Zebrafish as a model to investigate a biallelic gain-of-function variant in MSGN1, associated with a novel skeletal dysplasia syndrome.

BACKGROUND/OBJECTIVES: Rare genetic disorders causing specific congenital developmental abnormalities often manifest in single families. Investigation of disease-causing molecular features are most times lacking, although these investigations may open novel therapeutic options for patients. In this study, we aimed to identify the genetic cause in an Iranian patient with severe skeletal dysplasia and to model its molecular function in zebrafish embryos. RESULTS: The proband displays short stature and multiple skeletal abnormalities, including mesomelic dysplasia of the arms with complete humero-radio-ulna synostosis, arched clavicles, pelvic dysplasia, short and thin fibulae, proportionally short vertebrae, hyperlordosis and mild kyphosis. Exome sequencing of the patient revealed a novel homozygous c.374G > T, p.(Arg125Leu) missense variant in MSGN1 (NM_001105569). MSGN1, a basic-Helix-Loop-Helix transcription factor, plays a crucial role in formation of presomitic mesoderm progenitor cells/mesodermal stem cells during early developmental processes in vertebrates. Initial in vitro experiments show protein stability and correct intracellular localization of the novel variant in the nucleus and imply retained transcription factor function. To test the pathogenicity of the detected variant, we overexpressed wild-type and mutant msgn1 mRNA in zebrafish embryos and analyzed tbxta (T/brachyury/ntl). Overexpression of wild-type or mutant msgn1 mRNA significantly reduces tbxta expression in the tailbud compared to control embryos. Mutant msgn1 mRNA injected embryos depict a more severe effect, implying a gain-of-function mechanism. In vivo analysis on embryonic development was performed by clonal msgn1 overexpression in zebrafish embryos further demonstrated altered cell compartments in the presomitic mesoderm, notochord and pectoral fin buds. Detection of ectopic tbx6 and bmp2 expression in these embryos hint to affected downstream signals due to Msgn1 gain-of-function. CONCLUSION: In contrast to loss-of-function effects described in animal knockdown models, gain-of-function of MSGN1 explains the only mildly affected axial skeleton of the proband and rather normal vertebrae. In this context we observed notochord bending and potentially disruption of pectoral fin buds/upper extremity after overexpression of msgn1 in zebrafish embryos. The latter might result from Msgn1 function on mesenchymal stem cells or on chondrogenesis in these regions. In addition, we detected ectopic tbx6 and bmp2a expression after gain of Msgn1 function in zebrafish, which are interconnected to short stature, congenital scoliosis, limb shortening and prominent skeletal malformations in patients. Our findings highlight a rare, so far undescribed skeletal dysplasia syndrome associated with a gain-of-function mutation in MSGN1 and hint to its molecular downstream effectors.

Can Cochlear Nerve Size Assessment With Magnetic Resonance Enhance the Understanding of Idiopathic Sudden Sensorineural Hearing Loss?

BACKGROUND AND OBJECTIVES: Idiopathic sudden sensorineural hearing loss (ISSHL) is a rapid loss of hearing, exceeding 30 dB in at least 3 consecutive frequencies within 3 days, without any identifiable cause despite thorough investigations. Currently, the etiology and pathogenesis of ISSHL have not been fully elucidated. This study aimed to assess the size of the cochlear nerve in patients with ISSHL and explore its relationship with pretreatment audiograms and treatment response. Subjects and. METHODS: A total of 125 patients (59 [47.2%] women; mean age 47.7±13.8 years [minimum-maximum: 21-76]) and 60 healthy participants (27 [45%] women; mean age 45.7±16.8 years [minimum-maximum: 20-76]) as a control group were included in this study. The size of the cochlear nerve was assessed on the affected side, compared to the control group, as well as on the unaffected side. Pretreatment and posttreatment audiological values were also analyzed. RESULTS: The cross-sectional area (CSA), vertical diameter (VD), and horizontal diameter (HD) of the CN were found to be smaller on the affected side of ISSHL patients compared to the control group (p<0.01; p=0.04; p=0.02, respectively). In the study group (affected side of ISSHL patients), there were no significant differences in VD, HD, and CSA values between pretreatment audiogram types (p=0.23; p=0.53; p=0.39, respectively), and initial hearing levels (p=0.16; p=0.22; p=0.23, respectively). Furthermore, there were no significant differences in VD, HD, and CSA values between the recovery groups according to Furuhashi criteria (p=0.18; p=0.37; p=0.27, respectively). CONCLUSIONS: The size of the CN may be a risk factor for ISSHL, but it does not affect the type of audiogram curves and was not prognostic in terms of treatment response.

Stochastic gene expression and environmental stressors trigger variable somite segmentation phenotypes.

Mutations of several genes cause incomplete penetrance and variable expressivity of phenotypes, which are usually attributed to modifier genes or gene-environment interactions. Here, we show stochastic gene expression underlies the variability of somite segmentation defects in embryos mutant for segmentation clock genes her1 or her7. Phenotypic strength is further augmented by low temperature and hypoxia. By performing live imaging of the segmentation clock reporters, we further show that groups of cells with higher oscillation amplitudes successfully form somites while those with lower amplitudes fail to do so. In unfavorable environments, the number of cycles with high amplitude oscillations and the number of successful segmentations proportionally decrease. These results suggest that individual oscillation cycles stochastically fail to pass a threshold amplitude, resulting in segmentation defects in mutants. Our quantitative methodology is adaptable to investigate variable phenotypes of mutant genes in different tissues.

Using single-molecule fluorescence in situ hybridization and immunohistochemistry to count RNA molecules in single cells in zebrafish embryos.

Taming gene expression variability is critical for robust pattern formation during embryonic development. Here, we describe an optimized protocol for single-molecule fluorescence in situ hybridization and immunohistochemistry in zebrafish embryos. We detail how to count segmentation clock RNAs and calculate their variability among neighboring cells. This approach is easily adaptable to count RNA numbers of any gene and calculate transcriptional variability among neighboring cells in diverse biological settings. For complete details on the use and execution of this protocol, please refer to Keskin et al. (2018),1 Zinani et al. (2021),2 and Zinani et al. (2022).3.

Prognostic and Clinical Role of Contrast Enhancement on Magnetic Resonance Imaging in Patients with Bell's Palsy.

Objective: To investigate the prognostic value of the magnetic resonance imaging in Bell's palsy patients. Methods: Patients who were diagnosed and treated with Bell's palsy between October 2013 and March 2016 retrospectively selected. House-Brackmann grades, pre- and post-treatment pure tone audiograms, stapedial reflexes were analyzed and magnetic resonance imaging (MRI) scans with gadolinium-based contrast agents were evaluated. Contrast-enhanced segments of the facial nerve were determined. MRI findings were compared statistically with pre- and post-treatment grade, recurrence rate of Bell's palsy, MRI scanning timing, presence of stapes reflexes and posttreatment recovery data. Results: No significant correlation was observed between pretreatment House-Brackmann grades and enhancement (p>0.05). Similarly, there was no significant correlation between clinical recovery and enhancement (p>0.05). Also, no significant correlation was observed between MRI scanning time, the recurrence rate of Bell's palsy and MRI findings (p>0.05). None of the MRIs showed neoplastic contrast enhancement. Conclusion: The routine use of the contrast-enhanced temporal MRI is not recommended in the diagnosis and monitoring of Bell's palsy patients, because the contrast enhancement pattern of the facial nerve has no effect on the prognosis of Bell's palsy. MRI should be used in cases that do not heal despite treatment, for the differential diagnosis of facial nerve tumors and in patients who are candidates for surgical decompression.

Gene copy number and negative feedback differentially regulate transcriptional variability of segmentation clock genes.

Timely progression of a genetic program is critical for embryonic development. However, gene expression involves inevitable fluctuations in biochemical reactions leading to substantial cell-to-cell variability (gene expression noise). One of the important questions in developmental biology is how pattern formation is reproducibly executed despite these unavoidable fluctuations in gene expression. Here, we studied the transcriptional variability of two paired zebrafish segmentation clock genes (her1 and her7) in multiple genetic backgrounds. Segmentation clock genes establish an oscillating self-regulatory system, presenting a challenging yet beautiful system in studying control of transcription variability. In this study, we found that a negative feedback loop established by the Her1 and Her7 proteins minimizes uncorrelated variability whereas gene copy number affects variability of both RNAs in a similar manner (correlated variability). We anticipate that these findings will help analyze the precision of other natural clocks and inspire the ideas for engineering precise synthetic clocks in tissue engineering.

Management of deep neck infections in adults and importance of clinical and laboratory findings.

This study aimed to analyze laboratory and radiological imaging results in the prediction of treatment strategy in patients with deep neck infections. Eighty-three patients (55 (66.3%) men, mean age: 38.2±14.5 years) were included in the study. Patients were divided into three groups according to the treatment strategy: group 1 received only antibiotic treatment, group 2 underwent abscess drainage with needle puncture in addition to antibiotic treatment, and group 3 underwent surgical drainage with antibiotic treatment. Laboratory outcomes, imaging methods, duration of hospital stay, treatment strategy, and clinical outcomes were analyzed.According to the laboratory results, complete blood count values did not vary among the three groups, but C reactive protein (CRP) and erythrocyte sedimentation rate (ESR) values were higher in group 3 (p<0.01). Based on receiver operating characteristic (ROC) analysis, the cut-off levels for CRP and ESR associated with the need for surgical drainage were 133 mg/L and 42.5, respectively. According to radiological imaging results, the number of involved neck spaces was significantly different among the three groups (p=0.03), and group 3 had more spaces involved when compared with groups 1 and 2 (p=0.04). Gas formation in the neck tissues was noted in 10 patients in group 3 and 5 patients in groups 1 and 2 (p=0.02). ESR and CRP levels were higher in patients who underwent surgical drainage. In patients with deep neck space infections, the involvement of two or more neck spaces and gas formation on radiological images might indicate surgical drainage as a treatment strategy.

Best Practice Recommendations for Geriatric Dysphagia Management with 5 Ws and 1H.

BACKGROUND: Dysphagia is a geriatric syndrome. Changes in the whole body that occur with aging also affect swallowing functions and cause presbyphagia. This condition may progress to oropharyngeal and/or esophageal dysphagia in the presence of secondary causes that increase in incidence with aging. However, no study has been published that provides recommendations for use in clinical practice that addresses in detail all aspects of the management of dysphagia in geriatric individuals. This study aimed to answer almost all potential questions and problems in the management of geriatric dysphagia in clinical practice. METHODS: A multidisciplinary team created this recommendation guide using the seven-step and three-round modified Delphi method via e-mail. The study included 39 experts from 29 centers in 14 cities. RESULTS: Based on the 5W and 1H method, we developed 216 detailed recommendations for older adults from the perspective of different disciplines dealing with older people. CONCLUSION: This consensus-based recommendation is a useful guide to address practical clinical questions in the diagnosis, rehabilitation, and follow-up for the management of geriatric dysphagia and also contains detailed commentary on these issues.

Occult lymph node metastasis in patients with laryngeal cancer and relevant predicting factors: a single-center experience.

OBJECTIVE: To reveal the incidence and predictive parameters of occult cervical lymph node metastasis (LNM) in patients with cN0 laryngeal squamous cell cancer (LSCC) who underwent surgery as definitive treatment. METHODS: Patients with cN0 laryngeal cancer who had undergone elective neck dissection together with partial or total laryngectomy between January 2006 and November 2020 were retrospectively analyzed. Clinical and histopathologic predictors of occult metastasis were also analyzed. Follow-up data were used to obtain recurrence and survival analysis. RESULTS: A total of 86 patients with a mean age of 62.5 years were included in the study. Occult LNM was detected in 15 (17.4%) patients. Tumor grade, pT stage, thyroid cartilage invasion, and extralaryngeal extension were found to predict occult neck metastasis in univariate analysis. The mean follow-up time was 60.7 months and in the survival/recurrence analysis, pT stage, tumor location, tumor grade, presence of occult metastasis, pre-epiglottic space involvement. and extralaryngeal extension were found to predict poorer outcome. CONCLUSION: Overall occult LNM is low (17.4%) in N0 laryngeal cancer, but the presence of LNM is a poor prognostic factor. Correct determination of the neck status and proper treatment is crucial. The incidence of LNM is very low in T1-T2 stages and well-differentiated tumors. The "wait and see" strategy may be applied in T1-T2 cases as well as selected T3 cases with well-differentiated tumors.

Regulatory mechanisms ensuring coordinated expression of functionally related genes.

Coordinated spatiotemporal expression of large sets of genes is required for the development and homeostasis of organisms. To achieve this goal, organisms use myriad strategies where they form operons, utilize bidirectional promoters, cluster genes, share enhancers among genes by DNA looping, and form topologically associated domains and transcriptional condensates. Coexpression achieved by these different strategies is hypothesized to have functional importance in minimizing gene expression variability, establishing dosage balance to ensure stoichiometry of protein complexes, and minimizing accumulation of toxic intermediate metabolites. By combining gene-editing tools with computational modeling, recent studies tested the advantages of adjacent genes located in pairs and clusters. We propose that with the advancement of gene editing, single-cell sequencing, and imaging tools, one could readily test the functional importance of different coexpression strategies in a variety of biological processes.

Oncological Outcomes of Transoral Laryngeal Microsurgery with Fiber-Optic Diode Laser for Early Glottic Cancer: A Single-Center Experience.

Backgroud/Objectives: Transoral laser laryngeal microsurgery (LTLM) has been widely used in the treatment of early-stage glottic laryngeal squamous cell carcinoma (LSCC) for the past few decades. Although T stage, tumor grade, anterior commissure involvement, type of cordectomy, positive surgical margin, and postoperative additional therapies were accused as the prognostic factors for recurrence, there is still controversy about these data in the literature. The purpose of this study was to evaluate the oncological results of our patients with early glottic LSCC treated with LTLM as a single-modality therapy in a single-center study. METHODS: Patients with early-stage (Tis-1-2/N0) glottic LSCC who underwent LTLM as a primary treatment from 2011 to 2019 were retrospectively reviewed. The clinicopathological factors and oncologic outcomes were analyzed. RESULTS: One hundred and sixty-one patients were enrolled in this study. The 5-year overall (OS), disease-specific (DSS), disease-free (DFS), and laryngectomy-free survival rates were 84.5%, 97.9%, 79.2%, and 93.5%, respectively. The most common stage, histopathological type, and type of endoscopic cordectomy were T1 stage, well-differentiated cancer, and type 2 cordectomy, respectively. A positive surgical margin was defined in 20 (12.4%) patients. There was a significant relationship between histopathological grade and positive surgical margins (p = 0.038). OS and DSS rates of "wait and see" modality were lower, while DFS of radiotherapy was lower than that of other treatment modalities in patients with positive surgical margins, but the differences were not statistically significant. Nineteen (11.8%) patients had a recurrence. DSS was statistically significantly lower in patients with recurrence (p < 0.001). CONCLUSION: The results of our study showed that anterior commissure involvement, surgical margin positivity, and higher T stage statistically did not reduce survival rates in early-stage LSCC patients treated with LTLM. As the histopathological grade of the tumor worsens, the risk of surgical margin positivity increases. RT may have a negative effect on recurrence and organ preservation in the additional treatment of patient with positive surgical margins.

Cervical Vestibular-Evoked Myogenic Potentials and Balance Testing in Children with Down Syndrome.

Introduction Vestibular otolith function plays a major role in balance control. Objective To investigate the saccular and balance functions of children with Down syndrome (DS). Methods In total, 15 children with DS aged between 9 and 11 years were included. An age- and gender-matched control group (CG) composed of 15 normal participants was also included. The subjects with DS had trisomy 21, without hearing or organic problems, and they had independence in stance. The saccular function among the children with DS and among the controls was tested using air-conduction cervical vestibular-evoked myogenic potentials (cVEMPs). In addition, the static and dynamic balance statuses were evaluated using the following assessments; the Pediatric Balance Scale (PBS), the modified Clinical Test of Sensory Interaction on Balance (mCTSIB), the Romberg test, and the Timed Up and Go (TUG) test. Results In the present study, the results of the saccular function test showed that there was a significant difference between children with and without DS ( p < 0.05). The DS subjects had significantly earlier N1 latancy and lower amplitude of the cVEMPs (< 70 µV) compared with the control subjects. The static-dynamic balance ability was statistically and significantly different in children with DS compared with the controls ( p < 0.05). Conclusion These results revealed that saccular function seems to be affected in DS subjects. The dysfunction in static and dynamic balance abilities of the children with DS may be attributed to vestibular dysfunction as well as low gross motor skills. This knowledge should be taken into account when assessing motor performance in those subjects. Additional larger studies testing other dimensions of the vestibular system in children with DS are needed.

Early-auditory intervention in children with hearing loss and neurodevelopmental outcomes: cognitive, motor and language development.

BACKGROUND: To date, studies have mostly focused on the language outcome of early-auditory interventions including amplification for congenital hearing loss within the first 6 months. We aimed to examine the effect of early-auditory intervention in patients with congenital hearing loss on cognitive, motor and language outcomes, and determine the clinical variables that affect developmental outcomes. METHODS: The medical records of 104 patients were retrospectively reviewed. Children were evaluated by the Bayley Scales of Infant and Toddler Development, Third Edition. RESULTS: The median ages of confirmation of hearing loss, amplification, starting auditory-verbal intervention and cochlear implantation were 9, 10, 13 and 19 months, respectively. Of the patients, 26% received a hearingaid fitting ≤6 months of age. Fifty-one children (49%) had additional disabilities. The median cognitive, language and motor scores of children with no additional disabilities were 95 (65-115), 68 (47-103) and 97 (58- 130), respectively and children with early-auditory intervention (≤6 months) demonstrated higher cognitive, receptive and expressive language subscale scores than late-auditory intervention group (p < 0.05) whereas there was no significant difference in motor scores (p > 0.05). A significant negative correlation was found between additional disability and cognitive, language and motor outcomes (r=-0.78, r=-0.54 and r=-0.75, respectively p < 0.01). There was a significant negative correlation between language outcomes and the degree of hearing loss (r=-0.20, p < 0.05). Multiple regression analyses revealed that additional disability and early-auditory intervention showed a significant amount of variance in cognitive and language scores. The early intervention did not make a significant, independent contribution on motor outcomes whereas additional disability did. CONCLUSIONS: Presence of additional disability was the strongest significant variable on developmental outcomes in hearing-impaired children. In children with no additional disability, significantly better cognitive and language scores were associated with the early-auditory intervention. Motor skills were not affected by the early-auditory intervention.

Multifrequency multicomponent tympanometry in children with a history of ventilation tube insertion.

OBJECTIVES: To use multifrequency multicomponent tympanometry (MF-MCT) for evaluating the middle ear mechano-acoustics of children with a history of ventilation tube (VT) insertion and to determine the effects of tube insertion sequelae on middle ear function. METHODS: A prospective case-control study in a tertiary referral center involving 26 children (51 ears) aged 3-15 years. The children had undergone VT insertion surgery at least one-year previously and had no other known ear diseases. In addition, 13 age-matched healthy controls (26 ears) with no prior history of ear disease were included. The patients and control subjects underwent an otoscopic examination, standard 226 Hz tympanometry, and MF-MCT. RESULTS: In 13.7% of cases, the VT was still in place in the operated ears. Post-operative myringosclerosis and/or eardrum retraction were noticed in 30% of ears with intact tympanic membranes in the patient group. While patients exhibited a great variability of tympanometric types (with standard 226 Hz tympanometry and tympanometric patterns with 1000 Hz MF-MCT), all cases in the control group had type A tympanograms and 3B1G patterns. CONCLUSION: The effects of VT treatment on the mechano-acoustics of the middle ear have been revealed in this study. It has also been determined that VT application may increase the mass effect on the middle ear functions, which can be detected in the tympanometric shape and pattern.

Is Septal Cartilage Graft via Transmastoid Approach Safe Enough in the Repair of Large Tegmen Defects?

INTRODUCTION: Tegmen defect (TD) has a potential of intracranial spread of middle ear infection, meningoencephalic herniation (MEH), and cerebrospinal fluid leakage (CSFL). Especially the defects >1 cm with MEH or CSFL are generally repaired via the classical middle fossa or minicraniotomy technique. The aim of this study was to show the efficiency of the intracranial, extradural placement of the septal cartilage graft in the closure of the TD larger than 1 cm via the transmastoid (TM) approach. METHODS: The demographic, preoperative, intraoperative, and postoperative data of 11 patients with chronic otitis media (COM) who had TD larger than 1 cm were reviewed retrospectively. Hospitalization time and hearing preservation with respect to MEH or CSFL were analyzed. RESULTS: The most common etiology of TD was cholesteatoma (82%), and 91% of the patients had multiple COM surgery history. The mean TD size was 15.4 (10-25) mm. Fifty-five percent of the patients presented with either MEH or CSFL. The mean follow-up of the patients was 22.5 (8-42) months. There was no significant difference between preoperative and postoperative mean bone conduction thresholds. Mean hospitalization time was 5.2 (3-10) days. There was no significant difference in the hospitalization time between patients with MEH or CSFL and without MEH or CSFL. Neither recurrence nor graft infection was encountered. CONCLUSION: Extradural grafting with the septal cartilage in the large TD up to 25 mm can be repaired efficiently via the TM approach without application of a lumbar drainage.

Is There Any Effect of Subjective Tinnitus on Vestibular Evoked Myogenic Potentials.

Idiopathic subjective tinnitus has a complex pathophysiology in which not only cochlear and central classical auditory pathways but also nonclassical auditory pathways of different parts of the brain are involved. Vestibuloocular and vestibulocollic pathways are the central projections of utricle and saccule used in the vestibular evoked myogenic potential (VEMP) test. Aim of this study was to investigate the effects of idiopathic subjective tinnitus on vestibuloocular and vestibulocollic pathways via VEMP. We prospectively analyzed 30 unilateral idiopathic subjective tinnitus patient's cervical, ocular VEMP tests, tinnitus handicap index scores, symptom duration and compared with contralateral ear and 35 healthy volunteers. The latencies and amplitudes of P1 and N1 waves were recorded and pathologic wave criteria was calculated according to healthy volunteer's data. In cervical VEMP there were significant longer latencies of P1 and N1 waves with respect to contralateral ear and control group. In ocular VEMP test, N1 and P1 latencies and amplitudes were not significantly different. The percentages of pathologic wave of the tinnitus side were not significantly higher in both cervical VEMP and ocular VEMP tests with respect to contralateral side. Tinnitus handicap index scores and symptom duration had no relationship with latency and amplitude of VEMP tests. Although cervical VEMP P1 and N1 latencies were significantly longer, subjective tinnitus did not result in pathological alterations in the VEMP test. Presence of subjective tinnitus is not an influencing factor in the VEMP interpretation.

Pairing of segmentation clock genes drives robust pattern formation.

Gene expression is an inherently stochastic process1,2; however, organismal development and homeostasis require cells to coordinate the spatiotemporal expression of large sets of genes. In metazoans, pairs of co-expressed genes often reside in the same chromosomal neighbourhood, with gene pairs representing 10 to 50% of all genes, depending on the species3-6. Because shared upstream regulators can ensure correlated gene expression, the selective advantage of maintaining adjacent gene pairs remains unknown6. Here, using two linked zebrafish segmentation clock genes, her1 and her7, and combining single-cell transcript counting, genetic engineering, real-time imaging and computational modelling, we show that gene pairing boosts correlated transcription and provides phenotypic robustness for the formation of developmental patterns. Our results demonstrate that the prevention of gene pairing disrupts oscillations and segmentation, and the linkage of her1 and her7 is essential for the development of the body axis in zebrafish embryos. We predict that gene pairing may be similarly advantageous in other organisms, and our findings could lead to the engineering of precise synthetic clocks in embryos and organoids.

Impact of fetal brain tissue derived mesenchymal stem cell and fibrin glue on facial nerve crash injury

Background/aim: To evaluate the clinical and histopathological effects of fetal brain tissue derived mesenchymal stem cells (FBTMSC) and fibrin glue (FG) on the facial nerve (FN) regeneration in rats with traumatic FN injury. Materials and methods: Twenty-eight Sprague Dawley rats were included in the study and divided into 4 groups. Traumatic FN injury (FP) was created by a surgical clamp compression to the main trunk of left FN in all groups. In the control group (group 1) no treatment was applied, in group 2 (FBTMSC group) 2 × 106 FBTMSC was injected, in group 3 (FG group) only FG was applied, in group 4 (FBTMSC and FG groups) both FBTMSC and FG were applied to the injured section of the nerve. The FN functions were evaluated clinically, immediately after the procedure and at 3rd, 5th, and 8th weeks postoperatively. The FNs of all subjects were excised after the 8th week; then the rats were sacrificed. The presence of stem cells in the injured zone was assessed using bromo-deoxyuridine (BrdU), and apoptosis was determined by the TUNEL method. Results: After the damage, total FP was observed in all subjects. Statistically significant functional improvement was observed in group 4 compared to all other groups (P < 0.005). TUNEL-positive cell count was statistically significantly higher in the control group than the other groups (P < 0.001). TUNEL-positive cell count was statistically significantly lower in group 4 than the other groups. The proportion of BrdU-stained cells in group 4 (5%) was higher than group 2 (2%). Conclusion: Clinically and histopathologically FBTMSC applied with FG may play a promising role as a regenerative treatment in posttraumatic FP.

Prognostic role of homeostasis model assessment and oral glucose tolerance test in nondiabetic patients with Bell's palsy

Background/aim: We aimed to revealthe incidence and predictive role of insulin resistance and distorted oral glucose tolerance test in nondiabetic patients withBell's Palsy (BP). Materials and methods: Eighty-sixpatients with BP and 28 control subjects; all with normal blood glucose levels and no history of diabetes, were enrolled in the study. We investigated insulin resistance (IR) in all subjects, in terms of HOMA-IR greater than 2.7. Sixty-two of the patients also underwent an oral glucose tolerance test (OGTT). Results: The mean HOMA-IR value was significantly increased in patients, compared to the control group (3.2 vs 1.6; P < 0.01). IR was detected more in BP patients than in controls (P < 0.05). The patients with higher HOMA-IR values had more severe facial dysfunction at the initial presentation and complete recovery time took longer than the patients with normal HOMA-IR value (75 days vs 42 days; P < 0.05). Following a 2h-OGTT, impaired glucose tolerance and newly diagnosed DM were found in 60% of the patients. Recovery time was significantly longer in prediabetics and newly diagnosed diabetic patients than in patients with normal glycemia (68 days, 52 days, and 32 days, respectively; P < 0.01). Conclusion: There is a strong linkage between HOMA-IR value and BP prognosis so HOMA-IR value may have a significant role of predicting BP prognosis at presentation.