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The deformation-coordination ability between ductile metal and brittle dispersive ceramic particles is poor, which means that an improvement in strength will inevitably sacrifice ductility in dispersion-strengthened metallic materials. Here, we present an inspired strategy for developing dual-structure-based titanium matrix composites (TMCs) that achieve 12.0% elongation comparable to the matrix Ti6Al4V alloys and enhanced strength compared to homostructure composites. The proposed dual-structure comprises a primary structure, namely, a TiB whisker-rich region engendered fine grain Ti6Al4V matrix with a three-dimensional micropellet architecture (3D-MPA), and an overall structure consisting of evenly distributed 3D-MPA "reinforcements" and a TiBw-lean titanium matrix. The dual structure presents a spatially heterogeneous grain distribution with 5.8 µm fine grains and 42.3 µm coarse grains, which exhibits excellent hetero-deformation-induced (HDI) hardening and achieves a 5.8% ductility. Interestingly, the 3D-MPA "reinforcements" show 11.1% isotropic deformability and 66% dislocation storage, which endows the TMCs with good strength and loss-free ductility. Our enlightening method uses an interdiffusion and self-organization strategy based on powder metallurgy to enable metal matrix composites with the heterostructure of the matrix and the configuration of reinforcement to address the strength-ductility trade-off dilemma.
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Podocan, the fifth member of Small Leucine-Rich Proteoglycan (SLRP) family of extracellular matrix components, is poorly known in muscle development. Previous studies have shown that Podocan promotes C2C12 differentiation in mice. In this study, we elucidated the effect of Podocan on skeletal muscle post-injury regeneration and its underlying mechanism. Injection of Podocan protein promoted the process of mice skeletal muscle post-injury regeneration. This effect seemed to be from the acceleration of muscle satellite cell differentiation in vivo. Meanwhile, Podocan promoted myogenic differentiation in vitro by binding with TGF-ß1 to inhibit the activity of the TGF-ß signaling pathway. These results indicated that Podocan had the potential roles to enhance skeletal muscle post-injury regeneration. Its mechanism is likely the regulation of the expression of p-Smad2 and p-Smad4 related to the TGF-ß signaling pathway by interacting with TGF-ß1.
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Músculo Esquelético , Proteínas , Regeneración , Factor de Crecimiento Transformador beta1 , Animales , Ratones , Diferenciación Celular , Músculo Esquelético/lesiones , Músculo Esquelético/fisiología , Transducción de Señal , Factor de Crecimiento Transformador beta1/metabolismo , Proteínas/metabolismoRESUMEN
To advance the development of a compact and highly integrated fiber Bragg grating (FBG) interrogation system, to the best of our knowledge, this paper is the first to present the design and fabrication of a monolithic integration chip based on silicon-on-insulator (SOI), which is specifically intended for application in fiber grating sensing interrogation systems. By considering the impact of coupling structure dimensions on coupling efficiency as well as the effect of the photodetector (PD) parameters on the optical absorption efficiency of the device, we refine the structure of the monolithic integrated chip for arrayed waveguide grating (AWG) and PD. The test results reveal that the coupling loss between AWG and PD is -2.4â dB. The monolithic integrated interrogation chip achieves an interrogation accuracy of approximately 6.79 pm within a dynamic range of 1.56 nm, accompanied by a wavelength resolution of 1 pm. This exceptional performance highlights the potential of the monolithic integrated chip to enhance the integration of AWG-based fiber grating interrogation systems.
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Compact fiber Bragg grating (FBG) interrogator is a widely investigated topic in the field of fiber optic sensing. Here we report a dense spectral arrayed waveguide grating (AWG) chip designed for FBG interrogation. By integrating a multimode interference (MMI) coupler with the AWG, bilateral input phase-differential optical signals were achieved at the input port of the AWG. This chip effectively doubles the output channel count without altering the device footprint, while concurrently reducing the channel spacing without modifying the bandwidth and spectral slope of the output spectrum. We further optimized the method for selecting interrogation channels. The results demonstrate that the dynamic range of the interrogation reaches 13.5â nm with an absolute wavelength resolution of 4â pm and an absolute accuracy better than 20â pm.
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ABSTRACT: Targeting the mammalian target of rapamycin (mTOR) pathway represents a potentially novel approach to treat basal cell carcinoma (BCC), but activation of this pathway has not been well described in human BCCs. The purpose of this study was to assess whether mTOR pathway activation occurs in BCCs (both sporadic and syndromic) and report a case of a patient with Gorlin syndrome (GS) whose clinically suspicious BCCs responded to mTOR inhibition through topical sirolimus treatment. After Stanford Institutional Review Board Approval, archived BCCs from patients with GS (n = 25), sporadic BCCs (n = 35), and control tissues were subjected to immunohistochemical analysis for the activation of mTOR pathway, and immunohistochemical staining intensity was evaluated by a dermatopathologist. BCCs (compared with normal skin) had elevated levels of eIF4EBP1 ( Padjusted = 0.0336), which is downstream of mTOR. a serine/threonine kinase Phospho-(AKT), which interacts with mTOR, was also significantly elevated (perinuclear: Padjusted < 0.0001; cytoplasmic: Padjusted = 0.0021). When off-label topical 1% sirolimus was used on a pediatric patient with GS, we noted reduction of new BCC development and decreased size of existing neoplasms clinically suspicious for BCCs. This treatment was well tolerated after 2 years of continuous use, with no other treatments needed during this period. Topical sirolimus is a promising therapeutic candidate against both sporadic and GS-associated BCC. Multicenter, prospective studies are needed to understand the efficacy and safety of topical mTOR inhibitors in BCC treatment, and ascertain whether the immunohistochemical markers downstream of mTOR could have predictive value in identifying BCCs most likely to respond to topical mTOR inhibitors, such as sirolimus.
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Carcinoma Basocelular , Inhibidores mTOR , Transducción de Señal , Sirolimus , Neoplasias Cutáneas , Serina-Treonina Quinasas TOR , Humanos , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/metabolismo , Carcinoma Basocelular/tratamiento farmacológico , Carcinoma Basocelular/patología , Carcinoma Basocelular/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Sirolimus/farmacología , Sirolimus/uso terapéutico , Masculino , Femenino , Transducción de Señal/efectos de los fármacos , Persona de Mediana Edad , Inhibidores mTOR/farmacología , Inhibidores mTOR/uso terapéutico , Adulto , Anciano , Síndrome del Nevo Basocelular/tratamiento farmacológico , Síndrome del Nevo Basocelular/patología , Síndrome del Nevo Basocelular/metabolismo , Inmunohistoquímica , Antibióticos Antineoplásicos , Niño , Adolescente , Adulto Joven , Anciano de 80 o más Años , Proteínas Proto-Oncogénicas c-akt/metabolismo , Uso Fuera de lo Indicado , Resultado del Tratamiento , Proteínas de Ciclo Celular , Proteínas Adaptadoras Transductoras de SeñalesRESUMEN
Genetic testing is the gold standard for diagnosing different epidermolysis bullosa (EB) subtypes; however, testing rates are low. We conducted a pilot study to test feasibility of a novel, home-based registry that involved patients with EB submitting self-reported clinical symptoms using secure, online surveys (REDCap) and submitting buccal swabs for exome sequencing of EB-related genes (GeneDx). In total, 50 EB participants were enrolled, with an average age of 17 years and an average distance of 198 miles from EB specialty centers. All buccal swabs (N = 24) provided sufficient DNA for sequencing without causing mucosal trauma and 80% of participants were found to have pathogenic variants in COL7A1, the gene mutated in DEB. Participants with recessive dystrophic EB (RDEB) reported a higher prevalence of esophageal dilations (65.7% vs. 0%, p = .009) and mitten deformities of the feet (57.1% vs. 0%, p = .047) compared to non-RDEB participants.
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PURPOSE: The current study aims to explore the therapeutic effect of cochlear implants (CIs) on tinnitus in patients with single-sided deafness or asymmetric hearing loss (SSD/AHL) as well as the improvement of tinnitus-related quality of life and psychological status. In addition, we also explored whether the levels of quality of life and psychological status was related to the patient's implantation intention. METHODS: Seven patients decided to receive cochlear implantation. Before and after implantation, they completed the Visual Analogue Scale (VAS) and the Tinnitus Questionnaire (TQ) to assess tinnitus severity, the Speech, Spatial and Qualities of Hearing Scale (SSQ), and the Medical Outcomes Study Short Form 36 Health Survey Questionnaire (SF-36) to assess the quality of life, the Simplified Coping Style Questionnaire (SCSQ) to assess psychological status. The other 8 SSD patients refused cochlear implantation. Their scores of the above questionnaires were compared with those of patients received implantation. RESULTS: Six months after cochlear implantations, the tinnitus perception, loudness, and annoyance significantly decreased compared to that before implantation. In terms of quality of life and physiological status, no statistically significant changes were detected in SSQ, SF-36, and SCSQ measurements. The score of annoyance subcategory of VAS and all subcategories of SSQ of patients refused implantation were better than those of implanted patients before implantation. CONCLUSIONS: These results suggest that CIs can significantly reduce tinnitus severity. Patients refused implantation had better status in the annoyance of VAS and all subcategories of SSQ scores than those received implantation.
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Implantación Coclear , Implantes Cocleares , Sordera , Pérdida Auditiva Unilateral , Pérdida Auditiva , Percepción del Habla , Acúfeno , Humanos , Implantación Coclear/métodos , Acúfeno/psicología , Calidad de Vida , Pérdida Auditiva Unilateral/cirugía , Pérdida Auditiva/cirugía , Sordera/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: Leucine (Leu) is an essential amino acid that facilitates skeletal muscle satellite cell differentiation, yet its mechanism remains underexplored. Sestrin2 (SESN2) serves as a Leu sensor, binding directly to Leu, while ribophorin II (RPN2) acts as a signaling factor in multiple pathways. This study aimed to elucidate Leu's impact on mouse C2C12 cell differentiation and skeletal muscle injury repair by modulating RPN2 expression through SESN2, offering a theoretical foundation for clinical skeletal muscle injury prevention and treatment. RESULTS: Leu addition promoted C2C12 cell differentiation compared to the control, enhancing early differentiation via myogenic determinant (MYOD) up-regulation. Sequencing revealed SESN2 binding to and interacting with RPN2. RPN2 overexpression up-regulated MYOD, myogenin and myosin heavy chain 2, concurrently decreased p-GSK3ß and increased nuclear ß-catenin. Conversely, RPN2 knockdown yielded opposite results. Combining RPN2 knockdown with Leu rescued increased p-GSK3ß and decreased nuclear ß-catenin compared to Leu absence. Hematoxylin and eosin staining results showed that Leu addition accelerated mouse muscle damage repair, up-regulating Pax7, MYOD and RPN2 in the cytoplasm, and nuclear ß-catenin, confirming that the role of Leu in muscle injury repair was consistent with the results for C2C12 cells. CONCLUSION: Leu, bound with SESN2, up-regulated RPN2 expression, activated the GSK3ß/ß-catenin pathway, enhanced C2C12 differentiation and expedited skeletal muscle damage repair. © 2024 Society of Chemical Industry.
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Diferenciación Celular , Glucógeno Sintasa Quinasa 3 beta , Leucina , Transducción de Señal , beta Catenina , Animales , Ratones , beta Catenina/metabolismo , beta Catenina/genética , Línea Celular , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Glucógeno Sintasa Quinasa 3 beta/genética , Leucina/metabolismo , Leucina/farmacología , Músculo Esquelético/metabolismo , Músculo Esquelético/citología , Mioblastos/metabolismo , Mioblastos/citología , Proteína MioD/metabolismo , Proteína MioD/genética , Miogenina/metabolismo , Miogenina/genética , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , SestrinasRESUMEN
Transmembrane serine proteases are a group of enzymes that are implicated in diverse biological processes. Transmembrane serine protease 11E (TMPRSS11E) is expressed in epithelial cells. Previous studies on TMPRSS11E mainly focused on its function in tumor progression. In this study, we investigated the association of TMPRSS11E with the inflammatory response. We found that TMPRSS11E levels were upregulated in the BAL fluid of patients with acute respiratory distress syndrome and LPS-stimulated cultured epithelial cells. In an LPS-induced acute lung injury mouse model and a cercal ligation and puncture-induced sepsis model, increased expression levels of TMPRSS11E were also observed in the lung tissues. Knockdown of TMPRSS11E suppressed the proinflammatory cytokine release and alleviated lung injury. In addition, increased TMPRSS11E expression was detected in lung tissues of poly(I:C)-challenged mice, and overexpression of TMPRSS11E aggregated the lung injury. Unexpectedly, ectopic TMPRSS11E expression in macrophages was observed. Protease-activated receptor-1 was proteolytically activated by TMPRSS11E and enhanced the levels of proinflammatory cytokines. Taken together, our results indicate that TMPRSS11E can be induced during inflammatory response triggered by infection. Therefore, interventions with TMPRSS11E can aid in the treatment of pulmonary inflammation.
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Lesión Pulmonar Aguda , Lipopolisacáridos , Animales , Ratones , Lesión Pulmonar Aguda/patología , Citocinas/metabolismo , Inflamación/patología , Lipopolisacáridos/farmacología , Pulmón/patología , Poli I-C/farmacologíaRESUMEN
PAX5, a member of the paired box gene family of transcription factors, is a B-cell-specific activator protein that plays important roles during B lymphopoiesis. Two putative PAX5 binding sites in the human GINS1 promoter region were identified. EMSA, ChIP and luciferase assay showed that PAX5 functions as a positive transcription factor for GINS1 expression. Furthermore, coordinated expression of PAX5 and GINS1 was observed in mice B cells under physiological conditions and LPS stimulation situations. A similar pattern was also observed in human DLBCL cell lines under differentiation-inducing conditions. In addition, both PAX5 and GINS1 were highly expressed and significantly correlated in DLBCL specimens and cell lines. These findings suggested that dysregulation of PAX5 played an extremely important role in controlling the universal phenomenon of tumor progression through increased expression of GINS1 in DLBCL. In addition, circ1857 that was generated using back splicing of PAX5 pre-mRNA could further stabilize GINS1 mRNA, modulate GINS1 expression and promote lymphoma progression. To the best of our knowledge, this report is the first to demonstrate the role of GINS1 in DLBCL progression, and the mechanism of GINS1 upregulation using both circ1857 and PAX5 in DLBCL was revealed. Our results suggested that GINS1 may be a possible therapeutic target for DLBCL.
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Factor de Transcripción PAX5 , Factores de Transcripción , Ratones , Animales , Humanos , Factor de Transcripción PAX5/genética , Factor de Transcripción PAX5/metabolismo , Factores de Transcripción/genética , Regulación de la Expresión Génica , Línea Celular , Proliferación Celular/genética , Proteínas de Unión al ADN/genéticaRESUMEN
PURPOSE: The objective of this study is to analyze characteristics of recurrent acute urinary retention (AUR) in patients with benign prostatic hyperplasia (BPH), utilizing a population based data set. Also, we sought to report on how AUR was treated, specifically regarding the need and length of catheterization and types of procedures utilized for mitigation. MATERIALS & METHODS: A retrospective observational cohort study was performed using Optum's deidentified Clinformatics® Data Mart Database. We compared two groups, BPH patients with AUR (n = 180,737) and BPH patients without AUR (n = 1,139,760) from January 1, 2003 to December 31, 2017. Also, we analyzed the factors affecting the development of multiple episodes of AUR through age-adjusted multivariate analysis. RESULTS: In contrast to the 47.7% of patients who had a single AUR episode, 33.5% of AUR patients developed 3 or more subsequent episodes of retention. For age matched patients, the risks of additional episodes of retention increase significantly with older age, Caucasian race, diabetes, neurologic conditions, or low income. Overall, the rate of BPH surgery in AUR patients over the study period decreased and the most common procedure was transurethral resection of the prostate. CONCLUSIONS: Risk factors for multiple episodes of AUR included age (60 and older), Caucasian race, lower income socioeconomic status, diabetes, and neurological disorders. Patients with a high probability of developing recurrent episodes of AUR are recommended to receive preemptive BPH medication before such AUR occurrences. Also, more expeditious surgical treatment should be considered rather than temporary catheterization when AUR occurs.
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Hiperplasia Prostática , Resección Transuretral de la Próstata , Retención Urinaria , Masculino , Humanos , Estados Unidos/epidemiología , Hiperplasia Prostática/complicaciones , Hiperplasia Prostática/epidemiología , Hiperplasia Prostática/tratamiento farmacológico , Retención Urinaria/epidemiología , Retención Urinaria/etiología , Estudios Retrospectivos , Resección Transuretral de la Próstata/efectos adversos , Factores de Riesgo , Enfermedad AgudaRESUMEN
BACKGROUND: Waterlogging is one of the major abiotic stresses in barley and greatly reduces grain yield and quality. To explore the mechanism controlling waterlogging tolerance in barley, physiological, anatomical and transcriptional analyses were performed in two contrasting barley varieties, viz. Franklin (susceptible) and TX9425 (tolerant). RESULTS: Compared to Franklin, TX9425 had more adventitious roots and aerenchymas and higher antioxidant enzyme activities. A total of 3064 and 5693 differentially expressed genes (DEGs) were identified in TX9425 after 24 h and 72 h of waterlogging treatment, respectively, while 2297 and 8462 DEGs were identified in Franklin. The results suggested that TX9425 was less affected by waterlogging stress after 72 h of treatment. The DEGs were enriched mainly in energy metabolism, hormone regulation, reactive oxygen species (ROS) scavenging, and cell wall-modifying enzymes. Alcohol dehydrogenase (ADH) plays an important role in response to waterlogging stress. We found that HvADH4 was significantly upregulated under waterlogging stress in TX9425. Transgenic Arabidopsis overexpressing HvADH4 displayed higher activity of antioxidant enzymes and was more tolerant to waterlogging than the wild type (WT). CONCLUSIONS: The current results provide valuable information that will be of great value for the exploration of new candidate genes for molecular breeding of waterlogging tolerance in barley.
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Arabidopsis , Hordeum , Hordeum/genética , Arabidopsis/genética , Antioxidantes , Perfilación de la Expresión Génica , Raíces de Plantas/genética , Estrés Fisiológico/genéticaRESUMEN
PURPOSE: Priapism is a debilitating condition that affects sexual function. As a majority of cases are idiopathic, investigators have hypothesized underlying vascular dysfunction which may predispose men to priapism. We sought to determine if men are at risk for other sequelae of vascular dysfunction such as cardiovascular and thromboembolic disease after a priapism event. MATERIALS AND METHODS: Using a large commercial insurance claims data warehouse, we evaluated all men (age ≥20) with a diagnosis of priapism from 2003-2020 and matched them to a cohort of men with other urological disorders of sexual dysfunction (erectile dysfunction, Peyronie's disease, and premature ejaculation). We identified incident disease (cardiovascular disease, heart disease, embolism, thrombosis, cerebrovascular disease) for all cohorts. RESULTS: A total of 10,459 men with priapism were identified and were matched to men with erectile dysfunction, Peyronie's disease, or premature ejaculation. The mean age was 51.1 years old. Men with priapism showed increased incidence of heart disease, both ischemic (HR 1.24, 95% CI 1.09-1.42) and other heart disease (HR 1.24, 95% CI 1.12-1.38) in the years following the priapism diagnosis. Incident cerebrovascular disease was also more likely in men with a history of priapism (HR 1.33, 95% CI 1.15-1.55). Men requiring treatment for ischemic priapism had a higher hazard of cardiovascular and cerebrovascular disease. In addition, men with more priapism episodes had a higher rate of cardiovascular disease and thromboembolic events. CONCLUSIONS: Men with priapism are at increased risk for cardiovascular and cerebrovascular events in the years following a priapism.
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Enfermedades Cardiovasculares , Trastornos Cerebrovasculares , Disfunción Eréctil , Cardiopatías , Induración Peniana , Eyaculación Prematura , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/epidemiología , Trastornos Cerebrovasculares/complicaciones , Trastornos Cerebrovasculares/epidemiologíaRESUMEN
The development of circularly polarized thermally activated delayed fluorescence (CP-TADF) luminogens with stimuli-response characteristics remains challenging. Herein, a pair of organic enantiomers, S-CzTA and R-CzTA, with aggregation-induced emission properties, have been successfully developed by introducing chiral 1,2,3,4-tetrahydronaphthalene and carbazole to phthalimide. They present CP-TADF properties in toluene solutions, giving dissymmetric factors of 0.84×10-3 and -1.03×10-3 , respectively. In the crystalline state, both S-CzTA and R-CzTA can emit intense blue TADF and produce very bright sky-blue mechanoluminescence (ML) and remarkable mechanofluorochromism (MFC) under the stimuli of mechanical force. Single-crystal analysis and theoretical calculation results suggest that their ML activities are probably associated with their chiral and polar molecular structures and unique non-centrosymmetric molecular packing modes. Furthermore, the MFC properties of the enantiomers likely originate from the destruction of crystal structure, leading to the planarization of molecular conformation. This work may provide helpful guidance for developing new CP-TADF materials with force-stimuli-responsive properties.
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Tetrahidronaftalenos , FluorescenciaRESUMEN
BACKGROUND: Priapism, a urologic emergency, has known associations with certain medical conditions. Many cases are idiopathic, suggesting an opportunity to identify novel risk factors. AIM: We sought to identify medical conditions and pharmaceutical treatments that are associated with priapism using data-mining techniques. METHODS: Using deidentified data in a large insurance claims database, we identified all men (age ≥20 years) with a diagnosis of priapism from 2003 to 2020 and matched them to cohorts of men with other diseases of male genitalia: erectile dysfunction, Peyronie disease, and premature ejaculation. All medical diagnoses and prescriptions used prior to first disease diagnosis were examined. Predictors were selected by random forest, and conditional multivariate logistic regressions were applied to assess the risks of each predictor. OUTCOMES: We identified novel relationships of HIV and some HIV treatments with priapism and confirmed existing associations. RESULTS: An overall 10 459 men with priapism were identified and matched 1:1 to the 3 control groups. After multivariable adjustment, men with priapism had high associations of hereditary anemias (odds ratio [OR], 3.99; 95% CI, 2.73-5.82), use of vasodilating agents (OR, 2.45; 95% CI, 2.01-2.98), use of HIV medications (OR, 1.95; 95% CI, 1.36-2.79), and use of antipsychotic medications (OR, 1.90; 95% CI, 1.52-2.38) as compared with erectile dysfunction controls. Similar patterns were noted when compared with premature ejaculation and Peyronie disease controls. CLINICAL IMPLICATIONS: HIV and its treatment are associated with priapism, which may affect patient counseling. STRENGTHS AND LIMITATIONS: To our knowledge, this is the first study to identify risk factors for priapism utilizing machine learning. All men in our series were commercially insured, which limits the generalizability of our findings. CONCLUSION: Using data-mining techniques, we confirmed existing associations with priapism (eg, hemolytic anemias, antipsychotics) and identified novel relationships (eg, HIV disease and treatment).
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Anemia , Disfunción Eréctil , Infecciones por VIH , Induración Peniana , Eyaculación Prematura , Priapismo , Masculino , Humanos , Adulto Joven , Adulto , Priapismo/epidemiología , Priapismo/etiología , Priapismo/terapia , Disfunción Eréctil/tratamiento farmacológico , Disfunción Eréctil/epidemiología , Disfunción Eréctil/etiología , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Anemia/complicacionesRESUMEN
BACKGROUND: Phosphodiesterase 5 inhibitor (PDE5i) use has been linked to a number of ocular side effects, such as serous retinal detachment (SRD), retinal vascular occlusion (RVO), and ischemic optic neuropathy (ION). AIM: We investigated the risk for SRD, RVO, and ION in patients using PDE5is. METHODS: We utilized the IBM MarketScan (2007-2021) Commercial and Medicare Supplemental Databases (version 2.0) for this analysis. To estimate overall events risk, Cox proportional hazard models were applied to calculate the hazard ratios (HRs) for erectile dysfunction (ED) diagnosis and the different treatments, adjusting for region, median age, obesity, diabetes mellitus, hyperlipidemia, smoking, hypertension, coronary artery disease, and sleep apnea. Additionally, the same analyses were performed to calculate the HRs for benign prostatic hyperplasia (BPH) diagnosis and the different treatments. OUTCOMES: HRs for SRD, RVO, and ION. RESULTS: In total, 1 938 262 men with an ED diagnosis were observed during the study period. Among them, 615 838 (31.8%) were treated with PDE5is. In total, 2 175 439 men with a BPH diagnosis were observed during the study period. Among them, 175 725 (8.1%) were treated with PDE5is. On adjusted Cox regression analysis, PDE5i use was not associated with SRD, RVO, ION, and any ocular event when compared with ED diagnosis and other ED treatments. Importantly, as the intensity of ED treatment increased, so did the risk of ocular events. In addition, PDE5i use was not associated with SRD and ION when compared with BPH diagnosis and other BPH treatments. In contrast, in patients with BPH, PDE5i use was associated with RVO (HR, 1.14; 95% CI, 1.06-1.23). Importantly, patients with BPH receiving other medical treatment (ie, 5a reductase/alpha blocker; HR, 1.11; 95% CI, 1.06-1.16) or surgical treatment (HR, 1.10; 95% CI, 1.02-1.19) had a higher risk of RVO. CLINICAL IMPLICATIONS: We did not observe any consistent association between PDE5i use and any ocular adverse events (SRD, RVO, and ION). STRENGTHS AND LIMITATIONS: Because we did not have access to the patients' medical records, we recorded outcome definitions using ICD-9 and ICD-10 coding. CONCLUSIONS: Patients using PDE5is for ED or BPH indications did not have an increased risk of ocular events, even when compared with other treatments for ED or BPH.
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Disfunción Eréctil , Hipertensión , Hiperplasia Prostática , Masculino , Humanos , Anciano , Estados Unidos , Inhibidores de Fosfodiesterasa 5/efectos adversos , Hiperplasia Prostática/complicaciones , Hiperplasia Prostática/tratamiento farmacológico , Medicare , Disfunción Eréctil/inducido químicamente , Disfunción Eréctil/tratamiento farmacológico , Hipertensión/complicacionesRESUMEN
BACKGROUND: Chemoprotective effect of 5-alpha reductase inhibitors (5-ARi) on bladder cancer (BCa) risk in men with Benign Prostatic Hyperplasia (BPH) has been explored with conflicting results. We sought to examine the effect of 5-ARi on new BCa diagnoses in a large US database. METHODS: Men ≥ 50 y/o with a prescription for 5-ARi after BPH diagnosis were identified in the IBM® Marketscan® Research de-identified Databases between 2007 and 2016 and matched with paired controls. Incident BCa diagnoses were identified after BPH diagnosis and/or pharmacologic treatment. Multivariable regression modeling adjusting for relevant factors was implemented. Sub-group analyses by exposure risk were performed to explore the association between 5-ARi and BCa over time. Administration of alpha-blockers (α-B) w/o 5-ARi was also examined. RESULTS: In total, n = 24,036 men on 5-ARi, n = 107,086 on 5-ARi plus alpha-blockers, and n = 894,275 without medical therapy for BPH were identified. The percentage of men diagnosed with BCa was 0.8% for the 5-ARi, 1.4% for the 5-ARi + α-B, and 0.6% for the untreated BPH group of incident BCa (adjusted hazard ratio [aHR], 0.90, 95% confidence interval [CI] 0.56 - 1.47), and 1.08, 95%CI 0.89 - 1.30, respectively). This was also true at both shorter (≤ 2 yr) and longer-term (> 2 yr) follow up. In addition, α-B alone had no change in BCa risk (HR 1.06, 0.86-1.30). CONCLUSIONS: We did not find any diminished risk of new BCa in men treated with 5-ARi (i.e., chemoprotective effect). The current report suggests that 5-ARi do not change a man's bladder cancer risk.
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Seguro , Hiperplasia Prostática , Neoplasias de la Vejiga Urinaria , Masculino , Humanos , Estados Unidos/epidemiología , Inhibidores de 5-alfa-Reductasa/uso terapéutico , Hiperplasia Prostática/tratamiento farmacológico , Hiperplasia Prostática/epidemiología , Riesgo , Neoplasias de la Vejiga Urinaria/epidemiología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológicoRESUMEN
Tibet's ancient topography and its role in climatic and biotic evolution remain speculative due to a paucity of quantitative surface-height measurements through time and space, and sparse fossil records. However, newly discovered fossils from a present elevation of â¼4,850 m in central Tibet improve substantially our knowledge of the ancient Tibetan environment. The 70 plant fossil taxa so far recovered include the first occurrences of several modern Asian lineages and represent a Middle Eocene (â¼47 Mya) humid subtropical ecosystem. The fossils not only record the diverse composition of the ancient Tibetan biota, but also allow us to constrain the Middle Eocene land surface height in central Tibet to â¼1,500 ± 900 m, and quantify the prevailing thermal and hydrological regime. This "Shangri-La"-like ecosystem experienced monsoon seasonality with a mean annual temperature of â¼19 °C, and frosts were rare. It contained few Gondwanan taxa, yet was compositionally similar to contemporaneous floras in both North America and Europe. Our discovery quantifies a key part of Tibetan Paleogene topography and climate, and highlights the importance of Tibet in regard to the origin of modern Asian plant species and the evolution of global biodiversity.
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OBJECTIVE: To investigate the efficiency of additional intraoperative endoscopic inspection in reducing residual cholesteatoma in pediatric cholesteatoma involving the mastoid treated with classic canal-wall-up mastoidectomy and tympanoplasty. MATERIALS AND METHODS: 32 cases of pediatric cholesteatoma involving the mastoid were enrolled in this perspective study and treated with classic canal-wall-up mastoidectomy and tympanoplasty. Transmastoid posterior tympanotomy, atticotomy and transecting tendon of tympani tensor were conducted to achieve adequate visualization of hidden spaces in the middle ear. After complete removal of cholesteatoma, endoscopic inspection was additionally performed to check residual cholesteatoma. All cases had at least a 2-year follow-up by routine otoscopy examination, CT scan or MR imaging. Residual rates of both intraoperative and follow-up findings were used to evaluate the efficiency of the endoscopic inspection in reducing residual cholesteatoma and compared with published reports. RESULTS: The additional intraoperative endoscopic inspection did not find any residual in this case series. In the 2-year follow-up, 2 cases (2/32, 6.3%) with residual cholesteatoma and 3 cases with recurrence (3/32, 9.4%) were found. The mean duration of endoscopic inspection and microscopic procedure were 17.9 min and 93.6 min, respectively. CONCLUSIONS: This study suggested that the additional intraoperative endoscopic inspection in microscopic CWU surgery for pediatric cholesteatoma involving the mastoid had no obvious value in reducing residual cholesteatoma but took extra time.
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Colesteatoma del Oído Medio , Apófisis Mastoides , Humanos , Niño , Apófisis Mastoides/diagnóstico por imagen , Apófisis Mastoides/cirugía , Colesteatoma del Oído Medio/diagnóstico por imagen , Colesteatoma del Oído Medio/cirugía , Oído Medio/cirugía , Endoscopía/métodos , Timpanoplastia/métodos , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
In this work, an efficient polymer-based organic afterglow system, which shows reversible photochromism, switchable ultralong organic phosphorescence (UOP), and prominent water and chemical resistance simultaneously, has been developed for the first time. By doping phenoxazine (PXZ) and 10-ethyl-10H-phenoxazine (PXZEt) into epoxy polymers, the resulting PXZ@EP-0.25 % and PXZEt@EP-0.25 % films show unique photoactivated UOP properties, with phosphorescence quantum yields and lifetimes up to 10.8 % and 845â ms, respectively. It is found that the steady-state luminescence and UOP of PXZ@EP-0.25 % are switchable by light irradiation and thermal annealing. Moreover, the doped films can still produce conspicuous UOP after soaking in water, strong acid and base, and organic solvents for more than two weeks, exhibiting outstanding water and chemical resistance. Inspired by these exciting results, the PXZ@EP-0.25 % has been successfully exploited as an erasable transparent film for light printing.