New organotin(IV) complexes with L-Arginine,Nα-t-Boc-L-Arginine and L-Alanyl-L-Arginine.Synthesis, structural investigations and cytotoxic activity

Novel diorganotin(IV) derivatives of L-Arginine (HArg), Nα-(tert-Butoxycarbonyl)-L-Arginine (Boc-Arg-OH) and L-Ala-L-Arg (H2Ala-Arg), H2NC(=NH)NH(CH2)3CH(NHR)CO2H, where R = H in HArg, R = C(O)OC(CH3)3 in Boc-Arg-OH, R = H2NCH(CH3)CO in H2Ala-Arg and triorganotin(IV) derivatives of Boc-Arg-OH have been synthesized and structurally characterized. The complexes were investigated by FT-IR and 119Sn Mössbauer in the solid state and by 1H, 13C, 119Sn and 1H-1H COSY NMR spectroscopy, in solution. The spectroscopic characterization leading to the proposed molecular structures was accomplished on the basis of these experiments. L-Arginine appears to behave as a chelating ligand through carboxylate and -NH2 groups in Me2Sn(Arg)2, while in N-t-Boc-L-Arginine complex, the N-protected amino group being exempted from coordination, only the carboxylate groups are effectors of bonding to the organometallic moieties. FT-IR spectra give a clear indication that guanidino groups in all the complexes are not involved in coordination, since (C=N-H) frequency of the terminal guanidino group is fairly constant and unshifted relative to the free ligand. The biological activity of organotin(IV)-complexes was also investigated by use of human HT29 colorectal carcinoma cells. The cytotoxic activity of the compounds was determined by the MTT quantitative colorimetric assay, capable of detecting viable cells in comparison with that exerted by cisplatin. A marked cytotoxic activity for nearly all complexes, is evident being higher than that exerted by cisplatin, while no significant improvement of activity was observed for Me2Sn(Arg)2 and Me2Sn(Ala-Arg), which was confirmed by IC50 values. Then, we assessed whether the cytotoxicity induced by organotin(IV) complexes was associated with the induction of apoptosis. Light microscopy analysis, performed to study the morphological changes induced in HT29 cells, confirmed the results obtained with MTT test. No significant morphological alterations were observed in HT29 cells after treatment with Me2Sn(Ala-Arg) and Me2Sn(L-Arg)2. Cells treated with nBu2Sn(Boc-Arg)2, nBu2Sn(Ala-Arg), nBu3Sn(Boc-Arg) and Me3Sn(Boc-Arg), appeared rounded, isolated and detached from culture substrate, indicating the commitment to apoptotic cell death

Neuropsychological functions and audiological findings in elderly cochlear implant users: the role of attention in postoperative performance

Objectives: The present study aimed to investigate in a group of elderly CI users working memory and attention, conventionally considered as predictors of better CI performance and to try to disentangle the effects of these cognitive domains on speech perception, finding potential markers of cognitive decline related to audiometric findings. Methods Thirty postlingually deafened CI users aged >60 underwent an audiological evaluation followed by a cognitive assessment of attention and verbal working memory. A correlation analysis was performed to evaluate the associations between cognitive variables while a simple regression investigated the relationships between cognitive and audiological variables. Comparative analysis was performed to compare variables on the basis of subjects’ attention performance. Results: Attention was found to play a significant role in sound field and speech perception. Univariate analysis found a significant difference between poor and high attention performers, while regression analysis showed that attention significantly predicted recognition of words presented at Signal/Noise +10. Further, the high attention performers showed significantly higher scores than low attentional performers for all working memory tasks. Conclusion: Overall findings confirmed that a better cognitive performance may positively contribute to better speech perception outcomes, especially in complex listening situations. WM may play a crucial role in storage and processing of auditory-verbal stimuli and a robust attention may lead to better performance for speech perception in noise. Implementation of cognitive training in auditory rehabilitation of CI users should be investigated in order to improve cognitive and audiological performance in elderly CI users

Anandamide-induced apoptosis in Chang liver cells involves ceramide and JNK/AP-1 pathway

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Staff perceptions of Family-Centered Care in Italian Neonatal Intensive Care Units: A multicenter cross-sectional study

Family Centered Care (FCC) in Neonatal Intensive Care Units (NICUs) included family involvement in the care process of newborns and infants. Staff perceptions of FCC may influence clinical practice and management strategies in NICUs, with an impact on quality and humanization of the care. The Family-Centred Care Questionnaire-Revised (FCCQ-R) was adapted for the NICU setting, therefore the FCCQ-R@it-NICU was developed and used for the present study in 32 Italian NICUs. We calculated internal consistency using Cronbach's alpha correlation between Current and Necessary dimensions of the scale using the Pearson correlation coefficient. Furthermore, we investigated which characteristics could influence staff perceptions of FCC in NICUs. 921 NICU professionals participated in the study. The FCCQ-R@it-NICU revealed good internal consistency (0.96) and good correlation between dimensions (p < 0.05). Statistical and significant differences in Current and Necessary dimensions were found and some demographic characteristics were found predictable on FCC practice. The FCCQ-R@it-NICU is a valid tool to investigate staff perceptions about FCC in NICU settings. Profession, education level and work experience seem to positively influence the perception of what is required for FCC practice within NICUs

Neonatal intensive care parent satisfaction: a multicenter study translating and validating the Italian EMPATHIC-N questionnaire

Background: In Neonatal Intensive Care Units (NICUs), parent satisfaction and their experiences are fundamental to assess clinical practice and improve the quality of care delivered to infants and parents. Recently, a specific instrument, the EMpowerment of PArents in THe Intensive Care-Neonatology (EMPATHIC-N), has been developed in the Netherlands. This instrument investigated different domains of care in NICUs from a family-centered care perspective. In Italy, no rigorous instruments are available to evaluate parent satisfaction and experiences in NICU with family-centered care. The aim of this study was to translate and validate the EMPATHIC-N instrument into Italian language measuring parent satisfaction. Methods: A psychometric study was conducted in nine Italian NICUs. The hospitals were allocated across Italy: four in the North, four in Central region, one in the South. Parents whose infants were discharged from the Units were enrolled. Parents whose infants died were excluded. Results: Back-forward translation was conducted. Twelve parents reviewed the instrument to assess the cultural adaptation; none of the items fell below the cut-off of 80% agreement. A total of 186 parents of infants who were discharged from nine NICUs were invited to participate and 162 parents responded and returned the questionnaire (87%). The mean scores of the individual items varied between 4.3 and 5.9. Confirmatory factor analysis was performed and all factor loadings were statistically significant with the exception of item ‘Our cultural background was taken into account’. The items related to overall satisfaction showed a higher trend with mean values of 5.8 and 5.9. The Cronbach’s alpha’s (at domain level 0.73-0.92) and corrected item-total scale correlations revealed high reliability estimates. Conclusions: The Italian EMPATHIC-N showed to be a valid and reliable instrument measuring parent satisfaction in NICUs from a family-centered care perspective. Indeed, it had good psychometric properties, validity, and reliability. Furthermore, this instrument is fundamental for further research and internationally benchmarking

The clinical effectiveness of an integrated multidisciplinary evidence-based program to prevent intraoperative pressure injuries in high-risk children undergoing long-duration surgical procedures: a quality improvement study

The prevention of hospital-acquired pressure injuries (HAPIs) in children undergoing long-duration surgical procedures is of critical importance due to the potential for catastrophic sequelae of these generally preventable injuries for the child and their family. Long-duration surgical procedures in children have the potential to result in high rates of HAPI due to physiological factors and the difficulty or impossibility of repositioning these patients intraoperatively. We developed and implemented a multi-modal, multi-disciplinary translational HAPI prevention quality improvement program at a large European Paediatric University Teaching Hospital. The intervention comprised the establishment of wound prevention teams, modified HAPI risk assessment tools, specific education, and the use of prophylactic dressings and fluidized positioners during long-duration surgical procedures. As part of the evaluation of the effectiveness of the program in reducing intraoperative HAPI, we conducted a prospective cohort study of 200 children undergoing long-duration surgical procedures and compared their outcomes with a matched historical cohort of 200 children who had undergone similar surgery the previous year. The findings demonstrated a reduction in HAPI in the intervention cohort of 80% (p < 0.01) compared to the comparator group when controlling for age, pathology, comorbidity, and surgical duration. We believe that the findings demonstrate that it is possible to significantly decrease HAPI incidence in these highly vulnerable children by using an evidence-based, multi-modal, multidisciplinary HAPI prevention strategy

Complessi di Organostagno(IV) con amminoacidi e dipeptidi: sintesi, caratterizzazione e attività biologica in vitro.

Scopo della ricerca è la sintesi, caratterizzazione strutturale ed attività biologica di complessi di organostagno(IV) e amminoacidi quali L-arginina (Arg), N-Boc-L-arginina (Boc-Arg), L-ornitina (L-Orn) ed un dipeptide contenente L-arginina, Alanil-Arginina (Ala-Arg). I complessi di diorganostagno(IV) sono noti possedere attività antitumorale [1], antimicrobica [2] e antiinfiammatoria. I complessi di triorganostagno(IV) inibiscono la funzione mitocondriale almeno in tre modi: 1) reagendo con le membrane cellulari; 2) alterando lo scambio Cl-/OH- attraverso la membrana; 3) inibendo la fosforilazione ossidativa o l’idrolisi di ATP [3].L’arginina (Arg) è un amminoacido essenziale con un gruppo guanidinio nella catena laterale, con caratteristiche basiche ed inoltre viene utilizzato come sito per il riconoscimento biologico attraverso legami a idrogeno. Il riconoscimento molecolare, le reazioni enzimatiche e la struttura delle proteine dipendono dalle proprietà dell’arginina. L-Ornitina è un amminoacido che possiede un ruolo fondamentale nel ciclo dell’urea ed è un precursore di amminoacidi come citrullina, acido glutammico e prolina, oltre ad essere un intermedio nella biosintesi dell’arginina. I complessi R3SnL (R = Me, nBu; L = Boc-Arg), sintetizzati in rapporto molare 1:1, sono stati studiati sia allo stato solido con spettroscopia I.R. e 119Sn Mössbauer che in soluzione con 1H, 13C NMR L-Arginina è presente come chelante attraverso i gruppi carbossilato e i gruppi -NH2; nei complessi con N-Boc-L-Arginina, il gruppo amminico N-protetto è esente dalla coordinazione e soltanto i gruppi carbossilato sono gli effettori della coordinazione alle metà organometalliche. L’attività biologica dei complessi R2SnL (R = Me, nBu; L = Arg, Boc-Arg, Orn e Ala-Arg) è stata studiata utilizzando il kit di vitalità EZ4U ELISA (ALPCO diagnostics), sulle cellule HT29 di carcinoma colorettale umano in coltura. Le cellule sono state trattate per 24 e 48 h con 5 e 10 M dei complessi organostagno, in comparazione al cisplatino (1). I risultati ottenuti hanno dimostrato che i complessi Bu2Sn(Boc-Arg)2 (3) e Bu2Sn(Orn)•HCl (4) inducono una marcata riduzione della vitalità cellulare mentre il complesso Bu2Sn(Ala-Arg) (2) ed il cisplatino (1) non sembrano avere alcuna attività alle dosi impiegate. Ulteriori indagini, riguardanti lo studio del ciclo cellulare, verranno effettuate mediante analisi citofluorimetrica