navan
/
Daily-Dose
mirror of https://github.com/navanchauhan/Daily-Dose.git
1
0
Fork 0
Code Issues Projects Releases Wiki Activity

Added daily report

This commit is contained in:
Navan Chauhan 2023-12-01 12:45:58 +00:00
parent 75facd18c0
commit 230bb059cc
3 changed files with 900 additions and 2 deletions
Show Stats Download Patch File Download Diff File Expand all files Collapse all files

171
archive-covid-19/01 December, 2023.html Normal file
View File

@ -0,0 +1,171 @@
<!DOCTYPE html>
<html lang="" xml:lang="" xmlns="http://www.w3.org/1999/xhtml"><head>
<meta charset="utf-8"/>
<meta content="pandoc" name="generator"/>
<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
<title>01 December, 2023</title>
<style>
code{white-space: pre-wrap;}
span.smallcaps{font-variant: small-caps;}
span.underline{text-decoration: underline;}
div.column{display: inline-block; vertical-align: top; width: 50%;}
div.hanging-indent{margin-left: 1.5em; text-indent: -1.5em;}
ul.task-list{list-style: none;}
</style>
<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
<body>
<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-preprints">From Preprints</a></li>
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
<li><a href="#from-pubmed">From PubMed</a></li>
<li><a href="#from-patent-search">From Patent Search</a></li>
</ul>
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
<ul>
<li><strong>SARS-CoV-2 NSP13 suppresses the Hippo pathway downstream effector YAP</strong> -
<div>
The Hippo pathway plays critical roles in tissue development, regeneration, and immune homeostasis. The widespread pandemic of Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has resulted in a global healthcare crisis and strained health resources. How SARS-CoV-2 affects Hippo signaling in host cells has remained poorly understood. Here, we report that SARS-CoV-2 infection in patient lung cells and cardiomyocytes derived from human induced pluripotent stem cells (iPS-CMs) suppressed YAP target gene expression, as evidenced by RNA sequencing data. Furthermore, in a screening of nonstructural proteins from SARS-CoV-2, nonstructural protein 13 (NSP13) significantly inhibited YAP transcriptional activity independent of the YAP upstream suppressor kinase Lats1/2. Consistent with this, NSP13 suppressed active YAP (YAP5SA) in vivo, whereby NSP13 expression reverted the phenotype of YAP5SA transgenic mice. From a mechanistic standpoint, NSP13 helicase activity was shown to be required for its suppression of YAP. Furthermore, through the interaction of NSP13 with TEAD4, which is the most common YAP-interacting transcription factor in the nucleus, NSP13 recruited endogenous YAP suppressors such as CCT3 and TTF2 to inactivate the YAP/TEAD4 complex. These findings reveal the function and mechanism of the SARS-CoV-2 helicase NSP13 in host cells and partially explain the toxic effect of SARS-CoV-2 in particular host tissue with high YAP activity.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.30.569413v1" target="_blank">SARS-CoV-2 NSP13 suppresses the Hippo pathway downstream effector YAP</a>
</div></li>
<li><strong>Gut Microbiome Dynamics and Predictive Value in Hospitalized COVID-19 Patients: A Comparative Analysis of Shallow and Deep Shotgun Sequencing</strong> -
<div>
The COVID-19 pandemic caused by SARS-CoV-2 has led to a wide range of clinical presentations, with respiratory symptoms being common. However, emerging evidence suggests that the gastrointestinal (GI) tract is also affected, with angiotensin-converting enzyme 2, a key receptor for SARS-CoV-2, abundantly expressed in the ileum and colon. The virus has been detected in GI tissues and fecal samples, even in cases with negative respiratory results. GI symptoms have been associated with an increased risk of ICU admission and mortality. The gut microbiome, a complex ecosystem of around 40 trillion bacteria, plays a crucial role in immunological and metabolic pathways. Dysbiosis of the gut microbiota, characterized by a loss of beneficial microbes and decreased microbial diversity, has been observed in COVID-19 patients, potentially contributing to disease severity. We conducted a comprehensive gut microbiome study in 204 hospitalized COVID-19 patients using both shallow and deep shotgun sequencing methods. We aimed to track microbiota composition changes induced by hospitalization, link these alterations to clinical procedures (antibiotics administration) and outcomes (ICU referral, survival), and assess the predictive potential of the gut microbiome for COVID-19 prognosis. Shallow shotgun sequencing was evaluated as a cost-effective diagnostic alternative for clinical settings.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.29.568526v1" target="_blank">Gut Microbiome Dynamics and Predictive Value in Hospitalized COVID-19 Patients: A Comparative Analysis of Shallow and Deep Shotgun Sequencing</a>
</div></li>
<li><strong>Persistent immune imprinting after XBB.1.5 COVID vaccination in humans</strong> -
<div>
Immune imprinting - also known as original antigenic sin describes how the first exposure a virus shapes the immunological outcome of subsequent exposures to antigenically related strains. SARS-CoV-2 Omicron breakthrough infections and bivalent COVID-19 vaccination were shown to primarily recall cross-reactive memory B cells and antibodies induced by prior mRNA vaccination with the Wuhan-Hu-1 spike rather than priming naive B cells that recognize Omicron-specific epitopes. These findings underscored a strong immune imprinting resulting from repeated Wuhan-Hu-1 spike exposures. To understand if immune imprinting can be overcome, we investigated memory and plasma antibody responses after administration of the updated XBB.1.5 COVID mRNA vaccine booster. Our data show that the XBB.1.5 booster elicits neutralizing antibody responses against current variants that are dominated by recall of pre-existing memory B cells previously induced by the Wuhan-Hu-1 spike. These results indicate that immune imprinting persists even after multiple exposures to Omicron spikes through vaccination and infection, including post XBB.1.5 spike booster mRNA vaccination, which will need to be considered to guide the design of future vaccine boosters.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.28.569129v1" target="_blank">Persistent immune imprinting after XBB.1.5 COVID vaccination in humans</a>
</div></li>
<li><strong>Antiviral humoral immunity against SARS-CoV-2 Omicron subvariants induced by XBB.1.5 monovalent vaccine in infection-naive and XBB-infected individuals</strong> -
<div>
To control infection with SARS-CoV-2 Omicron XBB subvariants, the XBB.1.5 monovalent mRNA vaccine has been available since September 2023. However, we have found that natural infection with XBB subvariants, including XBB.1.5, does not efficiently induce humoral immunity against the infecting XBB subvariants. These observations raise the possibility that the XBB.1.5 monovalent vaccine may not be able to efficiently induce humoral immunity against emerging SARS-CoV-2 variants, including a variety of XBB subvariants (XBB.1.5, XBB.1.16, XBB.2.3, EG.5.1 and HK.3) as well as BA.2.86. To address this possibility, we collected two types of sera from individuals vaccinated with the XBB.1.5 vaccine; those who had not been previously infected with SARS-CoV-2 and those who had been infected with XBB subvariants prior to XBB.1.5 vaccination. We collected sera before and 3-4 weeks after vaccination, and then performed a neutralization assay using these sera and pseudoviruses.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.29.569330v1" target="_blank">Antiviral humoral immunity against SARS-CoV-2 Omicron subvariants induced by XBB.1.5 monovalent vaccine in infection-naive and XBB-infected individuals</a>
</div></li>
<li><strong>Mechanistic insights into ligand dissociation from the SARS-CoV-2 spike glycoprotein</strong> -
<div>
The COVID-19 pandemic, driven by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spurred an urgent need for effective therapeutic interventions. The spike glycoprotein of the SARS-CoV-2 is crucial for infiltrating host cells, rendering it a key candidate for drug development. By interacting with the human angiotensin-converting enzyme 2 (ACE2) receptor, the spike initiates the infection of SARS-CoV-2. Linoleate is known to bind the spike glycoprotein, subsequently reducing its interaction with ACE2. However, the detailed kinetics underlying the protein-ligand interaction remains unclear. In this study, we characterized the pathways of ligand dissociation and the conformational changes associated with the spike glycoprotein by using ligand Gaussian accelerated molecular dynamics (LiGaMD). Our simulations resulted in eight complete ligand dissociation trajectories, unveiling two distinct ligand unbinding pathways. The preference between these two pathways depends on the gate distance between two -helices in the receptor binding domain (RBD) and the position of the N-linked glycan at N343. Our study also highlights the essential contributions of K417, N121 glycan, and N165 glycan in ligand unbinding, which are equally crucial in enhancing spike-ACE2 binding. We suggest that the presence of the ligand influences the motions of these residues and glycans, consequently reducing accessibility for spike-ACE2 binding. These findings enhance our understanding of ligand dissociation from the spike glycoprotein and offer significant implications for drug design strategies in the battle against COVID-19.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.29.569184v1" target="_blank">Mechanistic insights into ligand dissociation from the SARS-CoV-2 spike glycoprotein</a>
</div></li>
<li><strong>Generalizable features for the diagnosis of infectious disease, autoimmunity and cancer from adaptive immune receptor repertoires</strong> -
<div>
Adaptive immune receptor repertoires (AIRRs) have emerged as promising biomarkers for disease diagnosis and clinical prognosis. However, their high diversity and limited sharing between donors pose unique challenges when employing them as features for machine learning based diagnostics. In this study, we investigate the commonly used approach of representing each receptor as a member of a "clonotype cluster". We then construct a feature vector for each donor from clonotype cluster frequencies (CCFs). We find that CCFs are sparse features and that classifiers trained on them do not generalize well to new donors. To overcome this limitation, we introduce a novel approach where we transform cluster frequencies using an adjacency matrix built from pairwise similarities of all receptors. This transformation produces a new feature, termed paratope cluster occupancies (PCOs). Leveraging publicly available AIRR datasets encompassing infectious diseases (COVID-19, HIV), autoimmune diseases (autoimmune hepatitis, type 1 diabetes), and cancer (colorectal cancer, non-small cell lung cancer), we demonstrate that PCOs exhibit lower sparsity compared to CCFs. Furthermore, we establish that classifiers trained on PCOs exhibited improved generalizability and overall classification performance (median ROC AUC 0.893) when compared to CCFs (median ROC AUC 0.714) over the six diseases. Our findings highlight the potential of utilizing PCOs as a feature representation for AIRR analysis in diverse disease contexts.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.28.569125v1" target="_blank">Generalizable features for the diagnosis of infectious disease, autoimmunity and cancer from adaptive immune receptor repertoires</a>
</div></li>
<li><strong>Human Cytokine and Coronavirus Nucleocapsid Protein Interactivity Using Large-Scale Virtual Screens</strong> -
<div>
In the battle against the ever-changing SARS-CoV-2 landscape, understanding the interactions between viral proteins and the human immune system is paramount as it helps to explain potential factors contributing to diverse immunological responses in infected individuals. In this study, we employed state-of-the-art molecular docking tools to conduct large-scale virtual screens, predicting the binding affinities between 64 human cytokines against 17 coronavirus nucleocapsid proteins. Our comprehensive in silico analyses reveal specific changes in cytokine-nucleocapsid protein interactions, shedding light on potential modulators of the host immune response during infection. These findings offer valuable insights into the molecular mechanisms underlying viral pathogenesis and may guide the future development of targeted interventions. This manuscript serves as insight into the comparison of deep learning based AlphaFold2-Multimer and the semi-physicochemical based HADDOCK for protein-protein docking. We show the two methods are complementary in their predictive capabilities. We also introduce a novel algorithm for rapidly assessing the binding interface of protein-protein docks using graph edit distance: graph-based residue assessment function (G-RAF). The high-performance computational framework presented here will not only aid in accelerating the discovery of effective interventions against emerging viral threats, but extend to other applications of high throughput protein-protein screens.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.28.569056v1" target="_blank">Human Cytokine and Coronavirus Nucleocapsid Protein Interactivity Using Large-Scale Virtual Screens</a>
</div></li>
<li><strong>Mechanism-based classification of SARS-CoV-2 Variants by Molecular Dynamics Resembles Phylogenetic Tree</strong> -
<div>
The COVID-19 pandemics has demonstrated the vulnerability of our societies to viral infectious disease. The mitigation of COVID-19 was complicated by the emergence of Variants of Concern (VOCs) with varying properties including increased transmissibility and immune evasion. Traditional population sequencing proved to be slow and not conducive for timely action. To tackle this challenge, we introduce the Persistence Score (PS) that assesses the pandemic potential of VOCs based on molecular dynamics of the interactions between the SARS-CoV-2 Receptor Binding Domain (RBD) and the ACE2 residues. Our mechanism-based classification approach successfully grouped VOCs into clinically relevant subgroups with higher sensitivity than classical affinity estimations and allows for risk assessment of hypothetical new VOCs. The PS-based interaction analysis across VOCs resembled the phylogenetic tree of SARS-Cov-2 demonstrating its predictive relevance for pandemic preparedness. Thus, PS allows for early detection of a variant's pandemic potential, and an early risk evaluation for data-driven policymaking.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.28.568639v1" target="_blank">Mechanism-based classification of SARS-CoV-2 Variants by Molecular Dynamics Resembles Phylogenetic Tree</a>
</div></li>
<li><strong>Functional and antigenic characterization of SARS-CoV-2 spike fusion peptide by deep mutational scanning</strong> -
<div>
The fusion peptide of SARS-CoV-2 spike protein is functionally important for membrane fusion during virus entry and is part of a broadly neutralizing epitope. However, sequence determinants at the fusion peptide and its adjacent regions for pathogenicity and antigenicity remain elusive. In this study, we performed a series of deep mutational scanning (DMS) experiments on an S2 region spanning the fusion peptide of authentic SARS-CoV-2 in different cell lines and in the presence of broadly neutralizing antibodies. We identified mutations at residue 813 of the spike protein that reduced TMPRSS2-mediated entry with decreased virulence. In addition, we showed that an F823Y mutation, present in bat betacoronavirus HKU9 spike protein, confers resistance to broadly neutralizing antibodies. Our findings provide mechanistic insights into SARS-CoV-2 pathogenicity and also highlight a potential challenge in developing broadly protective S2-based coronavirus vaccines.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.28.569051v1" target="_blank">Functional and antigenic characterization of SARS-CoV-2 spike fusion peptide by deep mutational scanning</a>
</div></li>
<li><strong>copepodTCR: Identification of Antigen-Specific T Cell Receptors with combinatorial peptide pooling</strong> -
<div>
T cell receptor (TCR) repertoire diversity enables the orchestration of antigen-specific immune responses against the vast space of possible pathogens. Identifying TCR/antigen binding pairs from the large TCR repertoire and antigen space is crucial for biomedical research. Here, we introduce copepodTCR, an open-access tool for the design and interpretation of high-throughput experimental assays to determine TCR specificity. copepodTCR implements a combinatorial peptide pooling scheme for efficient experimental testing of T cell responses against large overlapping peptide libraries, useful for "deorphaning" TCRs of unknown specificity. The scheme detects experimental errors and, coupled with a hierarchical Bayesian model for unbiased results interpretation, identifies the response-eliciting peptide for a TCR of interest out of hundreds of peptides tested using a simple experimental set-up. We experimentally validated our approach on a library of 253 overlapping peptides covering the SARS-CoV-2 spike protein. We provide experimental guides for efficient design of larger screens covering thousands of peptides which will be crucial for the identification of antigen-specific T cells and their targets from limited clinical material.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.28.569052v1" target="_blank">copepodTCR: Identification of Antigen-Specific T Cell Receptors with combinatorial peptide pooling</a>
</div></li>
<li><strong>Reasons for not getting vaccinated against COVID-19 in German-speaking Switzerland: An online survey among vaccine hesitant 16-60 year olds</strong> -
<div>
Background: Several research studies have examined the reasons why people are hesitant to be vaccinated against COVID-19. However, there is no published data to date on Switzerland. Identifying these reasons among the Swiss population who are vaccine hesitant may help inform campaigns to encourage vaccine confidence. Aims: The primary aim of this study is to identify the reasons for not getting vaccinated against COVID-19 among Swiss residents who are vaccine hesitant. The secondary aim is to examine whether reasons differ by age, gender, education, and likelihood of accepting a vaccination to better target campaigns and design interventions. Design: An online survey asked participants to indicate the reasons why they were hesitant to be vaccinated against COVID-19. Setting: German-speaking Swiss Cantons, the survey was administered online between 5 May 2021 and 16 May 2021. Participants: The participants in this analysis were a sample of (N=1191) Swiss residents age 16-60 years old from German-speaking Cantons, who could answer an online survey in German, who had yet not been vaccinated, who had not yet registered for a vaccination appointment, and who did not indicate that they would definitely be vaccinated if offered the chance. Findings: Among people who are vaccine hesitant in Switzerland, the most common reasons for being hesitant were side-effect, safety, and effectiveness concerns. It was also common for people to indicate that they were healthy/at low risk, would decide later, and that they wanted to build immunity naturally. Less common, but still prevalent concerns included wanting more information, thinking COVID-19 was not a real threat, and concerns that the vaccine may serve another purpose. Differences in reasons for being vaccine hesitant were found by age, gender, education, and likelihood of accepting a vaccination if offered. Conclusions: To increase the likelihood of accepting a vaccination, vaccination campaigns should address side-effect, safety, and effectiveness concerns. Campaigns could also consider informing people why it is necessary for people in lower risk groups to be vaccinated, and why vaccination is preferable to infection for building immunity. While campaigns may be effective in reaching some of the population, alternative strategies might be necessary to strengthen the trust relationship with vaccines and vaccine providers in some groups. Less prevalent concerns, such as not liking needles, could be addressed through individual level interventions.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/hnzke/" target="_blank">Reasons for not getting vaccinated against COVID-19 in German-speaking Switzerland: An online survey among vaccine hesitant 16-60 year olds</a>
</div></li>
<li><strong>Expression and fusogenic activity of SARS CoV-2 Spike protein displayed in the HSV-1 Virion.</strong> -
<div>
Severe acute respiratory syndrome coronavirus (SARS-CoV) is a zoonotic pathogen that can cause severe respiratory disease in humans. The new SARS-CoV-2 is the cause of the current global pandemic termed coronavirus disease 2019 (COVID-19) that has resulted in many millions of deaths world-wide. The virus is a member of the Betacoronavirus family, its genome is a positive strand RNA molecule that encodes for many genes which are required for virus genome replication as well as for structural proteins that are required for virion assembly and maturation. A key determinant of this virus is the Spike (S) protein embedded in the virion membrane and mediates attachment of the virus to the receptor (ACE2). This protein also is required for cell-cell fusion (syncytia) that is an important pathogenic determinant. We have developed a pseudotyped herpes simplex virus type 1 (HSV-1) recombinant virus expressing S protein in the virion envelop. This virus has also been modified to express a Venus fluorescent protein fusion to VP16, a virion protein of HSV-1. The virus expressing Spike can enter cells and generates large multi-nucleated syncytia which are evident by the Venus fluorescence. The HSV-1 recombinant virus is genetically stable and virus amplification can be easily done by infecting cells. This recombinant virus provides a reproducible platform for Spike function analysis and thus adds to the repertoire of pseudotyped viruses expressing Spike.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.28.568860v1" target="_blank">Expression and fusogenic activity of SARS CoV-2 Spike protein displayed in the HSV-1 Virion.</a>
</div></li>
<li><strong>Streamlining Computational Fragment-Based Drug Discovery through Evolutionary Optimization Informed by Ligand-Based Virtual Prescreening</strong> -
<div>
Recent advancements in computational methods provide the promise of dramatically accelerating drug discovery. While mathematical modeling and machine learning have become vital in predicting drug-target interactions and properties, there is untapped potential in computational drug discovery due to the vast and complex chemical space. This paper advances a novel computational fragment-based drug discovery (FBDD) method called Fragments from Ligands Drug Discovery (FDSL-DD), which aims to streamline drug design by applying a two-stage optimization process informed by machine learning and evolutionary principles. In this approach, in silico screening identifies ligands from a vast library, which are then fragmentized while attaching specific attributes based on predicted binding affinity and interaction with the target sub-domain. This process both shrinks the search space and focuses on promising regions within it. The first optimization stage assembles these fragments into larger compounds using evolutionary strategies, and the second stage iteratively refines resulting compounds for enhanced bioactivity. The methodology is validated across three diverse protein targets involved in human solid cancers, bacterial antimicrobial resistance, and SARS-CoV-2 viral entry, demonstrating the approach's broad applicability. Using the proposed FDSL-DD and two-stage optimization approach yields high-affinity ligand candidates more efficiently than other state-of-the-art computational methods. Furthermore, a multiobjective optimization is presented that accounts for druglikeness while still producing potential candidate ligands with high binding affinity. In conclustion, the results demonstrate that integrating detailed chemical information with a constrained search framework can markedly optimize the initial drug discovery process, offering a more precise and efficient route to developing new therapeutics.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.27.568919v1" target="_blank">Streamlining Computational Fragment-Based Drug Discovery through Evolutionary Optimization Informed by Ligand-Based Virtual Prescreening</a>
</div></li>
<li><strong>Epitope mapping of SARS-CoV-2 RBDs by hydroxyl radical protein footprinting reveals the importance of including negative antibody controls.</strong> -
<div>
Understanding protein-protein interaction is essential when designing drugs or investigating biological processes. A variety of techniques can be employed in order to map the regions on proteins that are involved in binding eg., CryoEM, X-ray spectroscopy, linear epitope mapping, or mass spectrometry-based methods. The most commonly utilized mass spectrometry-based techniques are cross-linking and hydrogen-deuterium exchange (HDX). An alternative technique for identifying residues on the three-dimensional structure of proteins, that are involved in binding, can be hydroxyl radical protein footprinting (HRPF). However, this method is currently hampered by high initial cost and complex experimental setup. Here we set out to present a generally applicable method using Fenton chemistry for mapping of epitopes in a standard mass spectrometry laboratory. Furthermore, the described method illustrates the importance of controls on several levels when performing mass spectrometry-based epitope mapping. In particular, the inclusion of a negative antibody control has not previously been widely utilized in epitope mapping by HRPF analysis. In order to limit the number of false positives, we further introduced quantification by TMT labelling, thereby allowing for direct comparison between sample conditions and biological triplicates. Lastly, up to six technical replicates were incorporated in the experimental setup in order to achieve increased depth of the final analysis. Both binding and opening of regions on receptor-binding domain (RBD) from SARS-CoV-2 Spike Protein, Alpha and Delta variants, were observed. The negative control antibody experiment combined with the high overlap between biological triplicates resulted in the exclusion of 40% of the significantly changed regions, including both binding and opening regions. The final identified binding region was mapped to a three-dimensional structure and agrees with the literature for neutralizing antibodies towards SARS-CoV-2 Spike Protein. The presented method is straightforward to implement for the analysis of HRPF in a generic MS-based laboratory. The high reliability of the data was achieved by increasing the number of technical and biological replicates combined with negative antibody controls.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.27.564378v2" target="_blank">Epitope mapping of SARS-CoV-2 RBDs by hydroxyl radical protein footprinting reveals the importance of including negative antibody controls.</a>
</div></li>
<li><strong>Generation and evaluation of protease inhibitor-resistant SARS-CoV-2 strains</strong> -
<div>
Since the start of the SARS-CoV-2 pandemic, the search for antiviral therapies has been at the forefront of medical research. To date, the 3CLpro inhibitor nirmatrelvir (Paxlovid) has shown the best results in clinical trials and the greatest robustness against variants. A second SARS-CoV-2 protease inhibitor, ensitrelvir (Xocova), has been developed. Ensitrelvir, currently in Phase 3, was approved in Japan under the emergency regulatory approval procedure in November 2022, and is available since March 31, 2023. One of the limitations for the use of antiviral monotherapies is the emergence of resistance mutations. Here, we experimentally generated mutants resistant to nirmatrelvir and ensitrelvir in vitro following repeating passages of SARS-CoV-2 in the presence of both antivirals. For both molecules, we demonstrated a loss of sensitivity for resistance mutants in vitro. Using a Syrian golden hamster infection model, we showed that the ensitrelvir M49L mutation confers a high level of in vivo resistance. Finally, we identified a recent increase in the prevalence of M49L-carrying sequences, which appears to be associated with multiple repeated emergence events in Japan and may be related to the use of Xocova in the country since November 2022. These results highlight the strategic importance of genetic monitoring of circulating SARS-CoV-2 strains to ensure that treatments administered retain their full effectiveness.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.22.568013v1" target="_blank">Generation and evaluation of protease inhibitor-resistant SARS-CoV-2 strains</a>
</div></li>
</ul>
<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effect of Metformin in Reducing Fatigue in Long COVID in Adolescents</strong> - <b>Conditions</b>: Long COVID <br/><b>Interventions</b>: Drug: Metformin; Other: Placebo <br/><b>Sponsors</b>: Trust for Vaccines and Immunization, Pakistan <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Randomized Trial Evaluating a mRNA VLP Vaccine’s Immunogenicity and Safety for COVID-19</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2 Infection <br/><b>Interventions</b>: Biological: AZD9838; Biological: Licensed mRNA vaccine <br/><b>Sponsors</b>: AstraZeneca <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>“The Effect of Aerobic Exercise and Strength Training on Physical Activity Level, Quality of Life and Anxiety-Stress Disorder in Young Adults With and Without Covid-19”</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Behavioral: Aerobic Exercise and Strength Training <br/><b>Sponsors</b>: Pamukkale University <br/><b>Active, not recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety Study of SLV213 for the Treatment of COVID-19.</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Other: Placebo for SLV213; Drug: SLV213 <br/><b>Sponsors</b>: National Institute of Allergy and Infectious Diseases (NIAID) <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Vale+Tú Salud: Corner-Based Randomized Trial to Test a Latino Day Laborer Program Adapted to Prevent COVID-19</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Behavioral: COVID-19 Group Problem Solving; Behavioral: Standard of Care; Behavioral: Booster session <br/><b>Sponsors</b>: The University of Texas Health Science Center, Houston; National Institute on Minority Health and Health Disparities (NIMHD) <br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Collection of Additional Biological Samples From Potentially COVID-19 Patients for Monitoring of Biological Parameters Carried Out as Part of the Routine</strong> - <b>Conditions</b>: SARS CoV 2 Infection <br/><b>Interventions</b>: Diagnostic Test: RIPH2 <br/><b>Sponsors</b>: CerbaXpert <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Promoting Engagement and COVID-19 Testing for Health</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Behavioral: COVID-19 Test Reporting; Behavioral: Personalized Nudges via Text Messaging; Behavioral: Non-personalized Nudges via Text Messaging <br/><b>Sponsors</b>: Emory University; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Morehouse School of Medicine; Georgia Institute of Technology <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Performance Evaluation of the Lucira COVID-19 &amp; Flu Test</strong> - <b>Conditions</b>: COVID-19; Influenza <br/><b>Interventions</b>: Device: Lucira COVID-19 &amp; Flu Test <br/><b>Sponsors</b>: Lucira Health Inc <br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Development and Qualification of Methods for Analyzing the Mucosal Immune Response to COVID-19</strong> - <b>Conditions</b>: Certain Disorders Involving the Immune Mechanism <br/><b>Interventions</b>: Biological: Sampling; Biological: PCR (polymerase chain reaction) SARS-CoV-2 <br/><b>Sponsors</b>: University Hospital, Tours <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy of Two Therapeutic Exercise Modalities for Patients With Persistent COVID</strong> - <b>Conditions</b>: Persistent COVID-19 <br/><b>Interventions</b>: Other: exercise programe <br/><b>Sponsors</b>: Facultat de ciencies de la Salut Universitat Ramon Llull <br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Mitigating Mental and Social Health Outcomes of COVID-19: A Counseling Approach</strong> - <b>Conditions</b>: Social Determinants of Health; Mental Health Issue; COVID-19 <br/><b>Interventions</b>: Behavioral: Individual counseling; Behavioral: Group counseling; Other: Resources <br/><b>Sponsors</b>: Idaho State University <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Water-based Activity to Enhance Recovery in Long COVID</strong> - <b>Conditions</b>: Long COVID <br/><b>Interventions</b>: Behavioral: WATER+CT; Behavioral: Usual Care <br/><b>Sponsors</b>: VA Office of Research and Development <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Robotic Assisted Hand Rehabilitation Outcomes in Adults After COVID-19</strong> - <b>Conditions</b>: Robotic Exoskeleton; Post-acute Covid-19 Syndrome; Rehabilitation Outcome; Physical And Rehabilitation Medicine <br/><b>Interventions</b>: Device: Training with a Robotic Hand Exoskeleton <br/><b>Sponsors</b>: University of Valladolid; Centro Hospitalario Padre Benito Menni <br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Cognitive Rehabilitation in Post-COVID-19 Syndrome</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome <br/><b>Interventions</b>: Behavioral: CO-OP Procedures; Behavioral: Inactive Control Group <br/><b>Sponsors</b>: University of Missouri-Columbia; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) <br/><b>Not yet recruiting</b></p></li>
</ul>
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Implementing PCR testing in general practice-a qualitative study using normalization process theory</strong> - CONCLUSION: In its current form, the added diagnostic value of using POC PCR testing in general practice was not sufficient for the professionals to justify the increased work connected to the usage of the diagnostic procedure in daily practice.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhibition of bradykinin in SARS-CoV-2 infection: a randomised, double-blind trial of icatibant compared with placebo (ICASARS)</strong> - SARS-CoV-2 binds to ACE2 receptors and enters cells. The symptoms are cough, breathlessness, loss of taste/smell and X-ray evidence of infiltrates on chest imaging initially caused by oedema, and subsequently by a lymphocytic pneumonitis. Coagulopathy, thrombosis and hypotension occur. Worse disease occurs with age, obesity, ischaemic heart disease, hypertension and diabetes.These features may be due to abnormal activation of the contact system. This triggers coagulation and the kallikrein-kinin…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Antiviral peptides inhibiting the main protease of SARS-CoV-2 investigated by computational screening and in vitro protease assay</strong> - The main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays an important role in viral replication and transcription and received great attention as a vital target for drug/peptide development. Therapeutic agents such as small-molecule drugs or peptides that interact with the Cys-His present in the catalytic site of Mpro are an efficient way to inhibit the protease. Although several emergency-approved vaccines showed good efficacy and drastically dropped the…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Plant-Derived Natural Compounds as an Emerging Antiviral in Combating COVID-19</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a human virus that burst at Wuhan in China and spread quickly over the world, leading to millions of deaths globally. The journey of this deadly virus to different mutant strains is still ongoing. The plethora of drugs and vaccines have been tested to cope up this pandemic. The herbal plants and different spices have received great attention during pandemic, because of their anti-inflammatory, and immunomodulatory properties in…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Enumeration of olive derived lignan, pinoresinol for activity against recent Omicron variant spike protein for structure-based drug design, DFT, molecular dynamics simulations, and MMGBSA studies</strong> - The coronavirus disease 2019 (COVID-19) was first found in Wuhan, China, in December 2019. Because the virus spreads quickly, it quickly became a global worry. Coronaviridae is the family that contains both SARS-CoV-2 and the viruses that came before (i.e., MERS-CoV and SARS-CoV). Recent sources portray that the COVID-19 virus has affected 344,710,576 people worldwide and killed about 5,598,511 people in the last 2 years. The B.1.1.529 strain, later called “Omicron,” was named a Variant of…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Amplification of poly(I:C)-induced interleukin-6 production in human bronchial epithelial cells by priming with interferon-γ</strong> - Proinflammatory cytokine interleukin (IL)-6 was associated with disease severity in patients with COVID-19. The mechanism underlying the excessive IL-6 production by SARS-Cov-2 infection remains unclear. Respiratory viruses initially infect nasal or bronchial epithelial cells that produce various inflammatory mediators. Here, we show that pretreatment of human bronchial epithelial cells (NCl-H292) with interferon (IFN)-γ (10 ng/mL) markedly increased IL-6 production induced by the toll-like…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Diabetic individuals with COVID-19 exhibit reduced efficacy of gliptins in inhibiting dipeptidyl peptidase 4 (DPP4). A suggested explanation for increased COVID-19 susceptibility in patients with type 2 diabetes mellitus (T2DM)</strong> - AIMS: Dipeptidyl peptidase 4 (DPP4) has been proposed as a coreceptor for SARS-CoV-2 cellular entry. Considering that type 2 diabetes mellitus (T2DM) has been identified as the most important risk factor for SARS-CoV-2, and that gliptins (DPP4 inhibitors) are a prescribed diabetic treatment, this study aims to unravel the impact of DPP4 in the intersection of T2DM/COVID-19.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Engineering irradiated tumor-derived microparticles as personalized vaccines to enhance anti-tumor immunity</strong> - The inadequate activation of antigen-presenting cells, the entanglement of T cells, and the highly immunosuppressive conditions in the tumor microenvironment (TME) are important factors that limit the effectiveness of cancer vaccines. Studies show that a personalized and broad antigen repertoire fully activates anti-tumor immunity and that inhibiting the function of transforming growth factor (TGF)-β facilitates T cell migration. In our study, we introduce a vaccine strategy by engineering…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Willow (<em>Salix</em> spp.) bark hot water extracts inhibit both enveloped and non-enveloped viruses: study on its anti-coronavirus and anti-enterovirus activities</strong> - CONCLUSION: Salix spp. bark extracts contain several virucidal agents that are likely to act synergistically and directly on the viruses.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Unveiling the role of PUS7-mediated pseudouridylation in host protein interactions specific for the SARS-CoV-2 RNA genome</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a positive single-stranded RNA virus, engages in complex interactions with host cell proteins throughout its life cycle. While these interactions enable the host to recognize and inhibit viral replication, they also facilitate essential viral processes such as transcription, translation, and replication. Many aspects of these virus-host interactions remain poorly understood. Here, we employed the catRAPID algorithm and utilized the…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Case report: Supratherapeutic tacrolimus concentrations with nirmatrelvir/ritonavir in a lung transplant patient: a case report using Rifampin for reversal</strong> - Paxlovid (nirmatrelvir/ritonavir) is an antiviral drug used to treat COVID-19, nirmatrelvir, a SARS-CoV-2 main protease inhibitor, works by inhibiting viral replication in the early stages, and ritonavir is a strong cytochrome P450 (CYP) 3A inhibitor that helps the nirmatrelvir reach and maintain the therapeutic concentrations. Paxlovid has a potential risk of drug interaction by elevating the plasma concentration of other drugs metabolized by CYP3A, like tacrolimus. This report examines the…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The spike protein of SARS-CoV-2 induces inflammation and EMT of lung epithelial cells and fibroblasts through the upregulation of GADD45A</strong> - Lung epithelial cells and fibroblasts poorly express angiotensin-converting enzyme 2, and the study aimed to investigate the role of the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on inflammation and epithelial-mesenchymal transition (EMT) in two lung cell lines and to understand the potential mechanism. Lung epithelial cells (BEAS-2B) and fibroblasts (MRC-5) were treated with the spike protein, then inflammatory and EMT phenotypes were detected by…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Exploring Novel Vitamin K Derivatives with Anti-SARS-CoV-2 Activity</strong> - From our compound library of vitamin K derivatives, we found that some compounds exhibited anti-SARS-CoV-2 activity in VeroE6/TMPRSS2 cells. The common structure of these compounds was menaquinone-2 (MK-2) with either the m-methylphenyl or the 1-naphthyl group introduced at the end of the side chain. Therefore, new vitamin K derivatives having more potent anti-SARS-CoV-2 activity were explored by introducing various functional groups at the ω-position of the side chain. MK-2 derivatives with a…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The role of tocilizumab in the treatment of post-transfusion hyperhaemolysis</strong> - Hyperhaemolysis syndrome (HHS) is a serious complication of transfusion mostly reported in patients with sickle cell disease. HHS is characterised by the destruction of both donor and autologous red blood cells. Tocilizumab is a recombinant humanised monoclonal antibody that inhibits the binding of interleukin-6 and has been used in the treatment of severe/critical coronavirus disease 2019 infection but also some cases of HHS. We describe two further cases of HHS successfully treated with…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immune responses and clinical outcomes following the third dose of SARS-CoV-2 mRNA-BNT162b2 vaccine in advanced breast cancer patients receiving targeted therapies: a prospective study</strong> - CONCLUSIONS: Our results confirm that the immune response to tozinameran is impaired by CDK4/6 inhibitors, increasing the odds of breakthrough infections despite the third vaccine dose. Current evidence recommends maintaining efforts to provide booster immunizations to the most vulnerable cancer patients, including those with advanced breast cancer undergoing CDK4/6 inhibition.</p></li>
</ul>
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
<script>AOS.init();</script></body></html>

727
archive-daily-dose/01 December, 2023.html Normal file
View File

@ -0,0 +1,727 @@
<!DOCTYPE html>
<html lang="" xml:lang="" xmlns="http://www.w3.org/1999/xhtml"><head>
<meta charset="utf-8"/>
<meta content="pandoc" name="generator"/>
<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
<title>01 December, 2023</title>
<style>
code{white-space: pre-wrap;}
span.smallcaps{font-variant: small-caps;}
span.underline{text-decoration: underline;}
div.column{display: inline-block; vertical-align: top; width: 50%;}
div.hanging-indent{margin-left: 1.5em; text-indent: -1.5em;}
ul.task-list{list-style: none;}
</style>
<title>Daily-Dose</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><style>*{overflow-x:hidden;}</style><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
<body>
<h1 data-aos="fade-down" id="daily-dose">Daily-Dose</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-new-yorker">From New Yorker</a></li>
<li><a href="#from-vox">From Vox</a></li>
<li><a href="#from-the-hindu-sports">From The Hindu: Sports</a></li>
<li><a href="#from-the-hindu-national-news">From The Hindu: National News</a></li>
<li><a href="#from-bbc-europe">From BBC: Europe</a></li>
<li><a href="#from-ars-technica">From Ars Technica</a></li>
<li><a href="#from-jokes-subreddit">From Jokes Subreddit</a></li>
</ul>
<h1 data-aos="fade-right" id="from-new-yorker">From New Yorker</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An “Academic Transformation” Takes On the Math Department</strong> - A series of cuts at West Virginia University has largely affected the humanities, but any program that is not seen as marketable may get the axe. - <a href="https://www.newyorker.com/news/us-journal/an-academic-transformation-takes-on-the-math-department">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Dead Children We Must See</strong> - It’s time for Americans to rethink their squeamishness about releasing the photos of the youngest victims of mass violence. - <a href="https://www.newyorker.com/news/our-columnists/the-dead-children-we-must-see">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What Would a Lasting Peace Between Israel and Palestine Really Look Like?</strong> - The need for a new paradigm after October 7th. - <a href="https://www.newyorker.com/news/q-and-a/what-would-a-lasting-peace-between-israel-and-palestine-really-look-like">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Bidenomics Is a Political Bust for Biden</strong> - On the perils of running a feel-good tour of America when the country is down in the dumps. - <a href="https://www.newyorker.com/news/letter-from-bidens-washington/bidenomics-is-a-political-bust-for-biden">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Henry Kissinger’s Hard Compromises</strong> - In his final years, the architect of America’s opening to China watched as Washington turned against his philosophy of engagement regardless of the costs. - <a href="https://www.newyorker.com/news/postscript/henry-kissingers-hard-compromises">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>Why psychedelics produce some of the most meaningful experiences in people’s lives</strong> -
<figure>
<img alt="A portrait of two overlapping outlines of human heads, colored in with hues of purple and pink, with an open door in the middle leading into floating planets and larger galactic vistas." src="https://cdn.vox-cdn.com/thumbor/_82lMfXmLgIVzivUbHiXXW6acH0=/771x0:7439x5001/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72919724/GettyImages_1475150659.0.jpg"/>
<figcaption>
Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Everything seems profound on psychedelics. Scientists are starting to ask why.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3A4eS4">
In 1882, sitting at his desk with a pen and open notebook, Harvard philosopher William James inhaled a thick cloud of nitrous oxide — better known today as laughing gas, the stuff your dentist uses to numb your mouth.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KPylIj">
As the fumes took effect, they bathed his mind in what <a href="https://www.cs.cmu.edu/~ehn/release/nitrous.html">James called</a> “the tremendously exciting sense of … metaphysical illumination.” What stuck with him after the drugs wore off, though, was not any particular thought — which he soberly conceded as “meaningless drivel” — but the intense feeling of meaning they came packaged in. He called that sense of significance the “<a href="https://www.mdpi.com/2077-1444/12/12/1058">noetic quality</a>” of mystical experience.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vPfi6b">
The noetic quality describes a sensation of encountering revelations of the highest order, where the secret workings of your mind and the world are unfolded before you. But as James also described, these encounters have an elusive quality that makes them difficult to communicate. And through the 20th century, mainstream <a href="https://www.vox.com/psychology">psychology</a> <a href="https://journals.sagepub.com/doi/full/10.1177/0952695119874009#body-ref-bibr30-0952695119874009-1">moved away</a> from nebulous ideas like noeticism and meaning, in favor of variables that were more objective and observable.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CS9Z4t">
Until 2006, when <a href="https://link.springer.com/article/10.1007/s00213-006-0457-5">a landmark paper</a> led by the late Roland Griffiths of Johns Hopkins University signaled that research on the profound sense of meaning that accompanies noetic insights was making its way back into mainstream psychology — this time by way of psychedelic drugs.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PiOchK">
Griffiths’s study found that, two months after taking <a href="https://www.vox.com/future-perfect/2020/10/9/21506664/psychedelics-mental-health-depression-ptsd-psilocybin-mdma">psilocybin</a>, the active ingredient in magic mushrooms, two-thirds out of 30 volunteers rated their subsequent trip as one of the five most meaningful experiences of their lives. Further studies that ask the same question have pushed that number to <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5641975/">as high as 87 percent</a> of participants, <a href="https://pubs.acs.org/doi/10.1021/acsptsci.0c00194">confirming the curious fact</a> that a group of molecules can reliably deliver on demand what the psychiatrist Viktor Frankl <a href="https://www.google.com/books/edition/Man_s_Search_for_Meaning/F-Q_xGjWBi8C?hl=en">called</a> <a href="https://ia601809.us.archive.org/19/items/mans-search-for-meaning_202104/Man%27s%20Search%20For%20Meaning.pdf"></a>the central human motivation: the search for meaning.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AFKcZO">
Despite the past two decades of research documenting the tight relationship between psychedelics and meaningful experiences, we still know surprisingly little about what’s actually going on in the brain when psychedelic-assisted meaning sets in. In <a href="https://www.frontiersin.org/articles/10.3389/fpsyg.2023.1125780/full">a paper</a> published earlier this year in the journal <em>Frontiers in Psychology,</em> psychologists Patric Plesa and Rotem Petranker pointed out that even “the best minds in psychedelic research … consistently report that psychedelics enhance a subjective sense of meaning without an explicit theory of meaning.” It’s strange that we lack a mechanical understanding of something so central to a life well lived. If we understood more about the neural mechanics of these bursts of revelation, could we learn anything about how to coax them into our sober lives more often?
</p>
<div class="c-float-right">
<aside id="P47ABt">
<q>On psychedelics … it seems like it’s not particular things that are imbued with meaning, but the whole of perception itself</q>
</aside>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pIbxmd">
The project of developing a mechanical theory of meaning is beginning to take shape. In the past, scientists couldn’t readily observe a nervous system feeling deep meaning. People aren’t generally hooked up to <a href="https://www.vox.com/neuroscience">neuroscience</a> gizmos when the noetic experience strikes. But the return of clinical research into psychedelics is making it easier to provoke these elusive states in the lab, and over the past few years, scientists have begun to develop hypotheses on what these drugs could teach us about the <a href="https://www.sciencedirect.com/science/article/abs/pii/S2451902223002410?via%3Dihub">neurobiology of meaningfulness</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bzV1E1">
However, confining the study of psychedelic experience to neurobiology would be repeating an all-too-common oversight in neuroscience of separating the mind from its social and cultural environments, shrinking the study of psychedelic meaningfulness to only what’s happening inside the skull. Subjective experiences — meaningful or otherwise — are shaped by their wider contexts, an insight around which many Indigenous cultures have designed their <a href="https://www.frontiersin.org/articles/10.3389/fphar.2021.651037/full">psychedelic rituals</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mQBZKY">
And even if we mapped out the precise brain regions that are active during psychedelic boosts of meaning — so what? It’s unclear how much pinpointing the neural correlates of psychedelic meaning will contribute to what matters: learning how to craft more meaningful lives, which is the broader project that has gripped humans since a handful of great religions and philosophies <a href="https://www.noemamag.com/religious-imagination-as-the-future-unfolds/">emerged over 2 millennia ago</a> <a href="https://www.noemamag.com/religious-imagination-as-the-future-unfolds/"></a>to grapple with questions of meaning, purpose, and significance.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ue1FRO">
You can’t just trip your way to a meaningful life; that requires more than the mere accumulation of disparate meaningful experiences. In addition, experts<a href="https://www.tandfonline.com/doi/abs/10.1080/17439760.2015.1137623"> suggest</a> that you need a wider architecture, a through line of goals and values that provides coherence and purpose to the narrative arc of your life on the whole. But studying psychedelics to learn more about the biological underpinnings of meaningful experiences could hold any number of fascinating lessons. Instead of providing conclusive answers, psychedelic meaning may reveal profound questions that change the course of action we take in the world.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="IWEWdc">
“Meaning,” <a href="https://www.sts-biu.org/ido-hartogsohn">Ido Hartogsohn</a>, author of <a href="https://mitpress.mit.edu/9780262539142/american-trip/"><em>American Trip: Set, Setting, and the Psychedelic Experience in the Twentieth Century</em></a>, told me, “is valuable not only for therapeutic breakthroughs. It’s helpful wherever we are looking for a way out of our ordinary ways of perceiving and thinking, since it helps us detect hidden paths and possibilities.” Put differently, meaningful experiences, like well-crafted psychedelic trips, can expand our search for how to live meaningful lives.
</p>
<h3 id="cxO36u">
Serotonin receptors are gateways to psychedelic meaning
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PmiNab">
Any explanation of how psychedelics are so good at conjuring meaning should include the brain’s serotonin 2A receptors, small proteins dusted across your central nervous system that play a vital <a href="https://www.frontiersin.org/articles/10.3389/fphar.2015.00225/full">role</a> in cognition. Each contains a small pocket, like a landing zone, where molecules of the correct shape can dock. Per the name, these receptors typically receive serotonin, a neurotransmitter involved in a wide <a href="https://my.clevelandclinic.org/health/articles/22572-serotonin">range of functions</a>, from mood to sleep. But psychedelics mimic the structure of serotonin, granting them access to the receptor.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="sb9BXY">
In 2017, <a href="https://www.uzh.ch/cmsssl/dppp/en/cfpr/researchgroups/external-research-groups/pharmaco-neuroimaging-and-cognitive-emotional-processing/team/preller.html">Katrin Preller</a>, a neuropsychologist at the University of Zurich, <a href="https://www.cell.com/current-biology/fulltext/S0960-9822(16)31510-X?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS096098221631510X%3Fshowall%3Dtrue">published the first experiment</a> to test the specific contribution of these serotonin receptors in the subjective effects of LSD in humans. Participants listened to three kinds of music: music that they found meaningless (often free jazz — no disrespect, Sun Ra fans), music they had preselected as highly meaningful to them, and “neutral” music that was similar to their preselected songs but that they had never heard before.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="q4TNPh">
They listened to each set on three different occasions: once while sober; once on LSD, which, they reported, made all three pieces of music more meaningful; and once on a combination of LSD and ketanserin, a drug that blocks the serotonin receptor so psychedelic molecules can’t dock there. The idea was to see if LSD still produces elevated levels of meaningfulness even when it can’t interact with the serotonin receptor.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FgBYdk">
The result? Blocking that receptor completely canceled the subjective effects of LSD; participants might as well have been sober. Preller’s findings helped establish that these receptors are critical to the noetic quality. No receptor activation, no extra meaningfulness.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MTihDX">
But explaining psychedelic meaningfulness via the activation of serotonin receptors is like saying that turning the keys in the ignition explains what makes a car go. Once the receptors are activated, there’s a whole lot of under-the-hood activity that’s important to understand the mechanisms of meaning.
</p>
<h3 id="RbTu9m">
The brain network that matters
</h3>
<figure class="e-image">
<img alt="Two circles comparing brain connections from a placebo condition (left circle) to being on psychedelics (right circle), the latter showing significantly more connections." src="https://cdn.vox-cdn.com/thumbor/L6WW1ws1BluRvUDC5zrnYRqHDxw=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/25106353/brain_network_large_1.jpg"/> <cite><a class="ql-link" href="http://rsif.royalsocietypublishing.org/content/11/101/20140873" target="_blank"><em>Journal of the Royal Society Interface</em></a></cite>
<figcaption>
From a 2014 study in the <a class="ql-link" href="http://rsif.royalsocietypublishing.org/content/11/101/20140873" target="_blank"><em>Journal of the Royal Society Interface</em></a> comparing a brain on a placebo (left) to one on psilocybin.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NoL2Mk">
In psychosis research, when people find meaning in what we believe is meaningless happenstance, experts call it “<a href="https://pubmed.ncbi.nlm.nih.gov/34253268/">aberrant salience</a>.” It’s a concept that may also <a href="https://aeon.co/essays/what-can-psychedelic-science-teach-psychiatry-about-psychosis">shed some light</a> on the psychedelic experience.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cBBwGS">
Like in bouts of psychosis, psychedelic-induced meaning can be found <em>everywhere and anywhere. </em>It’s no longer dependent on an external trigger that the sober mind would also find meaningful, like the birth of a child. On psychedelics, I could stare at tree bark for three hours, or dirt, or the back of my eyelids, and feel that I’ve discovered the hidden order behind all phenomena. It seems like it’s not particular things that are imbued with meaning, but the whole of perception itself.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="U9uUm1">
“I might call it a misattribution of meaning, where everything gets imbued with a sense of meaningfulness,” <a href="https://dellmed.utexas.edu/directory/manoj-doss">Manoj Doss</a>, a research fellow in the department of psychiatry at the University of Texas at Austin, told me. “A lot of times I can attribute the noeticism I’m getting to a memory. We’re usually good at aiming these feelings of knowing. But sometimes they get cut loose. Under psychedelics, I think there’s this misattribution process, where the prefrontal cortex is sending that off in all kinds of different directions where they don’t make sense.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RSg9ls">
The psychedelic misattribution of meaning can lead to finding meaning where we ordinarily wouldn’t — like in tree bark. And that noetic feeling can make <a href="https://www.vice.com/en/article/5dgkkn/the-insights-psychedelics-give-you-arent-always-true">objectively false insights feel true</a>, as researchers are cleverly <a href="https://osf.io/preprints/psyarxiv/97gjw/">finding in the lab</a>. The upshot is clear enough: Psychedelic insights should be treated with a good dose of critical reflection.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bZM9X5">
Still, looking past whether psychedelic insights are true or not, there remains the question of why they feel so meaningful in the first place. While we don’t know of a brain network specifically responsible for meaningfulness, we do have one that’s pretty close: the <a href="https://www.quantamagazine.org/inside-the-brains-salience-network-the-will-to-press-on-20131205/">salience network</a>, which helps prepare us to take action by prioritizing what stimuli from our environments stick out to us. In other words, the salience network helps determine what matters to us in our perceptual landscape among the flood of information we take in at any given moment.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XuZ0YT">
As Plesa and Petranker <a href="https://www.frontiersin.org/articles/10.3389/fpsyg.2023.1125780/full">explain in their <em>Frontiers </em>study on meaning</a>, we know that psychedelics <a href="https://journals.sagepub.com/doi/10.1177/0269881120909409">recalibrate</a> the salience network, altering what appears important to us. In other research on altered states of consciousness, like <a href="https://www.vox.com/future-perfect/23836358/meditation-mindfulness-enlightenment-science-contemplative-buddhism-spirituality">mindfulness meditation</a>, shifts in the <a href="https://www.sciencedirect.com/science/article/pii/S014976342100261X">salience landscape</a> are thought to be one of the <a href="https://link.springer.com/article/10.1007/s12671-019-01258-9">main mechanisms</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10445489/#ref56"></a>behind increasing a sense of meaning in life.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YYkB9f">
It’s possible that a riled-up salience network could explain why anything that falls into psychedelic perception may seem to hold the secrets of the cosmos. Activating the 2A receptor and disrupting the salience network could make everything seem to matter more, functioning as the neural key that opens what the philosopher Aldous Huxley called “<a href="https://maps.org/images/pdf/books/HuxleyA1954TheDoorsOfPerception.pdf">the doors of perception</a>.” But Plesa and Petranker argue that the picture is incomplete. There’s another step to get us from the brain mechanisms of mattering to the feeling of meaning: connection.
</p>
<h3 id="yjAw4a">
To get meaning from salience, you need connections
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GHW5Fo">
Psychedelics are known to disrupt another major cluster of brain regions: the default-mode network (DMN). The DMN is associated with self-referential thought, like daydreaming about the moment you win the Olympics, or recalling autobiographical memories, like winning the Olympics if you’d actually won the Olympics. It’s the brain’s hub for the narrative self.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yXw2Pn">
Psychedelics <a href="https://academic.oup.com/ijnp/article/26/3/155/6770039?login=false">reduce activity within the DMN</a>, while <a href="https://academic.oup.com/ijnp/article/26/3/155/6770039?login=false">increasing activity</a> between the DMN and other brain regions. <a href="https://www.imperial.ac.uk/people/c.timmermann-slater15">Christopher Timmermann</a>, a neuroscientist who leads the DMT Research Group at Imperial College London (DMT is a psychedelic drug, like LSD or psilocybin), explained to me earlier this year that “parts of the DMN become hyper-connected with the rest of the brain.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hSFmyn">
During interviews after their <a href="https://newrepublic.com/article/169525/psychonauts-training-psychedelics-dmt-extended-state">DMT trips</a>, he said that participants report things like “I was observing the experience, but at the same time I <em>was</em> everything. I <em>was</em> every possible concept in my mind.” Trippy, yes, but it “resonates with this idea of hyperconnectivity,” he said. “These resources we have when it comes to the sense of self become more promiscuous, and become attached to larger systems of meaning.”
</p>
<div class="c-float-right">
<aside id="ti4sxW">
<q>If connection is a crucial part of psychedelic meaning, we may want to reconsider cutting it out of the formal containers in which we legalize access</q>
</aside>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8xAJY8">
Other ways to describe what that hyperconnectivity feels like could be the “<a href="https://pubmed.ncbi.nlm.nih.gov/28795211/">connectedness</a>,” “unity,” or “oceanic boundlessness” that <a href="https://www.frontiersin.org/articles/10.3389/fpsyt.2022.917199/full">often accompanies</a> high-dose psychedelic experiences. Plesa and Petranker believe that the synergy between changes in our salience network and the increased connectedness of DMN disruption could offer the formula that underlies meaning, or an explanation of what happens in the engine after you turn the key.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="kaEg0O">
This is where, as they acknowledge, the car metaphor breaks down. The mind is <a href="https://www.technologyreview.com/2021/08/25/1030861/is-human-brain-computer/">not a machine</a>. No explanation of conscious states should ignore the social, cultural, and political threads that weave into the tapestry of experience. “It may be that a larger societal prism is required to reconstruct these parts into a coherent narrative,” they write, one that widens its view to include not only the brain but the environments they’re enmeshed in.
</p>
<h3 id="m0UaTD">
Don’t forget the set, setting, and matrix of psychedelic meaning
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2uLYBM">
If you were to jet over to Oregon, the first state to <a href="https://www.nytimes.com/2023/10/23/us/oregon-psychedelic-mushrooms.html#:~:text=Far%20from%20the%20days%20of,guidance%20of%20a%20certified%20facilitator.">offer legal psychedelic services</a>, the experience would be very different from most Indigenous cultures’ formats of psychedelic use, like the <a href="https://www.santodaime.org/site-antigo/doctrine/whatis.htm">Santo Daime</a>, a Brazilian religion founded in 1930 that uses ayahuasca (a psychoactive brew containing DMT) as a sacrament in psychedelic rituals.
</p>
<figure class="e-image">
<img alt=" " src="https://cdn.vox-cdn.com/thumbor/3tsnvwCh-Ac2m8xJtfc4c2sR5kE=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/25106198/GettyImages_1298456754.jpg"/> <cite>Giulio Paletta/Universal Images</cite>
<figcaption>
A Santo Daime ayahuasca ceremony, which can last up to 12 hours.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7Pl3jL">
In Oregon’s nascent regulated-use model, you have a preparatory session or two, trip alone (though under the supervision of a facilitator) and indoors, to a playlist while mostly sitting still or lying down, wearing eyeshades. In <a href="https://www.frontiersin.org/articles/10.3389/fphar.2021.651037/full">the Santo Daime tradition</a>, you begin with days of diets, abstinence, and prayer before you touch the drug. The ceremony itself is a group affair with sacred hymns and dancing performed throughout, and can go for eight hours or more.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wGZ52E">
There’s a huge variety of practices across Indigenous cultures, but each has a very particular “<a href="https://journals.sagepub.com/doi/10.1177/2050324516683325">set and setting</a>” that frames the experience. Even in the 1960s American go-round with psychedelics, set and setting were <a href="https://www.google.com/books/edition/The_Psychedelic_Experience/44dvPwAACAAJ?hl=en">understood</a> <a href="https://www.leathersmithe.com/politicshandcraftsenvironme/the-psychedelic-experience.pdf"></a>as primary parts of the equation for what kind of experience one has.
</p>
<aside id="6oslpd">
<div>
</div>
</aside>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="y7euHr">
Even set and setting fail to offer a full account of all the factors that shape psychedelic experiences. The American psychologist Betty Eisner suggested that we think in terms of set, setting, <a href="https://www.tandfonline.com/doi/abs/10.1080/02791072.1997.10400190">and matrix</a>. The matrix accounts for the everyday environments we’ve grown up in — how our families, societies, economies, and culture have <a href="https://www.musingmind.org/podcasts/barnaby-raine">shaped our ideas</a>, expectations, and ways of thinking, all of which play a role in directing psychedelic experience.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UQNQNr">
By fixing its gaze upon the brain alone, the neuroscience of psychedelic meaning can miss how these wider influences, from a room’s ambiance to a culture’s ideals, can play a direct role in the meaning-making process. “There is always hidden machinery and circuitry that is going on, and we’re not describing it,” the neuropharmacologist Suresh Muthukumaraswamy <a href="https://www.wired.com/story/psychedelics-study-design-research-rcts/">told Wired’s Shayla Love</a>. “There are all these hidden interactions that, frankly, we’re brushing under the carpet.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="B5e2so">
Plesa and Petranker see the past few decades of Western industrialized societies as a troubling context for psychedelic experience — and not just because the prohibition has left us without clear ways of supporting those who experience <a href="https://www.vox.com/future-perfect/23954347/psychedelics-bad-trips-ketamine-mdma-psilocybin-lsd-risks">rare but significant adverse effects</a>. They note the long line of philosophers and sociologists who’ve “warned that life in industrialized, technological societies is undergoing a process of impoverishment of meaning,” and the confluence of rising stress, <a href="https://news.gallup.com/opinion/gallup/512618/almost-quarter-world-feels-lonely.aspx">loneliness</a>, and depression together with the decline of civil society — from religions to <a href="https://www.vox.com/a/books-to-read-to-understand-the-world#Bowling-Alone">bowling leagues</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ohWhD7">
No matter how strong a psychedelic trip can be, connection remains a critical aspect of meaning-making. Psychedelics may help us forge new connections more easily — but the rest, like designing a society that does the same, is up to us.
</p>
<h3 id="598cLK">
Stockpiling psychedelic meaning won’t make for a meaningful life
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pWYwfg">
Let’s say scientists succeeded in mapping the precise neural correlates of psychedelic meaning, and went further, mapping all possible experiences, as the philosopher Robert Nozick <a href="https://www.hachettebookgroup.com/titles/robert-nozick/anarchy-state-and-utopia/9780465051007/?lens=basic-books">imagines</a> <a href="https://antilogicalism.files.wordpress.com/2018/04/anarchy-state-utopia.pdf"></a>in his thought experiment known as the “experience machine.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="sXGZMl">
The machine could make you feel anything you want. All the while, however, you’d be floating in a womb-like tank with electrodes stuck to your skull, engineering your experience through targeted bursts of electricity.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HXs4aI">
The experience machine could make you feel untold quantities of meaning — a seamless cascade of one meaningful experience after another. While plugged into the machine, you wouldn’t know it. But every two years or so, Nozick imagined, you’d come out, like briefly waking from a dream, to select your next two years of experiences from a menu.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="kwM1Oe">
He saw three main reasons that would drive people to generally choose against plugging into the machine. For one, “we want to <em>do</em> certain things, and not just have the experience of doing them.” Second, we want to <em>be</em> certain kinds of people, not just stagnant bodies floating in a tank. “Someone floating in a tank is an indeterminate blob,” as he put it. And third, the machine limits our experiences only to what human minds, with some added electrical stimulation, can conjure, closing us off to encounters with deeper or wider realities, whether of the natural world, other people, or extradimensional beings.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JuUb1g">
Whatever the reason, his point is that if you imagine such an experience machine and yet decide you would not want to pass your life plugged into it, you’re proving that something matters to you above and beyond just experience itself. Experience machines are meant as a cautionary tale, and yet already, legal <a href="https://www.curbed.com/2021/12/ketamine-clinic-nyc.html">ketamine clinics are halfway</a> to realizing them. Walk into any of the centers scattered around a place like New York City and you’ll find people floating, womb-like, in zero-gravity recliners, wearing eyeshades and earphones that cut them off from other people and the outside world, a ketamine IV pricked into their arms.
</p>
<aside id="69lPHv">
<div>
</div>
</aside>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="o6OSij">
The conclusion that something more than <em>just</em> experience matters applies to how we think about the role of psychedelic-assisted meaning, too. It shows that we want to live in ways that generate meaning, not just pump our brains full of molecules that make all experiences meaningful. Researchers <a href="https://www.tandfonline.com/doi/full/10.1080/17439760.2015.1137623">have valiantly tried to pin down</a> the multiplicities of meaning, where in addition to experiences of significance and mattering, things like particular aspirations and values that “direct our efforts toward desired futures” factor in.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WADfzZ">
Working toward particular desired futures calls for taking action in the world, not just modulating brain activity. That means that more skillfully grappling with the crisis of meaning so many of us suffer may call for efforts that change the matrix of everyday life — like, for example, <a href="https://www.vox.com/the-highlight/2023/10/10/23895776/four-day-workweek-leisure-progress-labor-economy-utopia-capitalism-burnout-worker-satisfaction">empowering workers to bargain for shorter work weeks</a>, so that they have more of a say in the kinds of lives they may lead, and through them, the kinds of meaning they generate.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="q7rHGb">
To be clear, I think legal access to psychedelic therapy, even within the strictures of a medical model, is good news. But if connection is a crucial part of psychedelic meaning, we may want to <a href="https://www.vox.com/future-perfect/23721486/ketamine-dmt-lsd-psychedelics-magic-mushrooms-legalization-recreation-psilocybin">reconsider cutting it out of the formal containers in which we legalize access</a>. Focusing only on fostering more connections within the boundaries of a single, atomized brain may undermine the scope of meaning that can be produced.
</p>
<figure class="e-image">
<img alt="A woman rests on a reclining chair. She wears headphones and an eye mask and has a blanket over her lap. The room is dimly lit." src="https://cdn.vox-cdn.com/thumbor/_TOaNVXjc8eHsPNpfnMcv5-cEks=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/25106190/GettyImages_1230122600__1_.jpg"/> <cite>Cole Burston/AFP via Getty Images</cite>
<figcaption>
A woman demonstrates what a patient would experience in a therapy room at Field Trip, a psychedelic therapy clinic in Canada, in 2020.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="K5NqrE">
One implication could be to introduce <a href="https://pubmed.ncbi.nlm.nih.gov/33150319/">psychedelic group therapy</a> as a standard practice alongside individual sessions. Or to pursue <a href="https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3438542">decriminalization</a> efforts together with <a href="https://transformdrugs.org/assets/files/How-to-regulate-psychedelics.pdf">regulated access</a>, allowing communities to decide for themselves how they’d like to structure their experiences. “Group therapy should be the norm because it dovetails with the psychedelic mechanism of action,” Plesa and Petranker <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10445489/#ref56">argue</a>. Allowing for more connectedness — literally, between people — in psychedelic settings could lay the foundation for stronger experiences of meaning, solidarity, and heck, maybe even collective action to emerge.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="zbpUoz">
Another implication is to study psychedelic meaning not just as an ingredient toward therapeutic outcomes but as its own variable of interest. While the so-called psychedelic renaissance has mostly been a matter of therapeutic research, the humanities are starting to <a href="https://www.musingmind.org/podcasts/psychedelic-therapy-politics-humanities-renaissance-oliver-davis">formalize their involvement</a>. UC Berkeley’s Center for the Science of Psychedelics and Harvard’s Mahindra Humanities Center recently <a href="https://psychedelics.berkeley.edu/research-art-history-culture/">announced a joint program</a> to study the “humanistic and societal significance of psychedelics.” Christiana Musk, who directs the <a href="https://www.flourishtrust.org/">trust</a> funding the project, added that the value of psychedelics isn’t “limited to their biological effects” but extends into their deep past, as well as potential future, of “cultural development and meaning-making.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vVsyur">
Given the centrality of meaning in human life, psychedelics offer an exciting opportunity to ask new questions, or revitalize ancient ones, of one of humanity’s most enduring and alluring dimensions. But no matter how meaningful a trip, we come down from all highs. What remains as the drugs fade is the everyday world, the set, setting, and matrix for ordinary consciousness, the trip that lasts the longest and matters the most.
</p></li>
<li><strong>Why Gavin Newsom and Ron DeSantis are debating each other</strong> -
<figure>
<img alt="Split image of Ron DeSantis and Gavin Newsom, both mid-speech." src="https://cdn.vox-cdn.com/thumbor/D8ZKoXSkpJ8o__Fp34JUbcC4jyQ=/120x0:1609x1117/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72546833/headshots_1692116306691.0.jpg"/>
<figcaption>
DeSantis and Newsom could do a live debate on Fox News later this fall. | Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The thirst for attention is real.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="F5nJCV">
<a href="https://www.motherjones.com/mojo-wire/2023/08/desantis-newsom-debate-why/">In what appears to be a blatant attention grab</a> by both politicians, California Gov. Gavin Newsom and <a href="https://www.vox.com/ron-desantis/2023/7/20/23801922/ron-desantis-2024-election-republican-primary-trump-cnn-staffing-finances">Florida Gov. Ron DeSantis</a> have agreed to debate one another on live <a href="https://www.vox.com/tv">television</a> this week. Given the fact that the two aren’t actually competing head-to-head in an election, it’s a somewhat confusing event and one that is ultimately an opportunity for both to raise their national profiles and score some political points.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jTjN7Q">
A debate like this is rare: It’s not common that politicians who aren’t running against one another would attempt to do such a public face-off. Although DeSantis is vying for the 2024 Republican nomination, Newsom has already <a href="https://www.theguardian.com/us-news/2023/jun/12/gavin-newsom-interview-sean-hannity-fox-news">expressed his support for President Joe Biden</a> and said he won’t be running this cycle.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3ylo8N">
That said, both politicians clearly feel like they have something to gain from this spectacle. For Newsom, who first proposed this debate in <a href="https://twitter.com/GavinNewsom/status/1570902190964998145">September 2022</a>, it’s a chance to directly confront Republicans and to buoy his political ambitions down the line. For DeSantis, it’s an attempt to try to get a breakout moment and deflect the attention from Trump as his 2024 presidential campaign has continued to stall.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PasLGR">
The event, which has been dubbed “The Great Red vs. Blue State Debate” will take place on Thursday, November 30, at 9 pm ET, and last for 90 minutes. It will be moderated by Fox host Sean Hannity, and air live without a studio audience. Topics the two governors are expected to cover include: “the economy, the border, immigration, crime, and inflation,” according to Fox. Viewers can tune in to Fox News Channel to watch or <a href="http://FoxNews.com">FoxNews.com</a>, if they have a cable subscription.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hUqO3l">
“I think for both of them, it’s simply a chance to get attention,” says David Barker, director of the Center for Congressional and Presidential Studies at American University. “DeSantis has a lot more to lose, because if he fares poorly he might as well go home. But right now, he has to take chances because if nothing changes he’s going to go down in flames to Trump.”
</p>
<h3 id="YFsOS6">
Why are Newsom and DeSantis debating?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5y9WkL">
The short answer is that this gives both Newsom and DeSantis a way to increase their national profiles and a platform to appear as fighters for their respective parties. Additionally, it builds on a longstanding feud between the two, which has been simmering for months as Newsom has confronted DeSantis over discriminatory rhetoric toward minorities and women, and lax policies on gun control.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TB9Ykx">
<a href="https://www.politico.com/news/2023/06/06/gavin-newsom-ron-desantis-feud-00100320">As Politico’s Jeremy White has explained,</a> it’s been useful for both men to use the other as a foil as a way to show how committed they are to their own respective bases.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xVunKh">
The two governors also have their own individual reasons for wanting to participate. Although he’s vocally expressed his support for Biden in the upcoming election, Newsom has long been rumored to be interested in higher office and positioned himself as a rising star in the Democratic Party. The debate against DeSantis keeps Newsom in the spotlight and helps bolster his image as a key champion for Democratic positions ahead of the 2028 elections.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1sWAQy">
Additionally, it enables him to take a more combative approach to Republican positions, after frequently criticizing his party for not being aggressive enough. “We’re getting crushed on narrative. We’re going to have to do better in terms of getting on the offense and stop being on the damn defense,” Newsom told CBS News <a href="https://thehill.com/homenews/campaign/3715468-newsom-democrats-getting-destroyed-on-messaging/#:~:text=California%20Gov.,re%20getting%20crushed%20on%20narrative.">ahead of the midterms last year</a>. Since then, he’s appeared on <a href="https://www.vox.com/media">Fox News</a> to fact-check Republican claims on topics like immigration and launched a new political action committee that targets policies in red states.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="aeoreB">
“Gov. Newsom has been critical of the lackluster messaging and lack of aggressive hand-to-hand combat that he believes Democrats nationally need to engage in to push back against the tactics of Republicans. This is an opportunity … to punch back,” California Democratic strategist Steven Maviglio told Vox. Newsom has also described the face-off as an opportunity to tout the accomplishments of the Biden administration, which has approved of him moving forward with the debate.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="E6Jgz2">
Whether this actually bolsters Biden in any way is an open question: Newsom could potentially be a helpful surrogate and use this opportunity to boost support and funding for the campaign, though it’s also a chance to effectively sell himself.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WmFXmr">
For DeSantis, the debate is similarly an opportunity to show Republican voters that he can authoritatively push GOP stances on issues like <a href="https://www.vox.com/abortion">abortion</a>, LGBTQ rights, and crime. A chief critique of him up to this point has been his lackluster and often awkward campaign appearances, something he could try to combat via this debate. It’s a way to try to convince Trump voters that he can be an effective messenger and confront a Democrat that many Republicans have long villainized.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Pzfp6R">
“Ron DeSantis is debating Gavin Newsom to highlight the choice facing American voters next year. The left wants America to follow the path of California’s decline — Ron DeSantis wants to reignite the American Dream, restore sanity, and ensure our nation’s best days are ahead,” read a memo the DeSantis team sent donors, <a href="https://www.cnn.com/2023/08/13/politics/ron-desantis-gavin-newsom-debate/index.html">first reported by CNN</a>.
</p>
<h3 id="GJPu97">
How did this happen?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="s0vPeh">
Newsom and DeSantis have been feuding for some time, with the California governor condemning many of the Floridian’s actions, including busing migrants, and the Floridian governor slamming California cities like San Francisco for being too liberal.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LleyCq">
Following months of back-and-forth, Newsom officially challenged DeSantis to a debate in September 2022 <a href="https://twitter.com/GavinNewsom/status/1570902190964998145">via a tweet</a>. “Since you have only one overriding need — attention —let’s take this up &amp; debate,” Newsom wrote at the time. “I’ll bring my hair gel. You bring your hairspray. Name the time before Election Day.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WOGNFj">
Newsom then officially agreed to the debate during an appearance on Sean Hannity’s show on Fox <a href="https://thehill.com/homenews/campaign/4046739-newsom-says-hed-agree-to-a-debate-against-desantis-moderated-by-hannity/">in June 2023</a>. And DeSantis did the same in early August 2023. “Let’s get it done. Just tell me when and where. We’ll do it,” he said.
</p>
<h3 id="dg4PmH">
What is the point?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hmEL06">
The most interesting thing to watch in this debate is probably DeSantis’s performance, which could either give him a much-needed boost or fully sink an already struggling campaign. If DeSantis can effectively go after Newsom on progressive proposals in California and the state’s struggles with issues like homelessness, it’s possible that could help convince some Republican voters to give him another look.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YQz0tM">
“Desantis’s campaign is floundering. He needs something, apparently anything, to illustrate his fight against the ‘enemy,’” Republican strategist Chip Felkel told Vox.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="r6TP1b">
The stakes are much higher for DeSantis, who needs to show that he can hold his own against Newsom to be considered seriously by Republican voters. Newsom, meanwhile, mostly benefits from the exposure and the chance to go on the offensive against a major GOP candidate. Since he was comfortably reelected to his gubernatorial seat in 2022 and won’t be up again for a few more years, there’s far less immediate risk for him even if things don’t go so well.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WwYXf6">
“He can defend his rhetoric and record and vision, and I’ll do my best to defend mine and promote Joe Biden,” <a href="https://www.cnn.com/2023/08/13/politics/ron-desantis-gavin-newsom-debate/index.html#:~:text=%E2%80%9CRon%20DeSantis%20is%20debating%20Gavin,the%20memo%2C%20obtained%20by%20CNN.">Newsom told CNN</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Iambi2">
<em><strong>Update, November 30, 4:25 pm ET: </strong></em><em>This story was originally published on August 15 and has been updated to include details about how to watch the debate. </em>
</p></li>
<li><strong>What Henry Kissinger wrought</strong> -
<figure>
<img alt="A black-and-white photo shows Nixon on the left with Kissinger on the right, both smiling with a microphone in the background." src="https://cdn.vox-cdn.com/thumbor/UcODj1gywvaGrkYzaAYaCYCy2dM=/80x0:3000x2190/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72916489/2203744.0.jpg"/>
<figcaption>
President Richard Nixon and newly appointed Secretary of State Henry Kissinger, in 1973. | David Hume Kennerly/Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
One of America’s most important statesmen gave the world a series of diplomatic breakthroughs, and hundreds of thousands of bodies.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Laj8LZ">
Henry Kissinger, the former secretary of state who crafted foreign policy for Presidents Nixon and Ford, with an eye toward supporting friendly dictatorships that could help the US balance Soviet power, and helped direct a massive bombing campaign killing tens of thousands of Cambodians and Vietnamese, has died. <a href="https://www.vox.com/world-politics/2023/5/27/23738792/henry-kissinger-100-birthday-foreign-policy-legacy-vietnam-consultant-white-house">He was 100</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bhbJbm">
Born to a Jewish family in Weimar Germany in 1923, Kissinger fled to New York City with his family in 1938 at the age of 15 to escape Nazi persecution. He would later fight against his birth country after being drafted into the US Army during World War II. He would retire as a sergeant and earn a Bronze Star for his service.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="c3fCuN">
Before entering government, Kissinger was a tenured professor of government at Harvard. His academic work was influential in expounding a “realist” vision of foreign affairs, where great powers are forced to jockey to advance their material interests to cope with an anarchic international system, and great statesmen are needed to build a global order to prevent war between great powers.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xTTVn9">
In 1969, Kissinger left academia to serve as Richard Nixon’s <a href="https://www.vox.com/defense-and-security">national security</a> adviser. In 1973 he became secretary of state, while preserving his earlier title. He continued to serve as secretary of state through the entirety of Gerald Ford’s presidency, though he relinquished the national security adviser title to his protégé Brent Scowcroft in 1975. Throughout, he emphasized support for dictatorships friendly to the US, like Indonesia’s Suharto and Pakistan’s Agha Muhammad Yahya Khan, even as they engaged in wars killing hundreds of thousands of civilians.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="P9HKRc">
Kissinger became well-known for his advocacy of “détente” with the Soviet Union, in which US-Soviet tensions were eased through arms control negotiations and other diplomatic outreach; while Soviet <a href="https://journals.sagepub.com/doi/10.2968/066004008">nuclear stockpiles doubled</a> during Kissinger’s time in office, making it hard to argue that détente was succeeding in the near term, the <a href="https://2001-2009.state.gov/t/ac/trt/5195.htm">SALT arms control talks</a> he oversaw arguably enabled <a href="https://en.wikipedia.org/wiki/Intermediate-Range_Nuclear_Forces_Treaty">deeper</a> <a href="https://en.wikipedia.org/wiki/START_I">breakthroughs</a> in the 1980s. Kissinger was most celebrated for <a href="https://www.wbur.org/hereandnow/2022/02/18/great-wager-kissinger-china">helping engineer the US opening to the People’s Republic of China</a>, culminating in Nixon’s historic visit to the country in 1972.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8cchWm">
As national security adviser, Kissinger arranged and oversaw a massive expansion of US bombings in not just Vietnam but Cambodia and Laos as well, with a death toll experts <a href="https://www.politifact.com/factchecks/2014/sep/11/henry-kissinger/kissinger-drones-have-killed-more-civilians-bombin/">estimate at as much as 50,000</a>. Before his time in office, he acted to sabotage peace talks in Paris to end the conflict, but brought those talks to a conclusion in 1973, winning a Nobel Peace Prize. The accord, however, completely failed to end the war, which concluded with a US-South Vietnamese defeat in 1975.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="o5JacX">
After his tenure in public life ended, Kissinger briefly returned to academia before starting the consulting firm Kissinger Associates, where he <a href="https://www.nytimes.com/1989/04/30/us/kissinger-and-friends-and-revolving-doors.html">offered his deep connections with various political players around the world to businesses willing to pay</a>.
</p>
<figure class="e-image">
<img alt="Kissinger, Zhou, and Mao in a black-and-white image, as they walk and talk together." src="https://cdn.vox-cdn.com/thumbor/07u9P297RDJRHBzlXscDVQmgeZI=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/25121625/1237267392.jpg"/> <cite>Xinhua/AFP via Getty Images</cite>
<figcaption>
During President Nixon’s administration, Kissinger (seen here with Chinese Communist Party Chair Mao Zedong and Premier Zhou Enlai in 1973) helped open US relations to the People’s Republic of China.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cQZ1bu">
Throughout his career, both before and after his time in government, Kissinger enjoyed an elite status as an oft-consulted foreign policy expert and occasional book author. He lived to see the dictatorships he supported in Chile and Argentina toppled, to see the occupation he enabled in East Timor reversed, and to hear human rights advocates the world over call for his prosecution for war crimes.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9tQDrI">
Their calls were never answered, but the <a href="https://www.vox.com/policy">policies</a> they have identified represent perhaps Kissinger’s most important legacy.
</p>
<h3 id="Gp4AaM">
Henry Kissinger supported Pakistan’s genocide in Bangladesh
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nn8XiC">
As Richard Nixon’s national security adviser in 1971, Kissinger was the prime mover behind the US’s choice to quietly back West Pakistan in its campaign against residents of East Pakistan (now Bangladesh), which would claim hundreds of thousands of lives.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YO7ifO">
Kissinger’s aim was to bolster a friendly regime that also could be a crucial node in his efforts to engage <a href="https://www.vox.com/china">China</a>. While the socialist-inclined <a href="https://www.vox.com/india">India</a> was non-aligned and broadly friendly to the Soviet Union, Pakistan had become friendly with the US and prevented leftist domination of the subcontinent. At the same time, it retained productive relations with Maoist China. That made it an ideal intermediary for Kissinger’s grand plan to realign China with the United States against the Soviet Union, dramatically shifting the global balance of power in the US’s favor.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="sX9tsd">
After Bengali leader Sheikh Mujibur Rahman won the country’s elections on a platform of autonomy for the East, Pakistan’s military ruler Gen. Agha Muhammad Yahya Khan launched a vicious crackdown that included genocide against Bengali Hindus seen as sympathetic to India. Kissinger <a href="https://www.politico.com/magazine/story/2014/01/indefensible-kissinger-102123/">did not urge Yahya to respect the election results</a>, or complain about the use of US weapons against civilians, or threaten to pull aid to Pakistan.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7eEQlY">
Instead, he and Nixon conspired to illegally transfer arms to Pakistan, once India entered the war in defense of East Pakistan in December 1971. Kissinger recalled Archer Blood, the top US diplomat in East Pakistan who criticized US backing of Pakistan’s mass slaughter, and <a href="http://www.washingtonpost.com/wp-dyn/articles/A43422-2004Sep22.html">sent him to a personnel office in Washington, DC</a>, effectively ending his career as punishment for caring about civilian lives. Throughout the conflict, Kissinger urged inaction, warning internal critics of US policy that even the slightest pressure on its allies in Pakistan would backfire.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YsZayc">
Midway through the slaughter, the <a href="https://www.cia.gov/library/readingroom/document/cia-rdp79r00967a000400010005-2">CIA privately estimated that 200,000</a> had been killed. A later study using <a href="http://www.bmj.com/content/336/7659/1482.full">world health survey statistics</a> puts the total at <a href="https://www.mitpressjournals.org/doi/10.1162/ISEC_a_00258?mobileUi=0">269,000 violent war deaths</a>. Some <a href="https://www.foreignaffairs.com/articles/india/2015-09-22/when-refugees-were-welcome">10 million Bangladeshis</a> were forced into India as refugees, and <a href="https://www.theguardian.com/global-development/2019/nov/05/bangladesh-1970s-camp-survivors-speak-out">over 200,000 Bangladeshi women were raped</a> as part of an organized campaign of intimidation and terror.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MHaSkP">
Kissinger and Nixon knew exactly what was going on. In <a href="https://books.google.com/books?id=9PnNZTp3BQYC&amp;lpg=PT13&amp;vq=significant%20complicity%20in%20the%20slaughter%20of%20the%20Bengalis&amp;pg=PT13#v=onepage&amp;q&amp;f=false"><em>The Blood Telegram</em></a>, a bracing history of Nixon and Kissinger’s complicity in the killings, Princeton professor Gary Bass relays an astounding conversation where the two entertain a comparison between Pakistan’s genocide and the Holocaust, and still conclude that doing literally anything to stop it would be unwise.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="q3cB9i">
Nixon and Kissinger faced huge pressure to act from Democrats in <a href="https://www.vox.com/congress">Congress</a> (notably Sen. Ted Kennedy), from the press, from advocacy initiatives like George Harrison’s Concert for Bangladesh, from the State Department, and from some of Kissinger’s own aides. They still did nothing, a favor that did not go unnoticed by Yahya. “Yahya was effusive in his gratitude to Nixon,” Bass writes. “In a warm letter, he sympathized about the American public pressure that Nixon was withstanding, and insisted that reports of atrocities were Indian-inspired exaggerations.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="87BUj5">
Apologists for Kissinger’s support of genocide — like the Bush administration’s ambassador to India <a href="http://nationalinterest.org/article/defense-kissinger-9642">Robert Blackwill</a> — argue that standing idly by was necessary because Pakistan helped America’s opening to China. But America’s support for Pakistan preceded its use as a secret back channel to China, and <a href="https://www.politico.com/magazine/story/2014/01/indefensible-kissinger-102123/">was not the only such channel that existed</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tCv9Y7">
Kissinger himself did not view China as the main reason for backing Pakistan. Indeed, he argued in his 1979 memoir <em>White House Years</em> that the policy was correct even excluding the China factor: “I considered a policy of restraint correct on the merits, above and beyond the China connection. For better or worse, the strategy of the Nixon Administration on humanitarian questions was not to lay down a challenge to sovereignty that would surely be rejected.”
</p>
<h3 id="DTNMt1">
Henry Kissinger supported Indonesia’s bloody invasion of East Timor
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mJEGle">
As Ford’s national security adviser and secretary of state in 1975, Kissinger gave Indonesian dictator Suharto an <a href="https://www.cnn.com/2001/WORLD/asiapcf/southeast/12/06/indonesia.timor.us/">explicit green light</a> to invade East Timor, an action which resulted in the deaths of at least 100,000 civilians.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="50f9WX">
East Timor, which shares the island of Timor with Indonesia, was a Portuguese colony when Portugal’s right-wing Estado Novo dictatorship collapsed. That caused instability and a brief civil war on the island, won by the leftist party Fretilin, which then unilaterally declared independence. Indonesia shortly thereafter decided to invade and annex the territory. The US, which had partnered with Suharto a decade earlier when he overthrew a president viewed as too communist-sympathetic, was willing to play along to stabilize the region and assist a loyal ally.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4xWzub">
“We want your understanding if we deem it necessary to take rapid or drastic action,” <a href="http://nsarchive.gwu.edu/NSAEBB/NSAEBB62/doc4.pdf">Suharto asked</a> in a December 6, 1975, meeting with Ford and Kissinger. Ford replied, “We will understand and will not press you on the issue. We understand the problem you have and the intentions you have.” Kissinger added later in the conversation, “Whatever you do, however, we will try to handle in the best way possible … Our main concern is that whatever you do does not create a climate that discourages investment.” The very next day, December 7, Suharto invaded East Timor, beginning a bloody 24-year occupation ending with East Timorese independence in 1999 after years of resistance.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yDLvfj">
The Indonesian military at the time was heavily supplied by the United States through Military Assistance Program (MAP) authorizations. <a href="https://www.tandfonline.com/doi/abs/10.1080/14682740500222028">University of Connecticut historian Brad Simpson</a>, in conjunction with the <a href="https://nsarchive2.gwu.edu/indonesia/">National Security Archive at George Washington University</a>, filed FOIA requests for relevant documents around the East Timor invasion, and found a telegram from American diplomats in Jakarta to DC reporting that roughly 90 percent of the weapons Indonesia used to take East Timor came from the United States.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="IfCMIM">
Veteran journalist and businessman Adam Schwarz, in his <a href="https://www.google.com/books/edition/A_Nation_In_Waiting/AJVLDwAAQBAJ?hl=en&amp;gbpv=1&amp;pg=PT293&amp;printsec=frontcover">modern history of Indonesia</a>, cites death toll figures ranging from 100,000 to 230,000, between the years 1976 and 1980, either due to military action or indirectly due to increased starvation and disease. For context, East Timor had a pre-invasion population of about 650,000, meaning the war wiped out somewhere between 15 to 35 percent of the country’s population. Hundreds of thousands more were put in camps that featured humanitarian conditions that <a href="https://www.google.com/books/edition/East_Timor_at_the_Crossroads/7QzqSd_9MX4C?hl=en&amp;gbpv=1&amp;pg=PA67&amp;printsec=frontcover">shocked even many war-zone veterans</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WCHtbQ">
“The tragedy of East Timor is how easily Indonesia’s invasion could have been prevented by the international community, in particular by the United States,” <a href="https://www.tandfonline.com/doi/abs/10.1080/14682740500222028">Simpson writes</a>. “As the Vietnam War wound to a close, the Ford Administration possessed an unusual degree of influence over Suharto, who remained committed to military modernization using US equipment, anxious to forge closer ties to Washington, and concerned about international opinion. There is no evidence, however, that the Ford Administration even considered exerting any pressure on Indonesia not to invade.”
</p>
<h3 id="1FOcpK">
Henry Kissinger backed brutal bombing raids in Cambodia
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cXBSiL">
Many of Kissinger’s and the Nixon and Ford administrations’ worst offenses were conducted through brutal allies, like Suharto and Yahya. But one notable mass casualty event was carried out on their direct orders: the mass bombing of Cambodia.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ayYCfh">
Bombing missions in Cambodia were not an invention of the Nixon administration. The US was dropping bombs on the country during Lyndon B. Johnson’s tenure commanding the war as well. “From 1965 to 1968, 2,565 sorties took place over Cambodia, with 214 tons of bombs dropped,” historians Taylor Owen and Ben Kiernan write in their <a href="https://apjjf.org/-Taylor-Owen/2420/article.html">groundbreaking article on the Cambodian air war</a>. “These early strikes were likely designed to support the nearly two thousand secret ground incursions conducted by the CIA and US Special Forces during that period.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="otNlG2">
But the air war under Johnson and the air war under Nixon were of completely different scales. Johnson dropped 214 tons of bombs on the country; the total payload dropped on Cambodia from 1969 to 1973 was <a href="https://apjjf.org/Ben-Kiernan/4313.html">on the order of 500,000 tons</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WmSp6F">
For the first two years of the Nixon bombing effort, Owen and Kiernan explain, the campaign was mostly limited to the Vietnamese border area, albeit with much larger payloads than under Johnson. The Viet Cong and North Vietnamese had substantial presences in the area, and Nixon and Kissinger viewed them as a legitimate military target despite a lack of congressional authorization.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tBG1gX">
Then the effort truly ramped up in December 1970 on direct orders from Nixon, who told then-National Security Adviser Kissinger he wanted more bombing, deeper into the country, with “no limitation on mileage and … no limitation on budget.” Kissinger dutifully passed along the order, telling Gen. Alexander Haig, “He wants a massive bombing campaign in Cambodia. He doesn’t want to hear anything. It’s an order, it’s to be done. Anything that flies, on anything that moves. You got that?” <a href="https://apjjf.org/-Taylor-Owen/2420/article.html">Owen and Kiernan note</a> that Haig’s response “barely audible on tape, sounds like laughter.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="d62qHd">
In humanitarian terms, these bombings were a disaster. <a href="https://www.politifact.com/factchecks/2014/sep/11/henry-kissinger/kissinger-drones-have-killed-more-civilians-bombin/">Kiernan’s preferred estimate</a> is that Nixon and Kissinger’s policy killed between 50,000 and 150,000 civilians directly through the bombings, with the high-end figure more likely. Other <a href="https://sites.tufts.edu/atrocityendings/2015/08/07/cambodia-u-s-bombing-civil-war-khmer-rouge/#1Fatalities">estimates run even higher</a>, up to 300,000 or so.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BnwcZV">
But Owen and Kiernan emphasize that <a href="https://apjjf.org/-Taylor-Owen/3380/article.html">the biggest cost of Kissinger’s policy may have been indirect</a>. The prolific bombing campaigns provided valuable propaganda material for the Khmer Rouge insurgency challenging Gen. Lon Nol, the pro-US military dictator who overthrew Cambodia’s king in 1970. The Khmer Rouge would eventually succeed in overthrowing Nol’s government in 1975, and would embark on one of the most rapid and brutal genocides in human history.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ma3Gn2">
“These successive tragedies are not unrelated,” Owen and Kiernan write. “It is only predictable that an insurgency in need of recruits may effectively exploit potential supporters’ hatred for those killing their family members or neighbors.”
</p>
<h3 id="oKhVRE">
Henry Kissinger sabotaged peace talks with Vietnam
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WxbERL">
Kissinger’s record influencing Vietnam policy began even before he joined the Nixon administration. While serving as an adviser to the Johnson-Hubert Humphrey administration in the Paris Peace Talks of 1968, <a href="https://www.vox.com/the-big-idea/2017/7/19/15994924/nixon-trump-vietnam-russia-historical-parallels">Kissinger fed confidential information from the proceedings to Nixon’s campaign</a>, which in turn passed the intelligence along to the South Vietnamese government. This contributed to the scuttling of the talks, and the continuation of the war for seven more years.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Hc7vTZ">
As Nixon <a href="https://www.vox.com/the-big-idea/2017/7/19/15994924/nixon-trump-vietnam-russia-historical-parallels">biographer John A. Farrell</a> has recounted, the plot centered around Anna Chennault, a Republican fundraiser and ardent anti-communist. Chennault met with Nixon, his campaign manager John Mitchell, and South Vietnamese ambassador to the US Bui Diem in 1968, where they arranged for Chennault to work as a conduit between the campaign and South Vietnam. Kissinger was aware of this connection, and that conversations with Mitchell could get back to South Vietnam.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bxjLxt">
In “late September, and again in early October 1968,” Kissinger (still working for LBJ at this point) leaked to Mitchell that there was “a better than even chance” that the Johnson administration would halt air strikes on North Vietnam in hopes of reaching a peace deal. The Soviet leadership, which as the North’s military and financial backer had deep influence over its government, had informed Johnson that a halt to bombings would “contribute to a breakthrough.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bmEV23">
“On October 31, Johnson announced his bombing halt,” Farrell writes, “But South Vietnamese President Nguyen Van Thieu dragged his feet, announcing his reluctance to join in peace talks. … Without Thieu’s support, the bombing halt looked like a cheap political trick, employed to get Humphrey elected.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tVjO30">
Chennault, it turned out, had passed along Kissinger’s intel to the South Vietnamese, convincing them to hold out for a better deal under Nixon rather than come to the table under Johnson (and his preferred successor Humphrey).
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xTK4fK">
Kissinger was hardly the only person involved in this plot, and, as Farrell makes clear, the Johnson administration was probably engaged in wishful thinking about the prospects for a diplomatic breakthrough. But Kissinger’s choice to assist the Nixon team’s efforts at sabotage certainly damaged whatever weak hope there was of a deal, and of the lives that would have been saved with a deal.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pekgLY">
The Paris talks would drag on for four more years before ending on January 27, 1973, with a deal that provided for the removal of all US troops; Kissinger shared a Nobel Peace Prize for finalizing talks he had sabotaged over four years and at least <a href="https://www.archives.gov/research/military/vietnam-war/casualty-statistics">21,126 American combat deaths</a> earlier (not to mention the untold tens of thousands of Vietnamese, Cambodian, and Lao deaths that took place in those years). Within months, though, North and South Vietnam began fighting again, and two years after the accords North Vietnam invaded and annexed the South.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="kSZ55Z">
Kissinger reportedly <a href="https://www.latimes.com/archives/la-xpm-1987-12-05-mn-6447-story.html">tried to return the Nobel Peace Prize</a> he won for negotiating the treaty when Saigon fell in 1975; his North Vietnamese counterpart, Lê Đức Thọ, <a href="https://time.com/4061794/nobel-peace-prize-winner-history/">refused the prize</a> in the first place, as no peace had been won.
</p>
<h3 id="zkqI4n">
Henry Kissinger supported military coups against democratic leaders in Chile and Argentina
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fWZ0Uz">
While it did not result in the same body count as his actions in regard to Cambodia, Bangladesh, and East Timor, Kissinger’s Latin American policy has long been a focus of critical assessments of his tenure from figures like <a href="https://smile.amazon.com/Trial-Henry-Kissinger-Christopher-Hitchens/dp/145552297X">Christopher Hitchens</a> and <a href="https://smile.amazon.com/Pinochet-File-Declassified-Atrocity-Accountability/dp/1595589120?sa-no-redirect=1">Peter Kornbluh</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pdXPrx">
Like American policymakers before and after him, Kissinger’s focus in Latin America was on disrupting or dislodging leftist regimes he feared would give the Soviet Union a foothold in the region, and on backing rightists, including right-wing autocrats if necessary, to ensure that happened. His most notable efforts in this regard were in Chile — resisting democratically elected socialist president Salvador Allende and backing Gen. Augusto Pinochet, who deposed Allende — and in Argentina, where Kissinger extended US support to the junta of Gen. Jorge Rafael Videla after Videla overthrew President Isabel Perón.
</p>
<figure class="e-image">
<img alt="A black-and-white photo shows Chilean President Salvador Allende surrounded by people and waving to the camera." src="https://cdn.vox-cdn.com/thumbor/aLzY_zUAcKxGuYE0KPqaNWjL1k4=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/25121639/514685624.jpg"/> <cite>Bettmann Archive</cite>
<figcaption>
After the democratic election of socialist President Salvador Allende, seen here in 1970, Nixon’s administration gave the CIA unprecedented authority to “save Chile.”
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="iXKFQI">
Kissinger’s involvement in Chile began in 1970, when Allende won a surprise narrow plurality in the year’s presidential elections. This led to a scramble in DC for plans to avoid Allende’s ascension to office, either through legal political maneuvering or through covert operations like fomenting a military coup. The former, legal option was known in the Nixon government as “Track I”; the latter, to be overseen by then-National Security Adviser Kissinger, was called “Track II.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GAwBil">
As historian Kristian Gustafson <a href="https://www.cia.gov/static/d4e6cc0b43a66a60efbca83b1ad0477f/CIA-Machinations-in-Chile.pdf">explains in an article</a> for the CIA’s Center for the Study of Intelligence, Nixon was fully panicked by the idea of another Marxist government — even one as relatively moderate as Allende’s — in the Western Hemisphere, and gave unprecedented authority to the CIA to take measures necessary to “save Chile.” Track II took shape less than four weeks after the 1970 election, when the CIA (on White House orders, with which Kissinger would have certainly been involved) sent four false-flag officers to Chile to make contact with military officers and reassure them of US support for a coup.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZE1zpa">
CIA deputy director of plans Thomas Karamessines <a href="https://nsarchive2.gwu.edu/NSAEBB/NSAEBB8/nsaebb8i.htm">sent a cable</a> to the agency’s station in Santiago, Chile, during this period in which he summarized Kissinger’s orders thusly: “It is firm and continuing policy that Allende be overthrown by a coup.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PLLa0l">
Track II options, it became clear, would involve either retired Gen. Roberto Viaux, an ultra-rightist who was (in Gustafson’s words) “unstable,” or active Gen. Camilo Valenzuela, who was more moderate. The CIA initially opened contact with Viaux but stopped working with him when they determined he had no support in the military. But Gustafson writes, “the pressure on Agency officers in Santiago to come up with a ‘solution’ to the Allende problem was massive.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5lcGnJ">
One of the first targets of Track II was Gen. René Schneider, the head of the Chilean military and a strong believer in civilian government. Schneider was a key bulwark within the military against coups targeting Allende, and his exile or death was viewed as an essential precondition to ousting Allende. The agency eventually provided submachine guns and tear gas grenades to support a plot by Valenzuela to kidnap Schneider.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uimgR4">
Valenzuela tried and failed twice, after which Viaux’s agent successfully murdered Schneider. Both Viaux and Valenzuela were eventually <a href="https://www.washingtonpost.com/archive/politics/2001/09/11/family-of-slain-chilean-sues-kissinger-helms/2439f3a4-dfe0-418c-9454-de6052e4df55/">found culpable in Chilean court</a> for their involvement in Schneider’s death, though defenders of Kissinger are quick to note that Valenzuela’s US-backed team did not actually succeed in killing or kidnapping Schneider. “In legal terms, a US judicial proceeding would surely have concluded that US agents (acting on presidential authority) had been at least accessories before the fact,” veteran diplomat and historian William Bundy concludes in his history of Nixon and Kissinger’s foreign policy, <a href="https://books.google.com/books?id=TeBaZtj7PDMC&amp;lpg=PT362&amp;ots=H8Ri1HTk_n&amp;dq=%22judicial%20proceeding%20would%20surely%20have%20concluded%20that%20U.S.%20agents%22&amp;pg=PT362#v=onepage&amp;q&amp;f=false"><em>A Tangled Web</em></a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lnlYdZ">
Flash forward three years, and the Allende administration was in crisis, with record inflation, escalating conflict bordering on a constitutional crisis with Congress, and widespread strikes (some <a href="https://www.nytimes.com/1974/09/20/archives/cia-is-linked-to-strikes-in-chile-that-beset-allende-intelligence.html">funded by the CIA</a>), particularly among white-collar workers and businessmen negatively affected by <a href="https://www.nytimes.com/1971/08/12/archives/strikes-adding-to-allende-woes.html">Allende’s nationalization of copper mines</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nur0ib">
On <a href="https://en.wikipedia.org/wiki/1973_Chilean_coup_d%27%C3%A9tat">September 11, 1973</a>, a group of conservative generals first seized the coastal city of Valparaiso, then moved onto the capital of Santiago; by the afternoon, an aerial and ground assault on the presidential palace had solidified the coup’s success. Allende died (most likely by suicide) after attempting to defend the palace with his aides. The junta swiftly banned Allende’s and allied leftist political parties and began sweeping up tens of thousands of leftists in a wave of repression; <a href="https://www.nytimes.com/2015/06/19/sports/soccer/in-chiles-national-stadium-dark-past-shadows-copa-america-matches.html">some 20,000 people</a> were detained in Santiago’s football stadium. Gen. Augusto Pinochet quickly became the dominant force in the new regime and would rule as a dictator until 1990.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3UhyUi">
An <a href="https://www.cbc.ca/news/world/chile-dictatorship-victim-toll-bumped-to-40-018-1.998542">official government report</a> would later conclude that the repression during Pinochet’s regime resulted in 40,018 people being killed, tortured, or imprisoned on political charges; of those, about 3,065 were killed or forcibly disappeared.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jaT9K2">
Kissinger has always stridently denied any personal or US government involvement in the 1973 coup, though it’s clear that the US was actively fomenting coup attempts only three years earlier, and was actively funding opposition groups to Allende throughout his presidency. Upon Pinochet’s usurpation of power, the US swiftly recognized and established friendly relations with the new regime.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9QSoQB">
Peter Kornbluh, the historian and journalist whose declassification efforts have revealed tremendous amounts about US involvement in Chile, concludes in his book <a href="https://books.google.com/books?id=fJNnAgAAQBAJ&amp;lpg=PP106&amp;ots=AoK9wTCb3y&amp;dq=%22the%20CIA%20does%20not%20appear%20to%20have%20been%20involved%20in%20the%20violent%20actions%20of%20the%20Chilean%20military%22&amp;pg=PP106#v=onepage&amp;q&amp;f=false"><em>The Pinochet File</em></a> that “By the most narrow definition of ‘direct role’ — providing planning, equipment, strategic support, and guarantees — the CIA does not appear to have been involved in the violent actions of the Chilean military on September 11, 1973.” But, he continues, “the Nixon White House sought, supported, and embraced the coup.” Or, as Kissinger put it in a recorded conversation with Nixon five days after the coup, “We didn’t do it. I mean we helped them. [inaudible] created the conditions as great as possible.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2HOvK9">
Kissinger took a similar attitude to the March 24, 1976, overthrow of Argentinian president Isabel Perón by Gen. Jorge Rafaél Videla and other military figures. State Department documents show that a month before the coup, the generals attempted to meet with Kissinger personally, viewing him as a friendly contact. Robert Hill, the American ambassador, discouraged this because of the risk of backlash if the meeting became public, but <a href="https://nsarchive.gwu.edu/document/20742-03">wrote in an internal cable</a>, “embassy has discreetly and through third parties already indicated to the military that the [US government] will recognize a new government in Argentina.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="go3FCr">
“There is no evidence that the US instigated the coup,” <a href="https://nsarchive.gwu.edu/briefing-book/southern-cone/2021-03-23/argentinas-military-coup-what-us-knew">Carlos Osorio of the National Security Archive said</a> upon the declassification of important documents from this period. “But the United States accepted, and tacitly supported, regime change because Washington shared the military’s position that the putsch was the only alternative to chaos in Argentina.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="w793MQ">
The support continued after the transition to military rule. Even having been warned by adviser William Rogers to “expect a fair amount of repression, probably a good deal of blood,” Kissinger then <a href="https://nsarchive2.gwu.edu/NSAEBB/NSAEBB185/index.htm">requested that Congress authorize $50 million</a> in funding for the Argentinian military; it complied.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1WOOY3">
In June, Kissinger met personally with the junta’s foreign minister, Adm. Cesar Augusto Guzzetti, and told him, “We wish the new government well. <a href="https://nsarchive2.gwu.edu/NSAEBB/NSAEBB133/">We wish it will succeed. We will do what we can to help it succeed</a> … It is a curious time, when political, criminal, and terrorist activities tend to merge without any clear separation. We understand you must establish authority.” He warned, though, “If there are things that have to be done, you should do them quickly.” Kissinger knew at the time that the junta was already engaged in large-scale repression, including murders and disappearances.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WcztpR">
Kissinger <a href="https://www.theguardian.com/world/2016/aug/09/henry-kissinger-mass-killings-argentina-declassified-files">continued supporting the junta as a private citizen</a>, most notably visiting during the 1978 <a href="https://www.vox.com/fifa-world-cup">World Cup</a> as a personal guest of Videla, causing serious problems for the Carter administration’s attempts to pressure the junta to halt the killing.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7dsErS">
After Argentina’s return to democracy in 1983, the national government <a href="https://www.icmp.int/the-missing/where-are-the-missing/argentina/">documented at least 8,961 specific deaths and disappearances</a> as part of the junta’s crackdown on dissent. That is almost certainly an undercount, and human rights groups <a href="https://www.hrw.org/news/2013/05/17/argentina-death-jorge-rafael-videla">cite death and disappearance tolls as high as 30,000</a>. Famously, many of the disappeared were <a href="http://www.cnn.com/WORLD/9603/argentina.war/index.html">dropped out of helicopters</a> into the Atlantic Ocean. Videla died in 2013 while in Argentinian prison for his crimes; he had been convicted in three separate trials of torture, kidnapping, and homicide, among other charges.
</p>
<h3 id="1cWE6X">
Henry Kissinger’s good deed: opening China
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qSZPgp">
Kissinger’s tenure in government is largely characterized by support for brutal dictatorships he saw as useful to American interests. In at least one case, this approach to diplomacy resulted in a breakthrough with largely positive consequences: the US opening to the People’s Republic of China.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="msimEe">
Much of Kissinger’s positive reputation rests on his central role in back-channel negotiations with the Chinese government in 1971 that culminated in his <a href="https://nsarchive2.gwu.edu/NSAEBB/NSAEBB66/">secret trip to Beijing that year</a> (the first by a senior American official since the Communist takeover in 1949) and President Nixon’s historic visit in 1972. By the Carter administration, the US and China had normalized diplomatic relations. This pivot not only changed the trajectory of the Cold War with the Soviet Union and weakened the latter’s power substantially, but paved the way for a <a href="https://www.aeaweb.org/articles?id=10.1257/aer.20141419">robust trade relationship between the US and China</a> that contributed to the latter’s <a href="https://data.worldbank.org/indicator/SI.POV.DDAY?locations=CN">monumental reduction in extreme poverty in recent decades</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rbE4zc">
Kissinger no doubt deserves substantial credit for these developments, a point he has made at great length in <a href="https://www.nytimes.com/2011/05/10/books/on-china-by-henry-kissinger-review.html">his own writings</a>. Some caveats are in order, though. For one thing, the opening was a two-way street: China had as much reason, or more, to engage as the US did. It was recovering from the chaos of the Cultural Revolution and in 1969 had <a href="https://en.wikipedia.org/wiki/Sino-Soviet_border_conflict">nearly faced a war with the Soviet Union</a>. Gaining the US as a strategic partner brought huge advantages. Nixon and Kissinger were hardly unique in seeing this as an opportunity; as journalist and historian James Mann notes, <a href="https://www.latimes.com/opinion/story/2022-02-21/richard-nixon-henry-kissinger-trip-to-china-50th-anniversary-taiwan-vietnam-war">Democratic Sens. Mike Mansfield</a> and <a href="https://www.nyujlpp.org/wp-content/uploads/2012/10/Jerome-A.-Cohen-Ted-Kennedys-Role-in-Restoring-Diplomatic-Relations-with-China.pdf">Ted Kennedy</a> had previously attempted to visit Beijing to thaw relations, only to have the Nixon administration shut them down.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="C5Itju">
Further, the exact way that Kissinger reached out has had major negative ramifications for the present day — specifically around Taiwan, and on US-China relations regarding that issue. As the diplomatic historian Nancy Bernkopf Tucker documented, Kissinger was uninterested in the Taiwan question (relative to securing Chinese cooperation on Vietnam and against the Soviets) and so <a href="https://www.jstor.org/stable/3660527">made astonishing concessions</a> on the topic to further negotiations on other fronts. These included a full US military withdrawal from the island, a pledge to never support Taiwan independence, and a conspicuous lack of any demand that China renounce the use of force in retaking the island.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nlJnsZ">
Kissinger’s statements, Tucker concludes, led Chinese leaders to believe that “the Americans would not stand in the way; Taiwan would be theirs.” That this proved untrue, and it became clear the US would resist a retaking of the island, led Beijing to feel betrayed, and helped create the current unsteady equilibrium between the US, China, and Taiwan. It’s unclear whether Kissinger or Nixon could have achieved an opening with China in which the latter accepted Taiwan’s independence, but in any case they did not try.
</p>
<h3 id="oSREmE">
Kissinger’s ultimate legacy
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6QowYt">
Kissinger’s time in power touched on nearly every region of the globe and arena of American foreign policy, and he even played a crucial role in the Watergate scandal and the denouement of the Nixon presidency. The president <a href="https://www.archivesfoundation.org/documents/richard-nixon-resignation-letter-gerald-ford-pardon/">famously addressed his resignation letter to his secretary of state</a>. It is not possible in a single article, even one of this length, to cover his entire career and every policy he touched.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="da7qLC">
While many of the effects of his decisions were calamitous, Kissinger had a clear and oft-articulate rationale for them. He viewed himself not as a crusader for just causes or as a moralist of any kind, but as a tenacious and tireless guarantor of international stability through the pursuit of a balance of superpowers. Attaining that balance required decisions with large humanitarian tolls, but the prize being won was the United States’ survival and the prevention of great-power war.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XXfk31">
As <a href="https://www.theatlantic.com/magazine/archive/2013/05/the-statesman/309283/">Robert Kaplan</a>, Kissinger’s friend and defender, once wrote, “Henry Kissinger believes that in difficult, uncertain times — times like the 1960s and ’70s in America, when the nation’s vulnerabilities appeared to outweigh its opportunities — the preservation of the status quo should constitute the highest morality.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="E1jpdU">
This is Kissinger’s defense, and one he had the opportunity to make in countless books, articles, and speeches over the decades. As we contemplate his life upon its end, the question is whether all the carnage was actually necessary for stability and peace — or whether that is just a comforting delusion.
</p></li>
</ul>
<h1 data-aos="fade-right" id="from-the-hindu-sports">From The Hindu: Sports</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Rasputin shines</strong> -</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ganguly bats for Rohit Sharma as Indian captain till 2024 T20 World Cup</strong> - Sourav Ganguly said Rohit Sharma and Virat Kohli deserved rest so that they come back “fresh” for the hectic calendar ahead.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Mitchell Marsh defends picture of resting feet on World Cup trophy, says he would do it again</strong> - Mitchell Marsh’s picture with the World Cup trophy, which went viral on social media, didn’t sit well with Indian fans</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Europa League | Liverpool advances after win over LASK; Aubameyang scores hat-trick for Marseille</strong> - Luis Diaz, Cody Gakpo and Mohamed Salah scored in Liverpool’s 4-0 win over LASK to advance to the Europa League Round of 16</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Dominica withdraws from hosting 2024 T20 World Cup matches</strong> - Dominica was one of seven countries in the West Indies selected to stage the World Cup matches in June 2024 along with the United States.</p></li>
</ul>
<h1 data-aos="fade-right" id="from-the-hindu-national-news">From The Hindu: National News</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Depression in Bay of Bengal may turn into cyclone</strong> - It is likely to cross the coast between Chennai and Machilipatnam, says APSDMA officials</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Andhra Pradesh| CPI writes to Governor Nazeer seeking intervention on beach sand mining contracts in State</strong> - Despite Union government’s restrictions on allowing private companies to do beach sand mining, attempts are being made to hand over mining project contract in the State to the Adani Group, Ramakrishna claims</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Here are the big stories from Karnataka today</strong> - Welcome to the Karnataka Today newsletter, your guide from The Hindu on the major news stories to follow today. Curated and written by Nalme Nachiyar.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>PIB fact-check unit flags nine YouTube channels for allegedly spreading fake news</strong> - They are alleged to have misattributed derogatory statements to persons occupying constitutional positions, including the Chief Justice of India, the Prime Minister, and the Chief Election Commissioner</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Paucity of funds, drought forces Kannada Sahitya Parishath to postpone 87th Akhila Bharata Kannada Sahitya Sammelana indefinitely</strong> - Kannada Sahitya Parishath had sought ₹25 crore from the government for the festival, but the money has not materialised</p></li>
</ul>
<h1 data-aos="fade-right" id="from-bbc-europe">From BBC: Europe</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ukraine war: Zelensky says fortifying front lines must be accelerated</strong> - Ukraine’s president meets frontline commanders and says winter is a new phase of the war with Russia.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Israel recalls ambassador in war spat with Spain PM Pedro Sánchez</strong> - Pedro Sánchez deepens a row, saying he has “serious doubts” Israel is complying with humanitarian law.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ukraine: Russian general ‘blown up on mine’</strong> - Several pro-Kremlin sources reported Maj-Gen Vladimir Zavadsky’s death, but his location is unclear.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Russian court bans ‘LGBT movement’</strong> - Russia’s Supreme Court declares the “international LGBT public movement” an extremist organisation.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Passengers stuck on Eurostar with no electricity</strong> - Eurostar posted on X that a train was “being detached from the overhead power lines”.</p></li>
</ul>
<h1 data-aos="fade-right" id="from-ars-technica">From Ars Technica</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Google researchers report critical zero-days in Chrome and all Apple OSes</strong> - Discoveries made by Google’s Threat Analysis Group, which tracks nation-state hacking. - <a href="https://arstechnica.com/?p=1987731">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Steam drops macOS Mojave support, effectively ending life for many 32-bit games</strong> - After February 15, all bets are off for Steam on High Sierra and Mojave Macs. - <a href="https://arstechnica.com/?p=1987721">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Automatic bike transmission concept is wild and spiky—and could be a big shift</strong> - Solo inventor says he’s not out to replace gears, just offer an alternative. - <a href="https://arstechnica.com/?p=1987481">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Elon’s Edsel? The Tesla Cybertruck went on sale today</strong> - Tesla handed over the first 10 trucks to customers, with more deliveries in 2024. - <a href="https://arstechnica.com/?p=1987661">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Reddit updates look after rough 6 months and ahead of reported IPO</strong> - “Edit: Obligatory ‘F— Spez’ for karma.” - <a href="https://arstechnica.com/?p=1987576">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-jokes-subreddit">From Jokes Subreddit</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Bubba died in a fire and his body was burned pretty badly.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Bubba died in a fire and his body was burned pretty badly. The morgue needed someone to identify the body, so they sent for his two best friends, Cooter and Gomer. The three men had always done everything together.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Cooter arrived first, and when the mortician pulled back the sheet, Cooter said, “Yup, his face is burned up pretty bad. You better roll him over.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The mortician rolled him over and Cooter said, “Nope, ain’t Bubba.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The mortician thought this was rather strange. So he brought Gomer in to confirm the identity of the body. Gomer looked at the body and said, “Yup, he’s pretty well burnt up… Roll him over.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The mortician rolled him over and Gomer said, “No, it ain’t Bubba.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The mortician asked, “How can you tell?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Gomer said, “Well, Bubba had two assholes.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“What? He had two assholes?” asked the mortician.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
"Yup, we never seen ‘em, but everybody used to say, ’There’s Bubba with them two assholes.’
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/SpiceCake68"> /u/SpiceCake68 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/18811hp/bubba_died_in_a_fire_and_his_body_was_burned/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/18811hp/bubba_died_in_a_fire_and_his_body_was_burned/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A guy gets too drunk while playing golf and forgets what hole he’s on</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
He sees a woman ahead of him and yells “what hole am I on?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
She says “you must be on the hole behind me and I’m on 5, so you must be on 4.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
He plays a few holes and forgets again. He sees her and yells “hey, what hole am I on now?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
She says “you’re on the hole behind me and I’m on 12, so you must be on 11.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
He eventually finishes and goes to the clubhouse bar for one last beer. He sees the woman, thanks her for the help, and asks what she does.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“It’s kind of embarrassing, please don’t laugh. But I sell menstrual supplies.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The man starts laughing hysterically and she glares at him, obviously upset at his laughing.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“No no no, I’m not laughing at what you do” he says. “It’s just that I sell toilet paper. So I’m on the hole behind you.”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Duke-Wonder"> /u/Duke-Wonder </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/187s3mx/a_guy_gets_too_drunk_while_playing_golf_and/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/187s3mx/a_guy_gets_too_drunk_while_playing_golf_and/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Little Johny was assigned to perform an experiment for his biology class</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
</p><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">Little Johny decided to run the experiment on the auditory system of his cockroach, Mark, since it didn’t pay rent anyway.</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"></p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
</p><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">To keep track of the things he performed, little Johny wrote down all the steps in his journal:</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"></p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
</p><ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">Day 1: I blew a vuvuzela directly to Mark’s ears. The cockroach run away.
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"></p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
</p><ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">Day 2: I broke Mark’s 2 front legs and blew the vuvuzela again. The cockroach run away, again.
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"></p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
</p><ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">Day 3: I broke all of Mark’s legs and blew the vuvuzela as hard as I could. The cockroach didn’t run anywhere. Conclusion: Without any legs, Mark can’t hear.
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"></p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
P. S.: It’s a stupid high-school joke I heard almost 30 years ago.
</p>
</li></ul></li></ul></li></ul></div>
<!-- SC_ON -->
submitted by <a href="https://www.reddit.com/user/virusnac"> /u/virusnac </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1887krz/little_johny_was_assigned_to_perform_an/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1887krz/little_johny_was_assigned_to_perform_an/">[comments]</a></span></li>
</ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A priest walks into a hotel and books a room.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The priest says to the clerk.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“I assume the porn is disabled?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The clerk says.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“No it’s just regular porn you filthy bastard.”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/controller4hire"> /u/controller4hire </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/18850si/a_priest_walks_into_a_hotel_and_books_a_room/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/18850si/a_priest_walks_into_a_hotel_and_books_a_room/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What do you even expect?</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Three friends bragged about who has more sex…. Friend A said “You all have nothing on me. I go to the bar and bring home a woman every night. Not only that but I drive a corvette into work everyday and have a 8 inch penis. I have slept with more than 1,000 women”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Friend B said “Oh yeah? Well I’m the top gynecologist doctor at the most highly rated hospitals in the world. I make $800,000 a year, have patients and nurses who have sex with me every hour I’m at work. All the women compliment me on my 12 inch penis. I have slept with well over 5,000 women.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Friend C said, “I have you all beat. I fucked over all the Redditors who were expecting a punchline to this joke.”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Alternative-Sense965"> /u/Alternative-Sense965 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1885ha1/what_do_you_even_expect/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1885ha1/what_do_you_even_expect/">[comments]</a></span></p></li>
<script>AOS.init();</script></body></html>

4
index.html
View File

File diff suppressed because one or more lines are too long