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1.
Artigo em Inglês | MEDLINE | ID: mdl-38649112

RESUMO

OBJECTIVE: Chemoradiation followed by esophagectomy is a standard treatment option for locally advanced esophageal cancer (LAEC) patients. Esophagectomy is a high-risk procedure, and recent evidence suggests select patients may benefit from omitting or delaying surgery. This study aims to compare surgery versus active surveillance for LAEC patients with complete clinical response (cCR) after neoadjuvant chemoradiotherapy (nCRT). METHODS: Decision analysis with Markov modelling was utilized. The base case was a 60-year-old male with T3N0M0 esophageal cancer with cCR after nCRT. The decision was modelled for a 5-year time horizon. Primary outcomes were life-years (LY) and quality-adjusted life-years (QALYs). Probabilities and utilities were derived through literature. Deterministic sensitivity analyses were performed using ranges from literature with consideration for clinical plausibility. RESULTS: Surgery was favoured for survival with an expected LY of 2.89 versus 2.64. After incorporating quality of life, active surveillance was favoured with an expected QALY of 1.70 versus 1.56. The model was sensitive to probability of recurrence on active surveillance (threshold value 0.598), probability of recurrence being resectable (0.318) and disutility of prior esophagectomy (-0.091). The model was not sensitive to perioperative morbidity and mortality. CONCLUSIONS: Our study finds that surgery increases life expectancy but decreases quality-adjusted life years. Although the incremental change in QALY for either modality is insufficient to make broad clinical recommendations, our study demonstrates that either approach is acceptable. As probabilities of key factors are further defined in the literature, treatment decisions for patients with LAEC and a cCR after nCRT should consider histology, patient values, and quality of life.

2.
Am J Gastroenterol ; 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38305278

RESUMO

INTRODUCTION: Both artificial intelligence (AI) and distal attachment devices have been shown to improve adenoma detection rate and reduce miss rate during colonoscopy. We studied the combined effect of Endocuff and AI on enhancing detection rates of various colonic lesions. METHODS: This was a 3-arm prospective randomized colonoscopy study involving patients aged 40 years or older. Participants were randomly assigned in a 1:1:1 ratio to undergo Endocuff with AI, AI alone, or standard high-definition (HD) colonoscopy. The primary outcome was adenoma detection rate (ADR) between the Endocuff-AI and AI groups while secondary outcomes included detection rates of polyp (PDR), sessile serrated lesion (sessile detection rate [SDR]), and advanced adenoma (advanced adenoma detection rate) between the 2 groups. RESULTS: A total of 682 patients were included (mean age 65.4 years, 52.3% male), with 53.7% undergoing diagnostic colonoscopy. The ADR for the Endocuff-AI, AI, and HD groups was 58.7%, 53.8%, and 46.3%, respectively, while the corresponding PDR was 77.0%, 74.0%, and 61.2%. A significant increase in ADR, PDR, and SDR was observed between the Endocuff-AI and AI groups (ADR difference: 4.9%, 95% CI: 1.4%-8.2%, P = 0.03; PDR difference: 3.0%, 95% CI: 0.4%-5.8%, P = 0.04; SDR difference: 6.4%, 95% CI: 3.4%-9.7%, P < 0.01). Both Endocuff-AI and AI groups had a higher ADR, PDR, SDR, and advanced adenoma detection rate than the HD group (all P < 0.01). DISCUSSION: Endocuff in combination with AI further improves various colonic lesion detection rates when compared with AI alone.

3.
Dis Esophagus ; 37(3)2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38018252

RESUMO

Esophagectomy for esophageal cancer is associated with high morbidity. It remains unclear whether prehabilitation, a strategy aimed at optimizing patients' physical and mental functioning prior to surgery, improves postoperative outcomes. A systematic review and meta-analysis was conducted to evaluate the effect of prehabilitation on post-operative outcomes after esophagectomy. Data sources included Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, and PEDro, with information from 1 January 2000 to 5 August 2023. The analysis included randomized controlled trials and observational studies that compared prehabilitation interventions to standard care prior to esophagectomy. A random effects model was used to generate a pooled estimate for pairwise meta-analysis, meta-analysis of proportions, and meta-analysis of means. A total of 1803 patients were included with 584 in randomized controlled trials (RCTs) and 1219 in observational studies. In the randomized evidence, there were no significant differences between prehabilitation and control in the odds of postoperative pneumonia (15.0 vs. 18.9%, odds ratio (OR) 1.06 [95% confidence interval (CI): 0.66;1.72]) or pulmonary complications (14 vs. 25.6%, OR 0.68 [95% CI: 0.32;1.45]). In the observational data, there was a reduction in both postoperative pneumonia (22.5 vs. 32.9%, OR 0.48 [95% CI: 0.28;0.83]) and pulmonary complications (26.1 vs. 52.3%, OR 0.35 [95% CI: 0.17;0.75]) with prehabilitation. Hospital and intensive care unit length of stay (days), operative mortality, and severe complications (Clavien-Dindo ≥ 3) did not differ between groups in both the randomized data and observational data. Prehabilitation demonstrated reductions in postoperative pneumonia and pulmonary complications in observational studies, but not RCTs. The overall certainty of these findings is limited by the low quality of the available evidence.


Assuntos
Neoplasias Esofágicas , Pneumonia , Humanos , Neoplasias Esofágicas/cirurgia , Esofagectomia/efeitos adversos , Unidades de Terapia Intensiva , Pneumonia/epidemiologia , Pneumonia/etiologia , Pneumonia/prevenção & controle , Exercício Pré-Operatório , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Observacionais como Assunto
4.
Gastrointest Endosc ; 99(3): 419-427.e6, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37858761

RESUMO

BACKGROUND AND AIMS: The importance of withdrawal time during colonoscopy cannot be overstated in mitigating the risk of missed lesions and postcolonoscopy colorectal cancer. We evaluated a novel colonoscopy quality metric called the effective withdrawal time (EWT), which is an artificial intelligence (AI)-derived quantitative measure of quality withdrawal time, and its association with various colonic lesion detection rates as compared with standard withdrawal time (SWT). METHODS: Three hundred fifty video recordings of colonoscopy withdrawal (from the cecum to the anus) were assessed by the new AI model. The primary outcome was adenoma detection rate (ADR) according to different quintiles of EWT. Multivariate logistic regression, adjusting for baseline covariates, was used to determine the adjusted odd ratios (ORs) for EWT on lesion detection rates, with the lowest quintile as reference. The area under the receiver-operating characteristic curve of EWT was compared with SWT. RESULTS: The crude ADR in different quintiles of EWT, from lowest to highest, was 10.0%, 31.4%, 33.3%, 53.5%, and 85.7%. The ORs of detecting adenomas and polyps were significantly higher in all top 4 quintiles when compared with the lowest quintile. Each minute increase in EWT was associated with a 49% increase in ADR (aOR, 1.49; 95% confidence interval [CI], 1.36-1.65). The area under the receiver-operating characteristic curve of EWT was also significantly higher than SWT on adenoma detection (.80 [95% CI, .75-.84] vs .70 [95% CI, .64-.74], P < .01). CONCLUSIONS: AI-derived monitoring of EWT is a promising novel quality indicator for colonoscopy, which is more associated with ADR than SWT.


Assuntos
Adenoma , Pólipos do Colo , Neoplasias Colorretais , Humanos , Inteligência Artificial , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/patologia , Colonoscopia , Pólipos do Colo/diagnóstico , Pólipos do Colo/patologia , Adenoma/diagnóstico , Adenoma/patologia
5.
Soc Cogn Affect Neurosci ; 18(1)2023 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-37952225

RESUMO

European Americans view high-intensity, open-mouthed 'excited' smiles more positively than Chinese because they value excitement and other high arousal positive states more. This difference is supported by reward-related neural activity, with European Americans showing greater Nucleus Accumbens (NAcc) activity to excited (vs calm) smiles than Chinese. But do these cultural differences generalize to all rewards, and are they related to real-world social behavior? European American (N = 26) and Chinese (N = 27) participants completed social and monetary incentive delay tasks that distinguished between the anticipation and receipt (outcome) of social and monetary rewards while undergoing Functional Magnetic Resonance Imaging (FMRI). The groups did not differ in NAcc activity when anticipating social or monetary rewards. However, as predicted, European Americans showed greater NAcc activity than Chinese when viewing excited smiles during outcome (the receipt of social reward). No cultural differences emerged when participants received monetary outcomes. Individuals who showed increased NAcc activity to excited smiles during outcome had friends with more intense smiles on social media. These findings suggest that culture plays a specific role in modulating reward-related neural responses to excited smiles during outcome, which are associated with real-world relationships.


Assuntos
Emoções , Motivação , Humanos , Núcleo Accumbens/fisiologia , Expressão Facial , Recompensa , Imageamento por Ressonância Magnética
6.
Front Oncol ; 13: 1266897, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37965457

RESUMO

EBV-positive inflammatory follicular dendritic cell sarcoma (EBV+ IFDCS) is an uncommon disease primarily observed in Asia. It is characterized by the development of tumors believed to originate from follicular dendritic cells (FDC). The consistent association between this condition and clonal EBV infection suggests EBV's involvement as an etiological factor. However, diagnosing EBV+ IFDCS can be challenging due to its morphological variability and diverse immunohistochemical staining patterns. The genetic characteristics of EBV+ IFDCS remain insufficiently understood. To address this knowledge gap, we present a case study of a 47-year-old male patient diagnosed with EBV+ IFDCS. We utilized a Next-generation sequencing (NGS) platform to investigate the genetic profile of the tumor cells. We identified a single pathogenic mutation (G618R) in the STAT3 gene. This finding provides valuable insights into the genetic alterations associated with EBV+ IFDCS and potentially contributes to our understanding of the disease's pathogenesis.

7.
PLoS Comput Biol ; 19(10): e1011462, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37856442

RESUMO

Measures of human movement dynamics can predict outcomes like injury risk or musculoskeletal disease progression. However, these measures are rarely quantified in large-scale research studies or clinical practice due to the prohibitive cost, time, and expertise required. Here we present and validate OpenCap, an open-source platform for computing both the kinematics (i.e., motion) and dynamics (i.e., forces) of human movement using videos captured from two or more smartphones. OpenCap leverages pose estimation algorithms to identify body landmarks from videos; deep learning and biomechanical models to estimate three-dimensional kinematics; and physics-based simulations to estimate muscle activations and musculoskeletal dynamics. OpenCap's web application enables users to collect synchronous videos and visualize movement data that is automatically processed in the cloud, thereby eliminating the need for specialized hardware, software, and expertise. We show that OpenCap accurately predicts dynamic measures, like muscle activations, joint loads, and joint moments, which can be used to screen for disease risk, evaluate intervention efficacy, assess between-group movement differences, and inform rehabilitation decisions. Additionally, we demonstrate OpenCap's practical utility through a 100-subject field study, where a clinician using OpenCap estimated musculoskeletal dynamics 25 times faster than a laboratory-based approach at less than 1% of the cost. By democratizing access to human movement analysis, OpenCap can accelerate the incorporation of biomechanical metrics into large-scale research studies, clinical trials, and clinical practice.


Assuntos
Modelos Biológicos , Smartphone , Humanos , Músculos/fisiologia , Software , Fenômenos Biomecânicos , Movimento/fisiologia
8.
BJR Case Rep ; 9(5): 20230056, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37780979

RESUMO

A 38-year-old male patient presenting with mild exertional dyspnea was noted to have a lingular opacity on chest radiograph. CT of the chest demonstrated an unusual complex inferior lingular vascular malformation with branches arising from the left internal thoracic artery and the left inferior diaphragmatic artery via the celiac artery. There was suspected communication with both pulmonary arterial and venous branches. Following thorough assessment and comprehensive clinical investigation, the patient elected to proceed to definitive surgical management due to potential risk of life-threatening hemoptysis. Interventional radiology performed pre-operative diagnostic angiography and embolization of the systemic feeding arteries. The patient proceeded to have an uncomplicated video-assisted thoracoscopic surgery segmentectomy and was discharged the next day. The patient was asymptomatic at follow-up with complete resolution of the malformation on CT at 6 months. We discuss an uncommon pathology which benefited from multidisciplinary management including successful pre-operative endovascular embolization.

9.
Gastrointest Endosc ; 98(5): 813-821.e3, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37307902

RESUMO

BACKGROUND AND AIMS: Blue-light imaging (BLI) is a new image-enhanced endoscopy with a wavelength filter similar to narrow-band imaging (NBI). We compared the 2 with white-light imaging (WLI) on proximal colonic lesion detection and miss rates. METHODS: In this 3-arm prospective randomized study with tandem examination of the proximal colon, we enrolled patients aged ≥40 years. Eligible patients were randomized in 1:1:1 ratio to receive BLI, NBI, or WLI during the first withdrawal from the proximal colon. The second withdrawal was performed using WLI in all patients. Primary outcomes were proximal polyp (pPDRs) and adenoma (pADRs) detection rates. Secondary outcomes were miss rates of proximal lesions found on tandem examination. RESULTS: Of 901 patients included (mean age, 64.7 years; 52.9% men), 48.1% underwent colonoscopy for screening or surveillance. The corresponding pPDRs of the BLI, NBI, and WLI groups were 45.8%, 41.6, and 36.6%, whereas the corresponding pADRs were 36.6%, 33.8%, and 28.3%. There was a significant difference in pPDR and pADR between BLI and WLI groups (difference, 9.2% [95% confidence interval {CI}, 3.3-16.9] and 8.3% [95% CI, 2.7-15.9]) and between NBI and WLI groups (difference, 5.0% [95% CI, 1.4-12.9] and 5.6% [95% CI, 2.1-13.3]). Proximal adenoma miss rates were significantly lower with BLI (19.4%) than with WLI (27.4%; difference, -8.0%; 95% CI, -15.8 to -.1) but not between NBI (27.2%) and WLI. CONCLUSIONS: Both BLI and NBI were superior to WLI on detecting proximal colonic lesions, but only BLI had lower proximal adenoma miss rates than WLI. (Clinical trial registration number: NCT03696992.).

10.
Cells ; 12(12)2023 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-37371121

RESUMO

Peptide Lv is a small endogenous secretory peptide that is proangiogenic through hyperpolarizing vascular endothelial cells (ECs) by enhancing the current densities of KCa3.1 channels. However, it is unclear how peptide Lv enhances these currents. One way to enhance the current densities of ion channels is to promote its trafficking and insertion into the plasma membrane. We hypothesized that peptide Lv-elicited KCa3.1 augmentation occurs through activating the mitogen-activated protein kinase kinase 1 (MEK1)-extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K)-protein kinase B (Akt) signaling pathways, which are known to mediate ion channel trafficking and membrane insertion in neurons. To test this hypothesis, we employed patch-clamp electrophysiological recordings and cell-surface biotinylation assays on ECs treated with peptide Lv and pharmaceutical inhibitors of ERK and Akt. Blocking ERK or Akt activation diminished peptide Lv-elicited EC hyperpolarization and increase in KCa3.1 current densities. Blocking PI3K or Akt activation decreased the level of plasma membrane-bound, but not the total amount of KCa3.1 protein in ECs. Therefore, the peptide Lv-elicited EC hyperpolarization and KCa3.1 augmentation occurred in part through channel trafficking and insertion mediated by MEK1-ERK and PI3K-Akt activation. These results demonstrate the molecular mechanisms of how peptide Lv promotes EC-mediated angiogenesis.


Assuntos
Células Endoteliais , MAP Quinases Reguladas por Sinal Extracelular , Proteínas Proto-Oncogênicas c-akt , Células Endoteliais/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , MAP Quinase Quinase 1/metabolismo , Peptídeos , Fosfatidilinositol 3-Quinase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
11.
JTCVS Open ; 13: 459-467, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37063147

RESUMO

Objective: Complex lung diseases are among the leading causes of death in Ethiopia. Access to thoracic surgery is limited, and before 2016 no thoracic surgeons were trained in minimally invasive surgery. A global academic partnership was formed between the University of Toronto and Addis Ababa University. We describe implementation of the first minimally invasive surgery training program in sub-Sahara Africa and evaluate its safety. Methods: We performed a retrospective cohort analysis of open versus minimally invasive thoracic and upper gastrointestinal procedures performed at Addis Ababa University from January 2016 to June 2021. Baseline demographic, diagnostic, operative, and postoperative outcomes including length of stay and complications were compared. Results: In our bilateral model of surgical education, training is provided in Ethiopia and Canada over 2 years with a focus on capacity building through egalitarian forms of knowledge exchange. Program features included certification in Fundamentals of Laparoscopic Surgery, high-fidelity lobectomy simulation, and hands-on training. Overall, 41 open and 56 minimally invasive surgery cases were included in the final statistical analysis. The average length of stay in the minimally invasive surgery group was 5.2 days versus 11.0 days in the open group (P < .001). The overall complication rate was 18% in the minimally invasive surgery group versus 39% in the open group (P = .020). Conclusions: We demonstrated the successful initiation of sub-Sahara Africa's first minimally invasive surgery program in thoracic and upper gastrointestinal surgery and characterize its patient safety. We envision the minimally invasive surgery program as a template to continue expanding global partnerships and improving surgical care in other resource-limited settings.

12.
Gastrointest Endosc ; 97(2): 325-334.e1, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36208795

RESUMO

BACKGROUND AND AIMS: Computer-assisted detection (CADe) is a promising technologic advance that enhances adenoma detection during colonoscopy. However, the role of CADe in reducing missed colonic lesions is uncertain. The aim of this study was to determine the miss rates of proximal colonic lesions by CADe and conventional colonoscopy. METHODS: This was a prospective, multicenter, randomized, tandem-colonoscopy study conducted in 3 Asian centers. Patients were randomized to receive CADe or conventional white-light colonoscopy during the first withdrawal of the proximal colon (cecum to splenic flexure), immediately followed by tandem examination of the proximal colon with white light in both groups. The primary outcome was adenoma/polyp miss rate, which was defined as any adenoma/polyp detected during the second examination. RESULTS: Of 223 patients (48.6% men; median age, 63 years) enrolled, 7 patients did not have tandem examination, leaving 108 patients in each group. There was no difference in the miss rate for proximal adenomas (CADe vs conventional: 20.0% vs 14.0%, P = .07) and polyps (26.7% vs 19.6%, P = .06). The CADe group, however, had significantly higher proximal polyp (58.0% vs 46.7%, P = .03) and adenoma (44.7% vs 34.6%, P = .04) detection rates than the conventional group. The mean number of proximal polyps and adenomas detected per patient during the first examination was also significantly higher in the CADe group (polyp: 1.20 vs .86, P = .03; adenoma, .91 vs .61, P = .03). Subgroup analysis showed that CADe enhanced proximal adenoma detection in patients with fair bowel preparation, shorter withdrawal time, and endoscopists with lower adenoma detection rate. CONCLUSIONS: This multicenter trial from Asia confirmed that CADe can further enhance proximal adenoma and polyp detection but may not be able to reduce the number of missed proximal colonic lesions. (Clinical trial registration number: NCT04294355.).


Assuntos
Adenoma , Neoplasias do Colo , Pólipos do Colo , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , Pólipos do Colo/diagnóstico por imagem , Pólipos do Colo/patologia , Estudos Prospectivos , Colonoscopia , Adenoma/diagnóstico , Adenoma/patologia , Computadores , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/patologia
13.
J Am Chem Soc ; 144(51): 23297-23312, 2022 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-36512516

RESUMO

This paper describes a novel synthetic approach for the conversion of zero-valent copper metal into a conductive two-dimensional layered metal-organic framework (MOF) based on 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP) to form Cu3(HHTP)2. This process enables patterning of Cu3(HHTP)2 onto a variety of flexible and porous woven (cotton, silk, nylon, nylon/cotton blend, and polyester) and non-woven (weighing paper and filter paper) substrates with microscale spatial resolution. The method produces conductive textiles with sheet resistances of 0.1-10.1 MΩ/cm2, depending on the substrate, and uniform conformal coatings of MOFs on textile swatches with strong interfacial contact capable of withstanding chemical and physical stresses, such as detergent washes and abrasion. These conductive textiles enable simultaneous detection and detoxification of nitric oxide and hydrogen sulfide, achieving part per million limits of detection in dry and humid conditions. The Cu3(HHTP)2 MOF also demonstrated filtration capabilities of H2S, with uptake capacity up to 4.6 mol/kgMOF. X-ray photoelectron spectroscopy and diffuse reflectance infrared spectroscopy show that the detection of NO and H2S with Cu3(HHTP)2 is accompanied by the transformation of these species to less toxic forms, such as nitrite and/or nitrate and copper sulfide and Sx species, respectively. These results pave the way for using conductive MOFs to construct extremely robust electronic textiles with multifunctional performance characteristics.


Assuntos
Estruturas Metalorgânicas , Estruturas Metalorgânicas/química , Nylons , Cobre/química , Têxteis , Eletrônica , Estresse Oxidativo
14.
PLoS One ; 17(10): e0276744, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36282858

RESUMO

Peptide Lv is a small endogenous secretory peptide that is expressed in various tissues and conserved across different species. Patients with diabetic retinopathy, an ocular disease with pathological angiogenesis, have upregulated peptide Lv in their retinas. The pro-angiogenic activity of peptide Lv is in part through promoting vascular endothelial cell (EC) proliferation, migration, and sprouting, but its molecular mechanism is not completely understood. This study aimed to decipher how peptide Lv promotes EC-dependent angiogenesis by using patch-clamp electrophysiological recordings, Western immunoblotting, quantitative PCR, and cell proliferation assays in cultured ECs. Endothelial cells treated with peptide Lv became significantly hyperpolarized, an essential step for EC activation. Treatment with peptide Lv augmented the expression and current densities of the intermediate-conductance calcium-dependent potassium (KCa3.1) channels that contribute to EC hyperpolarization but did not augment other potassium channels. Blocking KCa3.1 attenuated peptide Lv-elicited EC proliferation. These results indicate that peptide Lv-stimulated increases of functional KCa3.1 in ECs contributes to EC activation and EC-dependent angiogenesis.


Assuntos
Células Endoteliais , Canais de Potássio Ativados por Cálcio de Condutância Intermediária , Humanos , Células Endoteliais/metabolismo , Canais de Potássio Ativados por Cálcio de Condutância Intermediária/genética , Canais de Potássio Ativados por Cálcio de Condutância Intermediária/metabolismo , Cálcio/metabolismo , Neovascularização Patológica/metabolismo , Peptídeos/metabolismo , Potássio/metabolismo
15.
Int J Mol Sci ; 23(20)2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36292956

RESUMO

Diabetic retinopathy (DR) is a chronic disease associated with diabetes mellitus and is a leading cause of visual impairment among the working population in the US. Clinically, DR has been diagnosed and treated as a vascular complication, but it adversely impacts both neural retina and retinal vasculature. Degeneration of retinal neurons and microvasculature manifests in the diabetic retina and early stages of DR. Retinal photoreceptors undergo apoptosis shortly after the onset of diabetes, which contributes to the retinal dysfunction and microvascular complications leading to vision impairment. Chronic inflammation is a hallmark of diabetes and a contributor to cell apoptosis, and retinal photoreceptors are a major source of intraocular inflammation that contributes to vascular abnormalities in diabetes. As the levels of microRNAs (miRs) are changed in the plasma and vitreous of diabetic patients, miRs have been suggested as biomarkers to determine the progression of diabetic ocular diseases, including DR. However, few miRs have been thoroughly investigated as contributors to the pathogenesis of DR. Among these miRs, miR-150 is downregulated in diabetic patients and is an endogenous suppressor of inflammation, apoptosis, and pathological angiogenesis. In this review, how miR-150 and its downstream targets contribute to diabetes-associated retinal degeneration and pathological angiogenesis in DR are discussed. Currently, there is no effective treatment to stop or reverse diabetes-caused neural and vascular degeneration in the retina. Understanding the molecular mechanism of the pathogenesis of DR may shed light for the future development of more effective treatments for DR and other diabetes-associated ocular diseases.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , MicroRNAs , Humanos , Retinopatia Diabética/genética , Retinopatia Diabética/patologia , MicroRNAs/genética , Retina/patologia , Inflamação/genética , Inflamação/patologia , Neovascularização Patológica/patologia , Biomarcadores , Progressão da Doença , Diabetes Mellitus/patologia
17.
Am J Cardiovasc Dis ; 12(4): 254-261, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36147781

RESUMO

The vascular function curve (VFC) in cardiovascular physiology describes the relationship between the steady state venous return (VR in L/min, in the Y-axis) and the steady state right atrial pressure (RAP in mmHg, in the X-axis). However, in some literature, the RAP is considered the independent variable (IV) and the VR the dependent variable (DV), whereas in other literature, the VR is the IV and the RAP the DV. Because of this confusion, when the VFC is combined with the cardiac function curve (CFC), which describes the relationship between the steady state cardiac output and the RAP, it is not strange that the interpretations of the combination are problematic. Hence, in this article, we will trace the origin of the inconsistency, differentiate the VFC into two types based on who created them, and differentiate the RAP into RAP as the IV and DV respectively. Through these in-depth analyses, the confusion will be clarified and new insights into the combination of a VFC with the CFC will develop.

18.
J Cell Mol Med ; 25(22): 10724-10735, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34704358

RESUMO

Obesity-associated type 2 diabetes (T2D) is on the rise in the United States due to the obesity epidemic, and 60% of T2D patients develop diabetic retinopathy (DR) in their lifetime. Chronic inflammation is a hallmark of obesity and T2D and a well-accepted major contributor to DR, and retinal photoreceptors are a major source of intraocular inflammation and directly contribute to vascular abnormalities in diabetes. However, how diabetic insults cause photoreceptor inflammation is not well known. In this study, we used a high-fat diet (HFD)-induced T2D mouse model and cultured photoreceptors treated with palmitic acid (PA) to decipher major players that mediate high-fat-induced photoreceptor inflammation. We found that PA-elicited microRNA-150 (miR-150) decreases with a consistent upregulation of ETS-domain transcription factor 1 (Elk1), a downstream target of miR-150, in PA-elicited photoreceptor inflammation. We compared wild-type (WT) and miR-150 null (miR-150-/- ) mice fed with an HFD and found that deletion of miR-150 exacerbated HFD-induced photoreceptor inflammation in conjunction with upregulated ELK1. We further delineated the critical cellular localization of phosphorylated ELK1 at serine 383 (pELK1S383 ) and found that decreased miR-150 exacerbated the T2D-induced inflammation in photoreceptors by upregulating ELK1 and pELK1S383 , and knockdown of ELK1 alleviated PA-elicited photoreceptor inflammation.


Assuntos
Retinopatia Diabética/etiologia , Retinopatia Diabética/metabolismo , MicroRNAs/genética , Células Fotorreceptoras/metabolismo , Proteínas Elk-1 do Domínio ets/genética , Animais , Biomarcadores , Linhagem Celular , Diabetes Mellitus Tipo 2 , Retinopatia Diabética/patologia , Modelos Animais de Doenças , Suscetibilidade a Doenças , Regulação da Expressão Gênica , Masculino , Camundongos , Camundongos Knockout , Obesidade , Células Fotorreceptoras/patologia , Interferência de RNA
19.
J Pers Soc Psychol ; 121(5): 969-983, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34491077

RESUMO

Although social media plays an increasingly important role in communication around the world, social media research has primarily focused on Western users. Thus, little is known about how cultural values shape social media behavior. To examine how cultural affective values might influence social media use, we developed a new sentiment analysis tool that allowed us to compare the affective content of Twitter posts in the United States (55,867 tweets, 1,888 users) and Japan (63,863 tweets, 1,825 users). Consistent with their respective cultural affective values, U.S. users primarily produced positive (vs. negative) posts, whereas Japanese users primarily produced low (vs. high) arousal posts. Contrary to cultural affective values, however, U.S. users were more influenced by changes in others' high arousal negative (e.g., angry) posts, whereas Japanese were more influenced by changes in others' high arousal positive (e.g., excited) posts. These patterns held after controlling for differences in baseline exposure to affective content, and across different topics. Together, these results suggest that across cultures, while social media users primarily produce content that supports their affective values, they are more influenced by content that violates those values. These findings have implications for theories about which affective content spreads on social media, and for applications related to the optimal design and use of social media platforms around the world. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Assuntos
Mídias Sociais , Nível de Alerta , Comunicação , Humanos , Japão , Análise de Sentimentos , Estados Unidos
20.
Biomedicines ; 9(9)2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34572320

RESUMO

Diabetic retinopathy (DR) is a chronic complication associated with diabetes and the number one cause of blindness in working adults in the US. More than 90% of diabetic patients have obesity-associated type 2 diabetes (T2D), and 60% of T2D patients will develop DR. Photoreceptors undergo apoptosis shortly after the onset of diabetes, which contributes to the retinal dysfunction and microvascular complications leading to vision impairment. However, how diabetic insults cause photoreceptor apoptosis remains unclear. In this study, obesity-associated T2D mice and cultured photoreceptors were used to investigate how decreased microRNA-150 (miR-150) and its downstream target were involved in photoreceptor apoptosis. In the T2D retina, miR-150 was decreased with its target ETS-domain transcription factor (ELK1) and phosphorylated ELK1 at threonine 417 (pELK1T417) upregulated. In cultured photoreceptors, treatments with palmitic acid (PA), to mimic a high-fat environment, decreased miR-150 but upregulated ELK1, pELK1T417, and the translocation of pELK1T417 from the cytoplasm to the cell nucleus. Deletion of miR-150 (miR-150-/-) exacerbates T2D- or PA-induced photoreceptor apoptosis. Blocking the expression of ELK1 with small interfering RNA (siRNA) for Elk1 did not rescue PA-induced photoreceptor apoptosis. Translocation of pELK1T417 from cytoplasm-to-nucleus appears to be the key step of diabetic insult-elicited photoreceptor apoptosis.

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