the first time point at maximum treatment level (i.e. WHO grade 7) and weeks before the outcome, achieved accurate classification of survivors in an exploratory (AUROC 0.81) as well as in the independent validation cohort (AUROC of 1.0). The majority of proteins with high relevance in the prediction model belong to the coagulation system and complement cascade. Our study demonstrates that predictors derived from plasma protein levels have the potential to substantially outperform current prognostic markers in intensive care. +
++Sequencing SARS-CoV-2 from wastewater has become a useful tool in monitoring the spread of variants. We use a novel computation workflow with SARS-CoV-2 amplicon sequencing in order to track wastewater populations of the virus. As part of this workflow, we developed a program for both variant reporting and removal of PCR generated chimeric sequences. With these methods, we are able to track viral population dynamics over time. We observe the emergence of the variants of concern B.1.1.7 and P.1, and their displacement of the D614G B.1 variant. +
++Early warning signals (EWSs) aim to predict changes in complex systems from phenomenological signals in time series data. These signals have recently been shown to precede the initial emergence of disease outbreaks, offering hope that policy makers can make predictive rather than reactive management decisions. Here, using daily COVID-19 case data in combination with a novel, sequential analysis, we show that composite EWSs consisting of variance, autocorrelation, and return rate not only pre-empt the initial emergence of COVID-19 in the UK by 14 to 29 days, but also the following wave six months later. We also predict there is a high likelihood of a third wave as of the data available on 9th June 2021. Our work suggests that in highly monitored disease time series such as COVID-19, EWSs offer the opportunity for policy makers to improve the accuracy of time critical decisions based solely upon surveillance data. +
++Objectives The primary hypothesis was that the risk of incident or repeat psychiatric illness, fatigue and sleep problems increased following COVID-19 infection. The analysis plan was pre-registered (https://osf.io/n2k34/). Design Matched cohorts were assembled using a UK primary care registry (the CPRD-Aurum database). Patients were followed-up for up to 10 months, from 1st February 2020 to 9th December 2020. Setting Primary care database of 11,923,499 adults (>16 years). Participants From 232,780 adults with a positive COVID-19 test (after excluding those with <2 years historical data or <1 week follow-up), 86,922 without prior mental illness, 19,020 with anxiety or depression, 1,036 with psychosis, 4,152 with fatigue and 4,539 with sleep problems were matched to up to four controls based on gender, general practice and year of birth. A negative control used patients who tested negative for COVID-19 and patients negative for COVID with an influenza diagnosis. Main Outcomes and Measures Cox proportional hazard models estimated the association between a COVID-19 positive test and subsequent psychiatric morbidity (depression, anxiety, psychosis, or self-harm), sleep problems, fatigue or psychotropic prescribing. Models adjusted for comorbidities, ethnicity, smoking and BMI. Results After adjusting for observed confounders, there was an association between testing positive for COVID-19 and almost all markers of psychiatric morbidity, fatigue and sleep problems. The adjusted hazard ratio (aHR) for incident psychiatric morbidity was 1.75 (95% CI 1.56-1.96). However, there was a similar risk of incident psychiatric morbidity for those with a negative COVID-19 test (aHR 1.57, 95% CI 1.51-1.63) and a larger increase associated with influenza (aHR 2.97, 95% CI 1.36-6.48). Conclusions There is consistent evidence that COVID-19 infection elevates risk of fatigue and sleep problems, however the results from the negative control analysis suggests that residual confounding may be responsible for at least some of the association between COVID-19 and psychiatric morbidity. +
++The Delta SARS-CoV-2 variant has spread quickly since first being identified. To better understand its epidemiological characteristics and impact, we utilize multiple datasets and comprehensive model-inference methods to reconstruct COVID-19 pandemic dynamics in India, where Delta first emerged. Using model-inference estimates from March 2020 to May 2021, we estimate the Delta variant can escape adaptive immunity induced by prior wildtype infection roughly half of the time and is around 60% more infectious than wildtype SARS-CoV-2. In addition, our analysis suggests that the recent case decline in India was likely due to implemented non-pharmaceutical interventions and weather conditions less conducive for SARS-CoV-2 transmission during March - May, rather than high population immunity. Model projections show infections could resurge as India enters its monsoon season, beginning June, if intervention measures are lifted prematurely. +
++Importance: While COVID-19 vaccines are highly effective against disease, breakthrough infections may occur in the context of rising variants of concern. Objective: We paired random and passive surveillance nucleic acid testing with analysis of viral whole genomic sequences to detect and describe breakthrough infections, focusing in a university community. Design: Anterior nasal swabs were collected from individuals for a nucleic acid amplification test (NAAT) for detection of SARS-CoV-2. A subset of NAAT positive samples was sequenced to determine variants associated with infections. Included in the testing and sequencing protocol were individuals that were fully vaccinated. Setting: This study was performed as part of a surveillance program for SARS-CoV-2 on a university campus with 49,700 students and employees. Participants: Surveillance testing was random and included approximately 10% of the population each week. Additionally, individuals self-identified with COVID-19 related symptoms or those that had close contact with SARS-CoV-2 positive individuals were also tested. +
+Cognitive and Psychological Disorders After Severe COVID-19 Infection - Condition: COVID 19
Interventions: Diagnostic Test: Cognitive assessment; Diagnostic Test: Imaging; Diagnostic Test: Routine care; Other: Psychiatric evaluation
Sponsors: Central Hospital, Nancy, France; Centre Hospitalier Universitaire de Besancon; University Hospital, Strasbourg, France; Centre Hospitalier Régional Metz-Thionville; Centre hospitalier Epinal; Hopitaux Civils de Colmar
Not yet recruiting
MP1032 Treatment in Patients With Moderate to Severe COVID-19 - Condition: COVID-19
Interventions: Drug: MP1032; Drug: Placebo
Sponsors: MetrioPharm AG; Syneos Health, LLC
Not yet recruiting
Efficacy and Safety of XAV-19 for the Treatment of Moderate-to-severe COVID-19 - Condition: COVID-19
Interventions: Drug: XAV-19; Drug: Placebo
Sponsor: Xenothera SAS
Recruiting
Study of Codivir in Patients With COVID-19 - Condition: Covid19
Interventions: Drug: Covidir injections; Diagnostic Test: One Step Test; Diagnostic Test: IgM and IgG dosage; Diagnostic Test: RT-PCR SARS-CoV-2; Diagnostic Test: Screening blood test; Diagnostic Test: ECG; Diagnostic Test: Medical evaluation; Diagnostic Test: NEWS-2 score; Diagnostic Test: WHO score
Sponsors: Code Pharma; Zion Medical
Active, not recruiting
In Situ Thrombolysis With tPA and Inflow Perfusion Analysis in Patient With Severe Covid-19 Infection - Condition: COVID-19
Intervention: Drug: tPA
Sponsor: Grupo Mexicano para el Estudio de la Medicina Intensiva
Completed
Study to Evaluate the Safety and Concentrations of Monoclonal Antibody Against Virus That Causes COVID-19 Disease. - Condition: COVID-19 Virus Disease
Interventions: Biological: MAD0004J08; Other: Placebo
Sponsors: Toscana Life Sciences Sviluppo s.r.l.; Cross Research S.A.
Active, not recruiting
Clinical Trial With N-acetylcysteine and Bromhexine for COVID-19 - Condition: COVID-19
Interventions: Drug: Vitamin C; Drug: N-acetylcysteine (NAC); Drug: NAC + Bromhexine (BMX)
Sponsors: Universidade Federal do Ceara; Paulista School of Medicine-EPM, UNIFESP; Health Surveillance Secretariat - SVS; Central Laboratory of Public Health of Ceara - LACEN-CE; Leonardo da Vinci Hospital - HLV; São José Hospital for Infectious Diseases - HSJ; Ceará Health Secretariat - SESA; Municipal Health Secretary - SMS-Fortaleza
Not yet recruiting
Safety and Immunogenicity of LNP-nCOV saRNA-02 Vaccine Against SARS-CoV-2, the Causative Agent of COVID-19 - Condition: COVID-19
Intervention: Drug: LNP-nCOV saRNA-02 Vaccine
Sponsor: MRC/UVRI and LSHTM Uganda Research Unit
Not yet recruiting
Augmentation of Immune Response to COVID-19 mRNA Vaccination Through OMT With Lymphatic Pumps - Condition: Covid19
Intervention: Other: Osteopathic Manipulative Treatment (OMT)
Sponsors: Western University of Health Sciences; American College of Osteopathic Physicians; American Osteopathic Foundation; Osteopathic Physicians and Surgeons of California; Xavier-Nichols Foundation
Recruiting
Efficacy of Inhaled Therapies in the Treatment of Acute Symptoms Associated With COVID-19 - Condition: Covid19
Interventions: Drug: inhaled beclametasone; Drug: Inahaled beclomethasone / formoterol / glycopyrronium
Sponsors: UPECLIN HC FM Botucatu Unesp; Chiesi Farmaceutici S.p.A.
Not yet recruiting
Clinical Investigation for 2019-nCoV Antigen Saliva Rapid Test Kit and V-CHEK SARS-CoV-2 Antigen Detection Kit to Detect COVID-19 - Condition: Covid19
Intervention: Device: V-CHECK SARS-CoV-2 Antigen Detection Kit and 2019-nCoV Antigen Saliva Rapid Test Kit
Sponsors: Medical College of Wisconsin; Reliable, LLC.
Not yet recruiting
Dapsone Coronavirus SARS-CoV-2 Trial (DAP-CORONA) COVID-19 - Condition: COVID-19
Interventions: Drug: Dapsone 85 mg PO BID; Drug: Placebo 85 mg PO BID
Sponsors: McGill University Health Centre/Research Institute of the McGill University Health Centre; Pulmonem Inc.
Not yet recruiting
Ivermectin Versus Standard Treatment in Mild COVID-19 - Condition: Covid19
Intervention: Drug: Ivermectin Tablets
Sponsor: Assiut University
Not yet recruiting
Tolerability,Safety of JS016 in SARS-CoV-2 (COVID-19) - Conditions: COVID-19; SARS-CoV-2
Intervention: Drug: Combination Product: JS016 (anti-SARS-CoV-2 monoclonal antibody)
Sponsor: Peking Union Medical College Hospital
Recruiting
Open Label, Single-Center Study Utilizing BIOZEK COVID-19 Antigen Rapid Test - Condition: Covid-19 Testing
Intervention: Diagnostic Test: Biozek Covid-19 Antigen Rapid Test (Saliva)
Sponsor: Mach-E B.V.
Recruiting
Efficacy and safety of ReDuNing injection as a treatment for COVID-19 and its inhibitory effect against SARS-CoV-2 - CONCLUSIONS: RDN relieves clinical symptoms in patients with COVID-19 and reduces SARS-CoV-2 infection by regulating inflammatory cytokine-related disorders, suggestion that this medication might be a safe and effective treatment for COVID-19.
Identification of known drugs as potential SARS-CoV-2 Mpro inhibitors using ligand- and structure-based virtual screening - Background: The new coronavirus pandemic has had a significant impact worldwide, and therapeutic treatment for this viral infection is being strongly pursued. Efforts have been undertaken by medicinal chemists to discover molecules or known drugs that may be effective in COVID-19 treatment - in particular, targeting the main protease (Mpro) of the virus. Materials & methods: We have employed an innovative strategy - application of ligand- and structure-based virtual screening - using a special…
Rationale, study design and implementation of the LUCINDA Trial: Leuprolide plus cholinesterase inhibition to reduce neurologic decline in Alzheimer’s - The LUCINDA Trial (Leuprolide plus Cholinesterase Inhibition to reduce Neurologic Decline in Alzheimer’s) is a 52 week, randomized, placebo-controlled trial of leuprolide acetate (Eligard) in women with Alzheimer’s disease (AD). Leuprolide acetate is a gonadotropin analogue commonly used for hormone-sensitive conditions such as prostate cancer and endometriosis. This repurposed drug demonstrated efficacy in a previous Phase II clinical trial in those women with AD who also received a stable dose…
Rapid, reliable, and reproducible cell fusion assay to quantify SARS-Cov-2 spike interaction with hACE2 - COVID-19 is a global crisis of unimagined dimensions. Currently, Remedesivir is only fully licensed FDA therapeutic. A major target of the vaccine effort is the SARS-CoV-2 spike-hACE2 interaction, and assessment of efficacy relies on time consuming neutralization assay. Here, we developed a cell fusion assay based upon spike-hACE2 interaction. The system was tested by transient co-transfection of 293T cells, which demonstrated good correlation with standard spike pseudotyping for inhibition by…
SARS-CoV-2 viral proteins NSP1 and NSP13 inhibit interferon activation through distinct mechanisms - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a devastating global pandemic, infecting over 43 million people and claiming over 1 million lives, with these numbers increasing daily. Therefore, there is urgent need to understand the molecular mechanisms governing SARS-CoV-2 pathogenesis, immune evasion, and disease progression. Here, we show that SARS-CoV-2 can block IRF3 and NF-κB activation early during virus infection. We also identify that the SARS-CoV-2 viral…
Mechanism of inhibition of SARS-CoV-2 M(pro) by N3 peptidyl Michael acceptor explained by QM/MM simulations and design of new derivatives with tunable chemical reactivity - The SARS-CoV-2 main protease (M^(pro)) is essential for replication of the virus responsible for the COVID-19 pandemic, and one of the main targets for drug design. Here, we simulate the inhibition process of SARS-CoV-2 M^(pro) with a known Michael acceptor (peptidyl) inhibitor, N3. The free energy landscape for the mechanism of the formation of the covalent enzyme-inhibitor product is computed with QM/MM molecular dynamics methods. The simulations show a two-step mechanism, and give structures…
Inhibitors of thiol-mediated uptake - Ellman’s reagent has caused substantial confusion and concern as a probe for thiol-mediated uptake because it is the only established inhibitor available but works neither efficiently nor reliably. Here we use fluorescent cyclic oligochalcogenides that enter cells by thiol-mediated uptake to systematically screen for more potent inhibitors, including epidithiodiketopiperazines, benzopolysulfanes, disulfide-bridged γ-turned peptides, heteroaromatic sulfones and cyclic thiosulfonates,…
A microscopic description of SARS-CoV-2 main protease inhibition with Michael acceptors. Strategies for improving inhibitor design - The irreversible inhibition of the main protease of SARS-CoV-2 by a Michael acceptor known as N3 has been investigated using multiscale methods. The noncovalent enzyme-inhibitor complex was simulated using classical molecular dynamics techniques and the pose of the inhibitor in the active site was compared to that of the natural substrate, a peptide containing the Gln-Ser scissile bond. The formation of the covalent enzyme-inhibitor complex was then simulated using hybrid QM/MM free energy…
Hyper-Enriched Anti-RSV Immunoglobulins Nasally Administered: A Promising Approach for Respiratory Syncytial Virus Prophylaxis - Respiratory syncytial virus (RSV) is a public health concern that causes acute lower respiratory tract infection. So far, no vaccine candidate under development has reached the market and the only licensed product to prevent RSV infection in at-risk infants and young children is a monoclonal antibody (Synagis^(®)). Polyclonal human anti-RSV hyper-immune immunoglobulins (Igs) have also been used but were superseded by Synagis^(®) owing to their low titer and large infused volume. Here we report a…
Therapeutic Targeting of Transcription Factors to Control the Cytokine Release Syndrome in COVID-19 - Treatment of the cytokine release syndrome (CRS) has become an important part of rescuing hospitalized COVID-19 patients. Here, we systematically explored the transcriptional regulators of inflammatory cytokines involved in the COVID-19 CRS to identify candidate transcription factors (TFs) for therapeutic targeting using approved drugs. We integrated a resource of TF-cytokine gene interactions with single-cell RNA-seq expression data from bronchoalveolar lavage fluid cells of COVID-19 patients….
Clinical, Biochemical and Molecular Evaluations of Ivermectin Mucoadhesive Nanosuspension Nasal Spray in Reducing Upper Respiratory Symptoms of Mild COVID-19 - CONCLUSION: Local use of ivermectin mucoadhesive nanosuspension nasal spray is safe and effective in treatment of patients with mild COVID-19 with rapid viral clearance and shortening the anosmia duration.
Structure-guided design of a perampanel-derived pharmacophore targeting the SARS-CoV-2 main protease - There is a clinical need for direct-acting antivirals targeting SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic, to complement current therapeutic strategies. The main protease (M^(pro)) is an attractive target for antiviral therapy. However, the vast majority of protease inhibitors described thus far are peptidomimetic and bind to the active-site cysteine via a covalent adduct, which is generally pharmacokinetically unfavorable. We have reported the optimization of an existing…
It - ObjectiveMindStep™ is an Australian low-intensity cognitive behaviour therapy (LICBT) program for individuals with mild-to-moderate symptoms of anxiety and depression. UK-produced LICBT guided self-help (GSH) materials were originally used in the MindStep™ program. In 2017, Australian LICBT GSH materials were developed to better suit Australian users. This study explored whether the Australian-produced materials continued to achieve the benchmark recovery rates established in the UK and…
Structural basis of covalent inhibitory mechanism of TMPRSS2-related serine proteases by camostat - SARS-CoV-2 is the viral pathogen causing the COVID19 global pandemic. No effective treatment for COVID-19 has been established yet. TMPRSS2 is essential for viral spread and pathogenicity by facilitating the entry of SARS-CoV-2 onto host cells. The protease inhibitor camostat, an anticoagulant used in the clinic, has potential anti-inflammatory and anti-viral activities against COVID-19. However, the potential mechanisms of viral resistance and antiviral activity of camostat are unclear. Herein,…
SARS-CoV-2 spike protein induces paracrine senescence and leukocyte adhesionin endothelial cells - Increased mortality in COVID-19 often associates with microvascular complications. We have recently shown that SARS-CoV-2 spike protein promotes an inflammatory cytokine IL-6/IL-6R induced trans-signaling response and alarmin secretion. Virus infected or spike transfected human epithelial cells exhibited an increase in senescence state with the release of senescence associated secretory proteins (SASP) related inflammatory molecules. Introduction of BRD4 inhibitor AZD5153 to senescent epithelial…
SARS-CoV-2 anti-viral therapeutic - - link
폐마스크 밀봉 회수기 - 본 발명은 마스크 착용 후 버려지는 일회용 폐마스크를 비닐봉지에 넣은 후 밀봉하여 배출함으로써, 2차 감염을 예방하고 일반 생활폐기물과 선별 분리 배출하여 환경오염을 방지하는 데 그 목적이 있다. - link
백신 냉각 및 해동 기능을 갖는 백신 보관장치 - 본 발명은 백신 냉각 및 해동 기능을 갖는 백신 보관장치에 관한 것으로, 상, 하부하우징의 제1상, 하부누출방지공간에 냉각물질이 충입된 냉각파이프를 설치하되, 제2상, 하부누출방지공간에 가열물질이 충입된 가열파이프를 설치하여, 구획판부에 의해 구획된 백신냉각공간 및 백신해동공간 각각을 냉각 및 가열하고, 보조도어를 통해 백신냉각공간 내에 수용된 백신을 구획판부의 백신출구도어를 통해 백신해동공간으로 이동시켜, 백신해동공간 내에서 백신을 해동함으로써, 즉시 사용이 가능한 백신을 인출도어를 통해 인출할 수 있다. 본 발명에 따르면, 냉각파이프에 저장된 냉매에 의해 백신냉각공간 내의 온도가 극저온 상태로 변화되고, 극저온 상태를 유지하는 백신냉각공간 내에 백신을 저장하여, 안전하게 보관 할 수 있으며, 백신냉각공간 내의 백신을 백신해동공간 내로 이동시켜, 백신해동공간 내에서 백신을 해동할 수 있고, 이 해동된 백신을 인출도어를 통해 인출한 후 즉시 사용할 수 있어 백신을 해동하는 시간이 단축되며, 보조도어를 통해 백신냉각공간 내의 백신을 백신해동공간으로 이동시켜, 백신이 외기에 노출될 우려가 없으며, 백신냉각공간 내의 백신을 백신해동공간으로 이동시키거나 또는 인출도어를 통해 백신 인출시 정렬장치가 백신을 보조도어 및 인출도어 직하방에 자동 위치시킨다. - link
COST EFFECTIVE PORTABLE OXYGEN CONCENTRATOR FOR COVID-19 - - link
백신 인출용 보조도어를 갖는 백신 저온 보관장치 - 본 발명은 백신정렬 기능을 갖는 백신 저온 보관장치에 관한 것으로, 상, 하부하우징의 이중 격벽 안에 냉매가 충입된 냉매파이프를 설치하여, 이 냉매파이프에 의해 상, 하부하우징의 백신 보관 공간이 극저온 상태를 유지하도록 하고, 하부하우징의 가이드벽 사이에 수용된 백신을 정렬장치로 가압하여, 상부하우징의 보조도어 직하방에 백신이 위치되도록 하되, 이때, 보조도어를 개방하여 하부하우징 내에 수용된 백신을 인출하면, 정렬장치가 가이드벽 사이에 수용된 백신을 보조도어 방향으로 밀어내어, 보조도어 직하방에 백신이 순차적으로 자동 위치된다. 본 발명에 따르면, 상, 하부하우징의 이중 격벽 내에 냉매 파이프가 설치되어, 이 냉매 파이프에 저장된 냉매에 의해 백신 보관공간 내의 온도가 극저온 상태로 변화되고, 이 극저온 상태를 유지하는 백신 보관공간 내에 백신을 저장하여, 안전하게 보관 할 수 있으며, 수분이나 외부 공기 유입이 차단되어 백신을 안전하게 보관되고, 온도계와 압력계를 이용하여 백신 보관공간과 냉매 압력을 실시간으로 감지할 수 있고, 보조도어를 통해 백신 보관공간 내의 백신을 독립적으로 인출할 수 있으며, 보조도어를 통해 백신 인출시 정렬장치가 백신을 보조도어 방향으로 밀어내어, 보조도어 직하방에 백신이 자동 위치되고, 외기 유입 방지로 백신 보관공간 내의 온도가 극저온 상태로 유지된다. - link
SAFE TOUCH ANTI VIRAL LUGGAGE TROLLEY HANDLE - The invention is directed to a safe-touch, anti-viral luggage trolley handle, comprising PVC plastic with the addition of a silver-based antimicrobial additive. - link
METHOD OF IDENTIFYING SEVERE ACUTE RESPIRATORY SYNDROME CORONA VIRUS 2 (SARS-COV-2) RIBONUCLEIC ACID (RNA) - - link
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Erweiterbare Desinfektionsvorrichtung, umfassend: einen Hauptkörper, der eine umgekehrt U-förmige Basisplatte aufweist, wobei die umgekehrt U-förmige Basisplatte mit einer Öffnung versehen ist und jeweils eine Seitenplatte sich von zwei Seiten der umgekehrt U-förmigen Basisplatte nach außen erstreckt; und mindestens eine Desinfektionslampe, die in den auf zwei Seiten des Hauptkörpers befindlichen Seitenplatten angeordnet ist und eine Lichtemissionseinheit, eine Erfassungseinheit, eine Steuereinheit und eine Stromversorgungseinheit umfasst.
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Einfache Sterilisationsvorrichtung, mit einem Hauptkörper (11), der in Längsrichtung einen ersten Plattenabschnitt (111) und in Querrichtung einen zweiten Plattenabschnitt (112) aufweist, wobei der erste Plattenabschnitt (111) und der zweite Plattenabschnitt (112) L-förmig miteinander verbunden sind; und einer Sterilisationslampe (12), die an dem Hauptkörper (11) angeordnet ist und eine Lichtemissionseinheit (121), eine Sensoreinheit (122), eine Steuereinheit (123) und eine Stromeinheit (124) aufweist.
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Klemmarme aufweisende Desinfektionsvorrichtung, umfassend: einen Hauptkörper; eine Desinfektionslampe, die im Hauptkörper angeordnet ist und eine Lichtemissionseinheit, eine Erfassungseinheit, eine Steuereinheit und eine Stromversorgungseinheit umfasst; einen Klemmabschnitt, der auf einer Seite des Hauptkörpers angeordnet ist, wobei der Klemmabschnitt zwei gegenüberliegende Greifbacken umfasst, wobei mindestens eine der beiden Greifbacken mit einer Schwenkachse versehen ist, wobei ein Klemmraum durch passgenaues Schließen der beiden Greifbacken entsteht und die beiden Greifbacken jeweils mit einem Durchgangsloch versehen sind; einen Befestigungsabschnitt, der durch die Durchgangslöcher der beiden Greifbacken hindurchgeführt ist;und ein Schild, das auf einer Seite des Klemmabschnitts angeordnet und mit einem Aufnahmeloch versehen ist.
Bipartisanship Lives, and Biden Takes a Bow - Finally, Infrastructure Week is for real. - link
After the Lost Cause - Why are politics so consumed with the past? - link
Can Congress Insure Fair Elections? - The legal scholar Rick Hasen discusses the dangers of election subversion and voter suppression. - link
The Unexplained Phenomena of the U.F.O. Report - A new intelligence document examines a hundred and forty-three sightings that might have been caused by errant balloons, foreign drones, or “Other”—a reserved way of saying aliens. - link
It’s Not the Heat—It’s the Humanity - Rising air temperatures remind us that our bodies have real limits. - link
+Seniors want to age at home. But the US makes it hard. +
++The vast majority of Americans want to age in their home and community, spending their twilight years in a familiar and comfortable setting. But the choice is not always their own. +
++The US long-term care system — such as it is — is broken. Hundreds of thousands of Americans are on waiting lists for home-based care. More than 40 million people report that they have cared for a loved one over 50 without any pay in the last year. The United States ranks near the bottom of developed economies in the number of older adults who receive long-term care at home. Meanwhile, America’s nursing homes are staffed by overwhelmed and underpaid workers, and for-profit takeovers of those facilities have led to worse care for patients. +
++Covid-19 has made this long-term care crisis impossible to ignore. More than 130,000 nursing home residents have died in the pandemic, accounting for nearly one in four US deaths. Residents of large institutions died at higher rates than those who live in the community. +
++In America, aging people who need care — in a nursing facility or at home — either must be wealthy enough to pay for it themselves or must deplete their income and assets enough that they qualify for Medicaid. Almost by accident, the health insurance program for low-income Americans has become the main payer for nursing home and home-based care. Experts describe long-term care in the US with a sense of disbelief. +
++“If you were starting from scratch, you would never design a system this way,” David Grabowski, a Harvard professor who studies the economics of long-term care, told me. +
++Tricia Neuman, who studies long-term care at the Kaiser Family Foundation, put it even more baldly: “We do not have a system of long-term care in our country.” +
++America has been struggling for decades to figure out a balance between having people age in long-term care facilities and age at home. President Joe Biden has proposed a massive infusion of federal spending on home-based care. Experts say it should start to address these structural problems — but it’s only a start. +
++The story of America’s long-term care failure begins in earnest in the 1950s. +
++Before then, and really for all of human history, if you were lucky enough to age into your elder years, you probably aged at home. Nursing homes didn’t exist. But that also meant you needed somebody to take care of you — and that responsibility would often fall on a spouse or children or another family member. Women in particular often shouldered these duties. +
++Things started to change in the middle of the 20th century. More women entered the workforce during and after World War II. Americans became less likely to live as adults in the place where they grew up, with more people moving to other parts of the country to seek employment and settle down. Fewer family members were around to provide unpaid care, and so proto-nursing homes — alms houses, board-and-care homes — first appeared. +
++Then President Lyndon B. Johnson signed Medicaid into law in 1965. One of the benefits covered by the new program for America’s poor was nursing home care — but at first, there was no coverage for home and community care. +
++In the following years, and accelerating in the 1980s, more older people and people with disabilities were moved into institutional settings. The nursing home industry was born, and it boomed. Today, about 1.2 million Americans live in a nursing home. +
++Ideally, people would live in those facilities by choice. The most important principle for long-term care policy is personal agency: The patient and their family should have a right to determine what kind of care they receive. +
++But America has failed to live up to that ideal. More than three in four people over the age of 50 said in a 2018 AARP survey they want to stay in their community as long they can. But fewer than half thought that would be possible — and many of them may end up being right, as the long waiting lists for home- and community-based services attest. As of February 2020, more than 820,000 Americans were stuck on their state Medicaid program’s waiting list for home- and community-based services, according to the Kaiser Family Foundation, and their average wait time is longer than three years. +
++Even for those lucky enough to be able to afford in-home care, the US long-term care system hasn’t done them any favors. Virginia Veliz, a 70-year-old in Santa Clarita, California, has been coordinating care for her 90-year-old mother, who has Lewy body dementia and Parkison’s disease, for the past five years. +
++“You really have to treat it like a job,” she said. +
++Veliz lives with very specific fears about what would happen if her mom moved into a nursing home. Her mother is prone to urinary tract infections; they’ve put her in the hospital multiple times in the past decade. During a recent hospital stay, Veliz came to the room to find her mom, who has hallucinations because of her dementia, hanging over the side of her bed and “traumatized” by the isolation, she said. +
++With those experiences in her mind, Veliz cannot bear the idea of sending her mom to a nursing home, where she might be alone for hours at a time. Instead, she and her siblings are paying for home health aides five days a week, with physical therapists and physicians stopping by regularly. She knows they are lucky they can afford it, but, in the same breath, she jokes that they need a family therapist to navigate the stress of organizing their mom’s care. +
++“She just will not get the attention in a convalescent setting, because they don’t have the manpower,” Veliz told me. “What am I afraid of? I’m afraid of them not taking care of her. She’s very fragile.” +
++There are some people for whom institutional care makes sense — those with severe cognitive decline, for example. Others might simply prefer to live in a nursing home with other people instead of living alone at home. +
++But the idea is that it should be the patient’s choice. The US still has not found a way to put that decision entirely in the patient’s hands. +
++“There is a huge unmet need,” Neuman said. +
++The crisis has been decades in the making, but the Covid-19 pandemic has made it impossible to ignore. +
++“The pandemic was an accelerant and gave momentum about how to move people out of facilities,” Neuman said. “You had families going to nursing homes urgently to get their parent or grandparent out, even at a great cost personally or financially.” +
++Gene Dorio, a California doctor who cares for Virginia Veliz’s mother, says he lost three patients to the coronavirus in the past year. As somebody who makes house calls to seniors and cares for patients in nursing homes, he did not seem surprised about the loss of life experienced in the latter. +
++“They ended up being at the wrong place at the wrong time,” he said. “The long-term care setting … some of these places are abominations.” +
++Finding a better equilibrium between community-based care and nursing homes will require money. Biden, as part of his American Jobs Plan, has proposed a $400 billion investment over 10 years into home- and community-based services. Many of the details would need to be determined when legislation is drafted in Congress, but the size of the investment alone has caught the attention of experts who work on long-term care issues. +
++Experts agree that resources — read: money — are the biggest challenge for long-term care. The challenges are so great that they aren’t sure $400 billion is “enough.” +
++“If the question is, ‘Is that enough?’, I don’t know,” Grabowski said. “Hopefully that will buy you a lot of community-based care.” +
++Neuman said more or less the same thing. +
++“It’s remarkable and unusual to see such a huge proposed investment,” she said. “How far this would go, I don’t know. But it is a significant investment.” +
++The money would presumably be spent, in large part, on home health workers. But there is a tension created by putting a hard number on that investment. +
++Experts say long-term care workers are underpaid for their difficult work (the average pay can be as little as $10 a day), so better compensation could lead to more people entering the field and staying in the work once they’ve started. Recent research showing some nursing homes see roughly 100 percent turnover in a given year suggests that retention is a serious problem in long-term care. +
++“You’re not going to get very far in fixing this without money. You need good caregivers. You need to pay them,” Grabowski said. “How do we ensure going forward that this is basically a better job, that starts with better pay and benefits?” +
++But the more you pay for one worker, the fewer workers you can hire. It’s simple economics. +
++That doesn’t mean the Biden plan couldn’t still do a lot of good. A single staffer could potentially help a lot of people. +
++But still: Virginia’s family has hired caregivers who stay with their mother eight hours per day, every weekday. That’s one salaried position for a single patient — and, eventually, with enough of those, even $400 billion could eventually run out. +
++So the Biden plan isn’t a cure to the ills that afflict America’s long-term care, even if it is “a step in the right direction,” as Grabowski told me. +
++The pressure on the US’s broken long-term care system will keep growing. The number of Americans over 65 is projected to nearly double by 2060. Though Americans are working later in their lives, the number of people living in nursing homes could still reach 2 million, from the current 1.2 million, as soon as 2030. +
++That structural problem may eventually require structural reforms. Right now, the US doesn’t provide any government assistance to middle-income people who need long-term care. You are either wealthy enough to pay for your own care or you have to spend enough of your own money on long-term services that you become poor enough to qualify for Medicaid, and then that program takes responsibility for your bills. +
++“There still could be holes here for middle-income families,” Grabowski said, which he called “the forgotten middle.” +
++“There’s not a menu of services for this group,” he said. “That still isn’t here in this plan.” +
++There have been previous proposals to address that problem. The Affordable Care Act initially included what was called the CLASS Act, which would have created a voluntary public insurance program to cover long-term care. But the Obama administration quickly decided it would be too expensive and scrapped the program in 2011 before it ever got off the ground. +
++Prioritizing home-based care appears to be the preferred solution for both patients and policymakers. But it will cost money. The Netherlands, Norway, and Sweden are considered global leaders in providing community-based services, but they also spend a substantially higher share of their GDPs on long-term care (around 3 percent) than the US (0.5 percent). +
++On the other hand, the United States spends far more on other kinds of medical care than any other country. As Grabowski wrote in a recent Nature column, just 5 percent of that money is currently being spent on long-term care. +
++“Dollars could be taken from general health care spending and reallocated to [home and community-based services],” he argued. “This increased spending on HCBS would not only benefit the care recipients but also their family members, who often must take time away from their jobs and risk their own health to provide this care.” +
++And the choice is not binary between home-based care and nursing homes. The Netherlands in particular has experimented with small group homes, with much success. There is a similar model in the US, called Green House, a loose collective of homes with 10 to 12 beds that house seniors and are served by a small team of nurses. +
++Researchers have found that the residents of these small-group nursing homes were significantly less likely to contract Covid-19 or die of it compared to people who lived in larger institutions. The authors, from the University of North Carolina, concluded that small homes were “a promising model of care” as nursing homes are “reinvented” post Covid-19. +
++It’s hard to measure specific outcomes between aging in the community and aging in a nursing home. Tamara Konetzka, a University of Chicago professor, pointed out in a 2014 article that nobody was really sure which was “better” for patients from a health perspective, or which was more cost-effective. +
++But patient satisfaction and preference appears solidly on the side of aging at home. Rob Waters also covered Green House extensively in a recent issue of Health Affairs and clearly saw promise in the model. But he also highlighted how far it has to go: Right now, less than 1 percent of US nursing home residents live in a Green House. +
++“We just have a lot of ground to make up,” Grabowski said. “People want them. That’s where we should be directing services.” +
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+Blame John Roberts and Donald Trump. +
++Attorney General Merrick Garland announced on Friday that the Justice Department filed a lawsuit challenging several provisions of Georgia’s recently enacted voter suppression law. And the Justice Department has a strong case on the merits against this law. +
++Yet it is far from clear whether the strength of their case will matter: They will have to litigate this case before a judiciary that is increasingly hostile toward voting rights claims. +
++The complaint in United States v. Georgia, which is signed by the most senior lawyers in the DOJ’s Civil Rights Division, alleges that several provisions of the Georgia law “were adopted with the purpose of denying or abridging Black citizens’ equal access to the political process, in violation” of the Voting Rights Act. +
++The DOJ does not attack the entire Georgia law, and it does not directly attack the single most troubling provision of the law, which allows Republican officials to effectively take over local election boards that have the power to close polling places and disqualify voters. +
++Instead, the lawsuit focuses on several provisions making it harder to cast an absentee ballot in Georgia. It also targets provisions that disenfranchise many voters who cast a ballot in the wrong precinct, as well as the Georgia law’s provision prohibiting pro-democracy groups from distributing food and water to voters waiting in long lines to cast a ballot. +
++While the lawsuit only argues that these parts of the law violate the Voting Rights Act, it also asks the courts to invoke a rarely used provision of the Act which would place Georgia elections under federal supervision. +
++Before the Supreme Court’s decision in Shelby County v. Holder (2013), states with a history of racist voting practices, including Georgia, had to “preclear” any new election rules with officials in Washington, DC. Shelby County effectively deactivated this preclearance regime, but a provision of the Voting Rights Act still allows preclearance to be imposed on states that commit particularly egregious discrimination against voters of color. +
++And if preclearance were reimposed on Georgia, that would likely prevent GOP-controlled election boards from implementing policies intended to disenfranchise Black voters. +
++In another era, the Georgia lawsuit would have had a very good shot of prevailing. In Village of Arlington Heights v. Metropolitan Housing Development Corp. (1977), the Supreme Court laid out several factors which plaintiffs alleging race discrimination may point to in order to prove their case, including evidence that lawmakers departed from “the normal procedural sequence” that they ordinarily use to enact laws, the fact that a state has a history of racist practices, or the fact that a law’s impact “bears more heavily on one race than another.” +
++The DOJ’s complaint does an effective job of showing that many of these factors are present in Georgia. Yet while it has strong legal arguments on its side, the courts are now much more conservative than the Supreme Court that decided Arlington Heights — indeed, the current Supreme Court is even more conservative than the one that decided Shelby County. +
++The Georgia case, moreover, is assigned to Judge J.P. Boulee, a Trump judge. +
++The Justice Department, in other words, won’t simply need to prove its case, it will also need to overcome a judiciary stacked with judges who tend to be hostile to voting rights claims — and that are particularly hostile to claims that white lawmakers engaged in intentional race discrimination. +
++That will not be easy. +
++The DOJ’s complaint lays out a fairly straightforward narrative against the new Georgia law. +
++Georgia, of course, has a well-documented history of racist practices. Yet, despite that history, Georgia voters elected the state’s first Black senator, Raphael Warnock, in the most recent election cycle. And the state also voted to elect Vice President Kamala Harris, the first African American elected to that office, when it went for President Joe Biden in 2020. +
++Part of the reason why this historically white supremacist state voted this way — and why the once solidly Republican state now has two Democratic senators — is an influx of Black residents. “The number of Black residents increased 70.7 percent from 1990 to 2010 according to decennial Census counts,” the DOJ explains in its complaint, “and Black residents’ share of Georgia’s total population increased from 26.8 percent of the population in 1990 to 30.6 percent in 2010.” +
++These Black Georgians were especially likely to use absentee ballots in the 2020 election cycle — so the law’s provisions limiting absentee balloting will have a disproportionate impact on African Americans if this pattern continues into future elections. (Although most of the spike in absentee voting in 2020 can be attributed to the pandemic, Black activists in Georgia have a history of using absentee voting drives to increase turnout.) +
++Black Georgians have also been much more likely to face long lines when they vote in person, according to the DOJ, which is why a law preventing good Samaritans from providing food and water to people waiting to cast a ballot is likely to have an outsized impact on African Americans. +
++The state legislature, the DOJ alleges, enacted the new law “with knowledge of the disproportionate effect that these provisions … would have on Black voters’ ability to participate in the political process on an equal basis with white voters.” The law passed without any support from Black lawmakers, and the legislature used an unusually rushed process to pass the bill. +
++Among other things, the GOP-controlled legislature bypassed the legislative committee that ordinarily would have overseen such a bill, and assigned it instead to a special committee chaired by a lawmaker who’d previously compared the “always-suspect absentee balloting process” to the “shady part of town down near the docks you do not want to wander into because the chance of being shanghaied is significant.” +
++The legislature also bypassed a process typically requiring such a bill to receive a “fiscal note,” a document laying out the bill’s likely impact on state and county spending. +
++Taken together, this and other evidence suggests that Georgia’s largely white Republican Party saw their grip on the state slipping away. The state’s Black population was growing, in numbers and in political power, and it just managed to elect a Black senator for the first time in the state’s history. +
++Faced with this impending loss of power, the DOJ alleges, white state lawmakers intentionally enacted legal provisions that they knew would diminish Black turnout — all in an effort to prevent African Americans from exercising the kind of political power they wielded in 2020. +
++Even setting aside the fact that this case will be heard by a Trump-appointed trial judge, and then potentially by a federal appeals court and a Supreme Court dominated by Republican appointees, the DOJ will also have to overcome a raft of recent precedents undermining the Voting Rights Act. +
++The most harmful of these cases to the DOJ’s chances of prevailing is Abbott v. Perez (2018), a 5-4 Supreme Court decision handed down along party lines. +
++Perez held that lawmakers accused of acting with racist intent enjoy such a high presumption of racial innocence that few litigants will be able to overcome it. As Justice Samuel Alito wrote for his Court in Perez, “whenever a challenger claims that a state law was enacted with discriminatory intent, the burden of proof lies with the challenger, not the State.” +
++And Alito also went much further than simply placing the burden of proof on voting rights plaintiffs. The facts of Perez were simply extraordinary, and they suggest that few plaintiffs alleging race discrimination can ever prove their case. +
++In 2011, Texas enacted congressional maps that a federal court later struck down as an illegal racial gerrymander. In 2012, however, this litigation was still making its way through two separate trial courts, and the state did not have any lawful map that it could use to conduct its congressional elections that year. +
++Thus, to ensure that Texas could actually hold congressional elections in 2012, a federal judge drew interim maps that incorporated many of the districts that were later struck down. In drawing this temporary map, however, the judge emphasized that “this interim map is not a final ruling on the merits of any claims” that some parts of the map were illegal racial gerrymanders. +
++Then, in 2013, Texas’s Republican legislature took this interim map and adopted it as its own — effectively attempting to make the temporary map into a permanent map, despite the fact that it included several racially gerrymandered districts. And the Supreme Court upheld this 2013 law in Perez. +
++The 2013 map, Alito claimed, was “legitimate” because it wasn’t enacted with racist intent. Rather, he argued, it was enacted because Texas “wanted to bring the litigation about the State’s districting plans to an end as expeditiously as possible.” +
++Alito’s argument, in other words, was that the 2013 maps weren’t enacted to preserve a racial gerrymander; they were enacted to shut down litigation challenging a racial gerrymander. And, in Alito’s mind, that was enough to defeat that litigation. +
++The upshot of Perez is that the DOJ will now have to argue that the evidence that Georgia’s voter suppression law was enacted with racist intent is even more potent than the unusually compelling evidence of racist intent that was present in the Perez case. The DOJ will have to make that case before a Trump-appointed trial judge. And it may ultimately have to argue its case before a Supreme Court that is even more conservative than the one that decided Perez. +
++And then, if the Justice Department hopes to stop Georgia Republicans from taking over local election boards and using them to disenfranchise voters, it will have to convince the courts to impose a rarely imposed sanction on Georgia and restore preclearance in that state. +
++Perhaps the Justice Department can overcome all of these challenges. But the deck is heavily stacked against them, no matter how strong their case may be. +
+The emotional labor of creating a more accepting league should not fall to LGBTQ athletes. +
++This week, Carl Nassib, a defensive end for the Las Vegas Raiders, came out as gay on Instagram. He’s the first active player in the NFL to be out publicly — a major milestone for men’s sports. Nassib’s announcement was quickly supported by the NFL community and his team, making it seem like his roster spot will be safe for the upcoming season. In a masculine, cutthroat league where players can be released at a moment’s notice for any reason, broad acceptance of Nassib marks a shift. +
++Nassib is not the first high-profile football player to come out — that would be Wade Davis in 2012. However, Davis did not play in a regular season game, and he came out after retiring. On the eve of the 2014 NFL draft, another player, Michael Sam, came out. Sam was eventually drafted by the St. Louis Rams, but was cut by the team before the season began. After a short stint with the Montreal Alouettes in Canada, Sam retired. +
++While Sam has avoided the spotlight since retiring, Davis has become an activist and public speaker. In the aftermath of Nassib’s announcement, Davis spoke with Vox on what goes through an athlete’s mind when they play while closeted, and what steps he thinks both the NFL and society need to take to foster a culture of acceptance. +
++The following, in Wade Davis’s words, has been condensed and edited. +
++For me, playing sports while not disclosing my sexuality was a double-edged sword. In some ways, being gay offered me misguided motivation. Because I hadn’t wrestled with my own internalized homophobia, and I believed that I needed to prove something to heterosexual people, I felt I had to show that I was as good an athlete as the straight guys. It took me many years before realizing that I didn’t have to prove anything to anyone. +
++I wish I knew then what I know now: that not learning to love myself as gay was a much greater loss than the possibility of not playing football. And the journey back to myself was and is just as painful. What I am also learning is LGBTQ folks are not actually the ones that need to be accepted here. We have already done the really hard work of accepting ourselves. +
++Some of the work that is still left unchecked is in the language that we use. The language of “coming out” connotes this idea that we have something to hide and that we are monsters who exist in the closet. What’s true is that the world is acting monstrous toward us. +
+ ++We invite people in, as writer and activist Darnell Moore taught us. We extend an invitation to heterosexual people to not be so fearful of who we are. I would say that the work is for heterosexual people to see our ownership of our sexuality as a model for what it means to accept a part of yourself that the world says is unacceptable. +
++Because when they learn how to accept more of themselves, it makes it harder to reject someone else. If this shift happens and heterosexual people start sharing their stories of self-acceptance, it could crack open a space where you see more athletes who identify as LGBTQ, specifically in male-identifying sport spaces, because we trust that heterosexual folks have done the work. +
++Another shift that has to happen in sports is that coaches, other players, and owners have to get much more eloquent, much more sophisticated, and much more competent in their understanding of the differences between things like sex, sexual orientation, and gender identity, so they become less fearful of the fact that we’re going to be much more present, and much, much more visible in sports. +
++The majority of the labor right now is being done by women and LGBTQ folks. The work of women in soccer and women in the WNBA — who have had more openly LGBTQ athletes and coaches, and who have pushed social justice conversations further — has really been a model for other athletes. Women in sports have historically focused on building the collective power of the marginalized to effect social change, risking their careers, while too many men have been focused on the accumulation of individual power to dominate and control and not take the same risk. These women athletes, especially women of color, have had the right focus, and gay male athletes need to align ourselves with them. +
++The impact of Michael Sam cannot be denied, either. People saw Michael Sam, the kiss of him and his partner during the NFL Draft, as a spectacle. But what’s true is that it’s folks like Michael Sam who have used spectacle as a way to make it much easier for people to do what Carl Nassib did. We need to recognize the revolutionary spirit and action of Michael Sam, and not think that Carl’s announcement was somewhat better or more eloquent. +
++Transgender folks and folks who are deemed much more effeminate in their presentation have also done a lot of the labor that allows folks like myself and Carl Nassib to have the courage to be more open about our sexuality. Most people don’t imagine gay men being able to play sports like football, baseball, basketball, hockey, and soccer. Nassib’s announcement is part of a continual fracturing of that age-old myth. For younger folks who have had greater proximity to folks who identify as LGBTQ, this is the way it should always have been, and they’re saying, what’s taken everyone else so long. +
++Because when the labor of education and acceptance shifts, we will reach a new inflection point. Then we won’t see Carl Nassib’s invitation — as opposed to his coming out — as separate from other social movements. Because if marginalized groups can start to see a connection, then we will be able to move forward into a much more unified, collective front. +
++For now, though, Carl Nassib is another model for LGBTQ folks who like or play sports, showing that sports is a space not only where we exist, but where we belong. +
++As told to Sydney Bauer. +
++
++
Sri Lanka series a great opportunity for all off us to showcase talent: Shikhar Dhawan - There is positivity, confidence in our team and everybody is confident that we will do well, says the cricketer
Shafali Verma becomes youngest Indian to make debut in all formats - The Haryana girl took 17 years and 150 days to make her debut across format, making her the fifth youngest cricketer overall in the list, headed by Afghanistan’s Mujeeb Ur Rahman.
It’s raining gold for India at Archery World Cup Stage 3 - Earlier on Saturday, India won a gold medal through Abhishek Verma in the compound individual event.
Many Japan schools opt not to take children to Olympic Games - About 60% of the discount tickets intended for municipalities to purchase for their school children have been cancelled in the neighbouring prefectures of Chiba, Saitama and Kanagawa
PCB chief Ehsan Mani set to get another three-year term - According to insiders during a recent meeting with PM Imran Khan in Islamabad, Mani agreed to carry on for another term
4,081 houses built by Corporation under PMAY - Sanction accorded for a total of 10,000 houses
Multidisciplinary approach needed to manage mucormycosis, says CMC Professor - ‘Anti-fungal treatment should be started without waiting for test reports’
Coronavirus | India has capacity to store vaccines requiring low temperatures: Centre to SC - The Centre has said the requirement for cold storage may change with the arrival of other COVID-19 vaccines in the future and it is fully prepared to take appropriate steps
Drones favoured tool of Pakistan-based terror outfits - Undetected by radars, they are used to smuggle drugs and weapons, and conduct aerial surveillance
Another BJP leader criticises COVID-19 handling in Uttar Pradesh - State BJP working committee member Ram Iqbal Singh, who made the remarks on Saturday, is the latest among the party’s leaders who have questioned the management of the coronavirus infection in the State.
Germany knife attack: Three killed were all women - The suspect has been charged with three counts of murder and five counts of grievous bodily harm.
UK classified government papers found at bus stop - The papers contain details about UK warship HMS Defender and the British military.
A billion new trees might not turn Ukraine green - The country’s ambitious target to improve the environment could actually harm biodiversity.
Italy 2-1 Austria (aet): Azzurri survive scare to reach Euro 2020 quarter-finals - Italy require extra time to see off battling Austria at Wembley and set up a Euro 2020 quarter-final against Belgium or Portugal.
Euro 2020: Wales 0-4 Denmark - Wales knocked out as Danes cruise into last eight - Wales are knocked out of Euro 2020 in the second round by Denmark, whose inspiring journey at the tournament continues to the quarter-finals.
Google launches a new medical app—outside the United States - The dermatology AI app won approval for use in the EU but not with the FDA. - link
SolarWinds hackers breach new victims, including a Microsoft support agent - Discovery came as Microsoft was investigating new breaches by the same hacker group. - link
All the major players spent time in the Denisovan cave - Even the sediment in the floor of Denisova Cave has a story to tell. - link
Circling—or cycling—the track at F1’s famous Circuit of the Americas - Be warned: Calves needed to climb all 133 feet of Turn 1 if you’re using a road bike. - link
A well-meaning feature leaves millions of Dell PCs vulnerable - Firmware security tool flaws affect as many as 30M desktops, laptops, and tablets. - link
+They arrive at the gates of heaven and meet St. Peter. St. Peter says to them “Sisters, welcome to Heaven. In a moment I will let you all though the pearly gates, but before I may do that, I must ask each of you a single question.” +
++St. Peter turns to the first Nun in the line and asks her “Sister, have you ever touched a penis?” The Sister Responds “Well… there was this one time… that I kinda sorta… touched one with the tip of my pinky finger…” St. Peter says “Alright Sister, now dip the tip of your pinky finger in the Holy Water, and you may be admitted.” and she did so. +
++St. Peter now turns to the second nun and says “Sister, have you ever touched a penis?” “Well…. There was this one time… that I held one for a moment…” “Alright Sister, now just wash your hands in the Holy Water, and you may be admitted” and she does so. +
++Now at this, there is a noise, a jostling in the line. It seems that one nun is trying to cut in front of another! St. Peter sees this and asks the Nun “Sister Susan, what is this? There is no rush!” Sister Susan responds “Well if I’m going to have to gargle this stuff, I’d rather do it before Sister Mary sticks her ass in it!” +
+ submitted by /u/L3viathanINC
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+“Thanks Dad” +
++“You’re welcome Alan” +
+ submitted by /u/R_K_Emon
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+The three men broke into a conversation. The topic eventually reached the men’s jobs, and why they were at the beach. +
++“I’m a construction worker,” said the first man. “All year long I toil in the sun in very heavy clothes, so this seemed like the perfect vacation for me. If I can relax and do it naked, that’s a win-win.” +
++“I’m an accountant,” said the second man. “I just like how everyone here is dressed exactly the same.” +
++The first two men turned to the third, sad man. “What do you do?” they asked. +
++“I’m a pickpocket,” said the third man. “My doctor sent me here.” +
+ submitted by /u/wimpykidfan37
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+As she’s perusing, she notices the most gorgeous rose she’s ever seen sitting next to the cashier, and asks for its price. +
++“Oh, sorry,” the cashier replies. “That one’s not for sale. I got that as a gift from a fellow florist for hooking him up with a woman I met yesterday.” +
++“Yesterday?!” she gasps. “How did they hit it off so quickly?” +
++“Well, he’s a handsome man and a wonderful lover, for one. He’s a really nice guy, of course. And to top it off,” he says, leaning into a whisper, “he’s got a 10-inch cock!” +
++She giggles, blushing. “Sounds like a catch! Where can I find him?” +
++“He’s just a block over. But fair warning…he’s also a little…kooky. He’s only interested in women named after flowers. So if I ever meet a woman with a flowery name, I send her his way.” +
++He points at the rose. “Then, he sends me the flower as a thank you. Yesterday was Rose. A week ago, I recommended Violet to him,” he says, indicating a slightly wilted violet in a vase behind him. +
++The woman thanks him and leaves, bitterly cursing her own name. Nevertheless, she visits the well-endowed florist’s shop. Stepping up to the counter, she pointedly says, “I heard you are particularly…skilled… in certain areas?” +
++He smirks. “So I have been told. And who might you be?” +
++She grins. “I was referred by your friend down the street. Perhaps you can…assist me?” +
++“Perhaps,” he says, “but tell me…what is your name?” +
++She hesitates. Then, pouting slightly, she replies “Kristen, but everyone calls me Kris.” +
++His smile falters, and his head sinks as he shakes his head. Kris’s heart drops, knowing she’s blown her chance. +
++“Well then…if it’s not too much trouble, I’d like some flowers for my mother.” +
++“Of course, what kind of….” Suddenly, he brightens up again. Without another word, he locks the shop door, swoops upon her, and takes her into his arms. +
++Three hours of mind-altering orgasms later, she bids him goodbye with a kiss as he presents a complimentary bouquet for her mother. +
++“And please,” he says, “tell your sweet mama she is welcome to as many flowers from my shop as she would like.” +
++Flustered with ecstasy, she promises to convey the message, and calls her mother that night to tell her everything. +
++The next day, Kris feels incredible, and stops by the original florist’s shop. +
++“I just wanted to thank you for telling me about that dashing gentleman! He was AMAZING!” +
++He smiles sheepishly. “I suppose I should thank you too. I just got another beautiful flower for recommending you to him.” +
++“Really? What flower could he have possibly sent that was named after me?” +
++The florist sighs. “Chrysanthemum.” +
+ submitted by /u/KairuSmairukon
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+Because 7 was a registered 6 offender. +
+ submitted by /u/edder24
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