Polyamine–Drug Conjugates: Do They Boost Drug Activity?

Over the past two decades, the strategy of conjugating polyamine tails with bioactive molecules such as anticancer and antimicrobial agents, as well as antioxidant and neuroprotective scaffolds, has been widely exploited to enhance their pharmacological profile. Polyamine transport is elevated in many pathological conditions, suggesting that the polyamine portion could improve cellular and subcellular uptake of the conjugate via the polyamine transporter system. In this review, we have presented a glimpse on the polyamine conjugate scenario, classified by therapeutic area, of the last decade with the aim of highlighting achievements and fostering future developments

Cognitive reserve index and functional and cognitive outcomes in severe acquired brain injury: A pilot study

Background: Many variables affect outcome after brain injury. Cognitive reserve (CR) is a subjective factor that reflects a set of personal characteristics and that differentiates individuals. It may influence an individual’s capacity to react to brain injury. Objective: To study the effects of cognitive reserve on functional and cognitive outcome at the end of rehabilitation, in patients with severe acquired brain injury (sABI), by means of the Cognitive Reserve Index questionnaire (CRIq). Methods: We report a retrospective study of a continuous series of sABI patients on first admission to a rehabilitation center. Disability and cognitive outcomes were recorded. Results: In the 94 patients enrolled, the assessments after rehabilitation showed a significant gain measured with the disability Rating Scale for patients with a higher CR (CRIq≥ 85). A significant negative correlation was found: between CRIq scores and the interval elapsing before first access to neuropsychological assessment, between CRIq scores, especially level of education, and tests that measure the same domain (attention). Conclusions: Improvements in overall and cognitive disability emerged, but CR did not seem to substantially influence outcome in this sample of patients. This result may be partly due to the clinical severity of the population studied and the sample’s dimension, although quantitatively representative of the population

A heuristic algorithm for finding attractive fixed-length circuits in street maps

In this paper we consider the problem of determining fixed-length routes on a street map that start and end at the same location. We propose a heuristic for this problem based on finding pairs of edge-disjoint shortest paths, which can then be combined into a circuit. Various heuristics and filtering techniques are also proposed for improving the algorithm’s performance

From Monoamine Oxidase Inhibition to Antiproliferative Activity: New Biological Perspectives for Polyamine Analogs

Monoamine oxidases (MAOs) are well-known pharmacological targets in neurological and neurodegenerative diseases. However, recent studies have revealed a new role for MAOs in certain types of cancer such as glioblastoma and prostate cancer, in which they have been found overexpressed. This finding is opening new frontiers for MAO inhibitors as potential antiproliferative agents. In light of our previous studies demonstrating how a polyamine scaffold can act as MAO inhibitor, our aim was to search for novel analogs with greater inhibitory potency for human MAOs and possibly with antiproliferative activity. A small in-house library of polyamine analogs (2-7) was selected to investigate the effect of constrained linkers between the inner amine functions of a polyamine backbone on the inhibitory potency. Compounds 4 and 5, characterized by a dianiline (4) or dianilide (5) moiety, emerged as the most potent, reversible, and mainly competitive MAO inhibitors (Ki < 1 μM). Additionally, they exhibited a high antiproliferative activity in the LN-229 human glioblastoma cell line (GI50 < 1 μM). The scaffold of compound 5 could represent a potential starting point for future development of anticancer agents endowed with MAO inhibitory activity

Prevention and cure of rhinogenous deafness at the Thermal Baths ?Bagni delle Galleraie?

Introduction. Hearing is foundamental for human social life.Secretory Otitis Media (SOM) is the most important cause oftrasmissive hypoacusis in early childhood.Methods. The Hygiene Institute in the University of Siena incollaboration with the Thermal Baths ?Bagni delleGalleraie? proposed a prevention and cure campaign ofrhinogenous deafness in June 2002 in some primary schoolsin the Colle val D?Elsa district. A sample of 87 children wasinvolved in the study (average age of 5,64 ± 1,41 years). Onentering the thermal baths a questionnaire was administeredto the parents, to point out possible risk factors. Results.Results. Among the 87 children, 28 cases of SOM and 21cases of severe tubal disorder were found. Only 19 cases out of 49 were already known to the parents and only 28 joinedthe study and were examined for three years consecutively. Discussion. Out of the 35 children examined in 2002, 28 returned to ?The Galleraie? for the two following years. Theyrepeated the thermal cure for two years as a preventive measure. At present they are not affected by SOM and during thewinters suffered a lower number of infections in the primaryairways and took less antibiotics.Conclusions. Our study focuses on infant school childrenbecause of their critical age for linguistic and social development. Early diagnosis and therapy prevent any negativesocial development

Tunable Band Alignment with Unperturbed Carrier Mobility of On-Surface Synthesized Organic Semiconducting Wires

The tunable properties of molecular materials place them among the favorites for a variety of future generation devices. In addition, to maintain the current trend of miniaturisation of those devices, a departure from the present top-down production methods may soon be required and self-assembly appears among the most promising alternatives. On-surface synthesis unites the promises of molecular materials and of self assembly, with the sturdiness of covalently bonded structures: an ideal scenario for future applications. Following this idea, we report the synthesis of functional extended nanowires by self-assembly. In particular, the products correspond to one-dimensional organic semiconductors. The uniaxial alignment provided by our substrate templates allows us to access with exquisite detail their electronic properties, including the full valence band dispersion, by combining local probes with spatial averaging techniques. We show how, by selectively doping the molecular precursors, the product\u2019s energy level alignment can be tuned without compromising the charge carrier\u2019s mobility

Using location services to autonomously drive flying mobile sinks in Wireless Sensor Networks

International audienceThe use of mobility in a Wireless Sensor Network has already been indicated as a feature whose exploitation would increase the performances and the ease of mantainance in these environments. Expecially in a event-based WSN, where is necessary a prompt response in terms of data processing and o oading, a set of mobile ying sinks could be a good option for the role of autonomous data collectors. For those reasons in this paper we propose a distributed algorithm to independently and autonomously drive a mobile sink through the nodes of a WSN and we show its preferability over more classical routing approaches expecially in the presence of a localized generation of large amount of information. Our result shows that, in the case of fairly complete coverage of the area where the nodes lie, it is possible to promptly notify a mobile sink about the presence of data to o oad, drive it to the interested area and achieve interesting performances

Contribution of Rare and Low-Frequency Variants to Multiple Sclerosis Susceptibility in the Italian Continental Population

Genome-wide association studies identified over 200 risk loci for multiple sclerosis (MS) focusing on common variants, which account for about 50% of disease heritability. The goal of this study was to investigate whether low-frequency and rare functional variants, located in MS-established associated loci, may contribute to disease risk in a relatively homogeneous population, testing their cumulative effect (burden) with gene-wise tests. We sequenced 98 genes in 588 Italian patients with MS and 408 matched healthy controls (HCs). Variants were selected using different filtering criteria based on allelic frequency and in silico functional impacts. Genes showing a significant burden (n = 17) were sequenced in an independent cohort of 504 MS and 504 HC. The highest signal in both cohorts was observed for the disruptive variants (stop-gain, stop-loss, or splicing variants) located in EFCAB13, a gene coding for a protein of an unknown function (p < 10–4). Among these variants, the minor allele of a stop-gain variant showed a significantly higher frequency in MS versus HC in both sequenced cohorts (p = 0.0093 and p = 0.025), confirmed by a meta-analysis on a third independent cohort of 1298 MS and 1430 HC (p = 0.001) assayed with an SNP array. Real-time PCR on 14 heterozygous individuals for this variant did not evidence the presence of the stop-gain allele, suggesting a transcript degradation by non-sense mediated decay, supported by the evidence that the carriers of the stop-gain variant had a lower expression of this gene (p = 0.0184). In conclusion, we identified a novel low-frequency functional variant associated with MS susceptibility, suggesting the possible role of rare/low-frequency variants in MS as reported for other complex diseases

A fast and accurate energy source emulator for wireless sensor networks

The capability to either minimize energy consumption in battery-operated devices, or to adequately exploit energy harvesting from various ambient sources, is central to the development and engineering of energy-neutral wireless sensor networks. However, the design of effective networked embedded systems targeting unlimited lifetime poses several challenges at different architectural levels. In particular, the heterogeneity, the variability, and the unpredictability of many energy sources, combined to changes in energy required by powered devices, make it difficult to obtain reproducible testing conditions, thus prompting the need of novel solutions addressing these issues. This paper introduces a novel embedded hardware-software solution aimed at emulating a wide spectrum of energy sources usually exploited to power sensor networks motes. The proposed system consists of a modular architecture featuring small factor form, low power requirements, and limited cost. An extensive experimental characterization confirms the validity of the embedded emulator in terms of flexibility, accuracy, and latency while a case study about the emulation of a lithium battery shows that the hardware-software platform does not introduce any measurable reduction of the accuracy of the model. The presented solution represents therefore a convenient solution for testing large-scale testbeds under realistic energy supply scenarios for wireless sensor networks