Complexin-1 enhances ultrasound neurotransmission in the mammalian auditory pathway.

Unlike megabats, which rely on well-developed vision, microbats use ultrasonic echolocation to navigate and locate prey. To study ultrasound perception, here we compared the auditory cortices of microbats and megabats by constructing reference genomes and single-nucleus atlases for four species. We found that parvalbumin (PV)+ neurons exhibited evident cross-species differences and could respond to ultrasound signals, whereas their silencing severely affected ultrasound perception in the mouse auditory cortex. Moreover, megabat PV+ neurons expressed low levels of complexins (CPLX1-CPLX4), which can facilitate neurotransmitter release, while microbat PV+ neurons highly expressed CPLX1, which improves neurotransmission efficiency. Further perturbation of Cplx1 in PV+ neurons impaired ultrasound perception in the mouse auditory cortex. In addition, CPLX1 functioned in other parts of the auditory pathway in microbats but not megabats and exhibited convergent evolution between echolocating microbats and whales. Altogether, we conclude that CPLX1 expression throughout the entire auditory pathway can enhance mammalian ultrasound neurotransmission.

Presence of Epstein-Barr virus in cerebrospinal fluid is associated with increased mortality in HIV-negative cryptococcal meningitis.

Cryptococcus neoformans is the most common cause of fungal meningitis and is associated with a high mortality. The clinical significance of concurrent Epstein-Barr virus (EBV) in the cerebrospinal fluid (CSF) of human immunodeficiency virus (HIV)-negative patients with cryptococcal meningitis (CM) remains unclear. A retrospective cohort study was performed by analyzing CSF samples from 79 HIV-negative Chinese Han patients with confirmed CM. We identified CSF viral DNA in these patients by metagenomic next-generation sequencing (mNGS) and compared 10-week survival rates among those with and without EBV DNA in CSF. Of the 79 CSF samples tested, 44.3% (35/79) had detectable viral DNA in CSF, while 55.7% (44/79) were virus-negative. The most frequent viral pathogen was EBV, which was detected in 22.8% (18/79) patients. The median number of CSF-EBV DNA reads was 4 reads with a range from 1 to 149 reads. The 10-week mortality rates were 22.2% (4/18) in those with positive CSF-EBV and 2.3% (1/44) in those with negative CSF-virus (hazard ratio 8.20, 95% confidence interval [CI] 1.52-81.80; P = 0.014), which remained significant after a multivariate adjustment for the known risk factors of mortality (adjusted hazard ratio 8.15, 95% CI 1.14-92.87; P = 0.037). mNGS can identify viruses that coexist in CSF of HIV-negative patients with CM. EBV DNA is most commonly found together with C. neoformans in CSF and its presence is associated with increased mortality in HIV-negative CM patients.

We retrospectively analyzed CSF samples from 79 HIV-negative Chinese Han patients with confirmed CM. We identified CSF viral DNA by mNGS and compared 10-week survival rates among those with and without EBV DNA. Positive CSF-EBV DNA is associated with the increased mortality in HIV-negative CM patients.

Corrigendum: Case report: early recognition, treatment, and occupational safety protection are crucial for methanol toxicity.

[This corrects the article DOI: 10.3389/fmed.2022.918812.].

Exploring Shared Genetic Signatures of Alzheimer's Disease and Multiple Sclerosis: A Bioinformatic Analysis Study.

INTRODUCTION: Many clinical studies reported the coexistence of Alzheimer's disease (AD) and multiple sclerosis (MS), but the common molecular signature between AD and MS remains elusive. The purpose of our study was to explore the genetic linkage between AD and MS through bioinformatic analysis, providing new insights into the shared signatures and possible pathogenesis of two diseases. METHODS: The common differentially expressed genes (DEGs) were determined between AD and MS from datasets obtained from Gene Expression Omnibus (GEO) database. Further, functional and pathway enrichment analysis, protein-protein interaction network construction, and identification of hub genes were carried out. The expression level of hub genes was validated in two other external AD and MS datasets. Transcription factor (TF)-gene interactions and gene-miRNA interactions were performed in NetworkAnalyst. Finally, receiver operating characteristic (ROC) curve analysis was applied to evaluate the predictive value of hub genes. RESULTS: A total of 75 common DEGs were identified between AD and MS. Functional and pathway enrichment analysis emphasized the importance of exocytosis and synaptic vesicle cycle, respectively. Six significant hub genes, including CCL2, CD44, GFAP, NEFM, STXBP1, and TCEAL6, were identified and verified as common hub genes shared by AD and MS. FOXC1 and hsa-mir-16-5p are the most common TF and miRNA in regulating hub genes, respectively. In the ROC curve analysis, all hub genes showed good efficiency in helping distinguish patients from controls. CONCLUSION: Our study first identified a common genetic signature between AD and MS, paving the road for investigating shared mechanism of AD and MS.

Seasonality and meteorological factors of HIV-negative cryptococcal meningitis in Guangdong Province, China.

OBJECTIVE: Information about the seasonal characteristics of human immunodeficiency virus (HIV)-negative cryptococcal meningitis (CM) is quite limited. The aim of this study was to explore the seasonality and meteorological factors of HIV-negative patients with CM. METHODS: We performed a retrospective study of 469 HIV-negative CM patients admitted to the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China. Their initial onset symptoms of CM occurred from January 2011 to December 2020. The temperature, precipitation, sunlight, humidity and wind speed for the corresponding period and the associated topographic, ecological type and soil type parameters data were collected. The Poisson regression model was used to determine the meteorological factors associated with CM onset. The geographical detector method was used to detect other environmental factors associated with CM onset. RESULTS: CM onset did not showed a seasonal fluctuation, but was strongly associated with mean temperature (ß = .010, p = .028) and mean relative humidity (ß = -.011, p = .006). In the rainy season, only mean wind speed remained significantly associated with CM onset (ß = -.108, p = .041). In the dry season, mean temperature (ß = .014, p = .016), mean relative humidity (ß = -.016, p = .006) and hours of sunlight (ß = -.002, p = .016) were significantly associated with CM onset. Topographic, ecological type and soil type factors did not add explanatory power. CONCLUSIONS: Our findings add the knowledge about the environmental factors of HIV-negative CM. Meteorological factors, especially temperature and humidity, may be the main environmental factors affecting the onset of HIV-negative CM.

Characteristics of aseptic meningitis-like attack-an underestimated phenotype of myelin oligodendrocyte glycoprotein antibody-associated disease.

INTRODUCTION: Aseptic meningitis was recently reported and recognized as a novel phenotype of Myelin oligodendrocyte glycoprotein antibody-associated disease (MOG-AD). However, the frequency and clinical features of this specific subtype remain unclear. METHODS: We reported sixteen MOG-AD cases with aseptic meningitis from June 2018 to June 2022. Moreover, systematic literature of 17 reported cases was conducted. RESULTS: Upon reviewing the records of 91 patients diagnosed with MOG-AD in our center, we identified 16 patients (17.6%; 9 men and 7 women) with aseptic meningitis-like MOG-AD. The median age at onset was 23.5 ± 15.7 years. The common clinical presentations were fever (87.5%), headache (75.0%) and seizure (18.8%). Most patients had leukocytosis (62.5%) and a significantly elevated neutrophil-lymphocyte ratio (NLR, ≥3.0). Cerebrospinal fluid showed elevated intracranial hypertension (43.8%), elevated leukocytes (100%) and protein (56.3%). Negative brain magnetic resonance images were observed in 6 patients and only meningeal enhancement was observed in 8 patients at first. Almost all patients had a prolonged fever (over 2 weeks) and ineffectual antibiotic treatment. All patients experienced an effective response to immunotherapy. The majority had a benign course (low Expanded Disability Status Scale score and relapsing rate). Five patients (31.3%) progressed and four patients (25.0%) experienced recurrence. Aseptic meningitis-like MOG-AD of 17 cases reported in previous studies showed similar clinical features to our cases. CONCLUSION: Aseptic meningitis could be an initial or isolated manifestation of MOG-AD. It is an underestimated phenotype of MOG-AD.

Neurological worsening during treatment of HIV-negative cryptococcal meningitis in a patient with Evans syndrome.

A 49-year-old woman with a rare autoimmune hematological disease, Evans syndrome, was admitted to the authors' hospital with immune reconstitution inflammatory syndrome-like reconstitution syndrome after effective antifungal therapy for cryptococcal meningitis. She initially improved after receiving corticosteroid treatment; after prednisone was tapered, her clinical presentation and brain imaging deteriorated but finally improved with the addition of thalidomide. Immune reconstitution inflammatory syndrome-like reconstitution syndrome is a rare complication in cryptococcal meningitis patients receiving immunosuppressive therapy. Thalidomide can be given in addition to corticosteroid therapy to effectively control the paradoxical inflammatory response and improve clinical outcomes.

Failure of Early Mycological Clearance in HIV-Negative Cryptococcal Meningitis.

Background: Negative cerebrospinal fluid (CSF) cultures at 2 weeks after antifungal treatment (early mycological clearance [EMC]) should be a treatment goal of cryptococcal meningitis (CM). However, EMC in human immunodeficiency virus (HIV)-negative patients with CM is poorly understood. Methods: We conducted a retrospective review of medical records and 1-year follow-up of 141 HIV-negative patients with CM with an initial positive CSF culture for Cryptococcus neoformans. Multivariate logistic regression was performed to analyze clinical features and laboratory and CSF findings of patients with CM with different EMC statuses. Random forest models were used to predict failure of EMC. All-cause mortality and clinical functional status were analyzed. Results: Of 141 patients, 28 (19.9%) had EMC failure. The 1-year mortality rate was 5.7% (8/141). Multivariate analysis showed that non-amphotericin B (AmB)-based regimens, baseline log10 Cryptococcus count/mL, baseline CSF opening pressure (CSF-OP) >30 cm H2O, and baseline serum creatinine were significantly associated with EMC failure. A parsimonious predictive rule given by the decision tree identified patients with CM with non-AmB-based therapy and baseline CSF-OP >30 cm H2O as being at high risk of EMC failure. Incidence of all-cause mortality, the follow-up modified Rankin Scale, and Karnofsky performance status scores were not significantly related to EMC. Conclusions: EMC failure in HIV-negative CM is attributed to non-AmB-based therapy and is associated with log10 Cryptococcus count/mL and CSF-OP >30 cm H2O at baseline. Because of the small number of deaths, we are not able to comment on whether or not EMC is associated with mortality.

Case Report: Early Recognition, Treatment, and Occupational Safety Protection are Crucial for Methanol Toxicity.

Background: Despite significant progress in treating methanol poisoning, the lack of training, hazard communication, and occupational safety protection education contributes to the risk of occupational exposure and methanol toxicity. In addition, early diagnosis and timely medical care are essential to reduce the risk of morbidity and mortality, yet it remains a challenging procedure. Case Report: A 35-year-old man working in a fireworks factory came to our emergency department with acute mental change and progressive disturbance of consciousness. The patient's vital signs were stable, and he presented with enlargement of both pupils with a weak reaction to light. Head computed tomography showed low signal intensities in the bilateral basal ganglia. He was admitted to the neurologic intensive care unit, where additional laboratory workup showed high anion-gap metabolic acidosis. Methanol poisoning was thus considered. Before being treated with sodium bicarbonate infusion, hemodialysis, folate, and high-dose vitamin B, the blood and urine samples were collected for toxicity tests, which turned out to be methanol poisoning. After 8 hours of hemodialysis, the patient's consciousness recovered, but he complained of a complete loss of vision in both eyes. Brain and optic nerve magnetic resonance images showed bilateral symmetric putamen lesions and optic neuropathy. Ophthalmic tests indicated visual pathway impairment and optic disc swelling but no fluorescein leakage. The right eye's vision was partially restored on the third day, but he could only count fingers at 20 cm. Unfortunately, his eyesight ceased to improve during the 6 months of follow-up. Conclusions: Early diagnosis and prompt treatment will improve the prognosis of methanol poisoning in terms of vision and patient survival. Awareness and supervision of commercial alcohol use are indispensable for similar industrial processes.

Case Report: Diagnosis of Acute Q Fever With Aseptic Meningitis in a Patient by Using Metagenomic Next-Generation Sequencing.

Query fever (Q fever) is a widespread zoonotic disease caused by the bacterium of Coxiella burnetii (C. burnetii). Its neurological complications are rarely reported. But they may lead to severe consequences. It needs a rapid and accurate detective method to diagnose acute Q fever with neurological presentations in non-epidemic areas urgently. Here, we report an acute Q fever case with aseptic meningitis. The male patient, without any contact history in the epidemic area or with animals, was indicated to exhibit fever and headache symptoms. The cultures of blood, stool, urine, and sputum were all negative. But C. burnetii was repeatedly detected in blood by metagenomic next-generation sequencing (mNGS). He received Doxycycline therapy and quickly returned to normal. Therefore, for the diagnosis and identification of Q fever in non-reporting regions, mNGS has comparative advantages. Secondly, aseptic meningitis may be a direct infection of C. burnetii to central nervous system (CNS) or inflammatory reactions to systemic infection, we recommend detecting mNGS both in blood and cerebrospinal fluid (CSF).

Let-7a-5p regulated by lncRNA-MEG3 promotes functional differentiation to Schwann cells from adipose derived stem cells via directly inhibiting RBPJ-mediating Notch pathway.

Schwann cells (SCs) have important roles in supporting and repairing peripheral neurons, and thus have great potential for nerve injury treatment. Adipose tissue-derived stem cells (ADSCs) can be reliably induced to differentiate into SCs. However, the underlying molecular mechanisms are unclear. We explored the roles of MEG3/let-7a-5p/RBPJ axis in the differentiation into SCs from ADSCs. Primary ADSCs were induced to differentiate into SCs by appropriate reagents. ELISA, immunostaining, Western blotting, and qRT-PCR were employed to examine levels of SC-markers such as S100, GFAP, SOX10, p75NTR, GAP43, MPZ, ß-NGF, BDNF, and NCAM and let-7 family, MEG3, RBPJ, and Notch signaling related proteins. Dual luciferase assay and RNA immunoprecipitation were performed to validate interactions of let-7a-5p/RBPJ mRNA and MEG3/let-7a-5p. Cultured ADSCs could be induced to differentiate into functional SCs. Let-7a-5p and let-7d-5p were elevated during the differentiation while MEG3 and RBPJ/Notch-signaling were suppressed. Let-7a-5p mimics promoted ADSC differentiation into SCs and up-regulated the levels of SC-related markers including S100, GFAP, SOX10, p75NTR, GAP43, MPZ, ß-NGF, and NCAM, while RBPJ or MEG3 overexpression retarded the differentiation and reduced those levels. Let-7a-5p directly targeted RBPJ and MEG3 disinhibited Notch-RBPJ signaling via sponging let-7a-5p. RBPJ overexpression reversed the acceleration of let-7a-5p mimics on SC differentiation while let-7a-5p mimics blocked MEG3-mediated suppression on SC differentiation. Let-7a-5p sponged by MEG3 promotes differentiation of ADSCs into SCs via suppressing Notch signaling by targeting RBPJ. These findings shed light on mechanisms underlying the differentiation of ADSCs to SCs and provide avenues to accelerate the process.

Clinical Characteristics of Chinese Male Patients with Aquaporin-4 Antibody-Positive Late-Onset Neuromyelitis Optica Spectrum Disorder.

BACKGROUND AND OBJECTIVE: Limited studies are available for male patients with anti-aquaporin-4 antibody (AQP4-Ab)-positive late-onset neuromyelitis optica spectrum disease (LONMOSD). The aim of this study was to investigate the clinical characteristics of Chinese male patients with AQP4-Ab-positive LONMOSD. METHODS: We retrospectively reviewed the medical records of 12 male patients with LONMOSD, 16 male patients with early-onset NMOSD (EONMOSD), and 64 female patients with LONMOSD. These enrolled patients were classified according to the age of onset: LONMOSD (≥50 years of age at onset) versus EONMOSD (<50 years of age at onset). Clinical characteristics and magnetic resonance imaging (MRI) findings were collected. All included patients were positive for AQP4 antibody. RESULTS: Compared with female LONMOSD patients, male LONMOSD patients had less frequent transverse myelitis (TM) at onset (8.33 vs. 53.13%, p = 0.004) and lower Expanded Disability Status Scale (EDSS) scores (median 1 vs. 4, p = 0.036). Compared with male EONMOSD patients, male LONMOSD patients had a shorter time from onset to diagnosis (0.85 months vs. 6.00 months, p = 0.04). CONCLUSION: Less common TM at onset, less disease severity, and shorter time from onset to diagnosis probably occur in male LONMOSD patients.

The Effect on the Kidney in Patients With Anti-N-methyl D-aspartate Receptor Antibody Encephalitis.

Objectives: The function of the N-methyl-D-aspartate receptor (NMDAR) in the kidney has been studied. However, the effect on the kidney from anti-NAMDAR antibody encephalitis has not been investigated thus far. Methods: Case data were collected from 82 patients with anti-NMDAR antibody encephalitis and 166 age- and sex-matched healthy controls (HCs). Clinical characteristics, urinalysis [including urine pH and urine specific gravity (SG)], serum creatinine (Scr), and estimated glomerular filtration rate (eGFR) based on Cr levels were evaluated. Results: At initial admission, urine pH levels and urine SG levels in anti-NMDAR antibody encephalitis patients were significantly higher and lower, respectively, than HCs (both p < 0.001). There were no significant differences in Scr and eGFR between anti-NMDAR antibody encephalitis patients and HCs. Urine pH levels in patients with anti-NMDAR antibody <1:32 were significantly lower than those in patients with anti-NMDAR antibody ≥1:32 (p = 0.029). Urine pH levels were significantly lower (p = 0.004) and urine SG levels were significantly higher (p = 0.027) in a follow-up evaluation 3 months after treatment. Conclusions: The changes in urinalysis occur in patients with anti-NMDAR antibody encephalitis. The pathophysiological changes in anti-NMDAR antibody encephalitis were not limited to the CNS.

Serum antinuclear antibodies associate with worse prognosis in AQP4-positive neuromyelitis optica spectrum disorder.

BACKGROUND: Studies have demonstrated that antinuclear antibodies (ANAs) may be correlated with neuromyelitis optica spectrum disorder (NMOSD). However, the conflicting results of studies about the value of ANAs in AQP4 antibody-positive NMOSD patients need to be further investigated. MATERIAL: Case data were collected from 143 patients with AQP4 antibody-positive NMOSD. Patients were divided into two groups based on the ANA test results. The analysis of clinical characteristics, laboratory tests, and MRI examination results were compared between two groups: the NMOSD patients with ANA (+) and with ANA (-). RESULTS: Disease duration of NMOSD is shorter in the ANA (+) patients with EDSS < 4 than in the ANA (-) patients (12.05 ± 16.73 versus 29.43 ± 41.03, p-value = .013). The median time from disease onset to an EDSS score of 4.0 is significantly longer in the ANA (-) NMOSD patients than in the ANA (+) patients (48.2 months versus 24 months, p = .04). In addition, ANA (RR, 2.234; 95% CI, 1.078-4.629; p-value = .031) can predict the severity of NMOSD. CONCLUSIONS: Antinuclear antibodies seem to be associated with more severe disease activity in NMOSD patients.

Analysis of air quality characteristics of Beijing-Tianjin-Hebei and its surrounding air pollution transport channel cities in China.

Beijing-Tianjin-Hebei (BTH) and its surrounding areas are very important to air pollution control in China. To analyze the characteristics of BTH and its surrounding areas of China, we collected 5,641,440 air quality data from 161 air monitoring stations and 37,123,000 continuous monitoring data from air polluting enterprises in BTH and surrounding cities to establish an indicator system for urban air quality portraits. The results showed that particulate matter with aerodynamic diameters of <2.5 µm (PM2.5), particulate matter with aerodynamic diameters of <10 µm (PM10) and SO2 improved significantly in 31 cities from 2015 to 2018, but ozone deteriorated. Air quality in BTH and the surrounding areas showed obvious seasonal characteristics, among which PM2.5, PM10, SO2, and NO2 showed a "U" type distribution from January to December, while O3 had an "inverted U" distribution. The hourly changes in air quality revealed that peaks of PM2.5, PM10 and NO2 appeared from 8:00 to 10:00, while those for O3 appeared at 15:00-16:00. The exposure characteristics of the 31 cities showed that six districts in Beijing had the highest air quality population exposure, and that exposure levels in Zhengzhou, Puyang, Anyang, Jincheng were higher than the average of the 31 investigated cities. Additionally, multiple linear regression revealed a negative correlation between meteorological factors (especially wind and precipitation) and air quality, while a positive correlation existed between industrial pollution emissions and air quality in most of BTH and its surrounding cities.