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1.
Nature ; 627(8003): 399-406, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38448581

ABSTRACT

Immune cells rely on transient physical interactions with other immune and non-immune populations to regulate their function1. To study these 'kiss-and-run' interactions directly in vivo, we previously developed LIPSTIC (labelling immune partnerships by SorTagging intercellular contacts)2, an approach that uses enzymatic transfer of a labelled substrate between the molecular partners CD40L and CD40 to label interacting cells. Reliance on this pathway limited the use of LIPSTIC to measuring interactions between CD4+ T helper cells and antigen-presenting cells, however. Here we report the development of a universal version of LIPSTIC (uLIPSTIC), which can record physical interactions both among immune cells and between immune and non-immune populations irrespective of the receptors and ligands involved. We show that uLIPSTIC can be used, among other things, to monitor the priming of CD8+ T cells by dendritic cells, reveal the steady-state cellular partners of regulatory T cells and identify germinal centre-resident T follicular helper cells on the basis of their ability to interact cognately with germinal centre B cells. By coupling uLIPSTIC with single-cell transcriptomics, we build a catalogue of the immune populations that physically interact with intestinal epithelial cells at the steady state and profile the evolution of the interactome of lymphocytic choriomeningitis virus-specific CD8+ T cells in multiple organs following systemic infection. Thus, uLIPSTIC provides a broadly useful technology for measuring and understanding cell-cell interactions across multiple biological systems.


Subject(s)
B-Lymphocytes , CD8-Positive T-Lymphocytes , Cell Communication , Dendritic Cells , Epithelial Cells , T Follicular Helper Cells , T-Lymphocytes, Regulatory , CD8-Positive T-Lymphocytes/cytology , CD8-Positive T-Lymphocytes/immunology , Cell Communication/immunology , Dendritic Cells/cytology , Dendritic Cells/immunology , Ligands , T-Lymphocytes, Regulatory/cytology , T-Lymphocytes, Regulatory/immunology , T Follicular Helper Cells/cytology , T Follicular Helper Cells/immunology , B-Lymphocytes/cytology , B-Lymphocytes/immunology , Germinal Center/cytology , Single-Cell Gene Expression Analysis , Epithelial Cells/cytology , Epithelial Cells/immunology , Intestinal Mucosa/cytology , Intestinal Mucosa/immunology , Lymphocytic choriomeningitis virus/immunology , Lymphocytic Choriomeningitis/immunology , Lymphocytic Choriomeningitis/virology , Organ Specificity
2.
Int Ophthalmol ; 44(1): 104, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38378994

ABSTRACT

AIM: To investigate the difference in the initial surgical results between a new monofocal intraocular lens (IOL) with enhanced intermediate vision and the standard monofocal IOL in patients with retinal disease. METHODS: We retrospectively reviewed the medical records of patients with retinal disease who underwent cataract surgery due to accompanying cataracts. Types of retinal diseases were investigated and best-corrected distant visual acuity, distant uncorrected visual acuity (UCVA), intermediate UCVA, near UCVA, and spherical equivalent were recorded at each visit. The surgical results were investigated at 1 day, 1 week, and 1 month after surgery. RESULTS: Seventeen eyes treated with a new monofocal IOL enhanced for intermediate vision (ICB00 group) and 18 eyes treated with the standard monofocal IOL (AAB00 group) were included in this study. There were no significant differences in the baseline characteristics, including the type of underlying retinal disease, between the groups. There were no significant differences between the groups in terms of distant, intermediate, or near UCVA at day 1 and week 1 after surgery. However, at 1 month after surgery, the ICB00 group showed a significantly better intermediate vision improvement than the AAB00 group (p = 0.001). CONCLUSION: Even in patients with cataract accompanied by retinal disease, the use of the ICB00 IOL showed significant improvement in intermediate vision compared to the use of the AAB00 (standard monofocal) IOL. The ICB00 IOL might be a good option for patients with cataract and retinal disease in the era of increased intermediate vision needs in daily life.


Subject(s)
Cataract , Lenses, Intraocular , Phacoemulsification , Retinal Diseases , Humans , Lens Implantation, Intraocular/methods , Retrospective Studies , Cataract/complications , Retinal Diseases/complications , Retinal Diseases/surgery , Prosthesis Design , Phacoemulsification/methods , Patient Satisfaction
3.
Retina ; 44(2): 261-268, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-37782951

ABSTRACT

PURPOSE: To investigate the association between visual outcomes and choroidal changes in patients with macula-off rhegmatogenous retinal detachment. METHODS: This study retrospectively reviewed 63 eyes of patients with macula-off rhegmatogenous retinal detachment who underwent vitrectomy. Their fellow eyes were analyzed as a control group. The choroidal vascularity index (CVI), ellipsoid zone/external limiting membrane integrity, central foveal thickness, and subfoveal choroidal thickness were documented and analyzed. Linear regression analyses were performed to identify factors affecting the final best-corrected visual acuity. RESULTS: Eyes with rhegmatogenous retinal detachment showed increased CVI (68.8 ± 4.1) compared with the control group (66.1 ± 8.8, P = 0.028). Multivariate linear regression analysis revealed that patients with a poor final best-corrected visual acuity had a longer detachment duration ( P = 0.002), worse baseline best-corrected visual acuity ( P = 0.034), thinner central foveal thickness ( P = 0.005), and greater CVI ( P = 0.001) and were more likely to be tamponated with silicone oil ( P = 0.001). Choroidal vascularity index was particularly increased in eyes with poor ellipsoid zone/external limiting membrane integrity, prolonged detachment duration, thin central foveal thickness, and worse best-corrected visual acuity. CONCLUSION: Increased CVI could indicate poor visual outcomes in patients with macula-off rhegmatogenous retinal detachment. Choroidal remodeling could be associated with the disruption of the ellipsoid zone/external limiting membrane integrity.


Subject(s)
Macula Lutea , Retinal Detachment , Humans , Retinal Detachment/diagnosis , Retinal Detachment/surgery , Retrospective Studies , Tomography, Optical Coherence , Visual Acuity , Macula Lutea/surgery , Vitrectomy
4.
J Mech Behav Biomed Mater ; 146: 106077, 2023 10.
Article in English | MEDLINE | ID: mdl-37657297

ABSTRACT

This study presents a stacked autoencoder (SAE)-based assessment method which is one of the unsupervised learning schemes for the investigation of bone fracture. Relatively accurate health monitoring of bone fracture requires considering physical interactions among tissue, muscle, wave propagation and boundary conditions inside the human body. Furthermore, the investigation of fracture, crack and healing process without state-of-the-art medical devices such as CT, X-ray and MRI systems is challenging. To address these issues, this study presents the SAE method that incorporates bilateral symmetry of the human legs and low-frequency transverse vibration. To verify the presented method, several examples are employed with plastic pipes, cadaver legs and human legs. Virtual spectrograms, created by applying a short-time Fourier transform to the differences in vibration responses, are employed for image-based training in SAE. The virtual spectrograms are then classified and the fine-tuning is also carried out to increase the accuracy. Moreover, a confusion matrix is employed to evaluate classification accuracy and training validity.


Subject(s)
Fractures, Bone , Humans , Fractures, Bone/diagnostic imaging , Cadaver , Muscles , Plastics , Vibration
5.
Sci Rep ; 13(1): 5045, 2023 03 28.
Article in English | MEDLINE | ID: mdl-36977729

ABSTRACT

To investigate the changes in outer nuclear layer (ONL) thickness during anti-vascular endothelial growth factor (VEGF) treatment in type 1 choroidal neovascularization (CNV) and its impact on vision. Type 1 CNV eyes (n = 94) were retrospectively compared to normal control eyes (n = 35). Along with best-corrected visual acuity (BCVA), the location of CNV, foveal ONL thickness, and subretinal fluid height were measured using optical coherence tomography (OCT) and analyzed. Visual outcome and OCT biomarkers were compared. As a result, the CNV group had thinner foveal ONL and worse BCVA compared to the control group. ONL thickness recovered partially along with visual improvement following 3 monthly initial loading doses of aflibercept injections, and it correlated with the final BCVA during the 1-year follow-up. Eyes achieved foveal ONL recovery over + 10 µm had lower subfoveal CNV (45.5%) and showed better visual outcomes than eyes with stationary ONL or suboptimal ONL recovery (76.0%, p = 0.012). In conclusion, type 1 CNV eyes that recovered foveal ONL thickness at initial loading of anti-VEGF demonstrated good final visual outcome during the 1-year follow-up. Monitoring the foveal ONL thickness during early anti-VEGF treatment can give information about the visual outcomes in type 1 CNV.


Subject(s)
Choroidal Neovascularization , Macular Degeneration , Humans , Angiogenesis Inhibitors/therapeutic use , Retrospective Studies , Prognosis , Choroidal Neovascularization/diagnostic imaging , Choroidal Neovascularization/drug therapy , Vascular Endothelial Growth Factors , Tomography, Optical Coherence , Macular Degeneration/drug therapy , Intravitreal Injections
6.
Immunity ; 55(12): 2228-2230, 2022 12 13.
Article in English | MEDLINE | ID: mdl-36516817

ABSTRACT

Diverse intestinal components (e.g., gut-associated neurons, immune cells, gut microbes, and epithelium) are intimately intertwined with each other to maintain homeostasis in the gut. In a recent issue of Cell, Zhang et al. (2022) and Yang et al. (2022) present complementary studies uncovering interactions between nociceptor neurons, gut epithelium, and the microbiome to protect intestinal tissue from inflammation.


Subject(s)
Gastrointestinal Microbiome , Goblet Cells , Intestinal Mucosa , Homeostasis , Neurons
7.
J Clin Med ; 11(23)2022 Nov 29.
Article in English | MEDLINE | ID: mdl-36498627

ABSTRACT

Background: The purpose of this study was to investigate the association between responses to intravitreal bevacizumab injection and renal function in diabetic macular edema (DME) patients. Methods: A retrospective study of the medical records of 104 treatment-naïve DME patients who received intravitreal bevacizumab injection (IVBI) was conducted. Based on the estimated glomerular filtration rate (eGFR, mL/min/1.73 m2), the participants were classified into three groups. Intergroup comparisons of the best-corrected visual acuity (BCVA) and central subfield retinal thickness (CST) changes were performed after three-monthly consecutive IVBIs. In the groups with decreased renal function, the response to further treatment with a different drug was investigated. Results: A total of 104 participants were included in the study: 60 participants in the preserved renal function group (eGFR ≥ 60), 25 participants in the moderate chronic kidney disease (CKD) group (30 ≤ eGFR < 60), and 19 participants in the severe CKD group (eGFR < 30). After three-monthly consecutive IVBIs, BCVA (p < 0.001) and CST (p < 0.001) were significantly improved only in the preserved renal function group. Following further treatment of patients with decreased renal function, the treatment results were significantly better in those who were switched to aflibercept or dexamethasone implant than in those who were maintained on IVBI. Conclusions: From this preliminary study, we observed that renal function might affect the response to IVBI treatment in patients with DME. In the case of a poor response to initial IVBI treatment for DME in patients with moderate to severe CKD, our study supports switching to the aflibercept or dexamethasone implant.

8.
Sci Rep ; 12(1): 18637, 2022 11 03.
Article in English | MEDLINE | ID: mdl-36329178

ABSTRACT

Tandem welding is extensively used for welding large structures, such as ships and plants, for increased welding speed and volume. Seam tracking is essential because of a large amount of thermal deformation. However, in tandem welding, arc interference causes current and voltage to vary non-uniformly, leading to difficulties in seam tracking. Therefore, in this study, an optimal signal was identified for seam tracking in tandem welding and evaluated. To select the seam-tracking signal, an algorithm was developed that separates the welding signal into peak, average, and base. Based on the collected data, regression and signal-to-noise ratio analyses were performed to identify a suitable seam-tracking signal. To trace the welding line based on the selected signal, the welding signal was checked by weaving on the V-groove specimen. As a result, the current area difference of the welding signal generated between the left and right parts of the center of the V-groove could be calculated. An algorithm and equipment for seam tracking were constructed using the area difference of the welding current. Finally, the seam tracking system was verified by conducting an actual test using the equipment to which the algorithm was applied.


Subject(s)
Welding , Occupations
9.
J Control Release ; 341: 533-547, 2022 01.
Article in English | MEDLINE | ID: mdl-34902451

ABSTRACT

Herein, entecavir-3-palmitate (EV-P), an ester prodrug of entecavir (EV), was employed as a model drug, and the effect of drug particle size on in vivo pharmacokinetic profiles and local inflammatory responses, and those associations were evaluated following intramuscular (IM) injection. EV-P crystals with different median diameters (0.8, 2.3, 6.3, 15.3 and 22.6 µm) were prepared using the anti-solvent crystallization method, with analogous surface charges (-10.7 ~ -4.7 mV), and crystallinity (melting point, 160-170 °C). EV-P particles showed size-dependent in vitro dissolution profiles under sink conditions, exhibiting a high correlation between the median diameter and Hixon-Crowell's release rate constant (r2 = 0.94). Following IM injection in rats (1.44 mg/kg as EV), the pharmacokinetic profile of EV exhibited marked size-dependency; 0.8 µm-sized EV-P particles about 1.6-, 3.6-, and 5.6-folds higher systemic exposure, compared to 6.3, 15.3, and 22.6 µm-sized particles, respectively. This pharmacokinetic pattern, depending on particle size, was also highly associated with histopathological responses in the injected tissue. The smaller EV-P particles (0.8 or 2.3 µm) imparted the larger inflammatory lesion after 3 days, lower infiltration of inflammatory cells, and thinner fibroblastic bands around depots after 4 weeks. Conversely, severe fibrous isolation with increasing particle size augmented the drug remaining at injection site over 4 weeks, impeding the dissolution and systemic exposure. These findings regarding the effects of formulation variable on the in vivo behaviors of long-acting injectable suspension, provide constructive knowledge toward the improved design in poorly water-soluble compounds.


Subject(s)
Particle Size , Animals , Crystallization , Rats , Solubility , Solvents , Suspensions
10.
Neuron ; 110(2): 266-279.e9, 2022 01 19.
Article in English | MEDLINE | ID: mdl-34687664

ABSTRACT

Thermoregulatory behavior is a basic motivated behavior for body temperature homeostasis. Despite its fundamental importance, a forebrain region or defined neural population required for this process has yet to be established. Here, we show that Vgat-expressing neurons in the lateral hypothalamus (LHVgat neurons) are required for diverse thermoregulatory behaviors. The population activity of LHVgat neurons is increased during thermoregulatory behavior and bidirectionally encodes thermal punishment and reward (P&R). Although this population also regulates feeding and caloric reward, inhibition of parabrachial inputs selectively impaired thermoregulatory behaviors and encoding of thermal stimulus by LHVgat neurons. Furthermore, two-photon calcium imaging revealed a subpopulation of LHVgat neurons bidirectionally encoding thermal P&R, which is engaged during thermoregulatory behavior, but is largely distinct from caloric reward-encoding LHVgat neurons. Our data establish LHVgat neurons as a required neural substrate for behavioral thermoregulation and point to the key role of the thermal P&R-encoding LHVgat subpopulation in thermoregulatory behavior.


Subject(s)
Hypothalamic Area, Lateral , Prosencephalon , Body Temperature Regulation , Hypothalamic Area, Lateral/physiology , Neurons/physiology , Reward
11.
Front Cell Infect Microbiol ; 12: 1035641, 2022.
Article in English | MEDLINE | ID: mdl-36619744

ABSTRACT

Native Hawaiians and Pacific Islanders (NHPIs) suffer from higher prevalence of and mortality to type 2 diabetes mellitus (T2DM) than any other major race/ethnic group in Hawaii. Health inequities in this indigenous population was further exacerbated by the SARS-CoV-2 pandemic. T2DM progression and medical complications exacerbated by COVID-19 are partially regulated by the gut microbiome. However, there is limited understanding of the role of gut bacteria in the context of inflammation-related diseases of health disparities including T2DM and obesity. To address these gaps, we used a community-based research approach from a cohort enriched with NHPI residents on the island of Oahu, Hawaii (N=138). Gut microbiome profiling was achieved via 16s rDNA metagenomic sequencing analysis from stool DNA. Gut bacterial capacity for butyrate-kinase (BUK)-mediated fiber metabolism was assessed using quantitative PCR to measure the abundance of BUK DNA and RNA relative to total bacterial load per stool sample. In our cohort, age positively correlated with hemoglobin A1c (%; R=0.39; P<0.001) and body mass index (BMI; R=0.28; P<0.001). The relative abundance of major gut bacterial phyla significantly varied across age groups, including Bacteroidetes (P<0.001), Actinobacteria (P=0.007), and Proteobacteria (P=0.008). A1c was negatively correlated with the relative levels of BUK DNA copy number (R=-0.17; P=0.071) and gene expression (R=-0.33; P=0.003). Interestingly, we identified specific genera of gut bacteria potentially mediating the effects of diet on metabolic health in this cohort. Additionally, α-diversity among gut bacterial genera significantly varied across T2DM and BMI categories. Together, these results provide insight into age-related differences in gut bacteria that may influence T2DM and obesity in NHPIs. Furthermore, we observed overlapping patterns between gut bacteria and T2DM risk factors, indicating more nuanced, interdependent interactions among these factors as partial determinants of health outcomes. This study adds to the paucity of NHPI-specific data to further elucidate the biological characteristics associated with pre-existing health inequities in this racial/ethnic group that is significantly underrepresented in biomedical research.


Subject(s)
Diabetes Mellitus, Type 2 , Gastrointestinal Microbiome , Obesity , Humans , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/microbiology , Glycated Hemoglobin , Hawaii/epidemiology , Native Hawaiian or Other Pacific Islander , Obesity/epidemiology , Obesity/microbiology
12.
Sci Rep ; 11(1): 18353, 2021 09 15.
Article in English | MEDLINE | ID: mdl-34526548

ABSTRACT

To investigate the visual/anatomical outcome of diabetic macular edema (DME) patients lost to follow-up (LTFU) for more than 1 year during intravitreal anti-VEGF treatment. A retrospective review of 182 treatment-naïve DME patients was performed. Among them, we identified patients LTFU for more than 1 year during anti-VEGF treatment. Visual acuity and anatomic outcomes at the first visit, last visit before being LTFU, return visit, and after re-treatment were analyzed and compared with those of DME patients with regular follow-up. Patients who had continuous follow-up visits were assigned to the control group. Sixty patients (33%) with DME were LTFU for more than 1 year during anti-VEGF treatment. Multivariate analysis revealed that the ratio of male (p = 0.004), diabetes mellitus (DM) duration less than 5 years (p = 0.015), and poor early anatomic response (p = 0.012) were higher compared to the control group. Eighteen patients returned to the clinic and received re-treatment. After re-treatment with anti-VEGF, central subfield thickness (CST) was significantly improved to the CST of before LTFU. However, visual acuity did not recover to the level before LTFU (0.63 ± 0.26 vs. 0.45 ± 0.28, p = 0.003). About thirty percent of DME patients were LTFU for more than 1 year. Permanent visual loss was observed in these LTFU patients. Patients with a high risk of LTFU such as male, early DM, and poor response after initial injections should be treated more aggressively to improve the visual outcomes.


Subject(s)
Diabetic Retinopathy/drug therapy , Lost to Follow-Up , Macular Edema/drug therapy , Aged , Angiogenesis Inhibitors/administration & dosage , Angiogenesis Inhibitors/therapeutic use , Bevacizumab/administration & dosage , Bevacizumab/therapeutic use , Diabetic Retinopathy/epidemiology , Diabetic Retinopathy/pathology , Diabetic Retinopathy/physiopathology , Female , Humans , Macular Edema/epidemiology , Macular Edema/pathology , Macular Edema/physiopathology , Male , Middle Aged , Visual Acuity
13.
J Mech Behav Biomed Mater ; 124: 104801, 2021 12.
Article in English | MEDLINE | ID: mdl-34544018

ABSTRACT

Reliable fracture diagnosis monitoring and analyzing low-frequency transverse vibration data can be achieved through an in-depth understanding of the physical interactions between wave propagation and boundary conditions. The present study aims to investigate the effects of the boundary conditions on the low-frequency structural vibrations of bones. Time-frequency domain analysis of transverse vibration signals depending on the boundary conditions of bones is analyzed and investigated. These studies reveal that the responses of fractured or non-fractured bones are different and influenced by the displacement and force boundary conditions. These relationships can be considered in the development of a smart fracture diagnosis system considering the posture and boundary condition. To validate the present observations, the experiments with artificial specimens and cadaver are carried.


Subject(s)
Fractures, Bone , Bone and Bones , Cadaver , Humans , Mechanical Phenomena , Vibration
14.
BMC Ophthalmol ; 21(1): 294, 2021 Aug 10.
Article in English | MEDLINE | ID: mdl-34376158

ABSTRACT

BACKGROUND: To analyze the long-term effects of persistent subretinal fluid (SRF) on visual/anatomic outcomes according to the type of macular neovascularization (MNV) during relaxed treat-and-extend regimen with anti-vascular endothelial growth factor (anti-VEGF) agents in age-related macular degeneration (AMD) patients. METHODS: Patients with fovea-involving type 1 or type 2 MNV, treated with a relaxed treat-and-extend regimen for 2 years were retrospectively reviewed. Eyes with SRF observed more than three times per year were defined as the 'persistent SRF (+) group'. To exclude the effects of IRF as much as possible, the eyes with persistent IRF were excluded. The effects of persistent SRF on the best-corrected visual acuity (BCVA), central subfield retinal thickness (CST), and changes in the photoreceptor layer (PRL) thickness and outer retinal bands (external limiting membrane, ellipsoid zone, and cone outer segment tip line) after anti-VEGF injection were analyzed for each MNV type. RESULTS: Seventy-seven eyes with type 1 MNV (44 eyes with persistent SRF) and 53 eyes with type 2 MNV (18 eyes with persistent SRF) were enrolled. Following a relaxed treat-and-extend regimen with anti-VEGF agents, BCVA and CST improved for each MNV type. In comparison between persistent SRF (+) and persistent SRF (-) group, there were no differences in the amount of change in BCVA and CST between the two groups for each MNV type during 2-year follow-up periods. In addition, there were no differences in the amount of reduction in PRL thickness and state of the outer retinal bands between the two groups for each MNV type. CONCLUSIONS: Using a relaxed treat-and-extend regimen with anti-VEGF agents, persistent SRF did not have additional effects on visual and anatomic outcomes by 2 years, regardless of the MNV type.


Subject(s)
Macular Degeneration , Wet Macular Degeneration , Angiogenesis Inhibitors/therapeutic use , Fluorescein Angiography , Humans , Intravitreal Injections , Macular Degeneration/drug therapy , Retrospective Studies , Subretinal Fluid , Tomography, Optical Coherence , Vascular Endothelial Growth Factor A , Visual Acuity , Wet Macular Degeneration/drug therapy
15.
Nat Commun ; 12(1): 4730, 2021 08 05.
Article in English | MEDLINE | ID: mdl-34354063

ABSTRACT

Brain organoids derived from human pluripotent stem cells provide a highly valuable in vitro model to recapitulate human brain development and neurological diseases. However, the current systems for brain organoid culture require further improvement for the reliable production of high-quality organoids. Here, we demonstrate two engineering elements to improve human brain organoid culture, (1) a human brain extracellular matrix to provide brain-specific cues and (2) a microfluidic device with periodic flow to improve the survival and reduce the variability of organoids. A three-dimensional culture modified with brain extracellular matrix significantly enhanced neurogenesis in developing brain organoids from human induced pluripotent stem cells. Cortical layer development, volumetric augmentation, and electrophysiological function of human brain organoids were further improved in a reproducible manner by dynamic culture in microfluidic chamber devices. Our engineering concept of reconstituting brain-mimetic microenvironments facilitates the development of a reliable culture platform for brain organoids, enabling effective modeling and drug development for human brain diseases.


Subject(s)
Brain/growth & development , Brain/physiology , Lab-On-A-Chip Devices , Neurogenesis/physiology , Organoids/growth & development , Organoids/physiology , Animals , Brain/cytology , Culture Media , Electrophysiological Phenomena , Extracellular Matrix/physiology , Feasibility Studies , Gene Expression Profiling , Humans , Hydrogels , Induced Pluripotent Stem Cells/cytology , Induced Pluripotent Stem Cells/physiology , Models, Anatomic , Models, Neurological , Neurogenesis/genetics , Neuroglia/cytology , Neuroglia/physiology , Organ Culture Techniques/instrumentation , Organ Culture Techniques/methods , Organoids/cytology , Swine
16.
J Korean Med Sci ; 36(30): e201, 2021 Aug 02.
Article in English | MEDLINE | ID: mdl-34342186

ABSTRACT

BACKGROUND: We investigated the incidence and risk of retinal vein occlusion (RVO) in end-stage renal disease (ESRD) patients on dialysis in Korea. METHODS: In this nationwide cohort study, we used Korean National Health Insurance Service data between 2004 and 2013 for analysis. ESRD patients who started dialysis from 2004 to 2013 and an equal number of controls were selected through propensity score matching. RVO incidence in both cohorts were calculated for 2004-2013 using washout data from 2003. The multivariable Cox proportional hazards model was used to assess the risk of RVO in dialysis cohort. The Kaplan-Meier method was used to generate the cumulative RVO incidence curve. Whether the dialysis modality affects the development of RVO was also evaluated. RESULTS: In this study, 74,551 ESRD patients on dialysis and the same number of controls were included. The incidence of RVO was significantly higher in the dialysis cohort than in the control cohort (dialysis = 7.3/1,000 person-years [PY]; control = 1.9/1,000 PY; P < 0.001). The cumulative-incidence of RVO was also significantly higher in the dialysis cohort than in the control cohort (P < 0.001; log-rank test). However, there was no significant difference in the incidence of RVO between the two dialysis methods (P = 0.550; log-rank test). CONCLUSION: This study provided epidemiological evidence that receiving dialysis for ESRD could increase the risk of developing RVO. We also found a rapid increase in the incidence of RVO with a longer dialysis period. These results strengthen the relationship between retinal vascular disease and renal function.


Subject(s)
Kidney Failure, Chronic/therapy , Renal Dialysis/adverse effects , Retinal Vein Occlusion/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Case-Control Studies , Child , Child, Preschool , Cohort Studies , Female , Humans , Incidence , Infant , Infant, Newborn , Kaplan-Meier Estimate , Kidney Failure, Chronic/complications , Male , Middle Aged , Republic of Korea/epidemiology , Retinal Vein Occlusion/etiology , Retrospective Studies , Risk Factors
17.
Int J Biol Macromol ; 183: 1732-1742, 2021 Jul 31.
Article in English | MEDLINE | ID: mdl-34051251

ABSTRACT

Oral montelukast (MTK) is prescribed to treat asthma or rhinitis, and is clinically investigated as new medication in the treatment of Alzheimer's dementia. Herein, in order to better patient's compliance, microsuspensions (MSs)-based oral liquid preparations of montelukast (MTK) were formulated with polymeric suspending agents including hypromellose (HPMC), and those drug-polymer interaction, physicochemical stability, dissolution, and in vivo pharmacokinetic profile was evaluated. When amorphous MTK particle was suspended in aqueous vehicle, it was readily converted into crystalline form and grown into aggregates, drastically lowering dissolution rate. However, the addition of HPMC polymer markedly suppressed the crystal growth, providing both improved drug stability and profound dissolution profile. Raman spectrometry denoted the inter-molecular hydrogen boding between MTK particle and HPMC polymer. The crystal growth or dissolution profile of MSs was markedly affected by pharmaceutical additives (sucrose or simethicone) in the preparations or storage temperature. The optimized HPMC-based MS exhibited over 80% higher bioavailability, compared to marketed granule (Singulair®) in rats. Therefore, novel MTK-loaded MS can be a promising liquid preparation, bettering oral absorption and patient's compliance.


Subject(s)
Acetates/administration & dosage , Cyclopropanes/administration & dosage , Hypromellose Derivatives/chemistry , Quinolines/administration & dosage , Sulfides/administration & dosage , Acetates/chemistry , Acetates/pharmacokinetics , Administration, Oral , Animals , Crystallization , Cyclopropanes/chemistry , Cyclopropanes/pharmacokinetics , Drug Liberation , Drug Stability , Hydrogen Bonding , Male , Quinolines/chemistry , Quinolines/pharmacokinetics , Rats , Solubility , Sulfides/chemistry , Sulfides/pharmacokinetics , Suspensions
18.
Retina ; 41(10): 2140-2147, 2021 Oct 01.
Article in English | MEDLINE | ID: mdl-34029028

ABSTRACT

PURPOSE: To examine the incidence and risk of retinal artery occlusion (RAO) in patients who have undergone dialysis in Korea. METHODS: A nationwide, population-based study using South Korean national health insurance data from 2004 to 2013 was used for analysis. All patients who began dialysis between 2004 and 2013 and the same number of control subjects were selected via propensity score matching. The incidence of RAO in the dialysis and control cohorts was calculated for 2004 to 2013 using washout data from 2003. The multivariable Cox proportional hazards model was used to evaluate the risk of developing RAO in dialysis patients. Cumulative RAO incidence curves were generated using the Kaplan-Meier method. Whether dialysis modalities influenced the incidence of RAO was also evaluated. RESULTS: Seventy-six thousand seven hundred and eighty-two end-stage renal disease patients on dialysis were included in the dialysis cohort, and 76,782 individuals were included in the control cohort. During the study period, 293 patients in the dialysis cohort and 99 patients in the control cohort developed RAO. The person-years incidence of RAO was significantly higher in the dialysis cohort than in the control cohort (dialysis = 1.1/1,000 person-years; control = 0.3/1,000 person-years; P < 0.001). The incidence of RAO was not significantly different between the two methods of dialysis (hemodialysis vs. peritoneal dialysis; P = 0.25, log-rank test). CONCLUSION: The current study provided epidemiological evidence that undergoing dialysis for end-stage renal disease was associated with an increased risk of developing RAO. The incidence of RAO rapidly increased as the duration of dialysis increased. These results strengthen the significant role of the renal function in retinal vascular disease.


Subject(s)
Kidney Failure, Chronic/therapy , Renal Dialysis/adverse effects , Retinal Artery Occlusion/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Case-Control Studies , Child , Child, Preschool , Databases, Factual , Female , Humans , Incidence , Infant , Infant, Newborn , Kidney Failure, Chronic/physiopathology , Male , Middle Aged , National Health Programs/statistics & numerical data , Proportional Hazards Models , Republic of Korea/epidemiology , Retinal Artery Occlusion/physiopathology , Retrospective Studies , Risk Factors
19.
Semin Ophthalmol ; 36(8): 728-733, 2021 Nov 17.
Article in English | MEDLINE | ID: mdl-33750260

ABSTRACT

PURPOSE: To investigate the surgical outcomes of vitrectomy for macular hole-induced retinal detachment(MHRD), with respect to the surgical adjunctive method used. METHOD: We performed retrospective multicenter study of patients who underwent vitrectomy for MHRD. The visual/anatomical outcomes after vitrectomy were analyzed. We also analyzed these outcomes according to surgical method and the presence of persistent macular hole after the vitrectomy. RESULT: Thirty-four patients (34 eyes) from 6 hospitals were included in this study. The mean age of the patients was 64.56 ± 12.23 years; 31 patients (91.2%) were female. The mean LogMAR best-corrected visual acuity (BCVA) significantly improved 6 months after vitrectomy (p < .001). Retinal detachment completely improved in 32 eyes (94.1%). The visual prognoses and macular hole closure rates were not different depending on subretinal fluid drainage site. The presence or absence of a persistent macular hole after vitrectomy did not affect the visual outcomes. However, the recurrence of MHRD was significantly higher in eyes with persistent macular holes(p = .015). CONCLUSION: The surgeries to treat MHRD differed in terms of the procedure depending on the surgeons, but the visual outcomes did not differ depending on the surgical adjunctive method employed. There were no differences in the visual prognoses, regardless of whether there was a persistent macular hole; however, recurrence was significantly higher in eyes with persistent macular holes. Therefore, further surgical treatment might be considered for eyes with persistent macular holes after MHRD surgery.


Subject(s)
Myopia, Degenerative , Retinal Detachment , Retinal Perforations , Aged , Female , Humans , Middle Aged , Myopia, Degenerative/surgery , Retinal Detachment/etiology , Retinal Detachment/surgery , Retinal Perforations/diagnosis , Retinal Perforations/etiology , Retinal Perforations/surgery , Retrospective Studies , Tomography, Optical Coherence , Treatment Outcome , Visual Acuity , Vitrectomy
20.
Proc Inst Mech Eng H ; 235(5): 597-611, 2021 May.
Article in English | MEDLINE | ID: mdl-33691525

ABSTRACT

In this study, a new diagnostic system is developed to easily identify bone fractures in non-medical environments. It is difficult to determine the extent of cracks, fractures, and the healing process inside humans owing to the differences among people and limitations of state-of-the-art medical devices. Thus, various medical techniques, such as X-ray, computed tomography, or fork tuning systems have been developed, and more advanced technologies are emerging in the medical engineering field. In hazardous circumstances, medical devices to detect bone fracture are not available or cannot be easily applied. Thus, there is a need for the rapid detection of bone fractures without medical devices. To this end, this study analyzes the transverse vibration responses of bones because bone fractures cause different mechanical vibration reactions. By comparing the transverse vibration responses of both healthy and fractured bones, the modal assurance criterion can be calculated and applied to detect the existence of bone fractures. The transverse vibration responses at low and high frequencies are different and exhibit different modal assurance criteria depending on whether or not they are abnormal. Then, the virtual spectrogram of the differences between the signals from non-fractured and fractured bones is calculated. With the help of the present criterion with transverse vibration data, this difference can be analyzed quantitatively and effectively. To validate the proposed system, experiments with artificial specimens, animal legs, and a cadaver are performed.


Subject(s)
Fractures, Bone/diagnosis , Vibration , Aged, 80 and over , Animals , Bone and Bones , Cadaver , Humans , Male , Reproducibility of Results
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