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Unsatisfactory outcomes for relapsed/refractory lymphoma patients prompt continuing efforts to develop new therapeutic strategies. Our previous studies on pyrrole-based anti-lymphoma agents led us to synthesize a new series of twenty-six pyrrolo[3′,4':3,4]cyclohepta[1,2-d] [1,2]oxazole derivatives and study their antiproliferative effects against a panel of four non-Hodgkin lymphoma cell lines. Several candidates showed significant anti-proliferative effects, with IC50's reaching the sub-micromolar range in at least one cell line, with compound 3z demonstrating sub-micromolar growth inhibitory effects towards the entire panel. The VL51 cell line was the most sensitive, with an IC50 value of 0.10 μM for 3z. Our earlier studies had shown that tubulin was a prominent target of many of our oxazole derivatives. We therefore examined their effects on tubulin assembly and colchicine binding. While 3u and 3z did not appear to target tubulin, good activity was observed with 3d and 3p. Molecular docking and molecular dynamics simulations allowed us to rationalize the binding mode of the synthesized compounds toward tubulin. All ligands exhibited a better affinity for the colchicine site, confirming their specificity for this binding pocket. In particular, a better affinity and free energy of binding was observed for 3d and 3p. This result was confirmed by experimental data, indicating that, although both 3d and 3p significantly affected tubulin assembly, only 3d showed activity comparable to that of combretastatin A-4, while 3p was about 4-fold less active. Cell cycle analysis showed that compounds 3u and especially 3z induced a block in G2/M, a strong decrease in S phase even at low compound concentrations and apoptosis through the mitochondrial pathway. Thus, the mechanism of action of 3u and 3z remains to be elucidated. Very high selectivity toward cancer cells and low toxicity in human peripheral blood lymphocytes were observed, highlighting the good potential of these agents in cancer therapy and encouraging further exploration of this compound class to obtain new small molecules as effective lymphoma treatments.

The Covid-19 pandemic triggered governments and designers to revalue and redesign public spaces. This paper focuses on the various design responses to Covid-19 proposed and implemented in public spaces. In particular, we identify the kinds of challenges that such design responses address and the strategies that they use. We selected 56 design examples, largely collected from internet sources. By analyzing the design examples we identified five Covid-related challenges that were addressed in public space: sustaining amenities, keeping a distance, feeling connected, staying mentally healthy, and expanding health infrastructures. For each challenge, we articulated 2 to 6 design strategies. The challenges highlight the potential of public space to contribute to more resilient cities during times of pandemic, also in the future. The design strategies show the possible ways in which this potential can be fulfilled. In our next steps, we will use our findings to develop a program of possibilities; this program will contain a wide range of design strategies for responding to future pandemics and will be made publically accessible in an online database. The program contributes to more resilient post-Covid cities, by offering a variety of possibilities for coping with, and adapting to, pandemic-related shocks and stressors.

Background: The nipples-saving mastectomy (NSM), most recent technique, allows the whole mammary gland removal preserving the nipple-areola compound (NAC), obtaining oncologic safe results. When indicated, NSM is validated by the great aesthetic results obtained. Objectives: The objective of this review is the evaluation of the effectiveness and oncologic safety of the nipple-saving mastectomy, marking the most frequent complications. Moreover, the possibility to use the NSM procedure as prophylactic mastectomy in patients at high risk has been evaluated. Research Methods: A bibliographic research about clinical studies and previous reviews related to nipplessaving mastectomy has been conducted. No limitation about language was performed. Results: The study included 12 articles, for a total of 2859 patients and 3849 NSM. Patients candidate to NSM, either as a prophylactic or curative treatment of mammary carcinoma, must undergo a careful selection screening. Most frequently occurring surgery-related complications were necrosis and infections; though not altering the cosmetic results, that have been positively evaluated in almost all patients. Conclusion: Preservation of the areola-nipple compound seems to be oncologically safe and does not increase local recurrences, compared to the previous techniques. Moreover, it is associated with better aesthetic results and patients’ higher satisfaction.

Particular interest is now being given to the best treatment of papillary thyroid microcarcinoma (PTMC) due to its significantly increased incidence. PTMC typically shows indolent organic behavior but, in a low percentage of cases, it can express a relative aggressive behavior. Several risk factors have been shown to negatively influence the rate of regional recurrences and metastases such as tumor diameter, Romaage, sex, multifocality, capsular invasion, extracellular diffusion, lymph node metastases, histological variants, mutated Braf and incidentality. The identification of patients with aggressive PTMCs among the majority with low risk lesions is very important to plan an adequate clinical management, thus the most appropriate surgical treatment. The latter includes thyroid lobectomy and total thyroidectomy with central compartment lymphadenectomy, though several studies did not show statistically significant differences in terms of recurrence and mortality rates between the two techniques. At last, it seems crucial to better define those biological features able to improve selection making process of patients with PTMCs aiming to reserve more radical surgery to those patients carrying more aggressive clinicopathologic features and worse prognosis.

The Italian Law n. 9/2012 provided the Italian Regions with a new decisional role by demanding the management/rehabilitation of prisoners judged as partially/fully mentally ill to care and protection delivered by the psychiatric services of the Regional Health Service. Healthcare has to be guaranteed by the so-called High-Security Forensic Psychiatry Residences (Italian: Residenze per l'Esecuzione delle Misure di Sicurezza: REMS) and by community mental health centres. Ensuring patients' and professionals' health and safety is a complex issue which requires effective strategies to cope with several structural, technological, and organisational problems. The present paper summarises the historical evolution of the Italian laws towards the development of the High-Security Forensic Psychiatry Residences in Italy, focusing specifically on the Tuscany Region situation. The paper also presents the key issues emerging after the implementation of the Law 81/2014 which complemented the Law 9/2012. Since these reforms included the need for assessing to what extent the patient may be considered as a danger to society and for ensuring the safety of National Health Service (NHS) professionals, they underscored the importance of a preventive use of specific clinical governance tools aimed to reduce risk of adverse events. The present work has the strength of proposing a new, evidence-based scientific approach to the implementation of assessment and care pathways in High-Security Forensic Psychiatry Residences.