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.

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.

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.

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.

Structure-based discovery of selective positive allosteric modulators of antagonists for the M2 muscarinic acetylcholine receptor.

Subtype-selective antagonists for muscarinic acetylcholine receptors (mAChRs) have long been elusive, owing to the highly conserved orthosteric binding site. However, allosteric sites of these receptors are less conserved, motivating the search for allosteric ligands that modulate agonists or antagonists to confer subtype selectivity. Accordingly, a 4.6 million-molecule library was docked against the structure of the prototypical M2 mAChR, seeking molecules that specifically stabilized antagonist binding. This led us to identify a positive allosteric modulator (PAM) that potentiated the antagonist N-methyl scopolamine (NMS). Structure-based optimization led to compound '628, which enhanced binding of NMS, and the drug scopolamine itself, with a cooperativity factor (α) of 5.5 and a KB of 1.1 µM, while sparing the endogenous agonist acetylcholine. NMR spectral changes determined for methionine residues reflected changes in the allosteric network. Moreover, '628 slowed the dissociation rate of NMS from the M2 mAChR by 50-fold, an effect not observed at the other four mAChR subtypes. The specific PAM effect of '628 on NMS antagonism was conserved in functional assays, including agonist stimulation of [35S]GTPγS binding and ERK 1/2 phosphorylation. Importantly, the selective allostery between '628 and NMS was retained in membranes from adult rat hypothalamus and in neonatal rat cardiomyocytes, supporting the physiological relevance of this PAM/antagonist approach. This study supports the feasibility of discovering PAMs that confer subtype selectivity to antagonists; molecules like '628 can convert an armamentarium of potent but nonselective GPCR antagonist drugs into subtype-selective reagents, thus reducing their off-target effects.

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.

The matrix metalloproteinase in larynx cancer.

One of the most common carcinoma occurring in the head and neck is laryngeal cancer. Despite the rapid scientific advances in medicine the prognosis for patients with such type of disease is not satisfying. In the last few years matrix metalloproteinases ­ MMPs and their tissue inhibitors - TIMPs, mostly MMP­2 and MMP­9, arouses a great interest, especially in the process of carcinogenesis. It seems that their impact in the formation and development of laryngeal cancer is significant. MMPs a group of zinc­ and calcium­ dependent endopeptidases play crucial role extracellular matrix collagen degradation. That are enzymes, that degrade and the basement membrane by facilitating tumor growth, cell migration and tumor invasion. They are implicated in metastasis and angiogenesis potentiate within the tumor. Clear tendency was observed towards the higher MMPs and TIMPs expression in larynx cancer than in the stroma. Recent studies show correlations between increased MMP­2 gene expression in the tumor tissue and clinical status, histopathological grading and metastases occurrence. The similar MMP2 over expression dependence were found on tumor recurrence and survival. Many authors pointed out, significant higher MMP­2 expression as a potential marker of tumor invasiveness and worse prognosis in patients with larynx cancer. However, association of MMP 9 gene expression with laryngeal cancer clinicopathological features and survival of patients are ambiguous. Although, numerous researches show that this relationship does exists. Similar correlations could be found in TIMPs, but further studies are necessary because of small amount of literature.

[The matrix metalloproteinase in oral and oropharyngeol cancer - literature review]. / Metaloproteinazy w raku jamy ustnej i gardla ­ przeglad pismiennictwa.

The most common head and neck cancers are neoplasms that occur in the oral cavity and the throat. They are characterized by the high growth rate and clinical malignancy. The research on a significant role in the tumorigenesis of the matrix metalloproteinases MMP-2, MMP-8, MMP-9 and their tissue inhibitors is becoming more and more popular nowadays. MMPs are a group of proteolytic enzymes responsible for the stroma extracellular matrix (ECM) degradation, which enables the tumor growth, cell migration, and tumor invasion. The numerous studies reveal a significant growing trend in the level of the studied metalloproteinases expression and their inhibitors in the oral cavity and throat cancers in relation to healthy tissues. Moreover, it was proved that an increased gene MMP-2 expression in the tumor tissue correlates with the clinical staging, the histopathological grading, presence of metastases, cancer relapse, and the patient's survival time. In available articles there is evidence of increased gene MMP-2 expression as a potential marker of the tumor invasiveness and the worse prognosis in patients with the oral cavity and throat cancers. The relationships of the gene MMP-9 expression with the clinical and pathological features as well as with the survival time are inconclusive. A similar relationship is found in case of TIMPs, however this issue has not been commonly raised in the scientific literature.

Covalent docking predicts substrates for haloalkanoate dehalogenase superfamily phosphatases.

Enzyme function prediction remains an important open problem. Though structure-based modeling, such as metabolite docking, can identify substrates of some enzymes, it is ill-suited to reactions that progress through a covalent intermediate. Here we investigated the ability of covalent docking to identify substrates that pass through such a covalent intermediate, focusing particularly on the haloalkanoate dehalogenase superfamily. In retrospective assessments, covalent docking recapitulated substrate binding modes of known cocrystal structures and identified experimental substrates from a set of putative phosphorylated metabolites. In comparison, noncovalent docking of high-energy intermediates yielded nonproductive poses. In prospective predictions against seven enzymes, a substrate was identified for five. For one of those cases, a covalent docking prediction, confirmed by empirical screening, and combined with genomic context analysis, suggested the identity of the enzyme that catalyzes the orphan phosphatase reaction in the riboflavin biosynthetic pathway of Bacteroides.

Functional annotation and structural characterization of a novel lactonase hydrolyzing D-xylono-1,4-lactone-5-phosphate and L-arabino-1,4-lactone-5-phosphate.

A novel lactonase from Mycoplasma synoviae 53 (MS53_0025) and Mycoplasma agalactiae PG2 (MAG_6390) was characterized by protein structure determination, molecular docking, gene context analysis, and library screening. The crystal structure of MS53_0025 was determined to a resolution of 2.06 Å. This protein adopts a typical amidohydrolase (ß/α)8-fold and contains a binuclear zinc center located at the C-terminal end of the ß-barrel. A phosphate molecule was bound in the active site and hydrogen bonds to Lys217, Lys244, Tyr245, Arg275, and Tyr278. Both docking and gene context analysis were used to narrow the theoretical substrate profile of the enzyme, thus directing empirical screening to identify that MS53_0025 and MAG_6390 catalyze the hydrolysis of d-xylono-1,4-lactone-5-phosphate (2) with kcat/Km values of 4.7 × 10(4) and 5.7 × 10(4) M(-1) s(-1) and l-arabino-1,4-lactone-5-phosphate (7) with kcat/Km values of 1.3 × 10(4) and 2.2 × 10(4) M(-1) s(-1), respectively. The identification of the substrate profile of these two phospho-furanose lactonases emerged only when all methods were integrated and therefore provides a blueprint for future substrate identification of highly related amidohydrolase superfamily members.

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.

Functional annotation and three-dimensional structure of an incorrectly annotated dihydroorotase from cog3964 in the amidohydrolase superfamily.

The substrate specificities of two incorrectly annotated enzymes belonging to cog3964 from the amidohydrolase superfamily were determined. This group of enzymes are currently misannotated as either dihydroorotases or adenine deaminases. Atu3266 from Agrobacterium tumefaciens C58 and Oant2987 from Ochrobactrum anthropi ATCC 49188 were found to catalyze the hydrolysis of acetyl-(R)-mandelate and similar esters with values of k(cat)/K(m) that exceed 10(5) M(-1) s(-1). These enzymes do not catalyze the deamination of adenine or the hydrolysis of dihydroorotate. Atu3266 was crystallized and the structure determined to a resolution of 2.62 Å. The protein folds as a distorted (ß/α)(8) barrel and binds two zincs in the active site. The substrate profile was determined via a combination of computational docking to the three-dimensional structure of Atu3266 and screening of a highly focused library of potential substrates. The initial weak hit was the hydrolysis of N-acetyl-D-serine (k(cat)/K(m) = 4 M(-1) s(-1)). This was followed by the progressive identification of acetyl-(R)-glycerate (k(cat)/K(m) = 4 × 10(2) M(-1) s(-1)), acetyl glycolate (k(cat)/K(m) = 1.3 × 10(4) M(-1) s(-1)), and ultimately acetyl-(R)-mandelate (k(cat)/K(m) = 2.8 × 10(5) M(-1) s(-1)).

The impact of co-morbid factors on the psychological outcome of tinnitus patients.

The study was carried out to determine the impact of some co-morbid otological symptoms and demographic factors on the emotional distress and cognitive functioning in patients with tinnitus. One hundred consecutive patients, complaining of constant idiopathic tinnitus, were enrolled into the study. Four tests were administered: Beck Depression Inventory, Hospital Anxiety Depression Scale (HADS, A--anxiety, D--depression), Mini-Mental State Examination (MMSE) and Trail Making Test (TMT). A multivariate stepwise linear regression analysis was performed to estimate the relationship between the results of each of the tests and following co-morbid factors: age, sex, tinnitus duration, tinnitus laterality, hearing status (normal hearing, unilateral hearing loss and bilateral hearing loss) and vertigo/dizziness. It was found that the scores of MMSE and TMT were negatively correlated with age and with hearing status and the scores of HADS-A were slightly correlated with sex. In regression analysis, in HADS-A, sex and to a lesser extent tinnitus duration, in MMSE and TMT age and to a lesser extent tinnitus laterality were the variables that were comprised in the final model. Demographic factors had contributed more than overlapping otological symptoms to the psychological outcome in tinnitus patients.

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.

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.

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.

[Vestibular system in patients with systemic sclerosis]. / Stan ukladu przedsionkowego u pacjentów z twardzina ukladowa.

OBJECTIVES: In systemic sclerosis (SSc) there may occur hearing and balance disorders as a result of the immune-mediated inner ear damage, the etiology being vasculitis and fibrosis. The objective is the vestibular organ evaluation in patients with SSc regarding their prevalence and relationship to duration of the disease and Raynaud phenomenon and also to type and severity of SSc. MATERIAL: Twenty unselected, consecutive patients with diagnosed SSc, complying with international diagnostic criteria of the American Rheumatism Association (1982), were enrolled into the study. The control group consisted of 26 otologically healthy persons matched to the SSc group for age and sex. METHODS: In all patients the questionnaire about audiovestibular history, otolaryngological examination, static and dynamic vestibular tests and the electronystsgmography (ENG) were performed. The patients were investigated with the electronystsgmography (ENG) for spontaneous, positional and caloric-induced nystagmus. Also visual ocular-motor tests were performer. RESULTS: In the anamnesis 65% of patients reported vertigo, 55% - headaches, 50% - tinnitus, 40% - hyperacusis, 40% - hearing loss and 30% - ear fullness. Vertigo, dizziness balance disturbance and uncorrect results of Romberg and Utenberger tests were more frequent in patients with vestibular organ lesion. Abnormalities in vestibular organ in SSc patients were fund in 14 (70%) persons - the central type of lesion - 8 (40%), mixed type in 3 (15%) and peripheral in 3 (15%). CONCLUSIONS: Ear involvement is frequent in systemic sclerosis and should be taken into consideration during diagnostic and therapeutic procedures.

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.