Changing ideas about others' intentions: updating prior expectations tunes activity in the human motor system

Predicting intentions from observing another agent’s behaviours is often thought to depend on motor resonance – i.e., the motor system’s response to a perceived movement by the activation of its stored motor counterpart, but observers might also rely on prior expectations, especially when actions take place in perceptually uncertain situations. Here we assessed motor resonance during an action prediction task using transcranial magnetic stimulation to probe corticospinal excitability (CSE) and report that experimentally-induced updates in observers’ prior expectations modulate CSE when predictions are made under situations of perceptual uncertainty. We show that prior expectations are updated on the basis of both biomechanical and probabilistic prior information and that the magnitude of the CSE modulation observed across participants is explained by the magnitude of change in their prior expectations. These findings provide the first evidence that when observers predict others’ intentions, motor resonance mechanisms adapt to changes in their prior expectations. We propose that this adaptive adjustment might reflect a regulatory control mechanism that shares some similarities with that observed during action selection. Such a mechanism could help arbitrate the competition between biomechanical and probabilistic prior information when appropriate for prediction

Norms, Norms, and Norms: Validity, Existence and Referents of the Term Norm in Alexy, Conte, and Guastini

In this paper we examine the interplay between validity and existence of a norm. We compare Amedeo Giovanni Conte’s five-folded conception of norm with the “semantic” conception of Robert Alexy’s and Riccardo Guastini’s idea of existence-as-legal-membership. We show how Alexy’s model encompasses all the referents of Conte. We investigate the interplay between different theses on the relationships between validity and existence of norms and the referents for norm that a theory is able to admit. In particular, we show that if we want to encompass all five Contean referents we have to give up the (Kelsenian) validity-as-existence thesis

Norms, Norms, and Norms: Validity, Existence and Referents of the Term Norm in Alexy, Conte, and Guastini

In this paper we examine the interplay between validity and existence of a norm. We compare Amedeo Giovanni Conte’s five-folded conception of norm with the “semantic” conception of Robert Alexy’s and Riccardo Guastini’s idea of existence-as-legal-membership. We show how Alexy’s model encompasses all the referents of Conte. We investigate the interplay between different theses on the relationships between validity and existence of norms and the referents for norm that a theory is able to admit. In particular, we show that if we want to encompass all five Contean referents we have to give up the (Kelsenian) validity-as-existence thesis

“Pay attention when turning a corner”: an overview of mental health policies in Brazil

Introduction: Brazilian’s history of psychiatric care is complex and has some dark periods, but the country managed to get international recognition for its mental health policies in the last years. Those have been currently suffering setbacks. Purpose: Review the historical context of mental health in Brazil, assessing the changes made after 2016, and carry out a critical analysis of the current inclination. Methodology: literature and narrative review using official governmental documents. Results and Discussion: Through its history, Brazil’s had ups and downs in the care of mental health patients. After almost 30 years of policies that are centered around the individual, and not only the individual’s disease, the hospitalocentric model of care has been subtly making its comeback, together with normatives that revogue rights before acquired and corroborates with segregation of the mentally ill. Conclusions: The current changes in the Mental Health politics are not walking alongside the line with movements responsible for the implementation of a biopsychosocial care. It provokes and invites us to continue fighting for fair health programs and for the continuation of the Universal Health Syste

Vandetanib versus cabozantinib in medullary thyroid carcinoma:A focus on anti‐angiogenic effects in zebrafish model

Medullary thyroid carcinoma (MTC) is a tumor deriving from the thyroid C cells. Vandetanib (VAN) and cabozantinib (CAB) are two tyrosine kinase inhibitors targeting REar-ranged during Transfection (RET) and other kinase receptors and are approved for the treatment of advanced MTC. We aim to compare the in vitro and in vivo anti‐tumor activity of VAN and CAB in MTC. The effects of VAN and CAB on viability, cell cycle, and apoptosis of TT and MZ‐CRC‐1 cells are evaluated in vitro using an MTT assay, DNA flow cytometry with propidium iodide, and An-nexin V‐FITC/propidium iodide staining, respectively. In vivo, the anti‐angiogenic potential of VAN and CAB is evaluated in Tg(fli1a:EGFP)y1 transgenic fluorescent zebrafish embryos by ana-lyzing the effects on the physiological development of the sub‐intestinal vein plexus and the tu-mor‐induced angiogenesis after TT and MZ‐CRC‐1 xenotransplantation. VAN and CAB exert comparable effects on TT and MZ‐CRC‐1 viability inhibition and cell cycle perturbation, and stimulated apoptosis with a prominent effect by VAN in MZ‐CRC‐1 and CAB in TT cells. Regard-ing zebrafish, both drugs inhibit angiogenesis in a dose‐dependent manner, in particular CAB shows a more potent anti‐angiogenic activity than VAN. To conclude, although VAN and CAB show comparable antiproliferative effects in MTC, the anti‐angiogenic activity of CAB appears to be more relevant.</p

The Role of Uric Acid in Acute and Chronic Coronary Syndromes.

Uric acid (UA) is the final product of the catabolism of endogenous and exogenous purine nucleotides. While its association with articular gout and kidney disease has been known for a long time, new data have demonstrated that UA is also related to cardiovascular (CV) diseases. UA has been identified as a significant determinant of many different outcomes, such as all-cause and CV mortality, and also of CV events (mainly Acute Coronary Syndromes (ACS) and even strokes). Furthermore, UA has been related to the development of Heart Failure, and to a higher mortality in decompensated patients, as well as to the onset of atrial fibrillation. After a brief introduction on the general role of UA in CV disorders, this review will be focused on UA's relationship with CV outcomes, as well as on the specific features of patients with ACS and Chronic Coronary Syndrome. Finally, two issues which remain open will be discussed: the first is about the identification of a CV UA cut-off value, while the second concerns the possibility that the pharmacological reduction of UA is able to lower the incidence of CV events

Ancient origin of the CARD-coiled coil/Bcl10/MALT1-like paracaspase signaling complex indicates unknown critical functions

The CARD-coiled coil (CC)/Bcl10/MALT1-like paracaspase (CBM) signaling complexes composed of a CARD-CC family member (CARD-9, -10, -11, or -14), Bcl10, and the type 1 paracaspase MALT1 (PCASP1) play a pivotal role in immunity, inflammation, and cancer. Targeting MALT1 proteolytic activity is of potential therapeutic interest. However, little is known about the evolutionary origin and the original functions of the CBM complex. Type 1 paracaspases originated before the last common ancestor of planulozoa (bilaterians and cnidarians). Notably in bilaterians, Ecdysozoa (e.g., nematodes and insects) lacks Bcl10, whereas other lineages have a Bcl10 homolog. A survey of invertebrate CARD-CC homologs revealed such homologs only in species with Bcl10, indicating an ancient common origin of the entire CBM complex. Furthermore, vertebrate-like Syk/Zap70 tyrosine kinase homologs with the ITAM-binding SH2 domain were only found in invertebrate organisms with CARD-CC/Bcl10, indicating that this pathway might be related to the original function of the CBM complex. Moreover, the type 1 paracaspase sequences from invertebrate organisms that have CARD-CC/Bcl10 are more similar to vertebrate paracaspases. Functional analysis of protein-protein interactions, NF-kappa B signaling, and CYLD cleavage for selected invertebrate type 1 paracaspase and Bcl10 homologs supports this scenario and indicates an ancient origin of the CARD-CC/Bcl10/paracaspase signaling complex. By contrast, many of the known MALT1-associated activities evolved fairly recently, indicating that unknown functions are at the basis of the protein conservation. As a proof-of-concept, we provide initial evidence for a CBM- and NF-kappa B-independent neuronal function of the Caenorhabditis elegans type 1 paracaspase malt-1. In conclusion, this study shows how evolutionary insights may point at alternative functions of MALT1

Development of a Nomogram Predicting the Risk of Persistence/Recurrence of Cervical Dysplasia

Background: Cervical dysplasia persistence/recurrence has a great impact on women's health and quality of life. In this study, we investigated whether a prognostic nomogram may improve risk assessment after primary conization. Methods: This is a retrospective multi-institutional study based on charts of consecutive patients undergoing conization between 1 January 2010 and 31 December 2014. A nomogram assessing the importance of different variables was built. A cohort of patients treated between 1 January 2015 and 30 June 2016 was used to validate the nomogram. Results: A total of 2966 patients undergoing primary conization were analyzed. The median (range) patient age was 40 (18-89) years. At 5-year of follow-up, 6% of patients (175/2966) had developed a persistent/recurrent cervical dysplasia. Median (range) recurrence-free survival was 18 (5-52) months. Diagnosis of CIN3, presence of HR-HPV types, positive endocervical margins, HPV persistence, and the omission of HPV vaccination after conization increased significantly and independently of the risk of developing cervical dysplasia persistence/recurrence. A nomogram weighting the impact of all variables was built with a C-Index of 0.809. A dataset of 549 patients was used to validate the nomogram, with a C-index of 0.809. Conclusions: The present nomogram represents a useful tool for counseling women about their risk of persistence/recurrence after primary conization. HPV vaccination after conization is associated with a reduced risk of CIN2+

Beta-Blocker Use in Older Hospitalized Patients Affected by Heart Failure and Chronic Obstructive Pulmonary Disease: An Italian Survey From the REPOSI Register

Beta (β)-blockers (BB) are useful in reducing morbidity and mortality in patients with heart failure (HF) and concomitant chronic obstructive pulmonary disease (COPD). Nevertheless, the use of BBs could induce bronchoconstriction due to β2-blockade. For this reason, both the ESC and GOLD guidelines strongly suggest the use of selective β1-BB in patients with HF and COPD. However, low adherence to guidelines was observed in multiple clinical settings. The aim of the study was to investigate the BBs use in older patients affected by HF and COPD, recorded in the REPOSI register. Of 942 patients affected by HF, 47.1% were treated with BBs. The use of BBs was significantly lower in patients with HF and COPD than in patients affected by HF alone, both at admission and at discharge (admission, 36.9% vs. 51.3%; discharge, 38.0% vs. 51.7%). In addition, no further BB users were found at discharge. The probability to being treated with a BB was significantly lower in patients with HF also affected by COPD (adj. OR, 95% CI: 0.50, 0.37-0.67), while the diagnosis of COPD was not associated with the choice of selective β1-BB (adj. OR, 95% CI: 1.33, 0.76-2.34). Despite clear recommendations by clinical guidelines, a significant underuse of BBs was also observed after hospital discharge. In COPD affected patients, physicians unreasonably reject BBs use, rather than choosing a β1-BB. The expected improvement of the BB prescriptions after hospitalization was not observed. A multidisciplinary approach among hospital physicians, general practitioners, and pharmacologists should be carried out for better drug management and adherence to guideline recommendations

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population