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This study aimed to develop and evaluate a guinea pig model for glaucoma, comparing resultant eyeball enlargement with an existing myopia model. Thirty guinea pigs underwent intracameral injection of magnetic microspheres to induce chronic ocular hypertension (COH). Intraocular pressure (IOP) was systematically monitored, revealing a successful induction of COH in 73.33% of the guinea pigs. The mean IOP increased from a baseline of 18.04 ± 1.33 mmHg, reaching a peak at week 3 (36.31 ± 6.13 mmHg) and remaining elevated for at least 7 weeks. All data are presented as mean ± standard deviation of the mean. Subsequently, detailed assessments were conducted to validate the established glaucoma model. Immunofluorescent staining demonstrated a significant decrease in the density of retinal ganglion cells (RGC) in the glaucoma group. Optic disc excavation and notable thinning of the lamina cribrosa (LC) were observed. The quantity of optic nerve ax·ons in glaucoma group gradually decreased from baseline (44553 ± 3608/mm2) to week 4 (28687 ± 2071/mm2) and week 8 (17977 ± 3697/mm2). Moreover, regarding the global enlargement of eyeballs, both the transverse and longitudinal axis in glaucomatous eyes were found to be significantly larger than that in myopic eyes, particularly in the anterior chamber depth (1.758 ± 0.113 mm vs. 1.151 ± 0.046 mm). These findings indicate distinct patterns of structural changes associated with glaucoma and myopia in the guinea pig model. This guinea pig model holds promise for future research aimed at exploring biomechanical mechanisms, therapeutic interventions, and advancing our understanding of the relationship between glaucoma and myopia.
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Objective: This study aims to evaluate the effect of rehabilitation interventions based on the motive behavioral conversion concept on diabetic foot ulcer patients after artificial dermal transplantation. The focus is on enhancing self-management and quality of life by integrating intrinsic motivation and behavioral changes in postoperative care. It also aims to introduce and clarify this concept for readers less familiar with this approach in diabetic foot ulcer rehabilitation. Methods: The study involved 102 diabetic foot ulcer patients who had undergone artificial dermal transplantation, randomly divided into a control and an observation group. Both groups received standard post-surgical care including antimicrobial agents with alginate supplements and closed negative pressure drainage therapy. The control group underwent conventional rehabilitation, while the observation group received rehabilitation based on motivational behavior transformation. Key evaluation metrics included Visual Analog Scale (VAS) scores, frequency/time of dressing changes, wound healing time, incidence of adverse events, self-care ability scores, and Diabetes-Specific Quality of Life (DSQL) scores, allowing for a comprehensive comparison of outcomes between the two groups. Results: Before the intervention, there was no significant difference in the VAS pain scores between the groups. However, after 7, 10, and 14 days of intervention, the observation group showed a greater reduction in VAS pain scores. The observation group also had shorter dressing change times (12.77 ± 2.18 minutes) and wound healing times (25.77 ± 2.94 days) compared to the control group (16.56 ± 3.25 minutes for dressing change, 27.85 ± 3.26 days for wound healing). There were no significant differences in the frequency of dressing changes or the cumulative incidence of adverse events between the groups. After 6 months, the observation group demonstrated higher self-care ability scores in several domains and lower total DSQL scores, indicating better outcomes in quality of life dimensions. Conclusion: Rehabilitation interventions based on the motive behavioral conversion concept significantly enhanced postoperative recovery, demonstrating potential implications for clinical practices and future research.
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PURPOSE: To investigate the extent of iris trabecular contact (ITC) measured by anterior segment OCT (AS-OCT) and its association with primary angle-closure (PAC) and PAC glaucoma (PACG) in eyes with gonioscopic angle-closure and to determine the diagnostic performance of ITC for detection of gonioscopic angle-closure. DESIGN: Multicenter, prospective study. PARTICIPANTS: A total of 119 healthy participants with gonioscopic open-angle and 170 patients with gonioscopic angle-closure (94 with PAC suspect and 76 with PAC/PACG) were included. METHODS: One eye of each subject was randomly selected for AS-OCT imaging. Angle-opening distance (AOD500) and trabecular iris space area (TISA500) were measured every 10° for 360°. Two criteria of ITC500 were examined: (1) AOD500 = 0 mm and (2) TISA500 = 0 mm2. The association between the extent of ITC500 and PAC/PACG in eyes with gonioscopic angle-closure was analyzed with logistic regression analysis. MAIN OUTCOME MEASURES: Sensitivity and specificity of ITC500 for detection of gonioscopic angle-closure; odds ratio (OR) of PAC/PACG. RESULTS: The sensitivity of ITC500 ≥ 10° for detection of gonioscopic angle-closure ranged from 82.4% (AOD500 = 0 mm) to 84.7% (TISA500 = 0 mm2), and the specificity was 85.7% (for both AOD500 = 0 mm and TISA500 = 0 mm2). The extent of ITC500 determined by AS-OCT, not cumulative gonioscopy score (i.e., the sum of the modified Shaffer grades over 4 quadrants), was associated with the odds of PAC/PACG in eyes with gonioscopic angle-closure; the odds of PAC/PACG increased by 5% for every 10° increase in ITC500 (OR, 1.051, 95% confidence interval [CI], 1.022-1.080 for AOD500 = 0 mm; OR, 1.049, 95% CI, 1.022-1.078 for TISA500 = 0 mm2). Axial length and anterior chamber depth were not associated with PAC/PACG in eyes with gonioscopic angle-closure (P ≥ 0.574). CONCLUSIONS: A greater extent of ITC measured by AS-OCT, not angle-closure determined by gonioscopy, was associated with a greater odds of PAC/PACG in eyes with gonioscopic angle-closure.
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Segmento Anterior do Olho , Glaucoma de Ângulo Fechado , Humanos , Gonioscopia , Estudos Prospectivos , Pressão Intraocular , Tomografia de Coerência Óptica/métodos , Iris , Glaucoma de Ângulo Fechado/diagnósticoRESUMO
PURPOSE: To develop and validate the performance of a high myopia (HM)-specific normative database of peripapillary retinal nerve fiber layer (pRNFL) thickness in differentiating HM from highly myopic glaucoma (HMG). DESIGN: Cross-sectional multicenter study. PARTICIPANTS: A total of 1367 Chinese participants (2325 eyes) with nonpathologic HM or HMG were included from 4 centers. After quality control, 1108 eyes from 694 participants with HM were included in the normative database; 459 eyes from 408 participants (323 eyes with HM and 136 eyes with HMG) and 322 eyes from 197 participants (131 eyes with HM and 191 eyes with HMG) were included in the internal and external validation sets, respectively. Only HMG eyes with an intraocular pressure > 21 mmHg were included. METHODS: The pRNFL thickness was measured with swept-source (SS) OCT. Four strategies of pRNFL-specified values were examined, including global and quadrantic pRNFL thickness below the lowest fifth or the lowest first percentile of the normative database. MAIN OUTCOMES MEASURES: The accuracy, sensitivity, and specificity of the HM-specific normative database for detecting HMG. RESULTS: Setting the fifth percentile of the global pRNFL thickness as the threshold, using the HM-specific normative database, we achieved an accuracy of 0.93 (95% confidence interval [CI], 0.90-0.95) and 0.85 (95% CI, 0.81-0.89), and, using the first percentile as the threshold, we acheived an accuracy of 0.85 (95% CI, 0.81-0.88) and 0.70 (95% CI, 0.65-0.75) in detecting HMG in the internal and external validation sets, respectively. The fifth percentile of the global pRNFL thickness achieved high sensitivities of 0.75 (95% CI, 0.67-0.82) and 0.75 (95% CI, 0.68-0.81) and specificities of 1.00 (95% CI, 0.99-1.00) and 1.00 (95% CI, 0.97-1.00) in the internal and external validation datasets, respectively. Compared with the built-in database of the OCT device, the HM-specific normative database showed a higher sensitivity and specificity than the corresponding pRNFL thickness below the fifth or first percentile (P < 0.001 for all). CONCLUSIONS: The HM-specific normative database is more capable of detecting HMG eyes than the SS OCT built-in database, which may be an effective tool for differential diagnosis between HMG and HM. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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Glaucoma , Miopia , Humanos , Estudos Transversais , População do Leste Asiático , Miopia/diagnóstico , Retina , Glaucoma/diagnóstico , Fibras NervosasRESUMO
OBJECTIVES: Stress urinary incontinence is a common disease with many therapeutic ways, but it lacks long-term follow-up. This study aims to conduct a retrospective study on the long-term efficacy of women with mild and moderate stress urinary incontinence after pelvic floor rehabilitation treatment for 3-years so as to provide a more effective treatment plan for this disease. METHODS: Data were collected from 279 female patients, who were diagnosed with stress urinary incontinence at the Pelvic Floor Rehabilitation Center of the Third Xiangya Hospital of Central South University from January 2017 to January 2019. All patients received health education and were instructed to perform Kegel exercises for 20 min daily at home. According to the treatment pattern, patients were divided into 3 groups as A, B, and C. Group A (n=94) received pelvic floor biofeedback, electrical stimulation and electroacupuncture; Group B (n=99) received pelvic floor biofeedback and electrical stimulation; Group C (n=86) only got pelvic floor function examinations and did not receive any pelvic floor treatment. The pelvic floor functional examinations included a pelvic floor electrophysiological test, pelvic organ prolapse quantitive examination (POP-Q), and stress urinary incontinence severity assessment. All patients were followed up with questionnaire consisting of the International Committee on Urinary Incontinence Questionnaire-Short Form (ICI-Q-SF) and the Quality of Life questionnaire of Urinary Incontinence (I-QOL) before and after the treatment, as well as at 1-, 2-, and 3-years after the treatment (5 times in total). Among the patients who received the treatment, 43 returned to the hospital, including 21 in group A (Group Areturn) and 22 in group B (Group Breturn). Pelvic floor electrophysiological test and POP-Q were performed on the 2 groups. RESULTS: For the leakage rate at the end of the treatment and the following 1-, 2-, and 3-years: Group A
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Prolapso de Órgão Pélvico , Incontinência Urinária por Estresse , Incontinência Urinária , Humanos , Feminino , Incontinência Urinária por Estresse/terapia , Qualidade de Vida , Diafragma da Pelve , Estudos Retrospectivos , Terapia por Exercício , Resultado do TratamentoRESUMO
PURPOSE: To develop and validate a multimodal artificial intelligence algorithm, FusionNet, using the pattern deviation probability plots from visual field (VF) reports and circular peripapillary OCT scans to detect glaucomatous optic neuropathy (GON). DESIGN: Cross-sectional study. SUBJECTS: Two thousand four hundred sixty-three pairs of VF and OCT images from 1083 patients. METHODS: FusionNet based on bimodal input of VF and OCT paired data was developed to detect GON. Visual field data were collected using the Humphrey Field Analyzer (HFA). OCT images were collected from 3 types of devices (DRI-OCT, Cirrus OCT, and Spectralis). Two thousand four hundred sixty-three pairs of VF and OCT images were divided into 4 datasets: 1567 for training (HFA and DRI-OCT), 441 for primary validation (HFA and DRI-OCT), 255 for the internal test (HFA and Cirrus OCT), and 200 for the external test set (HFA and Spectralis). GON was defined as retinal nerve fiber layer thinning with corresponding VF defects. MAIN OUTCOME MEASURES: Diagnostic performance of FusionNet compared with that of VFNet (with VF data as input) and OCTNet (with OCT data as input). RESULTS: FusionNet achieved an area under the receiver operating characteristic curve (AUC) of 0.950 (0.931-0.968) and outperformed VFNet (AUC, 0.868 [95% confidence interval (CI), 0.834-0.902]), OCTNet (AUC, 0.809 [95% CI, 0.768-0.850]), and 2 glaucoma specialists (glaucoma specialist 1: AUC, 0.882 [95% CI, 0.847-0.917]; glaucoma specialist 2: AUC, 0.883 [95% CI, 0.849-0.918]) in the primary validation set. In the internal and external test sets, the performances of FusionNet were also superior to VFNet and OCTNet (FusionNet vs VFNet vs OCTNet: internal test set 0.917 vs 0.854 vs 0.811; external test set 0.873 vs 0.772 vs 0.785). No significant difference was found between the 2 glaucoma specialists and FusionNet in the internal and external test sets, except for glaucoma specialist 2 (AUC, 0.858 [95% CI, 0.805-0.912]) in the internal test set. CONCLUSIONS: FusionNet, developed using paired VF and OCT data, demonstrated superior performance to both VFNet and OCTNet in detecting GON, suggesting that multimodal machine learning models are valuable in detecting GON.
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Glaucoma de Ângulo Aberto/diagnóstico por imagem , Aprendizado de Máquina , Doenças do Nervo Óptico/diagnóstico por imagem , Tomografia de Coerência Óptica , Transtornos da Visão/fisiopatologia , Campos Visuais/fisiologia , Adulto , Idoso , Algoritmos , Área Sob a Curva , Estudos Transversais , Feminino , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Pressão Intraocular , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Fibras Nervosas/patologia , Doenças do Nervo Óptico/fisiopatologia , Curva ROC , Células Ganglionares da Retina/patologia , Testes de Campo VisualRESUMO
PURPOSE: To develop and evaluate the performance of a 3-dimensional (3D) deep-learning-based automated digital gonioscopy system (DGS) in detecting 2 major characteristics in eyes with suspected primary angle-closure glaucoma (PACG): (1) narrow iridocorneal angles (static gonioscopy, Task I) and (2) peripheral anterior synechiae (PAS) (dynamic gonioscopy, Task II) on OCT scans. DESIGN: International, cross-sectional, multicenter study. PARTICIPANTS: A total of 1.112 million images of 8694 volume scans (2294 patients) from 3 centers were included in this study (Task I, training/internal validation/external testing: 4515, 1101, and 2222 volume scans, respectively; Task II, training/internal validation/external testing: 378, 376, and 102 volume scans, respectively). METHODS: For Task I, a narrow angle was defined as an eye in which the posterior pigmented trabecular meshwork was not visible in more than 180° without indentation in the primary position captured in the dark room from the scans. For Task II, PAS was defined as the adhesion of the iris to the trabecular meshwork. The diagnostic performance of the 3D DGS was evaluated in both tasks with gonioscopic records as reference. MAIN OUTCOME MEASURES: The area under the curve (AUC), sensitivity, and specificity of the 3D DGS were calculated. RESULTS: In Task I, 29.4% of patients had a narrow angle. The AUC, sensitivity, and specificity of 3D DGS on the external testing datasets were 0.943 (0.933-0.953), 0.867 (0.838-0.895), and 0.878 (0.859-0.896), respectively. For Task II, 13.8% of patients had PAS. The AUC, sensitivity, and specificity of 3D DGS were 0.902 (0.818-0.985), 0.900 (0.714-1.000), and 0.890 (0.841-0.938), respectively, on the external testing set at quadrant level following normal clinical practice; and 0.885 (0.836-0.933), 0.912 (0.816-1.000), and 0.700 (0.660-0.741), respectively, on the external testing set at clock-hour level. CONCLUSIONS: The 3D DGS is effective in detecting eyes with suspected PACG. It has the potential to be used widely in the primary eye care community for screening of subjects at high risk of developing PACG.
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Córnea/patologia , Glaucoma de Ângulo Fechado/diagnóstico , Gonioscopia/métodos , Imageamento Tridimensional/métodos , Iris/patologia , Tomografia de Coerência Óptica/métodos , Malha Trabecular/patologia , Adulto , Idoso , Área Sob a Curva , Córnea/diagnóstico por imagem , Estudos Transversais , Diagnóstico por Computador , Feminino , Humanos , Pressão Intraocular , Iris/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
PURPOSE: To develop a classification system of visual field (VF) abnormalities in highly myopic eyes with and without glaucoma. DESIGN: Secondary analysis of VF data from a longitudinal cohort study. PARTICIPANTS: One thousand eight hundred ninety-three VF tests from 1302 eyes (825 individuals). METHODS: All participants underwent VF testing (Humphrey 24-2 Swedish interactive threshold algorithm standard program; Carl Zeiss Meditec) and detailed ophthalmic examination. A comprehensive set of VF defect patterns was defined via observation of the 1893 VF reports, literature review, and consensus meetings. The classification system comprised 4 major types of VF patterns, including normal type, glaucoma-like defects (paracentral defect, nasal step, partial arcuate defect, arcuate defect), high myopia-related defects (enlarged blind spot, vertical step, partial peripheral rim, nonspecific defect), and combined defects (nasal step with enlarged blind spot). A subset (n = 1000) of the VFs was used to evaluate the interobserver and intraobserver agreement and weighted κ values of the classification system by 2 trained readers. The prevalence of various VF patterns and their associated factors were determined. MAIN OUTCOME MEASURES: The classification of VF in highly myopic eyes and its associated risk factors. RESULTS: We found that normal type, glaucoma-like defects, high myopia-related defects, and combined defects accounted for 74.1%, 10.8%, 15.0%, and 0.1% of all unique VF tests, respectively. The interobserver and intraobserver agreements were > 89%, and the corresponding κ values were 0.86 or more between readers. Both glaucoma-like and high myopia-related VF defects were associated with older age (odds ratios [ORs], 1.07 [95% confidence interval (CI), 1.04-1.10; P < 0.001] and 1.06 [95% CI, 1.04-1.10; P < 0.001]) and longer axial length (ORs, 1.65 [95% CI, 1.32-2.07; P < 0.001] and 1.37 [95% CI, 1.11-1.68; P = 0.003]). Longer axial length showed a stronger effect on the prevalence of glaucoma-like VF defects than on the prevalence of high myopia-related VF defects (P = 0.036). CONCLUSIONS: We propose a new and reproducible classification system of VF abnormalities for nonpathologic high myopia. Applying a comprehensive classification system will facilitate communication and comparison of findings among studies.
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Glaucoma , Miopia , Disco Óptico , Glaucoma/complicações , Humanos , Pressão Intraocular , Estudos Longitudinais , Miopia/complicações , Miopia/diagnóstico , Miopia/epidemiologia , Disco Óptico/patologia , Estudos Retrospectivos , Escotoma/diagnóstico , Transtornos da Visão/patologia , Testes de Campo Visual , Campos VisuaisRESUMO
[This retracts the article DOI: 10.1016/j.jsps.2017.04.028.].
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Angiogenesis, the formation of new blood vessels from the pre-existing ones, is a hallmark characteristic of glioblastoma, making it an appealing target for treatment development. Given potent anti-cancer efficacy of mefloquine, FDA-approved anti-malarial drug, there is increasing interest in repurposing mefloquine for treatment of cancers, including glioblastoma. In line with these efforts, our work is the first to demonstrate that mefloquine is also an inhibitor of glioblastoma angiogenesis. Using glioblastoma microvascular endothelial cell (GMEC) isolated from glioblastoma patients, we show that mefloquine at clinically achievable concentration inhibits GMEC differentiation, capillary network formation, adhesion to Matrix, growth and survival. Mefloquine also inhibits growth and induces apoptosis in glioblastoma cells regardless of cellular origin and genetic background. We further show that mefloquine significantly inhibits glioblastoma growth but not formation, and this is associated with decreased glioblastoma angiogenesis in mice. Mechanistically, mefloquine disrupted lysosomal integrity and function in GMECs, leading to oxidative stress and lysosomal lipid damage. Rescue studies confirm that mefloquine acts on GMECs in a lysosomal disruption-dependent manner. Our findings demonstrate the anti-angiogenic activity of mefloquine via disrupting lysosomal function. The dual inhibitory role of mefloquine in glioblastoma angiogenesis and glioblastoma displays its advantage over other anti-cancer drugs for glioblastoma treatment. Our work also highlights the essential role of lysosome in both glioblastoma and its angiogenesis.
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Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Mefloquina/uso terapêutico , Neovascularização Patológica/tratamento farmacológico , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/uso terapêutico , Animais , Antineoplásicos/farmacologia , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Glioblastoma/patologia , Humanos , Masculino , Mefloquina/farmacologia , Camundongos SCID , Neovascularização Patológica/patologiaRESUMO
Primary or secondary forests around the world are increasingly being converted into plantations. Soil microorganisms are critical for all biogeochemical processes in ecosystems, but the effects of forest conversion on microbial communities and their functioning remain unclear. Here, we conducted a meta-analysis to quantify the impacts that converting forests to plantations has on soil microbial communities and functioning as well as on the associated plant and soil properties. We collected 524 paired observations from 138 studies globally. We found that conversion leads to broad range of adverse impacts on soils and microorganisms, including on soil organic carbon (-24%), total nitrogen (-29%), bacterial and fungal biomass (-36% and -42%, respectively), microbial biomass carbon (MBC, -31%) and nitrogen (-33%), and fungi to bacteria ratio (F:B, -16%). In addition, we found impacts on the ratio of MBC to soil organic C (qMBC, -20%), microbial respiration (-18%), N mineralization (-18%), and enzyme activities including ß-1,4-glucosidase (-54%), ß-1,4-N-acetylglucosaminidase (-39%), and acid phosphatase (ACP; -34%). In contrast, conversion to plantations increases bacterial richness (+21%) and microbial metabolic quotient (qCO2 , +21%). The effects of forest conversion were consistent across stand ages, stand types, and climate zone. Soil C and N contents as well as the C:N ratio were the main factors responsible for the changes of microbial C, F:B, and bacterial richness. The responses of qCO2 , N mineralization, and ACP activity were mainly driven by the reductions in F:B, MBC, and soil C:N. Applying macro-ecology theory on ecosystem disturbance in soil microbial ecology, we show that microbial groups shifted from K to r strategists after conversion to plantations. Our meta-analysis underlines the adverse effects of natural forests conversion to plantations on soil microbial communities and functioning, and suggests that the preservation of soil functions should be a consideration in forest management practices.
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Ecossistema , Solo , Carbono , Florestas , Nitrogênio/análiseRESUMO
n-Butylidenephthalide (NBDP) is one of the bioactive constituents originally isolated from Ligusticum chuanxiong Hort. The aim of this study was to study the metabolic profiles of NBDP in rat and human liver microsomes. NBDP was individually incubated with liver microsomes of rat and human at 37°C for 1 h and the samples incubated were analyzed by ultra-high-performance liquid chromatography combined with high-resolution mass spectrometry. The identities of the metabolites were identified by accurate masses, product ions and retention times. Under the current conditions, a total of 14 metabolites were detected and identified. M12, M13 and M14 were biosynthesized and unambiguously characterized by nuclear magnetic resonance spectroscopy. All the metabolites can be detected in rat liver microsomes, whereas in human liver microsomes, M1, M3, M4, M5, M6 and M7 were not detected. Our results demonstrated that the metabolic pathways of NBDP included hydroxylation, hydration, hydrolysis and glutathione conjugation. This study provides an overview of the metabolic profiles of NBDP in vitro, which is helpful to understand the action of this compound.
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Cromatografia Líquida de Alta Pressão/métodos , Microssomos Hepáticos/metabolismo , Anidridos Ftálicos , Espectrometria de Massas em Tandem/métodos , Animais , Humanos , Ligusticum , Masculino , Redes e Vias Metabólicas , Anidridos Ftálicos/análise , Anidridos Ftálicos/química , Anidridos Ftálicos/metabolismo , RatosRESUMO
OBJECTIVE: To minimize the adverse events of uterine compression suture in controlling postpartum hemorrhage (PPH) and to search for a prophylactic approach to potential PPH. METHODS: A retrospective analysis was performed in 39 women with removable retropubic uterine compression suture (RRUCS) to stop PPH due to uterine atony during cesarean section (CS). The procedure was to suspend and compress the uterus to the retropubic abdominal wall using an absorbable suture. RESULTS: The technique was sufficient to stanch bleeding immediately in 36 patients (92.31%, 36/39). No morbidity or abnormalities occurred in women who underwent RRUCS. Subsequent pregnancies occurred in 10 cases, but the others lacked the desire for future pregnancy. CONCLUSION: RRUCS is a simple, safe, and effective technique in controlling atonic PPH; it is also used as a prophylactic application in patients with potential PPH after CS.
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Cesárea , Hemorragia Pós-Parto , Inércia Uterina , Cesárea/efeitos adversos , Feminino , Humanos , Hemorragia Pós-Parto/prevenção & controle , Hemorragia Pós-Parto/cirurgia , Gravidez , Estudos Retrospectivos , Técnicas de Sutura , Suturas , Inércia Uterina/cirurgia , Útero/cirurgiaRESUMO
Emerging evidence has revealed significant roles for small nucleolar RNAs (snoRNAs) in tumorigenesis. However, the genetic and pharmacogenomic landscape of snoRNAs has not been characterized. Using the genotype and snoRNA expression data from The Cancer Genome Atlas, we characterized the effects of genetic variants on snoRNAs across 29 cancer types and further linked related alleles with patient survival as well as genome-wide association study risk loci. Furthermore, we characterized the impact of snoRNA expression on drug response in patients to facilitate the clinical utility of snoRNAs in cancer. We also developed a user-friendly data resource, GPSno (http://hanlab.uth.edu/GPSno), with multiple modules for researchers to visualize, browse, and download multi-dimensional data. Our study provides a comprehensive genetic and pharmacogenomic landscape of snoRNAs, which will shed light on future clinical considerations for the development of snoRNA-based targeted therapies.
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Antineoplásicos/farmacologia , Biomarcadores Tumorais/genética , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias/patologia , Farmacogenética , RNA Nucleolar Pequeno/genética , Estudo de Associação Genômica Ampla , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/genética , PrognósticoRESUMO
A series of novel anthranilic diamides derivatives (7a-s) containing halogen, trifluoromethyl group and cyano group were designed, synthesized, and characterized by melting point, 1H NMR, 13C NMR and elemental analyses. The bioactivity revealed that most of them showed moderate to excellent activities against oriental armyworm (Mythimna separata) and diamondback moth (Plutella xylostella). Above all, the larvicidal activity of 7o against oriental armyworm was 100% and 40% at 0.25 and 0.1â¯mgâ¯L-1, comparable to that of the standard chlorantraniliprole (100%, 0.25â¯mgâ¯L-1 and 20%, 0.1â¯mgâ¯L-1). What is more, 7o against diamondback moth displayed 90% insecticidal activity at 0.01â¯mgâ¯L-1, superior to chlorantraniliprole (45%, 0.01â¯mgâ¯L-1). The experiments 7o on the American cockroach (Periplaneta Americana) heart beating rates (Dorsal vessel) and contractile force were compared with chlorantraniliprole. In addition, 7o could affect the calcium homeostasis in the central neurons of the third larvae of oriental armyworm, which revealed that the ryanodine receptor is the potential target of 7o. The density functional theory (DFT) calculation results revealed the amide bridge, the benzene ring of anthraniloyl moiety and pyrazole ring might play an important role in the insecticidal activity through hydrophobic interactions and π-π conjugations.
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Diamida/química , Inseticidas/síntese química , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Animais , Baratas/efeitos dos fármacos , Baratas/fisiologia , Diamida/síntese química , Diamida/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Inseticidas/química , Inseticidas/toxicidade , Isoxazóis/química , Larva/efeitos dos fármacos , Mariposas/crescimento & desenvolvimento , Mariposas/metabolismo , Teoria Quântica , Canal de Liberação de Cálcio do Receptor de Rianodina/química , Relação Estrutura-AtividadeRESUMO
BACKGROUND: To develop a deep neural network able to differentiate glaucoma from non-glaucoma visual fields based on visual filed (VF) test results, we collected VF tests from 3 different ophthalmic centers in mainland China. METHODS: Visual fields obtained by both Humphrey 30-2 and 24-2 tests were collected. Reliability criteria were established as fixation losses less than 2/13, false positive and false negative rates of less than 15%. RESULTS: We split a total of 4012 PD images from 1352 patients into two sets, 3712 for training and another 300 for validation. There is no significant difference between left to right ratio (P = 0.6211), while age (P = 0.0022), VFI (P = 0.0001), MD (P = 0.0039) and PSD (P = 0.0001) exhibited obvious statistical differences. On the validation set of 300 VFs, CNN achieves the accuracy of 0.876, while the specificity and sensitivity are 0.826 and 0.932, respectively. For ophthalmologists, the average accuracies are 0.607, 0.585 and 0.626 for resident ophthalmologists, attending ophthalmologists and glaucoma experts, respectively. AGIS and GSS2 achieved accuracy of 0.459 and 0.523 respectively. Three traditional machine learning algorithms, namely support vector machine (SVM), random forest (RF), and k-nearest neighbor (k-NN) were also implemented and evaluated in the experiments, which achieved accuracy of 0.670, 0.644, and 0.591 respectively. CONCLUSIONS: Our algorithm based on CNN has achieved higher accuracy compared to human ophthalmologists and traditional rules (AGIS and GSS2) in differentiation of glaucoma and non-glaucoma VFs.
Assuntos
Glaucoma/diagnóstico , Testes de Campo Visual/métodos , Adulto , Idoso , Feminino , Humanos , Aprendizado de Máquina , Pessoa de Meia-Idade , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Neuromyelitis optica spectrum disorder-optic neuritis (NMOSD-ON) can now be distinguished from other types of ON as a specific disease by the Aquaporin-4 antibody (AQP4-Ab) test. NMOSD-ON can cause severe retinal nerve fiber layer (RNFL) damage. The optical coherence tomography (OCT) characteristics between NMOSD- ON and idiopathic optic neuritis (IDON) were seldom studied in Asians. METHODS: This prospective case-control study involved 152 eyes from 143 optic neuritis (ON) patients. All the patients were divided into either the NMOSD-ON group or the IDON group based on the AQP4-Ab test. The retinal nerve fiber layer thickness (RNFLT), retinal thickness (RT), and choroidal thickness (CT) were measured by spectral-domain OCT and compared to the 60 age- and gender-matched healthy controls. The association between RNFLT and best corrected visual acuity (BCVA) was examined. RESULTS: The RNFLT was significantly thinner in all ON patients than in healthy controls, while NMOSD-ON eyes were significantly more affected than IDON eyes in all quadrants (p < 0.01). NMOSD-ON patients had stronger visual function impairment than IDON patients (p < 0.01). RNFLT was related to BCVA in both the NMOSD-ON and IDON groups. Microcystic macular edema (MME) was identified in 28 patients (19.58%) and in 29 of 152 eyes (19.08%), including 20 of 40 eyes (50%) previously affected by ON. MME was more common in patients with NMOSD-ON (32.2%) than in those with IDON (10.75%) (p = 0.001). CONCLUSIONS: The NMOSD-ON group had more pronounced RNFLT thinning and visual function impairment than the IDON group. MME prevalence was higher in NMOSD-ON and was associated with higher frequency of clinical relapses.
Assuntos
Neuromielite Óptica/diagnóstico , Disco Óptico/patologia , Neurite Óptica/diagnóstico , Células Ganglionares da Retina/patologia , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Adulto , Estudos de Casos e Controles , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Fibras Nervosas/patologia , Estudos Prospectivos , Adulto JovemRESUMO
The effect of annealing temperature on the microstructure, phase constituents and mechanical properties of Al0.5CoCrFeMoxNi high-entropy complex alloys has been investigated at a fixed annealing time (10 h). The 600 °C-annealing has no obvious effect on their microstructures, while the annealing at 800-1200 °C enhances the precipitation of (Al,Ni)-rich ordered BCC phase or/and (Cr,Mo)-rich σ phase, and thereby greatly affects the microstructure and mechanical properties of the alloys. All the annealed Al0.5CoCrFeNi alloys are composed of FCC and (Al,Ni)-rich ordered BCC phases; the phase constituent of the Al0.5CoCrFeMo0.1Ni alloy changes from FCC + BCC (600 °C) to FCC + BCC + σ (800 °C) and then to FCC + BCC (1100 °C); the phase constituents of the Al0.5CoCrFeMo0.2Ni and Al0.5CoCrFeMo0.3Ni alloys change from FCC + BCC + σ to FCC + BCC with the annealing temperature rising from 600 to 1200 °C; while all the annealed Al0.5CoCrFeMo0.4Ni and Al0.5CoCrFeMo0.5Ni alloys consist of FCC, BCC and σ phases. The phase constituents of most of the alloys investigated are in good agreement with the calculated results from Thermo-Calc program. The alloys annealed at 800 °C under current investigation conditionshave relative fine precipitations and microstructure, and thereby higher hardness and yield stress.