Human tear proteomics and peptidomics in ophthalmology: Toward the translation of proteomic biomarkers into clinical practice

Publication date: Available online 13 May 2016
Source:Journal of Proteomics
Author(s): Mikel Azkargorta, Javier Soria, Arantxa Acera, Ibon Iloro, Tatiana Suarez, Felix Elortza
Tears are a complex biological mixture containing electrolytes, metabolites, lipids, mucins, some small organic molecules, and proteins. The film has various roles in the lubrication, protection from the external environment, and nutrition of the cornea; it is also involved in the modulation of the optical properties of the eye.Tear composition reflects the physiological condition of the underlying tissues. Therefore, the tear fluid is useful in the evaluation of health and disease statesand it is a valuable source of biomarkers for objective analysis of ocular and systemic diseases.The relatively high protein concentration of this fluid and the ease of noninvasive sample collection make it suitable for diagnostic and prognostic purposes. Efforts in proteomics research have positively affected to the field of ophthalmology, and the knowledge on the tear proteome has expanded considerably in the last few years. Nevertheless, despite a large amount of available data and the many biomarkers proposed for several eye and systemic diseases, the extent of translation to well-characterized and clinically useful tools has been largely insufficient. As for most of other biofluids, the road from discovery to clinical application is still long and full of pitfalls.In this review, we discuss the proteomic approaches used in the characterization of tear protein and peptide content, recapitulating the main studies and the progress done. We also present a brief summary of the path from discovery to clinical application of tear protein markers, with some representative examples of translation from the bench to the bedside.SignificanceIn this review we cover the most relevant proteomic approaches used in the characterization of tear proteome, and for the first time we also focus in advances performed in the nowadays emerging peptide content characterization. In this context, we recapitulate on the main studies and the progresses done in this field. We also present a concise overview of the course that may be happen from discovery to clinical application for tear protein markers. Finally we include some representative examples of translation from the bench to the bedside.



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White-collar sign as a predictor of outcome after endovascular treatment for cerebral aneurysms

Journal of Neurosurgery, Ahead of Print.
OBJECTIVE The white-collar sign (WCS) is known as a thick neointimal tissue formation at the aneurysm neck after endovascular coil embolization of cerebral aneurysms, which may prevent aneurysm recanalization. The purpose of this study was to evaluate factors involved in the appearance of WCS and to identify radiological and clinical outcomes of treated aneurysms with WCS. METHODS The study included 140 patients with 149 aneurysms in which it was possible to confirm the aneurysm neck between the aneurysm sac and parent artery by using conventional angiography. The WCS was defined as a radiolucent band at the aneurysm neck on the angiogram at 6 months after initial embolization. The radiological outcome was evaluated using MR angiography. RESULTS In 23 of 149 aneurysms (15.4%), a WCS appeared. The WCS-positive group had a significantly smaller neck size (3.3 ± 0.8 mm vs 4.2 ± 1.1 mm, p < 0.001) and smaller aneurysm size (4.3 ± 0.9 mm vs 6.0 ± 2.1 mm, p < 0.001) than the WCS-negative group. Multivariate analysis revealed that WCS appearance was associated with small neck size (OR 0.376, 95% CI 0.179–0.787; p = 0.009). In 106 of 149 aneurysms, the rate of complete occlusion was significantly higher in the WCS-positive group (18/18, 100%) than in the WCS-negative group (n = 54/88, 61.4%; p = 0.001) in the mean follow-up period of 31.0 ± 9.7 months (range 5–52 months). Neither major recanalization nor rupture of the aneurysm occurred in the WCS-positive group. CONCLUSIONS Appearance of the WCS was associated with complete occlusion and good clinical outcome after endovascular coil embolization. The WCS would help to determine the prognosis of cerebral aneurysms after endovascular treatment.

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Struthers' ligament and traumatic median nerve injury: case illustration

Journal of Neurosurgery, Ahead of Print.


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Posterior interosseous nerve discontinuity due to compression by lipoma: report of 2 cases

Journal of Neurosurgery, Ahead of Print.
Paralysis of the posterior interosseous nerve (PIN) secondary to compression is a rare clinical condition. Entrapment neuropathy may occur at fibrous bands at the proximal, middle, or distal edge of the supinator. Tumors are a relatively rare but well-known potential cause. The authors present 2 cases of PIN lesions in which compression by a benign lipoma at the level of the elbow resulted in near transection (discontinuity) of the nerve. They hypothesize a mechanism—a "sandwich effect"—by which compression was produced from below by the mass and from above by a fibrous band in the supinator muscle (i.e., the leading edge of the proximal supinator muscle [arcade of Fröhse] in one patient and the distal edge of the supinator muscle in the other). A Grade V Sunderland nerve lesion resulted from the advanced, chronic compression. The authors are unaware of a similar case with such an advanced pathoanatomical finding.

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Analysis of facial motor evoked potentials for assessing a central mechanism in hemifacial spasm

Journal of Neurosurgery, Ahead of Print.
OBJECTIVE Hemifacial spasm (HFS) is a cranial nerve hyperactivity disorder characterized by unique neurophysiological features, although the underlying pathophysiology remains disputed. In this study, the authors compared the effects of desflurane on facial motor evoked potentials (MEPs) from the spasm and nonspasm sides of patients who were undergoing microvascular decompression (MVD) surgery to test the hypothesis that HFS is associated with a central elevation of facial motor neuron excitability. METHODS Facial MEPs were elicited in 31 patients who were undergoing MVD for HFS and were administered total intravenous anesthesia (TIVA) with or without additional desflurane, an inhaled anesthetic known to centrally suppress MEPs. All measurements were completed before dural opening while a consistent mean arterial blood pressure was maintained and electroencephalography was performed. The activation threshold voltage and mean amplitudes of the MEPs from both sides of the face were compared. RESULTS There was a significantly lower mean activation threshold of facial MEPs on the spasm side than on the nonspasm side (mean ± SD 162.9 ± 10.1 vs 198.3 ± 10.1 V, respectively; p = 0.01). In addition, MEPs were also elicited more readily when single-pulse transcranial electrical stimulation was used on the spasm side (74% vs 31%, respectively; p = 0.03). Although desflurane (1 minimum alveolar concentration) suppressed facial MEPs on both sides, the suppressive effects of desflurane were less on the spasm side than on the nonspasm side (59% vs 79%, respectively; p = 0.03), and M waves recorded from the mentalis muscle remained unchanged, which indicates that desflurane did not affect the peripheral facial nerve or neuromuscular junction. CONCLUSIONS Centrally acting inhaled anesthetic agents can suppress facial MEPs and therefore might interfere with intraoperative monitoring. The elevated motor neuron excitability and differential effects of desflurane between the spasm and nonspasm sides support a mechanism of central pathophysiology in HFS. Clinical trial registration no.: B2012:099 (clinicaltrials.gov)

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Treatment of a skull-base giant cell tumor with endoscopic endonasal resection and denosumab: case report

Journal of Neurosurgery, Ahead of Print.
A 34-year-old man with a 1-week history of diplopia was referred to the authors' hospital. Neurological examination revealed left abducens nerve palsy. Computed tomography showed a lesion in the left sphenoid sinus involving the medial wall of the left internal carotid artery (ICA) and osteolytic change at the clivus bordering the lesion. Magnetic resonance imaging demonstrated an extensive soft-tissue mass occupying the left sphenoid sinus. Surgical intervention by the endoscopic transnasal method allowed most of the lesion to be removed. Only the portion attached to the medial wall of the ICA was not removed. Postoperatively, the lesion was diagnosed as a giant cell tumor (GCT) and the patient received 120 mg of subcutaneous denosumab every 4 weeks, with additional doses on Days 8 and 15 during the first month of therapy. MRI a week after starting denosumab revealed shrinkage of the initially fast-growing residual tumor. The patient was discharged upon completion of the third denosumab administration. GCT is an aggressive stromal tumor developing mainly in young adults. Complete resection is recommended for GCT in the literature. However, size and location of the CGT often limit this approach. Various adjuvant treatments for skull base GCTs have been reported, including radiation and chemotherapy. However, the roles of adjuvant therapies have yet to be clearly defined. Denosumab, a monoclonal antibody, was recently approved for GCT in several countries. Denosumab may permit less invasive treatments for patients with GCTs while avoiding deleterious outcomes, and may also limit disease progression and recurrence.

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Foramen magnum meningiomas: surgical results and risks predicting poor outcomes based on a modified classification

Journal of Neurosurgery, Ahead of Print.
OBJECTIVE This study aimed to evaluate neurological function and progression/recurrence (P/R) outcome of foramen magnum meningioma (FMM) based on a modified classification. METHODS This study included 185 consecutive patients harboring FMMs (mean age 49.4 years; 124 females). The authors classified the FMMs into 4 types according to the previous classification of Bruneau and George as follows: Type A (n = 49, 26.5%), the dural attachment of the lesion grows below the vertebral artery (VA); Type B (n = 39, 21.1%), the dural attachment of the lesion grows above the VA; Type C1 (n = 84, 45.4%), the VA courses across the lesion with or without VA encasement or large lesions grow both above and below the bilateral VA; and Type C2 (n = 13, 7.0%), Type C1 plus partial/total encasement of the VA and extradural growth. RESULTS The median preoperative Karnofsky Performance Scale (KPS) score was 80. Gross-total resection (GTR) was achieved in 154 patients (83.2%). Lower cranial nerve morbidity was lowest in Type A lesions (16.3%). Type C2 lesions were inherently larger (p = 0.001), had a greater percentage of ventrolateral location (p = 0.009) and VA encasement (p < 0.001), lower GTR rate (p < 0.001), longer surgical duration (p = 0.015), higher morbidity (38.5%), higher P/R rate (30.8%, p = 0.009), and poorer recent KPS score compared with other types. After a mean follow-up duration of 110.3 months, the most recent follow-up data were obtained in 163 patients (88.1%). P/R was observed in 13 patients (7.2%). The median follow-up KPS score was 90. Compared with preoperative status, recent neurological status was improved in 91 (49.2%), stabilized in 76 (41.1%), and worsened in 18 (9.7%) patients. The multivariate Cox proportional hazard regression model demonstrated Type C2 (HR 3.94, 95% CI 1.04–15.0, p = 0.044), nontotal resection (HR 6.30, 95% CI 1.91–20.8, p = 0.003), and pathological mitosis (HR 7.11, 95% CI 1.96–25.8, p = 0.003) as independent adverse predictors for tumor P/R. Multivariate logistic regression analysis identified nontotal resection (OR 4.06, 95% CI 1.16–14.2, p = 0.029) and pathological mitosis (OR 6.29, 95% CI 1.47–27.0, p = 0.013) as independent risks for poor outcome (KPS score < 80). CONCLUSIONS The modified classification helped to predict surgical outcome and P/R in addition to the position of the lower cranial nerves. Preoperative imaging studies and neurological function should be reviewed carefully to establish an individualized management strategy to improve long-term outcome.

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Connecting raised intracranial pressure and cognitive delay in craniosynostosis: many assumptions, little evidence

Journal of Neurosurgery: Pediatrics, Ahead of Print.


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Radiographic markers of clinical outcomes after endoscopic third ventriculostomy with choroid plexus cauterization: cerebrospinal fluid turbulence and choroid plexus visualization

Journal of Neurosurgery: Pediatrics, Ahead of Print.
OBJECTIVE Endoscopic third ventriculostomy (ETV) with choroid plexus (CP) cauterization (CPC) represents a viable treatment option for congenital hydrocephalus in infants younger than 2 years. Imaging studies complement clinical data in the evaluation of treatment success or failure. The objectives of this study were to investigate novel radiographic markers—cerebrospinal fluid (CSF) turbulence and CP visualization—and their ability to reflect or predict clinical outcomes following ETV/CPC. METHODS Hydrocephalic patients younger than 2 years who were initially treated by ETV/CPC at the senior authors' institution between March 2013 and February 2014 were retrospectively reviewed. Clinical data, as well as the visualization of CSF turbulence and CP on pre- and postoperative fast-sequence MRI, were recorded. Radiographic images were reviewed by a blinded observer based on specific criteria for the visualization of CSF turbulence and CP. Data were collected and analyzed using descriptive statistics, including Fisher's exact test for comparisons. The research team obtained appropriate institutional review board approval for this study, without the need for informed consent. RESULTS Among the 32 patients (53% male and 47% female) studied, 18 of 32 (56%) responded favorably to initial or repeat ETV/CPC, with 13 of 32 (41%) patients requiring 1 surgery. Of the 19 (59%) patients whose initial ETV/CPC failed, 8 of 19 (42%) patients underwent repeat ETV/CPC, with 5 of 8 (63%) patients responding favorably. Radiographic CSF turbulence appeared more frequently following ETV/CPC failure than after ETV/CPC success (55% vs 18%, respectively; p = 0.02). The sensitivity and specificity of CSF turbulence as a radiographic marker for ETV/CPC failure were 80% and 58%, respectively. The radiographic depiction of CP disappearance following ETV/CPC from pre- to postoperative imaging occurred in 20 of 30 patients (67%). Among the patients who responded unsuccessfully to ETV/CPC and ultimately required secondary shunt insertion, 71% (10 of 14 patients) demonstrated CP persistence on postoperative imaging. In contrast, 6% (1 of 18) of patients who were treated successfully by ETV/CPC demonstrated the presence of CP on follow-up imaging. This difference reached statistical significance (p = 0.0001). The visualization of CP persistence despite ETV/CPC reflected treatment failure with 91% sensitivity and 81% specificity. The sensitivity of either or both radiographic markers to suggest ETV/CPC failure was 77%, while their specificity (both markers absent, thereby indicating ETV/CPC success) was 81%. CONCLUSIONS Radiographic markers correlate with clinical outcomes following the treatment of infantile hydrocephalus with ETV/CPC. Specifically, CSF turbulence may indicate ongoing pathological CSF flow dynamics, while CP absence following ETV/CPC may predict shunt independence. Future studies that incorporate prospective review and formal intra- and interobserver reliability estimates may help corroborate the utility of these radiographic markers.

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Indirect and direct revascularization of ACTA2 cerebral arteriopathy: feasibility of the superficial temporal artery to anterior cerebral artery bypass with posterior auricular artery interposition graft: case report

Journal of Neurosurgery: Pediatrics, Ahead of Print.
Mutations in the smooth muscle–specific isoform of alpha actin (ACTA2) cause smooth muscle dysfunction in arteries. This rare loss-of-function mutation may cause a diffuse occlusive cerebral arteriopathy, resulting in stroke. While ACTA2 arteriopathy is often described as moyamoya-like, it has a distinct phenotype characterized by dilation of the proximal internal carotid artery (ICA) and occlusion of the terminal ICA and proximal middle cerebral artery. Intracranial arteries have an abnormally straight course, often with small aneurysms. There is limited experience with revascularization procedures for ACTA2 arteriopathy, and the safety and efficacy of these procedures are unknown. In this paper the authors present a symptomatic 6-year-old patient with ACTA2 cerebral arteriopathy who underwent both indirect revascularization and direct cerebrovascular bypass. Postoperatively, the patient suffered an ischemic infarct in a neighboring vascular territory. While direct cerebrovascular bypass is technically feasible, patients with ACTA2 arteriopathy may be at increased risk for perioperative stroke compared with patients with moyamoya disease.

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Human tear proteomics and peptidomics in ophthalmology: Toward the translation of proteomic biomarkers into clinical practice

Publication date: Available online 13 May 2016
Source:Journal of Proteomics
Author(s): Mikel Azkargorta, Javier Soria, Arantxa Acera, Ibon Iloro, Tatiana Suarez, Felix Elortza
Tears are a complex biological mixture containing electrolytes, metabolites, lipids, mucins, some small organic molecules, and proteins. The film has various roles in the lubrication, protection from the external environment, and nutrition of the cornea; it is also involved in the modulation of the optical properties of the eye.Tear composition reflects the physiological condition of the underlying tissues. Therefore, the tear fluid is useful in the evaluation of health and disease statesand it is a valuable source of biomarkers for objective analysis of ocular and systemic diseases.The relatively high protein concentration of this fluid and the ease of noninvasive sample collection make it suitable for diagnostic and prognostic purposes. Efforts in proteomics research have positively affected to the field of ophthalmology, and the knowledge on the tear proteome has expanded considerably in the last few years. Nevertheless, despite a large amount of available data and the many biomarkers proposed for several eye and systemic diseases, the extent of translation to well-characterized and clinically useful tools has been largely insufficient. As for most of other biofluids, the road from discovery to clinical application is still long and full of pitfalls.In this review, we discuss the proteomic approaches used in the characterization of tear protein and peptide content, recapitulating the main studies and the progress done. We also present a brief summary of the path from discovery to clinical application of tear protein markers, with some representative examples of translation from the bench to the bedside.SignificanceIn this review we cover the most relevant proteomic approaches used in the characterization of tear proteome, and for the first time we also focus in advances performed in the nowadays emerging peptide content characterization. In this context, we recapitulate on the main studies and the progresses done in this field. We also present a concise overview of the course that may be happen from discovery to clinical application for tear protein markers. Finally we include some representative examples of translation from the bench to the bedside.



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Sensors, Vol. 16, Pages 697: Measurement of Moisture in Wood for Application in the Restoration of Old Buildings

There are many historic buildings whose construction is based on timber frame walls. Most buildings built during the nineteenth and early twentieth centuries were based on timber frame walls with vertical support elements. These timber frame elements are affected by their moisture content and by the passage of time. If the interaction of the timber frame walls with hygrothermal fluctuations were known, the maintenance of these buildings could be improved significantly. To determine the moisture content of wood there are two types of meters on the market: on the one hand, capacitance meters which consist of two side ends and where the moisture content is measured locally between two peaks. On the other hand, there are meters based on the variation of electromagnetic transmittance of timber, which depends on the moisture of timber. The second ones are very expensive and difficult to handle. This work presents a new non-intrusive capacitive sensor that measures the global moisture content in a section of the timber frame walls and therefore its accuracy is similar to the accuracy that can be obtained with electromagnetic transmittance meters. Additionally, as it is a capacitive sensor, it is low cost and easy to operate.

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Sensors, Vol. 16, Pages 697: Measurement of Moisture in Wood for Application in the Restoration of Old Buildings

There are many historic buildings whose construction is based on timber frame walls. Most buildings built during the nineteenth and early twentieth centuries were based on timber frame walls with vertical support elements. These timber frame elements are affected by their moisture content and by the passage of time. If the interaction of the timber frame walls with hygrothermal fluctuations were known, the maintenance of these buildings could be improved significantly. To determine the moisture content of wood there are two types of meters on the market: on the one hand, capacitance meters which consist of two side ends and where the moisture content is measured locally between two peaks. On the other hand, there are meters based on the variation of electromagnetic transmittance of timber, which depends on the moisture of timber. The second ones are very expensive and difficult to handle. This work presents a new non-intrusive capacitive sensor that measures the global moisture content in a section of the timber frame walls and therefore its accuracy is similar to the accuracy that can be obtained with electromagnetic transmittance meters. Additionally, as it is a capacitive sensor, it is low cost and easy to operate.

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Double-Blind Sham-Controlled Crossover Trial of Repetitive Transcranial Magnetic Stimulation for Mal de Debarquement Syndrome.

Objective: To determine whether the chronic rocking dizziness that occurs in Mal de Debarquement Syndrome (MdDS) can be suppressed with repetitive transcranial magnetic stimulation (rTMS) beyond the treatment period. Methods: We performed a prospective randomized double-blind sham controlled crossover trial of 5-days of rTMS utilizing high frequency (10 Hz) stimulation over the left dorsolateral prefrontal cortex (DLPFC). Results: Eight right-handed women (44.5 [SD 7.0] yr) with classical motion-triggered MdDS (mean duration 42.1 [SD 13.2] mo) participated. Group level mixed effects repeated measures analysis of variance (ANOVA) showed improvement in our primary outcome measure, the Dizziness Handicap Inventory (DHI) at Post TMS Weeks 1, 3, and 4 (p

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Immunohistochemical evaluation of the mTOR pathway in intraoral minor salivary gland neoplasms

Abstract

Objectives

The aim of this study was to investigate the expression of upstream and downstream molecules of the oncogenic mTOR signaling pathway in intraoral minor salivary gland tumors (SGTs).

Materials and Methods

Tissue samples consisted of 39 malignant and 13 benign minor SGTs, and 8 controls of normal minor salivary glands (NMSG). An immunohistochemical analysis for phosphorylated Akt, 4EBP1, S6 (total and phosphorylated), and eIF4E was performed.

Results

Expression of pAkt and 4EBP1 was found in all SGTs and in most NMSG. p4EBP1 was detected in almost all SGT cases, NMSG being negative. S6 immunoreactivity was observed in 37.5% of NMSG, 92.3% of benign and 100% of malignant SGTs, while pS6 expression was found in 77% of benign and 95% of malignant SGTs, but not in NMSG. Finally, eIF4E was expressed in 12.5% of NMSG, 69.2% of benign and 76.9% of malignant tumors. All molecules studied had statistically significantly lower expression in NMSG compared to SGTs. Moreover, malignant neoplasms received higher scores compared to benign tumors for all molecules with the exception of eIF4E.

Conclusion

The mTOR signaling pathway is activated in SGTs, especially in malignancies. Therefore, the possible therapeutic role of targeting the mTOR pathway by Rapamycin analogs in SGTs needs further investigation.

This article is protected by copyright. All rights reserved.

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The cost effectiveness of transesophageal echocardiography for pediatric cardiac surgery: a systematic review

Summary

Background

Intraoperative transesophageal echocardiography (ITEE) for pediatric cardiac surgery has been described as clinically efficacious and cost-effective. There are a small number of publications supporting these claims.

Aims

The objectives were to assess the quality of the research, the variability of results across studies and, if possible, to make a consensus statement based on the results.

Methods

In March 2015, a systematic search of MEDLINE and MEDLINE In-Process, EMBASE, and the National Health Service Economic Evaluation Database was performed. The search was supplemented with a review of Health Technology Assessment reports through the Centre for Reviews and Dissemination database. English language articles including any quantitative economic evaluation were included. The quality of each study was assessed using the British Medical Journal economic evaluation quality checklist. Data extracted included the main outcomes from each study, study methodologies, itemized costs, sensitivity ranges, biases, and delayed reoperation prevented with ITEE. When possible, a cost-savings per ITEE was calculated to facilitate comparison across studies and used to create a synthesis of the results.

Results

Seven studies met the inclusion criteria; of these, five were included in the synthesis of results. The cost-savings per ITEE ranged from $194 to $4910 with a mean of $1930 (95%CI: $845 to $3015) (2015 USD). Prevented delayed reoperation rates using ITEE ranged from 2.8% to 10%. Earlier studies were of poorer quality (scores 8–17) and more recent studies were of higher quality (scores 22–25). Methodologies used were either retrospective chart reviews (57%) or prospective observational studies (43%) with a range of approaches to estimate costs.

Conclusion

ITEE for pediatric cardiac surgery is effective and cost-saving. This is a validation of the current practice patterns. These finding may influence the expansion of the use of this technology.

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The Association between Openness and Physiological Responses to Recurrent Social Stress

Publication date: Available online 13 May 2016
Source:International Journal of Psychophysiology
Author(s): Wei Lü, Zhenhong Wang, Brian M. Hughes
The association between openness (assessed by shortened Chinese version of NEO Five-Factor Inventory, NEO-FFI) and physiological reactivity to, and recovery from, social stress (a video-recorded, timed public speaking task with evaluators present in the room), and physiological adaptation to repeated social stress was examined in the present study. Subjective and physiological data were collected from 70 college students across five laboratory stages: baseline, stress exposure period 1, post-stress period 1, stress exposure period 2, and post-stress period 2. Results indicated that higher openness was associated with lesser heart rate (HR) reactivity to the first and second stress exposure, and lesser systolic blood pressure (SBP) reactivity to the second stress exposure. Higher openness was associated with higher resting respiratory sinus arrhythmia (RSA), lesser RSA withdrawals to the first stress exposure, and more complete RSA recovery after the first stress exposure. Moreover, higher openness was associated with pronounced systolic and diastolic blood pressure (SBP, DBP) adaptation with greater decreases in SBP and DBP reactivity across the two successive stress exposures. These findings might shed light on the biological basis linking openness to health.



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Increased N250 amplitudes for other-race faces reflect more effortful processing at the individual level

Publication date: Available online 14 May 2016
Source:International Journal of Psychophysiology
Author(s): Grit Herzmann
The N250 and N250r (r for repetition, signaling a difference measure of priming) has been proposed to reflect the activation of perceptual memory representations for individual faces. Increased N250r and N250 amplitudes have been associated with higher levels of familiarity and expertise, respectively. In contrast to these observations, the N250 amplitude has been found to be larger for other-race than own-race faces in recognition memory tasks. This study investigated if these findings were due to increased identity-specific processing demands for other-race relative to own-race faces and whether or not similar results would be obtained for the N250 in a repetition priming paradigm. Only Caucasian participants were available for testing and completed two tasks with Caucasian, African-American, and Chinese faces. In a repetition priming task, participants decided whether or not sequentially presented faces were of the same identity (individuation task) or same race (categorization task). Increased N250 amplitudes were found for African-American and Chinese faces relative to Caucasian faces, replicating previous results in recognition memory tasks. Contrary to the expectation that increased N250 amplitudes for other-race face would be confined to the individuation task, both tasks showed similar results. This could be due to the fact that face identity information needed to be maintained across the sequential presentation of prime and target in both tasks. Increased N250 amplitudes for other-race faces are taken to represent increased neural demands on the identity-specific processing of other-race faces, which are typically processed less holistically and less on the level of the individual.



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Double-Blind Sham-Controlled Crossover Trial of Repetitive Transcranial Magnetic Stimulation for Mal de Debarquement Syndrome.

Objective: To determine whether the chronic rocking dizziness that occurs in Mal de Debarquement Syndrome (MdDS) can be suppressed with repetitive transcranial magnetic stimulation (rTMS) beyond the treatment period. Methods: We performed a prospective randomized double-blind sham controlled crossover trial of 5-days of rTMS utilizing high frequency (10 Hz) stimulation over the left dorsolateral prefrontal cortex (DLPFC). Results: Eight right-handed women (44.5 [SD 7.0] yr) with classical motion-triggered MdDS (mean duration 42.1 [SD 13.2] mo) participated. Group level mixed effects repeated measures analysis of variance (ANOVA) showed improvement in our primary outcome measure, the Dizziness Handicap Inventory (DHI) at Post TMS Weeks 1, 3, and 4 (p

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White-collar sign as a predictor of outcome after endovascular treatment for cerebral aneurysms

Journal of Neurosurgery, Ahead of Print.
OBJECTIVE The white-collar sign (WCS) is known as a thick neointimal tissue formation at the aneurysm neck after endovascular coil embolization of cerebral aneurysms, which may prevent aneurysm recanalization. The purpose of this study was to evaluate factors involved in the appearance of WCS and to identify radiological and clinical outcomes of treated aneurysms with WCS. METHODS The study included 140 patients with 149 aneurysms in which it was possible to confirm the aneurysm neck between the aneurysm sac and parent artery by using conventional angiography. The WCS was defined as a radiolucent band at the aneurysm neck on the angiogram at 6 months after initial embolization. The radiological outcome was evaluated using MR angiography. RESULTS In 23 of 149 aneurysms (15.4%), a WCS appeared. The WCS-positive group had a significantly smaller neck size (3.3 ± 0.8 mm vs 4.2 ± 1.1 mm, p < 0.001) and smaller aneurysm size (4.3 ± 0.9 mm vs 6.0 ± 2.1 mm, p < 0.001) than the WCS-negative group. Multivariate analysis revealed that WCS appearance was associated with small neck size (OR 0.376, 95% CI 0.179–0.787; p = 0.009). In 106 of 149 aneurysms, the rate of complete occlusion was significantly higher in the WCS-positive group (18/18, 100%) than in the WCS-negative group (n = 54/88, 61.4%; p = 0.001) in the mean follow-up period of 31.0 ± 9.7 months (range 5–52 months). Neither major recanalization nor rupture of the aneurysm occurred in the WCS-positive group. CONCLUSIONS Appearance of the WCS was associated with complete occlusion and good clinical outcome after endovascular coil embolization. The WCS would help to determine the prognosis of cerebral aneurysms after endovascular treatment.

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Struthers' ligament and traumatic median nerve injury: case illustration

Journal of Neurosurgery, Ahead of Print.


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Posterior interosseous nerve discontinuity due to compression by lipoma: report of 2 cases

Journal of Neurosurgery, Ahead of Print.
Paralysis of the posterior interosseous nerve (PIN) secondary to compression is a rare clinical condition. Entrapment neuropathy may occur at fibrous bands at the proximal, middle, or distal edge of the supinator. Tumors are a relatively rare but well-known potential cause. The authors present 2 cases of PIN lesions in which compression by a benign lipoma at the level of the elbow resulted in near transection (discontinuity) of the nerve. They hypothesize a mechanism—a "sandwich effect"—by which compression was produced from below by the mass and from above by a fibrous band in the supinator muscle (i.e., the leading edge of the proximal supinator muscle [arcade of Fröhse] in one patient and the distal edge of the supinator muscle in the other). A Grade V Sunderland nerve lesion resulted from the advanced, chronic compression. The authors are unaware of a similar case with such an advanced pathoanatomical finding.

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Analysis of facial motor evoked potentials for assessing a central mechanism in hemifacial spasm

Journal of Neurosurgery, Ahead of Print.
OBJECTIVE Hemifacial spasm (HFS) is a cranial nerve hyperactivity disorder characterized by unique neurophysiological features, although the underlying pathophysiology remains disputed. In this study, the authors compared the effects of desflurane on facial motor evoked potentials (MEPs) from the spasm and nonspasm sides of patients who were undergoing microvascular decompression (MVD) surgery to test the hypothesis that HFS is associated with a central elevation of facial motor neuron excitability. METHODS Facial MEPs were elicited in 31 patients who were undergoing MVD for HFS and were administered total intravenous anesthesia (TIVA) with or without additional desflurane, an inhaled anesthetic known to centrally suppress MEPs. All measurements were completed before dural opening while a consistent mean arterial blood pressure was maintained and electroencephalography was performed. The activation threshold voltage and mean amplitudes of the MEPs from both sides of the face were compared. RESULTS There was a significantly lower mean activation threshold of facial MEPs on the spasm side than on the nonspasm side (mean ± SD 162.9 ± 10.1 vs 198.3 ± 10.1 V, respectively; p = 0.01). In addition, MEPs were also elicited more readily when single-pulse transcranial electrical stimulation was used on the spasm side (74% vs 31%, respectively; p = 0.03). Although desflurane (1 minimum alveolar concentration) suppressed facial MEPs on both sides, the suppressive effects of desflurane were less on the spasm side than on the nonspasm side (59% vs 79%, respectively; p = 0.03), and M waves recorded from the mentalis muscle remained unchanged, which indicates that desflurane did not affect the peripheral facial nerve or neuromuscular junction. CONCLUSIONS Centrally acting inhaled anesthetic agents can suppress facial MEPs and therefore might interfere with intraoperative monitoring. The elevated motor neuron excitability and differential effects of desflurane between the spasm and nonspasm sides support a mechanism of central pathophysiology in HFS. Clinical trial registration no.: B2012:099 (clinicaltrials.gov)

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Treatment of a skull-base giant cell tumor with endoscopic endonasal resection and denosumab: case report

Journal of Neurosurgery, Ahead of Print.
A 34-year-old man with a 1-week history of diplopia was referred to the authors' hospital. Neurological examination revealed left abducens nerve palsy. Computed tomography showed a lesion in the left sphenoid sinus involving the medial wall of the left internal carotid artery (ICA) and osteolytic change at the clivus bordering the lesion. Magnetic resonance imaging demonstrated an extensive soft-tissue mass occupying the left sphenoid sinus. Surgical intervention by the endoscopic transnasal method allowed most of the lesion to be removed. Only the portion attached to the medial wall of the ICA was not removed. Postoperatively, the lesion was diagnosed as a giant cell tumor (GCT) and the patient received 120 mg of subcutaneous denosumab every 4 weeks, with additional doses on Days 8 and 15 during the first month of therapy. MRI a week after starting denosumab revealed shrinkage of the initially fast-growing residual tumor. The patient was discharged upon completion of the third denosumab administration. GCT is an aggressive stromal tumor developing mainly in young adults. Complete resection is recommended for GCT in the literature. However, size and location of the CGT often limit this approach. Various adjuvant treatments for skull base GCTs have been reported, including radiation and chemotherapy. However, the roles of adjuvant therapies have yet to be clearly defined. Denosumab, a monoclonal antibody, was recently approved for GCT in several countries. Denosumab may permit less invasive treatments for patients with GCTs while avoiding deleterious outcomes, and may also limit disease progression and recurrence.

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Foramen magnum meningiomas: surgical results and risks predicting poor outcomes based on a modified classification

Journal of Neurosurgery, Ahead of Print.
OBJECTIVE This study aimed to evaluate neurological function and progression/recurrence (P/R) outcome of foramen magnum meningioma (FMM) based on a modified classification. METHODS This study included 185 consecutive patients harboring FMMs (mean age 49.4 years; 124 females). The authors classified the FMMs into 4 types according to the previous classification of Bruneau and George as follows: Type A (n = 49, 26.5%), the dural attachment of the lesion grows below the vertebral artery (VA); Type B (n = 39, 21.1%), the dural attachment of the lesion grows above the VA; Type C1 (n = 84, 45.4%), the VA courses across the lesion with or without VA encasement or large lesions grow both above and below the bilateral VA; and Type C2 (n = 13, 7.0%), Type C1 plus partial/total encasement of the VA and extradural growth. RESULTS The median preoperative Karnofsky Performance Scale (KPS) score was 80. Gross-total resection (GTR) was achieved in 154 patients (83.2%). Lower cranial nerve morbidity was lowest in Type A lesions (16.3%). Type C2 lesions were inherently larger (p = 0.001), had a greater percentage of ventrolateral location (p = 0.009) and VA encasement (p < 0.001), lower GTR rate (p < 0.001), longer surgical duration (p = 0.015), higher morbidity (38.5%), higher P/R rate (30.8%, p = 0.009), and poorer recent KPS score compared with other types. After a mean follow-up duration of 110.3 months, the most recent follow-up data were obtained in 163 patients (88.1%). P/R was observed in 13 patients (7.2%). The median follow-up KPS score was 90. Compared with preoperative status, recent neurological status was improved in 91 (49.2%), stabilized in 76 (41.1%), and worsened in 18 (9.7%) patients. The multivariate Cox proportional hazard regression model demonstrated Type C2 (HR 3.94, 95% CI 1.04–15.0, p = 0.044), nontotal resection (HR 6.30, 95% CI 1.91–20.8, p = 0.003), and pathological mitosis (HR 7.11, 95% CI 1.96–25.8, p = 0.003) as independent adverse predictors for tumor P/R. Multivariate logistic regression analysis identified nontotal resection (OR 4.06, 95% CI 1.16–14.2, p = 0.029) and pathological mitosis (OR 6.29, 95% CI 1.47–27.0, p = 0.013) as independent risks for poor outcome (KPS score < 80). CONCLUSIONS The modified classification helped to predict surgical outcome and P/R in addition to the position of the lower cranial nerves. Preoperative imaging studies and neurological function should be reviewed carefully to establish an individualized management strategy to improve long-term outcome.

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Connecting raised intracranial pressure and cognitive delay in craniosynostosis: many assumptions, little evidence

Journal of Neurosurgery: Pediatrics, Ahead of Print.


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Radiographic markers of clinical outcomes after endoscopic third ventriculostomy with choroid plexus cauterization: cerebrospinal fluid turbulence and choroid plexus visualization

Journal of Neurosurgery: Pediatrics, Ahead of Print.
OBJECTIVE Endoscopic third ventriculostomy (ETV) with choroid plexus (CP) cauterization (CPC) represents a viable treatment option for congenital hydrocephalus in infants younger than 2 years. Imaging studies complement clinical data in the evaluation of treatment success or failure. The objectives of this study were to investigate novel radiographic markers—cerebrospinal fluid (CSF) turbulence and CP visualization—and their ability to reflect or predict clinical outcomes following ETV/CPC. METHODS Hydrocephalic patients younger than 2 years who were initially treated by ETV/CPC at the senior authors' institution between March 2013 and February 2014 were retrospectively reviewed. Clinical data, as well as the visualization of CSF turbulence and CP on pre- and postoperative fast-sequence MRI, were recorded. Radiographic images were reviewed by a blinded observer based on specific criteria for the visualization of CSF turbulence and CP. Data were collected and analyzed using descriptive statistics, including Fisher's exact test for comparisons. The research team obtained appropriate institutional review board approval for this study, without the need for informed consent. RESULTS Among the 32 patients (53% male and 47% female) studied, 18 of 32 (56%) responded favorably to initial or repeat ETV/CPC, with 13 of 32 (41%) patients requiring 1 surgery. Of the 19 (59%) patients whose initial ETV/CPC failed, 8 of 19 (42%) patients underwent repeat ETV/CPC, with 5 of 8 (63%) patients responding favorably. Radiographic CSF turbulence appeared more frequently following ETV/CPC failure than after ETV/CPC success (55% vs 18%, respectively; p = 0.02). The sensitivity and specificity of CSF turbulence as a radiographic marker for ETV/CPC failure were 80% and 58%, respectively. The radiographic depiction of CP disappearance following ETV/CPC from pre- to postoperative imaging occurred in 20 of 30 patients (67%). Among the patients who responded unsuccessfully to ETV/CPC and ultimately required secondary shunt insertion, 71% (10 of 14 patients) demonstrated CP persistence on postoperative imaging. In contrast, 6% (1 of 18) of patients who were treated successfully by ETV/CPC demonstrated the presence of CP on follow-up imaging. This difference reached statistical significance (p = 0.0001). The visualization of CP persistence despite ETV/CPC reflected treatment failure with 91% sensitivity and 81% specificity. The sensitivity of either or both radiographic markers to suggest ETV/CPC failure was 77%, while their specificity (both markers absent, thereby indicating ETV/CPC success) was 81%. CONCLUSIONS Radiographic markers correlate with clinical outcomes following the treatment of infantile hydrocephalus with ETV/CPC. Specifically, CSF turbulence may indicate ongoing pathological CSF flow dynamics, while CP absence following ETV/CPC may predict shunt independence. Future studies that incorporate prospective review and formal intra- and interobserver reliability estimates may help corroborate the utility of these radiographic markers.

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Indirect and direct revascularization of ACTA2 cerebral arteriopathy: feasibility of the superficial temporal artery to anterior cerebral artery bypass with posterior auricular artery interposition graft: case report

Journal of Neurosurgery: Pediatrics, Ahead of Print.
Mutations in the smooth muscle–specific isoform of alpha actin (ACTA2) cause smooth muscle dysfunction in arteries. This rare loss-of-function mutation may cause a diffuse occlusive cerebral arteriopathy, resulting in stroke. While ACTA2 arteriopathy is often described as moyamoya-like, it has a distinct phenotype characterized by dilation of the proximal internal carotid artery (ICA) and occlusion of the terminal ICA and proximal middle cerebral artery. Intracranial arteries have an abnormally straight course, often with small aneurysms. There is limited experience with revascularization procedures for ACTA2 arteriopathy, and the safety and efficacy of these procedures are unknown. In this paper the authors present a symptomatic 6-year-old patient with ACTA2 cerebral arteriopathy who underwent both indirect revascularization and direct cerebrovascular bypass. Postoperatively, the patient suffered an ischemic infarct in a neighboring vascular territory. While direct cerebrovascular bypass is technically feasible, patients with ACTA2 arteriopathy may be at increased risk for perioperative stroke compared with patients with moyamoya disease.

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Human tear proteomics and peptidomics in ophthalmology: Toward the translation of proteomic biomarkers into clinical practice

Publication date: Available online 13 May 2016
Source:Journal of Proteomics
Author(s): Mikel Azkargorta, Javier Soria, Arantxa Acera, Ibon Iloro, Tatiana Suarez, Felix Elortza
Tears are a complex biological mixture containing electrolytes, metabolites, lipids, mucins, some small organic molecules, and proteins. The film has various roles in the lubrication, protection from the external environment, and nutrition of the cornea; it is also involved in the modulation of the optical properties of the eye.Tear composition reflects the physiological condition of the underlying tissues. Therefore, the tear fluid is useful in the evaluation of health and disease statesand it is a valuable source of biomarkers for objective analysis of ocular and systemic diseases.The relatively high protein concentration of this fluid and the ease of noninvasive sample collection make it suitable for diagnostic and prognostic purposes. Efforts in proteomics research have positively affected to the field of ophthalmology, and the knowledge on the tear proteome has expanded considerably in the last few years. Nevertheless, despite a large amount of available data and the many biomarkers proposed for several eye and systemic diseases, the extent of translation to well-characterized and clinically useful tools has been largely insufficient. As for most of other biofluids, the road from discovery to clinical application is still long and full of pitfalls.In this review, we discuss the proteomic approaches used in the characterization of tear protein and peptide content, recapitulating the main studies and the progress done. We also present a brief summary of the path from discovery to clinical application of tear protein markers, with some representative examples of translation from the bench to the bedside.SignificanceIn this review we cover the most relevant proteomic approaches used in the characterization of tear proteome, and for the first time we also focus in advances performed in the nowadays emerging peptide content characterization. In this context, we recapitulate on the main studies and the progresses done in this field. We also present a concise overview of the course that may be happen from discovery to clinical application for tear protein markers. Finally we include some representative examples of translation from the bench to the bedside.



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Sensors, Vol. 16, Pages 697: Measurement of Moisture in Wood for Application in the Restoration of Old Buildings

There are many historic buildings whose construction is based on timber frame walls. Most buildings built during the nineteenth and early twentieth centuries were based on timber frame walls with vertical support elements. These timber frame elements are affected by their moisture content and by the passage of time. If the interaction of the timber frame walls with hygrothermal fluctuations were known, the maintenance of these buildings could be improved significantly. To determine the moisture content of wood there are two types of meters on the market: on the one hand, capacitance meters which consist of two side ends and where the moisture content is measured locally between two peaks. On the other hand, there are meters based on the variation of electromagnetic transmittance of timber, which depends on the moisture of timber. The second ones are very expensive and difficult to handle. This work presents a new non-intrusive capacitive sensor that measures the global moisture content in a section of the timber frame walls and therefore its accuracy is similar to the accuracy that can be obtained with electromagnetic transmittance meters. Additionally, as it is a capacitive sensor, it is low cost and easy to operate.

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Sensors, Vol. 16, Pages 697: Measurement of Moisture in Wood for Application in the Restoration of Old Buildings

There are many historic buildings whose construction is based on timber frame walls. Most buildings built during the nineteenth and early twentieth centuries were based on timber frame walls with vertical support elements. These timber frame elements are affected by their moisture content and by the passage of time. If the interaction of the timber frame walls with hygrothermal fluctuations were known, the maintenance of these buildings could be improved significantly. To determine the moisture content of wood there are two types of meters on the market: on the one hand, capacitance meters which consist of two side ends and where the moisture content is measured locally between two peaks. On the other hand, there are meters based on the variation of electromagnetic transmittance of timber, which depends on the moisture of timber. The second ones are very expensive and difficult to handle. This work presents a new non-intrusive capacitive sensor that measures the global moisture content in a section of the timber frame walls and therefore its accuracy is similar to the accuracy that can be obtained with electromagnetic transmittance meters. Additionally, as it is a capacitive sensor, it is low cost and easy to operate.

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Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174

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Double-Blind Sham-Controlled Crossover Trial of Repetitive Transcranial Magnetic Stimulation for Mal de Debarquement Syndrome.

Objective: To determine whether the chronic rocking dizziness that occurs in Mal de Debarquement Syndrome (MdDS) can be suppressed with repetitive transcranial magnetic stimulation (rTMS) beyond the treatment period. Methods: We performed a prospective randomized double-blind sham controlled crossover trial of 5-days of rTMS utilizing high frequency (10 Hz) stimulation over the left dorsolateral prefrontal cortex (DLPFC). Results: Eight right-handed women (44.5 [SD 7.0] yr) with classical motion-triggered MdDS (mean duration 42.1 [SD 13.2] mo) participated. Group level mixed effects repeated measures analysis of variance (ANOVA) showed improvement in our primary outcome measure, the Dizziness Handicap Inventory (DHI) at Post TMS Weeks 1, 3, and 4 (p

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Immunohistochemical evaluation of the mTOR pathway in intraoral minor salivary gland neoplasms

Abstract

Objectives

The aim of this study was to investigate the expression of upstream and downstream molecules of the oncogenic mTOR signaling pathway in intraoral minor salivary gland tumors (SGTs).

Materials and Methods

Tissue samples consisted of 39 malignant and 13 benign minor SGTs, and 8 controls of normal minor salivary glands (NMSG). An immunohistochemical analysis for phosphorylated Akt, 4EBP1, S6 (total and phosphorylated), and eIF4E was performed.

Results

Expression of pAkt and 4EBP1 was found in all SGTs and in most NMSG. p4EBP1 was detected in almost all SGT cases, NMSG being negative. S6 immunoreactivity was observed in 37.5% of NMSG, 92.3% of benign and 100% of malignant SGTs, while pS6 expression was found in 77% of benign and 95% of malignant SGTs, but not in NMSG. Finally, eIF4E was expressed in 12.5% of NMSG, 69.2% of benign and 76.9% of malignant tumors. All molecules studied had statistically significantly lower expression in NMSG compared to SGTs. Moreover, malignant neoplasms received higher scores compared to benign tumors for all molecules with the exception of eIF4E.

Conclusion

The mTOR signaling pathway is activated in SGTs, especially in malignancies. Therefore, the possible therapeutic role of targeting the mTOR pathway by Rapamycin analogs in SGTs needs further investigation.

This article is protected by copyright. All rights reserved.

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The cost effectiveness of transesophageal echocardiography for pediatric cardiac surgery: a systematic review

Summary

Background

Intraoperative transesophageal echocardiography (ITEE) for pediatric cardiac surgery has been described as clinically efficacious and cost-effective. There are a small number of publications supporting these claims.

Aims

The objectives were to assess the quality of the research, the variability of results across studies and, if possible, to make a consensus statement based on the results.

Methods

In March 2015, a systematic search of MEDLINE and MEDLINE In-Process, EMBASE, and the National Health Service Economic Evaluation Database was performed. The search was supplemented with a review of Health Technology Assessment reports through the Centre for Reviews and Dissemination database. English language articles including any quantitative economic evaluation were included. The quality of each study was assessed using the British Medical Journal economic evaluation quality checklist. Data extracted included the main outcomes from each study, study methodologies, itemized costs, sensitivity ranges, biases, and delayed reoperation prevented with ITEE. When possible, a cost-savings per ITEE was calculated to facilitate comparison across studies and used to create a synthesis of the results.

Results

Seven studies met the inclusion criteria; of these, five were included in the synthesis of results. The cost-savings per ITEE ranged from $194 to $4910 with a mean of $1930 (95%CI: $845 to $3015) (2015 USD). Prevented delayed reoperation rates using ITEE ranged from 2.8% to 10%. Earlier studies were of poorer quality (scores 8–17) and more recent studies were of higher quality (scores 22–25). Methodologies used were either retrospective chart reviews (57%) or prospective observational studies (43%) with a range of approaches to estimate costs.

Conclusion

ITEE for pediatric cardiac surgery is effective and cost-saving. This is a validation of the current practice patterns. These finding may influence the expansion of the use of this technology.

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The Association between Openness and Physiological Responses to Recurrent Social Stress

Publication date: Available online 13 May 2016
Source:International Journal of Psychophysiology
Author(s): Wei Lü, Zhenhong Wang, Brian M. Hughes
The association between openness (assessed by shortened Chinese version of NEO Five-Factor Inventory, NEO-FFI) and physiological reactivity to, and recovery from, social stress (a video-recorded, timed public speaking task with evaluators present in the room), and physiological adaptation to repeated social stress was examined in the present study. Subjective and physiological data were collected from 70 college students across five laboratory stages: baseline, stress exposure period 1, post-stress period 1, stress exposure period 2, and post-stress period 2. Results indicated that higher openness was associated with lesser heart rate (HR) reactivity to the first and second stress exposure, and lesser systolic blood pressure (SBP) reactivity to the second stress exposure. Higher openness was associated with higher resting respiratory sinus arrhythmia (RSA), lesser RSA withdrawals to the first stress exposure, and more complete RSA recovery after the first stress exposure. Moreover, higher openness was associated with pronounced systolic and diastolic blood pressure (SBP, DBP) adaptation with greater decreases in SBP and DBP reactivity across the two successive stress exposures. These findings might shed light on the biological basis linking openness to health.



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Increased N250 amplitudes for other-race faces reflect more effortful processing at the individual level

Publication date: Available online 14 May 2016
Source:International Journal of Psychophysiology
Author(s): Grit Herzmann
The N250 and N250r (r for repetition, signaling a difference measure of priming) has been proposed to reflect the activation of perceptual memory representations for individual faces. Increased N250r and N250 amplitudes have been associated with higher levels of familiarity and expertise, respectively. In contrast to these observations, the N250 amplitude has been found to be larger for other-race than own-race faces in recognition memory tasks. This study investigated if these findings were due to increased identity-specific processing demands for other-race relative to own-race faces and whether or not similar results would be obtained for the N250 in a repetition priming paradigm. Only Caucasian participants were available for testing and completed two tasks with Caucasian, African-American, and Chinese faces. In a repetition priming task, participants decided whether or not sequentially presented faces were of the same identity (individuation task) or same race (categorization task). Increased N250 amplitudes were found for African-American and Chinese faces relative to Caucasian faces, replicating previous results in recognition memory tasks. Contrary to the expectation that increased N250 amplitudes for other-race face would be confined to the individuation task, both tasks showed similar results. This could be due to the fact that face identity information needed to be maintained across the sequential presentation of prime and target in both tasks. Increased N250 amplitudes for other-race faces are taken to represent increased neural demands on the identity-specific processing of other-race faces, which are typically processed less holistically and less on the level of the individual.



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Double-Blind Sham-Controlled Crossover Trial of Repetitive Transcranial Magnetic Stimulation for Mal de Debarquement Syndrome.

Objective: To determine whether the chronic rocking dizziness that occurs in Mal de Debarquement Syndrome (MdDS) can be suppressed with repetitive transcranial magnetic stimulation (rTMS) beyond the treatment period. Methods: We performed a prospective randomized double-blind sham controlled crossover trial of 5-days of rTMS utilizing high frequency (10 Hz) stimulation over the left dorsolateral prefrontal cortex (DLPFC). Results: Eight right-handed women (44.5 [SD 7.0] yr) with classical motion-triggered MdDS (mean duration 42.1 [SD 13.2] mo) participated. Group level mixed effects repeated measures analysis of variance (ANOVA) showed improvement in our primary outcome measure, the Dizziness Handicap Inventory (DHI) at Post TMS Weeks 1, 3, and 4 (p

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Sustainability, Vol. 8, Pages 480: Spatial Assessment of Cancer Incidences and the Risks of Industrial Wastewater Emission in China

China's rapid economic growth and social transitions have deteriorated environmental conditions and caused further public health issues in last three decades. This study examines the complex mechanisms of how socioeconomic transitions and physical environmental conditions impact public health, especially with respect to increasing cancer incidences in mainland China from a spatial-temporal perspective. Specifically, (1) spatial variations of seven types of cancer incidences were analyzed in relation to heavy metal emissions from industrial wastewater at the prefecture-level city scale from 2004 to 2009. Additionally; (2) spatial statistical methods were employed to explore the associations between health outcome, heavy metal emissions from industrial wastewater (arsenic, chromium, cadmium, mercury, lead), as well as socioeconomic transitions (industrialization, urbanization, globalization) and physical environmental factors (hydrology and vegetation coverage). Results showed a significant increase of cancer incidences between 2004 and 2009. Consistent with the spatial pattern of heavy metal emissions, cancer patient clusters were identified in both traditional industrial bases and newly industrialized economic zones, especially in major cities located at downstream watersheds, including Beijing, Shanghai, Guangzhou, Shenyang, and Wuhan. The results also revealed the double-edged effects of industrialization, economic growth, and urbanization on natural environment and human health. The findings provide informative knowledge of heavy metal pollution and cancer outbreaks in China and therefore offer valuable reference for authorities formulating regulations.

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Neural correlate of spatial (mis-)localization during smooth eye-movements

Abstract

The dependence of neuronal discharge on the position of the eyes in the orbit is a functional characteristic of many visual cortical areas of the macaque. It has been suggested that these eye-position signals provide relevant information for a coordinate transformation of visual signals into a non-eye-centered frame of reference. This transformation could be an integral part for achieving visual perceptual stability across eye movements. Previous studies demonstrated close to veridical eye-position decoding during stable fixation as well as characteristic erroneous decoding across saccadic eye-movements. Here we aimed to decode eye-position during smooth-pursuit. We recorded neural activity in macaque area VIP during steady fixation, saccades and smooth-pursuit and investigated the temporal and spatial accuracy of eye-position as decoded from the neuronal discharges. Confirming previous results, the activity of the majority of neurons depended linearly on horizontal and vertical eye-position. The application of a previously introduced computational approach (isofrequency-decoding) allowed eye-position decoding with considerable accuracy during steady fixation. We applied the same decoder on the activity of the same neurons during smooth-pursuit. On average, the decoded signal was leading the current eye position. A model combining this constant lead of the decoded eye-position with a previously described attentional bias ahead of the pursuit target describes the asymmetric mislocalization pattern for briefly flashed stimuli during smooth-pursuit eye-movements as found in human behavioral studies.

This article is protected by copyright. All rights reserved.

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Immunohistochemical evaluation of the mTOR pathway in intraoral minor salivary gland neoplasms

Abstract

Objectives

The aim of this study was to investigate the expression of upstream and downstream molecules of the oncogenic mTOR signaling pathway in intraoral minor salivary gland tumors (SGTs).

Materials and Methods

Tissue samples consisted of 39 malignant and 13 benign minor SGTs, and 8 controls of normal minor salivary glands (NMSG). An immunohistochemical analysis for phosphorylated Akt, 4EBP1, S6 (total and phosphorylated), and eIF4E was performed.

Results

Expression of pAkt and 4EBP1 was found in all SGTs and in most NMSG. p4EBP1 was detected in almost all SGT cases, NMSG being negative. S6 immunoreactivity was observed in 37.5% of NMSG, 92.3% of benign and 100% of malignant SGTs, while pS6 expression was found in 77% of benign and 95% of malignant SGTs, but not in NMSG. Finally, eIF4E was expressed in 12.5% of NMSG, 69.2% of benign and 76.9% of malignant tumors. All molecules studied had statistically significantly lower expression in NMSG compared to SGTs. Moreover, malignant neoplasms received higher scores compared to benign tumors for all molecules with the exception of eIF4E.

Conclusion

The mTOR signaling pathway is activated in SGTs, especially in malignancies. Therefore, the possible therapeutic role of targeting the mTOR pathway by Rapamycin analogs in SGTs needs further investigation.

This article is protected by copyright. All rights reserved.

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The cost effectiveness of transesophageal echocardiography for pediatric cardiac surgery: a systematic review

Summary

Background

Intraoperative transesophageal echocardiography (ITEE) for pediatric cardiac surgery has been described as clinically efficacious and cost-effective. There are a small number of publications supporting these claims.

Aims

The objectives were to assess the quality of the research, the variability of results across studies and, if possible, to make a consensus statement based on the results.

Methods

In March 2015, a systematic search of MEDLINE and MEDLINE In-Process, EMBASE, and the National Health Service Economic Evaluation Database was performed. The search was supplemented with a review of Health Technology Assessment reports through the Centre for Reviews and Dissemination database. English language articles including any quantitative economic evaluation were included. The quality of each study was assessed using the British Medical Journal economic evaluation quality checklist. Data extracted included the main outcomes from each study, study methodologies, itemized costs, sensitivity ranges, biases, and delayed reoperation prevented with ITEE. When possible, a cost-savings per ITEE was calculated to facilitate comparison across studies and used to create a synthesis of the results.

Results

Seven studies met the inclusion criteria; of these, five were included in the synthesis of results. The cost-savings per ITEE ranged from $194 to $4910 with a mean of $1930 (95%CI: $845 to $3015) (2015 USD). Prevented delayed reoperation rates using ITEE ranged from 2.8% to 10%. Earlier studies were of poorer quality (scores 8–17) and more recent studies were of higher quality (scores 22–25). Methodologies used were either retrospective chart reviews (57%) or prospective observational studies (43%) with a range of approaches to estimate costs.

Conclusion

ITEE for pediatric cardiac surgery is effective and cost-saving. This is a validation of the current practice patterns. These finding may influence the expansion of the use of this technology.

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The Association between Openness and Physiological Responses to Recurrent Social Stress

Publication date: Available online 13 May 2016
Source:International Journal of Psychophysiology
Author(s): Wei Lü, Zhenhong Wang, Brian M. Hughes
The association between openness (assessed by shortened Chinese version of NEO Five-Factor Inventory, NEO-FFI) and physiological reactivity to, and recovery from, social stress (a video-recorded, timed public speaking task with evaluators present in the room), and physiological adaptation to repeated social stress was examined in the present study. Subjective and physiological data were collected from 70 college students across five laboratory stages: baseline, stress exposure period 1, post-stress period 1, stress exposure period 2, and post-stress period 2. Results indicated that higher openness was associated with lesser heart rate (HR) reactivity to the first and second stress exposure, and lesser systolic blood pressure (SBP) reactivity to the second stress exposure. Higher openness was associated with higher resting respiratory sinus arrhythmia (RSA), lesser RSA withdrawals to the first stress exposure, and more complete RSA recovery after the first stress exposure. Moreover, higher openness was associated with pronounced systolic and diastolic blood pressure (SBP, DBP) adaptation with greater decreases in SBP and DBP reactivity across the two successive stress exposures. These findings might shed light on the biological basis linking openness to health.



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Increased N250 amplitudes for other-race faces reflect more effortful processing at the individual level

Publication date: Available online 14 May 2016
Source:International Journal of Psychophysiology
Author(s): Grit Herzmann
The N250 and N250r (r for repetition, signaling a difference measure of priming) has been proposed to reflect the activation of perceptual memory representations for individual faces. Increased N250r and N250 amplitudes have been associated with higher levels of familiarity and expertise, respectively. In contrast to these observations, the N250 amplitude has been found to be larger for other-race than own-race faces in recognition memory tasks. This study investigated if these findings were due to increased identity-specific processing demands for other-race relative to own-race faces and whether or not similar results would be obtained for the N250 in a repetition priming paradigm. Only Caucasian participants were available for testing and completed two tasks with Caucasian, African-American, and Chinese faces. In a repetition priming task, participants decided whether or not sequentially presented faces were of the same identity (individuation task) or same race (categorization task). Increased N250 amplitudes were found for African-American and Chinese faces relative to Caucasian faces, replicating previous results in recognition memory tasks. Contrary to the expectation that increased N250 amplitudes for other-race face would be confined to the individuation task, both tasks showed similar results. This could be due to the fact that face identity information needed to be maintained across the sequential presentation of prime and target in both tasks. Increased N250 amplitudes for other-race faces are taken to represent increased neural demands on the identity-specific processing of other-race faces, which are typically processed less holistically and less on the level of the individual.



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Double-Blind Sham-Controlled Crossover Trial of Repetitive Transcranial Magnetic Stimulation for Mal de Debarquement Syndrome.

Objective: To determine whether the chronic rocking dizziness that occurs in Mal de Debarquement Syndrome (MdDS) can be suppressed with repetitive transcranial magnetic stimulation (rTMS) beyond the treatment period. Methods: We performed a prospective randomized double-blind sham controlled crossover trial of 5-days of rTMS utilizing high frequency (10 Hz) stimulation over the left dorsolateral prefrontal cortex (DLPFC). Results: Eight right-handed women (44.5 [SD 7.0] yr) with classical motion-triggered MdDS (mean duration 42.1 [SD 13.2] mo) participated. Group level mixed effects repeated measures analysis of variance (ANOVA) showed improvement in our primary outcome measure, the Dizziness Handicap Inventory (DHI) at Post TMS Weeks 1, 3, and 4 (p

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Sustainability, Vol. 8, Pages 480: Spatial Assessment of Cancer Incidences and the Risks of Industrial Wastewater Emission in China

China's rapid economic growth and social transitions have deteriorated environmental conditions and caused further public health issues in last three decades. This study examines the complex mechanisms of how socioeconomic transitions and physical environmental conditions impact public health, especially with respect to increasing cancer incidences in mainland China from a spatial-temporal perspective. Specifically, (1) spatial variations of seven types of cancer incidences were analyzed in relation to heavy metal emissions from industrial wastewater at the prefecture-level city scale from 2004 to 2009. Additionally; (2) spatial statistical methods were employed to explore the associations between health outcome, heavy metal emissions from industrial wastewater (arsenic, chromium, cadmium, mercury, lead), as well as socioeconomic transitions (industrialization, urbanization, globalization) and physical environmental factors (hydrology and vegetation coverage). Results showed a significant increase of cancer incidences between 2004 and 2009. Consistent with the spatial pattern of heavy metal emissions, cancer patient clusters were identified in both traditional industrial bases and newly industrialized economic zones, especially in major cities located at downstream watersheds, including Beijing, Shanghai, Guangzhou, Shenyang, and Wuhan. The results also revealed the double-edged effects of industrialization, economic growth, and urbanization on natural environment and human health. The findings provide informative knowledge of heavy metal pollution and cancer outbreaks in China and therefore offer valuable reference for authorities formulating regulations.

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Neural correlate of spatial (mis-)localization during smooth eye-movements

Abstract

The dependence of neuronal discharge on the position of the eyes in the orbit is a functional characteristic of many visual cortical areas of the macaque. It has been suggested that these eye-position signals provide relevant information for a coordinate transformation of visual signals into a non-eye-centered frame of reference. This transformation could be an integral part for achieving visual perceptual stability across eye movements. Previous studies demonstrated close to veridical eye-position decoding during stable fixation as well as characteristic erroneous decoding across saccadic eye-movements. Here we aimed to decode eye-position during smooth-pursuit. We recorded neural activity in macaque area VIP during steady fixation, saccades and smooth-pursuit and investigated the temporal and spatial accuracy of eye-position as decoded from the neuronal discharges. Confirming previous results, the activity of the majority of neurons depended linearly on horizontal and vertical eye-position. The application of a previously introduced computational approach (isofrequency-decoding) allowed eye-position decoding with considerable accuracy during steady fixation. We applied the same decoder on the activity of the same neurons during smooth-pursuit. On average, the decoded signal was leading the current eye position. A model combining this constant lead of the decoded eye-position with a previously described attentional bias ahead of the pursuit target describes the asymmetric mislocalization pattern for briefly flashed stimuli during smooth-pursuit eye-movements as found in human behavioral studies.

This article is protected by copyright. All rights reserved.

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Early Glycogen Synthase Kinase-3β (GSK-3β) and Protein Phosphatase 2A (PP2A) independent tau dephosphorylation during global brain ischemia and reperfusion following cardiac arrest and the role of the Adenosine Monophosphate Kinase (AMPK) pathway

Abstract

Abnormal tau phosphorylation (p-tau) has been shown after hypoxic damage to the brain associated with traumatic brain injury and stroke. As the level of p-tau is controlled by Glycogen Synthase Kinase (GSK)-3β, Protein Phosphatase 2A (PP2A) and Adenosine Monophosphate Kinase (AMPK), different activity levels of these enzymes could be involved in tau phosphorylation following ischemia. This study assessed the effects of global brain ischemia/reperfusion on the immediate status of p-tau in a rat model of cardiac arrest (CA) followed by cardiopulmonary resuscitation (CPR). We reported an early dephosphorylation of tau at its AMPK sensitive residues, Ser³⁹⁶ and Ser²⁶²after 2 min of ischemia, which did not recover during up to two hours of reperfusion, while the tau phosphorylation at GSK-3β sensitive but AMPK insensitive residues, Ser²⁰²/Thr²⁰⁵ (AT8), as well as the total amount of tau remained unchanged. Our data showed no alteration in the activities of GSK-3β and PP2A during similar episodes of ischemia of up to 8 min and reperfusion of up to 2 hours, and 4 weeks recovery.

Dephosphorylation of AMPK followed the same pattern as tau dephosphorylation during ischemia/reperfusion. Catalase, another AMPK downstream substrate also showed a similar pattern of decline to p-AMPK, in ischemic/reperfusion groups. This suggests the involvement of AMPK in changing the p-tau levels, indicating that tau dephosphorylation following ischemia is not dependent on GSK-3β or PP2A activity, but is associated with AMPK dephosphorylation. We propose that a reduction of AMPK activity is a possible early mechanism responsible for tau dephosphorylation.

This article is protected by copyright. All rights reserved.

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Sustainability, Vol. 8, Pages 480: Spatial Assessment of Cancer Incidences and the Risks of Industrial Wastewater Emission in China

China's rapid economic growth and social transitions have deteriorated environmental conditions and caused further public health issues in last three decades. This study examines the complex mechanisms of how socioeconomic transitions and physical environmental conditions impact public health, especially with respect to increasing cancer incidences in mainland China from a spatial-temporal perspective. Specifically, (1) spatial variations of seven types of cancer incidences were analyzed in relation to heavy metal emissions from industrial wastewater at the prefecture-level city scale from 2004 to 2009. Additionally; (2) spatial statistical methods were employed to explore the associations between health outcome, heavy metal emissions from industrial wastewater (arsenic, chromium, cadmium, mercury, lead), as well as socioeconomic transitions (industrialization, urbanization, globalization) and physical environmental factors (hydrology and vegetation coverage). Results showed a significant increase of cancer incidences between 2004 and 2009. Consistent with the spatial pattern of heavy metal emissions, cancer patient clusters were identified in both traditional industrial bases and newly industrialized economic zones, especially in major cities located at downstream watersheds, including Beijing, Shanghai, Guangzhou, Shenyang, and Wuhan. The results also revealed the double-edged effects of industrialization, economic growth, and urbanization on natural environment and human health. The findings provide informative knowledge of heavy metal pollution and cancer outbreaks in China and therefore offer valuable reference for authorities formulating regulations.

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The Association between Openness and Physiological Responses to Recurrent Social Stress

Publication date: Available online 13 May 2016
Source:International Journal of Psychophysiology
Author(s): Wei Lü, Zhenhong Wang, Brian M. Hughes
The association between openness (assessed by shortened Chinese version of NEO Five-Factor Inventory, NEO-FFI) and physiological reactivity to, and recovery from, social stress (a video-recorded, timed public speaking task with evaluators present in the room), and physiological adaptation to repeated social stress was examined in the present study. Subjective and physiological data were collected from 70 college students across five laboratory stages: baseline, stress exposure period 1, post-stress period 1, stress exposure period 2, and post-stress period 2. Results indicated that higher openness was associated with lesser heart rate (HR) reactivity to the first and second stress exposure, and lesser systolic blood pressure (SBP) reactivity to the second stress exposure. Higher openness was associated with higher resting respiratory sinus arrhythmia (RSA), lesser RSA withdrawals to the first stress exposure, and more complete RSA recovery after the first stress exposure. Moreover, higher openness was associated with pronounced systolic and diastolic blood pressure (SBP, DBP) adaptation with greater decreases in SBP and DBP reactivity across the two successive stress exposures. These findings might shed light on the biological basis linking openness to health.



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Increased N250 amplitudes for other-race faces reflect more effortful processing at the individual level

Publication date: Available online 14 May 2016
Source:International Journal of Psychophysiology
Author(s): Grit Herzmann
The N250 and N250r (r for repetition, signaling a difference measure of priming) has been proposed to reflect the activation of perceptual memory representations for individual faces. Increased N250r and N250 amplitudes have been associated with higher levels of familiarity and expertise, respectively. In contrast to these observations, the N250 amplitude has been found to be larger for other-race than own-race faces in recognition memory tasks. This study investigated if these findings were due to increased identity-specific processing demands for other-race relative to own-race faces and whether or not similar results would be obtained for the N250 in a repetition priming paradigm. Only Caucasian participants were available for testing and completed two tasks with Caucasian, African-American, and Chinese faces. In a repetition priming task, participants decided whether or not sequentially presented faces were of the same identity (individuation task) or same race (categorization task). Increased N250 amplitudes were found for African-American and Chinese faces relative to Caucasian faces, replicating previous results in recognition memory tasks. Contrary to the expectation that increased N250 amplitudes for other-race face would be confined to the individuation task, both tasks showed similar results. This could be due to the fact that face identity information needed to be maintained across the sequential presentation of prime and target in both tasks. Increased N250 amplitudes for other-race faces are taken to represent increased neural demands on the identity-specific processing of other-race faces, which are typically processed less holistically and less on the level of the individual.



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