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Background/Objectives: Benign paroxysmal positional vertigo (BPPV) is the most common cause of recurrent vertigo and the most common peripheral vestibular disorder. It is characterized by intense vertigo triggered by head and position changes. This study investigates the risk of subsequent injury in BPPV patients and the effects of treatment. Methods: A population-based retrospective cohort study was conducted using data from the Longitudinal Health Insurance Database 2005 in Taiwan. Patients with and without BPPV were identified between 2000 and 2017. The study outcomes were diagnoses of all-cause injuries. The Kaplan-Meier method determined the cumulative incidence rates of injury in both cohorts, and a log-rank test analyzed the differences. Cox proportional hazard models calculated each cohort's 18-year hazard ratios (HRs). Results: We enrolled 50,675 patients with newly diagnosed BPPV and 202,700 matched individuals without BPPV. During follow-up, 47,636 patients were diagnosed with injuries (13,215 from the BPPV cohort and 34,421 from the non-BPPV cohort). The adjusted HR for injury in BPPV patients was 2.63 (95% CI, 2.49-2.88). Subgroup analysis showed an increased incidence of unintentional and intentional injuries in BPPV patients (aHR 2.86; 95% CI, 2.70-3.13 and 1.10; 95% CI, 1.04-1.21, respectively). A positive dose-response relationship was observed with increasing BPPV diagnoses. Treatment with canalith repositioning therapy (CRT) or medications reduced the risk of injury slightly but not significantly (aHR, 0.78; 95% CI, 0.37-1.29, 0.88; 95% CI, 0.40-1.40, respectively). Conclusions: BPPV is independently associated with an increased risk of injuries. CRT or medications have limited effects on mitigating this risk. Physicians should advise BPPV patients to take precautions to prevent injuries even after treatment.
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The synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) are the most vulnerable structures in the noise-exposed cochlea. Cochlear synaptopathy results from the disruption of these synapses following noise exposure and is considered the main cause of poor speech understanding in noisy environments, even when audiogram results are normal. Cochlear synaptopathy leads to the degeneration of SGNs if damaged IHC-SGN synapses are not promptly recovered. Oxidative stress plays a central role in the pathogenesis of cochlear synaptopathy. C-Phycocyanin (C-PC) has antioxidant and anti-inflammatory activities and is widely utilized in the food and drug industry. However, the effect of the C-PC on noise-induced cochlear damage is unknown. We first investigated the therapeutic effect of C-PC on noise-induced cochlear synaptopathy. In vitro experiments revealed that C-PC reduced the H2O2-induced generation of reactive oxygen species in HEI-OC1 auditory cells. H2O2-induced cytotoxicity in HEI-OC1 cells was reduced with C-PC treatment. After white noise exposure for 3 h at a sound pressure of 118 dB, the guinea pigs intratympanically administered 5 µg/mL C-PC exhibited greater wave I amplitudes in the auditory brainstem response, more IHC synaptic ribbons and more IHC-SGN synapses according to microscopic analysis than the saline-treated guinea pigs. Furthermore, the group treated with C-PC had less intense 4-hydroxynonenal and intercellular adhesion molecule-1 staining in the cochlea compared with the saline group. Our results suggest that C-PC improves cochlear synaptopathy by inhibiting noise-induced oxidative stress and the inflammatory response in the cochlea.
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Cóclea , Molécula 1 de Adhesión Intercelular , Ruido , Estrés Oxidativo , Ficocianina , Sinapsis , Animales , Estrés Oxidativo/efectos de los fármacos , Cobayas , Ficocianina/farmacología , Ficocianina/uso terapéutico , Cóclea/metabolismo , Cóclea/efectos de los fármacos , Cóclea/patología , Sinapsis/efectos de los fármacos , Sinapsis/metabolismo , Ruido/efectos adversos , Molécula 1 de Adhesión Intercelular/metabolismo , Pérdida Auditiva Provocada por Ruido/tratamiento farmacológico , Pérdida Auditiva Provocada por Ruido/metabolismo , Pérdida Auditiva Provocada por Ruido/patología , Especies Reactivas de Oxígeno/metabolismo , Masculino , Ganglio Espiral de la Cóclea/efectos de los fármacos , Ganglio Espiral de la Cóclea/metabolismo , Ganglio Espiral de la Cóclea/patología , Peróxido de Hidrógeno/metabolismo , Células Ciliadas Auditivas Internas/efectos de los fármacos , Células Ciliadas Auditivas Internas/metabolismo , Células Ciliadas Auditivas Internas/patología , Antioxidantes/farmacología , Línea Celular , Pérdida de Audición OcultaRESUMEN
The ability to sense prey-derived cues is essential for predatory lifestyles. Under low-nutrient conditions, Arthrobotrys oligospora and other nematode-trapping fungi develop dedicated structures for nematode capture when exposed to nematode-derived cues, including a conserved family of pheromones, the ascarosides. A. oligospora senses ascarosides via conserved MAPK and cAMP-PKA pathways; however, the upstream receptors remain unknown. Here, using genomic, transcriptomic and functional analyses, we identified two families of G protein-coupled receptors (GPCRs) involved in sensing distinct nematode-derived cues. GPCRs homologous to yeast glucose receptors are required for ascaroside sensing, whereas Pth11-like GPCRs contribute to ascaroside-independent nematode sensing. Both GPCR classes activate conserved cAMP-PKA signalling to trigger trap development. This work demonstrates that predatory fungi use multiple GPCRs to sense several distinct nematode-derived cues for prey recognition and to enable a switch to a predatory lifestyle. Identification of these receptors reveals the molecular mechanisms of cross-kingdom communication via conserved pheromones also sensed by plants and animals.
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Ascomicetos , Feromonas , Receptores Acoplados a Proteínas G , Animales , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Ascomicetos/metabolismo , Ascomicetos/genética , Ascomicetos/fisiología , Feromonas/metabolismo , Nematodos/microbiología , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Transducción de Señal , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/genética , Caenorhabditis elegans/microbiologíaRESUMEN
BACKGROUND: Hearing loss has been shown to be a risk factor for psychiatric disorders. In addition, long-term hearing loss is associated with increased hospitalization and mortality rates; however, the increased risk and duration of effect of hearing loss in combination with other chronic diseases on each psychiatric disorder are still not clearly defined. The purpose of this article is to clarify the risk of hearing loss for each disorder over time. METHODS: This was a retrospective cohort study, and a national health insurance research database in Taiwan was utilized. All (n = 1,949,101) Taiwanese residents who had a medical visit between 2000 and 2015 were included. Patients with hearing loss and a comparative retrospective cohort were analyzed. Every subject was tracked individually from their index date to identify the subjects who later received a diagnosis of a psychiatric disorder. The KaplanâMeier method was used to analyze the cumulative incidence of psychiatric disorders. Cox regression analysis was performed to identify the risk of psychiatric disorders. RESULTS: A total of 13,341 (15.42%) and 31,250 (9.03%) patients with and without hearing loss, respectively, were diagnosed with psychiatric disorders (P < 0.001). Multivariate analysis indicated that hearing loss significantly elevated the risk of psychiatric disorders (adjusted HR = 2.587, 95% CI 1.723-3.346, p < 0.001). CONCLUSION: Our findings indicate that patients with hearing loss are more likely to develop psychiatric disorders. Furthermore, the various psychiatric disorders are more likely to occur at different times. Our findings have important clinical implications, including a need for clinicians to implement early intervention for hearing loss and to pay close attention to patients' psychological status. Trial registration TSGHIRB No. E202216036.
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Pérdida Auditiva , Trastornos Mentales , Humanos , Estudios de Cohortes , Pérdida Auditiva/complicaciones , Pérdida Auditiva/epidemiología , Incidencia , Trastornos Mentales/complicaciones , Trastornos Mentales/epidemiología , Factores de Riesgo , Taiwán/epidemiologíaRESUMEN
OBJECTIVE: In patients with obstructive sleep apnea (OSA), epiglottic collapse (EC) constitutes a major factor in the failure of continuous positive airway pressure therapy and uvulopalatopharyngoplasty. This study explored treatments that can improve EC in patients with OSA through drug-induced sleep endoscopy with target-controlled infusion (TCI-DISE). STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary center. METHODS: This study screened 352 OSA patients who underwent TCI-DISE between 2016 and 2022. Fifty-four patients with EC were included in the final analysis. EC severity was assessed multiple times through TCI-DISE with different interventions. RESULTS: The application of these interventions in patients with anteroposterior epiglottic collapse (apEC) led to a significant decrease in apEC severity from total to partial or no obstruction in 60.0% of patients by head rotation, in 53.6% by mouth closure, in 47.4% who received oral appliances (OA), and in 28.0% who received intermittent negative airway pressure (iNAP). With simultaneous head rotation, apEC severity decreased more significantly from total to partial or no obstruction in 77.8% of patients by mouth closure, in 70.3% who received OA, and in 68.0% who received iNAP. Lateral epiglottic collapse (latEC) severity decreased in 53.8% of patients after OA use and in 61.5% of patients with OA use and head rotation. CONCLUSION: This study identified head rotation with mouth closure as the most effective treatment for apEC through TCI-DISE. Patients with latEC had higher weight, apnea-hypopnea index, and body mass index compared with patients with apEC. OA use with head rotation appeared more effective in latEC through TCI-DISE.
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Fenilglioxal/análogos & derivados , Apnea Obstructiva del Sueño , Sueño , Humanos , Estudios Retrospectivos , Apnea Obstructiva del Sueño/cirugía , EndoscopíaRESUMEN
Nutritional deprivation triggers a switch from a saprotrophic to predatory lifestyle in soil-dwelling nematode-trapping fungi (NTF). In particular, the NTF Arthrobotrys oligospora secretes food and sex cues to lure nematodes to its mycelium and is triggered to develop specialized trapping devices. Captured nematodes are then invaded and digested by the fungus, thus serving as a food source. In this study, we examined the transcriptomic response of A. oligospora across the stages of sensing, trap development, and digestion upon exposure to the model nematode Caenorhabditis elegans. A. oligospora enacts a dynamic transcriptomic response, especially of protein secretion-related genes, in the presence of prey. Two-thirds of the predicted secretome of A. oligospora was up-regulated in the presence of C. elegans at all time points examined, and among these secreted proteins, 38.5% are predicted to be effector proteins. Furthermore, functional studies disrupting the t-SNARE protein Sso2 resulted in impaired ability to capture nematodes. Additionally, genes of the DUF3129 family, which are expanded in the genomes of several NTF, were highly up-regulated upon nematode exposure. We observed the accumulation of highly expressed DUF3129 proteins in trap cells, leading us to name members of this gene family as Trap Enriched Proteins (TEPs). Gene deletion of the most highly expressed TEP gene, TEP1, impairs the function of traps and prevents the fungus from capturing prey efficiently. In late stages of predation, we observed up-regulation of a variety of proteases, including metalloproteases. Following penetration of nematodes, these metalloproteases facilitate hyphal growth required for colonization of prey. These findings provide insights into the biology of the predatory lifestyle switch in a carnivorous fungus and provide frameworks for other fungal-nematode predator-prey systems.
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Caenorhabditis elegans , Nematodos , Animales , Caenorhabditis elegans/genética , Carnivoría , Perfilación de la Expresión Génica , MetaloproteasasRESUMEN
OBJECTIVE: To identify the value of head rotation in the supine position and oral appliance (OA) use in drug-induced sleep endoscopy (DISE). STUDY DESIGN: Eighty-three sleep apnea adults undergoing target-controlled infusion-DISE (TCI-DISE) were recruited from a tertiary academic medical center. SETTING: During DISE, 4 positions were utilized: supine position (position 1), head rotation (position 2), mandibular advancement using an OA (position 3), and head rotation with an OA (position 4). METHODS: Polysomnography (PSG) data and anthropometric variables during DISE were analyzed. RESULTS: Eighty-three patients (65 men and 18 women; mean [standard deviation, SD], 48.5 [11.0] years) who underwent PSG and TCI-DISE were included. The mean (SD) apnea-hypopnea index (AHI) was 35.5 (22.4) events/h. Twenty-three patients had persistent complete concentric velopharyngeal collapse in the supine position, even with concurrent head rotation and OA (position 4). Their mean (SD) AHI was 54.7 (24.6) events/h, significantly higher than that of the 60 patients without such collapse in position 4 (p < .001). Their mean (SD) body mass index (BMI) was 29.0 (4.1) kg/m2 , also significantly higher (p = .005). After adjustment for age, BMI, tonsil size, and tongue position, the degree of velum and tongue base obstruction was significantly associated with sleep apnea severity in positions 2, 3, and 4. CONCLUSION: We showed the feasibility, safety, and usefulness of using simple edge-to-edge, reusable OA in DISE. Patients who are not responsive to head rotation and OA during TCI-DISE may need upper airway surgery and/or weight control.
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Apnea Obstructiva del Sueño , Masculino , Adulto , Humanos , Femenino , Apnea Obstructiva del Sueño/cirugía , Polisomnografía , Endoscopía , Índice de Masa Corporal , SueñoRESUMEN
OBJECTIVE: To investigate the risk of injury in patients with Ménière's disease (MD) and the effects of treatment. STUDY DESIGN: Population-based retrospective cohort study. SETTING: Data were collected from the Longitudinal Health Insurance Database 2005, containing the information of 2 million randomly selected individuals in Taiwan. METHODS: We enrolled 90,481 patients with newly diagnosed MD between 2000 and 2017 and 361,924 matched individuals without MD. The study outcomes were diagnoses of all-cause injuries. The Kaplan-Meier method was used to determine the cumulative incidence rates of injury in the MD and non-MD cohorts, and a log-rank test was used to analyze the differences between the cohorts. Cox proportional hazards models were used to calculate the 18-year hazard ratios of each cohort. RESULTS: A total of 80,151 patients were diagnosed with injuries during the follow-up period: 24,031 and 56,120 from the MD and non-MD cohorts, respectively. The adjusted hazard ratio (aHR) was 2.19 (95% CI, 2.16-2.35) after adjusting for demographic characteristics and comorbidities. Subgroup analysis revealed that MD was associated with an increased incidence of unintentional and intentional injuries (aHR, 2.24 [95% CI, 2.21-2.41] and 2.05 [95% CI, 2.01-2.19], respectively). Treatment with diuretics, antivertigo medications, or surgery did not reduce the risk of injury (aHR, 0.98 [95% CI, 0.59-1.54], 0.94 [95% CI, 0.58-1.50], and 0.99 [95% CI, 0.61-1.54]). CONCLUSION: MD is independently associated with an increased risk of injuries. Medical or surgical treatment for MD does not reduce the risk of injury in patients with MD. Physicians should counsel patients with MD regarding preventive measures for avoiding subsequent injuries.
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Enfermedad de Meniere , Humanos , Estudios Retrospectivos , Enfermedad de Meniere/epidemiología , Enfermedad de Meniere/terapia , Factores de Riesgo , Comorbilidad , Taiwán/epidemiología , IncidenciaRESUMEN
BACKGROUND: Ankylosing spondylitis (AS) is an autoimmune disease affecting mainly spine and sacroiliac joints and adjacent soft tissues. Genome-wide association studies (GWASs) are used to evaluate genetic associations and to predict genetic risk factors that determine the biological basis of disease susceptibility. We aimed to explore the race-specific SNP susceptibility of AS in Taiwanese individuals and to investigate the association between HLA-B27 and AS susceptibility SNPs in Taiwan. METHODS: Genotyping data were collected from a medical center participating in the Taiwan Precision Medicine Initiative (TPMI) in the northern district of Taiwan. We designed a case-control study to identify AS susceptibility SNPs through GWAS. We searched the genome browser to find the corresponding susceptibility genes and used the GTEx database to confirm the regulation of gene expression. A polygenic risk score approach was also applied to evaluate the genetic variants in the prediction of developing AS. RESULTS: The results showed that the SNPs located on the sixth chromosome were related to higher susceptibility in the AS group. There was no overlap between our results and the susceptibility SNPs found in other races. The 12 tag SNPs located in the MHC region that were found through the linkage disequilibrium method had higher gene expression. Furthermore, Taiwanese people with HLA-B27 positivity had a higher proportion of minor alleles. This might be the reason that the AS prevalence is higher in Taiwan than in other countries. We developed AS polygenic risk score models with six different methods in which those with the top 10% polygenic risk had a fivefold increased risk of developing AS compared to the remaining group with low risk. CONCLUSION: A total of 147 SNPs in the Taiwanese population were found to be statistically significantly associated with AS on the sixth pair of chromosomes and did not overlap with previously published sites in the GWAS Catalog. Whether those genes mapped by AS-associated SNPs are involved in AS and what the pathogenic mechanism of the mapped genes is remain to be further studied.
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Estudio de Asociación del Genoma Completo , Espondilitis Anquilosante , Humanos , Antígeno HLA-B27/genética , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple/genética , Espondilitis Anquilosante/genética , Espondilitis Anquilosante/patologíaRESUMEN
Sensing environmental factors and responding swiftly to them is essential for all living organisms. For instance, predators must act rapidly once prey is sensed. Nematode-trapping fungi (NTF) are predators that use "traps" differentiated from vegetative hyphae to capture, kill, and consume nematodes. These traps undergo drastic and rapid morphological changes upon nematode induction. Multiple signaling hubs have been shown to regulate this remarkable process. Here, we demonstrate that the conserved cAMP-PKA signaling pathway exerts a crucial role in trap morphogenesis of the nematode-trapping fungi Arthrobotrys oligospora. A gene deletion mutant of the PKA catalytic subunit TPK2 proved insensitive toward nematode presence. Moreover, we show that the G protein alpha subunit GPA2 acts upstream of adenylate cyclase, with GPA2 deletion resulting in substantially reduced trap formation, whereas exogenous provision of cAMP rescued the prey-sensing and trap morphogenesis defects of a gpa2 mutant. Thus, we show that cAMP production triggered by G protein signaling and downstream PKA activity are vital for prey-sensing and trap development in A. oligospora, demonstrating that this highly conserved signaling pathway is critical for nematode-trapping fungi and nematode predator-prey interactions.
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Ascomicetos , Nematodos , Adenilil Ciclasas/genética , Animales , Ascomicetos/genética , Subunidades alfa de la Proteína de Unión al GTP , MorfogénesisRESUMEN
Both the annotation and identification of genes in pathogenic parasites are still challenging. Although, as a survival factor, nitric oxide (NO) has been proven to be synthesized in Trichomonas vaginalis (TV), nitric oxide synthase (NOS) has not yet been annotated in the TV genome. We developed a witness-to-suspect strategy to identify incorrectly annotated genes in TV via the Smith-Waterman and Needleman-Wunsch algorithms through in-depth and repeated alignment of whole coding sequences of TV against thousands of sequences of known proteins from other organisms. A novel NOS of TV (TV NOS), which was annotated as hydrogenase in the NCBI database, was successfully identified; this TV NOS had a high witness-to-suspect ratio and contained all the NOS cofactor-binding motifs (NADPH, tetrahydrobiopterin (BH4), heme and flavin adenine dinucleotide (FAD) motifs). To confirm this identification, we performed in silico modeling of the protein structure and cofactor docking, cloned the gene, expressed and purified the protein, performed mass spectrometry analysis, and ultimately performed an assay to measure enzymatic activity. Our data showed that although the predicted structure of the TV NOS protein was not similar to the structure of NOSs of other species, all cofactor-binding motifs could interact with their ligands with high affinities. We clearly showed that the purified protein had high enzymatic activity for generating NO in vitro. This study provides an innovative approach to identify incorrectly annotated genes in TV and highlights a novel NOS that might serve as a virulence factor of TV.
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(1) Background: The etiologies of sudden sensorineural hearing loss (SSHL) remain unclear. The level of mean particulate matter with a diameter of 2.5 µm or less (PM2.5) was not associated with SSHL, but the maximum PM2.5 level exhibited a negative association with SSHL in Korea. Exposure to nitrogen dioxide (NO2) for 2 weeks increased the risk of SSHL. The lag effects of SSHL after air pollution exposure were limited. We aimed to evaluate the association of SSHL with air pollution exposure to determine whether air pollution exposure caused delayed effects. (2) Methods: This observational study used inpatient data obtained from electronic health records at the Tri-Service General Hospital from 2011 to 2019. The data of all SSHL patients were retrieved. The air quality dataset from Songshan station from 2011 to 2019 was used. The main outcomes were the relative risks (RRs) of SSHL associated with PM2.5, O3, and NO2 exposures within 1 month. The relationships between these factors were examined using distributed lag nonlinear time series models. (3) Results: The RR of SSHL associated with PM2.5 exposure was 1.195 (95% confidence interval (C.I.: 1.047-1.363) for a 10 unit increase at a lag of 7 days. The RR of SSHL associated with O3 exposure was 1.14 (95% C.I.: 1.003-1.3) for a 10 unit increase at a lag of 9 days. The RR of SSHL associated with NO2 exposure was 1.284 (95% C.I.: 1.05-1.57) for a 10 unit increase at a lag of 23 days. (4) Conclusions: In our study, SSHL was confirmed to be associated with air pollution exposure with a lag effect. We discussed possible mechanisms to explore possible biological hypotheses and support further research. Large-scale studies including participants with other ethnicities and causal relationships are needed to confirm our findings.
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Contaminación del Aire , Pérdida Auditiva Sensorineural , Pérdida Auditiva Súbita , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Pérdida Auditiva Sensorineural/inducido químicamente , Pérdida Auditiva Sensorineural/epidemiología , Pérdida Auditiva Súbita/epidemiología , Pérdida Auditiva Súbita/etiología , Humanos , Dióxido de Nitrógeno/análisis , Dióxido de Nitrógeno/toxicidad , Material Particulado/toxicidad , RiesgoRESUMEN
BACKGROUND: The COVID-19 outbreak has not only changed the lifestyles of people globally but has also resulted in other challenges, such as the requirement of self-isolation and distance learning. Moreover, people are unable to venture out to exercise, leading to reduced movement, and therefore, the demand for exercise at home has increased. OBJECTIVE: We intended to investigate the relationships between a Nintendo Ring Fit Adventure (RFA) intervention and improvements in running time, cardiac force index (CFI), sleep quality (Chinese version of the Pittsburgh Sleep Quality Index score), and mood disorders (5-item Brief Symptom Rating Scale score). METHODS: This was a randomized prospective study and included 80 students who were required to complete a 1600-meter outdoor run before and after the intervention, the completion times of which were recorded in seconds. They were also required to fill out a lifestyle questionnaire. During the study, 40 participants (16 males and 24 females, with an average age of 23.75 years) were assigned to the RFA group and were required to exercise for 30 minutes 3 times per week (in the adventure mode) over 4 weeks. The exercise intensity was set according to the instructions given by the virtual coach during the first game. The remaining 40 participants (30 males and 10 females, with an average age of 22.65 years) were assigned to the control group and maintained their regular habits during the study period. RESULTS: The study was completed by 80 participants aged 20 to 36 years (mean 23.20, SD 2.96 years). The results showed that the running time in the RFA group was significantly reduced. After 4 weeks of physical training, it took females in the RFA group 19.79 seconds (P=.03) and males 22.56 seconds (P=.03) less than the baseline to complete the 1600-meter run. In contrast, there were no significant differences in the performance of the control group in the run before and after the fourth week of intervention. In terms of mood disorders, the average score of the RFA group increased from 1.81 to 3.31 for males (difference=1.50, P=.04) and from 3.17 to 4.54 for females (difference=1.38, P=.06). In addition, no significant differences between the RFA and control groups were observed for the CFI peak acceleration (CFIPA)_walk, CFIPA_run, or sleep quality. CONCLUSIONS: RFA could either maintain or improve an individual's physical fitness, thereby providing a good solution for people involved in distance learning or those who have not exercised for an extended period. TRIAL REGISTRATION: ClinicalTrials.gov NCT05227040; https://clinicaltrials.gov/ct2/show/NCT05227040.
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Background: The long-term effects of statin use on rehospitalization due to ischemic stroke (reHospIS) in hyperlipidemic patients are still unknown. Therefore, we aimed to assess the long-term risks of reHospIS for hyperlipidemic patients who were taking statins and nonstatin lipid-lowering medicines on a regular basis. Methods and Materials: The National Health Insurance Research Database in Taiwan was used to conduct a 6-year cohort study of patients >45 years old (n = 9,098) who were newly diagnosed with hyperlipidemia and hospitalized for the first or second time due to ischemic stroke (IS). The risk of reHospIS was assessed using Cox proportional hazards regression model. Results: Nonstatin lipid-lowering medicines regular users were associated with a higher risk of reHospIS compared to stains users (hazard ratio, HR = 1.29-1.39, p < 0.05). Rosuvastatin was the most preferred lipid-lowering medicine with lower HRs of reHospIS in hyperlipidemic patients whether they developed diabetes or not. Bezafibrate regular users of hyperlipidemic patients developing diabetes (HR = 2.15, p < 0.01) had nearly 50% lower reHospIS risks than those without diabetes (HR = 4.27, p < 0.05). Age, gender, drug dosage, comorbidities of diabetes and heart failure (HF), and characteristics of the first hospitalization due to IS were all adjusted in models. Moreover, increasing trends of HRs of reHospIS were observed from Rosuvastatin, nonstatin lipid-lowering medicines, Lovastatin, and Gemfibrozil to Bezafibrate users. Conclusion: Statins were associated with long-term secondary prevention of reHospIS for hyperlipidemic patients. Rosuvastatin seemed to have the best protective effects. On the other hand, Bezafibrate appears to be beneficial for hyperlipidemic patients developing diabetes. Further research into the combination treatment of statin and nonstatin lipid-lowering medicines in hyperlipidemic patients developing diabetes is warranted.
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Genetic co-expression network (GCN) analysis augments the understanding of breast cancer (BC). We aimed to propose GCN-based modeling for BC relapse-free survival (RFS) prediction and to discover novel biomarkers. We used GCN and Cox proportional hazard regression to create various prediction models using mRNA microarray of 920 tumors and conduct external validation using independent data of 1056 tumors. GCNs of 34 identified candidate genes were plotted in various sizes. Compared to the reference model, the genetic predictors selected from bigger GCNs composed better prediction models. The prediction accuracy and AUC of 3 ~ 15-year RFS are 71.0-81.4% and 74.6-78% respectively (rfm, ACC 63.2-65.5%, AUC 61.9-74.9%). The hazard ratios of risk scores of developing relapse ranged from 1.89 ~ 3.32 (p < 10-8) over all models under the control of the node status. External validation showed the consistent finding. We found top 12 co-expressed genes are relative new or novel biomarkers that have not been explored in BC prognosis or other cancers until this decade. GCN-based modeling creates better prediction models and facilitates novel genes exploration on BC prognosis.
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Biomarcadores de Tumor , Neoplasias de la Mama , Bases de Datos de Ácidos Nucleicos , Regulación Neoplásica de la Expresión Génica , Modelos Biológicos , Biomarcadores de Tumor/biosíntesis , Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Supervivencia sin Enfermedad , Femenino , Perfilación de la Expresión Génica , Humanos , Análisis de Secuencia por Matrices de Oligonucleótidos , Tasa de SupervivenciaRESUMEN
Detection of surrounding organisms in the environment plays a major role in the evolution of interspecies interactions, such as predator-prey relationships. Nematode-trapping fungi (NTF) are predators that develop specialized trap structures to capture, kill, and consume nematodes when food sources are limited. Despite the identification of various factors that induce trap morphogenesis, the mechanisms underlying the differentiation process have remained largely unclear. Here, we demonstrate that the highly conserved pheromone-response MAPK pathway is essential for sensing ascarosides, a conserved molecular signature of nemaotdes, and is required for the predatory lifestyle switch in the NTF Arthrobotrys oligospora. Gene deletion of STE7 (MAPKK) and FUS3 (MAPK) abolished nematode-induced trap morphogenesis and conidiation and impaired the growth of hyphae. The conserved transcription factor Ste12 acting downstream of the pheromone-response pathway also plays a vital role in the predation of A. oligospora. Transcriptional profiling of a ste12 mutant identified a small subset of genes with diverse functions that are Ste12 dependent and could trigger trap differentiation. Our work has revealed that A. oligospora perceives and interprets the ascarosides produced by nematodes via the conserved pheromone signaling pathway in fungi, providing molecular insights into the mechanisms of communication between a fungal predator and its nematode prey.
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Ascomicetos/metabolismo , Sistema de Señalización de MAP Quinasas , Nematodos/microbiología , Animales , Ascomicetos/citología , Ascomicetos/genética , Ascomicetos/patogenicidad , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Quinasas de Proteína Quinasa Activadas por Mitógenos/genética , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Esporas Fúngicas/citología , Esporas Fúngicas/genética , Esporas Fúngicas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
Nematode-trapping fungi (NTF) and nematodes are common and sympatric in nature. The molecular basis that underlies this interkingdom predator-prey interaction remains largely uncharacterized. Both NTF and nematodes can be easily isolated from soil samples. NTF do not form traps in nutrient-rich environments, yet trap morphogenesis can be observed under nutrient-poor conditions and upon simultaneous sensing of the nematode cues. Here, we present protocols for laboratory maintenance and culturing of the model NTF Arthrobotrys oligospora. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Growth of nematode-trapping fungi on solid medium Basic Protocol 2: Growth of nematode-trapping fungi in liquid medium Basic Protocol 3: Collection of conidia from solid medium Support Protocol 1: Preparation of Miracloth filter funnel Basic Protocol 4: Induction of trap morphogenesis Alternate Protocol: Quantitative measurement of trap induction Support Protocol 2: Preparation of synchronized C. elegans L4 Basic Protocol 5: Establishing C. elegans survival rate upon exposure to A. oligospora Basic Protocol 6: Storage of nematode-trapping fungi strains.
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Ascomicetos , Nematodos , Animales , Caenorhabditis elegans , LaboratoriosRESUMEN
The aim of study is to investigate the risk of developing acquired cholesteatoma and external auditory canal (EAC) stenosis after traumatic brain injury (TBI) from the Taiwan National Health Insurance Research Database (NHIRD). Each subject was individually traced from their index date to identify those who received a diagnosis of acquired cholesteatoma and EAC stenosis. Cox regression analyses were applied to determine the risk of TBI-related acquired cholesteatoma and EAC stenosis. The follow-up data collected over 10 years were obtained from the TBI and comparison cohorts, of 455,834 and 911,668 patients, respectively. Multivariate analysis demonstrated that TBI significantly increased the risk of cholesteatoma (adjusted hazard ratio (HR), 1.777; 95% confidence interval (CI), 1.494-2.114, p < 0.001) and EAC stenosis (adjusted (HR), 3.549; 95% (CI), 2.713-4.644, p < 0.001). In our subgroup injury analysis, falls had the highest associated risk (4.308 times), followed by traffic injuries (66.73%; 3.718 times that of the control group). Otolaryngologists should not neglect the clinical importance and carefully investigate the possibility of subsequent cholesteatoma and EAC stenosis, which leads to hearing impairment in patients with TBI. Our research also shows the important role in preventing TBI, especially as a result of traffic injuries and falls.
Asunto(s)
Lesiones Traumáticas del Encéfalo , Colesteatoma , Conducto Auditivo Externo , Adulto , Anciano , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/epidemiología , Colesteatoma/epidemiología , Estudios de Cohortes , Constricción Patológica , Conducto Auditivo Externo/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Riesgo , Taiwán/epidemiologíaRESUMEN
Hearing impairment was observed in patients with chronic kidney disease (CKD). Our purpose was to investigate the relationship between sensorineural hearing loss (SNHL) and associated comorbidities in the CKD population. We conducted a retrospective, population-based study to examine the risk of developing SNHL in patients with CKD. Population-based data from 2000-2010 from the Longitudinal Health Insurance Database of the Taiwan National Health Insurance Research Database was used in this study. The population sample comprised 185,430 patients who were diagnosed with CKD, and 556,290 without CKD to determine SNHL risk factors. Cox proportional hazard regression analysis demonstrated the CKD group had a significantly increased risk of SNHL compared with the non-CKD group [adjusted hazard ratio (HR), 3.42; 95% confidence interval (CI), 3.01-3.90, p < 0.001]. In the CKD group, the risk of SNHL (adjusted HR, 5.92) was higher among patients undergoing hemodialysis than among those not undergoing hemodialysis (adjusted HR, 1.40). Furthermore, subgroup analysis revealed an increased risk of SNHL in patients with CKD and comorbidities, including heart failure (adjusted HR, 7.48), liver cirrhosis (adjusted HR, 4.12), type 2 diabetes mellitus (adjusted HR, 3.98), hypertension (adjusted HR, 3.67), and chronic obstructive pulmonary disease (adjusted HR, 3.45). CKD is an independent risk of developing SNHL. Additionally, hemodialysis for uremia can increase the risk of SNHL. Cardiovascular, lung, liver, and metabolic comorbidities in CKD patients may further aggravate the risk of SNHL by inter-organ crosstalk. We should pay attention to SNHL in this high-risk population.