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Background: The spread of the coronavirus disease 2019 (COVID-19) in Peru has been reported at the regional level, few studies have evaluated its spread at the provincial level, in which the mechanisms could be different., Methods: We conducted an analytical, cross-sectional, multistage observational population study to assess the seroprevalence of SARS-COV-2 at the provincial and urban/rural levels in a high-altitude setting. The sampling unit was the household, including a randomly selected family member. Sampling was performed using a data collection sheet on clinical and epidemiological variables. Chemiluminescence tests were used to detect total anti-SARS-COV-2 antibodies (IgG and IgM simultaneously). The percentages were adjusted to the sampling design., Results: The overall prevalence in the region of Cusco was 25.9%, with considerably different prevalence between the 13 provinces (from 15.9% in Acomayo to 40.1% in Canchis) and between rural (21.1%) and urban (31.7%) areas. In multivariable model, living in a rural area was a protective factor (adjusted prevalence ratio [aPR], 0.68; 95% confidence interval [CI], 0.61-0.76)., Conclusions: Geographic diversity and population density determine different prevalence rates, typically lower in rural areas, possibly due to natural social distancing or limited interaction with people at risk., Competing Interests: The authors declare no conflicts of interest. The funders nor authorities of the Gerencia Regional de Salud del Cusco had no role in the design of this study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results., (© 2023 Published by Elsevier Inc.)

Psychedelic drugs can exert potent anti-inflammatory effects. However, anti-inflammatory effects do not appear to correlate with behavioral activity, suggesting different underlying mechanisms. We hypothesized that the distinct structural features of psychedelics underlie functionally selective mechanisms at the target 5-HT 2A receptor to elicit maximal anti-inflammatory effects. In order to test this hypothesis, we developed a new rat-based screening platform for allergic asthma. Next, we investigated 21 agonists at the 5-HT 2A receptor from the three primary chemotypes (phenylalkylamine, ergoline, and tryptamine) for their ability to prevent airways hyperresponsiveness as a measure of pulmonary inflammation. Furthermore, we assessed each drug for in vitro activation of the canonical signaling pathway, calcium mobilization, from the 5-HT 2A receptor. We find that the drug 2,5-dimethoxyphenethylamine (2C-H) represents the pharmacophore for anti-inflammatory activity and identify structural modifications that are either permissive or detrimental to anti-inflammatory activity. Additionally, there is no correlation between the ability of a particular psychedelic to activate intracellular calcium mobilization and to prevent the symptoms of asthma or with behavioral potencies. Our results support the notions that specific structural features mediate functional selectivity underlying anti-inflammatory activity and that relevant receptor activated pathways necessary for anti-inflammatory activity are different from canonical signaling pathways. Our results inform on the nature of interactions between ligands at the 5-HT 2A receptor as they relate to anti-inflammatory activity and are crucial for the development of new 5-HT 2A receptor agonists for anti-inflammatory therapeutics in the clinic that may be devoid of behavioral activity., Competing Interests: The authors declare the following competing financial interest(s): C.D.N. is supported by a sponsored research contract from Eleusis Therapeutics and is a member of its Scientific Advisory Board.

Aims: Although the bulk of research into the biology of serotonin 5-HT 2A receptors has focused on its role in the CNS, selective activation of these receptors in peripheral tissues can produce profound anti-inflammatory effects. We previously demonstrated that the small molecule 5-HT 2 receptor agonist (R)-2,5-dimethoxy-4-iodoamphetamine [(R)-DOI] inhibits TNF-α-mediated proinflammatory signaling cascades and inflammation via 5-HT 2A receptor activation and prevents the development of, and inflammation associated with, acute allergic asthma in a mouse ovalbumin (OVA) model. Here, we investigated the ability of (R)-DOI to reverse inflammation and symptoms associated with established asthma in a newly developed model of chronic asthma., Methods: An 18-week ovalbumin challenge period was performed to generate persistent, chronic asthma in BALB/c mice. Four once daily intranasal treatments of (R)-DOI were administered one week after allergen cessation, with respiratory parameters being measured by whole-body plethysmography (WBP). Cytokine and chemokine levels were measured by quantitative real-time polymerase chain reaction (qRT-PCR) in homogenized lung tissue, bronchoalveolar (BALF) fluid was analyzed for chemokine modulation by multiplex assays, and Periodic Acid-Schiff and Masson's Trichrome staining was performed to determine goblet cell infiltration and overall changes to lung morphology., Key Findings: 5-HT 2 activation via (R)-DOI attenuates elevated airway hyperresponsiveness to methacholine, reduces pulmonary inflammation and mucus production, and reduces airway structural remodeling and collagen deposition by nearly 70%., Significance: Overall, these data provide support for the therapeutic potential of (R)-DOI and 5-HT 2 receptor activation for the treatment of asthma, and identifies (R)-DOI as a novel therapeutic compound against pulmonary fibrosis., (Copyright © 2019. Published by Elsevier Inc.)

Coronary artery disease (CAD) is a progressive cardiovascular syndrome characterized by cholesterol-induced focal arterial lesions that impair oxygen delivery to the heart. As both innate and adaptive immune cells play critical roles in the formation and progression of arterial plaques and endothelial cell dysfunction, CAD is commonly viewed as a chronic inflammatory disorder. Our lab has previously discovered that 5-HT 2A receptor activation with the 5-HT 2 receptor selective agonist (R)-2,5-dimethoxy-4-iodoamphetamine [(R)-DOI] has potent anti-inflammatory activity in both cell culture and whole animal models. Here we have examined the putative therapeutic effects of (R)-DOI in the ApoE -/- high fat model of cardiovascular disease. Subcutaneously implanted osmotic minipumps were used to infuse sustained low rates (0.15 μg / hr) of (R)-DOI∙HCl to mice fed a high-fat "Western" diet. (R)-DOI treated mice had significant reductions in expression levels of mRNA for inflammatory markers like Il6 in vascular tissue, normalized glucose homeostasis, and reduced circulating cholesterol levels. As cardiovascular disease is a leading cause of death both globally and in the Western world, activation of 5-HT 2A receptors at sub-behavioral levels may represent a new strategy to treat inflammation-based cardiovascular disease.