A worldwide struggle between democracy and authoritarianism set against a backdrop of global surveillance capitalism is unmistakable. Examples range from Myanmar, China, and the Philippines to ...Hungary, Turkey, Russia, and the United States. Fascism, Vulnerability, and the Escape from Freedom offers a multidisciplinary analysis drawing on psychology and literature to provide readers with a deeper understanding of the mechanisms that drive people to abandon democracy in favor of vertically organized authoritarianism and even fascism. In a comparative study of texts selected for their insights and occasional blind spots regarding fascist experiments of the past 100 years, Delogu examines fascism’s exploitation of fear (of change, loss, and death), disruption, and extreme inequality. The book offers an accessible and persuasive argument linking fascist authoritarianism, also called “right-wing populism,” to certain underlying conditions, such as a rise in us-versus-them thinking; distrust or simple apathy regarding democratic institutions, norms, and results; the vulnerabilities that result from extreme inequality (economic, social, racial); and addictions and codependency. Stressful events, such as a pandemic, an environmental disaster, or deep recession aggravate these harmful factors and make the fascist temptation, including the use of violence, almost irresistible. Delogu’s distinctive examination of texts that plumb the unconscious reveal linkages between actions and unavowable motives that purely historical and theoretical studies of fascism leave out. Erich Fromm’s neglected 1941 classic Escape from Freedom serves as a key reference in Delogu’s study, as does Robert Paxton’s authoritative history, The Anatomy of Fascism (2004). After underscoring the argument and urgent context around these two studies (Hitler’s Germany and George W. Bush’s post-9/11 America), Delogu examines novels, a diary, memoirs, and manifestos to show how vulnerability forces individuals to choose between exclusionary fascist authoritarianism and inclusive, collaborative democracy.
Curcumin is the major yellow pigment extracted from turmeric, a commonly used spice in Asian cuisine and extensively employed in ayurvedic herbal remedies. A number of studies have shown that ...curcumin can be a prevention and a chemotherapeutic agent for colon, skin, oral and intestinal cancers. Curcumin is also well known for its antiinflammatory and antioxidant properties, showing high reactivity towards peroxyl radicals, and thus acting as a free radical scavenger. Recently, experimental studies have demonstrated that curcumin might be used in the prevention and the cure of Alzheimer's disease. Indeed, curcumin injected peripherally in vivo into aged Tg mice crossed the blood-brain barrier and bound to amyloid plaques, reducing amyloid levels and plaque formation decisively. The present review will resume the most recent developments in the medicinal chemistry of curcumin and curcumin-like molecules.
Cancer represents one of the main causes of death in the world; hence the development of more specific approaches for its diagnosis and treatment is urgently needed in clinical practice. Here we aim ...at providing a comprehensive review on the use of 2-dimensional materials (2DMs) in cancer theranostics. In particular, we focus on graphene-related materials (GRMs), graphene hybrids, and graphdiyne (GDY), as well as other emerging 2DMs, such as MXene, tungsten disulfide (WS2), molybdenum disulfide (MoS2), hexagonal boron nitride (h-BN), black phosphorus (BP), silicene, antimonene (AM), germanene, biotite (black mica), metal organic frameworks (MOFs), and others. The results reported in the scientific literature in the last ten years (>200 papers) are dissected here with respect to the wide variety of combinations of imaging methodologies and therapeutic approaches, including drug/gene delivery, photothermal/photodynamic therapy, sonodynamic therapy, and immunotherapy. We provide a unique multidisciplinary approach in discussing the literature, which also includes a detailed section on the characterization methods used to analyze the material properties, highlighting the merits and limitations of the different approaches. The aim of this review is to show the strong potential of 2DMs for use as cancer theranostics, as well as to highlight issues that prevent the clinical translation of these materials. Overall, we hope to shed light on the hidden potential of the vast panorama of new and emerging 2DMs as clinical cancer theranostics.
Although the mechanisms underlying the pathophysiology of long COVID condition are still debated, there is growing evidence that autonomic dysfunction may play a role in the long-term complications ...or persisting symptoms observed in a significant proportion of patients after SARS-CoV-2 infection. However, studies focused on autonomic dysfunction have primarily been conducted in adults, while autonomic function has not yet been investigated in pediatric subjects. In this study, for the first time, we assessed whether pediatric patients with long COVID present abnormalities in autonomic cardiac function. Fifty-six long COVID pediatric patients (mean age 10.3 ± 3.8 y) and 27 age-, sex-, and body surface area-matched healthy controls (mean age 10.4 ± 4.5y) underwent a standard 12-lead electrocardiography (ECG) and 24-h ECG Holter monitoring. Autonomic cardiac function was assessed by time-domain and frequency-domain heart rate variability parameters. A comprehensive echocardiographic study was also obtained by two-dimensional echocardiography and tissue Doppler imaging. Data analysis showed that pediatric patients with long COVID had significant changes in HRV variables compared to healthy controls: significantly lower r-MSSD (root mean square of successive RR interval differences, 47.4 ± 16.9 versus 60.4 ± 29.1,
p
= 0.02), significant higher values VLF (very low frequency, 2077.8 ± 1023.3 versus 494.3 ± 1015.5 ms,
p
= 0.000), LF (low frequency, 1340.3 ± 635.6 versus 354.6 ± 816.8 ms,
p
= 0.000), and HF (high frequency, 895.7 ± 575.8 versus 278.9 ± 616.7 ms,
p
= 0.000). No significant differences were observed between the two groups both in systolic and diastolic parameters by echocardiography.
Conclusion
: These findings suggest that pediatric patients with long COVID have an imbalance of cardiac autonomic function toward a relative predominance of parasympathetic tone, as already reported in adult patients with long COVID. Further studies are needed to clarify the clinical significance of this autonomic dysfunction and demonstrate its role as a pathophysiological mechanism of long COVID, paving the way for effective therapeutic and preventive strategies.
What is Known:
• Long Covid in children has been described globally, but studies have mostly focused on collecting the temporal evolution of persisting symptoms.
What is New:
• Cardiac autonomic imbalance toward a relative predominance of parasympathetic tone is a mechanism underlying Long Covid in children, as also described in adults.
Increasing physical activity is a key therapeutic aim in chronic obstructive pulmonary disease (COPD). Pulmonary rehabilitation (PR) improves exercise capacity, but there is conflicting evidence ...regarding its ability to improve physical activity levels.
To determine whether using pedometers as an adjunct to PR can enhance time spent in at least moderate-intensity physical activity (time expending ≥3 metabolic equivalents METs) by people with COPD.
In this single-blind randomized controlled trial, participants were assigned 1:1 to receive a control intervention (PR comprising 8 wk, two supervised sessions per week) or the trial intervention (PR plus pedometer-directed step targets, reviewed weekly for 8 wk). In the randomization process, we used minimization to balance groups for age, sex, FEV
percent predicted, and baseline exercise capacity and physical activity levels. Outcome assessors and PR therapists were blinded to group allocation. The primary analysis was based on the intention-to-treat principle.
The primary outcome was change from baseline to 8 weeks in accelerometer-measured daily time expending at least 3 METs. A total of 152 participants (72% male; mean SD FEV
percent predicted, 50.5% 21.2; median first quartile, third quartile time expending ≥3 METs, 46 21, 92 min) were enrolled and assigned to the intervention (n = 76) or control (n = 76) arm. There was no significant difference in change in time expending at least 3 METs between the intervention and control groups at 8 weeks (median first quartile, third quartile difference, 0.5 -1.0, 31.0 min; P = 0.87) or at the 6-month follow-up (7.0 -9, 27 min; P = 0.16).
Pedometer-directed step-count targets during an outpatient PR program did not enhance moderate-intensity physical activity levels in people with COPD. Clinical trial registered with www.clinicaltrials.gov (NCT01719822).
•Benzofuran derivatives were shown to induce IFN-I expression in a STING-dependent luciferase assay.•Activity as STING agonist was confirmed by mutagenesis studies.•Antiviral effect of BZFs was ...demonstrated on HCoV-229E and SARS-CoV-2 replication.•IFN-I mediated antiviral effect was confirmed by immunofluorescent analysis.
The Stimulator of Interferon Genes (STING) is involved in cytosolic DNA sensing and type I Interferons (IFN-I) induction. Aiming to identify new STING agonists with antiviral activity and given the known biological activity of benzothiazole and benzimidazole derivatives, a series of benzofuran derivatives were tested for their ability to act as STING agonists, induce IFN-I and inhibit viral replication. Compounds were firstly evaluated in a gene reporter assay measuring luciferase activity driven by the human IFN-β promoter in cells expressing exogenous STING (HEK293T). Seven of them were able to induce IFN-β transcription while no induction of the IFN promoter was observed in the presence of a mutated and inactive STING, showing specific protein-ligand interaction. Docking studies were performed to predict their putative binding mode. The best hit compounds were then tested on human coronavirus 229E replication in BEAS-2B and MRC-5 cells and three derivatives showed EC50 values in the μM range. Such compounds were also tested on SARS-CoV-2 replication in BEAS-2B cells and in Calu-3 showing they can inhibit SARS-CoV-2 replication at nanomolar concentrations. To further confirm their IFN-dependent antiviral activity, compounds were tested to verify their effect on phospho-IRF3 nuclear localization, that was found to be induced by benzofuran derivatives, and SARS-CoV-2 replication in Vero E6 cells, lacking IFN production, founding them to be inactive. In conclusion, we identified benzofurans as STING-dependent immunostimulatory compounds and host-targeting inhibitors of coronaviruses representing a novel chemical scaffold for the development of broad-spectrum antivirals.
Trained immunity is a recently described phenomenon whereby cells of the innate immune system undergo long‐term epigenetic and/or metabolic reprogramming following a short‐term interaction with ...microbes or microbial products. Here, it is shown that 2D transition metal dichalcogenides (TMDs) trigger trained immunity in primary human monocyte‐derived macrophages. First, aqueous dispersions of 2D crystal formulations of MoS2 and WS2 are tested, and no cytotoxicity is found despite avid uptake of these materials by macrophages. However, when macrophages are pre‐exposed to TMDs, followed by a resting period, this causes a marked modulation of immune‐specific gene expression upon subsequent challenge with a microbial agent (i.e., bacterial lipopolysaccharides). Specifically, MoS2 triggers trained immunity through an epigenetic pathway insofar as the histone methyltransferase inhibitor methylthioadenosine reverses these effects. Furthermore, MoS2 triggers an elevation of cyclic adenosine monophosphate (cAMP) levels in macrophages and increased glycolysis is also evidenced in cells subjected to MoS2 training, pointing toward a metabolic rewiring of the cells. Importantly, it is observed that MoS2 triggers the upregulation of Mo‐dependent enzymes in macrophages, thus confirming that Mo is bioavailable in these cells. In conclusion, MoS2 is identified as a novel inducer of trained immunity. Thus, TMDs could potentially be harnessed as immunomodulatory agents.
The present study demonstrates that 2D transition metal dichalcogenides (TMDs) elicit trained immunity in primary human macrophages. Evidence is provided for a role of epigenetic and metabolic rewiring in macrophages exposed to TMDs, and MoS2 is also shown to act directly on the cAMP signaling pathway. Thus, biocompatible 2D TMDs are capable of evoking “memory” responses.
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