Search

Sensory symptoms, especially neuropathic pain, are common in polyneuropathy. Conventional diagnostic tools can evaluate structural or functional impairment of nerves but cannot reveal mechanisms of neuropathic pain. Changes in the brain after polyneuropathy may play roles in the genesis of neuropathic pain.This cross-sectional study investigated changes of cortical excitability within left primary motor cortex (M1) by measuring resting motor thresholds, short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), and afferent inhibition between polyneuropathy patients and controls, and investigated the correlates of these parameters with neuropathic pain and M1 structural and functional connectivity assessed by diffusion tractography imaging and functional magnetic resonance imaging.Thirty-three painful and 15 nonpainful neuropathic patients and 21 controls were enrolled. There were no differences in intraepidermal nerve fiber density, nerve conduction studies, thermal thresholds, or autonomic functional tests between patients with and without neuropathic pain. Compared to controls, neuropathic patients exhibited similar resting motor thresholds or afferent inhibition, but attenuated SICI and augmented ICF, especially in painful patients. Changes of intracortical excitability in neuropathic patients were correlated with intensities of neuropathic pain, and different presentations of SICI and ICF were noted between patients with and without thermal paresthesia. Additionally, short-latency afferent inhibition at an interstimulus interval of 20 ms was associated with structural connectivity of left M1 with brain areas associated with pain perception.Maladaptive cortical excitability with altered structural connectivity in left M1 developed after peripheral nerve degeneration and was associated with neuropathic pain and sensory symptoms in polyneuropathy.

Background Disease-modifying therapies provide new horizons for hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) to slow neuropathic progression. Initiating treatment at the earliest time requires biomarkers reflecting both small- and large-fiber degeneration in carriers. Methods This study included examinations of pathology [intraepidermal nerve fiber (IENF) density], physiology (nerve conduction studies, autonomic function test and nerve excitability), and psychophysics (thermal thresholds) in carriers to compare to healthy controls and asymptomatic diabetic patients. Results There were 43 carriers (44.2±11.4 years, p.Ala117Ser in 42 carriers), 43 controls (43.4±12.7 years) including 26 noncarrier families, and 50 asymptomatic diabetic patients (58.1±9.5 years). Carriers had lower IENF densities than controls and similar densities as diabetic patients. Median nerve conduction parameters, especially distal motor latency, (1) were the most frequent neurophysiological abnormality in carriers, (2) could differentiate carriers from controls and diabetic patients, (3) were correlated with IENF densities in carriers but not in controls and diabetic patients, and (4) were correlated with nerve excitability parameters in carriers but not in controls. Fifteen carriers (34.9%) with electrophysiological evidence of median nerve entrapment at wrist had lower IENF densities and more abnormal conduction parameters than carriers without. We defined nerve dysfunction index (the ratio of median distal motor latency to IENF density) which differentiated carriers from controls. Conclusions In late-onset ATTRv-PN carriers with predominant p.Ala117Ser, median conduction parameters were the most common neurophysiological abnormalities, and served as surrogate signatures of small- and large-fiber impairment. Combination of median distal motor latency and IENF density can reflect early neuropathy in carriers.

Background: As the average life expectancy of global citizens has increased, the prevalence of dementia has increased rapidly. The number of patients with dementia has increased by 6.7 times, reaching 300,000 in the past three decades in Taiwan. To realize the latest actual situation, the need for institutional care for elderly patients with dementia, and also a reference basis for government agencies to formulate dementia-related care policies, we investigated the institutional prevalence of dementia. Methods: We randomly sampled 299 out of the 1607 registered long-term care facilities including senior citizens’ institutions, nursing homes, and veteran homes in every administrative region of Taiwan. Then, a two-phase survey including MMSE screening, CDR, and clinical confirmation was conducted on each subject from 2019 to 2020. Results: Among 5753 enrolled subjects, 4765 from 266 facilities completed the examinations with a response rate of 82.8%. A total of 4150 subjects were diagnosed with dementia, 7.4% of whom had very mild dementia. The prevalence of all-cause dementia, including very mild dementia, was 87.1% in all facilities, 87.4% in senior citizens’ institutions, 87.1% in nursing homes, and 83.3% in veteran homes. Advanced age, low education, hypertension, Parkinsonism, respiratory disease, stroke, and intractable epilepsy were associated with dementia risk. Conclusions: We show that in an aged society, the prevalence of all-cause dementia in long-term care institutions can be as high as 87.1%. This study was completed before the outbreak of COVID-19 and provides a precious hallmark for future epidemiological research. We recommend that the long-term care policy in an aged society needs to take into account the increasing high prevalence of dementia in the institution.

Background: Cerebrovascular pathologies and hypertension could play a vital role in Alzheimer disease (AD) progression. However, whether cerebrovascular pathologies and hypertension accelerate the AD progression through an independent or interaction effect is unknown. Objective: To investigate the effect of the interactions of cerebrovascular pathologies and hypertension on AD progression. Method: A retrospective longitudinal study was conducted to compare AD courses in patients with different severities of cerebral White Matter Changes (WMCs) in relation to hypertension. Annual comprehensive psychometrics were performed. WMCs were rated using a rating scale for Age-related WMCs (ARWMC). Results: In total, 278 patients with sporadic AD were enrolled in this study. The mean age of the patients was 76.6 ± 7.4 years, and 166 patients had hypertension. Among AD patients with hypertension, those with deterioration in clinical dementia rating-sum of box (CDR-SB) and CDR had significantly severe baseline ARWMC scales in total (CDR-SB: 5.8 vs. 3.6, adjusted P = 0.04; CDR: 6.4 vs. 4.4, adjusted P = 0.04) and frontal area (CDR-SB: 2.4 vs. 1.2, adjusted P = 0.01; CDR: 2.4 vs. 1.7, adjusted P < 0.01) compared with those with no deterioration in psychometrics after adjustment for confounders. By contrast, among AD patients without hypertension, no significant differences in ARWMC scales were observed between patients with and without deterioration. Conclusion: The effect of cerebrovascular pathologies on AD progression between those with and without hypertension might differ. An interaction but not independent effect of hypertension and WMCs on the progression of AD is possible.

Long-term electroencephalogram (EEG) monitoring is effective for epilepsy diagnosis. However, it also takes a lot of time for clinicians to correctly interpret the long-time recordings. Real-time computer-based EEG monitoring and classification systems have attracted recently the attention of researchers to help clinicians locate online possible epileptic-form EEG signals. In this paper, we first present an accurate and fast EEG classification algorithm that can recognize three types of EEG signals: normal, spike, and seizure. 16-channel bipolar EEG recordings of epilepsy patients are preprocessed, segmented, and ensemble empirical mode decomposed (EEMD) into intrinsic mode functions (IMFs). Features are extracted and linear discriminant analysis (LDA) is applied to train two classifiers: one is for seizure and non-seizure discrimination, and the other is for normal and spike discrimination. In order to furthermore help the clinicians, the results of LDA are visualized and sonified. The changes of the discriminant in the LDA on continuous EEG segments are backtracked to each feature, and thus to each EEG channel. Accordingly, contours of the changes in EEG channels are depicted. At the same time, sinusoidal waves in 440 or 880 Hz are played when EEG segments are classified into spike or seizure respectively. In the experiment, EEG recordings of six subjects (two normal and four seizure patients) are examined. The experiment result shows that the accuracy of the proposed epileptic EEG classification algorithm is relatively high. In addition, the visualization and sonification algorithms of epileptic-form EEG may greatly help clinicians localize the focus of seizure and nurses take care of seizure patients, immediately.

Aim The response to donepezil in patients with Alzheimer's disease varies, and it is important to identify the potential responder before therapy. Cerebral white matter changes (WMC) are frequently observed in older patients, and the effect of WMC on therapeutic response remains controversial. The present study aimed to investigate the relationships between the location of WMC, severe WMC and the response to donepezil. Methods Among 418 patients with Alzheimer's disease receiving donepezil, 196 patients were eligible for analysis. Five brain areas on each side were analyzed using computed tomography scans and the Age-Related White Matter Changes Rating Scale before therapy. The Cognitive Abilities Screening Instrument was used annually. Patients were defined as responders if their baseline Cognitive Abilities Screening Instrument score minus their follow-up Cognitive Abilities Screening Instrument score was ≤0. Results There was no significant difference in demographic data between responder and non-responder groups. Patients in the responder group had significantly less involvement of WMC in the frontal area (P = 0.0213) and nearly a trend for less involvement of WMC in the basal ganglia (P = 0.1103). After adjustment for age, sex, education, polymorphism of apolipoprotein E, hypertension and diabetes, WMC in the frontal area (OR 0.446, P = 0.0139) and basal ganglia (OR 0.243, P = 0.0380) were significantly associated with a reduced therapeutic response. Conclusions Patients with WMC in the frontal area and basal ganglia had significant decreases in their therapeutic response to donepezil. The location of WMC, independent of their severity, might be associated with the therapeutic response in patient with Alzheimer's disease. Geriatr Gerontol Int 2018; 18: 123–129.

Alzheimer&rsquo, s disease (AD) is traditionally thought of as a neurodegenerative disease. Recent evidence shows that beta amyloid-independent vascular changes and beta amyloid-dependent neuronal dysfunction both equally influence the disease, leading to loss of structural and functional connectivity. White matter changes (WMCs) in the brain are commonly observed in dementia patients. The effect of vascular factors on WMCs and the relationship between WMCs and severity of AD in patients remain to be clarified. We recruited 501 clinically diagnosed probable AD patients with a series of comprehensive neuropsychological tests and brain imaging. The WMCs in cerebral CT or MRI were rated using both the modified Fazekas scale and the combined CT-MRI age related WMC (ARWMC) rating scale. Periventricular WMCs were observed in 79.4% of the patients and deep WMCs were also seen in 48.7% of the patients. WMC scores were significantly higher in the advanced dementia stage in periventricular WMCs (p = 0.001) and total ARWMCs (p &lt, 0.001). Age and disease severity were both independently associated with WMCs score, particularly in the total, frontal and parieto-occipital areas. Vascular factors including hypertension, diabetes mellitus, and gender were not significantly associated with WMCs. In conclusion, both age and severity of dementia were significantly associated with WMCs in AD patients. These associations highlight future research targets.

Aim The presence of cerebral white matter changes (WMC) has been reported as an important predictor of the rapidity of cognitive decline in Alzheimer's disease (AD). The association between the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and WMC in AD is yet to be elucidated. The present study aimed to examine the association between the ACE I/D polymorphism and WMC among AD patients in Taiwan. Methods A total of 403 patients clinically diagnosed with AD were recruited in a cross-sectional study carried out in an area hospital in Kaohsiung, Taiwan. The ACE I/D polymorphism was genotyped, and cerebral white matter rating was carried out using the visual rating scale for age-related white matter changes. Results The I allele was associated with a significantly lower total age-related white matter changes scale score compared with the D allele (4.83 vs 5.93, P = 0.013). The total age-related white matter changes scale score was significantly lower for the I/I genotype than for the I/D (4.37 vs 5.87, P = 0.009) and I/D + D/D genotypes (4.37 vs 5.91, P = 0.006), with no differences observed between the I/I + I/D and the D/D genotypes (5.08 vs 6.09, P = 0.373), after adjustment for age and hypertension. A stratified analysis by sex demonstrated that the I/I genotype was associated with significant lower WMC than other genotypes in women, but not in men. Conclusions The present study supports the hypothesis that the ACE I/D polymorphism is associated with the severity of WMC in patients with AD. Patients with AD who are homozygous for the I allele might be less likely to develop WMC, especially women. Geriatr Gerontol Int 2017; 17: 945-950.

In this paper, we present an epilepsy analysis system, referred to as EAS, for long-term electroencephalography (EEG) monitoring of patients with epilepsy. In our previous works, a high accuracy seizure detection algorithm had been devised. Six support vector machines (SVMs) had been trained to collaboratively classify EEG data into four types, i.e., normal, spike, sharp wave, and seizure. The EAS had initially extracted a total of 980 features from raw EEG data of patients, and then, for each SVM, it used a naive genetic algorithm (GA) to determine a feature subset of the 980 features. However, the feature subsets still included some low-impact features for the EEG classification, and the training process of the seizure detector was time consuming. In this study, the GA is enhanced to further exclude low-impact features from the feature subsets and MapReduce parallel processing is adopted to speed up the training process. In the experiment, a 363-h clinical EEG records were acquired from 28 participants, 3 of which were normal, and 25 were patients with epilepsy. The experiment results show that average size of the feature subsets is reduced from 133.5 to 92.5 and the overall classification accuracy increases from 88.8 to 90.1 %. The new seizure detector processes a 10-s EEG record within 0.6 s, meaning that it meets the real-time requirement for online EEG monitoring gracefully. When the number of servers increases from 1 to 15, the training time of the detector is reduced from 38.3 to 4.9 h. Our new approach improves the EAS significantly.

This study is an initiative to integrate corporate social responsibility (CSR) and apply mind-mapping techniques to demonstrate the mind map of CSR implementation and obstacles faced by companies listed on the Taiwan Stock Exchange (TWSE) and Gre Tai Securities Market (GTSM) in Taiwan. In addition, this study takes the initiative to conduct a compressive questionnaire on CSR of those companies listed. The results show that “shortage of human resources” is the major obstacle to CSR implementation and that “no mandatory regulations” is the first priority in terms of needing improvement for CSR implementation. In addition, an independent sample t-test produces a mean score of 73% for the items on CSR reports as regulated by the Global Reporting Initiative (GRI) is reported. Moreover, a factor analysis is used to identify four dimensional factors (namely, “company resources,” “regulations and international environment,” “knowledge of CSR” and “capital” variables) as the effective predictors. This research also determines that cross-level obstacles to CSR implementation are correlated and demonstrates a view of “cross-level ecosystem of obstacle factors of CSR implementation.” Finally, the results of Asia-Pacific Economic Cooperation (APEC) members to disclose CSR information after the financial crisis are also compared and analyzed with our research in this study.

BACKGROUND Rivastigmine has been approved in the treatment of Alzheimer's disease (AD) patients as it can inhibit acetyl- and butyryl-cholinesterase and provide neuroprotective effects involving the synapses. White matter changes (WMCs) are frequently observed in AD, and clinical-pathological correlations imply their possible impacts on cognitive function by interference with cortical and subcortical neuronal pathways. OBJECTIVE To evaluate the therapeutic effects of rivastigmine in AD patients with cerebral WMCs. METHODS Clinically diagnosed AD patients from Kaohsiung Municipal Ta-Tung hospital were recruited together with their cranial magnetic resonance imaging and a series of annual psychometric tests, including Mini-Mental State Examination (MMSE) and sum of boxes of clinical dementia rating scale (CDR-SB). WMCs were rated through the modified Fazekas scale for the periventricular and deep WMCs. RESULTS In total, 87 AD patients treated with rivastigmine were enrolled. Patients at severe stage of WMCs, compared to mild stage ones, had significant improvement evaluated by MMSE (periventricular WMCs, p = 0.025; deep WMCs, p = 0.030), but not CDR-SB. Compared to the worsening group, the clinically improving group had a significant higher ratio of pre-existing hypertension in terms of cognitive performance [p = 0.016, odds ratio (OR) = 3.48, 95% CI = 1.25-10.34], while having younger age (p = 0.043, OR = 0.11, 95% CI = 0.01-1.12) in terms of global status. CONCLUSION Rivastigmine may provide better benefits in cognitive function, but not global status, for AD patients with more advanced WMCs. The detailed mechanisms still have to be determined in future studies.

The presence of cerebral white matter changes (WMC) has been reported as an important predictor of the rapidity of cognitive decline in Alzheimer's disease (AD). The association between the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and WMC in AD is yet to be elucidated. The present study aimed to examine the association between the ACE I/D polymorphism and WMC among AD patients in Taiwan.A total of 403 patients clinically diagnosed with AD were recruited in a cross-sectional study carried out in an area hospital in Kaohsiung, Taiwan. The ACE I/D polymorphism was genotyped, and cerebral white matter rating was carried out using the visual rating scale for age-related white matter changes.The I allele was associated with a significantly lower total age-related white matter changes scale score compared with the D allele (4.83 vs 5.93, P = 0.013). The total age-related white matter changes scale score was significantly lower for the I/I genotype than for the I/D (4.37 vs 5.87, P = 0.009) and I/D + D/D genotypes (4.37 vs 5.91, P = 0.006), with no differences observed between the I/I + I/D and the D/D genotypes (5.08 vs 6.09, P = 0.373), after adjustment for age and hypertension. A stratified analysis by sex demonstrated that the I/I genotype was associated with significant lower WMC than other genotypes in women, but not in men.The present study supports the hypothesis that the ACE I/D polymorphism is associated with the severity of WMC in patients with AD. Patients with AD who are homozygous for the I allele might be less likely to develop WMC, especially women. Geriatr Gerontol Int 2017; 17: 945-950.

Seven monosomic addition plants, each containing the full complement of Nicotiana plumbaginifolia (2n = 20, genome constitution PP) and an aberrant chromosome of Nicotiana sylvestris (2n = 24, SS), were produced from backcrosses of hyperdiploid derivatives of the sesquidiploid hybrid PPS to N. plumbaginifolia. The N. sylvestris chromosomes in these plants were characterized by karyotype analysis, Southern hybridization with DNA markers previously localized on N. sylvestris chromosomes and a 269-bp fragment from the 3' end of 25S rDNA, and fluorescence in situ hybridization using 25S rDNA, 5S rDNA and telomere repeats (TTTAGGG)(n) as probes. The N. sylvestris chromosomes in these plants were identified to be telocentrics 6S, 7S and 8S, and deletions 7S, 10, 12S and 12L, respectively. The successful identification of aberrant chromosomes in these lines enabled us to assign DNA markers to arms and sub-arm regions of N. sylvestris chromosomes. All aberrant chromosomes in the addition lines could be transmitted through mitosis and meiosis. The potential applications of the addition lines in high-resolution physical mapping, the isolation of N. sylvestris chromosomes by flow cytometry, and an understanding of the chromosomal distribution of 45S rDNA in N. sylvestris are discussed.

We have constructed a genetic linkage map for Nicotiana plumbaginifolia/Nicotiana longiflora (2n= 2x=20), based on the segregation of 69 RFLP and 102 RAPD loci in 99 F2 plants from the cross N. plumbaginifolia×N. longiflora. The map consists of nine major linkage groups, each containing more than nine marker loci, and spans 1062 cM. Twenty of the RFLP markers were mapped previously to Nicotiana sylvestris (2n=2x=24) chromosomes using monosomic alien addition lines. Taxonomically, N. plumbaginifolia and N. sylvestris belong to the same section, namely the Alatae; however, cytogenetic evidence indicates that they are not closely related. Comparison of the distribution of markers common to both maps suggests that genome reorganization has occurred during the evolution of these two species. Evidence is also presented that genome reorganization may be accompanied by gain and loss of specific classes of DNA sequences in their genomes.

Pegylated interferon (Peg-IFN)-based therapy is effective in treating chronic hepatitis B (CHB) and C (CHC) but frequently induces adverse events (AEs). This study was conducted to compare the incidence of Peg-IFN-based therapy-associated AEs in Taiwanese patients with CHB and CHC.Fifty-six patients with CHB and 103 age-, sex- and treatment duration-matched patients with CHC were enrolled. Patients with CHB were treated with Peg-IFN-α-2a 180 μg/week for 24 weeks (HBeAg(+), n = 31) or 48 weeks (HBeAg(-), n = 25); patients with CHC were treated with Peg-IFN-α-2a 180 μg/week plus ribavirin 1,000-1,200 mg/day for 24 weeks (genotype 2/3, n = 57) or 48 weeks (genotype 1, n = 46).Significantly higher incidences of Peg-IFN-related AEs, especially neuropsychiatric symptoms, and ribavirin-associated skin manifestations were observed in patients with CHC compared with those with CHB, with either the 24- or 48-week regimen. Frequencies of laboratory abnormalities, except for anemia, were comparable in both groups. Neither group showed overt hepatic decompensation. Frequency of dose reduction was similar between the groups. Substantially higher rates of early termination and severe AEs were observed in patients with CHC.Patients with CHB treated with Peg-IFN had fewer AEs than patients with CHC treated with Peg-IFN/ribavirin. All patients were treated safely.

Although Nicotiana sylvestris and N. plumbaginifolia belong to the same section, viz., Alatae of the subgenus Petunioides, they differ markedly in morphology, geographic distribution, and karyotype (Goodspeed 1954). N. sylvestris is the maternal parent of cultivated allotetraploid N. tabacum (Gray et al. 1974), which is in the subgenus Tabacum, and possesses some morphological characters not present in the section Alatae. N. sylvestris occurs exclusively in northwestern Argentina, while N. plumbaginifolia has a much wider distribution, extending from northwestern Argentina to Brazil, Peru, Guatemala, Cuba, and Mexico. The chromosomes of N. sylvestris 2n=24) are rather uniform in size and are clearly bi-armed, while those of N. plumbaginifolia (2n=20) differ significantly in size and are telocentric or acrocentric (Fig. 1A,B).