diff --git a/archive-covid-19/24 September, 2023.html b/archive-covid-19/24 September, 2023.html new file mode 100644 index 0000000..ff9aa3b --- /dev/null +++ b/archive-covid-19/24 September, 2023.html @@ -0,0 +1,194 @@ + +
+ + + ++Background: Evidence on the impact of COVID-19 vaccination on symptoms, Health-Related Quality of Life (HRQoL), Work Productivity and Activity Impairment (WPAI) is scarce. We analyzed associations between bivalent BA.4/5 BNT162b2 and these patient-reported outcomes (PROs). Methods: Symptomatic US adults who tested positive for SARS-CoV-2 were recruited between 03/02-05/18/2023. PROs were assessed using a CDC-based symptom questionnaire, EQ-5D-5L, WPAI-GH, and PROMIS Fatigue, from pre-COVID to Week 4 following infection. Multivariable analysis using mixed models for repeated measures was conducted, adjusting for several covariates. Results: The study included 641 participants: 314 vaccinated with bivalent BA.4/5 BNT162b2 and 327 unvaccinated/not up-to-date. Mean (SD) age was 46.5 years (15.9), 71.2% were female, 44.2% reported prior infection, 25.7% had ≥1 comorbidity. The BA.4/5 BNT162b2 cohort reported fewer acute symptoms through Week 4, especially systemic and respiratory symptoms. All PROs were adversely affected, especially at Week 1; however, at that time point, the bivalent BA.4/5 BNT162b2 cohort reported better work performance, driven by less absenteeism, and fewer work hours lost. No significant differences were observed for HRQoL. Conclusions: COVID-19 negatively impacted patient outcomes. Compared with unvaccinated/not up-to-date participants, those vaccinated with bivalent BA.4/5 BNT162b2 reported fewer and less persistent symptoms and improved work performance. Clinicaltrials.gov NCT05160636 Keywords: SARS-CoV-2; BA.4/5 BNT162b2; Bivalent; COVID-19; COVID-19 symptoms; HRQoL; Humanistic; Quality of life; WPAI; PROMIS Fatigue. +
++Objective To investigate the impact of the COVID-19 pandemic on Group A streptococcal (GAS) cases and related antibiotic prescriptions. Design A retrospective cohort study with supporting dashboards with the approval of NHS England. Setting Primary care practices in England using TPP SystmOne software from January 2018 through March 2023. Participants Patients included were those registered at a TPP practice for each month of the study period. Patients with missing sex or age were excluded, resulting in a population of 23,816,470 in January 2018, increasing to 25,541,940 by March 2023. Main outcome measures We calculated monthly counts and crude rates of GAS cases (sore throat/tonsillitis, scarlet fever, invasive group A strep) and prescriptions linked with a GAS case, before (pre-April 2020), during and after (post-April 2021) COVID-19 restrictions. We calculated the maximum and minimum count and rate for each season (years running September-August), and the rate ratio (RR) of the 2022/23 season to the last comparably high season (2017/18). Results Recording of GAS cases and antibiotic prescription linked with a GAS case peaked in December 2022, higher than the 2017/2018 peak. The peak rate of monthly sore throat/tonsillitis (possible group A strep throat) recording was 5.33 per 1,000 (RR 2022/23 versus 2017/18 1.39 (CI: 1.38 to 1.40)). Scarlet fever recording peaked at 0.51 per 1,000 (RR 2.68 (CI: 2.59 to 2.77)), and invasive group A streptococcal infection (iGAS) at 0.01 per 1,000 (RR 4.37 (CI: 2.94 to 6.48)). First line antibiotics with a record of a GAS infection peaked at 2.80 per 1,000 (RR 1.37 (CI:1.35 to 1.38)), alternative antibiotics at 2.03 per 1,000 (RR 2.30 (CI:2.26 to 2.34)), and reserved antibiotics at 0.09 per 1,000 (RR 2.42 (CI:2.24 to 2.61). For individual antibiotics, azithromycin with GAS indication showed the greatest relative increase (RR 7.37 (CI:6.22 to 8.74)).This followed a sharp drop in recording of cases and associated prescriptions during the period of COVID-19 restrictions where the maximum count and rates were lower than any pre COVID-19 minimum. More detailed demographic breakdowns can be found in our regularly updated dashboard report. Conclusions Rates of scarlet fever, sore throat/tonsillitis and iGAS recording and associated antibiotic prescribing peaked in December 2022. Primary care data can supplement existing infectious disease surveillance through linkages with relevant prescribing data and detailed clinical and demographic subgroups. +
++Knockout of the ORF8 protein has repeatedly spread through the global viral population during SARS-CoV-2 evolution. Here we use both regional and global pathogen sequencing to explore the selection pressures underlying its loss. In Washington State, we identified transmission clusters with ORF8 knockout throughout SARS-CoV-2 evolution, not just on novel, high fitness viral backbones. Indeed, ORF8 is truncated more frequently and knockouts circulate for longer than for any other gene. Using a global phylogeny, we find evidence of positive selection to explain this phenomenon: nonsense mutations resulting in shortened protein products occur more frequently and are associated with faster clade growth rates than synonymous mutations in ORF8. Loss of ORF8 is also associated with reduced clinical severity, highlighting the diverse clinical impacts of SARS-CoV-2 evolution. +
++Objective: Beginning in October 2021 in the US and elsewhere, cases of severe pediatric hepatitis of unknown etiology were identified in young children. While the adenovirus and adenovirus-associated virus have emerged as leading etiologic suspects, we attempted to investigate a potential role for SARS-CoV-2 in the development of subsequent liver abnormalities. Design: We conducted a study utilizing retrospective cohorts of de-identified, aggregated data from the electronic health records of over 100 million patients contributed by US health care organizations. Results: Compared to propensity-score-matched children with other respiratory infections, children aged 1-10 years with COVID-19 had a higher risk of elevated transaminases (Hazard ratio (HR) (95% Confidence interval (CI)) 2.16 (1.74-2.69)) or total bilirubin (HR (CI) 3.02 (1.91-4.78)), or new diagnoses of liver diseases (HR (CI) 1.67 (1.21-2.30)) from one to six months after infection. Patients with pre-existing liver abnormalities, liver abnormalities surrounding acute infection, younger age (1-4 years), or illness requiring hospitalization all had similarly elevated risk. Children who developed liver abnormalities following COVID-19 had more pre-existing conditions than those who developed abnormalities following other infections. Conclusion: These results indicate that SARS-CoV-2 may prime the patient for subsequent development of liver infections or non-infectious liver diseases. While rare (~1 in 1,000), SARS-CoV-2 is a risk for subsequent abnormalities in liver function or the diagnosis of diseases of the liver. +
++Background: Given the high global seroprevalence of SARS-CoV-2, understanding the risk of reinfection becomes increasingly important. Models developed to track trends in reinfection risk should be robust against possible biases arising from imperfect data observation processes. Objectives: We performed simulation-based validation of an existing catalytic model designed to detect changes in the risk of reinfection by SARS-CoV-2. Methods: The catalytic model assumes the risk of reinfection is proportional to observed infections. Validation involved using simulated primary infections, consistent with the number of observed infections in South Africa. We then simulated reinfection datasets that incorporated different processes that may bias inference, including imperfect observation and mortality, to assess the performance of the catalytic model. A Bayesian approach was used to fit the model to simulated data, assuming a negative binomial distribution around the expected number of reinfections, and model projections were compared to the simulated data generated using different magnitudes of change in reinfection risk. We assessed the approach9s ability to accurately detect changes in reinfection risk when included in the simulations, as well as the occurrence of false positives when reinfection risk remained constant. Key Findings: The model parameters converged in most scenarios leading to model outputs aligning with anticipated outcomes. The model successfully detected changes in the risk of reinfection when such a change was introduced to the data. Low observation probabilities (10%) of both primary- and re-infections resulted in low numbers of observed cases from the simulated data and poor convergence. Limitations: The model9s performance was assessed on simulated data representative of the South African SARS-CoV-2 epidemic, reflecting its timing of waves and outbreak magnitude. Model performance under similar scenarios may be different in settings with smaller epidemics (and therefore smaller numbers of reinfections). Conclusions: Ensuring model parameter convergence is essential to avoid false-positive detection of shifts in reinfection risk. While the model is robust in most scenarios of imperfect observation and mortality, further simulation-based validation for regions experiencing smaller outbreaks is recommended. Caution must be exercised in directly extrapolating results across different epidemiological contexts without additional validation efforts. +
++Background: We assessed the association between antibody concentration within 5 days of symptom onset and COVID-19 illness among patients enrolled in a test-negative study. Methods: From October 2021 to June 2022, study sites in seven states enrolled and tested respiratory specimens from patients of all ages presenting with acute respiratory illness for SARS-CoV-2 infection using rRT-PCR. In blood specimens, we measured concentration of anti-SARS-CoV-2 antibodies against the ancestral strain spike protein receptor binding domain (RBD) and nucleocapsid (N) antigens in standardized binding antibody units (BAU/mL). Percent reduction in odds of symptomatic COVID-19 by anti-RBD antibody was estimated using logistic regression modeled as (1-adjusted odds ratio of COVID-19)x100, adjusting for COVID-19 vaccination status, age, site, and high-risk exposure. Results: A total of 662 (33%) of 2,018 symptomatic patients tested positive for acute SARS-CoV-2 infection. During the Omicron-predominant period, geometric mean anti-RBD binding antibody concentrations measured 823 BAU/mL (95% CI:690 to 981) among COVID-19 case-patients versus 1,189 BAU/mL (95% CI:1,050 to 1,347) among SARS-CoV-2 test-negative patients. In the adjusted logistic regression, increasing levels of anti-RBD antibodies were associated with reduced odds of COVID-19 for both Delta and Omicron infections. Conclusion: Higher anti-RBD antibodies in patients were associated with protection against symptomatic COVID-19 during emergence of SARS-CoV-2 Delta and Omicron variants. +
++Background: Myalgic encephalomyelitis (ME, also known as chronic fatigue syndrome or ME/CFS) is a debilitating, complex, multi-system illness. Developing a comprehensive understanding of the multiple and interconnected barriers to optimal care will help advance strategies and care models to improve quality of life for people living with ME in Canada. Objectives: To: (1) identify and systematically map the available evidence; (2) investigate the design and conduct of research; (3) identify and categorize key characteristics; and (4) identify and analyze knowledge gaps related to healthcare system barriers for people living with ME in Canada. Methods: The protocol was preregistered in July 2022. Peer-reviewed and grey literature was searched, and patient partners retrieved additional records. Eligible records were Canadian, included people with ME/CFS and included data or synthesis relevant to healthcare system barriers. Results: In total, 1821 records were identified, 406 were reviewed in full, and 21 were included. Healthcare system barriers arose from an underlying lack of consensus and research on ME and ME care; the impact of long-standing stigma, disbelief, and sexism; inadequate or inconsistent healthcare provider education and training on ME; and the heterogeneity of care coordinated by family physicians. Conclusions: People living with ME in Canada face significant barriers to care, though this has received relatively limited attention. This synthesis, which points to several areas for future research, can be used as a starting point for researchers, healthcare providers and decision-makers who are new to the area or encountering ME more frequently due to the COVID-19 pandemic. +
++The SARS-CoV-2 pandemic has been characterized by the repeated emergence of genetically distinct virus variants of increased transmissibility and immune evasion compared to pre-existing lineages. In many countries, their containment required the intervention of public health authorities and the imposition of control measures. While the primary role of testing is to identify infection, target treatment, and limit spread (through isolation and contact tracing), a secondary benefit is in terms of surveillance and the early detection of new variants. Here we study the spatial invasion and early spread of the Alpha, Delta, and Omicron (BA.1 and BA.2) variants in England from September 2020 to February 2022 using the random neighbourhood covering (RaNCover) method. This is a statistical technique for the detection of aberrations in spatial point processes, which we tailored here to community PCR (polymerase-chain-reaction) test data where the TaqPath kit provides a proxy measure of the switch between variants. Retrospectively, RaNCover detected the earliest signals associated with the four novel variants that led to large infection waves in England. With suitable data our method therefore has the potential to rapidly detect outbreaks of future SARS-CoV-2 variants, thus helping to inform targeted public health interventions. +
++Summary Background: The origin of novel SARS-CoV-2 spike sequences found in wastewater, without corresponding detection in clinical specimens, remains unclear. We sought to determine the origin of one such “cryptic” wastewater lineage by tracking and characterizing its persistence and genomic evolution over time. Methods: We first detected a cryptic lineage in Wisconsin municipal wastewater in January 2022. By systematically sampling wastewater from targeted sub-sewershed lines and maintenance holes using compositing autosamplers, we traced this lineage (labeled WI-CL-001) to its source at a single commercial building. There we detected WI-CL-001 at concentrations as high as 2.7 x 109 genome copies per liter (gc/L) via RT-dPCR. In addition to using metagenomic 12s rRNA sequencing to determine the virus9s host species, we also sequenced SARS-CoV-2 spike receptor binding domains (RBDs), and where possible, whole viral genomes to identify and characterize the evolution of this lineage over the 13 consecutive months that it was detectable. Findings: The vast majority of 12s rRNAs sequenced from wastewater leaving the identified source building were human. Additionally, we generated over 100 viral RBD and whole genome sequences from wastewater samples containing the cryptic lineage collected between January 2022 and January 2023. These sequences contained a combination of fixed nucleotide substitutions characteristic of Pango lineage B.1.234, which circulated in humans in Wisconsin at low levels from October 2020 to February 2021. Despite this, mutations in the spike gene, and elsewhere, resembled those subsequently found in Omicron variants. Interpretation: We propose that prolonged detection of WI-CL-001 in wastewater represents persistent shedding of SARS-CoV-2 from a single human initially infected by an ancestral B.1.234 virus. The accumulation of convergent “Omicron-like” mutations in WI-CL-0019s ancestral B.1.234 genome likely reflects persistent infection and extensive within-host evolution. Funding: The Rockefeller Foundation, Wisconsin Department of Health Services, Centers for Disease Control and Prevention (CDC), National Institute on Drug Abuse (NIDA), and the Center for Research on Influenza Pathogenesis and Transmission. Research in context Evidence before this study: To identify other studies that characterized unusual wastewater-specific SARS-CoV-2 lineages, we conducted a PubMed search using the keywords “cryptic SARS-CoV-2 lineages” or “novel SARS-CoV-2 lineages” in addition to “wastewater” on May 9, 2023. From the 18 papers retrieved, only two reported wastewater-specific cryptic lineages. These lineages were identified by members of our author team in wastewater from California, Missouri, and New York City. None of these could be definitively traced to a specific source. A third study in Nevada identified a unique recombinant variant (designated Pango lineage XL) in wastewater, which was also discovered in two clinical specimens from the same community. However, it was unclear whether the clinical specimens collected were from the same individual(s) responsible for the virus detected in the wastewater. To our knowledge, no prior study has successfully traced novel SARS-CoV-2 lineages detected in wastewater back to a specific location. How and where cryptic lineages are introduced into wastewater is not known. The added value of this study: This study documents the presence and likely source of a novel and highly divergent cryptic SARS-CoV-2 lineage detected in Wisconsin wastewater for 13 months. In contrast to previously reported cryptic lineages, we successfully traced the lineage (WI-CL-001) to a single commercial building with approximately 30 employees. The exceptionally high viral RNA concentrations at the source building facilitated the tracing effort and allowed for the sequencing of WI-CL-0019s whole genome, expanding our view of the lineage9s mutational landscape beyond the spike gene. Implications of all the available evidence: WI-CL-0019s persistence in wastewater, its heavily mutated Omicron-like genotype, and its identified point source at a human-occupied commercial building all support the hypothesis that cryptic wastewater lineages can arise from persistently infected humans. Because cryptic wastewater lineages have some amino acid changes that subsequently emerge in circulating viruses, increased global monitoring of such lineages could help forecast variants that may arise in the future. +
++Background: The world of work is undergoing profound changes towards agile, flexible, democratic, and digital forms of work, so called New Work (NW). The COVID-19 pandemic accelerated these changes and confronted the working world with new challenges. Effects on employee health are ambivalent and remain unclear. Moreover, there is a lack of evidence as to whether existing occupational health management (OHM) measures meet the needs of employees working in new forms of work. Methods/Design: This prospective mixed-method project will include four substudies to identify different NW forms, resulting health risk, benefits and protective factors in subgroups, and derive target group-specific OHM services. In the four substudies, the following methods will be used: (1) a scoping review, semi-standardized interviews, and an online survey, (2) a systematic review, an online survey, an expert workshop and qualitative interviews, (3) workplace observations, and (4) expert workshops. Recommendations for action will be derived from the findings of all substudies and summarized in a checklist for OHM in NW settings. Conclusion: Findings will expand the state of knowledge about NW settings and associated health effects. The development of an evidence-based checklist for target group-specific identification of NW settings and associated health risks, benefits and protective factors can be used as a basis for action regarding OHM in companies. The findings can provide guidance on how future OHM services should be designed to meet the needs of employees. +
++The COVID-19 pandemic has exposed a number of key challenges that need to be urgently addressed. In particular, rapid identification and validation of prognostic markers is required. Mass spectrometric studies of blood plasma proteomics provide a deep understanding of the relationship between the severe course of infection and activation of specific pathophysiological pathways. Analysis of plasma proteins in whole blood may also be relevant for the pandemic as it requires minimal sample preparation. Here, for the first time, frozen whole blood samples were used to analyze 189 plasma proteins using multiple reaction monitoring (MRM) mass spectrometry and stable isotope-labeled peptide standards (SIS). A total of 128 samples (FRCC, Russia) from patients with mild (n=40), moderate (n=36) and severe (n=19) COVID-19 infection and healthy controls (n=33) were analyzed. Levels of 114 proteins were quantified and compared. Significant differences between all of the groups were revealed for 61 proteins. Changes in the levels of 30 reproducible COVID-19 markers (SERPING1, CRP, C9, ORM1, APOA1, SAA1/SAA2, LBP, AFM, IGFALS, etc.) were consistent with studies performed with serum/plasma samples. Levels of 70 proteins correlated between whole blood and plasma samples. The best-performing classifier built with 13 significantly different proteins achieved the best combination of ROC-AUC (0.93-0.95) and accuracy (0.87-0.93) metrics and distinguished patients from controls, as well as patients by severity and risk of mortality. Overall, the results support the use of frozen whole blood for MRM analysis of plasma proteins and assessment of the status of patients with COVID-19. +
+ACTIV-6: COVID-19 Study of Repurposed Medications - Arm G (Metformin) - Condition: Covid19
Interventions: Other: Placebo; Drug: Metformin
Sponsors: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center
Recruiting
SA55 Injection: a Potential Therapy for the Prevention and Treatment of COVID-19 - Condition: COVID-19
Interventions: Drug: SA55 Injection; Other: Placebo for SA55 injection
Sponsor: Sinovac Life Sciences Co., Ltd.
Recruiting
A Study to Assess the Safety, Tolerability and Preliminary Efficacy of HH-120 for the Treatment of COVID-19 - Condition: COVID-19
Interventions: Drug: HH-120; Drug: placebo
Sponsor: Huahui Health
Completed
Psychosomatic, Physical Activity or Both for Post-covid19 Syndrom - Condition: Post-COVID-19 Syndrome
Interventions: Behavioral: Exercise Therapy; Behavioral: Psychotherapy
Sponsors: Hannover Medical School; Health Insurance Audi BKK; occupational health service Volkswagen AG; Helmholtz Centre for Infection Research
Not yet recruiting
A Study to Investigate the Prevention of COVID-19 withVYD222 in Adults With Immune Compromise and in Participants Aged 12 Years or Older Who Are at Risk of Exposure to SARS-CoV-2 - Conditions: COVID-19; SARS-CoV-2
Interventions: Drug: VYD222; Drug: Normal saline
Sponsor: Invivyd, Inc.
Recruiting
Omicron BA.4/5-Delta COVID-19 Vaccine Phase I Clinical Trial - Condition: COVID-19
Interventions: Biological: Omicron BA.4/5-Delta strain recombinant novel coronavirus protein vaccine (CHO cells); Biological: Placebo
Sponsors: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.; Hunan Provincial Center for Disease Control and Prevention
Not yet recruiting
Reducing COVID-19 Vaccine Hesitancy Among Hispanic Parents - Conditions: Vaccine-Preventable Diseases; COVID-19 Pandemic; Health-Related Behavior; Health Knowledge, Attitudes, Practice; Narration
Interventions: Behavioral: Baseline surveys; Behavioral: Digital Storytelling Intervention; Behavioral: Information Control Intervention
Sponsors: Arizona State University; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Not yet recruiting
Non-pharmacological and TCM-based Treatment for Long COVID Symptoms - Condition: Long Covid19
Intervention: Behavioral: Acupuncture and TCM-based lifestyle management
Sponsor: The Hong Kong Polytechnic University
Not yet recruiting
Evaluation of Safety and Immunogenicity of a SARS-CoV-2(Severe Acute Respiratory Syndrome Coronavirus 2) Booster Vaccine (LEM-mR203) - Conditions: COVID-19 Infection; COVID-19 Vaccine Adverse Reaction
Interventions: Biological: LEM-mR203; Biological: Placebo
Sponsor: Lemonex
Not yet recruiting
SA55 Novel Coronavirus Broad-spectrum Neutralizing Antibody Nasal Spray in Health People - Condition: COVID-19
Intervention: Drug: SA55 nasal spray
Sponsor: Sinovac Life Sciences Co., Ltd.
Recruiting
A Bioequivalence Trial of Fasting Single Oral STI-1558 Capsule in Healthy Chinese Subjects - Condition: COVID-19
Intervention: Drug: STI-1558
Sponsor: Zhejiang ACEA Pharmaceutical Co. Ltd.
Not yet recruiting
A Study to Determine the Tolerability of Intranasal LMN-301 - Condition: COVID-19
Intervention: Biological: LMN-301
Sponsor: Lumen Bioscience, Inc.
Not yet recruiting
Mind Body Intervention for Long COVID - Conditions: Long COVID; Post-Acute Sequelae of COVID-19; COVID Long-Haul
Intervention: Behavioral: Mind Body Intervention #1
Sponsor: Beth Israel Deaconess Medical Center
Not yet recruiting
Safety of Simultaneous mRNA COVID-19 Vaccine With Other Childhood Vaccines in Young Children - Conditions: Fever After Vaccination; Fever; Seizures Fever
Interventions: Biological: Pfizer-BioNTech COVID-19 Vaccine; Biological: Routine Childhood Vaccinations
Sponsors: Duke University; Kaiser Permanente; Columbia University; Children’s Hospital Medical Center, Cincinnati; Centers for Disease Control and Prevention
Not yet recruiting
SA55 Injection Phase II Study in the Treatment of Mild/Moderate COVID-19 Patients - Condition: Infection of Upper Respiratory Tract Caused by 2019-nCoV
Intervention: Drug: SA55 Injection
Sponsor: Sinovac Life Sciences Co., Ltd.
Recruiting
Green synthesis, characterization, anti-SARS-CoV-2 entry, and replication of lactoferrin-coated zinc nanoparticles with halting lung fibrosis induced in adult male albino rats - The ethanolic extract of Coleus forskohlii Briq leaves was employed in the green synthesis of zinc nanoparticles (Zn-NPs) by an immediate, one-step, and cost-effective method in the present study. Zn-NPs were coated with purified bovine lactoferrin (LF) and characterized through different instrumental analysis. The biosynthesized Zn-NPs were white in color revealing oval to spherical-shaped particles with an average size of 77 ± 5.50 nm, whereas LF-coated Zn-NPs (LF-Zn-NPs) revealed a larger…
Age and prior vaccination determine the antibody level in children with primary SARS-CoV-2 Omicron infection - CONCLUSIONS: In our study, children aged 6 months to 2 years have the highest antibody responses to SARS-CoV-2 Omicron variant infection. Age and prior vaccination are the main factors influencing the immunogenicity of SARS-CoV-2 infection.
A Brighton Collaboration standardized template with key considerations for a benefit/risk assessment for the Novavax COVID-19 Vaccine (NVX-CoV2373), a recombinant spike protein vaccine with Matrix-M adjuvant to prevent disease caused by SARS-CoV-2 viruses - Novavax, a global vaccine company, began evaluating NVX-CoV2373 in human studies in May 2020 and the pivotal placebo-controlled phase 3 studies started in November 2020; five clinical studies provided adult and adolescent clinical data for over 31,000 participants who were administered NVX-CoV2373. This extensive data has demonstrated a well-tolerated response to NVX-CoV2373 and high vaccine efficacy against mild, moderate, or severe COVID-19 using a two-dose series (Dunkle et al., 2022) [1],…
Impact of SARS-CoV-2 ORF6 and its variant polymorphisms on host responses and viral pathogenesis - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encodes several proteins that inhibit host interferon responses. Among these, ORF6 antagonizes interferon signaling by disrupting nucleocytoplasmic trafficking through interactions with the nuclear pore complex components Nup98-Rae1. However, the roles and contributions of ORF6 during physiological infection remain unexplored. We assessed the role of ORF6 during infection using recombinant viruses carrying a deletion or…
TGF-β1 reduces the differentiation of porcine IgA-producing plasma cells by inducing IgM+ B cells apoptosis via Bax/Bcl2-Caspase3 pathway - Transforming growth factor β1 (TGF-β1) performs a critical role in maintaining homeostasis of intestinal mucosa regulation and controls the survival, proliferation, and differentiation of many immune cells. In this study, we discovered that the infection of porcine epidemic diarrhea virus (PEDV), a coronavirus, upregulated TGF-β1 expression via activating Tregs. Besides, recombinant porcine TGF-β1 decreased the percentage of CD21^(+) B cells within the lymphocyte population in vitro. We further…
Therapeutic benefits of prophetic medicine remedies in treating hematological diseases (A review article) - Hematological disorders are common medical ailments constituting an important cause of morbidity and mortality worldwide, which may be managed efficiently using different prophetic medicine remedies as adjuvants to current therapeutics. Prophetic medicine includes the body of knowledge about medicine that has been derived from the deeds, customs (sunnah), ahadith (sayings), actions, and agreements of Prophet Muhammad, peace be upon him. This review article aims at exploring the magnitude of…
The binding mechanism of failed, in processing and succeed inhibitors target SARS-CoV-2 main protease - Since the outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), several variants have caused a persistent pandemic. Consequently, it is crucial to develop new potential anti-SARS-CoV-2 drugs with specificity. To minimize potential failures and preserve valuable clinical resources for the development of other useful drugs, researchers must enhance their understanding of the interactions between drugs and SARS-CoV-2. While numerous crystal structures of the SARS-CoV-2 main…
Chromone-embedded peptidomimetics and furopyrimidines as highly potent SARS-CoV-2 infection inhibitors: docking and MD simulation study - CONCLUSIONS: The study investigated the inhibition of viral replication using chromone derivatives, finding high inhibitory effects in the peptidomimetic family compared to other studies.
A viral RNA-dependent RNA polymerase inhibitor VV116 broadly inhibits human coronaviruses and has synergistic potency with 3CLpro inhibitor nirmatrelvir - During the ongoing pandemic, providing treatment consisting of effective, low-cost oral antiviral drugs at an early stage of SARS-CoV-2 infection has been a priority for controlling COVID-19. Although Paxlovid and molnupiravir have received emergency approval from the FDA, some side effect concerns have emerged, and the possible oral agents are still limited, resulting in optimized drug development becoming an urgent requirement. An oral remdesivir derivative, VV116, has been reported to have…
Identification of γ-Fagarine as a novel antiviral agent against respiratory virus (hMPV) infection - Human metapneumovirus (hMPV) causes significant upper and lower respiratory disease in all age groups worldwide. However, there is no licensed drugs or vaccine available against hMPV. γ-Fagarine, an alkaloida isolated from the root of zanthoxylum, has been reported to be effective in the treatment of cancer, inflammatory diseases and antivirals. However, little is known about the inhibitory effect of γ-Fagarine against respiratory virus infection and the mechanism. In this study, we aim to…
Structural basis for translation inhibition by MERS-CoV Nsp1 reveals a conserved mechanism for betacoronaviruses - All betacoronaviruses (β-CoVs) encode non-structural protein 1 (Nsp1), an essential pathogenicity factor that potently restricts host gene expression. Among the β-CoV family, MERS-CoV is the most distantly related member to SARS-CoV-2, and the mechanism for host translation inhibition by MERS-CoV Nsp1 remains controversial. Herein, we show that MERS-CoV Nsp1 directly interacts with the 40S ribosomal subunit. Using cryogenic electron microscopy (cryo-EM), we report a 2.6-Å structure of the…
Simultaneous Targeting of IL-1-Signaling and IL-6-Trans-Signaling Preserves Human Pulmonary Endothelial Barrier Function During a Cytokine Storm - CONCLUSIONS: These findings strongly suggest a major role for both IL-6 trans-signaling and IL-1β signaling in the pathological increase in permeability of the human lung microvasculature and reveal combinatorial strategies that enable the gradual control of pulmonary endothelial barrier function in response to a cytokine storm.
SARS-CoV-2 protein NSP2 enhances microRNA-mediated translational repression - Viruses use microRNAs (miRNAs) to impair the host antiviral response and facilitate viral infection by expressing their own miRNAs or co-opting cellular miRNAs. miRNAs inhibit translation initiation of their target mRNAs by recruiting the GIGYF2/4EHP translation repressor complex to the mRNA 5´-cap structure. We recently reported that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encoded non-structural protein 2 (NSP2) interacts with GIGYF2. This interaction is critical for…
De novo design of a stapled peptide targeting SARS-CoV-2 spike protein receptor-binding domain - Although effective vaccines have been developed against SARS-CoV-2, many regions in the world still have low rates of vaccination and new variants with mutations in the viral spike protein have reduced the effectiveness of most available vaccines and treatments. There is an urgent need for a drug to cure this disease and prevent infection. The SARS-CoV-2 virus enters the host cell through protein-protein interaction between the virus’s spike protein and the host’s angiotensin converting enzyme…
Assessment of safety and intranasal neutralizing antibodies of HPMC-based human anti-SARS-CoV-2 IgG1 nasal spray in healthy volunteers - An HPMC-based nasal spray solution containing human IgG1 antibodies against SARS-CoV-2 (nasal antibody spray or NAS) was developed to strengthen COVID-19 management. NAS exhibited potent broadly neutralizing activities against SARS-CoV-2 with PVNT(50) values ranging from 0.0035 to 3.1997 μg/ml for the following variants of concern (ranked from lowest to highest): Alpha, Beta, Gamma, ancestral, Delta, Omicron BA.1, BA.2, BA.4/5, and BA.2.75. Biocompatibility assessment showed no potential…
The Biden Administration’s Next Big Climate Decision - The liquefied-natural-gas buildout—and fossil-fuel exports—challenge progress on global warming. - link
Rupert Murdoch Takes a Step Back—Not Away - Although the media mogul announced that his son Lachlan will become the chair of News Corp. and Fox Corp., he was also careful to quash speculation that he would be retiring. - link
House Republicans Refuse to Host Zelensky Because They’re Too Busy Fighting One Another - Reflections on a day of self-parody on Capitol Hill. - link
Astra Taylor’s Age of Insecurity - The activist and writer sees capitalism as an insecurity-producing machine. - link
Kelly Clarkson on “Chemistry,” Her Divorce Record - The singer tells the staff writer Hanif Abdurraqib about chronicling the end of a marriage in real time. Plus, the novelist Hernan Diaz, and Robert Samuels on figure skating. - link
+“Exotic” cultivated meats claim to be harmless, but they could threaten actual endangered animals. +
++What is the strangest meat you’ve eaten? +
++For me, it’s reindeer. This was during a trip to Finland when I was 7. We’d gone to the Arctic Circle, where I hoped to meet Father Christmas. I remember being driven through dark forests on the back of a snowmobile to a firelit clearing where we ate reindeer sausages. Though my baby brain didn’t then realize I was eating one of Rudolph’s cousins and that Santa might disapprove, I enjoyed the meat. It was spiced and tender and warmed me after the freezing journey. +
++Eating reindeer remains one of my core memories, though I now consider eating all animals gross and unethical. But I’ve discovered reindeer is not a very exotic meat, at least compared with what my Instagram followers have been eating. When I posted the question: “What’s the most exotic meat you’ve eaten?” I discovered my followers had eaten everything, from alligator to minke whale. +
++Which animals we find acceptable to eat vary from person to person, according to our values, palates, and upbringing. Many consider eating cows and chickens okay, but not octopus, dolphin, or tiger. Right now, you’d be hard-pressed to find tiger meat in your local supermarket, but developments in tech are making a future possible in which eating exotic meats, from alligator to zebra, could be commonplace. +
++But, how? Well, factory-farmed tiger, thankfully, is not about to become a dystopian reality. But we might one day eat “ethical” tiger through innovations in cultured-cell technology. +
++Cultured meat, also known as cell-cultivated meat, is not pork reared on caviar and Italian neorealist cinema — it is meat that has been grown in a lab. It has the potential to liberate animals from exploitation, creating burgers and sausages from meat that has been grown in bioreactors and harvested without the death of a sentient being. The first cell-cultivated chicken in the US came to market this summer. It’s an exciting technology, as it could substantially reduce the number of animals slaughtered yearly (or, at least, limit the expansion of that number). +
++It’s not all chicken and pork, though. Recently, startups such as Primeval Foods and Vow have begun developing meat cultured from the cells of exotic (and even extinct) animals, such as tiger, zebra, or mammoth. A gigantic mammoth meatball produced by Vow earlier this year brought many people’s attention to the potential applications of cultured-cell technology, and advocates argue the novelty of nontraditional meats could help win over an otherwise hard-to-reach group of potential consumers. +
+ ++Some animal advocates, however, have voiced concerns that popularizing exotic meats could have unforeseen consequences. The tech, if successful (a big if), could create an appetite for real tiger meat, putting additional pressure on already-endangered wild big cat populations. And some vegans, who advocate against the commodification of animals, worry that eating cell-cultivated meat could entrench the belief that animals are something to be exploited and consumed, rather than beings to be protected; they argue the desire to manufacture cultured tiger meat reveals that “clean” meat is a fallacy promoted by meat producers developing new ways to exploit the animal kingdom. +
++In April, I spoke with Yilmaz Bora, CEO of Primeval Foods, a company developing cultured tiger meat. I’d imagined Bora to be a meat-lover, but I was surprised to discover that he was the opposite. +
++“I went vegan roughly three, four years ago,” Bora said. “It started with activism, supporting UK [animal rights] groups. After a while, I realized that was not going to work. We had to involve the economy, involve the capitalist system, to have a meaningful impact on animals.” +
++From there, Bora began developing alternative proteins that he hoped would convert diehard meat eaters from factory-farmed animals. According to Bora, exotic meat seemed a viable option because, he believes, the “masculine” group that drives meat consumption would find meat grown from big cats more compelling than meat grown from conventional livestock cells. +
++“If you are making barbecue every weekend in Texas and you have no interest in climate, no interest in animal welfare, there is not any product for you,” he said. “Tigers, or other wild cats such as lions, represent power. … There is this masculine profile [that is firmly anti-vegan], and they tend to not eat alternative plant-based or alternative protein on the market, but it will appeal to them because it represents something luxury.” +
++Developing meat from the cells of an animal that represents power might be a compelling method of marketing cultured meats. But problems will arise if the appetite for lab-grown tiger causes an upsurge in demand for meat from wild tiger populations. Only 4,500 tigers remain in the wild. John Goodrich, of the big cat conservation charity Panthera, explained the potential complications cultured tiger meat could create for tiger conservation. +
++“One of the biggest threats to big cats, especially tigers, is poaching for their body parts, primarily for use in traditional Chinese medicine,” Goodrich said. “You’d hope that [cultivated meat] would flood the market so that there would no longer be any market for wild tiger parts.” +
++It’s not at all clear that this would happen, even if cultivated tiger meat did become a success. “My concern is that there’s always going to be the contingent that wants the real thing,” Goodrich added. “By mainstreaming it, you are creating this much, much bigger market for tiger parts. … Let’s say your market is a billion people: If less than 1 percent of that wants the real thing, that’s still enough to put tremendous pressure on the remaining 4,500 tigers in the wild.” +
++“It’s not worth the risk,” he concludes. +
+ ++When I put this to Bora, I was met with a confusing response. He said he was “not aware” of the market for tiger in China, and added that he believed people would not consume wild tiger because sourcing it “is not convenient” and “it will taste really really bad … because they are very muscular animals, they move a lot … they have little to no fat.” +
++Cultivated meat technology, Bora added, allows Primeval Foods “to change the fat percentage on the end product. … We can do whatever we want to have that better mouthfeel, better texture, better taste.” +
++That’s fine, but, as Goodrich explained, what if even a small contingent of Primeval Foods’s future intended consumers decide they want to eat real tiger? With wild tiger populations dwindling, any increase in poaching would be catastrophic, and the fact that real tiger meat “tastes really really bad” can only be discovered after the animal has been slaughtered. +
++It’s hard to fathom that degree of ignorance from the CEO of a startup with potentially harmful environmental implications — especially since others in the industry have engaged with such concerns more deliberately. When I spoke to George Peppou, founder of Vow, he said that, in the preliminary stages of developing Vow’s cultured cell products, Vow “started to work with the Zoo and Aquarium Association in Australia,” who “scared the crap out of me about … unintentionally stimulating wildlife crime.” +
++Ultimately, the product that Vow aspires to bring to market is not mammoth or other exotic animals, but what Peppou describes as “the Cheerios of meat” — synthetic, branded meats made from combining different animals’ cell lines in a way that’s comparable to the mixing of oats, wheat, and barley to create breakfast cereals. This would avoid problems like stimulating wildlife crime, as the meat Vow takes to market cannot be traced to a single species. +
++Vow’s cultivated mammoth, according to Peppou, is a stunt intended to “challenge people’s perception of what meat is and get them comfortable with the idea that it can look different to what we have available to us now.” +
++The mammoth meatball was developed, Peppou explained, after the company asked itself the question, “How do we move the window of what’s acceptable in meat?” Right now, synthetic “chimera meats” seem strange, and many consumers would choose chicken over lab-grown hybrids. Making synthetic meats seem conventional — at least compared to mammoth meatballs — is the strategic goal of Vow’s stunt. +
++While Vow is embracing exotic cultivated meats with an eye toward preventing knock-on effects like further harming endangered species, there are also broader philosophical questions about cultured meats, whether conventional, exotic, or extinct, that are worth considering. +
++John Sanbonmatsu, an animal rights philosopher and professor at the Worcester Polytechnic Institute in Massachusetts, argues that cultivated meat only entrenches the commodification of animals and the idea that it’s okay to consume their flesh. +
++The development of tiger steaks by Primeval, he said, is “fundamentally disrespectful of their personhood.” +
++“One of the major problems with the way we relate to other animals is we treat them as commodities,” Sanbonmatsu told me. “If you look at the discourse of Primeval Foods or these other companies, the way they describe the rationale for their enterprise is reinforcing the idea that humans are meant to exploit nature and other animals for their purposes without any ethical limits.” +
++To Sanbonmatsu’s thinking, the assumption that animals are available for exploitation is only underscored by the development of exotic cultivated meat. Viewed through that lens, growing tiger meat is just another example of humanity’s disregard for the animal kingdom, demonstrating that the drive to find “ethical” ways to exploit them creates fresh problems that need solving further down the line. +
++For example, Sanbonmatsu and charities such as Food & Water Watch argue that because lab-grown meat doesn’t challenge the idea that animal flesh is edible, it will augment rather than replace factory farming. As the market for meat increases around the world, they predict, there could simply be no reduction in the number of animals currently slaughtered yearly (tens of billions of land animals and hundreds of millions or even trillions of fish). Rather, cultivated meat could merely limit the expansion of this number. While this is arguably a good thing, insofar as one dead cow is better than two, animal slaughter will continue to be a massive, cruel industry with an immense environmental impact. +
++Those ethical concerns bring up an underlying question animal rights advocates will have to confront: What does it take for meat to be “clean?” For vegans such as Sanbonmatsu, who believe in animal personhood and the absolute equality of animals and humans, there is no scenario where that is the case. +
++For others, the cleanest cultivated meat would be a product created without harming animals at all, but even this is proving to be a quixotic goal, as cultivated meat companies struggle to make their products without animal-derived ingredients. Cultivated meat companies are also taking funding from conventional meat companies like Tyson and Cargill, some of the world’s biggest perpetrators of animal suffering. +
++It might still be that the current fastest way to dramatically limit animal suffering is through embracing cultured meat companies while putting the total abolition of animal exploitation on the back burner. +
++Deeper ethical questions aside, it is undeniable that some advocates, such as Bora, are working to develop cultivated meat with the aspiration, however unlikely, of ending factory farming and conventional meat consumption. All I ask is that they confront the potential implications of the tech: Developing cultivated tiger, mammoth, or anything else might be a cool way to draw attention to cultured-meat technology, and it could succeed in drawing new consumers. But if people decide they want to eat “the real thing,” then many wild animals, from tigers to elephants to lions, could go the way of the woolly mammoth. +
+Speaking up for yourself in a medical setting is a skill. Here’s what to know. +
++In his medical school classes at Washington State University, Joel Bervell was constantly reminded of health care disparities during lectures, like how Black and brown people were more likely to die of Covid-19 and how where you live can impact life expectancy. But he was never taught why these inequities exist in the first place. So Bervell did some research on his own and began creating videos on TikTok explaining race bias in medicine and how race intersects with medical care. “A lot of my followers were saying things like, ‘There’s problems out there, what can I do to actually help myself out?’” Bervell, now a fourth-year medical student, says. +
++His tips, shared in a 2022 video, became a jumping-off point for Bervell to empower his audience. “Even if you don’t have the medical background,” he says, “you know your body better than anyone else.” Discrimination can look like a medical professional making you feel inferior, less-than, or outright unsafe because of your race, weight, sexual orientation, education level, physical disability, or age. Providers may also dismiss your pain by insisting your symptoms are a byproduct of psychological factors or that you’re “dramatic.” +
++Speaking up at the doctor’s office can be difficult for many people because of previous discrimination or dismissal by medical professionals. According to a 2022 Verywell survey, one in three Black Americans said they experienced racism within the health care system. Twenty-nine percent of women ages 18 to 64 reported that their doctor had dismissed their concerns, according to the 2022 KFF Women’s Health Survey. Nearly a quarter of LGBTQ+ Americans said they had been blamed for their health problems, a 19th News/SurveyMonkey poll found last year. Two-thirds of study participants who were treated negatively in the past because of their weight said they experienced weight stigma from doctors, per a 2021 study. Additionally, neurodivergent patients report experiencing lower-quality health care due to poor communication, increased anxiety, and sensory sensitivity, research suggests. +
++“Marginalized people can really start to blame themselves for our mistreatment and think that either we deserve it or we shouldn’t push back,” says board certified patient advocate Ragen Chastain. +
++Regardless of your past medical experiences, patients can take greater control over their interactions with providers, experts say. Here are some ways to advocate for yourself at the doctor’s to ensure you walk out of the exam room with a clear understanding of your health and a concrete path forward. +
++To prepare for your visit, experts advise making a list, either on your phone or a hard copy, of everything you want to discuss with the provider, in order of importance, so you can ensure the doctor is addressing all of your concerns. You can also write out your goals for the appointment, Chastain suggests. Maybe it’s to get a diagnosis, maybe it’s to get a prescription refilled. +
++You’ll want to be as specific as possible when describing any symptoms, so try keeping a symptom diary in the days leading up to your appointment, says Haley Collins, a nurse practitioner with FOLX Health, a digital health care provider for the LGBTQIA+ community. If you’re looking to get your migraines treated, keep track of what time you had a migraine, on what day, and the context of the migraine. (What did you eat? Were you stressed?) +
++Have a brief overview of your medical history available, including any chronic illnesses, medications you’re taking, when you last had blood work, and any relevant medical issues within your family, especially if it’s your first visit with the provider. “If you have a significant family history of diabetes or stroke,” Collins says, “that’s usually pretty important, particularly in … your immediate family.” It’s also helpful to have access to any data you keep track of at home, like blood sugar or blood pressure. +
++While some medical professionals caution against googling their symptoms, Chastain encourages responsible research. Reading studies or other trusted online medical advice can help inform your questions for the doctor. (Be wary of any content on TikTok or other forms of social media that aren’t created by someone with a medical degree — or will soon have a medical degree. Any content encouraging a self-diagnosis should also be taken with a huge grain of salt.) +
++While you’re making an appointment, whether it’s for a check-up or a colonoscopy, ask for the price of the visit, both with and without insurance, says Cynthia Fisher, the founder and chairman of PatientRightsAdvocate.org. “All patients have the right to know all prices from hospitals in advance of care and we have the right to compare our prices to other insurance plans if we have insurance,” she says. “Even if we have insurance, we have the right to pay the discounted cash price, which is oftentimes nearly 40 percent lower than insured rates.” +
++Patients are able to bring a relative or friend with them to their medical appointments. HIPAA allows a doctor to talk about a patient’s health, treatment, and payment with the patient’s spouse, family members, friends, or anyone else the patient gives permission to hear about their medical care. “People are entitled to an advocate,” Chastain says. This can be helpful to get an extra set of ears as well as another perspective for questions. Choose someone who makes you feel supported and will effectively communicate on your behalf, Chastain says. “Typically when I work with people, I have a physical signal that they give me when they want me to talk,” she says. “It might be tugging their ear lobe or something like that, so that I know this is where they want me to jump in.” +
++Your doctor may ask your support person to leave the room at some point during the appointment, Collins says, to ensure you can speak freely about sensitive issues. +
++Experts stress the importance of keeping track of the content of your appointment. Either keep notes on your phone, in a notebook, or ask your provider if you can record audio of the visit. “Ask for permission before you record,” Bervell says. “By recording a conversation, you can listen to it and say, there’s something I want to ask a question about. You can follow up on MyChart or some other way to reach out to the physician.” MyChart is an online portal for patients to message their providers and view some medical records. Interacting with a medical professional this way can be helpful for patients who are not comfortable talking on the phone, Collins says. +
++At the end of the appointment, you can review your notes with your provider to ensure you fully understand what was discussed, Chastain says. You can say, “This is what I understand you said…” Make sure you’ve asked all of your questions and are clear about next steps. +
++Bervell says patients should feel empowered to ask medical professionals to show their work. “Ask ‘What is your differential diagnosis?’” he says. A differential diagnosis is a list of potential conditions that fit your symptoms. For a patient with shortness of breath, the cause can range from asthma to cancer, Bervell says. If a provider orders a test to rule out any of these issues, patients should know why. Inquiring about a differential diagnosis lets a provider know you want to hear every potential outcome and options for next steps, Bervell says. Don’t be afraid to ask if there are other options for diagnoses and treatments, too. +
++You can defer to the provider’s expertise when asking for more clarity, Chastain says. Try saying, “I’m not a doctor, so I don’t quite understand this, but I’d really like to understand more. Can you tell me where you got that conclusion from?” or “Can you tell me more about your diagnosis or why you chose that treatment plan?” You can also ask the doctor if they have any research or other materials you can read about your condition or medication. +
++The average primary care provider visit clocks in at 18 minutes, according to a 2021 study. To make the most of this time, start by giving your nurse a detailed reason for your visit, Collins says. Oftentimes, the information you provide on the phone to the employee who makes the appointment doesn’t get passed along to your providers, she says. But the nurse has a direct line of communication with both you and your doctor. Nurses may be able to answer your questions, too, Collins says, so don’t be afraid to ask them during intake or after your appointment, while you’re checking out. +
++If you sense the doctor is in a rush to end the appointment, or their hand is on the door to leave and you have other topics to discuss, tell the provider you still have more questions and you’d love it if they sat down with you for a few moments more, Chastain says. “Let them know you see that they’re trying to run out of the room and that is not going to work for you,” she says. Next, recap the appointment: “You’re saying my diagnosis was X and your treatment plan is Y and you’ll be calling in this prescription.” Then ask about any next steps. You can also take this time to review the list of questions you prepared before the appointment to ensure you addressed all of your concerns. +
++Before ending the appointment, Bervell suggests asking your provider three questions. When should I see you next? Are there any medications I should pick up? What are the signs that my condition is worsening and what should I do if that happens? +
++There may be questions you forgot to ask or additional concerns that arise after your appointment. Don’t hesitate to follow up with your doctor through your online patient portal or call the office. +
++In the event your doctor shows any sort of racial or weight bias, misgenders you, or dismisses your pain, you should speak up. Again, this can be difficult for people who have experienced stigmatization or have been brushed off before. However, your self-advocacy may lead to better outcomes for future patients, Collins says. +
++There are a few things you can say to a provider if you are experiencing fatphobia, homophobia, transphobia, racism, or other forms of discrimination or if the doctor is minimizing your experience, according to experts. +
++It may not be easy for those with limited access to health care providers to push back against their doctor, Collins and Chastain note. For example, those in rural areas may only have one or two practitioners or specialists available. Or it may be difficult to get an appointment with another provider. “They may need care from this doctor,” Chastain says, “so they might choose how to push back or not to push back based on that.” If your goal for the appointment is to get a prescription filled and move on, you may want to let the doctor proceed and not speak up in response to insensitive remarks in order to get the result you want. +
++However, if the provider is not treating you with respect, is dismissing your discomfort, and is focusing on stereotypes, find another doctor, experts say. You can ask if there is another medical professional within the clinic you can see — perhaps one who shares a background and identity with you, Collins says — if you want to stay within the same practice. +
++To help guide your search for a provider at a new facility, check out reviews on Zocdoc and Healthgrades. You can also ask friends and people in your community if they would recommend their doctor. +
++Before making an appointment, ask the office staff questions about the provider, Chastain says. When you call, you can say something like, “I’m looking for a new practitioner. I need a doctor who is [weight neutral/anti-racist/sex worker positive/trans positive]. Is there a doctor there who meets that criteria?” In some states, such as South Carolina and Mississippi, medical providers can decline to treat patients based on their religious beliefs. If you live in one of these states, ask a new provider about their policy, Chastain says: Say, “I know in this state, doctors are allowed to bring their religious beliefs into consideration when treating transgender and non-binary people. Is that something that you do? And in what way?” You can remain anonymous or even have a loved one make the call for you if you’re nervous. +
++Sometimes it can be easier to advocate for a friend than yourself, Chastain says. So consider your body a friend that deserves your support both in and out of the doctor’s office. “We’re the CEO of our body,” she says. “So we’re going to walk in there to support our body.” +
+What a brilliant new book gets right — and wrong — about America’s democracy. +
++In The Odyssey, Odysseus and his crew are forced to navigate a strait bounded by two equally dangerous obstacles: Scylla, a six-headed sea serpent, and Charybdis, an underwater horror that sucks down ships through a massive whirlpool. Judging Charybdis to be a greater danger to the crew as a whole, Odysseus orders his crew to try and pass through on Scylla’s side. They make it, but six sailors are eaten in the crossing. +
++In their new book Tyranny of the Minority, Harvard political scientists Steven Levitsky and Daniel Ziblatt — the authors of How Democracies Die — argue America’s founders faced an analogous problem: navigating between two types of dictatorship that threatened to devour the new country. +
++The founders, per Levitsky and Ziblatt, were myopically focused on one of them: the fear of a majority-backed demagogue seizing power. As a result, they made it exceptionally difficult to pass new laws and amend the constitution. But the founders, the pair argues, lost sight of a potentially more dangerous monster on the other side of the strait: a determined minority abusing this system to impose its will on the democratic majority. +
++“By steering the republic so sharply away from the Scylla of majority tyranny, America’s founders left it vulnerable to the Charybdis of minority rule,” they write. +
++This is not a hypothetical fear. According to Levitsky and Ziblatt, today’s America is currently being sucked down the anti-democratic whirlpool. +
++The Republican Party, they argue, has become an anti-democratic institution, its traditional leadership cowed by Trump and a racially reactionary base. As such, it is increasingly willing to twist legal tools designed to check oppressive majorities into tools for imposing its policy preferences on an unwilling majority. The best way out of this dilemma, in their view, is radical legal constitutional reform that brings the American system more in line with other advanced democracies. +
++Tyranny of the Minority is an exceptionally persuasive book. I think it is almost inarguably correct about both the nature of the modern Republican Party and the ways in which it exploits America’s rickety Constitution to subvert its democracy. I come to some similar conclusions in my own forthcoming book on democracy, The Reactionary Spirit (which, full disclosure, has benefited significantly from Levitsky’s feedback in drafting). +
++Yet at the same time, I believe he and Ziblatt slightly overweight the significance of America’s institutions in its current democratic crisis. Institutions matter for how authoritarian parties take power, but ultimately they may be less decisive than the social strength of the forces arrayed against democracy. +
++If a reactionary movement is popular or aggressive enough, it’s not clear that any kind of institution can stop it from threatening democracy. Hence why other advanced democracies with distinct institutional arrangements, like Israel, are currently going through democratic crises with root causes strikingly similar to America’s. It’s true that America’s institutions have paved a swift road for the Trumpist right’s attack on democracy. But they may not be quite as central to the story of its rise as Tyranny of the Minority suggests. +
++Ziblatt and Levitsky are two of America’s very best comparative political scientists, with expertise that makes them uniquely well-equipped for the subject they’re examining. +
++Ziblatt is the author of an important study of European conservative parties, concluding that their strategic choices played a unique role in determining the health of continental democracy in the 19th and early 20th centuries. Conservative parties, by their nature, represent those forces in society — including the wealthy and powerful elite — opposed to radical social change. For this reason, Ziblatt found, they are especially important in determining whether defenders of the status quo attempt to stymie social change from within the democratic system or whether they reject elections and political equality altogether. +
++Levitsky is a Latin America specialist who, along with co-author Lucan Way, wrote a prescient analysis of a new style of autocracy back in 2002 — a system they termed “competitive authoritarianism” that subsequently emerged as the premier institutional means for turning a seemingly stable democracy into an autocracy (see: Hungary). Competitive authoritarian governments masquerade as democracies, even holding elections with real stakes. But these contests are profoundly unfair: The incumbent party ensures that the rules surrounding elections, like who gets to vote and what the media gets to say, are heavily tilted in their favor. The result is that the opposition has little chance to win elections, let alone pass their preferred policies. +
++Tyranny of the Minority analyzes the United States in light of these two broad themes, the importance of conservative parties and the ever-evolving institutional nature of authoritarianism. The first half of the book analyzes how and why the Republican Party went down an anti-democratic path. The second focuses on how the peculiar design of American institutions has created opportunities for the GOP to undermine democracy from within. +
++Around the world, they find two conditions that make political parties more likely to accept electoral defeats: “when they believe they stand a reasonable chance of winning again in the future” and when they believe “that losing power will not bring catastrophe — that a change of government will not threaten the lives, livelihoods, or most cherished principles.” +
+ ++In the 21st century, these conditions no longer held among the GOP’s conservative white base. Democrats were no longer a mere political rival, but avatars of a new and scary social order. +
++“Not only was America no longer overwhelmingly white, but once entrenched racial hierarchies were weakening. Challenges to white Americans’ long-standing social dominance left many of them with feelings of alienation, displacement, and deprivation,” Levitsky and Ziblatt write. “Many of the party’s voters feared losing … their country — or more accurately, their place in it.” +
++This, they say, is what made the party vulnerable to conquest by someone like Trump. Rather than fight the base in democracy’s name, traditional Republican elites like Sen. Mitch McConnell (R-KY) acted as “semi-loyal democrats”: leaders who say the right things about supporting democracy and the rule of law, but value partisan victory over everything else — including basic, non-partisan democratic principles. This enabled the entire party to become a vehicle for an anti-democratic agenda. +
++“Openly authoritarian figures — like coup conspirators or armed insurrectionists — are visible for all to see. By themselves, they often lack the public support or legitimacy to destroy a democracy. But when semi-loyalists — tucked away in the hallways of power — lend a hand, openly authoritarian forces become much more dangerous,” they explain. “Throughout history, cooperation between authoritarians and seemingly respectable semi-loyal democrats has been a recipe for democratic breakdown.” +
++In the US, Levitsky and Ziblatt see a democracy made vulnerable by its own Constitution. +
++The Constitution’s framers were the first to take Enlightenment ideas about freedom and translate them to an actual political system. The only historical democratic experiences they looked at were from antiquity, in places like Athens and Rome. Classical sources repeatedly chronicled threats to democracy, even outright collapse, emanating from mob rule. +
++Though the founders knew that democracy was at heart about majority rule, they took the Greco-Roman experience seriously and designed a system where majorities were severely constrained. The tripartite separation of powers, bicameral legislature, indirect election of the president and senators, lifetime Supreme Court tenure, the laborious process for amending the Constitution: all of these were built, in whole or in part, as limitations on the ability of majorities to impose their will on minorities. +
++Some American counter-majoritarian institutions emerged not from well-intentioned design but political necessity. Leading founders like James Madison bitterly resented the basic structure of the Senate, where each state gets two seats regardless of size; Alexander Hamilton called it “preposterous” during a constitutional convention debate. It was included purely to mollify small states like Delaware and Rhode Island, who were refusing to join the Union absent sufficient protections for their interests. +
+ ++Over time, the US shed some of these minoritarian trappings — senators are now directly elected, thanks to the 17th Amendment — but deepened others. In 1803’s Marbury v. Madison, the Supreme Court gave itself expansive power to strike down legislation that was not explicitly granted in the Constitution. More recently, the filibuster emerged as a de facto 60-vote requirement for passing legislation in the Senate — a practice similar to the supermajority vote that the founders explicitly rejected early on. +
++Levitsky and Ziblatt show that almost every other peer democracy went in the opposite direction. +
++The United States is “the only presidential democracy in the world in which the president is elected via an Electoral College,” “one of the few remaining democracies that retains a bicameral legislature with a powerful upper chamber,” and “the only democracy in the world with lifetime tenure for Supreme Court justices.” Moreover, they note, “the U.S. Constitution is the hardest in the world to change” — making it extremely difficult for reformers to do anything about America’s minority-empowering institutions. +
++These institutions allow the Republican Party to rule despite being a distinctly minority faction — one that holds extreme positions on issues like taxes and abortion, and has lost the popular vote in seven out of the last eight presidential elections. +
++So long as the party retains appeal among a hard core of racially resentful supporters, efficiently distributed around the country to take advantage of the Senate and Electoral College’s biases, it can remain nationally competitive. The right’s control over the Supreme Court will likely last decades, thanks to lifetime tenure, allowing it to remake American policy and institutions with impunity. The GOP’s disproportionate national power enables its cadres at the state and local level to pursue explicitly undemocratic policies for holding power, like felon disenfranchisement and extreme gerrymandering, without fear of federal intervention. +
++Hence the titular “tyranny of the minority”: The Republican Party, having broken with its core commitment to democracy, has now embraced a peculiarly American strategy for taking and wielding power undemocratically. +
++“America’s countermajoritarian institutions can manufacture authoritarian minorities into governing majorities,” they write. “Far from checking authoritarian power, our institutions have begun to augment it.” +
++Levitsky and Ziblatt are, in my mind, clearly correct about both of their two major points: that the GOP has become an anti-democratic faction, and that America’s minoritarian institutions have given them a straightforward pathway to wielding power undemocratically. The evidence for both propositions is overwhelming, and the book’s style — engaging historical case studies accompanied by a precise deployment of data — hammers them home persuasively. Tyranny of the Minority is an exceptional book, one of the very best in its genre. +
++But there are some tensions inside of it: in this case, a subtle conflict between the two halves of the argument. +
++The United States, Ziblatt and Levitsky note, is hardly the only wealthy democracy to have experienced the rise of far-right parties hostile to social change — citing the UK, France, Germany, the Netherlands, and “all of Scandinavia” as prominent examples. Yet those democracies, in their view, “remain relatively healthy.” +
++The key difference, Levitsky and Ziblatt argue, lies in the institutions. Because those countries are considerably more majoritarian, it is far harder for an authoritarian minority to corrode democracy at a national level. Therefore, they conclude, the best way to safeguard America’s institutions is to make them more like our peers abroad: abolish the Electoral College, eliminate lifetime tenure for Supreme Court justices, end the filibuster, switch to proportional representation in Congress, ban partisan gerrymandering, and make the Constitution easier to amend. +
++The obvious objection to these proposals is that they are impractical, that the very nature of the problem — Republican control over minoritarian institutions — makes reforming them infeasible. But there’s a deeper, and more interesting, question raised by Levitsky and Ziblatt’s diagnosis: Is it really the case that our institutions are what make America unique? +
++America’s minoritarian institutions certainly create a particular pathway for our domestic revanchist faction to gain power and wield it against democracy. But there are plenty of other ways for a democracy to eat itself. +
++Israel, for example, has an extraordinarily majoritarian political system. It is a parliamentary democracy, meaning limited separation of executive and legislative power, whose legislature is elected on a purely proportional basis. There is a simple majority requirement for passing legislation and even amending the Basic Law (its constitution-lite). The judiciary is, for all intents and purposes, the only check on unfettered majority rule. +
++Yet Israel is, at the moment, in the midst of a democratic crisis every bit as serious as America’s, perhaps even more so, in which an anti-democratic governing majority seeks to remove the court as a barrier to its radical agenda. The root cause of the crisis is very similar: a far-right faction of the population that wishes to protect existing social hierarchies from the threat of change. But the extremist strategy for cementing their power is the polar opposite: exploiting majoritarian institutions, not minoritarian ones. It’s the founders’ fear come to life, the Scylla to America’s Charybdis. +
+ ++The point here is not that there are only two options for institutional design, America’s vetocracy or Israel’s blunt majoritarianism. Most advanced democracies fall somewhere in the middle, adopting a mix of majoritarian and counter-majoritarian institutions designed to generally permit majority rule while also preventing abuses of power. +
++Rather, the United States and Israel put together illustrate that institutions are an at-best-imperfect check on far-right authoritarian movements. The American far right has built a strategy tailored to American institutions; the Israeli far right has adopted a strategic approach tailored to the Israeli context. In both cases, the root of the problem is that there’s a sufficient social foundation for far-right authoritarian politics: one that provides the raw political muscle for bad actors to attack democracy using its own institutions. +
++Other democracies are not immune to far-right surges, including some that Levitsky and Ziblatt cite as relatively healthy. +
++The AfD, Germany’s far-right party, is surging in popularity, topping recent polls in four German states. A survey in May found that Marine Le Pen, the leader of France’s far-right National Rally, would defeat President Emmanuel Macron in their second rematch by a 55-45 margin. The UK approved Brexit by a majority referendum. Even in Canada, one of the most democratically stable Western democracies, extremist-linked legislator Pierre Poilievre is leading the traditionally center-right Conservative Party, which is currently ahead of Prime Minister Justin Trudeau’s Liberals in the 2025 polls. +
++Not every far-right victory is a threat to democracy, of course, but it’s hard to be sure until they have power. Some Western far-right parties, like the AfD, are already showing troubling signs. +
++And in the US, where the far right is clearly undemocratic, surveys show a real chance that Trump wins the 2024 US election with an outright majority — not just in the Electoral College, but in the popular vote. +
++At root, Levitsky and Ziblatt appear a little too confident in their argument that the GOP’s extremism dooms the party to minority status. +
++It’s true that their agenda is out of step with the majority of Americans. But many voters, especially swing voters, don’t always vote on policy or ideology. They make ballot box decisions based on things like gas prices, inflation, and whether the party in power has been there for too long — factors that are often out of the president’s hands. Even if they do not agree with Trump that Mexicans are rapists or that the 2020 election was stolen, they’re willing to vote for him if they’re sufficiently frustrated with either the status quo or the other party’s option. +
++The same is true in other countries. In Israel, Prime Minister Benjamin Netanyahu’s right-wing government was briefly dethroned in the 2021 election — only to return to power in 2022 after voters experienced life under a fractious coalition that spanned the right-left continuum. Marine Le Pen’s recent rise seems to be less about a majority of voters agreeing with her on immigration than a sense that she’s the only real alternative to an unpopular Macron. +
++Far-right parties, even potentially anti-democratic ones, can be politically viable under nearly any set of institutions. The key is to establish sufficient support among a large segment of the population that agrees with them, enough for there to be a large ideologically driven backlash. Once that happens, the party can establish itself as a viable alternative to the mainstream. And once that happens, they gain the potential to win over less ideological swing voters who simply have frustrations with the political status quo and look to any port in a storm. +
++This is not to let America’s institutions off the hook. Levitsky and Ziblatt are absolutely right that its outdated constitution makes it easier for the GOP to travel down an authoritarian path. +
++But “easier” doesn’t mean “necessary.” While Levitsky and Ziblatt ultimately take an institutions-first approach, seeing their reform as our way out of America’s crisis, I take a more society-first view: that America’s problems are primarily the result of deep social fissures exacerbated by outdated and poorly designed institutions. Even if the United States had a more authentically democratic institution, we’d still be riven by divides over race and identity that have unerringly produced the worst political conflicts in the country’s history. +
++It follows from this that institutional reforms are not enough: In addition to policies for political reform, we also need to think about ways to reduce the social demand for extreme politics. More bluntly: If widespread hostility to social change enables the GOP’s far-right authoritarian lurch, we need to figure out ways to shift Americans’ beliefs in a more egalitarian direction. +
++But such a proposal should be considered in addition to Levitsky and Ziblatt’s proposals, not in replacement of them — much as my critique of their book more broadly is less a fundamental concern than a difference in emphasis. +
++Tyranny of the Minority is one of the best guides out there to the crisis of American democracy. It just puts a touch too much focus on institutions at the expense of the deeper social forces rotting their foundations. +
Asian Games 2023 | Indian women go down to Thailand 0-1; fail to enter knockout stage - A 52nd minute goal from Thongrong Parichat helped Thailand to emerge winner in their Group B football match against India
Srihari, women’s freestyle relay team advance to finals - The quartet of Olympian Maana Patel, Dhinidhi Desinghu, Janvi Choudhary and Shivangi Sarma clocked 3:53.80s to finish sixth in the 10-team affair and make the final
Hangzhou Asian Games | Boxer Preeti storms into women’s 54kg quarterfinals -
Formula One | Red Bull take constructors’ title as Verstappen wins in Japan - McLaren’s Lando Norris and Australian rookie Oscar Piastri, on a grand prix podium for the first time, finished second and third
Hangzhou Asian Games | Nagal steamrolls Macau’s Leung, moves into men’s tennis singles pre-quarterfinals - The fifth seed Nagal, who had got a first round bye, needed just 45 minutes to dispatch his opponent 6-0 6-0
Congress formidable on all 90 assembly seats in JK - Jammu and Kashmir Congress chief Vikar Rasool welcomed scores of political activists into the party and said that in the past one year a large number of activists from other parties have joined Congress
Ropeway project at Nandi Hills ascends in slow pace as land transfers remain pending - According to sources, the complex will have parking for over 200 cars, 110 bikes, eight buses and tempo travellers along with a food court which can accommodate more than 184 people among other things
Three new air routes to become operationalise in Arunachal in October: Scindia - Tezu airport is the fourth in the state after Donyi Polo, Pasighat and Ziro airports and 17th in the northeast.
School bags will become lighter from next year with 1/3rd reduction in textbook size: Madhu Bangarappa - ‘There will be no change in the content but the volume will be reduced, the Minister for School Education and Literacy said
Navies of India, U.S. explore ways to expand cooperation -
Karabakh humanitarian fears grow with thousands sleeping on Stepanakert streets - Azerbaijan shows off captured tanks but aid is slow to arrive for thousands sleeping on the streets.
Ukraine claims Sevastopol strike hit navy commanders - Kyiv says senior officials in Russia’s Black Sea fleet were present, but did not offer evidence.
Ukraine war: How Zelensky is grappling with Western war fatigue - Ukraine’s leader has always been comfortable campaigning for help - now he’s having to negotiate.
Kosovo police surround 30 gunmen in monastery after officer shot - PM urges “terrorists” to surrender hours after officer died in ambush near Serbian border.
AI-generated naked child images shock Spanish town of Almendralejo - More than 20 Spanish girls in the small town of Almendralejo have so far come forward as victims.
Inside the race to stop a deadly viral outbreak in India - With viral spillovers happening more frequently, containment is a fragile shield. - link
The history of syphilis is being rewritten by a medieval skeleton - Columbus may not have brought syphilis back to the Old World after all. - link
NASA’s asteroid sampling mission is on course for landing this weekend - “The spacecraft trajectory and performance have just been spot on.” - link
3 iOS 0-days, a cellular network compromise, and HTTP used to infect an iPhone - Apple patches 3 zero-days after they were used in a sophisticated attack. - link
RSV vaccine during pregnancy gets seasonal sign-off from CDC - The vaccine is recommended for use only in the run-up to RSV season. - link
Young Man Buys Condoms Thinking That Tonight’s The Night. Then This Happens: -
++A young man goes into a drug store to buy condoms. +
++The pharmacist says the condoms come in packs of 3, 9 or 12 and asks which the young man wants. +
++“Well,” he said, “I’ve been seeing this girl for a while and she’s really hot. I want the condoms because I think tonight’s”the" night. We’re having dinner with her parents, and then we’re going out. And I’ve got a feeling I’m gonna get lucky after that." +
++“Once she’s had me, she’ll want me all the time, so you’d better give me the 12 pack.” +
++The young man makes his purchase and leaves. +
++Later that evening, he sits down to dinner with his girlfriend and her parents. He asks if he might give the blessing and they agree. He begins the prayer, but continues praying for several minutes. +
++The girl leans over to him and says, “You never told me that you were such a religious person.” +
++The boy leans over to her and whispers, “You never told me that your father is a pharmacist.” +
+ submitted by /u/Fair_Willingness_629
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A bakery owner hires a young female clerk who likes to wear very short skirts and thong panties. -
++One day a young man enters the store, glances at the clerk and at the loaves of bread behind the counter. +
++Noticing her short skirt, and the location of the raisin bread, he has a brilliant idea. +
++“I’d like some raisin bread please,” the man says. +
++The clerk nods and climbs up a ladder to reach the raisin bread located on the very top shelf. +
++The man standing almost directly beneath her, is provided with an excellent view, just as he thought. +
++When she descends the ladder, he decides that he had better get two loaves, as he is “having company for dinner.” +
++As the clerk retrieves the second loaf of bread, one of the other male customers notices what’s going on and requests his own loaf of raisin bread. +
++After many trips, she is tired, irritated and begins to wonder “why the unusual interest in the raisin bread?” +
++Atop the ladder one more time, she looks down and glares at the men standing below. +
++Then, she notices an elderly man standing amongst the crowd. Thinking that she can save herself a trip, she yells at the elderly man, +
++Is it raisin for you too?” “No,” stammers the old man, “but it’s quivering a little.” +
+ submitted by /u/Fair_Willingness_629
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The last bed -
++A traveling salesman came to town late one night, and no hotels had a vacancy. “Please find me a bed” he begged at the last hotel, - “no matter how bad the room is!” +
++“Okay,” said the hotel manager, “I’ve got a double room where an Air Force guy is sleeping. But he snores so loudly that the people in the next room have already complained a dozen times!” +
++“It doesn’t matter,” said the man, “let me have the vacant bed” +
++The next morning the man showed up for breakfast fresh and rested. “How did it go?” wondered the hotel manager, “did you get to sleep?” +
++“I’ve never slept so well!” +
++“But what about the snorer?” +
++“I just got him to stop,” the man said. +
++“But how did you do it?” +
++“He was in bed snoring when I entered the room. So I went up to him, gave him a kiss, and said”Good night, handsome!" - and then he sat on the edge of the bed all night and kept an eye on me..!" +
+ submitted by /u/Snowandicefan
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Joe………. -
++Joe is on his last day at work as a mailman. +
++He receives many thank-you cards and monetary gifts along his route. +
++When he gets to the very last house, he is greeted by a gorgeous housewife, who invites him in for lunch. Joe happily accepts. +
++After lunch, the woman invites him up to the bedroom for some “dessert.” Joe happily accepts again. +
++When they are done, the woman gives him a dollar. Joe asks what the dollar is all about. The woman replies: "It was my husband’s suggestion. +
++When I told him that it was your last day at work, he told me ’F**k him, give him a dollar. The lunch was my idea." +
+ submitted by /u/MercyReign
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My ten year old daughter told this one… -
++A girl and a boy are locked out of their house. They can’t find any way in, so the girl leans forward and starts talking to the door lock… “Hey door lock you’re looking nice today, why don’t you go ahead and let us in.” +
++The door magically unlocks itself. The boy is shocked, “how did you do that?!?” +
++The girl replies, “communication is KEY.” +
++ +
++To the angry people in the comments… My kid did not make up the joke. She TOLD us the joke. +
++Also, chill out on the Jokes sub. It’s supposed to be fun in here. +
+ submitted by /u/mrmackz
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