The effect of Immersive Virtual Reality on balance: an exploratory study on the feasibility of head-mounted displays for balance evaluation.

Global interest in applying virtual reality (VR) in research and medicine has grown significantly, with potential benefits for patients suffering from balance disorders, instability, and a high risk of falling. This exploratory study assesses the impact of immersive VR (IVR) delivered through a head-mounted display (HMD) on balance and explores the feasibility of using the HMD VR unit as a standalone posturography tool. Using the Meta Quest 2 HMD and a mid-range Android smartphone equipped with standard sensors, the research employed a VR environment that simulated a ship at sea, with thirty-eight healthy participants with no otoneurologic abnormalities. Measurements were conducted in repeated trials, including static assessments on both stable ground and foam, as well as a 3-m walk. This was conducted in two settings: one within a VR environment with three different intensity levels and the other in non-VR settings. Statistical analysis and clinical evaluation revealed that IVR with HMD influences head-level sway velocity, which correlates with increased visual disturbance, suggesting its potential as a low-risk standalone posturography tool.

Discovery of PFI-6, a small-molecule chemical probe for the YEATS domain of MLLT1 and MLLT3.

Epigenetic proteins containing YEATS domains (YD) are an emerging target class in drug discovery. Described herein are the discovery and characterization efforts associated with PFI-6, a new chemical probe for the YD of MLLT1 (ENL/YEATS1) and MLLT3 (AF9/YEATS3). For hit identification, fragment-like mimetics of endogenous YD ligands (crotonylated histone-containing proteins), were synthesized via parallel medicinal chemistry (PMC) and screened for MLLT1 binding. Subsequent SAR studies led to iterative MLLT1/3 binding and selectivity improvements, culminating in the discovery of PFI-6. PFI-6 demonstrates good affinity and selectivity for MLLT1/3 vs. other human YD proteins (YEATS2/4) and engages MLLT3 in cells. Small-molecule X-ray co-crystal structures of two molecules, including PFI-6, bound to the YD of MLLT1/3 are also described. PFI-6 may be a useful tool molecule to better understand the biological effects associated with modulation of MLLT1/3.

Instrumental and Non-Instrumental Measurements in Patients with Peripheral Vestibular Dysfunctions.

Vestibular dysfunction is a disturbance of the body's balance system. The control of balance and gait has a particular influence on the quality of life. Currently, assessing patients with these problems is mainly subjective. New assessment options using wearables may provide complementary and more objective information. Posturography makes it possible to determine the extent and type of posture dysfunction, which makes it possible to plan and monitor the effectiveness of physical rehabilitation therapy. This study evaluates the effectiveness of non-instrumental clinical tests and the instrumental mobile posturography MediPost device for patients with unilateral vestibular disorders. The study group included 40 patients. A subjective description of the symptoms was evaluated using a questionnaire about the intensity of dizziness using the Dizziness Handicap Inventory (DHI) and Vertigo Syndrome Scale-short form (VSS-sf). The clinical protocol contained clinical tests and MediPost measurements using a Modified Clinical Test of Sensory Interaction on Balance. All patients underwent vestibular rehabilitation therapy (VRT) for four weeks. The non-instrumental measurement results were statistically significant, and the best was in the Timed Up and Go test (TUG). In MediPost, condition 4 was the most valuable. This research demonstrated the possibilities of using an instrumental test (MediPost) as an alternative method to assess balance.

Discovery of High-Affinity Small-Molecule Binders of the Epigenetic Reader YEATS4.

A series of small-molecule YEATS4 binders have been discovered as part of an ongoing research effort to generate high-quality probe molecules for emerging and/or challenging epigenetic targets. Analogues such as 4d and 4e demonstrate excellent potency and selectivity for YEATS4 binding versus YEATS1,2,3 and exhibit good physical properties and in vitro safety profiles. A new X-ray crystal structure confirms direct binding of this chemical series to YEATS4 at the lysine acetylation recognition site of the YEATS domain. Multiple analogues engage YEATS4 with nanomolar potency in a whole-cell nanoluciferase bioluminescent resonance energy transfer assay. Rodent pharmacokinetic studies demonstrate the competency of several analogues as in vivo-capable binders.

Virtual Reality-A Supplement to Posturography or a Novel Balance Assessment Tool?

Virtual reality (VR) is a well-established technology in medicine. Head-mounted displays (HMDs) have made VR more accessible in many branches of medical research. However, its application in balance evaluation has been vague, and comprehensive literature on possible applications of VR in posture measurement is scarce. The aim of this review is to conduct a literature search on the application of immersive VR delivered using a head-mounted display in posturographic measurements. A systematic search of two databases, PubMed and Scopus, using the keywords "virtual reality" and "posturography," was performed following PRISMA guidelines for systematic reviews. Initial search results returned 89 non-duplicate records. Two reviewers independently screened the abstracts. Sixteen papers fulfilled the inclusion criteria and none of the exclusion criteria and were selected for complete text retrieval. An additional 16 records were identified from citation searching. Ultimately, 21 studies were included in this review. virtual reality is often used as additional visual stimuli in static and dynamic posturography evaluation. Only one study has attempted to evaluate a VR environment in a head-mounted display as an independent method in the assessment of posture. Further research should be conducted to assess HMD VR as a standalone posturography replacement.

Innovative System for Evaluation and Rehabilitation of Human Imbalance.

<b>Introduction:</b> Mobile posturography is based on wearable inertial sensors; it allows to test static stability (static posturography) and gait disturbances. </br> </br> <b>Aim:</b> The aim of this work was to present the results of research on the innovative MEDIPOST system used for diagnosis and rehabilitation of balance disorders. </br> </br> <b>Material and methods:</b> Fourteen articles published in influenced foreign journals were presented and discussed. The deve-lopment and construction of the device was preceded by a literature review and methodological work. The Dizziness Handi-cap Inventory (DHI) questionnaire was translated and validated. The methodology of posturography with head movements with a frequency of 0.3 Hz was also developed in the group with chronic vestibular disorders. Simultaneous measurements were performed (static posturogrphy vs. MEDIPOST) in the CTSIB-M (Modified Clinical Test of Sensory Interaction in Balance) test in healthy subjects and patients with unilateral peripheral dysfunction.</br> </br> <b>Results:</b> In the posturography with head movements the improvement of sensitivity (67 to 74%) and specificity (65 to 71%) was noted. In the CTSIB-M test the intraclass correlation coefficients for both methods were 0.9. The greatest differences between examinations were observed for the mean angular velocity in the tests on the foam (trials no. 3 and 4), in particular on the foam with eyes closed (trial no. 4 - sensitivity 86.4%, specificity 87.7%). Two functional tests were analyzed: the Swap Seats test and the 360 degree turn test. In the former, the results are studied from 6 sensors - 86% of the true positives and 73% of the true negatives for the fall/ no-fall group classification. The second test differentiates people with vestibular impairment and healthy people. It can be analyzed with 1 (sensitivity 80%) and 6 sensors (sensitivity 86%, specificity 84%). Currently, the MEDIPOST device is in the development and certification phase.

Detection of balance disorders using rotations around vertical axis and an artificial neural network.

Vestibular impairments affect patients' movements and can result in difficulties with daily life activities. The main aim of this study is to answer the question whether a simple and short test such as rotation about a vertical axis can be an objective method of assessing balance dysfunction in patients with unilateral vestibular impairments. A 360˚ rotation test was performed using six MediPost devices. The analysis was performed in three ways: (1) the analytical approach based only on data from one sensor; (2) the analytical approach based on data from six sensors; (3) the artificial neural network (ANN) approach based on data from six sensors. For approaches 1 and 2 best results were obtained using maximum angular velocities (MAV) of rotation and rotation duration (RD), while approach 3 used 11 different features. The following sensitivities and specificities were achieved: for approach 1: MAV-80% and 60%, RD-69% and 74%; for approach 2: 61% and 85% and RD-74% and 56%; for approach 3: 88% and 84%. The ANN-based six-sensor approach revealed the best sensitivity and specificity among parameters studied, however one-sensor approach might be a simple screening test used e.g. for rehabilitation purposes.

Utility of the Novel MediPost Mobile Posturography Device in the Assessment of Patients with a Unilateral Vestibular Disorder.

Balance disorders are a growing problem worldwide. Thus, there is an increasing need to provide an inexpensive and feasible alternative to standard posturographic platforms (SP) used for the assessment of balance and to provide a possible solution for telemonitoring of patients. A novel mobile posturography (MP) MediPost device was developed to address these issues. This prospective study used a Modified Clinical Test of Sensory Interaction on Balance to evaluate healthy individuals and patients with a unilateral vestibular disorder through SP and MP simultaneously. The control group included 65 healthy volunteers, while the study group included 38 patients diagnosed with a unilateral vestibular deficit. The angular velocity values obtained from both methods were compared by intraclass correlation coefficients (ICC) and Bland−Altman plot analysis. Diagnostic capabilities were measured in terms of sensitivity and specificity. The ICC between the two methods for conditions 2−4 was indicative of excellent reliability, with the ICC > 0.9 (p < 0.001), except for Condition 1 (standing stance, eyes open) ICC = 0.685, p < 0.001, which is indicative of moderate reliability. ROC curve analysis of angular velocity for condition 4 represents the most accurate differentiating factor with AUC values of 0.939 for SP and 0.953 for MP. This condition also reported the highest sensitivity, specificity, PPV, and NPV values with 86.4%, 87.7%, 80%, and 90.5% for SP, and 92.1%, 84.6%, 77.8%, and 94.8% for MP, respectively. The newly developed MediPost device has high sensitivity and specificity in distinguishing between healthy individuals and patients with a unilateral vestibular deficit.

Long-term Results of Three-layered Closure of Oronasal Fistula: A Case Report.

An oronasal fistula is an interconnection between the oral and nasal cavities. It interferes with normal functioning and affects quality of life by impeding eating and speech. The most common management strategy is surgical treatment. The aim of our study was to present the results of a long-term follow-up of effective treatment of a case of oronasal fistula that occurred without any cause and comorbidities. A 46-year-old woman reported the sudden appearance of a painless oronasal fistula. She demonstrated nasal regurgitation-that is, loss of fluids through the nose while drinking-and slurred' nasal speech. Clinical examination revealed a soft tissue defect (diameter: 5 mm) on the left side of the palate. Computed tomography revealed a gap in the hard palate bone, measuring 25 × 30 mm. No complications were noted following the procedure, nor at 10-year follow-up. It seems that the use of bone substitute and palatal flap for spontaneous oronasal fistula closure was fully justified. The patient may have had an undiagnosed congenital defect of the hard palate, and the deficit may have appeared due to bone loss occurring in her forties. However, no consensus exists regarding the best treatment management for oronasal fistulae located in the palatal region, and further comparative studies between the existing techniques are needed.

A comparison of head movements tests in force plate and accelerometer based posturography in patients with balance problems due to vestibular dysfunction.

This study compares HS posturography on inertial sensors (MediPost) with force platform posturography in patients with unilateral vestibular dysfunction. The study group included 38 patients (age 50.6; SD 11.6) with unilateral vestibular weakness (UV) and 65 healthy volunteers (48.7; SD 11.5). HS tests were performed simultaneously on the force plate and with MediPost sensor attached at L4. Four conditions applied: eyes open/closed, firm/foam. The tests were performed twice, with the head moving at the frequency of 0.3 Hz (HS 0.3) and 0.6 Hz (HS 0.6). Mean sway velocity was significantly lower for MediPost than force plate in 4th condition both in UV and healthy group. For HS 0.3 the differences between devices were marginal; the highest sensitivity (87%) and specificity (95%) were in 4th condition. For HS 0.6 MediPost revealed lower sensitivity than force plate although the surface parameter improved results. MediPost IMU device and force platform posturography revealed a similar ability to differentiate between patients with balance problems in course of vestibular pathology and healthy participants, despite the differences observed between measuring methods. In some tests surface parameter may be more appropriate than sway velocity in improving MediPost sensitivity.

The Ototoxicity of Antimalarial Drugs-A State of the Art Review.

This review summarizes current knowledge about the occurrence of hearing and balance disorders after antimalarial drugs treatment. It also examines the clinical applications of antimalarials, their mechanisms behind this ototoxicity and how it can be monitored. It includes studies with larger numbers of patients and those in which auditory function was assessed using audiological tests. Some antimalarials have been repurposed for other conditions like autoimmune disorders, rheumatic diseases, some viral diseases and cancers. While old antimalarial drugs, such as quinoline derivatives, are known to demonstrate ototoxicity, a number of new synthetic antimalarial agents particularly artemisinin derivatives, demonstrate unknown ototoxicity. Adverse audiovestibular effects vary depending on the medication itself, its dose and route of administration, as well as the drug combination, treated disease and individual predispositions of the patient. Dizziness was commonly reported, while vestibular symptoms, hearing loss and tinnitus were observed much less frequently, and most of these symptoms were reversible. As early identification of ototoxic hearing loss is critical to introducing possible alternative treatments with less ototoxic medications, therefore monitoring systems of those drugs ototoxic side effects are much needed.

Dizziness Handicap Inventory in Clinical Evaluation of Dizzy Patients.

(1) Objectives: The evaluation of dizzy patients is difficult due to nonspecific symptoms that require a multi-specialist approach. The Dizziness Handicap Inventory (DHI) is widely used in the assessment of dizziness-related disability, but its clinical efficacy needs further expansion. The aim of this study was to identify the subscales of DHI that may correlate with some vestibular or nonvestibular dysfunctions. (2) Material and methods: This observational study included 343 dizzy patients with one of the following clinical conditions: Vestibular impairment noncompensated or compensated, central or bilateral, benign paroxysmal positional vertigo (BPPV), migraine and psychogenic dizziness. Principal component analysis was used to examine the factorial structure of the questionnaire. (3) Results: The DHI questionnaire total scoring and its vestibular subscale distinguished between patients with compensated and uncompensated vestibular dysfunction with positive predictive values of 76% and 79%, respectively. The DHI items composing the F3 (positional) subscale revealed the highest scoring in the BPPV group with 75% sensitivity and 92% negative predictive value (NPV) in reference to Dix-Hallpike tests. The DHI total score and the subscales scores correlated with anxiety-depression, and the highest correlation coefficients were calculated for vestibular (F2 0.56) and anxiety (F5 0.51) subscales. (4) Conclusions: Our analysis revealed that the DHI vestibular subscale distinguishes between patients with compensated and uncompensated vestibular dysfunction. The positional subscale showed the highest scoring in the BPPV group with high sensitivity and low specificity of the test. The DHI is highly correlated with patients' psychological status.

Fully Automatic Fall Risk Assessment Based on a Fast Mobility Test.

This paper presents a fall risk assessment approach based on a fast mobility test, automatically evaluated using a low-cost, scalable system for the recording and analysis of body movement. This mobility test has never before been investigated as a sole source of data for fall risk assessment. It can be performed in a very limited space and needs only minimal additional equipment, yet provides large amounts of information, as the presented system can obtain much more data than traditional observation by capturing minute details regarding body movement. The readings are provided wirelessly by one to seven low-cost micro-electro-mechanical inertial measurement units attached to the subject's body segments. Combined with a body model, these allow segment rotations and translations to be computed and for body movements to be recreated in software. The subject can then be automatically classified by an artificial neural network based on selected values in the test, and those with an elevated risk of falls can be identified. Results obtained from a group of 40 subjects of various ages, both healthy volunteers and patients with vestibular system impairment, are presented to demonstrate the combined capabilities of the test and system. Labelling of subjects as fallers and non-fallers was performed using an objective and precise sensory organization test; it is an important novelty as this approach to subject labelling has never before been used in the design and evaluation of fall risk assessment systems. The findings show a true-positive ratio of 85% and true-negative ratio of 63% for classifying subjects as fallers or non-fallers using the introduced fast mobility test, which are noticeably better than those obtained for the long-established Timed Up and Go test.

Posturography with head movements in the assessment of balance in chronic unilateral vestibular lesions.

The aim of our study was to validate the method of head-shake static posturography (HS-posturography) in healthy individuals and to establish the value of this novel method in the diagnostics of patients with unilateral vestibular lesion (UV). The study included 202 participants divided into two groups, one consisting of 133 patients with canal paresis CP > 19% and one of 69 healthy subjects. Participant was tested according to the standard protocol of static posturography (SP), and with head movements of 0.3 Hz (HS 40), 0.6 Hz (HS 70) in random order controlled by a metronome. HS-posturography revealed a similar repeatability and internal consistency as the standard posturography. In patients with UV, 4th condition revealed higher sensitivity (74%) and specificity (71%) in HS 40 than in the standard posturography (67%, 65% respectively) and HS 70 (54%, 70% respectively). Static posturography and HS- posturography revealed a high reliability of the testing method. The head movements added to static posturography improve the sensitivity and specificity of the method in group with vestibular impairment. The most important test for that purpose seems to be the one on unstable surface with the eyes closed, with low frequency of head movements.

Usefulness of Mobile Devices in the Diagnosis and Rehabilitation of Patients with Dizziness and Balance Disorders: A State of the Art Review.

OBJECTIVE: The gold standard for objective body posture examination is posturography. Body movements are detected through the use of force platforms that assess static and dynamic balance (conventional posturography). In recent years, new technologies like wearable sensors (mobile posturography) have been applied during complex dynamic activities to diagnose and rehabilitate balance disorders. They are used in healthy people, especially in the aging population, for detecting falls in the older adults, in the rehabilitation of different neurological, osteoarticular, and muscular system diseases, and in vestibular disorders. Mobile devices are portable, lightweight, and less expensive than conventional posturography. The vibrotactile system can consist of an accelerometer (linear acceleration measurement), gyroscopes (angular acceleration measurement), and magnetometers (heading measurement, relative to the Earth's magnetic field). The sensors may be mounted to the trunk (most often in the lumbar region of the spine, and the pelvis), wrists, arms, sternum, feet, or shins. Some static and dynamic clinical tests have been performed with the use of wearable sensors. Smartphones are widely used as a mobile computing platform and to evaluate the results or monitor the patient during the movement and rehabilitation. There are various mobile applications for smartphone-based balance systems. Future research should focus on validating the sensitivity and reliability of mobile device measurements compared to conventional posturography. CONCLUSION: Smartphone based mobile devices are limited to one sensor lumbar level posturography and offer basic clinical evaluation. Single or multi sensor mobile posturography is available from different manufacturers and offers single to multi-level measurements, providing more data and in some instances even performing sophisticated clinical balance tests.

An allosteric modulator binds to a conformational hub in the ß2 adrenergic receptor.

Most drugs acting on G-protein-coupled receptors target the orthosteric binding pocket where the native hormone or neurotransmitter binds. There is much interest in finding allosteric ligands for these targets because they modulate physiologic signaling and promise to be more selective than orthosteric ligands. Here we describe a newly developed allosteric modulator of the ß2-adrenergic receptor (ß2AR), AS408, that binds to the membrane-facing surface of transmembrane segments 3 and 5, as revealed by X-ray crystallography. AS408 disrupts a water-mediated polar network involving E1223.41 and the backbone carbonyls of V2065.45 and S2075.46. The AS408 binding site is adjacent to a previously identified molecular switch for ß2AR activation formed by I3.40, P5.50 and F6.44. The structure reveals how AS408 stabilizes the inactive conformation of this switch, thereby acting as a negative allosteric modulator for agonists and positive allosteric modulator for inverse agonists.

Vertigo and Severe Balance Instability as Symptoms of Lyme Disease-Literature Review and Case Report.

Lyme disease is caused by a tick-borne bacterium Borrelia sp. This zoonotic infection is common in the Northern Hemisphere, e.g., Europe. Clinical presentation may involve multisystem symptoms and depends on the stage of the disease. The involvement of nervous system in Lyme disease is commonly referred to as neuroborreliosis. Neuroborreliosis may involve meningitis, mononeuritis multiplex, or cranial neuritis including the inflammation of vestibulocochlear nerve. In the late or chronic stage of Lyme disease, vestibular involvement may be the sole presentation, although such cases are rare. Our study was designed to present our own case and review the available literature reporting cases of neuroborreliosis with vertigo/dizziness and severe balance instability as a main disease symptom. The studies were obtained by searching the following databases: PubMed, Medline, and Embase. We included case reports of Lyme disease presenting with vertigo or gait disorders as the main symptom, written in the English language. Initially, 60 papers were identified. After analyzing the abstracts, seven manuscripts focusing on 13 clinical cases were included in this review. We conclude that the patients with neuroborreliosis sometimes present vertigo/dizziness, but rarely gait ataxia as a sole symptom. These complaints are usually accompanied by a hearing loss. Antibiotic treatment is usually effective. Balance instability in the patients with neuroborreliosis may persist but it responds well to vestibular rehabilitation.

[Effectiveness of vestibular rehabilitation in patients with vestibular dysfunction]. / Ocena skutecznosci rehabilitacji przedsionkowej u pacjentów z dysfunkcja blednika.

BACKGROUND: Vertigo and instability due to vestibular dysfunction have been a frequent cause of work absence, with a clearly upward tendency observed in recent years. Uncompensated vestibular hypofunction requires vestibular rehabilitation, but access to this form of treatment remains limited. Therefore, innovative methods of rehabilitation utilizing new technologies, which could promote this therapy, are searched for. Virtual reality (VR) is becoming a popular method of rehabilitation used, for example, in the treatment of stroke or schizophrenia. The aim of this study was to compare and evaluate 2 methods of vestibular rehabilitation in patients with unilateral vestibular disorders. MATERIAL AND METHODS: Forty-three patients with unilateral vestibular disorders diagnosed at the Balance Disorders Unit, 1st Otolaryngology Department of the Medical University of Lodz, were included in this study. The patients, divided into 2 groups, received 10 sessions of rehabilitation. Group 1 (N = 22) was rehabilitated using a VR unit consisting of a forceplate and a motion sensor, while Group 2 (N = 21) performed training on a static posturography platform under physiotherapist supervision. The patients were examined at the baseline, 1 month and 3 months after rehabilitation. During each assessment, posturography was performed which recorded the center of pressure (CoP) displacement. The patients also filled out a questionnaire to quantify vertigo symptoms. RESULTS: The CoP parameters decreased in both groups, with no superiority of either form of training. Analysis of the subjective symptoms reduction revealed a decrease in the Vertigo Syndrome Scale - short form (VSS-sf) score in the second evaluation in both groups, which was slightly greater in the VR group. The improvement remained stable 3 months after rehabilitation. CONCLUSIONS: Both forms of rehabilitation are effective in increasing postural stability and reducing subjective symptoms. Virtual reality training achieves a slightly greater subjective improvement. Med Pr. 2019;70(5):545-53.

Matrix metalloproteinases (MMPs) and inhibitor of metalloproteinases (TIMP) mRNA and protein expression in laryngeal squamous cell carcinoma.

INTRODUCTION: The aim of the study was to investigate the mRNA expression and protein levels of matrix metalloproteinases (MMP) 2 (MMP-2), 9 (MMP-9), 7 (MMP-7) and their tissue inhibitor TIMP-2 in patients with laryngeal squamous cell carcinoma and control subjects and additionally to evaluate a possible correlation with clinicopathological features. MATERIAL AND METHODS: The expression levels of MMP-2, MMP-9, MMP-7, and TIMP-2 mRNA were detected by the real-time quantitative real time polymerase chain reaction method in 96 cases of laryngeal carcinoma vs. non-tumor tissue. The blood serum levels of MMP-2, MMP-9, MMP-7, and TIMP-2 in patients with laryngeal cancer and 100 healthy subjects were measured using the enzyme-linked immunosorbent assay (ELISA) method. RESULTS: The present study demonstrated that MMP-2, MMP-7, MMP-9 and TIMP-2 mRNA expression levels in carcinoma tissue vs. non-tumor tissue and protein levels in the preoperative serum vs. those obtained in healthy controls were statistically significantly higher than in the healthy controls (p = 0.001). The only significant correlation between mRNA or concentration of measured MMPs and TIMP and the clinicopathological features was found for TIMP-2 protein and for patients with lymph node metastasis. Serum levels of TIMP-2 were higher in cases with lymph node metastasis than in those without lymph node metastasis (p < 0.05). CONCLUSIONS: The results may suggest that MMPs and TIMP-2 are associated with laryngeal tumorigenesis, but we did not find any distinct correlation between the clinicopathological features of laryngeal squamous cell carcinoma patients and expression levels of MMPs and TIMP. The results suggest that the measurement of serum MMP-2, MMP-7, MMP-9 and TIMP-2 concentration might be helpful to diagnose laryngeal squamous cell carcinoma.