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We develop color-encoded multicompartmental hydrogel (MH) microspheres tailored for multiplexed bioassays using a drop-based microfluidic approach. Our method involves the creation of triple emulsion drops that feature thin sacrificial oil layers separating two prepolymer phases. This configuration leads to the formation of poly(ethylene glycol) (PEG) multi-compartmental core-shell microspheres through photopolymerization, followed by the removal of the thin oil layers. The core compartments stably incorporate pigments, ensuring their retention within the hydrogel network without leakage, which facilitates reliable color encoding across varying spatial positions. Additionally, we introduce small molecule fluorescent labeling into the chemically functionalized shell compartments, achieving consistent distribution of functional components without the core's contamination. Importantly, our integrated one-pot conjugation of these color-encoded microspheres with affinity peptides enables the highly sensitive and selective detection of influenza virus antigens using a fluorescence bioassay, resulting in an especially low detection limit of 0.18 nM and 0.66 nM for influenza virus H1N1 and H5N1 antigens, respectively. This approach not only highlights the potential of our microspheres in clinical diagnostics but also paves the way for their application in a wide range of multiplexed assays.
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BACKGROUND: This study aimed to validate apparent diffusion coefficient (ADC) values and thresholds to predict poor neurological outcomes in out-of-hospital cardiac arrest (OHCA) survivors by quantitatively analysing the ADC values via brain magnetic resonance imaging (MRI). METHODS: This observational study used prospectively collected data from two tertiary academic hospitals. The derivation cohort comprised 70% of the patients randomly selected from one hospital, whereas the internal validation cohort comprised the remaining 30%. The external validation cohort used the data from another hospital, and the MRI data were restricted to scans conducted at 3 T within 72-96 h after an OHCA experience. We analysed the percentage of brain volume below a specific ADC value at 50-step intervals ranging from 200 to 1200 × 10-6 mm2/s, identifying thresholds that differentiate between good and poor outcomes. Poor neurological outcomes were defined as cerebral performance categories 3-5, 6 months after experiencing an OHCA. RESULTS: A total of 448 brain MRI scans were evaluated, including a derivation cohort (n = 224) and internal/external validation cohorts (n = 96/128, respectively). The proportion of brain volume with ADC values below 450, 500, 550, 600, and 650 × 10-6 mm2/s demonstrated good to excellent performance in predicting poor neurological outcomes in the derivation group (area under the curve [AUC] 0.89-0.91), and there were no statistically significant differences in performances among the derivation, internal validation, and external validation groups (all P > 0.5). Among these, the proportion of brain volume with an ADC below 600 × 10-6 mm2/s predicted a poor outcome with a 0% false-positive rate (FPR) and 76% (95% confidence interval [CI] 68-83) sensitivity at a threshold of > 13.2% in the derivation cohort. In both the internal and external validation cohorts, when using the same threshold, a specificity of 100% corresponded to sensitivities of 71% (95% CI 58-81) and 78% (95% CI 66-87), respectively. CONCLUSIONS: In this validation study, by consistently restricting the MRI types and timing during quantitative analysis of ADC values in brain MRI, we observed high reproducibility and sensitivity at a 0% FPR. Prospective multicentre studies are necessary to validate these findings.
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Parada Cardíaca Extra-Hospitalar , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Parada Cardíaca Extra-Hospitalar/diagnóstico por imagem , Estudos Prospectivos , Prognóstico , Sobreviventes/estatística & dados numéricos , Estudos de Coortes , Imageamento por Ressonância Magnética/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Valor Preditivo dos Testes , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologiaAssuntos
Vertigem Posicional Paroxística Benigna , Nistagmo Patológico , Idoso , Humanos , Masculino , Vertigem Posicional Paroxística Benigna/diagnóstico , Infartos do Tronco Encefálico/complicações , Infartos do Tronco Encefálico/diagnóstico por imagem , Infartos do Tronco Encefálico/diagnóstico , Diagnóstico Diferencial , Nistagmo Patológico/etiologia , Nistagmo Patológico/diagnóstico , Ponte/diagnóstico por imagemRESUMO
BACKGROUND: To determine if the density distribution proportion of Hounsfield unit (HUdp) in head computed tomography (HCT) images can be used to quantitatively measure cerebral edema in survivors of out-of-hospital cardiac arrest (OHCA). METHODS: This retrospective observational study included adult comatose OHCA survivors who underwent HCT within 6 h (first) and 72-96 h (second), all performed using the same CT scanner. Semi-automated quantitative analysis was used to identify differences in HUdp at specific HU ranges across the intracranial component based on neurological outcome. Cerebral edema was defined as the increased displacement of the sum of HUdp values (ΔHUdp) at a specific range between two HCT scans. Poor neurological outcome was defined as cerebral performance categories 3-5 at 6 months after OHCA. RESULTS: Twenty-three (42%) out of 55 patients had poor neurological outcome. Significant HUdp differences were observed between good and poor neurological outcomes in the second HCT scan at HU = 1-14, 23-35, and 39-56 (all P < 0.05). Only the ΔHUdp = 23-35 range showed a significant increase and correlation in the poor neurological outcome group (4.90 vs. -0.72, P < 0.001) with the sum of decreases in the other two ranges (r = 0.97, P < 0.001). Multivariate logistic regression analysis demonstrated a significant association between ΔHUdp = 23-35 range and poor neurological outcomes (adjusted OR, 1.12; 95% CI: 1.02-1.24; P = 0.02). CONCLUSION: In this cohort study, the increased displacement in ΔHUdp = 23-35 range is independently associated with poor neurological outcome and provides a quantitative assessment of cerebral edema formation in OHCA survivors.
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Edema Encefálico , Parada Cardíaca Extra-Hospitalar , Adulto , Humanos , Edema Encefálico/etiologia , Edema Encefálico/complicações , Estudos de Coortes , Prognóstico , Parada Cardíaca Extra-Hospitalar/diagnóstico por imagem , Parada Cardíaca Extra-Hospitalar/terapia , Parada Cardíaca Extra-Hospitalar/complicações , Tomografia Computadorizada por Raios X/métodos , Estudos Retrospectivos , SobreviventesRESUMO
BACKGROUND AND OBJECTIVES: Weight gain is associated with imbalance in older people. In contrast, overweightness or mild obesity is less common in patients with chronic dizziness. This paradox may be, at least in part, related to differences in the body composition indices adopted in the previous studies. This study aimed to determine any association between the predicted body composition and chronic dizziness or imbalance of unknown causes. METHODS: We measured the lean body mass, body fat mass, and appendicular skeletal mass in 9243 people who participated in the Korean National Health and Nutrition Examination Survey 2019-2021. Sarcopenia was defined according to the Asian Working Group for Sarcopenia's guidelines. Obesity was defined as a body fat percentage of ≥ 25% for men and ≥ 35% for women. RESULTS: The participants with chronic dizziness had a lower body mass index than those without (p = 0.001). Furthermore, sarcopenia was more common in those with chronic dizziness. In contrast, the degree of obesity was comparable in both groups. Multiple logistic regression analysis showed that sarcopenia was associated with a higher risk of chronic dizziness (odds ratio = 1.6, 95% confidence interval: 1.1-2.5; p = 0.026). DISCUSSION: Given the association of sarcopenia with chronic dizziness or imbalance, muscle mass may play a role in maintaining balance and stability. Physical exercise could be recommended to increase muscle mass in patients with chronic dizziness/imbalance and sarcopenia. Additional research is required to establish a causal relationship between chronic dizziness and sarcopenia.
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Sarcopenia , Masculino , Humanos , Feminino , Idoso , Sarcopenia/epidemiologia , Sarcopenia/complicações , Sarcopenia/diagnóstico , Estudos Transversais , Inquéritos Nutricionais , Tontura/epidemiologia , Tontura/complicações , Obesidade/complicações , Obesidade/epidemiologia , Índice de Massa Corporal , Composição Corporal , Músculos , República da Coreia/epidemiologia , Músculo Esquelético/patologiaRESUMO
Military personnel in combat face a high risk of developing posttraumatic stress disorder (PTSD). In this study, a protocol-based scoping review was conducted to identify the current status of research on the efficacy of acupuncture for treating combat-related PTSD in military personnel. A literature search was conducted across 14 databases in November 2022, and data from the included studies were collected and descriptively analyzed. A total of eight studies were included. Participants were assessed for core PTSD symptoms using the PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders-5 and the Clinician-Administered PTSD Scale, as well as related symptoms, such as sleep issues. Although the efficacy of acupuncture has been substantiated in numerous studies, certain metrics did not exhibit improvement. Auricular acupuncture was the most commonly used treatment (50%) followed by manual acupuncture (25%) and a combination of both (25%). Shenmen and Kidney points were frequently targeted at auricular acupoints. The treatment period varied between 5 days and 2 months. While adverse events were reported in two of the fifty-five patients in the intervention group and in four of the sixty-four patients in the control group in the randomized controlled trial studies, no fatal adverse events were reported.
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Influenza viruses are known to cause pandemic flu outbreaks through both inter-human and animal-to-human transmissions. Therefore, the rapid and accurate detection of such pathogenic viruses is crucial for effective pandemic control. Here, we introduce a novel sensor based on affinity peptide-immobilized hydrogel microspheres for the selective detection of influenza A virus (IAV) H3N2. To enhance the binding affinity performance, we identified novel affinity peptides using phage display and further optimized their design. The functional hydrogel microspheres were constructed using the drop microfluidic technique, employing a structure composed of natural (chitosan) and synthetic (poly(ethylene glycol) diacrylate and PEG 6 kDa) polymers with the activation of azadibenzocyclooctyne for the subsequent click chemistry reaction. The binding peptide-immobilized hydrogel microsphere (BP-Hyd) was characterized by field emission scanning electron microscopy, X-ray photoelectron spectroscopy, and Fourier transform infrared spectroscopy and exhibited selective detection capability for the IAV H3N2. To capture the detected IAV H3N2, a Cy3-labeled IAV hemagglutinin antibody was utilized. By incorporating the affinity peptide with hydrogel microspheres, we achieved quantitative and selective detection of IAV H3N2 with a detection limit of 1.887 PFU mL-1. Furthermore, the developed suspension sensor exhibited excellent reproducibility and showed reusability potential. Our results revealed that the BP-Hyd-based fluorescence sensor platform could be feasibly employed to detect other pathogens because the virus-binding peptides can be easily replaced with other peptides through phage display, enabling selective and sensitive binding to different targets.
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BACKGROUND: This study aimed to quantitatively analyse ultra-early brain diffusion-weighted magnetic resonance imaging (DW-MRI) findings to determine the apparent diffusion coefficient (ADC) threshold associated with neurological outcomes in comatose survivors of out-of-hospital cardiac arrest (OHCA). METHODS: This retrospective study included adult survivors of comatose OHCA who underwent DW-MRI imaging scans using a 3-T MRI scanner within 6 h of the return of spontaneous circulation (ROSC). We investigated the association between neurological outcomes and ADC values obtained through voxel-based analysis on DW-MRI. Additionally, we constructed multivariable logistic regression models with pupillary light reflex (PLR), serum neuron-specific enolase (NSE), and ADC values as independent variables to predict poor neurological outcomes. The primary outcome was poor neurological outcome 6 months after ROSC, determined by the Cerebral Performance Category 3-5. RESULTS: Overall, 131 patients (26% female) were analysed, of whom 74 (57%) showed poor neurological outcomes. The group with a poor neurological outcome had lower mean whole brain ADC values (739.1 vs. 787.1 × 10-6 mm/s) and higher percentages of voxels with ADC below threshold in all ranges (250-1150) (all P < 0.001). The mean whole brain ADC values (area under the receiver operating characteristic curve [AUC] 0.83) and the percentage of voxels with ADC below 600 (AUC 0.81) had the highest sensitivity of 51% (95% confidence interval [CI] 39.4-63.1; cut-off value ≤ 739.2 × 10-6 mm2/s and > 17.2%, respectively) when the false positive rate (FPR) was 0%. In the multivariable model, which also included PLR, NSE, and mean whole brain ADC values, poor neurological outcome was predicted with the highest accuracy (AUC 0.91; 51% sensitivity). This model showed more accurate prediction and sensitivity at an FPR of 0% than did the combination of PLR and NSE (AUC 0.86; 30% sensitivity; P = 0.03). CONCLUSIONS: In this cohort study, early voxel-based quantitative ADC analysis after ROSC was associated with poor neurological outcomes 6 months after cardiac arrest. The mean whole brain ADC value demonstrated the highest sensitivity when the FPR was 0%, and including it in the multivariable model improved the prediction of poor neurological outcomes.
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Parada Cardíaca Extra-Hospitalar , Adulto , Humanos , Feminino , Masculino , Parada Cardíaca Extra-Hospitalar/complicações , Parada Cardíaca Extra-Hospitalar/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , Coma , Estudos de Coortes , Estudos Retrospectivos , Prognóstico , SobreviventesRESUMO
Here, we report PNIPAm-co-PEGDA hydrogel shelled microcapsules with a thin oil layer to achieve tunable thermo-responsive release of the encapsulated small hydrophilic actives. We use a microfluidic device integrated with a temperature-controlled chamber for consistent and reliable production of the microcapsules by utilizing triple emulsion drops (W/O/W/O) with a thin oil layer as capsule templates. The interstitial oil layer between the aqueous core and the PNIPAm-co-PEGDA shell provides a diffusion barrier for the encapsulated active until the temperature reaches a critical point above which the destabilization of interstitial oil layer occurs. We find that the destabilization of the oil layer with temperature increase is caused by outward expansion of the aqueous core due to volume increase and the radial inward compression from the deswelling of the thermo-responsive hydrogel shell. The copolymerization of NIPAm with PEGDA increases the biocompatibility of the resulting microcapsule while offering the ability to alter the compressive modulus in broad ranges by simply varying crosslinker concentrations thereby to precisely tune the onset release temperature. Based on this concept, we further demonstrate that the release temperature can be enhanced up to 62 °C by adjusting the shell thickness even without varying the chemical composition of the hydrogel shell. Moreover, we incorporate gold nanorods within the hydrogel shell to spatiotemporally regulate the active release from the microcapsules by illuminating with non-invasive near infrared (NIR) light.
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Hidrogéis , Polietilenoglicóis , Cápsulas/química , TemperaturaRESUMO
BACKGROUND: Epigenetic marks are encoded by DNA methylation and accumulate errors as organisms age. This drift correlates with lifespan, but the biology of how this occurs is still unexplained. We analyze DNA methylation with age in mouse intestinal stem cells and compare them to nonstem cells. RESULTS: Age-related changes in DNA methylation are identical in stem and nonstem cells, affect most prominently CpG islands and correlate weakly with gene expression. Age-related DNA methylation entropy, measured by the Jensen-Shannon Distribution, affects up to 25% of the detectable CpG sites and is a better measure of aging than individual CpG methylation. We analyze this entropy as a function of age in seven other tissues (heart, kidney, skeletal muscle, lung, liver, spleen, and blood) and it correlates strikingly with tissue-specific stem cell division rates. Thus, DNA methylation drift and increased entropy with age are primarily caused by and are sensors for, stem cell replication in adult tissues. CONCLUSIONS: These data have implications for the mechanisms of tissue-specific functional declines with aging and for the development of DNA-methylation-based biological clocks.
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Metilação de DNA , Epigênese Genética , Animais , Camundongos , Entropia , Envelhecimento/genética , Células-Tronco , Ilhas de CpGRESUMO
BACKGROUND: This study aimed to investigate the association between ultra-early (within 6 h after return of spontaneous circulation [ROSC]) brain diffusion-weighted magnetic resonance imaging (DW-MRI) and neurological outcomes in comatose survivors after out-of-hospital cardiac arrest. METHODS: We conducted a registry-based observational study from May 2018 to February 2022 at a Chungnam national university hospital in Daejeon, Korea. Presence of high-signal intensity (HSI) (PHSI) was defined as a HSI on DW-MRI with corresponding hypoattenuation on the apparent diffusion coefficient map irrespective of volume after hypoxic ischemic brain injury; absence of HSI was defined as AHSI. The primary outcome was the dichotomized cerebral performance category (CPC) at 6 months, defined as good (CPC 1-2) or poor (CPC 3-5). RESULTS: Of the 110 patients (30 women [27.3%]; median (interquartile range [IQR]) age, 58 [38-69] years), 48 (43.6%) had a good neurological outcome, time from ROSC to MRI scan was 2.8 h (IQR 2.0-4.0 h), and the PHSI on DW-MRI was observed in 46 (41.8%) patients. No patients in the PHSI group had a good neurological outcome compared with 48 (75%) patients in the AHSI group. In the AHSI group, cerebrospinal fluid (CSF) neuron-specific enolase (NSE) levels were significantly lower in the group with good neurological outcome compared to the group with poor neurological outcome (20.1 [14.4-30.7] ng/mL vs. 84.3 [32.4-167.0] ng/mL, P < 0.001). The area under the curve for PHSI on DW-MRI was 0.87 (95% confidence interval [CI] 0.80-0.93), and the specificity and sensitivity for predicting a poor neurological outcome were 100% (95% CI 91.2%-100%) and 74.2% (95% CI 62.0-83.5%), respectively. A higher sensitivity was observed when CSF NSE levels were combined (88.7% [95% CI 77.1-95.1%]; 100% specificity). CONCLUSIONS: In this cohort study, PHSI findings on ultra-early DW-MRI were associated with poor neurological outcomes 6 months following the cardiac arrest. The combined CSF NSE levels showed higher sensitivity at 100% specificity than on DW-MRI alone. Prospective multicenter studies are required to confirm these results.
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Parada Cardíaca Extra-Hospitalar , Feminino , Humanos , Pessoa de Meia-Idade , Encéfalo , Estudos de Coortes , Imagem de Difusão por Ressonância Magnética/métodos , Parada Cardíaca Extra-Hospitalar/complicações , Parada Cardíaca Extra-Hospitalar/diagnóstico por imagem , Fosfopiruvato Hidratase , Prognóstico , Estudos Prospectivos , Masculino , Adulto , IdosoRESUMO
Aortic dissection is one of the causes of acute ischemic stroke. Endovascular recanalization therapy (EVT) has emerged as an essential treatment for acute ischemic stroke due to large artery occlusion. However, it is rarely performed in the situation of hidden aortic dissection (AD). Two patients presented to the emergency room with focal neurologic deficits. The first patient was diagnosed with right internal carotid artery (ICA) occlusion. Angiography revealed that the ICA was occluded by the dissection flap. After a stent deployment in the proximal ICA, the antegrade flow was restored. The patient was diagnosed with AD on chest computed tomography (CT) after EVT. For the second patient, intraarterial thrombectomy was performed to treat left middle cerebral artery occlusion. AD was first detected on echocardiography, which was performed after EVT. Herein, we report successful endovascular recanalization therapy performed in two patients with acute ischemic stroke in the situation of undiagnosed aortic dissection. We also reviewed previous case reports and relevant literature.
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The COVID-19 pandemic and the resulting supply chain disruption have rekindled crucial needs for safe storage and transportation of essential items. Despite recent advances, existing temperature monitoring technologies for cold chain management fall short in reliability, cost, and flexibility toward customized cold chain management for various products with different required temperature. In this work, we report a novel capsule-based colorimetric temperature monitoring system with precise and readily tunable temperature ranges. Triple emulsion drop-based microfluidic technique enables rapid production of monodisperse microcapsules with an interstitial phase-change oil (PCO) layer with precise control over its dimension and composition. Liquid-solid phase transition of the PCO layer below its freezing point triggers the release of the encapsulated payload yielding drastic change in color, allowing user-friendly visual monitoring in a highly sensitive manner. Simple tuning of the PCO layer's compositions can further broaden the temperature range in a precisely controlled manner. The proposed simple scheme can readily be formulated to detect both temperature rise in the frozen environment and freeze detection as well as multiple temperature monitoring. Combined, these results support a significant step forward for the development of customizable colorimetric monitoring of a broad range of temperatures with precision.
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BACKGROUND: Little is known about the self-perceived level of disability of stroke survivors in the community. We aimed to characterise Health-related quality of life (HRQoL) 1 year after stroke and investigate how sociodemographic and stroke-related factors and medical adherence explain the self-perceived level of disability in a Korean stroke population. METHODS: This was a multicentre cross-sectional study. A total of 382 ischaemic stroke survivors at 1 year after onset from 11 university hospitals underwent a one-session assessment, including socioeconomic variables, the modified Rankin Scale (mRS), various neurological sequelae, the Morisky, Green and Levin-Medication Adherence Questionnaire (MGL), and the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) 36-items. The relationship between disability and different variables was analysed using ordinal logistic regression. RESULTS: The prevalence of disability based on global WHODAS 2.0 was 62.6% (mild, 41.6%; moderate, 16.0%; severe, 5.0%). The prevalence of severe disability was higher in participation in society (16.8%) and getting around (11.8%) than in other domains. Low MGL- motivation was the only factor determining a significant association between all six domains of disability after adjustment. Different predictors for specific domains were age, mRS, dysarthria, trouble seeing, cognition problems, and MGL-motivation for understanding and communicating; age, recurrent stroke, mRS, hemiplegia, facial palsy, general weakness, and MGL-motivation for getting around; age, education, mRS, hemiplegia, and MGL-motivation for self-care; education, recurrent stroke, hemiplegia, dysarthria, and MGL-motivation for getting along with people; age, education, income, mRS, hemiplegia, dysarthria, MGL-knowledge, and MGL-motivation for life activities; living without a spouse, mRS, hemiplegia, dysarthria, trouble seeing, cognition problems, general weakness, and MGL-motivation for participation in society. CONCLUSIONS: Self-perceived disability according to the WHODAS 2.0 at 1 year after stroke was highly prevalent. Each disability domain showed a different prevalence and associated factors. Interventions promoting medical adherence to motivation seemed to help achieve high HRQoL in all domains.
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Isquemia Encefálica , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/epidemiologia , Atividades Cotidianas , Estudos Transversais , Qualidade de Vida , Disartria , Hemiplegia , República da Coreia/epidemiologia , Avaliação da DeficiênciaRESUMO
Mesenchymal stem cells (MSCs) are an attractive candidate for the treatment of inflammatory bowel disease (IBD), but their poor delivery rate to an inflamed colon is a major factor hampering the clinical potential of stem cell therapies. Moreover, there remains a formidable hurdle to overcome with regard to survival and homing in to injured sites. Here, we develop a strategy utilizing monodisperse hydrogel microcapsules with a thin intermediate oil layer prepared by a triple-emulsion drop-based microfluidic approach as an in-situ oral delivering carrier. The oral delivery of stem-cell-loaded hydrogel microcapsules (SC-HM) enhances MSC survival and retention in the hostile stomach environment due to the intermediate oil layer and low value of the overall stiffness, facilitating programmable cell release during gastrointestinal peristalsis. SC-HM is shown to induce tissue repair, reduce the colonic macrophage infiltration responsible for the secretion of the pro-inflammatory factors, and significantly mitigate the severity of IBD in a mouse model, where MSCs released by SC-HM successfully accumulate at the colonic crypt. Moreover, a metagenomics analysis reveals that SC-HM ameliorates the dysbiosis of specific bacterial genera, including Bacteroides acidifaciens, Lactobacillus (L.) gasseri, Lactobacillus reuteri, and L. intestinalis, implying optimization of the microorganism's composition and abundance. These findings demonstrate that SC-HM is a potential IBD treatment candidate.
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Doenças Inflamatórias Intestinais , Células-Tronco Mesenquimais , Microbiota , Animais , Cápsulas , Hidrogéis/farmacologia , Inflamação , Doenças Inflamatórias Intestinais/tratamento farmacológico , CamundongosRESUMO
Antithrombotic therapy is a cornerstone of acute ischemic stroke (AIS) management and secondary stroke prevention. Since the first version of the Korean Clinical Practice Guideline (CPG) for stroke was issued in 2009, significant progress has been made in antithrombotic therapy for patients with AIS, including dual antiplatelet therapy in acute minor ischemic stroke or high-risk transient ischemic stroke and early oral anticoagulation in AIS with atrial fibrillation. The evidence is widely accepted by stroke experts and has changed clinical practice. Accordingly, the CPG Committee of the Korean Stroke Society (KSS) decided to update the Korean Stroke CPG for antithrombotic therapy for AIS. The writing members of the CPG committee of the KSS reviewed recent evidence, including clinical trials and relevant literature, and revised recommendations. A total of 35 experts were invited from the KSS to reach a consensus on the revised recommendations. The current guideline update aims to assist healthcare providers in making well-informed decisions and improving the quality of acute stroke care. However, the ultimate treatment decision should be made using a holistic approach, considering the specific medical conditions of individual patients.
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In nature, individual cells are compartmentalized by a membrane that protects the cellular elements from the surrounding environment while simultaneously equipped with an antioxidant defense system to alleviate the oxidative stress resulting from light, oxygen, moisture, and temperature. However, this mechanism has not been realized in cellular mimics to effectively encapsulate and retain highly reactive antioxidants. Here, we report cell-inspired hydrogel microcapsules with an interstitial oil layer prepared by utilizing triple emulsion drops as templates to achieve enhanced retention of antioxidants. We employ ionic gelation for the hydrogel shell to prevent exposure of the encapsulated antioxidants to free radicals typically generated during photopolymerization. The interstitial oil layer in the microcapsule serves as an stimulus-responsive diffusion barrier, enabling efficient encapsulation and retention of antioxidants by providing an adequate pH microenvironment until osmotic pressure is applied to release the cargo on-demand. Moreover, addition of a lipophilic reducing agent in the oil layer induces a complementary reaction with the antioxidant, similar to the nonenzymatic antioxidant defense system in cells, leading to enhanced retention of the antioxidant activity. Furthermore, we show the complete recovery and even further enhancement in antioxidant activity by lowering the storage temperature, which decreases the oxidation rate while retaining the complementary reaction with the lipophilic reducing agent.
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Antioxidantes/farmacologia , Materiais Biocompatíveis/farmacologia , Cápsulas/farmacologia , Hidrogéis/farmacologia , Óleo Mineral/química , Animais , Antioxidantes/química , Materiais Biocompatíveis/química , Células CACO-2 , Cápsulas/química , Humanos , Hidrogéis/química , Concentração de Íons de Hidrogênio , Teste de Materiais , Camundongos , Células NIH 3T3 , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismoRESUMO
Alcohol is one of the main causes of liver diseases such as fatty liver, alcoholic hepatitis, and chronic hepatitis with liver fibrosis or cirrhosis. To reproduce the conditions of alcohol-induced liver diseases and to identify the disease-causing mechanisms at the cellular level, several methods have been used to expose the cells to ethanol. As ethanol evaporates easily, it is difficult to mimic chronic alcohol exposure conditions at the cellular level. In this study, we developed a glass capillary system containing ethanol, which could steadily release ethanol from the polyethylene tubing and hydrogel portion at both sides of the capillary. The ethanol-containing capillary could release ethanol in the cell culture medium for up to 144 h, and the concentration of ethanol in the cell culture medium could be adjusted by controlling the number of capillaries. A long-term exposure to ethanol by the capillary system led to an increased toxicity of cells and altered the cellular physiologies, such as increasing the lipid accumulation and hepatic transaminase release in cells, as compared to the traditional direct ethanol addition method. Ethanol capillaries showed different gene expression patterns of lipid accumulation- or chronic alcoholism-related genes. Our results suggest that our ethanol-containing capillary system can be used as a valuable tool for studying the mechanism of chronic alcohol-mediated hepatic diseases at the cellular level.