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L’articolo indaga le ragioni del profondo impatto che le “rivoluzioni colorate” dei primi anni Duemila hanno avuto sulle percezioni politico-strategiche della Russia. Lo scopo del lavoro è quello di mettere in evidenza alcuni aspetti delle “rivoluzioni colorate” suscettibili di rafforzare la tendenza della Russia ad attribuire alle potenze occidentali intenzioni ostili nei suoi confronti, in particolare l’attivismo in Georgia e Ucraina di ONG occidentali già coinvolte nel political warfare condotto dagli Stati Uniti in Polonia negli anni di Reagan (sostegno a Solidarnošc) e ancora in Serbia nel dopo-Guerra fredda (aiuti alle opposizioni attive nel rovesciamento di Slobodan Miloševic nel 2000). L’articolo mostra come le locuzioni “rivoluzione colorata” e “guerra ibrida” siano diventate sinonimi nel recente discorso strategico russo, e come il political warfare statunitense in Polonia e il rovesciamento di Miloševic in Serbia vengano considerati dai russi come dei precedenti delle “rivoluzioni colorate”.

Abstract A plethora of different electronic and optoelectronic devices have been developed lately, for biosensing applications (e.g., label‐free, fast, and easier to operate) based on a detecting interface accommodating the biorecognition elements, anchored by thiolate self‐assembled monolayers (SAMs) on a gold surface. Here, a surface plasmon resonance (SPR) characterization of anti‐p24 anchored on different SAMs is performed to investigate the effect of the SAM structure on the antibodies’ packing efficiency and the sensors’ analytical figures of merit. Notably, the mixed SAM deposited from a solution 10:1 of 3‐mercaptopropionic acid and 11‐mercaptoundecanoic acid (11MUA) is compared to that resulting from a solution 10:1 of ad hoc synthesized N‐(2‐hydroxyethyl)‐3‐mercaptopropanamide (NMPA)/11MUA. Despite the improvement in the anti‐p24 surface coverage registered using the 11MUA/NMPA SAM, the latter produces a significant decrease in the antibodies’ binding efficiency against human immunodeficiency virus p24 protein. To provide a molecular rationale behind the SPR data, density functional theory calculations are also undertaken. A comprehensive physical view of the main competing phenomena affecting the biorecognition events at a biofunctionalized gold detecting interface is represented here.

The coumarin core (i.e., 1-benzopyran-2 (2H)-one) is a structural motif highly recurrent in both natural products and bioactive molecules. Indeed, depending on the substituents and branching positions around the byciclic core, coumarin-containing compounds have shown diverse pharmacological activities, ranging from anticoagulant activities to anti-inflammatory, antimicrobial, anti-HIV and antitumor effects. In this survey, we have reported the main scientific results of the 20-years investigation on the coumarin core, exploited by the research group headed by Prof. Angelo Carotti (Bari, Italy) either as a scaffold or a pharmacophore moiety in designing novel biologically active small molecules.

Acute monoblastic/monocytic leukemia (AMoL), previously defined as M5 according to FAB classification, is one of the most common subtypes of Acute Myeloid Leukemia (AML) in children, representing ~15–24% of all pediatric AMLs. Currently, the characterization of monocytic-lineage neoplasia at diagnosis includes cytomorphology, cytochemistry, immunophenotyping by multiparametric flow cytometry, cytogenetics, and molecular biology. Moreover, measurable residual disease (MRD) detection is critical in recognizing residual blasts refractory to chemotherapy. Nonetheless, diagnosis and MRD detection may still be challenging in pediatric AMoL since the morphological and immunophenotypic features of leukemic cells potentially overlap with those of normal mature monocytic compartment, as well as differential diagnosis can be troublesome, particularly with Juvenile Myelomonocytic Leukemia and reactive monocytosis in infants and young children. A failure or delay in diagnosis and inaccuracy in MRD assessment may worsen the AMoL prognosis. Therefore, improving diagnosis and monitoring techniques is mandatory to stratify and tailor therapies to the risk profile. This Mini Review aims to provide an updated revision of the scientific evidence on pediatric AMoL diagnostic tools.

Introduction: The study aims to compare the efficacy and safety of bulking agents and single-incision slings in the treatment of urinary incontinence in 159 patients during a 29-month follow-up period. Material and methods: Of the 159 patients suffering from stress urinary incontinence, 64 were treated with bulking agents (PAHG Bulkamid®) and 75 with a single-incision sling (Altis®). The ICIQ-UI-SF (Incontinence Questionnaire-Urine Incontinence-Short Form), PISQ-12 (Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaires short form), FSFI (Female Sexual Function Index), FSDS (Female Sexual Distress Scale), and PGI-I (Patient Global Improvement Index) were used to assess efficiency and quality of life. Results: The bulking agents showed high efficacy and safety during the 29-month follow-up. Post-operative complications were recorded in both groups, with only two significant differences. The Bulkamid group experienced no pain, while 10.8% of the ALTIS group experienced groin pain and 5% experienced de novo urgency. Furthermore, patients treated with bulking agents experienced reduced nicturia (0.78 vs. 0.92 in patients treated with single-incision slings.). In both groups, we noticed a significant improvement in QoL (quality of life), with a halved ICIQ-UI-SF (International Consultation on Incontinence Questionnaire-Urine Incontinence-Short Form) score which was completed to assess the impact of urine symptoms. After 24 months of therapy, the Bulkamid group saw a decrease from 14.58 ± 5.11 at baseline to 5.67 ± 1.90 (p < 0.0001), whereas the ALTIS group experience a decrease from 13.75 ± 5.89 to 5.83 ± 1.78. Similarly, we observed an improvement in sexual function, with the number of sexually active patients increasing from 29 to 44 (56.4%) in the Bulkamid group (p = 0.041) and from 31 to 51 (61.7%) in the ALTIS group (p = 0.034). According to the most recent statistics, the PISQ-12, FSFI, and FSDS scores all demonstrated an improvement in women's sexual function. Conclusions: In terms of efficacy and safety, bulking agents had notable results over the 29-month follow-up period. Furthermore, the patients treated with bulking agents reported a lower incidence of postoperative complications and a no discernible difference in terms of quality of life and sexual activity compared to the ones treated with single-incision slings. Bulking agents can be considered a very reliable therapeutic option based on accurate patient selection. [ABSTRACT FROM AUTHOR]

This comprehensive review, covering 2021-2023, explores the multifaceted chemical and pharmacological potential of coumarins, emphasizing their significance as versatile natural derivatives in medicinal chemistry. The synthesis and functionalization of coumarins have advanced with innovative strategies. This enabled the incorporation of diverse functional fragments or the construction of supplementary cyclic architectures, thereby the biological and physico-chemical properties of the compounds obtained were enhanced. The unique chemical structure of coumarine facilitates binding to various targets through hydrophobic interactions pi-stacking, hydrogen bonding, and dipole-dipole interactions. Therefore, this important scaffold exhibits promising applications in uncountable fields of medicinal chemistry (e.g., neurodegenerative diseases, cancer, inflammation). [ABSTRACT FROM AUTHOR]

The fusion oncoprotein Bcr-Abl is an aberrant tyrosine kinase responsible for chronic myeloid leukemia and acute lymphoblastic leukemia. The auto-inhibition regulatory module observed in the progenitor kinase c-Abl is lost in the aberrant Bcr-Abl, because of the lack of the N-myristoylated cap able to bind the myristoyl binding pocket also conserved in the Bcr-Abl kinase domain. A way to overcome the occurrence of resistance phenomena frequently observed for Bcr-Abl orthosteric drugs is the rational design of allosteric ligands approaching the so-called myristoyl binding pocket. The discovery of these allosteric inhibitors although very difficult and extremely challenging, represents a valuable option to minimize drug resistance, mostly due to the occurrence of mutations more frequently affecting orthosteric pockets, and to enhance target selectivity with lower off-target effects. In this perspective, we will elucidate at a molecular level the structural bases behind the Bcr-Abl allosteric control and will show how artificial intelligence can be effective to drive the automated de novo design towards off-patent regions of the chemical space.

Objective: This study was aimed to test the agreement between a manual and an automatic technique in measuring fetal brain volume (FBV) from three‐dimensional (3D) fetal head datasets. Methods: FBV were acquired independently by two operators from low risk singleton pregnancies at a gestational age between 19 and 34 weeks. FBV measurements were obtained using an automatic software (Smart ICV™) and manually by Virtual Organ Computer‐aided AnaLysis (VOCAL™). Intraclass correlation coefficient (ICC) were calculated to assess reliability, while bias and agreement were evaluate by examining Bland–Altman plots. The time spent in measuring volumes was calculated and values obtained compared. Results: Sixty‐three volumes were considered for the study. In all the included volumes successful volume analysis were obtained with both techniques. Smart ICV™ showed a high intra‐observer (0.996; 95% CI 0.994–0.998) and inter‐observer (ICC 0.995; 95% CI 0.991–0.997). An excellent degree of reliability was found when the two techniques were compared (ICC 0.995; 95% CI 0.987–0.998). The time required to perform FBV was significantly lower for Smart ICV™ than VOCAL™ (8.2 ± 4.5 vs. 121.3 ± 19.0 s; p < 0.0001). Conclusions: The measurement of FBV is feasible with both manual and automatic techniques. Smart ICV™ showed an excellent intra‐ and inter‐observer reliability associated with a valuable agreement with volume measurements obtained manually with VOCAL™. Volumes may be measured significantly faster with smart ICV™ than manually and this automatic software has the potential to become the preferred methods for the assessment of FBV. [ABSTRACT FROM AUTHOR]

Background Atherosclerosis is an arterial inflammatory process which causes associated tissue ischemia of different degrees. It is not yet calculated an index of plaque vulnerability as a histological marker of acute cardiac event risk at these patients. Aim of the study This retrospective study aimed to answer the question of whether the index of plaque vulnerability can appreciate the risk of atherothrombosis of the erosive plaques using histological measurements. Material and methods 30 patients were included in the study. American Heart Association (AHA) classification was used for appreciating the histological degree of ATS lesions on endarterectomy pieces. In all patients, intima-media thickness (IMT), erosion depth, and parietal thrombosis area were assessed. Results The proposed vulnerability index showed that about 50% of patients have a medium risk of plaque vulnerability and of associated acute coronary syndrome (ACS). Conclusions The index of plaque vulnerability may be used as a reference in ATS assessment by using intravascular ultrasound (IVUS) methods.

A plethora of different electronic and optoelectronic devices have been developed lately, for biosensing applications (e.g., label‐free, fast, and easier to operate) based on a detecting interface accommodating the biorecognition elements, anchored by thiolate self‐assembled monolayers (SAMs) on a gold surface. Here, a surface plasmon resonance (SPR) characterization of anti‐p24 anchored on different SAMs is performed to investigate the effect of the SAM structure on the antibodies' packing efficiency and the sensors' analytical figures of merit. Notably, the mixed SAM deposited from a solution 10:1 of 3‐mercaptopropionic acid and 11‐mercaptoundecanoic acid (11MUA) is compared to that resulting from a solution 10:1 of ad hoc synthesized N‐(2‐hydroxyethyl)‐3‐mercaptopropanamide (NMPA)/11MUA. Despite the improvement in the anti‐p24 surface coverage registered using the 11MUA/NMPA SAM, the latter produces a significant decrease in the antibodies' binding efficiency against human immunodeficiency virus p24 protein. To provide a molecular rationale behind the SPR data, density functional theory calculations are also undertaken. A comprehensive physical view of the main competing phenomena affecting the biorecognition events at a biofunctionalized gold detecting interface is represented here. [ABSTRACT FROM AUTHOR]

Multicomponent reactions (MCRs) have emerged as a powerful strategy in synthetic organic chemistry due to their widespread applications in drug discovery and development. MCRs are flexible transformations in which three or more substrates react to form structurally complex products with high atomic efficiency. They are being increasingly appreciated as a highly exploratory and evolutionary tool by the medicinal chemistry community, opening the door to more sustainable, cost-effective and rapid synthesis of biologically active molecules. In recent years, MCR-based synthetic strategies have found extensive application in the field of drug discovery, and several anticancer drugs have been synthesized through MCRs. In this review, we present an overview of representative and recent literature examples documenting different approaches and applications of MCRs in the development of new anticancer drugs. [ABSTRACT FROM AUTHOR]

The globalization process, even more obvious after the end of Cold War, offers the conditions to define human security, focusing on the normative priority of the impact of policies on the individual. The international space, transformed under the pressure of globalization, becomes relevant in the extent that an alternative discourse that encompasses all these transformations comes out. This new narrative transforms the individual in the referent object of security. The study stresses the main theoretical transformations appeared within the post-positivist framework of analysis in order to identify the central components of the new understanding of security – human security.

Trauma is the "wound of the soul", a destabilizing experience which disrupts the mind of those who experience it. Unprocessed traumatic memories are often fragmented, disorganized, and can be easily activated in the form of intrusive thoughts, hence traumatized individuals experience various forms of psychological distress. The expressive writing project has proved to be a valid tool as a support in stressful situations, highlighting a generalized positive effect on health. Expressive writing, by translating traumatic thoughts and feelings into language, helps traumatized individuals to make sense of upsetting events, to manage negative emotions, and improve their connections with the social world. The goal of this study was to verify the effect of an expressive writing protocol in a non-clinical context, represented by a sample of young adult university students and, particularly aiming at studying the effects of expressive writing in mitigating potential psychological problems related to stressful and/or traumatic events. Results have confirmed a fair efficacy of the expressive writing protocol, especially in supporting the enhancement of one's coping and adaptation resources with respect to the outcomes of stressful events experienced. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinases (MMP) are well-known biological targets implicated in tumour progression, homeostatic regulation, innate immunity, impaired delivery of pro-apoptotic ligands, and the release and cleavage of cell-surface receptors. Hence, the development of potent and selective inhibitors targeting these enzymes continues to be eagerly sought. In this paper, a number of alloxan-based compounds, initially conceived to bias other therapeutically relevant enzymes, were rationally modified and successfully repurposed to inhibit MMP-2 (also named gelatinase A) in the nanomolar range. Importantly, the alloxan core makes its debut as zinc binding group since it ensures a stable tetrahedral coordination of the catalytic zinc ion in concert with the three histidines of the HExxHxxGxxH metzincin signature motif, further stabilized by a hydrogen bond with the glutamate residue belonging to the same motif. The molecular decoration of the alloxan core with a biphenyl privileged structure allowed to sample the deep S(1)' specificity pocket of MMP-2 and to relate the high affinity towards this enzyme with the chance of forming a hydrogen bond network with the backbone of Leu116 and Asn147 and the side chains of Tyr144, Thr145 and Arg149 at the bottom of the pocket. The effect of even slight structural changes in determining the interaction at the S(1)' subsite of MMP-2 as well as the nature and strength of the binding is elucidated via molecular dynamics simulations and free energy calculations. Among the herein presented compounds, the highest affinity (pIC(50) = 7.06) is found for BAM, a compound exhibiting also selectivity (>20) towards MMP-2, as compared to MMP-9, the other member of the gelatinases.

The United States’ grand strategy has consistently been marked by a distinct tendency toward nuclear hypertrophy. Especially the inherent difficulties in extending deterrence to its allies and friends, compounded by the geopolitical characteristics of the US as an unassailable ‘insular’ fortress off Eurasia, have generated, rather paradoxically, a strong incentive for Washington to pursue a wide margin of nuclear superiority, if not nuclear primacy. This has implied, in turn, the deployment of redundant arsenals, robust counterforce capabilities and even a ballistic missile defence. Significantly, not even the Obama administration, though solemnly committed to nuclear disarmament, abstained from embracing a very ambitious modernisation program of American nuclear forces. [ABSTRACT FROM AUTHOR]

Many naturally occurring substances, traditionally used in popular medicines around the world, contain the coumarin moiety. Coumarin represents a privileged scaffold for medicinal chemists, because of its peculiar physicochemical features, and the versatile and easy synthetic transformation into a large variety of functionalized coumarins. As a consequence, a huge number of coumarin derivatives have been designed, synthesized, and tested to address many pharmacological targets in a selective way, e.g., selective enzyme inhibitors, and more recently, a number of selected targets (multitarget ligands) involved in multifactorial diseases, such as Alzheimer’s and Parkinson’s diseases. In this review an overview of the most recent synthetic pathways leading to mono- and polyfunctionalized coumarins will be presented, along with the main biological pathways of their biosynthesis and metabolic transformations. The many existing and recent reviews in the field prompted us to make some drastic selections, and therefore, the review is focused on monoamine oxidase, cholinesterase, and aromatase inhibitors, and on multitarget coumarins acting on selected targets of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Purpose. The main aim of the present study is to present a case of mandibular transposition between lateral incisor and canine in a paediatric patient. Materials and methods. A fixed multibracket orthodontic treatment was performed by means of a modified welded arch as to correct the transposition and obtaining a class I functional and symmetrical occlusion, also thanks to the early diagnosis of the eruption anomaly. Results. Our case report shows that a satisfactory treatment of mandibular transpositions is obtained when detected at an early stage of the tooth development. Conclusions. The main treatment options to be taken into consideration in case of a mandibular transposition are two: correcting the transposition or aligning it leaving the dental elements in their transposed order; in both cases, the followups show a stable condition, maintained without relapses. Several factors, such as age of the patient, occlusion, aesthetics, patient's collaboration, periodontal support and duration of treatment have to be considered as to prevent potential damage to dental elements and support appliances. The choice between the two treatment approaches for mandibular lateral incisor/canine transpositions mainly depends on the time the anomaly is detected. [ABSTRACT FROM AUTHOR]

Purpose. Fixed retainers are used to stabilize dental elements after orthodontic treatment. Being it a permanent treatment, it is necessary to instruct patients about a constant and continuous monitoring of their periodontal conditions and a correct oral hygiene. The aim of this study was to highlight the possible adverse effects of bonded retainers on parameters correlated to the health conditions of periodontal tissues. Materials and methods. We selected 16 patients, under treatment in the Orthodontics Department of University of Bari Dental School, who had undergone a lingual retainer insertion at the end of the orthodontic treatment. The patients were then divided into two groups (Control Group and Study Group) and monitored for 3 and 36 months, respectively. The following indexes were taken into consideration: gingival index (GI), plaque index (PI) and the presence of calculus (Calculus Index, CI), the probing depth and the presence of gingival recession on the six inferior frontal dental elements. Results. After the observation was carried out, any of the patients showed periodontal sockets and gingival recession. In the Study Group, only 1 patient had a PI score=3, the 7 left had scores between 0.66 and 2.83. In the Control Group, one patient had score=0, the other ones showed values between 0.5 and 1.66. The mean GI in the Study Group peaked at a score of 2.83, the minimum was 0.66; whereas in the Control Group the maximum value was 2 and the minimum 0.66. The CI in the Group Study was between 1 and 2. In the Control Group it was absent in only 1 patient, whereas in the remaining 7, it had a value between 0.3 and 1. The clinical data were studied by means of the Wilcoxon test. We found a statistically significant difference for what concerns the Plaque Indexes (PI) (P>0.05) and Calculus Indexes (CI) (P>0.1) in both groups, with higher scores in the Study Group, having retainers for 36 months. Any statistically significant difference was calculated for the GI. Conclusions. We can therefore conclude that patients with lingual retainers need periodontal hygiene and treatment as to prevent, in the course of time, periodontal damages non-detectable in short-term. [ABSTRACT FROM AUTHOR]

In a recent investigation carried out on a panel of trimethoxybenzanilides, we showed that the formation of an intramolecular hydrogen bond is a key element for tuning P-gp inhibitory activity. In this study, we designed new structurally simplified trimethoxy benzamides ( 5- 17, Table [ABSTRACT FROM AUTHOR]

Purpose. The aim of this retrospective case-control study was to identify, in a group of growing children and adolescents affected by malocclusion, specific dento-skeletal characteristics which could be correlated to the onset, in the above-mentioned subjects, of craniomandibular disorders (CMD). Materials and methods. Among the patients treated at the Paedodontics and Orthodontics department of Bari Dental School, we recruited a group of patients with malocclusion and symptoms of temporomandibular disorders, as an experimental group. We considered as controls those patients who, match-paired to their skeletal class depending on the ANB angle, did not show any CMD sign or symptom. Results. Of the 128 examined patients, 15 showed signs and/or symptoms of CMD (11.7%). When compared to 15 patients non-affected by CMD, we could not detect statistically significant differences in both skeletal and occlusal characteristics. It is still interesting to notice how in CMD patients, characteristics of skeletal hyperdivergence are often to be found. Conclusions. The present study seems to confirm that in growing children and adolescents, the presence of signs and/or symptoms of CMD is not associable to a specific vertical skeletal growth pattern or to other specific occlusal characteristics. [ABSTRACT FROM AUTHOR]

Computational methods have advanced toxicology towards the development of target-specific models based on a clear cause-effect rationale. However, the predictive potential of these models presents strengths and weaknesses. On the good side, in silico models are valuable cheap alternatives to in vitro and in vivo experiments. On the other, the unconscious use of in silico methods can mislead end-users with elusive results. The focus of this review is on the basic scientific and regulatory recommendations in the derivation and application of computational models. Attention is paid to examine the interplay between computational toxicology and drug discovery and development. Avoiding the easy temptation of an overoptimistic future, we report our view on what can, or cannot, realistically be done. Indeed, studies of safety/toxicity represent a key element of chemical prioritization programs carried out by chemical industries, and primarily by pharmaceutical companies. [ABSTRACT FROM AUTHOR]