Gut bacterium Burkholderia cepacia (BsNLG8) and immune gene Defensin A contribute to the resistance against Nicotine-induced stress in Nilaparvata lugens (Stål).

Nicotine, a naturally occurring alkaloid found in tobacco, is a potent neurotoxin extensively used to control Nilaparvata lugens (Stål), a destructive insect pest of rice crops. The insect gut harbors a wide array of resident microorganisms that profoundly influence several biological processes, including host immunity. Maintaining an optimal gut microbiota and immune homeostasis requires a complex network of reciprocal regulatory interactions. However, the underlying molecular mechanisms driving these symbiotic exchanges, particularly between specific gut microbe and immunity, remain largely unknown in insects. Our previous investigations identified and isolated a nicotine-degrading Burkholderia cepacia strain (BsNLG8) with antifungal properties. Building on those findings, we found that nicotine intake significantly increased the abundance of a symbiotic bacteria BsNLG8, induced a stronger bacteriostatic effect in hemolymph, and enhanced the nicotine tolerance of N. lugens. Additionally, nicotine-induced antimicrobial peptides (AMPs) exhibited significant antibacterial effects against Staphylococcus aureus. We adopted RNA-seq to explore the underlying immunological mechanisms in nicotine-stressed N. lugens. Bioinformatic analyses identified numerous differentially expressed immune genes, including recognition/immune activation (GRPs and Toll) and AMPs (i.e., Defensin, Lugensin, lysozyme). Temporal expression profiling (12, 24, and 48 hours) of immune genes revealed pattern recognition proteins and immune effectors as primary responders to nicotine-induced stress. Defensin A, a broad-spectrum immunomodulatory cationic peptide, exhibited significantly high expression. RNA interference-mediated silencing of Defensin A reduced the survival, enhanced nicotine sensitivity of N. lugens to nicotine, and decreased the abundance of BsNLG8. The reintroduction of BsNLG8 improved the expression of immune genes, aiding nicotine resistance of N. lugens. Our findings indicate a potential reciprocal immunomodulatory interaction between Defensin A and BsNLG8 under nicotine stress. Moreover, this study offers novel and valuable insights for future research into enhancing nicotine-based pest management programs and developing alternative biocontrol methods involving the implication of insect symbionts.

Prognostic factors associated with pulp status in patients with cracked teeth treated with occlusal veneer: A 6- through 24-month prospective clinical study.

BACKGROUND: The authors evaluated the prognostic factors associated with pulp status in patients with cracked teeth (CT) treated with occlusal veneer. METHODS: An analysis of 80 CT (71 patients) with 1 or more crack lines (CLs) and normal pulp vitality or reversible pulpitis was performed. All patients received occlusal veneer and their demographic and clinical data were recorded. Pulp status and clinical features were recorded at 1 week and posttreatment at 1, 2, 3, 6, 12, 18, and 24 months. RESULTS: Maxillary first molars were commonly involved (30 [38%]). The number of CLs on the finish line ranged from 1 through 7 and most had 3 CLs (24 [30%]). The number of CLs through preparation on the finish line ranged from 0 through 4, and 2 CLs (42 [53%]) were the most prevalent. During follow-up, 5 of 80 CT progressed to pulp disease, resulting in a success rate of 93.8%. Results of the Cox model and Kaplan-Meier analysis showed that probing depth greater than 6 mm, widening periodontal ligament of apical area, more than 4 CLs on finish line, and more than 2 CLs through preparation on the finish line were risk factors associated with pulp status (P < .05). CONCLUSIONS: Occlusal veneer can protect CT without preventive root canal therapy. PRACTICAL IMPLICATIONS: The success rate and risk factors of pulp disease in CT restored with occlusal veneer are reported.

Effect of Decentration, Rotation, and Tilt on Objective Optical Quality of Plate Haptic Toric Intraocular Lenses in the Early Postoperative Period.

Purpose: This study aimed to determine the influence of decentration, rotation, and tilt on objective optical quality of plate haptic toric intraocular lenses (tIOLs). Methods: The area ratio of modulation transfer function (MTF), strehl ratio of point spread function (PSF), and higher order aberrations (HOAs) for 3 mm and 5 mm pupil diameter (PD) were evaluated at postoperative 1 month. The retroillumination images pictured by OPD-scan III were used to quantify the degree of decentration and rotation, whereas the tIOL tilt was directly obtained by the tilt aberration. Patients were separated into two subgroups based on tIOL misalignment cutoff values. Results: There were 29 eyes (24 patients) in the study. The decentration of more than 0.25 mm did not substantially differ from those less than or equal to 0.25 mm. PSF of 3 mm PD and MTF, intraocular HOAs, and trefoil aberration for 3 mm and 5 mm PD significantly deteriorated with a rotation of more than 3 degrees, whereas only intraocular HOAs for 5 mm PD and coma for 3 mm and 5 mm PD were significantly severe with a tilt of more than 0.1 µm and 0.25 µm in corresponding PD. Furthermore, tIOL rotation and tilt were highly correlated with intraocular trefoil aberration and coma, respectively. Conclusions: The decentration of the monofocal bitoric IOLs is more tolerant to optical quality degradation after 1 month of surgery but more sensitive to intraocular trefoil aberration caused by rotation and coma aberration induced by tilt. Translational Relevance: As far as we know, this is the first study to investigate the relationship between the plate haptic bitoric IOL misalignment and objective optical quality measured by OPD-scan III in the real world, which may provide reference information for IOL selection to improve surgical outcomes.

Biting and thermal sensitivity relief of cracked tooth restored by occlusal veneer: A 12-to 24 months prospective clinical study.

OBJECTIVES: To analyze the relief time and risk factors of biting/thermal sensitivity in cracked tooth (CT) restored using occlusal veneer. METHODS: 63 CT were analyzed, and their demographic and clinical data and medical history were collected. Patients were followed-up to examine the relief of thermal/biting sensitivity. RESULTS: The maxillary first molar was the most prevalent (N = 25, 40%). The number of crack lines on the finish line ranged from 1 to 6 while the number of crack lines through preparation on the finish line from 0 to 4. Pain relief achieved steadily to 52% for thermal and 62% for biting at 1 week to over 90% for each by 3 months and was completely resolved (no pain) for each by 12 months. Painful of lateral percussion was related to a long period of thermal sensitivity (≥1 month) after restoration with occlusal veneer. The number of crack lines through preparation on the finish line >2 was correlated with biting sensitivity (≥1 month) post-treatment. CONCLUSIONS: Most patients (>90%) became asymptomatic of biting and thermal sensitivity within 3 months of CT restored by occlusal veneer. Lateral percussion and the number of crack lines through preparation on the finish line could be significant factors affecting postoperative symptoms. CLINICAL SIGNIFICANCE: Occlusal veneer is an ultrathin restoration and had no need for restricting clinical crown height, which could protect and relief the biting/thermal sensitivity of CT without preventive root canal therapy.

Management and prognosis of a vital cracked tooth by occlusal veneer for 14 months: A case report.

Key Clinical Message: An occlusal veneer is an ultrathin restoration method and a minimally invasive approach that can preserve more dental tissue and provide better aesthetic outcomes, thus increasing patient satisfaction. Abstract: An occlusal veneer is an ultrathin restoration method and a minimally invasive approach that can preserve more dental tissue and provide better aesthetic outcomes, thus increasing patient satisfaction; however, no previous studies reported on treating cracked teeth using occlusal veneer. Accordingly, we described the diagnosis and treatment process of a cracked tooth using occlusal veneer in a single case. A 29-year-old male presented at our dental clinic complaining of biting pain in the mandibular molar on the right-hand side. A routine oral examination with radiography was performed to evaluate the oral condition and treatment planning. The #16 tooth had a crack line surrounding the whole distal-lingual cusp from the occlusal surface. After discussing various therapeutic options with the patient, an occlusal veneer was performed. One week after treatment with occlusal veneer, the patient had no complaints. A 14-month follow-up showed promising clinical and radiographic outcomes. Occlusal veneer is an alternative treatment option for a cracked tooth, as it can preserve more dental tissue and potentially save pulp vitality.

PTCH/SMO gene mutations in odontogenic keratocysts and drug interventions.

BACKGROUND: Odontogenic keratocysts (OKCs) are odontogenic jaw lesions that cause destruction and dysfunction of the jawbone. OKCs can be sporadic or associated with nevoid basic cell carcinoma syndrome (NBCCS). However, the factors that initiate OKCs and the mechanism of cyst formation remain unclear. Here, we investigated the impact of PTCH1 and SMO mutations on disease progression, as well as the effects of sonic hedgehog (SHH) signaling pathway inhibitors GDC-0449 and GANT61 on OKC fibroblasts. METHODS: Eight sporadic OKC fibroblasts without gene mutations were used as the control, and six NBCCS-related fibroblasts were cultured in vitro. The effect of PTCH1 non-truncated mutation 3499G>A (p.G1167R) and SMO c.2081C>G (p.P694R) mutation on OKC fibroblast proliferation was examined by EdU assay. CCK8 and wound-healing assays detected the effects of OKC fibroblasts carrying PTCH1 c.3499G>A (p.G1167R) and SMO c.2081C>G (p.P694R) mutations on the proliferation and migration of HaCaT cells after co-culture. Quantitative real-time PCR detected the effects of GDC-0449 or GANT61 on the SHH signaling pathway in NBCCS-related OKCs with PTCH1 truncated mutations and PTCH1 c.3499G>A (p.G1167R) and/or SMO c.2081C>G (p.P694R) mutations. RESULTS: PTCH1 c.3499G>A (p.G1167R) and SMO c.2081C>G (p.P694R) promoted the proliferation of OKC fibroblasts. The proliferation and migration of HaCaT cells were affected by NBCCS-related OKC fibroblasts carrying PTCH1 c.3499G>A (p.G1167R) and SMO c.2081C>G (p.P694R) mutations. GDC-0449 significantly inhibited the SHH signaling pathway in NBCCS-related OKC fibroblasts with PTCH1 truncated mutations. An NBCCS-related OKC carrying PTCH1 c.3499G>A (p.G1167R) and SMO c.2081C>G (p.P694R) mutations were resistant to GDC-0449 but inhibited by GANT61. CONCLUSIONS: Genetic mutations in OKC fibroblasts may affect the biological behavior of epithelial and stromal cells and cause disease. GDC-0449 could be used to treat OKCs, especially NBCCS-related OKCs with PTCH1 truncated mutations. SMO c.2081C>G (p.P694R) may lead to resistance to GDC-0449; however, GANT61 may be used as an alternative inhibitor.

Nicotine perturbs the microbiota of brown planthopper (Nilaparvata lugens stål Hemiptera: Delphinidae).

Bacterial symbionts exhibiting co-evolutionary patterns with insect hosts play a vital role in the nutrient synthesis, metabolism, development, reproduction, and immunity of insects. The brown planthopper (BPH) has a strong ability to adapt to various environmental stresses and can develop resistance to broad-spectrum insecticides. We aimed to investigate whether gut symbionts of BPH play a major role in the detoxification of insecticides and host fitness in unfavorable environments. Nicotine-treated rice plants were exposed to BPH (early stage) and the gut microbiome of the emerging female adults were analyzed using high throughput sequencing (HTS). Nicotine administration altered the diversity and community structure of BPH symbionts with significant increases in bacterial members such as Microbacteriaceae, Comamondaceae, Enterobacteriaceae, and these changes may be associated with host survival strategies in adverse environments. Furthermore, the in-vitro study showed that four intestinal bacterial strains of BPH (Enterobacter NLB1, Bacillus cereus NL1, Ralstonia NLG26, and Delftia NLG11) could degrade nicotine when grown in a nicotine-containing medium, with the highest degradation (71%) observed in Delftia NLG11. RT-qPCR and ELISA analysis revealed an increased expression level of CYP6AY1 and P450 enzyme activities in Delftia NLG11, respectively. CYP6AY1 increased by 20% under the action of Delftia and nicotine, while P450 enzyme activity increased by 18.1%. After CYP6AY1 interference, nicotine tolerance decreased, and the mortality rate reached 76.65% on the first day and 100% on the third day. Moreover, Delftia NLG11 helped axenic BPHs to increase their survival rate when fed nicotine in the liquid-diet sac (LDS) feeding system. Compared with axenic BPHs, the survival rate improved by 25.11% on day 2% and 6.67% on day 3. These results revealed an altered gut microbiota and a cooperative relationship between Delftia NLG11 and CYP6AY1 in nicotine-treated BPH, suggesting that insects can adapt to a hostile environment by interacting with their symbionts and providing a new idea for integrated pest management strategies.

A Bayesian network meta-analysis on comparisons of intraocular lens power calculation methods for paediatric cataract eyes.

The study aimed to compare and rank the accuracy of formulas for calculating intraocular lens (IOL) power in paediatric eyes in a systematic way. A literature search was conducted in Pubmed, Web of Science, Cochrane Library, and EMBASE by December 2021. Combined with traditional and network meta-analysis, we analysed the percentages of paediatric eyes with prediction error (PE) within ±0.50 dioptres (D) and ±1.00 D as the outcome measurements among different formulas. Subgroup analyses stratified by age were also undertaken. Thirteen studies with 1781 eyes comparing 8 calculation formulas were included. For the traditional meta-analysis results, Sanders-Retzlaff-Kraff theoretical (SRK/T) (risk ratios (RR), 1.15; 95% confidence intervals (CI), 1.03-1.30) performed significantly better than the SRKII formula for the percentage of eyes with PE within ±0.50 D. In addition, SRK/T (RR, 1.10; 95% CI, 1.02-1.18) and Holladay 1(RR, 1.15; 95% CI, 1.01-1.30) both performed significantly better than the SRKII formula for the percentage of eyes with PE within ±1.00 D. Considering the ranking based on the surface under the cumulative ranking curve (SUCRA) by Bayesian method, the top four formulas were Barrett Universal II (UII), Haigis, Holladay 1, and SRK/T on the percentage of PE within ±0.50 D, whereas the top four formulas were Barrett UII, Holladay 1, SRK/T, and Hoffer Q formulas on the percentage of PE within ±1.00D. Concerning both outcome measurements of rank probabilities, the top three Barrett UII, SRK/T, and Holladay 1 formulas were considered to provide more accuracy for IOL power calculation in paediatric cataract eyes, and Barrett UII tends to perform better in older children.

ceRNA network construction and identification of hub genes as novel therapeutic targets for age-related cataracts using bioinformatics.

Background: The aim of this study is to investigate the genetic and epigenetic mechanisms involved in the pathogenesis of age-related cataract (ARC). Methods: We obtained the transcriptome datafile of th ree ARC samples and three healthy, age-matched samples and used differential expression analyses to identify the differentially expressed genes (DEGs). The differential lncRNA-associated competing endogenous (ceRNA) network, and the protein-protein network (PPI) were constructed using Cytoscape and STRING. Cluster analyses were performed to identify the underlying molecular mechanisms of the hub genes affecting ARC progression. To verify the immune status of the ARC patients, immune-associated analyses were also conducted. Results: The PPI network identified the FOXO1 gene as the hub gene with the highest score, as calculated by the Maximal Clique Centrality (MCC) algorithm. The ceRNA network identified lncRNAs H19, XIST, TTTY14, and MEG3 and hub genes FOXO1, NOTCH3, CDK6, SPRY2, and CA2 as playing key roles in regulating the pathogenesis of ARC. Additionally, the identified hub genes showed no significant correlation with an immune response but were highly correlated with cell metabolism, including cysteine, methionine, and galactose. Discussion: The findings of this study may provide clues toward ARC pathogenic mechanisms and may be of significance for future therapeutic research.

The growth and shape of the eyeball and crystalline lens in utero documented by fetal MR imaging.

Purpose: To study the growth model, shape, and developmental relationship of lens and eyeball, we used two-dimensional Magnetic Resonance (MR) imaging to investigate gestationally age-related changes in the selected ocular parameters in vivo. Materials and methods: We retrospectively reviewed the MR images from 126 fetuses ranging from 21 to 39 weeks' gestation. Ocular parameters on MR imaging of transverse plane were measured including lens diameter (LD), anteroposterior lens diameter (APLD), lens surface area (LS), globe diameter (GD), anteroposterior globe diameter (APGD), globe surface area (GS). The growth model of each biometric against gestational age (GA), aspect ratio of lens and globe (LD/APLD and GD/APGD), and growing relationship between the ratio of lens and globe surface area (LS/GS) were studied by statistical analysis. Results: The growth model of most biometry for gestational age is logarithmic, except for the diameter of the ocular globe (GD and APGD) showing a quadratic growth pattern. Our study showed that the lens was consistently larger in the transverse than the anteroposterior diameters during 21-39 weeks(P < 0.001). Besides, the ratio of surface area (LS/GS) was not significantly changing with GA(P = 0.4908), while the increase of LS was significantly accorded with that of GS(P < 0.001). Conclusion: The lens shape throughout fetal life may take part in the process, shape changing from vertical ellipsoid, spherical to transversal ellipsoid, based on the logarithmically increased ratio of lens transverse and anteroposterior diameters. In the meanwhile, the aspect ratio of eyeball in late fetal life may imply a gradually spherical shape during gestation. Nomogram data from this study may provide appropriate information about morphological changes in the fetal lens and the synchronous relationship between lens and eyeball.

[Establishment and Application of Foshan Ozone Concentration Forecast Equation].

The formation and changes of ozone (O3), a secondary pollutant in the atmosphere, are complex, and ozone forecasting has become one of the current problems in air pollution prevention and control. In this study, the relationships between the near-surface O3 concentration and meteorological elements (high- and low-level) in Foshan from 2014 to 2017 were analyzed, and the concentration forecasting equation was established, tested, and applied. The results showed that the near-surface O3 changed closely related to high- and low-level meteorological elements. Meteorological elements such as temperature and sunshine hours were significantly positively correlated with O3 concentration, whereas relative humidity, total (low) cloud cover, and wind speed were negatively correlated with O3. Heavy O3 pollution often occurred with meteorological conditions of low wind speed, sunny days and few clouds, low relative humidity, longer sunshine time, and higher temperature. The definitions of high-concentration O3 potential index (HOPI) and wind direction index (WDI) in the Foshan area could better characterize the meteorological conditions of O3 pollution. Considering 13 meteorological elements, such as HOPI and WDI at different heights, the O3 concentration forecasting equation in the Foshan area was established using multi-indicator stacking and multiple stepwise regression methods. Using the 2018 data, it was found that the correlation coefficient R between the simulated values and the measured values reached 0.82, and the forecast equation had a good fitting effect and predictability.

Prevalence and Risk Factors for Adult Cataract in the Jingan District of Shanghai.

Purpose: We report the prevalence of age-related cataract (ARC) in the Jingan district of Shanghai and analyze the risk factors for ARC to be better prepared for the increasing burden of cataracts as a significant cause of visual impairment worldwide. Methods: From March to June 2010, a population-based, cross-sectional study was conducted in a community selected by stratified cluster sampling in the Jingan district of Shanghai. Residents aged 40 and older were recruited and investigated by questionnaires and ophthalmic examination. Univariate and multivariate logistic regression models were used to evaluate the association of these risk factors with any cataract. Results: A total of 2894 subjects aged 40 years and above were included in our study. Nine hundred forty-eight people (32.8%) were diagnosed with cataract, including 845 with bilateral cataracts (29.2%) and 292 with moderate and severe visual impairment (low vision, 10.1%). There were significant differences in low vision among different age groups and gender (Χ2 age = 84.420, P age < 0.001, Χ2 gender = 7.696, P gender = 0.021). For any cataract, we found age (OR = 1.107, 95% CI: 1.094-1.120) and refractive error (OR = 1.352, 95% CI: 1.127-1.622) were independent risk factors. Conclusion: The prevalence of cataract is estimated to be nearly one-third of the sample, increasing with age. We provided further evidence that age and refractive error are independent cataract risk factors.

The power, potential, benefits, and challenges of implementing high-throughput sequencing in food safety systems.

The development and application of modern sequencing technologies have led to many new improvements in food safety and public health. With unprecedented resolution and big data, high-throughput sequencing (HTS) has enabled food safety specialists to sequence marker genes, whole genomes, and transcriptomes of microorganisms almost in real-time. These data reveal not only the identity of a pathogen or an organism of interest in the food supply but its virulence potential and functional characteristics. HTS of amplicons, allow better characterization of the microbial communities associated with food and the environment. New and powerful bioinformatics tools, algorithms, and machine learning allow for development of new models to predict and tackle important events such as foodborne disease outbreaks. Despite its potential, the integration of HTS into current food safety systems is far from complete. Government agencies have embraced this new technology, and use it for disease diagnostics, food safety inspections, and outbreak investigations. However, adoption and application of HTS by the food industry have been comparatively slow, sporadic, and fragmented. Incorporation of HTS by food manufacturers in their food safety programs could reinforce the design and verification of effectiveness of control measures by providing greater insight into the characteristics, origin, relatedness, and evolution of microorganisms in our foods and environment. Here, we discuss this new technology, its power, and potential. A brief history of implementation by public health agencies is presented, as are the benefits and challenges for the food industry, and its future in the context of food safety.

Prognostic factors for hearing outcomes in patients that undergo adjuvant hyperbaric oxygen therapy for sudden sensorineural hearing loss.

Introduction: The aim of this study is to explore the potential factors in hearing outcomes and verify the role of oxidant-antioxidant equilibrium on the prognosis of sudden sensorineural hearing loss (SSNHL) treated with hyperbaric oxygen therapy (HBOT). Methods: Ninety-two patients who were diagnosed with SSNHL between January 2018 and December 2019 in our hearing clinic center were included in this study. All patients were treated with intravenous dexamethasone, and 72 cases were treated with additional HBOT for 10 consecutive days. Peripheral blood was collected prior to any treatment to determine the blood cell count and hemoglobin (HGB), hematocrit (HCT), and superoxide dismutase (SOD) levels. Pure tone audiometry was measured before and after treatment. Complete and overall recovery rate was evaluated. Multivariate logistic analysis was used to identify prognostic factors. Results: The rate of overall recovery was significantly higher in the patient with combined therapy compared to patients treated with steroids only (51.4% vs 25.0%, p = .036). The levels of HGB, HCT, and SOD were much higher in the patients with better hearing outcomes (p = .027, .033, and .011, respectively). Multivariate logistic analysis demonstrated that patients with higher initial hearing thresholds, or hearing loss at overall frequency, were more prone to have poor hearing gains after HBOT. Conclusion: HBOT is effective as an early adjuvant therapy for SSNHL. Hearing loss at low frequency, low initial hearing thresholds, as well as high HBG, HCT, and SOD levels are positive prognostic factors for SSNHL patients treated with HBOT.

Presbyopia-Correcting Intraocular Lenses Implantation in Eyes After Corneal Refractive Laser Surgery: A Meta-Analysis and Systematic Review.

Purpose: To assess the efficacy, safety, and predictability of presbyopia-correcting intraocular lenses (IOLs) in cataract patients with previous corneal refractive surgery. Methods: A systematic literature search was performed to identify studies evaluating the clinical outcomes of presbyopia-correcting IOLs implantation in cataract surgery after laser refractive surgery. Outcomes were efficacy, safety and predictability parameters. Results: The authors identified 13 studies, involving a total of 128 patients and 445 eyes. Presbyopia-correcting IOLs were effective at improving distance, intermediate and near visual acuity aftercataract surgery. The proportion of post-laser surgery eyes with uncorrected distance visual acuity (UDVA) ≥ 20/25 was 0.82 [95% confidence interval (CI), 0.74-0.90] and the pooled rates of spectacle independence at near, intermediate, and far distances were 0.98 (95% CI, 0.94-1.00), 0.99 (95% CI, 0.95-1.00) and 0.78 (95% CI, 0.65-0.94) respectively. The percentage of participants who suffered from halos and glare was 0.40 (95% CI, 0.25-0.64) and 0.31 (95% CI, 0.16-0.60), respectively. The predictability had a percentage of 0.66 (95% CI, 0.57-0.75) and 0.90 (95% CI, 0.85-0.96) of eyes within ±0.5 diopters (D) and ±1.0 D from the targeted spherical equivalent. Conclusions: Presbyopia-correcting IOLs provide satisfactory results in terms of efficacy, safety and predictability in patients with previous corneal refractive surgery, but have a higher risk of photopic side effects such as halos and glare.

[The efficacy of modified mini-mental state examination in patients with severe to profound hearing loss].

Objective:To evaluate the efficacy of modified mini-mental state examination（MMSE） in elderly patients with severe to profound hearing loss. Methods:A total of 24 elderly patients with severe to profound hearing loss from April to June 2019 were involved. Severe to profound hearing loss was defined by a pure-tone average of hearing thresholds at 0.5, 1, 2, and 4 kHz in the better-hearing ear. Modified and original MMSE was completed for the patients at first visit. Two weeks later, they all return hospital and MMSE were carried out by the other method. The aggregate score and subitem score of MMSE by modified and original instrument were analyzed. The degree of cognitive impairment evaluated by two methods were compared. Results:Among the 24 patients, the mean MMSE score by routine method and improved method were 10.88±9.70 and 25.29±3.70（P<0.01）. The average score of sub-items of MMSE with routine method and improved method are as follows: orientation 3.21±4.03 vs 8.71±1.92（P<0.01）, registration 1.04±1.33 vs 2.79±0.51（P<0.01）, attention and calculation 1.63±2.02 vs 4.00±1.41（P<0.01）, recall 0.79±1.14 vs 2.50±0.72（P<0.01）, language 4.21±2.11 vs 7.29±1.33（P<0.01）. Compared with the routine method, the degree of cognitive impairment getting better in 83.3% patients with improved method, meanwhile, 16.7% of the patients remain the same and no deterioration. Conclusion:The routine method of MMSE should be improved to seek the real cognitive state of the patients with severe to profound hearing loss.

Audiometric Phenotypes of Noise-Induced Hearing Loss by Data-Driven Cluster Analysis and Their Relevant Characteristics.

Background: The definition of notched audiogram for noise-induced hearing loss (NIHL) is presently based on clinical experience, but audiometric phenotypes of NIHL are highly heterogeneous. The data-driven clustering of subtypes could provide refined characteristics of NIHL, and help identify individuals with typical NIHL at diagnosis. Methods: This cross-sectional study initially recruited 12,218 occupational noise-exposed employees aged 18-60 years from two factories of a shipyard in Eastern China. Of these, 10,307 subjects with no history of otological injurie or disease, family history of hearing loss, or history of ototoxic drug use were eventually enrolled. All these subjects completed health behavior questionnaires, cumulative noise exposure (CNE) measurement, and pure-tone audiometry. We did data-driven cluster analysis (k-means clustering) in subjects with hearing loss audiograms (n = 6,599) consist of two independent datasets (n = 4,461 and n = 2,138). Multinomial logistic regression was performed to analyze the relevant characteristics of subjects with different audiometric phenotypes compared to those subjects with normal hearing audiograms (n = 3,708). Results: A total of 10,307 subjects (9,165 males [88.9%], mean age 34.5 [8.8] years, mean CNE 91.2 [22.7] dB[A]) were included, 3,708 (36.0%) of them had completely normal hearing, the other 6,599 (64.0%) with hearing loss audiograms were clustered into four audiometric phenotypes, which were replicable in two distinct datasets. We named the four clusters as the 4-6 kHz sharp-notched, 4-6 kHz flat-notched, 3-8 kHz notched, and 1-8 kHz notched audiogram. Among them, except for the 4-6 kHz flat-notched audiogram which was not significantly related to NIHL, the other three phenotypes with different relevant characteristics were strongly associated with noise exposure. In particular, the 4-6 kHz sharp-notched audiogram might be a typical subtype of NIHL. Conclusions: By data-driven cluster analysis of the large-scale noise-exposed population, we identified three audiometric phenotypes associated with distinct NIHL subtypes. Data-driven sub-stratification of audiograms might eventually contribute to the precise diagnosis and treatment of NIHL.

Acute Recreational Noise-Induced Cochlear Synaptic Dysfunction in Humans With Normal Hearing: A Prospective Cohort Study.

OBJECTIVES: The objective of the study was to identify the acute high-intensity recreational noise-induced effects on auditory function, especially the cochlear synaptopathy-related audiological metrics, in humans with normal hearing. METHODS: This prospective cohort study enrolled 32 young adults (14 males and 18 females); the mean age was 24.1 ± 2.4 years (ranging from 20 to 29). All participants with normal hearing (audiometric thresholds ≤25 dB HL at frequencies of 0.25, 0.5, 1, 2, 3, 4, 6, and 8 kHz for both ears) had already decided to participate in the outdoor music festival. Participants were asked to measure the noise exposure dose and complete auditory examinations, including the air-conduction pure-tone audiometry (PTA), distortion product otoacoustic emission (DPOAE), contralateral suppression (CS) on transient evoked otoacoustic emission (TEOAE), auditory brainstem response (ABR) test and Mandarin Hearing in Noise Test (MHINT), at baseline and 1 day and 14 days after music festival noise exposure. RESULTS: The mean time of attending the music festival was 7.34 ± 0.63 h (ranging from 6.4 to 9.5), the mean time-weighted average (TWA) of noise exposure dose was 93.2 ± 2.39 dB(A) (ranging from 87.9 to 97.7). At neither 1 day nor 14 days post exposure, there were no statistically significant effects on PTA thresholds, DPOAE amplitudes, CS on TEOAEs, or MHINT signal-to-noise ratios (SNRs) of acute outdoor music festival noise exposure, regardless of sex. While the ABR wave I amplitudes significantly decreased at 1 day after exposure and recovered at 14 days after exposure, the exposed/unexposed ABR wave I amplitude ratio was significantly correlated with MHINT SNR change at 1 day after exposure, although it was not correlated with the noise exposure dose. CONCLUSION: In young adults with normal hearing, we found the self-compared decrement of ABR wave I amplitudes at 1 day post acute recreational noise exposure at high intensity, which also contributes to the change in speech perceptual ability in noisy backgrounds. This study indicated that auditory electrophysiological metric changes might be a more sensitive and efficient indicator of noise-induced cochlear synaptic dysfunction in humans. More attention should be paid to the recreational noise-induced cochlear synaptopathy and auditory perceptual disorder.

Porcine deltacoronavirus nsp10 antagonizes interferon-ß production independently of its zinc finger domains.

Porcine deltacoronavirus (PDCoV) is a novel swine enteropathogenic coronavirus that causes serious vomiting and diarrhea in piglets. Previous work demonstrated that PDCoV infection inhibits type I interferon (IFN) production. Here, we found that ectopic expression of PDCoV nsp10 significantly inhibited Sendai virus (SeV)-induced IFN-ß production by impairing the phosphorylation and nuclear translocation of two transcription factors, IRF3 and NF-κB p65 subunit. Interestingly, experiments with truncated mutants and site-directed mutagenesis revealed that PDCoV nsp10 mutants with missing or destroyed zinc fingers (ZFs) domains also impeded SeV-induced IFN-ß production, suggesting that nsp10 does not require its ZF domains to antagonize IFN-ß production. Further work found that co-expression of nsp10 with nsp14 or nsp16, two replicative enzymes, significantly enhanced the inhibitory effects of nsp10 on IFN-ß. Taken together, our results demonstrate that PDCoV nsp10 antagonizes IFN via a ZF-independent mechanism and has a synergistic effect with nsp14 and nsp16 on inhibiting IFN-ß production.