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1.
Sensors (Basel) ; 24(10)2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38793935

RESUMO

During the braking process of electric vehicles, both the regenerative braking system (RBS) and anti-lock braking system (ABS) modulate the hydraulic braking force, leading to control conflict that impacts the effectiveness and real-time capability of coordinated control. Aiming to enhance the coordinated control effectiveness of RBS and ABS within the electro-hydraulic composite braking system, this paper proposes a coordinated control strategy based on explicit model predictive control (eMPC-CCS). Initially, a comprehensive braking control framework is established, combining offline adaptive control law generation, online optimized control law application, and state compensation to effectively coordinate braking force through the electro-hydraulic system. During offline processing, eMPC generates a real-time-oriented state feedback control law based on real-world micro trip segments, improving the adaptiveness of the braking strategy across different driving conditions. In the online implementation, the developed three-dimensional eMPC control laws, corresponding to current driving conditions, are invoked, thereby enhancing the potential for real-time braking strategy implementation. Moreover, the state error compensator is integrated into eMPC-CCS, yielding a state gain matrix that optimizes the vehicle braking status and ensures robustness across diverse braking conditions. Lastly, simulation evaluation and hardware-in-the-loop (HIL) testing manifest that the proposed eMPC-CCS effectively coordinates the regenerative and hydraulic braking systems, outperforming other CCSs in terms of braking energy recovery and real-time capability.

2.
Sensors (Basel) ; 24(10)2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38794003

RESUMO

With the rapid development of the intelligent driving technology, achieving accurate path planning for unmanned vehicles has become increasingly crucial. However, path planning algorithms face challenges when dealing with complex and ever-changing road conditions. In this paper, aiming at improving the accuracy and robustness of the generated path, a global programming algorithm based on optimization is proposed, while maintaining the efficiency of the traditional A* algorithm. Firstly, turning penalty function and obstacle raster coefficient are integrated into the search cost function to increase the adaptability and directionality of the search path to the map. Secondly, an efficient search strategy is proposed to solve the problem that trajectories will pass through sparse obstacles while reducing spatial complexity. Thirdly, a redundant node elimination strategy based on discrete smoothing optimization effectively reduces the total length of control points and paths, and greatly reduces the difficulty of subsequent trajectory optimization. Finally, the simulation results, based on real map rasterization, highlight the advanced performance of the path planning and the comparison among the baselines and the proposed strategy showcases that the optimized A* algorithm significantly enhances the security and rationality of the planned path. Notably, it reduces the number of traversed nodes by 84%, the total turning angle by 39%, and shortens the overall path length to a certain extent.

3.
Cureus ; 16(3): e57021, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38681466

RESUMO

This report describes the case of an 18-year-old Micronesian pregnant woman at 32 weeks gestation, initially presumed to have eclampsia but later diagnosed with reversible cerebral vasoconstriction syndrome (RCVS). She presented with seizures, altered mental status, nystagmus, lower extremity weakness, and absent reflexes. An extensive workup ruled out infectious and autoimmune causes, but a computed tomography angiogram (CTA) revealed severe cerebral vasoconstriction. Treatment included levetiracetam, intravenous magnesium, and nimodipine. The case highlights the challenge of differentiating RCVS from eclampsia in the postpartum period, emphasizing the importance of considering alternative diagnoses and brain CTA when RCVS is suspected, with calcium channel blockers potentially contributing to favorable neurological outcomes.

5.
Ecotoxicol Environ Saf ; 263: 115223, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37418941

RESUMO

Swertia bimaculata (SB) is a medicinal herb in China having an array of therapeutic and biological properties. This study aimed to explore the attenuating effect of SB on carbon tetrachloride (CCl4) induced hepato-toxicity by regulation of gut microbiome in ICR mice. For this purpose, CCl4 was injected intraperitoneally in different mice groups (B, C, D and E) every 4th day for a period of 47 days. Additionally, C, D, and E groups received a daily dose (50 mg/kg, 100 mg/kg, and 200 mg/kg respectively) of Ether extract of SB via gavage for the whole study period. The results of serum biochemistry analysis, ELISA, H&E staining, and sequencing of the gut microbiome, indicated that SB significantly alleviates the CCl4-induced liver damage and hepatocyte degeneration. The serum levels of alanine transaminase, aspartate aminotransferase, malondialdehyde, interleukin 1 beta and tumor necrosis factor-alpha were significantly lower in SB treated groups compared to control while levels of glutathione peroxidase were raised. Also, the sequencing data indicate that supplementation with SB could restore the microbiome and its function in CCl4-induced variations in intestinal microbiome of mice by significantly downregulating the abundances of pathogenic intestinal bacteria species including Bacteroides, Enterococcus, Eubacterium, Bifidobacterium while upregulating the levels of beneficial bacteria like Christensenella in the gut. In conclusion, we revealed that SB depicts a beneficial effect against hepatotoxicity induced by CCl4 in mice through the remission of hepatic inflammation and injury, through regulation of oxidative stress, and by restoring gut microbiota dysbiosis.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Microbioma Gastrointestinal , Hepatopatias , Swertia , Camundongos , Animais , Fígado , Swertia/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Camundongos Endogâmicos ICR , Estresse Oxidativo , Aspartato Aminotransferases/metabolismo , Alanina Transaminase/metabolismo , Intestinos
6.
JAMA Ophthalmol ; 141(7): 677-685, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37289463

RESUMO

Importance: Best-corrected visual acuity (BCVA) is a measure used to manage diabetic macular edema (DME), sometimes suggesting development of DME or consideration of initiating, repeating, withholding, or resuming treatment with anti-vascular endothelial growth factor. Using artificial intelligence (AI) to estimate BCVA from fundus images could help clinicians manage DME by reducing the personnel needed for refraction, the time presently required for assessing BCVA, or even the number of office visits if imaged remotely. Objective: To evaluate the potential application of AI techniques for estimating BCVA from fundus photographs with and without ancillary information. Design, Setting, and Participants: Deidentified color fundus images taken after dilation were used post hoc to train AI systems to perform regression from image to BCVA and to evaluate resultant estimation errors. Participants were patients enrolled in the VISTA randomized clinical trial through 148 weeks wherein the study eye was treated with aflibercept or laser. The data from study participants included macular images, clinical information, and BCVA scores by trained examiners following protocol refraction and VA measurement on Early Treatment Diabetic Retinopathy Study (ETDRS) charts. Main Outcomes: Primary outcome was regression evaluated by mean absolute error (MAE); the secondary outcome included percentage of predictions within 10 letters, computed over the entire cohort as well as over subsets categorized by baseline BCVA, determined from baseline through the 148-week visit. Results: Analysis included 7185 macular color fundus images of the study and fellow eyes from 459 participants. Overall, the mean (SD) age was 62.2 (9.8) years, and 250 (54.5%) were male. The baseline BCVA score for the study eyes ranged from 73 to 24 letters (approximate Snellen equivalent 20/40 to 20/320). Using ResNet50 architecture, the MAE for the testing set (n = 641 images) was 9.66 (95% CI, 9.05-10.28); 33% of the values (95% CI, 30%-37%) were within 0 to 5 letters and 28% (95% CI, 25%-32%) within 6 to 10 letters. For BCVA of 100 letters or less but more than 80 letters (20/10 to 20/25, n = 161) and 80 letters or less but more than 55 letters (20/32 to 20/80, n = 309), the MAE was 8.84 letters (95% CI, 7.88-9.81) and 7.91 letters (95% CI, 7.28-8.53), respectively. Conclusions and Relevance: This investigation suggests AI can estimate BCVA directly from fundus photographs in patients with DME, without refraction or subjective visual acuity measurements, often within 1 to 2 lines on an ETDRS chart, supporting this AI concept if additional improvements in estimates can be achieved.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Edema Macular/fisiopatologia , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/complicações , Inibidores da Angiogênese/uso terapêutico , Inteligência Artificial , Fator A de Crescimento do Endotélio Vascular , Acuidade Visual , Algoritmos , Diabetes Mellitus/tratamento farmacológico
8.
Eye (Lond) ; 37(10): 2020-2025, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-35440699

RESUMO

AIMS: To assess time to, cumulative incidence of, and functional benefit of achieving sustained ≥2-step Diabetic Retinopathy Severity Scale (DRSS) improvement in diabetic macular oedema (DMO). METHODS: Post hoc analysis of VISTA/VIVID including eyes with DMO treated with intravitreal aflibercept injections (IAI), 2 mg q4 weeks (2q4, n = 250) or q8 weeks after 5 monthly doses (2q8, n = 249), or laser control (n = 249). Changes from baseline in best-corrected visual acuity (BCVA) and central subfield thickness (CST) were evaluated in sustained (≥2 consecutive visits) DRSS subgroups (≥1-step worsening, no change, ≥2-step improvement). RESULTS: Time to sustained ≥2-step DRSS improvement was shorter for both the IAI 2q4 and IAI 2q8 groups versus laser (both log-rank p < 0.001). Cumulative incidences of sustained ≥2-step DRSS improvement with IAI 2q4 and IAI 2q8 versus laser were 40.0% and 42.8% versus 15.5% (both p < 0.001) through week 100. Mean differences (95% CI) in BCVA gains from baseline at weeks 52 and 100 between eyes with sustained ≥2-step DRSS improvement versus sustained ≥1-step DRSS worsening were -3.0 (-8.9, 2.9) and 6.2 (0.2, 12.2) letters with laser, and 4.2 (0.8, 7.6) and 4.9 (1.3, 8.4) letters with IAI combined, respectively. Difference (95% CI) in CST reduction was significantly greater only with IAI combined at week 100 (-83.0 [-140.8, -25.3]). Correlations between BCVA and CST changes were weak. CONCLUSIONS: DMO eyes treated with IAI achieved sustained ≥2-step DRSS improvement significantly earlier and more frequently versus laser. This improvement was associated with greater BCVA gains, independent of CST reductions. TRIAL REGISTRATION: ClinicalTrials.gov ( https://clinicaltrials.gov/ ) identifiers: NCT01363440 and NCT01331681 .


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Humanos , Inibidores da Angiogênese/uso terapêutico , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/cirurgia , Injeções Intravítreas , Fotocoagulação a Laser/efeitos adversos , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Edema Macular/cirurgia , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Tomografia de Coerência Óptica , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/uso terapêutico , Ensaios Clínicos como Assunto
9.
Ophthalmol Retina ; 7(1): 24-32, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35843487

RESUMO

OBJECTIVE: To assess the relationship between baseline factors and time to diabetic macular edema (DME) resolution. DESIGN: Post hoc analysis of VISTA and VIVID. PARTICIPANTS: Eyes with baseline central subfield thickness (CST) of ≥ 290 µm. INTERVENTION: Eyes were treated with intravitreal aflibercept injection (IAI) 2 mg (n = 558; every 4 weeks or every 8 weeks after 5 monthly doses) or laser control (n = 274). The effect of baseline factors on the time to DME resolution (CST < 290 µm) was assessed in univariable and multivariable models and further evaluated by the Kaplan-Meier method. MAIN OUTCOME MEASURES: Time to and cumulative incidence of DME resolution. RESULTS: Eyes treated with IAI had a 2.5-fold higher DME resolution rate, with median time of 33.0 weeks (95% confidence interval [CI], 28.1-40.0), compared with DME resolution not being achieved in 50% of eyes treated with laser control. Multivariable analysis demonstrated that a lower DME resolution rate was associated with a thicker baseline CST (hazard ratio [HR] [95% CI] per 100-µm CST increase, 0.79 [0.72-0.86]) and better baseline best-corrected visual acuity (BCVA) (HR [95% CI] per 5-letter increase, 0.87 [0.83-0.92]) with IAI. Tertiles of increasing CST (T1CST ≤ 419 µm; T2CST > 419 to ≤ 541; T3CST > 541) were associated with longer median times to DME resolution (20.1, 39.1, and 49.1 weeks, respectively; P < 0.001 for T2CST and T3CST versus T1CST) and lower cumulative incidence of events (HR, 1.0, 0.6, and 0.6, respectively; P < 0.001 for T2CST and T3CST versus T1CST) with IAI. Tertiles of increasing BCVA (T1BCVA ≤ 57 letters; T2BCVA > 57 to ≤ 66; T3BCVA >66) were associated with longer median times to DME resolution (28.4, 31.7, and 44.1 weeks, respectively; P < 0.05 for T3BCVA versus T1BCVA) and lower cumulative incidence of events (HR, 1.0, 0.9, and 0.8, respectively; P < 0.05 for T3BCVA versus T1BCVA) with IAI. No other baseline factor was associated with the time to DME resolution. CONCLUSIONS: The median time to DME resolution was 33 weeks among IAI-treated eyes. A thicker baseline CST and better baseline BCVA in the IAI group were associated with a longer time to and a lower rate of DME resolution.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Humanos , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Retinopatia Diabética/complicações , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/tratamento farmacológico , Fotocoagulação a Laser/métodos , Fator A de Crescimento do Endotélio Vascular , Lasers
10.
Retina ; 43(2): 254-262, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36265076

RESUMO

PURPOSE: To characterize diabetic macular edema (DME) incidence in fellow eyes of patients treated for DME in the study eye. METHODS: This post hoc analysis of VISTA/VIVID data evaluated fellow eyes without DME at baseline through Week 100. Diabetic macular edema presence in the fellow eye was inferred by investigator-reported DME adverse events and use of DME treatments. RESULTS: Over 100 weeks, 44.9%, 44.2%, and 42.9% of fellow eyes developed DME in the intravitreal aflibercept injection 2 mg every 4 weeks (n = 245), intravitreal aflibercept injection 2 mg every 8 weeks (n = 258), and laser control (n = 252) groups, respectively. Mean time to DME development in combined treatment groups was ∼6 months. Multivariable regression analysis confirmed patients with shorter diabetes duration (hazard ratio per 10-year decrease, 1.16; 95% confidence interval, 1.03-1.30; P = 0.0160) and thicker baseline study eye central subfield thickness (hazard ratio per 10- µ m increase, 1.01; 95% confidence interval, 1.01-1.02; P = 0.0002) were at higher risk of developing DME in the fellow eye. CONCLUSION: Among patients with DME in one eye at baseline, almost half developed DME in the fellow eye over 2 years. Shorter duration of diabetes and thicker study eye central subfield thickness were predictors of DME development in the fellow eye.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Humanos , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Edema Macular/epidemiologia , Retinopatia Diabética/complicações , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/tratamento farmacológico , Incidência , Inibidores da Angiogênese , Fotocoagulação a Laser , Fator A de Crescimento do Endotélio Vascular , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Injeções Intravítreas , Proteínas Recombinantes de Fusão/uso terapêutico
11.
Graefes Arch Clin Exp Ophthalmol ; 260(12): 3799-3807, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35748935

RESUMO

PURPOSE: Assess correlation between change in central subfield thickness (CST) and change in best-corrected visual acuity (BCVA) in eyes with macular edema due to retinal vein occlusion (RVO) that received intravitreal aflibercept injections (IAI). METHODS: Post hoc analysis of COPERNICUS and GALILEO trials for CRVO and VIBRANT trial for BRVO with relationships determined using Pearson correlation coefficient. RESULTS: In COPERNICUS, correlations (r) between change in CST and change in BCVA from baseline at weeks 12, 24, 52, and 100 were -0.36 (95% CI: -0.52, -0.18; P < 0.001), -0.38 (95% CI: -0.53, -0.20; P < 0.001), -0.44 (95% CI: -0.58, -0.27; P < 0.001), and -0.41 (95% CI: -0.56, -0.23; P < 0.001), respectively. CST changes accounted for only 21% of the variance in BCVA changes; every 100-µm decrease in CST was associated with a 2.1-letter increase in BCVA (P = 0.003). Similar findings were noted for GALILEO (r, -0.45 to -0.23) and VIBRANT (r, -0.36 to -0.32) trials. CONCLUSION: In eyes treated with IAI for macular edema due to RVO, correlation between change in CST and change in BCVA was weak to moderate. While change in CST may be helpful in determining the need for anti-VEGF therapy, these findings do not support using changes in CST as a surrogate for changes in visual acuity outcomes.


Assuntos
Edema Macular , Oclusão da Veia Retiniana , Humanos , Inibidores da Angiogênese , Ensaios Clínicos como Assunto , Injeções Intravítreas , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Oclusão da Veia Retiniana/complicações , Oclusão da Veia Retiniana/diagnóstico , Oclusão da Veia Retiniana/tratamento farmacológico , Resultado do Tratamento , Acuidade Visual
12.
Am J Ophthalmol ; 238: 97-102, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34848169

RESUMO

PURPOSE: Determine correlation between change in central subfield thickness (CST) and change in best-corrected visual acuity (BCVA) in neovascular age-related macular degeneration receiving anti-vascular endothelial growth factor agents. DESIGN: A post hoc analysis of VIEW 1 and 2 randomized clinical trials. METHODS: This analysis included participants randomized to ranibizumab 0.5 mg every 4 weeks (Rq4), intravitreal aflibercept injection 2 mg every 4 weeks (2q4), and intravitreal aflibercept injection 2 mg every 8 weeks after 3 monthly doses (2q8) to week 52, followed by capped as-needed (at least every 12 weeks) dosing to week 96. Relationship between changes in CST and BCVA was determined using Pearson correlation coefficient. RESULTS: Of 1815 eyes, 595 were assigned to the Rq4, 613 to 2q4, and 607 to 2q8 arms. Correlations (95% confidence intervals [CI]) at weeks 12, 52, and 96 were -0.08 (95% CI, -0.17 to 0.00), -0.05 (95% CI, -0.14 to 0.04), and -0.15 (95% CI, -0.24 to -0.06) for Rq4; -0.13 (95% CI, -0.21 to -0.04), -0.06 (95% CI, -0.14 to 0.03) and -0.04 (95% CI, -0.13 to 0.05) for 2q4, and -0.04 (95% CI, -0.12 to 0.05), -0.01 (95% CI, -0.09 to 0.08), and -0.01 (95% CI, -0.10 to 0.09) for 2q8. Linear regression analysis adjusted for relevant baseline factors showed CST changes accounted for 11% of BCVA changes. Every 100 µm decrease in CST was associated with a 0.3 letter decrease (P = .25) at week 52 and a 0.14 letter decrease (P = .69) at week 96. CONCLUSIONS: Weak or no correlation was found between changes in CST and BCVA with either agent or regimen, suggesting changes in CST should not be used as a surrogate for visual acuity outcomes in neovascular age-related macular degeneration.


Assuntos
Inibidores da Angiogênese , Degeneração Macular Exsudativa , Inibidores da Angiogênese/uso terapêutico , Humanos , Injeções Intravítreas , Ranibizumab/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular , Acuidade Visual , Degeneração Macular Exsudativa/diagnóstico , Degeneração Macular Exsudativa/tratamento farmacológico
13.
J Vitreoretin Dis ; 6(4): 284-289, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-37007927

RESUMO

Purpose: To assess the correlation between the change in central subfield thickness (CST) and change in best-corrected visual acuity (BCVA) in eyes with diabetic macular edema (DME) treated with fixed-dosing intravitreal aflibercept injection (IAI). Methods: This post hoc analysis of the VISTA and VIVID randomized controlled clinical trials, in which 862 eyes with central-involved DME were randomly assigned to IAI 2 mg every 4 weeks (2q4; 290 eyes), IAI 2 mg every 8 weeks after 5 initial monthly doses (2q8; 286 eyes), or macular laser (286 eyes) and followed through 100 weeks. Correlations between the change in CST and change in BCVA from baseline to weeks 12, 52, and 100 were assessed using the Pearson correlation. Results: The respective correlations (r [95% CI]) at weeks 12, 52, and 100 were -0.39 (-0.49 to -0.29), -0.27 (-0.38 to -0.15), and -0.30 (-0.41 to -0.17) in the 2q4 arm and -0.28 (-0.39 to -0.17), -0.29 (-0.41 to -0.17), and -0.33 (-0.44 to -0.20) in the 2q8 arm. Linear regression analysis of the correlation at week 100, adjusted for relevant baseline factors, showed CST changes accounted for 17% of the variance in BCVA changes; every 100-µm decrease in CST was associated with a 1.2-letter increase in BCVA (P = .001). Conclusions: Correlations between the change in CST and change in BCVA after 2q4 or 2q8 fixed-dosing IAI for DME were modest. Although a change in CST might be important in determining the need for antivascular endothelial growth factor for DME at follow-up, it was not a good surrogate for VA outcomes.

14.
J Vitreoretin Dis ; 6(4): 295-301, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-37007930

RESUMO

Purpose: This work aimed to assess the incidence of proliferative diabetic retinopathy (PDR) events and improvement to mild non-PDR (NPDR) or better after intravitreal aflibercept injection (IAI) or laser treatment (control) in diabetic macular edema (DME). Methods: PDR events in the VISTA (NCT01363440) and VIVID (NCT01331681) phase 3 clinical trials were evaluated in a combined IAI-treated group (IAI 2 mg every 4 weeks or 2 mg every 8 weeks after 5 initial monthly doses; n = 475) and a macular laser control group (n = 235) through week 100 in eyes without PDR at baseline (Diabetic Retinopathy Severity Scale [DRSS] score ≤ 53). Improvement in the DRSS score to 35 or better was evaluated in those with a baseline DRSS score of 43 or greater. Results: A lower proportion of eyes in the IAI group than in the laser group developed a PDR event through week 100 (4.4% vs 11.1%; adjusted difference, -6.7%; 97.5% CI, -11.7 to -1.6; nominal P = .0008). All PDR events occurred in eyes with a baseline DRSS score of 43, 47, or 53 and not in those with a score of 35 or less. A greater proportion of eyes in the IAI group than in the control group achieved a DRSS score of 35 or less (20.0% vs 3.8%; nominal P < .0001). Conclusions: Fewer eyes with NPDR and DME treated with IAI than eyes treated with a laser had a PDR event. More eyes treated with IAI improved to mild NPDR or better (DRSS score ≤ 35) through 100 weeks.

16.
Ophthalmol Retina ; 5(2): 141-150, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32652314

RESUMO

PURPOSE: To assess the influence of baseline choroidal neovascularization (CNV) features on visual change and fluid resolution after anti-vascular endothelial growth factor (VEGF) treatment of eyes with neovascular age-related macular degeneration (nAMD). DESIGN: Post hoc analysis of 52-week data from the phase 3 Vascular Endothelial Growth Factor VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet Age-Related Macular Degeneration (AMD) Studies (VIEW) 1 and 2 clinical trials. PARTICIPANTS: One thousand eight hundred four patients with nAMD. METHODS: Integrated data from VIEW 1 and 2 of 1804 eyes receiving intravitreal aflibercept injections (IAIs) 2 mg every 4 weeks, IAIs 2 mg every 8 weeks after 3 initial monthly doses, and ranibizumab every 4 weeks with documented baseline CNV type, total area, and leakage area were analyzed. Time to an event and cumulative incidence were evaluated by Kaplan-Meier analysis, and relative risks were estimated using proportional hazards analysis. MAIN OUTCOMES MEASURES: Cumulative incidence of time to first sustained vision gain of 15 or more Early Treatment Diabetic Retinopathy Study letters, vision loss of more than 5 Early Treatment Diabetic Retinopathy Study letters from baseline, as well as first sustained absence of retinal fluid and intraretinal fluid as evaluated by OCT with respect to CNV type, total CNV, and leakage area. RESULTS: Eyes with predominantly classic CNV (mean best-corrected visual acuity [BCVA], 48.2 letters at baseline) showed a higher incidence rate of first sustained gain of 15 letters or more than eyes with occult CNV (mean BCVA, 57.9 letters at baseline; P < 0.01). Eyes with occult CNV at baseline showed higher incidence rates of first sustained absence of retinal fluid and of intraretinal fluid than eyes with predominantly classic CNV (both P < 0.01). With increasing baseline CNV total area and leakage area, the incidence rate of first sustained gain of 15 letters or more decreased. CONCLUSIONS: This post hoc analysis provided additional evidence for the role of baseline CNV features (CNV type, total area, and leakage area) in influencing visual and anatomic outcomes in eyes with nAMD after anti-VEGF treatment.


Assuntos
Corioide/patologia , Macula Lutea/patologia , Ranibizumab/administração & dosagem , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Acuidade Visual , Degeneração Macular Exsudativa/tratamento farmacológico , Inibidores da Angiogênese/administração & dosagem , Neovascularização de Coroide/diagnóstico , Neovascularização de Coroide/tratamento farmacológico , Método Duplo-Cego , Angiofluoresceinografia , Seguimentos , Fundo de Olho , Humanos , Injeções Intravítreas , Prognóstico , Estudos Prospectivos , Fatores de Tempo , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Degeneração Macular Exsudativa/diagnóstico
17.
Exp Neurol ; 327: 113223, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32032565

RESUMO

AIMS: Ischemic stroke has become one of the main causes of death worldwide. MicroRNAs (miRNAs) have been implicated in cerebral ischemia-reperfusion (I/R) injury and could serve as therapeutic targets. 5-Lipoxygenase (5-LOX) is a key enzyme in the biosynthesis of leukotrienes and has been implicated in inflammatory central nerve system disorders. The objective of this study was to explore the neuroprotective effects of miR-193b-3p against focal cerebral I/R injury in rats by regulating 5-LOX expression. METHODS AND MATERIALS: Adult male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion and reperfusion injury. The level of miR-193b-3p expression was observed in the rat cortical peri-infarct region after focal cerebral I/R injury. Bioinformatics analysis was used to predict the binding sites of miR-193b-3p, and a dual-luciferase reporter gene assay was applied to verify the potential interaction between 5-LOX mRNA and miR-193b-3p. Then, rats were injected with a miR-193b-3p agomir (modified and enhanced mimic) or antagomir (modified and enhanced inhibitor) in the right lateral ventricle of the brain. Neurological deficit scores, infarct volumes, neuron damage and 5-LOX enzymatic activity and expression were measured. In an in vitro experiment, cultured PC12 cells were exposed to oxygen-glucose deprivation and reperfusion (OGD/R). OGD/R-induced cells were treated with a miR-193b-3p mimic or inhibitor and 5-LOX siRNA. Cell viability, lactate dehydrogenase release, apoptosis rate and 5-LOX expression were evaluated. RESULTS: The level of miR-193b-3p expression was increased in the cortical peri-infarct region of rats with cerebral focal I/R injury. The results of the dual-luciferase reporter gene assay showed that a miR-193b-3p binding site was located in the 3' untranslated region (3'UTR) of 5-LOX mRNA. Neurological deficit scores, infarct volumes and neuronal injury were alleviated by miR-193b-3p agomir treatment but aggravated by miR-193b-3p antagomir. Furthermore, leukotriene B4, cysteinyl-leukotrienes and 5-LOX expression in the cortical peri-infarct region of rats with focal cerebral I/R injury were also downregulated by miR-193b-3p agomir treatment but upregulated by miR-193b-3p antagomir. In PC12 cells, miR-193b-3p mimic significantly decreased OGD/R-induced cell death and reduced lactate dehydrogenase release and 5-LOX expression. In contrast, miR-193b-3p inhibitor exacerbated OGD/R-induced injury in PC12 cells. Additionally, the in vitro effects of miR-193b-3p inhibitor on OGD/R-induced cell injury were partially reversed by 5-LOX siRNA treatment. CONCLUSION: MiR-193b-3p has a potentially neuroprotective effect on focal cerebral I/R-induced injury by inhibiting 5-LOX expression.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Inibidores de Lipoxigenase/uso terapêutico , MicroRNAs/agonistas , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Araquidonato 5-Lipoxigenase/metabolismo , Isquemia Encefálica/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Leucotrieno B4/metabolismo , Inibidores de Lipoxigenase/farmacologia , Masculino , MicroRNAs/antagonistas & inibidores , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Células PC12 , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo
18.
Ophthalmology ; 126(8): 1171-1180, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30946887

RESUMO

PURPOSE: To evaluate changes in retinal perfusion status with intravitreal aflibercept injection (IAI) and laser treatment in the phase 3 VISTA study of patients with diabetic macular edema (DME). DESIGN: Post hoc analysis of a double-masked, randomized, active-controlled, phase 3 trial. PARTICIPANTS: Patients with center-involved DME in the study eye. METHODS: VISTA randomized 466 patients to laser, IAI 2 mg every 4 weeks (2q4), or IAI 2 mg every 8 weeks after 5 monthly doses (2q8). One eye per patient was enrolled in the study. Retinal perfusion status was evaluated by fluorescein angiography based on the presence or absence of retinal nonperfusion (RNP) in quadrants intersecting at the optic nerve head by a masked independent reading center at weeks 24, 52, 72, and 100. Visual and anatomic outcomes were evaluated at all visits. In patients who received rescue treatment, data were censored from the time rescue treatment was given. MAIN OUTCOME MEASURES: Change in perfusion status from baseline through week 100. RESULTS: At week 100, the proportion of eyes with improvement in retinal perfusion (defined as a reduction from baseline in the total number of quadrants in which RNP is present) in the laser control, 2q4, and 2q8 groups was 14.6%, 44.7%, and 40.0%, respectively. The proportion of eyes that experienced worsening in retinal perfusion (defined as an increase from baseline in the total number of quadrants in which RNP is present) at week 100 in the laser control, 2q4, and 2q8 groups was 25.0%, 9.0%, and 8.6%, respectively. CONCLUSION: Post hoc analysis of the phase 3 VISTA study in patients with DME provides evidence that regular IAI dosing not only can slow worsening of retinal perfusion associated with diabetic retinopathy but also may be able to improve retinal perfusion in some cases by decreasing zones of RNP.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Retinopatia Diabética/terapia , Fotocoagulação a Laser , Edema Macular/terapia , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Vasos Retinianos/fisiologia , Idoso , Método Duplo-Cego , Feminino , Humanos , Injeções Intravítreas , Fotocoagulação a Laser/métodos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fluxo Sanguíneo Regional/fisiologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
19.
Adv Mater ; 29(26)2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28466974

RESUMO

Pressure sensors that can both directly visualize and record applied pressure/stress are essential for e-skin and medical/health monitoring. Here, using a WO3 -film electrochromic device (ECD) array (10 × 10 pixels) and a ZnO-nanowire-matrix pressure sensor (ZPS), a pressure visualization and recording (PVR) system with a spatial resolution of 500 µm is developed. The distribution of external pressures can be recorded through the piezotronic effect from the ZPS and directly expressed by color changes in the ECD. Applying a local pressure can generate piezoelectric polarization charges at the two ends of the ZnO nanowires, which leads to the tuning of the current to be transported through the system and thus the color of the WO3 film. The coloration and bleaching process in the ECD component show good cyclic stability, and over 85% of the color contrast is maintained after 300 cycles. In this PVR system, the applied pressure can be recorded without the assistance of a computer because of the color memory effect of the WO3 material. Such systems are promising for applications in human-electronic interfaces, military applications, and smart robots.

20.
Int J Antimicrob Agents ; 48(3): 317-20, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27449540

RESUMO

Scrub typhus, caused by Orientia tsutsugamushi, has recently emerged in northern China where the disease had not been known to exist. Although doxycycline and azithromycin are the recommended agents for the treatment of scrub typhus, clinical responses depend both on the susceptibilities of various O. tsutsugamushi strains and the severity of the disease. A retrospective analysis was conducted on patients diagnosed with mild scrub typhus from August 2013 to January 2016 in the Affiliated Hospital of Nantong University, northern China. A total of 40 patients who received minocycline treatment and 34 patients who received azithromycin treatment were included in the analysis. All patients except one defervesced within 120 h after initiating antimicrobial therapy. Kaplan-Meier curves in association with log-rank test showed that the median time to defervescence was significantly shorter for the minocycline-treated group than the azithromycin-treated group (P = 0.003). There were no serious adverse events during treatment. No relapse occurred in either group during the 1-month follow-up period. In conclusion, both minocycline and azithromycin are effective and safe for the treatment of mild scrub typhus, but minocycline is more active than azithromycin against O. tsutsugamushi infection acquired in northern China.


Assuntos
Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Minociclina/uso terapêutico , Tifo por Ácaros/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/efeitos adversos , Azitromicina/efeitos adversos , China , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Minociclina/efeitos adversos , Gravidez , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
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