Persistent inhibition of Candida albicans biofilm and hyphae growth on titanium by graphene nanocoating

ObjectivesCandida albicanscolonizes biomaterial surfaces and are highly resistant to therapeutics. Graphene nanocoating on titanium compromises initial biofilm formation. However, its sustained antibiofilm potential is unknown. The objective of this study was to investigate the potential of graphene nanocoating to decrease long-term fungal biofilm development and hyphae growth on titanium.MethodsGraphene nanocoating was deposited twice (TiGD) or five times (TiGV) on grade 4 titanium with vacuum assisted technique and characterized with Raman spectroscopy and atomic force microscope. The biofilm formation and hyphae growth of C. albicans was monitored for seven days by CFU, XTT, confocal, mean cell density and scanning electronic microscopy (SEM). Uncoated titanium was the Control. All tests had three independent biological samples and were performed in independent triplicates. Data was analyzed with one- or two-way ANOVA and Tukey's HSD (α = 0.05).ResultsBoth TiGD and TiGV presented less biofilms at all times points compared with Control. The confocal and SEM images revealed few adhered cells on graphene coated samples, absence of hyphae and no features of a mature biofilm architecture. The increase in number of layers of graphene nanocoating did not improve its antibiofilm potential.SignificanceThe graphene nanocoating exerted a long-term persistent inhibitory effect on the biofilm formation on titanium. The fewer cells that were able to attach on graphene coated titanium were scattered and unable to form a mature biofilm with hyphae elements. The findings open opportunities to prevent microbial attachment and proliferation on implantable materials without the use of antibiotics.     

Fighting viruses with materials science: Prospects for antivirus surfaces,drug delivery systems and artificial intelligence

ObjectiveViruses on environmental surfaces, in saliva and other body fluids represent risk of contamination for general population and healthcare professionals. The development of vaccines and medicines is costly and time consuming. Thus, the development of novel materials and technologies to decrease viral availability, viability, infectivity, and to improve therapeutic outcomes can positively impact the prevention and treatment of viral diseases.MethodsHerein, we discuss (a) interaction mechanisms between viruses and materials, (b) novel strategies to develop materials with antiviral properties and oral antiviral delivery systems, and (c) the potential of artificial intelligence to design and optimize preventive measures and therapeutic regimen.ResultsThe mechanisms of viral adsorption on surfaces are well characterized but no major breakthrough has become clinically available. Materials with fine-tuned physical and chemical properties have the potential to compromise viral availability and stability. Emerging strategies using oral antiviral delivery systems and artificial intelligence can decrease infectivity and improve antiviral therapies.SignificanceEmerging viral infections are concerning due to risk of mortality, as well as psychological and economic impacts. Materials science emerges for the development of novel materials and technologies to diminish viral availability, infectivity, and to enable enhanced preventive and therapeutic strategies, for the safety and well-being of humankind.     

Jet or conventional local anaesthesia? A randomized controlled split mouth study

Objectives

To compare the efficacy, acceptance and preference of conventional infiltration technique with a needleless jet anaesthetic device (Comfort-In).

Materials and methods

Non-fearful healthy adult volunteers, aged 19–40 years, were recruited in the Dental School of Aristotle University of Thessaloniki, Greece. Intact maxillary premolars were selected for local anaesthesia. Both techniques were applied sequentially with 35 min time gap on either buccal side on the same day by the same operator. The quadrant and the order of administration were randomly assigned using an online randomization generator. Immediately after administration, at 1, 3, 5, 10, 15, 20, 25 and 30 min, pulp vitality and soft tissue pain reaction tests were performed. Each participant was asked 6 questions in order to assess acceptance. At the end of the session, at 24 h and 7 days, all participants were asked to report any adverse events and their preference.

Results

In 63 volunteers who were successfully followed, 63 teeth received conventional local infiltration and 63 the Comfort-In. Both techniques presented with similar anaesthetic efficacy at 1, 3, 5, 10 and 15 min, whereas the conventional technique was more efficacious at 20 min (p < 0.005). Both presented similar acceptance apart from higher pain/discomfort during administration of Comfort-In (p = 0.002). Significantly higher preference was reported for the conventional technique immediately after the session, at 24 h and at 7 days (p < 0.0005); 19 (30.2%) reported the presence of ecchymosis or lacerations at the Comfort-In site as opposed to 5 (7.9%) with the conventional method (p < 0.0001).

Conclusion

Both techniques showed similar effectiveness. Conventional infiltration was preferred to needleless anaesthesia by non-fearful adult volunteers and was associated with less adverse events.

Clinical relevance

This study enhances the advantages of conventional local anaesthesia.

Trial registration

ISRCTN17400733

     

Tumors of the labial mucosa: a retrospective study of 1045 biopsies

Background To investigate the relative frequency of localized mucosal swellings of the upper and lower labial mucosa, the clinical-pathological diagnosis agreement and whether patient’s age and gender and tumor’s site and size may raise the suspicion of neoplasm. Material and Methods Retrospective analysis was performed on upper or lower labial mucosal tumors, histopathologically diagnosed between 2009-2018. The diagnostic categories developmental/reactive tumors, benign and malignant neoplasms were associated with patient’s age and gender and tumor’s site and size; clinical-pathological diagnosis agreement was, also, evaluated. Results Overall, 1000 (95.7%) developmental/reactive tumors, 35 (3.3%) benign and 10 (1%) malignant neoplasms were found. Upper/lower lip tumor ratio was 0.14:1. The diagnostic category was significantly associated with age (p<0.0001), site (p<0.0001) and diameter (p<0.0001). Age ≥60 years, tumor’s location on the upper lip and diameter >1cm were independent predictors for neoplasms. Patients presenting 2 or 3 of these variables were 20.2 times (p < 0.0001) or 33.6 times (p <0.0001), respectively, more likely to have a neoplasm. Complete/partial agreement between clinical and pathological diagnosis was seen in 96.3% of the cases. Conclusions Most lip tumors involve the lower lip and are reactive, but upper lip tumors measuring >1cm in patients≥60 years have significantly higher probability to be neoplasms. Key words:Lip, tumor, neoplasm, carcinoma, cyst.     

Posttraumatic Transdiaphragmatic Intercostal Hernia: Report of a Case and Review of the Literature

Intercostal hernias are rare, and usually occur following injuries of the thoracic wall. The scope of this report is to present a case of a 53-year-old obese patient that developed a transdiaphragmatic intercostal hernia. The patient presented with a palpable, sizeable, reducible mass in the right lateral thoracic wall, with evident bowel sounds in the area, 6 months after a motor-vehicle accident. On computed tomography (CT), the hernia sac contained part of the liver and part of the ascending colon. A surgical repair of the defect was performed, using a prosthetic patch. The patient''s postoperative course was uneventful and she remains recurrence free at 12 months after surgery. Intercostal hernias should be suspected following high-impact injuries of the thoracic wall, and CT scans will facilitate the diagnosis of intercostal hernia. We consider the surgical repair of the defect, with placement of a prosthetic mesh, as the treatment of choice to ensure a favorable outcome.Key words: Hernia, Transdiaphragmatic, Intercostal, Abdominal, MeshThe herniation of abdominal contents through the thoracic wall, as a result of the disruption of diaphragmatic and/or intercostal muscles, is an uncommon clinical entity.^1–3 This condition is usually reported to occur following penetrating or blunt injuries of the thoracic wall.⁴ However, there are several cases that have been described to be a consequence of a coughing–spell rib fracture, usually in patients with other predisposing factors such as chronic obstructive pulmonary disease, asthma, advanced age, or osteoporosis.^1,3,4The present report describes a case of a middle-aged obese patient that developed a transdiaphragmatic intercostal hernia involving the liver and the ascending colon 6 months after a traumatic incident. The underlying mechanism, the anatomical and diagnostic considerations, as well as the treatment options are also discussed.     

A phase II study of capecitabine plus oxaliplatin (XELOX): a new first-line option in metastatic colorectal cancer

Background: Capecitabine and oxaliplatin are both effective and well-tolerated monotherapies for the treatment of advanced colorectal cancer (CRC). Oxaliplatin has also been shown to be very effective when combined with 5-FU/LV in the first-line setting. Aim of the Study: Assess the efficacy and safety of capecitabine plus oxaliplatin (XELOX) in patients with previously untreated advanced CRC. Methods: Fifty-three patients with measurable disease received capecitabine 1,000 mg/m² twice daily on d 1–14 and oxaliplatin 130 mg/m² on d 1, every 3 wk. Of these, 52 were evaluable for safety and 49 for antitumor response. Results: There was a low rate of grade 1/2 adverse events; grade 3/4 events included leukopenia (10%), neutropenia (6%), thrombocytopenia (2%), nausea/vomiting (4%), and diarrhea (4%). The overall response rate was 39% (95% CI, 25–54%) and median time to disease progression was 7.8 mo. Conclusions: XELOX is an active and well-tolerated first-line treatment for advanced CRC. Randomized phase III studies are ongoing to compare XELOX with FOLFOX in view of the comparable efficacy and safety but superior convenience of XELOX therapy. Presented in part at the 39th American Society of Clinical Oncology Annual Meeting, Chicago, IL, May 31–June 3, 2003.     

KiSS-1/G protein-coupled receptor 54 metastasis suppressor pathway increases myocyte-enriched calcineurin interacting protein 1 expression and chronically inhibits calcineurin activity

OBJECTIVE: Tumor metastasis is a critical determinant of death from cancer. Metastin, a product of the KiSS-1 gene, is an endogenously expressed metastasis suppressor that is the ligand for G protein-coupled receptor 54 (GPR54), a Gq/11-coupled receptor. In the present study, our goal was to define the basis of GPR54 action using thyroid cancer cells as a model. DESIGN AND RESULTS: We used GPR54-null thyroid cancer cells to create a stable GPR54 overexpression model. Cell growth and cell migration of the GPR54-expressing lines were inhibited by recombinant metastin, and metastin stimulated the protein kinase C, ERK, and phosphatidylinositol-3-kinase pathways. To identify metastin-regulated genes, we performed microarray analyses using RNA isolated from GPR54 stable transfectants before and after 1 and 24 h of metastin stimulation. Consistent increases in expression of the gene encoding myocyte-enriched calcineurin interacting protein 1 (MCIP-1), an inhibitor of calcineurin, were identified and confirmed using real-time RT-PCR and Western blot. Functionally, metastin treatment of GPR54-expressing cells initially increased calcineurin activity, followed by a prolonged reduction in calcineurin activity for 24 and 48 h, consistent with the pattern of MCIP-1 expression. In addition, treatment with cyclosporin A, a calcineurin inhibitor, blocked cell migration. Lymph node metastasis in papillary thyroid cancers demonstrated loss of MCIP-1 expression in comparison with primary tumors. CONCLUSIONS: These data suggest a role for MCIP-1 and calcineurin inhibition in GPR54-mediated metastasis suppression in human cancers.     

KIT exon 11 codon 557/558 deletion/insertion mutations define a subset of gastrointestinal stromal tumors with malignant potential

AIM： To study the association of the frequency and pattern of KIT and PDGFRA mutations and clinicopathological factors in a group of patients with gastrointestinal stromal tumors （GIST）. METHODS： Thirty patients with GIST were examined. Exons 9, 11, 13, and 17 of the KIT and exons 12 and 18 of the PDGFRA gene were analyzed for the presence of mutations by PCR amplification and direct sequencing. RESULTS： KIT or PDGFRA mutations were detected in 21 of the 30 patients （70%）. Sixteen patients had mutations within KIT exon 11, three within KIT exon 9, and two within PDGFRA exon 18. GISTs with KIT exon 9 mutations were predominantly located in the small intestine, showed a spindle cell phenotype, and were assessed as potentially malignant. GISTs with KIT exon 11 mutations were located in the stomach and intestine, showed mainly a spindle cell phenotype, and were scored as potentially malignant （P 〈 0.05）. Tumors with KIT exon 11 codon 557/558 deletion/insertion mutations were found to be associated with a potentially malignant clinical behaviour （P 〈 0.003）. GISTs with PDGFRA mutations located in stomach showed a mixed cell phenotype and were classified as of very low or low moderate malignant potential. CONCLUSION： Determination of KIT and PDGFRA mutations should be additional parameters for the better prediction of GISTs clinical behaviour. Tumors with deletion/insertion mutations affecting codons 557/558 of the KIT gene seem to represent a distinct subset of malignant GISTs.     

Liver histology in ICU patients dying from sepsis：A clinico-pathological study

AIM：To determine end-stage pathologic changes in the liver of septic patients dying in the intensive care unit.
METHODS： Needle liver biopsies obtained immediately after death from 15 consecutive patients with sepsis and no underlying liver disease were subjected to routine histological examination. Liver function tests and clinical monitoring measurements were also recorded.
RESULTS： Liver biochemistries were increased in the majority of patients before death. Histology of liver biopsy specimens showed portal inflammation in 73.3%, centrilobular necrosis in 80%, lobular inflammation in 66.7%, hepatocellular apoptosis in 66.6% and cholangitis/cholangiolitis in 20% of patients. Mixed hepatitic/ cholestatic type of liver injury was observed in 6/15 （40%） patients and hepatitc in 9/15 （60%）. Steatosis was observed in 11/15 （73.3%） patients affecting 5%-80% of liver parenchyma. Among the histological features, the presence of portal inflammation in liver biopsy was associated with increased hospitalization in the ICU prior death （P = 0.026）.
CONCLUSION： Features of hepatitis and steatosis arethe main histological findings in the liver in the majority of patients dying from sepsis.