The p53 DNA damage response and Fanconi anemia DNA repair pathway protect against acetaldehyde-induced replication stress in esophageal keratinocytes.

Alcohol contributes to cellular accumulation of acetaldehyde, a primary metabolite of alcohol and a major human carcinogen. Acetaldehyde can form DNA adducts and induce interstrand crosslinks (ICLs) that are repaired by the Fanconi anemia DNA repair pathway (FA pathway). Individuals with deficiency in acetaldehyde detoxification or in the FA pathway have an increased risk of squamous-cell carcinomas (SCCs) including those of the esophagus. In a recent report, we described the molecular basis of acetaldehyde-induced DNA damage in esophageal keratinocytes [1]. We demonstrated that, at physiologically relevant concentrations, acetaldehyde induces DNA damage at the DNA replication fork. This resulted in replication stress, leading to activation of the ATR-Chk1-dependent cell cycle checkpoints. We also reported that the p53 DNA damage response is elevated in response to acetaldehyde and that the FA pathway limits acetaldehyde-induced genomic instability. Here, we highlight these findings and present additional results to discuss the role of the FA pathway and p53 DNA damage response in the protection against genomic instability and esophageal carcinogenesis.

Prevalence of depressive symptoms and associated factors in an urban, ophthalmic population.

OBJECTIVE: To determine the prevalence of depressive symptoms in an adult ophthalmic patient population and to delineate correlates. DESIGN: Cross-sectional study. PARTICIPANTS: Adult patients (⩾18 years) were approached in general and sub-specialty cornea, retina, and glaucoma ophthalmic clinics. A total of 367 patients from the four clinics were enrolled. METHODS: Depressive symptoms were assessed using the Patient Health Questionnaire-9. A cut-off score of ⩾10 was used to indicate clinically significant depressive symptoms. Patient Health Questionnaire-9 scores were used to evaluate bivariate relationships between depressive symptoms and distance visual acuity, ocular diagnosis, diabetes status, smoking status, demographic information, and medications. RESULTS: The majority of patients were female (52.9%) and Caucasian (48.6%). The mean age was 52.0 years (standard deviation: 16.7). Clinically significant depressive symptoms were present in 19.9% of patients overall; this rate varied slightly by clinic. Patients with low vision and blindness (visual acuity worse than 20/60) were more likely to have depressive symptoms (odds ratio = 2.82; 95% confidence interval: 1.90-4.21). Smoking and diabetes were also associated with depressive symptoms (odds ratio = 3.11 (2.66-3.64) and 3.42 (1.90-6.16), respectively). CONCLUSION: In a sample of urban ophthalmic adult patients, depressive symptoms were highly associated with low vision, smoking, and diabetes. This information can be used to target interventions to those at greatest risk of depressive symptoms.

Adherence to Follow-up Recommendations Among Individuals in the Philadelphia Glaucoma Detection and Treatment Project.

PURPOSE: To evaluate rates of adherence to free follow-up eye exam appointments among participants in the Philadelphia Glaucoma Detection and Treatment Project. PATIENTS AND METHODS: Ophthalmologists and testing equipment were brought directly to participants at risk for glaucoma at 43 community sites in Philadelphia. Those diagnosed with glaucoma-related pathology were recommended to return for follow-up to be reexamined on site. Rates of adherence and clinical and demographic risk factors for adherence were evaluated. RESULTS: Five hundred thirty-one participants were diagnosed with glaucoma-related conditions and recommended to attend community-based follow-up exams. Follow-up adherence rate was 61.2% (n=325/531). Significant factors associated with greater eye exam appointment adherence, based on our univariable analysis, included final diagnosis of glaucoma (risk ratio [RR]=1.33; 95% confidence interval [CI], 1.13-1.57), male sex (RR=1.19; 95% CI, 1.04-1.36), white race (RR=1.26; 95% CI, 1.08-1.48), age (RR=1.17; 95% CI, 1.00-1.37) recommendation for glaucoma medication (RR=1.52; 95% CI, 1.35-1.71), recommendation for laser peripheral iridotomy (RR=1.18; 95% CI, 1.02-1.35), diagnosis of age-related macular degeneration (RR=1.42; 95% CI, 1.13-1.77) and an increased intraocular pressure (>22 mm Hg in the worse eye) (RR=1.23; 95% CI, 1.06-1.42). On the basis of our multivariable model, diagnosis, sex, and recommended glaucoma medications were significantly associated with follow-up adherence. CONCLUSIONS: This study demonstrates that individuals living in underserved urban communities would take advantage of free eye exams in community sites and return for follow-up eye exams in these same settings. Future studies could investigate interventions to improve eye exam appointment adherence in community-based settings to detect glaucoma-eye conditions.

The Host Microbiome Regulates and Maintains Human Health: A Primer and Perspective for Non-Microbiologists.

Humans consider themselves discrete autonomous organisms, but recent research is rapidly strengthening the appreciation that associated microorganisms make essential contributions to human health and well being. Each person is inhabited and also surrounded by his/her own signature microbial cloud. A low diversity of microorganisms is associated with a plethora of diseases, including allergy, diabetes, obesity, arthritis, inflammatory bowel diseases, and even neuropsychiatric disorders. Thus, an interaction of microorganisms with the host immune system is required for a healthy body. Exposure to microorganisms from the moment we are born and appropriate microbiome assembly during childhood are essential for establishing an active immune system necessary to prevent disease later in life. Exposure to microorganisms educates the immune system, induces adaptive immunity, and initiates memory B and T cells that are essential to combat various pathogens. The correct microbial-based education of immune cells may be critical in preventing the development of autoimmune diseases and cancer. This review provides a broad overview of the importance of the host microbiome and accumulating knowledge of how it regulates and maintains a healthy human system. Cancer Res; 77(8); 1783-812. ©2017 AACR.