Appellationem recipere vel non. Il 'filtro' in appello

La fase del processo d’appello che si svolgeva innanzi al iudex a quo viveva quale primo e fondamentale momento quello in cui il giudice di primo grado era chiamato a decidere se recepire o meno l’impugnazione. Il naturale svolgimento del procedimento e la sua continuazione presso il giudice ad quem era certamente condizionato dal preliminare accertamento circa l’assenza di ragioni di improcedibilità legate a questioni di ordine formale. Secondo l’opinione tradizionale tramandata in dottrina tuttavia, il giudice di primo grado, per tutta l’età classica, era investito di un ulteriore e significativo potere, quello di bloccare il corso dell’appello qualora lo avesse ritenuto manifestamente privo di ogni fondamento. Con questa indagine si è cercato di sottoporre a vaglio critico la communis opinio, mostrando come considerazioni di ordine logico e dati testuali sembrerebbero sufficienti per ipotizzare uno scenario alternativo. Muovendo dai risultati di un recente studio condotto sulla poena appellationis e sulle altre sanzioni previste contro l’appellante temerario, si è provato a dimostrare che la necessaria funzione di ‘filtro’ degli appelli, indispensabile per preservare il corretto funzionamento dell’amministrazione della giustizia di secondo grado, fosse svolta non dal iudex a quo, sulla base di una sommaria valutazione circa la fondatezza del gravame proposto, ma prospettando all’appellante il rischio di vedersi applicate severe misure di natura pecuniaria nel caso in cui il giudice ad quem, nel respingere l’impugnazione, l’avesse giudicata priva di ogni motivo, proposta a mero scopo dilatorio e dunque temeraria

Contributo allo studio della responsabilità in duplum nel deposito

Con il presente contributo si intendono proporre, anche attraverso gli interessanti spunti di riflessione forniti dalla lettura di una declamatio minor di Quintiliano (decl. min. 254), alcune considerazioni su uno specifico e molto dibattuto aspetto relativo al depositum, rispetto al quale la componente ‘fiduciaria’ assume peculiari coloriture: oggetto di approfondimento è l’ambito, non scevro da zone d’ombra, nel quale la tutela per la mancata restituzione della res è rappresentata da un’actio in duplum, rimedio riparatorio connotato da un accentuato profilo sanzionatorio. In particolare, ci si sofferma sull’esame dei testi nei quali è fatta esplicita menzione di una sanzione nel doppio (Coll. 7.10.11 = Paul. Sent. 2.12.11; Ulp. 30 ad ed. D. 16.3.1.1; I. 4.6.26), avanzando l’ipotesi che anche in epoca decemvirale la punizione più severa del depositario fosse da collegare a depositi effettuati in situazioni di pericolo o di necessità

Exosite inhibition of ADAMTS-5 by a glycoconjugated arylsulfonamide

ADAMTS-5 is a major protease involved in the turnover of proteoglycans such as aggrecan and versican. Dysregulated aggrecanase activity of ADAMTS-5 has been directly linked to the etiology of osteoarthritis (OA). For this reason, ADAMTS-5 is a pharmaceutical target for the treatment of OA. ADAMTS-5 shares high structural and functional similarities with ADAMTS-4, which makes the design of selective inhibitors particularly challenging. Here we exploited the ADAMTS-5 binding capacity of β-N-acetyl-d-glucosamine to design a new class of sugar-based arylsulfonamides. Our most promising compound, 4b, is a non-zinc binding ADAMTS-5 inhibitor which showed high selectivity over ADAMTS-4. Docking calculations combined with molecular dynamics simulations demonstrated that 4b is a cross-domain inhibitor that targets the interface of the metalloproteinase and disintegrin-like domains. Furthermore, the interaction between 4b and the ADAMTS-5 Dis domain is mediated by hydrogen bonds between the sugar moiety and two lysine residues (K532 and K533). Targeted mutagenesis of these two residues confirmed their importance both for versicanase activity and inhibitor binding. This positively-charged cluster of ADAMTS-5 represents a previously unknown substrate-binding site (exosite) which is critical for substrate recognition and can therefore be targeted for the development of selective ADAMTS-5 inhibitors

Exosite inhibition of ADAMTS-5 by a glycoconjugated arylsulfonamide

ADAMTS-5 is a major protease involved in the turnover of proteoglycans such as aggrecan and versican. Dysregulated aggrecanase activity of ADAMTS-5 has been directly linked to the etiology of osteoarthritis (OA). For this reason, ADAMTS-5 is a pharmaceutical target for the treatment of OA. ADAMTS-5 shares high structural and functional similarities with ADAMTS-4, which makes the design of selective inhibitors particularly challenging. Here we exploited the ADAMTS-5 binding capacity of β-N-acetyl-d-glucosamine to design a new class of sugar-based arylsulfonamides. Our most promising compound, 4b, is a non-zinc binding ADAMTS-5 inhibitor which showed high selectivity over ADAMTS-4. Docking calculations combined with molecular dynamics simulations demonstrated that 4b is a cross-domain inhibitor that targets the interface of the metalloproteinase and disintegrin-like domains. Furthermore, the interaction between 4b and the ADAMTS-5 Dis domain is mediated by hydrogen bonds between the sugar moiety and two lysine residues (K532 and K533). Targeted mutagenesis of these two residues confirmed their importance both for versicanase activity and inhibitor binding. This positively-charged cluster of ADAMTS-5 represents a previously unknown substrate-binding site (exosite) which is critical for substrate recognition and can therefore be targeted for the development of selective ADAMTS-5 inhibitors

Metabolic Profiling of Inga Species with Antitumor Activity.

Funding: This research received no external funding. Acknowledgments: The authors thank Brazilian Research Agencies CNPq, CAPES, and FAPESP, as well as Albrn Care, India.Peer reviewedPublisher PD

Self-reported competencies related to end of life care among residents and attending physicians

Abstract Aims Research with residents demonstrates perceptions of insufficient skills and comfort with end of life (EOL) care, and there is a paucity of evidence regarding attending physicians' competencies in such care. The purpose of this study was to gain an understanding of self-reported competencies among medical school graduates and to assess the impact of a 3 rd year hospice rotation. Methods An online survey was sent to 510 medical school alumni assessing experiences, self-rated competencies and preparedness regarding EOL care, and perceptions of the hospice rotation. Analyses explored a range of possible variable associations. Results 116 surveys were completed. EOL care experience was substantial during undergraduate and residency training. More experience was predictive of greater skills and comfort. Pain management skills were rated lower than other skills. Completion of the hospice rotation was associated with confidence-building and perceptions of preparedness. Attending physicians did not report stronger skills than residents. There was strong support for training in EOL care. Conclusions Our findings support previous research about the benefits of EOL care experiences for residents and exposure to such care during undergraduate training, underscoring the importance of well-tailored EOL care education at all levels of training for optimal development of competencies

Comparisons of American, Israeli, Italian and Mexican physicians and nurses on the total and factor scores of the Jefferson scale of attitudes toward physician-nurse collaborative relationships

This cross-cultural study was designed to compare the attitudes of physicians and nurses toward physician–nurse collaboration in the United States, Israel, Italy and Mexico. Total participants were 2522 physicians and nurses who completed the Jefferson Scale of Attitudes Toward Physician–Nurse Collaboration (15 Likert-type items, (Hojat et al., Evaluation and the Health Professions 22 (1999a) 208; Nursing Research 50 (2001) 123). They were compared on the total scores and four factors of the Jefferson Scale (shared education and team work, caring as opposed to curing, nurses, autonomy, physicians’ dominance). Results showed inter- and intra-cultural similarities and differences among the study groups providing support for the social role theory (Hardy and Conway, Role Theory: Perspectives for Health Professionals, Appleton-Century-Crofts, New York, 1978) and the principle of least interest (Waller and Hill, The Family: A Dynamic Interpretation, Dryden, New York, 1951) in inter-professional relationships. Implications for promoting physician–nurse education and inter-professional collaboration are discussed