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The 1,3,4-oxadiazole is a widely encountered motif in the areas of pharmaceuticals, materials, and agrochemicals. This work has established a mediated electrochemical synthesis of 2,5-disubstituted 1,3,4-oxadiazoles from N-acyl hydrazones. Using DABCO as the optimal redox mediator has enabled a mild oxidative cyclisation, without recourse to stoichiometric oxidants. In contrast to previous methods, this indirect electrochemical oxidation has enabled a broad range of substrates to be accessed, with yields of up to 83 %, and on gram scale. The simplicity of the method has been further demonstrated by the development of a one-pot procedure, directly transforming readily available aldehydes and hydrazides into valuable heterocycles., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

The CO 2 absorption by Monoethanolamine (MEA) solutions as chemical absorption was conducted in the membrane gas absorption module with inserting 3D mini-channel turbulence promoters of the present work. A mathematical modeling of CO 2 absorption flux was analyzed by using the chemical absorption theory based on mass-transfer resistances in series. The membrane absorption module with embedding 3D mini-channel turbulence promoters in the current study indicated that the CO 2 absorption rate improvement is achieved due to the diminishing concentration polarization effect nearby the membrane surfaces. A simplified regression equation of the average Sherwood number was correlated to express the enhanced mass-transfer coefficient of the CO 2 absorption. The experimental results and theoretical predictions showed that the absorption flux improvement was significantly improved with implementing 3D mini-channel turbulence promoters. The experimental results of CO 2 absorption fluxes were performed in good agreement with the theoretical predictions in aqueous MEA solutions. A further absorption flux enhancement up to 30.56% was accomplished as compared to the results in the previous work, which the module was inserted the promoter without mini channels. The influences of the MEA absorbent flow rates and inlet CO 2 concentrations on the absorption flux and absorption flux improvement are also illustrated under both concurrent- and countercurrent-flow operations.

Purpose: Superficial siderosis, a progressive, debilitating, neurological disease, often presents with bilateral impairment of auditory and vestibular function. We highlight that superficial siderosis is often due to a repairable spinal dural defect of the type that can also cause spontaneous intracranial hypotension., Methods: Retrospective chart review of five patients presenting with moderate to severe, progressive bilateral sensorineural hearing loss as well as vestibular loss. All patients had developed superficial siderosis from spinal dural defects: three after trauma, one after spinal surgery and one from a thoracic discogenic microspur., Results: The diagnosis was made late in all five patients; despite surgical repair in four, hearing and vestibular loss failed to improve., Conclusions: In patients presenting with progressive bilateral sensorineural hearing loss, superficial siderosis should be considered as a possible cause. If these patients also have bilateral vestibular loss, cerebellar impairment and anosmia, then the diagnosis is likely and the inevitable disease progress might be halted by finding and repairing the spinal dural defect., (© 2022. The Author(s).)

A novel design of an air gap membrane distillation (AGMD) module was proposed to enhance the permeate flux improvement for the desalination of pure water productivity. The modeling equations for predicting permeate flux in the AGMD module by inserting Λ-ribs carbon-fiber open slots under various hydrodynamic angles were developed theoretically and experimentally. The temperature distributions of both hot and cold feed streams were represented graphically with the hot saline flow rate, inlet saline temperature, and carbon-fiber hydrodynamic angles as parameters. The results showed a good agreement between the experimental results and theoretical predictions. Designed by inserting Λ-ribs carbon-fiber open slots into the flow channel, the membrane distillation module was implemented to act as an eddy promoter and yield an augmented turbulence flow. The effect of Λ-ribs carbon-fiber open slots not only assured the membrane stability by preventing vibration but also increased the permeate flux by diminishing the temperature polarization of the thermal boundary layer. The permeate flux improvement by inserting Λ-ribs carbon-fiber open slots in the AGMD module provided the maximum relative increment of up to 15.6% due to the diminution of the concentration polarization effect. The experimental data was incorporated with the hydrodynamic angle of Λ-ribs carbon-fiber open slots to correlate the enhancement factor with the Nusselt numbers to confirm the theoretical predictions. The accuracy derivation between the experimental results and theoretical predictions was pretty good, within 9.95≤E≤1.85. The effects of operating and designing parameters of hot saline flow rate, inlet saline temperature, and hydrodynamic angle on the permeate flux were also delineated by considering both the power consumption increment and permeate flux enhancement.

Introduction: The head impulse test (HIT) and HIT combined with direction-changing Nystagmus-Test of Skew deviation (HINTS) have been proposed as bedside tests to differentiate between peripheral and central causes of vertigo in the emergency department (ED). We conducted a meta-analysis of the HIT and HINTS tests to diagnose peripheral vertigo (PV) and central vertigo., Methods: Pubmed, Google Scholar, EmBase, and articles references published in English up to July 2021 were searched for keywords "vertigo" or "acute vestibular syndrome" or "dizziness" and "head impulse" and "stroke." The bivariate method for meta-analysis was used to calculate positive (PLR) and negative likelihood ratios (NLR) and summary receiver operating characteristics area under the curve (AUC)., Results: A total of 11 studies were included analysing both HIT (8 studies, N = 417) and HINTS (6 studies, N = 405). HIT and HINTS were performed within 24 h in 4 of 11 studies. PLR and NLR for HIT in PV was 4.85 (95% CI: 2.83-8.08) and 0.19 (95% CI: 0.12-0.29, I2 63.25%), respectively. The AUC for HIT the diagnosis of PV and stroke was 0.90 and 0.92, respectively. PLR and NLR for a negative HIT in stroke was 5.85 (95% CI: 3.07-10.6) and 0.17 (95% CI: 0.08-0.30), respectively. PLR and NLR for peripheral HINTS pattern for PV was 17.3 (95% CI: 8.38-32.1) and 0.15 (95% CI: 0.07-0.26), respectively. PLR and NLR for central HINTS pattern for stroke: 5.61 (95% CI: 4.19-7.7) and 0.06 (95% CI: 0.03-0.12). In all included studies, HIT and HINTS exams were administered by neurology residents or neurology specialists with additional neuro-otology or neuro-ophthalmology subspeciality experience, and two studies included ED physicians. Raters reported high degree of bias and high concern regarding applicability in most domains of the quality assessment of diagnostic accuracy studies (QUADAS-2) tool. Meta-regression did not demonstrate a statistically significant effect of publication year, time to test, and type of assessor on sensitivity or false positive rate., Conclusion: The HIT and HINTS exams appear to be moderately good discriminators of central and PV. However, in most papers, the tests were administered by neurologists and were evaluated beyond 24 h, which may limit utility in the ED setting., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

The absorption efficiencies of CO 2 in hollow-fiber membrane contactors using an ethanolamine (MEA) solvent under both concurrent- and countercurrent-flow operations were investigated theoretically and experimentally. Two-dimensional mathematical modeling was developed by Happel's free surface model, and the resultant partial differential equations were solved analytically using the separated variables method with the use of an orthogonal expansion technique. A simplified expression of Sherwood number variations was reported by employing the relevant operations conditions and expressed in terms of the computed eigenvalues for predicting concentration distribution and absorption efficiency. It is emphasized that, in comparing various fiber packing configurations, both theoretical predictions and experimental results should be compared to find the absorption flux increment accomplished by the CO 2 /N 2 stream passing through the fiber cells under the same mass flow rate. The value of the present mathematical treatment is evident to propose a simplified expression of the averaged Sherwood number variations, and provides the predictions of the absorption flux, absorption efficiency, average Sherwood number with the absorbent Graetz number, inlet CO 2 concentration, and absorbent flow rates as parameters. The availability of such concise expressions, as developed directly from the analytical formulations, is the value of the present study. The experiments of the CO 2 absorption using MEA with alumina (Al 2 O 3 ) hollow fiber membranes are also set up to confirm the accuracy of the theoretical predictions. The accuracy derivations between the experimental results and theoretical predictions for concurrent- and countercurrent-flow operations are 4.10×10-2≤E≤1.50×10-2 and 1.40×10-2≤E≤9.0×10-1, respectively. The operations of the hollow-fiber membrane contactor implementing N = 7 fiber cells and N = 19 fiber cells offer an inexpensive method of improving absorption efficiency by increasing fiber numbers with consideration of device performance.

Background and Purpose: Susac syndrome (SuS) is an inflammatory condition of the brain, eye and ear. Diagnosis can be challenging, and misdiagnosis is common., Methods: This is a retrospective review of the medical records of 32 adult patients from an Australasian cohort of SuS patients., Results: An alternative diagnosis prior to SuS was made in 30 patients (94%) with seven patients receiving two or more diagnoses. The median time to diagnosis of SuS was 3 months (range 0.5-100 months). The commonest misdiagnoses were migraine in 10 patients (31%), cerebral vasculitis in six (19%), multiple sclerosis in five (16%) and stroke in five (16%). Twenty-two patients were treated for alternative diagnoses, 10 of whom had further clinical manifestations prior to SuS diagnosis. At presentation seven patients (22%) met criteria for definite SuS, 19 (59%) for probable SuS and six (19%) for possible SuS. Six patients (19%) presented with brain-eye-ear involvement, 14 with brain-ear (44%), six with brain-eye (19%) and six (19%) with only brain involvement. In patients with the complete triad of symptoms the median delay to diagnosis was 3 months (range 1-9 months) compared to 5.25 months (range 0.5-100 months) for patients with encephalopathy and ocular symptoms at presentation., Conclusions: Susac syndrome patients are frequently misdiagnosed at initial presentation, despite many having symptoms or radiological features that are red flags for the diagnosis. Delayed diagnosis can lead to patient morbidity. The varied ways in which SuS can present, and clinician failure to consider or recognize SuS, appear to be the main factors leading to misdiagnosis., (© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Persistent postural perceptual dizziness (PPPD) is a common chronic vestibular disorder characterized by persistent vestibular symptoms, including postural instability and non-spinning vertigo, which is aggravated by motion, upright posture and moving or complex visual stimuli. In our review of 198 cases seen over a 5 year period, we have confirmed a number of common precipitating conditions for PPPD, including anxiety disorders and vestibular migraine. Vestibular abnormalities, including a unilateral loss of vestibular hypofunction and isolated otolith abnormalities, were found on investigation in just under half the cases. The use of cognitive behavioral therapy (CBT) as a treatment for PPPD resulted in impressive reductions in anxiety and measures of dizziness over follow up periods of up to 6 months., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Waterston, Chen, Mahony, Gencarelli and Stuart.)

A new design of direct-contact membrane distillation (DCMD) modules with cross-diagonal carbon-fiber spacers of various hydrodynamic angles in flow channels to promote turbulence intensity was proposed to enhance pure water productivity. Attempts to reduce the temperature polarization coefficient were achieved by inserting cross-diagonal carbon-fiber spacers in channels, which create wakes and eddies in both heat and mass transfer behaviors to enhance the permeate flux enhancement. A simplified equation was formulated to obtain the theoretical predictions of heat transfer coefficients in the current DCMD device. The permeate fluxes and temperature distributions of both hot and cold feed streams are represented graphically with the inlet volumetric flow rate and inlet temperature of the hot saline feed stream as parameters. The higher distillate flux of countercurrent-flow operations for saline water desalination was accomplished as compared to the concurrent-flow operations of various hydrodynamic angles. The results show that the agreement between the theoretical predictions and experimental results is reasonably good. The effects of countercurrent-flow operations and inserting carbon fiber spacers have confirmed technical feasibility and device performance enhancement of up to 45%. The influences of operating and design parameters on the pure water productivity with the expense of energy consumption are also discussed.

Stress is a physiological state that hampers mental health and has serious consequences to physical health. More-over, the COVID-19 pandemic has increased stress levels among people across the globe. Therefore, continuous monitoring and detection of stress are necessary. The recent advances in wearable devices have allowed the monitoring of several physiological signals related to stress. Among them, wrist-worn wearable devices like smartwatches are most popular due to their convenient usage. And the photoplethysmography (PPG) sensor is the most prevalent sensor in almost all consumer-grade wrist-worn smartwatches. Therefore, this paper focuses on using a wrist-based PPG sensor that collects Blood Volume Pulse (BVP) signals to detect stress which may be applicable for consumer-grade wristwatches. Moreover, state-of-the-art works have used either classical machine learning algorithms to detect stress using hand-crafted features or have used deep learning algorithms like Convolutional Neural Network (CNN) which automatically extracts features. This paper proposes a novel hybrid CNN (H-CNN) classifier that uses both the hand-crafted features and the automatically extracted features by CNN to detect stress using the BVP signal. Evaluation on the benchmark WESAD dataset shows that, for 3-class classification (Baseline vs. Stress vs. Amusement), our proposed H-CNN outperforms traditional classifiers and normal CNN by ≈5% and ≈7% accuracy, and ≈10% and ≈7% macro F1 score, respectively. Also for 2-class classification (Stress vs. Non-stress), our proposed H-CNN outperforms traditional classifiers and normal CNN by ≈3% and ≈5% accuracy, and ≈3% and ≈7% macro F1score, respectively.

Background: Calcitonin gene-related peptide (CGRP) is expressed throughout the body and is a known mediator of migraine, exerting this biological effect through activation of trigeminovascular, meningeal and associated neuronal pathways located in close proximity to the central nervous system. Monoclonal antibodies (mAb) targeting the CGRP pathway are an effective new preventive treatment for migraine, with a generally favourable adverse event profile. Pre-clinical evidence supports an anti-inflammatory/immunoregulatory role for CGRP in other organ systems, and therefore inhibition of the normal action of this peptide may promote a pro-inflammatory response., Cases: We present a case series of eight patients with new or significantly worsened inflammatory pathology in close temporal association with the commencement of CGRP mAb therapy., Conclusion: This case series provides novel insights on the potential molecular mechanisms and side-effects of CGRP antagonism in migraine and supports clinical vigilance in patient care going forward., (© 2021. The Author(s).)

Two geometric shape turbulence promoters (circular and square of same areas) of different array patterns using three-dimensional (3D) printing technology were designed for direct contact membrane distillation (DCMD) modules in the present study. The DCMD device was performed at middle temperature operation (about 45 °C to 60 °C) of hot inlet saline water associated with a constant temperature of inlet cold stream. Attempts to reduce the disadvantageous temperature polarization effect were made inserting the 3D turbulence promoters to promote both the mass and heat transfer characteristics in improving pure water productivity. The additive manufacturing 3D turbulence promoters acting as eddy promoters could not only strengthen the membrane stability by preventing vibration but also enhance the permeate flux with lessening temperature polarization effect. Therefore, the 3D turbulence promoters were individually inserted into the flow channel of the DCMD device to create vortices in the flow stream and increase turbulent intensity. The modeling equations for predicting the permeate flux in DCMD modules by inserting the manufacturing 3D turbulence promoter were investigated theoretically and experimentally. The effects of the operating conditions under various geometric shapes and array patterns of turbulence promoters on the permeate flux with hot inlet saline temperatures and flow rates as parameters were studied. The distributions of the fluid velocities were examined using computational fluid dynamics (CFD). Experimental study has demonstrated a great potential to significantly accomplish permeate flux enhancement in such new design of the DCMD system. The permeate flux enhancement for the DCMD module by inserting 3D turbulence promoters in the flow channel could provide a maximum relative increment of up to 61.7% as compared to that in the empty channel device. The temperature polarization coefficient (τtemp) was found in this study for various geometric shapes and flow patterns. A larger τtemp value (the less thermal resistance) was achieved in the countercurrent-flow operation than that in the concurrent-flow operation. An optimal design of the module with inserting turbulence promoters was also delineated when considering both permeate flux enhancement and energy utilization effectiveness.

Objective: We characterised the clinical and neuro-otological characteristics of patients with Susac syndrome., Methods: The medical records of 30 patients with Susac syndrome were reviewed for details of their clinical presentation and course, neuro-otological symptoms, investigation results including audiology and vestibular function tests, treatment and outcomes., Results: Our findings demonstrate that 29 of our 30 patients with Susac syndrome developed neuro-otological symptoms such as hearing loss, disequilibrium, tinnitus or vertigo during their disease course. Hearing loss was the most common neuro-otological symptom occurring in 93% of patients. A rising configuration of low-frequency greater than the high-frequency sensorineural hearing loss was the most characteristic finding on audiological testing (37% of reviewed audiograms). Disproportionately poor speech discrimination was identified in 20% of cases, and one case demonstrated a retrocochlear pattern on electrophysiological testing. Four patients required hearing aids and a further two patients required a cochlear implant due to severe hearing loss. Two out of two treated patients had improvements in hearing after the prompt administration of corticosteroids, indicating the potential for recoverable hearing loss if relapses are treated early. Effects on vestibular function were variable in ten patients who were tested, with most showing preservation of function despite significant hearing loss., Conclusions: Neuro-otological symptoms in Susac syndrome are almost universal. In the correct clinical context, a rising configuration of low to high-frequency sensorineural hearing loss should prompt consideration of Susac syndrome. Treatment of inner ear symptoms in Susac syndrome requires further research as early immunotherapy may be beneficial.

We investigated the insertion of eddy promoters into a parallel-plate gas-liquid polytetrafluoroethylene (PTFE) membrane contactor to effectively enhance carbon dioxide absorption through aqueous amine solutions (monoethanolamide-MEA). In this study, a theoretical model was established and experimental work was performed to predict and to compare carbon dioxide absorption efficiency under concurrent- and countercurrent-flow operations for various MEA feed flow rates, inlet CO 2 concentrations, and channel design conditions. A Sherwood number's correlated expression was formulated, incorporating experimental data to estimate the mass transfer coefficient of the CO 2 absorption in MEA flowing through a PTFE membrane. Theoretical predictions were calculated and validated through experimental data for the augmented CO 2 absorption efficiency by inserting carbon-fiber spacers as an eddy promoter to reduce the concentration polarization effect. The study determined that a higher MEA feed rate, a lower feed CO 2 concentration, and wider carbon-fiber spacers resulted in a higher CO 2 absorption rate for concurrent- and countercurrent-flow operations. A maximum of 80% CO 2 absorption efficiency enhancement was found in the device by inserting carbon-fiber spacers, as compared to that in the empty channel device. The overall CO 2 absorption rate was higher for countercurrent operation than that for concurrent operation. We evaluated the effectiveness of power utilization in augmenting the CO 2 absorption rate by inserting carbon-fiber spacers in the MEA feed channel and concluded that the higher the flow rate, the lower the power utilization's effectiveness. Therefore, to increase the CO 2 absorption flux, widening carbon-fiber spacers was determined to be more effective than increasing the MEA feed flow rate.

Zinc oxide nanoparticles (ZnO-NPs) are increasingly used in sunscreens, food additives, pigments, rubber manufacture, and electronic materials. Several studies have shown that ZnO-NPs inhibit cell growth and induce apoptosis by the production of oxidative stress in a variety of human cancer cells. However, the anti-cancer property and molecular mechanism of ZnO-NPs in human gingival squamous cell carcinoma (GSCC) are not fully understood. In this study, we found that ZnO-NPs induced growth inhibition of GSCC (Ca9-22 and OECM-1 cells), but no damage in human normal keratinocytes (HaCaT cells) and gingival fibroblasts (HGF-1 cells). ZnO-NPs caused apoptotic cell death of GSCC in a concentration-dependent manner by the quantitative assessment of oligonucleosomal DNA fragmentation. Flow cytometric analysis of cell cycle progression revealed that sub-G1 phase accumulation was dramatically induced by ZnO-NPs. In addition, ZnO-NPs increased the intracellular reactive oxygen species and specifically superoxide levels, and also decreased the mitochondrial membrane potential. ZnO-NPs further activated apoptotic cell death via the caspase cascades. Importantly, anti-oxidant and caspase inhibitor clearly prevented ZnO-NP-induced cell death, indicating the fact that superoxide-induced mitochondrial dysfunction is associated with the ZnO-NP-mediated caspase-dependent apoptosis in human GSCC. Moreover, ZnO-NPs significantly inhibited the phosphorylation of ribosomal protein S6 kinase (p70S6K kinase). In a corollary in vivo study, our results demonstrated that ZnO-NPs possessed an anti-cancer effect in a zebrafish xenograft model. Collectively, these results suggest that ZnO-NPs induce apoptosis through the mitochondrial oxidative damage and p70S6K signaling pathway in human GSCC. The present study may provide an experimental basis for ZnO-NPs to be considered as a promising novel anti‑tumor agent for the treatment of gingival cancer.

Over 30 years ago, the head impulse test (HIT) was measured with search coil recordings and it provided robust evidence for a new test of vestibular function that could detect impairment of a single semicircular canal, that is, the lateral canal. Over the next two decades, the diagnostic spectrum of HIT was expanded to the testing of vertical canals, differentiation of central from peripheral vestibulopathy, and incorporation of visual interaction-the suppressed head impulse. However, HIT measurement was limited to very few specialized laboratories that were able to maintain the time-consuming and expensive operation of the scleral search coil system, which is the gold standard in eye movement recording. The video HIT (vHIT) was validated for the first time over 10 years ago, against the search coils, and its introduction into dizzy clinics worldwide has revolutionized the practice of neuro-otology. Here we review the basic physiology, practical aspects, and clinical application of the vHIT., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Bilateral vestibulopathy (BVP), which is due to peripheral lesions, may selectively involve certain semicircular canal (SCC). Recent eye movement recordings with search coil and video head impulse test (HIT) have provided insight in central lesions that can cause bilateral and selective SCC deficit mimicking BVP. Since neurological signs or ocular motor deficits maybe subtle or absent, it is critical to recognize central lesions correctly since there is prognostic and treatment implication. Acute floccular lesions cause bilateral horizontal SCC (HC) impairment while leaving vertical SCC function unaffected. Vestibular nuclear lesions affect bilateral HC and posterior SCC (PC) function, but anterior SCC (AC) function is spared. When both eyes are recorded, medial longitudinal fasciculus lesions cause horizontal dysconjugacy in HC function and catch-up saccades, as well as selective deficiency of PC over AC function. Combined peripheral and central lesions may be difficult to distinguish from BVP. Anterior inferior cerebellar artery stroke causes two types of deficits: 1. ipsilateral pan-SCC deficits and contralateral HC deficit and 2. bilateral HC deficit with vertical SCC sparing. Metabolic disorders such as Wernicke encephalopathy characteristically involve HC but not AC or PC function. Gaucher disease causes uniform loss of all SCC function but with minimal horizontal catch-up saccades. Genetic cerebellar ataxias and cerebellar-ataxia neuropathy vestibular areflexia syndrome typically do not spare AC function. While video HIT does not replace the gold-standard, search coil HIT, clinicians are now able to rapidly and accurately identify specific pattern of SCC deficits, which can aid differentiation of central lesions from BVP.

The medial longitudinal fasciculus (MLF) is the final common pathway for all conjugate adducting horizontal eye movements, as well as for the vertical-torsional vestibulo-ocular reflex (VOR). MLF lesion causes adduction paresis of ipsilesional (adducting) eye with dissociated nystagmus of contralesional (abducting) eye-the well-known clinical syndrome of internuclear ophthalmoplegia (INO). We measured the VOR stimulation and also any catch-up saccades, from individual semicircular canal (SCC) evoked by the head impulse test (HIT), using head and binocular 3-dimensional scleral search coils in 27 multiple sclerosis (MS) patients, 8 with unilateral, 19 with bilateral INO. In unilateral INO, VOR gain (normal >0.90) from ipsilesional lateral SCC stimulation was 0.48 for the adducting eye and 0.81 for the abducting eye; 0.61 from contralesional anterior SCC stimulation and only 0.29 from contralesional posterior SCC stimulation. In bilateral INO, there were VOR gain deficits from all six SCCs: lateral SCC gains were asymmetrically reduced to 0.45 in the adducting eye and 0.66 in the abducting eye; anterior SCC gain was 0.48 and posterior SCC gain was only 0.19. Horizontal VOR versional dysconjugacy between adducting and abducting eyes at 0.66 was less severe than horizontal catch-up saccade versional dysconjugacy (0.44); normal >0.80. Unexpected partial preservation of horizontal VOR with greater catch-up saccade impairment from the adducting than abducting eye suggests that the ascending tract of Deiters (ATD), an extra-MLF pathway, also mediates the horizontal VOR, but not adducting horizontal saccades. Vertical VOR deficits will produce vertical oscillopsia with any vertical head movement and measurement of the vertical VOR could help with the diagnosis and quantitative evaluation of MLF lesions in suspected MS. Horizontal VOR deficits and catch-up saccade versional dysconjugacy in INO will cause gaze instability and horizontal oscillopsia during active horizontal head movements.

In 1988, we introduced impulsive testing of semicircular canal (SCC) function measured with scleral search coils and showed that it could accurately and reliably detect impaired function even of a single lateral canal. Later we showed that it was also possible to test individual vertical canal function in peripheral and also in central vestibular disorders and proposed a physiological mechanism for why this might be so. For the next 20 years, between 1988 and 2008, impulsive testing of individual SCC function could only be accurately done by a few aficionados with the time and money to support scleral search-coil systems-an expensive, complicated and cumbersome, semi-invasive technique that never made the transition from the research lab to the dizzy clinic. Then, in 2009 and 2013, we introduced a video method of testing function of each of the six canals individually. Since 2009, the method has been taken up by most dizzy clinics around the world, with now close to 100 refereed articles in PubMed. In many dizzy clinics around the world, video Head Impulse Testing has supplanted caloric testing as the initial and in some cases the final test of choice in patients with suspected vestibular disorders. Here, we consider seven current, interesting, and controversial aspects of video Head Impulse Testing: (1) introduction to the test; (2) the progress from the head impulse protocol (HIMPs) to the new variant-suppression head impulse protocol (SHIMPs); (3) the physiological basis for head impulse testing; (4) practical aspects and potential pitfalls of video head impulse testing; (5) problems of vestibulo-ocular reflex gain calculations; (6) head impulse testing in central vestibular disorders; and (7) to stay right up-to-date-new clinical disease patterns emerging from video head impulse testing. With thanks and appreciation we dedicate this article to our friend, colleague, and mentor, Dr Bernard Cohen of Mount Sinai Medical School, New York, who since his first article 55 years ago on compensatory eye movements induced by vertical SCC stimulation has become one of the giants of the vestibular world.

Objectives: Easily palpable splenomegaly can be identified on physical examination, but it is difficult to detect lesser degrees of splenomegaly. Rapid bedside assessment can be conducted with hand-carried ultrasound. We performed this study to determine whether medical residents could reliably assess spleen size using hand-carried ultrasound after a brief educational intervention., Methods: Postgraduate year 1 internal medicine residents were shown a brief (45-minute) presentation on ultrasound basics, the use of hand-carried ultrasound, and principles of splenic ultrasound imaging. They practiced on each other, using hand-carried ultrasound to assess spleen size, for 1 hour in the presence of an instructor. Patients with varying degrees of splenomegaly and hospital staff were recruited at Vancouver General Hospital. A sonographer measured spleen size in each participant using conventional ultrasound. Subsequently, the trained residents scanned the participants using hand-carried ultrasound, blinded to the sonographer's measurements and the participants' diagnoses. The instructor was not present during scanning., Results: Twelve first-year residents (8 male and 4 female; mean age ± SEM, 28 ± 1 years; all with limited prior ultrasound training) and 19 patients and staff members (10 male and 9 female; mean age, 60 ± 4 years; body mass index, 24 ± 2 kg/m(2)) were recruited. The greatest longitudinal measurements were 14.0 ± 0.7 cm with conventional ultrasound administered by the sonographer and 13.2 ± 0.9 cm with hand-carried ultrasound administered by the residents (P > .05, not significant). The correlation between conventional and hand-carried ultrasound was r = 0.81 (P < .001)., Conclusions: Internal medicine residents can reliably assess spleen size at the point of care using hand-carried ultrasound with minimal training. Our findings, if replicated in other centers and in different clinical scenarios, may change the way that clinicians examine the spleen., (© 2015 by the American Institute of Ultrasound in Medicine.)

Objective: The objective of this paper is to inform the pathophysiology of medial longitudinal fasciculus (MLF) axonal dysfunction in patients with internuclear ophthalmoplegia (INO) due to multiple sclerosis (MS), and develop a composite structural-functional biomarker of axonal and myelin integrity in this tract., Methods: Eighteen patients with definite MS and clinically suspected INO underwent electrical vestibular stimulation and search-coil eye movement recording. Components of the electrically evoked vestibulo-ocular reflex (eVOR) were analyzed to probe the latency and fidelity of MLF axonal conduction. The MLF and T2-visible brainstem lesions were defined by high-resolution MRI. White matter integrity was determined by diffusion-weighted imaging metrics., Results: eVOR onset latency was positively correlated with MLF lesion length (left: r = 0.66, p = 0.004; right: r = 0.75, p = 0.001). The mean conduction velocity (±SD) within MLF lesions was estimated at 2.72 (±0.87) m/s. eVOR onset latency correlated with normalized axial diffusivity (r = 0.66, p < 0.001) and fractional anisotropy (r = 0.44, p = 0.02) after exclusion of cases with ipsilateral vestibular root entry zone lesions., Conclusions: Axonal conduction velocity through lesions involving the MLF was reduced below levels predicted for natively myelinated and remyelinated axons. Composite in vivo biomarkers enable delineation of axonal from myelin processes and may provide a crucial role in assessing efficacy of novel reparative therapies in MS., (© The Author(s), 2014.)

Objective: Describe the epidemiology of healthcare-related (ie, healthcare-associated and hospital-acquired) pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA) among hospitalized patients in community hospitals., Design: Retrospective cohort study., Setting: Twenty-four community hospitals in the southeastern United States affiliated with the Duke Infection Control Outreach Network (median size, 211 beds; range, 103-658 beds)., Methods: Adult patients with healthcare-related MRSA pneumonia admitted to study hospitals from January 1, 2008, to December 31, 2012, were identified using surveillance data. Seasonal and annual incidence rates (cases per 100,000 patient-days) were estimated using generalized estimating equation models. Characteristics of community-onset and hospital-onset cases were compared., Results: A total of 1,048 cases of healthcare-related pneumonia due to MRSA were observed during 5,863,941 patient-days. The annual incidence rate of healthcare-related MRSA pneumonia increased from 11.3 cases per 100,000 patient-days (95% confidence interval [CI], 6.8-18.7) in 2008 to 15.5 cases per 100,000 patient-days (95% CI, 8.4-28.5) in 2012 (P = .055). The incidence rate was highest in winter months and lowest in summer months (15.4 vs 11.1 cases per 100,000 patient-days; incidence rate ratio, 1.39 [95% CI, 1.06-1.82]; P = .016). A total of 814 cases (77.7%) were community-onset healthcare-associated pneumonia cases; only 49 cases (4.7%) were ventilator-associated cases. Of 811 patients whose disposition was known, 240 (29.6%) died during hospitalization or were discharged to hospice., Conclusions: From 2008 through 2012, the incidence of healthcare-related MRSA pneumonia among patients who were admitted to a large network of community hospitals increased, despite the decreasing incidence of invasive MRSA infections nationwide. Additional study is warranted to evaluate trends in this important and potentially modifiable public health problem.

Objective: We sought to quantify and compare angular vestibulo-ocular reflex (aVOR) gain and compensatory saccade properties elicited by the head impulse test (HIT) in pontine-cerebellar stroke (PCS) and vestibular neuritis (VN)., Methods: Horizontal HIT was recorded ≤7 days from vertigo onset with dual-search coils in 33 PCS involving the anterior inferior, posterior inferior, and superior cerebellar arteries (13 AICA, 17 PICA, 3 SCA) confirmed by MRI and 20 VN. We determined the aVOR gain and asymmetry, and compensatory overt saccade properties including amplitude asymmetry and cumulative amplitude (ipsilesional trials [I]; contralesional trials [C])., Results: The aVOR gain (normal: 0.96; asymmetry = 2%) was bilaterally reduced, greater in AICA (I = 0.39, C = 0.57; asymmetry = 20%) than in PICA/SCA strokes (I = 0.75, C = 0.74; asymmetry = 7%), in contrast to the unilateral deficit in VN (I = 0.22, C = 0.76; asymmetry = 54%). Cumulative amplitude (normal: 1.1°) was smaller in AICA (I = 4.2°, C = 3.0°) and PICA/SCA strokes (I = 2.1°, C = 3.0°) compared with VN (I = 8.5°, C = 1.3°). Amplitude asymmetry in AICA and PICA/SCA strokes was comparable, but favored the contralesional side in PICA/SCA strokes and the ipsilesional side in VN. Saccade asymmetry <61% was found in 97% of PCS and none of VN. Gain asymmetry <40% was found in 94% of PCS and 10% of VN., Conclusion: HIT gains and compensatory saccades differ between PCS and VN. VN was characterized by unilateral gain deficits with asymmetric large saccades, AICA stroke by more symmetric bilateral gain reduction with smaller saccades, and PICA stroke by contralesional gain bias with the smallest saccades. Saccade and gain asymmetry should be investigated further in future diagnostic accuracy studies., Classification of Evidence: This study provides Class II evidence that aVOR testing accurately distinguishes patients with PCS from VN (sensitivity 94%-97%, specificity 90%-100%)., (© 2014 American Academy of Neurology.)

Objectives: Physical examination can identify palpable splenomegaly easily, but evaluating lesser degrees of splenomegaly is problematic. Hand-carried ultrasound allows rapid bedside assessment of patients. We conducted this study to determine whether hand-carried ultrasound can reliably assess spleen size., Methods: Patients with varying degrees of splenomegaly were studied. Two sonographers blindly measured spleen size in each patient using either a hand-carried or conventional ultrasound device in random order. Sonographers completed a data sheet indicating the adequacy of the image, clinical measurements of enlargement, and confidence in their observations., Results: Sixteen patients (10 male and 6 female; mean age ± SEM, 60 ± 4 years) were recruited. Image quality was adequate or better in all scans with conventional ultrasound and in 15 of 16 scans with hand-carried ultrasound. The greatest longitudinal measurement recorded was statistically equivalent across ultrasound techniques, with mean values of 16.4 cm (95% confidence interval, 14.8-18.0 cm) for conventional ultrasound and 15.8 cm (95% confidence interval, 14.1-17.4 cm) for hand-carried ultrasound. The correlation between measurement techniques was r = 0.89 (P < .0001). Sonographers were somewhat or very confident in the outcomes of all scans with conventional ultrasound and in 15 of 16 cases with hand-carried ultrasound. In general, it took longer for sonographers to obtain images with hand-carried ultrasound., Conclusions: We have shown that hand-carried ultrasound can be used at the point of care by trained individuals to diagnose splenomegaly. However, hand-carried ultrasound images were less likely to be judged excellent, were accompanied by less diagnostic certainty, and took longer to obtain., (© 2014 by the American Institute of Ultrasound in Medicine.)

Gaucher's disease (GD) is a hereditary lysosomal storage disease characterized by abnormal deposition of glucocerebroside due to the enzyme glucocerebrosidase deficiency, resulting in multi-organ pathology. GD type III has a progressive neurological involvement. We studied the vestibular and saccadic abnormalities in GD type III to determine if these parameters may be useful for assessing neurological involvement. We evaluated the vestibular and saccadic responses of two siblings with genetically identified GD type III on enzyme replacement therapy. Vestibular functions were assessed with the head impulse test (HIT), vestibular evoked myogenic potentials (VEMPs), and electrical vestibular stimulation (EVS). Saccadic functions were investigated with volitional horizontal and vertical saccades to ±20°. Three-dimensional head and eye movements were recorded with dual-search coils and VEMP with surface electrodes. HIT showed impaired individual semicircular canal function with halved angular vestibulo-ocular reflex (VOR) gains and absent horizontal refixation saccade. Ocular and cervical VEMPs to air-conducted clicks were absent in the older sibling, and only cervical VEMP was present in the younger sibling indicating otolithic dysfunction. EVS showed prolonged onset latency and attenuated tonic and phasic responses suggesting impaired neural conduction and vestibular function. Horizontal saccadic velocity was miniscule (<30°/s) and multiple back-to-back saccades with saccade-vergence interaction were utilized to minimize eye position error in the older sibling. Vertical saccades were slightly abnormal, but vergence and smooth pursuit were normal in both siblings. Our findings suggest that GD affected the vestibular nuclei in addition to the paramedian pontine reticular formation. These vestibular and saccadic abnormalities may be useful biomarkers to monitor neurological deterioration.

Positional vertigo and nystagmus can be due to canalithiasis, cupulolithiasis and less commonly, an underlying peripheral or central vestibular disorder. We present a patient with vestibular schwannoma who initially sought treatment for positioning vertigo. Video-oculography on the roll-test revealed direction-changing horizontal apogeotropic nystagmus, consistent with horizontal cupulolithiasis. However, further audio-vestibular investigations and imaging confirmed a right vestibulopathy attributable to a schwannoma of the right vestibular nerve. This case report suggests that vestibular schwannoma should be considered as another potential mimicker of horizontal cupulolithiasis., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: As distributed undergraduate and postgraduate medical education becomes more common, the challenges with the teaching and learning process also increase., Aim: To collaboratively engage front line teachers in improving teaching in a distributed medical program., Method: We recently conducted a contest on teaching tips in a provincially distributed medical education program and received entries from faculty and resident teachers., Results: Tips that are helpful for teaching around clinical cases at distributed teaching sites include: ask "what if" questions to maximize clinical teaching opportunities, try the 5-min short snapper, multitask to allow direct observation, create dedicated time for feedback, there are really no stupid questions, and work with heterogeneous group of learners. Tips that are helpful for multi-site classroom teaching include: promote teacher-learner connectivity, optimize the long distance working relationship, use the reality television show model to maximize retention and captivate learners, include less teaching content if possible, tell learners what you are teaching and make it relevant and turn on the technology tap to fill the knowledge gap., Conclusion: Overall, the above-mentioned tips offered by front line teachers can be helpful in distributed medical education.

Chronic recurrent isolated vertigo is an uncommon manifestation of vertebrobasilar ischaemia. We report a 43-year-old female with 12-month history of recurrent attacks of isolated vertigo who presented with acute pontine infarctions. Clinical examination and vestibular function testing showed bilateral vestibular hypofunction affecting the horizontal and posterior semicircular canals and right saccule. Diffusion-weighted magnetic resonance imaging (MRI) demonstrated acute bilateral pontine infarcts and significant vertebrobasilar stenoses. The findings of recurrent isolated vertigo and bilateral vestibular hypofunction should not prevent a search for vertebrobasilar ischaemia, particularly in the presence of vascular risk factors.

Background: Carbamazepine, an anticonvulsant and a mood-stabilizing drug, is the main cause of the Stevens-Johnson syndrome (SJS) and its related disease, toxic epidermal necrolysis (TEN), in Southeast Asian countries. Carbamazepine-induced SJS-TEN is strongly associated with the HLA-B*1502 allele. We sought to prevent carbamazepine-induced SJS-TEN by using HLA-B*1502 screening to prospectively identify subjects at genetic risk for the condition., Methods: From 23 hospitals in Taiwan, we recruited 4877 candidate subjects who had not taken carbamazepine. We genotyped DNA purified from the subjects' peripheral blood to determine whether they carried the HLA-B*1502 allele. Those testing positive for HLA-B*1502 (7.7% of the total) were advised not to take carbamazepine and were given an alternative medication or advised to continue taking their prestudy medication; those testing negative (92.3%) were advised to take carbamazepine. We interviewed the subjects by telephone once a week for 2 months to monitor them for symptoms. We used the estimated historical incidence of SJS-TEN as a control., Results: Mild, transient rash developed in 4.3% of subjects; more widespread rash developed in 0.1% of subjects, who were hospitalized. SJS-TEN did not develop in any of the HLA-B*1502-negative subjects receiving carbamazepine. In contrast, the estimated historical incidence of carbamazepine-induced SJS-TEN (0.23%) would translate into approximately 10 cases among study subjects (P<0.001)., Conclusions: The identification of subjects carrying the HLA-B*1502 allele and the avoidance of carbamazepine therapy in these subjects was strongly associated with a decrease in the incidence of carbamazepine-induced SJS-TEN. (Funded by the National Science Council of Taiwan and the Taiwan Drug Relief Foundation.).

Introduction: Stroke-like migraine attacks after radiation therapy, or SMART syndrome, is characterised by migraine-like headache with or without aura, transient neurological dysfunction, including seizures, and gyriform enhancement on magnetic resonance imaging (MRI) which resolves over a period of weeks. Detailed neuropsychological characterisation in SMART syndrome is lacking and there are no published data on the course and pattern of neurocognitive recovery., Results: The acute clinical presentation was one of unstable, fluctuating neurocognitive disturbances, complicated by seizure activity, followed by a longer term lag in the recovery of focal neuropsychological deficits which, we believe, was due to the more slowly resolving cerebral effects of SMART., Conclusions: To our knowledge, this is the first case of SMART syndrome in which neuropsychological functioning has been comprehensively and serially examined. This case is also unique due to the development of complex partial seizures. We suggest that epileptiform activity during clinical seizures should not be regarded as inconsistent with a diagnosis of SMART, provided that the seizures do not explain the onset of the other clinical and radiological features.

Knowing one's HIV status is particularly important in the setting of recent tuberculosis (TB) exposure. Blood tests for assessment of tuberculosis infection, such as the QuantiFERON Gold in-tube test (QFT; Cellestis Limited, Carnegie, Victoria, Australia), offer the possibility of simultaneous screening for TB and HIV with a single blood draw. We performed a cross-sectional analysis of all contacts to a highly infectious TB case in a large meatpacking factory. Twenty-two percent were foreign-born and 73% were black. Contacts were tested with both tuberculin skin testing (TST) and QFT. HIV testing was offered on an opt-out basis. Persons with TST >or=10 mm, positive QFT, and/or positive HIV test were offered latent TB treatment. Three hundred twenty-six contacts were screened: TST results were available for 266 people and an additional 24 reported a prior positive TST for a total of 290 persons with any TST result (89.0%). Adequate QFT specimens were obtained for 312 (95.7%) of persons. Thirty-two persons had QFT results but did not return for TST reading. Twenty-two percent met the criteria for latent TB infection. Eighty-eight percent accepted HIV testing. Two (0.7%) were HIV seropositive; both individuals were already aware of their HIV status, but one had stopped care a year previously. None of the HIV-seropositive persons had latent TB, but all were offered latent TB treatment per standard guidelines. This demonstrates that opt-out HIV testing combined with QFT in a large TB contact investigation was feasible and useful. HIV testing was also widely accepted. Pairing QFT with opt-out HIV testing should be strongly considered when possible.