Novel Sugar-incorporated N-heterocyclic Carbene (NHC) Gold(I) Complexes as Potential Anticancer Agents

New metal complexes containing anticancer drugs are one of the major interests in bioinorganic or bioorganometallic medicinal chemistry. The development of novel metallodrugs is shifting to the use of non platinum central atoms coordinating different organic ligands in order to overcome the drawbacks (e.g. resistance, side effects) of the platinum antitumor agents. [1]. Gold(I) complexes show a very promising antiproliferative effects, but they are remarkable oxidizing properties. In order to reduce this character, in the last years, several studies have been reported based on gold(I) N-heterocyclic carbenes (NHCs) in vitro and in a few cases also in vivo [2]. Within this frame we have designed new gold(I) complexes based on sugar incorporated N-heterocyclic carbene. The presence of the sugar moiety allows to tune the lipophilicity behavior of the complexes. The complexes have been synthesized according to the scheme reported below. After the preparation of the NHC ligand, in the first step the corresponding Ag-complex (1AgBr) was prepared from Ag2O, to act as starting materials for transmetalation. The reaction of 1AgBr with gold(I) precursor, THTAuCl (THT = tetrahydrothiophene), in dichloromethane at room temperature overnight afford to gold complex. The compound was identified by NMR and RX. Starting from 1Cl, the cationic gold derivatives were prepared adding phosphorous and sulphur based neutral ligands, in the presence of silver tetrafluoroborate, as a chloride abstractor. The ligands have been selected in order to modulate electronic and hydrophilic complexes properties. The compounds will be investigated in screening on human cell line

The Italian tremor Network (TITAN): rationale, design and preliminary findings.

INTRODUCTION: The recently released classification has revised the nosology of tremor, defining essential tremor (ET) as a syndrome and fueling an enlightened debate about some newly conceptualized entities such as ET-plus. As a result, precise information of demographics, clinical features, and about the natural history of these conditions are lacking. METHODS: The ITAlian tremor Network (TITAN) is a multicenter data collection platform, the aim of which is to prospectively assess, according to a standardized protocol, the phenomenology and natural history of tremor syndromes. RESULTS: In the first year of activity, 679 patients have been recruited. The frequency of tremor syndromes varied from 32% of ET and 41% of ET-plus to less than 3% of rare forms, including focal tremors (2.30%), task-specific tremors (1.38%), isolated rest tremor (0.61%), and orthostatic tremor (0.61%). Patients with ET-plus were older and had a higher age at onset than ET, but a shorter disease duration, which might suggest that ET-plus is not a disease stage of ET. Familial aggregation of tremor and movement disorders was present in up to 60% of ET cases and in about 40% of patients with tremor combined with dystonia. The body site of tremor onset was different between tremor syndromes, with head tremor being most commonly, but not uniquely, associated with dystonia. CONCLUSIONS: The TITAN study is anticipated to provide clinically relevant prospective information about the clinical correlates of different tremor syndromes and their specific outcomes and might serve as a basis for future etiological, pathophysiological, and therapeutic research

Pharmacotherapy to prevent the onset of depression following traumatic brain injury

Introduction: Depressive symptoms may follow traumatic brain injury (TBI), affecting cognition, apathy, and overall general functioning. Pharmacotherapy to prevent the onset of depression following TBI is, therefore, crucial. Areas covered: The present report critically appraises current pharmacotherapy to prevent the onset of depression following TBI as well as novel potential pharmacological avenues on the matter. Both efficacy and safety issues are considered, emphasizing an evidence-based approach whenever feasible. The authors further provide the reader with their expert opinion and future perspectives on the subject. Expert opinion: Despite its clinical burden and relatively frequent occurrence, the prophylaxis of post-TBI depression warrants further research. The current clinical guidelines of depression do not account for people with a primary diagnosis of TBI. Prospective cohort studies supported by proof-of-concept trials are nonetheless urged toward more effective, patient-tailored pharmacotherapy to prevent the onset of depression and treatment-resistance phenomena following TBI

A Semi-Active Control Algorithm for Base-Isolated Structures

The possibility of enhancing the seismic structural response of base-isolated (BI) structures through the adoption of additional smart damping devices has been widely investigated in literature for many years. However, few experimental data are available on this subject. The proposed paper describes a research activity about the adoption of semi-actively (SA) controlled magnetorheological (MR) dampers in BI buildings. First, a control algorithm able to “re-shape” structural modes, frequencies and damping ratios is introduced in the paper and specialized to the case of BI structures with additional control devices. Then a clipped version of the proposed control algorithm is shown to be utilized in conjunction with SA MR dampers. An experimental mock up made up of a BI 1-story steel frame is then described. The main results of the seismic experimental tests on a shaking table are presented and commented

Clinimetrics of the Italian version of the Montreal Cognitive Assessment (MoCA) in adult-onset idiopathic focal dystonia.

This study aimed at assessing the clinimetrics of the Montreal Cognitive Assessment (MoCA) in an Italian cohort of patients with adult-onset idiopathic focal dystonia (AOIFD). N = 86 AOIFD patients and N = 92 healthy controls (HCs) were administered the MoCA. Patients further underwent the Trail-Making Test (TMT) and Babcock Memory Test (BMT), being also screened via the Beck Depression Inventory-II (BDI-II) and the Dimensional Apathy Scale (DAS). Factorial structure and internal consistency were assessed. Construct validity was tested against TMT, BMT, BDI-II and DAS scores, whilst diagnostics against the co-occurrence of a defective performance on at least one TMT measure and on the BMT. Case-control discrimination was examined. The association between MoCA scores and motor-functional measures was explored. The MoCA was underpinned by a mono-component structure and acceptably reliable at an internal level. It converged towards TMT and BMT scores, as well as with the DAS, whilst diverging from the BDI-II. Its adjusted scores accurately detected cognitive impairment (AUC = .86) at a cut-off of < 17.212. The MoCA discriminated patients from HCs (p < .001). Finally, it was unrelated to disease duration and severity, as well as to motor phenotypes. The Italian MoCA is a valid, diagnostically sound and feasible cognitive screener in AOIFD patients

Expanding SPG18 clinical spectrum: autosomal dominant mutation causes complicated hereditary spastic paraplegia in a large family.

BACKGROUND: SPG18 is caused by mutations in the endoplasmic reticulum lipid raft associated 2 (ERLIN2) gene. Autosomal recessive (AR) mutations are usually associated with complicated hereditary spastic paraplegia (HSP), while autosomal dominant (AD) mutations use to cause pure SPG18. AIM: To define the variegate clinical spectrum of the SPG18 and to evaluate a dominant negative effect of erlin2 (encoded by ERLIN2) on oligomerization as causing differences between AR and AD phenotypes. METHODS: In a four-generation pedigree with an AD pattern, a spastic paraplegia multigene panel test was performed. Oligomerization of erlin2 was analyzed with velocity gradient assay in fibroblasts of the proband and healthy subjects. RESULTS: Despite the common p.V168M mutation identified in ERLIN2, a phenoconversion to amyotrophic lateral sclerosis (ALS) was observed in the second generation, pure HSP in the third generation, and a complicated form with psychomotor delay and epilepsy in the fourth generation. Erlin2 oligomerization was found to be normal. DISCUSSION: We report the first AD SPG18 family with a complicated phenotype, and we ruled out a dominant negative effect of V168M on erlin2 oligomerization. Therefore, our data do not support the hypothesis of a relationship between the mode of inheritance and the phenotype, but confirm the multifaceted nature of SPG18 on both genetic and clinical point of view. Clinicians should be aware of the importance of conducting an in-depth clinical evaluation to unmask all the possible manifestations associated to an only apparently pure SPG18 phenotype. We confirm the genotype-phenotype correlation between V168M and ALS emphasizing the value of close follow-up

Correction to: The Italian tremor Network (TITAN): rationale, design and preliminary findings (Neurological Sciences, (2022), 10.1007/s10072-022-06104-w)

Originally, the article was published with an error. The affiliation of the author Giulia Paparella should only be " Neuromed Institute IRCCS, Pozzilli, IS, Italy”. The original article has been corrected

Phenotypic variability in acquired and idiopathic dystonia

BackgroundTo date, a few studies have systematically investigated differences in the clinical spectrum between acquired and idiopathic dystonias. ObjectivesTo compare demographic data and clinical features in patients with adult-onset acquired and idiopathic dystonias. MethodsPatients were identified from among those included in the Italian Dystonia Registry, a multicenter Italian dataset of patients with adult-onset dystonia. Study population included 116 patients with adult-onset acquired dystonia and 651 patients with isolated adult-onset idiopathic dystonia. ResultsComparison of acquired and idiopathic dystonia revealed differences in the body distribution of dystonia, with oromandibular dystonia, limb and trunk dystonia being more frequent in patients with acquired dystonia. The acquired dystonia group was also characterized by lower age at dystonia onset, greater tendency to spread, lower frequency of head tremor, sensory trick and eye symptoms, and similar frequency of neck pain associated with CD and family history of dystonia/tremor. ConclusionsThe clinical phenomenology of dystonia may differ between acquired and idiopathic dystonia, particularly with regard to the body localization of dystonia and the tendency to spread. This dissimilarity raises the possibility of pathophysiological differences between etiologic categories