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Acta Neuropathologica Communications Jun 2024Neurofibromatosis Type 1 (NF1) is caused by loss of function variants in the NF1 gene. Most patients with NF1 develop skin lesions called cutaneous neurofibromas (cNFs)....
snRNA-seq of human cutaneous neurofibromas before and after selumetinib treatment implicates role of altered Schwann cell states, inter-cellular signaling, and extracellular matrix in treatment response.
Neurofibromatosis Type 1 (NF1) is caused by loss of function variants in the NF1 gene. Most patients with NF1 develop skin lesions called cutaneous neurofibromas (cNFs). Currently the only approved therapeutic for NF1 is selumetinib, a mitogen -activated protein kinase (MEK) inhibitor. The purpose of this study was to analyze the transcriptome of cNF tumors before and on selumetinib treatment to understand both tumor composition and response. We obtained biopsy sets of tumors both pre- and on- selumetinib treatment from the same individuals and were able to collect sets from four separate individuals. We sequenced mRNA from 5844 nuclei and identified 30,442 genes in the untreated group and sequenced 5701 nuclei and identified 30,127 genes in the selumetinib treated group. We identified and quantified distinct populations of cells (Schwann cells, fibroblasts, pericytes, myeloid cells, melanocytes, keratinocytes, and two populations of endothelial cells). While we anticipated that cell proportions might change with treatment, we did not identify any one cell population that changed significantly, likely due to an inherent level of variability between tumors. We also evaluated differential gene expression based on drug treatment in each cell type. Ingenuity pathway analysis (IPA) was also used to identify pathways that differ on treatment. As anticipated, we identified a significant decrease in ERK/MAPK signaling in cells including Schwann cells but most specifically in myeloid cells. Interestingly, there is a significant decrease in opioid signaling in myeloid and endothelial cells; this downward trend is also observed in Schwann cells and fibroblasts. Cell communication was assessed by RNA velocity, Scriabin, and CellChat analyses which indicated that Schwann cells and fibroblasts have dramatically altered cell states defined by specific gene expression signatures following treatment (RNA velocity). There are dramatic changes in receptor-ligand pairs following treatment (Scriabin), and robust intercellular signaling between virtually all cell types associated with extracellular matrix (ECM) pathways (Collagen, Laminin, Fibronectin, and Nectin) is downregulated after treatment. These response specific gene signatures and interaction pathways could provide clues for understanding treatment outcomes or inform future therapies.
Topics: Humans; Schwann Cells; Skin Neoplasms; Benzimidazoles; Extracellular Matrix; Signal Transduction; Neurofibroma; Female; Male; RNA-Seq; Middle Aged; Adult; Neurofibromatosis 1; Protein Kinase Inhibitors; Transcriptome
PubMed: 38907342
DOI: 10.1186/s40478-024-01821-z -
Noise & HealthOtitis media (OM) refers to a common clinical ear disease. Noise seriously damages human hearing function. This study aimed to investigate the effects of various noise...
BACKGROUND
Otitis media (OM) refers to a common clinical ear disease. Noise seriously damages human hearing function. This study aimed to investigate the effects of various noise types on the hearing function of patients who have recovered from mild OM.
MATERIALS AND METHODS
A total of 160 patients with mild OM treated at our hospital from May 2020 to May 2023 were retrospectively selected for this study. Based on clinical data, the patients were divided into the non-noise group (n = 80) and the noise (n = 80) group. The hearing thresholds of the two groups were compared across various noise types at 500, 1000, and 2000 Hz. In addition, the hearing thresholds of the noise group were compared under the same conditions.
RESULTS
The noise group exhibited significantly higher hearing thresholds at 500, 1000, and 2000 Hz than the non-noise group (P < 0.05). Under traffic, urban construction, and industrial noises, the auditory thresholds at 500, 1000, and 2000 Hz in the noise group were significantly higher than those observed under domestic and speech noises (P < 0.05).
CONCLUSION
Noise shows a close relationship with the hearing function of patients with OM. Traffic, urban construction, and industrial noises greatly influence the hearing function of patients who have recovered from mild OM.
Topics: Humans; Otitis Media; Male; Female; Adult; Middle Aged; Retrospective Studies; Auditory Threshold; Noise; Hearing Loss, Noise-Induced; Aged
PubMed: 38904828
DOI: 10.4103/nah.nah_6_24 -
Noise & HealthDigital noise reduction (DNR) minimizes the effect of noise on speech signals by continuously monitoring frequency bands in the presence of noise. In the present study,...
AIMS
Digital noise reduction (DNR) minimizes the effect of noise on speech signals by continuously monitoring frequency bands in the presence of noise. In the present study, we explored the effect of DNR technology on speech intelligibility in individuals using hearing aids (HAs) and investigated implications for daily use.
METHODS AND MATERIAL
Eighteen participants with bilateral moderate sensorineural hearing loss (aged 16-45 years) were included. Bilateral receiver-in-the-ear HAs were fitted in the participants. The adaptive and nonadaptive (with a signal-to-noise ratio (SNR) of +5 and -5 dB, respectively) Turkish matrix sentence test (TURMatrix) in noise and free-field hearing assessments, including hearing thresholds with hearing aids, speech recognition thresholds (SRT), and speech discrimination scores, were conducted in two different conditions: HA in the DNR-on and DNR-off conditions.
RESULTS
No significant difference was observed between free-field hearing assessments with the HA in the DNR-off and DNR-on conditions (P > 0.05). Furthermore, the adaptive and nonadaptive TURMatrix revealed significant differences between the scores under the DNR-on and DNR-off conditions (P < 0.05). Nevertheless, under the DNR-on condition, there was no correlation between free-field hearing assessments with HA and TURMatrix results (P > 0.05). However, a significant correlation was observed between SRT scores with HA and TURMatrix scores (adaptive and nonadaptive, +5 and -5 dB SNR, respectively) under the DNR-off condition (P < 0.05).
CONCLUSION
Our study findings suggest that DNR can improve speech intelligibility in noisy environments. Therefore, DNR can enhance an individual's auditory comfort by improving their capacity to grasp speech in background noise.
Topics: Humans; Hearing Aids; Adult; Noise; Male; Middle Aged; Hearing Loss, Sensorineural; Female; Young Adult; Adolescent; Speech Intelligibility; Signal-To-Noise Ratio; Auditory Threshold; Speech Perception; Speech Reception Threshold Test
PubMed: 38904826
DOI: 10.4103/nah.nah_67_23 -
Noise & HealthPresbycusis can be mediated by the effects of inflammatory processes on the auditory system, and these aging biological mechanisms remain poorly studied.
CONTEXT
Presbycusis can be mediated by the effects of inflammatory processes on the auditory system, and these aging biological mechanisms remain poorly studied.
AIMS
The aim of this study was to determine whether plasma biomarkers are associated with hearing disorders caused by aging in the elderly.
SETTINGS AND DESIGN
Cross-sectional study with 106 participants in the Active Aging Project, 93 (88%) females and 13 (12%) males, with an average age of 70 years.
METHODS AND MATERIAL
Audiological evaluation was performed with pure tone audiometry and collection of peripheral blood for the measurement of plasma levels of interleukins 2, 4, 6, and 10, tumor necrosis factor-α, and interferon-γ by means of flow cytometry.
STATISTICAL ANALYSIS USED
The SPSS (v.0, SPSS Inc., Chicago, USA) was used for the analysis of the data obtained. For all data analyzed, the significance level adopted was P < 0.05 and 95% confidence interval.
RESULTS
There were statistically significant correlations between male and IL-2 (P = 0.031; rs = 0.210), mean II of the right ear (P = 0.004; rs = 0.279), longer in years (P = 0.002; rs = 0.307) and in hours (P = 0.004; rs = 0.281) of noise exposure also in males.
CONCLUSIONS
In the present study, there was an association between the male gender and higher plasma levels of IL-2, an increase in the average hearing in the right ear, and greater time in years and hours of exposure to noise. There was a predominance of mild sensorineural hearing loss and worsening of hearing related to age, characteristics of presbycusis.
Topics: Humans; Male; Female; Aged; Cross-Sectional Studies; Interleukin-2; Audiometry, Pure-Tone; Biomarkers; Presbycusis; Tumor Necrosis Factor-alpha; Interferon-gamma; Middle Aged; Aged, 80 and over; Aging
PubMed: 38904818
DOI: 10.4103/nah.nah_3_23 -
Ugeskrift For Laeger Jun 2024Ramsay Hunt syndrome (RHS) is an infection with the Varicella Zoster virus in the geniculate ganglion of the facial nerve. The syndrome consists of a triad of peripheral...
Ramsay Hunt syndrome (RHS) is an infection with the Varicella Zoster virus in the geniculate ganglion of the facial nerve. The syndrome consists of a triad of peripheral facial nerve palsy, ear pain and concurrent zoster rash in the ear canal. However, vesicles in the mouth can be seen. A rare complication of RHS is viral meningitis. This is a case report of a patient with orally manifested RHS and concurrent asymptomatic viral meningitis. This case aims to raise awareness of RHS with atypical presentation and concurrent viral meningitis and, thereby, the importance of a thorough neurological examination.
Topics: Humans; Herpes Zoster Oticus; Meningitis, Viral; Male; Female; Middle Aged
PubMed: 38903036
DOI: 10.61409/V02240092 -
NPJ Digital Medicine Jun 2024Middle-ear conditions are common causes of primary care visits, hearing impairment, and inappropriate antibiotic use. Deep learning (DL) may assist clinicians in...
Middle-ear conditions are common causes of primary care visits, hearing impairment, and inappropriate antibiotic use. Deep learning (DL) may assist clinicians in interpreting otoscopic images. This study included patients over 5 years old from an ambulatory ENT practice in Strasbourg, France, between 2013 and 2020. Digital otoscopic images were obtained using a smartphone-attached otoscope (Smart Scope, Karl Storz, Germany) and labeled by a senior ENT specialist across 11 diagnostic classes (reference standard). An Inception-v2 DL model was trained using 41,664 otoscopic images, and its diagnostic accuracy was evaluated by calculating class-specific estimates of sensitivity and specificity. The model was then incorporated into a smartphone app called i-Nside. The DL model was evaluated on a validation set of 3,962 images and a held-out test set comprising 326 images. On the validation set, all class-specific estimates of sensitivity and specificity exceeded 98%. On the test set, the DL model achieved a sensitivity of 99.0% (95% confidence interval: 94.5-100) and a specificity of 95.2% (91.5-97.6) for the binary classification of normal vs. abnormal images; wax plugs were detected with a sensitivity of 100% (94.6-100) and specificity of 97.7% (95.0-99.1); other class-specific estimates of sensitivity and specificity ranged from 33.3% to 92.3% and 96.0% to 100%, respectively. We present an end-to-end DL-enabled system able to achieve expert-level diagnostic accuracy for identifying normal tympanic aspects and wax plugs within digital otoscopic images. However, the system's performance varied for other middle-ear conditions. Further prospective validation is necessary before wider clinical deployment.
PubMed: 38902477
DOI: 10.1038/s41746-024-01159-9 -
World Journal of Clinical Cases Jun 2024Primary ciliary dyskinesia (PCD) is an inherited autosomal-recessive disorder of impaired mucociliary clearance characterized by chronic respiratory diseases,...
BACKGROUND
Primary ciliary dyskinesia (PCD) is an inherited autosomal-recessive disorder of impaired mucociliary clearance characterized by chronic respiratory diseases, otolaryngological diseases, central nervous system abnormalities, reproductive system abnormalities, and cardiac function abnormalities. General anesthesia in these patients is associated with a higher incidence of respiratory complications than in patients without the disease.
CASE SUMMARY
A 16-year-old male patient was referred to the emergency room complaining of right ankle pain due to distal tibiofibular fracture. Three years prior, he had been diagnosed with PCD. At that time, he had experienced several episodes of pneumonia, sinusitis, and chronic middle ear infections, for which he underwent surgical interventions. At the current admission, he presented with cough and sputum but no other respiratory symptoms. A chest computed tomography scan revealed centrilobular ground-glass opacities in both lower lobes and a calcified nodule in the left lower lobe. For the surgical procedure and postoperative pain management, combined spinal-epidural anesthesia was employed. The patient's postoperative pain score was measured by the numerical rating scale (NRS). On the day of surgery, his NRS was 5 points. By the second postoperative day, the NRS score had decreased to 2-3 points. The epidural catheter was removed on the fourth day following the operation. The patient was subsequently discharged no respiratory complications.
CONCLUSION
We performed combined spinal-epidural anesthesia in a patient with PCD. The patient experienced no additional respiratory complications and was discharged with a low NRS score for pain.
PubMed: 38898834
DOI: 10.12998/wjcc.v12.i17.3183 -
Scientific Reports Jun 2024This study examined the association between hearing loss in sporadic vestibular schwannoma patients and the proteome of perilymph (PL), cerebrospinal fluid (CSF), and...
This study examined the association between hearing loss in sporadic vestibular schwannoma patients and the proteome of perilymph (PL), cerebrospinal fluid (CSF), and vestibular schwannoma. Intraoperative sampling of PL and of CSF, and biopsy of vestibular schwannoma tissue, was performed in 32, 32, and 20 patients with vestibular schwannoma, respectively. Perilymph and CSF in three patients with meningioma and normal hearing were also sampled. The proteomes were identified by liquid chromatography coupled to high-resolution tandem mass spectrometry. Preoperative hearing function of the patients was evaluated with pure tone audiometry, with mean values at frequencies of 500, 1000, 2000, and 4000 Hz (PTA4) in the tumor-affected ear used to delineate three hearing groups. Analysis of the PL samples revealed significant upregulation of complement factor H-related protein 2 (CFHR2) in patients with severe to profound hearing loss after false discovery rate correction. Pathway analysis of biofunctions revealed higher activation scores in the severe/profound hearing loss group of leukocyte migration, viral infection, and migration of cells in PL. Upregulation of CFHR2 and activation of these pathways indicate chronic inflammation in the cochlea of vestibular schwannoma patients with severe to profound hearing loss compared with patients with normal hearing or mild hearing loss.
Topics: Humans; Neuroma, Acoustic; Female; Male; Middle Aged; Proteome; Perilymph; Hearing Loss; Adult; Aged; Cerebrospinal Fluid; Audiometry, Pure-Tone
PubMed: 38898156
DOI: 10.1038/s41598-024-64352-6 -
Scientific Reports Jun 2024The increasing incidence of oropharyngeal squamous cell carcinoma (OPSCC) is primarily due to human papillomavirus, and understanding the tumor biology caused by the...
The increasing incidence of oropharyngeal squamous cell carcinoma (OPSCC) is primarily due to human papillomavirus, and understanding the tumor biology caused by the virus is crucial. Our goal was to investigate the proteins present in the serum of patients with OPSCC, which were not previously studied in OPSCC tissue. We examined the difference in expression of these proteins between HPV-positive and -negative tumors and their correlation with clinicopathological parameters and patient survival. The study included 157 formalin-fixed, paraffin-embedded tissue samples and clinicopathological data. Based on the protein levels in the sera of OPSCC patients, we selected 12 proteins and studied their expression in HPV-negative and HPV-positive OPSCC cell lines. LRG1, SDR16C5, PIP4K2C and MVD proteins were selected for immunohistochemical analysis in HPV-positive and -negative OPSCC tissue samples. These protein´s expression levels were compared with clinicopathological parameters and patient survival to investigate their clinical relevance. LRG1 expression was strong in HPV-negative whereas SDR16C5 expression was strong in HPV-positive tumors. Correlation was observed between LRG1, SDR16C5, and PIP4K2C expression and patient survival. High expression of PIP4K2C was found to be an independent prognostic factor for overall survival and expression correlated with HPV-positive tumor status. The data suggest the possible role of LRG1, SDR16C5 and PIP4K2C in OPSCC biology.
Topics: Humans; Male; Oropharyngeal Neoplasms; Female; Middle Aged; Aged; Papillomavirus Infections; Glycoproteins; Carcinoma, Squamous Cell; Biomarkers, Tumor; Squamous Cell Carcinoma of Head and Neck; Papillomaviridae; Adult; Prognosis; Cell Line, Tumor
PubMed: 38898137
DOI: 10.1038/s41598-024-64823-w