Mapping interactions between geology, subsurface resource exploitation and urban development in transforming cities using InSAR Persistent Scatterers: two decades of change in Florence, Italy

Urban expansion and city transformation are increasing reality across the world. Now more than ever it is essential to understand and map at the appropriate scale the processes happening along the verticality and horizontality of cities, to gather robust evidence underpinning strategies for sustainable management of the built environment. This paper explores how established techniques of Persistent Scatterer Interferometry (PSI) can be shaped into a novel dedicated procedure to detect vertical and horizontal urban dynamics including: use and re-use of urban space (new building construction, intentional demolition, renovation projects); exploitation of groundwater resources (induced land subsidence); interactions between new foundations, superficial deposits and bedrock geology (settlement of recent buildings); ground and slope instability affecting settled buildings; susceptibility of heritage assets to structural damages; baseline characterisation prior to planned major infrastructure construction (tunnelling and transportation networks). Florence, central Italy, is used as a demonstration site. This city includes UNESCO World Heritage List historic centre, 20th-century residential, industrial and peri-urban quarters, and is currently in transition to metropolitan area of over 1 million of inhabitants. Velocity decomposition maps were generated based on millimetre-precise estimates of surface displacements retrieved from PSI processing of the full archives of satellite C-band radar images, including 79 ERS-1/2 descending (1992–2000), 70 ENVISAT ASAR ascending and descending (2003–2010) and 101 RADARSAT-1 ascending and descending (2003–2007). 12 macropatterns and 84 micropatterns in the final map of alert areas highlight a dualism which reflects the physical and urban geography of Florence. North-western and south-western quarters show hot spots of new building construction and regeneration projects for residential, business and tertiary service purposes, alongside issues due to groundwater exploitation and induced land subsidence up to 30–40 mm/yr. Local interactions with underlying geology and natural slope instability processes predominate in the southern and north-eastern sectors. At local scale, stable condition was found for the heritage assets and buildings located along the tracks of the planned subway railway and tramway, with motion rates averagely within ±1.5 mm/yr and localised deformation only up to −3.5 mm/yr. Structural assessment based on future PSI monitoring campaign will benefit of this baseline characterisation

Unexpected episodes of cyanosis in late preterm and term neonates prompted admission to a neonatal care unit

Abstract Background We studied late preterm and term infants who were admitted to our neonatal care unit in a tertiary hospital for unexpected episodes of cyanosis that occurred during rooming-in for evaluation of their frequency, most frequent associated diseases, and documentation of the diagnostic clinical approach. Methods We carried out a retrospective study of infants with a gestational age ≥35 weeks who were admitted from the nursery with the diagnosis of cyanosis from January 2009 to December 2016. Exclusion criteria were the occurrence of acrocyanosis and the diagnosis of sudden unexpected postnatal collapse (SUPC). Results We studied 49 infants with a mean gestational age of 38 ± 2 weeks. The frequency of admission for cyanosis was 1.8/1000 live births and was similar (p = 0.167) in late preterm and term infants. The majority of episodes occurred during the first 24 h of life (57%). Only 16 infants (33%) were discharged with a diagnosis, that was mostly (n = 5;10%) gastro-esophageal reflux. Conclusions Unexpected episodes of cyanosis caused admission of 1.8/1000 live births to the neonatal care unit without differences between late preterm and term infants. These episodes occurred mainly during the first day of life and infants were mostly discharged without a known diagnosis

Synthesis, chemical characterization, and biological evaluation of a novel auranofin derivative as an anticancer agent

A novel gold(I) complex inspired by the known medicinal inorganic compounds auranofin and thimerosal, namely ethylthiosalicylate(triethylphosphine)gold(I) (AFETT hereafter), was synthesized and characterised and its structure was resolved through X-ray diffraction. The solution behavior of AFETT and its interactions with two biologically relevant proteins (i.e. human serum albumin and haemoglobin) and with a synthetic dodecapeptide reproducing the C-terminal portion of thioredoxin reductase were comparatively analyzed through 31P NMR and ESI-MS. Remarkable binding properties toward these biomolecules were disclosed. Moreover, the cytotoxic effects produced by AFETT on two ovarian cancer cell lines (A2780 and A2780 R) and one colorectal cancer cell line (HCT116) were analyzed and found to be strong and nearly superimposable to those of auranofin. Interestingly, for both compounds, the ability to induce downregulation of vimentin expression in A2780 R cells was evidenced. Despite its close similarity to auranofin, AFETT is reported to exhibit some peculiar and distinctive features such as a lower lipophilicity, an increased water solubility and a faster reactivity towards the selected target biomolecules. These differences might confer to AFETT significant pharmaceutical and therapeutic advantages over auranofin itself

Highlights of New Strategies to Increase the Efficacy of Transition Metal Complexes for Cancer Treatments

Although important progress has been made, cancer still remains a complex disease to treat. Serious side effects, the insurgence of resistance and poor selectivity are some of the problems associated with the classical metal-based anti-cancer therapies currently in clinical use. New treatment approaches are still needed to increase cancer patient survival without cancer recurrence. Herein, we reviewed two promising-at least in our opinion-new strategies to increase the efficacy of transition metal-based complexes. First, we considered the possibility of assembling two biologically active fragments containing different metal centres into the same molecule, thus obtaining a heterobimetallic complex. A critical comparison with the monometallic counterparts was done. The reviewed literature has been divided into two groups: the case of platinum; the case of gold. Secondly, the conjugation of metal-based complexes to a targeting moiety was discussed. Particularly, we highlighted some interesting examples of compounds targeting cancer cell organelles according to a third-order targeting approach, and complexes targeting the whole cancer cell, according to a second-order targeting strategy

Thermodynamic Evaluation of the Interactions between Anticancer Pt(II) Complexes and Model Proteins

In this work, we have analysed the binding of the Pt(II) complexes ([PtCl(4′-phenyl-2,2′:6′,2″-terpyridine)](CF3SO3) (1), [PtI(4′-phenyl-2,2′:6′,2″-terpyridine)](CF3SO3) (2) and [PtCl(1,3-di(2-pyridyl)benzene) (3)] with selected model proteins (hen egg-white lysozyme, HEWL, and ribonuclease A, RNase A). Platinum coordination compounds are intensively studied to develop improved anticancer agents. In this regard, a critical issue is the possible role of Pt-protein interactions in their mechanisms of action. Multiple techniques such as differential scanning calorimetry (DSC), electrospray ionization mass spectrometry (ESI-MS) and UV-Vis absorbance titrations were used to enlighten the details of the binding to the different biosubstrates. On the one hand, it may be concluded that the affinity of 3 for the proteins is low. On the other hand, 1 and 2 strongly bind them, but with major binding mode differences when switching from HEWL to RNase A. Both 1 and 2 bind to HEWL with a non-specific (DSC) and non-covalent (ESI-MS) binding mode, dominated by a 1:1 binding stoichiometry (UV-Vis). ESI-MS data indicate a protein-driven chloride loss that does not convert into a covalent bond, likely due to the unfavourable complexes’ geometries and steric hindrance. This result, together with the significant changes of the absorbance profiles of the complex upon interaction, suggest an electrostatic binding mode supported by some stacking interaction of the aromatic ligand. Very differently, in the case of RNase A, slow formation of covalent adducts occurs (DSC, ESI-MS). The reactivity is higher for the iodo-compound 2, in agreement with iodine lability higher than chlorine

Potent in vitro antiproliferative properties for a triplatinum cluster toward triple negative breast cancer cells

The trinuclear platinum cluster [Pt3(μ-PBut2)3(CO)3]CF3SO3 (I) was designed featuring the presence of a nearly equilateral platinum triangle bridged by three di-tert-butylphosphide ligands; in addition, each platinum center bears a terminal carbonyl ligand. This triplatinum cluster was initially developed in view of applications in the field of cluster-containing innovative materials. Yet, due to the large success of platinum complexes in cancer treatment, we also decided to explore its cytotoxic and anticancer properties. Accordingly, the solubility profile of this compound in several solvents was preliminarily investigated, revealing a conspicuous solubility in DMSO and DMSO/buffer mixtures; this makes the biological testing of I amenable. UV–Vis measurements showed that the triplatinum cluster is stable for several hours under a variety of conditions, within aqueous environments. No measurable reactivity was observed for I toward two typical model proteins, i.e. lysozyme and cytochrome c. On the contrary, a significant reactivity was evidenced when reacting I with small sulfur-containing ligands. In particular, a pronounced reactivity with reduced glutathione and cysteine emerged from ESI-MS experiments, proving complete formation of I-GSH and I-Cys derivatives, with the loss of a single carbonyl ligand. Starting from these encouraging results, the cytotoxic potential of I was assayed in vitro against a panel of representative cancer cell lines, and potent cytotoxic properties were disclosed. Of particular interest is the finding that the triplatinum species manifests potent antiproliferative properties toward Triple Negative Breast Cancer Cells, often refractory to most anticancer drugs. Owing to the reported encouraging results, a more extensive biological and pharmacological evaluation of this Pt cluster is now warranted to better elucidate its mode of action

Chlorido and bromido oxaliplatin analogues as potential agents for CRC treatment: Solution behavior, protein binding and cytotoxicity evaluation

Despite the widespread use of platinum drugs in the treatment of colorectal cancer (CRC), due to the heavy side effects and to intrinsic or acquired Pt resistance, new and more efficient drugs are urgently needed. Starting from the encouraging results obtained for the complex PtI2(DACH), we summarise here our recent advances, reporting data on the synthesis and the chemical and biological features of two oxaliplatin analogues i.e. PtBr2(DACH) and PtCl2(DACH). The comparative approach of these studies reveals how these analogues possess interesting and differential pharmacological properties as well as some peculiar features that may be conveniently exploited to shed light in the mechanistic aspects involved in the pharmacological action of the parent drug oxaliplatin. Furthermore, these findings may inspire the design of more effective Pt-based anticancer drugs to be used in CRC treatment

Waist circumference correlates with Body Mass Index (B.M.I.) in school-aged children

Body Mass Index (B.M.I.) is a parameter deriving from a person’s weight and height and is routinely and easily recorded during children physical examination both at school and sport association. By contrast, waist circumference measurement, even if easy to be performed, due to the need of removing clothes, in some context, may cause certain degree of psychological discomfort, and may require parent’s authorization. On the other hand, it is well known that waist circumference may be predictive for metabolic syndrome. In particular waist-to-height ratio (WHtR) has been recently emerged as a valuable index for abdominal obesity and high cardiovascular risk. This index does not require percentile tables and may be applied to both sexes of all ages. A WHtR >0.5 has been proposed to be able to identify both children and adults with the highest cardiometabolic risk. Based on these premises, the aim of our study was to evaluate whether a relationship existed between B.M.I. and waist circumference in Italian school-aged children (141 boys and 108 girls aged 7 to 9 years; 103 boys and 50 girls aged 10 to 13 years). By using Pearson’s correlation coefficient we found the existence of a significant linear correlation between waist circumference and B.M.I. values in each age and sex group. Our data suggest the possibility to estimate indirectly waist circumference from height and weight, and provide an alternative method to predict the risk of metabolic syndrome by using B.M.I

Chemical Modification of Auranofin Yields a New Family of Anticancer Drug Candidates: The Gold(I) Phosphite Analogues

A panel of four novel gold(I) complexes, inspired by the clinically established gold drug auranofin (1-Thio-β-D-glucopyranosatotriethylphosphine gold-2,3,4,6-tetraacetate), was prepared and characterized. All these compounds feature the replacement of the triethylphosphine ligand of the parent compound auranofin with a trimethylphosphite ligand. The linear coordination around the gold(I) center is completed by Cl−, Br−, I− or by the thioglucose tetraacetate ligand (SAtg). The in-solution behavior of these gold compounds as well as their interactions with some representative model proteins were comparatively analyzed through 31PNMR and ESI-MS measurements. Notably, all panel compounds turned out to be stable in aqueous media, but significant differences with respect to auranofin were disclosed in their interactions with a few leading proteins. In addition, the cytotoxic effects produced by the panel compounds toward A2780, A2780R and SKOV-3 ovarian cancer cells were quantitated and found to be in the low micromolar range, since the IC50 of all compounds was found to be between 1 μM and 10 μM. Notably, these novel gold complexes showed large and similar inhibition capabilities towards the key enzyme thioredoxin reductase, again comparable to those of auranofin. The implications of these results for the discovery of new and effective gold-based anticancer agents are discussed