Vocalization Subsystem Responses to a Temporarily Induced Unilateral Vocal Fold Paralysis

Purpose

The purpose of this study is to quantify the interactions of the 3 vocalization subsystems of respiration, phonation, and resonance before, during, and after a perturbation to the larynx (temporarily induced unilateral vocal fold paralysis) in 10 vocally healthy participants. Using dynamic systems theory as a guide, we hypothesized that data groupings would emerge revealing context-dependent patterns in the relationships of variables representing the 3 vocalization subsystems. We also hypothesized that group data would mask important individual variability important to understanding the relationships among the vocalization subsystems.

Method

A perturbation paradigm was used to obtain respiratory kinematic, aerodynamic, and acoustic formant measures from 10 healthy participants (8 women, 2 men) with normal voices. Group and individual data were analyzed to provide a multilevel analysis of the data. A 3-dimensional state space model was constructed to demonstrate the interactive relationships among the 3 subsystems before, during, and after perturbation.

Results

During perturbation, group data revealed that lung volume initiations and terminations were lower, with longer respiratory excursions; airflow rates increased while subglottic pressures were maintained. Acoustic formant measures indicated that the spacing between the upper formants decreased (F3–F5), whereas the spacing between F1 and F2 increased. State space modeling revealed the changing directionality and interactions among the 3 subsystems.

Conclusions

Group data alone masked important variability necessary to understand the unique relationships among the 3 subsystems. Multilevel analysis permitted a richer understanding of the individual differences in phonatory regulation and permitted subgroup analysis. Dynamic systems theory may be a useful heuristic to model the interactive relationships among vocalization subsystems.

Supplemental Material

https://doi.org/10.23641/asha.5913532

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Assessment of the wish to hasten death in patients with advanced cancer: a comparison of two different approaches

Abstract

Introduction

The Desire for Death Rating Scale (DDRS) and the short form of the Schedule of Attitudes toward Hastened Death (SAHD-5) are different approaches to assessing the wish to hasten death (WTHD). Both have clinical threshold scores for identifying individuals with a meaningfully elevated WTHD. However, the agreement between the two measures, and patient opinions about assessment of the WTHD, are unknown.

Objectives

To compare the DDRS and SAHD-5 and to analyse patient opinions about assessment of the WTHD.

Methods: The WTHD was assessed in 107 patients with advanced cancer using both the DDRS and SAHD-5. Patients were subsequently asked their opinion about this assessment.

Results

Correlation between scores on the SAHD-5 and the DDRS was moderate, Spearman rho=.67 (p<.01). The SAHD-5 identified 13 patients (12.1%) at risk of the WTHD, and the DDRS identified 6 patients (5.6%) with a moderate-high WTHD (p>.05). Concordance between the DDRS and SAHD-5 in identifying individuals with an elevated WTHD was poor when using recommended cut-off scores, κ=.37 (p<.01), but could be improved by using different thresholds. Only 4 patients (3.8%) regarded the assessment questions as bothersome, and 90.6% considered it important that healthcare professionals inquire about the WTHD.

Conclusions

The SAHD-5 and DDRS appear to be appropriate methods for assessing the WTHD and could provide complementary information in clinical practice: the SAHD-5 to screen for risk of the WTHD and the DDRS as a clinical interview to explore it in greater detail. Assessment of the WTHD is well accepted by palliative care cancer patients.

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Jimmie Holland and the Development of Psycho-Oncology in Africa

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Use of ultrasonic scalpel and monopolar electrocautery for skin incisions in neck dissection: a prospective randomized trial

Abstract

Purpose

Ultrasonic scalpel (UC) and monopolar electrocautery (ME) are standard equipment for soft tissue surgery. The aim of the present study was to compare intraoperative and postoperative patterns of patients using either UC or ME for skin incisions in neck dissection.

Material and methods

In a prospective randomized study of 30 patients, the thermal effects of UC (n = 15) and ME (n = 15) were examined using real-time infrared thermographic imaging. Additionally, tissue damage was evaluated histopathologically. The other measured variables were operation and bleeding time, postoperative pain score (only neck incision area), in-patient time, and complications.

Results

UC significantly reduces the thermal effects, compared to ME (p < 0.001). The mean depth of tissue damage (i.e., necrosis) was 272.7 μm for UC and 284.7 μm for ME with no significant difference (p = 0.285). From the third postoperative day, patients treated using UC had noticeably less pain in the neck incision area (t3 p = 0.010; t4 p < 0.001; t5 p < 0.005). Cutting time was reduced for ME by 36.1 s (p < 0.001) and the bleeding time was decreased by 40.9 s for UC (p < 0.001). The total preparation time was the same (p = 0.402). When comparing in-patient time (p = 0.723), as well as complications, no significant differences were seen.

Conclusion

UC results in less postoperative pain and less bleeding in the neck incision area. Accordingly, UC is superior to ME for skin incisions in neck dissection.

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A Pilot Study to Investigate the Relationship Between Interaural Differences in Temporal Bone Anatomy and Normal Variations in Caloric Asymmetry

Purpose

This study assesses interaural differences in temporal bone anatomy in subjects with normal caloric findings.

Method

Eligible patients included those referred to the Duke University Medical Center otology clinic complaining of dizziness, with a head computed tomography scan and caloric stimulation results within normal ranges (inter-ear difference ≤ 10% or < 25% unilateral weakness). Three-dimensional reconstructions of computed tomography scans in 11 patients were used to calculate the surface area and volume of lateral semicircular canals (LSCCs), mastoid airspaces, mastoid bones, and internal auditory canal diameter and circumference. Percent differences in interaural temporal bone anatomy (i.e., left-to-right asymmetry) were analyzed and correlated with warm caloric inter-ear difference (WCD) and clinically indicated caloric predictor asymmetry.

Results

A multivariate model predicting WCD from 9 interaural anatomic variables demonstrated a Pearson's coefficient of 0.999. A similarly constructed model of the clinically indicated caloric predictor demonstrated a Pearson's coefficient of 0.999. The univariate correlation was strongest for WCD versus Proctor internal auditory canal diameter (r = 0.476; p = .139) and WCD versus lateral semicircular canal surface-area-to-volume ratio (r = −0.474; p = .141).

Conclusions

This pilot study provides multivariate models that predict caloric asymmetry in subjects without vestibular pathologic findings per caloric testing, based on interaural differences across variables of the temporal bone anatomy.

Supplemental Material

https://doi.org/10.23641/asha.5895988

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A Cross-Sectional Study on the Hearing Threshold Levels Among People in Qinling, Qinghai, and Nanjing, China

Purpose

This study aimed to investigate the hearing threshold among different age groups, genders, and geographic areas in China to provide some insight into the appropriate clinical interventions for hearing loss.

Method

Using a systematic random sampling technique, 562 participants from Qinling, Qinghai, and Nanjing were included. Participants in the same area were divided into 3 groups according to their age. Pure-tone audiometric thresholds were measured at octave and interoctave frequencies of 0.125–16 kHz for each subject.

Results

There were significant differences in auditory thresholds at nearly all frequencies among young, middle-aged, and elderly people, and hearing thresholds increased with increasing age. People generally had the best hearing ability in Nanjing, better hearing ability in Qinghai, and the worst hearing ability in Qinling. Significant differences in hearing thresholds were found between males and females at several frequencies in Qinling.

Conclusion

People living in the rural area of Qinling in China had higher hearing threshold levels, particularly males, and hearing thresholds increased with age.

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Selective Determination of Chromium(VI) in Industrial Wastewater Samples by Micro-Electromembrane Extraction Combined with Electrothermal Atomic Absorption Spectrometry

Abstract

This study describes application of free liquid membrane (FLM) in micro-electromembrane extraction (μ-EME) of Cr(VI) from wastewater samples. Amount of Cr(VI) was quantified by electrothermal atomic absorption spectrometry. The transportation of Cr(VI) across the FLM was explored by electrokinetic migration and ion-exchange process. FLM and acceptor solution types, pH of donor and acceptor solutions, applied electrical potential, as well as FLM thickness were optimized. Presence of an anion exchange carrier (methyl trialkyl-ammonium chloride, Aliquat 336) in FLM facilitated Cr(VI) transportation. The best performance was observed for 1-octanol (containing 5% Aliquat 336) with thickness of 1 mm used as FLM, under applied electrical potential of 75 V, when 0.5 M NaClO₄ and 0.1 M HCl were used as the acceptor and donor phases, respectively; and the extraction time was set to 5 min. Linearity was obtained in the working range of 0.5–14.0 ng mL⁻¹ Cr(VI) (R² > 0.98). The calculated limit of detection was below 0.06 ng mL⁻¹. Application of this method to wastewater samples showed that relative recoveries of the spiked Cr(VI) in the samples were in the range of 73.8–85.1%, based on the standard addition method.

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Human papillomavirus vaccine: Urgent need to promote gender parity

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Analytical and clinical performance of progesterone receptor antibodies in breast cancer

Publication date: Available online 27 February 2018
Source:Annals of Diagnostic Pathology
Author(s): Benjamin C. Calhoun, Brian Mosteller, Daniel Warren, Margie Smith, J. Jordi Rowe, Christopher P. Lanigan, Karen C. Mrazeck, Espen Walker, Amy Hanlon Newell, Raymond Jones
ObjectiveComparison of analytical and immunohistochemical performance of progesterone receptor (PR) antibodies with correlation to recurrence of invasive breast cancer treated with endocrine therapy.MethodsThe binding-affinity kinetics of PR clones 1E2, 1A6, 16 and 636 were compared using synthetic peptides derived from identified epitopes on a Biacore T200. A cohort of 351 cases (Hormone Receptor (HR)+/HER2−) were stained for PR expression with immunohistochemistry (IHC) and scored according to ASCO/CAP criteria.ResultsThe stability of the antigen/antibody complex was greater for the 1E2 clone compared to 1A6, 16 and 636 clones. PR IHC on archival tissue resulted in 94.3% (299/317) concordance with clones.ConclusionClones evaluated in this study had a high level of concordance with IHC despite PR (1E2) demonstrating higher analytical binding properties than other clones. In a minority of cases (1.3% for 1E2 and 2.5% for 636) IHC results could convert estrogen receptor (ER)−/PR− to ER−/PR+ tumors, making these patients potentially eligible for endocrine therapy.



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Dynamic Interactions between Top-Down Expectations and Conscious Awareness

It is well known that top–down expectations affect perceptual processes. Yet, remarkably little is known about the relationship between expectations and conscious awareness. We address three crucial outstanding questions: (1) how do expectations affect the likelihood of conscious stimulus perception?; (2) does the brain register violations of expectations nonconsciously?; and (3) do expectations need to be conscious to influence perceptual decisions? Using human participants, we performed three experiments in which we manipulated stimulus predictability within the attentional blink paradigm, while combining visual psychophysics with electrophysiological recordings. We found that valid stimulus expectations increase the likelihood of conscious access of stimuli. Furthermore, our findings suggest a clear dissociation in the interaction between expectations and consciousness: conscious awareness seems crucial for the implementation of top–down expectations, but not for the generation of bottom-up stimulus-evoked prediction errors. These results constrain and update influential theories about the role of consciousness in the predictive brain.

SIGNIFICANCE STATEMENT While the relationship between expectations and conscious awareness plays a major role in many prediction-based theories of brain functioning, thus far few empirical studies have examined this relationship. Here, we address this gap in knowledge in a set of three experiments. Our results suggest that the effect of expectations on conscious awareness varies between different steps of the hierarchy of predictive processing. While the active use of top–down expectations for perceptual decisions requires conscious awareness, prediction errors can be triggered outside of conscious awareness. These results constrain and update influential theories about the role of consciousness in the predictive brain.

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The Axon Initial Segment: An Updated Viewpoint

At the base of axons sits a unique compartment called the axon initial segment (AIS). The AIS generates and shapes the action potential before it is propagated along the axon. Neuronal excitability thus depends crucially on the AIS composition and position, and these adapt to developmental and physiological conditions. The AIS also demarcates the boundary between the somatodendritic and axonal compartments. Recent studies have brought insights into the molecular architecture of the AIS and how it regulates protein trafficking. This Viewpoints article summarizes current knowledge about the AIS and highlights future challenges in understanding this key actor of neuronal physiology.

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Role of Anterior Intralaminar Nuclei of Thalamus Projections to Dorsomedial Striatum in Incubation of Methamphetamine Craving

Relapse to methamphetamine (Meth) seeking progressively increases after withdrawal from drug self-administration (incubation of Meth craving). We previously demonstrated a role of dorsomedial striatum (DMS) dopamine D1 receptors (D1Rs) in this incubation. Here, we studied the role of afferent glutamatergic projections into the DMS and local D1R–glutamate interaction in this incubation in male rats. We first measured projection-specific activation on day 30 relapse test by using cholera toxin b (retrograde tracer) + Fos (activity marker) double-labeling in projection areas. Next, we determined the effect of pharmacological reversible inactivation of lateral or medial anterior intralaminar nuclei of thalamus (AIT-L or AIT-M) on incubated Meth seeking on withdrawal day 30. We then used an anatomical asymmetrical disconnection procedure to determine whether an interaction between AIT-L->DMS glutamatergic projections and postsynaptic DMS D1Rs contributes to incubated Meth seeking. We also determined the effect of unilateral inactivation of AIT-L and D1R blockade of DMS on incubated Meth seeking, and the effect of contralateral disconnection of AIT-L->DMS projections on nonincubated Meth seeking on withdrawal day 1. Incubated Meth seeking was associated with selective activation of AIT->DMS projections; other glutamatergic projections to DMS were not activated. AIT-L (but not AIT-M) inactivation or anatomical disconnection of AIT-L->DMS projections decreased incubated Meth seeking. Unilateral inactivation of AIT-L or D1R blockade of the DMS had no effect on incubated Meth craving, and contralateral disconnection of AIT-L->DMS projections had no effect on nonincubated Meth seeking. Our results identify a novel role of AIT-L and AIT-L->DMS glutamatergic projections in incubation of drug craving and drug seeking.

SIGNIFICANCE STATEMENT Methamphetamine seeking progressively increases after withdrawal from drug self-administration, a phenomenon termed incubation of methamphetamine craving. We previously found that D1R-mediated dopamine transmission in the dorsomedial striatum plays a critical role in this incubation phenomenon. Here, we used neuroanatomical and neuropharmacological methods in rats to demonstrate that an interaction between the glutamatergic projection from the lateral anterior intralaminar nuclei of the thalamus to the dorsomedial striatum and local dopamine D1 receptors plays a critical role in relapse to methamphetamine seeking after prolonged withdrawal. Our study identified a novel motivation-related thalamostriatal projection critical to relapse to drug seeking.

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A Role for Cellular Prion Protein in Late-Onset Alzheimer's Disease: Evidence from Preclinical Studies

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Endoplasmic Reticulum Stress Contributes to the Loss of Newborn Hippocampal Neurons after Traumatic Brain Injury

Adult hippocampal neurogenesis has been shown to be required for certain types of cognitive function. For example, studies have shown that these neurons are critical for pattern separation, the ability to store similar experiences as distinct memories. Although traumatic brain injury (TBI) has been shown to cause the loss of newborn hippocampal neurons, the signaling pathway(s) that triggers their death is unknown. Endoplasmic reticulum (ER) stress activates the PERK-eIF2α pathway that acts to restore ER function and improve cell survival. However, unresolved/intense ER stress activates C/EBP homologous protein (CHOP), leading to cell death. We show that TBI causes the death of hippocampal newborn neurons via CHOP. Using CHOP KO mice, we show that loss of CHOP markedly reduces newborn neuron loss after TBI. Injured CHOP mice performed significantly better in a context fear discrimination task compared with injured wild-type mice. In contrast, the PERK inhibitor GSK2606414 exacerbated doublecortin cell loss and worsened contextual discrimination. Administration of guanabenz (which reduces ER stress) to injured male rats reduced the loss of newborn neurons and improved one-trial contextual fear memory. Interestingly, we also found that the surviving newborn neurons in brain-injured animals had dendritic loss, which was not observed in injured CHOP KO mice or in animals treated with guanabenz. These results indicate that ER stress plays a key role in the death of newborn neurons after TBI. Further, these findings indicate that ER stress can alter dendritic arbors, suggesting a role for ER stress in neuroplasticity and dendritic pathologies.

SIGNIFICANCE STATEMENT The hippocampus, a structure in the temporal lobe, is critical for learning and memory. The hippocampus is one of only two areas in which neurons are generated in the adult brain. These newborn neurons are required for certain types of memory, and are particularly vulnerable to traumatic brain injury (TBI). However, the mechanism(s) that causes the loss of these cells after TBI is poorly understood. We show that endoplasmic reticulum (ER) stress pathways are activated in newborn neurons after TBI, and that manipulation of the CHOP cascade improves newborn neuron survival and cognitive outcome. These results suggest that treatments that prevent/resolve ER stress may be beneficial in treating TBI-triggered memory dysfunction.

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An Interaction between Serotonin Receptor Signaling and Dopamine Enhances Goal-Directed Vigor and Persistence in Mice

The functionally selective 5-HT2C receptor ligand SB242084 can increase motivation and have rapid onset anti–depressant-like effects. We sought to identify the specific behavioral effects of SB242084 treatment and elucidate the mechanism in female and male mice. Using a quantitative behavioral approach, we determined that SB242084 increases the vigor and persistence of goal-directed activity across different types of physical work, particularly when work requirements are demanding. We found this influence of SB242084 on effort, rather than reward to be reflected in striatal DA measured during behavior. Using in vivo fast scan cyclic voltammetry, we found that SB242084 has no effect on reward-related phasic DA release in the NAc. Using in vivo microdialysis to measure tonic changes in extracellular DA, we also found no changes in the NAc. In contrast, SB242084 treatment increases extracellular DA in the dorsomedial striatum, an area that plays a key role in response vigor. These findings have several implications. At the behavioral level, this work shows that the capacity to work in demanding situations can be increased, without a generalized increase in motor activity or reward value. At the circuit level, we identified a pathway restricted potentiation of DA release and showed that this was the reason for the increased response vigor. At the cellular level, we show that a specific serotonin receptor cross talks to the DA system. Together, this information provides promise for the development of treatments for apathy, a serious clinical condition that can afflict patients with psychiatric and neurological disorders.

SIGNIFICANCE STATEMENT Motivated behaviors are modulated by reward value, effort demands, and cost-benefit computations. This information drives the decision to act, which action to select, and the intensity with which the selected action is performed. Because these behavioral processes are all regulated by DA signaling, it is very difficult to influence selected aspects of motivated behavior without affecting others. Here we identify a pharmacological treatment that increases the vigor and persistence of responding in mice, without increasing generalized activity or changing reactions to rewards. We show that the 5-HT2C-selective ligand boosts motivation by potentiating activity-dependent DA release in the dorsomedial striatum. These results reveal a novel strategy for treating patients with motivational deficits, avolition, or apathy.

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Differential Sampling of Visual Space in Ventral and Dorsal Early Visual Cortex

A fundamental feature of cortical visual processing is the separation of visual processing for the upper and lower visual fields. In early visual cortex (EVC), the upper visual field is processed ventrally, with the lower visual field processed dorsally. This distinction persists into several category-selective regions of occipitotemporal cortex, with ventral and lateral scene-, face-, and object-selective regions biased for the upper and lower visual fields, respectively. Here, using an elliptical population receptive field (pRF) model, we systematically tested the sampling of visual space within ventral and dorsal divisions of human EVC in both male and female participants. We found that (1) pRFs tend to be elliptical and oriented toward the fovea with distinct angular distributions for ventral and dorsal divisions of EVC, potentially reflecting a radial bias; and (2) pRFs in ventral areas were larger (~1.5x) and more elliptical (~1.2x) than those in dorsal areas. These differences potentially reflect a tendency for receptive fields in ventral temporal cortex to overlap the fovea with less emphasis on precise localization and isotropic representation of space compared with dorsal areas. Collectively, these findings suggest that ventral and dorsal divisions of EVC sample visual space differently, likely contributing to and/or stemming from the functional differentiation of visual processing observed in higher-level regions of the ventral and dorsal cortical visual pathways.

SIGNIFICANCE STATEMENT The processing of visual information from the upper and lower visual fields is separated in visual cortex. Although ventral and dorsal divisions of early visual cortex (EVC) are commonly assumed to sample visual space equivalently, we demonstrate systematic differences using an elliptical population receptive field (pRF) model. Specifically, we demonstrate that (1) ventral and dorsal divisions of EVC exhibit diverging distributions of pRF angle, which are biased toward the fovea; and (2) ventral pRFs exhibit higher aspect ratios and cover larger areas than dorsal pRFs. These results suggest that ventral and dorsal divisions of EVC sample visual space differently and that such differential sampling likely contributes to different functional roles attributed to the ventral and dorsal pathways, such as object recognition and visually guided attention, respectively.

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Antagonistic Interactions Between Microsaccades and Evidence Accumulation Processes During Decision Formation

Despite their small size, microsaccades can impede stimulus detections if executed at inopportune times. Although it has been shown that microsaccades evoke both inhibitory and excitatory responses across different visual regions, their impact on the higher-level neural decision processes that bridge sensory responses to action selection has yet to be examined. Here, we show that when human observers monitor stimuli for subtle feature changes, the occurrence of microsaccades long after (up to 800 ms) change onset predicts slower reaction times and this is accounted for by momentary suppression of neural signals at each key stage of decision formation: visual evidence encoding, evidence accumulation, and motor preparation. Our data further reveal that, independent of the timing of the change events, the onset of neural decision formation coincides with a systematic inhibition of microsaccade production, persisting until the perceptual report is executed. Our combined behavioral and neural measures highlight antagonistic interactions between microsaccade occurrence and evidence accumulation during visual decision-making tasks.

SIGNIFICANCE STATEMENT When fixating on a location in space, we frequently make tiny eye movements called microsaccades. In the present study, we show that these microsaccades impede our ability to make perceptual decisions about visual stimuli and this impediment specifically occurs via the disruption of several processing levels of the sensorimotor network: the encoding of visual evidence itself, the accumulation of visual evidence toward a response, and effector-selective motor preparation. Furthermore, we show that the production of microsaccades is inhibited during the perceptual decision, possibly as a counteractive measure to mitigate their negative effect on behavior in this context. The combined behavioral and neural measures used in this study provide strong and novel evidence for the interaction of fixational eye movements and the perceptual decision-making process.

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Progranulin Gene Therapy Improves Lysosomal Dysfunction and Microglial Pathology Associated with Frontotemporal Dementia and Neuronal Ceroid Lipofuscinosis

Loss-of-function mutations in progranulin, a lysosomal glycoprotein, cause neurodegenerative disease. Progranulin haploinsufficiency causes frontotemporal dementia (FTD) and complete progranulin deficiency causes CLN11 neuronal ceroid lipofuscinosis (NCL). Progranulin replacement is a rational therapeutic strategy for these disorders, but there are critical unresolved mechanistic questions about a progranulin gene therapy approach, including its potential to reverse existing pathology. Here, we address these issues using an AAV vector (AAV-Grn) to deliver progranulin in Grn^–/– mice (both male and female), which model aspects of NCL and FTD pathology, developing lysosomal dysfunction, lipofuscinosis, and microgliosis. We first tested whether AAV-Grn could improve preexisting pathology. Even with treatment after onset of pathology, AAV-Grn reduced lipofuscinosis in several brain regions of Grn^–/– mice. AAV-Grn also reduced microgliosis in brain regions distant from the injection site. AAV-expressed progranulin was only detected in neurons, not in microglia, indicating that the microglial activation in progranulin deficiency can be improved by targeting neurons and thus may be driven at least in part by neuronal dysfunction. Even areas with sparse transduction and almost undetectable progranulin showed improvement, indicating that low-level replacement may be sufficiently effective. The beneficial effects of AAV-Grn did not require progranulin binding to sortilin. Finally, we tested whether AAV-Grn improved lysosomal function. AAV-derived progranulin was delivered to the lysosome, ameliorated the accumulation of LAMP-1 in Grn^–/– mice, and corrected abnormal cathepsin D activity. These data shed light on progranulin biology and support progranulin-boosting therapies for NCL and FTD due to GRN mutations.

SIGNIFICANCE STATEMENT Heterozygous loss-of-function progranulin (GRN) mutations cause frontotemporal dementia (FTD) and homozygous mutations cause neuronal ceroid lipofuscinosis (NCL). Here, we address several mechanistic questions about the potential of progranulin gene therapy for these disorders. GRN mutation carriers with NCL or FTD exhibit lipofuscinosis and Grn^–/– mouse models develop a similar pathology. AAV-mediated progranulin delivery reduced lipofuscinosis in Grn^–/– mice even after the onset of pathology. AAV delivered progranulin only to neurons, not microglia, but improved microgliosis in several brain regions, indicating cross talk between neuronal and microglial pathology. Its beneficial effects were sortilin independent. AAV-derived progranulin was delivered to lysosomes and corrected lysosomal abnormalities. These data provide in vivo support for the efficacy of progranulin-boosting therapies for FTD and NCL.

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Altered Baseline and Nicotine-Mediated Behavioral and Cholinergic Profiles in ChAT-Cre Mouse Lines

The recent development of transgenic rodent lines expressing cre recombinase in a cell-specific manner, along with advances in engineered viral vectors, has permitted in-depth investigations into circuit function. However, emerging evidence has begun to suggest that genetic modifications may introduce unexpected caveats. In the current studies, we sought to extensively characterize male and female mice from both the ChAT_(BAC)-Cre mouse line, created with the bacterial artificial chromosome (BAC) method, and ChAT_(IRES)-Cre mouse line, generated with the internal ribosome entry site (IRES) method. ChAT_(BAC)-Cre transgenic and wild-type mice did not differ in general locomotor behavior, anxiety measures, drug-induced cataplexy, nicotine-mediated hypolocomotion, or operant food training. However, ChAT_(BAC)-Cre transgenic mice did exhibit significant deficits in intravenous nicotine self-administration, which paralleled an increase in vesicular acetylcholine transporter and choline acetyltransferase (ChAT) hippocampal expression. For the ChAT_(IRES)-Cre line, transgenic mice exhibited deficits in baseline locomotor, nicotine-mediated hypolocomotion, and operant food training compared with wild-type and hemizygous littermates. No differences among ChAT_(IRES)-Cre wild-type, hemizygous, and transgenic littermates were found in anxiety measures, drug-induced cataplexy, and nicotine self-administration. Given that increased cre expression was present in the ChAT_(IRES)-Cre transgenic mice, as well as a decrease in ChAT expression in the hippocampus, altered neuronal function may underlie behavioral phenotypes. In contrast, ChAT_(IRES)-Cre hemizygous mice were more similar to wild-type mice in both protein expression and the majority of behavioral assessments. As such, interpretation of data derived from ChAT-Cre rodents must consider potential limitations dependent on the line and/or genotype used in research investigations.

SIGNIFICANCE STATEMENT Altered baseline and/or nicotine-mediated behavioral profiles were discovered in transgenic mice from the ChAT_(BAC)-Cre and ChAT_(IRES)-Cre lines. Given that these cre-expressing mice have become increasingly used by the scientific community, either independently with chemicogenetic and optogenetic viral vectors or crossed with other transgenic lines, the current studies highlight important considerations for the interpretation of data from previous and future experimental investigations. Moreover, the current findings detail the behavioral effects of either increased or decreased baseline cholinergic signaling mechanisms on locomotor, anxiety, learning/memory, and intravenous nicotine self-administration behaviors.

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This Week in The Journal

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Inhalation Frequency Controls Reformatting of Mitral/Tufted Cell Odor Representations in the Olfactory Bulb

In mammals, olfactory sensation depends on inhalation, which controls activation of sensory neurons and temporal patterning of central activity. Odor representations by mitral and tufted (MT) cells, the main output from the olfactory bulb (OB), reflect sensory input as well as excitation and inhibition from OB circuits, which may change as sniff frequency increases. To test the impact of sampling frequency on MT cell odor responses, we obtained whole-cell recordings from MT cells in anesthetized male and female mice while varying inhalation frequency via tracheotomy, allowing comparison of inhalation-linked responses across cells. We characterized frequency effects on MT cell responses during inhalation of air and odorants using inhalation pulses and also "playback" of sniffing recorded from awake mice. Inhalation-linked changes in membrane potential were well predicted across frequency from linear convolution of 1 Hz responses; and, as frequency increased, near-identical temporal responses could emerge from depolarizing, hyperpolarizing, or multiphasic MT responses. However, net excitation was not well predicted from 1 Hz responses and varied substantially across MT cells, with some cells increasing and others decreasing in spike rate. As a result, sustained odorant sampling at higher frequencies led to increasing decorrelation of the MT cell population response pattern over time. Bulk activation of sensory inputs by optogenetic stimulation affected MT cells more uniformly across frequency, suggesting that frequency-dependent decorrelation emerges from odor-specific patterns of activity in the OB network. These results suggest that sampling behavior alone can reformat early sensory representations, possibly to optimize sensory perception during repeated sampling.

SIGNIFICANCE STATEMENT Olfactory sensation in mammals depends on inhalation, which increases in frequency during active sampling of olfactory stimuli. We asked how inhalation frequency can shape the neural coding of odor information by recording from projection neurons of the olfactory bulb while artificially varying odor sampling frequency in the anesthetized mouse. We found that sampling an odor at higher frequencies led to diverse changes in net responsiveness, as measured by action potential output, that were not predicted from low-frequency responses. These changes led to a reorganization of the pattern of neural activity evoked by a given odorant that occurred preferentially during sustained, high-frequency inhalation. These results point to a novel mechanism for modulating early sensory representations solely as a function of sampling behavior.

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Prepubertal Development of GABAergic Transmission to Gonadotropin-Releasing Hormone (GnRH) Neurons and Postsynaptic Response Are Altered by Prenatal Androgenization

Gonadotropin-releasing hormone (GnRH) neurons regulate reproduction through pulsatile GnRH release. Women with polycystic ovary syndrome (PCOS) have persistently elevated luteinizing hormone release frequency, reflecting GnRH release; this exacerbates hyperandrogenemia and disrupted reproductive cycles that are characteristic of this disorder. Clinical evidence suggests that neuroendocrine features of PCOS may manifest peripubertally. Adult mice prenatally exposed to androgens (PNA) mimic several reproductive features of PCOS. GnRH neurons from these mice have increased firing activity and receive increased GABAergic transmission, which is excitatory. When changes emerge during development is unknown. To study the typical postnatal development of GABAergic transmission and the effects of PNA treatment and sex, whole-cell voltage-clamp recordings were made of GABAergic postsynaptic currents (PSCs) in GnRH neurons in brain slices from prepubertal through adult control and PNA female and male mice. GABAergic transmission was present by 1 week of age in females and males and increased in frequency, reaching adult levels at 3 and 4 weeks, respectively. GABAergic PSC frequency was elevated in 3-week-old PNA versus control females. PSC frequency in both controls and PNA mice was activity independent, suggesting that PNA induces changes in synapse organization. PNA also alters the functional response of GnRH neurons to GABA. GABA induced firing in fewer neurons from 3-week-old PNA than control females; membrane potential depolarization induced by GABA was also reduced in cells from PNA mice at this age. PNA thus induces changes during development in the presynaptic organization of the GABAergic network afferent to GnRH neurons as well as the postsynaptic GnRH neuron response, both of which may contribute to adult reproductive dysfunction.

SIGNIFICANCE STATEMENT The central neuronal network that regulates reproduction is overactive in polycystic ovary syndrome (PCOS), a leading cause of infertility. Recent evidence of neuroendocrine dysfunction in midpubertal girls suggests that the pathophysiological mechanisms underlying PCOS may arise before pubertal maturation. Prenatal exposure to androgens (PNA) in mice mimics several neuroendocrine features of PCOS. GABAergic transmission to gonadotropin-releasing hormone (GnRH) neurons is important for reproduction and is increased in adult PNA mice. The typical development of this network and when changes with PNA and sex arise relative to puberty are unknown. These studies provide evidence that PNA alters prepubertal development of the GABAergic network afferent to GnRH neurons, including both the presynaptic organization and postsynaptic response. These changes may contribute to reproductive dysfunction in adults.

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A Unique Homeostatic Signaling Pathway Links Synaptic Inactivity to Postsynaptic mTORC1

mTORC1-dependent translational control plays a key role in several enduring forms of synaptic plasticity such as long term potentiation (LTP) and mGluR-dependent long term depression. Recent evidence demonstrates an additional role in regulating synaptic homeostasis in response to inactivity, where dendritic mTORC1 serves to modulate presynaptic function via retrograde signaling. Presently, it is unclear whether LTP and homeostatic plasticity use a common route to mTORC1-dependent signaling or whether each engage mTORC1 through distinct pathways. Here, we report a unique signaling pathway that specifically couples homeostatic signaling to postsynaptic mTORC1 after loss of excitatory synaptic input. We find that AMPAR blockade, but not LTP-inducing stimulation, induces phospholipase D (PLD)-dependent synthesis of the lipid second messenger phosphatidic acid (PA) in rat cultured hippocampal neurons of either sex. Pharmacological blockade of PLD1/2 or pharmacogenetic disruption of PA interactions with mTOR eliminates mTORC1 signaling and presynaptic compensation driven by AMPAR blockade, but does not alter mTORC1 activation or functional changes during chemical LTP (cLTP). Overexpression of PLD1, but not PLD2, recapitulates both functional synaptic changes as well as signature cellular adaptations associated with homeostatic plasticity. Finally, transient application of exogenous PA is sufficient to drive rapid presynaptic compensation requiring mTORC1-dependent translation of BDNF in the postsynaptic compartment. These results thus define a unique homeostatic signaling pathway coupling mTORC1 activation to changes in excitatory synaptic drive. Our results further imply that more than one canonical mTORC1 activation pathway may be relevant for the design of novel therapeutic approaches against neurodevelopmental disorders associated with mTORC1 dysregulation.

SIGNIFICANCE STATEMENT Homeostatic and Hebbian forms of synaptic plasticity are thought to play complementary roles in regulating neural circuit function, but we know little about how these forms of plasticity are distinguished at the single neuron level. Here, we define a signaling pathway that uniquely links mTORC1 with homeostatic signaling in neurons.

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Timescales of Intrinsic BOLD Signal Dynamics and Functional Connectivity in Pharmacologic and Neuropathologic States of Unconsciousness

Environmental events are processed on multiple timescales via hierarchical organization of temporal receptive windows (TRWs) in the brain. The dependence of neural timescales and TRWs on altered states of consciousness is unclear. States of reduced consciousness are marked by a shift toward slowing of neural dynamics (<1 Hz) in EEG/ECoG signals. We hypothesize that such prolongation of intrinsic timescales are also seen in blood-oxygen-level-dependent (BOLD) signals. To test this hypothesis, we measured the timescales of intrinsic BOLD signals using mean frequency (MF) and temporal autocorrelation (AC) in healthy volunteers (n = 23; male/female 14/9) during graded sedation with propofol. We further examined the relationship between the intrinsic timescales (local/voxel level) and its regional connectivity (across neighboring voxels; regional homogeneity, ReHo), global (whole-brain level) functional connectivity (GFC), and topographical similarity (Topo). Additional results were obtained from patients undergoing deep general anesthesia (n = 12; male/female: 5/7) and in patients with disorders of consciousness (DOC) (n = 21; male/female: 14/7). We found that MF, AC, and ReHo increased, whereas GFC and Topo decreased, during propofol sedation. The local alterations occur before changes of distant connectivity. Conversely, all of these parameters decreased in deep anesthesia and in patients with DOC. We conclude that propofol synchronizes local neuronal interactions and prolongs the timescales of intrinsic BOLD signals. These effects may impede communication among distant brain regions. Furthermore, the intrinsic timescales exhibit distinct dynamic signatures in sedation, deep anesthesia, and DOC. These results improve our understanding of the neural mechanisms of unconsciousness in pharmacologic and neuropathologic states.

SIGNIFICANCE STATEMENT Information processing in the brain occurs through a hierarchy of temporal receptive windows (TRWs) in multiple timescales. Anesthetic drugs induce a reversible suppression of consciousness and thus offer a unique opportunity to investigate the state dependence of neural timescales. Here, we demonstrate for the first time that sedation with propofol is accompanied by the prolongation of the timescales of intrinsic BOLD signals presumably reflecting enlarged TRWs. We show that this is accomplished by an increase of local and regional signal synchronization, effects that may disrupt information exchange among distant brain regions. Furthermore, we show that the timescales of intrinsic BOLD signals exhibit distinct dynamic signatures in sedation, deep anesthesia, and disorders of consciousness.

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Fentanyl Induces Rapid Onset Hyperalgesic Priming: Type I at Peripheral and Type II at Central Nociceptor Terminals

Systemic fentanyl induces hyperalgesic priming, long-lasting neuroplasticity in nociceptor function characterized by prolongation of inflammatory mediator hyperalgesia. To evaluate priming at both nociceptor terminals, we studied, in male Sprague Dawley rats, the effect of local administration of agents that reverse type I (protein translation) or type II [combination of Src and mitogen-activated protein kinase (MAPK)] priming. At the central terminal, priming induced by systemic, intradermal, or intrathecal fentanyl was reversed by the combination of Src and MAPK inhibitors, but at the peripheral terminal, it was reversed by the protein translation inhibitor. Mu-opioid receptor (MOR) antisense prevented fentanyl hyperalgesia and priming. To determine whether type I and II priming occur in the same population of neurons, we used isolectin B4–saporin or [Sar⁹, Met(O₂)¹¹]-substance P–saporin to deplete nonpeptidergic or peptidergic nociceptors, respectively. Following intrathecal fentanyl, central terminal priming was prevented by both saporins, whereas that in peripheral terminal was not attenuated even by their combination. However, after intradermal fentanyl, priming in the peripheral terminal requires both peptidergic and nonpeptidergic nociceptors, whereas that in the central terminal is dependent only on peptidergic nociceptors. Pretreatment with dantrolene at either terminal prevented fentanyl-induced priming in both terminals, suggesting communication between central and peripheral terminals mediated by intracellular Ca²⁺ signaling. In vitro application of fentanyl increased cytoplasmic Ca²⁺ concentration in dorsal root ganglion neurons, which was prevented by pretreatment with dantrolene and naloxone. Therefore, acting at MOR in the nociceptor, fentanyl induces hyperalgesia and priming rapidly at both the central (type II) and peripheral (type I) terminal and this is mediated by Ca²⁺ signaling.

SIGNIFICANCE STATEMENT Fentanyl, acting at the μ-opioid receptor (MOR), induces hyperalgesia and hyperalgesic priming at both the central and peripheral terminal of nociceptors and this is mediated by endoplasmic reticulum Ca²⁺ signaling. Priming in the central terminal is type II, whereas that in the peripheral terminal is type I. Our findings may provide useful information for the design of drugs with improved therapeutic profiles, selectively disrupting individual MOR signaling pathways, to maintain an adequate long-lasting control of pain.

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Corticosterone Production during Repeated Social Defeat Causes Monocyte Mobilization from the Bone Marrow, Glucocorticoid Resistance, and Neurovascular Adhesion Molecule Expression

Repeated social defeat (RSD) stress promotes the release of bone marrow-derived monocytes into circulation that are recruited to the brain, where they augment neuroinflammation and cause prolonged anxiety-like behavior. Physiological stress activates the sympathetic nervous system and hypothalamic-pituitary-adrenal gland (HPA) axis, and both of these systems play a role in the physiological, immunological, and behavioral responses to stress. The purpose of this study was to delineate the role of HPA activation and corticosterone production in the immunological responses to stress in male C57BL/6 mice. Here, surgical (adrenalectomy) and pharmacological (metyrapone) interventions were used to abrogate corticosterone signaling during stress. We report that both adrenalectomy and metyrapone attenuated the stress-induced release of monocytes into circulation. Neither intervention altered the production of monocytes during stress, but both interventions enhanced retention of these cells in the bone marrow. Consistent with this observation, adrenalectomy and metyrapone also prevented the stress-induced reduction of a key retention factor, CXCL12, in the bone marrow. Corticosterone depletion with metyrapone also abrogated the stress-induced glucocorticoid resistance of myeloid cells. In the brain, these corticosterone-associated interventions attenuated stress-induced microglial remodeling, neurovascular expression of the adhesion molecule intercellular cell adhesion molecule-1, prevented monocyte accumulation and neuroinflammatory signaling. Overall, these results indicate that HPA activation and corticosterone production during repeated social defeat stress are critical for monocyte release into circulation, glucocorticoid resistance of myeloid cells, and enhanced neurovascular cell adhesion molecule expression.

SIGNIFICANCE STATEMENT Recent studies of stress have identified the presence of monocytes that show an exaggerated inflammatory response to immune challenge and are resistant to the suppressive effects of glucocorticoids. Increased presence of these proinflammatory monocytes has been implicated in neuropsychiatric symptoms and the development of chronic cardiovascular, autoimmune, and metabolic disorders. In the current study, we show novel evidence that corticosterone produced during stress enhances the release of proinflammatory monocytes from the bone marrow into circulation, augments their recruitment to the brain and the induction of a neuroinflammatory profile. Overproduction of corticosterone during stress is also the direct cause of glucocorticoid resistance, a key phenotype in individuals exposed to chronic stress. Inhibiting excess corticosterone production attenuates these inflammatory responses to stress.

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Notch Suppression Collaborates with Ascl1 and Lin28 to Unleash a Regenerative Response in Fish Retina, But Not in Mice

Müller glial (MG) cells in the zebrafish retina respond to injury by acquiring retinal stem-cell characteristics. Thousands of gene expression changes are associated with this event. Key among these changes is the induction of Ascl1a and Lin28a, two reprogramming factors whose expression is necessary for retina regeneration. Whether these factors are sufficient to drive MG proliferation and subsequent neuronal-fate specification remains unknown. To test this, we conditionally expressed Ascl1a and Lin28a in the uninjured retina of male and female fish. We found that together, their forced expression only stimulates sparse MG proliferation. However, in combination with Notch signaling inhibition, widespread MG proliferation and neuron regeneration ensued. Remarkably, Ascl1 and Lin28a expression in the retina of male and female mice also stimulated sparse MG proliferation, although this was not enhanced when combined with inhibitors of Notch signaling. Lineage tracing in both fish and mice suggested that the proliferating MG generated multipotent progenitors; however, this process was much more efficient in fish than mice. Overall, our studies suggest that the overexpression of Ascl1a and Lin28a in zebrafish, in combination with inhibition of Notch signaling, can phenocopy the effects of retinal injury in Müller glia. Interestingly, Ascl1 and Lin28a seem to have similar effects in fish and mice, whereas Notch signaling may differ. Understanding the different consequences of Notch signaling inhibition in fish and mice, may suggest additional strategies for enhancing retina regeneration in mammals.

SIGNIFICANCE STATEMENT Mechanisms underlying retina regeneration in fish may suggest strategies for stimulating this process in mammals. Here we report that forced expression of Ascl1 and Lin28a can stimulate sparse MG proliferation in fish and mice; however, only in fish does Notch signaling inhibition collaborate with Ascl1a and Lin28a to stimulate widespread MG proliferation in the uninjured retina. Discerning differences in Notch signaling between fish and mice MG may reveal strategies for stimulating retina regeneration in mammals.

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Age-Dependent Decline in Fate Switch from NG2 Cells to Astrocytes After Olig2 Deletion

NG2 cells are a resident glial progenitor cell population that is uniformly distributed throughout the developing and mature mammalian CNS. Those in the postnatal CNS generate exclusively myelinating and non-myelinating oligodendrocytes and are thus equated with oligodendrocyte precursor cells. Prenatally, NG2 cells in the ventral gray matter of the forebrain generate protoplasmic astrocytes as well as oligodendrocytes. The fate conversion from NG2 cells into protoplasmic astrocytes is dependent on downregulation of the key oligodendrocyte transcription factor Olig2. We showed previously that constitutive deletion of Olig2 in NG2 cells converts NG2 cells in the neocortex into protoplasmic astrocytes at the expense of oligodendrocytes. In this study, we show that postnatal deletion of Olig2 caused NG2 cells in the neocortex but not in other gray matter regions to become protoplasmic astrocytes. However, NG2 cells in the neocortex became more resistant to astrocyte fate switch over the first 3 postnatal weeks. Fewer NG2 cells differentiated into astrocytes and did so with longer latency after Olig2 deletion at postnatal day 18 (P18) compared with deletion at P2. The high-mobility group transcription factor Sox10 was not downregulated for at least 1 month after Olig2 deletion at P18 despite an early transient upregulation of the astrocyte transcription factor NFIA. Furthermore, inhibiting cell proliferation in slice culture reduced astrocyte differentiation from Olig2-deleted perinatal NG2 cells, suggesting that cell division might facilitate nuclear reorganization needed for astrocyte transformation.

SIGNIFICANCE STATEMENT NG2 cells are glial progenitor cells that retain a certain degree of lineage plasticity. In the normal postnatal neocortex, they generate mostly oligodendrocyte lineage cells. When the oligodendrocyte transcription factor Olig2 is deleted in NG2 cells in the neocortex, they switch their fate to protoplasmic astrocytes. However, the efficiency of the fate switch decreases with age over the first 3 postnatal weeks and is reduced when cell proliferation is inhibited. As the neocortex matures, sustained expression of the oligodendrocyte lineage-specific key transcription factor Sox10 becomes less dependent on Olig2. Together, our findings suggest a gradual stabilization of the oligodendrocyte lineage genes and loss of lineage plasticity during the first 3 weeks after birth, possibly due to nuclear reorganization.

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A Collaborator's Reputation Can Bias Decisions and Anxiety under Uncertainty

Informational social influence theory posits that under conditions of uncertainty, we are inclined to look to others for advice. This leaves us remarkably vulnerable to being influenced by others' opinions or advice. Rational agents, however, do not blindly seek and act on arbitrary information, but often consider the quality of its source before committing to a course of action. Here, we ask the question of whether a collaborator's reputation can increase their social influence and, in turn, bias perception and anxiety under changing levels of uncertainty. Human male and female participants were asked to provide estimations of dot direction using the random dot motion (RDM) perceptual discrimination task and were paired with transient collaborators of high or low reputation whom provided their own estimations. The RDM varied in degrees of uncertainty and joint performance accuracy was linked to risk of an electric shock. Despite providing identical information, we show that collaborating with a high reputation compared with a low reputation partner, led to significantly more conformity during the RDM task for uncertain perceptual decisions. Consequently, high reputation partners decreased the subjects' anxiety during the anticipatory shock periods. fMRI data showed that parametric changes in conformity resulted in increased activity in the ventromedial PFC, whereas dissent was associated with increased in activity in the dorsal anterior cingulate cortex (dACC). Furthermore, the dACC and insula, regions involved in anticipatory pain, were significantly more active when collaborating with a low reputation partner. These results suggest that information about reputation can influence both cognitive and affective processes and in turn alter the neural circuits that underlie decision-making and emotion.

SIGNIFICANCE STATEMENT Humans look to others for advice when making decisions under uncertainty. Rational agents, however, do not blindly seek information, but often consider the quality of its source before committing to a course of action. Here, we ask the question of whether a collaborators' reputation can increase social influence and in turn bias perception and anxiety in the context of perceptual uncertainty. We show that when subjects are partnered with collaborators with a high reputation, this leads to increased conformity during uncertain perceptual decision-making and reduces anxiety when joint performance accuracy leads to an electric shock. Furthermore, our results show that information about reputation alters the neural circuits that underlie decision-making and emotion.

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First Case of Lymphaticovenular Anastomosis for Treatment of Secondary Lymphedema in Costa Rica: Japanese Contribution to Microsurgery Development

Summary: Although a large number of treatments have been developed for lymphedema, definitive management still remains a challenge for plastic surgery, because not all surgical techniques have a positive effect on every patient, and good results are difficult to reproduce. However, it is important to recognize the efforts that Professor Isao Koshima and his colleagues together with the Government of Japan are carrying out to spread information to the different countries on the newest surgical techniques available in current plastic surgery and to motivate young doctors in developing countries to create a microsurgery unit in their home country, providing them with the necessary knowledge and skills to deliver real solutions to complex problems that were previously unanswered. As a result of this program, the authors present the first case of secondary lymphedema successfully treated with lymphaticovenular anastomosis in Costa Rica, Central America. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Published online 27 February 2018. Received for publication December 4, 2017; accepted December 27, 2017. Disclosure: The authors have no financial interest to declare in relation to the content of this article. The Article Processing Charge was paid for by the authors. Madelein Centeno-Rodriguez, MD, Universal Plastic Surgery, 1st Avenue, 24-26th Street, Paseo Colon, San Jose, Costa Rica 10102, E-mail: mcenteno@plasticsurgerycr.com Copyright © 2018 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons. All rights reserved.

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Heparin-enhanced Harvest and Decanting for Autologous Fat Transfer

No abstract available

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Predator-in-Chief: Wolves in Editors’ Clothing

No abstract available

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Management of Severely Atrophic Maxilla in Ectrodactyly Ectodermal Dysplasia-cleft Syndrome

Background: Ectrodactyly ectodermal dysplasia-cleft syndrome is a rare genetic syndrome with an incidence of 1/90,000 live births, characterized by cleft lip and palate, severely hypoplastic maxilla, and hypodontia. Patients diagnosed with ectrodactyly ectodermal dysplasia-cleft syndrome suffer from a severely hypoplastic maxilla that is highly difficult to treat using traditional orthognathic methods. In this study, we propose using distraction osteogenesis to achieve a major advancement while maintaining good stability and minimal relapse. To our knowledge, this is the first description of patients with this syndrome treated using distraction osteogenesis. Methods: Five patients diagnosed with ectrodactyly ectodermal dysplasia-cleft syndrome were included in the study. All patients had been operated on according to the well-established protocol of cleft lip and palate reconstruction before maxillary distraction osteogenesis. Hard and soft-tissue changes were evaluated by cone beam computed tomography and lateral cephalograms before distraction osteogenesis (T1), at the postdistraction point (T2) and after 1 year of follow-up (T3). Results: Examination revealed marked maxillary advancement in all our patients with a significant mean difference in hard tissue parameters (condylion to A point = 18 mm; nasion-sella line to A point = 15.2 degrees) and a notable improvement in facial convexity (20.9 degrees). One year follow-up measurements demonstrated mild relapse rates of 6% in the horizontal plane. Conclusions: We conclude that despite the challenging anatomic and physiological features of ectrodactyly ectodermal dysplasia-cleft patients, by enhancing current surgical techniques, there is promising potential for improved patient outcomes, achieving normognathic facial appearance with implant supported rehabilitation. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Published online 27 February 2018. Received for publication August 11, 2017; accepted December 21, 2017. Drs. Rachmiel and Turgeman contributed equally to this work. Disclosure: The authors have no financial interest to declare in relation to the content of this article. The Article Processing Charge was paid for by the authors. Shahar Turgeman, DMD, Department of Oral and Maxillofacial Surgery, Rambam Health Care Campus, POB 9602, Haifa 31096, Israel, E-mail: turgemanshahar@gmail.com Copyright © 2018 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons. All rights reserved.

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KRAS Mutation is Predictive of Outcome in Patients with Pulmonary Sarcomatoid Carcinoma

Abstract

Pulmonary Sarcomatoid Carcinoma (PSC) is a poorly-differentiated non-small cell lung carcinoma (NSCLC) with aggressive behavior. This study aimed to evaluate the prognostic clinicopathologic and genetic characteristics of PSCs. Fifty-three cases of surgically treated PSCs were selected, of which 23 were subjected to mutation and copy number variation analysis using 50-gene Ion AmpliSeq Cancer Panel. Majority of the patients were male (32/53, 60.3%) and smoker (51/53, 96.2%). Overall, 25 (47.1%) patients died within 2 to 105 months (mean 22.7 months, median 15 months) after diagnosis, and 28 were alive as of 3 to 141 months (mean 38.7 months, median 21.5 months) after diagnosis. Five-year overall survival was 12.5%. KRAS codon 12/13 mutation in adenocarcinomas (p= 0.01), age over 70 years (p=0.008) and tumor size ≥ 4.0 cm (p= 0.02) were strongly associated with worse outcome. TP53 (17/23, 74.0%) and KRAS codon 12/13 mutations (10/23, 43.4%) were the most common genetic alterations. Potentially actionable variants were identified including ATM (4/23, 17.3%), MET, FBXW7 and EGFR (2/23, 8.7%), AKT1, KIT, PDGFRA, HRAS, JAK3, and SMAD4 (1/23, 4.3%). MET exon 14 skipping and missense mutations were identified in two (11.1%) cases with adenocarcinoma histology. Copy number analysis showed loss of RB1 (3/23, 13%) and ATM (2/23, 8.7%). Copy number gains were seen in EGFR (2/23, 13.0%), and in one (4.3%) of each PIK3CA, KRAS, MET, and STK11. Potentially targetable mutations can be identified in a subset of PSC although most tumors harbor currently untargetable prognostically adverse TP53 and KRAS mutations.

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Extraskeletal Osteosarcoma: MDM2 and H3K27me3 analysis of 19 cases suggest disease heterogeneity

Abstract

Aims

Extraskeletal osteosarcoma (ESOS) is a sarcoma in the non-skeletal tissue that directly produces neoplastic osteoid or bone. Dedifferentiated liposarcoma (DDLPS) and malignant peripheral nerve sheath tumor (MPNST) are the two most common types of sarcoma that can harbor heterologous osteosarcomatous differentiation. We aimed to determine the potential relationship of ESOS to DDLPS and MPNST.

Methods and results

We investigated MDM2 and H3K27me3 status in 19 cases of ESOS, 2 of which contained a low-grade component. The ESOSs affected deep soft tissues (n=10), superficial soft tissues (n=3), and organs (n=6). Among 10 deep soft-tissue ESOSs, 6 showed MDM2 amplification, 4 of which also harbored CDK4 co-amplification. Both ESOSs with a low-grade component showed co-amplification for MDM2 and CDK4. Among the 6 organ-based ESOSs, 3 giant cell-rich ESOSs showed an H3K27me3 deficiency (1 in primary and 2 in metastatic sites). Using targeted next generation sequencing, an H3K27me3-deficient ESOS showed EED homozygous deletion, while none of the 3 showed alterations in NF1, CDKN2A, or SUZ12 genes. During median follow-up of 20 months, all 6 patients with MDM2-amplified ESOS lived for 3–103 months, while 2 of the 3 patients with H3K27me3-deficient ESOS died from this disease in 4 and 20 months, respectively.

Conclusion

We demonstrate that ESOS may include at least two small subsets: an MDM2-amplified deep soft-tissue ESOS (which may be related to DDLPS) and an H3K27me3-deficient organ-based ESOS (which is probably unrelated to MPNST). Larger studies are required to validate the present observations and investigate the clinical implications of such subcategorization.

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Expression of PD-L1, indoleamine 2,3-dioxygenase and the immune microenvironment in gastric adenocarcinoma

Abstract

Introduction

The tumor microenvironment is increasingly important in several tumors. We studied the relationship of key players of immune microenvironment with clinicopathological parameters in gastric adenocarcinomas.

Methods

Tissue microarrays were constructed from gastrectomy specimens, 2004-2013. Immunohistochemistry was performed for programmed death ligand 1 (PD-L1), indoleamine 2,3-dioxygenase (IDO), tryptophanyl-tRNA synthetase (WARS), guanylate-binding protein 5 (GBP5), tumor-infiltrating lymphocytes (TIL) expressing CD3/CD8/FoxP3/PD1, and mismatch repair proteins (MMRs) MLH1, PMS2, MSH2 and MSH6. Clinicopathological parameters and clinical follow-up were recorded.

Results

The study included 86 patients, median follow-up was 34 months (0-148). Tumor types were 45% tubular, 38% diffuse, 17% mixed. PD-L1 was positive in 70%, epithelial IDO in 58%, stromal IDO in 91%, epithelial WARS in 67%, stromal WARS in 100%, epithelial GBP5 in 53%, and stromal GBP5 in 71%. MMR-deficiency was found in 22%. There was no difference in biomarker expression by histological subtype, with exception fewer diffuse-type being MMR-deficient. Low stromal IDO was associated with decreased progression-free, overall and disease-specific survival. PD-L1-positive tumors were larger with MMR-deficiency and with increasing TILs, and had significantly higher FoxP3- TILs.

Conclusions

PD-L1 is expressed in a large proportion of gastric carcinomas suggesting that therapy targeting this pathway could be relevant to many patients. PD-L1 expression and MMR-deficiency are associated with increased TILs and larger tumor size, emphasizing their role in tumor biology. Higher stromal IDO expression is associated with better prognosis. Finally, we observed that immune modulators WARS and GBP5 are highly expressed in gastric adenocarcinomas, suggesting an important role in tumor pathobiology.

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Radiculomegaly: a case report of this rare dental finding with review of the associated oculo-facio-cardio-dental syndrome

Publication date: Available online 28 February 2018
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Molly Housley Smith, Donald M. Cohen, Indraneel Bhattacharyya, Nadim M. Islam, Deeba Kashtwari
Background: Radiculomegaly, or root gigantism, is a rare dental abnormality with important clinical implications. It is highly specific for oculo-facio-cardio-dental syndrome (OFCD), which places dentists at the forefront of diagnosis for this syndrome. Only one case of non-syndromic radiculomegaly has been reported in the literature since the description of OFCD in 1996. We present the second confirmed, non-syndromic/non-familial case and review the literature for dental treatments in patients with this dental finding. Methods: A review of the English-language literature was performed within PubMed for patients with radiculomegaly or OFCD. Teeth affected by radiculomegaly, gender, oro-dental findings, presence of OFCD syndrome, and dental treatment methods were recorded. Results: Sixty-seven cases of radiculomegaly and 92 OFCD cases were found in the literature. Only one confirmed case of non-syndromic/non-familial radiculomegaly existed prior to our report. Ten cases reported dental treatment or treatment plan details, and even fewer detailed the specific methods. Conclusions: Because dental anomalies, especially radiculomegaly, are a primary feature of OFCD, dentists should be aware of the clinical and radiographic features. Radiculomegaly poses a distinct challenge to dentists, and reports of dental therapy provided to these patients are sparse. Early diagnosis of the syndrome may prevent dental challenges and improve prognosis.



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The Influence of Hearing Aid Gain on Gap-Detection Thresholds for Children and Adults With Hearing Loss

Objectives: The objective of this experiment was to examine the contributions of audibility to the ability to perceive a gap in noise for children and adults. Sensorineural hearing loss (SNHL) in adulthood is associated with a deficit in gap detection. It is well known that reduced audibility in adult listeners with SNHL contributes to this deficit; however, it is unclear the extent to which hearing aid amplification can restore gap-detection thresholds, and the effect of childhood SNHL on gap-detection thresholds have not been described. For adults, it was hypothesized that restoring the dynamic range of hearing for listeners with SNHL would lead to approximately normal gap-detection thresholds. Children with normal hearing (NH) exhibit poorer gap-detection thresholds than adults. Because of their hearing loss, children with SNHL have less auditory experience than their peers with NH. Yet, it is unknown the extent to which auditory experience impacts their ability to perceive gaps in noise. Even with the provision of amplification, it was hypothesized that children with SNHL would show a deficit in gap detection, relative to their peers with normal hearing, because of reduced auditory experience. Design: The ability to detect a silent interval in noise was tested by adapting the stimulus level required for detection of gap durations between 3 and 20 ms for adults and children with and without SNHL. Stimulus-level thresholds were measured for participants with SNHL without amplification and with two prescriptive procedures—the adult and child versions of the desired sensation level i/o program—using a hearing aid simulator. The child version better restored the normal dynamic range than the adult version. Adults and children with NH were tested without amplification. Results: When fitted using the procedure that best restored the dynamic range, adults with SNHL had stimulus-level thresholds similar to those of adults with normal hearing. Compared to the children with NH, the children with SNHL required a higher stimulus level to detect a 5-ms gap, despite having used the procedure that better restored the normal dynamic range of hearing. Otherwise, the two groups of children had similar stimulus-level thresholds. Conclusion: These findings suggest that apparent deficits in temporal resolution, as measured using stimulus-level thresholds for the detection of gaps, are dependent on age and audibility. These novel results indicate that childhood SNHL may impair temporal resolution as measured by stimulus-level thresholds for the detection of a gap in noise. This work has implications for understanding the effects of amplification on the ability to perceive temporal cues in speech. ACKNOWLEDGMENTS: We thank Alex Baker, Brianna Byllesby, Evan Cordrey, and Clairissa Mollak for help in data collection and analysis. M. B. designed and performed experiments, analyzed data, and wrote the paper. All authors discussed analysis and implications and commented on the manuscript at all stages. This research was funded by grants R01 DC013591 (to R. M.), F32 DC12709 (to M. B.), P20 GM109023 (to M. B. and W. J.), and P30 DC4662 from the National Institutes of Health (NIH). Presented at the International Hearing Aid Research Conference, Lake Tahoe, Nevada, August 13, 2016. The authors have no conflicts of interest to disclose. Address for correspondence: Marc Brennan, University of Nebraska-Lincoln, 274 Barkley Center, Lincoln, NE 68583, USA. E-mail: marc.brennan@unl.edu Received February 21, 2017; accepted December 28, 2017. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Knorpel, Knochen, Chorda

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Adult Cranioplasty Reconstruction With Customized Cranial Implants: Preferred Technique, Timing, and Biomaterials

Introduction: Complex cranial defects requiring delayed reconstruction present numerous challenges. Delayed cranioplasties accompany frequent complications approaching an incidence of 35 to 40%. Therefore, the authors sought to collate their experience in hopes of sharing their perspective on several topics including technique, timing, and preferred biomaterials. Methods: The authors' 5-year consecutive experience over 430 customized cranial implants is described herein. Since its inception in 2012, the authors' team has employed the pericranial-onlay cranioplasty technique instead of the standard epidural approach. Optimal timing for cranioplasty is determined using objective criteria such as scalp healing and parenchymal edema, close collaboration with neuroplastic surgery, conversion from autologous bone to sterile implant in instances of questionable viability/storage, and the first-line use of solid poly(methylmethacrylate) implants for uncomplicated, delayed cases, first-line porous polyethylene (MEDPOR) implants for single-stage cranioplasty, and first-line polyether-ether-ketone implants for cases with short notice. Furthermore, the use of the pterional design algorithm with temporal bulking for all customized implants has helped to correct and/or prevent temporal hollowing deformities. Results: The authors' team has observed a three-fold reduction in reported complications as compared with the existing literature, with a major complication rate of 11%. The multidisciplinary center has provided an optimal stage for synergy and improved outcomes versus standard cranioplasty techniques. Conclusion: Secondary cranial reconstruction, or cranioplasty, can be challenging due to numerous reasons. These best practices, developed in collaboration with neuroplastic surgery and neurosurgery, appear to encompass the largest published experience to date. The authors find this approach to be both safe and reliable. Address correspondence and reprint requests to Chad Gordon, DO, FACS, Associate Professor of Plastic Surgery and Neurosurgery, Johns Hopkins University School of Medicine, 601 N. Caroline St, JHOC 8th floor, Baltimore, MD 21287; E-mail: cgordon@jhmi.edu Received 15 November, 2017 Accepted 22 December, 2017 CG is a consultant for Stryker Craniomaxillofacial (CMF) and Longeviti Neuro Solutions. The authors report no conflicts of interest. AW and GFS should be considered co-first authors. This paper was supported in part by a research grant received from Stryker Craniomaxillofacial (Kalamazoo, MI), which was reviewed and approved by the Johns Hopkins University in accordance with its conflict of interest policies. © 2018 by Mutaz B. Habal, MD.

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Pain Management for Nonsyndromic Craniosynostosis: Adequate Analgesia in a Pediatric Cohort?

Background: Postoperative pain following open craniosynostosis repair has not been studied extensively and is sometimes thought to be inconsequential. The purpose of this study was to assess postoperative pain in this pediatric population. Methods: We performed a retrospective chart review of patients (n = 54) undergoing primary open craniosynostosis repair from 2010 to 2016. Demographics, length of stay (LOS), pain scores, emesis events, and perioperative analgesics were reviewed. Multivariable regression models were designed to assess for independent predictors of LOS and emesis. Results: A high proportion had moderate to severe pain on postoperative day 0 (56.5%) and day 1 (60.9%). Opioid administered in postoperative period was 1.40 mg/kg/d in morphine milligram equivalent (MME) (±1.07 mg/kg/d MME). Majority of patients transitioned to enteral opioids on postoperative day 1 (24.5%) or day 2 (49.1%). Ketorolac was administered to 11.1% (n = 6). Emesis was documented in 50% of patients. LOS revealed a positive association with age (P = 0.006), weight (P = 0.009), and day of transition to enteral opioids (P 

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Maxillary Hypoplasia With Congenital Oligodontia Treated by Maxillary Distraction Osteogenesis

It is known that congenitally missing teeth can often cause differences in craniofacial morphology; however, there are few reported cases of orthognathic surgical treatment for these patients. Herein, the authors report a rare case of maxillary hypoplasia with congenital oligodontia treated by maxillary distraction osteogenesis with internal device. A 17-year-old male presenting with multiple tooth agenesis and maxillary recession was referred to our hospital for orthognathic surgical treatment. Preoperative simulation surgery was performed using Full-Color 3-dimensional salt model. After surgery, improvement in maxillary recession and occlusal stability was observed. This report demonstrates the advantages of the method used herein, which includes reduction in operating time with increase in the safety of the procedure. Address correspondence and reprint requests to Sayaka Mishima, DDS, Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan; E-mail: sayakams@kuhp.kyoto-u.ac.jp Received 5 April, 2017 Accepted 5 January, 2018 The authors report no conflicts of interest. © 2018 by Mutaz B. Habal, MD.

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Simple Technique for Reducing the Buccal Fat Pad During Mandibular Orthognathic Surgery

Sagittal split ramus osteotomy and intraoral vertical ramus osteotomy are commonly performed for the correction of jaw deformities. However, during mandibular orthognathic surgeries such as sagittal split ramus osteotomy and intraoral vertical ramus osteotomy , the authors sometimes encounter exposure of the buccal fat pad (BFP), which decreases the surgical field. The exposed BFP makes it difficult to perform these operations, may result in unexpected complications, and may increase the operation time. Therefore, the authors herein describe a simple, safe, and convenient technique for reducing the volume of the exposed BFP during mandibular orthognathic surgery using an electric knife in the coagulation mode. Address correspondence and reprint requests to Yoko Kawase-Koga, DDS, PhD, Department of Oral and Maxillofacial Surgery, Tokyo Medical University Hospital, 6-7-1 Nishishinjuku, Tokyo 160-0023, Japan; E-mail: kogay@tokyo-med.ac.jp Received 28 September, 2017 Accepted 5 January, 2018 The authors report no conflicts of interest. © 2018 by Mutaz B. Habal, MD.

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Evaluation of the Olfactory Function With the “Sniffin’ Sticks” Test After Endoscopic Transsphenoidal Pituitary Surgery

The aim of this study was to evaluate the olfactory function of patients who had undergone endoscopic transsphenoidal pituitary surgery. In this prospective study, the "Sniffin' Sticks" test was performed between June 2016 and April 2017 at Izmir Katip Celebi University Ataturk Training and Research Hospital. Thirty patients who were scheduled to undergo endoscopic transsphenoidal pituitary surgery were evaluated preoperatively and 8 weeks postoperatively using the Sniffin' Sticks test battery for olfactory function, odor threshold, smell discrimination, and odor identification. The patients were evaluated preoperatively by an otolaryngologist. The patients' demographic data and olfactory functions were analyzed with a t test and Wilcoxon-labeled sequential test. The study group comprised 14 women (46.7%) and 16 men (53.3%) patients. The mean age of the patients was 37.50 ± 9.43 years (range: 16–53 years). We found a significant difference in the preoperative and postoperative values of the odor recognition test (P = 0.017); however, there was no significant difference between the preoperative and postoperative odor threshold values (P = 0.172) and odor discrimination values (P = 0.624). The threshold discrimination identification test scores were not significant (P = 0.110). The olfactory function of patients who were normosmic preoperatively was not affected postoperatively. This study shows that the endoscopic transsphenoidal technique for pituitary surgery without nasal flap has no negative effect on the olfactory function. Address correspondence and reprint requests to Ceren Kizmazoglu, MD, Department of Neurosurgery, Dokuz Eylul University School of Medicine, 35340 Balçova, Izmir, Turkey; E-mail: ceren.kizmazoglu@gmail.com Received 17 October, 2017 Accepted 3 January, 2018 The authors have no conflicts of interest to disclose. © 2018 by Mutaz B. Habal, MD.

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Frontal Mucocele Extended Orbita and Endoscopic Marsupialization Technique

Mucocele is benign, slow-growing, mucous-filled cystic lesions that arise in the paranasal sinuses. It causes progressive distension of the bony walls and induces compressive symptoms. Surgical treatment of paranasal sinus mucoceles includes endoscopic approach or external approach. The authors report a patient of frontal mucocele who presented with a history of progressive unilateral protrusion. Computed tomography scan revealed a large mucocele of the frontal sinus with orbital extension on the same side. He was successfully treated with endoscopic marsupialization without any serious complications. Address correspondence and reprint requests to Banu Atalay Erdogan, MD, Department of Otolaryngology, Kartal Dr. Lutfi Kirdar Education and Research Hospital, 34890 Cevizli, Kartal, Istanbul, Turkey; E-mail: banuatalay81@gmail.com Received 24 October, 2017 Accepted 5 January, 2018 The authors report no conflicts of interest. © 2018 by Mutaz B. Habal, MD.

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A Reduction Technique for Depressed Medial Maxillary Fractures

The authors developed a technique for reducing the fractured segment by introducing an elevator through the accessory maxillary ostium (AMO). Through an upper gingivolabial vestibular incision, the fractured segments were exposed. In cases where no cleft was available for inserting the elevator, the blunt end of a Cottle elevator was inserted into the AMO via a nasal approach. The curved blunt end of a Cottle elevator was inserted into the middle meatus and the AMO was felt at the medial wall of the maxillary sinus. With gentle pressure, the tip was pushed into the maxillary sinus, and then pushed forward about 2 cm. An upward force was applied until the depressed segment was reduced to its original position. Through a gingivolabial vestibular incision, alignment of the reduced segments could be seen. Miniplate fixation can be applied. If the reduced segments are stable or too many segments are present, the fracture can be stabilized using tissue glue. The authors propose that in medial maxillary fractures where no cleft for the elevator is available, the fractured segment can be mobilized by introducing an elevator through the AMO. Address correspondence and reprint requests to Kun Hwang, MD, PhD, Department of Plastic Surgery, Inha University School of Medicine, 27 Inhang-ro, Jung-gu, Incheon 400-711, Korea; E-mail: jokerhg@inha.ac.kr Received 30 November, 2017 Accepted 5 January, 2018 This study was supported by a grant from National Research Foundation of Korea (NRF-2017R1A2B4005787). The authors report no conflicts of interest. © 2018 by Mutaz B. Habal, MD.

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Unilateral Orticochea Pharyngoplasty for Unilateral Velopharyngeal Dysfunction: Long-Term Outcomes Data

A unilateral deficit in velopharyngeal closure during speech production is an unusual presentation of velopharyngeal dysfunction (VPD) and few solutions have been described for this problem. This report details the long-term outcomes using this technique. We performed a retrospective chart review of all the patients who underwent a unilateral Orticochea pharyngoplasty for VPD. The authors identified 10 patients treated with 11 unilateral pharyngoplasty at a single tertiary care institutional setting. The mean age at repair was 8.6 years. The mean length of follow-up was 7.6 years. All the patients demonstrated improvement in velopharyngeal closure and speech resonance with 4 showing complete resolution of VPD. There were no revisions required or complications. One patient, after 10.7 years, required a unilateral procedure on the contralateral side which resulted in complete resolution of VPD postoperatively. Address correspondence and reprint requests to Arlen D. Denny, MD, FACS, Center for Craniofacial Disorders, P.O. Box 1997; MS C340, Milwaukee, WI 53201-1997; E-mail: adenny@chw.org Received 24 September, 2017 Accepted 7 January, 2018 The authors report no conflicts of interest. © 2018 by Mutaz B. Habal, MD.

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Ablation of Buccal Cancer and Functionality Buccal Reconstruction Using an Individuation Anterolateral Thigh Flap

The complex area for reconstruction of the head and the neck is the buccal because of difficult anatomy of this region. This article aimed to describe our individualized design for the reconstruction of the buccal using an different categories anterolateral thigh (ALT) flap. Ninety-four patients were involved in this study. Among 94cases, the number of using the musculocutaneous ALT flap was 57, using the fasciocutaneous ALT flap was 25, and using the thin ALT flap was 12. Postoperative vessel thrombosis occurred in 8 flaps, and required operative exploration in the perioperative period, 6 flaps were complete survival after the salvages, 2 flap was failure. The ALT flap represents a very good choice for the reconstruction of the complex defects at the cheek level. The flap can replace large volumes of tissues and the skin island is large and can be used both for the tegument reconstruction and for the oral mucosa reconstruction. Address correspondence and reprint requests to Dr. Guowen Sun, Department of Oral and Maxillofacial Surgery, Nangjing Stomatological Hospital,Medical School of Nanjing University,30 Zhongyang Road, Nanjing 210008, PR China; E-mail: guowensun@yahoo.com Received 3 September, 2017 Accepted 5 January, 2018 LZ and TZ contributed equally and should both be regarded as first authors. This research was supported by Jiangsu Provincial Special Program of Medical Science (BL2013005), Project of Health Department of Jiangsu province Nanjing science and technology development project (H201441), Nanjing science and technology development project (201503038) and Key project supported by Medical science and technology development Foundation Nanjing Department of Health (Ykk13150). The authors report no conflicts of interest. © 2018 by Mutaz B. Habal, MD.

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A Rare Cause of Recurrent Cerebral Ischemia and Syncope: Eagle Syndrome

Eagle syndrome is defined as symptomatic elongation of the styloid process or calcification of the stylohyoid and stilomandibular ligament. The syndrome was described by WW Eagle in 1937. The styloid process is located between the internal and external carotid arteries and laterally in the tonsillar fossa. Patients with cerebrovascular ischemia causing syncope or hemiparesia due to Eagle syndrome are rarely published in the literature. The authors presented a patient with recurrent cerebrovascular attacks due to long styloid process. Address correspondence and reprint requests to Kemal Koray Bal, Resident Doctor, MD, Department of Otorhinolaryngology, Faculty of Medicine, University of Mersin, Mersin 33010, Turkey; E-mail: dr.kemalkoraybal@gmail.com Received 25 October, 2017 Accepted 7 January, 2018 The authors report no conflicts of interest. © 2018 by Mutaz B. Habal, MD.

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Nasolabial Morphology Following Nasoalveolar Molding in Infants With Unilateral Cleft Lip and Palate

Aim: The aim of the present study is to evaluate the effects of nasoalveolar molding (NAM) therapy on nasolabial morphology three dimensionally, and compare the nasolabial linear and surface distance measurements in infants with unilateral cleft lip and palate. Methods: Facial plaster casts of 42 infants with unilateral cleft lip and palate taken at the onset (pre-NAM) and finishing stage (post-NAM) of NAM were scanned with 3dMDface stereophotogrammetry system (3dMD, Atlanta, GA). Nineteen nasolabial linear and surface distance measurements were performed on three-dimensional images. In addition to standard descriptive statistical calculations (means and SDs), pre- and post-NAM measurements were evaluated by paired t test. Results: All measurements except lip gap, nostril floor width, and nostril diameter increased between pre-NAM and post-NAM. Nostril and lip height increased significantly on the cleft side (P 

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Postextraction Dental Implant in the Aesthetic Zone, Socket Shield Technique Versus Conventional Protocol

The aim of this randomized controlled trial was to evaluate the survival rate, the marginal bone level, and the aesthetic outcome; at 3 years' follow-up, of dental implants placed into a high-esthetic aesthetic zone by comparing 2 techniques of postextraction implant with immediate loading: the socket shied technique and the conventional insertion technique. Several clinical studies suggested that the avulsion of a dental element causes dimensional alterations of both soft and hard tissues at the postextractive site. To increase the aesthetic outcomes, the "socket-shield technique" has been proposed. This method involves maintaining the vestibular root portion and immediate insertion of the dental implant in close proximity to the root. Patients enrolled in this study were randomized to receive a postextraction implant in the aesthetic zone, either with the socket shied technique or with the conventional insertion technique. Implant survival, marginal bone level, and the pink aesthetic score were the outcomes evaluated. Implant survival rate was 100% in both the groups at 3 years. Implants inserted with the socket shield technique showed better values of both marginal bone level and pink aesthetic score (P 

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Does the Degree of the Mastoid Pneumatization Affect the Side of Bell Palsy?

Objective: The aim is to investigate the impact of degree of mastoid pneumatization on the affected side of Bell palsy (BP). Study Design: Retrospective study in tertiary academic hospital. Methods: In total, 52 patients who were diagnosed with as BP were included in the study. Each patient was staged using House–Brackmann (HB) staging system. All patients underwent temporal bone computed tomography imaging. House–Brackmann scores, side of the BP, and mastoid pneumatization of all of patients were evaluated in the present study. Results: Regarding the degree of the mastoid pneumatization, there were no significant differences between the affected side and the unaffected side (P = 0.439). The degree of the mastoid pneumatization of the affected side and the unaffected side did not differ between males and females (P = 0.918 for the affected side, P = 0.765 for the unaffected side, respectively). A negative correlation between the age and mastoid pneumatization of each side was found (P = 0.001, P = 0.025, respectively). There was no significant correlation between HB score and the degree of the mastoid pneumatization of each side (P = 0.789, P = 0.703). Conclusion: As a conclusion, the degree of the mastoid pneumatization is not one of the risk factors for BP. Further randomized studies with larger numbers of patients are needed to confirm these findings. Address correspondence and reprint requests to Dr Mustafa Çelik, MD, Bakirköy Dr Sadi Konuk Eğitim ve Araştirma Hastanesi, Zuhuratbaba Mah. Tevfik Sağlam Cad. No: 11, Bakirköy, 34147 Istanbul, Turkey; E-mail: dr.mcelik@yahoo.com Received 8 July, 2017 Accepted 1 December, 2017 The protocol for this study was approved by the hospital's local ethics committee (ethical committee number 2017/05/05). The authors report no conflicts of interest. © 2018 by Mutaz B. Habal, MD.

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Demystifying the “Triple Point: ” Technical Nuances of the Fronto-Orbital Advancement

Removal of the fronto-orbital bandeau is one of the most critical components for procedures designed to correct anomalies of the craniofacial skeleton and remodel the anterior calvarial vault. It is also used to improve exposure of the anterior cranial fossa. It is arguably one of the more difficult portions of some craniofacial procedures. While the technique for fronto-orbito-sphenoid osteotomy has been frequently described, it has only been minimally detailed. Separation of bone in this region remains challenging due to the bone thickness, adjacent vital structures, and limited direct visibility. The present paper describes the anatomy of this particular region, which the authors have termed the "triple point", to facilitate successful osteotomy and avoid potential injury. Address correspondence and reprint requests to Peter J. Taub, MD, FACS, Professor, Surgery, Pediatrics, Dentistry, and Neurosurgery; Professor, Medical Education; Program Director, Plastic and Reconstructive Surgery; Chief, Craniomaxillofacial Surgery, Icahn School of Medicine at Mount Sinai; Chief, Pediatric Plastic Surgery, Kravis Children's Hospital, 5 East 98th Street, New York, NY 10029; E-mail: Peter.taub@mountsinai.org Received 2 March, 2017 Accepted 30 June, 2017 The authors report no conflicts of interest. © 2018 by Mutaz B. Habal, MD.

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Replacement of the distorted dentition of the Cone Beam Computed Tomography (CBCT) scans for orthognathic surgery planning

Publication date: Available online 28 February 2018
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Turki Almutairi, Kurt Naudi, Neil Nairn, Xiangyang Ju, John Whitters, Aashraf Ayoub
PurposeCBCT imaging does not record dental morphology accurately due to the scattering produced by metallic restorations and the reported magnification. The aim of this study was the development and the evaluation of a new method for the replacement of the distorted dentition of CBCT scans with 3D dental image captured by a digital intraoral camera.
Materials and MethodSix dried skulls with orthodontics brackets fixed on the teeth were used in this study. Three intra-oral markers made of dental stone were constructed and attached to orthodontics brackets. The skulls were CBCT scanned and occlusal surfaces were captured using TRIOS ^® 3D intraoral scanner. The digital intra-oral scan (IOS) was fused into the CBCT models. This produced a new composite digital model of the skull and dentition. The skulls were scanned again using the commercially accurate Laser Faro^® arm to produce the 3D model "gold standard" for the assessment of the accuracy of the developed method. This was assessed by measuring the distance between the occlusal surfaces of the new composite model and the "gold standard" 3D laser scanned modelResultsThe results showed the errors related to the superimposition of the intra-oral image on the CBCT to replace the distorted dentition were between 0.11 and 0.20 mm.ConclusionThe results of this study suggests that the dentition in the CBCT can be accurately replaced with the digital IOS captured by an intra-oral scanner to create a composite model which will improve the accuracy of the digital orthognathic surgical planning and the fabrication of an occlusal wafer.



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