A Randomized Double-blind Clinical Trial of Dentin Surface Treatments for Composite Restorations in Noncarious Cervical Lesions: A 36-month Evaluation.

OBJECTIVE:: This randomized, double-blind clinical trial aimed to evaluate the influence of different dentin surface treatments in noncarious cervical lesions (NCCLs). METHODS AND MATERIALS:: Twenty-nine patients participated in this study. One hundred sixty-five NCCLs were selected and randomly assigned to three groups: G0 (control group) with phosphoric acid etching for 15 seconds; G1: phosphoric acid etching for 30 seconds; and G2: ultrasound probe applied for 30 seconds on the dentin surface. Class V composite resin restorations were performed (Z350, 3M ESPE, St Paul, MN, USA). The restorations were evaluated at baseline and at six, 12, 24, and 36 months according to the World Dental Federation criteria. Survival curves were obtained using the Kaplan-Meier method and the log-rank test. Comparisons between groups and times were performed using the McNemar and Chi-square tests (α =0.05). RESULTS:: The presence of failures due to retention was statistically different among the groups ( p=0.012), and G0 and G2 showed better clinical performance than did G1. Sensitivity decreased over time in all groups. Marginal discoloration, postoperative sensitivity, and marginal adaptation were not different among the groups ( p>0.05). CONCLUSIONS:: The studied dentin surface treatments showed similar clinical performance to the conventional technique at 36 months in terms of marginal discoloration, marginal adaptation, and postoperative sensitivity. In contrast, increased acid-etching time resulted in a higher risk of failure due to retention over time in composite Class V restorations.

Validation of the Italian version of the Non-Communicating Children's Pain Checklist-Postoperative Version.

BACKGROUND: This study evaluated the validity and reliability of the Italian version of the Non-Communicating Children's Pain Checklist-Postoperative version (I-NCCPC-PV). METHODS: The original NCCPC-PV version was translated into Italian following the guidelines for "the translation, adaptation, and validation of instruments or scales for cross-cultural healthcare research". We tested the Italian NCCPC-PV version (I-NCCPC-PV) in 40 children (3-18 years of age) with severe to profound Intellectual Disability and no verbal communication. Each child's behavior was observed by a parent or caregiver and by an external observer in a quiet situation and a painful one. They independently assessed the child's level of pain using the translated Italian version of the NCCPCPV (I-NCCPC-PV). RESULTS: The results from 80 assessments showed that children's behavioral signs differed significantly between painful and calm situations (p < 0.001). The inter-rater reliability was poor in a quiet condition (ICC 0.62) and fair in a painful situation (ICC 0.77). The inter-rater agreement was good in both calm and painful conditions (72.50% and 77.50% respectively). CONCLUSION: The Italian version of the NCCPC-PV (I-NCCPC-PV) can be used for pain assessment in children with Intellectual Disability who lack verbal communication.

Relationship between maternal transfer of immunity and mother fecundity in an insect.

Trans-generational immune priming (TGIP) corresponds to the plastic adjustment of offspring immunity as a result of maternal immune experience. TGIP is expected to improve mother's fitness by improving offspring individual performance in an environment where parasitism becomes more prevalent. However, it was recently demonstrated that maternal transfer of immunity to the offspring is costly for immune-challenged female insects. Thus, these females might not provide immune protection to all their offspring because of the inherent cost of other fitness-related traits. Females are therefore expected to adjust their investment to individual offspring immune protection in ways that maximize their fitness. In this study, we investigated how bacterially immune-challenged females of the mealworm beetle, Tenebrio molitor, provision their eggs with immune protection according to egg production. We found that immune-challenged females provide a variable number of their eggs with internal antibacterial activity along egg-laying bouts. Furthermore, within the first immune-protected egg-laying bout (2-4 days after the maternal immune challenge), the number of eggs protected was strongly dependent on the number of eggs produced. Immune-challenged females might therefore adjust their investment into TGIP and fecundity according of their individual perception of the risk of dying from the infection and the expected parasitic conditions for the offspring.

Sealing ability, water sorption, solubility and toothbrushing abrasion resistance of temporary filling materials.

AIM: To evaluate marginal seal, water sorption, solubility and loss of mass after brushing of several temporary filling materials. METHODOLOGY: For marginal seal, Class I cavities, including endodontic access preparations, were made in human molar teeth and restored using one or other of several temporary filling materials (n = 10): zinc oxide/calcium sulphate-based cement (Cavit, 3M,ESPE, St. Paul, MN, USA), zinc oxide/eugenol cement (IRM, Dentsply Caulk, Milford, DE, USA), glass ionomer cement (Vidrion R, SSWhite, Rio de Janeiro, RJ, Brazil) or a dimethacrylate-based filling (Bioplic, Biodinâmica, Londrina, PR, Brazil). Dye penetration was assessed after thermocycling and immersion in 0.5% basic fuchsine solution. For water sorption, solubility and loss of mass analyses, disc-shaped specimens were made. Water sorption and solubility were evaluated by mass alteration after storage in distilled water for 7 days (n = 7). Loss of mass was calculated based on the difference of mass after abrasion with a toothbrush (n = 5), and surfaces were analysed by SEM. Data of water sorption, solubility and loss of mass were submitted to anova and Tukey's test, and marginal sealing data to Kruskal-Wallis test (P < 0.05). RESULTS: Statistically significant differences were observed for marginal sealing (P < 0.0001), water sorption (P < 0.01), solubility (P < 0.01) and loss of mass (P < 0.05). Bioplic had the best marginal seal. Cavit had the greatest water sorption and solubility. Vidrion R and Bioplic had the lowest solubility. Loss of mass after brushing was higher for Cavit, followed by Bioplic, IRM and Vidrion R. Cavit and Vidrion R were worn aggressively by brushing. CONCLUSIONS: The resin-based temporary filling Bioplic produced the best marginal seal, and was associated with the lowest water sorption, solubility and loss of mass.

Nanofiller loading level: Influence on selected properties of an adhesive resin.

OBJECTIVES: To evaluate the effect of the filler content in the cohesive strength (sigma), Weibull modulus (m) and degree of conversion (DC) of an experimental adhesive system. METHODS: A HEMA/Bis-GMA/TEGDMA-based adhesive was formulated and filled with silica nanofillers in the following weight percentages (wt%): R0=0%; R1=1%; R3=3%; R5=5% and R10=10%. The adhesive of Adper Scotchbond Multi-Purpose (SBMP) system was used as a commercial reference. Twenty dumbbell-shaped specimens with cross-sectional area of 0.5mm(2) were made per group and tensile tested with a crosshead speed of 0.5mm/min until fracture. The cohesive strength was calculated in MPa. DC was obtained through FTIR after light curing for 25s. Data were submitted to one-way ANOVA and Tukey's test (alpha=0.05) and to Weibull analysis. RESULTS: Mean sigma results were: R0=65.4+/-8.4; R1=73.2+/-8.8; R3=72.0+/-8.4; R5=73.1+/-9.7; R10=85.5+/-13.1 and SBMP=79.0+/-11.0MPa. R10 presented the highest sigma, while R0 showed the lowest. R5 and SBMP did not differ significantly (p<0.05). Weibull analysis revealed no significant difference in structural reliability between groups. The experimental adhesives presented similar results of DC, which, in turn, were significantly higher than the SBMP. CONCLUSIONS: The addition of 10% filler in weight improves the cohesive strength of the adhesive, not interfering in the structural reliability or the degree of conversion.

Imatinib ameliorates renal disease and survival in murine lupus autoimmune disease.

Platelet-derived growth factor (PDGF) has been proved to play an important role in progressive glomerular disease of systemic lupus. The present study investigated the tyrosine kinase inhibitor of PDGF receptor, imatinib, as a novel therapeutic approach for the cure of lupus nephritis in New Zealand Black/White (NZB/W)F1 hybrid mice with established disease. Two groups of NZB/W mice (N=30 each group), starting at 5 months of age, were given by gavage vehicle or imatinib (50 mg/kg b.i.d). Fifteen mice for each group were used for the survival study. The remaining were killed at 8 months. Imatinib significantly (P=0.0022) ameliorated animal survival with respect to vehicle. The drug significantly delayed the onset of proteinuria (% proteinuric mice, 7 and 8 months: 33 and 47 vs vehicle, 80 and 87, P<0.05) and limited the impairment of renal function. Imatinib protected the kidney against glomerular hypercellularity and deposits, tubulointerstitial damage, and accumulation of F4/80-positive mononuclear cells and alpha-smooth actin-positive myofibroblasts. The abnormal transforming growth factor-beta mRNA expression in kidneys of lupus mice was reduced by imatinib. In conclusion, findings of amelioration of animal survival and renal manifestations in NZB/W lupus mice with established disease by imatinib suggests the possibility to explore whether imatinib may function as steroid-sparing drug in human lupus nephritis.

Induction of apoptosis and stress response in ovarian carcinoma cell lines treated with ST1926, an atypical retinoid.

To understand the molecular mechanisms mediating apoptosis induction by a novel atypical retinoid, ST1926, the cellular response to drug treatment was investigated in IGROV-1 ovarian carcinoma cells carrying wild-type p53 and a cisplatin-resistant p53 mutant subline (IGROV-1/Pt1). Despite a similar extent of drug-induced DNA strand breaks, the level of apoptosis was substantially higher in p53 wild-type cells. p53 activation and early upregulation of p53-target genes were consistent with p53-dependent apoptosis in IGROV-1 cells. Stress-activated protein kinases were activated in both cell lines in response to ST1926. This event and activation of AP-1 were more pronounced in IGROV-1/Pt1 cells, in which the modulation of DNA repair-associated genes suggests an increased ability to repair DNA damage. Inhibition of JNK or p38 stimulated ST1926-induced apoptosis only in IGROV-1 cells, whereas inhibition of ERKs enhanced apoptosis in both the cell lines. Such a pattern of cellular response and modulation of genes implicated in DNA damage response supports that the genotoxic stress is a critical event mediating drug-induced apoptosis. The results are consistent with apoptosis induction through p53-dependent and -independent pathways, regulated by MAP kinases, which likely play a protective role.

Inactivation of Ret/Ptc1 oncoprotein and inhibition of papillary thyroid carcinoma cell proliferation by indolinone RPI-1.

Genetic alterations causing oncogenic activation of the RET gene are recognized as pathogenic events in papillary and medullary thyroid carcinomas. Inhibition of Ret oncoprotein functions could thereby represent a specific therapeutic approach. We previously described the inhibitory activity of the 2-indolinone derivative RPI-1 (formerly Cpdl) on the tyrosine kinase activity and transforming ability of the products of the RET/PTC1 oncogene exogenously expressed in murine cells. In the present study, we investigated the effects of RPI-1 in the human papillary thyroid carcinoma cell line TPC-1 spontaneously harboring the RET/PTC1 rearrangement. Treatment with RPI-1 inhibited cell proliferation and induced accumulation of cells at the G2 cell cycle phase. In treated cells, Ret/Ptc1 tyrosine phosphorylation was abolished along with its binding to Shc and phospholipase C(gamma), thereby indicating abrogation of constitutive signaling mediated by the oncoprotein. Activation of JNK2 and AKT was abolished, thus supporting the drug inhibitory efficacy on downstream pathways. In addition, cell growth inhibition was associated with a reduction in telomerase activity by nearly 85%. These findings in a cellular context relevant to the pathological function of RET oncogenes support the role of Ret oncoproteins as useful targets for therapeutic intervention, and suggest RPI-1 as a promising candidate for preclinical development in the treatment of thyroid tumors expressing RET oncogenes.

Incidence and predictors of sudden cardiac death during long-term follow-up in patients with dilated cardiomyopathy on optimal medical therapy.

BACKGROUND: In spite of a total mortality reduction in recent years, sudden cardiac death (SD) remains a major problem in patients with idiopathic dilated cardiomyopathy (IDC) and its occurrence is often unpredictable. Furthermore, the risk of SD may change during follow-up because of the natural history of the disease and the effects of therapeutic interventions. In our study, we evaluated the modifications of the risk of SD during follow-up in a cohort of patients with IDC and analyzed the variables predicting SD not only at enrolment but also at the last examination during optimal medical treatment. METHODS: Since 1978, 343 consecutive patients with IDC were enrolled in the Heart Muscle Disease Registry of Trieste (Italy) and submitted to complete invasive and non-invasive study. Patients were re-evaluated usually at intervals of 12 months. RESULTS: After a mean of 68+/-45 months, 125 events (death, heart transplantation or aborted SD) had occurred. The cumulative risk after 5 years was 30%, while after 10 years it almost doubled (54%). During the first 3 months after enrolment, the incidence of SD was high (3%). A plateau, lasting about 3.5 years, followed. A slow but progressive rise in the risk of mortality then occurred (6% at 5 years, 18% at 10 years). No variables evaluated at enrolment were associated with SD at multivariate analysis. On the other hand, the end-diastolic left ventricular diameter (> or = 38 mm/m2) and ejection fraction (< or = 0.30) were predictive of SD if evaluated within 1 year before the event. Beta-blocker treatment was associated with a non-significant reduction of risk. CONCLUSIONS: In patients with IDC the incidence of SD progressively increased during long-term follow-up, especially in those with persistent severe left ventricular dilation and dysfunction who were not on beta-blocker treatment. Serial clinical evaluation may help to select patients at higher risk for SD.

Protein traffic activates NF-kB gene signaling and promotes MCP-1-dependent interstitial inflammation.

Mononuclear cells accumulate in the renal interstitium and contribute to renal injury in proteinuric nephropathies. Angiotensin-converting enzyme (ACE) inhibitors reduce protein trafficking and also lessen renal structural and functional damage. Many proinflammatory genes, including monocyte chemoattractant protein-1 (MCP-1), a chemoattractant for monocytes and T lymphocytes, are transcriptionally regulated by nuclear factor-kappa B (NF-kB). We aimed to study NF-kB activation and MCP-1 expression over time in two models of progressive proteinuric nephropathies (5/6 nephrectomy and passive Heymann nephritis [PHN]) and evaluate the effect of antiproteinuric therapy with an ACE inhibitor on these factors. In both models, increased urinary protein excretion over time was associated with a remarkable increase in NF-kB activity, which was almost completely suppressed by reducing proteinuria with lisinopril. NF-kB activation was paralleled by upregulation of MCP-1 messenger RNA and interstitial accumulation of ED-1-positive monocytes/macrophages and CD8-positive T cells. Lisinopril inhibited MCP-1 upregulation and limited interstitial inflammation. In a group of PHN rats with advanced disease and severe proteinuria, a dose of lisinopril high enough to inhibit renal ACE activity failed to reduce proteinuria and also did not limit NF-kB activation, which was sustained over time, along with MCP-1 gene overexpression and interstitial inflammation. These data suggest that NF-kB is activated in the presence of increased protein traffic, enhancing the nuclear transcription of the MCP-1 gene with potent chemotactic and inflammatory properties. This mechanism may help explain the long-term renal toxicity of filtered proteins.

[Improvement of prognosis in idiopathic dilated cardiomyopathy: role of early diagnosis and optimized medical treatment. Study Group on Heart Muscle Diseases]. / Il miglioramento della prognosi nella cardiomiopatia dilatativa idiopatica: il ruolo della diagnosi precoce e della terapia medica ottimizzata. Gruppo di Studio sulle Malattie del Muscolo Cardiaco.

BACKGROUND: The aim of this study was to assess the extent to which a more widespread use of new effective treatments for heart failure associated with earlier detection of the disease may have contributed to enhancing the prognosis of idiopathic dilated cardiomyopathy (IDC) patients over the past 20 years. METHODS: Heart transplant-free survival curves were analyzed in 343 IDC patients, prospectively enrolled from January 1, 1978 to June 30, 1997 in the Heart Muscle Disease Registry of the Cardiology Department in Trieste (94 enrolled between 1978 and 1987, Group 1; 249 between 1988 and 1997, Group 2). At enrollment, 91 patients had no heart failure symptoms (NoHF), whereas the remaining 252 showed HF of recent (HF < or = 6 months, n = 132) or non-recent (HF > 6 months, n = 120) onset. RESULTS: In comparison to Group 1, Group 2 was treated more frequently with ACE-inhibitors and beta-blockers (p < 0.0001) and showed a better long-term survival (p = 0.0034), resulting from a reduction of death for refractory HF or need for heart transplant (p = 0.011). Conversely, the risk of sudden death did not significantly differ between the two groups. NoHF, HF > 6 months and HF < or = 6 months groups were similarly treated with ACE-inhibitors and beta-blockers. Long-term survival was better in patients without HF than in those with overt HF (p = 0.0015). As compared to Group HF > 6 months, Group HF < or = 6 months had a poorer one-year prognosis (p = 0.045), related to the presence of a subgroup of patients with refractory HF and need for heart transplant, but showed a better survival rate over the following years (p = 0.015). Over the two subsequent decades of enrollment, a significant improvement in patient survival was observed within Groups NoHF (p = 0.03) and HF > 6 months (p = 0.01), but not in Group HF < or = 6 months. CONCLUSIONS: Over the past 20 years, the increasing use of ACE-inhibitors and beta-blockers in IDC was associated with a significant improvement in long-term survival, resulting from a reduction in mortality for refractory heart failure or need for heart transplant. In addition, early diagnosis may have contributed significantly to enhancing the prognosis of IDC, since the benefits of medical therapy were lower in patients identified and treated in advanced stages of the disease. Moreover, early diagnosis was shown to be useful in recognizing patients with recent onset of heart failure who are not responders to aggressive medical treatments and urgently need heart transplant.

Biofeedback-assisted heart rate modification after myocardial infarction.

Four patients who had suffered a myocardial infarction were given biofeedback training in order to assess (1) the possibility of increasing heart rate variability with the help of a feedback; (2) the possible cardiac consequences, from the clinical viewpoint, of biofeedback treatment. A biofeedback procedure alternately increasing and decreasing heart rate under instruction and feedback-plus-instruction conditions, was used. Evaluation of clinical parameters was effected by Holter dynamic ECG and by means of a graded submaximal effort test on the cycloergometer. The results show: (1) poor capacity to increase heart rate variability, but a tendency towards small unidirectional modifications; (2) no significant clinical modification except in isolated parameters. Further study is necessary to assess the usefulness of biofeedback training in the rehabilitation treatment of post-infarction patients. The datum, confirmed elsewhere, concerning apparent cardiovascular "rigidity' in such patients, is interesting but requires clarification.