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Background Obstructive sleep apnea (OSA) is linked to hearing loss (HL). Another sleep characteristics, sleep duration might also be associated with HL, but prior evidence is limited. This study is aimed to investigate the association between sleep duration and hearing level in the adult US population. Methods In total, a sample of 2777 individuals aged 20–69 years from the 2015–2016 National Health and Nutrition Examination Survey cycle (NHANES, 2015–2016) were investigated in this study. Self-reported sleep duration data was classified into the short-sleep (< 7 h), normal-sleep (7–9 h), and long-sleep (> 9 h) group. Multivariable linear regression models between sleep duration and hearing threshold shifts were estimated. Interactions between sleep duration and age, gender, race, OSA were also considered, and the study population was stratified by age, gender, race, and OSA to analyze the potential disparities among adults in different subgroups. Results Long-sleep duration was positively associated with speech- and high-frequency pure-tone average (PTA) thresholds with statistical significance (β = 1.31, 95%CI: 0.10, 2.53, P  = 0.0347, and β = 2.71, 95%CI: 0.69, 4.74, P  = 0.0087, respectively). When stratified by age, short sleep duration was positively associated with low-, and speech-frequency PTAs ( P  = 0.0140 and 0.0225, respectively) for adults aged 40–59 years, and long-sleep duration was positively associated with low-, and speech-frequency PTAs ( P  = 0.0495 and 0.0142, respectively) for adults aged 60–69 years with statistical significance. There was statistically significant interaction between OSA and sleep duration on speech-frequency PTA, but no significant interaction between either gender or race with sleep duration on hearing thresholds among US adults. Conclusion Short/long sleep durations are associated with worse hearing level comparing to sleep 7–9 h in the American adults. Nonoptimal sleep duration may be a potential risk factor for HL.

Hearing loss (HL) is a global health problem with a high prevalence and profound socioeconomic impact. Pyrethroids are one of the most commonly used insecticides. Although previous studies have reported the relationship between pyrethroids and neurotoxicity, little is known about the effect of pyrethroid exposure on the auditory system among the general population. This study is aimed to investigate the association of pyrethroid exposure with hearing threshold shifts of adults in the United States. A total of 726 adults, aged from 20 to 69 years from the 2011–2012 National Health and Nutrition Examination Survey (NHANES) data were included in the study. Urinary 3-phenoxybenzoic acid (3-PBA), a general pyrethroid metabolite, was used as a biomarker for pyrethroid exposure. HL was defined as a pure-tone average (PTA) at 0.5, 1, 2, 4 kHz ≥ 20 dB in the better ear. Analyses by using multivariate linear regressions were conducted to explore the associations of urinary 3-PBA with PTA hearing threshold shifts. There were no statistically significant correlations between Ln-transformed 3-PBA and either low-frequency or high-frequency hearing thresholds after adjusting for age, gender, race/ethnicity, education level, firearm noise exposure, occupational noise exposure, recreational noise exposure, serum cotinine, BMI, hypertension, and diabetes. However, associations of 3-PBA with both low-frequency and high-frequency hearing thresholds depended on age ( P interaction < 0.0396 and 0.0017, respectively). Positive associations between Ln-transformed 3-PBA and both low-frequency and high-frequency hearing thresholds were observed in participants aged 20–39 years after adjusting confounders (β = 1.53, 95% CI: 0.04–3.01, and β = 3.14, 95% CI: 0.99–5.29, respectively) with the highest tertile (≥ 0.884 μg/g creatinine) of 3-PBA compared with the lowest tertile (< 0.407 μg/g creatinine). The possibility of interaction between 3-PBA and age on the hearing threshold shifts indicated that pyrethroid insecticides were prone to be more toxic to auditory system in younger adults than in older ones. Further studies will be required to confirm these findings.

Hearing loss (HL) is a highly prevalent public health concern. Organochlorine pesticides (OCPs) are widely used environmental pollutants harmful to human health. Studies investigating the effects of OCPs exposure on the auditory system in the general population are rare. To explore the association between OCPs exposure and HL in adults, 366 adults aged 20–69 years who participated in the National Health and Nutrition Examination Survey (NHANES, 2003–2004) were investigated. HL was defined as a pure-tone average (PTA) ≥ 20 dB in the better ear. Multivariate linear and logistic regression analyses were conducted to evaluate the association of four selected serum OCPs with PTAs and the risk of HL. In participants aged < 60 years, hexachlorobenzene (HCB) and dichlorodiphenyldichloroethylene (p, p'-DDE) exposure was positively associated with low- and speech-frequency PTAs, and with low-frequency HL, respectively. Risk of HL increased in the highest tertile compared with the lowest tertile of serum HCB and p, p'-DDE (odds ratio [OR]: 4.38, 95% confidence interval [CI]: 0.97–19.80; OR: 16.66, 95% CI: 2.64–105.09, respectively). In this study of US adults aged < 60 years, HCB and p, p'-DDE exposure was positively associated with HL. HCB and p, p'-DDE may be potential risk factors for HL.

Previous studies have reported the relationship between effect of caffeine and many diseases. However, studies to evaluate the association between caffeine and hearing loss are contradictory. To examine the relationship of urinary caffeine metabolites with the hearing threshold in US adults, a total of 849 adults aged 20–69 years who participated in the National Health and Nutrition Examination Survey (NHANES, 2011–2012) were enrolled in this study. Urinary caffeine and its 14 metabolites were applied as biomarkers to assess caffeine exposure. Hearing loss was defined as mean pure tone averages > 25 dB HL at 500, 1000, and 2000 Hz in both ears (low frequency); and 3000, 4000, and 6000 Hz in both ears (high frequency). Univariate and multivariate linear regression analyses were conducted to examine the associations of urinary caffeine metabolites with low- and high-frequency hearing thresholds, respectively. Low-frequency hearing loss were 5.08% and 6.10% in male and female participants, respectively; and high-frequency hearing loss were 31.81% and 15.14% in male and female participants, respectively. In the unadjusted model, the P value for trend shows that urinary caffeine metabolites 137X and AAMU were significantly associated with low-frequency PTA, and that 17X, 137X, AAMU were significantly associated with high-frequency PTA, but when the model was adjusted for sex, age, education level, firearm noise exposure, occupational noise exposure, recreational noise exposure, serum cotinine, body mass index, diabetes, hypertension, these were no longer statistically significant. In conclusion, urinary caffeine metabolites were not associated with the hearing threshold shifts in US adults.

Alport syndrome is a hereditary kidney disease with significant variations in onset and prognosis. While 80–85% of cases are due to pathogenic variants in the COL4A5 gene, there is a notable lack of mouse models with Col4a5 mutations for basic research. Our research presents an 8-year-old child with Alport syndrome, exhibiting facial edema and abnormal urine. Next-generation sequencing revealed a c.1517-1G > T mutation in the intron sequence of the COL4A5 gene. Minigene experiments confirmed that this intronic mutation affects mRNA splicing. Using the CRISPR/Cas9 system, we developed a Col4a5 -c.1517-1G > T mutant mouse model. Col4α5 -deficient mice exhibited growth retardation and reduced lifespan. Renal function analysis indicated progressive deterioration, with high levels of BUN and creatinine. Histological and ultrastructural analyses revealed abnormalities such as mesangial sclerosis, interstitial fibrosis and severe irregularity in membrane thickness. Additionally, significant immune cell infiltration was observed in the renal interstitium. This mouse model provides a valuable tool for studying the role of immune cells in the pathogenesis and treatment of XLAS. It is also the first reported X-linked Alport syndrome mouse model caused by a splicing mutation.

Background: Although telomere length has a significant relationship with various age-related diseases, studies on its relationship with hearing status in adults are limited and equivocal. This study investigated the associations between mean telomere length (MTL) and low-, speech-, and high-frequency hearing threshold shifts of adults in the United States. Methods: A total of 2027 adults aged 20-69 years from the National Health and Nutrition Examination Surveys (NHANES, 1999–2002) were included in the analytic sample. The quantitative polymerase chain reaction method was used for the MTL assay, and MTL was expressed using the telomere-to-single copy gene (T/S) ratio. Hearing loss was defined as a pure tone average (PTA) for the better ear ≥ 20 dB HL at frequencies 500, 1000, 2000 and 4000 Hz. Univariate and multivariate linear regression analyses and smooth curve fittings were conducted to evaluate the correlation between MTL and low-, speech-, and high-frequency hearing levels. Results: The mean age of the participants was 40.60 ± 12.76 years, including 952 men (weighted, 48.67%) and 303 (weighted, 12.88%) participants with hearing loss. After adjusting for potential confounders in the multivariate linear regression model, the relationship between MTL and hearing thresholds was not statistically significant. Smooth curve fittings indicated a nonlinear relationship between MTL and high-frequency PTA hearing threshold shifts. MTL was inversely related to high-frequency PTA to the turning point (T/S ratio = 0.82) (adjusted β -21.45, 95% CI -37.28, -5.62; P = 0.008). When the T/S ratio exceeded 0.82, MTL was not associated with high-frequency PTA (adjusted β 0.18, 95% CI -2.21, 2.57; P = 0.8809). Conclusions: Our findings revealed That MTL was associated with high-frequency PTA hearing threshold shifts of adults in the United States in a non-linear manner.

Brucellosis, a zoonosis, can cause an inflammatory response in most organs and continues to be a public health problem in some endemic areas, whereas neurobrucellosis is a morbid form of brucellosis that affects the central nervous system (CNS) with poor prognosis. Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is an autoimmune disease, and there have been no reports of a Brucella infection, leading to GFAP astrocytopathy. We report the case of a patient with a positive and high level of GFAP antibodies in the cerebrospinal fluid (CSF), following a Brucella infection. Although this patient did not show any responsible lesions in the diffusion sequence of the magnetic resonant imaging (MRI) scan, we found an evidence of thoracolumbar (T12) involvement on fluorodeoxyglucose (FDG) positron emission tomography (PET). The symptoms of spinal cord involvement were only partly relieved after initial treatment [doxycycline (0.1 g Bid) and rifampicin (0.6 g Qd) for 6 weeks]; however, they markedly improved after the subsequent immunosuppressive therapy [intravenous methylprednisolone (1,000 mg for 3 days)], followed by a 50% reduction from the preceding dose after 3 days, and subsequently, oral prednisone tablets (60 mg/day) was started, which was then gradually tapered [reduced to 10 mg/day every 1–2 weeks)]. The positive response to immunosuppressive therapy and treatment outcome strongly indicated the presence of an autoimmune neurological disease probably triggered by some infectious factors. Therefore, our findings reveal that a Brucella infection is one of the causes of autoimmune GFAP astrocytopathy, and when this infection is difficult to be identified by regular MRI, FDG PET can be used as a supplementary method for diagnosis and treatment.

Background: An increasing number of observational studies have revealed an association between the gut microbiota, gut metabolites, and epilepsy. However, this association is easily influenced by confounders such as diet, and the causality of this association remains obscure. Methods: Aiming to explore the causal relationship and ascertain specific gut microbe taxa for epilepsy, we conducted a bi-directional Mendelian randomization (MR) study based on the genome-wide association study (GWAS) data of epilepsy from the International League Against Epilepsy, with the gut microbiota GWAS results from MiBioGen and summary-level GWAS data of gut microbiota-dependent metabolites trimethylamine N-oxide and its predecessors. Results: Nine phyla, 15 classes, 19 orders, 30 families, and 96 genera were analyzed. A suggestive association of host-genetic-driven increase in family Veillonellaceae with a higher risk of childhood absence epilepsy (odds ratio [OR]: 1.033, confidential interval [CI]: 1.015–1.051, PIVW=0.0003), class Melainabacteria with a lower risk of generalized epilepsy with tonic-clonic seizures (OR=0.986, CI=0.979–0.994, PIVW=0.0002), class Betaproteobacteria (OR=0.958, CI=0.937–0.979, PIVW=0.0001) and order Burkholderiales (OR=0.960, CI=0.937–0.984, PIVW=0.0010) with a lower risk of juvenile myoclonic epilepsy were identified after multiple-testing correction. Our sensitivity analysis revealed no evidence of pleiotropy, reverse causality, weak instrument bias, or heterogeneity. Conclusions: This is the first MR analysis to explore the potential causal relationship between the gut microbiota, metabolites, and epilepsy. Four gut microbiota features (two class levels, one order level, and one family level) were identified as potential interventional targets for patients with childhood absence epilepsy, generalized epilepsy with tonic-clonic seizures, and juvenile myoclonic epilepsy. Previous associations in numerous observational studies may have been interfered with by confounders. More rigorous studies are needed to ascertain the relationship between the gut microbiota, metabolites, and epilepsy.

Epilepsy is a neurological network disease with genetics playing a much greater role than was previously appreciated. Unfortunately, the relationship between genetic basis and imaging phenotype is by no means simple. Imaging genetics integrates multidimensional datasets within a unified framework, providing a unique opportunity to pursue a global vision for epilepsy. This review delineates the current knowledge of underlying genetic mechanisms for brain networks in different epilepsy syndromes, particularly from a neural developmental perspective. Further, endophenotypes and their potential value are discussed. Finally, we highlight current challenges and provide perspectives for the future development of imaging genetics in epilepsy.

Studies have shown that neurogenesis and angiogenesis do exist in temporal lobe epilepsy (TLE). The ephrin ligands and Eph receptors are the largest members of receptor tyrosine kinases, and their interaction via cell–cell contact participates in cell proliferation, differentiation, migration, and tissue remodeling. However, there is little information about the function of the ephrin-A5/EphA4 complex in TLE. In the current study, we found that ephrin-A5 was expressed in astrocytes, while EphA4 existed in endothelial cells in the hippocampus in a mouse model of TLE. Furthermore, the messenger RNA (mRNA) and protein levels of both ephrin-A5 and EphA4 and the binding capacity of ephrin-A5/EphA4 showed gradual increase in spatiotemporal course. When ephrin-A5-Fc was injected into the hippocampus at 3 days post-status epilepticus (SE) for 7 days, the spontaneous recurrent seizure (SRS) frequency and intensity of the mice attenuated in the following 2 weeks. Furthermore, doublecortin-positive neuronal progenitor cells were reduced in the subgranular zone, and the density of microvessels decreased in the hilus. The molecular mechanism was attributed to ephrin-A5-Fc-induced inhibition of phosphorylated ERK (p-ERK) and phosphorylated Akt (p-Akt), and also EphA4 and VEGF reduction. In summary, interaction between ephrin-A5 and EphA4 could mediate the ERK and Akt signaling pathways in pilocarpine-induced epilepsy, and intervention of the ephrin/Eph interaction may play an essential role in the suppression of newborn neuron generation, microvessel remodeling, and SRS in a mouse model of TLE. The ephrin-A5/EphA4 communication may provide a potential therapy for the treatment of TLE.