Promoter DNA methylation patterns in oral, laryngeal and oropharyngeal anatomical regions are associated with tumor differentiation, nodal involvement and survival.

Differentially methylated regions (DMRs) can be used as head and neck squamous cell carcinoma (HNSCC) diagnostic, prognostic and therapeutic targets in precision medicine workflows. DNA from 21 HNSCC and 10 healthy oral tissue samples was hybridized to a genome-wide tiling array to identify DMRs in a discovery cohort. Downstream analyses identified differences in promoter DNA methylation patterns in oral, laryngeal and oropharyngeal anatomical regions associated with tumor differentiation, nodal involvement and survival. Genome-wide DMR analysis showed 2,565 DMRs common to the three subsites. A total of 738 DMRs were unique to laryngeal cancer (n=7), 889 DMRs were unique to oral cavity cancer (n=10) and 363 DMRs were unique to pharyngeal cancer (n=6). Based on the genome-wide analysis and a Gene Ontology analysis, 10 candidate genes were selected to test for prognostic value and association with clinicopathological features. TIMP3 was associated with tumor differentiation in oral cavity cancer (P=0.039), DAPK1 was associated with nodal involvement in pharyngeal cancer (P=0.017) and PAX1 was associated with tumor differentiation in laryngeal cancer (P=0.040). A total of five candidate genes were selected, DAPK1, CDH1, PAX1, CALCA and TIMP3, for a prevalence study in a larger validation cohort: Oral cavity cancer samples (n=42), pharyngeal cancer tissues (n=25) and laryngeal cancer samples (n=52). PAX1 hypermethylation differed across HNSCC anatomic subsites (P=0.029), and was predominantly detected in laryngeal cancer. Kaplan-Meier survival analysis (P=0.043) and Cox regression analysis of overall survival (P=0.001) showed that DAPK1 methylation is associated with better prognosis in HNSCC. The findings of the present study showed that the HNSCC subsites oral cavity, pharynx and larynx display substantial differences in aberrant DNA methylation patterns, which may serve as prognostic biomarkers and therapeutic targets.

Cigarette Smoking Modulation of Saliva Microbial Composition and Cytokine Levels.

Tobacco use has been implicated as an immunomodulator in the oral cavity and contributes to the development of oral cancer. In the present study, we investigated the effects of cigarette smoking on bacterial diversity and host responses compared to healthy nonsmoking controls. Saliva samples were collected from eighteen smokers and sixteen nonsmoking individuals by passive drool. The 16S rRNA gene was used to characterize the salivary microbiome by using the Illumina MiSeq platform. Cytokine and chemokine expression analyses were performed to evaluate the host response. Significant differences in cytokine and chemokine expression levels of MDC, IL-10, IL-5, IL-2, IL-4, IL-7, adrenocorticotropic hormone (ACTH), insulin, and leptin were observed between smokers and nonsmokers. Taxonomic analyses revealed differences between the two groups, and some bacterial genera associated with the smokers group had correlations with hormones and cytokines identified as statistically different between smokers and nonsmokers. These factors have been associated with inflammation and carcinogenesis in the oral cavity. The data obtained may aid in the identification of the interactions between the salivary microbiome, host inflammatory responses, and metabolism in smokers.

Prescribing patterns and safety of mezclitas for respiratory illnesses.

OBJECTIVE: To evaluate the prescribing patterns of compound mixtures of cough and cold liquid medications, known as mezclitas, which are prescribed to patients with respiratory illnesses in Puerto Rico. Secondary objectives include assessing the potential safety of these mixtures and patients' perception of them. METHODS: Using a cross sectional study approach, a convenience sample was obtained from five pharmacies in Puerto Rico, from October 2008 to October 2009. Patients were asked to complete a 9-item questionnaire about demographic information, in addition to their mezclita prescription data. RESULTS: The mean age of patients was 43 years with a range of less than 12 months to 101 years. For children < four years of age, 71% were prescribed cough and cold medications. Sixty-four percent of the prescriptions were given to females. The most prevalent ingredient employed was guaifenesin, which appeared in about 77% of the mezclitas. 'Common cold' was the principal diagnosis for 62% of the prescriptions, of which 75% of these prescriptions contained a corticosteroid and 17% contained a beta2 agonist bronchodilator. The top medical prescribing specialty was general medicine (51%). Thirty-eight percent of hypertensive patients were prescribed a decongestant. The majority of diabetic patients (60%) were dispensed a corticosteroid. Most (74%) patients reported that they had a rapid and good response to their mezclita. CONCLUSION: Mezclitas were most commonly prescribed for acute symptoms of upper respiratory illness by general physicians despite possible side effects. This study suggests that the prescription patterns of mezclitas do not always consider evidence-based medicine treatment guidelines.

[Alzheimer-type dementia in a sample of Puerto Rican elderly: pilot study on the usefulness and assessment of a screening battery]. / Demencia tipo Alzheimer en una muestra de ancianos puertorriqueños: estudio piloto sobre la utilidad y evaluación de una batería de cernimiento.

Dementia is one of the most prevalent conditions in the elderly. Dementia is defined as a decrease in memory, thinking and reasoning having its most common form as Alzheimer dementia. Alzheimer dementia (AD) economic cost to society is around 100 billion dollars annually. Unfortunately, at this point Puerto Rico, have neuro-psychopathology instruments limitations to perform valid and sensitive screening of DA. This study was directed to evaluate a battery of neuropsychological screening instruments for Puerto Rican elderly (60 to 100 years, n = 50) with Alzheimer's dementia. In addition, calculate the sensitivity and specificity of the instruments. The tests where composed as screening battery and included CERAD (Instruments created by the Consortium to Establish a Registry for Alzheimer's Disease), MMSE (Mini mental Status Evaluation), EIWA-III (specifically the digit retention and similarities subtest that try to evaluated memory, concentration and abstract thinking) and the Tuokkos' test (clock drawing in order to evaluated visual-constructional skills). As show by ROC Curve (Receiver Operating Characteristic Curve) for our research, the sensitivity for CERAD was 95.7% with an specificity of 49%; MMSE (Mini Mental Status Evaluation) account for 89 sensitivity and 60% specificity; EIWA-III and subtest (specifically the digit retention and similarities subtest) respectively was 80.4% sensitivity and 44.7% specificity; and sensitivity of 82.6% and specificity of 44.7%. Tuokkos' Clock Test accounted for 76.1% sensitivity, and 23.4% specificity. Reported indexes were within acceptable limits for screening tests. We suggest a sample increment and new testing with additional instruments.