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1.
Nat Commun ; 15(1): 1441, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38383596

RESUMO

Bacteria adapt to selective pressure in their immediate environment in multiple ways. One mechanism involves the acquisition of independent mutations that disable or modify a key pathway, providing a signature of adaptation via convergent evolution. Extra-intestinal pathogenic Escherichia coli (ExPEC) belonging to sequence type 95 (ST95) represent a global clone frequently associated with severe human infections including acute pyelonephritis, sepsis, and neonatal meningitis. Here, we analysed a publicly available dataset of 613 ST95 genomes and identified a series of loss-of-function mutations that disrupt cellulose production or its modification in 55.3% of strains. We show the inability to produce cellulose significantly enhances ST95 invasive infection in a rat model of neonatal meningitis, leading to the disruption of intestinal barrier integrity in newborn pups and enhanced dissemination to the liver, spleen and brain. Consistent with these observations, disruption of cellulose production in ST95 augmented innate immune signalling and tissue neutrophil infiltration in a mouse model of urinary tract infection. Mutations that disrupt cellulose production were also identified in other virulent ExPEC STs, Shigella and Salmonella, suggesting a correlative association with many Enterobacteriaceae that cause severe human infection. Together, our findings provide an explanation for the emergence of hypervirulent Enterobacteriaceae clones.


Assuntos
Infecções por Escherichia coli , Proteínas de Escherichia coli , Meningite , Camundongos , Animais , Ratos , Humanos , Virulência/genética , Infecções por Escherichia coli/microbiologia , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Fatores de Virulência/genética , Filogenia
2.
J Clin Sleep Med ; 20(1): 39-47, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38163942

RESUMO

STUDY OBJECTIVES: We aimed to identify the relationship between duration of categorized catch-up sleep on free days (CUS) and measured body mass index (BMI) in adults using the data from the seventh Korean National Health and Nutrition Examination Survey (KNHANES VII), 2016. METHODS: CUS duration was classified as ≤ 0, > 0-1, > 1-2, and > 2 hours. Being overweight or obese was defined as having a BMI ≥ 25.0 kg/m2 or ≥ 30.0 kg/m2, respectively. RESULTS: Of 6,382 participants aged 19-80 years in the KNHANES VII survey of 2016, 201 and 583 participants were excluded because of shift-working and insufficient data, respectively. Of 5,598 participants, CUS was observed in 2,274 (44.9%) participants, of which 3,324 (55.1%), 1,043 (19.4%), 724 (14.7%), and 507 (10.8%) had CUS of ≤ 0, > 0-1, > 1-2, and > 2 hours, respectively; the prevalence of obesity was 5.6%, 5.6%, 4.8%, and 6.1%, respectively. The association between BMI and CUS duration showed a significant negative association in the CUS ≤ 0 hours group (beta [95% confidence interval], -0.394 [-0.646, -0.143], P = .002); however, other CUS groups did not show any significant association with BMI (CUS > 0-1 hours: -0.196 [-1.258, 0.865], P = .716; CUS > 1-2 hours, -0.542 [-1.625, 0.541], P = .325; CUS > 2 hours, -0.113 [-0.459, 0.233], P = .519). CONCLUSIONS: Our findings provide an understanding of the relationship between CUS and BMI and can serve as an instructive basis for the management of BMI. CITATION: Lee HJ, Cho S, Lee SH, Kim SJ, Kim KM, Chu MK. Catch-up sleep on free days and body mass index: results from the seventh Korea National Health and Nutrition Examination Survey, 2016. J Clin Sleep Med. 2024;20(1):39-47.


Assuntos
Obesidade , Sono , Adulto , Humanos , Índice de Massa Corporal , Inquéritos Nutricionais , Obesidade/epidemiologia , República da Coreia/epidemiologia
3.
Brain Behav Immun ; 117: 181-194, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38211634

RESUMO

Traumatic brain injury (TBI) results in prolonged and non-resolving activation of microglia. Forced turnover of these cells during the acute phase of TBI aids recovery, but the cell-intrinsic pathways that underpin the pro-repair phenotype of these repopulating microglia remain unclear. Here, we show that selective targeting of ROCK2 with the small molecule inhibitor KD025 impairs the proliferative response of microglia after TBI as well as during genetically induced turnover of microglia. KD025 treatment abolished the substantial neuroprotective and cognitive benefits conferred by repopulating microglia, preventing these cells from replenishing the depleted niche during the early critical time window post-injury. Delaying KD025 treatment to the subacute phase of TBI allowed microglial repopulation to occur, but this did not enhance the benefits conferred by repopulating microglia. Taken together, our data indicate that ROCK2 mediates neuronal survival and microglial population dynamics after TBI, including the emergence of repopulating microglia with a pro-repair phenotype.


Assuntos
Lesões Encefálicas Traumáticas , Microglia , Humanos , Proliferação de Células , Sobrevivência Celular , Hidrolases , Quinases Associadas a rho
4.
J Neuroinflammation ; 20(1): 300, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38102698

RESUMO

Graft-versus-host disease (GVHD) is a serious complication of otherwise curative allogeneic haematopoietic stem cell transplants. Chronic GVHD induces pathological changes in peripheral organs as well as the brain and is a frequent cause of late morbidity and death after bone-marrow transplantation. In the periphery, bone-marrow-derived macrophages are key drivers of pathology, but recent evidence suggests that these cells also infiltrate into cGVHD-affected brains. Microglia are also persistently activated in the cGVHD-affected brain. To understand the involvement of these myeloid cell populations in the development and/or progression of cGVHD pathology, we here utilized the blood-brain-barrier permeable colony stimulating factor-1 receptor (CSF-1R) inhibitor PLX3397 (pexidartinib) at varying doses to pharmacologically deplete both cell types. We demonstrate that PLX3397 treatment during the development of cGVHD (i.e., 30 days post-transplant) improves disease symptoms, reducing both the clinical scores and histopathology of multiple cGVHD target organs, including the sequestration of T cells in cGVHD-affected skin tissue. Cognitive impairments associated with cGVHD and neuroinflammation were also attenuated by PLX3397 treatment. PLX3397 treatment prior to the onset of cGVHD (i.e., immediately post-transplant) did not change in clinical scores or histopathology. Overall, our data demonstrate significant benefits of using PLX3397 for the treatment of cGVHD and associated organ pathologies in both the periphery and brain, highlighting the therapeutic potential of pexidartinib for this condition.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Camundongos , Animais , Transplante de Medula Óssea , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/patologia , Receptores Proteína Tirosina Quinases , Receptores de Fator Estimulador de Colônias , Encéfalo/patologia , Doença Crônica
5.
PLoS One ; 18(11): e0289729, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38019845

RESUMO

Recently, the most bothersome symptom has been recommended as a co-primary endpoint in clinical trials on the acute treatment of migraine. Probable migraine is a subtype of migraine that fulfills all but one criterion for migraine diagnosis. We aimed to compare the most bothersome symptom between probable migraine and migraine. This study analyzed data from a nationwide study conducted in Korea, and the most bothersome symptom was assessed by requesting the participants to select one of the four typical accompanying symptoms of migraine. Responses to acute treatment were evaluated using the migraine Treatment Optimization Questionnaire-6. Nausea was the most bothersome symptom, followed by phonophobia and vomiting in the migraine group (nausea, 61.8%; phonophobia, 25.3%; vomiting, 10.0%; and photophobia, 2.9%) and the probable migraine group (nausea, 82.2%; phonophobia, 9.5%; vomiting, 5.6%; and photophobia, 2.7%). In participants with migraine, vomiting (adjusted odds ratio = 6.513; 95% confidence interval, 1.763-24.057) and phonophobia (adjusted odds ratio = 0.437; 95% confidence interval, 0.206-0.929) were significantly associated with severe headache intensity and nausea was significantly associated with >3 headache days per 30 days (adjusted odds ratio = 0.441; 95% confidence, 0.210-0.927). Different patterns of associations were observed in probable migraine.


Assuntos
Transtornos de Enxaqueca , Fotofobia , Humanos , Fotofobia/epidemiologia , Fotofobia/complicações , Hiperacusia/epidemiologia , Transtornos de Enxaqueca/complicações , Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/epidemiologia , Náusea/epidemiologia , Náusea/tratamento farmacológico , Vômito/complicações , Cefaleia/complicações , Inquéritos e Questionários , Método Duplo-Cego
6.
J Allergy Clin Immunol ; 152(5): 1141-1152.e2, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37562753

RESUMO

BACKGROUND: Dendritic cells (DCs) are heterogeneous, comprising multiple subsets with unique functional specifications. Our previous work has demonstrated that the specific conventional type 2 DC subset, CSF1R+cDC2s, plays a critical role in sensing aeroallergens. OBJECTIVE: It remains to be understood how CSF1R+cDC2s recognize inhaled allergens. We sought to elucidate the transcriptomic programs and receptor-ligand interactions essential for function of this subset in allergen sensitization. METHODS: We applied single-cell RNA sequencing to mouse lung DCs. Conventional DC-selective knockout mouse models were employed, and mice were subjected to inhaled allergen sensitization with multiple readouts of asthma pathology. Under the clinical arm of this work, human lung transcriptomic data were integrated with mouse data, and bronchoalveolar lavage (BAL) specimens were collected from subjects undergoing allergen provocation, with samples assayed for C1q. RESULTS: We found that C1q is selectively enriched in lung CSF1R+cDC2s, but not in other lung cDC2 or cDC1 subsets. Depletion of C1q in conventional DCs significantly attenuates allergen sensing and features of asthma. Additionally, we found that C1q binds directly to human dust mite allergen, and the C1q receptor CD91 (LRP1) is required for lung CSF1R+cDC2s to recognize the C1q-allergen complex and induce allergic lung inflammation. Lastly, C1q is enriched in human BAL samples following subsegmental allergen challenge, and human RNA sequencing data demonstrate close homology between lung IGSF21+DCs and mouse CSF1R+cDC2s. CONCLUSIONS: C1q is secreted from the CSF1R+cDC2 subset among conventional DCs. Our data indicate that the C1q-LRP1 axis represents a candidate for translational therapeutics in the prevention and suppression of allergic lung inflammation.


Assuntos
Asma , Pneumonia , Animais , Humanos , Camundongos , Alérgenos/metabolismo , Asma/metabolismo , Complemento C1q/metabolismo , Células Dendríticas , Camundongos Knockout , Pneumonia/metabolismo , Receptores Proteína Tirosina Quinases , Receptores de Fator Estimulador de Colônias/metabolismo
7.
J Korean Med Sci ; 38(31): e237, 2023 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-37550805

RESUMO

BACKGROUND: Visual aura (VA) occurs mostly in migraine with aura (MA), but some case studies have reported aura in non-migraine headaches. Thus, information of VA in non-migraine headaches is scarce. Aim of this study was to investigate the prevalence and impact of VA in non-migraine headache and compare it with that of migraine headache. METHODS: This study was a nationwide population-based study. We used an internet-based headache diagnosis questionnaire to diagnose headache, and various modules to evaluate clinical features and comorbidities of participants with headache. We defined migraine headache as migraine and probable migraine (PM), whereas non-migraine headache was defined as a headache but not migraine or PM. VA was defined as a self-reporting VA rating scale score ≥ 3. RESULTS: Of the 3,030 participants, 1,431 (47.2%) and 507 (16.7%) had non-migraine headache and migraine headache, respectively. VA prevalence was much lower in the non-migraine headache group than in the migraine headache group (14.5% [207/1,431] vs. 26.0% [132/507], P < 0.001). In subjects with non-migraine headache, those with VA had a markedly higher number of headache days per 30 days (median [25th-75th percentiles]: 2.0 [1.0-5.0] vs. 2.0 [1.0-3.0], P < 0.001), and headache-related disability (6.0 [3.0-16.0] vs. 2.0 [0.0-7.0], P < 0.001) than those without VA. VA prevalence did not differ significantly according to age and sex. CONCLUSION: Non-migraine headache with VA patients had more severe symptoms than those without VA. These findings may improve the understanding of VA and the management of individuals with non-migraine headache.


Assuntos
Epilepsia , Transtornos de Enxaqueca , Enxaqueca com Aura , Humanos , Transtornos de Enxaqueca/complicações , Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/epidemiologia , Cefaleia/complicações , Cefaleia/diagnóstico , Cefaleia/epidemiologia , Enxaqueca com Aura/complicações , Enxaqueca com Aura/diagnóstico , Enxaqueca com Aura/epidemiologia , Comorbidade
8.
Int J Biol Macromol ; 236: 123878, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-36894057

RESUMO

Recently, the number of people suffering from visual loss due to eye diseases is increasing rapidly around the world. However, due to the severe donor shortage and the immune response, corneal replacement is needed. Gellan gum (GG) is biocompatible and widely used for cell delivery or drug delivery, but its strength is not suitable for the corneal substitute. In this study, a GM hydrogel was prepared by blending methacrylated gellan gum with GG (GM) to give suitable mechanical properties to the corneal tissue. In addition, lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP), a crosslinking initiator, was added to the GM hydrogel. After the photo-crosslinking treatment, it was named GM/LAP hydrogel. GM and GM/LAP hydrogels were analyzed for physicochemical properties, mechanical characterization, and transparency tests to confirm their applicability as carriers for corneal endothelial cells (CEnCs). Also, in vitro studies were performed with cell viability tests, cell proliferation tests, cell morphology, cell-matrix remodeling analysis, and gene expression evaluation. The compressive strength of the GM/LAP hydrogel was improved compared to the GM hydrogel. The GM/LAP hydrogel showed excellent cell viability, proliferation, and cornea-specific gene expression than the GM hydrogel. Crosslinking-improved GM/LAP hydrogel can be applied as a promising cell carrier in corneal tissue engineering.


Assuntos
Células Endoteliais , Hidrogéis , Humanos , Hidrogéis/farmacologia , Hidrogéis/química , Polissacarídeos Bacterianos/farmacologia , Polissacarídeos Bacterianos/química , Engenharia Tecidual
9.
J Korean Med Sci ; 38(10): e74, 2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-36918028

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has greatly altered the daily lives of people in unprecedented ways, causing a variety of mental health problems. In this study, we aimed to evaluate the prevalence of depression among Korean adults during the COVID-19 pandemic and explore the factors associated with depressive mood using data from the Korea National Health and Nutrition Survey (KNHANES). METHODS: We analyzed participants aged ≥ 19 years from KNHANES 2018 (n = 5,837) and 2020 (n = 5,265) to measure and compare the prevalence of depression before and during the COVID-19 pandemic. Depression was defined as a score ≥ 10 on the Patient Health Questionnaire-9. Furthermore, we performed a multivariate logistic regression analysis to investigate the independent predictors of depressive mood during the COVID-19 pandemic. RESULTS: The prevalence of depression was notably higher during the COVID-19 pandemic than in the pre-pandemic period (5.2% vs. 4.3%, P = 0.043). In a multivariate model, female sex (adjusted odds ratio [aOR], 1.63; 95% confidence interval [CI], 1.10-2.41), age < 50 years (19-29 years: aOR, 7.31; 95% CI, 2.40-22.21; 30-39 years: aOR, 7.38; 95% CI, 2.66-20.47; 40-49 years: aOR, 4.94; 95% CI, 1.84-13.31 compared to ≥ 80 years), unemployment (aOR, 2.00; 95% CI, 1.41-2.85), upper-middle class household income (aOR, 1.83; 95% CI, 1.18-2.85 compared to upper-class income), being a beneficiary of Medicaid (aOR, 2.35; 95% CI, 1.33-4.14), poor self-rated health (aOR, 4.99; 95% CI, 1.51-3.47 compared to good self-rated health), and current smoking (aOR, 2.29; 95% CI, 1.51-3.47) were found to be significant risk factors for depression during the pandemic. CONCLUSION: Depression was significantly more prevalent among Korean adults during the COVID-19 pandemic than in the pre-pandemic era. Therefore, more attention should be paid to individuals vulnerable to depression during pandemics. Implementing psychological support public policies and developing interventions to prevent the adverse outcomes of COVID-19-related depression should be considered.


Assuntos
COVID-19 , Adulto , Humanos , Feminino , COVID-19/epidemiologia , Pandemias , Inquéritos Nutricionais , Prevalência , República da Coreia/epidemiologia
10.
Am J Respir Crit Care Med ; 207(11): 1451-1463, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36790376

RESUMO

Rationale: The resolution of inflammation is an active process coordinated by mediators and immune cells to restore tissue homeostasis. However, the mechanisms for resolving eosinophilic allergic lung inflammation triggered by inhaled allergens have not been fully elucidated. Objectives: Our objectives were to investigate the cellular mechanism of tissue-resident macrophages involved in the resolution process of eosinophilic lung inflammation. Methods: For the study, we used the institutional review board-approved protocol for human subsegmental bronchoprovocation with allergen, mouse models for allergic lung inflammation, and novel transgenic mice, including a conditional CCL26 knockout. The samples were analyzed using mass cytometry, single-cell RNA sequencing, and biophysical and immunological analyses. Measurements and Main Results: We compared alveolar macrophage (AM) subsets in the BAL before and after allergen provocation. In response to provocation with inhaled allergens, the subsets of AMs are dynamically changed in humans and mice. In the steady state, the AM subset expressing CX3CR1 is a relatively small fraction in bronchoalveolar space and lung tissue but drastically increases after allergen challenges. This subset presents unique patterns of gene expression compared with classical AMs, expressing high C1q family genes. CX3CR1+ macrophages are activated by airway epithelial cell-derived CCL26 via a receptor-ligand interaction. The binding of CCL26 to the CX3CR1+ receptor induces CX3CR1+ macrophages to secrete C1q, subsequently facilitating the clearance of eosinophils. Furthermore, the depletion of CX3CR1 macrophages or CCL26 in airway epithelial cells delays the resolution of allergic lung inflammation displaying prolonged tissue eosinophilia. Conclusions: These findings indicate that the CCL26-CX3CR1 pathway is pivotal in resolving eosinophilic allergic lung inflammation.


Assuntos
Alveolite Alérgica Extrínseca , Hipersensibilidade , Pneumonia , Eosinofilia Pulmonar , Humanos , Camundongos , Animais , Complemento C1q/metabolismo , Pulmão/metabolismo , Macrófagos , Alérgenos , Inflamação/metabolismo , Pneumonia/metabolismo , Quimiocina CCL26/metabolismo
11.
Adv Healthc Mater ; 12(2): e2201665, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36213983

RESUMO

Materials with physicochemical properties and biological activities similar to those of the natural extracellular matrix are in high demand in tissue engineering. In particular, Mo3 Se3 - inorganic molecular wire (IMW) is a promising material composed of bioessential minerals and possess nanometer-scale diameters, negatively charged surfaces, physical flexibility, and nanotopography characteristics, which are essential for interactions with cell membrane proteins. Here, an implantable 3D Mo3 Se3 - IMW enhanced gelatin-GMA/silk-GMA hydrogel (IMW-GS hydrogel) is developed for osteogenesis and bone formation, followed by biological evaluations. The mechanical properties of the 3D printed IMW-GS hydrogel are improved by noncovalent interactions between the Mo3 Se3 - IMWs and the positively charged residues of the gelatin molecules. Long-term biocompatibility with primary human osteoblast cells (HOBs) is confirmed using the IMW-GS hydrogel. The proliferation, osteogenic gene expression, collagen accumulation, and mineralization of HOBs improve remarkably with the IMW-GS hydrogel. In in vivo evaluations, the IMW-GS hydrogel implantation exhibits a significantly improved new bone regeneration of 87.8 ± 5.9% (p < 0.05) for 8 weeks, which is higher than that from the gelatin-GMA/silk-GMA hydrogel without Mo3 Se3 - IMW. These results support a new improved strategy with in vitro and in vivo performance of 3D IMW enhanced scaffolds in tissue engineering.


Assuntos
Hidrogéis , Alicerces Teciduais , Humanos , Hidrogéis/farmacologia , Hidrogéis/química , Alicerces Teciduais/química , Gelatina/farmacologia , Regeneração Óssea , Engenharia Tecidual/métodos , Osteogênese , Seda , Impressão Tridimensional
12.
PLoS One ; 17(12): e0279585, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36584009

RESUMO

Gait asymmetry is a common symptom in groups with neurological disorders and significantly reduces gait efficiency. To develop efficient training for gait rehabilitation, we propose a novel gait rehabilitation paradigm that combines two distinct perturbation strategies: visual feedback distortion (VFD) and split-belt treadmill (SBT) walking. In SBT walking, spatiotemporal gait adaptation can be readily achieved, but it quickly fades after training. Gait adaptation to implicit VFD in an unconscious manner tends to persist longer, potentially due to a greater engagement of implicit learning during training. Thus, we investigated whether the combined strategies would lead to more effective changes in symmetric gait patterns with longer retention periods. We compared the retention of the preserved asymmetric pattern acquired by "implicit VFD+SBT walking" with "SBT-only walking" and with "SBT walking with conscious correction". In the implicit VFD+SBT walking, the speed of the two belts was gradually changed, the visual representation of gait symmetry was implicitly distorted, and no instructions were given to subjects except to watch the visual feedback. In the SBT walking with conscious correction, subjects were instructed to consciously correct their steps with the help of visual feedback while SBT walking. The SBT-only walking consisted of SBT walking with no visual feedback. After the 7-minute adaptation period, we removed the visual feedback and the split-belt perturbations, and we assessed the retention of the preserved asymmetric pattern while subjects continued walking for the 15-minute post-adaptation period. In a group of subjects who spontaneously showed visuomotor adaptation in response to the implicit VFD (16 out of 27 subjects), we found a greater retention rate during the implicit VFD+SBT walking trial than the SBT-only walking or the SBT walking with conscious correction trials. The implicit visual distortion paradigm delivered in an attention-independent (unconscious) manner can be utilized and integrated into SBT walking to improve the efficacy of symmetric gait adaptation by producing longer-lasting effects on the retention of a newly learned motor pattern.


Assuntos
Marcha , Caminhada , Humanos , Caminhada/fisiologia , Marcha/fisiologia , Adaptação Fisiológica/fisiologia , Aprendizagem/fisiologia , Aclimatação , Teste de Esforço
13.
ACS Omega ; 7(45): 41331-41340, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36406493

RESUMO

The damage to retinal pigment epithelium (RPE) cells can lead to vision loss and permanent blindness. Therefore, an effective therapeutic strategy has emerged to replace damaged cells through RPE cell delivery. In this study, we fabricated injectable gellan gum (GG)/silk sericin (SS) hydrogels as a cell carrier by blending GG and SS. To determine the appropriate concentration of SS for human RPE ARPE-19, 0, 0.05, 0.1, and 0.5% (w/v) of SS solution were blended in 1% (w/v) GG solution (GG/SS 0%, GG/SS 0.05%, GG/SS 0.1%, and GG/SS 0.5%, respectively). The physical and chemical properties were measured through Fourier-transform infrared spectroscopy, scanning electron microscopy, mass swelling, and weight loss. Also, viscosity, injection force, and compressive tests were used to evaluate mechanical characteristics. Cell proliferation and differentiation of ARPE-19 were evaluated using quantitative dsDNA analysis and real-time polymerase chain reaction, respectively. The addition of SS gave GG/SS hydrogels a compressive strength similar to that of natural RPE tissue, which may well support the growth of RPE and enhance cell proliferation and differentiation. In particular, the GG/SS 0.5% hydrogel showed the most similar compressive strength (about 10 kPa) and exhibited the highest gene expression related to ARPE-19 cell proliferation. These results indicate that GG/SS 0.5% hydrogels can be a promising biomaterial for cell delivery in retina tissue engineering.

14.
Int J Biol Macromol ; 222(Pt B): 2144-2157, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36216106

RESUMO

This study shows tunable stress relaxing gellan gum (GG) hydrogel for enhanced cell growth and regenerative medicine. The molecular weight and physical crosslinking density of GG were tuned and characterized with physicochemical analysis and mechanical tests. The result showed that a decrease in the molecular weight of the GG correlated with a decline in the mechanical properties but faster stress relaxing character. We also discovered that human-derived bone marrow stem cells (hBMSC) showed active viability, proliferation, and remodeling in the fast stress relaxing GG hydrogel. In particular, hBMSC showed an enhanced release profile of growth factors and exosomes (Exo) in the fast stress relaxing GG hydrogel. The secretome obtained from hBMSC embedded in hydrogel exhibited similar cytotoxicity and wound healing properties to that of secretome extracted from hBMSC cultured in a tissue culture plate (TCP) a standard culture condition. Thus, this work demonstrates the potential of fast stress relaxing GG hydrogels for medical application.


Assuntos
Células-Tronco Mesenquimais , Polissacarídeos Bacterianos , Humanos , Polissacarídeos Bacterianos/farmacologia , Polissacarídeos Bacterianos/química , Hidrogéis/farmacologia , Hidrogéis/química , Osso e Ossos , Engenharia Tecidual
15.
Sci Rep ; 12(1): 4050, 2022 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-35260781

RESUMO

Post-stroke depression (PSD), a prevalent complication of stroke, causes poor outcomes. However, little is known about its prevalence and management among community-dwelling stroke survivors. Thus, we investigated the prevalence, awareness, and treatment of PSD in a community setting. A cross-sectional study was performed using representative data from the Korea National Health and Nutrition Surveys 2014, 2016, and 2018. A total of 11,122 participants aged ≥ 40 years were categorized, including 343 stroke survivors and 10,779 non-stroke survivors. We then calculated and compared the prevalence, awareness (formal diagnosis of depression by a doctor), and treatment rates of depression between the two groups. Depression was defined as a score ≥ 10 in the nine-item Patient Health Questionnaire (PHQ-9). Depression was significantly more prevalent among stroke survivors than in non-stroke survivors (22.2% vs. 8.5%, respectively), while the differences in the awareness and treatment rates were insignificant. However, only 46.8% of stroke survivors with PSD were aware of their condition, and only 20.5% were receiving treatment. These results suggest that clinicians should more actively screen for and treat depression among stroke survivors.


Assuntos
Vida Independente , Acidente Vascular Cerebral , Estudos Transversais , Depressão/epidemiologia , Depressão/etiologia , Humanos , Prevalência , República da Coreia/epidemiologia , Fatores de Risco , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapia , Sobreviventes
16.
BMC Neurol ; 21(1): 349, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34507550

RESUMO

BACKGROUND: We tried to evaluate the prevalence of premature discontinuation of antiplatelets and its affecting factors after ischemic stroke using large-sized representative national claims data. METHODS: Patients aged 20 years or older with newly confirmed ischemic stroke who started aspirin or clopidogrel for the first time were selected from 2003 to 2010 National Health Insurance Service-National Sample Cohort (NHIS-NSC) of South Korea (n = 4621), a randomly collected sample which accounts for 2.2% (n = 1,017,468) of total population (n = 46,605,433). The prevalence of discontinuation of antiplatelets was measured every 6 months until the 24 months since the first prescription. Then we classified the participants into 2 groups according to the discontinuation status at 12 months and assessed the factors influencing premature discontinuation of antiplatelets within 12 months. RESULTS: Among total participants, 35.5% (n = 1640) discontinued antiplatelets within 12 months and 58.5% (n = 2704) discontinued them within 24 months. The remaining 41.5% (n = 1917) continued them for 24 months or more. In the multivariate logistic regression analysis, initiating treatment with aspirin monotherapy [adjusted OR (aOR), 2.66, 95% CI 2.17-3.25] was the most prominent determinant of premature discontinuation within 12 months followed by CCI score ≥ 6 (aOR 1.50, 95% CI 1.31-1.98), and beginning treatment with clopidogrel monotherapy (aOR 1.41, 95% CI 1.15-1.72). Rural residency (aOR 1.36, 95% CI 1.14-1.62), < 4 total prescribed drugs (aOR 1.24, 95% CI 1.05-1.47), lower income (aOR 1.20, 95% CI 1.03-1.40 for middle income class and OR 1.21, 95% CI 1.02-1.45 for low income class), and ages ≥70 years (aOR 1.15, 95% CI 1.00-1.31) were also significantly associated with premature discontinuation of antiplatelets within 12 months. CONCLUSIONS: The prevalence of premature discontinuation of antiplatelets after ischemic stroke was quite high. Thus, by understanding factors associated with premature discontinuation, a more strategic approach is required for the physicians to improve persistence with antiplatelets.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Inibidores da Agregação Plaquetária/uso terapêutico , Prevalência , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/epidemiologia
17.
Vaccines (Basel) ; 9(7)2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34358179

RESUMO

Few studies have examined the influenza vaccination rates among stroke survivors despite the importance of vaccines in preventing influenza- and stroke-related complications. Thus, we investigated the vaccination rates and the associated factors among stroke survivors using the representative Korea National Health and Nutrition Examination Survey 2014-2018. We measured and compared the vaccination rates of 591 stroke survivors and 17,997 non-stroke survivors. Multivariate logistic regression analyses of all stroke survivors and age subgroups (<65 and ≥65 years) were performed to identify the factors influencing vaccination. The overall vaccination rate was significantly higher in the stroke survivors (64.8%) than in the non-stroke survivors (41.1%), but it was low compared to global standards. Among stroke survivors aged <65 years, the rate was low (37.5%), but it improved in those aged ≥65 years (85.6%). Age ≥ 65 years, the eligible age for the national free vaccination program was the most prominent predictor of vaccination for all stroke survivors, while smoking was a negative predictor. No significant factors were found in the subgroup analyses according to age (<65 and ≥65 years). Therefore, implementing strategic public health policies, such as expanding the free vaccination program to stroke survivors aged <65 years, may improve vaccine coverage.

18.
PLoS One ; 16(7): e0254907, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34324532

RESUMO

BACKGROUND: Family history (FH) is one of important risk factors for cardiovascular disease (CVD). However, little is known about its impact on dyslipidemia prevalence and management status. Thus, we aimed to investigate the impact of FH of CVD on dyslipidemia prevalence, awareness, treatment, control, and healthy behaviors in Korean adults. METHODS: We conducted a cross-sectional study using representative data from the Korea National Health and Nutrition Examination Survey (KNHANES) 2014-2018. A total of 22,024 participants aged ≥ 19 years without histories of CVDs were classified into two groups according to the presence of FH of CVD (with FH, n = 3,778; without FH, n = 18,246). FH of CVD was defined as having a first-degree relative with ischemic heart disease or stroke. Multivariate logistic regression analyses were performed to evaluate the association between FH of CVD and dyslipidemia prevalence, awareness, treatment, control, and healthy behaviors (weight control, non-smoking, non-risky drinking, sufficient physical activity, and undergoing health screening). RESULTS: FH of CVD was significantly associated with a higher dyslipidemia prevalence (adjusted odds ratio [aOR] 1.34, 95% confidence interval [CI] 1.18-1.51), better awareness (aOR 1.54, 95%CI 1.19-2.00), and treatment rates (aOR 1.34, 95%CI 1.12-1.60), but not control. Having an FH of CVD was not predictive of any healthy behaviors in dyslipidemia patients. For non-dyslipidemia patients, FH of CVD even showed significant association with smoking (aOR 1.18, 95%CI 1.02-1.36), and risky drinking (aOR 1.20, 95%CI 1.03-1.40) while it was predictive of receiving health screening (aOR 1.14, 95% CI 1.02-1.27). CONCLUSIONS: Having an FH of CVD might positively trigger dyslipidemia patients to start pharmacological intervention, but not non-pharmacological interventions. Therefore, physicians should make more efforts to educate and promote the importance of non-pharmacological behavioral modification in dyslipidemia patients with an FH of CVD.


Assuntos
Doenças Cardiovasculares , Comportamentos Relacionados com a Saúde , Adulto , Idoso , Doenças Cardiovasculares/epidemiologia , Estudos Transversais , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Prevalência , República da Coreia/epidemiologia , Fatores de Risco
19.
BMC Geriatr ; 21(1): 232, 2021 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-33827445

RESUMO

BACKGROUND: We aimed to provide real-world evidence on the benefit of persistence with antiplatelet therapy (APT) on long-term all-cause mortality (ACM) in ischemic stroke patients aged 75 years and older. METHODS: Newly diagnosed ischemic stroke patients aged 75 years and older who initiated aspirin or clopidogrel for the first time were chosen from 2003 to 2010 National Health Insurance Service-National Sample Cohort (NHIS-NSC) of Korea (n = 887), a random cohort sample accounting for 2.2% (n = 1,017,468) of total population (n = 46,605,433). Then subjects were divided into persistent (n = 556) and non-persistent (n = 321) groups according to the persistent status at 6 months. Survivor analysis was performed between the two groups and predictors of non-persistence were analyzed by multivariate logistic regression analysis. Patients were followed up until death or December 31, 2013. RESULTS: Non-persistence with APT was significantly associated with increased risk of ACM (adjusted hazard ration [aHR] 2.13, 95% confidence interval [CI] 1.72-2.65), cerebro-cardiovascular disease (CVD) mortality (aHR 2.26, 95% CI 1.57-3.24), and non-CVD mortality (aHR 2.06, 95% CI 1.5702.70). More comorbidities (Charlson comorbidity index score ≥ 6) (adjusted odds ratio [aOR], 2.56, 95% CI 1.43-4.55), older age (aOR 1.52, 95% CI 1.11-2.09 for 80-84 years, aOR 1.73, 95% CI 1.17-2.57 for ≥85 years), and less than 4 total prescribed drugs (aOR 1.54, 95% CI 1.08-2.21) were independent predictors of non-persistence. CONCLUSIONS: Persistent with APT after ischemic stroke featured long-term mortality benefit even in patients aged 75 years and older. Thus, improving APT persistence for ischemic stroke patients in this age group is also recommended by understanding factors associated with non-persistence.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Idoso , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/tratamento farmacológico , Estudos de Coortes , Humanos , Inibidores da Agregação Plaquetária/uso terapêutico , República da Coreia/epidemiologia , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/tratamento farmacológico
20.
PLoS One ; 16(3): e0247829, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33765030

RESUMO

BACKGROUND AND PURPOSE: Previous studies have reported that early hospital arrival improves clinical outcomes in patients with acute ischemic stroke; however, whether early arrival is associated with favorable outcomes regardless of reperfusion therapy and the type of stroke onset time is unclear. Thus, we investigated the impact of onset-to-door time on outcomes and evaluated the predictors of pre-hospital delay after ischemic stroke. METHODS: Consecutive acute ischemic stroke patients who arrived at the hospital within five days of onset from September 2019 to May 2020 were selected from the prospective stroke registries of Seoul National University Hospital and Chung-Ang University Hospital of Seoul, Korea. Patients were divided into early (onset-to-door time, ≤4.5 h) and late (>4.5 h) arrivers. Multivariate analyses were performed to assess the effect of early arrival on clinical outcomes and predictors of late arrival. RESULTS: Among the 539 patients, 28.4% arrived early and 71.6% arrived late. Early hospital arrival was significantly associated with favorable outcomes (three-month modified Rankin Scale [mRS]: 0-2, adjusted odds ratio [aOR]: 2.03, 95% confidence interval: [CI] 1.04-3.96) regardless of various confounders, including receiving reperfusion therapy and type of stroke onset time. Furthermore, a lower initial National Institute of Health Stroke Scale (NIHSS) score (aOR: 0.94, 95% CI: 0.90-0.97), greater pre-stroke mRS score (aOR: 1.58, 95% CI: 1.18-2.13), female sex (aOR: 1.71, 95% CI: 1.14-2.58), unclear onset time, and ≤6 years of schooling (aOR: 1.76, 95% CI: 1.03-3.00 compared to >12 years of schooling) were independent predictors of late arrival. CONCLUSIONS: Thus, the onset-to-door time of≤4.5 h is crucial for better clinical outcome, and lower NIHSS score, greater pre-stroke mRS score, female sex, unclear onset times, and ≤6 years of schooling were independent predictors of late arrival. Therefore, educating about the importance of early hospital arrival after acute ischemic stroke should be emphasized. More strategic efforts are needed to reduce the prehospital delay by understanding the predictors of late arrival.


Assuntos
AVC Isquêmico/terapia , Tempo para o Tratamento , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
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