Protective Effects of Coptis chinensis Rhizome Extract and Its Constituents (Berberine, Coptisine, and Palmatine) against α-Synuclein Neurotoxicity in Dopaminergic SH-SY5Y Cells.

Parkinson's disease (PD) is a common neurodegenerative disease with progressive loss of dopaminergic neurons in substantia nigra and the presence of α-synuclein-immunoreactive inclusions. Gaucher's disease is caused by homozygous mutations in ß-glucocerebrosidase gene (GBA). GBA mutation carriers have an increased risk of PD. Coptis chinensis (C. chinensis) rhizome extract is a major herb widely used to treat human diseases. This study examined the association of GBA L444P mutation with Taiwanese PD in 1016 cases and 539 controls. In addition, the protective effects of C. chinensis rhizome extract and its active constituents (berberine, coptisine, and palmatine) against PD were assayed using GBA reporter cells, LC3 reporter cells, and cells expressing mutated (A53T) α-synuclein. Case-control study revealed that GBA L444P carriers had a 3.93-fold increased risk of PD (95% confidence interval (CI): 1.37-11.24, p = 0.006) compared to normal controls. Both C. chinensis rhizome extract and its constituents exhibited chemical chaperone activity to reduce α-synuclein aggregation. Promoter reporter and endogenous GBA protein analyses revealed that C. chinensis rhizome extract and its constituents upregulated GBA expression in 293 cells. In addition, C. chinensis rhizome extract and its constituents induced autophagy in DsRed-LC3-expressing 293 cells. In SH-SY5Y cells expressing A53T α-synuclein, C. chinensis rhizome extract and its constituents reduced α-synuclein aggregation and associated neurotoxicity by upregulating GBA expression and activating autophagy. The results of reducing α-synuclein aggregation, enhancing GBA expression and autophagy, and protecting against α-synuclein neurotoxicity open up the therapeutic potentials of C. chinensis rhizome extract and constituents for PD.

Application of blood-based biomarkers of Alzheimer's disease in clinical practice: Recommendations from Taiwan Dementia Society.

Blood-based biomarkers (BBM) are potentially powerful tools that assist in the biological diagnosis of Alzheimer's disease (AD) in vivo with minimal invasiveness, relatively low cost, and good accessibility. This review summarizes current evidence for using BBMs in AD, focusing on amyloid, tau, and biomarkers for neurodegeneration. Blood-based phosphorylated tau and the Aß42/Aß40 ratio showed consistent concordance with brain pathology measured by CSF or PET in the research setting. In addition, glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are neurodegenerative biomarkers that show the potential to assist in the differential diagnosis of AD. Other pathology-specific biomarkers, such as α-synuclein and TAR DNA-binding protein 43 (TDP-43), can potentially detect AD concurrent pathology. Based on current evidence, the working group from the Taiwan Dementia Society (TDS) achieved consensus recommendations on the appropriate use of BBMs for AD in clinical practice. BBMs may assist clinical diagnosis and prognosis in AD subjects with cognitive symptoms; however, the results should be interpreted by dementia specialists and combining biochemical, neuropsychological, and neuroimaging information. Further studies are needed to evaluate BBMs' real-world performance and potential impact on clinical decision-making.

More than a piece of cake: Noun classifier processing in primary progressive aphasia.

INTRODUCTION: Clinical understanding of primary progressive aphasia (PPA) has been primarily derived from Indo-European languages. Generalizing certain linguistic findings across languages is unfitting due to contrasting linguistic structures. While PPA patients showed noun classes impairments, Chinese languages lack noun classes. Instead, Chinese languages are classifier language, and how PPA patients manipulate classifiers is unknown. METHODS: We included 74 native Chinese speakers (22 controls, 52 PPA). For classifier production task, participants were asked to produce the classifiers of high-frequency items. In a classifier recognition task, participants were asked to choose the correct classifier. RESULTS: Both semantic variant (sv) PPA and logopenic variant (lv) PPA scored significantly lower in classifier production task. In classifier recognition task, lvPPA patients outperformed svPPA patients. The classifier production scores were correlated to cortical volume over left temporal and visual association cortices. DISCUSSION: This study highlights noun classifiers as linguistic markers to discriminate PPA syndromes in Chinese speakers. HIGHLIGHTS: Noun classifier processing varies in the different primary progressive aphasia (PPA) variants. Specifically, semantic variant PPA (svPPA) and logopenic variant PPA (lvPPA) patients showed significantly lower ability in producing specific classifiers. Compared to lvPPA, svPPA patients were less able to choose the accurate classifiers when presented with choices. In svPPA, classifier production score was positively correlated with gray matter volume over bilateral temporal and left visual association cortices in svPPA. Conversely, classifier production performance was correlated with volumetric changes over left ventral temporal and bilateral frontal regions in lvPPA. Comparable performance of mass and count classifier were noted in Chinese PPA patients, suggesting a common cognitive process between mass and count classifiers in Chinese languages.

Investigating Therapeutic Effects of Indole Derivatives Targeting Inflammation and Oxidative Stress in Neurotoxin-Induced Cell and Mouse Models of Parkinson's Disease.

Neuroinflammation and oxidative stress have been emerging as important pathways contributing to Parkinson's disease (PD) pathogenesis. In PD brains, the activated microglia release inflammatory factors such as interleukin (IL)-ß, IL-6, tumor necrosis factor (TNF)-α, and nitric oxide (NO), which increase oxidative stress and mediate neurodegeneration. Using 1-methyl-4-phenylpyridinium (MPP+)-activated human microglial HMC3 cells and the sub-chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD, we found the potential of indole derivative NC009-1 against neuroinflammation, oxidative stress, and neurodegeneration for PD. In vitro, NC009-1 alleviated MPP+-induced cytotoxicity, reduced NO, IL-1ß, IL-6, and TNF-α production, and suppressed NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in MPP+-activated HMC3 cells. In vivo, NC009-1 ameliorated motor deficits and non-motor depression, increased dopamine and dopamine transporter levels in the striatum, and reduced oxidative stress as well as microglia and astrocyte reactivity in the ventral midbrain of MPTP-treated mice. These protective effects were achieved by down-regulating NLRP3, CASP1, iNOS, IL-1ß, IL-6, and TNF-α, and up-regulating SOD2, NRF2, and NQO1. These results strengthen the involvement of neuroinflammation and oxidative stress in PD pathogenic mechanism, and indicate NC009-1 as a potential drug candidate for PD treatment.

Long-term cognitive and multimodal imaging outcomes after carotid artery stenting vs intensive medication alone for severe asymptomatic carotid stenosis.

BACKGROUND: Severe carotid stenosis is associated with cognitive impairment, which may be attributed to asymptomatic microembolism and/or chronic hypoperfusion. We aim to evaluate the long-term cognitive and brain connectivity outcomes of carotid artery stenting (CAS) for asymptomatic ≥70% stenosis of the extracranial internal carotid artery (ICA). METHODS: We conducted a non-randomized controlled study to compare intensive medical therapy alone (Med) or in combination with carotid artery stenting for the composite vascular events, neuropsychological, and multimodal magnetic resonance perfusion imaging and diffusion tensor imaging outcomes. RESULTS: Sixty-nine patients were followed for a mean of 2.3 years (31 Med, 38 CAS) and 11 patients had composite vascular events of all-cause death, ischemic stroke, or myocardial infarction (6 Med vs 5 CAS). Forty-six asymptomatic subjects completed neuropsychological and multimodality imaging follow-ups (23 Med, 23 CAS). Compared to the Med group, the CAS group had a modest improvement of 12-item delayed verbal memory (8.9 ± 2.4 to 9.8 ± 2.7 vs 9.0 ± 2.1 to 8.9 ± 2.3, p = 0.04), but not in global cognition, attention or executive function, which was associated with increased structural connectivity of fractional anisotropy at the ipsilateral deep white matter. Importantly, the memory improvement was correlated with the perfusion increment at the ipsilateral middle cerebral artery territory. CONCLUSION: For asymptomatic extracranial carotid steno-occlusion, successful carotid revascularization in addition to intensive medical treatment may potentially benefit cognitive reserve and connectivity strength which are partly attributed to restoration of non-critical hypoperfusion.

Exploring the impacts of COVID-19 on the lifestyles of community-living adults in Singapore: A qualitative study.

INTRODUCTION: Disruptions caused by the COVID-19 pandemic have not only restricted people from performing occupations but also adversely affected their health and quality of life. However, the impact of the pandemic on Singaporean adults at different life stages remains unclear. This study aimed to understand the impact of COVID-19 on a range of community-living age groups' occupations and sense of well-being. METHODS: Community-living adults in Singapore were invited to participate in this qualitative descriptive study. Thematic analysis was conducted to generate themes and identify common patterns (e.g. impacts on different occupations) in different age groups. FINDINGS: Twenty-nine semi-structured interviews (young adults: 10, middle-aged adults: 10, older adults: 9) were conducted and thematically analysed, revealing three main themes: (1) impact on occupations, (2) impacts on personal well-being, and (3) responses to COVID-19 situation. Participants from all age groups experienced both positive and negative impacts across various occupations, such as productivity (work and study), leisure, and self-care activities. Young and middle-aged adults were less affected as they were more proficient in using technology to make adequate adaptations. Older adults were least equipped with coping strategies and thus the most compromised. In response to the impacts of the pandemic on occupations and well-being, participants from different age groups adjusted differently (e.g. adopting a sedentary lifestyle and developing different coping strategies). CONCLUSION: This study identified the impacts of COVID-19 on the daily occupations of Singaporean adults and how it is intricately linked with their well-being. Findings also revealed the significant role of technology in adapting to the COVID-19 situation. The younger Singaporean adults were more agile to make occupational changes and adaptations. More can be done by occupational therapists to assist community-living older adults to enable continued participation in meaningful occupations during pandemics.

Neuromagnetic evidence of abnormal automatic inhibitory function in subjective memory complaint.

Subjective memory complaint (SMC), a self-perceived worsening in memory capacity concurrent with normal performance on standardized cognitive assessments, is considered a risk factor for the development of Alzheimer's disease (AD). Deficient sensory gating (SG), referring to the lack of automatic inhibition of neural responses to the second identical stimulus, has been documented in prodromal and incident AD patients. However, it remains unknown whether the cognitively normal elderly with SMC demonstrate alterations of SG function compared with those without SMC. A total of 19 healthy controls (HC) and 16 SMC subjects were included in the present study. Neural responses to the auditory paired-stimulus paradigm were recorded by the magnetoencephalography and analyzed by the distributed source imaging method of minimum norm estimate. The SG of M50 and M100 components were measured using the amplitude ratio of the second response over the first response at the cortical level. Compared to HC, subjects with SMC showed significantly increased M50 SG ratios in the inferior parietal lobule (IPL). Furthermore, M50 SG ratios in the right IPL yielded an acceptable discriminative ability to distinguish SMC from HC. However, we did not find a significant association between SG ratios and cognitive function requiring inhibitory control either in the HC or SMC group. In conclusion, although SMC subjects have intact cognitive functioning revealed by objective neuropsychological tests, their deficits in automatic inhibitory function could be detected through neurophysiological recordings. Our results suggest that altered brain function occurs in SMC prior to the obvious decline of cognitive performance.

Upregulation of Cisd2 attenuates Alzheimer's-related neuronal loss in mice.

CDGSH iron-sulfur domain-containing protein 2 (Cisd2), a protein that declines in an age-dependent manner, mediates lifespan in mammals. Cisd2 deficiency causes accelerated aging and shortened lifespan, whereas persistent expression of Cisd2 promotes longevity in mice. Alzheimer's disease (AD) is the most prevalent form of senile dementia and is without an effective therapeutic strategy. We investigated whether Cisd2 upregulation is able to ameliorate amyloid ß (Aß) toxicity and prevent neuronal loss using an AD mouse model. Our study makes three major discoveries. First, using the AD mouse model (APP/PS1 double transgenic mice), the dosage of Cisd2 appears to modulate the severity of AD phenotypes. Cisd2 overexpression (∼two-fold) significantly promoted survival and alleviated the pathological defects associated with AD. Conversely, Cisd2 deficiency accelerated AD pathogenesis. Secondly, Cisd2 overexpression protected against Aß-mediated mitochondrial damage and attenuated loss of neurons and neuronal progenitor cells. Finally, an increase in Cisd2 shifted the expression profiles of a panel of genes that are dysregulated by AD toward the patterns observed in wild-type mice. These findings highlight Cisd2-based therapies as a potential disease-modifying strategy for AD. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Large-Scale Structural Covariance Networks Predict Age in Middle-to-Late Adulthood: A Novel Brain Aging Biomarker.

The aging process is accompanied by changes in the brain's cortex at many levels. There is growing interest in summarizing these complex brain-aging profiles into a single, quantitative index that could serve as a biomarker both for characterizing individual brain health and for identifying neurodegenerative and neuropsychiatric diseases. Using a large-scale structural covariance network (SCN)-based framework with machine learning algorithms, we demonstrate this framework's ability to predict individual brain age in a large sample of middle-to-late age adults, and highlight its clinical specificity for several disease populations from a network perspective. A proposed estimator with 40 SCNs could predict individual brain age, balancing between model complexity and prediction accuracy. Notably, we found that the most significant SCN for predicting brain age included the caudate nucleus, putamen, hippocampus, amygdala, and cerebellar regions. Furthermore, our data indicate a larger brain age disparity in patients with schizophrenia and Alzheimer's disease than in healthy controls, while this metric did not differ significantly in patients with major depressive disorder. These findings provide empirical evidence supporting the estimation of brain age from a brain network perspective, and demonstrate the clinical feasibility of evaluating neurological diseases hypothesized to be associated with accelerated brain aging.

Untargeted GC/TOFMS unravel metabolic profiles in cerebrospinal fluid of Chinese people living with HIV.

BACKGROUND: Metabolic syndrome becomes a focus of clinical cares to people living with HIV (PLHIV) globally. This study aimed to explore the metabolic profiles in cerebrospinal fluid (CSF) of Chinese people living with HIV (PLHIV). METHODS: Cerebrospinal fluid samples from PLHIV and healthy controls were collected from our hospital. Then, the metabolic profiles of CSFs were analyzed PLHIV with healthy individual as the normal controls using the untargeted GC/TOFMS. Following this, kyoto encyclopedia of genes and genomes annotation and pathway analysis were performed to further explore the underlying mechanism of these metabolic alterations in cognitive impairment of PLHIV. RESULTS: Both PCA analysis and OPLS-DA had presented that most samples were localized in 95% CI and the gap between control and HIV could significantly separate from each other. Upon this quality control, a total of 82 known metabolites were identified in CSF between PLHIV and healthy controls. Clustering of these metabolites presented that these differentially expressed metabolites could markedly distinguish HIV from healthy controls. Further pathway analyses showed that TCA cycle (citric acid, fumaric acid, lactate, et al.), amino acid (arginine, proline, alanine, aspartate, glutamine, et al.), lipid (cholesterol, butyrate, et al.) metabolisms were significantly changed in CSF of PLHIV, which might affect the cognitive status of PLHIV via affecting neuron energy support, signaling transduction, and neuroinflammation. CONCLUSION: Metabolic profiles were significantly altered in CSF and might play key roles in the etiology of cognitive impairment of PHLIV. Further explore the exact mechanism for these metabolic changes might be useful for cognitive impairment management of PHLIV.

Discovery of a Metabolic Signature Predisposing High Risk Patients with Mild Cognitive Impairment to Converting to Alzheimer's Disease.

Assessing dementia conversion in patients with mild cognitive impairment (MCI) remains challenging owing to pathological heterogeneity. While many MCI patients ultimately proceed to Alzheimer's disease (AD), a subset of patients remain stable for various times. Our aim was to characterize the plasma metabolites of nineteen MCI patients proceeding to AD (P-MCI) and twenty-nine stable MCI (S-MCI) patients by untargeted metabolomics profiling. Alterations in the plasma metabolites between the P-MCI and S-MCI groups, as well as between the P-MCI and AD groups, were compared over the observation period. With the help of machine learning-based stratification, a 20-metabolite signature panel was identified that was associated with the presence and progression of AD. Furthermore, when the metabolic signature panel was used for classification of the three patient groups, this gave an accuracy of 73.5% using the panel. Moreover, when specifically classifying the P-MCI and S-MCI subjects, a fivefold cross-validation accuracy of 80.3% was obtained using the random forest model. Importantly, indole-3-propionic acid, a bacteria-generated metabolite from tryptophan, was identified as a predictor of AD progression, suggesting a role for gut microbiota in AD pathophysiology. Our study establishes a metabolite panel to assist in the stratification of MCI patients and to predict conversion to AD.

Effect of Times to Blood Processing on the Stability of Blood Proteins Associated with Dementia.

BACKGROUND: The stability of proteins in the collecting tubes after blood draw is critical to the measured concentrations of the proteins. Although the guidelines issued by the Clinical and Laboratory Standards Institute (CLSI) suggest centrifugation should take place within 2 h of drawing blood, it is very difficult to follow these guidelines in hospitals or clinics. It is necessary to study the effect of times to blood processing on the stability of the proteins of interest. METHODS: In this work, the plasma proteins of interest were those relevant to dementia, such as amyloid ß 1-40 (Aß1-40), Aß1-42, Tau protein (Tau), and α-synuclein. The times to blood processing after blood draw ranged from 0.5 to 8 h. The storage temperatures of blood were room temperature (approx. 25°C) and 30°C. After storage, blood samples were centrifuged at room temperature to obtain plasma samples. Ultrasensitive immunomagnetic reduction was applied to assay these proteins in the plasma. RESULTS: The levels of plasma Aß1-40, Tau, and α-synuclein did not significantly change until 8 h after blood draw when stored at room temperature. Plasma Aß1-42 levels did not change significantly after 8 h of storage at room temperature before blood processing. Higher storage temperatures, such as 30°C, for blood samples accelerated the significant variations in the measured concentrations of Aß1-40, Tau, and α-synuclein in plasma. CONCLUSION: According to these results, for clinical practice, it is suggested that blood samples be stored at room temperature for no longer than 4.5 h after blood draw until centrifugation for the assay of dementia biomarkers in plasma.

Changes in Plasma Amyloid and Tau in a Longitudinal Study of Normal Aging, Mild Cognitive Impairment, and Alzheimer's Disease.

BACKGROUND: Changes in cerebrospinal fluid, neuroimaging, and cognitive functions have been used as diagnostic biomarkers of Alzheimer's disease (AD). This study aimed to investigate the temporal trajectories of plasma biomarkers in subjects with mild cognitive impairment (MCI) and patients with AD relative to healthy controls (HCs). METHODS: In this longitudinal study, 82 participants (31 HCs, 33 MCI patients, and 18 AD patients) were enrolled. After 3 years, 7 HCs had transitioned to MCI and 10 subjects with MCI had converted to AD. We analyzed plasma amyloid beta (Aß) and tau proteins at baseline and annually to correlate with biochemical data and neuropsychological scores. RESULTS: Longitudinal data analysis showed an evolution of Aß-related biomarkers over time within patients, whereas tau-related biomarkers differed primarily across diagnostic classifications. An initial steady increase in Aß42 in the MCI stage was followed by a decrease just prior to clinical AD onset. Hyperphosphorylated tau protein levels correlated with cognitive decline in the MCI stage, but not in the AD stage. CONCLUSION: Plasma Aß and tau levels change in a dynamic, nonlinear, nonparallel manner over the AD continuum. Changes in plasma Aß concentration are time-dependent, whereas changes in hyperphosphorylated tau protein levels paralleled the clinical progression of MCI. It remains to be clarified whether diagnostic efficiency can be improved by combining multiple plasma markers or combining plasma markers with other diagnostic biomarkers.

Associations between low circulatory low-density lipoprotein cholesterol level and brain health in non-stroke non-demented subjects.

Low-density lipoprotein cholesterol (LDL-C) and hypertension have independent and synergistic effects on atherosclerotic cardiovascular disease. However, the role of circulatory LDL-C and its possible interactions with hypertension in brain health have been poorly investigated. The study aimed to investigate the relationship between the circulatory LDL-C level and (1) brain structures, grey-matter volume (GMV) and white matter hyperintensity (WMH) and (2) cognitive functions, and whether hypertension plays a role in these relationships. Subjects who were non-stroke and non-demented were prospectively recruited from the community-based I-Lan Longitudinal Aging Study. High-resolution 3T MRI was performed with GM and WMH segmentation. GMVs, total and regional including Alzheimer's disease-susceptible area, and WMH volumes were measured. Neurological tests including verbal memory, visuospatial, and verbal executive functions were assessed. Eight-hundred-and-two participants (59.2 ±â€¯5.7 years; 44% men) were included. Multivariate linear regression analyses showed that low circulatory LDL-C levels (<98 mg/dL) were significantly associated with reduced GMVs in frontal (standardized ß = -0.130; p = 0.003) and posterior cingulate (ß = -0.113; p = 0.032) regions in hypertensive but not normotensive subjects. In addition, low circulatory LDL-C levels, combined with hypertension, had the lowest posterior cingulate GMV (ß = -0.073; p = 0.021), highest periventricular WMH (ß = 0.089; p = 0.011) and lowest verbal memory test scores (ß = -0.088; p = 0.035) compared with neither low circulatory LDL-C level nor hypertension, and either hypertension or low circulatory LDL-C level. Age, sex, total intracranial volume, vascular risk factors, level of other circulatory lipids, and the taking of anti-hypertensive and lipid-lowering medications were adjusted. In conclusion, the role of circulatory LDL-C level and its interactive effect with hypertension on brain health are firstly demonstrated. A low circulatory LDL-C level was associated with reduced regional brain GMVs in hypertensive but not normotensive subjects. In addition, there seems a combined detrimental-effect of low circulatory LDL-C levels with hypertension on posterior cingulate GMV, WMH, and verbal memory.

Somatosensory gating is altered and associated with migraine chronification: A magnetoencephalographic study.

Background Brain excitability is changed in migraine but not fully characterized yet. This study explored if somatosensory gating is altered in migraine and linked to migraine chronification. Methods Paired electrical stimuli were delivered to the left index fingers of 21 patients with migraine without aura (MO), 22 patients with chronic migraine (CM), and 36 controls. The first and second responses to the paired stimuli were obtained from the contralateral primary (cSI), contralateral secondary (cSII) and ipsilateral secondary (iSII) somatosensory cortices to compute the gating ratios (second vs. first response strengths). Results The first and second cSI responses and gating ratios differed in all groups ( p < 0.05); the responses were typically smaller in the MO and CM groups. The cSI gating ratio increased as a continuum across controls (0.73 ± 0.04, p < 0.001), MO (0.83 ± 0.04) to CM (0.97 ± 0.06) and was higher in CM vs. controls ( p < 0.001). When MO and CM were combined, cSI gating ratio was associated with headache frequency (r = 0.418, p = 0.005). Paired responses and gating ratios of cSII and iSII did not differ among the groups. Conclusions Somatosensory gating is altered in migraine and associated with headache chronification. Further studies must clarify if this abnormal sensory modulation is a true gating deficit independent of low preexcitation level.

Mixed yeast infections in Taiwan.

Clinically significant yeast isolates were collected via Taiwan Surveillance of Antimicrobial Resistance of Yeasts (TSARY) in 2014, and mixed infections were investigated. Among 44 out of 1092 specimens containing multiple species, 17, 11, 5, 3, and 8 were from urine, sputum, blood, ascites, and 6 others, respectively. There predominant combinations of mixed infection were 14 Candida albicans/Candida glabrata, 13 C. albicans/Candida tropicalis, and 9 C. glabrata/C. tropicalis. Furthermore, we also detected fluconazole resistant isolates Candida norvegensis and Candida krusei. Hence, it is important to accurately identify the species with different drug susceptibilities when they are in the same specimen.

Diagnostic accuracy of Instrumental Activities of Daily Living for dementia in community-dwelling older adults.

BACKGROUND: many people living with dementia remain underdiagnosed and unrecognised. Screening strategies are important for early detection. OBJECTIVE: to examine whether the Lawton's Instrumental Activities of Daily Living (IADL) scale, compared with other cognitive screening tools-the Mini-Mental State Examination (MMSE), and the Ascertain Dementia 8-item Informant Questionnaire (AD8)-can identify older (≥ 65 years) adults with dementia. DESIGN: population-based cross-sectional observational study. SETTING: all 19 counties in Taiwan. PARTICIPANTS: community-dwelling older adults (n = 10,340; mean age 74.87 ± 6.03). METHODS: all participants underwent a structured in-person interview. Dementia was identified using National Institute on Aging-Alzheimer's Association core clinical criteria for all-cause dementia. Receiver operator characteristic curves were used to determine the discriminant abilities of the IADL scale, MMSE and AD8 to differentiate participants with and without dementia. RESULTS: we identified 917 (8.9%) participants with dementia, and 9,423 (91.1%) participants without. The discriminant abilities of the MMSE, AD8 and IADL scale (cutoff score: 6/7; area under curve = 0.925; sensitivity = 89%; specificity = 81%; positive likelihood ratio = 4.75; accuracy = 0.82) were comparable. Combining IADL with AD8 scores significantly improved overall accuracy: specificity = 93%; positive likelihood ratio = 11.74; accuracy = 0.92. CONCLUSIONS: our findings support using IADL scale to screen older community-dwelling residents for dementia: it has discriminant power comparable to that of the AD8 and MMSE. Combining the IADL and the AD8 improves specificity.

Uniform magnetic targeting of magnetic particles attracted by a new ferromagnetic biological patch.

A new non-toxic ferromagnetic biological patch (MBP) was designed in this paper. The MBP consisted of two external layers that were made of transparent silicone, and an internal layer that was made of a mixture of pure iron powder and silicon rubber. Finite-element analysis showed that the local inhomogeneous magnetic field (MF) around the MBP was generated when MBP was placed in a uniform MF. The local MF near the MBP varied with the uniform MF and shape of the MBP. Therefore, not only could the accumulation of paramagnetic particles be adjusted by controlling the strength of the uniform MF, but also the distribution of the paramagnetic particles could be improved with the different shape of the MBP. The relationship of the accumulation of paramagnetic particles or cells, magnetic flux density, and fluid velocity were studied through in vitro experiments and theoretical considerations. The accumulation of paramagnetic particles first increased with increment in the magnetic flux density of the uniform MF. But when the magnetic flux density of the uniform MF exceeded a specific value, the magnetic flux density of the MBP reached saturation, causing the accumulation of paramagnetic particles to fall. In addition, the adsorption morphology of magnetic particles or cells could be improved and the uniform distribution of magnetic particles could be achieved by changing the shape of the MBP. Also, MBP may be used as a new implant to attract magnetic drug carrier particles in magnetic drug targeting. Bioelectromagnetics. 39:98-107, 2018. © 2017 Wiley Periodicals, Inc.

Comparison of acoustoelastic Lamb wave propagation in stressed plates for different measurement orientations.

High order Lamb waves are investigated for the effects of stress on both symmetrical and anti-symmetrical modes in an aluminum plate for wave propagation and load parallel. Data are compared with those for the case of load and measurement axis perpendicular. It is the S1 mode which exhibits significantly higher sensitivity to stress than other Lamb modes. For aluminum the use of the S1 mode for stress measurement is found to be about six times more sensitive, than bulk waves, for the load-measurement axes parallel case and this compares with about ten times for the case of load-measurement axes perpendicular.

Altered insula-default mode network connectivity in fibromyalgia: a resting-state magnetoencephalographic study.

BACKGROUND: Fibromyalgia (FM) is a disabling chronic pain syndrome with unknown pathophysiology. Functional magnetic resonance imaging studies on FM have suggested altered brain connectivity between the insula and the default mode network (DMN). However, this connectivity change has not been characterized through direct neural signals for exploring the embedded spectrotemporal features and the pertinent clinical relevance. METHODS: We recorded the resting-state magnetoencephalographic activities of 28 patients with FM and 28 age- and sex-matched controls, and analyzed the source-based functional connectivity between the insula and the DMN at 1-40 Hz by using the minimum norm estimates and imaginary coherence methods. We also measured the connectivity between the DMN and the primary visual (V1) and somatosensory (S1) cortices as intrapatient negative controls. Connectivity measurement was further correlated with the clinical parameters of FM. RESULTS: Compared with the controls, patients with FM reported more tender points (15.2±2.0 vs. 5.9±3.7) and higher total tenderness score (TTS; 29.1±7.0 vs. 7.7±5.5; both p < 0.001); they also had decreased insula-DMN connectivity at the theta band (4-8 Hz; left, p = 0.007; right, p = 0.035), but displayed unchanged V1-DMN and S1-DMN connectivity (p > 0.05). When patients with FM and the controls were combined together, the insula-DMN theta connectivity was negatively correlated with the number of tender points (left insula, r = -0.428, p = 0.001; right insula, r = -0.4, p = 0.002) and TTS score (left insula, r = -0.429, p = 0.001; right insula, r = -0.389, p = 0.003). Furthermore, in patients with FM, the right insula-DMN connectivity at the beta band (13-25 Hz) was negatively correlated with the number of tender points (r = -0.532, p = 0.004) and TTS (r = -0.428, p = 0.023), and the bilateral insula-DMN connectivity at the delta band (1-4 Hz) was negatively correlated with FM Symptom Severity (left: r = -0.423, p = 0.025; right: r = -0.437, p = 0.020) and functional disability (Fibromyalgia Impact Questionnaire; left: r = -0.415, p = 0.028; right: r = -0.374, p = 0.050). CONCLUSIONS: We confirmed the frequency-specific reorganization of the insula-DMN connectivity in FM. The clinical relevance of this connectivity change may warrant future studies to elucidate its causal relationship and potential as a neurological signature for FM.