Periodontal evaluation of palatally impacted maxillary canines treated by closed approach with ultrasonic surgery and orthodontic treatment: a retrospective pilot study

Aim of this study is the evaluation of the periodontal status of impacted canines treated by closed approach with ultrasonic surgery and orthodontic treatment compared with contralateral spontaneously erupted teeth. The periodontal conditions of the teeth adjacent to the canines (lateral incisors and first premolar) were also considered. 17 patients (9 females and 8 males; mean age: 15.2 years) with unilateral palatal impaction of maxillary canine were selected. All patients were treated by closed-flap surgery with ultrasonic instruments. Periodontal status was evaluated by assessing probing depth (PD), gingival recession and width of keratinized tissue (KT) 4.6 months after the end of the orthodontic treatment, on average. Test group was composed by impacted elements and adjacent teeth and control group by contralateral spontaneously erupted canines and adjacent teeth. Student's t-test was used to compare test and control group values of PD and width of KT. Significance threshold for Student's t-test was set at p < 0.05. The average probing depth values show no significant clinical differences between the test and control groups. Probing depths recorded at the mesiovestibular and distopalatal sides of the impacted canine were statistically significant compared to the control elements (p < 0.05). No gingival recession was detected on the treated canines. The measurement of KT did not differ significantly between the test and the control groups. In conclusion, the ultrasonic surgery for disinclusion associated with a closed approach and orthodontic traction allows the alignment of an impacted palatal canine without damaging the periodontium

Samarium-153-EDTMP (Quadramet®) With or Without Vaccine in Metastatic Castration-Resistant Prostate Cancer: A Randomized Phase 2 Trial

PSA-TRICOM is a therapeutic vaccine in late stage clinical testing in metastatic castration-resistant prostate cancer (mCRPC). Samarium-153-ethylene diamine tetramethylene phosphonate (Sm-153-EDTMP; Quadramet®), a radiopharmaceutical, binds osteoblastic bone lesions and emits beta particles causing local tumor cell destruction. Preclinically, Sm-153-EDTMP alters tumor cell phenotype facilitating immune-mediated killing. This phase 2 multi-center trial randomized patients to Sm-153-EDTMP alone or with PSA-TRICOM vaccine. Eligibility required mCRPC, bone metastases, prior docetaxel and no visceral disease. The primary endpoint was the proportion of patients without radiographic disease progression at 4 months. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and immune responses. Forty-four patients enrolled. Eighteen and 21 patients were evaluable for the primary endpoint in Sm-153-EDTMP alone and combination arms, respectively. There was no statistical difference in the primary endpoint, with two of 18 (11.1%) and five of 21 (23.8%) in Sm-153-EDTMP alone and combination arms, respectively, having stable disease at approximately the 4-month evaluation time point (P = 0.27). Median PFS was 1.7 vs. 3.7 months in the Sm-153-EDTMP alone and combination arms (P = 0.041, HR = 0.51, P = 0.046). No patient in the Sm-153-EDTMP alone arm achieved prostate-specific antigen (PSA) decline \u3e 30% compared with four patients (of 21) in the combination arm, including three with PSA decline \u3e 50%. Toxicities were similar between arms and related to number of Sm-153-EDTMP doses administered. These results provide the rationale for clinical evaluation of new radiopharmaceuticals, such as Ra-223, in combination with PSA-TRICOM

Adaptive remodeling of the bacterial proteome by specific ribosomal modification regulates Pseudomonas infection and niche colonisation

Post-transcriptional control of protein abundance is a highly important, underexplored regulatory process by which organisms respond to their environments. Here we describe an important and previously unidentified regulatory pathway involving the ribosomal modification protein RimK, its regulator proteins RimA and RimB, and the widespread bacterial second messenger cyclic-di-GMP (cdG). Disruption of rimK affects motility and surface attachment in pathogenic and commensal Pseudomonas species, with rimK deletion significantly compromising rhizosphere colonisation by the commensal soil bacterium P. fluorescens, and plant infection by the pathogens P. syringae and P. aeruginosa. RimK functions as an ATP-dependent glutamyl ligase, adding glutamate residues to the C-terminus of ribosomal protein RpsF and inducing specific effects on both ribosome protein complement and function. Deletion of rimK in P. fluorescens leads to markedly reduced levels of multiple ribosomal proteins, and also of the key translational regulator Hfq. In turn, reduced Hfq levels induce specific downstream proteomic changes, with significant increases in multiple ABC transporters, stress response proteins and non-ribosomal peptide synthetases seen for both ΔrimK and Δhfq mutants. The activity of RimK is itself controlled by interactions with RimA, RimB and cdG. We propose that control of RimK activity represents a novel regulatory mechanism that dynamically influences interactions between bacteria and their hosts; translating environmental pressures into dynamic ribosomal changes, and consequently to an adaptive remodeling of the bacterial proteome

Asymmetry of Chromosome Replichores Renders the DNA Translocase Activity of FtsK Essential for Cell Division and Cell Shape Maintenance in Escherichia coli

Bacterial chromosomes are organised as two replichores of opposite polarity that coincide with the replication arms from the ori to the ter region. Here, we investigated the effects of asymmetry in replichore organisation in Escherichia coli. We show that large chromosome inversions from the terminal junction of the replichores disturb the ongoing post-replicative events, resulting in inhibition of both cell division and cell elongation. This is accompanied by alterations of the segregation pattern of loci located at the inversion endpoints, particularly of the new replichore junction. None of these defects is suppressed by restoration of termination of replication opposite oriC, indicating that they are more likely due to the asymmetry of replichore polarity than to asymmetric replication. Strikingly, DNA translocation by FtsK, which processes the terminal junction of the replichores during cell division, becomes essential in inversion-carrying strains. Inactivation of the FtsK translocation activity leads to aberrant cell morphology, strongly suggesting that it controls membrane synthesis at the division septum. Our results reveal that FtsK mediates a reciprocal control between processing of the replichore polarity junction and cell division

One ligand, two regulators and three binding sites: How KDPG controls primary carbon metabolism in Pseudomonas

Effective regulation of primary carbon metabolism is critically important for bacteria to successfully adapt to different environments. We have identified an uncharacterised transcriptional regulator; RccR, that controls this process in response to carbon source availability. Disruption of rccR in the plant-associated microbe Pseudomonas fluorescens inhibits growth in defined media, and compromises its ability to colonise the wheat rhizosphere. Structurally, RccR is almost identical to the Entner-Doudoroff (ED) pathway regulator HexR, and both proteins are controlled by the same ED-intermediate; 2-keto-3-deoxy-6-phosphogluconate (KDPG). Despite these similarities, HexR and RccR control entirely different aspects of primary metabolism, with RccR regulating pyruvate metabolism (aceEF), the glyoxylate shunt (aceA, glcB, pntAA) and gluconeogenesis (pckA, gap). RccR displays complex and unusual regulatory behaviour; switching repression between the pyruvate metabolism and glyoxylate shunt/gluconeogenesis loci depending on the available carbon source. This regulatory complexity is enabled by two distinct pseudo-palindromic binding sites, differing only in the length of their linker regions, with KDPG binding increasing affinity for the 28 bp aceA binding site but decreasing affinity for the 15 bp aceE site. Thus, RccR is able to simultaneously suppress and activate gene expression in response to carbon source availability. Together, the RccR and HexR regulators enable the rapid coordination of multiple aspects of primary carbon metabolism, in response to levels of a single key intermediate

A Defined Terminal Region of the E. coli Chromosome Shows Late Segregation and High FtsK Activity

Background: The FtsK DNA-translocase controls the last steps of chromosome segregation in E. coli. It translocates sister chromosomes using the KOPS DNA motifs to orient its activity, and controls the resolution of dimeric forms of sister chromosomes by XerCD-mediated recombination at the dif site and their decatenation by TopoIV. Methodology: We have used XerCD/dif recombination as a genetic trap to probe the interaction of FtsK with loci located in different regions of the chromosome. This assay revealed that the activity of FtsK is restricted to a,400 kb terminal region of the chromosome around the natural position of the dif site. Preferential interaction with this region required the tethering of FtsK to the division septum via its N-terminal domain as well as its translocation activity. However, the KOPSrecognition activity of FtsK was not required. Displacement of replication termination outside the FtsK high activity region had no effect on FtsK activity and deletion of a part of this region was not compensated by its extension to neighbouring regions. By observing the fate of fluorescent-tagged loci of the ter region, we found that segregation of the FtsK high activity region is delayed compared to that of its adjacent regions. Significance: Our results show that a restricted terminal region of the chromosome is specifically dedicated to the last step

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Severe side effects on all the anterior lower teeth of a bonded retainer: a clinical case : Gravi effetti collaterali sui denti anteriori inferiori di un retainer fisso: un caso clinico

OBJECTIVES This case report presents the possible and unexpected clinical severe complications of a bonded mandibular lingual retainer and an achievable therapeutic solution. MATERIALS AND METHODS 18-year-old boy comes to our observation; he reports a previous orthodontic treatment and not to carry out regular check-ups. Intraoral examination shows: class I malocclusion, flexible and intact spiral wire retainer bonded on the lingual surface of the lower front teeth, inferior midline deviated to the left side, lower incisors proclined and inclined to the left side, both mandibular canines and incisors wrongly torqued. Orthopantomography (OPT) shows a moderate root resorption of the lower front teeth with a very important divergence of the roots of left canine and lower incisors. Cone beam computed tomography shows the root of the right canine almost completely out of the bone on its lingual side and the root of the left canine out of the bone on its buccal side. We start a new orthodontic treatment to realign the teeth and to correct the transverse malocclusion. At the end of treatment, the smile of the patient was normalized with a good balance of the occlusal plane. RESULTS AND CONCLUSIONS At the end of treatment, the smile of the patient was normalized with a good balance of the occlusal plane. A good and stable molar and canine class I occlusion was achieved with correct overjet, overbite and transversal relationships. Orthopantomography showed the correction of the inclination of the lower front teeth with a moderate apical root resorption of the four lower incisors that was present also in the initial OPT. CBCT showed the correction of the axial inclination of the right canine with a good lingual bone thickness. On the left canine the good axial inclination achieved was evident; lingual bone thickness was ideal but on the buccal side there was no adequate amount of cortical bone. Although fixed retainers are generally adequate in preventing relapse, sometimes their inadvertent activity causes distortion of the dental arch. If not periodically checked by clinicians, such reported in this case report, fixed retainers may cause devastating complications and orthodontic retreatment could be the solution in restoring the physiological arch shape. CLINICAL SIGNIFICANCE Fixed retainers can cause major complications for the dental elements affected by the retainer in terms of unwanted inclinations and movements with consequent damage to the periodontal structures. Regular monitoring by clinicians is therefore highly recommended. Orthodontic retreatment may prove to be the ideal solution to restore the physiological shape of the arch and the correct inclination of the roots of the affected teeth. OBJECTIVES This case report presents the pos sible and unexpected clinical se vere complications of a bonded mandibular lingual retainer and an achievable therapeutic solution. MATERIALS AND METHODS 18-year-old boy comes to our ob servation; he reports a previous orthodontic treatment and not to carry out regular check-ups. In traoral examination shows: class I malocclusion, flexible and intact spiral wire retainer bonded on the lingual surface of the lower front teeth, inferior midline deviated to the left side, lower incisors pro clined and inclined to the left side, both mandibular canines and in cisors wrongly torqued. Orthop antomography (OPT) shows a moderate root resorption of the lower front teeth with a very important divergence of the roots of left canine and lower incisorsCone beam computed tomogra phy shows the root of the right canine almost completely out of the bone on its lingual side and the root of the left canine out of the bone on its buccal side. We start a new orthodontic treat ment to realign the teeth and to correct the transverse malocclu sion. At the end of treatment, the smile of the patient was normal ized with a good balance of the occlusal plane. RESULTS AND CONCLUSIONS At the end of treatment, the smile of the patient was normal ized with a good balance of the occlusal plane. A good and sta ble molar and canine class I oc clusion was achieved with cor rect overjet, overbite and transversal relationships. Orthopan tomography showed the correc tion of the inclination of the lower front teeth with a moderate apical root resorption of the four lower incisors that was present also in the initial OPT. CBCT showed the correction of the axial inclination of the right canine with a good lin gual bone thickness. On the left canine the good axial inclination achieved was evident; lingual bone thickness was ideal but on the buccal side there was no ade quate amount of cortical bone. Although fixed retainers are gener ally adequate in preventing relapse, sometimes their inadvertent activi ty causes distortion of the dental arch. If not periodically checked by clinicians, such reported in this case report, fixed retainers may cause devastating complications and orthodontic retreatment could be the solution in restoring the physiological arch shape. CLINICAL SIGNIFICANCE Fixed retainers can cause major complications for the dental ele ments affected by the retainer in terms of unwanted inclinations and movements with consequent dam age to the periodontal structures. Regular monitoring by clinicians is therefore highly recommended. Orthodontic retreatment may prove to be the ideal solution to restore the physiological shape of the arch and the correct inclination of the roots of the affected teeth

Problemi di chirurgia oculare nella sindrome di Lowe.

Si descrive un caso di Sindrome di Lowe con presenza di cataratta e dermoide corneale associato. Si mettono in evidenza le problematiche di chirurgia oculare