Expansion of the piriform cortex contributes to corticothalamic pathfinding defects in Gli3 conditional mutants.

The corticothalamic and thalamocortical tracts play essential roles in the communication between the cortex and thalamus. During development, axons forming these tracts have to follow a complex path to reach their target areas. While much attention has been paid to the mechanisms regulating their passage through the ventral telencephalon, very little is known about how the developing cortex contributes to corticothalamic/thalamocortical tract formation. Gli3 encodes a zinc finger transcription factor widely expressed in telencephalic progenitors which has important roles in corticothalamic and thalamocortical pathfinding. Here, we conditionally inactivated Gli3 in dorsal telencephalic progenitors to determine its role in corticothalamic tract formation. In Emx1Cre;Gli3(fl/fl) mutants, only a few corticothalamic axons enter the striatum in a restricted dorsal domain. This restricted entry correlates with a medial expansion of the piriform cortex. Transplantation experiments showed that the expanded piriform cortex repels corticofugal axons. Moreover, expression of Sema5B, a chemorepellent for corticofugal axons produced by the piriform cortex, is similarly expanded. Finally, time course analysis revealed an expansion of the ventral pallial progenitor domain which gives rise to the piriform cortex. Hence, control of lateral cortical development by Gli3 at the progenitor level is crucial for corticothalamic pathfinding.

Integration of gold nanoparticles into bilayer structures via adaptive surface chemistry.

We describe the spontaneous incorporation of amphiphilic gold nanoparticles (Au NPs) into the walls of surfactant vesicles. Au NPs were functionalized with mixed monolayers of hydrophilic (deprotonated mercaptoundecanoic acid, MUA) and hydrophobic (octadecanethiol, ODT) ligands, which are known to redistribute dynamically on the NP surface in response to changes in the local environment. When Au NPs are mixed with preformed surfactant vesicles, the hydrophobic ODT ligands on the NP surface interact favorably with the hydrophobic core of the bilayer structure and guide the incorporation of NPs into the vesicle walls. Unlike previous strategies based on small hydrophobic NPs, the present approach allows for the incorporation of water-soluble particles even when the size of the particles greatly exceeds the bilayer thickness. The strategy described here based on inorganic NPs functionalized with two labile ligands should in principle be applicable to other nanoparticle materials and bilayer structures.

Acute Acetabular Protrusion: the Hardinge Approach for Implant Removal and One-stage Hip Reconstruction.

Acute penetration of a total hip arthroplasty into the pelvic cavity is a grave and potentially catastrophic scenario. Fortunately, this complication is uncommon and rarely encountered during a surgical career. Currently, a two-stage procedure is favoured by most surgeons, but the evidence for this is unconvincing and may expose the patient to unnecessary risks. Furthermore, a two-stage approach may be more suitable for the more common chronic migration of a loose acetabular shell, which fundamentally differs from acute pelvic penetration. We present the case of a 76-year-old man referred to our institution for reconstructive surgery following acute pelvic penetration of the acetabular shell during total hip arthroplasty. We used a single-stage Hardinge approach to retrieve the shell and successfully reconstruct the acetabulum. Specific indications for using this method are proposed. In carefully selected cases of intrapelvic implants, a single-stage method can improve patient outcomes while minimising unnecessary risks associated with the conventional two-stage approach.

Not making the cut: Techniques to prevent RNA cleavage in structural studies of RNase-RNA complexes.

RNases are varied in the RNA structures and sequences they target for cleavage and are an important type of enzyme in cells. Despite the numerous examples of RNases known, and of those with determined three-dimensional structures, relatively few examples exist with the RNase bound to intact cognate RNA substrate prior to cleavage. To better understand RNase structure and sequence specificity for RNA targets, in vitro methods used to assemble these enzyme complexes trapped in a pre-cleaved state have been developed for a number of different RNases. We have surveyed the Protein Data Bank for such structures and in this review detail methodologies that have successfully been used and relate them to the corresponding structures. We also offer ideas and suggestions for future method development. Many strategies within this review can be used in combination with X-ray crystallography, as well as cryo-EM, and other structure-solving techniques. Our hope is that this review will be used as a guide to resolve future yet-to-be-determined RNase-substrate complex structures.

Neurosarcoidosis Presenting Initially as Idiopathic Vocal Cord Paralysis.

INTRODUCTION:: The presentation, course, and management of a rare laryngeal manifestation of neurosarcoidosis due to central nervous system (as opposed to peripheral nervous system) injury are described. METHODS:: The authors present 3 cases of vocal cord paralysis as the initial symptom of isolated neurosarcoidosis at a tertiary care laryngology clinic. RESULTS:: Laryngoscopy diagnosed unilateral vocal cord paralysis. Laryngeal electromyography revealed high vagal injury, prompting workup on brain magnetic resonance imaging. On magnetic resonance imaging, 2 cases showed basilar leptomeningeal inflammation and 1 case showed a brainstem mass. Patients were found at follow-up to have severe, progressive vagal injury, with patients developing severe quality of life impairments and medical complications. CONCLUSIONS:: Neurosarcoidosis is not usually considered in the differential diagnosis of vocal cord paralysis. At initial presentation, all patients lacked other cranial neuropathies and systemic sarcoidosis manifestations, making diagnosis difficult. Otolaryngologists should be aware of this rare presentation, as prompt diagnosis by brain magnetic resonance imaging with or without central nervous system biopsy, as opposed to traditional chest radiography or computed tomography for the workup of peripheral nerve injury, is necessary. Serial laryngeal examinations are recommended for close monitoring of progressive disease and recommending treatment. Injection or medialization laryngoplasty can provide improvements in voicing but not swallow.

Systematic review of surgery for persistent pediatric tracheocutaneous fistula.

OBJECTIVES: To compare the treatment outcomes and adverse event rates for primary closure compared to simple excision with healing by secondary intention for persistent tracheocutaneous fistula (TCF) in children. STUDY DESIGN: Systematic review. METHODS: Systematic review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting standards. MEDLINE, Embase, Cochrane Library, and manual search were used to identify articles. Inclusion criteria were case series or comparative studies of surgery for persistent TCF in children under age 18 years. Exclusion criteria were age 18 years or older, duplicate patient series, case series with less than two patients, or case reports. Data were pooled using random effects meta-analysis to assess outcomes, adverse events, and comparative effectiveness. RESULTS: We identified 14 articles with 413 patients treated with excision with primary closure and 233 patients treated with excision with closure by secondary intention. Pooled success rates were 95.7% with primary closure (95% confidence interval [CI]: 93.1% to 97.4%) and 92.7% with secondary intention (95% CI: 88.4% to 95.4%). Subcutaneous emphysema or urgent airway problems were uncommon, occurring in 3.8% and 3.6% of patients, respectively. Five studies had data suitable for comparative meta-analysis, which showed no differences by closure technique for treatment success (P = .480), overall complications (P = .551), need for revision surgery (P = .624), or the incidence of subcutaneous emphysema or pneumothorax (P = .512), urgent airway problems (P = .126), wound infection (P = 1.00), or wound dehiscence or fistula (P = .818). CONCLUSIONS: There are no differences in the rates of success or complications with surgical closure of TCF in children, whether performed by primary closure or by secondary intention. Both techniques have high success rates with a low incidence of serious complications. Laryngoscope, 127:241-246, 2017.

Systematic review for surgical treatment of adult and adolescent laryngotracheal stenosis.

OBJECTIVES/HYPOTHESIS: To determine if open surgical treatment options for adult and adolescent laryngotracheal stenosis are more successful than endoscopic procedures. STUDY DESIGN: Systematic review. METHODS: Embase and MEDLINE were searched for publications on adult and adolescent patients (>13 years old) with laryngotracheal stenosis. Cause of stenosis (intubation, idiopathic, or trauma) and treatments (open laryngotracheal resection with anastomosis, open laryngotracheal reconstruction with expansion grafting, or endoscopic procedures) were included. Primary outcomes are decreased additional surgery performed and success of decannulation, if previously tracheostomy. RESULTS: There were 297 abstracts reviewed, 104 articles selected for full-text review, and 39 articles, with 834 pooled patients, included in the analysis. Patients who had an open procedure (resection with anastomosis or reconstruction with expansion grafting) had significantly different outcomes rates; 32% versus 38% (P <.001) received additional surgery and 89%and 83% (P <.001) were decannulated, respectively. For patients who had endoscopic repair, 44% received additional surgery, and 63% were decannulated. Patients with idiopathic stenosis were more likely to receive additional surgery than those with traumatic (54% vs. 25%) and intubation/tracheostomy etiologies (54% vs. 35%). Etiology of stenosis did affect decannulation rates, patients with intubation/tracheostomy etiology had decannulation rates of 88%, compared to traumatic etiologies (78%, P <.001) and idiopathic stenosis (63%, P <.001). Risk of bias did not impact study results and was assessed using a validated instrument, Methodological Index for Non-randomized Studies criteria. CONCLUSIONS: Patients with adult laryngotracheal stenosis who undergo laryngotracheal resection with anastomosis receive less surgery compared to those who undergo endoscopic treatment or laryngotracheal reconstruction with augmentation/grafting. Patients with idiopathic stenosis are less likely to receive further surgery compared to those from trauma or intubation/tracheostomy, but have the lowest rate of decannulation. LEVEL OF EVIDENCE: NA Laryngoscope, 127:191-198, 2017.

A Novel Patient Safety Event Reporting Tool in Otolaryngology.

Objective To report the results of a preliminary analysis of a quality improvement initiative aimed to identify potential latent systems defects. Methods A pilot study of an anonymous, voluntary, event reporting system made available to all members of the American Academy of Otolaryngology-Head and Neck Surgery was performed. The National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) index was used to classify error types. Descriptive statistics were used to summarize submissions to the database. Results In the 53 cases reported to the database over 22 months, the majority involved errors that had resulted in harm (n = 34, 64%), followed by errors that occurred and did not result in harm (n = 7, 13%). Errors occurred predominantly in the hospital (n = 23, 44%) and operating room (n = 19, 35%). Most entries were classified as either technical (n = 21, 39%) or related to postoperative care (n = 15, 30%). Discussion This preliminary descriptive analysis of a novel otolaryngology patient safety event reporting tool shows that this platform brings unique value to the identification of errors and adverse events in our specialty. Most reported events were classified as errors resulting in harm. The most common type of reported event was a technical error, most often resulting in a nerve injury. Implications for Practice This reporting tool will likely allow for identification and prioritization of improvement opportunities. This example may serve as a guide for other societies to create similar platforms as we strive for a standardized process for event reporting.

Effects of antihypertensive drugs on ultrasound production and cardiovascular responses in 15-day-old rats.

When exposed to extreme cold or injected with the alpha(2)-adrenoceptor agonist, clonidine, infant rats emit ultrasonic vocalizations (USVs). Based upon the cardiovascular changes that accompany these two manipulations, especially decreased venous return, it was hypothesized that USVs are the acoustic by-product of the abdominal compression reaction (ACR), a maneuver that increases venous return. If this hypothesis is correct, then other anithypertensive drugs that decrease venous return should evoke USVs. In Experiment 1, sodium nitroprusside (SNP, 400 microg/kg), a direct-acting dilator of arteries and veins, was administered to 15-day-old rats under thermoneutral conditions while cardiac rate and ultrasound production were monitored. In Experiment 2, femoral artery pressure was monitored after SNP administration. Infants responded to SNP administration with decreased arterial pressure and tachycardia and, in addition, significantly increased ultrasound production. In Experiment 3, chlorisondamine (5 mg/kg), a ganglionic blocker that causes vasodilation and bradycardia, and hydralazine (20 mg/kg), a selective dilator of arteries, was administered to 15-day-olds. As predicted, chlorisondamine evoked ultrasound production and hydralazine did not. These results introduce SNP and chlorisondamine as only the second and third known agents capable of independently evoking USVs in thermoneutral conditions, and provide further support for the notion that ultrasound production is triggered by decreased venous return.

Self-assembly of nanoparticle amphiphiles with adaptive surface chemistry.

We investigate the self-assembly of amphiphilic nanoparticles (NPs) functionalized with mixed monolayers of hydrophobic and hydrophilic ligands in water. Unlike typical amphiphilic particles with "fixed" surface chemistries, the ligands used here are not bound irreversibly but can rearrange dynamically on the particles' surface during their assembly from solution. Depending on the assembly conditions, these adaptive amphiphiles form compact micellar clusters or extended chain-like assemblies in aqueous solution. By controlling the amount of hydrophobic ligands on the particles' surface, the average number of nearest neighbors--that is, the preferred coordination number--can be varied systematically from ∼ 1 (dimers) to ∼ 2 (linear chains) to ∼ 3 (extended clusters). To explain these experimental findings, we present an assembly mechanism in which hydrophobic ligands organize dynamically to form discrete patches between proximal NPs to minimize contact with their aqueous surroundings. Monte Carlo simulations incorporating these adaptive hydrophobic interactions reproduce the three-dimensional assemblies observed in experiment. These results suggest a general strategy based on reconfigurable "sticky" patches that may allow for tunable control over particle coordination number within self-assembled structures.

Incubation temperature modulates post-hatching thermoregulatory behavior in the Madagascar ground gecko, Paroedura pictus.

All vertebrates regulate body temperature within narrow limits, regardless of their physiological capabilities. When do these limits develop, and can they be modified by manipulations of the developmental thermal environment? We addressed these questions by incubating the eggs of the Madagascar ground gecko, Paroedura pictus, at three temperatures and by assessing thermoregulatory behavior in hatchlings. Thermoregulatory behavior was assessed using a two-choice shuttle paradigm, and skin temperatures were measured non-invasively using infrared thermography. The shuttling behavior of hatchlings was systematically affected by the temperature at which they were incubated, and follow-up tests suggested that this effect persisted for at least three weeks post-hatching. The body temperature data from the shuttling experiment were used to model thermoregulatory behavior in a complex thermal environment; the model predicted systematic effects of incubation temperature on thermal preference. The specificity of the alteration in thermoregulatory behavior by incubation temperature is compelling and provides evidence for powerful pre-hatching influences on a fundamental, life-sustaining behavioral process.