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PURPOSE: To determine the association between pentosan polysulfate (PPS) use and the subsequent development of maculopathy in Asian population. DESIGN: A nationwide population-based retrospective cohort study using the Health Insurance Review and Assessment Service database. PARTICIPANTS: 103,553 individuals in the PPS user group and 205,792 individuals in the PPS non-user group, all newly diagnosed with cystitis between 2009 and 2020. METHODS: The association between PPS use and maculopathy was evaluated using a time dependent Cox proportional hazard model. Additionally, two sensitivity analyses were conducted by defining PPS users as individuals with an observation period over 6 months from the initial prescription or those with cumulative dose exceeding 9 g, employing the same analysis. MAIN OUTCOME MEASURES: The outcome measures included the hazard ratios (HR) representing the association between PPS use and maculopathy. RESULTS: PPS use was associated with an increased risk of subsequent maculopathy in univariate (HR, 1.7; 95% confidence intervals [CI], 1.66-1.75) and multivariate analysis (HR, 1.34; 95% CI, 1.31-1.38). These results were also confirmed in two sensitivity analyses. The mean cumulative dose of PPS for the cohort was 37.2 ± 76.7 g. CONCLUSIONS: In this nationwide cohort study involving an Asian population, individuals with cystitis using PPS exhibit an increased risk of developing subsequent maculopathy.
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PURPOSE: To investigate the significance of intravitreal anti-vascular endothelial growth factor treatment in patients with neovascular age-related macular degeneration and poor visual acuity. METHODS: Retrospective study of patients with neovascular age-related macular degeneration with baseline best-corrected visual acuity of ≤20/200. Patients were divided into regular treatment and scarce treatment groups according to whether they underwent consecutive intravitreal anti-vascular endothelial growth factor treatments at intervals of ≤4 months or not. RESULTS: A total of 131 eyes were included: 87 and 44 eyes in the regular treatment and scarce treatment groups, respectively. The regular treatment group showed significantly improved preservation of lesion size at both Years 1 and 2, with significantly fewer incidences of new subretinal hemorrhage. Improvements in visual acuity, reduction in central subfield macular thickness, and maximal height of choroidal neovascularization were significantly favorable in the regular treatment group at Year 1, and central subfield macular thickness was significantly decreased at Year 2. Survival analysis revealed that the regular treatment group had significantly greater preservation of visual acuity and lesion size than that in the scarce treatment group. CONCLUSION: Maintaining intravitreal anti-vascular endothelial growth factor treatment for patients with neovascular age-related macular degeneration and poor vision showed significant advantages in visual acuity and lesion size stability and reduced the incidence of new subretinal hemorrhage, which suggests preservation of paracentral vision.
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Inhibidores de la Angiogénesis , Bevacizumab , Inyecciones Intravítreas , Ranibizumab , Tomografía de Coherencia Óptica , Factor A de Crecimiento Endotelial Vascular , Agudeza Visual , Degeneración Macular Húmeda , Humanos , Agudeza Visual/fisiología , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/uso terapéutico , Estudios Retrospectivos , Masculino , Femenino , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Anciano , Degeneración Macular Húmeda/tratamiento farmacológico , Degeneración Macular Húmeda/fisiopatología , Degeneración Macular Húmeda/diagnóstico , Ranibizumab/administración & dosificación , Anciano de 80 o más Años , Bevacizumab/administración & dosificación , Bevacizumab/uso terapéutico , Angiografía con Fluoresceína , Estudios de SeguimientoRESUMEN
BACKGROUND: The prevalence of diabetes is increasing globally, highlighting the importance of preventive healthcare. This study aimed to identify the diabetic retinopathy (DR) screening rates and risk factors linked to DR screening nonadherence in the Korean population through a nationally representative sample survey. METHODS: Among the Korea National Health and Nutrition Examination Survey database from 2016 to 2021, participants aged ≥ 40 years with diabetes were included. The weighted estimate for nonadherence to DR screening within a year was calculated. Risk factor analyses were conducted using univariate and multivariate logistic regression. RESULTS: Among the 3,717 participants, 1,109 (29.5%) underwent DR screening within the past year, and this national estimate exhibited no statistically significant difference from 2016 to 2021 (P = 0.809). Nonadherence to annual DR screening was associated with residing in rural areas, age ≥ 80 years, low educational level, self-reported good health, absence of ocular disease, current smoking, lack of exercise and dietary diabetes treatment, and no activity limitation (all P < 0.05). CONCLUSION: The recent DR screening rate in Korea was relatively low. Factors associated with apathy and complacency towards personal health were associated with the nonadherence to DR screening. Educational interventions have the potential to enhance the annual screening rate for diabetic patients.
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Retinopatía Diabética , Tamizaje Masivo , Encuestas Nutricionales , Humanos , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/epidemiología , República de Corea/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Anciano , Adulto , Factores de Riesgo , Anciano de 80 o más Años , Modelos Logísticos , Prevalencia , Oportunidad RelativaRESUMEN
Background and Objectives: Endoscopic epidural neuroplasty (EEN) facilitates adhesiolysis through direct epiduroscopic visualization, offering more precise neural decompression than that exhibited by percutaneous epidural neuroplasty (PEN). We aimed to compare the effects of EEN and PEN for 6 months after treatment with lower back and radicular pain in patients. Methods: This retrospective study compared the visual analog scale (VAS) and Oswestry disability index (ODI) scores in patients with low back and radicular pain who underwent EEN or PEN with a steering catheter. The medical records of 107 patients were analyzed, with 73 and 34 undergoing EEN and PEN, respectively. Results: The VAS and ODI scores decreased at all time points after EEN and PEN. VAS and ODI scores decreased more in the EEN group than those in the PEN group at 1 day and 1- and 6-months post-procedure, indicating superior pain relief for both lower back and radicular pain through EEN. Conclusions: EEN is a superior treatment of pain control than PEN in lower back and radicular pain patients.
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Dolor de la Región Lumbar , Humanos , Dolor de la Región Lumbar/cirugía , Dolor de la Región Lumbar/terapia , Femenino , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Estudios de Seguimiento , Anciano , Adulto , Endoscopía/métodos , Dimensión del Dolor/métodos , Espacio Epidural , Descompresión Quirúrgica/métodosRESUMEN
OBJECTIVE: To compare the risk of blindness and vision-threatening ocular comorbidities in patients with Behçet's disease (BD) vs the general population. METHODS: Using 2002-2017 Korea National Health Insurance Service database, we did a population-based cohort study comparing newly diagnosed BD patients and age- and sex-matched non-BD controls at a 1:5 ratio. The primary outcome was blindness, defined as a best-corrected visual acuity of ≤20/500 in the better-seeing eye. Secondary outcomes were vision-threatening ocular comorbidities (cataract, glaucoma and retinal disorders) that require surgical interventions and incident uveitis. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs. We performed subgroup analyses by sex and BD diagnosis age. RESULTS: We included 31 228 BD patients and 156 140 controls. During a follow-up of 9.39 years, the incidence rate of blindness per 1000 person-years was 0.24 in BD and 0.02 in controls with an HR of 10.73 (95% CI 7.10, 16.22). The HR for secondary outcomes was 2.06 (95% CI 1.98, 2.15) for cataract surgery, 5.43 (4.57, 6.45) for glaucoma surgery and 2.71 (2.39, 3.07) for retinal surgery. The HR of incident uveitis was 6.19 (95% CI 5.83, 6.58). Males suffered a disproportionately higher risk of blindness than females due to greater severity rather than a lower incidence of uveitis. The risk of uveitis and blindness decreased as BD diagnosis age increased. CONCLUSIONS: In this large population-based cohort study, BD patients compared with the general population have a 10.73-fold risk of blindness in 10 years and also a substantially higher risk of diverse ocular comorbidities that pose potential threats to vision.
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Síndrome de Behçet , Catarata , Glaucoma , Uveítis , Masculino , Femenino , Humanos , Síndrome de Behçet/complicaciones , Estudios de Cohortes , Uveítis/etiología , Glaucoma/complicaciones , Glaucoma/epidemiología , Ceguera/complicaciones , Catarata/complicaciones , Estudios RetrospectivosRESUMEN
Homodimeric class 1 cytokine receptors include the erythropoietin (EPOR), thrombopoietin (TPOR), granulocyte colony-stimulating factor 3 (CSF3R), growth hormone (GHR), and prolactin receptors (PRLR). These cell-surface single-pass transmembrane (TM) glycoproteins regulate cell growth, proliferation, and differentiation and induce oncogenesis. An active TM signaling complex consists of a receptor homodimer, one or two ligands bound to the receptor extracellular domains, and two molecules of Janus Kinase 2 (JAK2) constitutively associated with the receptor intracellular domains. Although crystal structures of soluble extracellular domains with ligands have been obtained for all of the receptors except TPOR, little is known about the structure and dynamics of the complete TM complexes that activate the downstream JAK-STAT signaling pathway. Three-dimensional models of five human receptor complexes with cytokines and JAK2 were generated here by using AlphaFold Multimer. Given the large size of the complexes (from 3220 to 4074 residues), the modeling required a stepwise assembly from smaller parts, with selection and validation of the models through comparisons with published experimental data. The modeling of active and inactive complexes supports a general activation mechanism that involves ligand binding to a monomeric receptor followed by receptor dimerization and rotational movement of the receptor TM α-helices, causing proximity, dimerization, and activation of associated JAK2 subunits. The binding mode of two eltrombopag molecules to the TM α-helices of the active TPOR dimer was proposed. The models also help elucidate the molecular basis of oncogenic mutations that may involve a noncanonical activation route. Models equilibrated in explicit lipids of the plasma membrane are publicly available.
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Citocinas , Receptores de Citocinas , Humanos , Janus Quinasa 2 , Ligandos , Transducción de SeñalRESUMEN
PURPOSE: This study aims to investigate the association between incident central retinal artery occlusion (CRAO) and the subsequent development of cancer. METHODS: We included incident CRAO patients from the 2002-2013 National Health Insurance Service database in South Korea. For the patient cohort, we included patients diagnosed with CRAO from the database, and excluded patients having CRAO or any cancer history during the first 2-year washout period (2002-2003). Then, we defined their 1:4 propensity-score matched non-CRAO subjects as controls, all of whom also had no history of cancer during the washout period. Time-varying covariate Cox regression models were conducted to determine the association of CRAO with cancer. Kaplan-Meier curves with log-rank test were also analyzed. RESULTS: A total of 9712 patients with CRAO and 38,848 controls were included in the study. CRAO was associated with an increased risk of subsequent cancer (hazard ratio = 1.27; 95% confidence interval, 1.19-1.35). The incidence rate of overall cancer during the study period was 29.12 per 1000 person-years in the CRAO group and 22.77 per 1000 person-years in the control group. Incidence probability of overall cancer was significantly higher among CRAO patients than controls (P < 0.001, log-rank test). CONCLUSION: The risk of cancer occurrence was increased in patients with CRAO. The results supported that CRAO could be attributed to one of the consequences of arterial thrombosis in cancer patients.
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Neoplasias , Oclusión de la Arteria Retiniana , Humanos , Estudios de Cohortes , Oclusión de la Arteria Retiniana/complicaciones , Oclusión de la Arteria Retiniana/diagnóstico , Oclusión de la Arteria Retiniana/epidemiología , Neoplasias/complicaciones , Neoplasias/diagnóstico , Neoplasias/epidemiología , República de Corea/epidemiología , Estudios RetrospectivosRESUMEN
INTRODUCTION: The aim of this study was to report surgical outcomes and risk factors for primary surgical failure following rhegmatogenous retinal detachment (RRD) repair. METHODS: In this retrospective cohort study, RRD patients who underwent primary surgery at a tertiary center between January 1, 2006, and December 31, 2020, were enrolled. Surgical failure was defined as reoperation within 60 days postoperatively due to retinal re-detachment and putative risk factors for surgical failure were analyzed. RESULTS: Of 2,383 eyes (2,335 patients), 1,342 (56.3%) underwent vitrectomy and 1,041 (43.7%) underwent scleral buckling. The surgical failure rate was 9.1% overall, and 6.0% and 13.1% for the vitrectomy and scleral buckling groups, respectively. In the multivariate logistic regression analysis, surgical failure was associated with surgical experience (first-year fellow vs. senior professor) (odds ratio [OR]: 1.66; p = 0.018), scleral buckling (OR: 2.33; p < 0.001), and longer axial length (AL; ≥26.5 mm) (OR: 1.49; p = 0.017). In each surgical approach, age <40 years (OR: 2.11; p = 0.029) in the vitrectomy group and age >40 years (OR, 1.84; p = 0.004), male sex (OR: 1.65; p = 0.015), and first-year fellows compared to senior professors (OR: 1.95; p = 0.013) in the scleral buckling group were associated with surgical failure. Lens status were not associated with the surgical failure rate. CONCLUSION: In this large retrospective study using data from Korea, vitrectomy was superior to scleral buckling in terms of primary anatomical outcomes in the management of RRD. First-year fellows were a risk factor for surgical failure, especially for scleral buckling. Longer AL was a significant parameter for predicting the success rates.
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Desprendimiento de Retina , Curvatura de la Esclerótica , Vitrectomía , Adulto , Humanos , Masculino , Desprendimiento de Retina/diagnóstico , Desprendimiento de Retina/cirugía , Desprendimiento de Retina/etiología , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Agudeza Visual , Vitrectomía/efectos adversosRESUMEN
INTRODUCTION: The aim of the study was to determine the short-term real-world safety and efficacy of intravitreal brolucizumab injections in Korean patients with neovascular age-related macular degeneration (nAMD). METHODS: This multicenter retrospective study involved 294 eyes (treatment naïve 20 eye [6.8%] and nontreatment naïve 274 eyes [93.2%]) of 290 patients from 13 hospitals or retinal centers in South Korea. Patients with nAMD who received brolucizumab injection(s) between April 1 and November 30, 2021, with a follow-up ≥1 month, were included. Primary outcomes were safety, incidence of intraocular inflammation (IOI), and potential risk factors. The secondary outcome was efficacy, i.e., change in best-corrected visual acuity (BCVA) and optical coherence tomography-measured macular thickness and retinal fluid. RESULTS: The mean age was 71.63 ± 8.66. The follow-up period was 2.38 ± 0.79 months. The mean number of brolucizumab injections during the follow-up was 1.52 ± 0.58. The overall incidence of IOI was 13.9% (n = 41 eyes). Most IOI cases were of anterior uveitis (8.8%, 26 eyes), followed by retinal vasculitis (2.4%, seven eyes) and occlusive retinal vasculitis (0.3%, one eye). Most eyes showed IOI resolution (n = 40, 97.5%) and BCVA restoration (n = 39, 95.1%) with or without corticosteroid treatment during the follow-up. Age, sex, IOI history, or other anti-vascular endothelial growth factor injection histories were not associated with the occurrence of IOI. However, only thin subfoveal choroidal thickness (SFCT) was associated with the occurrence of IOI (odds ratio = 0.995, p = 0.020). BCVA at 1 month improved from baseline (baseline 0.518 ± 0.356 vs. 1 month 0.503 ± 0.383, p = 0.023), but the improvement was not maintained. Anatomical improvement was significant after 3 months. CONCLUSION: In Korean patients with nAMD, the incidence of IOI following brolucizumab injections was 13.9%. IOI was well-controlled with or without steroid treatment. Most IOI eyes (95.1%) were restored to the level of vision before. IOI occurrence and occlusive vasculitis was rare. In the short term, brolucizumab injection effectively improved vision at 1 month and dried retinal fluid for 3 months.
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Degeneración Macular , Vasculitis Retiniana , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Estudios Retrospectivos , Inflamación , RetinaRESUMEN
BACKGROUND: During medial opening wedge high tibial osteotomy (MOWHTO), sometimes the plate tends to be positioned anteromedially. The plate position can affect the length of the proximal screw, which significantly affects stability after osteotomy. Therefore, research on the correlation among plate position, screw length, and clinical outcomes is needed. METHODS: This retrospective review examines 196 knees in 175 patients who underwent MOWHTO from May 2012 to December 2018, for symptomatic medial compartment osteoarthritis with a varus alignment of > 5°. We evaluated the anteroposterior plate position, length of proximal screw, and postoperative computed tomography (CT). We reviewed patients' clinical outcome scores, presence of lateral hinge fracture, neurovascular complications, and infection. The correlation among proximal plate position, proximal screw length, and clinical outcomes was evaluated using Pearson's correlation analysis. A subgroup analysis by screw angle (> 48 ° or < 48 °) was also performed using chi-square test and Student t-test. RESULTS: The mean proximal plate position was 16.28% (range, 5.17-44.74) of the proximal tibia's anterior-to-posterior distance ratio, and the proximal screw length averaged 63.8 mm (range, 44-80 mm). Proximal posteromedial plate position and proximal screw length were significantly correlated (r2 = 0.667, P < .001), as were screw angle and length (r2 = 0.746, P < .001). Medial plating (< 48°) can use a longer proximal screw; nevertheless, no significant difference occurred in clinical outcomes between the two groups. Also, no differences occurred in complication rate, including hinge fracture. CONCLUSION: With more medially positioned plating during MOWHTO, we can use longer proximal screws. However, there was no significant difference in clinical outcomes and the incidence of lateral hinge fractures regardless of plate position and screw length.
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Fracturas Óseas , Osteoartritis de la Rodilla , Humanos , Placas Óseas , Tornillos Óseos/efectos adversos , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/cirugía , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/cirugía , Osteotomía/efectos adversos , Osteotomía/métodos , Tibia/diagnóstico por imagen , Tibia/cirugíaRESUMEN
BACKGROUND: A paucity of data addressing real-world treatment of myopic choroidal neovascularization (mCNV) in the era of anti-vascular endothelial growth factor (VEGF) drugs led us to investigate real-world treatment intensity and treatment patterns in patients with mCNV. METHODS: This is a retrospective, observational study using the Observational Medical Outcomes Partnership-Common Data Model database of treatment-naïve patients with mCNV over the 18-year study period (2003-2020). Outcomes were treatment intensity (time trends of total/average number of prescriptions, mean number of prescriptions in the first year and the second year after initiating treatment, proportion of patients with no treatment in the second year) and treatment patterns (subsequent patterns of treatment according to the initial treatment). RESULTS: Our final cohort included 94 patients with at-least 1-year observation period. Overall, 96.8% of patients received anti-VEGF drugs as first-line treatment, with most of injections from bevacizumab. The number of anti-VEGF injections in each calendar year showed an increasing trend over time; however, there was a drop in the mean number of injections in the second year compared to the first year from 2.09 to 0.47. About 77% of patients did not receive any treatment in their second year of treatment regardless of drugs. Most of patients (86.2%) followed non-switching monotherapy only and bevacizumab was the most popular choice either in the first-line (68.1%) or in the second-line (53.8%) of treatment. Aflibercept was increasingly used as the first-line treatment for patients with mCNV. CONCLUSION: Anti-VEGF drugs have become the treatment of choice and second-line treatment for mCNV over the past decade. Anti-VEGF drugs are effective for the treatment of mCNV as the non-switching monotherapy is the main treatment regimen in most cases and the number of treatments decreases significantly in the second year of treatment.
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Oftalmología , Humanos , Bevacizumab , Bases de Datos Factuales , PacientesRESUMEN
An increasing number of studies have indicated that alterations in gut microbiota affect brain function, including cognition and memory ability, via the gut-brain axis. In this study, we aimed to determine the protective effect of Bifidobacterium bifidum BGN4 (B. bifidum BGN4) and Bifidobacterium longum BORI (B. longum BORI) on age-related brain damage in mice. We found that administration of B. bifidum BGN4 and B. longum BORI effectively elevates brain-derived neurotrophic factor expression which was mediated by increased histone 3 lysine 9 trimethylation. Furthermore, administration of probiotic supplementation reversed the DNA damage and apoptotic response in aged mice and also improved the age-related cognitive and memory deficits of these mice. Taken together, the present study highlights the anti-aging effects of B. bifidum BGN4 and B. longum BORI in the aged brain and their beneficial effects for age-related brain disorders.
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Bifidobacterium bifidum , Bifidobacterium longum , Microbioma Gastrointestinal , Probióticos , Animales , Bifidobacterium bifidum/genética , Ratones , RejuvenecimientoRESUMEN
Explicit treatment of electronic polarizability in empirical force fields (FFs) represents an extension over a traditional additive or pairwise FF and provides a more realistic model of the variations in electronic structure in condensed phase, macromolecular simulations. To facilitate utilization of the polarizable FF based on the classical Drude oscillator model, Drude Prepper has been developed in CHARMM-GUI. Drude Prepper ingests additive CHARMM protein structures file (PSF) and pre-equilibrated coordinates in CHARMM, PDB, or NAMD format, from which the molecular components of the system are identified. These include all residues and patches connecting those residues along with water, ions, and other solute molecules. This information is then used to construct the Drude FF-based PSF using molecular generation capabilities in CHARMM, followed by minimization and equilibration. In addition, inputs are generated for molecular dynamics (MD) simulations using CHARMM, GROMACS, NAMD, and OpenMM. Validation of the Drude Prepper protocol and inputs is performed through conversion and MD simulations of various heterogeneous systems that include proteins, nucleic acids, lipids, polysaccharides, and atomic ions using the aforementioned simulation packages. Stable simulations are obtained in all studied systems, including 5 µs simulation of ubiquitin, verifying the integrity of the generated Drude PSFs. In addition, the ability of the Drude FF to model variations in electronic structure is shown through dipole moment analysis in selected systems. The capabilities and availability of Drude Prepper in CHARMM-GUI is anticipated to greatly facilitate the application of the Drude FF to a range of condensed phase, macromolecular systems.
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Simulación de Dinámica Molecular , Programas InformáticosRESUMEN
Unlike the ideal circular whispering gallery cavities, those without mirror symmetry intrinsically support resonant modes exhibiting chirality which indicates an imbalance between clockwise and counterclockwise wave components. In extreme cases, nearly degenerate pairs of copropagating modes can be found around the chiral exceptional points (EPs) in parameter spaces. The chiral EPs have been studied in various schemes; however, most attention has been focused on the cases with piecewise constant or periodic refractive index profiles. In this Letter, we report the formation of a chiral EP in a gradient-index cavity designed by conformal transformation optics. Here, the mirror symmetry of the cavity is broken solely by its gradient index profile, and the parameter space is constructed with coordinate transformation parameters. We unveil the chirality, nonorthogonality, and complex-square-root topology near the chiral EP, which can be explained by the non-Hermitian model Hamiltonian.
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INTRODUCTION: Patients with Parkinson's disease (PD) showed an increased risk of fractures in previous studies and a high prevalence of osteoporosis is reportedly a potential contributor. We conducted a nationwide database study on the risk of fractures and the impact of osteoporosis on patients with PD compared to controls. MATERIALS AND METHODS: Using a nationwide database in South Korea, we identified incident patients with PD in 2004-2006 and selected four age- and sex-matched controls. We checked the occurrence rates of overall and hip fractures and plotted Kaplan-Meier curves and a Cox proportional hazards model to determine risk. We also conducted stratified analyses according to the presence or absence of osteoporosis. RESULTS: We identified 9126 patients with PD and 35,601 controls. Patients with PD had a greater probability of fractures throughout the study period in Kaplan-Meier curves, and an increased risk of overall (aHR 1.35, 95% CI 1.297-1.405) and hip (aHR 1.814, 95% CI 1.66-1.983) fractures in a Cox proportional hazards model. In the stratified analysis, the increased risk of overall fracture (aHR 1.333, 95% CI 1.273-1.396 and aHR 1.412, 95% CI 1.301-1.532, respectively) and hip fracture (aHR 1.773, 95% CI 1.604-1.96 and aHR 2.008, 95% CI 1.657-2.434, respectively) due to PD was similar between patients with and without osteoporosis. DISCUSSION: Patients with PD, with or without osteoporosis, are more likely to experience fractures, especially hip fractures. There seems to be no interaction between PD and osteoporosis in regard to the occurrence of fractures, and therefore no effect modification by osteoporosis.
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Fracturas de Cadera , Osteoporosis , Fracturas Osteoporóticas , Enfermedad de Parkinson , Fracturas de Cadera/complicaciones , Fracturas de Cadera/epidemiología , Humanos , Incidencia , Osteoporosis/complicaciones , Osteoporosis/epidemiología , Fracturas Osteoporóticas/epidemiología , Fracturas Osteoporóticas/etiología , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/epidemiología , Modelos de Riesgos Proporcionales , Factores de RiesgoRESUMEN
Protein-carbohydrate interactions underlie essential biological processes. Elucidating the mechanism of protein-carbohydrate recognition is a prerequisite for modeling and optimizing protein-carbohydrate interactions, which will help in discovery of carbohydrate-derived therapeutics. In this work, we present a survey of a curated database consisting of 6,402 protein-carbohydrate complexes in the Protein Data Bank (PDB). We performed an all-against-all comparison of a subset of nonredundant binding sites, and the result indicates that the interaction pattern similarity is not completely relevant to the binding site structural similarity. Investigation of both binding site and ligand promiscuities reveals that the geometry of chemical feature points is more important than local backbone structure in determining protein-carbohydrate interactions. A further analysis on the frequency and geometry of atomic interactions shows that carbohydrate functional groups are not equally involved in binding interactions. Finally, we discuss the usefulness of protein-carbohydrate complexes in the PDB with acknowledgement that the carbohydrates in many structures are incomplete.
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Carbohidratos/química , Biología Computacional , Bases de Datos de Proteínas , Proteínas/químicaRESUMEN
During postnatal lung development, metabolic changes that coincide with stages of alveolar formation are poorly understood. Responding to developmental and environmental factors, metabolic changes can be rapidly and adaptively altered. The objective of the present study was to determine biological and technical determinants of metabolic changes during postnatal lung development. Over 118 metabolic features were identified by liquid chromatography with tandem mass spectrometry (LC-MS/MS, Sciex QTRAP 5500 Triple Quadrupole). Biological determinants of metabolic changes were the transition from the postnatal saccular to alveolar stages and exposure to 85% hyperoxia, an environmental insult. Technical determinants of metabolic identification were brevity and temperature of harvesting, both of which improved metabolic preservation within samples. Multivariate statistical analyses revealed the transition between stages of lung development as the period of major metabolic alteration. Of three distinctive groups that clustered by age, the saccular stage was identified by its enrichment of both glycolytic and fatty acid derivatives. The critical transition between stages of development were denoted by changes in amino acid derivatives. Of the amino acid derivatives that significantly changed, a majority were linked to metabolites of the one-carbon metabolic pathway. The enrichment of one-carbon metabolites was independent of age and environmental insult. Temperature was also found to significantly influence the metabolic levels within the postmortem sampled lung, which underscored the importance of methodology. Collectively, these data support not only distinctive stages of metabolic change but also highlight amino acid metabolism, in particular one-carbon metabolites as metabolic signatures of the early postnatal lung.
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Carbono/metabolismo , Ácidos Grasos/metabolismo , Glucólisis , Pulmón/citología , Pulmón/metabolismo , Metaboloma , Animales , Animales Recién Nacidos , Cromatografía Liquida , Masculino , Redes y Vías Metabólicas , Ratones , Ratones Endogámicos C57BL , Espectrometría de Masas en TándemRESUMEN
MOTIVATION: Glycan microarrays are capable of illuminating the interactions of glycan-binding proteins (GBPs) against hundreds of defined glycan structures, and have revolutionized the investigations of protein-carbohydrate interactions underlying numerous critical biological activities. However, it is difficult to interpret microarray data and identify structural determinants promoting glycan binding to glycan-binding proteins due to the ambiguity in microarray fluorescence intensity and complexity in branched glycan structures. To facilitate analysis of glycan microarray data alongside protein structure, we have built the Glycan Microarray Database (GlyMDB), a web-based resource including a searchable database of glycan microarray samples and a toolset for data/structure analysis. RESULTS: The current GlyMDB provides data visualization and glycan-binding motif discovery for 5203 glycan microarray samples collected from the Consortium for Functional Glycomics. The unique feature of GlyMDB is to link microarray data to PDB structures. The GlyMDB provides different options for database query, and allows users to upload their microarray data for analysis. After search or upload is complete, users can choose the criterion for binder versus non-binder classification. They can view the signal intensity graph including the binder/non-binder threshold followed by a list of glycan-binding motifs. One can also compare the fluorescence intensity data from two different microarray samples. A protein sequence-based search is performed using BLAST to match microarray data with all available PDB structures containing glycans. The glycan ligand information is displayed, and links are provided for structural visualization and redirection to other modules in GlycanStructure.ORG for further investigation of glycan-binding sites and glycan structures. AVAILABILITY AND IMPLEMENTATION: http://www.glycanstructure.org/glymdb. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Glicómica , Polisacáridos , Sitios de Unión , Bases de Datos Factuales , Análisis por Micromatrices , ProteínasRESUMEN
OBJECTIVE: Patients with RA commonly use gastrointestinal (GI) protective drugs for treatment and prevention of drug-associated GI injuries. However, how these drugs affect the gut microbiota in RA patients remains unknown. The objective of this study was to examine the gut microbiota of RA patients according to use of GI protective drugs such as proton pump inhibitors (PPIs), histamine 2-receptor antagonists and rebamipide. METHODS: Faecal samples were obtained from 15 healthy controls and 32 RA patients who were receiving PPI, histamine 2-receptor antagonist or rebamipide. Bacterial DNA was extracted from the faecal samples and 16S rRNA sequencing was performed. Microbial composition and function were analysed using Quantitative Insights Into Microbial Ecology and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States. RESULTS: RA patients exhibited reduced diversity and altered composition of the gut microbiota compared with healthy controls. The gut microbiota of RA patients receiving acid-suppressing drugs, particularly PPIs, was distinct from that of RA patients receiving rebamipide (PPI vs rebamipide, P = 0.005). Streptococcus was enriched in RA patients receiving PPI, while Clostridium bolteae was enriched in RA patients receiving rebamipide. The gut microbiota of PPI users was abundant with microbial functional pathway involved in the production of virulence factors. This featured microbial function was positively correlated with relative abundance of Streptococcus, the differentially abundant taxa of PPI users. CONCLUSION: The gut microbiota of RA patients receiving PPIs was distinguishable from that of those receiving rebamipide. The enriched virulent function in the gut microbiota of PPI users suggests that inappropriate PPI use may be harmful in RA patients.