Fabrizio Bisconti. In Memoriam

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Clinical Research Nurse involvement to foster a community based transcultural research in RODAM European study

Background and aim of the work: The Clinical Research Nurse (CRN) can be considered the fulcrum of clinical studies, being a vital link between patient, principal investigator, study sponsor and administrative staff. The clinical research’s way is still long and the contribution that CRNs can provide is crucial. In Italy, a CRN was employed in the study: Research on Obesity & Type 2 Diabetes among African Migrants (RODAM). The aim of the paper is to explore and describe the experience of this involvement. Methods: The CRN managed the project in order to gain a complete collaboration from the Ghanaian population. From the first contact, the CRN decided to adopt a transcultural approach with the aim to create a relationship of understanding, mutual trust respect for each other’s cultural diversity. The CRN also used organizational, technical and linguistic skills. Results: The day-to-day trial management from CRN included the following activities: obtaining local Ethics Committee study approval; recruiting the study staff; planning the study activities; identifying potential study participants; collaborating with the mediators; managing contacts with other RODAM centers; conducting a follow-up of patients. The most important results of CRN involvement have been the empowerment of Ghanaian community and the effective healthcare promotion. Conclusions: The project encouraged the Ghanaian community to increase their healthcare awareness and encouraged the Ghanaian population to create new strategies to face the hard health challenges. The CRN is the most versatile and appropriate health professional to deal the entire study

Collective awareness platforms and digital social innovation mediating consensus seeking in problem situations

In this paper we show the results of our studies carried out in the framework of the European Project SciCafe2.0 in the area of Participatory Engagement models. We present a methodological approach built on participative engagements models and holistic framework for problem situation clarification and solution impacts assessment. Several online platforms for social engagement have been analysed to extract the main patterns of participative engagement. We present our own experiments through the SciCafe2.0 Platform and our insights from requirements elicitation

The narrative interview for the assessment of the assisted person: structure, method and data analysis

Background and aim: If it is true that the impact of the symptoms of the disease is differently perceived by each person and that there is an incommunicability of the experiences of suffering, it is equally true that the narration provides an understandable representation, which derives from the network of representations that are part of a personal history. The aim of this study was to offer an in-depth analysis of the “narrative interview” collected during the assessment of a 74 years old diabetic woman. Methods: A case study was conducted by a nurse with advanced expertise in conducting narrative interview. Content analysis and Meaning analysis were performed using a Grounded theory approach and according with Gee’s Poetic Method. Results: The patient after the diagnosis felt disbelief, anger and confusion. The illness forces her to change her life, habits and social role, with high suffering. However she adjusted to this new condition and thanks to her strong and positive attitude and the social support she received, she has succeeded in activating her “post traumatic growth”. Conclusions: A good narrative interview starts long before the interview itself and it requires: a specific training in the use of the instrument; the strengthening of specific skills (e.g. the active listening); the choice of optimal setting and timing for the patient; the ability to offer encouragement in the expression of the subjective experience and to conduct an analysis of the patient’s words with a subjective lens, reflecting the uniqueness of each illness experience

Naturally Occurring PCSK9 Inhibitors

Genetic, epidemiological and pharmacological data have led to the conclusion that antagonizing or inhibiting Proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces cardiovascular events. This clinical outcome is mainly related to the pivotal role of PCSK9 in controlling low-density lipoprotein (LDL) cholesterol levels. The absence of oral and affordable anti-PCSK9 medications has limited the beneficial effects of this new therapeutic option. A possible breakthrough in this field may come from the discovery of new naturally occurring PCSK9 inhibitors as a starting point for the development of oral, small molecules, to be used in combination with statins in order to increase the percentage of patients reaching their LDL-cholesterol target levels. In the present review, we have summarized the current knowledge on natural compounds or extracts that have shown an inhibitory effect on PCSK9, either in experimental or clinical settings. When available, the pharmacodynamic and pharmacokinetic profiles of the listed compounds are described

Social Requests and Social Affordances: How They Affect the Kinematics of Motor Sequences during Interactions between Conspecifics

The present study aimed at determining whether and what factors affect the control of motor sequences related to interactions between conspecifics. Experiment 1 demonstrated that during interactions between conspecifics guided by the social intention of feeding, a social affordance was activated, which modified the kinematics of sequences constituted by reaching-grasping and placing. This was relative to the same sequence directed to an inanimate target. Experiments 2 and 4 suggested that the related-to-feeding social request emitted by the receiver (i.e. the request gesture of mouth opening) is prerequisite in order to activate a social affordance. Specifically, the two experiments showed that the social request to be fed activated a social affordance even when the sequences directed towards a conspecific were not finalized to feed. Experiment 3 showed that moving inside the peripersonal space of a conspecific, who did not produce any social request, marginally affected the sequence. Finally, experiments 5 and 6 indicated that the gaze of a conspecific is necessary to make a social request effective at activating a social affordance. Summing up, the results of the present study suggest that the control of motor sequences can be changed by the interaction between giver and receiver: the interaction is characterized by a social affordance that the giver activates on the basis of social requests produced by the receiver. The gaze of the receiver is a prerequisite to make a social request effective

Three-Dimensional Radiographic Evaluation of the Malar Bone Engagement Available for Ideal Zygomatic Implant Placement

Zygomatic implant rehabilitation is a challenging procedure that requires an accurate prosthetic and implant plan. The aim of this study was to evaluate the malar bone available for three-dimensional zygomatic implant placement on the possible trajectories exhibiting optimal occlusal emergence. After a preliminary analysis on 30 computed tomography (CT) scans of dentate patients to identify the ideal implant emergencies, we used 80 CT scans of edentulous patients to create two sagittal planes representing the possible trajectories of the anterior and posterior zygomatic implants. These planes were rotated clockwise on the ideal emergence points and three different hypothetical implant trajectories per zygoma were drawn for each slice. Then, the engageable malar bone and intra- and extra-sinus paths were measured. It was possible to identify the ideal implant emergences via anatomical landmarks with a high predictability. Significant differences were evident between males and females, between implants featuring anterior and those featuring posterior emergences, and between the different trajectories. The use of internal trajectories provided better bone engagement but required a higher intra-sinus path. A significant association was found between higher intra-sinus paths and lower crestal bone heights

Tuning the cytotoxicity of ruthenium(ii) para-cymene complexes by mono-substitution at a triphenylphosphine/phenoxydiphenylphosphine ligand

The new complexes [RuCl2(η6-p-cymene)(κP-Ph2PR)] [R = 4-C6H4OSiMe2tBu, 1; R = 4-C6H4Br, 2; R = OC(O)CHCl2, 3; R = OPh, 4; R = O(2-C6H4SiMe2tBu), 5] and [Ru(C2O4)(η6-p-cymene)κP-Ph2PO(2-C6H4(SiMe2tBu))], 6, were obtained in 83-98% yield from Ru(ii) arene precursors by three different synthetic strategies. The unprecedented phosphine Ph2P(O(2-C6H4SiMe2tBu)) was synthesized in 86% yield from 2-C6H4Br(OSiMe2tBu) and Ph2PCl, via intramolecular oxygen to carbon 1,3 migration of the silyl group (retro-Brook rearrangement). All the complexes were fully characterized by analytical and spectroscopic methods, and by single crystal X-ray diffraction in the cases of 3, 4, 5 and 6. Complexes 1-6 and the model compounds [RuCl2(η6-p-cymene)(κP-PPh3)] (Ru-PPh3) and [Ru(C2O4)(η6-p-cymene)(κP-PPh3)] (Ru-PPh3-O) underwent slow degradation in chloroform solutions upon air contact; the mixed valence complex [(η6-p-cymene)Ru(μ-Cl)3RuCl2(κP-PPh3)], 7, was isolated from a solution of Ru-PPh3in CHCl3, and X-ray identified. The antiproliferative activity of 1-6 and Ru-PPh3, Ru-PPh3-O and [RuCl2(η6-p-cymene)(κP-PTA)] (RAPTA-C) was assessed towards the triple-negative breast cancer cell line MDA-MB-231, the ovarian carcinoma cell line A2780 and human skin fibroblasts (HSF). Complexes 1, 2, 5 and 6 displayed IC50values significantly lower than that of cisplatin, with 2 providing a more potent cytotoxic effect on MDA-MB-231 and A2780 cancer cells compared to the noncancerous cell line (HSF). The stability of all complexes in DMSO/water solution was elucidated by NMR and conductivity measurements, and in particular35Cl NMR spectroscopy was helpful to check the possible chloride dissociation. The stability studies suggest that the cytotoxic activity in vitro of the compounds is mainly ascribable to Ru(ii) species still bound to the phosphorus ligand

Pharmacological aspects of ANGPTL3 and ANGPTL4 inhibitors: new therapeutic approaches for the treatment of atherogenic dyslipidemia

Among the determinants of atherosclerotic cardiovascular disease (ASCVD), genetic and experimental evidence has provided data on a major role of angiopoietin-like proteins 3 and 4 (ANGPTL3 and ANGPTL4) in regulating the activity of lipoprotein lipase (LPL), antagonizing the hydrolysis of triglycerides (TG). Indeed, beyond low-density lipoprotein cholesterol (LDL-C), ASCVD risk is also dependent on a cluster of metabolic abnormalities characterized by elevated fasting and post-prandial levels of TG-rich lipoproteins and their remnants. In a head-to-head comparison between murine models for ANGPTL3 and ANGPTL4, the former was found to be a better pharmacological target for the treatment of hypertriglyceridemia. In humans, loss-of-function mutations of ANGPTL3 are associated with a marked reduction of plasma levels of VLDL, low-density lipoprotein (LDL) and high-density lipoprotein (HDL). Carriers of loss-of-function mutations of ANGPTL4 show instead lower TG-rich lipoproteins and a modest but significant increase of HDL. The relevance of ANGPTL3 and ANGPTL4 as new therapeutic targets is proven by the development of monoclonal antibodies or antisense oligonucleotides. Studies in animal models, including non-human primates, have demonstrated that short-term treatment with monoclonal antibodies against ANGPTL3 and ANGPTL4 induces activation of LPL and a marked reduction of plasma TG-rich-lipoproteins, apparently without any major side effects. Inhibition of both targets also partially reduces LDL-C, independent of the LDL receptor. Similar evidence has been observed with the antisense oligonucleotide ANGPTL3-LRX. The genetic studies have paved the way for the development of new ANGPTL3 and 4 antagonists for the treatment of atherogenic dyslipidemias. Conclusive data of phase 2 and 3 clinical trials are still needed in order to define their safety and efficacy profile