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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 324: 124947, 2025 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-39163769

RESUMO

Plasmonic nanoparticles (NPs) hold considerable potential as photocatalysts owing to their robust light-matter interactions across diverse electromagnetic wavelengths, which significantly influence the photophysical characteristics of the adjacent molecular entities. Despite the widespread use of noble-metal NPs in surface-enhanced Raman scattering (SERS) applications, little is known about the kinetics of nanoparticle aggregation and how it affects their configurations. This study investigates the plasmon-driven photochemical conversion of 4-nitrobenzenethiol (NBT) to 4,4'-dimercaptoazobenzene (DMAB) on Au and Ag nanorods (NRs) through SERS. Significantly, photoconversion phenomena were observed on Ag NRs but not on Au NRs upon laser excitation at 633 nm. Finite-difference time-domain simulations revealed the presence of stronger electromagnetic fields on Ag NRs than on Au NRs. The aspect ratios and gaps between individual NPs in dimer configurations were determined to elucidate their effects on electromagnetic fields. The Ag NR dimer with an end-to-end configuration, an aspect ratio of 3.3, and a 1-nm gap exhibited the highest enhancement factor of 1.05 × 1012. Our results demonstrate that the primary contribution from diverse configurations in NR aggregates is the end-to-end configuration. The proposed NP design with adjustable parameters is expected to advance research in plasmonics, sensing, and wireless communications. These findings also contribute to the understanding of plasmon-driven photochemical processes in metallic nanostructures.

2.
Blood ; 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39226462

RESUMO

Genetic studies have identified numerous regions associated with plasma fibrinogen levels in Europeans, yet missing heritability and limited inclusion of non-Europeans necessitates further studies with improved power and sensitivity. Compared with array-based genotyping, whole genome sequencing (WGS) data provides better coverage of the genome and better representation of non-European variants. To better understand the genetic landscape regulating plasma fibrinogen levels, we meta-analyzed WGS data from the NHLBI's Trans-Omics for Precision Medicine (TOPMed) program (n=32,572), with array-based genotype data from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium (n=131,340) imputed to the TOPMed or Haplotype Reference Consortium panel. We identified 18 loci that have not been identified in prior genetic studies of fibrinogen. Of these, four are driven by common variants of small effect with reported MAF at least 10 percentage points higher in African populations. Three signals (SERPINA1, ZFP36L2, and TLR10) contain predicted deleterious missense variants. Two loci, SOCS3 and HPN, each harbor two conditionally distinct, non-coding variants. The gene region encoding the fibrinogen protein chain subunits (FGG;FGB;FGA), contains 7 distinct signals, including one novel signal driven by rs28577061, a variant common in African ancestry populations but extremely rare in Europeans (MAFAFR=0.180; MAFEUR=0.008). Through phenome-wide association studies in the VA Million Veteran Program, we found associations between fibrinogen polygenic risk scores and thrombotic and inflammatory disease phenotypes, including an association with gout. Our findings demonstrate the utility of WGS to augment genetic discovery in diverse populations and offer new insights for putative mechanisms of fibrinogen regulation.

3.
Clin Nurs Res ; : 10547738241273862, 2024 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-39245928

RESUMO

Neutropenic sepsis (NS) is one of the leading causes of death among patients with hematologic malignancies. Identifying its predictive factors is fundamental for early detection. Few studies have evaluated the predictive factors in relation to microbial infection confirmation, which is clinically important for initiating sepsis treatment. This study aimed to determine whether selected biomarkers (i.e., body temperature, C-reactive protein, albumin, procalcitonin), treatment-related characteristics (i.e., diagnosis, duration of neutropenia, treatment modality), and infection-related characteristics (i.e., infection source, causative organisms) can predict NS in patients with hematologic malignancies. We also aimed to identify the optimal predictive cutoff points for these parameters. This retrospective case-control study used the data from a total of 163 patients (58 in the sepsis group and 105 in the non-sepsis group). We collected data with reference to the day of specimen collection, with which microbial infection was confirmed. Multiple logistic regression was used to determine predictive risk factors and the area under the curve (AUC) of the receiver operating characteristic for the optimal predictive cutoff points. The independent predictors of NS were average body temperature during a fever episode and procalcitonin level. The odds for NS rose by 9.97 times with every 1°C rise in average body temperature (95% confidence interval, CI [1.33, 75.05]) and by 2.09 times with every 1 ng/mL rise in the procalcitonin level (95% CI [1.08, 4.04]). Average body temperature (AUC = 0.77, 95% CI [0.68, 0.87]) and procalcitonin levels (AUC = 0.71, 95% CI [0.59, 0.84]) have fair accuracy for predicting NS, with the optimal cutoff points of 37.9°C and 0.55 ng/mL, respectively. This study found that average body temperature during a fever episode and procalcitonin are useful in predicting NS. Thus, nurses should carefully monitor body temperature and procalcitonin levels in patients with hematologic malignancies to detect the onset of NS.

4.
Elife ; 132024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39269281

RESUMO

We identified a novel mouse plasmacytoid dendritic cell (pDC) lineage derived from the common lymphoid progenitors (CLPs) that is dependent on expression of Bcl11a. These CLP-derived pDCs, which we refer to as 'B-pDCs', have a unique gene expression profile that includes hallmark B cell genes, normally not expressed in conventional pDCs. Despite expressing most classical pDC markers such as SIGLEC-H and PDCA1, B-pDCs lack IFN-α secretion, exhibiting a distinct inflammatory profile. Functionally, B-pDCs induce T cell proliferation more robustly than canonical pDCs following Toll-like receptor 9 (TLR9) engagement. B-pDCs, along with another homogeneous subpopulation of myeloid-derived pDCs, display elevated levels of the cell surface receptor tyrosine kinase AXL, mirroring human AXL+ transitional DCs in function and transcriptional profile. Murine B-pDCs therefore represent a phenotypically and functionally distinct CLP-derived DC lineage specialized in T cell activation and previously not described in mice.


Assuntos
Células Dendríticas , Animais , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Camundongos , Ativação Linfocitária , Linfócitos T/imunologia , Linfócitos T/metabolismo , Camundongos Endogâmicos C57BL , Perfilação da Expressão Gênica , Células Progenitoras Linfoides/metabolismo , Células Progenitoras Linfoides/citologia , Linhagem da Célula
5.
BMJ Open ; 14(9): e083890, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39260841

RESUMO

OBJECTIVES: While older adults showed higher mortality during COVID-19 pandemic, protective behaviours (knowledge regarding coping with COVID-19 symptoms and preventive behaviours) were highlighted to be important to prevent the spread of infection. This study aimed to identify individual and community-level variables influencing deficient knowledge regarding coping with COVID-19 and not-practicing COVID-19 of older adults during the pandemic. DESIGN: This is a secondary analysis of a cross-sectional study using the 2020 Korea Community Health Survey (KCHS). SETTING: 255 community public health centres nationwide, South Korea. METHODS AND ANALYSIS: Using 2020 KCHS data, multilevel logistic regression analysis was conducted on 55 005 adults aged 65 years or older. RESULTS: Older adults who reside alone, as opposed to with their spouse and who lack the support of another individual exhibited insufficient COVID-19 coping-related knowledge (OR: 1.142, p<0.001) and poor preventive behaviours (OR: 1.177, p<0.001). Furthermore, lower municipal social welfare budget levels were associated with worse health behaviours (OR: 0.062, p<0.001). Specifically, older adults living in rural areas were less likely to engage in COVID-19 preventive behaviours compared with those in urban areas (OR: 1.247, p<0.001). Additionally, the effectiveness of mass media as a motivating factor for adopting preventive measures was only significant in rural populations (OR: 0.944, p<0.05). CONCLUSIONS: Both individual-level and community-level approaches are necessary as an initial response during the pandemic. Since elderly people living alone with low socioeconomic status are vulnerable groups with poor health behaviours, it is helpful to provide social support on how to respond to infectious diseases and manage symptoms. In addition, it is important to expand the municipal social welfare budget to promote health equity between regions through appropriate health behaviour education and the strengthening of public medical services.


Assuntos
COVID-19 , Comportamentos Relacionados com a Saúde , Conhecimentos, Atitudes e Prática em Saúde , Análise Multinível , SARS-CoV-2 , Humanos , COVID-19/prevenção & controle , COVID-19/epidemiologia , Idoso , Masculino , Feminino , Estudos Transversais , República da Coreia/epidemiologia , Idoso de 80 Anos ou mais , Adaptação Psicológica , Pandemias/prevenção & controle
6.
Front Endocrinol (Lausanne) ; 15: 1424761, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39296715

RESUMO

Introduction: Childhood obesity is a growing global health concern, but few studies have investigated dietary factors specifically related to obesity and abdominal obesity in children and adolescents. Herein, we aimed to identify the dietary factors affecting childhood obesity in Korean children and adolescents. Methods: Data from the Korea National Health and Nutrition Survey (KNHANES) VIII were analyzed using K-means clustering analysis to identify distinct clusters based on nine variables related to dietary habit, nutritional status, and nutritional education. Multiple logistic regression analysis was used to examine the association between incident obesity risk and the different clusters. We enrolled 2,290 participants aged 6-18 years, and separated them into two distinct clusters; Healthy and Unhealthy Dietary Habit Groups, clusters 1 and 2, respectively. Results: Cluster 1 was characterized by a lower obesity prevalence, healthier dietary habits (regular breakfast consumption; fruit and vegetable, reduced total energy, and lower protein and fat intakes), and greater nutritional education than Cluster 2. After adjusting for confounders, compared with Cluster 1, Cluster 2 demonstrated a significantly higher prevalence (OR [95% CI]) of both general and abdominal obesity (1.49 [1.05-2.13], p=0.027 and 1.43 [1.09-1.88], p=0.009). Discussion: Maintaining optimal dietary quality and patterns are crucial to prevent childhood obesity. Further research is warranted to explore specific dietary interventions tailored to different clusters to effectively address childhood obesity.


Assuntos
Comportamento Alimentar , Inquéritos Nutricionais , Obesidade Abdominal , Obesidade Infantil , Humanos , Adolescente , Criança , Masculino , Feminino , República da Coreia/epidemiologia , Obesidade Abdominal/epidemiologia , Análise por Conglomerados , Obesidade Infantil/epidemiologia , Prevalência , Dieta , Estado Nutricional , Estudos Transversais
7.
Front Nutr ; 11: 1463502, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39296514

RESUMO

Introduction: Emerging evidence highlights the potential advantages of the Mediterranean diet (MD) in preserving kidney function and slowing chronic kidney disease (CKD) progression. However, interventional studies on the MD are scarce in East Asian populations. Methods: This randomized crossover trial aimed to assess the safety and short-term impact of the Mediterranean Proper Optimal Balance (MEDi-POB) diet in Korean patients with stage 3-4 CKD. Kidney function was assessed using the estimated glomerular filtration rate, which was calculated using the CKD Epidemiology Collaboration equation. Fifty patients with CKD were randomly assigned to two groups, each starting with a different 4-week intervention, followed by a 4-week washout period, followed by a switch to the other 4-week intervention. During the MEDi-POB intervention, patients received home delivery of meals twice daily, 5 days a week, while the control intervention comprised a conventional diet. Forty-six patients successfully completed the entire 12-week trial. Paired t-tests were conducted to assess mean differences between the two groups. A linear mixed model was used to adjust for sequence and period. Results: Dietary fat, fiber, and niacin intake were significantly higher following the MEDi-POB diet than following the control diet (p = 0.001 for fat, p < 0.001 for fiber, and p = 0.007 for niacin). The MEDi-POB diet also yielded slightly increased total CO2 levels (p = 0.043), indicating effective management of metabolic acidosis. Conversely, sodium and copper intake were significantly lower with the MEDi-POB diet (p = 0.032 and p = 0.037, respectively). Caloric intake increased, but body mass index slightly decreased from baseline after consuming the MEDi-POB diet. Dietary potassium intake exhibited a non-significant increase (p = 0.053), and no significant changes in serum (p = 0.883) and urine potassium levels (p = 0.087) occurred. Kidney function remained well-preserved following the MEDi-POB diet. Conclusion: These results indicate that the MEDi-POB diet is safe even in patients with advanced CKD, as it does not adversely affect serum and urine potassium levels and helps maintain kidney function.

8.
PLoS One ; 19(9): e0309011, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39231172

RESUMO

PURPOSE: To represent 24-2 visual field (VF) losses of individual patients using a hybrid approach of archetypal analysis (AA) and fuzzy c-means (FCM) clustering. METHODS: In this multicenter retrospective study, we classified characteristic patterns of 24-2 VF using AA and decomposed them with FCM clustering. We predicted the change in mean deviation (MD) through supervised machine learning from decomposition coefficient change. In addition, we compared the areas under the receiver operating characteristic curves (AUCs) of the decomposition coefficient slopes to detect VF progression using three criteria: MD slope, Visual Field Index slope, and pointwise linear regression analysis. RESULTS: We identified 16 characteristic patterns (archetypes or ATs) of 24-2 VF from 132,938 VFs of 18,033 participants using AA. The hybrid approach using FCM revealed a lower mean squared error and greater correlation coefficient than the AA single approach for predicting MD change (all P ≤ 0.001). Three of 16 AUCs of the FCM decomposition coefficient slopes outperformed the AA decomposition coefficient slopes in detecting VF progression for all three criteria (AT5, superior altitudinal defect; AT10, double arcuate defect; AT13, total loss) (all P ≤ 0.028). CONCLUSION: A hybrid approach combining AA and FCM to analyze 24-2 VF can visualize VF tests in characteristic patterns and enhance detection of VF progression with lossless decomposition.


Assuntos
Progressão da Doença , Glaucoma , Campos Visuais , Humanos , Campos Visuais/fisiologia , Estudos Retrospectivos , Feminino , Masculino , Glaucoma/diagnóstico , Glaucoma/fisiopatologia , Pessoa de Meia-Idade , Lógica Fuzzy , Análise por Conglomerados , Testes de Campo Visual/métodos , Idoso , Curva ROC , Área Sob a Curva
9.
J Integr Med ; 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39153935

RESUMO

OBJECTIVE: This study investigated the clinical details and usage of Sa-am acupuncture in Korean medicine clinics and explored how practicing Korean medicine doctors (KMDs) think about Sa-am acupuncture. METHODS: We conducted a questionnaire-based survey of KMDs who utilize Sa-am acupuncture in their practice. The study comprehensively investigated issues related to clinical application of Sa-am acupuncture, needling techniques used during treatment, training methods, and directions for its future improvement. RESULTS: We analyzed 572 responses. An average of 50% of the patients visiting Korean medicine clinics were receiving Sa-am acupuncture. The most prevalent indication for Sa-am acupuncture use was digestive disorders. The patients' appetite level and digestive function were most frequently used indicators for selecting acupuncture points. Regarding prescription compositions, Jung-Gyuk formulas were more frequently used than Seung-Gyuk formulas. Inserting the needle along the flow of the channel or against the flow of the channel was most popular. The acupuncture style most frequently used in combination with Sa-am acupuncture was Ashi point acupuncture. Strengths of Sa-am acupuncture included its versatility, easy application, and good outcomes. Limitations included the lack of rigorous education and training programs, difficulty in applying the principles for beginners, and insufficient clinical research evidence. CONCLUSION: In clinics where Sa-am acupuncture is available, KMDs were providing Sa-am acupuncture to about half of their patients. Practitioners were not using all of the tonification and sedation techniques which may be due to time constraints or simply a lack of necessity. Sa-am acupuncture demonstrated high utility in clinical practice and high satisfaction based on the efficacy and safety. More training programs and high-quality research are needed to help expand the use of Sa-am acupuncture. Please cite this article as: Park JY, Lee YS, Park HJ, Lee SK, Lee JW, Kim SY. A survey on the real-world clinical utilization of a traditional acupuncture in Republic of Korea: Sa-am acupuncture. J Integr Med. 2024; Epub ahead of print.

10.
Curr Sleep Med Rep ; 10(2): 232-256, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39156226

RESUMO

Purpose of Review: Insomnia is the most common sleep disorder experienced by older adults. There is a wide range of pharmacological and non-pharmacological treatment options in existing literature. The purpose of this systematic review was to synthesize randomized controlled trials of insomnia treatment modalities for adults aged 55 and older over the last 5 years. We searched four databases, and after screening, there were 34 full-text manuscripts that met the inclusion/exclusion criteria. Recent Findings: We found non-pharmacological interventions, including exercise and behavioral/psychoeducational therapies, remain effective and favorable. Complementary and alternative therapies ranged across studies and warrant further testing in larger, more diverse samples. Dual orexin receptor antagonist medications were tested in a few studies with positive benefits for sleep and minimal side effects. Finally, measures of insomnia/sleep disturbance outcomes varied among the studies, with the Pittsburgh Sleep Quality Index being used most frequently. Summary: Non-pharmacological interventions for insomnia in older adults are effective, and some newer medications may be safer, with less side effects, at managing insomnia in this population.

11.
Comput Biol Med ; 180: 108906, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39089110

RESUMO

We propose on/offline hard example mining (HEM) techniques to alleviate the degradation of the generalization performance in the sparse distribution of events in non-relevant segment (NRS) recognition and to examine their utility for long-duration surgery. Through on/offline HEM, higher recognition performance can be achieved by extracting hard examples that help train NRS events, for a given training dataset. Furthermore, we provide two performance measurement metrics to quantitatively evaluate NRS recognition in the clinical field. The existing precision and recall-based performance measurement method provides accurate quantitative statistics. However, it is not an efficient evaluation metric in tasks where false positive recognition errors are fatal, such as NRS recognition. We measured the false discovery rate (FDR) and threat score (TS) to provide quantitative values that meet the needs of the clinical setting. Finally, unlike previous studies, the utility of NRS recognition was improved by applying our model to long-duration surgeries, instead of short-length surgical operations such as cholecystectomy. In addition, the proposed training methodology was applied to robotic and laparoscopic surgery datasets to verify that it can be robustly applied to various clinical environments.


Assuntos
Mineração de Dados , Humanos , Mineração de Dados/métodos , Algoritmos
12.
Clin Nutr ESPEN ; 63: 805-812, 2024 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-39159831

RESUMO

BACKGROUND & AIMS: The effect of dietary macronutrient balance on longevity and metabolic health remains a subject of considerable interest. We aimed to investigate the association of carbohydrate-to-protein and carbohydrate-to-fat ratios with all-cause and cardiovascular mortalities. METHODS: In this population-based study, data from the Korean Genome and Epidemiology Study were integrated with those from national data sources, including mortality records from the Korea National Statistical Office. The primary outcomes were all-cause and cardiovascular mortalities. Carbohydrate-to-protein and carbohydrate-to-fat ratios were evaluated based on dietary habits assessed through a food frequency questionnaire. Harrell's C-index was employed to determine optimal cut-off points for carbohydrate-to-protein and carbohydrate-to-fat ratios. Cox proportional hazards regression models were used to assess associations. RESULTS: A total of 143,050 participants aged ≥40 years were included in the analyses. Compared with individuals with non-elevated carbohydrate-to-protein ratios (<5.2), those with elevated carbohydrate-to-protein ratios (>9.9) exhibited a higher all-cause mortality (hazard ratio 1.09, 95% confidence interval 1.01-1.17); however, no correlation between carbohydrate-to-protein ratio and cardiovascular mortality (hazard ratio 1.13, 95% confidence interval 0.96-1.32) was observed. Compared with those with non-elevated carbohydrate-to-fat ratios (<5.1), those with higher carbohydrate-to-fat ratios (>7.1) exhibited increased all-cause (hazard ratio 1.08, 95% confidence interval 1.00-1.16) and cardiovascular (hazard ratio 1.27, 95% confidence interval 1.06-1.52) mortalities. CONCLUSIONS: Our findings regarding macronutrient ratios and their association with mortality suggest that reducing excessive carbohydrate intake and increasing the consumption of protein and fats may have beneficial effects on longevity and cardiovascular health. Further studies are needed to understand the underlying mechanisms of these effects.

13.
Nutrients ; 16(16)2024 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-39203890

RESUMO

Proper nutrition during childhood is crucial for preventing chronic diseases and ensuring optimal growth. This study aimed to develop and validate the Korean version of the KIDMED (K-KIDMED) questionnaire to accurately measure Mediterranean diet (MD) adherence among Korean children and adolescents. A total of 226 parents, representing their children and adolescents, completed the K-KIDMED, a 112-item food frequency questionnaire (FFQ), and a 24-h dietary recall method through an anonymous online survey. The K-KIDMED comprised 11 questions, with five excluded from the original scoring as they did not apply to the FFQ. Scores were categorized into three levels of adherence to the MD: low (1 or less), average (2-4), and good (5 or more). The agreement between total MD scores from the Korean version of the Mediterranean diet adherence screener and the FFQ was moderate (intraclass correlation coefficient = 0.455, 95% confidence interval: 0.346, 0.553). Among the 226 children and adolescents, 36.7% had low adherence to the KIDMED, 43.3% had intermediate adherence, and 19.9% had good adherence. Higher K-KIDMED scores were correlated with greater intakes of fiber, vitamin K, vitamin B6, and potassium (all p < 0.05). We developed the K-KIDMED as a valid tool to assess MD adherence in Korean children and adolescents.


Assuntos
Dieta Mediterrânea , Humanos , Dieta Mediterrânea/estatística & dados numéricos , Feminino , Masculino , Adolescente , Criança , República da Coreia , Inquéritos e Questionários , Reprodutibilidade dos Testes , Cooperação do Paciente/estatística & dados numéricos , Inquéritos sobre Dietas , Comportamento Alimentar
14.
J Neuroinflammation ; 21(1): 196, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39107821

RESUMO

Multinucleated microglia have been observed in contexts associated with infection, inflammation, and aging. Though commonly linked to pathological conditions, the larger cell size of multinucleated microglia might enhance their phagocytic functions, potentially aiding in the clearance of brain debris and suggesting a reassessment of their pathological significance. To assess the phagocytic capacity of multinucleated microglia and its implications for brain debris clearance, we induced their formation by inhibiting Pyk2 activity using the pharmacological inhibitor PF-431396, which triggers cytokinesis regression. Multinucleated microglia demonstrate enhanced phagocytic function, as evidenced by their increased capacity to engulf ß-amyloid (Aß) oligomers. Concurrently, the phosphorylation of Pyk2, induced by Aß peptide, was diminished upon treatment with a Pyk2 inhibitor (Pyk2-Inh, PF-431396). Furthermore, the increased expression of Lamp1, a lysosomal marker, with Pyk2-inh treatment, suggests an enhancement in proteolytic activity. In vivo, we generated an acute Alzheimer's disease (AD) model by infusing Aß into the brains of Iba-1 EGFP transgenic (Tg) mice. The administration of the Pyk2-Inh led to an increased migration of microglia toward amyloid deposits in the brains of Iba-1 EGFP Tg mice, accompanied by morphological activation, suggesting a heightened affinity for Aß. In human microglia, lipopolysaccharide (LPS)-induced inflammatory responses showed that inhibition of Pyk2 signaling significantly reduced the transcription and protein expression of pro-inflammatory markers. These results suggest that Pyk2 inhibition can modulate microglial functions, potentially reducing neuroinflammation and aiding in the clearance of neurodegenerative disease markers. This highlights Pyk2 as a promising target for therapeutic intervention in neurodegenerative diseases.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Modelos Animais de Doenças , Quinase 2 de Adesão Focal , Camundongos Transgênicos , Microglia , Fagocitose , Quinase 2 de Adesão Focal/metabolismo , Quinase 2 de Adesão Focal/antagonistas & inibidores , Animais , Peptídeos beta-Amiloides/metabolismo , Microglia/efeitos dos fármacos , Microglia/metabolismo , Camundongos , Fagocitose/efeitos dos fármacos , Fagocitose/fisiologia , Doença de Alzheimer/patologia , Doença de Alzheimer/metabolismo , Humanos , Camundongos Endogâmicos C57BL
15.
Adv Ther ; 41(8): 3426-3436, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38976126

RESUMO

INTRODUCTION: SB11 (Byooviz™; Samsung Bioepis Co., Ltd.) is a ranibizumab (Lucentis®; Genentech, Inc.) biosimilar targeting vascular endothelial growth factor A for the treatment of retinal diseases. The pre-filled syringe (PFS) presentation of SB11 offers an alternative administration method to the vial, with the potential for enhanced safety and efficient syringe preparation. The objective of this study was to assess the ability of healthcare professionals (HCPs) to follow the instructions for use to prepare and administer SB11 PFS intravitreal (IVT) injections to patients with neovascular age-related macular degeneration (nAMD) or macular edema secondary to retinal vein occlusion (RVO). METHODS: This study was an open-label, single-arm, single-dose clinical study to evaluate the usability of the SB11 PFS in patients with nAMD or macular edema secondary to RVO. Four HCPs prepared and administered 0.5 mg SB11 PFS IVT injections to 34 patients. Product use task completion (12 tasks in total) was assessed by independent observers. Safety was assessed up to 7 days after injection of the investigational product. RESULTS: A total of 34 patients were enrolled and completed the study. All 12 tasks were successfully completed in 34 (100%) patients without a use-related failure. Most patients (32 patients, 94.1%) experienced no adverse events (AEs), whereas 2 (5.9%) patients experienced three treatment-emergent AEs (TEAEs) which were mild to moderate in severity. There were no severe or serious TEAEs reported during the study. CONCLUSIONS: This study showed that HCPs were able to successfully prepare and administer the SB11 PFS via IVT injection. No unexpected safety issues were identified. The SB11 PFS is a promising alternative for therapeutic administration of SB11 in patients with retinal disease. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT06176963; EudraCT number 2021-003566-12.


Assuntos
Injeções Intravítreas , Edema Macular , Ranibizumab , Oclusão da Veia Retiniana , Seringas , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/uso terapêutico , Inibidores da Angiogênese/efeitos adversos , Medicamentos Biossimilares/uso terapêutico , Medicamentos Biossimilares/administração & dosagem , Degeneração Macular/tratamento farmacológico , Degeneração Macular/complicações , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Ranibizumab/administração & dosagem , Ranibizumab/uso terapêutico , Doenças Retinianas/tratamento farmacológico , Oclusão da Veia Retiniana/tratamento farmacológico , Oclusão da Veia Retiniana/complicações
16.
J Cell Sci ; 137(20)2024 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-38962997

RESUMO

Lipid droplets (LDs) are organelles that are central to lipid and energy homeostasis across all eukaryotes. In the malaria-causing parasite Plasmodium falciparum the roles of LDs in lipid acquisition from its host cells and their metabolism are poorly understood, despite the high demand for lipids in parasite membrane synthesis. We systematically characterised LD size, composition and dynamics across the disease-causing blood infection. Applying split fluorescence emission analysis and three-dimensional (3D) focused ion beam-scanning electron microscopy (FIB-SEM), we observed a decrease in LD size in late schizont stages. LD contraction likely signifies a switch from lipid accumulation to lipid utilisation in preparation for parasite egress from host red blood cells. We demonstrate connections between LDs and several parasite organelles, pointing to potential functional interactions. Chemical inhibition of triacylglyerol (TAG) synthesis or breakdown revealed essential LD functions for schizogony and in counteracting lipid toxicity. The dynamics of lipid synthesis, storage and utilisation in P. falciparum LDs might provide a target for new anti-malarial intervention strategies.


Assuntos
Eritrócitos , Gotículas Lipídicas , Malária Falciparum , Plasmodium falciparum , Plasmodium falciparum/metabolismo , Gotículas Lipídicas/metabolismo , Humanos , Malária Falciparum/parasitologia , Malária Falciparum/metabolismo , Eritrócitos/parasitologia , Eritrócitos/metabolismo , Metabolismo dos Lipídeos , Triglicerídeos/metabolismo
17.
Small ; : e2402988, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38982943

RESUMO

Zero-excess Li-metal batteries (ZE-LMBs) have emerged as the ultimate battery platform, offering an exceptionally high energy density. However, the absence of Li-hosting materials results in uncontrolled dendritic Li deposition on the Cu current collector, leading to chronic loss of Li inventory and severe electrolyte decomposition, limiting its full utilization upon cycling. This study presents the application of ultrathin (≈50 nm) coatings comprising six metallic layers (Cu, Ag, Au, Pt, W, and Fe) on Cu substrates in order to provide insights into the design of Li-depositing current collectors for stable ZE-LMB operation. In contrast to non-alloy Cu, W, and Fe coatings, Ag, Au, and Pt coatings can enhance surface lithiophilicity, effectively suppressing Li dendrite growth, thereby improving Li reversibility. Considering the distinct Li-alloying behaviors, particularly solid-solution and/or intermetallic phase formation, Pt-coated Cu current collectors maintain surface lithiophilicity over repeated Li plating/stripping cycles by preserving the original coating layer, thereby attaining better cycling performance of ZE-LMBs. This highlights the importance of selecting suitable Li-alloy metals to sustain surface lithiophilicity throughout cycling to regulate dendrite-less Li plating and improve the electrochemical stability of ZE-LMBs.

18.
Cells ; 13(13)2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38994939

RESUMO

The increasing burden of Alzheimer's disease (AD) emphasizes the need for effective diagnostic and therapeutic strategies. Despite available treatments targeting amyloid beta (Aß) plaques, disease-modifying therapies remain elusive. Early detection of mild cognitive impairment (MCI) patients at risk for AD conversion is crucial, especially with anti-Aß therapy. While plasma biomarkers hold promise in differentiating AD from MCI, evidence on predicting cognitive decline is lacking. This study's objectives were to evaluate whether plasma protein biomarkers could predict both cognitive decline in non-demented individuals and the conversion to AD in patients with MCI. This study was conducted as part of the Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD), a prospective, community-based cohort. Participants were based on plasma biomarker availability and clinical diagnosis at baseline. The study included MCI (n = 50), MCI-to-AD (n = 21), and cognitively unimpaired (CU, n = 40) participants. Baseline plasma concentrations of six proteins-total tau (tTau), phosphorylated tau at residue 181 (pTau181), amyloid beta 42 (Aß42), amyloid beta 40 (Aß40), neurofilament light chain (NFL), and glial fibrillary acidic protein (GFAP)-along with three derivative ratios (pTau181/tTau, Aß42/Aß40, pTau181/Aß42) were analyzed to predict cognitive decline over a six-year follow-up period. Baseline protein biomarkers were stratified into tertiles (low, intermediate, and high) and analyzed using a linear mixed model (LMM) to predict longitudinal cognitive changes. In addition, Kaplan-Meier analysis was performed to discern whether protein biomarkers could predict AD conversion in the MCI subgroup. This prospective cohort study revealed that plasma NFL may predict longitudinal declines in Mini-Mental State Examination (MMSE) scores. In participants categorized as amyloid positive, the NFL biomarker demonstrated predictive performance for both MMSE and total scores of the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet (CERAD-TS) longitudinally. Additionally, as a baseline predictor, GFAP exhibited a significant association with cross-sectional cognitive impairment in the CERAD-TS measure, particularly in amyloid positive participants. Kaplan-Meier curve analysis indicated predictive performance of NFL, GFAP, tTau, and Aß42/Aß40 on MCI-to-AD conversion. This study suggests that plasma GFAP in non-demented participants may reflect baseline cross-sectional CERAD-TS scores, a measure of global cognitive function. Conversely, plasma NFL may predict longitudinal decline in MMSE and CERAD-TS scores in participants categorized as amyloid positive. Kaplan-Meier curve analysis suggests that NFL, GFAP, tTau, and Aß42/Aß40 are potentially robust predictors of future AD conversion.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Biomarcadores , Disfunção Cognitiva , Proteínas tau , Humanos , Disfunção Cognitiva/sangue , Disfunção Cognitiva/diagnóstico , Biomarcadores/sangue , Doença de Alzheimer/sangue , Doença de Alzheimer/diagnóstico , Masculino , Feminino , Idoso , Estudos Longitudinais , Peptídeos beta-Amiloides/sangue , Proteínas tau/sangue , Pessoa de Meia-Idade , Progressão da Doença , Proteínas de Neurofilamentos/sangue , Proteína Glial Fibrilar Ácida/sangue , Estudos Prospectivos
19.
J Transl Med ; 22(1): 591, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918799

RESUMO

BACKGROUNDS: Metabolic dysfunction-associated steatotic liver disease (MASLD) has gained attention owing to its severe complications. This study aimed to explore the interaction between Mediterranean-diet (MD) adherence, genetic factors, and MASLD risk in a Korean population. METHODS: In total, 33,133 individuals aged 40 years and older from the Korean Genome and Epidemiology Study (KoGES) were analyzed. Participants were assessed for MASLD based on criteria and MD adherence measured by the Korean version of the Mediterranean-Diet Adherence Screener (K-MEDAS). Individuals were categorized into two groups based on their MD adherence: high adherence (K-MEDAS > 6) and low adherence (K-MEDAS < 5). Single nucleotide polymorphism (SNP) genotypes were obtained using the Korea Biobank array. Logistic regression was used to examine the single-marker variants for genetic associations with MASLD prevalence. RESULTS: Individuals were categorized into MASLD (10,018 [30.2%]) and non-MASLD (23,115 [69.8%]) groups. A significant interaction was observed between the rs780094 glucokinase regulatory protein (GCKR) gene and K-MEDAS on MASLD (p < 10 - 2 ). Of individuals with K-MEDAS > 6, those carrying the minor allele (C) of the GCKR gene rs780094 exhibited a lower risk of MASLD compared to those without the allele (odds ratio [OR] = 0.88 [0.85-0.91], p-value = 5.54e-13). CONCLUSION: The study identified a significant interaction involving the rs780094 variant near the GCKR gene, with carriers of the minor allele exhibiting a lower MASLD risk among those adhering well to the MD. Dietary habits influence the MASLD risk associated with the rs780094 allele, emphasizing the need for personalized nutrition recommendations.


Assuntos
Dieta Mediterrânea , Cooperação do Paciente , Polimorfismo de Nucleotídeo Único , Humanos , Masculino , Feminino , República da Coreia/epidemiologia , Polimorfismo de Nucleotídeo Único/genética , Pessoa de Meia-Idade , Fatores de Risco , Fígado Gorduroso/genética , Predisposição Genética para Doença , Adulto , Proteínas Adaptadoras de Transdução de Sinal/genética , Idoso , Doenças Metabólicas/genética , Doenças Metabólicas/epidemiologia
20.
Artigo em Inglês | MEDLINE | ID: mdl-38864988

RESUMO

OBJECTIVES: A country's social welfare system may play an important role in maternal employment. This study compared the labor market participation of mothers of children within the United States (U.S.) and Norway to examine whether the child's age and severity of the ASD affected mothers' employment differently between the two countries. METHODS: The 2019 National Survey of Children's Health was used for the U.S. analysis, and the 2019 administrative register data were used for the Norwegian analysis. A logit model was used to analyze the impact of a child's age and ASD severity on maternal employment in the U.S. and Norway. We presented the results as average marginal effects obtained from the logistic regression analyses. RESULTS: After adjusting for mothers' sociodemographic variables and the child's age, U.S. mothers of children with mild ASD and moderate/severe ASD had respectively 12 and 25% points lower probability of being employed than U.S. mothers of children without special health care needs. In Norway, mothers of children with moderate/severe ASD had a 13% points lower probability of employment than mothers without special health care needs. The probability of being employed for mothers caring for a child with ASD was significantly greater as the child got older in both countries. CONCLUSIONS FOR PRACTICE: The employment gap was more substantial in the U.S. than in Norway. A general high employment participation rate among women and an elaborated welfare state and policy package seem to benefit employment among mothers of children with ASD in Norway.

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