Nevus of Ota with midface tumors and a vanishing orbital mass.

Nevus of Ota, also known as oculodermal melanocytosis, is a benign melanocytic lesion that develops along the distribution of the V1 and V2 branches of the trigeminal nerve. Prior reports have described the typical imaging and clinical features of nevus of Ota. We present a rare case of a 31 year-old female with midface tumors and presumed hemorrhage into an orbital lesion in the setting of nevus of Ota resulting in acute loss of vision.

Differential maturation of vesicular glutamate and GABA transporter expression in the mouse auditory forebrain during the first weeks of hearing.

Vesicular transporter proteins are an essential component of the presynaptic machinery that regulates neurotransmitter storage and release. They also provide a key point of control for homeostatic signaling pathways that maintain balanced excitation and inhibition following changes in activity levels, including the onset of sensory experience. To advance understanding of their roles in the developing auditory forebrain, we tracked the expression of the vesicular transporters of glutamate (VGluT1, VGluT2) and GABA (VGAT) in primary auditory cortex (A1) and medial geniculate body (MGB) of developing mice (P7, P11, P14, P21, adult) before and after ear canal opening (~P11-P13). RNA sequencing, in situ hybridization, and immunohistochemistry were combined to track changes in transporter expression and document regional patterns of transcript and protein localization. Overall, vesicular transporter expression changed the most between P7 and P21. The expression patterns and maturational trajectories of each marker varied by brain region, cortical layer, and MGB subdivision. VGluT1 expression was highest in A1, moderate in MGB, and increased with age in both regions. VGluT2 mRNA levels were low in A1 at all ages, but high in MGB, where adult levels were reached by P14. VGluT2 immunoreactivity was prominent in both regions. VGluT1 (+) and VGluT2 (+) transcripts were co-expressed in MGB and A1 somata, but co-localization of immunoreactive puncta was not detected. In A1, VGAT mRNA levels were relatively stable from P7 to adult, while immunoreactivity increased steadily. VGAT (+) transcripts were rare in MGB neurons, whereas VGAT immunoreactivity was robust at all ages. Morphological changes in immunoreactive puncta were found in two regions after ear canal opening. In the ventral MGB, a decrease in VGluT2 puncta density was accompanied by an increase in puncta size. In A1, perisomatic VGAT and VGluT1 terminals became prominent around the neuronal somata. Overall, the observed changes in gene and protein expression, regional architecture, and morphology relate to-and to some extent may enable-the emergence of mature sound-evoked activity patterns. In that regard, the findings of this study expand our understanding of the presynaptic mechanisms that regulate critical period formation associated with experience-dependent refinement of sound processing in auditory forebrain circuits.

Transcriptional maturation of the mouse auditory forebrain.

BACKGROUND: The maturation of the brain involves the coordinated expression of thousands of genes, proteins and regulatory elements over time. In sensory pathways, gene expression profiles are modified by age and sensory experience in a manner that differs between brain regions and cell types. In the auditory system of altricial animals, neuronal activity increases markedly after the opening of the ear canals, initiating events that culminate in the maturation of auditory circuitry in the brain. This window provides a unique opportunity to study how gene expression patterns are modified by the onset of sensory experience through maturity. As a tool for capturing these features, next-generation sequencing of total RNA (RNAseq) has tremendous utility, because the entire transcriptome can be screened to index expression of any gene. To date, whole transcriptome profiles have not been generated for any central auditory structure in any species at any age. In the present study, RNAseq was used to profile two regions of the mouse auditory forebrain (A1, primary auditory cortex; MG, medial geniculate) at key stages of postnatal development (P7, P14, P21, adult) before and after the onset of hearing (~P12). Hierarchical clustering, differential expression, and functional geneset enrichment analyses (GSEA) were used to profile the expression patterns of all genes. Selected genesets related to neurotransmission, developmental plasticity, critical periods and brain structure were highlighted. An accessible repository of the entire dataset was also constructed that permits extraction and screening of all data from the global through single-gene levels. To our knowledge, this is the first whole transcriptome sequencing study of the forebrain of any mammalian sensory system. Although the data are most relevant for the auditory system, they are generally applicable to forebrain structures in the visual and somatosensory systems, as well. RESULTS: The main findings were: (1) Global gene expression patterns were tightly clustered by postnatal age and brain region; (2) comparing A1 and MG, the total numbers of differentially expressed genes were comparable from P7 to P21, then dropped to nearly half by adulthood; (3) comparing successive age groups, the greatest numbers of differentially expressed genes were found between P7 and P14 in both regions, followed by a steady decline in numbers with age; (4) maturational trajectories in expression levels varied at the single gene level (increasing, decreasing, static, other); (5) between regions, the profiles of single genes were often asymmetric; (6) GSEA revealed that genesets related to neural activity and plasticity were typically upregulated from P7 to adult, while those related to structure tended to be downregulated; (7) GSEA and pathways analysis of selected functional networks were not predictive of expression patterns in the auditory forebrain for all genes, reflecting regional specificity at the single gene level. CONCLUSIONS: Gene expression in the auditory forebrain during postnatal development is in constant flux and becomes increasingly stable with age. Maturational changes are evident at the global through single gene levels. Transcriptome profiles in A1 and MG are distinct at all ages, and differ from other brain regions. The database generated by this study provides a rich foundation for the identification of novel developmental biomarkers, functional gene pathways, and targeted studies of postnatal maturation in the auditory forebrain.

Older Adults and Unanticipated Hospital Admission within 30 Days of Ambulatory Surgery: An Analysis of 53,667 Ambulatory Surgical Procedures.

OBJECTIVES: To evaluate whether age is independently associated with greater rate of unanticipated hospital admission within 30 days of ambulatory surgery. DESIGN: Retrospective database study. SETTING: The 2012 National Surgical Quality Improvement Project data set. PARTICIPANTS: All individuals with "outpatient" recorded as their status in the data set. MEASUREMENTS: The primary outcome of interest was all-cause hospital admission in the 30-day period after surgery. Multivariate models were constructed to control for covariate bias. Assessment of interactions of terms in the final model was performed using a conditional tree analysis. RESULTS: The final analysis included 53,667 ambulatory surgical cases. There were 1,370 (2.5%, 99% confidence interval (CI) = 2.4-2.7%) hospital admissions among the cases evaluated. After adjusting for potential confounders, age (<70 vs ≥70) was independently associated with hospital admission (odds ratio = 1.54, 99% CI = 1.29-1.84). A classification tree analysis of the cases without postoperative morbidity identified age (<60 vs ≥60) as an important decision point leading to greater likelihood of admission (P < .001) within 30 days after ambulatory surgery. CONCLUSION: Even after adjusting for comorbidities, older adults are at greater risk of unanticipated hospital admission within 30 days of ambulatory surgery. Renal failure, chronic obstructive pulmonary disease, current cancer treatment, diabetes mellitus, and history of amputation or revascularization were also associated with greater likelihood of hospital admission. Interventions to improve transitions of care for older adults after ambulatory surgery are needed.

ASA class is a reliable independent predictor of medical complications and mortality following surgery.

METHODS: The American Society of Anesthesiologists Physical Status classification system (ASA PS) is a method of characterizing patient operative risk on a scale of 1-5, where 1 is normal health and 5 is moribund. Every anesthesiologist is trained in this measure, and it is performed before every procedure in which a patient undergoes anesthesia. We measured the independent predictive value of ASA-PS for complications and mortality in the ACS-NSQIP database by multivariate regression. We conducted analogous regressions after standardizing ASA-PS to control for interprocedural variations in risk in the overall model and sub-analyses by surgical specialty and the most common procedures. RESULTS: For 2,297,629 cases (2005-2012; median age 55, min = 16, max > 90 [90 and above are coded as 90+]), at increasing levels of ASA-PS (2-5), odds ratios (OR's) from 2.05 to 63.25 (complications, p < 0.001) and 5.77-2011.92 (mortality, p < 0.001) were observed, with non-overlapping 95% confidence intervals. Standardization of ASA-PS (OR = 1.426 [per standard deviation above the mean ASA-PS per procedure], p < .001) and subgroup analyses yielded similar results. DISCUSSION: ASA PS was not only found to be associated with increased morbidity and mortality, but independently predictive when controlling for other comorbidities. Even after standardization based on procedure type, increases in ASA predicted significant increases in complication rates for morbidity and mortality post-operatively. CONCLUSIONS: ASA PS has strong, independent associations with post-operative medical complications and mortality across procedures. This capability, along with its simplicity, makes it a valuable prognostic metric.