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+ + + ++Background:The coronavirus disease (COVID-19) pandemic has led to an unprecedented public health crisis. Insufficient testing continues to limit the effectiveness of the global response to the COVID-19 pandemic. Molecular testing methods such as reverse transcriptase polymerase chain reaction (RT-PCR) continue to be highly centralized and are a sub-optimal option for population surveillance. Rapid antigen tests (Ag-RDTs) offer multiple benefits including low costs, high flexibility to conduct tests in a wide variety of settings, and faster return of results. Recently, self-test Ag-RDTs (STs) have gained approval in several markets and offer the possibility to expand testing, reaching at-risk populations. While STs have the potential to assist the COVID-19 response, test result integrity, reporting, and appropriate linkage to care continue to hinder the widespread implementation of self-testing programs. Methods:This protocol presents a mixed-methods pragmatic trial (ISRCTN91602092) to better understand the feasibility of self-testing as part of a contact tracing strategy within the Brazilian public health system. Approximately 604 close contacts of 150 index cases testing positive for COVID-19 will be enrolled. Close contacts will be randomized to either serial (daily) self-testing over a 10-day follow-up period or a more traditional approach to contact tracing with a professional Ag-RDT at one time point post-exposure. Usability workshops and focus group discussions will also be conducted. Discussion:This study protocol presents a comprehensive plan to assess the effectiveness, operational feasibility, and stakeholder preferences of a serial self-testing strategy for contact tracing within the Brazilian public health system. Our results will contribute to better understanding of the feasibility of a self-testing strategy within the public sector. Potential risks and limitations are discussed. Our findings will have important implications as governments continue working to mitigate the impact of COVID-19, particularly in the context of where to direct limited resources for testing and healthcare infrastructure. +
++Importance Investigating the role of preâinfection humoral immunity against Omicron BA.5 infection risk and long COVID development is critical to inform public health guidance. Objective To investigate the association between preâinfection immunogenicity after the third vaccine dose and the risks of Omicron BA.5 infection and long coronavirus disease. Design, Setting, and Participants This nested caseâcontrol analysis was conducted among tertiary hospital staff in Tokyo, Japan who donated blood samples in June 2022 (1 month before Omicron BA.5 dominant wave onset [JulyâSeptember 2022]) approximately 6 months after receiving the third dose of the historical monovalent coronavirus disease 2019 mRNA vaccine. Exposures Live virusâneutralizing antibody titers against Wuhan and Omicron BA.5 (NT50) and antiâSARSâCoVâ2 spike protein antibody titers with Abbott (AU/mL) and Roche (U/mL) assays at preâinfection. Main Outcomes and Measures Symptomatic SARSâCoVâ2 breakthrough infections during the Omicron BA.5 dominant wave vs. undiagnosed controls matched using a propensity score. Incidence of long COVID (persistent symptoms â„4 weeks after infection) among breakthrough infection cases. Results Antiâspike antibody titers were compared between 243 breakthrough infection cases and their matched controls among the 2360 staff members who met the criteria. Neutralizing antibodies in 50 randomly selected matched pairs were measured and compared. Preâinfection anti-spike and neutralizing antibody titers were lower in breakthrough cases than in undiagnosed controls. Neutralizing antibody titers against Wuhan and Omicron BA.5 were 64% (95% CI: 42â77) and 72% (95% CI: 53â83) lower, respectively, in breakthrough cases than in undiagnosed controls. Individuals with previous SARS-CoV-2 infections were more frequent among undiagnosed controls than breakthrough cases (19.3% vs. 4.1%), and their neutralizing antibody titers were higher than those of infectionânaive individuals. Among the breakthrough cases, preâinfection antibody titers were not associated with the incidence of long COVID. Conclusions and Relevance Preâinfection immunogenicity against SARSâCoVâ2 may play a role in protecting against the Omicron BA.5 infection, but not in preventing long COVID. +
++Introduction: Despite representing only 3% of the US population, immunocompromised (IC) individuals account for nearly half of the COVID-19 breakthrough hospitalizations. IC individuals generate a lower immune response following vaccination in general, and the US CDC recommended a third dose of either mRNA-1273 or BNT162b2 COVID-19 vaccines as part of their primary series. Influenza vaccine trials have shown that increasing dosage could improve effectiveness in IC populations. The objective of this systematic literature review and pairwise meta-analysis was to evaluate the clinical effectiveness of mRNA-1273 (50 or 100 mcg/dose) versus BNT162b2 (30 mcg/dose) in IC populations using the GRADE framework. Methods: The systematic literature search was conducted in the World Health Organization COVID-19 Research Database. Studies were included in the pairwise meta-analysis if they reported comparisons of mRNA-1273 and BNT162b2 in IC individuals â„18 years of age; outcomes of interest were SARS-CoV-2 infection, hospitalization due to COVID-19, and mortality due to COVID-19. Risk ratios (RR) were pooled across studies using random-effects meta-analysis models. Outcomes were also analyzed in subgroups of patients with cancer, autoimmune disease, and solid organ transplant. Risk of bias was assessed for randomized and observational studies using the Risk of Bias 2 tool and the Newcastle-Ottawa Scale, respectively. Evidence was evaluated using the GRADE framework. Results: Overall, 22 studies were included in the pairwise meta-analysis. Compared with BNT162b2, mRNA-1273 was associated with significantly reduced risk of SARS-CoV-2 infection (RR 0.87, 95% CI 0.79-0.96; P=0.0054; I2=61.9%), COVID-19-associated hospitalization (RR 0.83, 95% CI 0.76-0.90; P<0.0001; I2=0%), and COVID-19-associated mortality (RR 0.62, 95% CI 0.43-0.89; P=0.011; I2=0%) in IC populations. Results were consistent across subgroups. Because of sample size limitations, relative effectiveness of COVID-19 mRNA vaccines in IC populations cannot be studied in randomized trials and evidence certainty among comparisons was type 3 (low) and 4 (very low), reflecting potential biases in observational studies. Conclusion: This GRADE meta-analysis based on a large number of consistent observational studies showed that the mRNA-1273 COVID-19 vaccine is associated with improved clinical effectiveness in IC populations compared with BNT162b2. +
++Background: The role of Nirmatrelvir plus ritonavir (NMV-r) in preventing post-acute sequelae of SARS-CoV-2 infection (PASC) is unknown. The objective of this study is to assess the effect of NMV-r in non-hospitalized, vaccinated patients on the occurrence of PASC. Methods: We performed a comparative retrospective cohort study utilizing data from the TriNetX research network, including vaccinated patients â„18 years old who subsequently developed Covid-19 between December 2021-April 2022. Cohorts were based on NMV-r administration within five days of diagnosis. Based on previously validated broad and narrow definitions, the main outcome was the presence of symptoms associated with PASC. Outcomes were assessed between 30-180 days and 90-180 days after the index Covid-19 infection. Results 1,004 patients remained in each cohort after propensity-score matching. PASC (broad definition) occurred in 425 patients (42%) in the NMV-r cohort, vs. 480 patients (48%) in the control cohort (OR 0.8 CI 0.67-0.96; p=0.01) from 30-180 days and in 273 patients (27%) in the NMV-r cohort, as compared to 347 patients (35%) in the control cohort (OR 0.707, CI 0.59-0.86; p<0.001) from 90-180 days. Narrowly defined PASC was reported in 337 (34%) patients in the NMV-r and 404 (40%) in the control cohort between 30-180 days (OR=0.75, CI 0.62-0.9, p=0.002) and in 221 (22%) in the NMV-r cohort as compared to in 278 (28%) patients in the control cohort (OR=0.7, CI 0.63-0.9, p=0.003) between 90 -180 days. Conclusions NMV-r treatment in non-hospitalized vaccinated patients with Covid-19 was associated with a reduction in the development of symptoms commonly observed with PASC and healthcare utilization. +
++Background During the pandemic period, healthcare systems were substantially reorganized for managing COVID-19 cases. The corresponding changes on the standard care of persons with chronic diseases and the potential consequences on their outcomes remain insufficiently documented. This observational study investigates the direct and indirect impact of the pandemic period on the survival of kidney transplant recipients (KTR), in particular in those not hospitalized for COVID-19. Methods We conducted a cohort study using the French national health data system which contains all healthcare consumptions in France. Incident persons with end stage kidney disease between January 1, 2015 and December 31, 2020 who received a kidney transplant were included and followed-up from their transplantation date to December 31, 2021. The survival of KTR during the pre-pandemic and pandemic periods was investigated using Cox models with time-dependent covariates, including vaccination and hospitalization events. Findings There were 10,637 KTR included in the study, with 324 and 430 deaths observed during the pre-pandemic (15,115 person-years of follow-up) and pandemic periods (14,657 person-years of follow-up), including 127 deaths observed among the 659 persons with a COVID-19-related hospitalization. In multivariable analyses, the risk of death during the pandemic period was similar to that observed during the pre-pandemic period (hazard ratio (HR) [95% confidence interval]: 0.92 [0.77-1.11]), while COVID-19-related hospitalization was associated with an increased risk of death (HR: 10.62 [8.46-13.33]). In addition, pre-emptive kidney transplantation was associated with a lower risk of death (HR: 0.71 [0.56-0.89]), as well as a third vaccine dose (HR: 0.42 [0.30-0.57]), while age, diabetes and cardiovascular diseases were associated with higher risks of death. Interpretation Considering persons living with a kidney transplant with no severe COVID-19-related hospitalization, the pandemic period was not associated with a higher risk of death. +
+A Nasal Treatment for COVID-19 - Condition: Â COVID-19
Interventions: Â Drug:Â Optate; Â Drug:Â Placebo
Sponsor:  Indiana University
Not yet recruiting
Effect of a Health Pathway for People With Persistent Symptoms Covid-19 - Condition: Â COVID-19
Interventions:  Other: usual care and follow-up by a nurse;  Other: Personalized Multifactorial Intervention (IMP)
Sponsor:  Centre Hospitalier Universitaire de Saint Etienne
Not yet recruiting
RCT for Yinqiaosan-Maxingganshitang in the Treatment of COVID-19 - Condition: Â COVID-19
Interventions:  Drug: Chinese Herb;  Diagnostic Test: Placebo
Sponsor:  Chinese University of Hong Kong
Not yet recruiting
Tailored COVID-19 Testing Support Plan for Francophone African Born Immigrants - Condition: Â COVID19Â Testing
Interventions:  Behavioral: FABI tailored COVID-19 testing pamphlet;  Behavioral: Standard COVID-19 home-based test kit
Sponsors:  Texas Womanâs University;  National Institutes of Health (NIH)
Not yet recruiting
A Study to Understand the Effect and Safety of the Study Medicine PF-07817883 in Adults Who Have Symptoms of COVID-19 But Are Not Hospitalized. - Condition: Â SARS-CoV-2Â Infection
Interventions: Â Drug:Â PF-07817883; Â Drug:Â Placebo
Sponsor: Â Pfizer
Not yet recruiting
Traditional Chinese Medicine or Low-dose Dexamethasone in COVID-19 Pneumonia - Condition: Â COVID-19Â Pneumonia
Interventions:  Other: conventional western medicine treatment;  Drug: Dexamethasone oral tablet;  Other: Traditional Chinese medicine decoction
Sponsor:  China-Japan Friendship Hospital
Recruiting
A Clinical Study on Safety and Effectiveness of Mesenchymal Stem Cell Exosomes for the Treatment of COVID-19. - Condition: Â COVID-19Â Pneumonia
Intervention: Â Biological: Extracellular Vesicles from Mesenchymal Stem Cells
Sponsors:  First Affiliated Hospital of Wenzhou Medical University;  REGEN-αGEEK (SHENZHEN) MEDICAL TECHNOLOGY CO., LTD.
Recruiting
Inpatient COVID-19 Lollipop Study - Conditions:  COVID-19;  Diagnostic Test
Intervention: Â Device:Â Lollipop
Sponsor:  University of Wisconsin, Madison
Not yet recruiting
Study of the Safety, Tolerability and Efficacy of NP-101 in Treating High Risk Participants Who Are Covid-19 Positive. - Condition: Â COVID-19
Interventions: Â Drug:Â NP-101; Â Other:Â Placebo
Sponsor:  Novatek Pharmaceuticals
Recruiting
Effectiveness of Testofen Compared to Placebo on Long COVID Symptoms - Condition:  Long Covid19
Interventions:  Drug: Testofen;  Drug: Microcrystalline cellulose
Sponsor:  RDC Clinical Pty Ltd
Not yet recruiting
Building Resilience During the COVID-19 Pandemic: a Randomized Controlled Trial - Conditions:  Healthy;  COVID-19;  Distress, Emotional
Interventions:  Behavioral: RASMUS Resilience Training;  Behavioral: Progressive Muscle Relaxation
Sponsor:  Medical University Innsbruck
Recruiting
Care for Veterans Post-COVID - Condition:  Post-Acute COVID-19 Syndrome
Interventions:  Behavioral: Concordant Care Training;  Behavioral: Education Packet Training
Sponsor:  VA Office of Research and Development
Not yet recruiting
Complementary Self-help Strategies for Patients With Post-COVID Syndrome - Condition: Â Post-COVID-19Â Syndrome
Interventions:  Behavioral: Complementary self-help strategies in addition to treatment as usual;  Other: Treatment as usual
Sponsor:  UniversitÀt Duisburg-Essen
Not yet recruiting
Safety & Immunogenicity of RVM-V001/RVM-V002 or RVMV001+RVMV002 (Co Administered as Separate Injections) in Healthy Individuals - Conditions:  Infectious Disease;  COVID-19
Interventions:  Biological: RVM-V001 30 ”g;  Biological: RVM-V002 30 ”g;  Biological: RVM-V001 (15 ”g) + RVM-V002 (15 ”g) co-administration
Sponsor:  RVAC Medicines (US), Inc.
Recruiting
HH-120 Nasal Spray for Post-exposure Prevention of SARS-CoV-2 - Condition: Â COVID-19
Interventions:  Drug: HH-120 Nasal Spray;  Drug: Placebo
Sponsor:  Huahui Health
Not yet recruiting
Suramin binds and inhibits infection of SARS-CoV-2 through both spike protein-heparan sulfate and ACE2 receptor interactions - SARS-CoV-2 receptor binding domains (RBDs) interact with both the ACE2 receptor and heparan sulfate on the surface of host cells to enhance SARS-CoV-2 infection. We show that suramin, a polysulfated synthetic drug, binds to the ACE2 receptor and heparan sulfate binding sites on the RBDs of wild-type, Delta, and Omicron variants. Specifically, heparan sulfate and suramin had enhanced preferential binding for Omicron RBD, and suramin is most potent against the live SARS-CoV-2 Omicron variantâŠ
Metabolic dysregulation impairs lymphocyte function during severe SARS-CoV-2 infection - Cellular metabolic dysregulation is a consequence of SARS-CoV-2 infection that is a key determinant of disease severity. However, how metabolic perturbations influence immunological function during COVID-19 remains unclear. Here, using a combination of high-dimensional flow cytometry, cutting-edge single-cell metabolomics, and re-analysis of single-cell transcriptomic data, we demonstrate a global hypoxia-linked metabolic switch from fatty acid oxidation and mitochondrial respiration towardsâŠ
Development of a Peptide Sensor Derived from Human ACE2 for Fluorescence Polarization Assays of the SARS-CoV-2 Receptor Binding Domain - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the continuing emergence of infectious variants have caused a serious pandemic and a global economic slump since 2019. To overcome the situation and prepare for future pandemic-prone diseases, there is a need to establish a convenient diagnostic test that is quickly adaptable to unexpected emergence of virus variants. Here we report a fluorescent peptide sensor 26-Dan and its application to the fluorescence polarization (FP) assayâŠ
Comparison of a rapid fluorescence immunochromatographic test with an enzyme-linked immunosorbent assay for measurement of SARS-CoV-2 spike protein antibody neutralizing activity - CONCLUSION: FIC had good qualitative agreement with ELISA in the detection of positive NAbs-RBD(%) and could be an alternative for rapid NAbs-RBD(%) testing.
Comparison of antibody response to coronavirus disease 2019 vaccination between patients with solid or hematologic cancer patients undergoing chemotherapy - CONCLUSION: Hematologic cancer patients receiving chemotherapy tended to respond poorly to both COVID-19 mRNA and vector vaccines and had a significantly lower antibody titer compared to those with solid cancers.
A covalent inhibitor targeting the papain-like protease from SARS-CoV-2 inhibits viral replication - Covalent inhibitors of the papain-like protease (PLpro) from SARS-CoV-2 have great potential as antivirals, but their non-specific reactivity with thiols has limited their development. In this report, we performed an 8000 molecule electrophile screen against PLpro and identified an α-chloro amide fragment, termed compound 1, which inhibited SARS-CoV-2 replication in cells, and also had low non-specific reactivity with thiols. Compound 1 covalently reacts with the active site cysteine of PLpro,âŠ
Factor Xa cleaves SARS-CoV-2 spike protein to block viral entry and infection - Serine proteases (SP), including furin, trypsin, and TMPRSS2 cleave the SARS-CoV-2 spike (S) protein, enabling the virus to enter cells. Here, we show that factor (F) Xa, an SP involved in blood coagulation, is upregulated in COVID-19 patients. In contrast to other SPs, FXa exerts antiviral activity. Mechanistically, FXa cleaves S protein, preventing its binding to ACE2, and thus blocking viral entry and infection. However, FXa is less effective against variants carrying the D614G mutationâŠ
TRPC6 inhibitor (BI 764198) to reduce risk and severity of ARDS due to COVID-19: a phase II randomised controlled trial - CONCLUSIONS: TRPC6 inhibition was not effective in reducing the risk and/or severity of ARDS in patients with COVID-19 requiring non-invasive, supplemental oxygen support.
SARS-CoV-2 Inhibits NRF2-Mediated Antioxidant Responses in Airway Epithelial Cells and in the Lung of a Murine Model of Infection - Several viruses have been shown to modulate the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2), the master regulator of redox homeostasis. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, also seems to disrupt the balance between oxidants and antioxidants, which likely contributes to lung damage. Using in vitro and in vivo models of infection, we investigated how SARS-CoV-2 modulates the transcription factor NRF2âŠ
Chemical Composition of Honeysuckle (Lonicerae japonicae) Extracts and Their Potential in Inhibiting the SARS-CoV-2 Spike Protein and ACE2 Binding, Suppressing ACE2, and Scavenging Radicals - Honeysuckle (Lonicerae japonicae) has been used in functional tea products. The chemical compositions of the water and ethanol extracts of honeysuckle were examined in the present study, along with their potential in inhibiting SARS-CoV-2 spike protein binding to ACE2, suppressing ACE2 activity, and scavenging reactive free radicals. Thirty-six compounds were tentatively identified from the honeysuckle extracts using HPLC-MS/MS, with ten reported for the first time in honeysuckle. BothâŠ
Surfactin-like lipopeptides from Bacillus clausii efficiently bind to spike glycoprotein of SARS-CoV-2 - The coronavirus disease 2019 (COVID-19) rapidly spread across the globe, infecting millions and causing hundreds of deaths. It has been now around three years but still, it remained a serious threat worldwide, even after the availability of some vaccines. Bio-surfactants are known to have antiviral activities and might be a potential alternative for the treatment of SARS-CoV-2 infection. In the present study, we have isolated and purified, a surfactin-like lipopeptide produced by a probioticâŠ
Repurposing immune boosting and anti-viral efficacy of Parkia bioactive entities as multi-target directed therapeutic approach for SARS-CoV-2: exploration of lead drugs by drug likeness, molecular docking and molecular dynamics simulation methods - The COVID-19 pandemic has caused adverse health (severe respiratory, enteric and systemic infections) and environmental impacts that have threatened public health and the economy worldwide. Drug repurposing and small molecule multi-target directed herbal medicine therapeutic approaches are the most appropriate exploration strategies for SARS-CoV-2 drug discovery. This study identified potential multi-target-directed Parkia bioactive entities against SARS-CoV-2 receptors (S-protein, ACE2,âŠ
Attitudes and concerns regarding booster dose of COVID-19 vaccine among Egyptian patients with autoimmune and rheumatic diseases: a cross-sectional survey study - CONCLUSIONS: There is a low acceptability rate of booster dose of COVID-19 vaccine among Egyptian patients with ARD diseases. Public health workers and policymakers need to make sure that all ARD patients get clear messages about accepting the COVID-19 booster dose.
Paxlovid (Nirmatrelvir/Ritonavir): A new approach to Covid-19 therapy? - Despite the need for novel, effective therapeutics for the COVID-19 pandemic, no curative regimen is yet available, therefore patients are forced to rely on supportive and nonspecific therapies. Some SARS-CoV-2 proteins, like the 3 C-like protease (3CLpro) or the major protease (Mpro), have been identified as promising targets for antiviral drugs. The Mpro has major a role in protein processing as well as pathogenesis of the virus, and could be a useful therapeutic target. The antiviral drugâŠ
Efficacy of pentasodium diethylenetriamine pentaacetate in ameliorating anosmia post COVID-19 - CONCLUSION: This study confirmed the efficacy of DTPA in treating post-COVID-19 anosmia.
Inside the Hush-Money Payments That May Decide Trumpâs Legal Fate - Years of interviews with potential witnesses provide insights into the Manhattan D.A.âs case. - link
How Putin Criminalized Journalism in Russia - The case of Evan Gershkovich, a Wall Street Journal reporter being held in Moscow on espionage charges, is only the most recent example of the Kremlinâs crackdown on reporters. - link
The Same Ole Line Dudes Are Waiting for You - Donald Trumpâs arraignment was a circus for the media, but it was just another day at the office for New Yorkâs professional line sitters. - link
Whatâs Behind the Fight Between Pope Francis and the Latin Mass Movement? - The discord has become a stand-in for conflicts over the decline in Catholicsâ participation in Mass, over the progressive orientation of Francisâs pontificate, and over Vatican II itself. - link
Fighting for the Right to Come and Go - In Mexico, return-migrant activists are asserting their âpochaâ heritage and working to end legal and cultural exclusion. - link
+Text a friend, write a thank-you note, compliment a stranger â people appreciate these gestures. +
++Think about the last time someone showed you a small token of appreciation. Perhaps a stranger gave you a compliment, or maybe you got a check-in text from a friend, or received a particularly heartfelt thank-you note from a mentee. Chances are, that tiny act brightened your day. After all, thereâs a delight in knowing you were on someoneâs mind for even a brief moment. +
++When the roles are reversed, though, you might often psych yourself out of performing these simple bids, convincing yourself you must initiate a follow-up after that initial text or that stranger will rebuff your kind remark. +
++âI think people felt like there was an obligation,â says Gillian Sandstrom, a senior lecturer in the psychology of kindness at the University of Sussex, who is currently studying peopleâs reluctance to reach out to friends with whom theyâd lost touch. âThere is no commitment. I can just have a one-off thing, walk away. Thereâs something really beautiful about that.â +
++Research suggests, across multiple studies, that people have overwhelmingly similar impulses to not do the nice thing: They underestimate how much other people value the reach-out, the random act of kindness. These seemingly minor deeds are appreciated, though. Turning down the naysaying voice in your head allows for more opportunities to show warmth to those around you. +
++Since humans lack the ability to read minds, we simply guess at what other people think of us. These hypotheses are informed by how people perceive themselves, and not by real-world feedback and criticism from those theyâve actually interacted with. These self-perceptions are often marred by negativity; when recalling past social interactions, people worried their jokes were subpar or that their conversation partner found them uncool. âWe assume other people are thinking what weâre thinking,â Sandstrom says. +
++Psychologist and friendship expert Marisa Franco credits these pessimistic assumptions to a concept called the negativity bias, wherein people remember negative events and feelings more acutely than positive ones. As a result, people tend to avoid socially risky behaviors â like telling a stranger on the subway you like their shoes â in order to avoid potential awkwardness. âAcross the board,â says Franco, who is also the author of Platonic: How the Science of Attachment Can Help You Make â and Keep â Friends, âin pretty much every act of connection, we tend to underestimate how much people will be receptive to our overtures in connection.â Of course, there will be instances where a stranger, in particular, will not be amenable to your overtures (this isnât permission to harass people on the street), but your intention should be to brighten someoneâs day without worrying what they think about you. +
++The persistent underestimation of how much others enjoy our company is known as the liking gap, dubbed by Sandstrom and her colleagues in a 2018 paper. Through both short conversations and long ones, with both strangers and acquaintances, study participants consistently misjudged how much their conversation partners liked them. (Participants took surveys after each chat and reported that they liked their conversation partner much more than they perceived their conversation partner to have liked them.) +
++This mismatch of appreciation extends to other domains, such as writing thank-you notes, sending text messages, and gifting a cup of hot chocolate. âBeing kind to other people, doing nice things for others â those are the activities that tend to improve our well-being,â says Amit Kumar, assistant professor of marketing and psychology at the University of Texas at Austin. âFolks have lots of opportunities for acting in these other-oriented ways that they donât take advantage of. I think the interesting question then becomes, well, why donât people act in ways that are likely to make them feel better?â +
++If small, kind gestures have a positive impact on the receiverâs day, why are people so hesitant to do them? According to Kumar, who has studied the positive impact of acts of kindness and gratitude letters, we donât often recognize the power of these benevolent acts on others. Instead of focusing on the warm intention (literally and figuratively) associated with buying a stranger a cup of coffee, we fixate on the value of what weâre presenting. âWhen youâre doing something for someone else, youâre thinking about the thing that youâre giving and what its value is,â Kumar says. Recipients, on the other hand, are âthinking about the warmth associated with the fact that it was given to them by another person out of kindness.â +
++Surprise also generates appreciation from recipients, says Peggy Liu, the Ben L. Fryrear Chair in Marketing and an associate professor of business administration at the University of Pittsburgh Katz Graduate School of Business. In her recent studies demonstrating the power of a brief check-in text to friends, Liu found that when recipients werenât expecting to hear from the initiator â maybe it had been a few months since they last spoke â they appreciated that someone thought about them enough to reach out. While Liu did not identify what prevented would-be initiators from sending the text, she suspects thoughts of worry held them back: Is my friend going to think itâs strange that I just reached out? Does what I wrote to them sound okay? +
++There is also an inherent anxiety that something as simple as a text must come with strings attached: a phone call, a coffee date. In Sandstromâs as-of-yet unpublished study about reconnecting with friends, participants often didnât reach out because they lacked the time to commit to the relationship beyond the initial message. During a time when so many are stretched thin, just the small act itself is enough. âA brief text,â Liu says, âdoesnât create that much obligation in the other person and allows the other person to decide when and how they want to respond.â +
++That nagging negativity bias creates doubt. There will inevitably be times when our attempts at conversations with strangers fall flat â and those memories will prevail over those of successful acts of kindness. Still, pursuing these bids with regularity helps break the assumption that they wonât be appreciated. With each positive interaction, anxiety is replaced by joy. +
++In other words, donât fixate on picking out the best flowers for your partner or fear a distant friend will criticize your grammar in a text message. The gesture itself is more consequential than the content â because itâs always worth it to do the nice thing rather than to avoid doing it out of fear of rejection or awkwardness. In his studies, not only did the recipients feel appreciated, but the do-gooders reported feeling happy, too, Kumar says. +
++To avoid talking ourselves out of performing friendly exploits, itâs helpful to catch ourselves in the act of second-guessing and remind ourselves how lovely it felt when we were on the receiving end of, say, a check-in text, Liu says. No one criticizes a kind note they werenât expecting. +
++These small gestures can be just that: a quick chat, a thinking-of-you message, gifting unused public transit fare to a stranger. âIâm a working mom,â Liu says. âIt can be hard to actually have a more lengthy get-together. So I think thatâs partly why these brief reach outs are so appreciated.â +
++The consequence of ignoring our impulse to reach out is missed opportunities for social connection. Instead, says Franco, assume people like you. âWhen people are told that theyâre going into a group and [will] be accepted, they become warmer, friendlier, and more open,â she says. âWhereas people that have rejection sensitivity, who tend to assume theyâll be rejected, they tend to become cold and withdrawn, thus rejecting other people and getting rejected back.â +
++Opt for a touch of optimism, put yourself out there, and, Franco says, consider potential rejection as the price worth paying for meaningful interactions. +
+Contradictory court orders put the abortion drug mifepristone in âuncharted territory.â +
++Federal judges in Texas and Washington handed down two opposing rulings on the abortion pill mifepristone on Friday, jeopardizing access to the drug and putting the US Food and Drug Administration in an impossible situation. +
++Matthew Kacsmaryk, a conservative federal district court judge in Texas, issued a long-awaited ruling Friday evening calling for the FDA to stay its approval of mifepristone, which has been deemed safe and legal for 23 years, while Thomas Rice, a federal court judge in Washington state, swiftly issued a directly contradictory decision. +
+ ++Kacsmarykâs order to halt mifepristoneâs approval was widely expected given his conservative views and background in the Christian right, and hinges on the idea that medication abortion is not safe. That claim, though, is disputed by decades of evidence to the contrary, and in the Washington state order enjoining the FDA from making changes to mifepristoneâs availability in the 17 states and Washington, DC, Rice also argued that it isnât the role of a court to determine a drugâs safety. +
++As of now, medication abortion â most frequently a two-drug regimen consisting of mifepristone and misoprostol â remains legal in the US, and both drugs, mifepristone and misoprostol, are approved by the FDA. Kacsmarykâs order would have invalidated mifepristoneâs approval after a seven-day stay of the order to allow for potential emergency relief. But Riceâs ruling further complicates Kacsmarykâs, since the FDA would be unable to fully comply with both orders at once. +
++âThere is now directly conflicting federal court decisions on what the status of mifepristone is,â Rachel RebouchĂ©, dean of Temple Universityâs Beasley School of Law told Vox in an interview. âSo nothing changes for the next week, and weâll see litigation start to move as the FDA and DOJ ask the Fifth Circuit and Supreme Court to clarify.â +
+ ++Not only does the Texas ruling endanger access to medication abortion, it also calls into question the ability of the FDA and other federal agencies to follow through with their mandates, according to several experts. Kacsmarykâs ruling cites dubious claims about mifepristoneâs supposed dangers, and experts told Vox that the fact that a court has now decided it can arbitrate scientific fact better than medical experts is unprecedented and potentially quite dangerous. +
++Contrary to Kacsmarykâs order, mifepristone is extremely safe, and along with misoprostol is widely used to end abortions within the first trimester. As Voxâs Rachel Cohen explains: +
++++Medication abortion â referring to the combination of both mifepristone and misoprostol â accounts for more than half of all abortions in the US, and is used typically within the first 10 to 12 weeks of a pregnancy. Itâs become the most common method for ending pregnancies in the United States, partly due to its safety record, its lower cost, diminished access to in-person care, and greater opportunities for privacy. +
+
+Medication abortion is just the latest battleground in reproductive rights after the Supreme Court overturned Roe v. Wade last summer, voiding the constitutional right to an abortion. Kacsmarykâs case has been the highest-profile attacks on mifepristone, itâs not the only one; in March, Wyomingâs governor signed a bill banning medication abortion effective July 1, though that law is being challenged in court. +
++Fridayâs contradictory rulings are by no means the last word on medication abortion; both the Justice Department and Danco Laboratories, which manufactures mifepristone under the name Mifeprex, have filed appeals to the Fifth Circuit Court, and itâs likely the issue will end up before the Supreme Court. However, given the recent track record of both the Fifth Circuit and the Supreme Court on abortion issues, the outcome for medication abortion is far from clear. +
++For its part, the FDA made a statement to the Washington Post defending mifepristone and its approval for the market. âFDA stands behind its determination that mifepristone is safe and effective under its approved conditions of use for medical termination of early pregnancy, and believes patients should have access to FDA-approved medications that FDA has determined to be safe and effective for their intended uses,â an agency spokesperson said. +
++The decisions came down rapid-fire Friday evening; Riceâs order became public just after Kacsmarykâs, fueling confusion over the future of the drug. Kacsmarykâs 67-page order rules on the idea that the FDA didnât properly study the effects of medication abortion and fast-tracked its approval, siding with the plaintiffs â four anti-abortion medical groups and four anti-abortion doctors. +
++According to Greer Donley, an associate professor of law at the University of Pittsburghâs center for bioethics and health law, âif the Texas order goes into effect in seven days â if thereâs no appeal that changes that â the drug will become unapproved. Thereâs nothing for the FDA to do. The order was specifically written to avoid any action on the FDAâs part, the drug just becomes unapproved in seven days.â +
++That outcome is complicated by the injunction from a Washington state federal court: Riceâs decision orders that the FDA maintain the status quo for mifepristone by not blocking its availability. While Kacsmarykâs order would apply nationally, Riceâs only applies to DC and the 17 states named as plaintiffs. +
++Itâs unlikely, however, that the limited scope of the Washington state ruling clears the way for Kacysmarykâs injunction in any meaningful way. According to Steve Vladeck, the Charles Alan Wright Chair in Federal Courts at the University of Texas, itâs âa distinction without a difference given what it orders the FDA to not do.â +
++âSo there would be no way for the FDA to comply with both if Kacsmarykâs ruling ever goes into effect,â Vladeck tweeted Friday evening. âHence, #SCOTUS.â +
+++The WA ruling is not nationwide (although I think thatâs a distinction without a difference given what it orders the FDA to not do), but Kacsmarykâs would be. So there would be no way for the FDA to comply with both if Kacsmarykâs ruling ever goes into effect. Hence, #SCOTUS. +
+â Steve Vladeck (@steve_vladeck) April 7, 2023 +
+Itâs possible the courts could find a way to square the circle, Donley told Vox, by issuing an âenforcement discretion notice to say, âEven though itâs technically illegal in seven days, barring any appeal, for a manufacturer to market mifepristone because itâs going to be unapproved, weâre not going to go after anyone who does that.ââ But more likely, the contradictory orders will expedite the casesâ trip to the Supreme Court. +
++Vox reached out to the FDA regarding the possibility of an enforcement discretion notice, but did not receive a response before press time. +
++Kacsmaryk stated in his order that mifepristoneâs safety hadnât been well-established, even though the FDA re-approved the drug in 2016 and 2019 after its initial approval in 2000. Certain assertions in the order, including an assertion that âchemical abortions are over fifty percent more likely than surgical abortion to result in an emergency room visit within thirty days,â are used without context or are not borne out by data. +
++But some of the damage may already have been done â in addition to Fridayâs contradictory rulings on medication abortion, restrictions in states and court challenges to those restrictions have created an atmosphere of fear and confusion that makes it difficult for providers to operate. +
++âPeople are very afraid, criminal laws are very scary, understandably, to providers,â Donley said. âSo youâre seeing that chaos is really impacting and affecting abortion access.â +
++Whatever the outcome of the fight over medication abortion â whether mifepristoneâs approval status is decided in the Fifth Circuit or the Supreme Court â the Kacsmaryk case in particular has the potential to set some alarming precedents. +
++In terms of abortion access, Cohen wrote, there are still some options for people who need them: +
++++If mifepristone is ultimately pulled from the market, people seeking abortions could still access care at in-person clinics for surgical abortions. But those procedures typically cost more money, and require more time and resources from already-strapped abortion clinics. In its legal filing opposing the Texas case, the Justice Department warned that taking mifepristone off the market would lead to delays and overcrowding at these clinics, which were already managing an influx of out-of-state patients since Roeâs overturn. +
+
+And at least one state has gone even further to protect medication abortion access: Washington has stockpiled tens of thousands of doses of mifepristone against the possibility of a decision like Kacsmarykâs. +
++If the Fifth Circuit or the Supreme Court allow Kacsmarykâs order to stand, however, RebouchĂ© told Vox that it would have significant implications regarding the role of the FDA and other federal agencies and their ability to carry out their mandates. +
++âNo matter your feelings about abortion, whatâs your track record on federal power?â she said. Should the case make it to the Supreme Court, âthey would have the same questions about not just the nature of abortion or the nature around the fact-finding of the safety of medication abortion, but also the role of the FDA in all of this.â +
++As Donley told Vox, the Kacsmaryk ruling is unprecedented â and if the Fifth Circuit or Supreme Court were to agree with its logic, it would create a precedent for the courts to not only call into question the power of federal agencies, but also for the courts to overrule matters of settled medical science which could have wide-ranging implications. +
++âThis is uncharted territory,â Donley said. +
++The federal courts are dominated by Republicans, so the appeals process could be rough. +
++If youâve followed the fight over where and whether abortion should remain legal in the United States, youâve probably heard the name âMatthew Kacsmaryk.â +
++Kacsmaryk is a former lawyer for a religious right law firm, who was appointed by former President Donald Trump to a federal court in Texas. On Friday, he issued a decision ordering the Food and Drug Administration to withdraw its approval of mifepristone, a medication used in more than half of all abortions within the United States. +
+ ++His decision in this lawsuit, Alliance for Hippocratic Medicine v. FDA, wonât go into effect for seven days, but it is clear about its stance. +
++Make no mistake, there is no legal basis whatsoever for a federal judge to endorse a lawsuit trying to ban this medication, which has been lawful in the United States since 2000. +
++But now that Kacsmaryk has ruled in a way that wonât surprise anyone familiar with his record of partisan rulings, it will immediately test whether the rule of law still exists in a judiciary dominated by Republican appointees. +
++Hereâs what happens next in the federal court system: There will likely be two parallel appeals processes â a relatively quick process seeking to temporarily block Kacsmarykâs order, and then a much more drawn-out process seeking to permanently reverse his decision. (In fact, Kacsmaryk explicitly acknowledges the likelihood that the US government will quickly seek an emergency stay; thatâs why he says heâs delaying his ruling from taking effect for seven days.) +
+ ++This ordinary process may be fast-tracked, however, because a different federal judge in Washington State handed down a contradictory order requiring the FDA to allow mifepristone to be sold in 17 states. That means that, once Kacsmarykâs order takes effect, FDA will be subject to competing orders and it will literally be impossible for it to comply with both. +
++In these sorts of extraordinary circumstances, the Supreme Court may permit the federal government to bypass the ordinary appeals process and seek immediate relief from the justices themselves â assuming that the Justice Department asks the high Court to do so. +
++If the federal courts could be trusted to apply the law in a fair and non-partisan manner, even when hot-button issues like abortion are at stake, then we could expect a higher court to step in almost immediately to quash a decision seeking to ban mifepristone. As attorney Adam Unikowsky, a former law clerk to Justice Antonin Scalia, writes in a scathing prebuttal of Kacsmarykâs expected decision, âif the subject matter of this case were anything other than abortion, the plaintiffs would have no chance of succeeding in the Supreme Court.â +
++But in these courts ⊠well, buckle up, because itâs not entirely clear where this ride ends. +
++Now that Kacsmaryk has issued an order seeking to remove mifepristone from the market, President Joe Biden said the Justice Department will file an appeal and seek an immediate stay of the decision to temporarily block that order as fast as it can. This is ordinarily the first step the government takes when a judge imposes a nationwide injunction upon it. +
++Realistically, the DOJ will probably need at least several days to review Kacsmarykâs opinion, to consult with other federal agencies that are impacted by that decision, and to draft a motion seeking a stay of Kacsmarykâs decision. But, in a case as important as this one, it is likely that the Justice Department will move as fast as it reasonably can to invoke the authority of a higher court. +
++Federal appellate courts are divided into 13 different circuits, most of which have jurisdiction over appeals from federal trial courts in a handful of states. Appeals arising out of Texas are typically heard by the United States Court of Appeals for the Fifth Circuit, which is probably the most right-wing appeals court in the entire federal system. +
+ ++In the last year or so, the Fifth Circuit declared an entire federal agency unconstitutional. It permitted Texas Republicans to effectively seize control of content moderation at social media sites like Twitter, Facebook, and YouTube. And it even tried to override the US Navyâs decisions about which military personnel are fit for deployment. +
++Simply put, this court is not where you want to be if you are trying to block a trial judgeâs decision restricting abortion. +
++That said, it is possible to draw a reasonable panel of judges in the Fifth Circuit. Typically, federal appeals courts hear cases in three-judge panels, randomly selected from among the courtâs judges. Four of the Fifth Circuitâs 16 active judges were appointed by Democrats, and some of the Courtâs older Republican appointees are more moderate than the newer crop appointed by Trump. So it is still possible that the Fifth Circuit will grant the DOJâs request to temporarily block Kacsmarykâs order. +
++Should the Fifth Circuit deny this request, however, the Justice Departmentâs next move is to ask the Supreme Court to block Kacsmarykâs order by invoking the Supreme Courtâs enigmatic âshadow docket.â +
++The shadow docket is a mix of emergency motions and other matters that the Court decides on an expedited basis, often without full briefing or oral argument. Although most shadow docket orders are brief and say little more than whether the Court has decided to block a lower court decision or not, the Court occasionally hands down important precedent-setting decisions on its shadow docket. Its shadow docket decision in Roman Catholic Diocese of Brooklyn v. Cuomo (2020) revolutionized the law governing when people with religious objections to a law may violate it. +
++Unfortunately, the shadow docket has become a politicized area of the Courtâs work. When Trump was in the White House, the justices frequently blocked lower court decisions within days or a few weeks of the Trump Justice Departmentâs request asking them to do so. Under Democratic President Joe Biden, by contrast, the justicesâ ordinary practice has been to reject such requests â even in cases where the Court ultimately concludes, months later, that the lower court decision was wrong. +
++That said, the Court did intervene on the Biden administrationâs behalf in at least one truly egregious case. In Austin v. U.S. Navy SEALs 1-26 (2022), the Court largely halted the decision ordering the Navy to deploy servicemembers that the military deemed unfit for such service. As Justice Brett Kavanaugh wrote in a brief concurring opinion, the lower court in the Navy SEALs case âin effect inserted itself into the Navyâs chain of command, overriding military commandersâ professional military judgments.â +
++Kacsmarykâs decision ordering the FDA to withdraw its approval of mifepristone is no less egregious than the lower courtâs action in Navy SEALs. Among other things, it effectively strips the FDA â an agency made up of scientists with considerable expertise in drug efficacy and safety â of its ability to definitively rule on which medicines should be available in the United States, making the judiciary the final word on such decisions. +
++Thatâs an extraordinary threat to public health. And one that five justices may have the good sense to avoid. +
++One additional complicating factor here is that a federal judge in Washington State issued a directly contradictory ruling on Friday evening, moments after Kacsmarykâs, prohibiting the FDA from pulling mifepristone from the market. +
++That increases the likelihood that this case makes its way up to the Supreme Court quite quickly. Even if the Supreme Court doesnât rule on the underlying issue about whether mifepristone should be legal or not, the two conflicting orders put the FDA in such a legal bind â it cannot comply with both â that they may ask the justices to invoke a rarely used process, known as âcertiorari before judgment,â which allows the Supreme Court to hear a case before it is decided by an appeals court. +
++Under the Courtâs rules, a request to use this process âwill be granted only upon a showing that the case is of such imperative public importance as to justify deviation from normal appellate practice and to require immediate determination in this Court.â But the justices may very well determine that this highly unusual situation, where the federal government faces contradictory orders from competing federal judges, warrants such review. +
++Regardless of whether the Fifth Circuit or the Supreme Court grants emergency relief to the Justice Department, blocking Kacsmarykâs order while the case is fully litigated on appeal, at least one appeals court will need to determine whether to reverse Kacsmaryk and permanently restore the FDAâs authority to determine which medicines should be available. +
++This process, however, will move very slowly if no court grants emergency relief blocking Kacsmarykâs decision. Each side will likely need weeks to prepare briefs for the Fifth Circuit, and the panel of Fifth Circuit judges assigned to the case will most likely take just as much time to prepare for an oral argument. Then, after that argument takes place, the Court could spend months pondering the case before a final decision is released. +
++And then, whichever side loses is likely to seek review in the Supreme Court â which will require its own time-consuming process of briefing, oral arguments, and deliberation if it agrees to hear the case (which it almost certainly will if the Fifth Circuit does not reverse Kacsmaryk). +
++To give you a sense of how long this process could take, in August of 2021, Kacsmaryk handed down an unlawful order requiring the Biden administration to reinstate a Trump-era border policy known as âRemain in Mexico.â The Supreme Court rejected the Biden administrationâs request to block this order on the Courtâs shadow docket, but it did eventually reverse Kacsmaryk â 10 months later at the end of June 2022. +
++Realistically, in other words, if the Justice Department cannot obtain emergency relief from either the Fifth Circuit or the Supreme Court, Kacsmarykâs unlawful order attacking mifepristone could be in effect for months, if not longer. +
++That said, the conflicting Washington order significantly increases the chances that higher federal courts will move quickly here as, again, the Biden administration cannot comply with Kacsmarykâs order and the Washington order simultaneously. +
++The answer is unclear. +
++There is no plausible legal argument that could justify a federal court decision requiring the FDA to unapprove mifepristone. To list just a few reasons why, the plaintiffs in this lawsuit, Alliance for Hippocratic Medicine v. FDA, waited too long to bring their suit â the statute of limitations to challenge the FDAâs approval of a drug is six years. Kacsmaryk also does not have jurisdiction over this lawsuit. And, as Unikowsky writes in his prebuttal of Kacsmarykâs expected decision, âno statute exists that the FDA could possibly have violatedâ when it approved mifepristone. +
++But five of the current justices have shown an extraordinary willingness to bend the law in order to restrict access to abortion. +
++Specifically, the Courtâs decision in Whole Womanâs Health v. Jackson (2021), which was decided before the Court overruled Roe v. Wade, held that states can effectively immunize an anti-abortion law from federal judicial review if the law can only be enforced by private bounty hunters, and not by state employees. Indeed, the Courtâs reasoning in Jackson was so sweeping that it could effectively allow a state to neutralize any constitutional right using this same tactic. +
++That said, in Dobbs v. Jackson Womenâs Health Organization (2022), the decision overruling Roe, the Court did claim that there were limits to its efforts to restrict abortion rights. Justice Samuel Alitoâs majority opinion declared that âit is time to heed the Constitution and return the issue of abortion to the peopleâs elected representatives.â In a concurring opinion, Kavanaugh added that his Court âmust scrupulously adhere to the Constitutionâs neutral position on the issue of abortion.â +
++We are likely to find out in the coming months, in other words, whether we can trust the justices to draw the line where they said they would draw it in Dobbs. Or whether the judiciary will decide for all of us â regardless of whether we live in red states or blue states â if medication abortion is legal. +
++Update, April 8, 3 pm ET: This story, originally published March 16, has been updated with news of Kacsmarykâs decision. +
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On day six of the Creation, God announced to his archangel underlings, "Today weâre creating a place called Canada. -
++âToday weâre creating a place called Canada. Pull out all the stops. Give it beautiful mountains, lakes, planes, forests, and sandy beaches. Underground, give it oil, gold, etc. Oh, and plenty of fish and wildlife.â +
++âSir,â interjected an archangel, âarenât you being overly generous to these Canadians?â +
++âDonât worry, Iâll balance it out,â said God. âWait âtill you see the neighbours Iâm giving them.â +
+ submitted by /u/Boofrick
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Wife: Am I the only one youâve ever slept with? -
++Husband: Yes. The others were sixes and sevens. +
+ submitted by /u/xboxgamer2122
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Whatâs the difference between a prostitute and Jesus? -
++The sound they make when youâre nailing them. +
++Happy Easter you filthy degenerates. +
+ submitted by /u/DavetheGeo
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As it is the month of Ramadan -
++A man goes to an imam and says âI want to get married, find me a spouse.â +
++The imam says âI canât promise I can find you a spouse but if you fast tomorrow, by sunset youâll have a date.â +
+ submitted by /u/dajjalnextdoor
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Rest in peace, boiling water. -
++You will be mist. +
+ submitted by /u/jharish
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