Mini Crestal Sinus Lift With Bone Grafting and Simultaneous Insertion of Implants in Severe Maxillary Conditions as an Alternative to Lateral Sinus Lift: Multicase Study Report of Different Techniques.

The present study evaluates the efficacy and clinical outcomes of crestal sinus lift techniques used to elevate the sinus floor simultaneously with bone grafting and implant placement as a possible and reproducible alternative to lateral sinus lift. Patients underwent different crestal sinus elevation techniques. The heterologous biomaterial was used as graft material, and multiple implants were placed simultaneously after sinus augmentation. Radiographic and clinical examinations were performed during follow-up. All procedures were successfully performed without any apparent perforation of the Schneider membrane. The sinus floor was augmented with an average height of 5 mm (range: 2.8-7.4 mm). The implants healed smoothly with healing screws. Peri-implant marginal bone was stable with a mean follow-up of 50 months (range: 33-71 mo). No complications were observed during the follow-up. Based on the limited data collected in this study, the new crestal sinus elevation approach can effectively raise the sinus floor and reduce the incidence of postoperative complications. Other cases with long-term follow-up are needed to confirm and improve this crestal sinus lift technique.

Treatment of Oral Mucositis Using Platelet-Rich-Fibrin: A Retrospective Study on Oncological Patients.

Oral mucositis is an inflammatory mucosal demolition frequently observed during treatments for neoplastic diseases such as chemotherapy or radiation therapy. The side effects of these treatments often drastically reduce patients' quality of life. Oral mucositis is the result of the systemic consequences of chemotherapy and radiotherapy, which due to their cytotoxic and local effects, lead to pain and severe ulceration with a consequent decrease in the quality of life of affected subjects. Plasma rich in fibrin is often used to enhance soft tissue wound healing and fight bacterial sepsis through the presence of leukocytes within it. The retrospective study aimed to evaluate the efficacy and safety of the topic use of platelet gel in the clinical management of oral mucositis to improve the life quality of patients. The results of the study were promising even though the topical application of platelet-rich-fibrin is like a skin-care treatment. Future studies with a larger sample of patients will be needed to understand the real benefits of platelet-rich-fibrin.

Oral Manifestations of Graft vs. Host Disease: A Comprehensive Review for Best Practice in Dentistry.

Graft-versus-host disease (GVHD) is a complication of hematopoietic stem cell transplantation (HSCT). GVHD may also develop following solid transplants or blood transfusions if white blood cells are transferred. GVHD affects multiple organs, including the oral tissues. This pictorial review provides a background of GVHD to dental practitioners, describes the most common oral manifestations of GVHD, and highlights the main treatment modifications needed to deliver dental care to patients with GVHD. A narrative review enriched with clinical data was performed by searching the scientific literature for all articles regarding GVHD and oral manifestations/therapies. All articles without exclusion criteria, except animal tests, were included in the above review. Acute GVHD may manifest in the oral mucosa; however, it often develops immediately following HSCT when routine dental treatment is postponed. Chronic GVHD may manifest in the oral mucosa, the salivary glands, and the musculoskeletal compartment. It may indirectly affect the teeth and the oral flora, putting the patient at risk for infections. Importantly, GVHD poses an increased risk for oral cancer. GVHD has a wide range of oral manifestations, some of which may affect dental treatment.

Périgord black truffle genome uncovers evolutionary origins and mechanisms of symbiosis.

The Périgord black truffle (Tuber melanosporum Vittad.) and the Piedmont white truffle dominate today's truffle market. The hypogeous fruiting body of T. melanosporum is a gastronomic delicacy produced by an ectomycorrhizal symbiont endemic to calcareous soils in southern Europe. The worldwide demand for this truffle has fuelled intense efforts at cultivation. Identification of processes that condition and trigger fruit body and symbiosis formation, ultimately leading to efficient crop production, will be facilitated by a thorough analysis of truffle genomic traits. In the ectomycorrhizal Laccaria bicolor, the expansion of gene families may have acted as a 'symbiosis toolbox'. This feature may however reflect evolution of this particular taxon and not a general trait shared by all ectomycorrhizal species. To get a better understanding of the biology and evolution of the ectomycorrhizal symbiosis, we report here the sequence of the haploid genome of T. melanosporum, which at approximately 125 megabases is the largest and most complex fungal genome sequenced so far. This expansion results from a proliferation of transposable elements accounting for approximately 58% of the genome. In contrast, this genome only contains approximately 7,500 protein-coding genes with very rare multigene families. It lacks large sets of carbohydrate cleaving enzymes, but a few of them involved in degradation of plant cell walls are induced in symbiotic tissues. The latter feature and the upregulation of genes encoding for lipases and multicopper oxidases suggest that T. melanosporum degrades its host cell walls during colonization. Symbiosis induces an increased expression of carbohydrate and amino acid transporters in both L. bicolor and T. melanosporum, but the comparison of genomic traits in the two ectomycorrhizal fungi showed that genetic predispositions for symbiosis-'the symbiosis toolbox'-evolved along different ways in ascomycetes and basidiomycetes.

The role of anxiety in patients with hereditary angioedema during oral treatment: a narrative review.

Objective: The present study investigated the clinical potential of managing anxiety during dental procedures to reduce acute attacks in patients with hereditary angioedema (HAE). HAE is a rare disease, little known to physicians and dentists, but with an increased hospitalization rate over the years. HAE is due to a deficiency/dysfunction of the C1 esterase inhibitor, leading to increased vascular permeability. Recommendations for HAE management include long-term and short-term prophylaxis and treatment of acute attacks, but the importance of anxiety control is underestimated. Materials and methods: The authors reviewed the literature to provide the scientific community with an overview of possible protocols for managing anxiety in dental practice and their effectiveness. Management can be used in prosthetics, periodontal and implant surgery, endodontics, and oral surgery. Discussions: Our analysis shows that although there are few articles in the indexed literature, protocols for managing anxiety in HAE patients in dentistry will become increasingly prevalent in the daily clinical practice of dentists due to its benefits. Conclusions: The benefits and better control of intraoperative complications and risks may lead clinicians to use sedation, assessment, or anxiety control techniques in daily clinical practice to reduce such attacks. Clinical relevance: This study suggests that controlling and managing anxiety can help prevent and reduce acute angioedema attacks.

Gabapentin for the prevention of chemotherapy- induced nausea and vomiting: a pilot study.

INTRODUCTION: Chemotherapy-induced nausea and vomiting (CINV) is a distressing side effect that affects many patients undergoing emetogenic chemotherapy, despite the use of antiemetic medications. The purpose of this trial was to evaluate the efficacy and safety of gabapentin for the prevention of CINV during the first cycle of treatment in patients receiving moderately or highly emetogenic chemotherapy. METHODS: Eighty chemotherapy-naive patients, scheduled to receive moderately and highly emetogenic chemotherapy, were enrolled in this randomised, double-blind, placebo-controlled clinical trial. All patients received intravenous ondansetron 8 mg, dexamethasone 10 mg and ranitidine 50 mg before chemotherapy on day 1 and oral dexamethasone 4 mg twice a day on days 2 and 3. Patients were randomly assigned to take gabapentin 300 mg or placebo on the following schedule: 5 and 4 days before chemotherapy once daily, 3 and 2 days before chemotherapy twice daily, 1 day before to 5 days after chemotherapy thrice daily. The primary endpoint was complete overall protection from both vomiting and nausea over the course of the entire study (day 1 through day 5), and complete protection during the delayed period (24-120 h after chemotherapy). RESULTS: The proportion of patients achieving complete response improved from 40% to 62.5%, (p = 0.04) when comparing the control group and the gabapentin group, respectively. In the subset of patients who achieved complete control in the acute phase, the percentage of patients who achieved delayed complete control was higher in the gabapentin group (89.3 × 60.7%, p = 0.01). Adverse events did not significantly differ between study arms. CONCLUSIONS: Gabapentin is a low-cost strategy to improve complete control of CINV, specially delayed CINV control.

Use of unnecessary medications by patients with advanced cancer: cross-sectional survey.

BACKGROUND: Cancer patients at the end of life take numerous medications. However, it has not been assessed what proportion of patients take unnecessary medications and which patients are at risk for doing so. METHODS: Cross-sectional survey of medications utilized by terminally ill ambulatory cancer patients, with the aim of identifying medications considered unnecessary as per explicit criteria. The criteria took into account whether drugs could benefit patients with terminal cancer. RESULTS: Among 87 patients, 21 (24%, 95% confidence interval [CI] 15.6-34.5%) were taking at least one unnecessary medication, the most common being gastric protectors. In multivariable analyses, patients with Charlson Comobidity Index≤1 (OR: 4.49, CI95% 1.32-15.26; p=0.01) or whose medication list had not been reconciled by physicians (OR: 6.38, CI95% 1.21-33.40; p=0.02) were more likely to use an unnecessary medication. CONCLUSION: Patients with advanced cancer take many medications considered unnecessary. Medication reconciliation should be performed routinely for these patients.

Eradication of therapy-resistant human prostate tumors using an ultrasound-guided site-specific cancer terminator virus delivery approach.

Intratumoral injections of a replication-incompetent adenovirus (Ad) expressing melanoma differentiation-associated gene-7/interleukin-24 (Ad.mda-7), a secreted cytokine displaying cancer-selective, apoptosis-inducing properties, profoundly inhibits prostate cancer (PC) growth in immune-incompetent animals. In contrast, Ad.mda-7 is ineffective in PCs overexpressing antiapoptotic proteins such as Bcl-2 or Bcl-x(L). However, intratumoral injections of a conditionally replication-competent Ad (CRCA) in which expression of the adenoviral E1A gene is driven by the cancer-specific promoter of progression-elevated gene-3 (PEG-3) and which simultaneously expresses mda-7/interleukin (IL)-24 in the E3 region of the Ad (Ad.PEG-E1A-mda-7), a cancer terminator virus (CTV), is highly active in these cells. A major challenge for gene therapy is systemic delivery of nucleic acids directly into an affected tissue. Ultrasound (US) contrast agents (microbubbles-MBs) are viable candidates for gene delivery/therapy. Here, we show that MB/Ad.mda-7 complexes targeted to DU-145 cells using US dramatically reduced tumor burden in xenografted nude mice. Additionally, US-guided MB/CTV delivery completely eradicated not only targeted DU-145/Bcl-x(L)-therapy-resistant tumors, but also nontargeted distant tumors (established in the opposite flank), thereby implementing a cure. These findings highlight potential therapeutic applications of this novel image-guided gene therapy technology for advanced PC patients with metastatic disease.

The Role of Platelet-Rich Fibrin (PRF) in the Prevention of Medication-Related Osteonecrosis of the Jaw (MRONJ).

Dentoalveolar surgery is probably the major risk factor for MRONJ and for other complications following a tooth extraction, especially in patients affected by systemic diseases. The aim of this retrospective study is to evaluate whether a PRF plug inserted in the post extraction socket can prevent the onset of MRONJ. The patients were divided into two groups according to the surgical protocol that included the insertion or not of the PRF following the extraction and all the anamnestic, and clinical data were analyzed. In the control group, 5 patients developed MRONJ (19.23%) while in the study group, any case of MRONJ was reported. In the control group, patients who developed MRONJ had a CTX with less than 100 pg/mL (5 high-risk patients, Spearman's rank r = .547, p < .001). The use of platelet concentrates in patients with high risk of MRONJ is a user-friendly technique with an excellent cost-benefit ratio in oral surgery.

Transcriptional analysis of tyrosinase gene expression during Bufo bufo development.

Tyrosinase (EC.1.14.18.1.) is a widespread enzyme, in the phylogenetic scale, that produces melanin, from bacteria to man, by using as substrates monophenols, o-diphenols and molecular oxygen. In this work we have confirmed and demonstrated that during Bufo bufo development tyrosinase activity and gene expression first occur at developmental stages 17-18 (tail bud-muscular response) as detected by a spectrophotometric assay and qRT-PCR. As expected, also during B. bufo development tyrosinase gene is expressed after the late gastrula (stage 12), differently from Rana pipiens development when tyrosinase mRNA appears at the neural plate stage and enzyme activity at stage 20 (gill circulation). We have cloned and sequenced the B. bufo tyrosinase cDNA in order to prepare B. bufo tyrosinase cDNA specific primers (forward and reverse). Tyrosinase mRNA cloning has been performed by using degenerate primers prepared according to the anuran tyrosinase gene sequence coding for the copper binding sites. The expressions of tyrosinase gene and enzymatic activity during B. bufo development support that until the developmental stage 17, embryo melanin is of maternal origin and at this stage can start embryo melanin synthesis. A correlation exists between tyrosinase expression and O2 consumption during B. bufo development.

Glanzmann's Thrombastenia: The Role of Tranexamic Acid in Oral Surgery.

Glanzmann's thrombastenia (GT) is the most frequent inherited condition. GT is a genetic autosomal recessive disease caused by the alteration of the genes ITGA2B and ITGB3, located on the chromosome 17. The incidence of GT is calculated in 1 on 1000000. The patients, during their life, show episodes of mucocutaneous bleeding, epistaxis, and gingival bleeding. Some subjects required continuous bleeding transfusion. The aim of this case report is to demonstrate that oral assumption of tranexamic acid is a gold standard to prevent excessive bleeding. The patient GM of 36 years old with GT type 1 needs dental extractions of the teeth 4.7 and 4.8 at the "Tor Vergata" University Hospital in Rome. The specialist suggests that 3 days before surgery, the patient must take 6 vials every day of tranexamic acid that is used in obstetrics and gynecology. The teeth were extracted and applied suture. The patient is observed and is recommended mouth rinse with tranexamic acid. No bleeding complications were observed.

The genomic tool-kit of the truffle Tuber melanosporum programmed cell death.

A survey of the truffle Tuber melanosporum genome has shown the presence of 67 programmed cell death (PCD)-related genes. The 67 genes are all expressed during fruit body (FB) development of T. melanosporum development; their expression has been detected by DNA microarrays and qPCR. A set of 14 PCD-related genes have been chosen, those with the highest identities to the homologs of other species, for a deeper investigation. That PCD occurs during T. melanosporum development has been demonstrated by the TUNEL reaction and transmission electron microscopy. The findings of this work, in addition to the discovery of PCD-related genes in the T. melanosporum genome and their expression during the differentiation and development of the FB, would suggest that one of the PCD subroutines, maybe autophagy, is involved in the FB ripening, i.e., sporogenesis.

Amphibian transition to the oxidant terrestrial environment affects the expression of glutathione S-transferases isoenzymatic pattern.

It has been postulated that glutathione S-transferases (GST; EC 2.5.1.18) may play a role in protecting against oxidative stress. In previous studies, we have purified and characterised from Bufo bufo embryos a GST isoenzyme (BbGSTP1-1), which falls at very low level in the adult liver, where a novel isoform (BbGSTP2-2), starts to be highly expressed. During transition to adult life, B. bufo leaves the aquatic environment to live predominantly in the terrestrial environment, characterised by higher oxygen concentration. It has been found that BbGSTP2-2 is more efficient in scavenging from organic hydroperoxides. Therefore, the appearance of BbGSTP2-2 may respond to the necessity of providing the adult toad with a more suitable protection against oxygen toxic by-products. In this work, we performed experiments aimed at verifying if oxidative stress (hyperoxic and H(2)O(2) treatments) could act as a modulator of BbGSTP2-2 expression. Results show that: (a) BbGSTP2 mRNA starts to be expressed in the late embryonic period, while protein appears during metamorphosis; (b) oxidative stress induces anticipation of BbGSTP2 gene expression at both transcriptional and translational levels. These findings seem to indicate that the appearance of BbGSTP2-2 is aimed at endowing the adult toad with more efficient antioxidant defence in the terrestrial atmosphere.

Truffles contain endocannabinoid metabolic enzymes and anandamide.

Truffles are the fruiting body of fungi, members of the Ascomycota phylum endowed with major gastronomic and commercial value. The development and maturation of their reproductive structure are dependent on melanin synthesis. Since anandamide, a prominent member of the endocannabinoid system (ECS), is responsible for melanin synthesis in normal human epidermal melanocytes, we thought that ECS might be present also in truffles. Here, we show the expression, at the transcriptional and translational levels, of most ECS components in the black truffle Tuber melanosporum Vittad. at maturation stage VI. Indeed, by means of molecular biology and immunochemical techniques, we found that truffles contain the major metabolic enzymes of the ECS, while they do not express the most relevant endocannabinoid-binding receptors. In addition, we measured anandamide content in truffles, at different maturation stages (from III to VI), through liquid chromatography-mass spectrometric analysis, whereas the other relevant endocannabinoid 2-arachidonoylglycerol was below the detection limit. Overall, our unprecedented results suggest that anandamide and ECS metabolic enzymes have evolved earlier than endocannabinoid-binding receptors, and that anandamide might be an ancient attractant to truffle eaters, that are well-equipped with endocannabinoid-binding receptors.

Validation of reference genes for quantitative real-time PCR in Périgord black truffle (Tuber melanosporum) developmental stages.

The symbiotic fungus Tuber melanosporum Vittad. (Périgord black truffle) belongs to the Ascomycota and forms mutualistic symbiosis with tree and shrub roots. This truffle has a high value in a global market and is cultivated in many countries of both hemispheres. The publication of the T. melanosporum genome has given researchers unique opportunities to learn more about the biology of the fungus. Real-time quantitative PCR (qRT-PCR) is a definitive technique for quantitating differences in transcriptional gene expression levels between samples. To facilitate gene expression studies and obtain more accurate qRT-PCR data, normalization relative to stable housekeeping genes is required. These housekeeping genes must show stable expression under given experimental conditions for the qRT-PCR results to be accurate. Unfortunately, there are no studies on the stability of housekeeping genes used in T. melanosporum development. In this study, we present a morphological and microscopical classification of the developmental stages of T. melanosporum fruit body, and investigate the expression levels of 12 candidate reference genes (18S rRNA; 5.8S rRNA; Elongation factor 1-alpha; Elongation factor 1-beta; α-tubulin; 60S ribosomal protein L29; ß-tubulin; 40S ribosomal protein S1; 40S ribosomal protein S3; Glucose-6-phosphate dehydrogenase; ß-actin; Ubiquitin-conjugating enzyme). To evaluate the suitability of these genes as endogenous controls, five software-based approaches and one web-based comprehensive tool (RefFinder) were used to analyze and rank the tested genes. We demonstrate here that the 18S rRNA gene shows the most stable expression during T. melanosporum development and that a set of three genes, 18S rRNA, Elongation factor 1-alpha and 40S ribosomal protein S3, is the most suitable to normalize qRT-PCR data from all the analyzed developmental stages; conversely, 18S rRNA, Glucose-6-phosphate dehydrogenase and Elongation factor 1-alpha are the most suitable genes for fruiting body developmental stages.

Scavenging system efficiency is crucial for cell resistance to ROS-mediated methylglyoxal injury.

Methylglyoxal is a reactive dicarbonyl compound endogenously produced mainly from glycolytic intermediates. Recent research indicates that methylglyoxal is a potent growth inhibitor and genotoxic agent. The antiproliferative activity of methylglyoxal has been investigated for pharmacological application in cancer chemotherapy. However, various cells are not equally sensitive to methylglyoxal toxicity. Therefore, it would be important to establish the cellular factors responsible for the different cell-type specific response to methylglyoxal injury, in order to avoid the risk of failure of a therapy based on increasing the intracellular level of methylglyoxal. To this purpose, we comparatively evaluated the signaling transduction pathway elicited by methylglyoxal in human glioblastoma (ADF) and neuroblastoma (SH-SY 5Y) cells. Results show that methylglyoxal causes early and extensive reactive oxygen species generation in both cell lines. However, SH-SY 5Y cells show higher sensitivity to methylglyoxal challenge due to a defective antioxidant and detoxifying ability that, preventing these cells from an efficient scavenging action, elicits extensive caspase-9 dependent apoptosis. These data emphasize the pivotal role of antioxidant and detoxifying systems in determining the grade of sensitivity of cells to methylglyoxal.

Truffle thio-flavours reversibly inhibit truffle tyrosinase.

Tyrosinase is an enzyme having two copper atoms at the reactive site occurring in prokaryotic and eukaryotic organisms. In animals tyrosinase is responsible for pigmentation, in plants for protection of injured tissues or, as in fungi, to harden cell walls. Some of us have previously shown that tyrosinase is involved in truffle development and differentiation. Here we present the purification, the molecular properties and the reversible inhibition of Tuber melanosporum tyrosinase by dimethyl-sulfide and bis[methylthio]methane, the main flavour compounds of black and whitish truffles. The MW(r) is 39000. L-3,4-dihydroxyphenylalanine and L-tyrosine stain corresponding bands as expected for a true tyrosinase. Phenylthiourea, diethyldithiocarbamate and mimosine inhibit L-tyrosine and L-3,4-dihydroxyphenylalanine oxidation.

Transcriptional, biochemical and histochemical investigation on laccase expression during Tuber melanosporum Vittad. development.

The cDNAs of Tuber melanosporum laccases (Tmellcc1 and Tmellcc2) have been cloned. From the cloned cDNAs probes were prepared to investigate the expression levels of the Tmellcc1 and Tmellcc2 genes in the free living mycelium (FLM), ectomycorrhizae (ECM) and different developmental stages of fruit body (FB) by quantitative PCR (qPCR). The mRNA expression levels agree with the changes of laccase activities. The histochemical data agree with the qPCR and biochemical results. The highest laccase expression occurs in the ECM, when the host plant roots are invaded by the fungal mycelium.

The prevalence and influence of self-reported conflicts of interest by editorial authors of phase III cancer trials.

PURPOSE: To assess the frequency with which editorial authors report personal conflict of interest and investigate a possible association between the presence of such conflicts and favorable opinion. METHODS: Eligible studies were editorials of phase III clinical trials of antitumor drugs or symptom management published from January 2007 to December 2009 in four top oncology journals. Data from the editorials were collected and each editorial opinion was classified as favorable, neutral or unfavorable with respect to the experimental therapy. RESULTS: Fifty-four editorials were included: 23 (43%) reported at least one conflict of interest, with the most frequent one being consultancy fees. Conclusions of editorial authors were classified as favorable in 18 editorials (33%). Sensitivity analysis found an association between self-reported conflict of interest of the editorial author and editorial favorable opinion (RR:2.7; 95% CI 1.2-6.1; p=0.019). DISCUSSION: Besides the high proportion of conflict of interest among editorial authors discussing phase III clinical trials, study interpretation may be influenced by their financial relationships with industry.

Adverse drug reactions and drug interactions as causes of hospital admission in oncology.

CONTEXT: Although several studies have evaluated the frequency of adverse drug reactions (ADRs) and drug-drug interactions (DDIs) in general medicine, few studies have looked at the epidemiology of adverse drug events (ADEs) in oncology. OBJECTIVES: We sought to investigate how many hospital admissions in oncology are related to a DDI or an ADR. METHODS: All cancer patients admitted to an oncology ward during an eight-month period had their charts retrospectively evaluated for reasons of hospitalization, using a 4-point scale (definitely, probably, possibly, or unlikely associated) to classify admissions by their probability of being associated with either a DDI or an ADR. RESULTS: From September 2007 to May 2008, there were 550 hospital admissions and 458 were eligible. Among unplanned admissions (n=298), 39 (13.0%, 95% confidence interval [CI] 9.4%-17.4%) were considered to be associated with an ADE, 33 (11.0%, 95% CI 7.7%-15.2%) with an ADR, and six (2.0%, 95% CI 0.7%-4.3%) with a DDI. The most common DDIs involved warfarin, captopril, and anti-inflammatory agents, and the most frequent ADR was neutropenic fever post-chemotherapy. Most patients were discharged completely recovered, but two patients died. CONCLUSION: Approximately one in 10 unplanned hospitalizations of cancer patients is associated with an ADE. Prospective and population-based studies are warranted to evaluate their magnitude in oncology.