The human enteric flora plays a significant role in intestinal health and disease. Populations of enteric bacteria can inhibit the NF-κB pathway by blockade of IκB-α ubiquitination, a process catalyzed by the E3-SCFβ-TrCP ubiquitin ligase. The activity of this ubiquitin ligase is regulated via covalent modification of the Cullin-1 subunit by the ubiquitin-like protein NEDD8. We previously reported that interaction of viable commensal bacteria with mammalian intestinal epithelial cells resulted in a rapid and reversible generation of reactive oxygen species (ROS) that modulated neddylation of Cullin-1 and resulted in suppressive effects on the NF-κB pathway. Herein, we demonstrate that butyrate and other short chain fatty acids supplemented to model human intestinal epithelia in vitro and human tissue ex vivo results in loss of neddylated Cul-1 and show that physiological concentrations of butyrate modulate the ubiquitination and degradation of a target of the E3- SCFβ-TrCP ubiquitin ligase, the NF-κB inhibitor IκB-α. Mechanistically, we show that physiological concentrations of butyrate induces reactive oxygen species that transiently alters the intracellular redox balance and results in inactivation of the NEDD8-conjugating enzyme Ubc12 in a manner similar to effects mediated by viable bacteria. Because the normal flora produces significant amounts of butyrate and other short chain fatty acids, these data provide a functional link between a natural product of the intestinal normal flora and important epithelial inflammatory and proliferative signaling pathways.

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During the last 10 years, computerized dynamic posturography has yielded various patterns of sway on the sensory organization test and the motor control test that have been associated with a variety of organic balance disorders. Some aspects of performance during computerized dynamic posturography, however, are under conscious control. Voluntary movements not indicative of physiologic response to balance system stimulation can also affect computerized dynamic posturography results. Quantification of nonorganic or "aphysiologic" response patterns in normal subjects, patients, and suspected malingerers is crucial to justify use of computerized dynamic posturography for identification of physiologically inconsistent results. For this purpose the computerized dynamic posturography records of 122 normal subjects, 347 patients with known or suspected balance disorders, and 72 subjects instructed to feign a balance disturbance were critically evaluated by use of seven measurement criteria, which were postulated as indicating aphysiologic sway. Each criterion was scored with a standard calculation of the raw data in a random, blinded fashion. The results of this multicenter study show that three of the seven criteria are significantly different in the suspected "malingerer" group when compared with either the normal or patient group. The relative strength of each criterion in discerning organic from nonorganic sway provides the examiner with a measure of reliability during platform posture testing. This study demonstrates that computerized dynamic posturography can accurately identify and document nonorganic sway patterns during routine assessment of posture control.

We describe the clinical and laboratory features of 13 patients with bilateral loss of peripheral vestibular sensitivity of no known cause. In the office, screening for this condition was possible using illegible e-testing and examination of the patient for refixation saccades after brisk head movements while attempting visual fixation. Diagnosis was confirmed by bilaterally reduced caloric responses (< 20 degrees/second on all 4 caloric irrigations) and abnormally low gain of the vestibulo-ocular reflex on rotational chair testing. The mean age of the patients was 68 years. We noted two patterns of symptom onset: onset associated with vertigo (10 patients) and insidious progressive disequilibrium not associated with vertigo (3 patients). Only 38% of the patients complained of subjective oscillopsia. The subjects performed poorly on platform posturography, particularly when deprived of visual and somatosensory feedback. When associated with vertigo, bilateral vestibular loss may be the result of bilateral sequential vestibular neuritis; when not associated with vertigo, disequilibrium may be caused by slow, symmetrical loss of peripheral function as a result of aging. Although the subjects in this report were elderly, idiopathic bilateral vestibular loss has been reported in patients of all ages.

Blastomycosis is a relatively uncommon fungal disease that most commonly affects the lungs. Other organs may be involved, usually secondary to dissemination of the organism. Laryngeal blastomycosis may occur in isolation from active pulmonary disease. The signs, symptoms, clinical features, and pathological findings of laryngeal blastomycosis mimic those of squamous cell carcinoma. Misdiagnosis may result in inappropriate treatment with potential morbidity. Proper understanding of the clinical presentation and familiarity with the histopathologic features of this disease are therefore imperative. In this paper, we report 2 cases of laryngeal blastomycosis, 1 of which was misdiagnosed as squamous cell carcinoma, clinically and microscopically, with consequent radiotherapy and laryngectomy. In the other case, a clinical diagnosis of glottic squamous cell carcinoma was rendered. However, blastomycosis was identified in a biopsy specimen. We also review cases of isolated laryngeal blastomycosis that have been reported in the English-language literature during the last 80 years. A number of those cases were misdiagnosed clinically and microscopically as squamous cell carcinoma.