An improved procedure for integrated behavioral z-scoring illustrated with modified Hole Board behavior of male inbred laboratory mice

Publication date: Available online 20 September 2017
Source:Journal of Neuroscience Methods
Author(s): M. Maaike Labots, M.C. Marijke Laarakker, D. Dustin Schetters, S.S. Saskia Arndt, H.A. Hein van Lith
BackgroundGuilloux et al. introduced: integrated behavioral z-scoring, a method for behavioral phenotyping of mice. Using this method multiple ethological variables can be combined to show an overall description of a certain behavioral dimension or motivational system. However, a problem may occur when the control group used for the calculation has a standard deviation of zero or when no control group is present to act as a reference group.New MethodIn order to solve these problems, an improved procedure is suggested: taking the pooled data as reference. For this purpose a behavioral study with male mice from three inbred strains was carried out. The integrated behavioral z-scoring methodology was applied, thereby taking five different reference group options. The outcome regarding statistical significance and practical importance was compared.ResultsSignificant effects and effect sizes were influenced by the choice of the reference group. In some cases it was impossible to use a certain population and condition, because one or more behavioral variables in question had a standard deviation of zero. Based on the improved method, male mice from the three inbred strains differed regarding activity and anxiety.Comparison with Existing MethodTaking the method described by Guilloux et al. as basis, the present procedure improved the generalizability to all types of experimental designs in animal behavioral research.ConclusionsTo solve the aforementioned problems and to avoid getting the diagnosis of data manipulation, the pooled data (combining the data from all experimental groups in a study) as reference option is recommended.



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A Case of the nephrotic syndrome in bone marrow transplantation recipient, histologically showing overlapped glomerular lesions of thrombotic microangiopathy and membranous nephropathy

Nephrotic syndrome (NS) rarely occurs in post-hematopoietic stem cell transplantation (HSCT) recipients but represents the renal manifestation of graft-versus-host disease (GVHD). Membranous nephropathy (MN) accounts for almost two thirds of post-HSCT NS and is caused by immune complex deposition. Renal thrombotic microangiopathy (TMA) without fulfillment of clinical criteria for TMA has been underreported because of reduced opportunity for histological examination. However, renal TMA has recently been reported in association with GVHD and humoral immunological reactions. Although both MN and TMA after HSCT are associated with GVHD and immunological abnormalities, these diseases are exceptionally coexistent in renal biopsy specimens. We herein describe a case of post-HSCT NS, histologically showing overlapped lesions of TMA and MN. Renal biopsy specimen after presentation of NS revealed early stage MN and TMA with evidence of chronicity. TMA was thought to have preceded MN, and renal biopsy at the phase of pre-nephrotic proteinuria might reveal earlier histological changes of isolated renal TMA. Detection of subclinical renal TMA earlier by spontaneous renal biopsy can help prevent progression of renal injury or overlapping of other renal pathologies. We also demonstrated Th2 predominant intraglomerular infiltration of lymphocytes by immunohistochemistry.

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Perforators of the fibular artery and suprafascial network

Abstract

Introduction

Soft tissue defect on lower limb can result in an intractable wound. Surgeons resort in flaps to cover these injuries. Including fascia as in the case of a fasciocutaneous flap increases survey of the flap. Rising a perforator flap avoids to sacrifice a major vessel whence the nourishing perforator artery is born. We wanted to explore suprafascial distribution of the fibular skin perforator arteries supposing possible to find out a vascular axis composed of anastomoses of the fibular perforator vessels.

Materials and methods

Systematic observation was carried out on ten injected legs about the fibular perforator distribution, and especially their suprafascial course.

Results

Dissection allowed us to raise in all specimens a large fasciocutaneous paddle including a fine arteriolar vessel connecting fibular perforators. Perforators were isolated along from the leg and we found suprafascial arteriole connecting all perforators from the fibular head to the lateral malleolus. There were a total number of 126 perforators for 10 legs. The mean length of the fibula was 32.9 cm. No perforator was located at more than 2 cm from fibular posterior border. Proximal perforators were closer to posterior fibular side than distal perforators. We found that fibular perforators clustered in the middle and upper third of the leg.

Conclusion

This study proves the real existence of a microvascular suprafascial axis formed by fibular perforator anastomoses and stretching over the entire length of the fibula, from the fibular head to the distal tip of the lateral malleolus. This suprafascial vascular axis could be an anatomical basis for a fasciocutaneous fibular flap.

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Sandwich compression with rubbery tourniquet sheets and cotton balls for auricular pseudocyst

Objectives/Hypothesis

Pseudocyst of the auricle is a benign, noninflammatory cystic disease that is more common in Asians than in Caucasians. When managed conservatively, the results are often unsatisfactory and recurrences are common. We aimed to introduce a novel modified surgical method that involves a deroofing technique followed by a sandwich compression suture using two rubber tourniquet sheets and an iodine-soaked cotton ball for the treatment of auricular pseudocysts and to ascertain its effectiveness.

Study Design

Case series with or without comparison.

Methods

The charts of 100 patients with auricular pseudocysts who were treated with this new method from 2004 to 2016 in a university-affiliated tertiary teaching hospital were retrospectively reviewed and analyzed.

Results

The mean patient age was 37.7 years, and 84% were male. All of the patients had unilateral lesions, with right-side lesions (53.0%) being slightly predominant. The cymba concha (44.1%) was the most common site. Seven patients (7.0%) had trauma to the ear within 3 months before presentation. Previous aspiration or drainage had been performed for the cysts in 35 patients (35.0%), and the recurrences had been treated conservatively. In comparison, 98 of the 100 patients recovered smoothly from surgery without further recurrence or complications after follow-up for at least 1 year.

Conclusions

Based on our experience, not only does this surgical procedure yield reliable results in the treatment of pseudocysts of auricles, but it also has advantages such as using readily available materials, being simple to perform, improving efficacy, and lowering recurrence rates.

Level of Evidence

4 Laryngoscope, 2017

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Adipose-derived mesenchymal stromal cells prevented rat vocal fold scarring

Objectives/Hypothesis

This study aimed to reveal the effects of adipose-derived mesenchymal stromal cells (ASCs) on prevention of vocal fold scarring by investigating how the immediate ASCs transplantation into the injured rat vocal fold affect the levels of gene transcription and translation.

Study Design

Prospective animal experiments with controls.

Methods

ASCs harvested from green fluorescent protein transgenic rat (ASCs group) or saline (sham group) were injected into the thyroarytenoid muscle of Sprague-Dawley rats immediately after stripping the vocal fold. For histological examinations, larynges were extirpated at 3, 14, and 56 days after the injection. Quantitative real-time polymerase chain reaction (PCR) analyses were performed at 3 and 14 days after the injection.

Results

Transplanted ASCs were detected only in larynges at day 3. At days 14 and 56, histological examination showed significantly higher amounts of hyaluronic acid and lower deposition of collagen in the ASCs group compared to the sham group. Real-time PCR revealed that the ASCs group showed low expression of procollagen (Col)1a1, Col1a3, matrix metalloproteinase (Mmp)1 and Mmp8 in each time points. The ASCs group showed high expression of fibroblast growth factor (Fgf)2 and Hepatocyte growth factor (Hgf) compared to the sham group at day 14.

Conclusions

ASCs increased expressions of Fgf2 and Hgf, and suppressed excessive collagen deposition during vocal fold wound healing. Given the fact that ASCs survived no more than 14 days, ASCs were thought to induce upregulations of growth factors' genes in surrounding cells. These results suggested that ASCs have potential to prevent vocal fold scarring.

Level of Evidence

N/A Laryngoscope, 2017

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Targeting metabolic abnormalities to reverse fibrosis in iatrogenic laryngotracheal stenosis

Objective

Management of laryngotracheal stenosis (LTS) remains primarily surgical, with a critical need to identify targets for adjuvant therapy. Laryngotracheal stenosis scar fibroblasts exhibit a profibrotic phenotype with distinct metabolic shifts, including an increased glycolysis/oxidative phosphorylation ratio. This study examines the effects of the glutamine antagonist 6-diazo-5-oxo-l-norleucine (DON) on collagen production, gene expression, proliferation, and metabolism of human LTS-derived fibroblasts in vitro.

Method

Paired normal and scar-derived fibroblasts isolated from subglottic and proximal tracheal tissue in patients with iatrogenic laryngotracheal stenosis (iLTS) were cultured. Proliferation rate, gene expression, protein production, and cellular metabolism were assessed in two conditions: 1) fibroblast growth medium, and 2) fibroblast growth medium with 1 × 10⁻⁴ M DON.

Results

DON treatment reduced cellular proliferation rate (n = 7, P =  0.0150). Expression of genes collagen 1 and collagen 3 both were reduced (n = 7, P =  0.0102, 0.0143, respectively). Soluble collagen production decreased (n = 7, P =  0.0056). As measured by the rate of extracellular acidification, glycolysis and glycolytic capacity decreased (n = 7, P =  0.0082, 0.0003, respectively). adenosine triphosphate (ATP) production and basal respiration decreased (n = 7, P = 0.0045, 0.0258, respectively), determined by measuring the cellular rate of oxygen consumption.

Conclusion

The glutamine antagonist DON reverses profibrotic changes by inhibiting both glycolysis and oxidative phosphorylation in iLTS scar fibroblasts. In contrast to untreated iLTS scar fibroblasts, collagen gene expression, protein production, metabolic rate, and proliferation were significantly reduced. These results suggest DON and/or its derivatives as strong candidates for adjuvant therapy in the management of iatrogenic laryngotracheal stenosis. Enzymes involved in glutamine metabolism inhibited by DON offer targets for future investigation.

Level of Evidence

NA. Laryngoscope, 2017

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Diagnostic accuracy of current glossoptosis classification systems: A nested cohort cross-sectional study

Objectives/Hypothesis

To assess the performance of endoscopic grading systems of glossoptosis in identifying severe clinical manifestations in children with Robin sequence (RS).

Study Design

Nested cohort cross-sectional study.

Methods

All RS patients diagnosed at Hospital Clinics of Porto Alegre from October 2012 to June 2016 were enrolled in this cohort. Patients underwent sleep endoscopy and were classified according to Yellon (Y) and de Sousa et al. (S) scales. Symptom severity evaluation was performed as defined by Cole et al. The outcome of interest was Cole's clinical classification grade 3.

Results

Eighty patients were eligible for analysis. Sensitivity (Y: 56.2%, S: 28.1%, P < .001) and specificity (Y: 85.4%, S: 93.8%, P = .038) in identifying severe clinical symptoms patients (i.e., Cole grade 3) were statistically different between Y and S classifications. A low but significant overall correlation was observed for both Y (rho = 0.372, P < .001) and S (rho = 0.439, P < .001) classifications when compared with Cole classification. Diagnostic odds ratio (DOR) for Y (DOR: 7.53, 95% confidence interval [CI]: 4.15-10.90) and S (DOR: 5.87, 95% CI: 1.86-9.87) were equivalent (P = .92). Also, receiver operating characteristic curves area under the curve were not significantly different between them. The positive likelihood ratio was 3.86 (95% CI: 1.82-8.16) and 4.50 (95% CI: 1.32-15.36) for Y and S, respectively.

Conclusions

Y and S grading systems showed a low sensitivity and moderate to high specificity in detecting patients with severe clinical manifestations. Correlation between Y/S and Cole et al. grading were also considered low. Development of a more discriminative anatomic grading system is still needed for this specific disorder.

Level of Evidence

2b Laryngoscope, 2017

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Computed tomography image navigation patient tracker on the cheek during osteoplastic flaps

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Tobacco exposure and wound healing in head and neck surgical wounds

Objective

Smoking impairs wound healing, yet the underlying pathophysiological mechanisms are unclear. We evaluated tobacco-altered healing in head and neck surgery by studying the association between biomarkers and tobacco exposure, as well as cutaneous perfusion by smoking status.

Study Design

Prospective cohort study, tertiary/academic care center, 2011 to present.

Methods

Patients who required head and neck surgery were enrolled prospectively. Postsurgical drain fluid was collected 24 hours postoperatively. Biomarkers associated with postulated mechanisms of smoking-impaired healing were assayed. These included interleukin-1, -6, and -8; tumor necrosis factor- alpha; transforming growth factor-beta; epidermal growth factor (EGF); basic fibroblastic growth factor (bFGF); C-reactive protein; vascular endothelial growth factor; soluble FMS-like tyrosine kinase-1 (sFLT-1); and placental growth factor. Tobacco exposure and clinical outcomes were recorded. Two sample two-sided t tests evaluated the differences in cytokine levels by tobacco exposure. In a second cohort, cutaneous vascular assessment via indocyanine green angiography was compared by smoking status.

Results

Twenty-eight patients were enrolled with drain fluid collection. Twenty-one subjects were current/former smokers, whereas seven were never smokers. EGF was higher in never smokers than smokers in a statistically significant manner (P = 0.030). Likewise, sFLT-1 was significantly higher in never smokers (P = 0.011). Cutaneous angiography revealed nonsmokers to have significantly higher cutaneous perfusion than smokers.

Conclusion

In this head and neck surgical cohort, significantly higher EGF and sFLT-1 levels in wound fluid were associated with never smoking, suggesting that smoking has adverse effects on the inflammatory phase of wound healing. Cutaneous angiography supports the detrimental effect of smoking on skin perfusion. These findings suggest the need for further study as well as therapeutic targets for smokers undergoing surgery.

Level of Evidence

IIb. Laryngoscope, 2017

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Impact of vocal fold augmentation and laryngoplasty on dyspnea in patients with glottal incompetence

Objectives/Hypothesis

Given that the vocal folds are active organs of respiration, reports of dyspnea in the context of glottic insufficiency are not uncommon. We hypothesize that improved glottal closure via framework surgery or vocal fold augmentation improves dyspnea symptoms.

Study Design

Retrospective review.

Methods

Charts of patients undergoing procedures to correct glottal insufficiency, either via vocal fold augmentation (VFA) or medialization laryngoplasty (ML) between December 2012 and September 2015 were reviewed (n = 189). Modified Borg Dyspnea Scale (MBDS) and Modified Medical Research Council Dyspnea Scale (MMRCDS) data were collected before and after intervention. Age, body mass index (BMI), and sex, as well as pulmonary and cardiac comorbidities were considered. Subgroup analysis was performed on individuals with subjective dyspnea prior to intervention.

Results

For the entire cohort, differences in the MMRCDS and MBDS were not statistically different pre- and postintervention (P = .20 and P = .12, respectively). Patients with BMI <30 experienced more improvement on the MBDS (P = .03). Both the MMRCDS and MMBDS improved post-procedure (P = .001 and P = .001, respectively) in patients reporting dyspnea prior to intervention.

Conclusions

Patients with glottic insufficiency and dyspnea prior to intervention to improve glottic closure had a significant reduction in dyspnea following treatment. Conversely, subjects without complaints of dyspnea prior to intervention had variable outcomes with regard to dyspnea symptoms. Additionally, based on data from the entire cohort, VFA or ML did not worsen dyspnea symptoms. These data may assist in counseling and/or selection of patients considered for procedures to improve glottic closure.

Level of Evidence

4 Laryngoscope, 2017

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Is topical high-volume budesonide sinus irrigation safe?

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Corneal Warpage due to Massage Following Eyelid Surgery.

No abstract available

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Rational and simplified nomenclature for buccinator myomucosal flaps

Abstract

Background

Reconstruction of moderate-sized mucosal defects of the oral cavity or oropharynx represents a surgical challenge. Buccinator myomucosal flaps seem to provide "ideal reconstruction" of oral/oropharyngeal defects because they carry a thin, mobile, well-vascularized, and sensitive tissue, like that excised or lost. Nevertheless, these flaps are not immediately popular because of confusion surrounding the complex terminology used to name them.

Methods

After a retrospective study on our experience and a literature review, the authors propose a new rational and simplified nomenclature for the classification of buccinator myomucosal flaps, which clarifies the source vessel, the composition of the flap, and the type of transfer.

Results

According to this nomenclature, six types of buccinator myomucosal flaps are described.

Conclusions

This proposed nomenclature may bring a consensus on the classification of buccinator myomucosal flaps and can help their spread.

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Measurement of Active and Sedentary Behavior in Context of Large Epidemiologic Studies.

Introduction/Purpose: To assess the utility of measurement methods that may be more accurate and precise than traditional questionnaire-based estimates of habitual physical activity and sedentary behavior we compared the measurement properties of a past year questionnaire (AARP) and more comprehensive measures: an internet-based 24-hour recall (ACT24), and a variety of estimates from an accelerometer (ActiGraph). Methods: Participants were 932 adults (50-74 y) in a 12-month study that included reference measures of energy expenditure from doubly labeled water (DLW) and active and sedentary time via activPAL. Results: Accuracy at the group level (mean differences) was generally better for both ACT24 and ActiGraph than the AARP questionnaire. AARP accuracy for energy expenditure ranged from -4 to -13% lower than DLW, but its accuracy was poorer for physical activity duration (-48%) and sedentary time (-18%) vs. activPAL. In contrast, ACT24 accuracy was within 3 to 10% of DLW expenditure measures and within 1 to 3% of active and sedentary time from activPAL. For ActiGraph, accuracy for energy expenditure was best for the Crouter 2-regression method (-2 to -7%), and for active and sedentary time the 100 count/minute cut-point was most accurate (-1% to 2%) at the group level. One administration of the AARP questionnaire was significantly correlated with long-term average from the reference measures ([rho]XT=0.16-0.34) overall, but 4 ACT24 recalls had higher correlations ([rho]XT=0.48-0.60), as did 4-days of ActiGraph assessment ([rho]XT=0.54-0.87). Conclusion: New exposure assessments suitable for use in large epidemiologic studies (ACT24, ActiGraph) were more accurate and had higher correlations than a traditional questionnaire. Use of better more comprehensive measures in future epidemiologic studies could yield new etiologic discoveries and possibly new opportunities for prevention. (C) 2017 American College of Sports Medicine

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Neural Correlates to the Increase in Maximal Force after Dexamethasone Administration.

Purpose: This study investigated the effects of short-term glucocorticoid administration on voluntary activation and intracortical inhibitory and facilitatory circuits. Methods: Seventeen healthy men participated in a pseudo randomized double-blind study to receive either dexamethasone (8 mg[middle dot]d-1, n = 9 subjects) or placebo (n = 8 subjects) for 7 days. The ankle dorsiflexion torque, corresponding electromyography (EMG) of the tibialis anterior, and voluntary activation assessed by the interpolated twitch method using transcranial magnetic stimulation (TMS) were measured during a maximal voluntary contraction (MVC). Short-latency intracortical inhibition (SICI) and intracortical facilitation (ICF) were assessed at rest and during submaximal contraction (50% MVC torque) by paired-pulse TMS with the conditioning stimulus set at 0.8x of motor threshold (0.8x MT) and delivered 2 ms (SICI) and 13 ms (ICF) prior to the test stimulus (1.2x MT). Results: The MVC torque (+14%), tibialis anterior EMG (+31%) and voluntary activation (+3%) increased after glucocorticoid treatment (p

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An Innovative Ergometer to Measure Neuromuscular Fatigue Immediately after Cycling.

Purpose: When assessing neuromuscular fatigue (NMF) from dynamic exercise using large muscle mass (e.g. cycling), most studies have delayed measurement for 1-3 min after task failure. This study aimed to determine the reliability of an innovative cycling ergometer permitting the start of fatigue measurement within 1 s after cycling. Methods: Twelve subjects participated in two experimental sessions. Knee-extensor NMF was assessed by electrical nerve and transcranial magnetic stimulation with both a traditional chair set-up (PRE and POST-Chair, 2 min post-exercise) and the new cycling ergometer (PRE, every 3 min during incremental exercise and POST-Bike, at task failure). Results: The reduction in maximal voluntary contraction (MVC) force POST-Bike (63 +/- 12% PRE; P 0.05). Vastus lateralis and rectus femoris M-wave and motor-evoked potential areas showed fair to excellent reliability (ICC = 0.45 to 0.88). The reduction in MVC and Db100 was greater on the cycling ergometer than the isometric chair. Conclusion: The innovative cycling ergometer is a reliable tool to assess NMF during and immediately post-exercise. This will allow fatigue etiology during dynamic exercise with large muscle mass to be revisited in various populations and environmental conditions. (C) 2017 American College of Sports Medicine

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Corneal Warpage due to Massage Following Eyelid Surgery.

No abstract available

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The Temporal Artery Island Flap: A Good Reconstructive Option for Small to Medium Sized Facial Defects

Publication date: Available online 19 September 2017
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Said Algan, Murat Kara, Hakan Cinal, Ensar Zafer Barin, Akin Inaloz, Onder Tan
PurposeThe reconstruction of facial defects is esthetically vital due to unique skin color and texture of the face. The aim of this study is to show the effectiveness of different styles of the temporal artery island flap for the reconstruction of upper and middle facial defects without losing color and texture of the face.Materials and MethodsThis study is retrospective case series conducted between November 2004 and May 2015. Patients over 18 years old, having upper and middle facial defects less than 5 cm were included.ResultsWe used the temporal artery island flapin 34 patients (21 males and 13 females) in our clinic. The etiologies were skin tumor in 17 patients, trauma in 10 patients, and burns in 7 patients. Major defect localization was the temporal area in 12 patients, followed by ear in 9 patients, cheek in 6 patients, eyebrow in 4 patients and nose in 3 patients The flaps' styles composed of antegrade flowed island flap, V-Y flap and reverse flowed island flap in 23, 7 and 4 patients, respectively. All flaps survived completely except of only one partial flap necrosis. Scars in the donor areas were inconspicuous. The median age was 47.5 years (quartiles 40.75-54), 61.8% male and median duration of follow-up was 11 months (ranging from 6 to 18 months).ConclusionsThe temporal artery island flap may be a good option for closure of minor to medium sized defects of the upper and middle face with its advantages including good color and texture match, constant and reliable pedicle, wide pivotal movement, low donor site morbidity, and use in reverse flow pattern.



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A rare, unusual presentation of primary tuberculosis in the temporomandibular joint

Publication date: Available online 19 September 2017
Source:Journal of Oral and Maxillofacial Surgery
Author(s): N.T. Geetha, Amarnath P. Upasi, K.V. Umashakara, Kirthikumar Rai
Tuberculosis (TB) is a very common health problem in developing nations like India. It can present as either its primary form or in secondary forms which are called extrapulmonary tuberculosis. Maxillofacial manifestations of tuberculosis form nearly 10% of all extrapulmonary manifestations of the disease. Extrapulmonary TB involving the maxillofacial region is very rare and it can present in any of the tissues. These infections generally involve the head and neck through haematogenous or lymphatic routes. Very few cases of primary TB of the temporomandibular joint (TMJ) have been reported in the literature. The presentation of TB infection of the TMJ may resemble an arthritis, osteomyelitis, or any other kind of chronic joint disease. It is very important to diagnose this disease at an early stage. If left untreated, it may prove fatal within 5 years in more than half of the cases. So early diagnosis and management of these cases is needed. In this article we describe a case of primary tuberculosis of the TMJ which presented as a preauricular swelling.



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Re: Dr Yang's Meta-Analysis

Publication date: Available online 19 September 2017
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Hongpu Wei, Xudong Wang




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Enhance Surgical Outcomes in Patients with Skeletal Class III Facial Asymmetry by 3D Surgical Simulation

Publication date: Available online 19 September 2017
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Ellen Wen-Ching Ko, Cheng-Hui Lin, Ying-An Chen, Yu-Ray Chen
PurposeWith the advance of the image fusion techniques, the creation of the 3D virtual head and 3D surgical simulations provided previews of the surgical procedures. The aim of the study was to investigate the surgical outcomes in patients receiving orthognathic surgery (OGS) with the guidance of 3D computer-assisted surgical simulation.MethodsThe study included 34 consecutive patients (15 men and 19 women, 18.1–33.0 years of age) with skeletal Class III facial asymmetry who had bimaxillary OGS. The 1-week postoperative cone-beam computed tomography craniofacial images (Ta) were constructed and superimposed on preoperative simulated virtual images (Ts) at the cranial base and surfaces of the frontal and periorbital regions. The 3D cephalometric landmarks were measured relative to three reference planes. The outcomes among different experience level of surgeons were also compared.ResultsAlthough the means of Ta−Ts were small, statistical differences were observed in center of maxillary and mandibular incisors and B point relative to the midline, and in the maxillary first molar in vertical distances, sagittal dental–skeletal dimensions, and pitch angles. The root mean square deviation (RMSDL) of measurement variables relative to the center landmark accuracy was 1.5 mm and <2 mm at the maxilla and mandible, respectively. RMSDL >2 mm were located at the maxillary first molar in the vertical distance and in the sagittal dimension at points ANS and B point. Variables related to centering the midline structures were highly interrelated. The roll angle deviation was associated with centering the midline landmarks. The yaw angle deviation was not associated with midline correction.ConclusionWith guidance from 3D surgical simulation, surgeons were able to achieve similar outcomes to correct facial asymmetry regardless of their years of practice.



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Reply

Publication date: Available online 19 September 2017
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Le Yang, Guiqing Liao




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Masthead

Publication date: September–October 2017
Source:Brachytherapy, Volume 16, Issue 5





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Table of Contents

Publication date: September–October 2017
Source:Brachytherapy, Volume 16, Issue 5





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Editorial Board

Publication date: September–October 2017
Source:Brachytherapy, Volume 16, Issue 5





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Movement-related activity in the periarcuate cortex of monkeys during coordinated eye and hand movements

To determine the role of the periarcuate cortex during coordinated eye and hand movements in monkeys, the present study examined neuronal activity in this region during movement with the hand, eyes, or both as effectors toward a visuospatial target. Similar to the primary motor cortex (M1), the dorsal premotor cortex contained a higher proportion of neurons that were closely related to hand movements, whereas saccade-related neurons were frequently recorded from the frontal eye field (FEF). Interestingly, neurons that exhibited activity related to both eye and hand movements were recorded most frequently in the ventral premotor cortex (PMv), located between the FEF and M1. Neuronal activity in the periarcuate cortex was highly modulated during coordinated movements compared to either eye or hand movement only. Additionally, a small number of neurons were active specifically during one of the three task modes, which could be dissociated from the effector activity. In this case, neuron onset was either ahead of or behind the onset of eye and/or hand movement, and some neuronal activity lasted until reward delivery signaled successful completion of reaching. The present findings indicate that the periarcuate cortex, particularly the PMv, plays important roles in orchestrating coordinated movements from the initiation to the termination of reaching.

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Feature-coding transitions to conjunction-coding with progression through human visual cortex

Identifying an object and distinguishing it from similar items depends upon the ability to perceive its component parts as conjoined into a cohesive whole, but the brain mechanisms underlying this ability remain elusive. The ventral visual processing pathway in primates is organized hierarchically: Neuronal responses in early stages are sensitive to the manipulation of simple visual features whereas neuronal responses in subsequent stages are tuned to increasingly complex stimulus attributes. It is widely assumed that feature-coding dominates in early visual cortex whereas later visual regions employ conjunction-coding in which object representations are different from the sum of their simple-feature parts. However, no study in humans has demonstrated that putative object-level codes in higher visual cortex cannot be accounted for by feature-coding and that putative feature-codes in regions prior to ventral temporal cortex are not equally well characterized as object-level codes. Thus the existence of a transition from feature- to conjunction-coding in human visual cortex remains unconfirmed, and, if a transition does occur, its location remains unknown. By employing multivariate analysis of functional imaging data, we measure both feature-coding and conjunction-coding directly, using the same set of visual stimuli, and pit them against each other to reveal the relative dominance of one versus the other throughout cortex. Our results reveal a transition from feature-coding in early visual cortex to conjunction-coding in both inferior temporal and posterior parietal cortices. This novel method enables the use of experimentally controlled stimulus features to investigate population-level feature- and conjunction-codes throughout human cortex.

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Phase-Dependent deficits during Reach-to-Grasp after Human Spinal Cord Injury

Most cervical spinal cord injuries result in asymmetrical functional impairments in hand and arm function. However, the extent to which reach-to-grasp movements are affected in humans with incomplete cervical spinal cord injury (SCI) remains poorly understood. Using kinematics and electromyographic (EMG) recordings in hand and arm muscles we studied the different phases of unilateral self-paced reach-to-grasp movements (arm acceleration, hand opening and closing) to a small cylinder in the more and less affected arms of individuals with cervical SCI and age-matched controls. We found that SCI subjects showed prolonged movement duration during arm acceleration, hand opening and closing compared with controls in both arms. Notably, the more affected arm showed an additional increase in movement duration at the time to close the hand compared with the less affected arm. Also, the time at which the index finger and thumb contacted the object and the variability of finger movement trajectory were increased in the more compared with the less affected arm of SCI participants. Participants with prolonged movement duration during hand closing were those with more pronounce deficits in sensory function. The muscle activation ratio between the first dorsal interosseous and abductor pollicis brevis muscles decreased during hand closing in the more compared with the less affected arm of SCI participants. Our results suggest that deficits in movement kinematics during reach-to-grasp movements are more pronounced at the time to close the hand in the more affected arm of SCI participants, likely related to deficits in EMG muscle activation and sensory function.

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Cue-induced changes in the stability of finger force-production tasks revealed by the uncontrolled-manifold analysis

A motor system configured to maximize the stability of its current state cannot dexterously transition between states. Yet, we routinely resolve the stability-dexterity conflict and rapidly change our current behavior without allowing it to become unstable prior to the desired transition. The phenomenon called anticipatory synergy adjustment (ASA) partly describes how the central nervous system handles this conflict. ASA is a continuous decrease in the stability of the current motor state beginning 150-400 ms prior to a rapid state transition accomplished using redundant sets of motor inputs (more input variables than task-specific output variables). So far, ASAs have been observed only when the timing of the upcoming transition is known. We utilized a multi-finger, isometric force production task to demonstrate that compared to a condition where no state transition is expected, the stability of the current state is lower by about 12% when a participant is cued to make a transition - even when the nature and timing of that transition are unknown. This result (stage-1 ASA) is distinct from its traditional version (stage-2 ASA), and it describes early destabilization that occurs solely in response to the expectation to move. Stage-2 ASA occurs later, only if the timing of the transition is known sufficiently in advance. Stage-1 ASA lasts much longer (~ 1.5 seconds), and may scale in response to the perceived difficulty of the upcoming task. Therefore, this work reveals a much-refined view of the processes that underlie the resolution of the stability-dexterity conflict.

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Interacting networks of brain regions underlie human spatial navigation: A review and novel synthesis of the literature

Navigation is an inherently dynamic and multimodal process, making isolation of the unique cognitive components underlying it challenging. The assumptions of much of the literature on human spatial navigation are that: 1) spatial navigation involves modality independent, discrete metric representations (i.e., egocentric vs. allocentric) 2) such representations can be further distilled to elemental cognitive processes 3) these cognitive processes can be ascribed to unique brain regions. Here, we argue that modality independent spatial representations, instead of providing exact metrics about our surrounding environment, more often involve heuristics for estimating spatial topology useful to the current task at hand. We also argue that egocentric (body-centered) and allocentric (world-centered) representations are better conceptualized as involving a continuum rather than as discrete. We propose a neural model to accommodate these ideas, arguing that such representations also involve a continuum of network interactions centered on retrosplenial and posterior parietal cortex, respectively. Our model thus helps explain both behavioral and neural findings otherwise difficult to account for with classic models of spatial navigation and memory, providing a testable framework for novel experiments.

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The coupling of synaptic inputs to local cortical activity differs among neurons and adapts following stimulus onset

Cortical activity contributes significantly to the high variability of sensory responses of interconnected pyramidal neurons, which has crucial implications for sensory coding. Yet, largely because of technical limitations of in vivo intracellular recordings, the coupling of a pyramidal neuron's synaptic inputs to the local cortical activity has evaded full understanding. Here, we obtained excitatory synaptic conductance (g) measurements from putative pyramidal neurons and local field potential (LFP) recordings from adjacent cortical circuits during visual processing in the turtle whole-brain ex vivo preparation. We found a range of g-LFP coupling across neurons. Importantly, for a given neuron, g-LFP coupling increased at stimulus onset, and then relaxed towards intermediate values during continued visual stimulation with naturalistic movies. A model network with clustered connectivity and synaptic depression reproduced both the diversity and the dynamics of g-LFP coupling. In conclusion, these results establish a rich dependence of single-neuron responses on anatomical, synaptic, and emergent network properties.

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Non-uniform surround suppression of visual responses in mouse V1

Complex receptive field characteristics, distributed across a population of neurons, are thought to be critical for solving perceptual inference problems that arise during motion and image segmentation. For example, in a class of neurons referred to as 'end-stopped', increasing the length of stimuli outside of the bar-responsive region into the surround suppresses responsiveness. It is unknown whether these properties exist for receptive field surrounds in the mouse. We examined surround modulation in layer 2/3 neurons of the primary visual cortex in mice using two-photon calcium imaging. We found that surround suppression was significantly asymmetric in 17% of the visually responsive neurons examined. Furthermore, the magnitude of asymmetry was correlated with orientation selectivity. Our results demonstrate that neurons in mouse primary visual cortex are differentially sensitive to the addition of elements in the surround and that individual neurons can be described as being either uniformly suppressed by the surround, end-stopped, or side-stopped.

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Evidence for the representation of movement kinematics in the discharge of F5 mirror neurons during the observation of transitive and intransitive actions.

Mirror neurons (MirNs) are sensorimotor neurons that fire both when an animal performs a goal-directed action and when the same animal observes another agent performing the same or a similar transitive action. It has been claimed that the observation of intransitive actions does not activate MirNs in a monkey's brain. Prompted by recent evidence indicating that the discharge of MirNs is modulated also by non object-directed actions, we investigated thoroughly the efficacy of intransitive actions to trigger MirNs' discharge. Using representational similarity analysis, we also studied whether the elements constituting the visual scene presented to the monkey during the observation of actions (both transitive and intransitive) are represented in the discharge of MirNs. For this purpose, the moving hand was modelled by its kinematics and the object by features of its geometry. We found that MirNs respond to the observation of both transitive and intransitive actions and that the discharge differences evoked by the observation of object- and non object-directed actions are correlated more with the kinematic differences of these actions than with the differences of the objects' features. These findings support the view that observed action kinematics contribute to action mirroring.

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Cranial nerve non-invasive neuromodulation improves gait and balance in stroke survivors: A pilot randomised controlled trial

Publication date: Available online 20 September 2017
Source:Brain Stimulation
Author(s): Mary P. Galea, L. Eduardo Cofré Lizama, Andisheh Bastani, Maya G. Panisset, Fary Khan




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Short- and long-latency afferent inhibition; uses, mechanisms and influencing factors

Publication date: Available online 20 September 2017
Source:Brain Stimulation
Author(s): Claudia V. Turco, Jenin El-Sayes, Mitchell J. Savoie, Hunter J. Fassett, Mitchell B. Locke, Aimee J. Nelson
Transcranial magnetic stimulation (TMS) is an ideal technique for non-invasively stimulating the brain and assessing intracortical processes. By delivering electrical stimuli to a peripheral nerve prior to a TMS pulse directed to the motor cortex, the excitability and integrity of the sensorimotor system can be probed at short and long time intervals (short latency afferent inhibition, long latency afferent inhibition). The goal of this review is to detail the experimental factors that influence the magnitude and timing of afferent inhibition in the upper limb and these include the intensity of nerve and TMS delivery, and the nerve composition. Second, the neural mechanisms of SAI are discussed highlighting the lack of existing knowledge pertaining to LAI. Third, the usage of SAI and LAI as a tool to probe cognition and sensorimotor function is explored with suggestions for future avenues of research.



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Anesthesia and Perioperative Care for Organ Transplantation.

No abstract available

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Acute Lung Injury and Repair: Scientific Fundamentals and Methods.

No abstract available

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Factors Influencing the Choice of Anesthesia as a Career by Undergraduates of the University of Rwanda.

No abstract available

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Administration of Hypertonic Solutions for Hemorrhagic Shock: A Systematic Review and Meta-analysis of Clinical Trials.

BACKGROUND: Several clinical trials on hypertonic fluid administration have been completed, but the results have been inconclusive. The objective of this study is to summarize current evidence for treating hypovolemic patients with hypertonic solutions by performing a systematic review and meta-analysis. METHODS: Major electronic databases were searched from inception through June 2014. We included only randomized controlled trials involving hemorrhagic shock patients treated with hypertonic solutions. After screening 570 trials, 12 were eligible for the final analysis. Pooled effect estimates were calculated with a random effect model. RESULTS: The 12 studies included 6 trials comparing 7.5% hypertonic saline (HS) with 0.9% saline or Ringer's lactate solution and 11 trials comparing 7.5% hypertonic saline with dextran (HSD) with isotonic saline or Ringer's lactate. Overall, there were no statistically significant survival benefits for patients treated with HS (relative risk [RR], 0.96; 95% confidence interval [CI], 0.82-1.12) or HSD (RR, 0.92; 95% CI, 0.80-1.06). Treatment with hypertonic solutions was also not associated with increased complications (RR, 1.03; 95% CI, 0.78-1.36). Subgroup analysis on trauma patients in the prehospital or emergency department settings did not change these conclusions. There was no evidence of significant publication bias. Metaregression analysis did not find any significant sources of heterogeneity. CONCLUSIONS: Current evidence does not reveal increased mortality when the administration of isotonic solutions is compared to HS or HSD in trauma patients with hemorrhagic shock. HS or HSD may be a viable alternative resuscitation fluid in the prehospital setting. Further studies are needed to determine the optimum volume and regimen of intravenous fluids for the treatment of trauma patients. (C) 2017 International Anesthesia Research Society

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The Little ICU Book, 2nd ed.

No abstract available

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Preventing Mistransfusions: An Evaluation of Institutional Knowledge and a Response.

BACKGROUND: Blood product mistransfusions occur when a process error causes transfusion of incompatible blood products. These events are known sources of negative patient outcomes. One such event demonstrated an institutional knowledge gap and an opportunity to reduce this source of transfusion errors. The focus of this study was to evaluate the application of point of care cognitive aids to bridge potentially lethal knowledge gaps in blood product to patient compatibility. METHODS: A patient-donor ABO antigen compatibility grid for red blood cells (RBC) and fresh frozen plasma (FFP) was developed for creation of a cognitive aid and a blood product safety quiz. Participants included 117 registered nurses and postgraduate medical interns who were given 2 minutes to complete the quiz for establishing institutional controls. A separate group of 111 registered nurses and interns were given the same timed quiz twice, without and then with a blood product compatibility cognitive aid. An analysis of covariance was used to evaluate without cognitive aid versus with cognitive aid quiz results while taking the specialty (nurse versus interns) and baseline score into consideration. The blood bank adopted the grid as a forcing function to be completed before release of blood products. RESULTS: The correct RBC answer percentage increased from 84.7% to 98.3% without and with cognitive aid (average improvement 13.6%, standard deviation [SD] = 18.3%, 95% confidence interval, 10.1%-17.1%, P

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Other Specialties Might Have a GPS.

No abstract available

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CT and MR imaging findings of inflammatory pseudotumors in the abdomen and pelvis: Current concepts and pictorial review

The group of inflammatory pseudotumors (IPTs) encompasses a variety of rare neoplastic and non-neoplastic entities described to occur in almost every location in the body and whose clinical features and aggressive imaging findings (varying from infiltrative to mass-forming lesions), frequently mimic those of malignant tumors. The radiologic features of IPTs are variable and nonspecific, the imaging findings depending on the body location and involved organ. Abdominopelvic IPTs are rare and the purposes of this review, therefore, are to familiarize the radiologist with the wide spectrum of CT and MR imaging findings of IPTs in various locations throughout the abdomen and pelvis, discussing the imaging features that allow consideration of IPTs in the differential diagnosis of soft-tissue masses within the pertinent clinical setting.

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Contents

Publication date: October 2017
Source:European Journal of Vascular and Endovascular Surgery, Volume 54, Issue 4





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One year on: Test your knowledge from the previous year

Publication date: October 2017
Source:European Journal of Vascular and Endovascular Surgery, Volume 54, Issue 4





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Editorial Board

Publication date: October 2017
Source:European Journal of Vascular and Endovascular Surgery, Volume 54, Issue 4





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EJVES vol. 54, issue 4 (October 2017) - Spanish Translated Abstracts

Publication date: October 2017
Source:European Journal of Vascular and Endovascular Surgery, Volume 54, Issue 4





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Selected Abstracts from the October Issue of the Journal of Vascular Surgery

Publication date: October 2017
Source:European Journal of Vascular and Endovascular Surgery, Volume 54, Issue 4





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Doppler ultrasonography can be useful to determine the etiology of idiopathic sudden sensorineural hearing loss

This study aims to evaluate clinical features of both carotid and vertebral arteries in the idiopathic sudden sensorineural hearing loss (ISSNHL) patients and healthy individuals to contribute additional knowledge on vascular compromise theory.

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Lamina papyracea position in patients with nasal polypi: A computed tomography analysis

This study aimed to describe the positions of the lamina papyracea (LP) in patients who had nasal polypi, by computed tomography (CT) analysis.

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Resident Editors of the Journal of Voice Editorial Board

Traditional medical education provides virtually no formal training regarding publication. Not even basic writing techniques are taught, let alone information about the editorial process or skills required to participate effectively on an editorial board. Most nonmedical graduate training programs have similar weaknesses. This problem has been addressed in prior publications.1–5 More than a decade ago, the Ear, Nose and Throat Journal started inviting a small number of residents to participate as student members of the editorial board.

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Indications and Controversies for Abdominally-Based Complete Autologous Tissue Breast Reconstruction

Publication date: Available online 19 September 2017
Source:Clinics in Plastic Surgery
Author(s): Blake D. Murphy, Isabel Kerrebijn, Jian Farhadi, Jaume Masia, Stefan O.P. Hofer

Teaser

This article reviews the indications and controversies in abdominally based autologous breast reconstruction. The evidence regarding these indications and controversies will be appraised and summarized. Finally, we will provide a summary of our approach and technique for the patient undergoing autologous breast reconstruction using abdominally based free flaps.


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Allergic sensitization in American children of Middle Eastern ethnicity at age 2

Children of Middle Eastern ethnicity (MEE) born in the United States are seldom specifically examined in allergic disease research, and the prevalence of allergic sensitization in these children is unknown.1 For analyses, these children can be combined with white children not of MEE or excluded entirely because of the small sample, as we have previously done.2,3 However, this subgroup could have a unique set of cultural norms and/or environmental exposures that distinguish them from white, black, non–Middle Eastern, and non-Hispanic children with respect to allergic disease risk factors.

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Serum periostin during omalizumab therapy in asthma: a tool for patient selection and treatment evaluation

Omalizumab is an effective treatment for severe allergic asthma.1 Nevertheless, even in patients meeting the prescription criteria, lack of efficacy has been described as the most common reason for treatment discontinuation, at least in the real-life setting.2 An association between baseline serum periostin (SP) levels, evaluated before the start of treatment, and omalizumab efficacy has been recently described,3,4 suggesting the relevance of this molecule as a biomarker for patient selection and predictor of treatment response.

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Impaired objective and subjective sleep in children and adolescents with inflammatory bowel disease compared to healthy controls

Poor sleep and higher inflammation markers are associated, and impaired sleep quality is common among patients with inflammatory bowel disease (IBD). However, information on sleep among children and adolescents with IBD is currently lacking. The aims of the present study were to compare subjective and objective sleep of children and adolescents with IBD with healthy controls and to shed more light on the relationship between sleep and inflammation. We expected that poor sleep, as assessed via sleep electroencephalography recordings, would be observed among participants with IBD, but particularly among participants in an active state of disease.

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Subjective Evaluation of Dreams in pregnant women in the different trimesters and in non-pregnant women

Sleep disturbances are prevalent among pregnant women (PW). Sleep is more fragmented during the third trimester, which consequently increases the ability to remember the content of dreams.

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Sleep-Related Hypermotor Syndrome: An arousal parasomnia or nocturnal frontal lobe epilepsy?

A variety of complex (as well as simple) movements may occur during sleep in an apparently normal individual. Physicians at the sleep or epilepsy clinics often encounter patients referred for such nocturnal movements seeking answer to the question: Is it a parasomnia or a nocturnal seizure, particularly nocturnal frontal lobe epilepsy (NFLE) [originally called nocturnal paroxysmal dystonia (NPD) and recently renamed sleep-related hypermotor epilepsy (SHE)]? Nocturnal motor events may be classified into epileptic paroxysmal motor events and non-epileptic motor events consisting of parasomnias, sleep-related movement disorders, and isolated symptoms, apparently normal variants (eg, hypnic jerks, propriospinal myoclonus at sleep onset, fragmentary myoclonus, periodic limb movements in sleep, rhythmic leg movements, hypnagogic foot tremor and alternating leg movement activity.

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Determination of VEGF, collagen type 1 and versican in the discus articularis of the temporomandibular joint in relation to dental status

The aim of this study was the investigation and comparison of the presence of vascular endothelial growth factor (VEGF), collagen type 1 and the proteoglycan versican in the discus articularis in relation to dental status (full dentition [1], partial dentition [2] and edentulous [3]). The right disci articulares were removed from 17 donated bodies (6 with full dentition, 5 with partial dentition and 6 edentulous). The specimens were immunohistochemically stained for VEGF, collagen type 1 and versican.

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A worldwide comparison of the management of T1 and T2 anterior floor of the mouth and tongue squamous cell carcinoma – extent of surgical resection and reconstructive measures

Microvascular surgery following tumor resection has become an important field of oral maxillofacial surgery (OMFS). Following the results on general aspects of current reconstructive practice in German speaking countries, Europe and worldwide, this paper presents specific concepts for the management of resection and reconstruction of T1/T2 squamous cell carcinoma (SCC) of the anterior floor of the mouth and tongue.

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Custom-milled individual allogeneic bone grafts for alveolar cleft osteoplasty - a technical note

Bone grafts from the iliac crest are most commonly used for osteoplasties of the cleft alveolus. To preclude undue donor–site morbidity custom-milled allogeneic bone grafts might be an appropriate choice.This technical note showcases the repair of an alveolar cleft using an individualized allogeneic bone graft in a 36-year old female patient. She was asking for an alternative to the iliac crest bone grafting. Her alveolus was successfully build up by a custom-milled cancellous bone block allograft (maxgraft® bonebuilder).

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Nipple-sparing Mastectomy Safe for Women With BRCA Mutations

Reuters Health Information

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Erratum to: Gait characteristics and their discriminative power in geriatric patients with and without cognitive impairment

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Striatonigral Direct Pathway Activation is Sufficient to Induce Repetitive Behaviors

Publication date: Available online 20 September 2017
Source:Neuroscience Research
Author(s): Youcef Bouchekioua, Iku Tsutsui-Kimura, Hiromi Sano, Miwako Koizumi, Kenji F. Tanaka, Keitaro Yoshida, Yutaka Kosaki, Shigeru Watanabe, Masaru Mimura
Pharmacological intervention in the substantia nigra is known to induce repetitive behaviors in rodents, but a direct causal relationship between a particular neural circuit and repetitive behavior has not yet been established. Here we demonstrate that acute excitation in dopamine D1 receptor-expressing MSNs terminals in the substantia nigra pars reticulata by optogenetics resulted in sustained and chronic repetitive behaviors. These data show for the first time that activation of the striatonigral direct pathway is sufficient to generate motor stereotypies.



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Qualitative differences in offline improvement of procedural memory by daytime napping and overnight sleep: an fMRI study

Publication date: Available online 20 September 2017
Source:Neuroscience Research
Author(s): Sho K. Sugawara, Takahiko Koike, Hiroaki Kawamichi, Kai Makita, Yuki H. Hamano, Haruka K. Takahashi, Eri Nakagawa, Norihiro Sadato
Daytime napping offers various benefits for healthy adults, including enhancement of motor skill learning. It remains controversial whether napping can provide the same enhancement as overnight sleep, and if so, whether the same neural underpinning is recruited. To investigate this issue, we conducted functional MRI during motor skill learning, before and after a short day-nap, in 13 participants, and compared them with a larger group (N=47) who were tested following regular overnight sleep. Training in a sequential finger-tapping task required participants to press a keyboard in the MRI scanner with their non-dominant left hand as quickly and accurately as possible. The nap group slept for 60minutes in the scanner after the training run, and the previously trained skill was subsequently re-tested. The whole-night sleep group went home after the training, and was tested the next day. Offline improvement of speed was observed in both groups, whereas accuracy was significantly improved only in the whole-night sleep group. Correspondingly, the offline increment in task-related activation was significant in the putamen of the whole-night group. This finding reveals a qualitative difference in the offline improvement effect between daytime napping and overnight sleep.



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Role of the epigenetic factor Sirt7 in neuroinflammation and neurogenesis

Publication date: Available online 20 September 2017
Source:Neuroscience Research
Author(s): Nicolas Burg, Stefan Bittner, Erik Ellwardt
Epigenetic regulators are increasingly recognized as relevant modulators in the immune and nervous system. The class of sirtuins consists of NAD⁺-dependent histone deacetylases that regulate transcription. Sirtuin family member Sirt1 has already been shown to influence the disease course in an animal model of autoimmune neuroinflammation (experimental autoimmune encephalomyelitis (EAE)). A role of Sirt7, a related epigenetic regulator, on immune system regulation has been proposed before, as these mice are more susceptible to develop inflammatory cardiomyopathy. Sirt7^−/− animals showed no differences in clinical score compared to wild-type littermates after EAE induction with myelin oligodendrocyte glycoprotein (MOG) peptide 35-55, although we found subtle immune alterations at different phases of EAE and decreased survival of newly generated neurons in the hippocampus. Our data indicate that Sirt7 has a slight protective impact on both the adaptive immune system and neurogenesis. However, overall this epigenetic factor is not capable of impacting the acute or chronic phase of neuroinflammation.



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So What Did You Hear This Summer?

The lawn is starting to slow down. The kids are back in school. The leaves are threatening to turn. And the white slacks are put away. Summer must be behind us. Talk around the water cooler or around the block while walking pets is soon going to turn to speculation about the winter. Is it going to be a bad one? Is it going to be another one of those late winters?

Tweet

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Study of factors responsible for recidivism in allergic fungal rhinosinusitis

Bipin Kishore Prasad, MS

Abstract

Patients with allergic fungal rhinosinusitis (AFRS) are typically atopic and immunocompetent. Despite combined modality treatment based on surgery and immunomodulation, the potential for recidivism is well recognized. A study was conducted in a military hospital in India to identify the factors responsible for recidivism in AFRS and to suggest measures to overcome it. Sixty patients with AFRS (42 new cases and 18 cases that required revision surgery) were managed between January 2009 and July 2013. Patients underwent endoscopic, radiologic, and laboratory evaluation for AFRS followed by functional endoscopic sinus surgery. Each patient received oral prednisolone, 1 mg/kg/day, for 1 week preoperatively and 0.5 mg/kg/day for 4 weeks postoperatively. A randomly selected group of 30 patients (group A) received oral prednisolone 0.4 mg/kg/day for the next 4 weeks, tapered to 0.2 mg/kg/day for the next 2 months and to 0.1 mg/kg/day for the last 2 months. The drug was stopped after 6 months. In the remaining 30 patients (group B), oral prednisolone was tapered within 2 months. Topical steroid sprays were advised in all patients. Recidivism was observed in 12 of 42 (28.6%) patients presenting for the first time with AFRS: 9 patients from group B (30%) and 3 patients from group A (10%). Besides inadequate postoperative oral steroid therapy, suboptimal functional endoscopic sinus surgery, noncompliance with intranasal sprays, nonadherence to Kupferberg staging, inadequate follow-up, failure of surgeons to impart health education to patients, and unavailability of ENT consultation in rural belts were found to be factors causing recidivism.

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Markers of proliferation and cytokeratins in the differential diagnosis of jaw cysts

Nikola D. Zivkovic, PhD; Dragan S. Mihailovic, PhD; Milos S. Kostic, PhD; Ana S. Cvetanovic, MD; Zaklina Z. Mijovic, PhD; Maja V. Jovicic Milentijevic, PhD; Tijana V. Dencic, MD

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Social media in otolaryngology-head and neck surgery

Modupe Oyewumi, MD; John Lee, MD, MSc, FRCSC; Allan Vescan, MD, FRCSC

Abstract

The objective of this study was to assess the current use of social media tools within Canadian otolaryngology-head and neck surgery (OHNS) programs and to assess the interest within these programs to integrate social media for networking, social, and educational programs. A prospective study from September 2013 to February 2014 was performed involving residents and faculty in Canadian OHNS programs. A 26-item questionnaire was created and sent to staff and resident physicians who met the study inclusion criteria using an online survey tool (surveymonkey.com). There were 101 respondents for a 10% response rate. More than half (58.4%) of respondents reported use of social media for personal and/or professional matters. Residents and junior faculty physicians 39 years and younger were more likely to have social media accounts and used them more frequently than their older counterparts. Among staff physicians, pediatric otolaryngologists had the highest rate of use, and otologists exhibited the lowest rate. Cellular phones were the most commonly used devices to access social media sites. Fewer than 35% of social media users failed to separate their personal and professional accounts. Although OHNS trainees and practicing physicians identified the potential benefits of social media tools in their specialty, most were unsure how to apply these tools to their practice. Ours is the first study to assess social media use in OHNS. Otolaryngologists are currently using social media; however, their application as a communication and educational tool in otolaryngology remains to be defined.

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Management decisions for Zenker diverticulum in the elderly

Karen Kost, MD, FRCSC; Kourosh Parham, MD

Zenker diverticulum is primarily a geriatric condition, usually requiring surgical management.

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Long-standing, near total tympanic membrane perforation

J. Scott Greene, MD, FACS

Although most spontaneous perforations heal, repeated ruptures and chronic suppuration can lead to permanent perforations.

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Hereditary hemorrhagic telangiectasia-laser treatment of epistaxis

Gorazd Poje, MD; Marcel Marjanovic Kavanagh, MD

Abstract

Hereditary hemorrhagic telangiectasia (HHT) is a rare, autosomal dominant disorder characterized by recurrent epistaxis, telangiectasias, and multiorgan vascular dysplasia. Various modalities exist for the treatment of HHT-related chronic epistaxis, although no method is preferred over another. The aim of this study was to review the effectiveness of diode laser photocoagulation in the treatment of epistaxis in patients with HHT. The study included 17 patients (7 men, 10 women) treated with diode laser photocoagulation from year 2008 to 2012. All patients met the Curaçao criteria for a diagnosis of HHT. Patients were followed for 1 year. Treatment success was assessed using a custom questionnaire and total blood counts. After laser photocoagulation, the frequency and intensity of bleeds were reduced significantly and average hemoglobin concentrations improved at the 4-month assessment. After laser treatment, no patient required septodermoplasty; therefore, we suggest that every patient with HHT should be treated with laser photocoagulation. Diode laser treatment is a simple and effective procedure that should be considered when treating HHT.

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Congenital ear malformations: Effectively correcting cryptotia with neonatal ear molding

Collin Rozanski, BA; Joseph J. Rousso, MD

Cryptotia is a relatively common congenital ear malformation that can be difficult to correct with surgery. Treatment should be started before the first 6 weeks of life.

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Maxillary sinus mucoceles and other side effects of external-beam radiation in the pediatric patient: A cautionary tale

Anthony Sheyn, MD; Tate Naylor, MD; Felicity Lenes-Voit, MD; Eric Berg, MD

Abstract

A sinonasal mucocele can develop after the obstruction of a sinus ostium, which can occur secondary to trauma, infection, a neoplasm, or an iatrogenic cause. These mucoceles typically arise in the frontal and ethmoid sinuses. Sinonasal mucoceles are epithelium-lined cysts that can gradually expand to fill a paranasal sinus. They can present with ophthalmologic, rhinologic, and neurologic symptoms. There are reports in the literature of sinonasal mucocele development after radiation for nasopharyngeal carcinoma. However, these cases are rare; when they do occur, they tend to arise in the sphenoid sinus. We describe the case of a 21-year-old man who had undergone external-beam radiotherapy for a right maxillary sinus rhabdomyosarcoma at the age of 4 years and who subsequently developed bilateral maxillary sinus mucoceles and multiple other known complications of radiation therapy. To the best of our knowledge, this is the first case of postirradiation bilateral maxillary sinus mucoceles to be reported in the literature.

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Ear fetal rhabdomyoma

Lester D. Thompson, MD

The soft tissues of the orbit, ear, and oral cavity are the most frequent sites of involvement, although adult-type rhabdomyomas are more common in the parapharyngeal and laryngeal spaces.

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Endoscopy-assisted Coblation for nasopharyngeal stenosis: A report of 2 cases

Omer Karakoc, MD; Bahtiyar Polat, MD; M. Timur Akcam, MD; Mustafa Gerek, MD

Abstract

Acquired nasopharyngeal stenosis, the standard treatments for which carry a high risk of restenosis, is an uncommon complication of both velopharyngeal surgery and radiotherapy to the nasopharynx. We present the cases of 2 men, aged 41 and 52 years, who underwent surgical treatment for nasopharyngeal stenosis with endoscopy-assisted Coblation. The two surgeries lasted 23 and 18 minutes, respectively. Neither patient experienced any surgical complication, and a nasopharyngeal stent was not needed in either case. At follow-up 12 months postoperatively, both patients exhibited a patent nasopharyngeal passage. Endoscopy-assisted Coblation appears to be a safe, effective, and less painful option for the treatment of nasopharyngeal stenosis.

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A collagen membrane containing osteogenic protein-1 facilitates bone regeneration in a rat mandibular bone defect

Publication date: December 2017
Source:Archives of Oral Biology, Volume 84
Author(s): Manami Ozaki, Tadahiro Takayama, Takanobu Yamamoto, Yasumasa Ozawa, Mayu Nagao, Natsuko Tanabe, Akira Nakajima, Naoto Suzuki, Masao Maeno, Seiichi Yamano, Shuichi Sato
ObjectivesOsteogenic protein-1 (OP-1) has shown osteoinductive activities and is useful for clinical treatments, including bone regeneration. Regenerative procedures using a bioabsorbable collagen membrane (BCM) are well established in periodontal and implant dentistry. We evaluated the subsequent effects of the BCM in combination with OP-1 on bone regeneration in a rat mandibular circular critical-sized bone defect in vivo.DesignWe used 8 rats that received surgery in both sides of the mandible, and created the total 16 defects which were divided into 4 groups: Group 1; no treatment, as a control, Group 2; BCM alone, Group 3; BCM containing low dose 0.5μg of OP-1 (L-OP-1), and Group 4; BCM containing high dose 2.0μg of OP-1 (H-OP-1). Newly formed bone was evaluated by micro computed tomography (micro-CT) and histological analyses at 8 weeks postoperatively. In quantitative and qualitative micro-CT analyses of the volume of new bone formation, bone density, and percentage of new bone area was evaluated.ResultsBCM with rhOP-1 significantly increased and accelerated bone volume, bone mineral density, and percentage of new bone area compared to control and BCM alone at 8 weeks after surgery; these enhancements in bone regeneration in the OP-1-treated groups were dose-dependent.ConclusionsOP-1 delivered with a BCM may have effective osteoinductive potency and be a good combination for bone regeneration. The use of such a combination device for osteogenesis may result in safer and more predictable bone regenerative outcomes in the future.



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De Gruyter veröffentlicht Enzyklopädie des Märchens als Paperback-Ausgabe und Online-Datenbank

 

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How Teotihuacan’s urban design was lost and found

A unique Mesoamerican city

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Overcoming the Challenges of Metastatic Cancer: An Interview with Dr. Rosandra Kaplan

NCI's Dr. Rosandra Kaplan discusses important trends in metastatic cancer research and new ideas for treating and preventing metastatic cancer.

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In Reply

Abstract

We appreciate the comments and concerns raised by members of SAEM's Academy of Diversity and Inclusion in Emergency Medicine¹ regarding the findings of our article, "A Systematic Review of the Impact of Physician Implicit Racial Bias on Clinical Decision Making."² We agree with Samuels et al.¹ that there are notable methodological limitations of earlier studies examining the influence of physician implicit bias on clinical decision making that must be considered when interpreting the findings of our systematic review.

This article is protected by copyright. All rights reserved.

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Cell free nucleic acids as diagnostic and prognostic marker in leukemia

Summary

Nucleic acids in circulation, called cell free DNA (cfDNA) and cell free RNA (cfRNA), have recently been analyzed as suitable diagnostic and prognostic markers in cancer. There have also been several reports about the role of this type of marker in leukemia. The relevant literature was identified by a PubMed search (2000–2017) of English-language literature using the terms "cell free DNA", "Leukemia" and Micro-RNA. Many quantitative and qualitative cfDNA biomarkers including copy number alteration, mutation, LOH and micro-RNA deregulated expression have been investigated in different studies, indicating promising results to distinguish patients from healthy individuals. The findings of this study indicate that nucleic acids in circulation have a high diagnostic and prognostic value in leukemic patients and, thus, have the potential to be used alongside the usual methods in the management of this disease.

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Experimental and numerical assessment of hyperthermic laser lipolysis with 1,064 nm Nd: YAG laser on a porcine fatty tissue model

Background and Objectives

The aim of this study was to develop experimental and numerical models for a better understanding of hyperthermic laser lipolysis (HHL).

Study Design

A 3 cm thick porcine fat sample was irradiated over a 4.3 × 4.7 cm² area for 2 minutes with a 1,064 nm Nd:YAG laser using 1.2 W/cm² irradiance. Two irradiation scenarios were considered: without and with forced air cooling. Following the irradiation, the sample was left to cool down by natural convection. During the irradiation period, the surface temperature of the sample was continuously recorded by an infrared camera. Additionally, temperature depth profiles during the cooling period were also obtained. A one-dimensional model of the laser irradiation procedure was developed, including light and heat transport. The model was used to determine the absorption coefficient of the fat and the heat convection coefficients from the measured data, and to evaluate the treatment by varying the parameters.

Results

The measured temperature depth profiles revealed a maximum temperature (45.5°C) at the surface for a non-cooled sample, and a surface temperature of 38°C with a subsurface temperature peak of 42.6°C at a depth of 5.7 mm for a cooled sample. This corresponded well with the measured surface temperature increase following the irradiation as a result of heat diffusion from the heated deeper fat layers. The developed numerical model was used to fit the measured data. A good agreement between the model and the measurements was obtained. By varying the treatment parameters, basic empirical relations connecting the treatment, thermal signal, and temperature depth profile parameters were found.

Conclusions

The results of this study provide a better understanding of transcutaneous laser lipolysis. The developed numerical model can be extended to transcutaneous laser lipolysis of human subjects. Lasers Surg. Med. © 2017 Wiley Periodicals, Inc.

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The Atypical MAP Kinase SWIP-13/ERK8 Regulates Dopamine Transporters through a Rho-Dependent Mechanism

The neurotransmitter dopamine (DA) regulates multiple behaviors across phylogeny, with disrupted DA signaling in humans associated with addiction, attention-deficit/ hyperactivity disorder, schizophrenia, and Parkinson's disease. The DA transporter (DAT) imposes spatial and temporal limits on DA action, and provides for presynaptic DA recycling to replenish neurotransmitter pools. Molecular mechanisms that regulate DAT expression, trafficking, and function, particularly in vivo, remain poorly understood, though recent studies have implicated rho-linked pathways in psychostimulant action. To identify genes that dictate the ability of DAT to sustain normal levels of DA clearance, we pursued a forward genetic screen in Caenorhabditis elegans based on the phenotype swimming-induced paralysis (Swip), a paralytic behavior observed in hermaphrodite worms with loss-of-function dat-1 mutations. Here, we report the identity of swip-13, which encodes a highly conserved ortholog of the human atypical MAP kinase ERK8. We present evidence that SWIP-13 acts presynaptically to insure adequate levels of surface DAT expression and DA clearance. Moreover, we provide in vitro and in vivo evidence supporting a conserved pathway involving SWIP-13/ERK8 activation of Rho GTPases that dictates DAT surface expression and function.

SIGNIFICANCE STATEMENT Signaling by the neurotransmitter dopamine (DA) is tightly regulated by the DA transporter (DAT), insuring efficient DA clearance after release. Molecular networks that regulate DAT are poorly understood, particularly in vivo. Using a forward genetic screen in the nematode Caenorhabditis elegans, we implicate the atypical mitogen activated protein kinase, SWIP-13, in DAT regulation. Moreover, we provide in vitro and in vivo evidence that SWIP-13, as well as its human counterpart ERK8, regulate DAT surface availability via the activation of Rho proteins. Our findings implicate a novel pathway that regulates DA synaptic availability and that may contribute to risk for disorders linked to perturbed DA signaling. Targeting this pathway may be of value in the development of therapeutics in such disorders.

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Synaptic Excitation in Spinal Motoneurons Alternates with Synaptic Inhibition and Is Balanced by Outward Rectification during Rhythmic Motor Network Activity

Regular firing in spinal motoneurons of red-eared turtles (Trachemys scripta elegans, either sex) evoked by steady depolarization at rest is replaced by irregular firing during functional network activity. The transition caused by increased input conductance and synaptic fluctuations in membrane potential was suggested to originate from intense concurrent inhibition and excitation. We show that the conductance increase in motoneurons during functional network activity is mainly caused by intrinsic outward rectification near threshold for action potentials by activation of voltage and Ca²⁺ gated K channels. Intrinsic outward rectification facilitates spiking by focusing synaptic depolarization near threshold for action potentials. By direct recording of synaptic currents, we also show that motoneurons are activated by out-of-phase peaks in excitation and inhibition during network activity, whereas continuous low-level concurrent inhibition and excitation may contribute to irregular firing.

SIGNIFICANCE STATEMENT Neurons embedded in active neural networks can enter a high-conductance state. High-conductance states were observed in spinal motoneurons during rhythmic motor behavior. Assuming no change in intrinsic conductance, it was suggested that the high-conductance state in motoneurons originated from balanced inhibition and excitation. In this study, we demonstrate that intrinsic outward rectification significantly contributes to the high-conductance state. Outward rectification balances synaptic excitation and maintains membrane potential near spike threshold. In addition, direct synaptic current recordings show out-of-phase excitation and inhibition in motoneurons during rhythmic network activity.

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UPF1 Governs Synaptic Plasticity through Association with a STAU2 RNA Granule

Neuronal mRNAs can be packaged in reversibly stalled polysome granules before their transport to distant synaptic locales. Stimulation of synaptic metabotropic glutamate receptors (mGluRs) reactivates translation of these particular mRNAs to produce plasticity-related protein; a phenomenon exhibited during mGluR-mediated LTD. This form of plasticity is deregulated in Fragile X Syndrome, a monogenic form of autism in humans, and understanding the stalling and reactivation mechanism could reveal new approaches to therapies. Here, we demonstrate that UPF1, known to stall peptide release during nonsense-mediated RNA decay, is critical for assembly of stalled polysomes in rat hippocampal neurons derived from embryos of either sex. Moreover, UPF1 and its interaction with the RNA binding protein STAU2 are necessary for proper transport and local translation from a prototypical RNA granule substrate and for mGluR-LTD in hippocampal neurons. These data highlight a new, neuronal role for UPF1, distinct from its RNA decay functions, in regulating transport and/or translation of mRNAs that are critical for synaptic plasticity.

SIGNIFICANCE STATEMENT The elongation and/or termination steps of mRNA translation are emerging as important control points in mGluR-LTD, a form of synaptic plasticity that is compromised in a severe monogenic form of autism, Fragile X Syndrome. Deciphering the molecular mechanisms controlling this type of plasticity may thus open new therapeutic opportunities. Here, we describe a new role for the ATP-dependent helicase UPF1 and its interaction with the RNA localization protein STAU2 in mediating mGluR-LTD through the regulation of mRNA translation complexes stalled at the level of elongation and/or termination.

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Effect of Threat on Right dlPFC Activity during Behavioral Pattern Separation

It has long been established that individuals with anxiety disorders tend to overgeneralize attributes of fearful stimuli to nonfearful stimuli, but there is little mechanistic understanding of the neural system that supports overgeneralization. To address this gap in our knowledge, this study examined effect of experimentally induced anxiety in humans on generalization using the behavioral pattern separation (BPS) paradigm. Healthy subjects of both sexes encoded and retrieved novel objects during periods of safety and threat of unpredictable shocks while we recorded brain activity with fMRI. During retrieval, subjects were instructed to differentiate among new, old, and altered images. We hypothesized that the hippocampus and dorsolateral prefrontal cortex (dlPFC) would play a key role in the effect of anxiety on BPS. The dlPFC, but not the hippocampus, showed increased activity for altered images compared with old images when retrieval occurred during periods of threat compared with safety. In addition, accuracy for altered items retrieved during threat was correlated with dlPFC activity. Together, these results suggest that overgeneralization in anxiety patients may be mediated by an inability to recruit the dlPFC, which mediates the cognitive control needed to overcome anxiety and differentiate between old and altered items during periods of threat.

SIGNIFICANCE STATEMENT Anxiety and posttraumatic stress disorder patients generalize fear to nonfearful fear stimuli, making it difficult to regulate anxiety. Understanding how anxiety affects generalization is key to understanding the overgeneralization experienced by these patients. We examined this relationship in healthy subjects by studying how threat of shock affects neural responses to previously encountered stimuli. Although previous studies point to hippocampal involvement, we found that threat affected activity in the dorsolateral prefrontal cortex (dlPFC), rather than the hippocampus, when subjects encountered slightly altered versions of the previously encountered items. Importantly, this dlPFC activity predicted performance for these items. Together, these results suggest that the dlPFC is important for discrimination during elevated anxiety and that overgeneralization may reflect a deficit in dlPFC-mediated cognitive control.

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Correction: Zhao et al., "Sox2 Sustains Recruitment of Oligodendrocyte Progenitor Cells following CNS Demyelination and Primes Them for Differentiation during Remyelination"

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Synaptic Adhesion Molecule Pcdh-{gamma}C5 Mediates Synaptic Dysfunction in Alzheimer's Disease

Synaptic dysfunction and neuronal excitatory/inhibitory imbalance have been implicated in Alzheimer's disease (AD) pathogenesis. Although intensive studies have been focused on the excitatory synaptic system, much less is known concerning the mechanisms mediating inhibitory synaptic dysfunction in AD. We reported previously that protocadherin-C5 (Pcdh-C5), a member of clustered Pcdh- subfamily of cadherin-type synaptic adhesion proteins, functions to promote GABAergic synaptic transmission. We reveal here that Pcdh-C5 is enriched in vesicular GABA transporter-positive synaptic puncta and its expression levels are increased in neuronal hyperexcitation conditions, upon β-amyloid (Aβ) treatment, and in amyloid precursor protein (APP)/presenilin-1 (PS1)-transgenic mice of both sexes. This is associated with elevated levels of GABAergic proteins and enhanced synaptic inhibition. Genetic knock-down experiments showed that Pcdh-C5 modulates spontaneous synaptic currents and Aβ-induced synaptic alterations directly. Our results support a model in which Pcdh-C5 senses neuronal hyperexcitation to augment GABAergic inhibition. This adaptive mechanism may be dysregulated under chronic excitation conditions such as AD, leading to aberrant Pcdh-C5 expression and associated synaptic dysfunction.

SIGNIFICANCE STATEMENT Synaptic dysfunction is causal for Alzheimer's disease (AD). Here, we reveal a novel pathway that contributes GABAergic synaptic dysfunction in AD mediated by protocadherin-C5. Our study not only identifies a new mechanism mediating excitatory/inhibitory balance in AD, but may also offer a new target for potential therapeutic intervention.

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Feedback Signal from Motoneurons Influences a Rhythmic Pattern Generator

Motoneurons are not mere output units of neuronal circuits that control motor behavior but participate in pattern generation. Research on the circuit that controls the crawling motor behavior in leeches indicated that motoneurons participate as modulators of this rhythmic motor pattern. Crawling results from successive bouts of elongation and contraction of the whole leech body. In the isolated segmental ganglia, dopamine can induce a rhythmic antiphasic activity of the motoneurons that control contraction (DE-3 motoneurons) and elongation (CV motoneurons). The study was performed in isolated ganglia where manipulation of the activity of specific motoneurons was performed in the course of fictive crawling (crawling). In this study, the membrane potential of CV was manipulated while crawling was monitored through the rhythmic activity of DE-3. Matching behavioral observations that show that elongation dominates the rhythmic pattern, the electrophysiological activity of CV motoneurons dominates the cycle. Brief excitation of CV motoneurons during crawling episodes resets the rhythmic activity of DE-3, indicating that CV feeds back to the rhythmic pattern generator. CV hyperpolarization accelerated the rhythm to an extent that depended on the magnitude of the cycle period, suggesting that CV exerted a positive feedback on the unit(s) of the pattern generator that controls the elongation phase. A simple computational model was implemented to test the consequences of such feedback. The simulations indicate that the duty cycle of CV depended on the strength of the positive feedback between CV and the pattern generator circuit.

SIGNIFICANCE STATEMENT Rhythmic movements of animals are controlled by neuronal networks that have been conceived as hierarchical structures. At the basis of this hierarchy, we find the motoneurons, few neurons at the top control global aspects of the behavior (e.g., onset, duration); and within these two ends, specific neuronal circuits control the actual rhythmic pattern of movements. We have investigated whether motoneurons are limited to function as output units. Analysis of the network that controls crawling behavior in the leech has clearly indicated that motoneurons, in addition to controlling muscle activity, send signals to the pattern generator. Physiological and modeling studies on the role of specific motoneurons suggest that these feedback signals modulate the phase relationship of the rhythmic activity.

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Location of the Mesopontine Neurons Responsible for Maintenance of Anesthetic Loss of Consciousness

The transition from wakefulness to general anesthesia is widely attributed to suppressive actions of anesthetic molecules distributed by the systemic circulation to the cerebral cortex (for amnesia and loss of consciousness) and to the spinal cord (for atonia and antinociception). An alternative hypothesis proposes that anesthetics act on one or more brainstem or diencephalic nuclei, with suppression of cortex and spinal cord mediated by dedicated axonal pathways. Previously, we documented induction of an anesthesia-like state in rats by microinjection of small amounts of GABA_A-receptor agonists into an upper brainstem region named the mesopontine tegmental anesthesia area (MPTA). Correspondingly, lesioning this area rendered animals resistant to systemically delivered anesthetics. Here, using rats of both sexes, we applied a modified microinjection method that permitted localization of the anesthetic-sensitive neurons with much improved spatial resolution. Microinjected at the MPTA hotspot identified, exposure of 1900 or fewer neurons to muscimol was sufficient to sustain whole-body general anesthesia; microinjection as little as 0.5 mm off-target did not. The GABAergic anesthetics pentobarbital and propofol were also effective. The GABA-sensitive cell cluster is centered on a tegmental (reticular) field traversed by fibers of the superior cerebellar peduncle. It has no specific nuclear designation and has not previously been implicated in brain-state transitions.

SIGNIFICANCE STATEMENT General anesthesia permits pain-free surgery. Furthermore, because anesthetic agents have the unique ability to reversibly switch the brain from wakefulness to a state of unconsciousness, knowing how and where they work is a potential route to unraveling the neural mechanisms that underlie awareness itself. Using a novel method, we have located a small, and apparently one of a kind, cluster of neurons in the mesopontine tegmentum that are capable of effecting brain-state switching when exposed to GABA_A-receptor agonists. This action appears to be mediated by a network of dedicated axonal pathways that project directly and/or indirectly to nearby arousal nuclei of the brainstem and to more distant targets in the forebrain and spinal cord.

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