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1.
Nutr J ; 23(1): 113, 2024 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-39342232

RESUMO

BACKGROUND: Although nuts are a well-known healthy food group, the relationship between nut consumption and mortality remains unclear, particularly among Asians. This prospective cohort study examined the association between nut consumption and the risk of all-cause, cardiovascular disease (CVD), and cancer mortality in Korean adults. METHODS: Data from two cohorts (the Ansan-Ansung and Health-Examinees) from the Korean Genome and Epidemiology Study were used. A total of 114,140 individuals aged 40-79 years were included in the data analyses. Nut consumption was assessed using a validated semi-quantitative food frequency questionnaire and categorized into four groups: non-consumers, less than 1 serving/week, 1-2 servings/week, and 2 or more servings/week (one serving was 15 g of nuts). Mortality outcomes were determined based on the 2001-2021 death records from Statistics Korea. Cox proportional hazard regression analysis was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality across nut consumption categories. A stratified subgroup analysis by health-related variables was also performed. RESULTS: During a mean follow-up of 12.3 years, 4,559 deaths were recorded. After adjusting for covariates, the HR for all-cause mortality was 0.877 (95% CI = 0.772-0.996, p for trend = 0.006) in individuals with a nut consumption of 2 or more servings/week compared with that in non-consumers. Multivariable HRs for CVD mortality were 0.800 (95% CI = 0.681-0.939) in individuals consuming less than 1 serving/week, 0.656 (95% CI = 0.469-0.918) in those consuming 1-2 servings/week, and 1.009 (95% CI = 0.756-1.347) in those consuming 2 or more servings/week compared with that in non-consumers (p for trend = 0.080). No association was observed between nut consumption and cancer mortality. Stratified analysis identified significant interactions in the association between nut consumption and all-cause mortality by age, body mass index, and physical activity. CONCLUSIONS: Nut consumption was linearly associated with the reduced risk of all-cause mortality and showed a non-linear dose-response relationship with CVD mortality in Koreans, but had no association with cancer mortality. The effects of nut consumption, which have been inadequately investigated in this population, varied across different subgroups. These findings suggest that incorporating nuts into the diet should be encouraged for long-term health of Korean adults.


Assuntos
Doenças Cardiovasculares , Dieta , Neoplasias , Nozes , Humanos , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Masculino , Feminino , Adulto , Doenças Cardiovasculares/mortalidade , Idoso , Estudos Prospectivos , Dieta/métodos , Dieta/estatística & dados numéricos , Estudos de Coortes , Neoplasias/mortalidade , Fatores de Risco , Mortalidade , Modelos de Riscos Proporcionais
2.
BMB Rep ; 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39219048

RESUMO

Epigenetic alterations play a crucial role in developmental processes, tissue regeneration, and cellular differentiation. Epigenetic changes are dynamically reversible. Various drugs that target DNA methyltransferases or histone deacetylases have demonstrated their ability to restore normal epigenetic patterns in a number of diseases. While the involvement of epigenetic modifications has been identified in chronic inflammatory diseases, their specific impact on skin inflammation in stromal cells remains unclear. This mini-review explores the role of stromal cells in chronic inflammatory skin diseases, focusing on epigenetic modifications of stromal cells such as fibroblasts, lymphatic, and blood vascular endothelial cells in both healthy and diseased skin. We also provide an overview of recent findings that highlight the contribution of stromal cells, including fibroblasts, to inflammatory and remodeling processes through epigenetic changes in the context of chronic inflammatory conditions. Investigating epigenetic reprogramming of stromal cells might lead to novel strategies for treating chronic inflammatory skin diseases.

3.
Heliyon ; 10(17): e37134, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39286105

RESUMO

Radioactive Cs+ and I- ions are major components of nuclear wastewater, typically existing as counter ions. Due to their high water solubility and mobility, these ions can spread through contaminated water and soil into ecosystems, necessitating continuous removal and management. In this study, we synthesized a reusable bifunctional Ni@Pt/K2NiFe(CN)6 composite that can simultaneously remove radioactive Cs+ and I- ions and, for the first time, enable their separate recovery in aqueous solutions. In this material, K2NiFe(CN)6 acted as an electrochemically switched ion exchanger, controlling the adsorption/desorption of Cs+, while Pt enabled the spontaneous adsorption and electrochemical desorption of I-, and the magnetic Ni core allowed for efficient adsorbent recovery. The adsorption isotherms of both Cs+ and I- were best fitted using the Langmuir model, and the corresponding adsorption capacities were comparable to those of conventional adsorbents used for the separate removal of Cs+ and I-. Furthermore, the composite demonstrated stability over 100 sorption cycles, maintaining high recovery efficiencies of 97.9 % for Cs+ and 99.7 % for I-, thereby proving its reusability. Thus, the developed composite holds great promise for radioactive wastewater treatment and environmental restoration.

4.
Health Aff (Millwood) ; 43(9): 1209-1218, 2024 09.
Artigo em Inglês | MEDLINE | ID: mdl-39226509

RESUMO

Value-based care models, such as Medicaid accountable care organizations (ACOs), have the potential to improve access to and quality of care for pregnant and postpartum Medicaid enrollees. We leveraged a natural experiment in Massachusetts to evaluate the effects of Medicaid ACOs on quality-of-care-sensitive measures and care use across the prenatal, delivery, and postpartum periods. Using all-payer claims data on Medicaid-covered live deliveries in Massachusetts, we used a difference-in-differences approach to compare measures before (the first quarter of 2016 through the fourth quarter of 2017) and after (the third quarter of 2018 through the fourth quarter of 2020) Medicaid ACO implementation among ACO and non-ACO patients. After three years of implementation, the Medicaid ACO was associated with statistically significant increases in the probability of a timely postpartum visit, postpartum depression screening, and number of all-cause office visits in the prenatal and postpartum periods, with no changes in severe maternal morbidity, preterm birth, postpartum glucose screening, or prenatal or postpartum emergency department visits. Changes in cesarean deliveries were inconclusive. Results suggest that implementing Medicaid ACOs in the thirty-eight states without them could improve maternal health care outpatient engagement, but alone it may be insufficient to improve maternal health outcomes.


Assuntos
Organizações de Assistência Responsáveis , Medicaid , Humanos , Feminino , Gravidez , Estados Unidos , Massachusetts , Organizações de Assistência Responsáveis/estatística & dados numéricos , Adulto , Qualidade da Assistência à Saúde , Período Pós-Parto , Cuidado Pré-Natal/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Cuidado Pós-Natal/estatística & dados numéricos , Melhoria de Qualidade
5.
Nat Commun ; 15(1): 8355, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39333516

RESUMO

Virus-specific nasal resident T cells are important for protection against subsequent infection with a similar virus. Here we examine the phenotypes and functions of SARS-CoV-2-specific T cells in the nasal mucosa of vaccinated individuals with breakthrough infection (BTI) or without infection. Nasal tissues are obtained from participants during sinus surgery. Analysis of activation-induced markers implicates that a considerable proportion of spike (S)-reactive nasal CD8+ T cells express CD103, a tissue-resident marker. MHC-I multimer staining is performed to analyze the ex vivo phenotype and function of SARS-CoV-2 S-specific CD8+ T cells. We detect multimer+CD8+ T cells with tissue-resident phenotypes in nasal tissue samples from vaccinees without infection as well as vaccinees with BTI. Multimer+CD8+ T cells remain present in nasal tissues over one year after the last exposure to S antigen, although the frequency decreases. Upon direct ex vivo stimulation with epitope peptides, nasal multimer+CD8+ T cells-particularly the CD49a+ subset-exhibit immediate effector functions, including IFN-γ production. CITE-seq analysis of S-reactive AIM+CD8+ T cells confirms the enhanced effector function of the CD49a+ subset. These findings indicate that among individuals previously exposed to S antigen by vaccination or BTI, S-specific nasal-resident CD49a+CD8+ memory T cells can rapidly respond to SARS-CoV-2 during infection or reinfection.


Assuntos
Linfócitos T CD8-Positivos , COVID-19 , Interferon gama , Células T de Memória , Mucosa Nasal , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Humanos , Glicoproteína da Espícula de Coronavírus/imunologia , Linfócitos T CD8-Positivos/imunologia , Interferon gama/imunologia , Interferon gama/metabolismo , SARS-CoV-2/imunologia , Mucosa Nasal/imunologia , Mucosa Nasal/virologia , COVID-19/imunologia , COVID-19/virologia , Células T de Memória/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Integrina alfa1/imunologia , Integrina alfa1/metabolismo , Vacinas contra COVID-19/imunologia , Antígenos CD/metabolismo , Antígenos CD/imunologia , Memória Imunológica/imunologia , Cadeias alfa de Integrinas
6.
Micromachines (Basel) ; 15(8)2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39203678

RESUMO

The ability to perceive and adapt to environmental changes is crucial for the survival of all organisms. Neural functional imaging, particularly in model organisms, such as Caenorhabditis elegans, provides valuable insights into how animals sense and process external cues through their nervous systems. Because of its fully mapped neural anatomy, transparent body, and genetic tractability, C. elegans serves as an ideal model for these studies. This review focuses on advanced methods for neural functional imaging in C. elegans, highlighting calcium imaging techniques, lab-on-a-chip technologies, and their applications in the study of various sensory modalities, including chemosensation, mechanosensation, thermosensation, photosensation, and magnetosensation. We discuss the benefits of these methods in terms of precision, reproducibility, and ability to study dynamic neural processes in real time, ultimately advancing our understanding of the fundamental principles of neural activity and connectivity.

7.
Healthcare (Basel) ; 12(16)2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39201159

RESUMO

Low fertility is a critical social problem worldwide, and infertility has a prevalence of 15%. This cross-sectional study aimed to understand the factors affecting the usage and satisfaction of Korean medicine (KM) in subfertile women. An online survey was conducted from 3 November to 8 November 2021. The survey collected basic information, KM treatment experience, and satisfaction from women who experienced poor pregnancy. The t-test and chi-square test (χ2-test) were used to determine the overall characteristics of the subjects and factors affecting the utilization and satisfaction of KM treatment. Of the total of 29,465 people, 4922 read the survey email, and 601 responded. After excluding 51 respondents with questionable response patterns, 550 respondents were included in the final analysis. Of these, 43.1% (n = 237) had experience with conventional treatment, and 16.5% (n = 91) had received KM treatment. The group that received both KM treatment and CM treatment (n = 59, 24.9%) was significantly more prevalent than the group that received KM treatment alone (n = 32, 10.2%) (p = 0.00). Women who had given birth more than once or held a master's degree were significantly more willing to participate in the 'KM Support Project for Subfertility' program. Our findings suggest that subfertile patients prefer integrated treatment that combines KM and CM treatments. Further studies are needed to assess the status of integrative medicine treatment, satisfaction with each KM intervention, factors for low satisfaction, and patient requirements.

8.
Histochem Cell Biol ; 162(5): 415-428, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39134731

RESUMO

Sepsis has a high mortality rate and leads to multi-organ failure, including lung injury. Inactive rhomboid protease family protein (iRhom2) has been identified as accountable for the release of TNF-α, a crucial mediator in the development of sepsis. This study aimed to evaluate the role of iRhom2 in sepsis and sepsis-induced acute lung injury (ALI). TNF-α and IL-6 secretion in vitro by peritoneal macrophages from wild-type (WT) and iRhom2 knoukout (KO) mice was assessed by enzyme-linked immunosorbent assay. Cecal ligation and puncture (CLP)-induced murine sepsis model was used for in vivo experiments. To evaluate the role of iRhom2 deficiency on survival during sepsis, both WT and iRhom2 KO mice were monitored for 8 consecutive days following the CLP. For histologic and biochemical examination, the mice were killed 18 h after CLP. iRhom2 deficiency improved the survival of mice after CLP. iRhom2 deficiency decreased CD68+ macrophage infiltration in lung tissues. Multiplex immunohistochemistry revealed that the proportion of Ki-67+ CD68+ macrophages was significantly lower in iRhom2 KO mice than that in WT mice after CLP. Moreover, CLP-induced release of TNF-α and IL-6 in the serum were significantly inhibited by iRhom2 deficiency. iRhom2 deficiency reduced NF-kB p65 and IκBα phosphorylation after CLP. iRhom2 deficiency reduces sepsis-related mortality associated with attenuated macrophage infiltration and proliferation in early lung injury. iRhom2 may play a pivotal role in the pathogenesis of sepsis and early stage of sepsis-induced ALI. Thus, iRhom2 may be a potential therapeutic target for the management of sepsis and sepsis-induced ALI.


Assuntos
Camundongos Endogâmicos C57BL , Camundongos Knockout , Sepse , Animais , Sepse/metabolismo , Sepse/patologia , Camundongos , Masculino , Proteínas de Transporte/metabolismo , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/patologia , Macrófagos/metabolismo , Macrófagos/patologia , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia
9.
Brain Stimul ; 17(5): 1048-1059, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39214184

RESUMO

BACKGROUND AND OBJECTIVES: The effects of noninvasive focused magnetothermal brain stimulation using magnetic nanoparticles (MNPs) on post-stroke motor deficits and metabolic dormancy in subacute ischemic injury are not well-established. This study examined if magnetothermal brain stimulation using magnetic nanoparticles (Nano-MS) enhances motor recovery after stroke. METHODS: We randomly distributed rats into Sham, Control, MNP injection only, and Nano-MS groups. We administered focused magnetic stimulation for 30 min daily following an MNP injection (15 mg/mL) into the targeted motor cortex via the carotid artery three weeks after the transient (90 min) middle cerebral artery occlusion. We assessed motor functionality via behavioral tests and conducted positron emission tomography (PET) imaging to verify cerebral metabolic activity. We assessed neuronal excitability, neuroinflammation, blood-brain barrier (BBB) integrity, and neurogenesis four weeks post-stroke. RESULTS: The Nano-MS group exhibited significantly improved motor deficits and cerebral metabolic activity compared to the Control and MNP groups (p < 0.05). Focused Nano-MS modulated neuronal excitability, evident by a depolarized action potential threshold for spike initiation and reduced firing frequency post-stroke. The Nano-MS group demonstrated markedly decreased inflammatory markers, such as IL-1ß, IL-6, TNF-α, MCP-1, and ICAM-1, compared to the Control and MNP groups. BBB integrity and immunofluorescence for neurogenesis markers were substantially improved in the Nano-MS group. CONCLUSIONS: Focused Nano-MS facilitates the recovery of motor deficits and metabolic inactivity in the brain by effectively modulating excitability, reducing neuroinflammation, enhancing BBB stability, and promoting neurogenesis. Nano-MS is a potential novel, noninvasive therapy for stroke rehabilitation. Further investigation is warranted.

10.
Comput Methods Programs Biomed ; 254: 108302, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38996805

RESUMO

BACKGROUND AND OBJECTIVE: To develop a healthcare chatbot service (AI-guided bot) that conducts real-time conversations using large language models to provide accurate health information to patients. METHODS: To provide accurate and specialized medical responses, we integrated several cancer practice guidelines. The size of the integrated meta-dataset was 1.17 million tokens. The integrated and classified metadata were extracted, transformed into text, segmented to specific character lengths, and vectorized using the embedding model. The AI-guide bot was implemented using Python 3.9. To enhance the scalability and incorporate the integrated dataset, we combined the AI-guide bot with OpenAI and the LangChain framework. To generate user-friendly conversations, a language model was developed based on Chat-Generative Pretrained Transformer (ChatGPT), an interactive conversational chatbot powered by GPT-3.5. The AI-guide bot was implemented using ChatGPT3.5 from Sep. 2023 to Jan. 2024. RESULTS: The AI-guide bot allowed users to select their desired cancer type and language for conversational interactions. The AI-guided bot was designed to expand its capabilities to encompass multiple major cancer types. The performance of the AI-guide bot responses was 90.98 ± 4.02 (obtained by summing up the Likert scores). CONCLUSIONS: The AI-guide bot can provide medical information quickly and accurately to patients with cancer who are concerned about their health.


Assuntos
Neoplasias , Humanos , Neoplasias/terapia , Inteligência Artificial , Processamento de Linguagem Natural , Algoritmos , Comunicação
11.
Am J Med Genet A ; : e63716, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847211

RESUMO

Primary congenital glaucoma (PCG) is one of the leading causes of visual damage and blindness, severely affecting the quality of life of affected children. It is characterized by cupping of the optic disc and loss of ganglion cells due to elevated intraocular pressure. While most PCG patients exhibit epiphora, photophobia, and buphthalmos with corneal opacity, variability in phenotypic manifestations is not uncommon. Prompt diagnosis and treatment of PCG affected individuals becomes relevant to preserve visual function throughout their lives. Most PCG cases are sporadic or autosomal recessive; however, an incompletely dominant autosomal dominant form arising from mutations in the TEK gene has recently been demonstrated. Here, we describe the clinical and mutational features of a cohort of Mexican patients with TEK-related PCG. Our results support the involvement of the TEK gene as an important cause of the disease in our ethnic group and expand the mutational spectrum causing PCG by reporting 10 novel disease-causing variants.

12.
J Clin Med ; 13(12)2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38930077

RESUMO

(1) Background: The aim of this study was to investigate the circadian rhythms of tongue features according to the effects of physiological phases over a 24 h period. (2) Methods: Fifteen healthy participants aged 20 to 69 years were recruited. The participants did not have current chronic diseases or past diseases and had to meet the inclusion and exclusion criteria. The participants stayed at the Gil Hospital for a duration of 2 nights and 3 days. On the first day, at 18:00, they consumed their allocated portions of food and water and then completed a questionnaire. At approximately 21:00, their tongue images were acquired using a computerized tongue image acquisition system, following which they slept for 8 h, commencing at 23:00. Measurements were taken from 07:00 through 21:00 on the second day, and the final acquisition was taken at 07:00 on the following morning, resulting in a total of eight images. The circadian rhythm was authenticated and quantified utilizing the single cosinor analysis, a technique for periodic regression analysis for fitting a 24 h cosine curve. (3) Results: Cosinor analysis revealed that all tongue features were significantly related to circadian rhythm. (4) Conclusions: The results of this study may be important for considering the time of day at which the tongue is observed and tongue status is evaluated.

13.
Pediatr Allergy Immunol ; 35(6): e14176, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38899598

RESUMO

BACKGROUND: It has been suggested that allergic diseases may increase after Kawasaki disease (KD). We aimed to analyze the temporal patterns of allergic disease incidence after KD. METHODS: A nationwide population-based matched cohort study was conducted using data from the Korean National Health Insurance claims database. Patients aged <5 years diagnosed with KD and their 1:3 propensity score-matched controls were included. Three cohorts were established: Cohort A, patients with allergies; Cohort B, patients without allergies; and Cohort C, patients without allergies, but excluding patients with birth history and underlying medical conditions. Cumulative incidence rates (%) and associated hospital visits for allergic rhinitis, atopic dermatitis, urticaria, and asthma were compared between the cases and controls during the 6-year follow-up period. RESULTS: The study population comprised 8678 patients diagnosed with KD and 26,034 controls. In Cohort A, although initially, there were intergroup differences in the number of hospital visits for certain allergic diseases, these differences were inconsistent and varied depending on the type of allergic disease. Over time, the differences narrowed, and by the sixth year, the gap had decreased significantly. In Cohorts B and C, the initial incidence rates of the four allergic diseases and associated hospital visits were lower in patients with KD as compared to controls. However, with a faster rate of increase, the incidence rates and number of hospital visits eventually surpassed those of the controls. CONCLUSIONS: The pattern of delayed increase in cumulative incidence rates and hospital visits for allergic diseases after KD suggests the possibility of a shared genetic or immunologic susceptibility between KD and allergic diseases, which becomes evident over time, rather than a direct influence of KD resulting in allergic diseases.


Assuntos
Hipersensibilidade , Síndrome de Linfonodos Mucocutâneos , Humanos , Síndrome de Linfonodos Mucocutâneos/epidemiologia , Masculino , Feminino , Pré-Escolar , Incidência , República da Coreia/epidemiologia , Lactente , Hipersensibilidade/epidemiologia , Estudos de Coortes , Seguimentos , Dermatite Atópica/epidemiologia
14.
Clin Nutr ; 43(6): 1447-1453, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38703511

RESUMO

BACKGROUND & AIMS: Plant-based dietary patterns have been associated with lower risk of cardiovascular disease (CVD), some cancers, and related mortality in U.S. POPULATIONS: However, the quality of plant foods has rarely been considered in the association between plant-based diets and mortality, especially in a population with various racial and ethnic backgrounds. We investigated whether the adherence to plant-based dietary patterns and the healthiness of plant foods are associated with mortality from all causes, CVD, and cancer and evaluated how the association varies by race and ethnicity. METHODS: A total of 144,729 African American, Japanese American, Latino, Native Hawaiian, and White men and women who participated in the Multiethnic Cohort Study (1993-2019) were included. Cox models were used to estimate HR and 95% CI of mortality from all causes, CVD, and cancer across quintiles of three plant-based diet scores: overall plant-based diet index (PDI), healthful plant-based diet index (hPDI), and unhealthful plant-based diet index (uPDI). RESULTS: Over an average 21 years of follow-up, we identified 65,087 deaths, including 18,663 from CVD and 16,171 from cancer. Comparing the highest versus lowest quintiles, greater scores of PDI and hPDI were associated with a lower risk of all-cause mortality in both men (HR = 0.85, 95% CI: 0.82-0.89 for PDI; HR = 0.88, 95% CI: 0.85-0.91 for hPDI; both P for trend <0.0001) and women (HR = 0.89, 95% CI: 0.86-0.93 for PDI; HR = 0.86, 95% CI: 0.83-0.89 for hPDI; both P for trend <0.0001). An increased risk of all-cause mortality with uPDI was observed only in women (HR = 1.11, 95% CI: 1.07-1.15, P for trend <0.0001; P for heterogeneity by sex = 0.019). A similar trend was shown for CVD mortality with a significant increase in risk with uPDI for both men and women. PDI was associated with a lower risk of cancer mortality in men (HR = 0.86, 95% CI: 0.80-0.92, P for trend <0.0001), while neither hPDI nor uPDI was associated in either sex. Compared with the other racial and ethnic groups within each sex, the association of uPDI with all-cause mortality was stronger in White men (P for heterogeneity by race and ethnicity = 0.009) and weaker in Latino women (P for heterogeneity = 0.002). CONCLUSION: A healthy plant-based dietary pattern emphasizing the quality of plant foods was associated with a lower risk of all-cause and CVD mortality in both men and women, although the magnitude of the associations varied across racial and ethnic groups.


Assuntos
Doenças Cardiovasculares , Dieta Vegetariana , Neoplasias , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/etnologia , Causas de Morte , Estudos de Coortes , Dieta Saudável/estatística & dados numéricos , Dieta Vegetariana/estatística & dados numéricos , Padrões Dietéticos , Etnicidade/estatística & dados numéricos , Neoplasias/mortalidade , Neoplasias/etnologia , Fatores de Risco , Estados Unidos/epidemiologia , Negro ou Afro-Americano , Asiático , Hispânico ou Latino , Havaiano Nativo ou Outro Ilhéu do Pacífico , Brancos
15.
Ophthalmol Glaucoma ; 7(5): 499-511, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38723778

RESUMO

PURPOSE: Excessive dietary sodium intake has known adverse effects on intravascular fluid volume and systemic blood pressure, which may influence intraocular pressure (IOP) and glaucoma risk. This study aimed to assess the association of urinary sodium excretion, a biomarker of dietary intake, with glaucoma and related traits, and determine whether this relationship is modified by genetic susceptibility to disease. DESIGN: Cross-sectional observational and gene-environment interaction analyses in the population-based UK Biobank study. PARTICIPANTS: Up to 103 634 individuals (mean age: 57 years; 51% women) with complete urinary, ocular, and covariable data. METHODS: Urine sodium:creatinine ratio (UNa:Cr; mmol:mmol) was calculated from a midstream urine sample. Ocular parameters were measured as part of a comprehensive eye examination, and glaucoma case ascertainment was through a combination of self-report and linked national hospital records. Genetic susceptibility to glaucoma was calculated based on a glaucoma polygenic risk score comprising 2673 common genetic variants. Multivariable linear and logistic regression, adjusted for key sociodemographic, medical, anthropometric, and lifestyle factors, were used to model associations and gene-environment interactions. MAIN OUTCOME MEASURES: Corneal-compensated IOP, OCT derived macular retinal nerve fiber layer and ganglion cell-inner plexiform layer (GCIPL) thickness, and prevalent glaucoma. RESULTS: In maximally adjusted regression models, a 1 standard deviation increase in UNa:Cr was associated with higher IOP (0.14 mmHg; 95% confidence interval [CI], 0.12-0.17; P < 0.001) and greater prevalence of glaucoma (odds ratio, 1.11; 95% CI, 1.07-1.14; P < 0.001) but not macular retinal nerve fiber layer or ganglion cell-inner plexiform layer thickness. Compared with those with UNa:Cr in the lowest quintile, those in the highest quintile had significantly higher IOP (0.45 mmHg; 95% CI, 0.36-0.53, P < 0.001) and prevalence of glaucoma (odds ratio, 1.30; 95% CI, 1.17-1.45; P < 0.001). Stronger associations with glaucoma (P interaction = 0.001) were noted in participants with a higher glaucoma polygenic risk score. CONCLUSIONS: Urinary sodium excretion, a biomarker of dietary intake, may represent an important modifiable risk factor for glaucoma, especially in individuals at high underlying genetic risk. These findings warrant further investigation because they may have important clinical and public health implications. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.


Assuntos
Glaucoma , Pressão Intraocular , Sódio , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Transversais , Reino Unido/epidemiologia , Pressão Intraocular/fisiologia , Glaucoma/epidemiologia , Glaucoma/fisiopatologia , Sódio/urina , Fatores de Risco , Idoso , Biomarcadores/urina , Células Ganglionares da Retina/patologia , Fibras Nervosas/patologia , Tomografia de Coerência Óptica/métodos , Vigilância da População
16.
PLoS Comput Biol ; 20(5): e1012072, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38753874

RESUMO

Cells use signaling pathways to sense and respond to their environments. The transforming growth factor-ß (TGF-ß) pathway produces context-specific responses. Here, we combined modeling and experimental analysis to study the dependence of the output of the TGF-ß pathway on the abundance of signaling molecules in the pathway. We showed that the TGF-ß pathway processes the variation of TGF-ß receptor abundance using Liebig's law of the minimum, meaning that the output-modifying factor is the signaling protein that is most limited, to determine signaling responses across cell types and in single cells. We found that the abundance of either the type I (TGFBR1) or type II (TGFBR2) TGF-ß receptor determined the responses of cancer cell lines, such that the receptor with relatively low abundance dictates the response. Furthermore, nuclear SMAD2 signaling correlated with the abundance of TGF-ß receptor in single cells depending on the relative expression levels of TGFBR1 and TGFBR2. A similar control principle could govern the heterogeneity of signaling responses in other signaling pathways.


Assuntos
Transdução de Sinais , Fator de Crescimento Transformador beta , Fator de Crescimento Transformador beta/metabolismo , Humanos , Receptor do Fator de Crescimento Transformador beta Tipo II/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo II/genética , Receptor do Fator de Crescimento Transformador beta Tipo I/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo I/genética , Proteína Smad2/metabolismo , Biologia Computacional , Modelos Biológicos , Linhagem Celular Tumoral , Proteínas Smad/metabolismo , Receptores de Fatores de Crescimento Transformadores beta/metabolismo
17.
Nanoscale Horiz ; 9(7): 1099-1119, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38716614

RESUMO

Gallium-based liquid metals (GaLMs) are promising for a variety of applications-especially as a component material for soft devices-due to their fluidic nature, low toxicity and reactivity, and high electrical and thermal conductivity comparable to solid counterparts. Understanding the interfacial properties and behaviors of GaLMs in different environments is crucial for most applications. When exposed to air or water, GaLMs form a gallium oxide layer with nanoscale thickness. This "oxide nano-skin" passivates the metal surface and allows for the formation of stable microstructures and films despite the high-surface tension of liquid metal. The oxide skin easily adheres to most smooth surfaces. While it enables effective printing and patterning of the GaLMs, it can also make the metals challenging to handle because it adheres to most surfaces. The oxide also affects the interfacial electrical resistance of the metals. Its formation, thickness, and composition can be chemically or electrochemically controlled, altering the physical, chemical, and electrical properties of the metal interface. Without the oxide, GaLMs wet metallic surfaces but do not wet non-metallic substrates such as polymers. The topography of the underlying surface further influences the wetting characteristics of the metals. This review outlines the interfacial attributes of GaLMs in air, water, and other environments and discusses relevant applications based on interfacial engineering. The effect of surface topography on the wetting behaviors of the GaLMs is also discussed. Finally, we suggest important research topics for a better understanding of the GaLMs interface.

18.
J Thromb Haemost ; 22(8): 2261-2269, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38782299

RESUMO

BACKGROUND: Increased risk of venous thromboembolism (VTE) is a life-threatening side effect for users of oral contraceptives (OCs) or hormone therapy (HT). OBJECTIVES: To investigate the potential for genetic predisposition to VTE in OC or HT users, we conducted a gene-by-environment case-only meta-analysis of genome-wide association studies (GWAS). METHODS: Use or nonuse of OCs (7 studies) or HT (8 studies) at the time of the VTE event was determined by pharmacy records or self-report. A synergy index (SI) was modeled for each variant in each study and submultiplicative/supramultiplicative gene-by-environment interactions were estimated. The SI parameters were first meta-analyzed across OC and HT studies and subsequently meta-analyzed to obtain an overall estimate. The primary analysis was agnostic GWAS and interrogated all imputed genotypes using a P value threshold of <5.0 × 10-8; secondary analyses were candidate-based. RESULTS: The VTE case-only OC meta-analysis included 2895 OC users and 6607 nonusers; the case-only HT meta-analysis included 2434 HT users and 12 793 nonusers. In primary GWAS meta-analyses, no variant reached genome-wide significance, but the smallest P value approached statistical significance: rs9386463 (P = 5.03 × 10-8). We tested associations for 138 candidate variants and identified 2 that exceeded statistical significance (0.05/138 = 3.62 × 10-4): F5 rs6025 (P = 1.87 × 10-5; SI, 1.29; previously observed) and F11 rs2036914 (P = 2.0 × 10-4; SI, 0.91; new observation). CONCLUSION: The candidate variant approach to identify submultiplictive/supramultiplicative associations between genetic variation and OC and HT use identified a new association with common genetic variation in F11, while the agnostic interrogations did not yield new discoveries.


Assuntos
Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/genética , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/induzido quimicamente , Feminino , Fatores de Risco , Adulto , Interação Gene-Ambiente , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Medição de Risco , Anticoncepcionais Orais Hormonais/efeitos adversos , Anticoncepcionais Orais Hormonais/administração & dosagem , Variação Genética , Terapia de Reposição de Estrogênios/efeitos adversos
19.
Obstet Gynecol Sci ; 67(4): 343-355, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38817104

RESUMO

Significant progress has been made in the molecular diagnosis of cancer. It provides personalized medicine, including cancer diagnosis, prognosis, targeted therapy, and risk detection. These advances allow physicians to identify patients at risk for cancer before it develops and offer them an opportunity to prevent its development. Mutations in breast cancer susceptibility genes 1 and 2 (BRCA1 and 2) are one of the most well-known cancer-related gene mutations since actor Angelina Jolie shared her experience with genetic mutations and risk-reducing surgery in the media. In Korea, tests for germline BRCA1/2 mutations have been covered by insurance since May 2012 and the number of women of BRCA1/2 mutations has continued to increase over the past decade. Most carriers of BRCA1/2 mutations consider risk-reducing salpingo-oophorectomy (RRSO) resulting in early menopause and want to know the lifetime risks and benefits of RRSO. However, despite the increasing number of carriers of BRCA1/2 mutations, the counseling and management of patients requiring RRSO varies among physicians. This article provides basic knowledge on RRSO to help physicians comprehensively assess its risks and benefits and manage at-risk women.

20.
Int J Biol Macromol ; 268(Pt 1): 131815, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38670192

RESUMO

We report on the extraction of ß-chitin from pens (or Gladius) of Uroteuthis edulis, a squid species prevalent in the Pacific coastal regions of East Asia. In particular, we employ cryogenic mechanical grinding (or cryomilling) as a pre-treatment process for the raw squid pens. We show that the cryomilling step enables an effective pulverization of the raw materials, which facilitates the removal of protein residues allowing the extraction of high-purity ß-chitin with a high acetylation degree (∼97 %) and crystallinity (∼82 %). We also demonstrate that the Uroteuthis edulis extract ß-chitin affords a free-standing film with excellent optical transmittance and mechanical properties.


Assuntos
Quitina , Decapodiformes , Quitina/química , Quitina/isolamento & purificação , Decapodiformes/química , Animais , Acetilação
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