Obsessions and compulsions are driven by the goal of preventing or neutralizing guilt. We investigated whether inducing deontological versus altruistic guilt in healthy volunteers could activate ...checking behaviors and physical cleaning. Participants were asked to listen to stories that induced deontological guilt, altruistic guilt, or a neutral control state, and then were asked to classify 100 colored capsules into 12 small pots (Study 1) or to clean a Plexiglas cube (Study 2). Before and after hearing the story and after completing the task, participants completed a visual analog scale that assessed their current emotions. Finally, participants completed a self-report questionnaire about discomfort, doubts, and perceived performance. Participants in the deontological group checked more (Study 1), cleaned the cube more times (Study 2), and scored higher in doubts and discomfort than did participants in the altruistic or control groups. These data suggest that deontological guilt is the mental state specifically related to checking and cleaning compulsions.
Abstract
Clinical outcomes of COVID-19 patients are worsened by the presence of co-morbidities, especially cancer leading to elevated mortality rates. SARS-CoV-2 infection is known to alter immune ...system homeostasis. Whether cancer patients developing COVID-19 present alterations of immune functions which might contribute to worse outcomes have so far been poorly investigated. We conducted a multi-omic analysis of immunological parameters in peripheral blood mononuclear cells (PBMCs) of COVID-19 patients with and without cancer. Healthy donors and SARS-CoV-2-negative cancer patients were also included as controls. At the infection peak, cytokine multiplex analysis of blood samples, cytometry by time of flight (CyTOF) cell population analyses, and Nanostring gene expression using Pancancer array on PBMCs were performed. We found that eight pro-inflammatory factors (IL-6, IL-8, IL-13, IL-1ra, MIP-1a, IP-10) out of 27 analyzed serum cytokines were modulated in COVID-19 patients irrespective of cancer status. Diverse subpopulations of T lymphocytes such as CD8
+
T, CD4
+
T central memory, Mucosal-associated invariant T (MAIT), natural killer (NK), and γδ T cells were reduced, while B plasmablasts were expanded in COVID-19 cancer patients. Our findings illustrate a repertoire of aberrant alterations of gene expression in circulating immune cells of COVID-19 cancer patients. A 19-gene expression signature of PBMCs is able to discriminate COVID-19 patients with and without solid cancers. Gene set enrichment analysis highlights an increased gene expression linked to Interferon α, γ, α/β response and signaling which paired with aberrant cell cycle regulation in cancer patients. Ten out of the 19 genes, validated in a real-world consecutive cohort, were specific of COVID-19 cancer patients independently from different cancer types and stages of the diseases, and useful to stratify patients in a COVID-19 disease severity-manner. We also unveil a transcriptional network involving gene regulators of both inflammation response and proliferation in PBMCs of COVID-19 cancer patients.
The association between Type 1 Diabetes Mellitus (T1DM) and obesity (Ob) is no longer unexpected due to unhealthy lifestyle mostly in adolescents. We compared clinical-biochemical characteristics, ...adherence to the Mediterranean Diet (MD), lifestyle habits and physical fitness across different weight categories of T1DM adolescents from Campania Region. As second aim, we assessed the relationship among lifestyle and physical fitness in these patients.
74 adolescents (35M; 39F; 13–18 y), with T1DM diagnosed at least 6 mo before the study, were enrolled at the Regional Center for Pediatric Diabetology of Vanvitelli University of Naples. Height, weight, Body Mass Index (BMI), BMI z-score, and Clinical Biochemical health-related parameters were determined. MD adherence, physical activity (PA) amount and sedentary habits were assessed by questionnaires. Handgrip strength, 2-Min Step test (2-MST) cardiorespiratory endurance and Timed up and go test (TUG) for agility and balance were used for physical fitness evaluation.
Our sample included 22 normal weight (NW), 37 overweight (OW) and 15 with Obese (Ob) adolescents. Across the three groups, adolescents showed similar Clinical-Biochemical parameters, MD adherence, PA amount, mostly walking (9.3 h/w), daily video exposure (8.5 h/d) and similar handgrip or 2-MST performance. Better performance was observed in NW compared to OW or Ob for TUG (7 vs 8 vs 9 s; p < 0.05). A positive correlation was found between TUG test and BMI, while no correlation was found between HbA1c (glycated haemoglobin) and BMI z score or 2-MST.
T1DM adolescents did not meet the recommendations for active lifestyle, despite a medium/good adherence to MD, in particular in NW and OW youths. Sedentary habits correlated with a poor HbA1c. Further, reduced agility and balance were observed in adolescents with obesity compared to NW participants.
Future research should be aimed to examine wider samples and to design health promotion interventions for T1DM adolescents.
A growing number of emerging SARS-CoV-2 variants is being identified worldwide, potentially impacting the effectiveness of current vaccines. We report the data obtained in several Italian regions ...involved in the SARS-CoV-2 variant monitoring from the beginning of the epidemic and spanning the period from October 2020 to March 2021.
Multiple sclerosis is a debilitating autoimmune disease, characterized by chronic inflammation of the central nervous system. While the significance of the gut microbiome on multiple sclerosis ...pathogenesis is established, the underlining mechanisms are unknown. We found that serum levels of the microbial postbiotic tryptophan metabolite indole-3-carboxaldehyde (3-IAld) inversely correlated with disease duration in multiple sclerosis patients. Much like the host-derived tryptophan derivative L-Kynurenine, 3-IAld would bind and activate the Aryl hydrocarbon Receptor (AhR), which, in turn, controls endogenous tryptophan catabolic pathways. As a result, in peripheral lymph nodes, microbial 3-IAld, affected mast-cell tryptophan metabolism, forcing mast cells to produce serotonin via Tph1. We thus propose a protective role for AhR-mast-cell activation driven by the microbiome, whereby natural metabolites or postbiotics will have a physiological role in immune homeostasis and may act as therapeutic targets in autoimmune diseases.
Objectives/Hypothesis:
To investigate the efficacy of an intratympanic steroid as a first‐line therapy in patients affected by moderate idiopathic sudden sensorineural hearing loss (ISSNHL).
Study ...Design:
Prospective, randomized, triple‐blind, placebo‐controlled trial.
Methods:
Fifty patients presenting with moderate idiopathic sudden sensorineural hearing loss involving all frequencies from 250 Hz to 8,000 Hz (a flat audiogram) were enrolled. Patients were randomized into two groups of 25 each. The first group (intratympanic steroid) underwent a daily intratympanic administration of prednisolone for 3 consecutive days. Subjects in the second group (control) received a daily intratympanic injection of a saline solution for 3 consecutive days. Audiometric tests were performed at day 7 after the beginning of therapy (T1), and then 10 and 30 days after T1. The patients in both groups who did not show a complete recovery at T1 were treated with oral prednisone at a tapering dose.
Results:
In the intratympanic steroid group, 19 out of 25 patients presented at T1 complete recovery (76%), whereas in the control group the number patients who recovered completely at T1 was five out of 25 (20%). The mean pure‐tone average (PTA) recorded at T1 shows a statistically significant improvement in the hearing threshold of the first group compared to the control group (P < .01).
Conclusions:
The mean PTA recorded after the first‐line approach (T1) demonstrated a significant therapeutic action of the short‐duration intratympanic steroid therapy on moderate ISSNHL, with a flat audiogram shape, compared to the natural course of the disease and the placebo effect at that time point. Laryngoscope, 2013
Since February 21 2020, when the Italian National Institute of Health (Istituto Superiore di Sanità–ISS) reported the first autochthonous case of infection, a dedicated surveillance system for ...SARS‐CoV‐2‐positive (COVID+) cases has been created in Italy. These data were cross‐referenced with those inside the Information Transplant System in order to assess the cumulative incidence (CI) and the outcome of SARS‐COV‐2 infection in solid organ transplant recipients (SOTRs) who are assumed to be most at risk. We compared our results with those of COVID+ nontransplanted patients (Non‐SOTRs) with follow‐up through September 30, 2020. The CI of SARS‐CoV‐2 infection in SOTRs was 1.02%, higher than in COVID+ Non‐SOTRs (0.4%, p < .05) with a greater risk in the Lombardy region (2.89%). The CI by type of organ transplant was higher for heart (CI 1.57%, incidence rate ratio IRR 1.36) and lower for liver (CI 0.63%, IRR 0.54). The 60‐day CI of mortality was 30.6%, twice as much that of COVID+ Non‐SOTRs (15.4%) with a 60‐day gender and age adjusted odds ratio (adjusted‐OR) of 3.83 for COVID+ SOTRs (95% confidence interval 3.03–4.85). The lowest 60‐day adjusted‐OR was observed in liver SOTRs (OR 0.46, 95% confidence interval 0.25–0.86). More detailed studies on disease management and evolution will be necessary in these patients at greater risk of COVID‐19.
In Italy, SARS‐CoV‐2 infection risk for solid organ recipients compared to the general population is two times higher and mortality risk is four times higher, with heart recipients at the highest risk of infection and liver recipients at the lowest risk of both infection and mortality.
The failure of clinical trials largely focused on mild to moderate stages of Alzheimer disease has suggested to the scientific community that the effectiveness of Amyloid-β (Aβ)-centered treatments ...should be evaluated starting as early as possible, well before irreversible brain damage has occurred. Accordingly, also the preclinical development of new therapies should be carried out taking into account this suggestion. In the present investigation we evaluated the efficacy of a treatment with liposomes multifunctionalized for crossing the blood-brain barrier and targeting Aβ, carried out on young APP/PS1 Tg mice, taken as a model of pre-symptomatic disease stage.
Liposomes were administered once a week to Tg mice for 7months, starting at the age of 5months and up to the age of 12 when they display AD-like cognitive and brain biochemical/anatomical features. The treatment prevented the onset of the long-term memory impairment and slowed down the deposition of brain Aβ; at anatomical level, prevented both ventricle enlargement and entorhinal cortex thickness reduction, otherwise occurring in untreated mice. Strikingly, these effects were maintained 3months after treatment discontinuation. An increase of Aβ levels in the liver was detected at the end of the treatment, then followed also by reduction of brain Amyloid Precursor Protein and increase of Aβ-degrading enzymes. These results suggest that the treatment promotes brain Aβ clearance by a peripheral ‘sink’ effect and ultimately affects Aβ turnover in the brain.
Worth of note, the treatment was apparently not toxic for all the organs analyzed, in particular for brain, as suggested by the lower brain TNF-α and MDA levels, and by higher level of SOD activity in treated mice. Together, these findings promote a very early treatment with multi-functional liposomes as a well-tolerated nanomedicine-based approach, potentially suitable for a disease-modifying therapy of AD, able to delay or prevent relevant features of the disease.
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BackgroundImmune checkpoint inhibitors are still unable to provide clinical benefit to the large majority of non-small cell lung cancer (NSCLC) patients. A deeper characterization of the tumor immune ...microenvironment (TIME) is expected to shed light on the mechanisms of cancer immune evasion and resistance to immunotherapy. Here, we exploited malignant pleural effusions (MPEs) from lung adenocarcinoma (LUAD) patients as a model system to decipher TIME in metastatic NSCLC.MethodsMononuclear cells from MPEs (PEMC) and peripheral blood (PBMC), cell free pleural fluid and/or plasma were collected from a total of 24 LUAD patients and 12 healthy donors. Bulk-RNA sequencing was performed on total RNA extracted from PEMC and matched PBMC. The DEseq2 Bioconductor package was used to perform differential expression analysis and CIBERSORTx for the regression-based immune deconvolution of bulk gene expression data. Cytokinome analysis of cell-free pleural fluid and plasma samples was performed using a 48-Plex Assay panel. THP-1 monocytic cells were used to assess macrophage polarization. Survival analyses on NSCLC patients were performed using KM Plotter (LUAD, N=672; lung squamous cell carcinoma, N=271).ResultsTranscriptomic analysis of immune cells and cytokinome analysis of soluble factors in the pleural fluid depicted MPEs as a metastatic niche in which all the components required for an effective antitumor response are present, but conscripted in a wound-healing, proinflammatory and tumor-supportive mode. The bioinformatic deconvolution analysis revealed an immune landscape dominated by myeloid subsets with the prevalence of monocytes, protumoral macrophages and activated mast cells. Focusing on macrophages we identified an MPEs-distinctive signature associated with worse clinical outcome in LUAD patients.ConclusionsOur study reports for the first time a wide characterization of MPEs LUAD microenvironment, highlighting the importance of specific components of the myeloid compartment and opens new perspectives for the rational design of new therapies for metastatic NSCLC.
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