Panel 1 : Epidemiology and Diagnosis

Objective To create a literature review between 2011 and June 1, 2015, on advances in otitis media (OM) epidemiology and diagnosis (including relevant audiology studies). Data Sources Electronic search engines (PubMed, EMBASE, and Cochrane Library) with a predefined search strategy. Review Methods Articles with appropriate epidemiologic methodology for OM, including acute mastoiditis wand eustachian tube dysfunction. Items included OM worldwide and in high-risk populations, OM-related hearing loss, news in OM diagnostics, prenatal risk factors and comorbidities, postnatal risk factors, genetics, microbiological epidemiology, guidelines, and quality of life. Conclusions Diagnostic evidence and genetic studies are increasing; guidelines are introduced worldwide; and there is evidence of benefit of pneumococcal conjugate vaccines. New risk factors and comordities are identified in the study period, and quality of life is affected in children and their families. Implications for Practice Chronic suppurative OM occurs worldwide and contributes to lifelong hearing loss. Uniform definitions are still lacking and should be provided. An association between HIV and chronic suppurative OM has been found. Tympanometry is recommended for diagnosis, with or without pneumatic otoscopy. Video otoscopy, algorithms, and validated questionnaires may assist clinicians. Childhood obesity is associated with OM. Heritability accounts for 20% to 50% of OM diagnoses. OM-prone children seem to produce weaker immunologic responses to pneumococcal conjugate vaccines. Clinicians tend to individualize treatment without adhering to guidelines

Nuclear Interaction between ADR-Induced p65 and p53 Mediates Cardiac Injury in iNOS (−/−) Mice

Adriamycin (ADR) treatment causes an imbalance in the levels of nitric oxide ((•)NO) and superoxide (O(2) (•−)) production leading to cardiac injury. Previously we demonstrated that mice lacking inducible nitric oxide synthase (iNOS) have increased oxidative stress and mitochondrial injury. The molecular events leading to increased mitochondrial injury in iNOS deficient mice is unknown. ADR in the absence of iNOS preferentially activates a proapoptotic pathway without a concurrent increase in prosurvival pathways. Treatment with ADR leads to an increase in DNA binding activity of nuclear factor kappa B (NFκB) and p53 in wildtype mice. Following ADR treatment, p53, but not NFκB DNA binding activity, as well as the level of Bax, a p53 target gene, was increased in iNOS (−/−) mice. This apoptotic signaling effect in iNOS (−/−) is alleviated by overexpression of manganese superoxide dismutase (MnSOD). Increases in NFκB and p53 in ADR-treated wildtype mice did not lead to increases in target genes such as MnSOD, bcl-xL, or Bax. Moreover, co-immunoprecipitation analysis revealed that p65, a prominent member of the NFκB family, interacts with p53 in the nucleus. These results suggest that NFκB and p53 may counter act one another's actions in ADR-treated wildtype (WT) mice. Further, these results identify a novel mechanism by which oxidative stress may regulate transcription of proapoptotic genes