The small heat shock protein B8 (HSPB8) modulates proliferation and migration of breast cancer cells

open12noBreast cancer (BC) is one of the major causes of cancer death in women and is closely related to hormonal dysregulation. Estrogen receptor (ER)-positive BCs are generally treated with anti hormone therapy using antiestrogens or aromatase inhibitors. However, BC cells may become resistant to endocrine therapy, a process facilitated by autophagy, which may either promote or suppress tumor expansion. The autophagy facilitator HSPB8 has been found overexpressed in some BC. Here we found that HSPB8 is highly expressed and differentially modulated by natural or synthetic selective ER modulators (SERMs), in the triple-positive hormone-sensitive BC (MCF-7) cells, but not in triple-negative MDA-MB-231 BC cells. Specific SERMs induced MCF-7 cells proliferation in a HSPB8 dependent manner whereas, did not modify MDA-MB-231 cell growth. ER expression was unaffected in HSPB8-depleted MCF-7 cells. HSPB8 over-expression did not alter the distribution of MCF-7 cells in the various phases of the cell cycle. Conversely and intriguingly, HSPB8 downregulation resulted in an increased number of cells resting in the G0/G1 phase, thus possibly reducing the ability of the cells to pass through the restriction point. In addition, HSPB8 downregulation reduced the migratory ability of MCF-7 cells. None of these modifications were observed, when another small HSP (HSPB1), also expressed in MCF-7 cells, was downregulated. In conclusion, our data suggest that HSPB8 is involved in the mechanisms that regulate cell cycle and cell migration in MCF-7 cells.openPiccolella, Margherita; Crippa, Valeria; Cristofani, Riccardo; Rusmini, Paola; Galbiati, Mariarita; Elena Cicardi, Maria; Meroni, Marco; Ferri, Nicola; Morelli, Federica F; Carra, Serena; Messi, Elio; Poletti, AngeloPiccolella, Margherita; Crippa, Valeria; Cristofani, Riccardo; Rusmini, Paola; Galbiati, Mariarita; Elena Cicardi, Maria; Meroni, Marco; Ferri, Nicola; Morelli, Federica F; Carra, Serena; Messi, Elio; Poletti, Angel

Risk perception of heat related disorders on the workplaces: a survey among health and safety representatives from the autonomous province of Trento, Northeastern Italy

Introduction. This study will investigate knowledge, attitude and practices towards heat-related health issues in a sample of safety representatives from Northern Italy (HSRs). Methods: A cross-sectional questionnaire survey was conducted in 2016-2017 among 298 HSR. Knowledge status was measured both in general but as well and focusing on first-aid issues. Assessment of risk perception included severity and frequency of heat-related events. Multivariate logistic regression analysis assessed individual and work-related characteristics associated with HSRs’ risk perception. Results: 258 questionnaires were retrieved (participation rate 86.6%; mean age 48.2±8.4 years). Knowledge status was relatively good on technical/preventive issues (62.3%%±16.8) and first aid measures (72.6%±27.2), but a large share of respondents ignored the risk from exertional heat stroke (35.9%), and for heat strokes elicited by non-environmental heat (e.g. machineries, use of protective equipment, etc. 47.9%). The majority of respondents acknowledged the high frequency of HW events (62.0%), but only 44.6% agreed on their potential health threat, with an unsatisfying cumulative risk perception score (55.4%±23.5). A specific first-aid formation course was reported by 49.2% of respondents, while 10.9% had any previous interaction with heat-related disorders. Specific countermeasures for heat waves had been put in place by parent company in 20.1% of cases. Eventually, higher educational achievements (mOR 2.239, 95%CI 1.184 - 4.233) and a better general knowledge status (mOR 1.703, 95%CI 1.073 - 2.979) were positive predictors for higher risk perception. Conclusions: Although HSRs exhibited a good understanding of heat-related health issues, stakeholders should improve the implementation of specific countermeasures on the workplaces

Remdesivir treatment in hospitalized patients affected by COVID-19 pneumonia: a case-control study

Background: to date the optimal antiviral treatment against severe coronavirus disease 2019 (COVID-19) has not been proven; remdesivir is a promising drug with in vitro activity against several virus, but in COVID-19 the clinical results are currently not definitive. Methods: in this retrospective observational study we analyzed the clinical outcomes (survival analysis, efficacy and safety) in a group of hospitalized patients with COVID-19 treated with remdesivir in comparison with a control group of patients treated with other antiviral or supportive therapies. Results: we included 163 patients treated with remdesivir and 403 subjects in the control group; the baseline characteristics were similar in the two groups; mortality rate was higher in control group (24.8% vs 2.4%, p<0.001), the risk of intensive-care-unit (ICU) admission was higher in control group (17.8% vs 9.8%, p=0.008); hospitalization time was significantly lower in patients treated with remdesivir (9.5 vs 12.5 days, p<0.001). The safety of remdesivir was good and no significant adverse events were reported. In multivariate analysis the remdesivir treatment was independently associated with a 34% lower mortality rate (OR=0.669; p=0.014). Conclusions: in this analysis the treatment with remdesivir was associated with lower mortality, lower rate of ICU admission, shorter time of hospitalization. No adverse events were observed. This promising antiviral treatment should also be confirmed by other studies. This article is protected by copyright. All rights reserved

ANHEDONIA IN THE PSYCHOSIS RISK SYNDROME: STATE AND TRAIT CHARACTERISTICS

Background: Previous studies reported deficits in pleasure experience in schizophrenia, but little is known about anhedonia in psychosis risk syndrome. Aim of this study was: (1) to assess anhedonia in distinct help-seeking subgroups of young people identified through the Ultra-High Risk (UHR) criteria, (2) to explore its association with functioning and psychopathology in the UHR group, and (3) to monitor longitudinally its stability in UHR individuals along 1-year follow-up period. Subjects and methods: All participants (78 UHR, 137 with a First Episode Psychosis (FEP), and 95 non-UHR/FEP), aged 13-35 years, completed the Comprehensive Assessment of At-Risk Mental States (CAARMS), the Beck Depression Inventory-II (BDI-II), the Schizotypal Personality Questionnaire - Brief version (SPQ-B), the Brief O-LIFE questionnaire (BOL), and the World Health Organization Quality of Life - Brief version (WHOQOL-BREF). We adopted two different indexes of anhedonia: i.e. CAARMS “Anhedonia” item 4.3 and BOL “Introvertive Anhedonia” subscale scores. Results: In comparison with non-UHR/FEP, UHR individuals showed higher baseline CAARMS item 4.3 and BOL “Introvertive Anhedonia” subscale scores. No difference in anhedonia scores between UHR and FEP patients was found. After 1-year follow up period, UHR subjects had a significant decrease in severity exclusively on CAARMS item 4.3 subscore. Conclusions: In the UHR group, CAARMS anhedonia showed significant correlations with functioning deterioration, negative symptoms, and comorbid depression (including suicide ideation), while BOL anhedonia with a poorer self-perceived quality of life and specific schizotypal personality traits (i.e. interpersonal deficits and disorganization). Anhedonia is prominent in the psychosis risk syndrome and its severity is indistinguishable from that of FEP patients

Diagnostic properties of the Italian ECAS Carer Interview (ECAS-CI)

Background This study aimed at providing diagnostic properties and normative cut-offs for the Italian ECAS Carer Interview (ECAS-CI). Materials N = 292 non-demented ALS patients and N = 107 healthy controls (HCs) underwent the ECAS-CI and the Frontal Behavioural Inventory (FBI). Two ECAS-CI measures were addressed: (1) the number of symptoms (NoS; range = 0-13) and (2) that of individual symptom clusters (SC; range = 0-6). Diagnostics were explored against an FBI score &gt;= than the 95th percentile of the patients' distribution. Results Both the NoS and SC discriminated patient from HCs. High accuracy, sensitivity, and specificity were detected for both the NoS and SC; however, at variance with SC, the NoS showed better post-test features and did not overestimate the occurrence of behavioural changes. The ECAS-CI converged with the FBI and diverged from the cognitive section of the ECAS. Discussion The ECAS-CI is a suitable screener for behavioural changes in ALS patients, with the NoS being its best outcome measure (cut-off: &gt;= 3)

Validity and diagnostics of the Reading the Mind in the Eyes Test (RMET) in non-demented amyotrophic lateral sclerosis (ALS) patients

BackgroundThe aim of this study was to explore the construct validity and diagnostic properties of the Reading the Mind in the Eyes Test (RMET) in non-demented patients with amyotrophic lateral sclerosis (ALS). MaterialsA total of 61 consecutive patients and 50 healthy controls (HCs) were administered the 36-item RMET. Additionally, patients underwent a comprehensive assessment of social cognition via the Story-Based Empathy Task (SET), which encompasses three subtests targeting Causal Inference, Emotion Attribution (SET-EA), and Intention Attribution (SET-IA), as well as global cognitive [the Edinburgh Cognitive and Behavioral ALS Screen (ECAS)] and behavioral screening [the Frontal Behavioral Inventory (FBI); the Dimensional Apathy Scale (DAS); the Beck Depression Inventory (BDI); and the State and Trait Anxiety Inventory-Y]. The construct validity of the RMET was tested by regressing it within a stepwise model that encompassed as predictors the abovementioned cognitive and behavioral measures, covarying for demographic and motor confounders. Receiver-operating characteristics (ROC) analyses allowed exploring intrinsic and post-test properties of the RMET both in discriminating patients from HCs and in identifying patients with a defective SET-EA performance. ResultsThe RMET was solely predicted by the SET-EA (p = 0.003) and SET-IA (p = 0.005). RMET scores showed high accuracy both in discriminating patients from HCs (AUC = 0.81) and in identifying patients with a defective SET-EA score (AUC = 0.82), with adequate-to-optimal both intrinsic and post-test properties. DiscussionThe RMET is a convergently and divergently valid measure of affective social cognition in non-demented ALS patients, also featuring optimal intrinsic and post-test diagnostic properties in both case-control and case-finding scenarios

Prevalence and determinants of language impairment in non-demented amyotrophic lateral sclerosis patients

Background and purpose: This study aimed at estimating the prevalence of language impairment (LI) in a large, clinic-based cohort of non-demented amyotrophic lateral sclerosis (ALS) patients and assessing its underpinnings at motor and non-motor levels. Methods: Non-demented ALS patients (N = 348) underwent the Edinburgh Cognitive and Behavioural ALS Screen (ECAS), as well as an assessment of behavioural/psychiatric and motor-functional features. The prevalence of LI was estimated based on the proportion of patients showing a performance below the age- and education-adjusted cut-off on the ECAS-Language. Multiple regression models were run to assess the determinants of language functioning and impairment. Results: The prevalence of LI was 22.7%. 46.6% of the variance of ECAS-Language scores remained unexplained, with only the ECAS-Executive positively predicting them (p &lt; 0.001; eta(2) = 0.07). Similarly, only a lower score on the ECAS-Executive predicted a higher probability of a below cut-off ECAS-Language performance (p &lt; 0.001). Spelling and Naming tasks were the major drivers of ECAS-Language performance. Conclusions: This study suggests that, in non-demented ALS patients, LI occurs in asymptotic to 23% of cases, is significantly driven by executive dysfunction but, at the same time, partially independent of it and is not associated with other motor or non-motor features

Feasibility and diagnostics of the Frontal Assessment Battery (FAB) in amyotrophic lateral sclerosis

Background The present study aimed at evaluating the diagnostic properties of the Frontal Assessment Battery (FAB) in non-demented ALS patients by addressing the Edinburgh Cognitive Behavioural ALS Screen (ECAS) as the gold standard, as well as by examining the association between its administrability and scores with motor-functional measures. Materials N = 348 consecutive patients were administered the ECAS and FAB. Disease severity (ALSFRS-R), duration, progression rate (Delta FS), and stages (via King's and Milano-Torino systems) were considered. Administrability rates and prevalence of below-cut-off FAB scores were compared across clinical stages; regression models allowed to test whether, net of the ECAS-Total, motor features predicted the probability of the FAB not being administrable and of a defective FAB score. Intrinsic and post-test diagnostics were explored against a combined defective ECAS-Executive and ECAS-Fluency scores. Results 85.3% of patients managed to complete the FAB. FAB administrability rates decreased with advanced clinical stages, whereas the prevalence of below-cut-off FAB scores did not. The probability of the FAB not being administrable was predicted only by lower ALSFRS-R-bulbar and ALSFRS-R-upper-limb scores; no motor features, but the ECAS-Total, predicted a below-cut-off performance on the FAB. Raw and adjusted FAB scores showed high accuracy (AUC = .85 and .81, respectively) and good intrinsic and post-test properties. Discussion The FAB is featured by optimal diagnostics for detecting executive deficits in ALS, provided that it can be administered according to its original, standardized procedure, and thus that patients have sufficiently spared motor abilities to complete the test

Anhedonia and suicidal ideation in young people with early psychosis: Further findings from the 2-year follow-up of the ReARMS program.

Hedonic deficits have been extensively studied in schizophrenia, but little is known about their association with suicidal ideation in early psychosis. The aim of this research was to examine the relationship between anhedonia and suicidal thoughts across a 2-year follow-up period in people with First Episode Psychosis (FEP) and at Ultra High Risk (UHR) of psychosis. Ninty-six UHR and 146 FEP, aged 13–35 years, completed the Comprehensive Assessment of At-Risk Mental States (CAARMS) and the Beck Depression Inventory-II (BDI-II). The BDI-II “Anhedonia” subscale score to assess anhedonia and the CAARMS “Depression” item 7.2 subscore to measure depression were used across the 2 years of follow-up. Hierarchical regression analyses were performed. No difference in anhedonia scores between FEP and UHR individuals was found. In the FEP group, a significant enduring association between anhedonia and suicidal ideation was found at baseline and across the follow-up, independent of clinical depression. In the UHR subgroup, the enduring relationship between anhedonia and suicidal thoughts were not completely independent from depression severity. Anhedonia is relevant in predicting suicidal ideation in early psychosis. Specific pharmacological and/or psychosocial interventions on anhedonia within specialized EIP program could reduce suicide risk overtime