Correlation between parodontal indexes and orthodontic retainers: prospective study in a group of 16 patients

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

Early mandibular canine-lateral incisor transposition: case report

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

Bcr-Abl Allosteric Inhibitors: Where We Are and Where We Are Going to

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

Bcr-abl tyrosine kinase inhibitors in the treatment of pediatric cml

The therapeutic approach to Chronic Myeloid Leukemia (CML) has changed since the advent of the tyrosine kinase inhibitor (TKI) imatinib, which was then followed by the second generation TKIs dasatinib, nilotinib, and, finally, by ponatinib, a third-generation drug. At present, these therapeutic options represent the first-line treatment for adults. Based on clinical experience, imatinb, dasatinib, and nilotinib have been approved for children even though the studies that were concerned with efficacy and safety toward pediatric patients are still awaiting more specific and high-quality data. In this scenario, it is of utmost importance to prospectively validate data extrapolated from adult studies to set a standard therapeutic management for pediatric CML by employing appropriate formulations on the basis of pediatric clinical trials, which allow a careful monitoring of TKI-induced adverse effects especially in growing children exposed to long-term therapy

Quality of life in fibromyalgia patients with craniomandibular disorders

Fibromyalgia (FM) is a rheumatic disease which affects fibrous tissues and muscles; it is characterized by chronic pain and it is often associated with craniomandibular disorders (CMD). 31 patients were assessed from March 2012 to October 2012 through the administration of specific questionnaires and following neurologic and gnatologic assessment. A relevant corre-lation between FM and CMD emerges from the present study, as 80.6% of our patients report CMD symptoms with high prevalence of myofascial pain (84%). Multivariate regression analysis revealed that the patients in the present study did not differ in score of quality of life questionnaires from patients with fibromyalgia. The neuropathic pain diagnostic question-naire (DN4) scores were positively affected by belonging to group II of Research Diagnostic Criteria of Temporomandibular Disorders (RDC/ TDM) classification, suggesting the possibility of a neuropathic component in chronic pain in this CMD group, as already speculated in our study on the correlation between burning mouth syndrome and CMD and by other au-thors in studies on chronic low back pain. However, further clinic and instrumental studies are needed in order to test this as-sumption

Enhancing the Sensitivity of Biotinylated Surfaces by Tailoring the Design of the Mixed Self-Assembled Monolayer Synthesis

Thiolated self-assembled monolayers (SAMs) are typically used to anchor on a gold surface biomolecules serving as recognition elements for biosensor applications. Here, the design and synthesis of N-(2-hydroxyethyl)-3-mercaptopropanamide (NMPA) in biotinylated mixed SAMs is proposed as an alternative strategy with respect to on-site multistep functionalization of SAMs prepared from solutions of commercially available thiols. In this study, the mixed SAM deposited from a 10:1 solution of 3-mercaptopropionic acid (3MPA) and 11-mercaptoundecanoic acid (11MUA) is compared to that resulting from a 10:1 solution of NMPA:11MUA. To this end, surface plasmon resonance (SPR) and attenuated total reflectance infrared (ATR-IR) experiments have been carried out on both mixed SAMs after biotinylation. The study demonstrated how the fine tuning of the SAM features impacts directly on both the biofunctionalization steps, i.e., the biotin anchoring, and the biorecognition properties evaluated upon exposure to streptavidin analyte. Higher affinity for the target analyte with reduced nonspecific binding and lower detection limit has been demonstrated when NMPA is chosen as the more abundant starting thiol. Molecular dynamics simulations complemented the experimental findings providing a molecular rationale behind the performance of the biotinylated mixed SAMs. The present study confirms the importance of the functionalization design for the development of a highly performing biosensor

Hydroxy-propil-β-cyclodextrin inclusion complexes of two biphenylnicotinamide derivatives: Formulation and anti-proliferative activity evaluation in pancreatic cancer cell models

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies, with poor outcomes largely due to its unique microenvironment, which is responsible for the low response to drugs and drug-resistance phenomena. This clinical need led us to explore new therapeutic approaches for systemic PDAC treatment by the utilization of two newly synthesized biphenylnicotinamide derivatives, PTA73 and PTA34, with remarkable antitumor activity in an in vitro PDAC model. Given their poor water solubility, inclusion complexes of PTA34 and PTA73 in Hydroxy-Propil-β-Cyclodextrin (HP-β-CD) were prepared in solution and at the solid state. Complexation studies demonstrated that HP-β-CD is able to form stable host–guest inclusion complexes with PTA34 and PTA73, characterized by a 1:1 apparent formation constant of 503.9 M−1 and 369.2 M−1, respectively (also demonstrated by the Job plot), and by an increase in aqueous solubility of about 150 times (from 1.95 µg/mL to 292.5 µg/mL) and 106 times (from 7.16 µg/mL to 762.5 µg/mL), in the presence of 45% w/v of HP-β-CD, respectively. In vitro studies confirmed the high antitumor activity of the complexed PTA34 and PTA73 towards PDAC cells, the strong G2/M phase arrest followed by induction of apoptosis, and thus their eligibility for PDAC therapy

Particle Energies and Filling Fractions of Radio Bubbles in Cluster Cores

Using Chandra images of cluster cores with clear radio bubbles, we have determined k, which is the ratio of the total particle energy to that of the electrons radiating between 10 MHz and 10 GHz. Radiative and dynamical constraints on the bubbles indicate that the ratio of the energy factor, k, to the volume filling factor, f, lies within the range 1 < k/f < 1000. Assuming pressure equilibrium between the radio-emitting plasma and the surrounding X-ray gas, none of the lobes have equipartition between relativistic particles and magnetic field. There is no evidence for any dependence of the upper limit of the k/f ratio on any physical parameter of the cluster or the radio source. The distribution of the upper limit on k/f appears to be bimodal, the value for some clusters being ~3 and for the others ~300. We show that this is may due to the composition of the jet which forms the bubbles, the variation in the volume filling fraction or variation in the amount of re-acceleration occurring in the bubble.Comment: 12 pages, 9 figures; accepted for publication in MNRA

Insights into the Complex Formed by Matrix Metalloproteinase-2 and Alloxan Inhibitors: Molecular Dynamics Simulations and Free Energy Calculations

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 S1′ 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 S1′ 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 (pIC50 = 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