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Hearing loss is known to exacerbate cognitive decline in humans. However, the variability in the impact of cognitive function is large, making predictions and drawing causal links difficult. We tested cognitive function in mice using an 8 arm radial maze (8ARM) that has no auditory cues and found that deafened mice showed a dramatic deficit in working memory. We used a hearing loss model that placed the human diphtheria toxin receptor (HDTR) in inner hair cells (IHCs) so that upon exposure to diphtheria toxin (DT), IHCs were selectively ablated. Despite this very uniform and complete deafening, there was a large variance in cognitive function loss, implicating a biological cause to the variance. We are creating a battery of behavioral tests to better investigate this variance and to test the fundamental hypothesis that the impact of hearing loss is in part dependent on how the individual animal weights hearing in sensory integration circuits. This battery of tests has the added advantage of being utilized for assessing the impact of hearing restoration treatments and for defining thresholds of hearing loss that lead to cognitive deficits. We will include the Y-maze and Novel object recognition test (NORT) as tests for memory both short term and consolidation and with the added advantage of repeated measures. We are including visual and auditory training to assess both learning and acuity as a proxy for sensory weighting. And finally, we are measuring auditory evoked potentials in awake animals in an attempt to identify correlations that can be used as predictors of cognitive function sensitivity. [ABSTRACT FROM AUTHOR]

Introduction: Excess abdominal fat is an independent predictor of the risk factors and the morbidity of obesity related diseases such as type 2 diabetes, hypertension, dyslipidaemia and cardiovascular diseases. The Waist Circumference (WC) is positively correlated with the abdominal fat. Hence, the waist circumference is a valuable, convenient and a simple measurement method which can be used for identifying the individuals who are at an increased risk for the above mentioned diseases. Objectives: 1. To assess the abdominal obesity by measuring the waist circumference among the women who were aged 20 years and above in an urban slum of Chennai, India. 2. To identify the socio -demographic factors which were associated with the abdominal obesity in the above study population. Settings and Design: A community based and a cross sectional study was carried out in an urban slum of Chennai, India. Methods and Materials: The present study was undertaken in an urban slum of Chennai city, among the women who were aged 20 years and above. One slum was selected randomly and the households in the slum were sampled by a systematic random sampling method. A pre-designed and a pre-tested questionnaire was used to collect the information regarding the socio-demographic profile of the women. Their waist circumference was measured by using a flexible inch tape. As per the World Health Organization (WHO), the International Obesity Task Force (IOTF) and the International Association for the Study of Obesity (IASO)(2000), the following cut off values for the waist circumference were used to assess the abdominal obesity for women: WC<80cms - normal and WC ≥ 80cms-abdominal obesity. Statistical Analysis: It was done by using the Statistical Package For Social Science (SPSS ), version 11.5. The prevalence was expressed in percentage and the Chi square test was used to find its association with the factors. Results: In the study population, the prevalence of abdominal obesity (WC ≥ 80 cms) was 29.8% (95% Confidence Interval [CI] 25.9-34 %). A significant association was found between the age, religion, a higher socio-economic status and the abdominal obesity. No significant association was noted between the educational status, occupation, marital status, type of family and the abdominal obesity. Conclusion: Abdominal obesity among the urban slum women is on the rise. The abdominal obesity was found to be significantly higher among the slum women with increasing age and in those who belonged to the muslim religion and to a higher socio-economic status. [ABSTRACT FROM AUTHOR]

Introduction: Cochlear afferent synapses connecting inner hair cells to spiral ganglion neurons are susceptible to excitotoxic trauma on exposure to loud sound, resulting in a noise-induced cochlear synaptopathy (NICS). Here we assessed the ability of cyclic AMP-dependent protein kinase (PKA) signaling to promote cochlear synapse regeneration, inferred from its ability to promote axon regeneration in axotomized CNS neurons, another system refractory to regeneration., Methods: We mimicked NICS in vitro by applying a glutamate receptor agonist, kainic acid (KA) to organotypic cochlear explant cultures and experimentally manipulated cAMP signaling to determine whether PKA could promote synapse regeneration. We then delivered the cAMP phosphodiesterase inhibitor rolipram via implanted subcutaneous minipumps in noise-exposed CBA/CaJ mice to test the hypothesis that cAMP signaling could promote cochlear synapse regeneration in vivo ., Results: We showed that the application of the cell membrane-permeable cAMP agonist 8-cpt-cAMP or the cAMP phosphodiesterase inhibitor rolipram promotes significant regeneration of synapses in vitro within twelve hours after their destruction by KA. This is independent of neurotrophin-3, which also promotes synapse regeneration. Moreover, of the two independent signaling effectors activated by cAMP - the cAMP Exchange Protein Activated by cAMP and the cAMP-dependent protein kinase - it is the latter that mediates synapse regeneration. Finally, we showed that systemic delivery of rolipram promotes synapse regeneration in vivo following NICS., Discussion: In vitro experiments show that cAMP signaling promotes synapse regeneration after excitotoxic destruction of cochlear synapses and does so via PKA signaling. The cAMP phosphodiesterase inhibitor rolipram promotes synapse regeneration in vivo in noise-exposed mice. Systemic administration of rolipram or similar compounds appears to provide a minimally invasive therapeutic approach to reversing synaptopathy post-noise., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Hemachandran, Hu, Kane and Green.)

Aminoglycosides are potent antibiotics that are commonly prescribed worldwide. Their use carries significant risks of ototoxicity by directly causing inner ear hair cell degeneration. Despite their ototoxic side effects, there are currently no approved antidotes. Here we review recent advances in our understanding of aminoglycoside ototoxicity, mechanisms of drug transport, and promising sites for intervention to prevent ototoxicity., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: To investigate prognostic factors for retinal sensitivity assessed by microperimetry in patients with Vogt-Koyanagi-Harada (VKH) disease., Methods: In total, 34 patients with initial-onset acute disease and 19 patients with chronic recurrent disease were retrospectively evaluated., Results: The mean follow-up period was 40.4 ± 40.5 months. Sensitivity was significantly worse in eyes with more severe anterior segment inflammation at presentation, as indicated by the presence of mutton-fat keratic precipitates, anterior chamber reaction ≥2+, and posterior synechiae. Chronic recurrent presentation, development of complications, and 'sunset glow fundus' were significantly associated with worse sensitivity. Using logistic regression analysis, better sensitivity was significantly associated with initial-onset acute presentation (odds ratio, OR = 6.9; 95% confidence interval, CI = 1.53-9.66)., Conclusions: Chronic recurrent presentation and development of complications and 'sunset glow fundus' are associated with a worse sensitivity outcome.

Purpose: To evaluate the effectiveness and safety of mycophenolate mofetil (MMF) as first-line therapy combined with systemic corticosteroids in initial-onset acute uveitis associated with Vogt-Koyanagi-Harada (VKH) disease., Methods: This prospective study included 38 patients (76 eyes). The main outcome measures were final visual acuity, corticosteroid-sparing effect, progression to chronic recurrent granulomatous uveitis and development of complications, particularly 'sunset glow fundus'., Results: The mean follow-up period was 37.0 ± 29.3 (range 9-120 months). Visual acuity of 20/20 was achieved by 93.4% of the eyes. Corticosteroid-sparing effect was achieved in all patients. The mean interval between starting treatment and tapering to 10 mg or less daily was 3.8 ± 1.3 months (range 3-7 months). Twenty-two patients (57.9%) discontinued treatment without relapse of inflammation. The mean time observed off of treatment was 28.1 ± 19.6 months (range 1-60 months). None of the eyes progressed to chronic recurrent granulomatous uveitis. The ocular complications encountered were glaucoma in two eyes (2.6%) and cataract in five eyes (6.6%). None of the eyes developed 'sunset glow fundus', and none of the patients developed any systemic adverse events associated with the treatment., Conclusions: Use of MMF as first-line therapy combined with systemic corticosteroids in patients with initial-onset acute VKH disease prevents progression to chronic recurrent granulomatous inflammation and development of 'sunset glow fundus'., (© 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To investigate the incidence and risk factors of secondary glaucoma among uveitis patients., Methods: Retrospective review of medical records of 642 patients (1220 eyes)., Results: Glaucoma was diagnosed in 169 (13.9%) eyes and was most common in eyes with anterior uveitis (19.1%) (p < 0.001). HLA-B27-positive anterior uveitis (27.6%), Fuchs' uveitis (23.3%), juvenile idiopathic arthritis (23.1%), herpetic uveitis (20.3%), and Vogt-Koyanagi-Harada disease (16.3%) were the leading clinical entities associated with glaucoma (p < 0.001). Significant risk factors at presentation included worse visual acuity, elevated intraocular pressure, keratic precipitates, granulomatous inflammation, anterior chamber reaction≥ 2+, posterior synechiae, and cataract. Female gender and iris nodules significantly predicted the need for glaucoma surgery. Visual outcome was worse in eyes with glaucoma than in eyes without glaucoma., Conclusions: Incidence of glaucoma differed depending on anatomic and etiologic diagnoses of uveitis. There is a significant association between severity of inflammation at presentation and development of glaucoma.

Purpose: To study the features of Indocyanine green angiography (ICGA) in patients with initial-onset acute Vogt-Koyanagi-Harada (VKH) disease., Methods: Retrospective cohort study of ICGA performed with the use of Heidelberg scanning laser ophthalmoscope on a consecutive series of patients with initial-onset acute VKH disease. The following signs were analysed: choroidal perfusion inhomogeneity, early hyperfluorescent stromal vessels, hypofluorescent dark dots (HDDs), fuzzy or lost pattern of large stromal choroidal vessels, disc hyperfluorescence, and, diffuse late choroidal hyperfluorescence. In addition, we looked for any new ICGA findings., Results: Thirty-six patients (72 eyes) from a single academic institution were studied. The following findings were identified: HDDs in all eyes (100%), fuzzy or lost pattern of large stromal vessels in all eyes (100%), early hyperfluorescent stromal vessels were seen in 60 eyes (83%), diffuse late choroidal hyperfluorescence was present in 51 eyes (71%), choroidal perfusion inhomogeneity was seen in 44 eyes (61%), disc hyperfluorescence was seen in 25 cases (69%), and choroidal folds were present in only six eyes. New ICGA findings detected in this study were hypofluorescent patches corresponding to areas of exudative retinal detachment in 60 eyes (83%) and 'starry sky' pattern of late widespread punctate choroidal hyperfluorescence in 37 eyes (51%)., Conclusions: The most prevalent ICGA findings were HDDs, fuzzy stromal vessels and early hyperfluorescent stromal vessels in patients with initial-onset acute VKH disease. Novel ICGA findings in this group of patients included hypofluorescent patches corresponding to areas of exudative retinal detachment, and late widespread punctate choroidal hyperfluorescence taking on a 'starry sky' pattern., (© 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To investigate the referral patterns and diagnosis of uveitis in a university-based tertiary referral center in Riyadh, Saudi Arabia., Methods: We retrospectively reviewed the medical records of 642 patients (1220 eyes)., Results: There were 295 (46%) males and 347 (54%) female patients, with a mean age of 36.4 ± 16.1 years at presentation. Panuveitis was most common (47.1%), followed by anterior uveitis (36.8%), posterior uveitis (10.7%), and intermediate uveitis (5.4%). Nongranulomatous (85.2%) and noninfectious (69.3%) were the most frequent types of uveitis. The most identifiable specific diagnoses were Vogt-Koyanagi-Harada (VKH) disease (19.6%), presumed tuberculous uveitis (PTU) (17.8%), Behçet disease (BD) (8.4%), and toxoplasmosis (6.9%). After a mean follow-up period of 31.3 ± 31.5 months, 73.5% of the eyes achieved visual acuity of 20/40 or better., Conclusions: The most common anatomic diagnosis was panuveitis. VKH disease, PTU, BD, and toxoplasmosis are the most frequently diagnosed entities.

Objective: Current treatment options for lupus are far from optimal. Previously, we reported that phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin, MEK-1/ERK-1,2, p38, STAT-3, STAT-5, NF-κB, multiple Bcl-2 family members, and various cell cycle molecules were overexpressed in splenic B cells in an age-dependent and gene dose-dependent manner in mouse strains with spontaneous lupus. Since the synthetic triterpenoid methyl-2-cyano-3,12-dioxooleana-1,9-dien-28-oate (CDDO-Me) has been shown to inhibit AKT, MEK-1/2, and NF-κB, and to induce caspase-mediated apoptosis, we tested the therapeutic potential of this agent in murine lupus nephritis., Methods: The synthetic triterpenoid CDDO-Me or placebo was administered to 2-month-old B6.Sle1.Sle3 mice or MRL/lpr mice, which develop spontaneous lupus. All mice were phenotyped for disease., Results: CDDO-Me-treated mice exhibited significantly reduced splenic cellularity, with decreased numbers of both CD4+ T cells and activated CD69+/CD4+ T cells compared to the placebo-treated mice. These mice also exhibited a significant reduction in serum autoantibody levels, including anti-double-stranded DNA (anti-dsDNA) and antiglomerular antibodies. Finally, CDDO-Me treatment attenuated renal disease in mice, as indicated by reduced 24-hour proteinuria, blood urea nitrogen, and glomerulonephritis. At the mechanistic level, CDDO-Me treatment dampened MEK-1/2, ERK, and STAT-3 signaling within lymphocytes and oxidative stress. Importantly, the NF-E2-related factor 2 pathway was activated after CDDO-Me treatment, indicating that CDDO-Me may modulate renal damage in lupus via the inhibition of oxidative stress., Conclusion: These findings underscore the importance of AKT/MEK-1/2/NF-κB signaling in engendering murine lupus. Our findings indicate that the blockade of multiple signaling nodes and oxidative stress may effectively prevent and reverse the hematologic, autoimmune, and pathologic manifestations of lupus., (Copyright © 2014 by the American College of Rheumatology.)

Purpose: To determine prognostic factors in patients with Vogt-Koyanagi-Harada (VKH) disease who were treated with high-dose corticosteroids., Methods: Retrospective analysis of 87 patients (174 eyes)., Results: At presentation, there were 53 patients with initial-onset acute VKH disease and 34 patients with chronic recurrent VKH disease. Chronic recurrent presentation was significantly associated with more severe anterior segment inflammation at presentation as indicated by presence of mutton-fat keratic precipitates, anterior chamber reaction ≥2+, iris nodules and posterior synechiae (p < 0.001 for all comparisons), less exudative retinal detachment at presentation (p < 0.001), more complications during the follow-up period (p < 0.001) and a worse visual outcome (p < 0.001). The use of immunomodulatory therapy (cyclosporine and mycophenolate mofetil) as first-line therapy significantly reduced the development of complications in the whole study group (p = 0.006) and in initial-onset acute group (p = 0.024) and improved visual outcome in the whole study group (p = 0.004) and in chronic recurrent group (p = 0.024). In the whole study group, final visual acuity of 20/20 was significantly associated with good initial visual acuity of >20/200 [odds ratio = 4.25; 95% Confidence interval (CI) = 1.53-11.89] and age older than 16 years was significantly associated with the development of complications (odds ratio = 3.15; 95% CI = 1.04-9.48)., Conclusions: Chronic recurrent VKH disease is significantly associated with more severe anterior segment inflammation and less exudative retinal detachment at presentation, more ocular complications and a worse visual outcome than initial-onset acute VKH disease. Use of immunomodulatory therapy significantly improved the clinical outcomes., (© 2013 Acta Ophthalmologica Scandinavica Foundation. Published by Blackwell Publishing Ltd.)

Purpose: To study the effectiveness of mycophenolate mofetil (MMF) as first-line therapy combined with systemic corticosteroids in acute uveitis associated with Vogt-Koyanagi-Harada (VKH) disease. The outcomes in this group were compared with those of another group of patients with VKH disease who were treated with corticosteroid monotherapy or with delayed addition of immunomodulatory therapy., Methods: This prospective study included 19 patients (38 eyes) diagnosed with acute uveitis associated with VKH disease., Results: The mean follow-up period was 27.0 ± 11.1 months (range 16-54 months). Corticosteroid-sparing effect was achieved in all patients. The mean interval between starting treatment and tapering prednisone to 10 mg or less daily was 5.1 ± 1.2 months (range 3-7 months). Ten (53%) patients discontinued treatment without relapse of inflammation. The mean time observed of treatment was 17.3 ± 11.9 months (range 3-41.5 months). Visual acuity of 20/20 was achieved by 38% of the eyes in the corticosteroid group and by 74% in the corticosteroid + MMF group (p < 0.001). Recurrent inflammation of ≥3 times was reduced significantly (p = 0.0383) in the corticosteroid + MMF group (3%) as compared to corticosteroid group (18%). Development of all complications was significantly higher in the corticosteroid group (43%) compared with the corticosteroid + MMF group (8%) (p < 0.001). None of the eyes in the corticosteroid + MMF group developed 'sunset glow fundus'., Conclusions: Addition of MMF as first-line therapy to corticosteroids in patients with acute uveitis associated with VKH disease leads to significant reduction in recurrences of uveitis and development of late complications and significantly improves visual outcome., (© 2012 The Authors. Acta Ophthalmologica © 2012 Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To evaluate the effect of immunosuppressive therapy on best-corrected visual acuity (BCVA), fixation stability, and central retinal sensitivity in patients with Vogt-Koyanagi-Harada (VKH) disease in the acute uveitic phase. Methods. In this prospective study, 14 patients (28 eyes) were evaluated. Best-corrected visual acuity and MP-1 microperimetric evaluation of retinal sensitivity in the central 12 degrees and fixation stability were assessed at baseline and at 1, 3, 6, 9, and 12 months after treatment. Results. At baseline, logarithm of the minimum angle of resolution (logMAR) BCVA, fixation stability, and mean retinal sensitivity levels were 0.685 ± 0.6 (Snellen equivalent, 20/100), 61.2% ± 29.0%, and 2.75 ± 3.8 dB, respectively. At 3 months, logMAR BCVA (0.11 ± 0.2, Snellen equivalent 20/25) and fixation stability (86.4% ± 13.4%) were almost maximum (p<0.001 for both comparisons), and thereafter remained almost unchanged. Mean retinal sensitivity continued to improve up to 12 months (12.0 ± 2.3 dB, p<0.001); however, it was still significantly decreased. There were significant correlations between logMAR BCVA and mean retinal sensitivity at all time points. The percentages of BCVA improvement were significantly higher than the percentages of mean retinal sensitivity improvement at all time points (p<0.001 for all comparisons). Conclusions. Compared with microperimetry, BCVA significantly underestimates macular dysfunction in VKH disease.