Combination of a membrane bioreactor with a rotating biological contactor holding several diverse metazoans can reduce excess sludge with fouling mitigation.

In a membrane bioreactor (MBR) system, in situ sludge reduction techniques induce membrane fouling. To address this challenge, we incorporated a rotating mesh carrier, which can adsorb organic matter and provide a habitat for metazoans, into the anoxic tank of a conventional anoxic/oxic-MBR (A/O-MBR) system, termed rotating biological contactor-MBR (RBC-MBR), and evaluated treatment performance. Over 151 days, lab-scale RBC-MBR and A/O-MBR were used to treat municipal sewage. Both reactors showed similar COD and NH4+ removal rates. However, RBC-MBR reduced excess sludge by approximately 45 % compared with A/O-MBR. Microscopic observation and 18S rRNA gene-based microbial analysis revealed the persistence of microfauna and metazoans (oligochaetes, nematodes, and rotifers) in RBC, which are typically absent in activated sludge. Additionally, the metazoan's population in the RBC-MBR membrane tank was two-fold that of A/O-MBR, indicating enhanced sludge reduction through predation. Despite these reductions, the increase in transmembrane pressure was similar between RBC-MBR and A/O-MBR, suggesting that sludge holding by RBC mesh media degrade fouling substances, such as proteins and polysaccharides and improves sludge filterability, resulting in membrane fouling mitigation. Microbial communities in both reactors were similar, indicating that the installation of RBC did not alter the microbial community of sludge. Network analysis suggested potential symbiotic or prey-predator relationships between bacteria and metazoans. This study reveals that RBC-MBR effectively reduced the excess sludge while mitigating membrane fouling, highlighting one of the promising technology for applying metazoan predation into MBR.

Tympanic Membrane Regeneration Therapy for Pediatric Tympanic Membrane Perforation.

OBJECTIVE: To evaluate tympanic membrane regeneration therapy (TMRT) for pediatric tympanic membrane perforations (TMPs). STUDY DESIGN: Intervention study. SETTING: Research institute hospital. PATIENTS: In this study, 20 patients with chronic TMP (M/F: 13/7, 13/8 ears, age 0-15 years) treated with TMRT were evaluated. As comparison, 20 pediatric patients with chronic TMP who underwent myringoplasty/tympanoplasty were included. INTERVENTIONS: For the TM repair procedure, the edge of the TMP was disrupted mechanically, and gelatin sponge immersed in basic fibroblast growth factor was placed inside and outside the tympanic cavity and covered with fibrin glue. The TMP was examined 4 ± 1 weeks later. The protocol was repeated up to four times until closure was complete. MAIN OUTCOME MEASURES: Closure of the TMP and hearing improvement were evaluated at 16 weeks after the final regenerative procedure. Adverse events were monitored. RESULTS: The mean follow-up period was 427.1 days. The TM regenerated in all cases, but pinhole reperforation occurred in two cases, and the final closure rate was 90.5% (19 of 21). Hearing improved to 24.9 ± 7.6 dB on average before surgery and to 13.8 ± 5.4 dB after surgery. The AB gap improved from 12.9 ± 8.0 to 5.2 ± 3.5 dB.The myringoplasty/tympanoplasty group had significantly lower AB gap improvement compared with the TMRT group. There were no adverse events. CONCLUSIONS: TMRT can be expected to regenerate near-normal TMs with a high closure ratio, resulting in better-hearing improvement compared with the myringoplasty/tympanoplasty group, and is an effective treatment for children with long life expectancy.

Optimizing Tinnitus Management: The Important Role of Hearing Aids with Sound Generators.

Hearing aids (HAs), especially those with sound generators (SGs), are used in the management of tinnitus. However, their comparative efficacies and long-term outcomes remain unknown. Therefore, we investigated the efficacy and long-term outcomes of tinnitus therapy using various HA SG models. We retrospectively reviewed 666 patients with chronic tinnitus characterized by persistent symptoms for >6 months. At the initial visit, the patients received educational counselling on tinnitus (Utsunomiya method) and completed a comprehensive questionnaire comprising the tinnitus handicap inventory, a visual analog scale, the state-trait anxiety inventory, and the emotional intelligence scale. The scores were compared among various models of HA SGs and SGs. The patients underwent follow-ups for up to 2 years. Our results indicated that tinnitus retraining therapy using SGs and conventional HAs effectively managed chronic tinnitus. The prolonged use of HAs appeared to exacerbate tinnitus symptoms, emphasizing the superior long-term effectiveness of SG HAs, particularly ZEN (Widex ZEN, WS Audiology, Lynge, Denmark). Our findings indicate that HAs are useful in the first year, but their prolonged use may exacerbate tinnitus symptoms, whereas HA SGs are effective in the long term. Future studies should account for the variations in tinnitus treatment effects based on the type of sound employed.

Evaluating the Efficacy of Omalizumab in Severe Cedar Seasonal Allergic Rhinitis in Japan.

BACKGROUND: Traditional treatments for cedar seasonal allergic rhinitis include second-generation antihistamines, nasal corticosteroids, and sublingual immunotherapy (SLIT). Omalizumab (Xolair®), an anti-immunoglobulin E (IgE) monoclonal antibody, is an additional option for severe cases unresponsive to existing therapies. Numerous studies have demonstrated the therapeutic effectiveness of omalizumab for cedar seasonal allergic rhinitis; however, most reported results after only up to four weeks of follow-up. Therefore, this study evaluates the clinical efficacy of omalizumab throughout one whole cedar pollen season.   Subjects and methods: This study included patients from our department and the Otorhinolaryngology Department of Minami Osaka Hospital between 2021 and 2023 who were ≥ 12 years old and had serum total IgE levels of 30-1,500 IU/mL, a baseline weight of 30-150 kg, and persistent severe nasal symptoms despite conventional treatments. Patients taking oral steroids at the time of enrollment or had fewer than two omalizumab doses were excluded. Forty-six patients (26 males, 20 females; mean age, 19.1 ± 11.2 years) met these criteria and received subcutaneous omalizumab every 2 or 4 weeks based on their IgE levels and weight. Symptoms were assessed at baseline and 4, 8, and 12 weeks post-administration using the Total Nasal Symptom Score (TNSS) and the Japanese Standard Quality of Life Questionnaire (JRQLQ No. 1) for allergic rhinitis.   Results: Thirty-six patients were followed up for 8 weeks and 13 for 12 weeks. TNSS significantly improved from 6.6 to 4.5 at 4 weeks, 4.2 at 8 weeks, and 4.1 at 12 weeks (p<0.05). Nasal discharge, sneezing, nasal obstruction, itchy eyes, and tearfulness showed significant improvements (p<0.05). Quality of life scores improved in daily activities, sleep, and physical health from week 4 to week 12.   Discussion: Consistent with previous findings, omalizumab significantly improved nasal and ocular symptoms and quality of life in patients with severe cedar seasonal allergic rhinitis. Despite many patients discontinuing the drug after eight weeks due to high costs, the drug's effectiveness in preventing symptom recurrence suggests potential long-term benefits. Combining omalizumab with SLIT showed no significant differences in outcomes; however, further pharmacoeconomic studies are warranted to evaluate cost-effectiveness.   Conclusion: Omalizumab proved to be an effective treatment for severe cedar seasonal allergic rhinitis, providing significant symptom relief and quality of life improvements. Further studies should investigate its long-term efficacy and safety, including potential adverse effects and the development of anti-omalizumab antibodies.

Effectiveness of Anti-Calcitonin Gene-Related Peptide Medication in Vestibular Migraine: A Retrospective Cohort Study in an Asian Population.

BACKGROUND: Migraine and dizziness often coexist, with vestibular migraine (VM) presenting with vestibular symptoms and headaches. Calcitonin gene-related peptide (CGRP) may be involved in motion-induced symptoms; however, studies on the use of anti-CGRP monoclonal antibodies (mAbs) for the treatment of VM have yielded conflicting results. This study aimed to clarify the effectiveness of anti-CGRP mAbs in VM treatment. METHODS: This retrospective observational cohort study, conducted between 1 January 2021 and 31 March 2023, assessed 12 Japanese patients with VM who were treated with anti-CGRP mAbs (CGRP group) for 6 months and 11 Japanese patients who received standard of care for VM and served as controls. Clinical questionnaires and equilibrium tests were administered, with primary outcomes including changes in Dizziness Handicap Inventory (DHI) scores compared with baseline values. Objective variables included the DHI score and explanatory variables included demographic data, balance test results, head-up tilt (HUT) test results, vestibular test results and questionnaire survey results. Analysis of variance was used to assess the treatment effects of anti-CGRP mAbs, and multivariate regression analysis was performed to identify mAb responders. RESULTS: After 6 months, the CGRP group showed significant improvements in DHI scores [0 versus 6 months, odds ratio (95% confidence interval): 22.01 (0.13-43.88)] and number of vertigo/dizziness attacks per month [0 versus 6 months: 10.28 (2.80-17.76)]. No significant difference was observed in the control group [DHI scores, 0 versus 6 months: 0.65 (-26.84 to 28.14); number of vertigo/dizziness attacks per month, 0 versus 6 months: - 8.07 (- 23.77 to 7.62)]. Multivariate regression analysis showed that autonomic function at baseline was associated with mAb response in patients [ß estimates (95% confidence interval): 3.63 (0.21-7.06)]. CONCLUSIONS: Treatment with anti-CGRP mAbs was more effective than conventional treatment in preventing migraine in patients with VM. While the identified factors associated with treatment responsiveness offer valuable insights into personalised treatment approaches, further prospective studies are warranted to validate the findings due to our study's retrospective design and limited sample size.

Comprehensive Equilibrium Function Tests for an Accurate Diagnosis in Vertigo: A Retrospective Analysis.

Background/Objectives: An accurate diagnosis of vertigo is crucial in patient care. Traditional balance function tests often fail to offer independent, conclusive diagnoses. This study aimed to bridge the gap between traditional diagnostic approaches and the evolving landscape of automated diagnostic tools, laying the groundwork for advancements in vertigo care. Methods: A cohort of 1400 individuals with dizziness underwent a battery of equilibrium function tests, and diagnoses were established based on the criteria by the Japanese Society for Vertigo and Equilibrium. A multivariate analysis identified the key diagnostic factors for various vestibudata nlar disorders, including Meniere's disease, vestibular neuritis, and benign paroxysmal positional vertigo. Results: This study underscored the complexity of diagnosing certain disorders such as benign paroxysmal positional vertigo, where clinical symptoms play a crucial role. Additionally, it highlighted the utility of specific physical balance function tests for differentiating central diseases. These findings bolster the reliability of established diagnostic tools, such as audiometry for Meniere's disease and spontaneous nystagmus for vestibular neuritis. Conclusions: This study concluded that a multifaceted approach integrating multiple diagnostic indicators is crucial for accurate clinical decisions in vestibular disorders. Future studies should incorporate novel tests, quantitative assessments, and advanced technologies to enhance the diagnostic capabilities of vestibular medicine.

Gap Junction Beta-2 p.Val84Met Can Cause Autosomal Dominant Syndromic Hearing Loss With Keratoderma.

In this study, we report a case of bilateral mild hearing loss and keratoderma caused by a gap junction beta-2 (GJB2) variant. The proband was a nine-year-old Japanese boy with bilateral mild hearing loss at birth. The proband's father, sister, paternal aunt, and cousins had mild sensorineural hearing loss. Further evaluation revealed keratoderma on the feet of the proband, father, sister, paternal aunt, and cousins. We identified a heterozygous c.250G>A (p.Val84Met) variant in GJB2 as the cause of the autosomal dominant syndromic hearing loss with the skin disorder in this Japanese family and delineated the pathological significance of the variant. The Val84Met variant in GJB2 contributes to the autosomal dominant form of syndromic hearing loss with keratoderma.

Contribution of circulating monocytes in maintaining homeostasis of resident macrophages in postnatal and young adult mouse cochlea.

The percentage of macrophage subpopulations based on their origins in the adult cochlea remains unclear. This study aimed to elucidate the origins of cochlear macrophages during the onset phase and development of auditory function. We used three types of mice: wildtype ICR mice, colony-stimulating factor 1 receptor (Csf1r)-deficient mice, and Ms4a3Cre-Rosa tdTomato (Ms4a3tdT) transgenic mice. Macrophages were labeled with ionized calcium-binding adapter molecule 1 (Iba1), which is specific to more mature macrophages, and CD11b, which is specific to monocyte lineage. We investigated the spatial and temporal distribution patterns of resident macrophages in the cochlea during the postnatal and early adult stages. During the adult stages, the rate of monocytes recruited from the systemic circulation increased; moreover, Iba1+/CD11b- cochlear macrophages gradually decreased with age. Fate mapping of monocytes using Ms4a3tdT transgenic mice revealed an increased proportion of bone marrow-derived cochlear macrophages in the adult stage. Contrastingly, the proportion of yolk sac- and fetal liver-derived tissue-resident macrophages decreased steadily with age. This heterogeneity could be attributed to differences in environmental niches within the tissue or at the sub-tissue levels. Future studies should investigate the role of cochlear macrophages in homeostasis, inflammation, and other diseases, including infection, autoimmune, and metabolic diseases.

Outcomes of regenerative treatment for over 200 patients with tympanic membrane perforation.

OBJECTIVE: To evaluate outcomes of a regenerative treatment (RT) for over 200 patients with tympanic membrane perforation (TMP). The RT-TMP method involves a gelatin sponge, basic fibroblast growth factor (bFGF) and fibrin glue. METHODS: The study population included 216 patients and 234 ears (male: female =100:116; age 1-93 years). All enrolled patients were treated with RT-TMP in which TMP edges were disrupted mechanically and a gelatin sponge immersed in bFGF was inserted into the perforation. Fibrin glue was then dripped over the sponge. Patient outcomes including TMP closure rates, change in hearing level, and complications were obtained from retrospective medical chart reviews. The TMP was examined three or more weeks after surgery. The treatment was repeated up to 4 times until complete TMP closure was achieved. RESULTS: After mechanical disruption, the perforation size was Grade I, ≤1/3 of entire TM area in 22 ears (9.4 %), Grade II, 1/3-2/3 of entire TM in 77 ears (32.9 %) and Grade III, ≥2/3 of entire TM area in 135 ears (57.7 %). The overall TMP closure rates were 97.0 % (227/234). Complete TMP closure was achieved in 68.8 % (161/234), 22.6 % (53/234), 4.7 % (11/234) and 0.9 % (2/234) of ears after 1, 2, 3 and 4 treatments, respectively. In 7 of 234 ears (3.0 %), the TMPs were not closed completely after 4 treatments. There was no correlation between TMP size after mechanical disruption and number of treatments required to achieve complete closure (Fisher's exact test p = 0.70). The mean air-conduction hearing threshold at low frequency improved from 57.3 ± 16.7 dB before treatment to 37.3 ± 16.0 dB (p < 0.0001) after closure of TMPs. For middle and high frequencies, the improvement was 49.0 ± 19.3 dB to 36.9 ± 17.9 dB (p < 0.0001) and 57.7 ± 22.9 dB to 49.2 ± 23.3 dB (p < 0.0001), respectively. The mean air-bone gaps also improved significantly, and were within 10 dB at 250 Hz, 500 Hz and 1 kHz, and 11 dB at 2 kHz. One or more complications occurred in 32 patients (32/216; 14.8 %). The most common complication was formation of an epithelial pearl (16 ears; 6.8 %), followed by severe TM retraction (9 ears; 3.8 %) and otitis media with effusion (6 ears; 2.6 %). There were no serious complications that caused deterioration of the patient's general condition. CONCLUSION: Our results showed that RT-TMP had high success rates for TMP closure and good hearing improvement and produced no severe complications that could affect general health status. This novel therapy is simple, safe and minimally invasive, and could help improve the quality of life in patients with TMP.

Diagnosing Middle Ear Malformation by Pure-Tone Audiometry Using a Three-Dimensional Finite Element Model: A Case-Control Study.

BACKGROUND: Hearing loss caused by middle ear malformations is treated by tympanoplasty to reconstruct the acoustic conduction system. The mobility of the ossicles plays a crucial role in postoperative success. However, identifying the location of ossicular malformation based solely on preoperative audiograms is challenging due to the complex relationship between fixation location, deformity levels, and ossicular mobility. METHODS: Middle ear finite element models for simulating ossicular malformations were created, and the results were compared with the actual preoperative audiograms. RESULTS: This approach objectively diagnosed ossicular fixation and disarticulation, bypassing traditional criteria reliant on physician examination or imaging. CONCLUSION: This study suggests that future research should focus on developing a diagnostic framework utilizing large-scale data.

Different solubilizing ability of cyclodextrin derivatives for cholesterol in Niemann-Pick disease type C treatment.

BACKGROUND: Niemann-Pick disease type C (NPC) is a fatal neurodegenerative disorder caused by abnormal intracellular cholesterol trafficking. Cyclodextrins (CDs), the most promising therapeutic candidates for NPC, but with concerns about ototoxicity, are cyclic oligosaccharides with dual functions of unesterified cholesterol (UC) shuttle and sink that catalytically enhance the bidirectional flux and net efflux of UC, respectively, between the cell membrane and the extracellular acceptors. However, the properties of CDs that regulate these functions and how they could be used to improve treatments for NPC are unclear. METHODS: We estimated CD-UC complexation for nine CD derivatives derived from native α-, ß-, and γ-CD with different cavity sizes, using solubility and molecular docking analyses. The stoichiometry and complexation ability of the resulting complexes were investigated in relation to the therapeutic effectiveness and toxicity of each CD derivative in NPC experimental models. FINDINGS: We found that shuttle and sink activities of CDs are dependent on cavity size-dependent stoichiometry and substituent-associated stability of CD-UC complexation. The ability of CD derivatives to form 1:1 and 2:1 complexes with UC were correlated with their ability to normalize intracellular cholesterol trafficking serving as shuttle and with their cytotoxicity associated with cellular UC efflux acting as sink, respectively, in NPC model cells. Notably, the ability of CD derivatives to form an inclusion complex with UC was responsible for not only efficacy but ototoxicity, while a representative derivative without this ability negligibly affected auditory function, underscoring its preventability. CONCLUSIONS: Our findings highlight the importance of strategies for optimizing the molecular structure of CDs to overcome this functional dilemma in the treatment of NPC.

Initiation and progression of Early-Stage microbial-driven membrane fouling in membrane bioreactors: a review.

Microbial biofilm development on the membrane surface of bioreactors results in membrane flux decline (biofouling). Biofouling is one of the most severe problems limiting the use of these bioreactors. For detailed understanding of the biofouling, microbial community and dissolved organic matter analyses have been performed in recent decades. Although most previous studies have focused on mature biofilms at the end point of biofouling, understanding of the early stages is crucial to mitigate biofilm formation. Thus, recent studies have focused on the impact of early-stage biofilm development and indicated a clear difference in microbial communities between early-stage and mature biofilms. In addition, certain bacteria play a significant role in early-stage biofilms. The present mini-review systematically summarizes the foulants present during early-stage fouling, provides novel perspectives on fouling mechanisms, and discusses the neglected effect of planktonic bacteria.

Arginine-Rich Cell-Penetrating Peptide-Mediated Transduction of Mouse Nasal Cells with FOXP3 Protein Alleviates Allergic Rhinitis.

Intranasal corticosteroids are effective medications against allergic rhinitis (AR). However, mucociliary clearance promptly eliminates these drugs from the nasal cavity and delays their onset of action. Therefore, a faster, longer-lasting therapeutic effect on the nasal mucosa is required to enhance the efficacy of AR management. Our previous study showed that polyarginine, a cell-penetrating peptide, can deliver cargo to nasal cells; moreover, polyarginine-mediated cell-nonspecific protein transduction into the nasal epithelium exhibited high transfection efficiency with minimal cytotoxicity. In this study, poly-arginine-fused forkhead box P3 (FOXP3) protein, the "master transcriptional regulator" of regulatory T cells (Tregs), was administered into the bilateral nasal cavities of the ovalbumin (OVA)-immunoglobulin E mouse model of AR. The effects of these proteins on AR following OVA administration were investigated using histopathological, nasal symptom, flow cytometry, and cytokine dot blot analyses. Polyarginine-mediated FOXP3 protein transduction induced Treg-like cell generation in the nasal epithelium and allergen tolerance. Overall, this study proposes FOXP3 activation-mediated Treg induction as a novel and potential therapeutic strategy for AR, providing a potential alternative to conventional intranasal drug application for nasal drug delivery.

Mitochondrial alterations in the cochlea of Cdk5rap1-knockout mice with age-related hearing loss.

Previous studies have revealed that age-related hearing loss (AHL) in Cdk5 regulatory subunit-associated protein 1 (Cdk5rap1)-knockout mice is associated with pathology in the cochlea. Here, we aimed to identify mitochondrial alterations in the cochlea of Cdk5rap1-knockout mice with AHL. Mitochondria in the spiral ganglion neurons (SGNs) and hair cells (HCs) were normal despite senescence; however, the mitochondria of types I, II, and IV spiral ligament fibrocytes were ballooned, damaged, and ballooned, respectively, in the stria vascularis. Our results suggest that the accumulation of dysfunctional mitochondria in the lateral wall, rather than the loss of HCs and SGNs, leads to the onset of AHL. Our results provide valuable information regarding the underlying mechanisms of AHL and the relationship between aberrant tRNA modification-induced hearing loss and mitochondrial dysfunction.

Inoculation of lymphocytes from young mice prevents progression of age-related hearing loss in a senescence-associated mouse model.

Despite the increase in age-related hearing loss (ARHL) prevalence owing to increased population aging, preventive measures against ARHL have not yet been established. The immune system becomes one of the most dysfunctional systems upon aging, and immunosenescence greatly affects homeostasis and promotes systemic aging along with chronic inflammation and oxidative stress. This study aimed to determine whether immuno-rejuvenation procedures can prevent ARHL and have clinical applications as well as to analyze the communication mechanisms between the systemic immune system and the cochlea using a murine model. Lymphocytes from young mice inhibited the progression of ARHL. The method of cryopreserving these lymphocytes and inoculating them at the onset of ARHL suggests their clinical application. Mice that were administered this treatment not only maintained auditory threshold but also avoided spinal ganglion degeneration, cellular immune aging, and nitric oxide production, which causes age-related tissue damage. These findings coincide with our previous strategies against immunosenescence and neuronal aging. Therefore, the manipulation of systemic immune function may contribute not only to the prevention of ARHL but also to the development of novel anti-aging clinical measures, paving the way to healthy longevity with preserved organ function.

Modified Fukuda stepping motion assessment of young healthy adults using portable inertial measurement units.

Currently, vestibular rehabilitation approaches used to monitor body position and movement during rehabilitation training require specialized equipment or rely on clinician observation. Thus, a simpler position-sensing approach that can be used to monitor movement during vestibular rehabilitation is required. This study used wearable motion sensors with built-in accelerometers and gyrometers to assess movement in adults. We explored stepping patterns in adults using this motion-sensing system. Six healthy adults (men, age 27.3 ± 5.8 years) underwent a modified Fukuda stepping test (Foulage test [FT]) while wearing a six-axis motion sensor (accelerometer: X-axis, Y-axis, Z-axis; gyrometer: X-axis, Y-axis, Z-axis) positioned at the head, thorax, and lumbar spine. For motion sensor parameters, we calculated the root mean square (RMS), autocorrelation coefficient (AC), power spectrum (PS) of the AC, and Euler angles from the six-axis motion sensor. For the FT parameters, the FT value, step variance, and θ values were calculated. Data were analyzed, and multivariable regression analysis was performed using the FT value, step variance, and θ value as the dependent variables to investigate their influence on dynamic equilibrium. The explanatory variables included the motion sensor parameters, RMS, AC, and PS. Our results suggested that almost no head and lumbar spine movement occurred while stepping with eyes open. Contrastingly, the head and lumbar spine swayed with eyes closed. This accelerometric and gyroscopic device is easy to use, does not require specialized equipment, and can be used to analyze performance in the modified Fukuda stepping test in clinical practice. Inertial sensors have many advantages over other sensing technologies.

Long-term exposure to high-concentration dexamethasone in the inner ear via intratympanic administration.

The first-line treatment for inner ear disorders is usually oral/systemic steroids. Intratympanic steroid therapy is an alternative option; however, it requires multiple office visits owing to the short residence time of steroids in the inner ear (systemic: 24 h, intratympanic: 2-3 h). Therefore, intratympanic injections of higher steroid concentrations could result in longer drug exposure, providing better treatment outcomes. This study aimed to develop a prototype for high-concentration steroids and examine their safety and feasibility in vivo. Using wild-type Institute for Cancer Research mice, high-concentration steroids (50 mg/mL dexamethasone), typical steroid concentrations (3.3 mg/mL dexamethasone), and sterile saline were administrated into the middle ear cavity via tympanic membrane injection. Auditory brainstem response analysis, vestibular function tests, and morphological analyses were performed to examine the safety and utility of High-conc Dex. One month post-injection, the frequency-averaged auditory brainstem response thresholds of high-dose dexamethasone-treated mice were not significantly different from those of low-dose dexamethasone- and saline-treated mice at all tested frequencies. Furthermore, the total points on vestibular function tests were similar between the three groups. Morphologically, no damage to the inner ear/middle ear mucosa was observed in all groups. Two months post-injection, dexamethasone could still be detected in the high-dose dexamethasone group. Altogether, our data successfully demonstrates the feasibility and safety of high-dose dexamethasone for in vivo use in the middle ear and ensure that the drug localizes to the inner ear. Further research is warranted to develop this new treatment strategy and further characterize its effects in vivo.

Metformin Reduces the Incidence of Sensorineural Hearing Loss in Patients With Type 2 Diabetes Mellitus: A Retrospective Chart Review.

Introduction and objectives Acquired sensorineural hearing loss (SNHL) has become a critical societal issue in recent years. SNHL is considered a risk factor for type 2 diabetes mellitus (T2DM). Metformin is commonly used to treat T2DM. However, its effects on SNHL have not been reported yet. Hence, this study aimed to evaluate the association between the use of metformin and SNHL incidence. Patients and methods In this retrospective matched-cohort study, the medical records of 1219 patients with T2DM aged >18 years from our hospital's inpatient database from January 1, 2012, to December 31, 2019, were examined, and matched cohorts were generated (76 patients receiving metformin and 76 not receiving metformin). A multivariable logistic regression analysis was performed to investigate the factors influencing the incidence of SNHL. Results After adjustment by propensity matching, multivariable logistic regression analysis revealed that the non-use of metformin increased the risk of developing SNHL (odds ratio, 0.26; 95% confidence interval, 0.07-0.93; p = 0.03). Conclusions This study demonstrated an association between the use of metformin and a reduced incidence of SNHL among patients with T2DM.

An increase in sludge loading rate induces gel fouling in membrane bioreactors treating real sewage.

The main objective of this study was to investigate the cause of gel fouling in membrane bioreactors (MBRs) treating real sewage in terms of soluble microbial products (SMPs) and microbial aspects. Two anoxic/oxic-MBRs were operated as the control reactor (S1) and the sludge loading rate increased reactor (S2). The reactors were operated under low-temperature around 11 °C conditions. Membrane permeability substantially decreased in S2, and gel layer biofilm was formed on membrane surface. In contrast, the permeability of S1 gradually decreased and cake layer formed. When gel fouling occurred, the protein and polysaccharide of SMP in S2 were 47 and 23 mg L-1, which were significantly lower than those recorded in S1 accounted for 118 and 68 mg L-1, respectively. Furthermore, the total organic carbon concentration of SMPs was 24 mg L-1, which was lower than the influent in S2, accounted for 62 mg L-1. Finally, Campylobacteraceae which exists in sewage and uncultured OD1, dominated the gel layer biofilm in S2, unlike the cake layer biofilm in S1. These results indicated that the gel layer biofilm might be composed of influent substances, demonstrating the importance of influent decomposition in MBR for gel fouling mitigation.

Effects of Kampo medicine hangebyakujutsutemmato on persistent postural-perceptual dizziness: A retrospective pilot study.

BACKGROUND: Persistent postural-perceptual dizziness (PPPD) is a functional disorder, typically preceded by acute vestibular disorders. It is characterized by a shift in processing spatial orientation information, to favor visual over vestibular and somatosensory inputs, and a failure of higher cortical mechanisms. To date, no therapies for PPPD have been approved. Kampo medicine hangebyakujutsutemmato (HBT) has been reported to alleviate disturbances of equilibrium. We hypothesized that HBT would be a beneficial treatment for PPPD. AIM: To examine the efficacy of HBT for the treatment of PPPD. METHODS: Patients with PPPD were enrolled and divided into two groups: The HBT group (n = 24) and the non-HBT group (n = 14). The participants completed questionnaire surveys [Niigata PPPD questionnaire (NPQ), dizziness handicap inventory, hospital anxiety and depression scale (HADS), orthostatic dysregulation questionnaire, pittsburg sleep quality index (PSQI), and motion sickness scores] before and after HBT treatment. Additionally, to identify HBT responders, multivariate regression analysis was performed using the results of the questionnaire surveys and equilibrium tests; including stabilometry, and caloric, vestibular evoked myogenic response, and head-up tilt tests. RESULTS: Thirty-eight outpatients were included in this study, of which 14 patients (3 men, 11 women; mean age, 63.5 ± 15.9 years) received treatment without HBT, and 24 (1 man, 23 women; mean age, 58.2 ± 18.7 years) received combination treatment with HBT. Following HBT treatment, NPQ scores decreased significantly (baseline 40.1 ± 10.0 vs 2 mo 24.6 ± 17.7, P < 0.001). No statistically significant changes were observed in the NPQ scores in the non-HBT group (baseline 38.6 ± 12.2 vs 2 mo 39.4 ± 14.4, P = 0.92). Multivariable regression analysis revealed that the results of stabilometry (P = 0.02) and the caloric (P = 0.03), and head-up tilt tests (P < 0.001), HADS (P = 0.003), and PSQI (P = 0.01) were associated with HBT responsiveness in PPPD patients. CONCLUSION: HBT may be an effective adjunct therapy for PPPD. Patients with autonomic dysfunction, unstable balance, semicircular canal paresis, anxiety, and poor sleep quality may be high responders to HBT.