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1.
Clin Radiol ; 79(7): e908-e915, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38649313

ABSTRACT

AIM: To compare the image quality of virtual noncontrast (VNC) and true noncontrast (TNC) CT images and to evaluate the clinical feasibility of VNC CT images for assessing osteochondral lesions of the talus (OLTs). MATERIALS AND METHODS: Forty-five OLT patients who underwent ankle CT arthrography (CTA) using dual-layer spectral detector CT were enrolled. Reconstruction of VNC and three-dimensional volume rendering images was performed. Afterward, image noise, the signal-to-noise ratio (SNR), and the contrast-to-noise ratio (CNR) were measured. For the subjective evaluation, two board-certified musculoskeletal radiologists [R2-1] assessed spatial resolution, overall image quality, and lesion conspicuity. The accuracy rate for OLT grading was determined in 23 patients who underwent arthroscopic surgery. RESULTS: While VNC images showed significantly less noise than TNC images, TNC images showed better SNRs and CNRs (p<.01). In the subjective analysis, TNC images showed better overall image quality (p<.001). For the 3D volume rendering images, VNC images scored significantly higher for lesion conspicuity (p<.001). The accuracy rates of CTA and CTA with VNC images for OLT grading were 79.2% and 83.3%, respectively. Regarding confidence level, when CTA and VNC images were evaluated together, the confidence level was significantly higher than that when only CTA images were evaluated (p<.001). CONCLUSION: VNC imaging can provide better confidence level of OLT grading and evaluation of the integrity of the subchondral bone plate when combined with conventional CTA without additional radiation dose to the patient. In addition, VNC images-based 3D volume rendering reconstruction would be helpful for preoperative planning in OLT patients.


Subject(s)
Arthrography , Feasibility Studies , Talus , Tomography, X-Ray Computed , Humans , Talus/diagnostic imaging , Male , Female , Adult , Middle Aged , Tomography, X-Ray Computed/methods , Arthrography/methods , Imaging, Three-Dimensional/methods , Young Adult , Aged , Adolescent , Signal-To-Noise Ratio , Retrospective Studies , Radiographic Image Interpretation, Computer-Assisted/methods
2.
J Endocrinol Invest ; 2024 Mar 17.
Article in English | MEDLINE | ID: mdl-38493245

ABSTRACT

BACKGROUND: Menopause, a dramatical estrogen-deficient condition, is considered the most significant milestone in women's health. PURPOSE: To investigate the metabolite changes attributed to estrogen deficiency using random forest (RF)-based machine learning (ML) modeling strategy in ovariectomized (OVX) mice as well as determine the clinical relevance of selected metabolites in older women. METHODS AND RESULTS: Untargeted and targeted metabolomic analyses revealed that metabolites related to TCA cycle, sphingolipids, phospholipids, fatty acids, and amino acids, were significantly changed in the plasma and/or muscle of OVX mice. Subsequent ML classifiers based on RF algorithm selected alpha-ketoglutarate (AKG), arginine, carnosine, ceramide C24, phosphatidylcholine (PC) aa C36:6, and PC ae C42:3 in plasma as well as PC aa 34:1, PC aa C34:3, PC aa C36:5, PC aa C32:1, PC aa C36:2, and sphingosine in muscle as top featured metabolites that differentiate the OVX mice from the sham-operated group. When circulating levels of AKG, arginine, and carnosine, which showed the most significant changes in OVX mice blood, were measured in postmenopausal women, higher plasma AKG levels were associated with lower bone mass, weak grip strength, poor physical performance, and increased frailty risk. CONCLUSIONS: Metabolomics- and ML-based methods identified the key metabolites of blood and muscle that were significantly changed after ovariectomy in mice, and the clinical implication of several metabolites was investigated by looking at their correlation with body composition and frailty-related parameters in postmenopausal women. These findings provide crucial context for understanding the diverse physiological alterations caused by estrogen deficiency in women.

3.
Nat Commun ; 14(1): 7440, 2023 Nov 17.
Article in English | MEDLINE | ID: mdl-37978193

ABSTRACT

Real-time probing of electrons can uncover intricate relaxation mechanisms and many-body interactions in strongly correlated materials. Here, we introduce time, momentum, and energy resolved pump-probe tunneling spectroscopy (Tr-MERTS). The method allows the injection of electrons at a particular energy and observation of their subsequent decay in energy-momentum space. Using Tr-MERTS, we visualize electronic decay processes, with lifetimes from tens of nanoseconds to tens of microseconds, in Landau levels formed in a GaAs quantum well. Although most observed features agree with simple energy-relaxation, we discovered a splitting in the nonequilibrium energy spectrum in the vicinity of a ferromagnetic state. An exact diagonalization study suggests that the splitting arises from a maximally spin-polarized state with higher energy than a conventional equilibrium skyrmion. Furthermore, we observe time-dependent relaxation of the splitting, which we attribute to single-flipped spins forming skyrmions. These results establish Tr-MERTS as a powerful tool for studying the properties of a 2DES beyond equilibrium.

4.
Int J Dev Disabil ; 69(6): 797-810, 2023.
Article in English | MEDLINE | ID: mdl-37885836

ABSTRACT

Background: Within Family Quality of Life (FQoL) research, perceptions of siblings of people with intellectual and developmental disabilities (IDD) in the setting of a family are limited studied. The aim of this systematic review is to find relevant information about quality of life perceptions of siblings of people with IDD. Two main questions guided this review: (1) what are the siblings' perceptions on quality of life in the context of their family? (2) what needs and challenges do siblings have regarding their quality of life as siblings of individuals with IDD? Methods: A systematic search was conducted using Scopus, PsycInfo, ERIC and Web of Science databases, involving keywords and combinations such as Intellectual and Developmental Disabilities, Family Quality of Life and siblings. Results: We identified a total of 48 articles. Analysis showed siblings' diverse perceptions of quality of life and their multiple experiences, needs, desires and concerns. Conclusions: Results contribute to knowledge about the quality of life and well-being of siblings of all ages. Suggestions for support, interventions and future research are given, such as the necessity of educating local communities regarding siblings' needs, the study of siblings' experiences in different cultural contexts or the importance of conducting research with clear theoretical frameworks and focused on the multiple components that might be influencing siblings' quality of life.

5.
Phys Rev E ; 107(4-2): 045306, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37198775

ABSTRACT

The numerical instability of the lattice Boltzmann method (LBM) at high Mach or high Reynolds number flow is well identified, and it remains a major barrier to its application in more complex configurations such as moving geometries. This work combines the compressible lattice Boltzmann model with rotating overset grids (the so-called Chimera method, sliding mesh, or moving reference frame) for high Mach flows. This paper proposes to use the compressible hybrid recursive regularized collision model with fictitious forces (or inertial forces) in a noninertial rotating reference frame. Also, polynomial interpolations are investigated, which allow fixed inertial and rotating noninertial grids to communicate with each other. We suggest a way to effectively couple the LBM with the MUSCL-Hancock scheme in the rotating grid, which is needed to account for thermal effect of compressible flow. As a result, this approach is demonstrated to have an extended Mach stability limit for the rotating grid. It also demonstrates that this complex LBM scheme can maintain the second-order accuracy of the classic LBM by appropriately using numerical methods like polynomial interpolations and the MUSCL-Hancock scheme. Furthermore, the method shows a very good agreement on aerodynamic coefficients compared to experiments and the conventional finite-volume scheme. This work presents a thorough academic validation and error analysis of the LBM for simulating moving geometries in high Mach compressible flows.

6.
Anaesthesia ; 78(8): 970-978, 2023 08.
Article in English | MEDLINE | ID: mdl-37145935

ABSTRACT

In patients with cervical spine immobilisation, tracheal intubation devices other than a direct laryngoscope are frequently used to facilitate tracheal intubation and avoid related complications. In this randomised controlled trial, we compared videolaryngoscopic and fibrescopic tracheal intubation in patients with a cervical collar. Tracheal intubation was performed using either a videolaryngoscope with a non-channelled Macintosh blade (n = 166) or a flexible fibrescope (n = 164) in patients having elective cervical spine surgery whose neck was immobilised with a cervical collar to simulate a difficult airway. The primary outcome was the first attempt success rate of tracheal intubation. Secondary outcomes were the overall success rate of tracheal intubation; time to tracheal intubation; use of additional airway manoeuvres; and incidence and severity of tracheal intubation-related airway complications. First attempt success rate was higher in the videolaryngoscope group than in the fibrescope group (164/166 (98.8%) vs. 149/164 (90.9%), p = 0.003). Tracheal intubation was successful within three attempts in all patients. Median (IQR [range]) time to tracheal intubation was shorter (50.0 (41.0-72.0 [25.0-170.0]) s vs. 81.0 (65.0-107.0 [24.0-178.0]) s, p < 0.001) and additional airway manoeuvres were less frequent (30/166 (18.1%) vs. 91/164 (55.5%), p < 0.001) in the videolaryngoscope group compared with the fibrescope group. The incidence and severity of intubation-related airway complications were not different between the two groups. When performing tracheal intubation in patients with a cervical collar, videolaryngoscopy with a non-channelled Macintosh blade was superior to flexible fibrescopy.


Subject(s)
Laryngoscopes , Humans , Laryngoscopy , Intubation, Intratracheal , Cervical Vertebrae/surgery
7.
J Commun Disord ; 100: 106266, 2022.
Article in English | MEDLINE | ID: mdl-36150239

ABSTRACT

INTRODUCTION: Depression may influence treatment participation and outcomes of people with post-stroke aphasia, yet its prevalence and associated characteristics in aphasia are poorly understood. Using retrospective data from an overarching experimental study, we examined depressive symptoms and their relationship to demographic and language characteristics in people with chronic aphasia. As a secondary objective, we compared prevalence of depressive symptoms among the overarching study's included and excluded participants. METHODS: We examined retrospective data from 121 individuals with chronic aphasia including depression scale scores, demographic information (sex, age, time post onset of stroke, education, race/ethnicity, and Veteran status), and scores on assessments of general and modality-specific language impairments. RESULTS: Approximately 50% of participants reported symptoms indicative of depressive disorders: 23% indicative of major depression and 27% indicative of mild depression. Sex (males) and comparatively younger age emerged as statistically significant variables associated with depressive symptoms; naming ability was minimally associated with depressive symptoms. Time post onset of stroke, education level, race/ethnicity, Veteran status, and aphasia severity were not significantly associated with depressive symptoms. Depression-scale scores were significantly higher for individuals excluded from the overarching study compared to those who were included. CONCLUSIONS: The rate of depressive disorders in this sample was higher than rates of depression reported in the general stroke literature. Participant sex, age, and naming ability emerged as factors associated with depressive symptoms, though these links appear complex, especially given variable reports from prior research. Importantly, depressive symptoms do not appear to diminish over time for individuals with chronic aphasia. Given these results and the relatively limited documentation of depression in aphasia literature, depression remains a pressing concern for aphasia research and routine clinical care.


Subject(s)
Aphasia , Language Development Disorders , Stroke , Male , Humans , Depression/etiology , Retrospective Studies , Aphasia/etiology , Stroke/complications , Prevalence
8.
Low Urin Tract Symptoms ; 13(1): 31-37, 2021 Jan.
Article in English | MEDLINE | ID: mdl-32515894

ABSTRACT

OBJECTIVES: This study aimed to compare the safety and efficacy of laser vaporization with 532 nm GreenLight High Performance System (HPS) laser 120 W (PVP) and 980 nm diode laser 300 W (CVP) for the treatment of benign prostatic hyperplasia (BPH) in a prospective, single-center, randomized clinical trial. METHODS: A total of 153 consecutive patients with symptomatic BPH were included; 79 patients were treated with PVP and 74 with CVP. Patients were assessed preoperatively and at 3, 6, and 12 months postoperatively using the International Prostate Symptom Score, quality of life index, peak urinary flow rate, and postvoid residual urine volume. All perioperative and postoperative complications were noted. RESULTS: There were significant and comparable improvements in each of the outcome variables over a follow-up period of 12 months in both groups. The mean operation/vaporization duration (minutes) was comparable at 74/38 (PVP) and 76/34 (CVP), whereas the mean applied laser energy was significantly higher with CVP than with PVP at 260 vs 195 (kJ), respectively. The mean vaporization rate (mL/min) was not significantly different between the two groups (0.53 PVP vs 0.56 CVP). Immediately after surgery, the rate of recatheterization for urinary retention was significantly higher with CVP than with PVP (17.6% vs 6.8%; P < 0.05). CONCLUSIONS: Both laser systems provided comparable improvement in the subjective and objective parameters with excellent hemostatic properties. Although our results suggest that both procedures are useful treatment choices, further follow-up is needed to draw definitive conclusions regarding the most ideal laser for treating patients with symptomatic BPH.


Subject(s)
Lasers, Semiconductor/therapeutic use , Lasers, Solid-State/therapeutic use , Prostatic Hyperplasia/surgery , Aged , Aged, 80 and over , Humans , Japan , Lasers, Semiconductor/adverse effects , Lasers, Solid-State/adverse effects , Male , Middle Aged , Prostate/surgery , Treatment Outcome
9.
Diabetes Metab ; 47(3): 101195, 2021 05.
Article in English | MEDLINE | ID: mdl-33039669

ABSTRACT

AIM: Despite the recognized association between type 2 diabetes (T2D) and Parkinson's disease (PD), the implications of glycaemic variability for patients with PD are as yet unknown. For this reason, our study assessed the future risk of incident PD according to visit-to-visit fasting plasma glucose (FPG) variability, as calculated by standard deviation (FPG-SD), coefficient variance (FPG-CV) and variability independent of the mean (FPG-VIM). METHODS: Using the Korean National Health Insurance Service Health Screening Cohort, 131,625 Korean adults without diabetes were followed. They were divided into a midlife group (age<65 years) and an elderly group (age≥65 years) throughout a median follow-up of 8.4 years. RESULTS: Adjusted hazard ratios (HRs) were calculated using multivariable Cox proportional-hazards analysis. In the midlife group, HRs for incident PD in the highest quartile of FPG variability (as measured by SD, CV and VIM) were 1.37 [95% confidence interval (CI): 1.09-1.73], 1.33 (95% CI: 1.06-1.68) and 1.35 (95% CI: 1.07-1.70), respectively, vs the lowest variability quartile group. However, while incident PD did not differ according to FPG variability in the elderly group, Kaplan-Meier curves of PD probability in the midlife group showed a progressively increasing risk of PD the higher the FPG variability. According to a multivariable adjusted model, every 1-SD unit increment in glycaemic variability was associated with a 9% higher risk of incident PD in the midlife group. CONCLUSION: Increased long-term glycaemic variability may be a precipitating risk factor for developing PD in the midlife population without diabetes.


Subject(s)
Blood Glucose , Fasting , Parkinson Disease , Aged , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/epidemiology , Fasting/blood , Humans , Middle Aged , Parkinson Disease/epidemiology , Risk Factors
10.
Eur J Neurol ; 27(10): 1948-1956, 2020 10.
Article in English | MEDLINE | ID: mdl-32441832

ABSTRACT

BACKGROUND AND PURPOSE: As a major antioxidant, uric acid (UA) is known to be associated with the clinical progression of Parkinson's disease (PD). This study investigated whether baseline UA levels are associated with the risk for levodopa-induced dyskinesia (LID) in PD in a sex-dependent manner. METHODS: In all, 152 patients with de novo PD (78 males and 74 females) who were followed up for >2 years were enrolled. The effect of baseline serum UA levels on LID-free survival was assessed by Cox regression, separately for sex, whilst being adjusted for potential confounding factors. The optimal UA level cut-off value to determine the high-risk group for LID was set using Contal and O'Quigley's method. RESULTS: Levodopa-induced dyskinesia developed in 23 (29.5%) male patients and 30 (40.5%) female patients. Cox regression showed a significant interaction between UA level and sex. Higher UA levels were associated with a higher risk for LID in male PD patients (hazard ratio 1.380; 95% confidence interval 1.038-1.835; P = 0.027), although this relationship was not observed in female PD patients. The optimal UA level cut-off for LID in male PD was 7.2 mg/dl, and the high UA group had a 5.7-fold higher risk of developing LID than the low UA group. CONCLUSIONS: Contrary to a presumptive beneficial role of UA, the present study demonstrated that higher UA levels are associated with increased risk of LID occurrence in male patients with PD, suggesting a sex-dependent role of UA in LID.


Subject(s)
Dyskinesia, Drug-Induced , Parkinson Disease , Antiparkinson Agents/adverse effects , Dyskinesia, Drug-Induced/etiology , Female , Humans , Levodopa/adverse effects , Male , Parkinson Disease/drug therapy , Uric Acid
11.
Eur J Neurol ; 27(6): 951-958, 2020 06.
Article in English | MEDLINE | ID: mdl-32090410

ABSTRACT

BACKGROUND AND PURPOSE: Anosognosia refers to a deficit of self-awareness or impaired insight for cognitive and behavioral problems. Cognitive anosognosia was explored in de novo patients with Parkinson's disease (PD) and its relationship to cognitive function and neuropsychiatric symptoms was investigated. METHODS: The cross-sectional study enrolled 340 drug-naïve patients with PD. According to the presence of mild cognitive impairment (MCI) and subjective cognitive complaint, patients were classified as patients with cognitive anosognosia (PD-CA, n = 74), with normal cognitive recognition (PD-NR, n = 184) or with cognitive underestimation (PD-CU, n = 82). After controlling for covariates, cognitive performance and neuropsychiatric symptoms were compared between the PD groups. RESULTS: Cognitive anosognosia was found in 21.8% of patients with de novo PD. The PD-CA group showed poorer performance in all cognitive domains except for attention. Amongst PD patients with MCI, those with cognitive anosognosia showed lower composite z-scores in the Stroop color reading test than those without. The Beck Depression Inventory score in the PD-NR group was lower than that in the PD-CU group and higher than that in the PD-CA group. The Cognitive Complaints Interview score mediated the association between cognitive anosognosia and Beck Depression Inventory score. CONCLUSIONS: Cognitive anosognosia in PD was associated with greater frontal dysfunction and lower depression. Since cognitive anosognosia has a harmful impact on PD patients and their caregivers due to overestimation of their abilities in everyday life, early identification of cognitive anosognosia in PD is important in management and prognosis.


Subject(s)
Agnosia , Cognitive Dysfunction , Parkinson Disease , Agnosia/etiology , Cognition , Cognitive Dysfunction/etiology , Cross-Sectional Studies , Depression/etiology , Humans , Neuropsychological Tests , Parkinson Disease/complications
12.
Eur J Neurol ; 27(5): 773-778, 2020 05.
Article in English | MEDLINE | ID: mdl-31994785

ABSTRACT

BACKGROUND AND PURPOSE: The aim was to investigate the relationship between the serum urate (UA) levels and patterns of striatal dopamine depletion in patients with de novo Parkinson's disease (PD). METHODS: In all, 167 de novo PD patients who underwent 18 F-fluorinated N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane positron emission tomography scans were enrolled. After quantifying dopamine transporter (DAT) availability in each striatal subregion, sex-dependent patterns of striatal dopamine depletion were analysed by measuring (i) dopamine depletion in the other striatal subregions and posterior putamen (intersubregional ratio, ISR) and (ii) the interhemispheric asymmetry of dopamine depletion in the posterior putamen (asymmetric ratio, AR). RESULTS: The interaction analysis revealed a significant interaction effect of sex and serum UA levels on the ISR but not on the AR. The ISR was negatively correlated with the serum UA levels in all patients with PD (r = -0.156, P = 0.045), and this association was more prominent in male PD patients (r = -0.422, P < 0.001). However, no significant association between the AR and serum UA levels was found in any of the patients. In addition, serum UA levels were significantly associated with DAT availability in the posterior putamen on both the more affected side (r = 0.312, P = 0.005) and the less affected side (r = 0.312, P = 0.005) only in male PD patients. CONCLUSIONS: The present study demonstrated the potentially close sex-specific relationship between the serum UA levels and the anterior-posterior gradient of DAT patterns, suggesting a sex-specific protective effect of UA on nigrostriatal dopaminergic neurons in de novo PD.


Subject(s)
Corpus Striatum/metabolism , Dopamine/blood , Dopamine/deficiency , Parkinson Disease/metabolism , Sex Characteristics , Uric Acid/blood , Aged , Corpus Striatum/diagnostic imaging , Dopamine Plasma Membrane Transport Proteins/metabolism , Female , Humans , Male , Parkinson Disease/diagnostic imaging , Positron-Emission Tomography
13.
Clin Microbiol Infect ; 26(5): 646.e9-646.e14, 2020 May.
Article in English | MEDLINE | ID: mdl-31648000

ABSTRACT

OBJECTIVE: To compare outcomes of early and delayed treatment with cidofovir for human adenovirus (HAdV) pneumonia. METHODS: A retrospective cohort study in Korean military hospitals was conducted between January 2012 and December 2018. Patients with potentially severe HAdV pneumonia with risk factors for respiratory failure were included and divided into early (within 7 days from symptom onset) and delayed (after 7 days from symptom onset) treatment groups. The primary outcome was respiratory failure development within 21 days after symptom onset. RESULTS: A total of 89 patients with potentially severe HAdV pneumonia were enrolled in the cohort; they included 62 early and 27 delayed treatment patients. All patients were males in their early 20s. Significantly fewer patients in the early treatment group progressed to respiratory failure (8/62, 12.9%), compared to the delayed group (18/27, 66.7%, p < 0.001). Early treatment was associated with a lower 21-day probability of respiratory failure by the Kaplan-Meier method (p < 0.001). On multivariate analysis, monocyte count, hypoxaemia, confusion, whole lung involvement, and early cidofovir treatment within 7 days from symptom onset were included, and monocyte count (HR 0.995, 95%CI 0.991-1.000, p 0.042), confusion (HR 4.964, 95%CI 1.189-20.721, p = 0.028), and early cidofovir treatment (HR 0.319, 95%CI 0.115-0.883, p = 0.028) were significantly associated with respiratory failure. CONCLUSIONS: Early administration of cidofovir was associated with a lower hazard for respiratory failure development. It is suggested that cidofovir be administered within 7 days from symptom onset to prevent respiratory failure in patients with potentially severe HAdV pneumonia.


Subject(s)
Adenovirus Infections, Human/drug therapy , Antiviral Agents/therapeutic use , Cidofovir/therapeutic use , Pneumonia, Viral/drug therapy , Respiratory Insufficiency/prevention & control , Adenovirus Infections, Human/pathology , Adenoviruses, Human/drug effects , Hospitals, Military , Humans , Male , Pneumonia, Viral/pathology , Republic of Korea , Retrospective Studies , Time Factors , Treatment Outcome , Young Adult
14.
Eur J Neurol ; 27(2): 318-326, 2020 02.
Article in English | MEDLINE | ID: mdl-31487756

ABSTRACT

BACKGROUND AND PURPOSE: Subcortical structures are affected by neurodegeneration in Alzheimer's disease (AD) and Lewy body disease (LBD). Although the co-occurrence of AD and LBD pathologies and their possible interaction have been reported, the effect of AD and LBD on subcortical structures remains unknown. The effects of AD and LBD on subcortical atrophy and their relationship with cognitive dysfunction were investigated. METHODS: The cross-sectional study recruited 42 patients with pure AD related cognitive impairment (ADCI), 30 patients with pure LBD related cognitive impairment (LBCI), 58 patients with mixed ADCI and LBCI, and 29 normal subjects. A general linear model was used to compare subcortical volume and shape amongst the groups, to investigate the independent and interaction effects of ADCI and LBCI on subcortical shape and volume, and to analyze the relationship between subcortical volume and cognitive dysfunction in each group. RESULTS: Alzheimer's disease related cognitive impairment and LBCI were independently associated with subcortical atrophies in the hippocampus and amygdala and in the hippocampus and putamen respectively, but their interaction effect was not significant. Compared to the control group, the pure LBCI group exhibited additional local atrophies in the amygdala, caudate and thalamus. Subcortical atrophies correlated differently with cognitive dysfunction according to the underlying causes of cognitive dysfunction. CONCLUSIONS: The patterns of subcortical atrophies and their correlation with cognitive dysfunction differ according to the underlying AD, LBD or concomitant AD and LBD.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Lewy Body Disease , Alzheimer Disease/complications , Atrophy , Cognitive Dysfunction/etiology , Cross-Sectional Studies , Humans , Lewy Body Disease/complications
15.
Ann Oncol ; 30(12): 1959-1968, 2019 12 01.
Article in English | MEDLINE | ID: mdl-31562758

ABSTRACT

BACKGROUND: Patients with metastatic pancreatic cancer often have a detriment in health-related quality of life (HRQoL). In the randomized, double-blind, phase III POLO trial progression-free survival was significantly longer with maintenance olaparib, a poly(ADP-ribose) polymerase inhibitor, than placebo in patients with a germline BRCA1 and/or BRCA2 mutation (gBRCAm) and metastatic pancreatic cancer whose disease had not progressed during first-line platinum-based chemotherapy. The prespecified HRQoL evaluation is reported here. PATIENTS AND METHODS: Patients were randomized to receive maintenance olaparib (300 mg b.i.d.; tablets) or placebo. HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item module at baseline, every 4 weeks until disease progression, at discontinuation, and 30 days after last dose. Scores ranged from 0 to 100; a ≥10-point change or difference between arms was considered clinically meaningful. Adjusted mean change from baseline was analysed using a mixed model for repeated measures. Time to sustained clinically meaningful deterioration (TSCMD) was analysed using a log-rank test. RESULTS: Of 154 randomized patients, 89 of 92 olaparib-arm and 58 of 62 placebo-arm patients were included in HRQoL analyses. The adjusted mean change in Global Health Status (GHS) score from baseline was <10 points in both arms and there was no significant between-group difference [-2.47; 95% confidence interval (CI) -7.27, 2.33; P = 0.31]. Analysis of physical functioning scores showed a significant between-group difference (-4.45 points; 95% CI -8.75, -0.16; P = 0.04). There was no difference in TSCMD for olaparib versus placebo for GHS [P = 0.25; hazard ratio (HR) 0.72; 95% CI 0.41, 1.27] or physical functioning (P = 0.32; HR 1.38; 95% CI 0.73, 2.63). CONCLUSIONS: HRQoL was preserved with maintenance olaparib treatment with no clinically meaningful difference compared with placebo. These results support the observed efficacy benefit of maintenance olaparib in patients with a gBRCAm and metastatic pancreatic cancer. CLINCALTRIALS.GOV NUMBER: NCT02184195.


Subject(s)
BRCA1 Protein/genetics , BRCA2 Protein/genetics , Pancreatic Neoplasms/drug therapy , Phthalazines/administration & dosage , Piperazines/administration & dosage , Poly(ADP-ribose) Polymerase Inhibitors/administration & dosage , Adult , Aged , Double-Blind Method , Female , Germ-Line Mutation/genetics , Humans , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/pathology , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Phthalazines/adverse effects , Piperazines/adverse effects , Poly(ADP-ribose) Polymerase Inhibitors/adverse effects , Progression-Free Survival , Quality of Life
16.
Nutr Metab Cardiovasc Dis ; 29(4): 409-420, 2019 04.
Article in English | MEDLINE | ID: mdl-30799179

ABSTRACT

BACKGROUND AND AIM: Metabolic syndromes are prevalent worldwide and result in various complications including obesity, cardiovascular disease and type II diabetes. Betulinic acid (BA) is a naturally occurring triterpenoid that has anti-inflammatory properties. We hypothesized that treatment with BA may result in decreased body weight gain, adiposity and hepatic steatosis in a diet-induced mouse model of obesity. METHODS AND RESULTS: Mice fed a high-fat diet and treated with BA showed less weight gain and tissue adiposity without any change in calorie intake. Gene expression profiling of mouse tissues and cell lines revealed that BA treatment increased expression of lipid oxidative genes and decreased that of lipogenesis-related genes. This modulation was mediated by increased AMP-activated protein kinase (AMPK) phosphorylation, which facilitates energy expenditure, lipid oxidation and thermogenic capacity and exerts protective effects against obesity and nonalcoholic fatty liver disease. Overall, BA markedly inhibited the development of obesity and nonalcoholic fatty liver disease in mice fed a high-fat diet, and AMPK activation in various tissues and enhanced thermogenesis are two possible mechanisms underlying the antiobesity and antisteatogenic effects of BA. CONCLUSIONS: The current findings suggest that treatment with BA is a potential dietary strategy for preventing obesity and nonalcoholic fatty liver disease.


Subject(s)
AMP-Activated Protein Kinases/metabolism , Adipocytes/drug effects , Anti-Obesity Agents/pharmacology , Energy Metabolism/drug effects , Liver/drug effects , Non-alcoholic Fatty Liver Disease/prevention & control , Obesity/prevention & control , Triterpenes/pharmacology , 3T3-L1 Cells , Adipocytes/enzymology , Adipocytes/pathology , Adiposity/drug effects , Animals , Diet, High-Fat , Disease Models, Animal , Enzyme Activation , Liver/enzymology , Liver/pathology , Male , Mice , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease/enzymology , Non-alcoholic Fatty Liver Disease/pathology , Non-alcoholic Fatty Liver Disease/physiopathology , Obesity/enzymology , Obesity/pathology , Obesity/physiopathology , Pentacyclic Triterpenes , Phosphorylation , Signal Transduction , Weight Gain/drug effects , Betulinic Acid
17.
Osteoporos Int ; 30(5): 1071-1078, 2019 May.
Article in English | MEDLINE | ID: mdl-30719549

ABSTRACT

The plasma n-3 fatty acid level was 26.2% lower in patients with osteoporotic hip fracture than in those with osteoarthritis. In all patients, n-3 fatty acid was positively associated with bone mineral density and inversely associated with tartrate-resistant acid phosphatase-5b level in bone marrow aspirates, reflecting the bone microenvironment. INTRODUCTION: Despite the potential beneficial role of n-3 fatty acid (FA) on bone metabolism, the specific mechanisms underlying these effects in humans remain unclear. Here, we assessed whether the plasma n-3 level, as an objective indicator of its status, is associated with osteoporosis-related phenotypes and bone-related markers in human bone marrow (BM) samples. METHODS: This was a case-control and cross-sectional study conducted in a clinical unit. n-3 FA in the blood and bone biochemical markers in the BM aspirates were measured by gas chromatography/mass spectrometry and immunoassay, respectively. BM fluids were collected from 72 patients who underwent hip surgery because of either osteoporotic hip fracture (HF; n = 28) or osteoarthritis (n = 44). RESULTS: After adjusting for confounders, patients with HF had 26.2% lower plasma n-3 levels than those with osteoarthritis (P = 0.006), and each standard deviation increment in plasma n-3 was associated with a multivariate-adjusted odds ratio of 0.40 for osteoporotic HF (P = 0.010). In multivariate analyses including all patients, a higher plasma n-3 level was associated with higher bone mass at the lumbar spine (ß = 0.615, P = 0.002) and total femur (ß = 0.244, P = 0.045). Interestingly, the plasma n-3 level was inversely associated with the tartrate-resistant acid phosphatase-5b level (ß = - 0.633, P = 0.023), but not with the bone-specific alkaline phosphatase level, in BM aspirates. CONCLUSIONS: These findings provide clinical evidence that n-3 FA is a potential inhibitor of osteoclastogenesis that favors human bone health.


Subject(s)
Bone Density/physiology , Fatty Acids, Omega-3/blood , Hip Fractures/physiopathology , Osteoporotic Fractures/physiopathology , Tartrate-Resistant Acid Phosphatase/metabolism , Aged , Aged, 80 and over , Bone Marrow/metabolism , Bone Resorption/physiopathology , Case-Control Studies , Cross-Sectional Studies , Fatty Acids, Omega-3/physiology , Fatty Acids, Omega-6/blood , Female , Femur/physiopathology , Hip Fractures/blood , Humans , Lumbar Vertebrae/physiopathology , Male , Osteoporotic Fractures/blood
18.
Oper Dent ; 44(1): 8-12, 2019.
Article in English | MEDLINE | ID: mdl-30106331

ABSTRACT

The purpose of this case report is to present success and failure outcomes of seven-year follow-up of resin infiltration treatment (RIT) used for the proximal caries of maxillary premolars. Although resin infiltration can be a good option for micro-invasive treatment, long-term follow-up data are not sufficient, and the outcome of this technique can be affected by factors such as technique sensitivity of procedure, patient's caries risk, and depth of caries progression. Therefore, careful case selection, application, and follow-up are needed.


Subject(s)
Dental Caries/therapy , Dental Restoration, Permanent/methods , Resins, Synthetic/therapeutic use , Acid Etching, Dental , Adult , Bicuspid/diagnostic imaging , Composite Resins/therapeutic use , Humans , Male , Resin Cements/therapeutic use
19.
Eur J Neurol ; 26(5): 766-773, 2019 05.
Article in English | MEDLINE | ID: mdl-30565368

ABSTRACT

BACKGROUND AND PURPOSE: To clarify whether subtyping of amnestic and non-amnestic mild cognitive impairment (MCI) is clinically relevant in Parkinson's disease (PD) by analyzing patterns of neuroimaging and longitudinal cognitive changes. METHODS: We performed comparative analyses of cortical thickness, hippocampal volume, white matter integrity and resting-state functional connectivity between the patients with de-novo PD with amnestic MCI (PD-aMCI) (n = 50) and non-amnestic MCI (PD-naMCI) (n = 50) subtypes. Additionally, we assessed the longitudinal rate of cognitive decline in each cognitive domain over time and the rate of dementia conversion in patients with de-novo PD-aMCI (n = 125) and PD-naMCI (n = 61). RESULTS: The demographic data showed that scores in memory domains were lower in the PD-aMCI group compared with the PD-naMCI group. There were no significant differences in cortical thickness, hippocampal volume and white matter integrity between the two groups, although the PD-aMCI group exhibited more cortical thinning and hippocampal atrophy relative to the control group. The PD-aMCI group exhibited increased functional connectivity in the left posterior parietal region with the salience network relative to the PD-naMCI group. The longitudinal cognitive assessment demonstrated that patients with PD-aMCI exhibited a more rapid cognitive decline in frontal/executive function than those with PD-naMCI (P = 0.022). In addition, the PD-aMCI group had a higher risk of dementia conversion than the PD-naMCI group. CONCLUSIONS: This study suggests that the designation of PD-MCI subtypes based on memory function would highlight the heterogeneity of functional correlates as well as the longitudinal cognitive prognosis.


Subject(s)
Amnesia/psychology , Cognitive Dysfunction/psychology , Parkinson Disease/classification , Parkinson Disease/psychology , Aged , Aged, 80 and over , Cerebral Cortex/diagnostic imaging , Cognitive Dysfunction/diagnostic imaging , Dementia/etiology , Dementia/psychology , Disease Progression , Executive Function , Female , Hippocampus/diagnostic imaging , Humans , Longitudinal Studies , Male , Middle Aged , Nerve Net/diagnostic imaging , Neuroimaging , Neuropsychological Tests , Parkinson Disease/diagnostic imaging , Prognosis , White Matter/diagnostic imaging
20.
Science ; 362(6419): 1153-1156, 2018 12 07.
Article in English | MEDLINE | ID: mdl-30523109

ABSTRACT

Graphene is an atomically thin plasmonic medium that supports highly confined plasmon polaritons, or nano-light, with very low loss. Electronic properties of graphene can be drastically altered when it is laid upon another graphene layer, resulting in a moiré superlattice. The relative twist angle between the two layers is a key tuning parameter of the interlayer coupling in thus-obtained twisted bilayer graphene (TBG). We studied the propagation of plasmon polaritons in TBG by infrared nano-imaging. We discovered that the atomic reconstruction occurring at small twist angles transforms the TBG into a natural plasmon photonic crystal for propagating nano-light. This discovery points to a pathway for controlling nano-light by exploiting quantum properties of graphene and other atomically layered van der Waals materials, eliminating the need for arduous top-down nanofabrication.

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