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BackgroundSalivary gland adenoid cystic carcinoma (ACC) is a rare cancer, accounting for only 1% of all head and neck malignancies. ACC is well known for perineural invasion and distant metastasis, but its underlying molecular mechanisms of carcinogenesis are still unclear.Principal FindingsHere, we show that a novel oncogenic candidate, suprabasin (SBSN), plays important roles in maintaining the anchorage-independent and anchorage-dependent cell proliferation in ACC by using SBSN shRNA stably transfected ACC cell line clones. SBSN is also important in maintaining the invasive/metastatic capability in ACC by Matrigel invasion assay. More interestingly, SBSN transcription is significantly upregulated by DNA demethylation induced by 5-aza-2′-deoxycytidine plus trichostatin A treatment and the DNA methylation levels of the SBSN CpG island located in the second intron were validated to be significantly hypomethylated in primary ACC samples versus normal salivary gland tissues.Conclusions/SignificanceTaken together, these results support SBSN as novel oncogene candidate in ACC, and the methylation changes could be a promising biomarker for ACC.

Similar to previous studies, children had weight gain after TA. In this analysis, younger age (≤ 6 years) was a significant predictor of postoperative weight gain. Future research should prospectively evaluate the association between weight gain and demographic factors in children undergoing TA, with special attention to the relationship with age.

Background The impact of delirium on survival of elderly patients remains undetermined with conflicting results from clinical studies and meta-analysis. In this study we assessed the relationship between long-term mortality and incident postoperative delirium in elderly patients undergoing hip fracture repair. Methods Patients ≥ 65 years old who were not delirious before undergoing hip fracture repair were included in a database maintained prospectively from March 1999 until July 2009. All participating patients underwent delirium assessment on the 2nd postoperative day using the confusion assessment method. Survival of the participants was determined as of October 2012. Results In 459 patients the mean (SD) period of evaluation from surgery until death or study closure was 4.1 (3.5) years with patients followed for as long as 13.6 years. Preoperative cognitive impairment was present in 120 patients (26.1%) and delirium on the 2nd postoperative day was observed in 151 (32.9%) of these. Although univariate analysis demonstrated a strong association between incident postoperative delirium and survival, this relationship did not persist in a multivariate model. Survival was a function of age at the time of surgery (p < 0.001), illness severity as determined by the ASA physical status score (p < 0.001), and duration of admission to the intensive care unit after surgery (p < 0.001). Incorporation of incident postoperative delirium did not meaningfully (p = 0.22) enhance the final survival model. In such a model, the hazard ratio [CI95] for incident postoperative delirium was 1.25 [0.92, 1.48]. Conclusions Incident postoperative delirium was not significantly associated with decreased survival in elderly patients undergoing hip fracture repair.

Objective To investigate the feasibility of using a digital language processor (DLP) to objectively quantify the auditory and social environment of older adults. Design Thirty-seven participants aged 64–91 residing in a retirement community were asked to wear a DLP to record their auditory and language environment during one waking day. Recordings were analyzed with specialized software to derive quantitative estimates such as the number of spoken words heard and percent of time spent around meaningful speech versus television/radio. Results Adequate DLP recordings that began before 10 A.M. and lasted for ≥ 10 hours were collected from 24 participants. The mean duration of recording was 13 hours and 13 minutes, and individuals spent a mean of 26.7% (range=4% – 58%) of their waking day near a television or other electronic sounds. The projected mean word count over a maximum of 16 hours was 33,141 with nearly a 14-fold range between the lowest and highest observed values (range=5120 – 77,882). Conclusions High-quality objective data on the auditory environment of older adults can be feasibly measured with the DLP. Findings from this study may guide future studies investigating auditory and language outcomes in older adults.

These results indicate that age and device placement play important roles in terms of intranasal deposition, when administering aerosol with Accuspray(™) to children.

Objective: DNA methylation alterations, with either gain or loss of CpG methylation in the promoter region, can alter the expression of tumor suppressor genes or oncogenes. This contributes to the tumorigenesis of human cancers, including salivary adenoid cystic carcinoma (ACC). In this study, we used a DNA methylation array (Illumina HumanMethylation27 BeadChip, San Diego, CA) to screen for novel oncogene and tumor suppressor gene (TSG) candidates under the control of promoter methylation in ACC. Methods: The Illumina HumanMethylation27 BeadChip Array was used to analyze the DNA methylation patterns of ∼14.000 genes at 27,578 CpG sites in 21 ACC and 13 normal salivary gland tissues. With our basic screening algorithm, we narrowed the list down to ∼100 tumor suppressor gene candidates (hypermethylated in tumor) and oncogene candidates (hypomethylated in tumor). Next, the differential methylation levels in the promoter region of candidates were validated by bisulfite genomic sequencing in four primary ACC and four normal salivary gland tissues. Candidate genes that showed differential methylation were then confirmed by analyzing gene re-expression in seven cell lines treated with 5-Aza deoxycytidine, a global demethylating agent. Furthermore, the expression levels of the candidate genes were examined by quantitative reverse transcription PCR (qRT-PCR) in a separate ACC cohort. Lastly, the DNA methylation levels of promising candidate genes were validated by quantitative methylation specific PCR (qMSP) in a larger ACC cohort. Results: With the methylation array, we initially identified 28 oncogene candidates which displayed relative hypomethylation and 64 TSG candidates that showed relative hypermethylation in ACC compared to normal tissues. After the above mentioned additional validation steps were performed, we settled on two promising candidates, PDE9A and TP53TG3, that were significantly hypomethylated and overexpressed in primary ACC tumors compared to normal salivary gland tissue. Furthermore, the expression of PDE9A and TP53TG3 demonstrated consistent upregulation after 5-aza-cytidine treatment of cancer cell lines, suggesting that promoter methylation does play in a role in controlling gene expression. Conclusions: The Illumina HumanMethylation27 BeadChip array is a reliable and efficient tool for analyzing global gene methylation. It is useful in screening for novel oncogene and TSG candidates controlled by promoter methylation in salivary gland ACC. PDE9A and TP53TG3 were identified as promising novel oncogene candidates in salivary gland ACC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5017. doi:1538-7445.AM2012-5017