Combining neuropsychological assessment and structural neuroimaging to identify early Alzheimer's disease in a memory clinic cohort.

INTRODUCTION: The current study examined the contributions of comprehensive neuropsychological assessment and volumetric assessment of selected mesial temporal subregions on structural magnetic resonance imaging (MRI) to identify patients with amnestic mild cognitive impairment (aMCI) and mild probable Alzheimer's disease (AD) dementia in a memory clinic cohort. METHODS: Comprehensive neuropsychological assessment and automated entorhinal, transentorhinal, and hippocampal volume measurements were conducted in 40 healthy controls, 38 patients with subjective memory symptoms, 16 patients with aMCI, 16 patients with mild probable AD dementia. Multinomial logistic regression was used to compare the neuropsychological and MRI measures. RESULTS: Combining the neuropsychological and MRI measures improved group membership prediction over the MRI measures alone but did not improve group membership prediction over the neuropsychological measures alone. CONCLUSION: Comprehensive neuropsychological assessment was an important tool to evaluate cognitive impairment. The mesial temporal volumetric MRI measures contributed no diagnostic value over and above the determinations made through neuropsychological assessment.

Validating ASHS-T1 automated entorhinal and transentorhinal cortical segmentation in Alzheimer's disease.

The current study aimed to validate entorhinal and transentorhinal cortical volumes measured by the automated segmentation tool Automatic Segmentation of Hippocampal Subfields (ASHS-T1). The study sample comprised 34 healthy controls (HCs), 37 individuals with amnestic mild cognitive impairment (aMCI), and 29 individuals with Alzheimer's disease (AD) dementia from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Entorhinal and transentorhinal cortical volumes were assessed using ASHS-T1, manual segmentation, as well as a widely used automated segmentation tool, FreeSurfer v6.0.1. Mean differences, intraclass correlation coefficients, and Bland-Altman plots were computed. ASHS-T1 tended to underestimate entorhinal and transentorhinal cortical volumes relative to manual segmentation and FreeSurfer. There was variable consistency and low agreement between ASHS-T1 and manual segmentation volumes. There was low-to-moderate consistency and low agreement between ASHS-T1 and FreeSurfer volumes. There was a trend toward higher consistency and agreement for the entorhinal cortex in the aMCI and AD groups compared to the HC group. Despite the differences in volume measurements, ASHS-T1 was sensitive to entorhinal and transentorhinal cortical atrophy in both early and late disease stages. Based on the current study, ASHS-T1 appears to be a promising tool for automated entorhinal and transentorhinal cortical volume measurement in individuals with likely underlying AD.

Making shared decisions with older men selecting treatment for lower urinary tract symptoms secondary to benign prostatic hyperplasia (LUTS/BPH): a pilot randomized trial.

BACKGROUND: Making high-quality decisions when selecting treatment for lower urinary tract symptoms due to benign prostatic hyperplasia (LUTS/BPH) requires a shared decision-making approach. However, older people with lower health literacy face barriers. The pilot study aimed to evaluate the feasibility of recruiting participants and evaluate the effectiveness of a multi-level intervention on decision quality for the treatment of LUTS/BPH. METHOD: In this 2-arm, randomized controlled trial, multi-ethnic Asian men aged ≥ 50 years with moderate or severe symptoms (IPSS ≥ 8 and/or QOL ≥ 3) and physicians were recruited at a Singapore public primary care clinic. Men were randomized to either physicians trained in shared decision-making and used a pictorial patient-reported symptom score (Visual Analogue Uroflowmetry Score) during the consultation or to physicians untrained in shared decision-making who did not use the score. Decision quality was measured using SDMQ-9 scores from men and their physicians after the consultation. RESULTS: 60 men (intervention [n = 30], control [n = 30]) receiving care from 22 physicians were recruited. Men's mean age was 70 ± 9 years: 87% were Chinese, 40% had no formal education, and 32% were of lower socioeconomic status. No difference in decision quality from the men's nor their physicians' perspectives was noted [for men: mean score = 70.8 (SD 20.3) vs. 59.5 (SD 22.4); adjusted p = 0.352] [for physicians: mean score = 78.1 (SD 14.1) vs. 73.2 (SD 19.8); adjusted p > 0.999]. CONCLUSION: It was feasible to recruit the intended participants. There was no difference in decision quality between men who used shared decision-making and usual care for the treatment of LUTS/BPH.

Agreement Between Automated and Manual MRI Volumetry in Alzheimer's Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Automated magnetic resonance imaging (MRI) volumetry is a promising tool to evaluate regional brain volumes in dementia and especially Alzheimer's disease (AD). PURPOSE: To compare automated methods and the gold standard manual segmentation in measuring regional brain volumes on MRI across healthy controls, patients with mild cognitive impairment, and patients with dementia due to AD. STUDY TYPE: Systematic review and meta-analysis. DATA SOURCES: MEDLINE, Embase, and PsycINFO were searched through October 2021. FIELD STRENGTH: 1.0 T, 1.5 T, or 3.0 T. ASSESSMENT: Two review authors independently identified studies for inclusion and extracted data. Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). STATISTICAL TESTS: Standardized mean differences (SMD; Hedges' g) were pooled using random-effects meta-analysis with robust variance estimation. Subgroup analyses were undertaken to explore potential sources of heterogeneity. Sensitivity analyses were conducted to examine the impact of the within-study correlation between effect estimates on the meta-analysis results. RESULTS: Seventeen studies provided sufficient data to evaluate the hippocampus, lateral ventricles, and parahippocampal gyrus. The pooled SMD for the hippocampus, lateral ventricles, and parahippocampal gyrus were 0.22 (95% CI -0.50 to 0.93), 0.12 (95% CI -0.13 to 0.37), and -0.48 (95% CI -1.37 to 0.41), respectively. For the hippocampal data, subgroup analyses suggested that the pooled SMD was invariant across clinical diagnosis and field strength. Subgroup analyses could not be conducted on the lateral ventricles data and the parahippocampal gyrus data due to insufficient data. The results were robust to the selected within-study correlation value. DATA CONCLUSION: While automated methods are generally comparable to manual segmentation for measuring hippocampal, lateral ventricle, and parahippocampal gyrus volumes, wide 95% CIs and large heterogeneity suggest that there is substantial uncontrolled variance. Thus, automated methods may be used to measure these regions in patients with AD but should be used with caution. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

Causal Relations between Exposome and Stroke: A Mendelian Randomization Study / 대한뇌졸중학회지

Background@#and Purpose To explore the causal relationships of elements of the exposome with ischemic stroke and its subtypes at the omics level and to provide evidence for stroke prevention. Methods We conducted a Mendelian randomization study between exposure and any ischemic stroke (AIS) and its subtypes (large-artery atherosclerotic disease [LAD], cardioembolic stroke [CE], and small vessel disease [SVD]). The exposure dataset was the UK Biobank involving 361,194 subjects, and the outcome dataset was the MEGASTROKE consortium including 52,000 participants. @*Results@#We found that higher blood pressure (BP) (systolic BP: odds ratio [OR], 1.02; 95% confidence interval [CI], 1.01 to 1.04; diastolic BP: OR, 1.03; 95% CI, 1.01 to 1.05; pulse pressure: OR, 1.03; 95% CI, 1.00 to 1.06), atrial fibrillation (OR, 1.18; 95% CI, 1.13 to 1.25), and diabetes (OR, 1.13; 95% CI, 1.07 to 1.18) were significantly associated with ischemic stroke. Importantly, higher education (OR, 0.69; 95% CI, 0.60 to 0.79) decreased the risk of ischemic stroke. Higher systolic BP (OR, 1.06; 95% CI, 1.02 to 1.10), pulse pressure (OR, 1.08; 95% CI, 1.02 to 1.14), diabetes (OR, 1.28; 95% CI, 1.13 to 1.45), and coronary artery disease (OR, 1.58; 95% CI, 1.25 to 2.00) could cause LAD. Atrial fibrillation could cause CE (OR, 1.90; 95% CI, 1.71 to 2.11). For SVD, higher systolic BP (OR, 1.04; 95% CI, 1.00 to 1.07), diastolic BP (OR, 1.06; 95% CI, 1.01 to 1.12), and diabetes (OR, 1.22; 95% CI, 1.10 to 1.36) were causal factors. @*Conclusions@#The study revealed elements of the exposome causally linked to ischemic stroke and its subtypes, including conventional causal risk factors and novel protective factors such as higher education.

Comparative Utility of Manual versus Automated Segmentation of Hippocampus and Entorhinal Cortex Volumes in a Memory Clinic Sample.

Structural neuroimaging is a useful non-invasive biomarker commonly employed to evaluate the integrity of mesial temporal lobe structures that are typically compromised in Alzheimer's disease. Advances in quantitative neuroimaging have permitted the development of automated segmentation protocols (e.g., FreeSurfer) with significantly increased efficiency compared to earlier manual techniques. While these protocols have been found to be suitable for large-scale, multi-site research studies, we were interested in assessing the practical utility and reliability of automated FreeSurfer protocols compared to manual volumetry on routinely acquired clinical scans. Independent validation studies with newer automated segmentation protocols are scarce. Two FreeSurfer protocols for each of two regions of interest-the hippocampus and entorhinal cortex-were compared against manual volumetry. High reliability and agreement was found between FreeSurfer and manual hippocampal protocols, however, there was lower reliability and agreement between FreeSurfer and manual entorhinal protocols. Although based on a the relatively small sample of subjects drawn from a memory clinic (n = 27), our study findings suggest further refinements to improve measurement error and most accurately depict true regional brain volumes using automated segmentation protocols are required, especially for non-hippocampal mesial temporal structures, to achieve maximal utility for routine clinical evaluations.

In vitro-in vivo correlation of goserelin acetate microspheres / 药学学报

The objective of this paper was to establish a level A in vitro-in vivo correlation (IVIVC) for goserelin acetate extended release microspheres for injection. Three kinds of goserelin acetate microspheres with different release rates were prepared and the critical physicochemical properties, such as drug loading, particle size, glass transition temperature and morphology were characterized. In vitro dissolution test of the prepared goserelin acetate microspheres was performed using sample-and-separate method at 45 ℃ in 5% (v/v) methanol. The morphology of the microspheres and the molecular weight of poly (lactic-co-glycolic acid) (PLGA) of the prepared goserelin acetate microspheres were investigated to research the release mechanism of microspheres. The plasma concentration of goserelin was detected after intramuscular injection of goserelin acetate microspheres to SD rats, and correlated with the in vitro release profiles after processing by percent AUC method. The pharmacokinetic experimental protocol of goserelin acetate microspheres for injection in SD rats was approved by the Animal Ethics Committee of Shandong Luye Pharmaceutical Co., Ltd. The results indicated that the developed sample and separate method was able to detect differences in the release characteristics of the prepared goserelin acetate microspheres, and the in vitro-in vivo correlation of goserelin acetate microspheres was excellent (r > 0.98) and had good predictive ability in SD rats.

Effect of salmon calcitonin on RANK/RANKL/OPG osteolysis pathway in human macrophages after particle induction / 中国医师杂志

Objective To explore the effect of salmon calcitonin on the receptor activator of NF-κB/receptor activator of NF-κB ligand/osteoprotegerin (RANK/RANKL/OPG) osteolysis pathway in human macrophages after particles induction.Methods The polyethylene wear particles were extracted from the periacetabular boundary membrane tissue of a patient with hip prosthesis loosening.The optimal reaction cell concentration of human macrophages to polyethylene wear particles (with a concentration of 0.1 mg/ml) was measured by methyl thiazolyl tetrazolium (MTT) assay.Particles were used to stimulate human macrophages,while salmon calcitonin with different drug concentrations was used for intervention.They were randomly divided into five groups,with six parts in each group:Group A,control group;Group B,particle group;Group C,particle + salmon calcitonin (10-8 mol/L) group;Group D,particle + salmon calcitonin (10-10 mol/L) group;Group E,particle+salmon calcitonin (10-12 mol/L) group.After cocultured for 48 hours,quantitative polymerase chain reaction (qPCR) assay was used to detect the mRNA expression of RANK,RANKL and OPG in macrophages.Results After induction with particles,Group B had a higher expression in RANK and RANKL,and lower OPG expression than Group A.After salmon calcitonin intervention,the expression of RANK and RANKL were significantly decreased,and OPG expression was significantly increased.Group B had the highest RANKL/OPG rate.After drug intervention,the RANKL/OPG rate in C,D,E group were reduced.Conclusions The particles can induce the transformation of macrophages into osteoclasts.In addition to directly inhibiting osteoclast activity,salmon calcitonin prevents macrophage from differentiating into osteoclasts through modulating RANKL/RANK/OPG signaling pathway.

Effect of edaravone in diabetes mellitus-induced nephropathy in rats.

Edaravone, a synthetic-free radical scavenger, has been reported to reduce ischemia-reperfusion-induced renal injury by improving tubular cell function, and lowering serum creatinine and renal vascular resistance. The present study investigated the effect of edaravone in diabetes mellitus-induced nephropathy in rats. A single administration of streptozotocin (STZ, 55 mg/kg, i.p.) was employed to induce diabetes mellitus in rats. The STZ-administered diabetic rats were allowed for 10 weeks to develop nephropathy. Mean body weight, lipid alteration, renal functional and histopathology were analysed. Diabetic rats developed nephropathy as evidenced by a significant increase in serum creatinine and urea, and marked renal histopathological abnormalities like glomerulosclerosis and tubular cell degeneration. The kidney weight to body weight ratio was increased. Moreover, diabetic rats showed lipid alteration as evidenced by a signifi cant increase in serum triglycerides and decrease in serum high-density lipoproteins. Edaravone (10 mg/kg, i.p., last 4-weeks) treatment markedly prevented the development of nephropathy in diabetic rats by reducing serum creatinine and urea and preventing renal structural abnormalities. In addition, its treatment, without significantly altering the elevated glucose level in diabetic rats, prevented diabetes mellitus-induced lipid alteration by reducing serum triglycerides and increasing serum high-density lipoproteins. Interestingly, the renoprotective effect of edaravone was comparable to that of lisinopril (5 mg/kg, p.o, 4 weeks, standard drug). Edaravone prevented renal structural and functional abnormalities and lipid alteration associated with experimental diabetes mellitus. Edaravone has a potential to prevent nephropathy without showing an anti-diabetic action, implicating its direct renoprotection in diabetic rats.

Volcanic air pollution over the Island of Hawai'i: Emissions, dispersal, and composition. Association with respiratory symptoms and lung function in Hawai'i Island school children.

BACKGROUND: Kilauea Volcano on the Island of Hawai'i has erupted continuously since 1983, releasing approximately 300-12000metrictons per day of sulfur dioxide (SO2). SO2 interacts with water vapor to produce an acidic haze known locally as "vog". The combination of wind speed and direction, inversion layer height, and local terrain lead to heterogeneous and variable distribution of vog over the island, allowing study of respiratory effects associated with chronic vog exposure. OBJECTIVES: We characterized the distribution and composition of vog over the Island of Hawai'i, and tested the hypotheses that chronic vog exposure (SO2 and acid) is associated with increased asthma prevalence, respiratory symptoms, and reduced pulmonary function in Hawai'i Island schoolchildren. METHODS: We compiled data of volcanic emissions, wind speed, and wind direction over Hawai'i Island since 1992. Community-based researchers then measured 2- to 4-week integrated concentrations of SO2 and fine particulate mass and acidity in 4 exposure zones, from 2002 to 2005, when volcanic SO2 emissions averaged 1600metrictons per day. Concurrently, community researchers recruited schoolchildren in the 4th and 5th grades of 25 schools in the 4 vog exposure zones, to assess determinants of lung health, respiratory symptoms, and asthma prevalence. RESULTS: Environmental data suggested 4 different vog exposure zones with SO2, PM2.5, and particulate acid concentrations (mean±s.d.) as follows: 1) Low (0.3±0.2ppb, 2.5±1.2µg/m(3), 0.6±1.1nmolH+/m(3)), 2) Intermittent (1.6±1.8ppb, 2.8±1.5µg/m(3), 4.0±6.6nmolH+/m(3)), 3) Frequent (10.1±5.2ppb, 4.8±1.9µg/m(3), 4.3±6.7nmolH+/m(3)), and 4) Acid (1.2±0.4ppb, 7.2±2.3µg/m(3), 25.3±17.9nmolH+/m(3)). Participants (1957) in the 4 zones differed in race, prematurity, maternal smoking during pregnancy, environmental tobacco smoke exposure, presence of mold in the home, and physician-diagnosed asthma. Multivariable analysis showed an association between Acid vog exposure and cough and strongly suggested an association with FEV1/FVC <0.8, but not with diagnosis of asthma, or chronic persistent wheeze or bronchitis in the last 12months. CONCLUSIONS: Hawai'i Island's volcanic air pollution can be very acidic, but contains few co-contaminants originating from anthropogenic sources of air pollution. Chronic exposure to acid vog is associated with increased cough and possibly with reduced FEV1/FVC, but not with asthma or bronchitis. Further study is needed to better understand how volcanic air pollution interacts with host and environmental factors to affect respiratory symptoms, lung function, and lung growth, and to determine acute effects of episodes of increased emissions.

Effect of edaravone in diabetes mellitus-induced nephropathy in rats

Edaravone, a synthetic-free radical scavenger, has been reported to reduce ischemia-reperfusion-induced renal injury by improving tubular cell function, and lowering serum creatinine and renal vascular resistance. The present study investigated the effect of edaravone in diabetes mellitus-induced nephropathy in rats. A single administration of streptozotocin (STZ, 55 mg/kg, i.p.) was employed to induce diabetes mellitus in rats. The STZ-administered diabetic rats were allowed for 10 weeks to develop nephropathy. Mean body weight, lipid alteration, renal functional and histopathology were analysed. Diabetic rats developed nephropathy as evidenced by a significant increase in serum creatinine and urea, and marked renal histopathological abnormalities like glomerulosclerosis and tubular cell degeneration. The kidney weight to body weight ratio was increased. Moreover, diabetic rats showed lipid alteration as evidenced by a signifi cant increase in serum triglycerides and decrease in serum high-density lipoproteins. Edaravone (10 mg/kg, i.p., last 4-weeks) treatment markedly prevented the development of nephropathy in diabetic rats by reducing serum creatinine and urea and preventing renal structural abnormalities. In addition, its treatment, without significantly altering the elevated glucose level in diabetic rats, prevented diabetes mellitus-induced lipid alteration by reducing serum triglycerides and increasing serum high-density lipoproteins. Interestingly, the renoprotective effect of edaravone was comparable to that of lisinopril (5 mg/kg, p.o, 4 weeks, standard drug). Edaravone prevented renal structural and functional abnormalities and lipid alteration associated with experimental diabetes mellitus. Edaravone has a potential to prevent nephropathy without showing an anti-diabetic action, implicating its direct renoprotection in diabetic rats.