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1.
Nat Mater ; 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38486095

RESUMO

Unlike proteins, which have a wealth of validated structural data, experimentally or computationally validated DNA origami datasets are limited. Here we present a graph neural network that can predict the three-dimensional conformation of DNA origami assemblies both rapidly and accurately. We develop a hybrid data-driven and physics-informed approach for model training, designed to minimize not only the data-driven loss but also the physics-informed loss. By employing an ensemble strategy, the model can successfully infer the shape of monomeric DNA origami structures almost in real time. Further refinement of the model in an unsupervised manner enables the analysis of supramolecular assemblies consisting of tens to hundreds of DNA blocks. The proposed model enables an automated inverse design of DNA origami structures for given target shapes. Our approach facilitates the real-time virtual prototyping of DNA origami, broadening its design space.

2.
Anal Chem ; 96(25): 10246-10255, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38858132

RESUMO

Hypoxia is a representative tumor characteristic associated with malignant progression in clinical patients. Engineered in vitro models have led to significant advances in cancer research, allowing for the investigation of cells in physiological environments and the study of disease mechanisms and processes with enhanced relevance. In this study, we propose a U-shape pillar strip for a 3D cell-lumped organoid model (3D-COM) to study the effects of hypoxia on lung cancer in a high-throughput manner. We developed a U-pillar strip that facilitates the aggregation of PDCs mixed with an extracellular matrix to make the 3D-COM in 384-plate array form. The response to three hypoxia-activated prodrugs was higher in the 3D-COM than in the 2D culture model. The protein expression of hypoxia-inducible factor 1 alpha (HIF-1α) and HIF-2α, which are markers of hypoxia, was also higher in the 3D-COM than in the 2D culture. The results show that 3D-COM better recapitulated the hypoxic conditions of lung cancer tumors than the 2D culture. Therefore, the U-shape pillar strip for 3D-COM is a good tool to study the effects of hypoxia on lung cancer in a high-throughput manner, which can efficiently develop new drugs targeting hypoxic tumors.


Assuntos
Ensaios de Triagem em Larga Escala , Neoplasias Pulmonares , Organoides , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Organoides/metabolismo , Organoides/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Hipóxia Celular , Técnicas de Cultura de Células em Três Dimensões , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo
3.
BMC Med ; 22(1): 251, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38886720

RESUMO

BACKGROUND: We investigated the association between exercise habits before or after thyroidectomy and incident type 2 diabetes mellitus (T2DM) in patients with thyroid cancer. METHODS: An observational cohort study of 69,526 thyroid cancer patients who underwent thyroidectomy for the treatment of thyroid cancer between 2010 and 2016 was performed using the Korean National Health Information Database. Regular exercise was defined as mid-term or vigorous exercise at least 1 day in a week based on a self-reported questionnaire. Patients were divided into four groups according to exercise habits before and after thyroidectomy: persistent non-exercisers, new exercisers, exercise dropouts, and exercise maintainers. RESULTS: During a median follow-up of 4.5 years, 2,720 (3.91%) patients developed T2DM. The incidence of T2DM per 1,000 person years was lower in patients who performed regular exercise before or after thyroidectomy than in persistent non-exercisers (10.77 in persistent non-exerciser group, 8.28 in new exerciser group, 8.59 in exercise dropout group, and 7.61 in exercise maintainer group). Compared with the persistent non-exerciser group, the new exerciser group (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.78-0.97), the exercise dropout group (HR 0.81, 95% CI 0.72-0.91), and the exercise maintainer group (HR 0.84, 95% CI 0.76-0.93) had lower risks of incident T2DM. Exercising < 1,500 MET-minutes/week in the exercise maintainer group was associated with a lower risk of incident T2DM compared with persistent non-exercisers (< 500: HR 0.80, 95% CI 0.67-0.96, P = 0.002; 500 to < 1,000: HR 0.81, 95% CI 0.71-0.93, P < 0.001; 1,000 to < 1,500: HR 0.81, 95% CI 0.69-0.94, P < 0.001). CONCLUSIONS: Regular exercise before or after thyroidectomy was associated with a lower risk of incident T2DM in patients with thyroid cancer.


Assuntos
Diabetes Mellitus Tipo 2 , Exercício Físico , Neoplasias da Glândula Tireoide , Tireoidectomia , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Masculino , Feminino , Pessoa de Meia-Idade , Exercício Físico/fisiologia , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/cirurgia , Incidência , Adulto , República da Coreia/epidemiologia , Tireoidectomia/efeitos adversos , Idoso , Estudos de Coortes
4.
Dysphagia ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38922423

RESUMO

Clinicians should consider disorders of masticatory muscle including lateral pterygoid muscle as a differential diagnosis in patients presenting with dysphagia and trismus after tooth extraction.

5.
J Craniofac Surg ; 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38252535

RESUMO

The utilization of fillers, notably hyaluronic acid, has increased due to their proven effectiveness, versatility, and generally favorable safety profile. In the field of rhinoplasty, hyaluronic acid dermal fillers have been employed for the correction of nasal deformities and surface irregularities. Nevertheless, the intricate vascular network of the nasal region, involving anastomoses between the external and internal carotid arteries, predisposes it to serious vascular complications. We report a case of a severe septal ulcer secondary to local ischemia following an injection of a hyaluronic acid nasal filler. The patient presented with immediate pain and nasal discomfort; however, there was an unfortunate delay in diagnosis and treatment. This report discusses the intricacies of the case and imparts crucial insights gleaned from the incident.

6.
Clin Otolaryngol ; 49(3): 306-313, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38199861

RESUMO

OBJECTIVE: To investigate the clinical characteristics associated with measured gustatory dysfunction in patients with chemosensory (smell and taste) discomfort. STUDY DESIGN: Retrospective study. DESIGN: Hospital-based cohort. SETTING: The clinical characteristics associated with the measured diagnosis of gustatory dysfunction were statistically analysed. PARTICIPANTS: Patients who underwent all the psychophysical olfactory and chemical gustatory function tests (YSK olfactory function test and chemical gustometry exam) and the subjective questionnaires between October 2021 and February 2023. MAIN OUTCOME MEASURES: YSK olfactory function test and chemical gustometry results, subjective questionnaire score about chemosensory (smell and taste) functions. The Medical records of patients who visited the smell and taste centre in a tertiary. RESULTS: A total of 219 patients were enrolled; 180 were diagnosed as having normal gustatory function, and 39 were diagnosed as having gustatory dysfunction. Subjective recognition of gustatory function was not associated with the measured gustatory function. Age, sex, measured olfactory function and the threshold and discrimination scores for the olfactory function test were significant factors in the multivariate analysis. When the patients were further divided according to age, the threshold test scores rather than other subsets in the olfactory function test were significantly associated with measured gustatory dysfunction in patients 60 and older. CONCLUSION: In older adult male patients with olfactory dysfunction, gustatory function should be considered regardless of subjective gustatory dysfunction.


Assuntos
Transtornos do Olfato , Paladar , Humanos , Masculino , Idoso , Estudos Retrospectivos , Distúrbios do Paladar/diagnóstico , Distúrbios do Paladar/etiologia , Olfato , Transtornos do Olfato/diagnóstico , Transtornos do Olfato/etiologia
7.
Kidney Int ; 104(4): 820-827, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37490954

RESUMO

Acromegaly is a chronic systemic disease caused by excess levels of growth hormone and insulin-like growth factor-1 and is associated with numerous complications. Significantly, there is a lack of longitudinal data on kidney complications in patients with acromegaly. As such, we investigated the risk of end-stage kidney disease (ESKD) (stage 5D, 5T) in these patients with nationwide data obtained from the National Health Information Database of the National Health Insurance Service in Republic of Korea. A retrospective cohort study was conducted of 2.187 patients with acromegaly and 10,935 age- and sex-matched (1:5) control subjects without acromegaly over a mean follow-up period of 6.51 years. The study outcomes were analyzed using Cox proportional hazards regression analysis controlling for age, sex, household income, residential area, type 2 diabetes, hypertension, dyslipidemia, urolithiasis, congestive heart failure, myocardial infarction, stroke, and atrial fibrillation. The incidence (per 1,000 person-years) ESKD was 2.00 among patients with acromegaly but only 0.46 among controls, (hazard ratio 4.35 (95% confidence interval 2.63-7.20)) implicating a significantly higher risk. After adjustment for covariates, the risk of ESKD (2.36 (1.36-4.12)) was still significantly higher in patients with acromegaly than that in controls. Among the covariates, diabetes and hypertension were significant facilitators between acromegaly and ESKD in mediation analysis. Pituitary surgery and somatostatin analogues did not significantly change these associations. Thus, acromegaly may be linked with a higher risk for ESKD both independently and through mediators such as diabetes and hypertension.


Assuntos
Acromegalia , Diabetes Mellitus Tipo 2 , Hipertensão , Falência Renal Crônica , Humanos , Acromegalia/complicações , Acromegalia/epidemiologia , Estudos de Coortes , Diabetes Mellitus Tipo 2/complicações , Hipertensão/complicações , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/etiologia , Estudos Retrospectivos , Fatores de Risco , Masculino , Feminino
8.
Diabetes Obes Metab ; 25(1): 110-120, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36053813

RESUMO

AIM: To evaluate the efficacy of intermittent short-term use of a real-time continuous glucose monitoring (RT-CGM) system in non-insulin-treated patients with type 2 diabetes (T2D) uncontrolled with oral antidiabetic drugs (OADs). MATERIALS AND METHODS: In this multicentre, randomized prospective study, 61 participants were randomly assigned to treatment group 1 (one session of RT-CGM), treatment group 2 (two sessions of RT-CGM with a 3-month interval between sessions) and a control group. All participants used blinded continuous glucose monitoring for up to 6 days with education before randomization, and RT-CGM was additionally applied for 1 week in the intervention groups. The primary outcome was change in HbA1c at 6 months. RESULTS: Among 61 participants, 48 subjects completed the study (baseline HbA1c 8.2% ± 0.5%). At 3 months, a significant HbA1c reduction was observed in treatment group 1 (adjusted difference = -0.60%, P = .044) and treatment group 2 (adjusted difference = -0.64%, P = .014) compared with the control group. However, at 6 months, only treatment group 2 achieved a significant HbA1c reduction (adjusted difference = -0.68%, P = .018). Especially in the treatment groups, patients performing self-monitoring of blood glucose (SMBG) at least 1.5 times/day showed a significant HbA1c improvement, at both 3 and 6 months, but those performing SMBG less than 1.5 times/day showed no significant improvement. CONCLUSIONS: In non-insulin-treated patients with T2D uncontrolled with OADs, intermittent short-term use of RT-CGM was an effective method for glucose control, especially in those performing SMBG frequently.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Automonitorização da Glicemia , Glicemia , Estudos Prospectivos
9.
Diabetes Obes Metab ; 25(7): 1865-1873, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36872067

RESUMO

AIMS: To evaluate the efficacy and safety of a novel sodium-glucose cotransporter 2 inhibitor, enavogliflozin 0.3 mg monotherapy, in Korean people with type 2 diabetes mellitus (T2DM) inadequately controlled with diet and exercise. MATERIALS AND METHODS: This study was a randomized, double-blind, placebo-controlled trial conducted in 23 hospitals. Individuals with haemoglobin A1c (HbA1c) of 7.0%-10.0% after at least 8 weeks of diet and exercise modification were randomized to receive enavogliflozin 0.3 mg (n = 83) or placebo (n = 84) for 24 weeks. The primary outcome was a change in HbA1c at week 24 from baseline. Secondary outcomes included the proportion of participants achieving HbA1c <7.0%, change in fasting glucose, body weight and lipid levels. Adverse events were investigated throughout the study. RESULTS: At week 24, the placebo-adjusted mean change in HbA1c from baseline in the enavogliflozin group was -0.99% (95% confidence interval -1.24%, -0.74%). The proportions of patients achieving HbA1c <7.0% (71% vs. 24%) at week 24 was significantly higher in the enavogliflozin group (p < .0001). Placebo-adjusted mean changes in fasting plasma glucose (-40.1 mg/dl) and body weight (-2.5 kg) at week 24 were statistically significant (p < .0001). In addition, a significant decrease in blood pressure, low-density lipoprotein cholesterol, triglyceride, and homeostasis model assessment of insulin resistance were observed, along with a significant increase in high-density lipoprotein cholesterol. No significant increase in treatment-related adverse events was observed for enavogliflozin. CONCLUSIONS: Monotherapy with enavogliflozin 0.3 mg improved glycaemic control in people with T2DM. Enavogliflozin therapy also exerted beneficial effects on body weight, blood pressure and lipid profile.


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Glicemia , Peso Corporal , Colesterol , Método Duplo-Cego , Hemoglobinas Glicadas , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Lipídeos , República da Coreia/epidemiologia , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Resultado do Tratamento
10.
Diabetes Obes Metab ; 25(8): 2096-2104, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37016484

RESUMO

AIMS: The study aimed to evaluate and compare the efficacy and safety of enavogliflozin, a newly developed sodium-glucose cotransporter 2 inhibitor, with placebo in Korean patients with type 2 diabetes mellitus. MATERIALS AND METHODS: Patients with glycated haemoglobin (HbA1c) of 7.0-10.0%, entered a 2-week placebo run-in period, and were randomized to receive once-daily enavogliflozin (0.1, 0.3 or 0.5 mg) or placebo for 12 weeks. The primary efficacy endpoint was the change in HbA1c from baseline at week 12. RESULTS: Overall, 194 patients were included in the full analysis set [placebo, n = 46; enavogliflozin (0.1 mg, n = 49; 0.3 mg, n = 50; 0.5 mg, n = 49)]. Patients receiving 0.1, 0.3 and 0.5 mg enavogliflozin showed significantly reduced HbA1c compared with those receiving placebo at week 12 (-0.79%, -0.89%, -0.92% and -0.08%, respectively; p < .001 vs. placebo). Mean changes in fasting plasma glucose from baseline at week 12 were -30.5, -31.1, -35.0 and 4.9 mg/dl in patients receiving enavogliflozin doses and placebo, respectively. The proportion of patients achieving HbA1c <7.0% at week 12 was significantly higher in the three enavogliflozin groups than in the placebo group (42.9%, 44.0%, 61.2% and 17.4%, respectively). A higher proportion of patients showed HbA1c reduction by >0.5% after receiving enavogliflozin doses than those receiving placebo (61.2%, 72.0%, 65.3% and 26.1%, respectively). There were no significant differences in incidences of adverse events of hypoglycaemia and genital infection between the groups. CONCLUSIONS: Once-daily enavogliflozin monotherapy for 12 weeks is an effective, safe, and well-tolerated treatment for Korean patients with type 2 diabetes mellitus.


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Hipoglicemiantes/efeitos adversos , Hemoglobinas Glicadas , Resultado do Tratamento , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Quimioterapia Combinada , Método Duplo-Cego , República da Coreia/epidemiologia , Glicemia
11.
BMC Geriatr ; 23(1): 56, 2023 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-36721099

RESUMO

BACKGROUND: Research on gustatory dysfunction among older adults has been scarce relative to research on olfactory dysfunction, and the relationship between subjective and objective gustatory dysfunction has not been studied in detail. We aimed to evaluate whether subjective recognition of gustatory dysfunction correlates with objective diagnosis of gustatory dysfunction among older adults. METHODS: In this retrospective, cross-sectional study, we reviewed the medical records of 138 patients of ages ≥ 60 years for whom data were available on self-reported and objectively measured gustatory and olfactory function from January 2018 through April 2021 at a specialized smell/taste center of a single institution. We reviewed self-reported and measured outcomes of gustatory and olfactory function using patient data including clinical characteristics, including age, sex, smoking history, and medical history. RESULTS: We found that the subjective recognition of gustatory dysfunction does not correlate with the objective diagnosis of gustatory dysfunction based on the measured results of gustatory function tests. Subjective gustatory dysfunction, however, was correlated with subjective olfactory dysfunction. Among clinical and demographic characteristics, age and sex were significantly associated with measured gustatory function outcomes. CONCLUSION: We suggest that subjective gustatory dysfunction underestimates objective dysfunction and recommend that older men with diminished olfactory function undergo gustatory function testing regardless of their self-reported gustatory function status.


Assuntos
Instalações de Saúde , Transtornos do Olfato , Masculino , Humanos , Idoso , Estudos Transversais , Estudos Retrospectivos , Prontuários Médicos , Transtornos do Olfato/diagnóstico , Transtornos do Olfato/epidemiologia
12.
Nucleic Acids Res ; 49(21): 12591-12599, 2021 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-34850119

RESUMO

Recent advances in DNA nanotechnology led the fabrication and utilization of various DNA assemblies, but the development of a method to control their global shapes and mechanical flexibilities with high efficiency and repeatability is one of the remaining challenges for the realization of the molecular machines with on-demand functionalities. DNA-binding molecules with intercalation and groove binding modes are known to induce the perturbation on the geometrical and mechanical characteristics of DNA at the strand level, which might be effective in structured DNA assemblies as well. Here, we demonstrate that the chemo-mechanical response of DNA strands with binding ligands can change the global shape and stiffness of DNA origami nanostructures, thereby enabling the systematic modulation of them by selecting a proper ligand and its concentration. Multiple DNA-binding drugs and fluorophores were applied to straight and curved DNA origami bundles, which demonstrated a fast, recoverable, and controllable alteration of the bending persistence length and the radius of curvature of DNA nanostructures. This chemo-mechanical modulation of DNA nanostructures would provide a powerful tool for reconfigurable and dynamic actuation of DNA machineries.


Assuntos
Benzoxazóis/química , DNA/química , Doxorrubicina/química , Etídio/química , Substâncias Intercalantes/química , Nanoestruturas/química , Compostos de Quinolínio/química , Benzoxazóis/metabolismo , DNA/genética , DNA/metabolismo , Doxorrubicina/metabolismo , Etídio/metabolismo , Análise de Elementos Finitos , Substâncias Intercalantes/metabolismo , Ligantes , Microscopia de Força Atômica , Nanotecnologia/métodos , Compostos de Quinolínio/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectrofotometria
13.
Eur Heart J ; 43(15): 1491-1499, 2022 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-34864952

RESUMO

AIMS: Cardiovascular disease is a common complication in acromegaly. We investigated the risk of cardiovascular disease and mortality in patients with acromegaly in a large-scale population using nationwide data in Korea. METHODS AND RESULTS: We performed a nationwide, retrospective, observational, cohort study of patients with acromegaly (n = 1874) and age- and sex-matched subjects without acromegaly (n = 9370) for a mean follow-up of 7.5 ± 3.2 years. The study outcomes were myocardial infarction, stroke, atrial fibrillation, congestive heart failure, and all-cause death. All outcomes were analysed by Cox proportional hazards regression analysis while controlling for age, sex, household income, place, Type 2 diabetes, hypertension, and dyslipidaemia. The incidence (per 1000 person-years) of atrial fibrillation (3.06 vs. 1.70; P = 0.001), congestive heart failure (3.11 vs. 1.63; P < 0.001), and all-cause mortality (6.31 vs. 4.03; P < 0.001) in patients with acromegaly was higher than in controls. However, the incidence of myocardial infarction and stroke did not differ between groups. After adjustment for covariates, the risk for atrial fibrillation [hazard ratio (HR): 1.59; 95% confidence interval (CI): 1.09-2.31], congestive heart failure (HR: 1.54; 95% CI: 1.06-2.25), and all-cause mortality (HR: 1.31; 95% CI: 1.01-1.69) was significantly higher in patients with acromegaly. In time lag sensitivity analysis, a higher risk for atrial fibrillation was observed only in the first 4 years after diagnosis in acromegaly patients compared with controls (HR: 3.05; 95% CI: 1.94-4.79). CONCLUSION: Patients with acromegaly were at higher risk for atrial fibrillation, congestive heart failure, and all-cause death. The risk of atrial fibrillation had a time-dependent association with acromegaly.


Assuntos
Acromegalia , Fibrilação Atrial , Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Infarto do Miocárdio , Acidente Vascular Cerebral , Acromegalia/complicações , Acromegalia/epidemiologia , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Estudos de Coortes , Diabetes Mellitus Tipo 2/complicações , Insuficiência Cardíaca/complicações , Humanos , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/etiologia
14.
Molecules ; 28(7)2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-37049874

RESUMO

Recently, semiconductor wastewater treatment has received much attention due to the emergence of environmental issues. Acid-resistant coatings are essential for metal prefilters used in semiconductor wastewater treatment. Perfluoroalkoxy alkane is mainly used as an acid-resistant coating agent, since PFA has inherent superhydrophobicity, water permeability is lowered. To solve this problem, the surface of the PFA-coated metal mesh was treated via an oxyfluorination method in which an injected mixed gas of fluorine and oxygen reacted with the surface functional groups. Surface analysis, water contact angle measurement, and water permeability tests were performed on the surface-treated PFA-coated mesh. Consequently, the superhydrophobic surface was effectively converted to a hydrophobic surface as the PFA coating layer was surface-modified with C-O-OH functional groups via the oxyfluorination reaction. As a result of using simulation solutions that float silica particles of various sizes, the permeability and particle removal rate of the surface-modified PFA-coated stainless-steel mesh were improved compared to those before surface modification. Therefore, the oxyfluorination treatment used in this study was suitable for improving the filtration performance of SiO2 microparticles in the PFA-coated stainless-steel mesh.

15.
Geriatr Nurs ; 50: 109-116, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36774677

RESUMO

Chronic pain is a common and bothersome experience for older adults. Consequently, pain management is critical to maintaining their function and well-being. Art making, a non-pharmacological approach, has gained empirical support and is used for functional and cognitive improvement in older adults. However, it has rarely been used to manage chronic pain. The purpose of this descriptive qualitative study was to understand older adults' experience using a newly designed art making intervention and its influence on their pain. Overall, 11 older adults used the intervention and reported its quality to be appropriate. Moreover, older adults reported that art making was an engaging, diversional activity which reduced their pain severity and improved their mood. The findings of this study will be used to inform a future pilot study to assess the impact of art making on pain management in older adults with chronic pain.


Assuntos
Dor Crônica , Humanos , Idoso , Dor Crônica/terapia , Dor Crônica/psicologia , Manejo da Dor , Projetos Piloto , Pesquisa Qualitativa , Afeto
16.
Am J Physiol Heart Circ Physiol ; 322(5): H867-H879, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35333113

RESUMO

Peripheral artery disease (PAD) is an atherosclerotic disease that impairs blood flow and muscle function in the lower limbs. A skeletal muscle myopathy characterized by mitochondrial dysfunction and oxidative damage is present in PAD; however, the underlying mechanisms are not well established. We investigated the impact of chronic ischemia on skeletal muscle microcirculatory function and its association with leg skeletal muscle mitochondrial function and oxygen delivery and utilization capacity in PAD. Gastrocnemius samples and arterioles were harvested from patients with PAD (n = 10) and age-matched controls (Con, n = 11). Endothelium-dependent and independent vasodilation was assessed in response to flow (30 µL·min-1), acetylcholine, and sodium nitroprusside (SNP). Skeletal muscle mitochondrial respiration was quantified by high-resolution respirometry, microvascular oxygen delivery, and utilization capacity (tissue oxygenation index, TOI) were assessed by near-infrared spectroscopy. Vasodilation was attenuated in PAD (P < 0.05) in response to acetylcholine (Con: 71.1 ± 11.1%, PAD: 45.7 ± 18.1%) and flow (Con: 46.6 ± 20.1%, PAD: 29.3 ± 10.5%) but not SNP (P = 0.30). Complex I + II state 3 respiration (P < 0.01) and TOI recovery rate were impaired in PAD (P < 0.05). Both flow and acetylcholine-mediated vasodilation were positively associated with complex I + II state 3 respiration (r = 0.5 and r = 0.5, respectively, P < 0.05). Flow-mediated vasodilation and complex I + II state 3 respiration were positively associated with TOI recovery rate (r = 0.8 and r = 0.7, respectively, P < 0.05). These findings suggest that chronic ischemia attenuates skeletal muscle arteriole endothelial function, which may be a key mediator for mitochondrial and microcirculatory dysfunction in the PAD leg skeletal muscle. Targeting microvascular dysfunction may be an effective strategy to prevent and/or reverse disease progression in PAD.NEW & NOTEWORTHY Ex vivo skeletal muscle arteriole endothelial function is impaired in claudicating patients with PAD, and this is associated with attenuated skeletal muscle mitochondrial respiration. In vivo skeletal muscle oxygen delivery and utilization capacity is compromised in PAD, and this may be due to microcirculatory and mitochondrial dysfunction. These results suggest that targeting skeletal muscle arteriole function may lead to improvements in skeletal muscle mitochondrial respiration and oxygen delivery and utilization capacity in claudicating patients with PAD.


Assuntos
Oxigênio , Doença Arterial Periférica , Acetilcolina/metabolismo , Arteríolas , Humanos , Isquemia/metabolismo , Microcirculação , Mitocôndrias , Músculo Esquelético/irrigação sanguínea , Oxigênio/metabolismo , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/metabolismo , Doença Arterial Periférica/terapia , Respiração
17.
J Gen Intern Med ; 37(16): 4153-4159, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35676587

RESUMO

OBJECTIVE: The triglyceride and glucose (TyG) index is a useful marker of insulin resistance and is a predictor of several metabolic diseases. The aim of this study was to evaluate the association between the TyG index and all-cause or cardiovascular mortality using a large population-based cohort study database. METHODS: A total of 255,508 subjects in the Kangbuk Samsung Health Study cohort were enrolled. Cox proportional hazards models were used to analyze the risk of mortality. RESULTS: During a median 5.7-year follow-up, the cumulative all-cause and cardiovascular mortality was 0.47% and 0.07%. There was a nonlinear relationship between the TyG index and death, and moving from moderate to high, the TyG index levels were associated with an increase in the risk of death. The hazard ratio (HR) for all-cause and cardiovascular mortality of the TyG index was 1.21 [95% confidence interval (CI) 1.14-1.28] and 1.45 (95% CI 1.26-1.66) in the unadjusted model, respectively. After adjustment for covariates, the association between the TyG index and all-cause and cardiovascular mortality was attenuated. In the multivariable-adjusted model, the TyG index was associated with an elevated risk of all-cause mortality in women (HR 1.13, 95% CI 1.02-1.26) and a decreased risk in men (HR 0.92, 95% CI 0.85-0.99). The association between cardiovascular mortality and the TyG index was not statistically significant among either men or women in the multivariable-adjusted model. CONCLUSIONS: The TyG index in a young, relatively healthy, population is associated with an elevated risk of all-cause and cardiovascular mortality. This association between the TyG index and all-cause mortality persists in women after multivariable adjustment.


Assuntos
Doenças Cardiovasculares , Glucose , Masculino , Feminino , Humanos , Triglicerídeos , Glicemia/metabolismo , Estudos de Coortes , Medição de Risco , Biomarcadores , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Fatores de Risco
18.
J Craniofac Surg ; 33(5): e503-e505, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34897200

RESUMO

ABSTRACT: Barbed thread rhinoplasty for nasal tip projection, dorsal length elongation, and nostril correction is usually performed at private clinics. The procedure is minimally invasive and does not cause permanent external scarring, which is a common challenge in rhinoplasty. Limited studies have described the complications of this procedure, with no reports on its late complications. A patient presented to the authors' clinic with a nasal septal mass, which had developed 3 months before the visit. She had undergone rhinoplasty 10 years prior. During excisional biopsy, the authors found barbed threads impacted in the mass, which may have been inserted during the rhinoplasty. The mass was pathologically demonstrated as a chronic inflammatory lesion that may have originated due to the foreign body. The use of barbed threads in rhinoplasty can induce complications as late as 10 years after surgery; clinicians should consider this and explain the possible late complications to patients before surgery.


Assuntos
Septo Nasal , Rinoplastia , Técnicas de Sutura , Adulto , Cicatriz/cirurgia , Feminino , Humanos , Septo Nasal/cirurgia , Nariz/cirurgia , Rinoplastia/efeitos adversos , Rinoplastia/métodos , Software
19.
J Craniofac Surg ; 33(6): e552-e553, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34907948

RESUMO

ABSTRACT: Rhinoplasty via a closed approach is rarely performed due to provide limited exposure and inadequate operative field. Nevertheless, there are some cases in which closed approach is performed using L-shaped silicone implants. The authors recently encountered an interesting complication in a 33-year-old woman who had previously undergone rhinoplasty via a closed approach and who sought revision rhinoplasty at our institution. The authors accidently found a fractured silicone implant on lateral nasal x-ray. She had no nasal trauma history since previous rhinoplasty. The authors assumed that the silicone implant can be fractured as 1 of complications during the rhinoplasty via a closed approach.


Assuntos
Implantes Dentários , Fraturas Ósseas , Rinoplastia , Adulto , Feminino , Humanos , Próteses e Implantes , Reoperação , Rinoplastia/efeitos adversos , Silicones/efeitos adversos
20.
Clin Sci (Lond) ; 135(3): 483-494, 2021 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-33458745

RESUMO

The function of high-mobility group box 1 (HMGB1) varies according to its location. However, the translocation mechanism behind HMGB1 remains unclear. We hypothesize that type 2 helper T cell (Th2) cytokines are involved in the translocation of HMGB1 in the upper airway epithelium. We investigated the mechanism behind HMGB1 translocation using Th2 cytokine stimulation and examined the clinical significance of HMGB1 translocation in allergic rhinitis (AR). Cytoplasmic and extracellular HMGB1 were increased in AR. Inhibiting HMGB1 translocation with glycyrrhizic acid (GA) decreased the level of antigen-specific immunoglobulin E (IgE), the degree of Periodic Acid-Schiff (PAS), and Sirius Red staining in the murine model. The in vivo reactive oxygen species (ROS) level in the nasal mucosa was higher in the mice with AR than in the controls. Th2 cytokine-induced up-regulation of the ROS and translocation of HMGB1 by Th2 cytokines was dependent on the generated ROS. The ROS level also increased in the murine model. We suggest that the Th2 cytokine-dual oxidase (DUOX)2-ROS-HMGB1 translocation axis is important in AR pathogenesis.


Assuntos
Oxidases Duais/metabolismo , Proteína HMGB1/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Rinite Alérgica/patologia , Adulto , Animais , Células Cultivadas , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Mucosa Nasal/metabolismo , Células Th2/metabolismo
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