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Interoception is the perception of internal bodily signals. It is considered fundamental to developing emotional awareness. For this reason, interoceptive deficits are often associated with alexithymia, a condition characterized by difficulty identifying feelings (DIF), difficulty describing feelings (DDF), and an externally-oriented style of thinking (EOT). Yet, the atypical interoception found in alexithymia might be of a similar type and/or more serious than those found in other partially overlapping constructs that entail emotional difficulties and behavioural patterns associated with specific emotional styles. Our study explores this issue by examining the relationship between the interoceptive deficits associated with alexithymia and the Big Five personality traits. A non-clinical sample (N = 504) completed the Toronto Alexithymia Scale, the Big Five Inventory and the Multidimensional Assessment of Interoceptive Awareness. Data were analysed using a network analytic approach that conceives psychological traits as networks of interacting symptoms. The estimated network highlighted that EOT is the alexithymia component least associated with interoception and most associated with lower Openness to Experience. Conversely, DIF and Neuroticism are, respectively, the dimensions of alexithymia and the Big Five most highly associated with interoception. We also compared interoceptive abilities in the four groups of participants whose scores were a) high for both alexithymia and neuroticism, b) high only for alexithymia c), high only for neuroticism, and d) low for both. High alexithymia was especially associated with the tendency to ignore sensations of pain or discomfort, while neuroticism was more indicative of the tendency to worry about these sensations. These results suggest that while high alexithymia and neuroticism share some interoceptive deficits, others are unique to alexithymia and contribute to overall lower interoceptive ability in this condition. Our findings suggest that interventions to enhance awareness of bodily sensations can be beneficial especially for profiles who present high neuroticism and alexithymia., Competing Interests: The authors have declared that no competing interests exist.

The long-standing hypothesis that emotions rely on bodily states is back in the spotlight. This has led some researchers to suggest that alexithymia, a personality construct characterized by altered emotional awareness, reflects a general deficit in interoception. However, tests of this hypothesis have relied on heterogeneous assessment methods, leading to inconsistent results. To shed some light on this issue, we administered a battery of self-report questionnaires of interoception and alexithymia to three samples from Italy, the U.S., and Singapore (N = 814). Correlation and machine learning analyses showed that alexithymia was associated with deficits in both subjective interoceptive accuracy and attention. Alexithymics' interoceptive deficits were primarily related to difficulty identifying and describing feelings. Interoception showed a weaker association with externally-oriented thinking as operationalized by the Toronto Alexithymia Scale (TAS-20) and no association with the affective dimension of alexithymia later introduced by the Bermond-Vorst Alexithymia Questionnaire (BVAQ). We discuss our results with reference to the theoretical and psychometric differences between these two measures of alexithymia and their shortcomings. Overall, our results support the view that interoceptive deficits are a core component of alexithymia, although the latter cannot be reduced to the former., Competing Interests: The authors have declared that no competing interests exist.

Background: The coronavirus disease (COVID-19) pandemic has brought significant challenges worldwide, with high mortality, increased use of hospital resources, and the collapse of healthcare systems. We aimed to describe the clinical outcomes of critically ill COVID-19 patients and assess the impact on the use of hospital resources and compare with critically ill medical patients without COVID-19., Methods and Findings: In this retrospective cohort study, we included patients diagnosed with COVID-19 admitted to a private ICU in Sao Paulo, Brazil from March to June 2020. We compared these patients with those admitted to the unit in the same period of the previous year. A total of 212 consecutive patients with a confirmed diagnosis of COVID-19 were compared with 185 medical patients from the previous year. Patients with COVID-19 were more frequently males (76% vs. 56%, p<0.001) and morbidly obese (7.5% vs. 2.2%, p = 0.027), and had lower SAPS 3 (49.65 (12.19) vs. 55.63 (11.94), p<0.001) and SOFA scores (3.78 (3.53) vs. 4.48 (3.11), p = 0.039). COVID-19 patients had a longer ICU stay (median of 7 vs. 3 days, p<0.001), longer duration of mechanical ventilation (median of 9 vs. 4 days, p = 0.003), and more frequent tracheostomies (10.8 vs. 1.1%, p<0.001). Survival rates until 28 days were not statistically different (91% vs. 85.4%, p = 0.111). After multivariable adjustment for age, gender, SAPS 3, and Charlson Comorbidity Index, COVID-19 remained not associated with survival at 28 days (HR 0.59, 95% CI 0.33-1.06, p = 0.076). Among patients who underwent invasive mechanical ventilation, the observed mortality at 28-days was 16.2% in COVID-19 patients compared to 34.6% in the previous year., Conclusions: COVID-19 required more hospital resources, including invasive and non-invasive ventilation, had a longer duration of mechanical ventilation, and a more prolonged ICU and hospital length of stay. There was no difference in all-cause mortality at 28 and 60 days, suggesting that health systems preparedness be an important determinant of clinical outcomes., Competing Interests: The authors have declared that no competing interests exist.

In the last decades, cellular senescence is viewed as a complex mechanism involved in different processes, ranging from tumor suppression to induction of age-related degenerative alterations. Senescence-inducing stimuli are myriad and, recently, we and others have demonstrated the role exerted by microRNAs in the induction and maintenance of senescence, by the identification of a subset of Senescence-Associated microRNAs (SAmiRs) up-regulated during replicative or stress-induced senescence and able to induce a premature senescent phenotype when over-expressed in human primary cells. With the intent to find novel direct targets of two specific SAmiRs, SAmiR-494 and -486-5p, and cellular pathways which they are involved in, we performed a comparative analysis of gene expression profiles available in literature to select genes down-regulated upon replicative senescence of human primary fibroblasts. Among them, we searched for SAmiR's candidate targets by analyzing with different target prediction algorithms their 3'UTR for the presence of SAmiR-binding sites. The expression profiles of selected candidates have been validated on replicative and stress-induced senescence and the targeting of the 3'UTRs was assessed by luciferase assay. Results allowed us to identify Cell Division Cycle Associated 2 (CDCA2) and Inhibitor of DNA binding/differentiation type 4 (ID4) as novel targets of SAmiR-494 and SAmiR-486-5p, respectively. Furthermore, we demonstrated that the over-expression of CDCA2 in human primary fibroblasts was able to partially counteract etoposide-induced senescence by mitigating the activation of DNA Damage Response.

Background: While it is accepted that a majority of invasive breast cancer progresses from a ductal carcinoma in situ (DCIS) precursor stage, very little is known about the factors that promote survival of DCIS neoplastic cells within the hypoxic, nutrient deprived intraductal microenvironment., Methodology and Principal Findings: We examined the hypothesis that fresh human DCIS lesions contain pre-existing carcinoma precursor cells. We characterized these cells by full genome molecular cytogenetics (Illumina HumanCytoSNP profile), and signal pathway profiling (Reverse Phase Protein Microarray, 59 endpoints), and demonstrated that autophagy is required for survival and anchorage independent growth of the cytogenetically abnormal tumorigenic DCIS cells. Ex vivo organoid culture of fresh human DCIS lesions, without enzymatic treatment or sorting, induced the emergence of neoplastic epithelial cells exhibiting the following characteristics: a) spontaneous generation of hundreds of spheroids and duct-like 3-D structures in culture within 2-4 weeks; b) tumorigenicity in NOD/SCID mice; c) cytogenetically abnormal (copy number loss or gain in chromosomes including 1, 5, 6, 8, 13, 17) compared to the normal karyotype of the non-neoplastic cells in the source patient's breast tissue; d) in vitro migration and invasion of autologous breast stroma; and e) up-regulation of signal pathways linked to, and components of, cellular autophagy. Multiple autophagy markers were present in the patient's original DCIS lesion and the mouse xenograft. We tested whether autophagy was necessary for survival of cytogenetically abnormal DCIS cells. The lysosomotropic inhibitor (chloroquine phosphate) of autophagy completely suppressed the generation of DCIS spheroids/3-D structures, suppressed ex vivo invasion of autologous stroma, induced apoptosis, suppressed autophagy associated proteins including Atg5, AKT/PI3 Kinase and mTOR, eliminated cytogenetically abnormal spheroid forming cells from the organ culture, and abrogated xenograft tumor formation., Conclusions: Cytogenetically abnormal spheroid forming, tumorigenic, and invasive neoplastic epithelial cells pre-exist in human DCIS and require cellular autophagy for survival.

Background: Although the mouse is the animal model most widely used to study the pathogenesis and treatment of human diseases, reference values for biochemical parameters are scanty or lacking for the most frequently used strains. We therefore evaluated these parameters in the C57BL/6J, 129SV/EV and C3H/HeJ mice., Methodology/principal Findings: We measured by dry chemistry 26 analytes relative to electrolyte balance, lipoprotein metabolism, and muscle/heart, liver, kidney and pancreas functions, and by automated blood counter 5 hematological parameters in 30 animals (15 male and 15 female) of each mouse strain at three age ranges: 1-2 months, 3-8 months and 9-12 months. Whole blood was collected from the retro-orbital sinus. We used quality control procedures to investigate analytical imprecision and inaccuracy. Reference values were calculated by non parametric methods (median and 2.5(th) and 97.5(th) percentiles). The Mann-Whitney and Kruskal-Wallis tests were used for between-group comparisons. Median levels of GLU, LDH, Chol and BUN were higher, and LPS, AST, ALP and CHE were lower in males than in females (p range: 0.05-0.001). Inter-strain differences were observed for: (1) GLU, t-Bil, K+, Ca++, PO(4)- (p<0.05) and for TAG, Chol, AST, Fe++ (p<0.001) in 4-8 month-old animals; (2) for CK, Crea, Mg++, Na++, K+, Cl- (p<0.05) and BUN (p<0.001) in 2- and in 10-12 month-old mice; and (3) for WBC, RBC, HGB, HCT and PLT (p<0.05) during the 1 year life span., Conclusion/significance: Our results indicate that metabolic variations in C57BL/6J, 129SV/EV and C3H/HeJ mice after therapeutic intervention should be evaluated against gender- and age-dependent reference intervals.