Effects of Interval Time of the Epley Manoeuvre

Objective: The Epley maneuver (EM) has an immediate effect: rapid reduction of positional nystagmus. Benign paroxysmal positional vertigo (BPPV) causes BPPV fatigue, which constitutes fatigability of positional nystagmus and vertigo with repeated performance of the Dix-Hallpike test; notably, BPPV fatigability becomes ineffective over time. We hypothesized that the immediate effect of the EM is caused by BPPV fatigue. Therefore, we suspected that performance of the EM with intervals between head positions would worsen the immediate reduction of positional nystagmus in patients with BPPV, because BPPV fatigability would become ineffective during performance of this therapy. Methods: Forty patients with newly diagnosed BPPV were randomly assigned to the following two groups; one group performed the EM without intervals between positions (group A), and the other group performed the EM with 3 min intervals between positions (group B). The primary outcome measure was the ratio of maximum slow-phase eye velocity (MSPEV) of positional nystagmus soon after the EM, compared with that measured before the EM. Secondary outcome included whether a 30 min interval after the EM enabled recovery of MSPEV of positional nystagmus to the original value. This study followed the CONSORT 2010 reporting standards. Results: In both groups A and B, the immediate effect of the EM could be observed, because MSPEV during the second Dix-Hallpike test was significantly smaller than MSPEV during the first Dix-Hallpike test (p < 0.0001 in group A, p < 0.0001 in group B). The primary outcome measure was larger in group B than in group A (p = 0.0029). The immediate effect faded 30 min later (secondary outcome). Conclusions: This study showed that the EM had an immediate effect both with and without interval time in each head position of the EM. Because setting interval time in each head position of the EM reduced the immediate effect of the EM, interval time during the EM adds less benefit. This finding can reduce the effort exerted by doctors, as well as the discomfort experienced by patients with pc-BPPV, during EM. However, this immediate effect may be caused by BPPV fatigue, and may fade rapidly

Gram Staining for the Treatment of Peritonsillar Abscess

Objective. To examine whether Gram staining can influence the choice of antibiotic for the treatment of peritonsillar abscess. Methods. Between 2005 and 2009, a total of 57 cases of peritonsillar abscess were analyzed with regard to cultured bacteria and Gram staining. Results. Only aerobes were cultured in 16% of cases, and only anaerobes were cultured in 51% of cases. Mixed growth of aerobes and anaerobes was observed in 21% of cases. The cultured bacteria were mainly aerobic Streptococcus, anaerobic Gram-positive cocci, and anaerobic Gram-negative rods. Phagocytosis of bacteria on Gram staining was observed in 9 cases. The bacteria cultured from these cases were aerobic Streptococcus, anaerobic Gram-positive cocci, and anaerobic Gram-negative rods. The sensitivity of Gram staining for the Gram-positive cocci and Gram-negative rods was 90% and 64%, respectively. The specificity of Gram staining for the Gram-positive cocci and Gram-negative rods was 62% and 76%, respectively. Most of the Gram-positive cocci were sensitive to penicillin, but some of anaerobic Gram-negative rods were resistant to penicillin. Conclusion. When Gram staining shows only Gram-positive cocci, penicillin is the treatment of choice. In other cases, antibiotics effective for the penicillin-resistant organisms should be used

VOG to Measure 3D Rotation Vector of Murine Eye Movements

Background The mouse is the most commonly used animal model in biomedical research because of recent advances in molecular genetic techniques. Studies related to eye movement in mice are common in fields such as ophthalmology relating to vision, neuro-otology relating to the vestibulo-ocular reflex (VOR), neurology relating to the cerebellum’s role in movement, and psychology relating to attention. Recording eye movements in mice, however, is technically difficult. Methods We developed a new algorithm for analyzing the three-dimensional (3D) rotation vector of eye movement in mice using high-speed video-oculography (VOG). The algorithm made it possible to analyze the gain and phase of VOR using the eye’s angular velocity around the axis of eye rotation. Results When mice were rotated at 0.5 Hz and 2.5 Hz around the earth’s vertical axis with their heads in a 30° nose-down position, the vertical components of their left eye movements were in phase with the horizontal components. The VOR gain was 0.42 at 0.5 Hz and 0.74 at 2.5 Hz, and the phase lead of the eye movement against the turntable was 16.1° at 0.5 Hz and 4.88° at 2.5 Hz. Conclusions To the best of our knowledge, this is the first report of this algorithm being used to calculate a 3D rotation vector of eye movement in mice using high-speed VOG. We developed a technique for analyzing the 3D rotation vector of eye movements in mice with a high-speed infrared CCD camera. We concluded that the technique is suitable for analyzing eye movements in mice. We also include a C++ source code that can calculate the 3D rotation vectors of the eye position from two-dimensional coordinates of the pupil and the iris freckle in the image to this article

High-resolution melting curve analysis for rapid detection of mutations in a Medaka TILLING library

<p>Abstract</p> <p>Background</p> <p>During the last two decades, DNA sequencing has led to the identification of numerous genes in key species; however, in most cases, their functions are still unknown. In this situation, reverse genetics is the most suitable method to assign function to a gene. TILLING (Targeting Induced Local Lesions IN Genomes) is a reverse-genetic strategy that combines random chemical mutagenesis with high-throughput discovery of the induced mutations in target genes. The method has been applied to a variety of plant and animal species. Screening of the induced mutations is the most important step in TILLING. Currently, direct sequencing or nuclease-mediated screening of heteroduplexes is widely used for detection of mutations in TILLING. Both methods are useful, but the costs are substantial and turnaround times are relatively long. Thus, there is a need for an alternative method that is of higher throughput and more cost effective.</p> <p>Results</p> <p>In this study, we developed a high resolution melting (HRM) assay and evaluated its effectiveness for screening ENU-induced mutations in a medaka TILLING library. We had previously screened mutations in the <it>p53 </it>gene by direct sequencing. Therefore, we first tested the efficiency of the HRM assay by screening mutations in <it>p53</it>, which indicated that the HRM assay is as useful as direct sequencing. Next, we screened mutations in the <it>atr </it>and <it>atm </it>genes with the HRM assay. Nonsense mutations were identified in each gene, and the phenotypes of these nonsense mutants confirmed their loss-of-function nature.</p> <p>Conclusions</p> <p>These results demonstrate that the HRM assay is useful for screening mutations in TILLING. Furthermore, the phenotype of the obtained mutants indicates that medaka is an excellent animal model for investigating genome stability and gene function, especially when combined with TILLING.</p

Effects of Interval Time of the Epley Maneuver on Immediate Reduction of Positional Nystagmus: A Randomized, Controlled, Non-blinded Clinical Trial

Objective: The Epley maneuver (EM) has an immediate effect: rapid reduction of positional nystagmus. Benign paroxysmal positional vertigo (BPPV) causes BPPV fatigue, which constitutes fatigability of positional nystagmus and vertigo with repeated performance of the Dix-Hallpike test; notably, BPPV fatigability becomes ineffective over time. We hypothesized that the immediate effect of the EM is caused by BPPV fatigue. Therefore, we suspected that performance of the EM with intervals between head positions would worsen the immediate reduction of positional nystagmus in patients with BPPV, because BPPV fatigability would become ineffective during performance of this therapy.Methods: Forty patients with newly diagnosed BPPV were randomly assigned to the following two groups; one group performed the EM without intervals between positions (group A), and the other group performed the EM with 3 min intervals between positions (group B). The primary outcome measure was the ratio of maximum slow-phase eye velocity (MSPEV) of positional nystagmus soon after the EM, compared with that measured before the EM. Secondary outcome included whether a 30 min interval after the EM enabled recovery of MSPEV of positional nystagmus to the original value. This study followed the CONSORT 2010 reporting standards.Results: In both groups A and B, the immediate effect of the EM could be observed, because MSPEV during the second Dix-Hallpike test was significantly smaller than MSPEV during the first Dix-Hallpike test (p &lt; 0.0001 in group A, p &lt; 0.0001 in group B). The primary outcome measure was larger in group B than in group A (p = 0.0029). The immediate effect faded 30 min later (secondary outcome).Conclusions: This study showed that the EM had an immediate effect both with and without interval time in each head position of the EM. Because setting interval time in each head position of the EM reduced the immediate effect of the EM, interval time during the EM adds less benefit. This finding can reduce the effort exerted by doctors, as well as the discomfort experienced by patients with pc-BPPV, during EM. However, this immediate effect may be caused by BPPV fatigue, and may fade rapidly.Classification of Evidence: 1

Development of a new method for assessing otolith function in mice using three-dimensional binocular analysis of the otolith-ocular reflex

In the interaural direction, translational linear acceleration is loaded during lateral translational movement and gravitational acceleration is loaded during lateral tilting movement. These two types of acceleration induce eye movements via two kinds of otolith-ocular reflexes to compensate for movement and maintain clear vision: horizontal eye movement during translational movement, and torsional eye movement (torsion) during tilting movement. Although the two types of acceleration cannot be discriminated, the two otolith-ocular reflexes can distinguish them effectively. In the current study, we tested whether lateral-eyed mice exhibit both of these otolith-ocular reflexes. In addition, we propose a new index for assessing the otolith-ocular reflex in mice. During lateral translational movement, mice did not show appropriate horizontal eye movement, but exhibited unnecessary vertical torsion-like eye movement that compensated for the angle between the body axis and gravito-inertial acceleration (GIA; i.e., the sum of gravity and inertial force due to movement) by interpreting GIA as gravity. Using the new index (amplitude of vertical component of eye movement)/(angle between body axis and GIA), the mouse otolith-ocular reflex can be assessed without determining whether the otolith-ocular reflex is induced during translational movement or during tilting movement

Viewing Targets in Infantile Nystagmus

The aim of this study was to propose a new pathophysiological hypothesis for involuntary eye oscillation in infantile nystagmus (IN): patients with IN exhibit impaired gaze fixation, horizontal smooth pursuit and optokinetic nystagmus (OKN) and use saccadic eye movements for these underlying impairments. In order to induce saccades, they make enough angle between gaze and target by precedent exponential slow eye movements. IN consists of the alternate appearance of the saccade and the slow eye movements. Unlike most previous theories, IN is therefore considered a necessary strategy allowing for better vision and not an obstacle to clear vision. In five patients with IN, eye movements were analyzed during the smooth pursuit test, saccadic eye movement test, OKN test and vestibulo-ocular reflex (VOR) test. Their gaze fixation, horizontal smooth pursuit, OKN and the last half of the slow phase of VOR were impaired. The lines obtained by connection of the end eye positions of fast phase of nystagmus coincided with the trajectories of targets. The findings indicate that patients followed the target by the fast but not the slow phase of nystagmus, which supports our hypothesis. By setting the direction of slow phase of nystagmus opposite to the direction of the OKN stimulation, enough angle can be effectively made between the gaze and target for the induction of saccade. This is the mechanism of reversed OKN response. In darkness and when eyes are closed, IN weakens because there is no visual target and neither the saccade for catching up the target or slow phase for induction of the saccade is needed

The effect of visual-vestibulosomatosensory conflict induced by virtual reality on postural stability in humans

In this study, we examined the effects of sensory inputs of visual-vestibulosomatosensory conflict induced by virtual reality (VR) on subjective dizziness, posture stability and visual dependency on postural control in humans. Eleven healthy young volunteers were immersed in two different VR conditions. In the control condition, subjects walked voluntarily with the background images of interactive computer graphics proportionally synchronized to their walking pace. In the visual-vestibulosomatosensory conflict condition, subjects kept still, but the background images that subjects experienced in the control condition were presented. The scores of both Graybiel’s and Hamilton’s criteria, postural instability and Romberg ratio were measured before and after the two conditions. After immersion in the conflict condition, both subjective dizziness and objective postural instability were significantly increased, and Romberg ratio, an index of the visual dependency on postural control, was slightly decreased. These findings suggest that sensory inputs of visual-vestibulosomatosensory conflict induced by VR induced motion sickness, resulting in subjective dizziness and postural instability. They also suggest that adaptation to the conflict condition decreases the contribution of visual inputs to postural control with re-weighing of vestibulosomatosensory inputs. VR may be used as a rehabilitation tool for dizzy patients by its ability to induce sensory re-weighing of postural control

Single-cell transcriptomics of human cholesteatoma identifies an activin A-producing osteoclastogenic fibroblast subset inducing bone destruction

Cholesteatoma, which potentially results from tympanic membrane retraction, is characterized by intractable local bone erosion and subsequent hearing loss and brain abscess formation. However, the pathophysiological mechanisms underlying bone destruction remain elusive. Here, we performed a single-cell RNA sequencing analysis on human cholesteatoma samples and identify a pathogenic fibroblast subset characterized by abundant expression of inhibin βA. We demonstrate that activin A, a homodimer of inhibin βA, promotes osteoclast differentiation. Furthermore, the deletion of inhibin βA /activin A in these fibroblasts results in decreased osteoclast differentiation in a murine model of cholesteatoma. Moreover, follistatin, an antagonist of activin A, reduces osteoclastogenesis and resultant bone erosion in cholesteatoma. Collectively, these findings indicate that unique activin A-producing fibroblasts present in human cholesteatoma tissues are accountable for bone destruction via the induction of local osteoclastogenesis, suggesting a potential therapeutic target.Shimizu K., Kikuta J., Ohta Y., et al. Single-cell transcriptomics of human cholesteatoma identifies an activin A-producing osteoclastogenic fibroblast subset inducing bone destruction. Nature Communications 14, 4417 (2023); https://doi.org/10.1038/s41467-023-40094-3

Initial Evaluation of [18F]FAPI-74 PET for Various Histopathologically Confirmed Cancers and Benign Lesions

The 18F-labeled fibroblast activation protein inhibitor (FAPI) [18F]FAPI- 74 has the benefit of a higher synthetic yield and better image resolution than 68Ga-labeled FAPI. We preliminarily evaluated the diagnostic performance of [18F]FAPI-74 PET in patients with various histopathologically confirmed cancers or suspected malignancies. Methods: We enrolled 31 patients (17 men and 14 women) with lung cancer (n = 7), breast cancer (n = 5), gastric cancer (n = 5), pancreatic cancer (n = 3), other cancers (n = 5), and benign tumors (n = 6). Twenty-seven of the 31 patients were treatment-naïve or preoperative, whereas recurrence was suspected in the remaining 4 patients. Histopathologic confirmation was obtained for the primary lesions of 29 of the 31 patients. In the remaining 2 patients, the final diagnosis was based on the clinical course. [18F]FAPI-74 PET scanning was performed 60min after the intravenous injection of [18F]FAPI-74 (240631 MBq). The [18F]FAPI-74 PET images were compared between the primary or local recurrent lesions of malignant tumors (n = 21) and nonmalignant lesions (n 5 8: type-B1 thymomas, granuloma, solitary fibrous tumor, and postoperative or posttherapeutic changes). The uptake and number of detected lesions on [18F]FAPI-74 PET were also compared with those on [18F]FDG PET for available patients (n = 19). Results: [18F]FAPI-74 PET showed higher uptake in primary lesions of various cancers than in nonmalignant lesions (median SUVmax, 9.39 [range, 1.83-25.28] vs. 3.49 [range, 2.21-15.58]; P = 0.053), but some of the nonmalignant lesions showed high uptake. [18F]FAPI-74 PET also showed significantly higher uptake than [18F]FDG PET (median SUVmax, 9.44 [range, 2.50-25.28] vs. 5.45 [range, 1.22-15.06] in primary lesions [P 5 0.010], 8.86 [range, 3.51-23.33] vs. 3.84 [range, 1.01-9.75] in lymph node metastases [P 5 0.002], and 6.39 [range, 0.55-12.78] vs. 1.88 [range, 0.73-8.35] in other metastases [P 5 0.046], respectively). In 6 patients, [18F]FAPI-74 PET detected more metastatic lesions than [18F]FDG PET. Conclusion: [18F]FAPI-74 PET showed higher uptake and detection rates in primary and metastatic lesions than did [18F]FDG PET. [18F]FAPI-74 PET is a promising novel diagnostic modality for various tumors, especially for precise staging before treatment, including characterization of tumor lesions before surgery. Moreover, 18F-labeled FAPI ligand might serve a higher demand in clinical care in the future.This research was originally published in JNM. Tadashi Watabe, Sadahiro Naka, Mitsuaki Tatsumi et.al. Initial Evaluation of [18F]FAPI-74 PET for Various Histopathologically Confirmed Cancers and Benign Lesions. J Nucl Med. 2023, 64(8), 1225-1231. © SNMMI