An overview of trends in the regulation of clinical ethics committee; an opinion from the Italian National Bioethics Committee [Una visión general de las tendencias en la regulación por los comités de ética clínica: una opinión del Comité Nacional Italiano de Bioética]

In 2017, the Italian National Bioethics Commttee (INBC) released an opinion paper titled "Clinical ethics committees". Said document advocates for the creation of "clinical bioethics committees" in every suitable setting and lays out a set of guidelines aimed at regulationg such committees' function. The recommendations deal primarily with the independence, requirements for counselling, structures, composition, tasks, placement, coordination, requisite competences, regulations. In the opinion's contents there are: a) the need to entrust counselling and training on ethical issues within clinical practice to different committees than those that deal with ethical assessment of scientific trial and experimentation; b) the laying out of all the various functions and related competences required of the ethics committes' members; c) the necessity that all counselling pratices be carried out by each committee as a whole, rather than a single expert member; d) Committee's independece. The authors elaborate on each one of the above mentioned aspects and highlight the importance of INBC's recommendations in order to improve the quality standards of care delivered "to each patient's bed".En el 2017, el Comité Nacional Italiano de Bioética (CNIB) publicó un artículo de opinión titulado “Comités de Ética Clínica”. Dicho documento aboga por la creación de “comités clínicos de bioética” en cada entorno adecuado, y establece un conjunto de directrices destinadas a regular las funciones de tales comités. Las recomendaciones se refieren principalmente a la independencia, los requisitos para el asesoramiento, las estructuras, la composición, las tareas, la ubicación, la coordinación, las competencias requeridas, las regulaciones. En los contenidos de la opinión se plantean: a) la necesidad de confiar el asesoramiento y la capacitación en cuestiones éticas dentro de la práctica clínica a diferentes comités que aquellos que se ocupan de las evaluaciones éticas de los ensayos científicos y la experimentación; b) la presentación de las diversas funciones y competencias requeridas por los miembros de los comités de ética; c) la necesidad de que todas las prácticas de asesoramiento sean llevadas a cabo por cada comité como un todo, y no por un solo miembro experto; d) independencia del comité. Los autores detallan cada uno de los aspectos mencionados anteriormente y resaltan la importancia de las recomendaciones de CNIB para mejorar los estándares de calidad de la atención brindada “a la cabecera de la cama de cada paciente”

Professional Concerns: Reading Comprehension and Essay Writing

Glenda C. Petrini, a Social Studies teacher at Thoreau Intermediate School in Vienna, Virginia, had tried for five years to teach the inquiry method to her students before she tried using reading skills as a vehicle for the comprehension of inquiry. In her article which follows, Ms. Petrini tells how she used the knowledge which she gained of reading skills to instruct her students in ways that would significantly strengthen their essay writing. Ms. Petrini presents convincing evidence that the teaching of reading and the teaching of writing can be combined very effectively

The Music of Your Emotions: Neural Substrates Involved in Detection of Emotional Correspondence between Auditory and Visual Music Actions

In humans, emotions from music serve important communicative roles. Despite a growing interest in the neural basis of music perception, action and emotion, the majority of previous studies in this area have focused on the auditory aspects of music performances. Here we investigate how the brain processes the emotions elicited by audiovisual music performances. We used event-related functional magnetic resonance imaging, and in Experiment 1 we defined the areas responding to audiovisual (musician's movements with music), visual (musician's movements only), and auditory emotional (music only) displays. Subsequently a region of interest analysis was performed to examine if any of the areas detected in Experiment 1 showed greater activation for emotionally mismatching performances (combining the musician's movements with mismatching emotional sound) than for emotionally matching music performances (combining the musician's movements with matching emotional sound) as presented in Experiment 2 to the same participants. The insula and the left thalamus were found to respond consistently to visual, auditory and audiovisual emotional information and to have increased activation for emotionally mismatching displays in comparison with emotionally matching displays. In contrast, the right thalamus was found to respond to audiovisual emotional displays and to have similar activation for emotionally matching and mismatching displays. These results suggest that the insula and left thalamus have an active role in detecting emotional correspondence between auditory and visual information during music performances, whereas the right thalamus has a different role

Informed consent in elderly people: assessing the patient’s decision-making capacity = Consenso informato al trattamento medico: valutazione della capacità decisionale del paziente anziano

La capacit\ue0 di un paziente anziano di prendere delle decisioni mediche deve essere considerata sempre valida, indipendentemente dall\u2019et\ue0. Quando il paziente, per\uf2, non \ue8 in grado di accettare o rifiutare un trattamento, non pu\uf2 comprendere e ricordare le informazioni ricevute e/o non pu\uf2 utilizzare tali informazioni quando deve esprimere la propria decisione, \ue8 necessario valutare la sua capacit\ue0 decisionale mediante strumenti clinici obiettivi, poich\ue9 il consenso ottenuto da un paziente privo di capacit\ue0 decisionale non \ue8 legalmente valido. Lo strumento per la valutazione della capacit\ue0 decisionale dovrebbe essere semplice e di facile uso, obiettivo e replicabile; dovrebbe poter essere somministrato in breve tempo e, possibilmente, non richiedere alcun addestramento formale. MATERIALI E METODI Nel presente lavoro sono stati presi in considerazione i metodi di screening pi\uf9 frequentemente utilizzati per valutare la capacit\ue0 decisionale del paziente: il MacArthur Competence Assessment Tool for Treatment (MacCAT-T), l\u2019Aid to Capacity Evaluation (ACE) e il Mini Mental State Examination (MMSE). RISULTATI Il MMSE \ue8 uno strumento clinico di semplice utilizzo, non richiede una formazione specifica, pu\uf2 essere somministrato in meno di 10 minuti, \ue8 un test obiettivo e, anche se non \ue8 stato creato specificamente per valutare l\u2019incapacit\ue0, utilizza punteggi facilmente fruibili dal medico. Il punteggio va da 0 a 30: un punteggio MMSE da 0 a 17 si associa a elevata probabilit\ue0 di incapacit\ue0 decisionale; un punteggio da 18 a 23 indica un lieve deficit cognitivo, mentre il punteggio da 24 a 30 riduce significativamente la probabilit\ue0 di perdita dell\u2019autonomia decisionale. CONCLUSIONI Il Mini Mental State Examination pu\uf2 essere considerato lo strumento clinico pi\uf9 adatto per il medico nella pratica quotidiana. Nei pazienti con un basso punteggio MMSE, che suggerisce la probabilit\ue0 di mancanza di capacit\ue0 decisionale, sar\ue0 necessario che il consenso alle procedure mediche sia concesso da un tutore legale o dall\u2019amministratore di sostegno, secondo le leggi e la giurisdizione del paese coinvolto.OBJECTIVE Elderly patients are legally assumed to be competent to give consent to medical treatment. When patients are unable to make a decision on assenting or refusing treatment; if they cannot understand and remember the information provided, andor cannot use that information when considering their decision, the decision-making capacity of the patient should be evaluated with specific clinical tools, since consent obtained from an incompetent patient is invalid. The clinical tool should be simple and easy to use, be replicable, and should require a short administration time and, possibly, no formal training. MATERIALS AND METHODS We have considered frequently used clinical screening methods for cognitive impairment, such as the MacArthur Competence Assessment Tool for Treatment (Mac-CAT-T), the Aid to Capacity Evaluation (ACE) and the Mini Mental State Examination (MMSE), to evaluate the decision-making capacity of the patient. RESULTS The MMSE is a very simple bedside clinical tool, does not require specific training, takes less than 10 minutes to complete, is objective and uses scores indicating decreasing cognitive function. The scores range from 0 to 30: a MMSE score of 0 to 17 increases the likelihood of lack of capacity, a score of 18 to 23 indicates mild cognitive impairment, while a score of 24 to 30 significantly reduces the likelihood of incapacity. CONCLUSIONS The Mini Mental State Examination can be considered the clinical tool more suitable for the physician in the daily practice. In patients with a low MMSE score, suggesting likelihood of lack of capacity, it will be necessary that the consent to medical procedures be granted by a surrogate decision maker, according to the laws and jurisdiction of the country involved

Microbiological-chemical sourced chondroitin sulfates protect neuroblastoma SH-SY5Y cells against oxidative stress and are suitable for hydrogel-based controlled release

Chondroitin sulfates (CS) are a class of sulfated glycosaminoglycans involved in many biological processes. Several studies reported their protective effect against neurodegenerative conditions like Alzheimer’s disease. CS are commonly derived from animal sources, but ethi-cal concerns, the risk of contamination with animal proteins, and the difficulty in controlling the sulfation pattern have prompted research towards non-animal sources. Here we exploited two microbiological-chemical sourced CS (i.e., CS-A,C and CS-A,C,K,L) and Carbopol 974P NF/agarose semi-interpenetrating polymer networks (i.e., P.NaOH.0 and P.Ethanol.0) to set up a release system, and tested the neuroprotective role of released CS against H2 O2-induced oxidative stress. After assessing that our CS (1–100 µM) require a 3 h pre-treatment for neuroprotection with SH-SY5Y cells, we evaluated whether the autoclave type (i.e., N-or B-type) affects hydrogel viscoelastic properties. We selected B-type autoclaves and repeated the study after loading CS (1 or 0.1 mg CS/0.5 mL gel). After loading 1 mg CS/0.5 mL gel, we evaluated CS release up to 7 days by 1,9-dimethylmethylene blue (DMMB) assay and verified the neuroprotective role of CS-A,C (1 µM) in the supernatants. We observed that CS-A,C exhibits a broader neuroprotective effect than CS-A,C,K,L. Moreover, sulfation pattern affects not only neuroprotection, but also drug release

New supersymmetric AdS4 type II vacua

Building on our recent results on dynamic SU(3)xSU(3) structures we present a set of sufficient conditions for supersymmetric AdS4xM6 backgrounds of type IIA/IIB supergravity. These conditions ensure that the background solves, besides the supersymmetry equations, all the equations of motion of type II supergravity. The conditions state that the internal manifold is locally a codimension-one foliation such that the five dimensional leaves admit a Sasaki-Einstein structure. In type IIA the supersymmetry is N=2, and the total six-dimensional internal space is locally an S^2 bundle over a four-dimensional Kaehler-Einstein base; in IIB the internal space is the direct product of a circle and a five-dimensional squashed Sasaki-Einstein manifold. Given any five-dimensional Sasaki-Einstein manifold we construct the corresponding families of type IIA/IIB vacua. The precise profiles of all the fields are determined at the solution and depend on whether one is in IIA or in IIB. In particular the background does not contain any sources, all fluxes (including the Romans mass in IIA) are generally non-zero, and the dilaton and warp factor are non-constant.Comment: 19 pages; clarifications added, version to appear in JHE

Differential regulation of iron regulatory element-binding protein(s) in cell extracts of activated lymphocytes versus monocytes-macrophages.

The intracellular iron level exerts a negative feedback on transferrin receptor (TfR) expression in cells requiring iron for their proliferation, in contrast to the positive feedback observed in monocytes-macrophages. It has been suggested recently that modulation of TfR and ferritin synthesis by iron is mediated through a cytoplasmic protein(s) (iron regulatory element-binding protein(s) (IRE-BP)), which interacts with ferritin and TfR mRNA at the level of hairpin structures (IRE), thus leading to inhibition of transferrin mRNA degradation and repression of ferritin mRNA translation. In the present study we have evaluated in parallel the level of TfR expression, ferritin, and IRE-BP in cultures of: (i) circulating human lymphocytes stimulated to proliferate by phytohemagglutinin (PHA) and (ii) circulating human monocytes maturing in vitro to macrophages. The cells were grown in either standard or iron-supplemented culture. TfR and ferritin expression was evaluated at both the protein and mRNA level. IRE-BP activity was measured by gel retardation assay in the absence or presence of beta-mercaptoethanol (spontaneous or total IRE-BP activity, respectively). Spontaneous IRE-BP activity, already present at low level in quiescent T lymphocytes, shows a gradual and marked increase in PHA-stimulated T cells from day 1 of culture onward. This increase is directly and strictly correlated with the initiation and gradual rise of TfR expression, which is in turn associated with a decrease of ferritin content. Both the rise of TfR and spontaneous IRE-BP activity are completely inhibited in iron-supplemented T cell cultures. In contrast, the total IRE-BP level is similar in both quiescent and PHA-stimulated lymphocytes, grown in cultures supplemented or not with iron salts. Monocytes maturing in vitro to macrophages show a sharp increase of spontaneous and, to a lesser extent, total IRE-BP; the addition of iron moderately stimulates the spontaneous IRE-BP activity but not the total one. Here again, the rise of spontaneous IRE-BP from very low to high activity is strictly related to the parallel increase of TfR expression and, suprisingly, also with a very pronounced rise of ferritin expression observed at both the mRNA and protein level. It is noteworthy the effect of beta-mercaptoethanol is cell specific, i.e. the ratio of total versus spontaneous IRE-BP activity is different in activated lymphocytes and maturing monocytes.(ABSTRACT TRUNCATED AT 400 WORDS

Dipeptidyl-Peptidase 4 (Cd26): a Possible Therapeutic Target in Covid-19

ARS-COV-2, a novel β-coronavirus, is the cause of a severe inflammatory infectious disease of the respiratory tract (COVID-19). The spread has already taken on pandemic proportions, affecting over 2,5 million people and causing more than 170,000 deaths. The mechanisms and strategies underlying the virus power of penetrating human cells and causing the well-known spectrum of diseases induced by SARS-COV-2 have been explored worldwide. Two host receptors able to specifically inducing virus-host linkage, entry and, consequently, productive infection, have been suggested to interact with the outer membrane spike viral glycoprotein: the angiotensin converting enzyme 2 (ACE2) and the dipeptidyl-peptidase 4 (DPP4), also known as CD26. Both these receptors are highly expressed on several human tissues (i.e. kidney, pancreas, gut, lung, endothelium, pleura, myocardium, connective tissue) accounting for the variable clinical manifestations of COVID-19. CD26 is also over-expressed in stimulated T, B, and NK cells, thus representing an activation marker of the immune system. However, CD26 is not only the functional host receptor for SARS- CoV-2. Indeed, published data available from the previous SARS-CoV and MERS-CoV outbreaks showed that CD26 is also utilized for sustaining inflammation and counteracting the host immune response. Specifically, through CD26, coronavirus may increase inflammatory cytokine production, down- modulate the autophagy, and increase levels of adenosine, hence further deactivating the host immune response. Thus, compounds able to inhibit the DPP4/CD26 pathway might be useful against COVID-19. In this respect, promising therapeutic approaches could include: 1) DPP4 inhibitors, such as sitagliptin, already used for treating diabetic patients; 2) Begelomab, the anti-CD26 monoclonal antibody already successfully employed in the treatment of graft-versus-host disease, and 3) adenosine deaminase agonists, already used in the immunodeficiencies sustained by the adenosine deaminase gene mutations. The article will review some pathogenic landscapes and will hypothesize some promising drugs to face the COVID-19 emergency