A suggested protocol to increase the accuracy of prosthetic phases in case of full-arch model-free fully guided computer-aided implant placement and immediate loading.

PURPOSE: The accuracy of fully digital model-free surgical and prosthetic procedures depends on the cumulative effect and interaction of all errors gathered along the entire workflow process. In the present case series, a technique is described that increases the accuracy in the transition from the surgical to the prosthetic phase to reduce the risk of developing prosthetic complications in the case of immediate loading protocols. METHODS: Overall, 86 dental implants were placed and immediately loaded with definitive prostheses in 11 edentulous patients following computer-guided implant surgery according to a fully digital model-free workflow. The same reference template used to anchor the surgical stent during computer-aided implant placement was used to guide the insertion of the definitive abutments and to seat in the correct position the final screw-retained implant-supported fixed restoration. The template used during all surgical and prosthetic procedures, which served as a stable and reproducible connection between the digital and surgical environments, was finally removed. RESULTS: Healing proceeded uneventfully in all subjects. The implant survival and success rates were 100% over a minimum follow-up period of 1 year from the prosthetic loading. No biological or prosthetic complications were clinically and radiographically observed up to the last follow-up recall. CONCLUSION: The use of a reference template used to transfer the digital project to the surgical field increased the accuracy and the integration of the surgical and prosthetic phases during the entire workflow.

Deconstructing vulnerability for psychosis: Meta-analysis of environmental risk factors for psychosis in subjects at ultra high-risk.

BACKGROUND: Subjects at ultra high-risk (UHR) for psychosis have an enhanced vulnerability to develop the disorder but the risk factors accounting for this accrued risk are undetermined. METHOD: Systematic review of associations between genetic or environmental risk factors for psychosis that are widely established in the literature and UHR state, based on comparisons to controls. RESULTS: Forty-four studies encompassing 170 independent datasets and 54 risk factors were included. There were no studies on association between genetic or epigenetic risk factors and the UHR state that met the inclusion criteria. UHR subjects were more likely to show obstetric complications, tobacco use, physical inactivity, childhood trauma/emotional abuse/physical neglect, high perceived stress, childhood and adolescent low functioning, affective comorbidities, male gender, single status, unemployment and low educational level as compared to controls. CONCLUSIONS: The increased vulnerability of UHR subjects can be related to environmental risk factors like childhood trauma, adverse life events and affective dysfunction. The role of genetic and epigenetic risk factors awaits clarification.

What to Do, and What Not to Do, When Diagnosing and Treating Breakthrough Cancer Pain (BTcP): Expert Opinion.

Clinical management of breakthrough cancer pain (BTcP) is still not satisfactory despite the availability of effective pharmacological agents. This is in part linked to the lack of clarity regarding certain essential aspects of BTcP, including terminology, definition, epidemiology and assessment. Other barriers to effective management include a widespread prejudice among doctors and patients concerning the use of opioids, and inadequate assessment of pain severity, resulting in the prescription of ineffective drugs or doses. This review presents an overview of the appropriate and inappropriate actions to take in the diagnosis and treatment of BTcP, as determined by a panel of experts in the field. The ultimate aim is to provide a practical contribution to the unresolved issues in the management of BTcP. Five 'things to do' and five 'things not to do' in the diagnosis and treatment of BTcP are proposed, and evidence supporting said recommendations are described. It is the duty of all healthcare workers involved in managing cancer patients to be mindful of the possibility of BTcP occurrence and not to underestimate its severity. It is vital that all the necessary steps are carried out to establish an accurate and timely diagnosis, principally by establishing effective communication with the patient, the main information source. It is crucial that BTcP is treated with an effective pharmacological regimen and drug(s), dose and administration route prescribed are designed to suit the particular type of pain and importantly the individual needs of the patient.

Long-term survival rate of implants placed in conjunction with 246 sinus floor elevation procedures: results of a 15-year retrospective study.

OBJECTIVES: The aim of the present long-term study was to retrospectively evaluate the survival rate of implants placed in regenerated maxillary sinuses and to assess the influence of hypothetical predictors of implant failure. METHODS: A database including 218 patients who received dental implants after sinus lift procedures was analyzed. The following variables were systematically included and evaluated: type of graft material used, number of surgeries performed, and use of membranes to cover the lateral antrostomy and/or to repair accidental Schneiderian membrane perforations. The Kaplan-Meier estimator was used for comparisons among the groups. RESULTS: A total of 589 dental implants were positioned in 246 grafted sinuses and were in function for 3-186 months. The Kaplan-Meier cumulative survival rate was 98.3% after 15.5 years of follow-up. All implant losses occurred within 52 months (4.3 years) after augmentation. According to the log-rank test, no statistically significant difference was shown between each patient/implant variable (p>0.05). CONCLUSIONS: Despite the limitations inherent in this type of study, no statistically significant differences between the groups could be found. Intraoperative Schneiderian membrane perforations did not affect the outcome of the implants positioned. CLINICAL SIGNIFICANCE: The present long-term study is intended as a reference for clinicians approaching sinus floor elevation surgery in order to provide them with relevant operative findings. Since all the drawbacks occurred within the first 5 years, medium-term follow-up studies could be suitable for further retrospective evaluations.

Minimally invasive surgical approach in a large mandibular solitary cyst: case report and review of the literature.

Solitary bone cyst (SBC) is an intraosseus radiolucent lesions that defers from real cysts for the fact that peripheral epithelial lining is totally absent. It could be classified as a psudocyst and occurs most frequently in young patients. In most cases SBC doesn't cause symptoms and it is often diagnosed accidentally during routine radiographic examination. A right diagnosis of this disease is also complicated because there are no pathognomonic radiographic signs and symptoms: so this form of pseudocyst is often misdiagnosed as a common odontogenic cyst. Despite numerous studies, the pathogenesis of the SBC is not yet established: the most widely accepted theory is that it could be the result of an intramedullary necrosis determined by a trauma. In this article we report a case of SBC in child treated with a minimal surgical approach. This new kind of treatment is much more conservative than the traditional one, it can be performed as outpatients, under local anesthesia and with few postoperative discomfort: For these reasons this minimal invasive technique appears to be particulary suitable for pediatric patients.

Combined treatment of odontogenic keratocysts: initial marsupialization and successive enucleation with peripheral ostectomy plus Carnoy's solution application. A five-year follow-up experience.

AIM: The odontogenic keratocyst (KCOT) is a locally aggressive, cystic jaw lesion with a high growth potential and a propensity for recurrence. Considering its neoplastic features, treatments of keratocysts are required and they are generally classified as conservative or aggressive. However, although in literature there are several studies, the choice of treatment strategies remains controversial. We report a two-stage protocol based on initial marsupialization and successive enucleation. METHODS: Three cases of large KCOTs have been treated by initial marsupialization and, after a mean period of six months, successive enucleation with peripheral ostectomy and application of Carnoy's solution was performed. RESULTS: All patients were instructed in daily irrigation using chlorhexidine 0.2% during the period of marsupialization. After enucleation, good healing was obtained in all cases and from two up to five years of follow-up, there is no evidence of recurrence. CONCLUSION: Two-stage surgical treatment protocol of keratocyst leads to complete healing, preservation of important anatomical structures and absence of recurrence.

Aspergillus nidulans as a biological system to detect the genotoxic effects of mercury fumes on eukaryotes.

Mercury (Hg) pollution is one of the most serious environmental problems. Due to public concern prompted by the symptoms displayed by people who consumed contaminated fish in Minamata, Japan in 1956, Hg pollution has since been kept under constant surveillance. However, despite considerable accumulation of knowledge on the noxious effects of ingested or inhaled Hg, especially for humans, there is virtually nothing known about the genotoxic effects of Hg. Because increased mitotic crossing over is assumed to be the first step leading to carcinogenesis, we used a sensitive short-term test (homozygotization index) to look for DNA alterations induced by Hg fumes. In one Aspergillus nidulans diploid strain (UT448//UT184), the effects of the Hg fumes appeared scattered all over the DNA, causing 3.05 times more recombination frequencies than the mean for other strains. Another diploid (Dp II-I//UT184) was little affected by Hg. This led us to hypothesize that a genetic factor present in the UT184 master strain genome, close to the nicB8 genetic marker, is responsible for this behavior. These findings corroborate our previous findings that the homozygotization index can be used as a bioassay for rapid and efficient assessment of ecotoxicological hazards.

Depression after lung transplantation: causes and treatment.

During the postoperative course of lung transplantation, patients may experience depressive symptoms that negatively influence their ability to cope with the new organ, their adherence to rehabilitation and pharmacologic therapy, and their overall quality of life (QoL). To date, no review has explored the causes of depression following transplantation or the efficacy and safety of therapeutic interventions in this patient group. We conducted a comprehensive 1966-2006 MEDLINE, EMBASE, and PsycINFO search for studies of the causes and treatments of depression in lung transplant recipients. We identified 25 studies of variable methodologic quality. Depression rates are high among candidates for lung transplantation. In the short term, after surgery depressive symptoms remain low with an improvement in QoL, whereas in the long term (>3 years), the decline of functional status is associated with a dramatic increase in such symptomatology. Personality disorders, coping strategies, stressful life events, physical complications, corticosteroid medications, age, gender, and psychosocial support all play a central role in causing depressive states in lung transplant recipients. Serotonin reuptake inhibitors (SSRIs) and new-generation antidepressants (mirtazapine) represent the best therapeutic choices for this group of patients. The risk of serious drug-drug interactions should be carefully monitored by experienced clinicians. Complementary therapies and psychoeducational intervention also help recipients to strengthen their coping strategies, offering further advantages after transplantation. Additional well-conducted randomized controlled trials are needed to clarify the epidemiologic course of depression following lung transplantation and to tailor effective pharmacologic or psychological interventions accordingly.

Long-surviving case of adenosquamous carcinoma of the larynx: case report and review of literature.

A singularly long-surviving (15 years) disease-free case of a stage II adenosquamous carcinoma of the larynx is described. A review of the literature reveals that prognosis of this aggressive malignant neoplasm is poor (mean 2-3 years free of disease) on account of local recurrences, early cervical lymph node metastasis and distant dissemination. This long survival rate emphasises the importance of early radical surgical treatment and the choice of total laryngectomy with neck dissection in stage II laryngeal neoplasm.

Evaluation of the genotoxicity induced by the fungicide fenarimol in mammalian and plant cells by use of the single-cell gel electrophoresis assay.

Fenarimol, a systemic pyrimidine carbinol fungicide, is considered to be not genotoxic or weakly genotoxic, although the available toxicological data are controversial and incomplete. Our results obtained in vitro with leukocytes of two different rodent species (rat and mouse) show that fenarimol affects DNA, as detected by the single-cell gel electrophoresis (SCGE, Comet) assay. This fungicide is able to induce DNA damage in a dose-related manner, with significant effectiveness at 36 nM, but without significant interspecies differences. Simultaneous exposure of rat leukocytes to fenarimol (36-290 nM) and a model genotoxic compound (50 microg/ml bleomycin) produced a supra-additive cytotoxic and genotoxic effect. This supports previous findings suggesting possible co-toxic, co-mutagenic, cancer-promoting and co-carcinogenic potential of fenarimol, and modification of the effects of other xenobiotics found to be influenced by this agrotoxic chemical, with consequent different toxicological events. The potential for DNA strand breaks to act as a biomarker of genetic toxicity in plants in vivo was also considered, in view of the fact that higher plants represent reliable sensors in an ecosystem. Significant DNA breakage was observed in the nuclei of Impatiens balsamina leaves after in vivo treatment with fenarimol (145 nM, 1h). More than 50% of the cells showed such DNA damage.

Evaluation of the migration of mutagens/carcinogens from PET bottles into mineral water by Tradescantia/micronuclei test, Comet assay on leukocytes and GC/MS.

This study monitored the release of mutagenic/carcinogenic compounds into mineral water (natural and carbonated) from polyethylene terephthalate (PET) bottles, using a plant mutagenicity test which reveals micronuclei formation in Tradescantia pollen cells (Trad/MCN test), a DNA damage assay (Comet assay) on human leukocytes and gas chromatography/mass spectrometry (GC/MS) for the characterisation of migrants. The water samples were collected at a bottling plant and stored in PET bottles for a period ranging from 1 to 12 months. Every month some samples were randomly collected and lyophilised, the residual powders were extracted with organic solvents and then analysed by GC/MS and tested for DNA damage in human leukocytes, or reconstituted with distilled water to obtain concentrates for the exposure of Tradescantia inflorescences. Micronuclei increase in pollen was found only in natural mineral water stored for 2 months. DNA-damaging activity was found in many of the natural and carbonated water samples. Spring water was negative in the plant micronuclei test and the Comet assay, whereas distributed spring water showed DNA-damaging effects, suggesting a possible introduction of genotoxins through the distribution pipelines. GC/MS analysis showed the presence in mineral water of di(2-ethylhexyl)phthalate, a nongenotoxic hepatocarcinogenic plasticizer, after 9 months of storage in PET bottles.

Assessment of depression among cancer patients: the role of pain, cancer type and treatment.

One hundred consecutive cancer patients were assessed using two structured methods for assessing major depressive disorder-Structured Clinical Interview for DSM III-R (SCID) and Endicott criteria-and using a depression rating scale-Hamilton Depression Rating Scale (HAMD). Forty-nine percent of patients were depressed using SCID (DSM III-R criteria), whereas 29% of patients were depressed using Endicott criteria. Twenty-eight percent of patients were depressed using both criteria. Age and sex did not have any influence on the assessment of major depression. Both the structured interview and the rating scale were able to identify suicide ideation. Depressed patients were not shown to have more lifetime depression than non-depressed patients using both structured methods. Patients who were depressed using both assessments of depression had more metastasis and pain than non-depressed patients.

Amifostine (WR-2721) selective protection against melphalan genotoxicity.

Amifostine (WR-2721) is an aminothiol compound dephosphorylated at the tissue site by alkaline phosphatase to the active metabolite, which is able to inactivate electrophilic substances and scavenge free radicals. Amifostine effects against melphalan-induced DNA strand breaks were studied in normal human white blood cells (WBC) and K562 leukemic cells using the single cell gel electrophoresis (SCGE) or Comet assay, a reported method for measuring DNA damage in individual cells. Prior to treatment (1 h, 37 degrees C) with increasing doses of melphalan, with or without S9, the cells were treated (15 min, 37 degrees C) with a control medium or amifostine (3 mg/ml). Treatment of normal and leukemic cells with melphalan induced a dose-dependent 'comet formation'. Melphalan-induced DNA damage follows a normal distribution in WBC. On the other hand, in K562, a significant proportion of undamaged cells remains even with doses at which mean DNA damage is serious. Pretreatment with WR-2721 protects WBC, but not K562, against the genotoxic effect of melphalan. Amifostine might even strengthen the action of the antiblastic drug against K562 cells. S9 addition appears to enhance melphalan effectiveness. SCGE appears as a suitable primary screening method for in vitro and in vivo studies on drug-DNA interactions and their modulations by endogenous/exogenous factors.

DNA damage by tobacco smoke and some antiblastic drugs evaluated using the Comet assay.

The Comet assay was used in human leukocytes to detect, in vivo, DNA strand-breaks induced by smoking habit to evaluate the test sensitivity to an environmental factor, and by several antiblastic drugs to note their effectiveness at single cell level. Differences related to smoking habit, gender and age are evident. Melphalan shows the widest DNA damage. The damage induced by etoposide can be ascribed to the balancing between the production of strand-breaks and cross-links which limit the migration of DNA fragments. Interferon, fludarabine, prednisone, and oncocarbide appear to induce unexpected strand-breaks. Single cell gel electrophoresis (SCGE) is highly effective in revealing the association between DNA damage and environmental, genetic, and acquired factors, providing further data on the possible applicability of this assay in genotoxic human surveillance in addition to established tests. Moreover, the ability to point out cell subpopulations varying in mean damage levels could allow detection of potentially emerging drug-resistant populations.

Bleomycin genotoxicity alteration by glutathione and cytochrome P-450 cellular content in respiratory proficient and deficient strains of Saccharomyces cerevisiae.

The genotoxic effects of the antiblastic drug bleomycin were studied in the D7 strain of Saccharomyces cerevisiae and on its derivative mitochondrial mutant rho degree at different cellular concentrations of two drug metabolizing systems, glutathione (GSH) and cytochrome P-450. Bleomycin mutagenic activity was evaluated as frequencies of mitotic gene conversion, reversion and total aberrations under different physiological conditions. In the D7 strain, petite mutant induction was also detected. This is important due to the role of the mitochondrial genome in cancer induction, ageing and degenerative diseases. Both strains showed higher convertant than revertant induction. At high cytochrome P-450 levels, bleomycin-induced gene conversion was enhanced in both strains although mitochondrial functionality showed a detoxicant role while cellular GSH content decreased the induction of convertants only in the respiratory proficient strain. Cell metabolic conditions, such as cell cycle, aerobic/hypoxic conditions of the cell and content of drug metabolizing enzymes, appeared to interact with the genotoxic effectiveness of bleomycin. Moreover, the usefulness of S.cerevisiae as a model organism for drug assessment for mutagenicity was emphasized.

Modulation of mitomycin C mutagenicity on Saccharomyces cerevisiae by glutathione, cytochrome P-450, and mitochondria interactions.

It is well established that most anticancer drugs also have mutagenic effects and require metabolic activation before exerting their mutagenic/antiblastic activity. Antitumoral compound effects strongly depend on the biochemical/physiological conditions of the tumoral cells, and especially on the activation of specific drugs metabolizing enzymes and on respiration. We examined the mitomycin C-induced mutagenic effects on the D7 strain of Saccharomyces cerevisiae and on its derivative mitochondrial mutant p degrees at different contents of glutathione and cytochrome P-450, molecules able to activate/detoxicate xenobiotics. The mutagenic activity of the drug was evaluated as frequency of mitotic gene conversion and reversion in different physiological conditions. The highest frequencies of reversion and especially of gene conversion were observed at the highest cytochrome P-450 contents in the D7 strain with a further increase at high glutathione level. In the respiratory-deficient strain, the highest frequency of convertants was shown at low glutathione level and lack of cytochrome P-450. These results suggest the relevance of mitochondrial functionality for the expression of genotoxic activity of this anticancer drug.

Malignant fibrous histiocytoma of the floor of the mouth: case report.

Malignant fibrous histiocytoma (MFH) is a common neoplasm of soft tissue. The floor of the mouth is an unusual site of origin and has not been described in the literature previously. Its rarity, aspecific clinical symptoms and complex histopathology combine to make the diagnosis difficult. The treatment of choice is wide surgical excision with adjunctive irradiation.

Occupational genotoxicity assessment by mutagenicity assays.

Mutagenic activity measured by Ames test and by gene conversion, point mutation and mitochondrial mutability in Saccharomyces cerevisiae D7 strain was determined in the indoor environment of a glass factory. The results suggest that the increase in mutagenicity of air sample collected near the machinery is due to the thermal decomposition of oils. Modified assays were therefore compared for their ability to detect mutagens contained in urinary concentrates of exposed workers. The bacterial tests were performed by microsuspension assay in TA98, TA100 strains and in YG1024, YG1029 strains which overproduce O-acetyltransferase. Significant differences are evidenced both in the eukaryotic and prokaryotic systems.