Characterisation and microleakage of a new hydrophilic fissure sealant – UltraSeal XT® hydro™

Objectives: The new hydrophilic fissure sealant, UltraSeal XT® hydro™ (Ultradent Products, USA), was characterised and its in vitro resistance to microleakage after placement on conventionally acid etched and sequentially lased and acid etched molars was investigated. Materials and Methods: The sealant was characterised by Fourier transform infra-red spectroscopy, (FTIR), scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX) and Vickers indentation test. Occlusal surfaces of extracted human molars were either conventionally acid etched (n = 10), or sequentially acid etched and laser irradiated (n = 10). UltraSeal XT® hydro™ was applied to both groups of teeth which were then subjected to 2500 thermocycles between 5 and 55 °C prior to microleakage assessment by fuchsin dye penetration. Results: UltraSeal XT® hydro™ is an acrylate-based sealant which achieved a degree of conversion of 50.6 ± 2.2% and a Vickers microhardness of 24.2 ± 1.5 under standard light curing (1000 mWcm-2 for 20 s). Fluoride ion release was negligible within a 14-day period. SEM and EDX analyses indicated that the sealant comprises irregular sub-micron and nano-sized silicon-, barium- and aluminium-bearing filler phases embedded within a ductile matrix. Laser preconditioning was found to significantly reduce microleakage (Mann-Whitney U test, p < 0.001). The lased teeth presented enhanced surface roughness on a 50 to 100 μm scale which caused the segregation and concentration of the filler particles at the enamel-sealant interface. Conclusion: Laser preconditioning significantly decreased microleakage and increased enamel surface roughness which caused zoning of the filler particles at the enamel-sealant interface

Needle stick injuries among dental students: risk factors and recommendations for prevention

Aim: To evaluate the risk factors of needle stick injuries (NSIs) sustained by undergraduate dental students and nurse students at the King&#x0027;s College London (KCL) Dental Institute. Materials and methods: A retrospective study evaluated the incident reports relating to NSIs reported over a period of 2 years. Factors including the dental department, study year, and when the injury took place during administration of local anaesthesia (LA) and recapping conventional syringe or clearing work surface or during disposal. Results: This report showed that students are at the highest risk of NSIs at the fourth year of their 5-year BDS course. About one-third of injuries were reported among this group of students followed by year 5 students (25%). Oral surgery clinics were the major source of incident reporting when compared with other specialised dental clinics within the institute. The left hands of the students were the most frequently affected by such injuries and then the right hands of student dental nurses. The attempt of needle recapping of conventional syringes was the least reported mechanism of injuries and constituted only 15% of the total injuries and mainly occurred in third year students. The most frequent injuries among student nurses were during disposal of the needle. Conclusion: Less NSIs occur when using safety syringes. A non-recapping policy with immediate disposal of either the conventional or safety syringe systems after injection would prevent all clearance-related NSIs sustained by nurses. To avoid NSIs, education plays a vital role particularly with effective implementation of the change to safety syringes with appropriate training

Blockade of insulin-like growth factors increases efficacy of paclitaxel in metastatic breast cancer.

Breast cancer remains the leading cause of cancer death in women owing to metastasis and the development of resistance to established therapies. Macrophages are the most abundant immune cells in the breast tumor microenvironment and can both inhibit and support cancer progression. Thus, gaining a better understanding of how macrophages support cancer could lead to the development of more effective therapies. In this study, we find that breast cancer-associated macrophages express high levels of insulin-like growth factors 1 and 2 (IGFs) and are the main source of IGFs within both primary and metastatic tumors. In total, 75% of breast cancer patients show activation of insulin/IGF-1 receptor signaling and this correlates with increased macrophage infiltration and advanced tumor stage. In patients with invasive breast cancer, activation of Insulin/IGF-1 receptors increased to 87%. Blocking IGF in combination with paclitaxel, a chemotherapeutic agent commonly used to treat breast cancer, showed a significant reduction in tumor cell proliferation and lung metastasis in pre-clinical breast cancer models compared to paclitaxel monotherapy. Our findings provide the rationale for further developing the combination of paclitaxel with IGF blockers for the treatment of invasive breast cancer, and Insulin/IGF1R activation and IGF+ stroma cells as potential biomarker candidates for further evaluation

Activated CD4+ T cells enhance radiation effect through the cooperation of interferon-γ and TNF-α

<p>Abstract</p> <p>Background</p> <p>Approaches that enhance radiation effect may lead to improved clinical outcome and decrease toxicity. Here we investigated whether activated CD4+ T cells (aCD4) can serve as an effective radiosensitizer.</p> <p>Methods</p> <p>CD4+ T cells were activated with anti-CD3 and anti-CD28 mAbs. Hela cells were presensitized with aCD4 or conditioned supernatant (aCD4S) or recombinant cytokines for 2 days, followed γ-irradiation. The treated cells were cultured for an additional 2 to 5 days for cell proliferation, cell cycle, and western blot assays. For confirmation, other cancer cell lines were also used.</p> <p>Results</p> <p>Presensitization of tumor cells with aCD4 greatly increased tumor cell growth inhibition. Soluble factors secreted from activated CD4⁺T cells were primarily responsible for the observed effect. IFN-γ seemed to play a major role. TNF-α, though inactive by itself, significantly augmented the radiosensitizing activity of IFN-γ. aCD4S, but not IFN-γ or IFN-γ/TNF-α combination, was found to enhance the γ-irradiation-induced G2/M phase arrest. Bax expression was highly upregulated in Hela cells presensitized with aCD4S followed by γ-irradiation. The radio-sensitizing activity of aCD4 is not uniquely observed with Hela cell line, but also seen with other cancer cell lines of various histology.</p> <p>Conclusions</p> <p>Our findings suggest possible molecular and cellular mechanisms that may help explain the radio-sensitization effect of activated lymphocytes, and may provide an improved strategy in the treatment of cancer with radiotherapy.</p

Interleukin-4 enhances proliferation of human pancreatic cancer cells: evidence for autocrine and paracrine actions

Interleukin-4 (IL-4) is an immunomodulatory cytokine, which can inhibit the growth of tumour cells. Pancreatic cancer cells and tissues express high levels of IL-4 receptors. The aim of this study was to characterise the effects of IL-4 on the growth and signalling pathways of pancreatic cancer cells. Cell growth was determined by cell counting and MTT assays in association with fluorescence-activated cell sorter analysis, IL-4 expression using ELISA and real-time PCR techniques, and signal transduction using immunoprecipitation or immunoblot analysis. We now report for the first time that IL-4 significantly enhanced the growth of five out of six cultured pancreatic cancer cell lines in a dose-dependent manner in association with an increased fraction of cells in S-phase. Surprisingly, all six cell lines expressed endogenous IL-4, and IL-4 was detectable in the supernatant. Incubating cells with neutralising IL-4 antibodies resulted in a significant inhibition of basal growth in three cell lines, including IL-4-unresponsive MIA PaCa-2 cells, which however expressed the highest endogenous IL-4 levels. Interleukin-4 enhanced activity of MAPK, Akt-1, and Stat3 in IL-4-responsive, but not in IL-4-unresponsive MIA PaCa-2 cells; however, IL-4 enhanced tyrosine phosphorylation of insulin receptor substrate-1 and -2 in all cell lines. Our results demonstrate for the first time that pancreatic cancer cells produce IL-4 and that IL-4 can act as a growth factor in pancreatic cancer cells. Together with the observation that neutralising IL-4 antibodies can inhibit the growth of these cells, our results suggest that IL-4 may act as an autocrine growth factor in pancreatic cancer cells and also give rise to the possibility that cancer-derived IL-4 may suppress cancer-directed immunosurveillance in vivo in addition to its growth-promoting effects, thereby facilitating pancreatic tumour growth and metastasis

Mast cells and eosinophils in invasive breast carcinoma

<p>Abstract</p> <p>Background</p> <p>Inflammatory cells in the tumour stroma has gained increasing interest recently. Thus, we aimed to study the frequency and prognostic impact of stromal mast cells and tumour infiltrating eosinophils in invasive breast carcinomas.</p> <p>Methods</p> <p>Tissue microarrays containing 234 cases of invasive breast cancer were prepared and analysed for the presence of stromal mast cells and eosinophils. Tumour infiltrating eosinophils were counted on hematoxylin-eosin slides. Immunostaining for tryptase was done and the total number of mast cells were counted and correlated to the proliferation marker Ki 67, positivity for estrogen and progesterone receptors, clinical parameters and clinical outcome.</p> <p>Results</p> <p>Stromal mast cells were found to correlate to low grade tumours and estrogen receptor positivity. There was a total lack of eosinophils in breast cancer tumours.</p> <p>Conclusion</p> <p>A high number of mast cells in the tumours correlated to low-grade tumours and estrogen receptor positivity. Eosinophils are not tumour infiltrating in breast cancers.</p

IGF-I induced genes in stromal fibroblasts predict the clinical outcome of breast and lung cancer patients

<p>Abstract</p> <p>Background</p> <p>Insulin-like growth factor-1 (IGF-I) signalling is important for cancer initiation and progression. Given the emerging evidence for the role of the stroma in these processes, we aimed to characterize the effects of IGF-I on cancer cells and stromal cells separately.</p> <p>Methods</p> <p>We used an <it>ex vivo </it>culture model and measured gene expression changes after IGF-I stimulation with cDNA microarrays. <it>In vitro </it>data were correlated with <it>in vivo </it>findings by comparing the results with published expression datasets on human cancer biopsies.</p> <p>Results</p> <p>Upon stimulation with IGF-I, breast cancer cells and stromal fibroblasts show some common and other distinct response patterns. Among the up-regulated genes in the stromal fibroblasts we observed a significant enrichment in proliferation associated genes. The expression of the IGF-I induced genes was coherent and it provided a basis for the segregation of the patients into two groups. Patients with tumours with highly expressed IGF-I induced genes had a significantly lower survival rate than patients whose tumours showed lower levels of IGF-I induced gene expression (<it>P </it>= 0.029 - Norway/Stanford and <it>P </it>= 7.96e-09 - NKI dataset). Furthermore, based on an IGF-I induced gene expression signature derived from primary lung fibroblasts, a separation of prognostically different lung cancers was possible (<it>P </it>= 0.007 - Bhattacharjee and <it>P </it>= 0.008 - Garber dataset).</p> <p>Conclusion</p> <p>Expression patterns of genes induced by IGF-I in primary breast and lung fibroblasts accurately predict outcomes in breast and lung cancer patients. Furthermore, these IGF-I induced gene signatures derived from stromal fibroblasts might be promising predictors for the response to IGF-I targeted therapies.</p> <p>See the related commentary by Werner and Bruchim: <url>http://www.biomedcentral.com/1741-7015/8/2</url></p

Gene Set Enrichment Analysis Identifies LIF as a Negative Regulator of Human Th2 Cell Differentiation

In this study we show that IL-4 is crucial during reinforcement window of human Th2 differentiation for optimal Th2 development. We have also shown here that during this stage, IL-4 helps in cellular decision-making process of differentiation versus proliferation. We have combined computational and experimental methods to analyze Th2 transcription network to name novel players of the process of Th2 differentiation. Here we report that LIF through STAT3 negatively regulates Th2 differentiation. This approach can be generalized to analyze “omics” data to identify key regulatory modules

Dental sealant knowledge, opinion, values and practice of Spanish dentists

[Background] Multiple guidelines and systematic reviews recommend sealant use to reduce caries risk. Yet, multiple reports also indicate that sealants are significantly underutilized. This study examined the knowledge, opinions, values, and practice (KOVP) of dentists concerning sealant use in the southwest region of Andalusia, Spain. This is a prelude to the generation of a regional plan for improving children’s oral health in Andalusia.[Methods] The survey’s target population was dentists working in western Andalusia, equally distributed in the provinces of Seville, Cadiz, and Huelva (N=2,047). A convenience sample of meeting participants and meeting participant email lists (N=400) were solicited from the annual course on Community and Pediatric Dentistry. This course is required for all public health sector dentists, and is open to all private sector dentists. Information on the dentist’s KOVP of sealants was collected using four-part questionnaire with 31, 5-point Likert-scaled questions.[Results] The survey population demographics included 190 men (48%) and 206 women (52%) with an average clinical experience of 10.6 (± 8.4) years and 9.3 (± 7.5) years, respectively. A significant sex difference was observed in the distribution of place of work (urban/suburb) (p=0.001), but no sex differences between working sector (public/private). The mean ± SD values for each of the four KOVP sections for pit and fissure sealants were: knowledge = 3.57 ± 0.47; opinion = 2.48 ± 0.47; value = 2.74 ± 0.52; and practice = 3.48 ± 0.50. No sex differences were found in KOVP (all p >0.4). Independent of sex: knowledge statistically differed by years of experience and place of work; opinion statistically differed by years of experience and sector; and practice statistically differed by years of experience and sector. Less experienced dentists tended to have slightly higher scores (~0.25 on a Likert 1–5 scale). Statistically significant correlations were found between knowledge and practice (r=0.44, p=0.00) and between opinion and value (r=0.35, p=0.00).[Conclusions] The results suggest that, similar to other countries, Andalusian dentists know that sealants are effective, have neutral to positive attitudes toward sealants; though, based on epidemiological studies, underuse sealants. Therefore, methods other than classical behavior change (eg: financial or legal mechanisms) will be required to change practice patterns aimed at improving children's oral health.We acknowledge the following sources for invaluable financial support NIMHD 1 R34 DE022272 (NIH2385) and NIDCR 1 U24 MD006964