Photobiomodulation therapy in improvement of harmful neural plasticity in sodium salicylate-induced tinnitus.

Tinnitus is a common annoying symptom without effective and accepted treatment. In this controlled experimental study, photobiomodulation therapy (PBMT), which uses light to modulate and repair target tissue, was used to treat sodium salicylate (SS)-induced tinnitus in a rat animal model. Here, PBMT was performed simultaneously on the peripheral and central regions involved in tinnitus. The results were evaluated using objective tests including gap pre-pulse inhibition of acoustic startle (GPIAS), auditory brainstem response (ABR) and immunohistochemistry (IHC). Harmful neural plasticity induced by tinnitus was detected by doublecortin (DCX) protein expression, a known marker of neural plasticity. PBMT parameters were 808 nm wavelength, 165 mW/cm2 power density, and 99 J/cm2 energy density. In the tinnitus group, the mean gap in noise (GIN) value of GPIAS test was significantly decreased indicated the occurrence of an additional perceived sound like tinnitus and also the mean ABR threshold and brainstem transmission time (BTT) were significantly increased. In addition, a significant increase in DCX expression in the dorsal cochlear nucleus (DCN), dentate gyrus (DG) and the parafloccular lobe (PFL) of cerebellum was observed in the tinnitus group. In PBMT group, a significant increase in the GIN value, a significant decrease in the ABR threshold and BTT, and also significant reduction of DCX expression in the DG were observed. Based on our findings, PBMT has the potential to be used in the management of SS-induced tinnitus.

S100a9 might act as a modulator of the Toll-like receptor 4 transduction pathway in chronic rhinosinusitis with nasal polyps.

Chronic rhinosinusitis with nasal polyp (CRSwNP) is a highly prevalent disorder characterized by persistent nasal and sinus mucosa inflammation. Despite significant morbidity and decreased quality of life, there are limited effective treatment options for such a disease. Therefore, identifying causal genes and dysregulated pathways paves the way for novel therapeutic interventions. In the current study, a three-way interaction approach was used to detect dynamic co-expression interactions involved in CRSwNP. In this approach, the internal evolution of the co-expression relation between a pair of genes (X, Y) was captured under a change in the expression profile of a third gene (Z), named the switch gene. Subsequently, the biological relevancy of the statistically significant triplets was confirmed using both gene set enrichment analysis and gene regulatory network reconstruction. Finally, the importance of identified switch genes was confirmed using a random forest model. The results suggested four dysregulated pathways in CRSwNP, including "positive regulation of intracellular signal transduction", "arachidonic acid metabolic process", "spermatogenesis" and "negative regulation of cellular protein metabolic process". Additionally, the S100a9 as a switch gene together with the gene pair {Cd14, Tpd52l1} form a biologically relevant triplet. More specifically, we suggested that S100a9 might act as a potential upstream modulator in toll-like receptor 4 transduction pathway in the major CRSwNP pathologies.

Mesenchymal Stem/Stromal Cell Therapy for Radiation-Induced Xerostomia in Previous Head and Neck Cancer Patients: A Phase II Randomized, Placebo-Controlled Trial.

PURPOSE: No effective treatment exists for radiation-induced xerostomia. The objective of this study was to compare the effect of adipose-derived mesenchymal stem/stromal cell (ASC) injection, relative to placebo, on salivary gland function in patients with radiation-induced xerostomia. PATIENT AND METHODS: In this single-centre, double-blind, placebo-controlled trial, patients with hyposalivation were randomised to receive ultrasound-guided injections of allogeneic ASCs or placebo into the submandibular glands. Patients were followed for 4 months. We evaluated unstimulated whole salivary flow rate (UWS), stimulated salivary flow rate, and patient-reported outcomes. Adverse events were recorded and immune response determined in blood samples. RESULTS: We enrolled 120 patients. ASC treatment resulted in a statistically significant UWS increase of 0.04 [95% confidence interval (CI), 0.02-0.06] mL/min (38%) compared with pretreatment baseline whereas placebo treatment did not cause a significant increase [0.01 (95% CI, -0.01 to 0.04) mL/min (21%)]. Both the ASC and placebo treatment yielded notable symptom reductions, with dry mouth decreasing by 13.6 and 7.7 units, sticky saliva decreased by 14.8 and 9.3 units, swallowing difficulties decreased by 7.9 and 8.0 units, and the summary score of the Xerostomia Questionnaire decreased 5.9 and 5.1 units for the ASC and placebo arms, respectively. We found no statistically significant group difference between the ASC and placebo arms for any of the outcomes. CONCLUSIONS: We could not confirm superiority of the ASC relative to placebo. ASC therapy significantly improved UWS in previous patients with head and neck cancer, whereas placebo resulted in an insignificant increase.

Cochlear Implantation in Children with Meningitis: A Multicenter Study on Auditory Performance and Speech Production Outcomes.

BACKGROUND: This study aims to evaluate speech production outcomes and auditory performance in children with post-meningitis deafness who were treated with cochlear implants. Additionally, the study assesses the impact of electrode insertion depth on surgical outcomes.". METHODS: We conducted a study on 66 pediatric patients with bilateral postmeningitis hearing loss who were being prepared for cochlear implantation at four tertiary referral academic institutions. The speech intelligibility rating (SIR) and categories of auditory performance (CAP) were evaluated after the first and second years following implantation. The patients were divided into two groups based on electrode insertion depth: one group had full electrode insertion (more than two-thirds), while the other had partial electrode insertion (less than two-thirds). We compared the SIR and CAP scores between the two groups to assess the impact of electrode insertion depth on outcomes. RESULTS: Before implantation, the median CAP score was one, but it improved significantly to six within two years after the procedure (P-value < 0.001). Similarly, the median SIR score before implantation was one, but it improved significantly to three within two years after surgery (P-value < 0.001). However, there was no significant difference between the partial and full electrode insertion groups in terms of CAP and SIR scores during the follow-up evaluations conducted after the first and second years. CONCLUSION: The study found that cochlear implantation significantly improved speech production skills and auditory performance in children with postmeningitis deafness. Importantly, the amount of electrode insertion at the time of implantation did not have a significant impact on the outcomes.

Olfactory status in neurodegeneration with brain iron accumulation disorders.

BACKGROUND: Olfactory dysfunction has been suggested as a diagnostic and discriminative biomarker in some neurodegenerative disorders. However, there are few studies regarding the olfactory status in rare diseases including neurodegeneration with brain iron accumulation (NBIA) disorders. METHODS: Genetically-confirmed NBIA patients were enrolled. Neurological and cognitive examinations were conducted according to the Pantothenate Kinase-Associated Neurodegeneration-Disease Rating Scale (PKAN-DRS) and the Mini-Mental State Examination (MMSE) questionnaire, respectively. Olfaction was assessed in three domains of odor threshold (OT), odor discrimination (OD), odor identification (OI), and total sum (TDI) score by the Sniffin' Sticks test. The olfactory scores were compared to a control group and a normative data set. RESULTS: Thirty-seven patients, including 22 PKAN, 6 Kufor Rakeb syndrome, 4 Mitochondrial membrane Protein-Associated Neurodegeneration (MPAN), 5 cases of other 4 subtypes, and 37 controls were enrolled. The mean PKAN-DRS score was 51.83±24.93. Sixteen patients (55.2%) had normal cognition based on MMSE. NBIA patients had significantly lower olfactory scores compared to the controls in TDI and all three subtests, and 60% of them were hyposmic according to the normative data. Including only the cognitively-normal patients, still, OI and TDI scores were significantly lower compared to the controls. The phospholipase A2-Associated Neurodegeneration (PLAN) and MPAN patients had a significantly lower OI score compared to the cognitively-matched PKAN patients. CONCLUSION: Olfactory impairment as a common finding in various subtypes of NBIA disorder can potentially be considered a discriminative biomarker. Better OI in PKAN compared to PLAN and MPAN patients may be related to the different underlying pathologies.

Non-thermal CO2 Laser Therapy (NTCLT): A Novel Photobiomodulative Approach for Immediate Pain Relief of Patchy Oral Mucositis Due to Chemotherapy of Solid Tumors.

Introduction: Chemotherapy-induced oral mucositis (COM) is a prominent complication of chemotherapy (CT). Non-thermal CO2 laser therapy (NTCLT) has been demonstrated as an innovative and safe photobiomodulative approach in some kinds of painful oral lesions. The purpose of this study was to evaluate the palliative effects of one session of NTCLT on COM lesions. Methods: Patients with painful COM (WHO grade:≥2) were included in this before-after clinical trial based on the eligibility criteria. The oral lesions were irradiated with a CO2 laser (power: 1 W, scanning the lesions with the rapid circular motion of the defocused handpiece) through a thick layer (3-4 mm) of a transparent gel containing a high-water content. The severity of pain in the lesions was self-assessed using a 0-to-10 visual analogue scale (VAS) for 7 consecutive days. The evaluating physician visited the patients on the 3rd and 7th days in search of any kind of complications. Results: Seventeen adult patients with 35 patches of OM due to chemotherapy of solid tumors completed the trial. Immediately after NTCLT, the mean for non-contact VAS pain scores of the lesions significantly declined from 4.91±2.356 to 0.29±0.622 (P<0.001) and the mean for contact VAS pain scores from 7.77±1.57 to 1.31±1.18 (P<0.001). The mean VAS pain scores of the lesions showed statistically significant differences between the follow-up periods compared to the baseline (P<0.001). The process was completely pain-free and required no anesthesia. After NTCLT, no kind of thermal adverse effects such as irritation, destruction, aggravation and even erythema were observed. Conclusion: Based on the results of this before-after clinical trial, NTCLT has the potential to be considered as a non-invasive and safe palliative option for the pain management of patchy OM due to chemotherapy of solid tumors.

Genetic insights into PHARC syndrome: identification of a novel frameshift mutation in ABHD12.

BACKGROUND: Mutations in ABHD12 (OMIM: 613,599) are associated with polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract (PHARC) syndrome (OMIM: 612674), which is a rare autosomal recessive neurodegenerative disease. PHARC syndrome is easily misdiagnosed as other neurologic disorders, such as retinitis pigmentosa, Charcot-Marie-Tooth disease, and Refsum disease, due to phenotype variability and slow progression. This paper presents a novel mutation in ABHD12 in two affected siblings with PHARC syndrome phenotypes. In addition, we summarize genotype-phenotype information of the previously reported patients with ABHD12 mutation. METHODS: Following a thorough medical evaluation, whole-exome sequencing was done on the proband to look for potential genetic causes. This was followed by confirmation of identified variant in the proband and segregation analysis in the family by Sanger sequencing. The variants were interpreted based on the American College of Medical Genetics and Genomics (ACMG) guidelines. RESULTS: A novel pathogenic homozygous frameshift variant, NM_001042472.3:c.601dup, p.(Val201GlyfsTer4), was identified in exon 6 of ABHD12 (ACMG criteria: PVS1 and PM2, PM1, PM4, PP3, and PP4). Through Sanger sequencing, we showed that this variant is co-segregated with the disease in the family. Further medical evaluations confirmed the compatibility of the patients' phenotype with PHARC syndrome. CONCLUSIONS: Our findings expand the spectrum of mutations in the ABHD12 and emphasize the significance of multidisciplinary diagnostic collaboration among clinicians and geneticists to solve the differential diagnosis of related disorders. Moreover, a summary based on mutations found so far in the ABHD12 gene did not suggest a clear genotype-phenotype correlation for PHARC syndrome.

Electrophysiological and molecular changes following neuroprotective placental protein administration on tinnitus-induced rats.

Objective: Despite 6%-20% of the adult population suffering from tinnitus, there is no standard treatment for it. Placenta extract has been used for various therapeutic purposes, including hearing loss. Here, we evaluate the effect of a novel neuroprotective protein composition (NPPC) extract on electrophysiological and molecular changes in the medial geniculate body (MGB) of tinnitus-induced rats. Methods: To evaluate the protein analysis by western blot, the rats were divided into three groups: (1) saline group (intraperitoneal injection of 200 mg/kg saline twice a day for 28 consecutive days, (2) chronic Na-Sal group received sodium salicylate as in the first group, and (3) chronic treatment group (received salicylate 200 mg/kg twice daily for 2 weeks, followed by 0.4 mg NPPC daily from day 14 to day 28). Single-unit recordings were performed on a separate group that was treated as in group 4. Gap-prepulse inhibition of the acoustic startle (GPIAS) and pre-pulse inhibition (PPI) was performed to confirm tinnitus in all groups at the baseline, 14th and 28th days. Results: Western blot analysis showed that the expression of γ-Aminobutyric acid Aα1 subunit (GABA Aα1), N-methyl-d-aspartate receptor subtype 2B (NR2B or NMDAR2B), α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors subunit GluR1 (GluR1), and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors subunit GluR2 (GluR2) decreased after Na-Sal injection, while NPPC upregulated their expression. MGB units in rats with tinnitus showed decreased spontaneous firing rate, burst per minute, and a spike in a burst. After NPPC administration, neural activity patterns showed a significant positive effect of NPPC on tinnitus. Conclusion: NPPC can play an effective role in the treatment of tinnitus in salicylate-induced rats, and MGB is one of the brain areas involved in these processes. Level of Evidence: NA.

Fabrication and optimization of multilayered composite scaffold made of sulfated alginate-based nanofiber/decellularized Wharton's jelly ECM for tympanic membrane tissue engineering.

In this study, we fabricated a novel multilayer polyvinyl alcohol (PVA)/alginate sulfate (ALG-S) nanofiber/decellularized Wharton's Jelly ECM (d-ECM) composite for tympanic membrane perforations (TMPs) tissue engineering (TE). Initially, electrospun PVA/ALG-S scaffolds with different blend ratios were fabricated. The influence of ALG-S ratio on surface morphology, mechanical, physical and biological properties of the nanofibers was studied. Secondly, 3-layer composites were developed as a combination of PVA/ALG-S nanofibers and d-ECM to take synergic advantages of electrospun mats and d-ECM. As part of the evaluation of the effects of d-ECM incorporation, the composite's mechanical properties, in vitro degradation, swelling ratio, and biological activities were assessed. The MTT assay showed that PVA/ALG-S nanofibers with 50:50 ratio provided a more desirable environment to support cell growth. A composite containing 25 mg/cm2 d-ECM was determined as the optimal composite through MTT assay, and this composite was used for animal studies inducing TMP regeneration. According to the in vivo studies, the optimal composite not only stimulated the healing of TMPs but also shortened the healing period. These results suggest that a multilayer nanofiber/hydrogel composite could be a potential platform for regenerating TMPs.

Consistency in contouring of organs at risk by artificial intelligence vs oncologists in head and neck cancer patients.

BACKGROUND: In the Danish Head and Neck Cancer Group (DAHANCA) 35 trial, patients are selected for proton treatment based on simulated reductions of Normal Tissue Complication Probability (NTCP) for proton compared to photon treatment at the referring departments. After inclusion in the trial, immobilization, scanning, contouring and planning are repeated at the national proton centre. The new contours could result in reduced expected NTCP gain of the proton plan, resulting in a loss of validity in the selection process. The present study evaluates if contour consistency can be improved by having access to AI (Artificial Intelligence) based contours. MATERIALS AND METHODS: The 63 patients in the DAHANCA 35 pilot trial had a CT from the local DAHANCA centre and one from the proton centre. A nationally validated convolutional neural network, based on nnU-Net, was used to contour OARs on both scans for each patient. Using deformable image registration, local AI and oncologist contours were transferred to the proton centre scans for comparison. Consistency was calculated with the Dice Similarity Coefficient (DSC) and Mean Surface Distance (MSD), comparing contours from AI to AI and oncologist to oncologist, respectively. Two NTCP models were applied to calculate NTCP for xerostomia and dysphagia. RESULTS: The AI contours showed significantly better consistency than the contours by oncologists. The median and interquartile range of DSC was 0.85 [0.78 - 0.90] and 0.68 [0.51 - 0.80] for AI and oncologist contours, respectively. The median and interquartile range of MSD was 0.9 mm [0.7 - 1.1] mm and 1.9 mm [1.5 - 2.6] mm for AI and oncologist contours, respectively. There was no significant difference in ΔNTCP. CONCLUSIONS: The study showed that OAR contours made by the AI algorithm were more consistent than those made by oncologists. No significant impact on the ΔNTCP calculations could be discerned.

Socioeconomic position and the pre-diagnostic interval among patients diagnosed with head and neck squamous cell carcinoma - a population-based study from DAHANCA.

BACKGROUND: The socioeconomic differences in survival are pronounced for patients diagnosed with head and neck cancer; disease stage at diagnosis is suggested to be a main driver of this association. This nationwide, population-based study investigates socioeconomic differences in the pre-diagnostic interval and disease stage at diagnosis. MATERIAL AND METHODS: Information on patient-reported symptoms, symptom onset and disease-specific factors was obtained from the nationwide population-based Danish Head and Neck Cancer Group (DAHANCA) database for patients diagnosed with head and neck squamous cell carcinoma between 2008 and 2019 in Denmark. Socioeconomic position (SEP) was measured by individual-level education, income and cohabitation status obtained from administrative registers. Socioeconomic differences in the interval from symptom onset to diagnosis were investigated in general linear models with 95% confidence intervals (CIs); overall and by subsite, symptom and comorbidity score. Consultation patterns prior to diagnosis were examined using methods for change-point detection. Associations with advanced-stage disease were estimated in logistic regression models. RESULTS: Patients with low, medium and high SEP had a similar interval from patient-reported symptom onset to diagnosis of 10 weeks. Although this interval varied according to primary symptom and anatomical subsite, no apparent socioeconomic differences were observed within these subgroups. Aligned with the patient-reported symptom onset, a distinct increase in consultation rates was observed at 9 weeks (95% CI [7.3; 10.7]) for patients with low SEP and 7 weeks (95% CI [4.8; 9.2]) for patients with high SEP, with overlapping CIs. Patients with low compared to high SEP had increased odds for advanced-stage glottic and oral cavity squamous cell carcinoma. For the remaining subsites the association varied according to SEP-indicator and TNM-edition. CONCLUSION: The interval from symptom onset to diagnosis and consultation patterns were similar across SEP groups. Still, socioeconomic differences in stage at diagnosis were observed for some - but not all - subsites.

Effectiveness and safety of mesenchymal stem/stromal cell for radiation-induced hyposalivation and xerostomia in previous head and neck cancer patients (MESRIX-III): a study protocol for a single-centre, double-blinded, randomised, placebo-controlled, phase II study.

BACKGROUND: A predominant side effect of radiotherapy for head and neck cancer is salivary gland hypofunction and xerostomia leading to debilitating oral disorders and impaired quality of life (QoL). Intraglandular mesenchymal stem cell therapy has shown promising results as a treatment for xerostomia. METHODS: This is a randomised, double-blinded, placebo-controlled, parallel-group, prospective, single-centre trial investigating the safety, tolerability, and effectiveness of allogeneic stem cells as a treatment for radiation-induced hyposalivation and xerostomia for previous head and neck cancer patients. We will include a total of 120 patients who previously have been treated with radiotherapy for a head and neck cancer in Denmark. Participants will be randomly assigned using block randomisation to one of two parallel groups in a 1:1 ratio to receive ultrasound-guided injection of allogeneic adipose-derived mesenchymal stem cell (ASC) (n = 60) or placebo (n = 60) into the submandibular glands. Placebo will consist of CryoStor10 (BiolifeSolutions), the freeze media for ASCs containing 10% dimethyl sulfoxide (DMSO). The primary endpoint is change in unstimulated whole saliva flow rate. The secondary endpoints are change in stimulated whole saliva flow rate, QoL, and composition of saliva. Further secondary endpoints are safety and immune response (human leukocyte antigen (HLA) response) to the stem cells will be assessed. Patients are evaluated at baseline (before treatment), after 4 months, and after 12 months. All study personnel, except study personnel thawing and preparing the treatment for injection, and participants will be blinded to group assignment. Unblinded study personnel will not participate in the outcome assessment. DISCUSSION: The trials will investigate the efficacy and safety of ASC injection to the submandibular gland as a potential new treatment for post-radiation xerostomia. We hope the results will pave the way for a clinically relevant treatment to ameliorate patients with xerostomia, a severely hampering condition. TRIAL REGISTRATION: The study is approved by the Danish Data Protection Agency (protocol number P-2020-1164), the National Ethics Committee protocol number: (Protocol number: 1802872), and the Danish Medical Agency (2018-000348-24). The protocol was registered at the ClinicalTrials.gov database (NCT04776538).

Antibacterial aligned nanofibrous chitosan/PVA patch for repairing chronic tympanic membrane perforations.

Chronic tympanic membrane (TM) perforation is a consequence of trauma or chronic otitis media, and these chronic TM perforations often lead to conduction hearing loss. This study focuses on the development of a patch using a combination of chitosan (CS) and polyvinyl alcohol (PVA) as graft material for repairing chronic tympanic membrane (TM) perforations. Aligned nanofibers were created using a specially designed collector (SDC) through the electrospinning method. The scanning electron microscopy (SEM) analysis revealed that the CS/PVA ratio of (15:85) resulted in uniform and bead-free nanofibers. The aligned nanofibers had a diameter of 131.11 ± 28 nm, indicating that the influence of the electrostatic field introduced by the SDC affected not only the nanofiber alignment but also the nanofiber diameter. The nanofiber angles demonstrated effective alignment. This patch is infused with thyme essential oil (TEO) for antibacterial properties. The results showed that its antibacterial property for Pseudomonas aeruginosa bacteria was enhanced in such a way that the diameter of the antibacterial halo increased from zero to 25 mm. Cell viability assays showed >80 % viability. A preclinical case study on six patients demonstrated the biocompatibility and promising potential of the fabricated patch for eardrum repair.

The human neuroprotective placental protein composition suppressing tinnitus and restoring auditory brainstem response in a rodent model of sodium salicylate-induced ototoxicity.

The effect of neuroprotective placental protein composition (NPPC) on the suppression of tinnitus and the restoration of the auditory brainstem response (ABR) characteristics was explored in tinnitus-induced rats. The animals were placed into two groups: (1) the study group, rats received sodium salicylate (SS) at the dose of 200 mg/kg twice a day for two weeks, and then 0.4 mg of the NPPC per day, between the 14th and 28th days, (2) the placebo group, rats received saline for two weeks, and then the NPPC alone between the 14th and 28th days. The gap pre-pulse inhibition of the acoustic startle (GPIAS), the pre-pulse inhibition (PPI), and the ABR assessments were performed on animals in both groups three times (baseline, day 14, and 28). The GPIAS value declined after 14 consecutive days of the SS injection, while NPPC treatment augmented the GPIAS score in the study group on the 28th day. The PPI outcomes revealed no significant changes, indicating hearing preservation after the SS and NPPC administrations. Moreover, some changes in ABR characteristics were observed following SS injection, including (1) higher ABR thresholds, (2) lowered waves I and II amplitudes at the frequencies of 6, 12, and 24 kHz and wave III at the 12 kHz, (3) elevated amplitude ratios, and (4) prolongation in brainstem transmission time (BTT). All the mentioned variables returned to their normal values after applying the NPPC. The NPPC use could exert positive therapeutic effects on the tinnitus-induced rats and improve their ABR parameters.

The brain functional connectivity alterations in traumatic patients with olfactory disorder after low-level laser therapy demonstrated by fMRI.

BACKGROUND: Low-level laser therapy (LLLT) has been clinically accepted to accelerate the nerve regeneration process after a nerve injury or transection. We aimed to investigate the neuronal basis and the influence of LLLT on brain functional networks in traumatic patients with olfactory dysfunction. METHODS: Twenty-four Patients with traumatic anosmia/hyposmia were exposed to pleasant olfactory stimuli during a block-designed fMRI session. After a 10-week period, patients as control group and patients who had completed the sessions of LLLT were invited for follow-up testing using the same fMRI protocol. Two-sample t-tests were conducted to explore group differences in activation responding to odorants (p-FDR-corrected <0.05). Differences of functional connectivity were compared between the two groups and the topological features of the olfactory network were calculated. Correlation analysis was performed between graph parameters and TDI score. RESULTS: Compared to controls, laser-treated patients showed increased activation in the cingulate, rectus gyrus, and some parts of the frontal gyrus. Shorter pathlength (p = 0.047) and increased local efficiency (p = 0.043) within the olfactory network, as well as decreased inter-network connectivity within the whole brain were observed in patients after laser surgery. Moreover, higher clustering and local efficiency were related to higher TDI score, as manifested in increased sensitivity to identify odors. CONCLUSIONS: The results support that low-level laser induces neural reorganization process and make new connections in the olfactory structures. Furthermore, the connectivity parameters may serve as potential biomarkers for traumatic anosmia or hyposmia by revealing the underlying neural mechanisms of LLLT.

Intranasal delivery of stem cells labeled by nanoparticles in neurodegenerative disorders: Challenges and opportunities.

Neurodegenerative disorders occur through progressive loss of function or structure of neurons, with loss of sensation and cognition values. The lack of successful therapeutic approaches to solve neurologic disorders causes physical disability and paralysis and has a significant socioeconomic impact on patients. In recent years, nanocarriers and stem cells have attracted tremendous attention as a reliable approach to treating neurodegenerative disorders. In this regard, nanoparticle-based labeling combined with imaging technologies has enabled researchers to survey transplanted stem cells and fully understand their fate by monitoring their survival, migration, and differentiation. For the practical implementation of stem cell therapies in the clinical setting, it is necessary to accurately label and follow stem cells after administration. Several approaches to labeling and tracking stem cells using nanotechnology have been proposed as potential treatment strategies for neurological diseases. Considering the limitations of intravenous or direct stem cell administration, intranasal delivery of nanoparticle-labeled stem cells in neurological disorders is a new method of delivering stem cells to the central nervous system (CNS). This review describes the challenges and limitations of stem cell-based nanotechnology methods for labeling/tracking, intranasal delivery of cells, and cell fate regulation as theragnostic labeling. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease.

Acoustic and optoacoustic stimulations in auditory brainstem response test in salicylate induced tinnitus.

As a common debilitating disorder worldwide, tinnitus requires objective assessment. In the auditory brainstem response (ABR) test, auditory potentials can be evoked by acoustic or optoacoustic (induced by laser light) stimulations. In order to use the ABR test in the objective assessment of tinnitus, in this study, acoustic ABR (aABR) and optoacoustic ABR (oABR) were compared in the control and tinnitus groups to determine the changes caused by sodium salicylate (SS)-induced tinnitus in rat. In both aABR and oABR, wave II was the most prominent waveform, and the amplitude of wave II evoked by oABR was significantly higher than that of aABR. Brainstem transmission time (BTT), which represents the time required for a neural stimulation to progress from the auditory nerve ending to the inferior colliculus, was significantly shorter in oABR. In the tinnitus group, there was a significant increase in the threshold of both ABRs and a significant decrease in the amplitude of wave II only in the oABR. Based on our findings, the ABR test has the potential to be used in the assessment of SS-induced tinnitus, but oABR has the advantages of producing more prominent waveforms and significantly reducing the amplitude of wave II in tinnitus.

The Therapeutic Outcome of Sialendoscopy in Patients with Sialoadenitis.

Introduction: Recent advances have led to the development of sialendoscopy, an accurate, minimally invasive procedure with high diagnostic and therapeutic capabilities in treating sialolithiasis. This study aimed to evaluate the results and complications of sialendoscopy in patients suffering from sialoadenitis. Materials and Methods: This study was a prospective interventional case series study on patients with sialoadenitis due to sludge or stone formation preoperatively confirmed by sonography or computed tomography (CT) scanning. Diagnostic sialendoscopy was performed, and the presence of stenosis, sludge, or stones inside the gland or duct was examined, and surgery was done. During follow-up time (18.8 ± 7.4 months), recurrence of symptoms, the need for reoperation, and postoperative complications were also assessed. Results: The sialendoscopy was performed in 51 patients, including 55 glands. Forty-five Patients (88.2%) reported pain relief, and 46 patients (90.2%) reported that the treatment using sialendoscopy was better than conservative methods. The duct restenosis also occurred in one patient requiring open surgery. In assessing the main factors predicting the need for reoperation, the site of involvement (parotid versus submandibular glands) and the size of the stone were identified as the main determinants. The best cut-off value for stone size in predicting reoperation requirement was 7.0mm, with a sensitivity of 100% and a specificity of 85.7%. Conclusion: Intraoperative sialendoscopy is a successful diagnostic and therapeutic tool with minimal postoperative complications in salivary gland duct involvement patients.

The genetic landscape and possible therapeutics of neurofibromatosis type 2.

Neurofibromatosis type 2 (NF2) is a genetic condition marked by the development of multiple benign tumors in the nervous system. The most common tumors associated with NF2 are bilateral vestibular schwannoma, meningioma, and ependymoma. The clinical manifestations of NF2 depend on the site of involvement. Vestibular schwannoma can present with hearing loss, dizziness, and tinnitus, while spinal tumor leads to debilitating pain, muscle weakness, or paresthesias. Clinical diagnosis of NF2 is based on the Manchester criteria, which have been updated in the last decade. NF2 is caused by loss-of-function mutations in the NF2 gene on chromosome 22, leading the merlin protein to malfunction. Over half of NF2 patients have de novo mutations, and half of this group are mosaic. NF2 can be managed by surgery, stereotactic radiosurgery, monoclonal antibody bevacizumab, and close observation. However, the nature of multiple tumors and the necessity of multiple surgeries over the lifetime, inoperable tumors like meningiomatosis with infiltration of the sinus or in the area of the lower cranial nerves, the complications caused by the operation, the malignancies induced by radiotherapy, and inefficiency of cytotoxic chemotherapy due to the benign nature of NF-related tumors have led a march toward exploring targeted therapies. Recent advances in genetics and molecular biology have allowed identifying and targeting of underlying pathways in the pathogenesis of NF2. In this review, we explain the clinicopathological characteristics of NF2, its genetic and molecular background, and the current knowledge and challenges of implementing genetics to develop efficient therapies.