Tip-based Lithography with a Sacrificial Layer.

The fabrication of a highly controlled gold (Au) nanohole (NH) array via tip-based lithography is improved by incorporating a sacrificial layer-a tip-crash buffer layer. This inclusion mitigates scratches during the nano-indentation process by employing a 300 nm thick poly(methyl methacrylate) layer as a sacrificial layer on top of the Au film. Such a precaution ensures minimal scratches on the Au film, facilitating the creation of sub-50 nm Au NHs with a 15 nm gap between the Au NHs. The precision of this method exceeds that of fabricating Au NHs without a sacrificial layer. Demonstrating its versatility, this Au NH array is utilized in two distinct applications: as a dry etching mask to form a molybdenum disulfide hole array and as a catalyst in metal-assisted chemical etching, resulting in conical-shaped silicon nanostructures. Additionally, a significant electric field is generated when Au nanoparticles (NPs) are placed within the Au NHs. This effect arises from coupling electromagnetic waves, concentrated by the Au NHs and amplified by the Au NPs. A notable result of this configuration is the enhancement factor of surface-enhanced Raman scattering, which is an order of magnitude greater than that observed with just Au NHs and Au NPs alone.

Long-Term Impact of Delirium on the Risk of Dementia in Hospitalized Older Patients: A Real-World Multicenter Study.

BACKGROUND: The association between delirium and dementia has been suggested, but mostly in the postoperative setting. This study aims to explore this relationship in a broader inpatient population, leveraging extensive real-world data to provide a more generalized understanding. METHODS: In this retrospective cohort study, electronic health records of 11,970,475 hospitalized patients aged over 60 from nine institutions in South Korea were analyzed. Patients with and without delirium were identified, and propensity score matching (PSM) was used to create comparable groups. A 10-year longitudinal analysis was conducted using the Cox proportional hazards model, which calculated the hazard ratio (HR) and 95% confidence interval (CI). Additionally, a meta-analysis was performed, aggregating results from all nine medical institutions. Lastly, we conducted various subgroup and sensitivity analyses to demonstrate the consistency of our study results across diverse conditions. RESULTS: After 1:1 PSM, a total of 47,306 patients were matched in both the delirium and nondelirium groups. Both groups had a median age group of 75-79 years, with 43.1% being female. The delirium group showed a significantly higher risk of all dementia compared with the nondelirium group (HR: 2.70 [95% CI: 2.27-3.20]). The incidence risk for different types of dementia was also notably higher in the delirium group (all dementia or mild cognitive impairment, HR: 2.46 [95% CI: 2.10-2.88]; Alzheimer's disease, HR: 2.74 [95% CI: 2.40-3.13]; vascular dementia, HR: 2.55 [95% CI: 2.07-3.13]). This pattern was consistent across all subgroup and sensitivity analyses. CONCLUSIONS: Delirium significantly increases the risk of onset for all types of dementia. These findings highlight the importance of early detection of delirium and prompt intervention. Further research studies are warranted to investigate the mechanisms linking delirium and dementia.

Factors associated with cognitive reserve according to education level.

INTRODUCTION: We investigated distinctive factors associated with cognitive reserve (CR) based on education level. METHODS: Among 1247 participants who underwent neuropsychological assessment, amyloid positron emission tomography, and brain magnetic resonance imaging, 336 participants with low education (≤6 years) and 697 with high education (≥12 years) were selected. CR was measured as the difference between the predicted and observed value of cognitive function based on cortical thickness. Multiple linear regression was conducted in each group after controlling for age and sex. RESULTS: In the low-education group, low literacy, long sleep duration(>8 h/day), and diabetes were negatively associated with CR, whereas cognitive and physical activity were positively associated with CR. In the high-education group, cognitive activity was positively related to CR, whereas low literacy, long sleep duration (> 8 h/day), and depression were negatively related to CR. DISCUSSION: This study provides insights into different strategies for enhancing CR based on educational background. HIGHLIGHTS: Factors associated with cognitive reserve (CR) varied according to the education level. Diabetes and physical activity were associated with CR in the low-education group. Depression was related to CR in the high-education group. Low literacy, sleep duration, and cognitive activity were associated with CR in both groups. Dementia-prevention strategies should be tailored according to educational level.

Long-Range Electrification of an Air/Electrolyte Interface and Probing Potential of Zero Charge by Conductive Amplitude-Modulated Atomic Force Microscopy.

The structure of an electrical double layer (EDL) at the interface of electrode/electrolyte or air/electrode/electrolyte is a fundamental aspect, however not fully understood. The potential of zero charge (PZC) is one of the clues to dictate the EDL, where the excess charge on the electrode surface is zero. Here, a nanoscale configuration of immersion method was proposed by integrating an electrochemical system into conductive atomic force spectroscopy under the amplitude modulation (AM) mode and agarose gel as the solid-liquid electrolyte. The PZC of boron-doped diamond was determined to be at 0.2 V (vs Ag/AgCl). By AM spectroscopy, the capacitive force shows remote electrification without direct electrode/electrolyte contact, which is dependent on the population of ions at the air/electrolyte interface. The surface potential by alignment of water is also evaluated. Prospectively, our study could benefit applications such as PZC measurement and non-electrode electrochemical processes at the air/electrolyte interface.

Evidence of risky driving in Korean older adults: A longitudinal cohort.

OBJECTIVES: The aim of this study was to determine the differences in the risk factors for dangerous driving between older adults with normal cognition and those with cognitive impairment. DESIGN: The driving risk questionnaire (DRQ) that was applied to a community-dwelling older adult cohort and 2 years of accident/violation records from the National Police Agency were analyzed. We conducted regression analyses with the presence or absence of risky driving based on records (accidents + violations) 2 years before and after evaluation as a dependent variable and dichotomized scores of each risky driving factor as independent variables. RESULTS: According to four identified factors-crash history, safety concern, reduced mileage, and aggressive driving-significant associations were found between risky driving over the past 2 years and crash history and for aggressive driving in the normal cognition group. In the cognitive impairment group, only crash history was significantly associated, although safety concerns showed a trend toward significance. CONCLUSIONS: In this study, it was suggested that the factors of DRQ have a significant association with actual risky driving. Our results are expected to contribute to establishing the evidence for evaluating and predicting risky driving and advising whether to continue driving in clinics.

Machine learning application for classification of Alzheimer's disease stages using 18F-flortaucipir positron emission tomography.

BACKGROUND: The progression of Alzheimer's dementia (AD) can be classified into three stages: cognitive unimpairment (CU), mild cognitive impairment (MCI), and AD. The purpose of this study was to implement a machine learning (ML) framework for AD stage classification using the standard uptake value ratio (SUVR) extracted from 18F-flortaucipir positron emission tomography (PET) images. We demonstrate the utility of tau SUVR for AD stage classification. We used clinical variables (age, sex, education, mini-mental state examination scores) and SUVR extracted from PET images scanned at baseline. Four types of ML frameworks, such as logistic regression, support vector machine (SVM), extreme gradient boosting, and multilayer perceptron (MLP), were used and explained by Shapley Additive Explanations (SHAP) to classify the AD stage. RESULTS: Of a total of 199 participants, 74, 69, and 56 patients were in the CU, MCI, and AD groups, respectively; their mean age was 71.5 years, and 106 (53.3%) were men. In the classification between CU and AD, the effect of clinical and tau SUVR was high in all classification tasks and all models had a mean area under the receiver operating characteristic curve (AUC) > 0.96. In the classification between MCI and AD, the independent effect of tau SUVR in SVM had an AUC of 0.88 (p < 0.05), which was the highest compared to other models. In the classification between MCI and CU, the AUC of each classification model was higher with tau SUVR variables than with clinical variables independently, which yielded an AUC of 0.75(p < 0.05) in MLP, which was the highest. As an explanation by SHAP for the classification between MCI and CU, and AD and CU, the amygdala and entorhinal cortex greatly affected the classification results. In the classification between MCI and AD, the para-hippocampal and temporal cortex affected model performance. Especially entorhinal cortex and amygdala showed a higher effect on model performance than all clinical variables in the classification between MCI and CU. CONCLUSIONS: The independent effect of tau deposition indicates that it is an effective biomarker in classifying CU and MCI into clinical stages using MLP. It is also very effective in classifying AD stages using SVM with clinical information that can be easily obtained at clinical screening.

Enhanced recovery after surgery pathway with modified biportal endoscopic transforaminal lumbar interbody fusion using a large cage. Comparative study with minimally invasive microscopic transforaminal lumbar interbody fusion.

PURPOSE: Studies about the clinical efficacy of endoscopic lumbar interbody fusion using an enhanced recovery after surgery (ERAS) pathway are insufficient. Thus, the purpose of this study was to investigate clinical usefulness of biportal endoscopic transforaminal lumbar interbody fusion (TLIF) using an ERAS compared with microscopic TLIF. METHODS: Prospectively collected data were retrospectively analyzed. Patients who received modified biportal endoscopic TLIF with ERAS were grouped into an endoscopic TLIF group. Those who received microscopic TLIF without ERAS were grouped into a microscopic TLIF group. Clinical and radiologic parameters were compared between two groups. Fusion rate was evaluated using sagittal reconstruction images of postoperative computed tomographic (CT) scan. RESULTS: There were 32 patients in the endoscopic TLIF group with ERAS and 41 patients in the microscopic TLIF group without ERAS. Visual analog scale (VAS) scores for back pain preoperatively at day one and day two were significantly (p < 0.05) higher in the non-ERAS microscopic TLIF group than in the ERAS endoscopic TLIF group. Preoperative Oswestry Disability Index were significantly improved at the last follow-up in both groups. The fusion rate at postoperative one year was 87.5% in the endoscopic TLIF group and 85.4% in the microscopic TLIF group. CONCLUSION: Biportal endoscopic TLIF with ERAS pathway may have good aspect to accelerate recovery after surgery. There was no inferiority of fusion rate of endoscopic TLIF comparing to microscopic TLIF. Biportal endoscopic TLIF using a large cage with ERAS pathway may be a good alternative treatment for lumbar degenerative disease.

Privacy-Preserving Federated Model Predicting Bipolar Transition in Patients With Depression: Prediction Model Development Study.

BACKGROUND: Mood disorder has emerged as a serious concern for public health; in particular, bipolar disorder has a less favorable prognosis than depression. Although prompt recognition of depression conversion to bipolar disorder is needed, early prediction is challenging due to overlapping symptoms. Recently, there have been attempts to develop a prediction model by using federated learning. Federated learning in medical fields is a method for training multi-institutional machine learning models without patient-level data sharing. OBJECTIVE: This study aims to develop and validate a federated, differentially private multi-institutional bipolar transition prediction model. METHODS: This retrospective study enrolled patients diagnosed with the first depressive episode at 5 tertiary hospitals in South Korea. We developed models for predicting bipolar transition by using data from 17,631 patients in 4 institutions. Further, we used data from 4541 patients for external validation from 1 institution. We created standardized pipelines to extract large-scale clinical features from the 4 institutions without any code modification. Moreover, we performed feature selection in a federated environment for computational efficiency and applied differential privacy to gradient updates. Finally, we compared the federated and the 4 local models developed with each hospital's data on internal and external validation data sets. RESULTS: In the internal data set, 279 out of 17,631 patients showed bipolar disorder transition. In the external data set, 39 out of 4541 patients showed bipolar disorder transition. The average performance of the federated model in the internal test (area under the curve [AUC] 0.726) and external validation (AUC 0.719) data sets was higher than that of the other locally developed models (AUC 0.642-0.707 and AUC 0.642-0.699, respectively). In the federated model, classifications were driven by several predictors such as the Charlson index (low scores were associated with bipolar transition, which may be due to younger age), severe depression, anxiolytics, young age, and visiting months (the bipolar transition was associated with seasonality, especially during the spring and summer months). CONCLUSIONS: We developed and validated a differentially private federated model by using distributed multi-institutional psychiatric data with standardized pipelines in a real-world environment. The federated model performed better than models using local data only.

Abnormalities of Rest-Activity and Light Exposure Rhythms Associated with Cognitive Function in Patients with Mild Cognitive Impairment (MCI).

We aimed to examine the difference in rest-activity rhythm (RAR) and light exposure rhythm (LER) between patients with mild cognitive impairment (MCI) and normal controls (NC), and to verify their relationships with cognitive functions. The neuropsychological battery was administered to participants above 50 years old. The MCI diagnosis was made according to Petersen's criteria. Ten patients with MCI (77.90 ± 6.95 years) and eight NC (74.75 ± 5.06 years) were studied. Actigraphy (Actiwatch 2; Philips Respironics) was recorded at home for 5 days. RAR and LER variables, including interdaily stability (IS), intradaily variability (IV) and relative amplitude, were calculated using nonparametric analyses. The associations between cognitive performance and RAR and LER variables were explored using generalized linear models. There were no significant differences in RAR or LER variables between MCI and NC. There was a significant main effect of RAR-IS on the Stroop Color and Word Test (SCWT), indicating a positive relationship between RAR stability and SCWT performance. There was a significant group by RAR-IS interaction on Trail Making Test-A, indicating a negative relationship in MCI compared to NC. There was a significant group by LER-IV interaction on the Boston Naming Test, indicating a positive relationship in MCI compared to NC. There was no disruption in RAR and LER in patients with MCI. Our study showed that circadian rhythm abnormality was associated with a decline in executive function. However, circadian rhythm abnormality was not associated with declines in processing speed and language function in patients with MCI, implying an altered pathophysiology compared to NC.

Predicting cognitive stage transition using p-tau181, Centiloid, and other measures.

BACKGROUND: A combination of plasma phospho-tau (p-tau), amyloid beta (Aß)-positron emission tomography (PET), brain magnetic resonance imaging, cognitive function tests, and other biomarkers might predict future cognitive decline. This study aimed to investigate the efficacy of combining these biomarkers in predicting future cognitive stage transitions within 3 years. METHODS: Among the participants in the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE-V) study, 49 mild cognitive impairment (MCI) and 113 cognitively unimpaired (CU) participants with Aß-PET and brain imaging data were analyzed. RESULTS: Older age, increased plasma p-tau181, Aß-PET positivity, and decreased semantic fluency were independently associated with cognitive stage transitions. Combining age, p-tau181, the Centiloid scale, semantic fluency, and hippocampal volume produced high predictive value in predicting future cognitive stage transition (area under the curve = 0.879). CONCLUSIONS: Plasma p-tau181 and Centiloid scale alone or in combination with other biomarkers, might predict future cognitive stage transition in non-dementia patients. HIGHLIGHTS: -Plasma p-tau181 and Centiloid scale might predict future cognitive stage transition. -Combining them or adding other biomarkers increased the predictive value. -Factors that independently associated with cognitive stage transition were demonstrated.

Surface Functionalization of Enzyme-Coronated Gold Nanoparticles with an Erythrocyte Membrane for Highly Selective Glucose Assays.

Colorimetric glucose sensors using enzyme-coronated gold nanoparticles have been developed for high-throughput assays to monitor the blood glucose levels of diabetic patients. Although those sensors have shown sensitivity and wide linear detection ranges, they suffer from poor selectivity and stability in detecting blood glucose, which has limited their practical use. To address this limitation, herein, we functionalized glucose-oxidase-coronated gold nanoparticles with an erythrocyte membrane (EM-GOx-GNPs). Because the erythrocyte membrane (EM) selectively facilitates the permeation of glucose via glucose transporter-1 (GLUT1), the functionalization of GOx-GNPs with EM improved the stability, selectivity (3.3- to 15.8-fold higher), and limit of detection (LOD). Both membrane proteins, GLUT1 and aquaporin-1 (AQP1), on EM were shown to be key components for selective glucose detection by treatment with their inhibitors. Moreover, we demonstrated the stability of EM-GOx-GNPs in high-antioxidant-concentration conditions, under long-term storage (∼4 weeks) and a freeze-thaw cycle. Selectivity of the EM-GOx-GNPs against other saccharides was increased, which improved the LOD in phosphate-buffered saline and human serum. Our results indicated that the functionalization of colorimetric glucose sensors with EM is beneficial for improving selectivity and stability, which may make them candidates for use in a practical glucose sensor.

Association between Baseline Cognitive Function and Longitudinal Functional Outcome Change after Ischemic Stroke.

INTRODUCTION: Ischemic stroke can cause impairment of daily function and cognitive function. Higher cognitive function is reported in many studies to be associated with better functional outcomes; however, evidence from longitudinal study is lacking. Therefore, in the present study, the association between cognitive function and longitudinal changes of functional outcome was investigated based on stroke severity. Furthermore, whether the effect of cognitive function remained consistent after controlling for depression was investigated. METHODS: The data of 423 stroke patients (292 minor strokes, 93 moderate strokes, and 38 severe strokes) were collected. Baseline Mini-Mental State Examination (MMSE) score was considered a predictor, and change of modified Rankin Scale (mRS) score during 12 months of follow-up was the outcome. First, the association between the baseline MMSE score and longitudinal change in the mRS score was analyzed using linear mixed-effects models. Fixed effects were MMSE score group, time, and MMSE score group × time interaction. Additional adjustment was made for the Geriatric Depression Scale (GDS) score. RESULTS: Among the 423 subjects, the mean age was 73.5 years, and 43.4% were female. In the minor stroke group, the high MMSE score group had a decreased mRS score, and the low MMSE score group had an increased mRS score (p < 0.001). This association remained after additional adjustment of the GDS score. Association was not observed between cognitive function and functional recovery in the moderate or severe stroke group. CONCLUSION: After ischemic stroke, higher baseline global cognitive function was a predictive factor for better functional recovery regardless of depression symptoms in the minor stroke group.

Mass Fabrication of 3D Silicon Nano-/Microstructures by Fab-Free Process Using Tip-Based Lithography.

Methods for the mass fabrication of 3D silicon (Si) microstructures with a 100 nm resolution are developed using scanning probe lithography (SPL) combined with metal-assisted chemical etching (MACE). Protruding Si structures, including Si nanowires of over 10 µm in length and atypical shaped Si nano- and micropillars, are obtained via the MACE of a patterned gold film (negative tone) on Si substrates by dip-pen nanolithography (DPN) with polymer or by nanoshaving alkanethiol self-assembled monolayers (SAMs). Furthermore, recessed Si structures with arbitrary patterning and channels less than 160 nm wide and hundreds of nanometers in depth are obtained via the MACE of a patterned gold film (positive tone) on Si substrates by alkanethiol DPN. As an example of applications using protruded Si structures, nanoimprinting in an area of up to a centimeter is demonstrated through 1D and 2D SPL combined with MACE. Similarly, submicrometer polydimethylsiloxane (PDMS) stamps are employed over millimeter-scale areas for applications using recessed Si structures. In particular, the mass production of arbitrarily shaped Si microparticles at submicrometer resolution is developed using silicon-on-insulator substrates, as demonstrated using optical microresonators, surface-enhanced Raman scattering templates, and smart microparticles for fluorescence signal coding.

Evaluation of the efficacy and safety of conventional and biportal endoscopic decompressive laminectomy in patients with lumbar spinal stenosis (ENDO-B trial): a protocol for a prospective, randomized, assessor-blind, multicenter trial.

BACKGROUND: Recent studies on biportal endoscopic spine surgery in patients with lumbar spinal stenosis have reported good clinical results. However, these studies have been limited by the small sample sizes and use of a retrospective study design. Therefore, we aim to compare the efficacy and safety of biportal endoscopic decompressive laminectomy with those of conventional decompressive laminectomy in a multicenter, prospective, randomized controlled trial. METHODS: This study will include 120 patients (60 per group, aged 20-80 years) with 1- or 2-level lumbar spinal stenosis, who will be recruited from six hospitals. The study will be conducted from July 2021 to December 2024. The primary outcome (Oswestry Disability Index at 12 months after surgery) will be evaluated through a modified intention-to-treat method. The secondary outcomes will include the following: visual analog scale score for low back and lower extremity radiating pain, EuroQol 5-dimensions score, surgery satisfaction, walking time, postoperative return to daily life period, postoperative surgical scars, and some surgery-related variables. Radiographic outcomes will be analyzed using magnetic resonance imaging or computed tomography. All outcomes will be evaluated before the surgery and at 2 weeks, 3 months, 6 months, and 12 months postoperatively. This protocol adheres to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines for reporting of clinical trial protocols. DISCUSSION: It is hypothesized that the efficacy and safety of biportal endoscopic and conventional decompressive laminectomy will be comparable in patients with lumbar spinal stenosis. The results of this trial will provide a high level of evidence for the efficacy and safety of the biportal endoscopic technique in patients with lumbar spinal stenosis and facilitate the development of clinical practice guidelines. Furthermore, the results of this study may indicate the feasibility of the biportal endoscopic technique for other types of spinal surgery. TRIAL REGISTRATION: The ENDO-B trial is registered at Clinical Research Information Service (CRIS, cris.nih.go.kr ) (KCT0006057; April 52,021).

Baseline, delta, and achieved low-density lipoprotein cholesterol levels and cardiovascular risk in patients on statin therapy: A post-hoc resampling mediation analysis of treating new targets [TNT] trial.

Clinical guidelines for monitoring low-density lipoprotein cholesterol (LDL-C) after statin therapy do not clearly define the clinical roles of baseline LDL-C, ΔLDL-C, and achieved LDL-C according to statin intensity. We performed post-hoc analysis of the Treating to New Target (TNT) study to evaluate individual LDL-C parameters after statin therapy. Primary outcome was the risk for total major adverse cardiovascular events (MACE). We use resampling multilevel mediation analysis to analyze complex relationships among LDL-C parameters based on similar statin intensities. Tertiles for resample A (matched baseline LDL-C; distinct achieved LDL), resample B (matched ΔLDL-C; distinct baseline LDL-C), and resample C (matched achieved LDL-C; distinct ΔLDL-C) were analyzed using Cox proportional hazard ratios. In original data analysis, the incidence of MACE was reduced in those with lower achieved LDL-C in total, low, and high intensity statin users (hazard ratios [HRs] = 0.990, 0.992, 0.992; respectively; all P-values < .001). In mediation analysis, resample A showed consistently high incidence for MACE in the middle tertile (HR = 1.237; 95% confidential interval [CI] = 1.008-1.517; P-value = .041) and highest tertile (HR = 1.275; 95% CI = 1.021-1.592; P-value = .032) compared to the lowest tertile. However, resamples B and C did not show consistent differences. Similarly, no consistent statistical difference in MACE according to statin intensity. Lower achieved LDL-C decreased MACE in participants with a similar baseline LDL-C after statin therapy. However, the change in absolute values of ΔLDL-C and achieved LDL-C should be interpreted in an individualized manner due to their complex collinearity, and statin intensity should also be taken into consideration.

Risk of insulin resistance with statin therapy in individuals without dyslipidemia: A propensity-matched analysis in a registry population.

Several studies suggest the higher vulnerability of individuals with lower low-density lipoprotein cholesterol (LDL-C) levels to diabetes mellitus. However, the discordance between high and low baseline LDL-C levels shown by statin-induced insulin resistance is not fully understood. This study aimed to explore the relationship between baseline LDL-C levels and the risk of statin-induced insulin resistance during statin therapy. In total, 2660 (451 with dyslipidemia and 2209 without dyslipidemia) consecutive patients were enrolled. Their baseline clinical data were adjusted using a propensity score matching analysis, using the logistic regression model. Insulin resistance index was based on the homeostatic model assessment-insulin resistance (HOMA-IR) and was monitored for a median of 2 years. Among the individuals who received statin therapy, those with and without dyslipidemia showed significantly decreased LDL-C levels (all P < .0001) and significantly increased fasting plasma insulin levels (Δ = +24.1%, P = .0230; Δ = +30.1%, P < .0001); however, their glycated haemoglobin A1c and fasting blood glucose levels did not change (all P > .05). Although HOMA-IR was positively associated with statin therapy in individuals with and without dyslipidemia, statistically significant difference during follow-ups was observed only in individuals without dyslipidemia (Δ = +15.6%, P = .1609; Δ = 24.0%; P = .0001). Insulin resistance was higher in statin users without baseline dyslipidemia than in those with dyslipidemia. Thus, statin therapy could increase the risk of statin-induced insulin resistance in individuals with normal baseline cholesterol levels.

A Microfluidic System for Stable and Continuous EEG Monitoring from Multiple Larval Zebrafish.

Along with the increasing popularity of larval zebrafish as an experimental animal in the fields of drug screening, neuroscience, genetics, and developmental biology, the need for tools to deal with multiple larvae has emerged. Microfluidic channels have been employed to handle multiple larvae simultaneously, even for sensing electroencephalogram (EEG). In this study, we developed a microfluidic chip capable of uniform and continuous drug infusion across all microfluidic channels during EEG recording. Owing to the modular design of the microfluidic channels, the number of animals under investigation can be easily increased. Using the optimized design of the microfluidic chip, liquids could be exchanged uniformly across all channels without physically affecting the larvae contained in the channels, which assured a stable environment maintained all the time during EEG recording, by eliminating environmental artifacts and leaving only biological effects to be seen. To demonstrate the usefulness of the developed system in drug screening, we continuously measured EEG from four larvae without and with pentylenetetrazole application, up to 60 min. In addition, we recorded EEG from valproic acid (VPA)-treated zebrafish and demonstrated the suppression of seizure by VPA. The developed microfluidic system could contribute to the mass screening of EEG for drug development to treat neurological disorders such as epilepsy in a short time, owing to its handy size, cheap fabrication cost, and the guaranteed uniform drug infusion across all channels with no environmentally induced artifacts.

Depressive symptoms are associated with worse cognitive prognosis in patients with newly diagnosed idiopathic Parkinson disease.

BACKGROUND: Although depression is very common in patients with Parkinson disease (PD), only a few studies have investigated the longitudinal effects of initial depression on cognitive decline in these patients. The purpose of this study was to investigate the effect of depression on cognitive functions in patients with PD. METHODS: We used data from the Parkinson Progression Markers Initiative (PPMI) to investigate the relationship between depression and PD. Depressive symptoms were measured in patients with PD based on the Geriatric Depression Scale (GDS) or Neuropsychiatric Inventory-Questionnaire (NPI-Q) scores obtained at baseline. We evaluated cognitive decline as whether a patient with PD progressed to PD with mild cognitive impairment (MCI) during a 4-year follow-up period. Multivariate Cox regression analysis was done to know whether depression can predict the conversion to MCI. In addition, a voxel-based morphometric analysis using volumetric brain magnetic resonance imaging was used to compare structural changes related to future cognitive decline as well as to reveal longitudinal effect of baseline depression on cortical atrophy. RESULTS: Data from 263 patients with cognitively normal de novo PD who were available for longitudinal cognitive testing were analysed. The multivariate Cox regression analysis revealed that the depressive symptoms were independent risk factors for conversion to MCI in patients with de novo PD after adjusting for covariates (hazards ratio (95% CI)) of depression defined by the GDS (1.753 (1.084-2.835)) and the NPI (1.815 (1.083-3.042)) scores, respectively. The significant structural changes in PD with MCI as well as longitudinal effect of baseline depression on subsequent cortical atrophy were found in multiple areas on the voxel-based morphometric analysis (P < 0.001, family-wise error rate corrected). CONCLUSIONS: Our study indicates that the presence of depressive symptoms in patients with early PD is associated with a higher risk of progression to MCI and early depression may reflect subsequent cortical atrophy.

The usefulness of visual rating of posterior atrophy in predicting rapid cognitive decline in Alzheimer disease: A preliminary study.

BACKGROUND: Approximately 10% to 30% of Alzheimer disease (AD) patients progress rapidly in severity and become more dependent on caregivers. Although several studies have investigated whether imaging biomarkers such as medial temporal atrophy (MTA) and posterior atrophy (PA) are useful for predicting the rapid progression of AD, their results have been inconsistent. OBJECTIVE: The study aims to investigate the association of visually rated MTA and PA with rapid disease progression in AD. METHODS: This was a retrospective cohort study of 159 AD patients who were initially diagnosed with mild AD and were followed for 1 year to determine whether they progressed rapidly (a decrease of three points or more on the Mini-Mental State Examination over 1 year). We used 5-point and 4-point visual rating scales to assess MTA and PA, respectively. MTA and PA scores for each patient were dichotomized as normal (without atrophy) or abnormal (atrophy). We performed a logistic regression analysis to determine the odds ratios (ORs) of MTA and PA for rapid disease progression with adjustment for covariates. RESULTS: Within the study population, 47 (29.6%) patients progressed rapidly. Visual assessment of the magnetic resonance imaging (MRI) scans revealed that 112 patients (70.4%) showed MTA, whereas 80 patients (50.3%) showed PA. The ORs with 95% confidence intervals for MTA and PA were 1.825 (0.819-4.070) and 2.844 (1.378-5.835), respectively. The association of visually assessed PA, but not MTA, with rapid progression was significant after adjustment for covariates. CONCLUSION: In patients with mild AD, visual assessment of PA exhibits independent predictive value for rapid disease progression.

Antibiotic-impregnated articulating cement spacer maintained for 7 years in situ for two-stage primary total knee arthroplasty: a case report.

BACKGROUND: Antibiotic-impregnated articulating cement spacers can maintain interim joint motion with the potential to enhance functional status and improve patient satisfaction. Articular surfaces with cement against cement have raised concerns regarding mechanical complications and cement debris during knee motion. However, long-term clinical conditions regarding these concerns are not well addressed. CASE PRESENTATION: We report a case in which articulating cement spacers were maintained in situ for 7 years. The patient had severe left knee pain with an ankylosing knee and severe tricompartmental arthritis due to tuberculous infection. We planned to perform one- or two-stage primary total knee arthroplasty (TKA), depending on the presence of infection. Persistent osteomyelitis was found intraoperatively. The second-stage TKA was delayed on the patient's request. As the patient was satisfied with the improved knee function and pain relief after using articulating cement spacers. No symptom or sign that suggested recurrent infection or systemic toxicity was found during the 7-year follow-up. However, it seemed that the bone loss progressed insidiously. At the 7-year follow-up, a broken articulating cement spacer and medial femoral condylar fracture were found. The second-stage TKA was performed, and a considerable amount of bone loss surrounded by dense granulation tissue was observed intraoperatively. Excisional biopsy of the tissue revealed chronic foreign body reaction with infiltration of giant cells and macrophages. CONCLUSION: Although the articular spacers were maintained for 7 years without major complications, regular observation of the development and progress of bone loss was required. Surgeons should take considerable bone loss into account during conversion TKA in patients with a prolonged retention of articulating cement spacers.