Publications by authors named "Roberto D"

86 Publications

Big data in the healthcare system: a synergy with artificial intelligence and blockchain technology.

J Integr Bioinform 2021 Aug 18. Epub 2021 Aug 18.

Department of Technology Innovation, hdm.world, Florida, USA.

In the last decades big data has facilitating and improving our daily duties in the medical research and clinical fields; the strategy to get to this point is understanding how to organize and analyze the data in order to accomplish the final goal that is improving healthcare system, in terms of cost and benefits, quality of life and outcome patient. The main objective of this review is to illustrate the state-of-art of big data in healthcare, its features and architecture. We also would like to demonstrate the different application and principal mechanisms of big data in the latest technologies known as blockchain and artificial intelligence, recognizing their benefits and limitations. Perhaps, medical education and digital anatomy are unexplored fields that might be profitable to investigate as we are proposing. The healthcare system can be revolutionized using these different technologies. Thus, we are explaining the basis of these systems focused to the medical arena in order to encourage medical doctors, nurses, biotechnologies and other healthcare professions to be involved and create a more efficient and efficacy system.
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http://dx.doi.org/10.1515/jib-2020-0035DOI Listing
August 2021

Occurrence of hyperventilation-induced high amplitude rhythmic slowing with altered awareness after successful treatment of typical absence seizures and a network hypothesis.

Clin Neurophysiol Pract 2021 11;6:185-188. Epub 2021 Jun 11.

Section of Child Neuropsychiatry, Department of Medical, Surgical and Experimental Sciences, University of Sassari, Italy.

Background: Typical absence seizures (AS) are epileptic phenomena typically appearing in children 4-15 years of age and can be elicited by hyperventilation (HV). Hyperventilation-induced high-amplitude rhythmic slowing (HIHARS) represents a paraphysiological response during HV and may manifest with alteration of awareness (HIHARSAA). To date, HIHARSAA has mostly been described in patients without epilepsy.

Aim: To describe five patients with treatment-responsive typical AS who, after becoming seizure free, presented with HIHARSAA.

Methods: By using video-electroencephalographic recording (Video-EEG), we describe differential clinical characteristics and ictal electrophysiological patterns of both typical AS and HIHARSAA.

Results: We demonstrate that when HIHARSAA occurs in patients with typical AS there is a temporal window between the two phenomena. This suggests that the presence of typical AS precludes the appearance of HIHARSAA.

Conclusions: We hypothesize that alkalosis and dysfunction of the same neural network are involved in both typical AS and HIHARSAA and that their distinct electroclinic manifestations are due to the involvement of different ion channels.

Significance: A better understanding of the characteristics of typical AS and HIHARSAA and of the role of alkalosis in both, can help avoiding misdiagnosis and identifying more suitable therapies for typical AS.
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http://dx.doi.org/10.1016/j.cnp.2021.03.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255168PMC
June 2021

True Crime Consumption as Defensive Vigilance: Psychological Mechanisms of a Rape Avoidance System.

Arch Sex Behav 2021 07 23;50(5):2085-2108. Epub 2021 Jun 23.

Department of Psychology, Oakland University, Rochester, MI, 48309, USA.

The circumvention of female reproductive choice via rape is a costly and evolutionarily persistent threat to women's reproductive fitness. This is argued to have generated selection pressure for a precautionary threat management system for rape avoidance among women. Such a system would regulate women's fear of rape as a functional emotional response to inputs providing information about the current risk and reproductive cost of rape. Fear of rape is expected to subsequently motivate adaptive behavior to avoid threats to one's reproductive choice. The current research tested key tenets of this proposed system and found that women report greater fear of rape as a function of characteristics that alter the likelihood of being victimized, including being younger, living in a neighborhood perceived as dangerous, living in close proximity to family, and having been the victim of a sexual assault in the past. We also discuss mixed and null results with respect to the role of relationship status and mate value. In turn, fear of rape was associated with behavior expected to reduce one's risk of being victimized. Specifically, women who were more fearful of rape reported consuming true crime media with greater frequency and indicated that this consumption was specifically motivated by the desire to learn strategies to prevent or escape an attack. Overall, results were fairly consistent with a threat management system approach and may help to explain why fear of rape is a powerful feature of women's psychology.
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http://dx.doi.org/10.1007/s10508-021-01990-1DOI Listing
July 2021

Uric acid: A new marker for metabolic syndrome? Results of a population-based study with adults.

Nutr Metab Cardiovasc Dis 2021 06 24;31(7):2077-2080. Epub 2021 Mar 24.

Programa de Pós-Graduação em Nutrição, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.

Background And Aims: Recently, studies have shown a positive association between serum uric acid (UA) and metabolic syndrome (MS). To evaluate the predictive capacity and the association of serum UA with pre-MS and MS, by sex, in adults.

Methods And Results: Cross-sectional study with 932 adults, of both sexes, from Viçosa, Minas Gerais (MG), Brazil. Sociodemographic and behavioral data were obtained through a questionnaire and anthropometric, clinical, and biochemical evaluation. We used multinomial logistic regression and the area under receiver operating characteristic curve (AUC). The prevalence of pre-MS was 17.8% and of MS was 26.5%. The fitted models showed positive association of serum UA with pre-MS (OR = 1.62, 95% CI = 1.09-2.40) and MS (OR = 2.61, 95% CI = 1.99-3.42) among men. For women, similar results were found for MS (OR = 2.59, 95% CI = 1.81-3.73). The optimal cutoff points obtained by AUC for pre-MS and MS were 4.7 and 4.9 mg/dL among men and 3.1 and 3.4 mg/dL among women, respectively.

Conclusion: The results point to a positive association of UA with pre-MS and MS, with no significant differences between sexes. Therefore, UA can be used as an additional marker in the screening of these conditions.
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http://dx.doi.org/10.1016/j.numecd.2021.03.012DOI Listing
June 2021

Immunosuppressive therapy withdrawal after remission achievement in patients with lupus nephritis.

Rheumatology (Oxford) 2021 Apr 28. Epub 2021 Apr 28.

Rheumatology Unit, Department of Medicine, University of Padova, Padua, Italy.

Aim: Whether immunosuppressive therapy (IS) may be safely withdrawn in lupus nephritis (LN) is still unclear. We assessed rate and predictors of flare after IS withdrawal in patients with LN in remission.

Methods: Patients with biopsy-proven LN treated with IS between 1980 and 2020 were considered. Remission was defined as normal serum creatinine, proteinuria <0.5 g/24h, inactive urine sediment, and no extra-renal SLE activity on stable immunosuppressive and/or antimalarial therapy and/or prednisone ≤5mg/day. IS discontinuation was defined as the complete withdrawal of immunosuppressants, flares according to SLEDAI Flare Index. Predictors of flare were analyzed by multivariate logistic regression analysis.

Results: Among 513 SLE patients included in our database, 270 had LN. Of them, 238 underwent renal biopsy and were treated with ISs. Eighty-three patients (34.8%) discontinued IS, 46 ± 30 months after remission achievement. During a mean±SD follow-up of 116.5 ± 78 months, 19 patients (22.8%) developed a flare (8/19 renal) and were re-treated; 14/19 (73.7%) re-achieved remission after restarting therapy. Patients treated with IS therapy for at least three years after remission achievement had the lowest risk of relapse (OR 0.284, 95% CI 0.093-0.867, p= 0.023). At multivariate analysis, antimalarial maintenance therapy (OR 0.194, 95%CI 0.038-0.978, p= 0.047), age at IS discontinuation (OR 0.93, 95%CI 0.868-0.997, p= 0.040), remission duration >3 years before IS discontinuation (OR 0.231, 95%CI 0.058-0.920, p= 0.038) were protective against disease flares.

Conclusions: Withdrawal of IS is feasible in LN patients in remission for at least 3 years and on antimalarial therapy. Patients who experience flares can re-achieve remission with an appropriate treatment.
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http://dx.doi.org/10.1093/rheumatology/keab373DOI Listing
April 2021

Copper Complexes as Alternative Redox Mediators in Dye-Sensitized Solar Cells.

Molecules 2021 Jan 2;26(1). Epub 2021 Jan 2.

Department of Chemistry, University of Milan, UdR-INSTM, Via C. Golgi 19, I-20133 Milan, Italy.

Thirty years ago, dye-sensitized solar cells (DSSCs) emerged as a method for harnessing the sun's energy and converting it into electricity. Since then, a lot of work has been dedicated to improving their global photovoltaic efficiency and their eco-sustainability. Recently, various articles showed the great potential of copper complexes as a convenient and cheap alternative to the traditional ruthenium dyes. In addition, copper complexes demonstrate that they can act as redox mediators for DSSCs, thus being an answer to the problems related to the I/I redox couple. The aim of this review is to report on the most recent impact made by copper complexes as alternative redox mediators. The coverage, mainly from 2016 up to now, is not exhaustive, but allows us to understand the great role played by copper complexes in the design of eco-sustainable DSSCs.
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http://dx.doi.org/10.3390/molecules26010194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796243PMC
January 2021

Diagnosis of pediatric anti-NMDAR encephalitis at the onset: A clinical challenge.

Eur J Paediatr Neurol 2021 Jan 7;30:9-16. Epub 2020 Dec 7.

Department of Neurological and Psychiatric Sciences, Bambino Gesù Children Hospital, Rome, Italy; Center for Sensory-Motor Interaction, Aalborg University, Aalborg, Denmark. Electronic address:

Backgrounds: To investigate the clinical and instrumental features at the onset addressing to the diagnosis of anti-NMDAR encephalitis.

Methods: Twenty children (age: 15 months-17 years; 7 males, 13 females) with initial suspected diagnosis of autoimmune encephalitis, observed between January 2008 and March 2018, were included. The final diagnosis was anti-NMDAR encephalitis in 7 children, other/probable autoimmune encephalitis in 7 children, and primary psychosis in the remaining 6 children.

Results: At the clinical onset, anxiety disorder was the main symptom that helped in distinguishing the group of psychotic children from children with non-infectious encephalitis (P = 0.05 OR = 0.001), while epileptic seizures strongly predicted anti-NMDAR encephalitis (P = 0.04 OR = 28.6). At the onset, anti-NMDAR encephalitis could be distinguished from other/probable autoimmune encephalitis for the presence of sleep/wake rhythm alteration (P = 0.05 OR = 15). Among the symptoms occurring during the hospitalization, movement disorders (P = 0.031 OR = 12) were predictive of non-infectious encephalitis rather than primary psychosis. More specifically, the occurrence of language impairment (P = 0.03 OR = 33), epileptic seizures (P = 0.04 OR = 28.6) and catatonia (P = 0.03, OR = 33), were predictive of anti-NMDAR encephalitis. Also at this stage, anxiety disorder (P = 0.03 OR = 0.033) was predictive of primary psychosis.

Conclusion: Our findings suggest that at the clinical onset epileptic seizures and sleep/wake rhythm alteration represent the main features addressing to the diagnosis of anti-NMDAR encephalitis rather than primary psychosis and other/probable autoimmune encephalitis, while anxiety disorder could be a solid predictor of primary psychosis.
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http://dx.doi.org/10.1016/j.ejpn.2020.12.004DOI Listing
January 2021

Impact of secukinumab on patient-reported outcomes in moderate to severe plaque psoriasis: a review of clinical studies.

Expert Opin Biol Ther 2021 02 7;21(2):191-200. Epub 2021 Jan 7.

Dermatology Unit, Fondazione Policlinico "Tor Vergata" , Rome, Italy.

: Perception of illness varies among individuals and psoriasis of the same severity can be perceived in different ways by patients, making it essential to evaluate quality of life (QoL) since it can provide information on the impact of the disease on the patient's overall well-being. The use of patient-reported outcomes in clinical trials provides the ability to integrate objective clinical assessment with the patient's perception of their own state of health. : The introduction of anti-IL17 agents in clinical practice has given patients the possibility to achieve a PASI90 response (almost clear skin) or even higher (complete clear skin) in the majority of patients. There is accumulating evidence in support of PASI90 response as the new standard goal for therapy based on its greater correlation with health-related QoL. The present review summarizes current knowledge of the effects of secukinumab on the QoL of patients with psoriasis using patient-reported outcome measures. : Secukinumab, the first approved drug of this new class, has fully reached a new therapeutic paradigm not only in terms of clinical efficacy, but also in terms of patient satisfaction and self-rated health.
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http://dx.doi.org/10.1080/14712598.2021.1849131DOI Listing
February 2021

Meal and snack patterns of 7-13-year-old schoolchildren in southern Brazil.

Public Health Nutr 2021 06 29;24(9):2542-2553. Epub 2020 Oct 29.

Department of Nutrition, Center of Health Sciences, Federal University of Santa Catarina, Campus Universitário Reitor João David Ferreira Lima Trindade, Florianopolis, SC88040-900, Brazil.

Objective: The aim of the current study was to identify and describe the meal and snack patterns (breakfast, mid-morning snack, lunch, mid-afternoon snack, dinner and evening snack) of public schoolchildren.

Design: Cross-sectional study. Information on the previous day's food intake was obtained through the Web-CAAFE (Food Intake and Physical Activity of Schoolchildren), an interactive questionnaire, which divides daily food consumption into three meals (breakfast, lunch and dinner) and three snacks (mid-morning, mid-afternoon and evening). Each meal contains thirty-one food items and the schoolchildren clicked on the food items consumed in each meal. Factor analysis was used to identify meal and snack patterns. The descriptions of the dietary patterns (DP) were based on food items with factor loads ≥ 0·30 that were considered representative of each DP.

Setting: Schoolchildren, Florianopolis, Brazil.

Participants: Children (n 1074) aged 7-13 years.

Results: Lunch was the most consumed meal (96·0 %), followed by dinner (86·4 %), breakfast (85·3 %) and mid-afternoon snack (81·7 %). Four DP were identified for breakfast, mid-morning snack, lunch, dinner and evening snack, and three for mid-afternoon snack. Breakfast, lunch and dinner patterns included traditional Brazilian foods. DP consisting of fast foods and sugary beverages were also observed, mainly for the evening snack.

Conclusions: The results of the current study provide important information regarding the meal and snack patterns of schoolchildren to guide the development of nutrition interventions in public health.
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http://dx.doi.org/10.1017/S1368980020003808DOI Listing
June 2021

Re-laparoscopy in the treatment of anastomotic leak following laparoscopic right colectomy with intracorporeal anastomosis.

Surg Endosc 2021 11 26;35(11):6173-6178. Epub 2020 Oct 26.

Department of Gastrointestinal Surgery, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy.

Background: Anastomotic leak still represents the most feared surgical complication following colorectal resection and is associated with high morbidity and mortality rates. The aim of this study is to assess the feasibility and safety of laparoscopic reoperation for symptomatic anastomotic leak (AL) after laparoscopic right colectomy with mechanical intracorporeal anastomosis (IA).

Methods: From January 2012 to December 2019, 428 consecutive laparoscopic right colectomy with IA were performed. Overall symptomatic AL rate requiring reoperation was 5.8% (26/428). Data on patient demographics as well as operative findings, time elapsed from primary surgery and from the onset of symptoms of anastomotic leak, time and duration of re-laparoscopy, ICU stay, morbidity, mortality rate, length of hospital stay and readmission, were all retrospectively reviewed.

Results: Laparoscopic approach was attempted in 23 (88.4%) hemodynamically stable patients. Conversion rate was 21.4%. Reasons for conversion were gross fecal peritonitis (n = 2), colonic ischemia (n = 1), severe bowel distension (n = 2). Eighteen (78.2%) patients underwent successfully laparoscopic (LPS) reoperation. A repair of the anastomotic defect was done in 11 (61.1%) patients, while in 7 patients the intracorporeal mechanical anastomosis was refashioned. A diverting ileostomy was done in 22.2% of cases (n = 4). A second reoperation for leak persistence was necessary in two cases (11.1%). Median (range) length of postoperative hospital stay from re-laparoscopy was 15.5 (9-53) days. Overall morbidity rate was 38.7%. Mortality rate was 5.5% (n = 1) CONCLUSION: laparoscopic re-intervention for the treatment of anastomotic leak following LPS right colectomy with intracorporeal anastomosis in hemodynamically stable and highly selected patients in the experienced hands of dedicated laparoscopic surgeons, is a safe option with acceptable morbidity and mortality rate.
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http://dx.doi.org/10.1007/s00464-020-08113-2DOI Listing
November 2021

NLO-active Y-shaped ferrocene conjugated imidazole chromophores as precursors for SHG polymeric films.

Dalton Trans 2020 Feb;49(6):1854-1863

Department of Chemistry, School of Advanced Science, Vellore Institute of Technology, Vellore 632014, Tamilnadu, India.

New Y-shaped ferrocene conjugated imidazole chromophores were prepared and fully characterized. The Y-shaped structure was confirmed by the single crystal X-ray diffraction technique. The chromophores show interesting second-order nonlinear optical (NLO) properties in solution, as determined by the Electric-Field Induced Second Harmonic generation (EFISH) technique. Remarkably, the trifluoro substituted compound 3 is characterized by a high μβEFISH value and has good potential as a molecular building block for composite films with Second Harmonic Generation (SHG) properties. For all compounds, the dipole moments and frontier orbital energies were calculated by the Density Functional Theoretical method.
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http://dx.doi.org/10.1039/c9dt03637gDOI Listing
February 2020

Functional validation of metabolic genes that distinguish Gleason 3 from Gleason 4 prostate cancer foci.

Prostate 2019 11 10;79(15):1777-1788. Epub 2019 Sep 10.

Department of Surgery (Urology), Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.

Background: Gleason grade is among the most powerful clinicopathological classification systems used to assess risk of lethal potential in prostate cancer, yet its biologic basis is poorly understood. Notably, pure low-grade cancers, comprised predominantly of Gleason pattern 3 (G3) are typically indolent, with lethal potential emerging with the progression of higher-grade Gleason patterns 4 (G4) or 5. One of the hallmarks of more aggressive cancer phenotypes is the stereotyped set of metabolic characteristics that transformed cells acquire to facilitate unregulated growth. In the present study, we profiled expression signatures of metabolic genes that are differentially expressed between G3 and G4 cancer foci and investigated the functional role of two of the profiled genes, PGRMC1 and HSD17B4, in prostate cancer cells.

Methods: Gene expression profiling was conducted using 32 G3 and 32 G4 cancer foci from patients with 3+3 and ≥4+3 tumors, respectively. A 95-gene Nanostring probe set was used to probe genes associated with energy metabolism. Two out of five genes (PGRMC1 and HSD17B4) that significantly distinguish between G3 and G4 were functionally validated in vitro using established prostate cancer cells (PC3, DU145). Expression of PGRMC1 and HSD17B4 was knocked down and subsequent studies were performed to analyze cell proliferation, migration, invasion, and apoptosis. Mechanistic studies that explored the epidermal growth factor receptor (EGFR) pathway were performed by Western blot.

Results: Multivariate analysis identified five metabolic genes that were differentially expressed between G3 and G4 stroma (P < .05). Functional validation studies revealed that knockdown of PGRMC1 and HSD17B4 significantly decreased cell proliferation, migration, and invasion, and increased apoptosis in PC3 and DU145 cells. Mechanistic studies showed that these effects, after PGRMC1 knockdown, were possibly mediated through alterations in downstream components of the EGFR, protein kinase B, and nuclear factor kappa-light-chain-enhancer of activated B cells pathways.

Conclusion: The following study provides evidence supporting the use of metabolic genes PGRMC1 and HSD17B4 as a prognostic biomarker for the distinction between G3 and G4 prostate cancers.
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http://dx.doi.org/10.1002/pros.23903DOI Listing
November 2019

Improving the efficiency of copper-dye-sensitized solar cells by manipulating the electrolyte solution.

Dalton Trans 2019 Jul;48(26):9818-9823

Research Center for Renewable Energy & Enviromental Istituto Donegani, Eni S.p.A., via Fauser 4, I-28100, Novara, Italy.

The use of a copper(i) dye, bearing a 2,9-dimesityl-1,10-phenanthroline and a 6,6'-dimethyl-2,2'-bipyridine-4,4'-dibenzoic acid, was investigated in DSSCs with various electrolyte solutions based on two different redox mediators, namely the common I-/I3- couple and an interesting copper electron shuttle. The experimental results provide evidence of the importance of the redox mediator concentration and the crucial role of additives such as 4-tert-butylpyridine and lithium bis(trifluoromethanesulfonyl)imide in the performance of sustainable "full-copper" DSSCs, consolidating the way to DSSCs with Earth-abundant components.
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http://dx.doi.org/10.1039/c9dt01448aDOI Listing
July 2019

A Highly Luminescent Tetrahydrocurcumin Ir Complex with Remarkable Photoactivated Anticancer Activity.

Chemistry 2019 Jun 13;25(33):7948-7952. Epub 2019 May 13.

IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Via Adamello 16, 20145, Milan, Italy.

Curcumin has chemopreventative properties against a variety of tumours, but has poor bioavailability. Here, two new bis-cyclometallated iridium(III) complexes have been prepared, featuring the natural product curcumin (CUR) or its reduced form, tetrahydrocurcumin (THC), as bidentate, anionic O O-binding ligands. The iridium THC complex is highly luminescent in deoxygenated solution and efficiently generates singlet oxygen under aerated conditions, whereas in the CUR analogue, other non-radiative decay pathways are competitive. The complexes are rapidly taken up by a variety of human tumour cell lines from solutions of micromolar concentration. They show negligible cytotoxicity in the absence of irradiation. When briefly irradiated with visible light, Ir-THC becomes highly phototoxic, inducing rapid apoptosis within 2 h. The results show the high potential of such complexes as sensitizers in photodynamic therapy (PDT).
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http://dx.doi.org/10.1002/chem.201901527DOI Listing
June 2019

Towards efficient sustainable full-copper dye-sensitized solar cells.

Dalton Trans 2019 Jul;48(26):9703-9711

Dipartimento di Chimica dell'Università degli Studi di Milano, UdR-INSTM, via Golgi 19, I-20133, Milano, Italy.

Two new heteroleptic copper(i) sensitizers bearing 6,6'-dimethyl-2,2'-bipyridine-4,4'-dibenzoic acid, to anchor the dye on the titania surface, and a π-delocalized 2-(R-phenyl)-1H-phenanthro[9,10-d]imidazole (R = NPh2 or O-hexyl) ancillary ligand were prepared and well characterized. Their performance as dyes in DSSCs is quite similar to that of the related complex bearing 2,9-dimesityl-1,10-phenanthroline as an ancillary ligand, when using the common I-/I3- redox couple or homoleptic copper complexes as electron shuttles. The experimental results along with theoretical calculations confirm the great potential of full-copper DSSCs.
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http://dx.doi.org/10.1039/c9dt00790cDOI Listing
July 2019

Combining Desmopressin and Docetaxel for the Treatment of Castration-Resistant Prostate Cancer in an Orthotopic Model.

Anticancer Res 2019 Jan;39(1):113-118

Department of Surgery, Division of Urology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada

Background/aim: Desmopressin is a synthetic analogue of the antidiuretic hormone vasopressin. It has recently been demonstrated to inhibit tumor progression and metastasis in breast cancer models. Docetaxel is a chemotherapy agent for castrate-resistant prostate cancer (CRPC). In this study, the ability of CRPC cells to grow and develop in vivo tumors in an animal model was evaluated, in order to investigate the anti-tumor effect of desmopressin in combination with docetaxel.

Materials And Methods: The CRPC cell line PC3 was used for orthotopic inoculation in male athymic nude mice. The mice were randomly assigned to one of the four treatment groups: Control, docetaxel, desmopressin or combination therapy. Following the last treatment, tumors were excised and measured. Blood samples were processed for CTC analysis.

Results: Docetaxel treatment resulted in a significant reduction in tumor volume compared to control. The combination therapy resulted in even more significant reduction (31.2%) in tumor volume. There was a complete absence of CTCs in the combination group.

Conclusion: Our pilot study demonstrated an enhanced efficacy of docetaxel-based therapy in combination with desmopressin.
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http://dx.doi.org/10.21873/anticanres.13086DOI Listing
January 2019

Novel cyclometallated 5-π-delocalized donor-1,3-di(2-pyridyl)benzene platinum(ii) complexes with good second-order nonlinear optical properties.

Dalton Trans 2018 Dec;48(1):202-208

Dipartimento di Chimica dell'Università degli Studi di Milano, UdR-INSTM, via Golgi 19, I-20133, Milano, Italy.

Five new platinum(ii) complexes bearing a cyclometallated 5-π-delocalized donor-1,3-di(2-pyridyl)benzene were prepared and fully characterized. Their second-order nonlinear optical (NLO) properties were determined by the Electric-Field Induced Second Harmonic generation (EFISH) technique, working in DMF solution with an incident wavelength of 1907 nm, whereas the dipole moments were determined by Density Functional Theory (DFT) calculations. Remarkably, the platinum(ii) complex with a cyclometallated 5-guaiazulene-CH[double bond, length as m-dash]CH-1,3-di(2-pyridyl)benzene appears as a very good candidate for application in photonics, being characterized by the largest second-order NLO response. Besides, it appeared that the nature of substituents on thiophene, chosen as π-delocalized moiety in position 5 of the 1,3-di(2-pyridyl)benzene, strongly affects the NLO properties.
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http://dx.doi.org/10.1039/c8dt03622eDOI Listing
December 2018

Cannabinoid WIN 55,212-2 induces cell cycle arrest and apoptosis, and inhibits proliferation, migration, invasion, and tumor growth in prostate cancer in a cannabinoid-receptor 2 dependent manner.

Prostate 2019 02 21;79(2):151-159. Epub 2018 Sep 21.

Department of Surgery (Urology), Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.

Background: Cannabinoids have demonstrated anticarcinogenic properties in a variety of malignancies, including in prostate cancer. In the present study, we explored the anti-cancer effects of the synthetic cannabinoid WIN 55,212-2 (WIN) in prostate cancer.

Methods: Established prostate cancer cells (PC3, DU145, LNCaP) were treated with varying concentrations of WIN. Cell proliferation was determined by the MTS assay. The anti-migration and anti-invasive potential of WIN was examined by the wound healing assay and the matrigel invasion assay. Cell cycle analysis was performed by flow cytometry, and mechanistic studies were performed by Western blot. Athymic mice (n = 10) were inoculated with human PC3 cells. Once tumors reached 100 mm , animals were randomized into two groups: saline control and WIN (5 mg/kg), delivered by intraperitoneal injection three times per week for 3 weeks.

Results: WIN significantly reduced prostate cancer cell proliferation, migration, invasion, induced apoptosis, and arrested cells in Go/G1 phase in a dose-dependent manner. Mechanistic studies revealed these effects were mediated through a pathway involving cell cycle regulators p27, Cdk4, and pRb. Pre-treatment with a CB antagonist, AM630, followed by treatment with WIN resulted in a reversal of the anti-proliferation and cell cycle arrest previously seen with WIN alone. In vivo, administration of WIN resulted in a reduction in the tumor growth rate compared to control (P < 0.05).

Conclusions: The following study provides evidence supporting the use of WIN as a novel therapeutic for prostate cancer.
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http://dx.doi.org/10.1002/pros.23720DOI Listing
February 2019

An investigation on the second-order nonlinear optical response of cationic bipyridine or phenanthroline iridium(iii) complexes bearing cyclometallated 2-phenylpyridines with a triphenylamine substituent.

Dalton Trans 2018 Jun;47(25):8292-8300

Univ Rennes, CNRS, ISCR (Institut des Sciences Chimiques de Rennes) - UMR 6226, F-35000 Rennes, France.

The synthesis and characterisation of six new cationic iridium(iii) complexes bearing either 4,4'-di-tert-butyl-2,2'-bipyridine (dtBubpy) or 5-NO2-1,10-phenanthroline along with two cyclometallated 2-phenylpyridine derivative ligands, decorated with triphenylamine groups either meta or para to the Ir-CC^N bond or para to the Ir-NC^N bond, are reported. The second-order nonlinear optical (NLO) properties of all the compounds have been determined by the electric field induced second harmonic generation technique and show that the μβEFISH value can be tuned by the nature of the iridium coordination sphere. The dipole moment, μ, necessary to evaluate the quadratic hyperpolarizability βEFISH, was theoretically determined. The linear optical properties of the complexes are also presented and rationalised by quantum-chemical calculations. One of the prepared iridium compounds was incorporated into a polystyrene film, affording the first example of a second-order NLO active polymeric film based on a cationic organometallic complex.
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http://dx.doi.org/10.1039/c8dt00754cDOI Listing
June 2018

Photochromic DTE-Substituted-1,3-di(2-pyridyl)benzene Platinum(II) Complexes: Photomodulation of Luminescence and Second-Order Nonlinear Optical Properties.

Inorg Chem 2018 Jun 5;57(12):7051-7063. Epub 2018 Jun 5.

Univ Rennes, CNRS, ISCR - UMR6226 , F-35000 Rennes , France.

We disclose a new family of photochromic cyclometalated platinum(II) complexes (PtDTE1 and PtDTE2), where a dithienylethene (DTE) unit is connected at the para-position of the central phenyl ring of (N^C^N) cyclometalated ligand, through two different linkages. Their syntheses are presented along with the X-ray characterizations of both the open and closed isomers of PtDTE1. The investigation of their photophysical properties is made, including absorption, photochromism, emission, and second-order nonlinear properties. We report a quantitative photoisomerization for both PtDTE1 and PtDTE2, irrespective of the nature of the connecting mode between the DTE unit and the platinum(II) moiety. The efficient photochromism allows a significant NLO photomodulation, both in solution and in thin films. In addition, we show that the photoluminescence of the PtDTE1 and PtDTE2 can be controlled by the open/closed isomerization of the DTE unit.
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http://dx.doi.org/10.1021/acs.inorgchem.8b00733DOI Listing
June 2018

Intriguing C-HCu interactions in bis-(phenanthroline)Cu(i) redox mediators for dye-sensitized solar cells.

Dalton Trans 2018 Jan;47(4):1018-1022

Dipartimento di Chimica and UdR INSTM di Milano, Università degli Studi di Milano, Via Golgi, 19, Milano, Italy.

We have synthesized and characterized a series of bis-(phenanthroline)Cu(i) complexes of interest as redox mediators for dye-sensitized solar cells. This study led to the discovery of intriguing anagostic interactions between the hydrogen atom and the copper center as evidenced by X-ray diffraction studies on a single crystal. Remarkably, an anagostic interaction was found between a H atom of a methyl group and a copper site.
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http://dx.doi.org/10.1039/c7dt04045hDOI Listing
January 2018

Controlling the emission in flexibly-linked (N^C^N)platinum dyads.

Dalton Trans 2017 Dec;47(1):224-232

Institut des Sciences Chimiques de Rennes, UMR CNRS 6226, Université de Rennes 1, Campus de Beaulieu, 35042 Rennes Cedex, France.

The synthesis, spectroscopic and theoretical characterizations of dinuclear Pt(ii) complexes where the two chromophoric units are connected though a polyether chain via either the central benzene ring of the tridentate ligand dpyb (Pt-2), or the phenylacetylide ligand (Pt-3), are described. The spacer, which contains four oxyethylene -CHCHO- units, is flexible and long enough to allow a self-association of the Pt units by folding, as shown by DFT calculations. Comparison of the photophysical properties of the dinuclear complex Pt-2 with those of the mononuclear complex Pt-1, used as reference, demonstrates the key role played by the linker group in the interaction processes. In addition, the emission of complex Pt-2 was found to be affected by the temperature, nature of the solvent, and cation coordination as evidenced by luminescence and H NMR studies. The interacting processes are highly dependent on the solvent polarity that controls the - extended vs folded - arrangement and, consequently, induces solvatochromic shifts. This unique photophysical behavior of Pt-2 allows the modulation of the emission from green to deep-red (up to 125 nm) over the visible part of the spectrum. By contrast, complex Pt-3 has a high propensity to form a red-shifted intense emissive excimer. DFT and TD-DFT investigations of the excimers in Pt-2 and Pt-3 consistently show a much stronger interaction in the latter complex.
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http://dx.doi.org/10.1039/c7dt03695gDOI Listing
December 2017

Coupling of Zinc Porphyrin Dyes and Copper Electrolytes: A Springboard for Novel Sustainable Dye-Sensitized Solar Cells.

Inorg Chem 2017 Nov 1;56(22):14189-14197. Epub 2017 Nov 1.

Dipartimento Scienze Chimiche e Farmaceutiche, Università di Ferrara , Via F. di Mortara, 44121 Ferrara, Italy.

The combination of β-substituted Zn porphyrin dyes and copper-based electrolytes represents a sustainable route for economic and environmentally friendly dye-sensitized solar cells. Remarkably, a new copper electrolyte, [Cu(2-mesityl-1,10-phenanthroline)], exceeds the performance reached by Co and I/I reference electrolytes.
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http://dx.doi.org/10.1021/acs.inorgchem.7b02323DOI Listing
November 2017

Acetolactate synthase regulatory subunits play divergent and overlapping roles in branched-chain amino acid synthesis and Arabidopsis development.

BMC Plant Biol 2017 04 7;17(1):71. Epub 2017 Apr 7.

Department of Biological Sciences, University of Windsor, Windsor, ON, Canada.

Background: Branched-chain amino acids (BCAAs) are synthesized by plants, fungi, bacteria, and archaea with plants being the major source of these amino acids in animal diets. Acetolactate synthase (ALS) is the first enzyme in the BCAA synthesis pathway. Although the functional contribution of ALS to BCAA biosynthesis has been extensively characterized, a comprehensive understanding of the regulation of this pathway at the molecular level is still lacking.

Results: To characterize the regulatory processes governing ALS activity we utilized several complementary approaches. Using the ALS catalytic protein subunit as bait we performed a yeast two-hybrid (Y2H) screen which resulted in the identification of a set of interacting proteins, two of which (denoted as ALS-INTERACTING PROTEIN1 and 3 [AIP1 and AIP3, respectively]) were found to be evolutionarily conserved orthologues of bacterial feedback-regulatory proteins and therefore implicated in the regulation of ALS activity. To investigate the molecular role AIPs might play in BCAA synthesis in Arabidopsis thaliana, we examined the functional contribution of aip1 and aip3 knockout alleles to plant patterning and development and BCAA synthesis under various growth conditions. Loss-of-function genetic backgrounds involving these two genes exhibited differential aberrant growth responses in valine-, isoleucine-, and sodium chloride-supplemented media. While BCAA synthesis is believed to be localized to the chloroplast, both AIP1 and AIP3 were found to localize to the peroxisome in addition to the chloroplast. Analysis of free amino acid pools in the mutant backgrounds revealed that they differ in the absolute amount of individual BCAAs accumulated and exhibit elevated levels of BCAAs in leaf tissues. Despite the phenotypic differences observed in aip1 and aip3 backgrounds, functional redundancy between these loci was suggested by the finding that aip1/aip3 double knockout mutants are severely developmentally compromised.

Conclusions: Taken together the data suggests that the two regulatory proteins, in conjunction with ALS, have overlapping but distinct functions in BCAA synthesis, and also play a role in pathways unrelated to BCAA synthesis such as sodium-ion homeostasis, extending to broader aspects of patterning and development.
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http://dx.doi.org/10.1186/s12870-017-1022-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5384131PMC
April 2017

Tuning the dipolar second-order nonlinear optical properties of 5-π-delocalized-donor-1,3-di(2-pyridyl)benzenes, related cyclometallated platinum(ii) complexes and methylated salts.

Dalton Trans 2017 Jan;46(4):1179-1185

Department of Chemistry, University of Durham, South Road, Durham, DH1 3LE, UK.

The synthesis and characterization of three 5-π-delocalized-donor-1,3-di(2-pyridyl)benzenes is reported along with that of their related cyclometallated platinum(ii) complexes and N,N-dimethylated iodide salts. The second-order nonlinear optical (NLO) properties of all the compounds have been determined by the Electric Field Induced Second Harmonic generation technique, showing how the μβ absolute value of 1,3-di(2-pyridyl)benzenes can be tuned by the nature of the substituent on position 5 of the central benzene ring, and greatly increased by cyclometallation to Pt or by N-methylation.
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http://dx.doi.org/10.1039/c6dt04359cDOI Listing
January 2017

Oligomerization of SCFTIR1 Is Essential for Aux/IAA Degradation and Auxin Signaling in Arabidopsis.

PLoS Genet 2016 09 12;12(9):e1006301. Epub 2016 Sep 12.

Department of Biological Sciences, University of Windsor, Windsor, Ontario, Canada.

The phytohormone auxin is a key regulator of plant growth and development. Molecular studies in Arabidopsis have shown that auxin perception and signaling is mediated via TIR1/AFB-Aux/IAA co-receptors that assemble as part of the SCFTIR1/AFB E3 ubiquitin-ligase complex and direct the auxin-regulated degradation of Aux/IAA transcriptional repressors. Despite the importance of auxin signaling, little is known about the functional regulation of the TIR1/AFB receptor family. Here we show that TIR1 can oligomerize in planta via a set of spatially clustered amino acid residues. While none of the residues identified reside in the interaction interface of the TIR1-Aux/IAA degron, they nonetheless regulate the binding of TIR1 to Aux/IAA substrate proteins and their subsequent degradation in vivo as an essential aspect of auxin signaling. We propose oligomerization of TIR1 as a novel regulatory mechanism in the regulation of auxin-mediated plant patterning and development.
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http://dx.doi.org/10.1371/journal.pgen.1006301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5019376PMC
September 2016

Contrasted photochromic and luminescent properties in dinuclear Pt(ii) complexes linked through a central dithienylethene unit.

Chem Commun (Camb) 2016 Jul;52(63):9833-6

Laboratoire CEISAM, UMR CNRS 6230, Université de Nantes, 2 rue de la houssinière, 44322 Nantes Cedex 03, France. and Institut Universitaire de France, 1 rue Descartes, F-75005 Paris Cedex 05, France.

We disclose two unprecedented complexes built with a central dithienylethene photochrome connecting two cyclometalated Pt(ii) moieties either on the reactive carbon atoms or on the lateral non-reactive carbon atoms of the photochrome. The two systems show vastly different properties that are rationalised thanks to quantum-chemical calculations.
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http://dx.doi.org/10.1039/c6cc03431dDOI Listing
July 2016

Tetracoordinated Bis-phenanthroline Copper-Complex Couple as Efficient Redox Mediators for Dye Solar Cells.

Inorg Chem 2016 06 23;55(11):5245-53. Epub 2016 May 23.

CBN-Fondazione Istituto Italiano di Tecnologia, Via Barsanti, Arnesano (Lecce), Italy.

A tetracoordinated redox couple, made by [Cu(2-mesityl-4,7-dimethyl-1,10-phenanthroline)2][PF6], 1, and its Cu(II) form [Cu(2-mesityl-4,7-dimethyl-1,10-phenanthroline)2][PF6]2, 2, has been synthesized, and its electrochemical and photochemical features have been investigated and compared with those of a previously published Cu(2+)/Cu(+) redox shuttle, namely, [Cu(2,9-dimethyl-1,10-phenanthroline)2][PF6], 3, and its pentacoordinated oxidized form [Cu(2,9-dimethyl-1,10-phenanthroline)2Cl][PF6], 4. The detrimental effect of the fifth Cl(-) ancillary ligand on the charge transfer kinetics of the redox shuttles has been exhaustively demonstrated. Appropriately balanced Cu-based electrolytes have been then formulated and tested in dye solar cells in combination with a π-extended benzothiadiazole dye. The bis-phenanthroline Cu-complexes, 1 and 2, have been found to provide an overall 4.4% solar energy conversion efficiency, which is more than twice that of the literature benchmark couple, 3 and 4, employing a Cl-coordinated oxidized species and even comparable with the performances of a I(-)/I3(-) electrolyte of analogous concentration. A fast counter-electrode reaction, due to the excellent electrochemical reversibility of 2, and a high electron collection efficiency, allowed through the efficient dye regeneration kinetics exerted by 1, represents two major characteristics of these copper-based electron mediators and may constitute a pivotal step toward the development of a next generation of copper-based efficient iodine-free redox shuttles.
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http://dx.doi.org/10.1021/acs.inorgchem.6b00204DOI Listing
June 2016

Genotype/Phenotype Correlations in Tuberous Sclerosis Complex.

Semin Pediatr Neurol 2015 Dec 21;22(4):259-73. Epub 2015 Oct 21.

(⁎)Child Neurology and Psychiatry Unit, Systems Medicine Department, Tor Vergata University Hospital of Rome, Rome, Italy.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by the development of widespread hamartomatous lesions in various organs, including brain, skin, kidneys, heart, and eyes. Central nervous system is almost invariably involved, with up to 85% of patients presenting with epilepsy, and at least half of patients having intellectual disability or other neuropsychiatric disorders including autism spectrum disorder. TSC is caused by the mutation in one of the 2 genes TSC1, at 9q34, and TSC2, at 16p13.3. They respectively encode for hamartin and tuberin, which form an intracellular complex inhibiting the mammalian target of rapamycin. Mammalian target of rapamycin overactivation following the genetic defect determines the cell growth and proliferation responsible for TSC-related lesions, as well as the alterations in neuronal excitability and synaptogenesis leading to epilepsy and neuropsychiatric disorders. A causative mutation for the disorder is identified in about 85% of patients with a clinical diagnosis of TSC. Mosaicism and technology limits likely explain most of the no mutation identified cases. This review confirms that patients with TSC2 mutations considered as a group usually present a more severe phenotype, characterized by higher number of tubers, earlier age at seizure onset and higher prevalence of intellectual disability. However, the clinical phenotype of the disease presents a high variability, thus making the prediction of the phenotype on an individual basis still challenging. The increasing application of new molecular techniques to subjects with TSC has the potential to significantly reduce the rate of patients with no mutation demonstrated and to identify an increasing higher number of mutations. This would hopefully allow a better characterization of higher risk mutations, which might help clinicians to plan individualized surveillance plans. Furthermore, the increasing availability of disease registries to collect clinical and genetics data of patients help to define more valid and clinically oriented genotype or phenotype correlations.
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http://dx.doi.org/10.1016/j.spen.2015.10.002DOI Listing
December 2015

Two-photon absorption properties and (1)O2 generation ability of Ir complexes: an unexpected large cross section of [Ir(CO)2Cl(4-(para-di-n-butylaminostyryl)pyridine)].

Dalton Trans 2015 Sep;44(35):15712-20

Dipartimento di Chimica dell'Università degli Studi di Milano, UdR- INSTM, Italy.

The new complexes cis-[Ir(CO)2Cl(4-(para-di-n-butylaminostyryl)pyridine)] () and [Ir(cyclometallated-2-phenylpyridine)2(4,4'-(para-di-n-butylaminostyryl)-2,2'-bipyridine)][PF6] () were synthesized and fully characterized along with the known complex Ir(cyclometallated-2-phenylpyridine)2(5-Me-1,10-phenanthroline)][PF6] (). Remarkably, complex , with an Ir(i) centre, displays fluorescence - as opposed to the phosphorescence typical of many Ir(iii) complexes - with a modestly high quantum yield in solution, opening a new route for the design of iridium-based emitters which should not be limited to the +3 oxidation state. It is also characterized by an unexpectedly large two-photon absorption (TPA) cross section, an order of magnitude higher than that previously reported for Ir(iii) or Pt(ii) complexes. The great potential of cyclometallated Ir(iii) complexes for photodynamic therapy was confirmed, with and showing a good singlet oxygen generation ability, coupled with a modest TPA activity for .
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http://dx.doi.org/10.1039/c5dt00552cDOI Listing
September 2015
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