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1.
Nat Commun ; 15(1): 7147, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39168999

RESUMEN

Integrating tactile feedback through haptic interfaces enhances experiences in virtual and augmented reality. However, electrotactile systems, which stimulate mechanoreceptors directly, often yield inconsistent tactile results due to variations in pressure between the device and the finger. In this study, we present the integration of a transparent electrotactile screen with pressure-sensitive transistors, ensuring highly consistent quantitative haptic sensations. These transistors effectively calibrate tactile variations caused by touch pressure. Additionally, we explore remote-distance tactile stimulations achieved through the interference of electromagnetic waves. We validated tactile perception using somatosensory evoked potentials, monitoring the somatosensory cortex response. Our haptic screen can stimulate diverse electrotactile sensations and demonstrate various tactile patterns, including Morse code and Braille, when integrated with portable smart devices, delivering a more immersive experience. Furthermore, interference of electric fields allows haptic stimulation to facilitate diverse stimulus positioning at lower current densities, extending the reach beyond direct contact with electrodes of our screen.


Asunto(s)
Potenciales Evocados Somatosensoriales , Percepción del Tacto , Tacto , Transistores Electrónicos , Humanos , Potenciales Evocados Somatosensoriales/fisiología , Masculino , Percepción del Tacto/fisiología , Tacto/fisiología , Femenino , Adulto , Corteza Somatosensorial/fisiología , Presión , Dedos/fisiología , Adulto Joven , Mecanorreceptores/fisiología , Retroalimentación Sensorial/fisiología
2.
Contact (Thousand Oaks) ; 7: 25152564231223480, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39108634

RESUMEN

In this News and Views, I discuss our recent publication that established how steroidogenic acute regulatory-related lipid transfer domain-3 (STARD3), a membrane contact protein situated at lysosomal membranes, plays a role in the detoxification of cholesterol hydroperoxide. STARD3's methionine residues can be oxidized to methionine sulfoxide by cholesterol hydroperoxide, after which methionine sulfoxide reductases reduce the methionine sulfoxide residues back to methionine. The reaction also results in the reduction of the cholesterol hydroperoxide to an alcohol. The cyclic oxidation and reduction of methionine residues in STARD3 at membrane contact sites creates a catalytically efficient mechanism for detoxification of cholesterol hydroperoxide during cholesterol transport, thus protecting membrane contact sites and the entire cell against the toxicity of cholesterol hydroperoxide.

3.
Exp Hematol Oncol ; 13(1): 86, 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39160629

RESUMEN

BACKGROUND: Gastric cancer (GC) is a type of cancer with high incidence and mortality rates. Although various chemical interventions are being developed to treat gastric cancer, there is a constant demand for research into new GC treatment targets and modes of action (MOAs) because of the low effectiveness and side effects of current treatments. METHODS: Using the TCGA data portal, we identified EHMT2 overexpression in GC samples. Using RNA-seq and EHMT2-specific siRNA, we investigated the role of EHMT2 in GC cell proliferation and validated its function with two EHMT2-specific inhibitors. Through the application of 3D spheroid culture, patient-derived gastric cancer organoids (PDOs), and an in vivo model, we confirmed the role of EHMT2 in GC cell proliferation. RESULTS: In this study, we found that EHMT2, a histone 3 lysine 9 (H3K9) methyltransferase, is significantly overexpressed in GC patients compared with healthy individuals. Knockdown of EHMT2 with siRNA induced G1 cell cycle arrest and attenuated GC cell proliferation. Furthermore, we confirmed that TP53INP1 induction by EHMT2 knockdown induced cell cycle arrest and inhibited GC cell proliferation. Moreover, specific EHMT2 inhibitors, BIX01294 and UNC0638, induced cell cycle arrest in GC cell lines through TP53INP1 upregulation. The efficacy of EHMT2 inhibition was further confirmed in a 3D spheroid culture system, PDOs, and a xenograft model. CONCLUSIONS: Our findings suggest that EHMT2 is an attractive therapeutic target for GC treatment.

4.
Anim Biosci ; 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39210788

RESUMEN

Objective: The study aimed to improve the efficiency of Leghorn Male Hepatoma (LMH) cells for animal virus vaccine production by transitioning from adherent to suspension culture and evaluating the effects of dextran sulfate (DS) on preventing cell aggregation. The goal was to enhance cell growth, viability, and glucose metabolism and to develop efficient suspension-adapted LMH cells for large-scale vaccine production. Methods: LMH cells previously cultured in an adherent state were transferred to 125 mL Erlenmeyer flasks to conduct suspension culture. Cell culture performance, including cell density, viability, and glucose metabolism, during the cultures was measured, along with an assessment of cell aggregation. Additionally, mRNA expression levels of genes associated with cell adhesion and apoptosis were monitored. Results: DS supplementation in suspension culture enhanced cell viability and growth, with higher cell densities and viabilities compared to control media. Additionally, DS supplementation reduced glucose consumption and waste production, indicating improved metabolic efficiency. DS also delayed cell aggregation, possibly by downregulating integrin expression and promoting anti-apoptotic gene expression. However, even after 2 months, cell aggregation persisted in both control and DS-supplemented cultures, suggesting further optimization is needed for LMH cell adaptation to suspension culture. Conclusion: DS supplementation in LMH cell suspension cultures led to notable improvements in cell growth, viability, and glucose metabolism, while also decreasing the cell aggregation.

5.
ACS Nano ; 18(35): 24364-24378, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39167771

RESUMEN

Cardiovascular disease is a major public health issue, and smart diagnostic approaches play an important role in the analysis of electrocardiograms. Here, we present three-dimensional, soft electrodes of liquid metals that can be conformably attached to the surfaces of the heart and skin for long-term cardiac analysis. The fine micropillar structures of biocompatible liquid metals enable precise targeting to small tissue areas, allowing for spatiotemporal mapping and modulation of cardiac electrical activity with high resolution. The low mechanical modulus of these liquid-metal electrodes not only helps avoid inflammatory responses triggered by modulus mismatch between the tissue and electrodes, but also minimizes pain when embedded in biological tissues such as the skin and heart. Furthermore, in vivo experiments with animal models and human trials demonstrate long-term and accurate monitoring of electrocardiograms over a period of 30 days.


Asunto(s)
Electrodos , Animales , Humanos , Electrocardiografía , Metales/química , Tecnología Inalámbrica , Corazón , Ratas
6.
Nat Commun ; 15(1): 6021, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39019856

RESUMEN

The bioinspired camera, comprising a single lens and a curved image sensor-a photodiode array on a curved surface-, was born of flexible electronics. Its economical build lends itself well to space-constrained machine vision applications. The curved sensor, much akin to the retina, helps image focusing, but the curvature also creates a problem of image distortion, which can undermine machine vision tasks such as object recognition. Here we report an anti-distortion single-lens camera, where 4096 silicon photodiodes arrayed on a curved surface in a nonuniform pattern assimilated to the distorting optics are the key to anti-distortion engineering. That is, the photo-pixel distribution pattern itself is warped in the same manner as images are warped, which correctively reverses distortion. Acquired images feature no appreciable distortion across a 120° horizontal view, as confirmed by their neural-network recognition accuracies. This distortion correction via photo-pixel array reconfiguration is a form of in-sensor computing.

7.
Endocrinol Metab (Seoul) ; 39(3): 521-530, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38858821

RESUMEN

BACKGRUOUND: Aging leads to sarcopenia, which is characterized by reduced muscle mass and strength. Many factors, including altered muscle protein turnover, diminished neuromuscular function, hormonal changes, systemic inflammation, and the structure and composition of muscle fibers, play a crucial role in age-related muscle decline. This study explored differences in muscle fiber types contributing to overall muscle function decline in aging, focusing on individuals with hip fractures from falls. METHODS: A pilot study at Chungnam National University Hospital collected muscle biopsies from hip fracture patients aged 20 to 80 undergoing surgical treatment. Muscle biopsies from the vastus lateralis and gluteus maximus were obtained during hip arthroplasty or internal fixation. Handgrip strength, calf and thigh circumference, and bone mineral density were evaluated in individuals with hip fractures from falls. We analyzed the relationships between each clinical characteristic and muscle fiber type. RESULTS: In total, 26 participants (mean age 67.9 years, 69.2% male) were included in this study. The prevalence of sarcopenia was 53.8%, and that of femoral and lumbar osteoporosis was 19.2% and 11.5%, respectively. Vastus lateralis analysis revealed an age-related decrease in type IIx fibers, a higher proportion of type IIa fibers in women, and an association between handgrip strength and type IIx fibers in men. The gluteus maximus showed no significant correlations with clinical parameters. CONCLUSION: This study identified complex associations between age, sex, handgrip strength, and muscle fiber composition in hip fracture patients, offering insights crucial for targeted interventions combating age-related muscle decline and improving musculoskeletal health.


Asunto(s)
Fracturas de Cadera , Músculo Cuádriceps , Sarcopenia , Humanos , Masculino , Femenino , Anciano , Fracturas de Cadera/patología , Sarcopenia/patología , Músculo Cuádriceps/patología , Persona de Mediana Edad , Proyectos Piloto , Anciano de 80 o más Años , Fuerza de la Mano , Adulto , Densidad Ósea , Fibras Musculares Esqueléticas/patología , Fibras Musculares Esqueléticas/metabolismo , Adulto Joven , Envejecimiento/fisiología , Envejecimiento/patología , Fibras Musculares de Contracción Rápida/patología , Fibras Musculares de Contracción Rápida/metabolismo
8.
Adv Ther ; 41(8): 3119-3137, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38880822

RESUMEN

INTRODUCTION: Several studies have reported that pravastatin can mitigate the progression of kidney disease, but limited evidence exists regarding its effects on kidney function in Asian patients. This multicenter prospective observational study aimed to assess the effect of pravastatin on kidney function in Korean patients with dyslipidemia and type 2 diabetes mellitus (T2DM) in clinical practice. METHODS: This 48-week prospective multicenter study included 2604 of 2997 eligible patients with dyslipidemia and T2DM who had available estimated glomerular filtration rate (eGFR) measurements. The primary endpoint was eGFR percent change at week 24 from baseline. We also assessed secondary endpoints, which included percent changes in eGFR at weeks 12 and 48 from baseline, as well as changes in eGFR, metabolic profiles (lipid and glycemic levels) at 12, 24, and 48 weeks from baseline, and safety. RESULTS: We noted a significant improvement in eGFR, with mean percent changes of 2.5%, 2.5%, and 3.0% at 12, 24, and 48 weeks, respectively (all adjusted p < 0.05). The eGFR percent changes significantly increased in subgroups with baseline eGFR 30-90 mL/min/1.73 m2, glycated hemoglobin (HbA1c) ≥ 7 at baseline, no hypertension history, T2DM duration > 5 years, or previous statin therapy. Lipid profiles were improved and remained stable throughout the study, and interestingly, fasting glucose and HbA1c were improved at 24 weeks. CONCLUSION: Our findings suggest that pravastatin may have potential benefits for improving eGFR in Korean patients with dyslipidemia and T2DM. This could make it a preferable treatment option for patients with reduced kidney function. TRIAL REGISTRATION NUMBER: NCT05107063 submitted October 27, 2021.


Asunto(s)
Diabetes Mellitus Tipo 2 , Dislipidemias , Tasa de Filtración Glomerular , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Pravastatina , Humanos , Pravastatina/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Dislipidemias/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Tasa de Filtración Glomerular/efectos de los fármacos , Estudios Prospectivos , Anciano , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , República de Corea , Adulto , Riñón/efectos de los fármacos , Riñón/fisiopatología
9.
J Mech Behav Biomed Mater ; 155: 106552, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38701678

RESUMEN

This study aimed to evaluate and compare the mechanical properties of dental training teeth with subtractive and additive computer-aided design/computer-aided manufacturing (CAD/CAM) materials used to fabricate dental simulation models. Therefore, the three-axis load generated during cutting movements, including drilling and milling performed using a dental handpiece, was measured and compared. The samples were cut vertically downward by 1.5 mm, horizontally by 6 mm, and vertically upward at a constant speed (1 mm/s), while the rotational speed of the bur was maintained at 200,000 rotations per minute. A three-axis load cell was used to measure the X-, Y-, and Z-axis loads on the specimen. The median value of the X-, Y-, and Z-axis measurements and the resultant load during the vertical-downward, horizontal, and vertical-upward movements were compared using a one-way analysis of variance and Tukey's post hoc test. For vertical downward movement, the drilling force of the dental training teeth was lower than that of Vita Enamic® and similar to that of Lava™ Ultimate. In contrast to subtractive CAD/CAM blocks, the drilling force of the dental training teeth was higher than that of 3D-printed resin blocks. Regarding horizontal movement, the milling force of dental training teeth was lower than that of Vita Enamic®. In contrast, the milling force of Nissin was similar to that of Lava™ Ultimate, while that of Frasaco was lower. Furthermore, compared to additive CAD/CAM blocks, the milling force of the dental training teeth was higher than that of 3D-printed resin blocks. Regarding vertical upward movement, the resultant loads of dental training teeth was lower than that of Vita Enamic®. Similarly, the resultant load of Nissin was similar to that of Lava™ Ultimate, while that of Frasaco was lower. Additionally, compared to additive CAD/CAM blocks, the resultant loads of the dental training teeth were similar to those of the 3D-printed resin blocks.


Asunto(s)
Diseño Asistido por Computadora , Fenómenos Mecánicos , Ensayo de Materiales , Pruebas Mecánicas , Diente/fisiología
10.
bioRxiv ; 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38766211

RESUMEN

Binding of autoantibodies to keratinocyte surface antigens, primarily desmoglein 3 (Dsg3) of the desmosomal complex, leads to the dissociation of cell-cell adhesion in the blistering disorder pemphigus vulgaris (PV). After the initial disassembly of desmosomes, cell-cell adhesions actively remodel in association with the cytoskeleton and focal adhesions. Growing evidence highlights the role of adhesion mechanics and mechanotransduction at cell-cell adhesions in this remodeling process, as their active participation may direct autoimmune pathogenicity. However, a large part of the biophysical transformations after antibody binding remains underexplored. Specifically, it is unclear how tension in desmosomes and cell-cell adhesions changes in response to antibodies, and how the altered tensional states translate to cellular responses. Here, we showed a tension loss at Dsg3 using fluorescence resonance energy transfer (FRET)-based tension sensors, a tension loss at the entire cell-cell adhesion, and a potentially compensatory increase in junctional traction force at cell-extracellular matrix adhesions after PV antibody binding. Further, our data indicate that this tension loss is mediated by the inhibition of RhoA at cell-cell contacts, and the extent of RhoA inhibition may be crucial in determining the severity of pathogenicity among different PV antibodies. More importantly, this tension loss can be partially restored by altering actomyosin based cell contractility. Collectively, these findings provide previously unattainable details in our understanding of the mechanisms that govern cell-cell interactions under physiological and autoimmune conditions, which may open the window to entirely new therapeutics aimed at restoring physiological balance to tension dynamics that regulates the maintenance of cell-cell adhesion.

11.
Sci Rep ; 14(1): 9909, 2024 04 30.
Artículo en Inglés | MEDLINE | ID: mdl-38688952

RESUMEN

Three-dimensional (3D) printing, otherwise known as additive manufacturing in a non-technical context, is becoming increasingly popular in the field of dentistry. As an essential step in the 3D printing process, postwashing with organic solvents can damage the printed resin polymer and possibly pose a risk to human health. The development of water-washable dental resins means that water can be used as a washing agent. However, the effects of washing agents and washing times on the mechanical and biocompatibility properties of water-washable resins remain unclear. This study investigated the impact of different washing agents (water, detergent, and alcohol) and washing time points (5, 10, 20, and 30 min) on the flexural strength, Vickers hardness, surface characterization, degree of conversion, biocompatibility, and monomer elution of 3D printed samples. Using water for long-term washing better preserved the mechanical properties, caused a smooth surface, and improved the degree of conversion, with 20 min of washing with water achieving the same biological performance as organic solvents. Water is an applicable agent option for washing the 3D printing water-washable temporary crown and bridge resin in the postwashing process. This advancement facilitates the development of other water-washable intraoral resins and the optimization of clinical standard washing guidelines.


Asunto(s)
Materiales Biocompatibles , Ensayo de Materiales , Impresión Tridimensional , Agua , Agua/química , Materiales Biocompatibles/química , Ensayo de Materiales/métodos , Humanos , Resinas Sintéticas/química , Dureza , Coronas , Propiedades de Superficie
12.
Plants (Basel) ; 13(5)2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38475583

RESUMEN

A plant factory equipped with artificial lights is a comparatively new concept when growing seed potatoes (Solanum tuberosum L.) for minituber production. The shortage of disease-free potato seed tubers is a key challenge to producing quality potatoes. Quality seed tuber production all year round in a controlled environment under an artificial light condition was the main purpose of this study. The present study was conducted in a plant factory to investigate the effects of distinct spectrum compositions of LEDs on potato tuberization when grown in an aeroponic system. The study was equipped with eight LED light combinations: L1 = red: blue: green (70 + 25 + 5), L2 = red: blue: green (70 + 20 + 10), L3 = red: blue: green (70 + 15 + 15), L4 = red: blue: green (70 + 10 + 20), L5 = red: blue: far-red (70 + 25 + 5), L6 = red: blue: far-red (70 + 20 + 10), L7 = red: blue: far-red (70 + 15 + 15), L8 = red: blue: far-red (70 + 10 + 20), and L9 = natural light with 300 µmol m-2 s-1 of irradiance, 16/8 h day/night, 65% relative humidity, while natural light was used as the control treatment. According to the findings, treatment L4 recorded a higher tuber number (31/plant), tuber size (>3 g); (9.26 ± 3.01), and GA3 content, along with better plant growth characteristics. Moreover, treatment L4 recorded a significantly increased trend in the stem diameter (11.08 ± 0.25), leaf number (25.32 ± 1.2), leaf width (19 ± 0.81), root length (49 ± 2.1), and stolon length (49.62 ± 2.05) compared to the control (L9). However, the L9 treatment showed the best performance in plant fresh weight (67.16 ± 4.06 g) and plant dry weight (4.46 ± 0.08 g). In addition, photosynthetic pigments (Chl a) (0.096 ± 0.00 mg g-1, 0.093 ± 0.00 mg g-1) were found to be the highest in the L1 and L2 treatments, respectively. However, Chl b and TCL recorded the best results in treatment L4. Finally, with consideration of the plant growth and tuber yield performance, treatment L4 was found to have the best spectral composition to grow quality seed potato tubers.

13.
Int J Med Sci ; 21(4): 644-655, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38464836

RESUMEN

Vascular dementia (VD) is the second most prevalent dementia type, with no drugs approved for its treatment. Here, the effects of Banhabaekchulcheonma-Tang (BBCT) on ischemic brain injury and cognitive function impairment were investigated in a bilateral carotid artery stenosis (BCAS) mouse model. Mice were divided into sham-operated, BCAS control, L-BBCT (40 ml/kg), and H-BBCT (80 ml/kg) groups. BBCT's effects were characterized using the Y-maze test, novel object recognition test (NORT), immunofluorescence staining, RNA sequencing, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analyses. The NORT revealed cognitive function improvement in the H-BBCT group, while the Y-maze test revealed no significant difference among the four groups. The CD68+ microglia and GFAP+ astrocyte numbers were reduced in the H-BBCT group. Furthermore, H-BBCT treatment restored the dysregulation of gene expression caused by BCAS. The major BBCT targets were predicted to be cell division cycle protein 20 (CDC20), Epidermal growth factor (EGF), and tumor necrosis factor receptor-associated factor 1 (TRAF1). BBCT regulates the neuroactive ligand-receptor interaction and neuropeptide signaling pathways, as predicted by KEGG and GO analyses, respectively. BBCT significantly improved cognitive impairment in a BCAS mouse model by inhibiting microglial and astrocyte activation and regulating the expression of CDC20, EGF, TRAF1, and key proteins in the neuroactive ligand-receptor interaction and neuropeptide signaling pathways.


Asunto(s)
Lesiones Encefálicas , Isquemia Encefálica , Estenosis Carotídea , Disfunción Cognitiva , Neuropéptidos , Animales , Ratones , Estenosis Carotídea/complicaciones , Estenosis Carotídea/tratamiento farmacológico , Factor de Crecimiento Epidérmico/metabolismo , Ligandos , Factor 1 Asociado a Receptor de TNF/metabolismo , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/etiología , Cognición , Modelos Animales de Enfermedad , Neuropéptidos/metabolismo , Ratones Endogámicos C57BL
14.
Adv Ther ; 41(5): 1967-1982, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38512540

RESUMEN

INTRODUCTION: The TOujeo BEyond glucose control (TOBE) study evaluated clinical outcomes with insulin glargine 300 units/mL (Gla-300) in insulin-naïve Korean people with type 2 diabetes mellitus (T2DM) in a real-world setting. METHODS: This 24-week, prospective, non-interventional, multicenter, open-label, single-arm, observational study included adults aged ≥ 20 years with T2DM suboptimally controlled with oral hypoglycemic agents and/or glucagon-like peptide 1 receptor agonists who require basal insulin. Eligible participants were assigned to either general target glycated hemoglobin (HbA1c < 7%) or individualized target groups as per physician's discretion considering guidelines and participants' characteristics. The primary endpoint was the proportion of participants achieving the HbA1c target (individualized or general) at 24 weeks. RESULTS: Among 369 participants, 19.5% (72/369) of participants achieved the HbA1c target at week 24; 37.5% (33/88) in the individualized and 13.9% (39/281) in the general target group. In both target groups, similar reductions in fasting plasma glucose and body weight were observed, with low incidence of hypoglycemia, and T2DM duration was significantly shorter in participants who did versus those who did not achieve the target HbA1c (individualized target group: 9.6 ± 8.0 versus 13.1 ± 8.4 years, P = 0.0454; general target group: 10.2 ± 8.6 versus 12.8 ± 7.4 years, P = 0.0378). CONCLUSIONS: This study showed that initiation of insulin therapy with Gla-300 in people with T2DM using an individualized approach is more effective in achieving an HbA1c target. Moreover, earlier initiation of insulin therapy in people with suboptimally controlled T2DM may increase the success rate of glycemic control. A graphical abstract is available with this article.


Despite various efforts in managing diabetes, individuals with type 2 diabetes mellitus (T2DM) encounter numerous challenges to achieve good glycemic control. The major cause is failure to initiate insulin therapy in a timely manner, primarily because of the fear of hypoglycemia. Insulin glargine 300 units/mL (Gla-300) has smooth and prolonged activity resulting in stable and sustained glycemic control, thus reducing the risk of hypoglycemia. Studies on efficacy and safety of Gla-300 in various populations have been published globally. However, there are limited real-world studies in Asian populations. This study evaluated effectiveness and safety of Gla-300 in Korean people with T2DM who were not on insulin prior to this study but were taking oral glucose-lowering medications. The participants were assigned to two groups: general glycated hemoglobin (HbA1c) target (HbA1c < 7%) and individualized HbA1c target according to the participant's characteristics. Results showed that Gla-300 helped to achieve the glycemic target more effectively using an individualized approach. In both groups, similar reductions in fasting plasma glucose and body weight were observed, with low incidence of hypoglycemia. People who achieve glycemic target had a shorter duration of T2DM than those who did not achieve their glycemic target. This suggests that earlier insulin initiation may be a better approach and may increase the success rate of insulin therapy.


Asunto(s)
Glucemia , Diabetes Mellitus Tipo 2 , Hemoglobina Glucada , Hipoglucemiantes , Insulina Glargina , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Insulina Glargina/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Hipoglucemiantes/uso terapéutico , Hemoglobina Glucada/análisis , República de Corea , Estudios Prospectivos , Anciano , Glucemia/efectos de los fármacos , Glucemia/análisis , Medicina de Precisión/métodos , Resultado del Tratamiento , Adulto , Hipoglucemia/inducido químicamente
15.
Redox Biol ; 71: 103097, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38442648

RESUMEN

Phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] is implicated in various processes, including hormone-induced signal transduction, endocytosis, and exocytosis in the plasma membrane. However, how H2O2 accumulation regulates the levels of PtdIns(4,5)P2 in the plasma membrane in cells stimulated with epidermal growth factors (EGFs) is not known. We show that a plasma membrane PtdIns(4,5)P2-degrading enzyme, synaptojanin (Synj) phosphatase, is inactivated through oxidation by H2O2. Intriguingly, H2O2 inhibits the 4-phosphatase activity of Synj but not the 5-phosphatase activity. In EGF-activated cells, the oxidation of Synj dual phosphatase is required for the transient increase in the plasma membrane levels of phosphatidylinositol 4-phosphate [PtdIns(4)P], which can control EGF receptor-mediated endocytosis. These results indicate that intracellular H2O2 molecules act as signaling mediators to fine-tune endocytosis by controlling the stability of plasma membrane PtdIns(4)P, an intermediate product of Synj phosphoinositide dual phosphatase.


Asunto(s)
Peróxido de Hidrógeno , Proteínas del Tejido Nervioso , Fosfatidilinositoles , Peróxido de Hidrógeno/metabolismo , Fosfatidilinositol 4,5-Difosfato/metabolismo , Monoéster Fosfórico Hidrolasas/metabolismo , Membrana Celular/metabolismo , Transducción de Señal , Endocitosis
16.
J Chest Surg ; 57(2): 195-204, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38326895

RESUMEN

Background: Extracorporeal membrane oxygenation (ECMO) is an intervention for severe heart and lung failure; however, it poses the risk of complications, including gastrointestinal bleeding (GIB). Comprehensive analyses of GIB in patients undergoing ECMO are limited, and its impact on clinical outcomes remains unclear. Methods: This retrospective study included 484 patients who received venovenous and venoarterial ECMO between January 2015 and December 2022. Data collected included patient characteristics, laboratory results, GIB details, and interventions. Statistical analyses were performed to identify risk factors and assess the outcomes. Results: GIB occurred in 44 of 484 patients (9.1%) who received ECMO. Multivariable analysis revealed that older age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.01-1.06; p=0.0130) and need to change the ECMO mode (OR, 3.74; 95% CI, 1.75-7.96; p=0.0006) were significant risk factors for GIB, whereas no association was found with antiplatelet or systemic anticoagulation therapies during ECMO management. Half of the patients with GIB (22/44, 50%) underwent intervention, with endoscopy as the primary modality (19/22, 86.4%). Patients who underwent ECMO and developed GIB had higher rates of mortality (40/44 [90.9%] vs. 262/440 [59.5%]) and ECMO weaning failure (38/44 [86.4%] vs. 208/440 [47.3%]). Conclusion: GIB in patients undergoing ECMO is associated with adverse outcomes, including increased risks of mortality and weaning failure. Even in seemingly uncomplicated cases, it is crucial to avoid underestimating the significance of GIB.

17.
Front Public Health ; 12: 1250945, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38410670

RESUMEN

Introduction: Low-renin hypertension (LRH) accounts for approximately one-third of patients with hypertension and are more prevalent in women and the older adult population. Previous study has found a link between the renin-angiotensin-aldosterone system (RAAS) and sex hormones. However, there are insufficient data on the relationship between LRH and metabolic or musculoskeletal outcomes in older adults. Methods and materials: Among the 343 participants from a population-based cohort study conducted between May 2018 and August 2019, a total of 256 (86 men older than 50 years and 170 postmenopausal women) were included. The presence of LRH was defined as plasma renin activity (PRA) <1 ng/mL/h and systolic blood pressure (BP) ≥130 or diastolic BP ≥80 mmHg based on the 2017 ACC/AHA guidelines. Individuals with missing data, and those who had used medications that could affect PRA within the past six months were excluded. Bone mineral density (BMD), trabecular bone score (TBS), and appendicular lean mass (ALM) index were assessed using dual-energy X-ray absorptiometry; degraded TBS was defined as partially degraded to degraded levels (≤1.350). Muscle function was assessed according to the Asian Working Group for Sarcopenia guidelines. PRA was measured using radioimmunoassay. Results: The median age was 66 [61-72] years, and the body mass index (BMI) was 24.7 [23.0-26.4] kg/m2. Individuals with LRH, accounting for 34.8%, had lower diabetes mellitus; more dyslipidemia; and poorer muscle function, BMD, and TBS than those in the non-LRH group. In addition, PRA was positively correlated with C-peptide, HOMA-IR, TBS, and ALM index. After adjusting for covariates including age and BMI, LRH was negatively associated with femur neck T-score (adjusted ß = -0.30, 95% CI [-0.55 to -0.05], p = 0.021) and the presence of LRH was significantly associated with degraded TBS in women (adjusted odds ratio = 3.00, 95% CI [1.36-6.58], p = 0.006). Conclusion: Our findings suggest that LRH can influence clinical features and metabolic risk in older adults. Notably, LRH in postmenopausal women was linked to lower femur neck T-scores and degraded TBS, indicating sex-specific effects of LRH on bone health. Larger prospective studies are required to elucidate how changes in the RAAS affect metabolic and musculoskeletal outcomes in older adults.


Asunto(s)
Densidad Ósea , Renina , Masculino , Humanos , Femenino , Anciano , Estudios de Cohortes , Densidad Ósea/fisiología , Absorciometría de Fotón/métodos , República de Corea/epidemiología
18.
Foot Ankle Int ; 45(5): 485-495, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38348624

RESUMEN

BACKGROUND: This study examines the correction of lesser toe valgus deviation following proximal chevron metatarsal osteotomy (PCMO) and Akin osteotomy in moderate to severe hallux valgus patients, while identifying influencing factors. METHOD: Among 89 patients (116 feet), those with moderate to severe hallux valgus underwent PCMO and Akin osteotomy. Radiologic assessments included preoperative metatarsus adductus angle (MAA), hallux valgus angle (HVA), intermetatarsal angle (IMA), valgus angles of the second to fourth metatarsophalangeal joints, and hallux valgus recurrence. Assessments included visual analog scale (VAS) pain scores, American Orthopaedic Foot & Ankle Society (AOFAS) scores, and patient satisfaction over an average follow-up of 30.6 ± 21.2 (range, 12-99) months. RESULTS: The mean preoperative HVA of 34.4 degrees decreased to 8.7 degrees at final follow-up. The valgus angles of the second, third, and fourth toes improved by 37.1%, 27%, and 44.5%, respectively. In metatarsus adductus patients, lesser toe valgus angles were significantly higher both preoperatively and at final follow-up. Hallux valgus recurrence patients had higher preoperative and final follow-up IMA and valgus angles in the second and third toes. Nonrecurrence patients showed greater decreases in these angles. A larger HVA correction corresponded to a greater decrease in lesser toe valgus deviation. VAS and AOFAS scores improved significantly at the last follow-up. CONCLUSION: The study found a significant reduction in the valgus angle of the second, third, and fourth toes after PCMO and Akin osteotomy in moderate to severe hallux valgus cases, without additional surgeries on lesser toes. The lesser toe angular reductions were less pronounced in patients with metatarsus adductus or with hallux valgus recurrence. LEVEL OF EVIDENCE: Level IV, case series.


Asunto(s)
Hallux Valgus , Huesos Metatarsianos , Osteotomía , Humanos , Hallux Valgus/cirugía , Hallux Valgus/diagnóstico por imagen , Hallux Valgus/fisiopatología , Osteotomía/métodos , Huesos Metatarsianos/cirugía , Huesos Metatarsianos/diagnóstico por imagen , Femenino , Masculino , Persona de Mediana Edad , Adulto , Radiografía , Estudios Retrospectivos , Anciano , Satisfacción del Paciente , Articulación Metatarsofalángica/cirugía , Articulación Metatarsofalángica/fisiopatología , Articulación Metatarsofalángica/diagnóstico por imagen , Dedos del Pie/cirugía , Dimensión del Dolor
19.
Lasers Med Sci ; 39(1): 40, 2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38240855

RESUMEN

Laser ablation (LA) has been evaluated for the minimally invasive thermal treatment of various cancers, but conventional unidirectional endoscopic ultrasound (EUS)-guided LA has limitations. Therefore, we developed a cylindrical laser diffuser to overcome the limitations of unidirectional EUS-guided LA. The purpose of this study was to compare the efficacies and safeties of EUS-guided LA using a novel cylindrical laser diffuser and radiofrequency ablation (RFA) in vivo in swine pancreas. EUS-guided RFA (15 W, 30 s, 450 J) and cylindrical interstitial LA (CILA) (5 W, 90 s, 450 J) were applied to normal pancreatic tissue in six anesthetized pigs (three per group). Laboratory tests were performed at baseline, immediately after ablation (day 0), and 2 days after procedures (day 2). Two days after procedures, all pigs were sacrificed, and histopathological safety and efficacy assessments were performed. Technically, EUS-guided RFA and CILA were performed successfully in all cases. No major complications, including perforation or acute pancreatitis, occurred during the experiment in either group. All animals remained in excellent condition throughout the experimental period, and laboratory tests provided no evidence of a major complication. Average necrotic volumes in the RFA and CILA groups were 424.2 mm3 and 3747.4 mm3, respectively, and average necrotic volume was significantly larger in CILA group (p < 0.001). EUS-guided RFA and CILA had acceptable safety profiles in the normal swine pancreas model. Our findings indicate EUS-guided CILA has potential for the effective local treatment of pancreatic cancer as an alternative to EUS-guided RFA.


Asunto(s)
Ablación por Catéter , Terapia por Láser , Pancreatitis , Ablación por Radiofrecuencia , Animales , Porcinos , Enfermedad Aguda , Ablación por Catéter/métodos , Pancreatitis/cirugía , Páncreas/diagnóstico por imagen , Páncreas/cirugía
20.
Hypertension ; 81(3): 604-613, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38174562

RESUMEN

BACKGROUND: Primary aldosteronism (PA) has been broadly dichotomized into unilateral and bilateral forms. Adrenal vein sampling (AVS) lateralization indices (LI) ≥2 to 4 are the standard-of-care to recommend unilateral adrenalectomy for presumed unilateral PA. We aimed to assess the rates and characteristics of residual PA after AVS-guided adrenalectomy. METHODS: We conducted an international, retrospective, cohort study of patients with PA from 7 referral centers who underwent unilateral adrenalectomy based on LI≥4 on baseline and/or cosyntropin-stimulated AVS. Aldosterone synthase (CYP11B2) immunohistochemistry and next generation sequencing were performed on available formalin-fixed paraffin-embedded adrenal tissue. RESULTS: The cohort included 283 patients who underwent AVS-guided adrenalectomy, followed for a median of 326 days postoperatively. Lack of PA cure was observed in 16% of consecutive patients, and in 22 patients with lateralized PA on both baseline and cosyntropin-stimulated AVS. Among patients with residual PA postoperatively, 73% had multiple CYP11B2 positive areas within the resected adrenal tissue (versus 23% in those cured), wherein CACNA1D mutations were most prevalent (63% versus 33% in those cured). In adjusted regression models, independent predictors of postoperative residual PA included Black versus White race (odds ratio, 5.10 [95% CI, 1.45-17.86]), AVS lateralization only at baseline (odds ratio, 8.93 [95% CI 3.00-26.32] versus both at baseline and after cosyntropin stimulation), and CT-AVS disagreement (odds ratio, 2.75 [95% CI, 1.20-6.31]). CONCLUSIONS: Multifocal, asymmetrical bilateral PA is relatively common, and it cannot be excluded by robust AVS lateralization. Long-term postoperative monitoring should be routinely pursued, to identify residual PA and afford timely initiation of targeted medical therapy.


Asunto(s)
Hiperaldosteronismo , Humanos , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/genética , Hiperaldosteronismo/cirugía , Estudios Retrospectivos , Aldosterona , Cosintropina , Estudios de Cohortes , Citocromo P-450 CYP11B2 , Glándulas Suprarrenales/cirugía , Glándulas Suprarrenales/irrigación sanguínea , Adrenalectomía
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