A synaptic corollary discharge signal suppresses midbrain visual processing during saccade-like locomotion.

In motor control, the brain not only sends motor commands to the periphery, but also generates concurrent internal signals known as corollary discharge (CD) that influence sensory information processing around the time of movement. CD signals are important for identifying sensory input arising from self-motion and to compensate for it, but the underlying mechanisms remain unclear. Using whole-cell patch clamp recordings from neurons in the zebrafish optic tectum, we discovered an inhibitory synaptic signal, temporally locked to spontaneous and visually driven locomotion. This motor-related inhibition was appropriately timed to counteract visually driven excitatory input arising from the fish's own motion, and transiently suppressed tectal spiking activity. High-resolution calcium imaging revealed localized motor-related signals in the tectal neuropil and the upstream torus longitudinalis, suggesting that CD enters the tectum via this pathway. Together, our results show how visual processing is suppressed during self-motion by motor-related phasic inhibition. This may help explain perceptual saccadic suppression observed in many species.

Motion vision: Course control in the developing visual system.

As we move around, the image pattern on our retina is constantly changing. Nervous systems have evolved to detect such global 'optic flow' patterns. A new study reveals how optic flow is encoded in the larval zebrafish brain and could be used for the estimation of self-motion.

Negative Pressure Wound Therapy in the Head and Neck: An Evidence-Based Approach.

OBJECTIVE: To perform an evidence-based review with recommendations that evaluates the indications and utility of negative pressure wound therapy (NPWT) in the head and neck. METHODS: The authors searched the PubMed, Medline, Embase, Web of Science, and Cochrane Library databases for relevant literature. The primary outcome was successful intended use of NPWT, be it for granulation tissue formation, infection control, or complete wound closure. Patient demographics, etiology, and other clinical characteristics were explored. Meta-analysis of observational studies was used to examine response rates and wound sizes. RESULTS: Fifty-seven articles encompassing 522 patients were included. The most common etiologies reported included: neoplasm (343 patients [65.7%]), oro-/pharyngocutaneous fistula (9.8%), infection (10.5%), and trauma (9.6%). The majority of wounds treated were in the neck (61.6%). Potential risk factors that may compromise wound healing were noted in 217 of 522 patients (41.6%). Of these 217 patients, 135 had properly documented risk factors, with the most common being prior irradiation (63%). The overall mean response across studies was 85.7% (95% confidence interval: 0.806-0.896, P < 0.001, I2 = 0 %). CONCLUSION: Negative pressure wound therapy is useful for the management of head and neck wounds and should be considered for patients in whom wound healing is progressing insufficiently, including those with a history of head and neck cancer, oro-/pharyngocutaenous fistula, and trauma. Randomized controlled trials further comparing NPWT versus other modalities may be invaluable in further delineating its appropriate role. Laryngoscope, 129:671-683, 2019.

Endoscopic Resection of Pediatric Skull Base Tumors: An Evidence-Based Review.

Objectives To perform a systematic review examining experiences with endoscopic resection of skull base lesions in the pediatric population, with a focus on outcomes, recurrence, and surgical morbidities. Methods PubMed/MEDLINE, Cochrane Library, Embase, and Web of Science databases were evaluated. Studies were assessed for level of evidence. Bias risk was evaluated using the Cochrane Bias tool, Grades of Recommendation, Assessment, Development and Evaluation (GRADE), and Methodological Index for Non-Randomized Studies (MINORS) criteria. Patient characteristics, pathology, site of primary disease, presenting symptoms, stage, procedure specific details, and complications were evaluated. Results were reported using the Preferred Reporting Systems for Systematic Reviews and Meta-Analysis guidelines. Results Ninety-three studies met criteria for inclusion, encompassing 574 patients with skull base tumors. The GRADE and MINORS criteria determined the overall evidence to be moderate quality. The most common benign and malignant pathologies included juvenile nasopharyngeal angiofibromas ( n = 239) and chondrosarcomas ( n = 11) at 41.6 and 1.9%, respectively. Of all juvenile nasopharyngeal angiofibroma tumors, most presented at stage IIIa and IIIb (25.8 and 27.3%, respectively). Nasal obstruction (16.5%) and headache (16.0%) were common symptoms at initial presentation. Surgical approaches included endoscopic endonasal ( n = 193, 41.2%) and endoscopic extended transsphenoidal ( n = 155, 33.1%). Early (< 6 weeks) and late (>6 weeks) complications included cerebrospinal fluid leak ( n = 36, 17.3%) and endocrinopathy ( n = 43, 20.7%). Mean follow-up time was 37 months (0.5-180 months), with 86.5% showing no evidence of disease and 2.1% having died from disease at last follow-up. Conclusion Endoscopic skull base surgery has been shown to be a safe and effective method of treating a variety of pediatric skull base tumors. If appropriately employed, the minimally invasive approach can provide optimal results in the pediatric population.

Wet and wounded: Pediatric facial trauma from swimming and diving.

OBJECTIVES: Swimming has been reported as the most common recreational activity among American youths, while diving remains a popular youth activity as well. We characterize the most common facial injuries occurring during these activities and evaluate facial fracture mechanisms and demographic trends, as this information may be helpful in preventative counseling as well as diagnosis. METHODS: The National Electronic Injury Surveillance System was assessed for swimming- and diving-related facial injuries in children from 2007 to 2016. Estimates of national injury incidence were recorded, and patient diagnoses, demographics, and injury mechanisms were evaluated. RESULTS: In the 10-year period assessed, 789 NEISS entries extrapolated to an estimated 27,709 patients nationwide were analyzed. The yearly incidence fluctuated but steadily rose from 2013 to 2016. Males comprised a majority of injuries (58%), and laceration was the most common diagnosis (65%), followed by abrasion/contusion (22%) and fracture (9%). Facial fractures were most likely to involve the nasal bones (87%). Swimming injuries were more numerous overall (74%), but a greater proportion of diving injuries resulted in fracture (12% vs. 7%). Teenagers were also more likely to suffer fractures than were younger children involved in the same activities. CONCLUSION: Most analyses of swimming and diving injuries have focused on spinal and orthopedic trauma. Nevertheless, the nature of headfirst diving and swim strokes suggest facial trauma is an underappreciated concern for clinicians. These findings reinforce the need for safer swimming and diving practices and serve as a useful resource for physicians managing pediatric facial injuries.

Evolving Trends in Cochlear Implantation: A Critical Look at the Older Population.

OBJECTIVES/HYPOTHESIS: Cochlear implantation (CI) is a well-accepted surgical option for the treatment of moderate to profound deafness. The purpose of this study was to evaluate the temporal and geographic trends of this procedure nationwide in the Medicare population in an attempt to explore the impact of evolving technologies and changes in healthcare policy. METHODS: Medicare Part B national summary procedural datasets from 2007 to 2016 were obtained. Current Procedural Terminology codes for CI as well as auditory osseointegrated implantation were obtained. Centers for Medicare and Medicaid Services (CMS) datasets were evaluated to determine temporal trends. For geographic trends, specific carrier datasets from 2007 and 2016 were used. RESULTS: From 2007 through 2016, the number of CI procedures increased annually from 1603 to 3600 (124.6%). Other procedures to treat hearing loss including bone-anchored implantation exhibited comparatively modest increases (23%, 90%). CI procedures increased every year in contrast to bone-anchored implants. Controlling for Medicare population, the greatest number of CI procedures performed per capita in the United States was in the West North Central, with an average 1.05 CIs per 10,000 beneficiaries. CONCLUSION: The number of CI procedures performed in the elderly population has increased markedly over the past 10 years, far outpacing growth in other hearing surgeries. Potential reasons may relate to changes in criteria for CI candidacy over the past decade, although significant regional variability demonstrated suggests a lack of consensus. Further studies would be necessary to ascertain the true reason for geographic disparities.

Evolving BioAssay Ontology (BAO): modularization, integration and applications.

The lack of established standards to describe and annotate biological assays and screening outcomes in the domain of drug and chemical probe discovery is a severe limitation to utilize public and proprietary drug screening data to their maximum potential. We have created the BioAssay Ontology (BAO) project (http://bioassayontology.org) to develop common reference metadata terms and definitions required for describing relevant information of low-and high-throughput drug and probe screening assays and results. The main objectives of BAO are to enable effective integration, aggregation, retrieval, and analyses of drug screening data. Since we first released BAO on the BioPortal in 2010 we have considerably expanded and enhanced BAO and we have applied the ontology in several internal and external collaborative projects, for example the BioAssay Research Database (BARD). We describe the evolution of BAO with a design that enables modeling complex assays including profile and panel assays such as those in the Library of Integrated Network-based Cellular Signatures (LINCS). One of the critical questions in evolving BAO is the following: how can we provide a way to efficiently reuse and share among various research projects specific parts of our ontologies without violating the integrity of the ontology and without creating redundancies. This paper provides a comprehensive answer to this question with a description of a methodology for ontology modularization using a layered architecture. Our modularization approach defines several distinct BAO components and separates internal from external modules and domain-level from structural components. This approach facilitates the generation/extraction of derived ontologies (or perspectives) that can suit particular use cases or software applications. We describe the evolution of BAO related to its formal structures, engineering approaches, and content to enable modeling of complex assays and integration with other ontologies and datasets.

Formalization, annotation and analysis of diverse drug and probe screening assay datasets using the BioAssay Ontology (BAO).

Huge amounts of high-throughput screening (HTS) data for probe and drug development projects are being generated in the pharmaceutical industry and more recently in the public sector. The resulting experimental datasets are increasingly being disseminated via publically accessible repositories. However, existing repositories lack sufficient metadata to describe the experiments and are often difficult to navigate by non-experts. The lack of standardized descriptions and semantics of biological assays and screening results hinder targeted data retrieval, integration, aggregation, and analyses across different HTS datasets, for example to infer mechanisms of action of small molecule perturbagens. To address these limitations, we created the BioAssay Ontology (BAO). BAO has been developed with a focus on data integration and analysis enabling the classification of assays and screening results by concepts that relate to format, assay design, technology, target, and endpoint. Previously, we reported on the higher-level design of BAO and on the semantic querying capabilities offered by the ontology-indexed triple store of HTS data. Here, we report on our detailed design, annotation pipeline, substantially enlarged annotation knowledgebase, and analysis results. We used BAO to annotate assays from the largest public HTS data repository, PubChem, and demonstrate its utility to categorize and analyze diverse HTS results from numerous experiments. BAO is publically available from the NCBO BioPortal at http://bioportal.bioontology.org/ontologies/1533. BAO provides controlled terminology and uniform scope to report probe and drug discovery screening assays and results. BAO leverages description logic to formalize the domain knowledge and facilitate the semantic integration with diverse other resources. As a consequence, BAO offers the potential to infer new knowledge from a corpus of assay results, for example molecular mechanisms of action of perturbagens.