Faculty Bibliography

Ependymal tumors across age groups are currently classified and graded solely by histopathology. It is, however, commonly accepted that this classification scheme has limited clinical utility based on its lack of reproducibility in predicting patients' outcome. We aimed at establishing a uniform molecular classification using DNA methylation profiling. Nine molecular subgroups were identified in a large cohort of 500 tumors, 3 in each anatomical compartment of the CNS, spine, posterior fossa, supratentorial. Two supratentorial subgroups are characterized by prototypic fusion genes involving RELA and YAP1, respectively. Regarding clinical associations, the molecular classification proposed herein outperforms the current histopathological classification and thus might serve as a basis for the next World Health Organization classification of CNS tumors.

A number of secondary plant metabolites (e.g., flavonoids) possess antiviral/antimicrobial activity. Most flavonoids, however, are difficult to study, as they are immiscible in water-based systems. The relatively new semisynthetic alpha-glucosyl hesperitin (GH), and the natural plant product epigallocatechin gallate (EGCG) are unique among most flavonoids, as these flavonoids are highly soluble. The antiviral activity of these plant metabolites were investigated using the rotavirus as a model enteric virus system. Direct loss of virus structural integrity in cell-free suspension and titration of amplified RTV in host cell cultures was measured by a quantitative enzyme-linked immunosorbent assay (qEIA). After 30 min. 100 x 10(3) mug/ml GH reduced RTV antigen levels by ca. 90%. The same compound reduced infectivity (replication in cell culture) by a similar order of magnitude 3 to 4 days post inoculation. After 3 days in culture, EGCG concentrations of 80, 160, and 320 mug/ml reduced RTV infectivity titer levels to ca. 50, 20, and 15% of the control, respectively. Loss of RTV infectivity titers occurred following viral treatment by parallel testing of both GH and EGCG, with the latter, markedly more effective. Cytotoxicity testing showed no adverse effects by the phenolic concentrations used in this study. The unique chemical structure of each flavonoid rather than each phenolic's inherent solubility may be ascribed to those marked differences between each molecule's antiviral (anti-RTV) effects. The solubility of EGCG and GH obviated our need to use potentially confounding or obfuscating carrier molecules (e.g., methanol, ethanol, DMSO) denoting our use of a pure system environ. Our work further denotes the need to address the unique chemical nature of secondary plant metabolites before any broad generalizations in flavonoid (antiviral) activity may be proposed.

The Mauthner cell (M-cell) is a command-like neuron in teleost fish whose firing in response to aversive stimuli is correlated with short-latency escapes [1-3]. M-cells have been proposed as evolutionary ancestors of startle response neurons of the mammalian reticular formation [4], and studies of this circuit have uncovered important principles in neurobiology that generalize to more complex vertebrate models [3]. The main excitatory input was thought to originate from multisensory afferents synapsing directly onto the M-cell dendrites [3]. Here, we describe an additional, convergent pathway that is essential for the M-cell-mediated startle behavior in larval zebrafish. It is composed of excitatory interneurons called spiral fiber neurons, which project to the M-cell axon hillock. By in vivo calcium imaging, we found that spiral fiber neurons are active in response to aversive stimuli capable of eliciting escapes. Like M-cell ablations, bilateral ablations of spiral fiber neurons largely eliminate short-latency escapes. Unilateral spiral fiber neuron ablations shift the directionality of escapes and indicate that spiral fiber neurons excite the M-cell in a lateralized manner. Their optogenetic activation increases the probability of short-latency escapes, supporting the notion that spiral fiber neurons help activate M-cell-mediated startle behavior. These results reveal that spiral fiber neurons are essential for the function of the M-cell in response to sensory cues and suggest that convergent excitatory inputs that differ in their input location and timing ensure reliable activation of the M-cell, a feedforward excitatory motif that may extend to other neural circuits.

INTRODUCTION: Congenital maxillomandibular syngnathia, or fusion of the jaws, is a rare condition that has a broad spectrum of presentations. The restricted mouth opening can lead to issues with feeding, swallowing, and respiration resulting in failure to thrive and temporomandibular joint ankylosis. Early recognition and treatment is necessary for proper growth and development. CASE REPORT: We report a 1-day-old male with isolated bilateral soft tissue alveolar fibrous bands. He presented with difficulty feeding secondary to trismus. No bony or muscular involvement in the synechiae was noted and the remainder of the physical exam was unremarkable. The bilateral alveolar synechiae were divided under local anesthesia using surgical scissors. The patient immediately showed improvement in mouth opening and had resolution of his feeding problems. He is now gaining weight and developing appropriately. DISCUSSION: The accompanying review of the literature demonstrates only 11 cases worldwide of isolated maxillomandibular fusion. Depending upon the composition of the synechiae, simple surgical division under local anesthesia can be curative.

OBJECTIVES: To examine the variables affecting outcomes for sequential bilateral cochlear implantation patients in the adolescent population. STUDY DESIGN: Retrospective chart review at tertiary care center. METHODS: Main outcome measures were open set speech recognition tests at the word (Consonant-Nucleus-Consonant/Phonetically Balanced Kindergarten List Test [CNC/PBK]) and sentence levels in noise (Hearing in Noise Test-Noise [HINT-N]) in different test conditions with respect to the age at first and sequential implantation, as well as the interval between implants. RESULTS: Despite a mean age at sequential implantation of 13.5 years, sequential bilateral implanted adolescents revealed significant improvement in the sequential cochlear implant (CI2) ear. The mean time interval between implants was 8.2 years. A wide range of performance was noted, and age at implantation and interval between first cochlear implant (CI1) and CI2 did not predict outcome. Mean CNC/PBK score with CI1 alone was 83.0%, with the CI2 alone was 56.5%, and with bilateral implants was 86.8%. Sentence scores (HINT-N) were 89.5% for CI1, 74.2% for CI2, and 94.4% for bilateral CI condition. The clinical relevance of these enhanced perception abilities requires attention to individual device use, performance with the first implant, and subjective benefits reported by patients. CONCLUSIONS: Bilateral sequential cochlear implantation leads to improved speech perception in the adolescent population and should be considered in this population, even after a long period of deafness and despite a prolonged interval between implants. Numerous factors affect the ability to predict performance, but age at implantation and interimplant interval were not correlated with performance measures. Extensive preoperative counseling and individualized evaluation are critical to ensure that patients and families understand the range of possible outcomes. LEVEL OF EVIDENCE: 6. Laryngoscope, 2015.

OBJECTIVE: This study examined the statistical properties of normal air-conduction thresholds obtained with automated and manual audiometry to test the hypothesis that thresholds are normally distributed and to examine the distributions for evidence of bias in manual testing. DESIGN: Four databases were mined for normal thresholds. One contained audiograms obtained with an automated method. The other three were obtained with manual audiometry. Frequency distributions were examined for four test frequencies (250, 500, 1000, and 2000 Hz). STUDY SAMPLE: The analysis is based on 317 569 threshold determinations of 80 547 subjects from four clinical databases. RESULTS: Frequency distributions of thresholds obtained with automated audiometry are normal in form. Corrected for age, the mean thresholds are within 1.5 dB of reference equivalent threshold sound pressure levels. Frequency distributions of thresholds obtained by manual audiometry are shifted toward higher thresholds. Two of the three datasets obtained by manual audiometry are positively skewed. CONCLUSIONS: The positive shift and skew of the manual audiometry data may result from tester bias. The striking scarcity of thresholds below 0 dB HL suggests that audiologists place less importance on identifying low thresholds than they do for higher-level thresholds. We refer to this as the Good enough bias and suggest that it may be responsible for differences in distributions of thresholds obtained by automated and manual audiometry.

This study aims to identify the long-term outcomes of total knee arthroplasty (TKA) treated for deep infection. 3270 consecutive primary and 175 revision TKAs were followed prospectively. There were 39 deep infections (1.16%): 29 primary (0.9%) and 10 revision (5.7%) cases. Two-stage resection and re-implantation procedure was performed in 13 primary cases with 10/13 (77%) successfully resolved. Early (<1month) Irrigation and Debridement (I&D) was performed in 16 primary cases with 100% success. Late (>4months) I&D was performed in 6 cases with 5/6 (83.3%) successful. Infection following revision TKA resulted in poor outcomes with both two-stage (2/4 successful) and I&D (2/6 successful). Deep infection after primary TKA can be successfully resolved with I&D and appropriate antibiotic treatment in the early postoperative course.

OBJECTIVE: To determine the efficacy and safety of interventions for mucous membrane pemphigoid (MMP). STUDY DESIGN: We conducted a systematic review from 2003 to 2013 according to the Cochrane Collaboration methodology. Randomized controlled trials (RCTs) or controlled clinical trials and observational studies were included, with diagnosis confirmed by clinical, histopathologic, and immunofluorescence criteria. The primary outcome was lesion remission or healing; several relevant secondary outcomes were also included. RESULTS: In the final analysis, 1 RCT and 32 observational studies were included. The one included RCT with a high risk of bias in multiple domains found limited evidence that pentoxifylline, combined with corticosteroid and cyclophosphamide, was more effective than standard therapy (corticosteroid + cyclophosphamide alone) for ocular MMP. We summarize here the outcomes from 32 observational studies examining 242 patients across 19 unique treatments. Interventions that show promise include rituximab and intravenous immunoglobulin. CONCLUSIONS: This systematic review is the most recent since 2003-2009. There is still lack of high-quality research providing evidence-based MMP treatments.

The first World Workshop on Oral Medicine (WWOM) was held in 1988. The portfolio has continued to expand in scope and impact over the past 26 years. Five World Workshops were conducted between 1988 and 2010, focusing on creation of systematic reviews in biomedicine and health care of importance to the international oral medicine community. WWOM VI was conducted in April 2014 and further extended this modeling. This most recent Workshop also fostered creation of the inaugural joint meeting between the American Academy of Oral Medicine and the European Association of Oral Medicine, together with The British Society for Oral Medicine and the Oral Medicine Academy of Australasia. The goal of the WWOM portfolio is to strategically enhance international oral medicine research, education, and clinical practice. To this end, this report summarizes subject areas for WWOM IV (2004) and research recommendations for WWOM V (2010), as well as citation metrics relative to publications from these two conferences. The information is designed to provide research and clinical context for key issues in oral medicine as delineated by the WWOM portfolio over the past 10 years, as well as for projected outcomes of WWOM VI over the next 12 months.