Unity-order magnetochiral effects exhibited by a single metamolecule.

A numerical study predicts that a single metamolecule with magnetism and chirality has giant magnetochiral (MCh) effects at microwave frequencies. The magnetism is provided by the ferromagnetic resonance of ferrite under dc bias magnetic fields, while the chirality is provided by the spiral arrangement of dielectric cubes with Mie resonance. The dielectric and magnetic resonances interfere in the metamolecule, resulting in a two-order of magnitude enhancement of the MCh effect compared with that reported in previous studies. This prediction is verified experimentally. A unity-order directional difference in the refractive index caused by the MCh effect is also demonstrated. This study is a significant milestone in the practical use of the MCh effect.

Early use of donepezil against psychosis and cognitive decline in Parkinson's disease: a randomised controlled trial for 2 years.

OBJECTIVES: Brain acetylcholine is decreased even in patients with cognitively preserved Parkinson's disease (PD). We investigated whether early and long-term use of donepezil prevents psychosis in non-demented PD patients. METHODS: A double-blinded, placebo-controlled trial was conducted. A total of 145 non-demented PD patients were randomly assigned to receive 5 mg/day donepezil (n=72) or placebo (n=73) for 96 weeks. Medications for PD were not restricted, but antipsychotic drugs were not permitted throughout the study. The primary outcome measure was survival time to psychosis that was predefined by Parkinson's Psychosis Questionnaire (PPQ) B score ≥2 or C score ≥2. Secondary outcome measures included psychosis developing within 48 weeks, total PPQ score, Mini-Mental State Examination (MMSE), Wechsler Memory Scale (WMS) and subgroup analysis by apolipoprotein ε4 genotyping. RESULTS: Kaplan-Meier curves for psychosis development were very similar between the two groups, and the Cox proportional hazard model revealed an adjusted HR of 0.87 (95%CI 0.48 to 1.60). The changes in MMSE and WMS-1 (auditory memory) were significantly better with donepezil than in placebo. In the subgroup analysis, donepezil provided an HR of 0.31 (0.11-0.86) against psychosis in 48 weeks for apolipoprotein ε4 non-carriers. CONCLUSIONS: Although donepezil provided beneficial effects on PPQ, MMSE and auditory WMS score changes in 2 years, it had no prophylactic effect on development of psychosis in PD. Apolipoprotein ε4 may suppress the antipsychotic effect of donepezil. TRIAL REGISTRATION NUMBER: UMIN000005403.

Direct observation of magnetochiral effects through a single metamolecule in microwave regions.

We report direct observation of magnetochiral (MCh) effects for the X-band microwaves through a single metamolecule consisting of a copper chiral structure and ferrite rod. A fictitious interaction between chirality and magnetism is realized in the metamolecule without intrinsic electronic interactions. The MCh effects are induced at the resonant optical activities by applying a weak dc magnetic field of 1 mT, and are increased with the magnetic field. The nonreciprocal differences in refractive indices are evaluated to be 10^{-3} at 200 mT.

Trigger medications and patient-related risk factors for Parkinson disease psychosis requiring anti-psychotic drugs: a retrospective cohort study.

BACKGROUND: Psychoses such as hallucinations are a frequent non-motor problem in patients with Parkinson disease (PD) and serious psychosis requires anti-psychotic medications that worsen Parkinsonism. Although psychosis could be associated with patient-related or biological factors such as cognition, age, and severity of PD, it can also be associated with medications.Therefore we aimed to investigate patient-related and medication-related risks of psychosis requiring anti-psychotic medications (serious psychosis). METHODS: A retrospective cohort of 331 PD patients was followed for 2 years. Patient-related factors associated with risk of psychosis were identified by a survival time analysis. In patients who developed psychosis, medications during the hazard period (1-14 days before psychosis) were contrasted with those during the control periods (1 and 3 months before psychosis) using a case-crossover analysis to identify medication-related risks of psychosis. RESULTS: Serious psychosis was detected in 52 patients and the incidence was estimated to be 116 (95% confidence interval [CI], 85-148) per 1,000 person-years. Analyses of baseline characteristics revealed the risk to be higher in patients with a modified Hoehn-Yahr stage of ≥4 (hazard ratio [HR], 2.22; 95% CI, 1.11-4.40), those with a longer duration of PD (HR, 1.25; 95% CI, 1.00-1.55, per 5 years) and those with Mini-Mental State Examination scores of ≤24 (HR, 2.66; 95% CI, 1.37-5.16). The case-crossover analysis revealed that anti-cholinergics use (HR, 19.7; 95% CI, 2.39-162) elevated the risk, while donepezil use reduced it (HR, 0.48; 95% CI, 0.27-0.85). CONCLUSIONS: Risk of psychosis was elevated by increasing severity of PD, cognitive dysfunction and duration of the disease. It was elevated by use of anti-cholinergic drugs and reduced by use of donepezil. The medication-related risk was higher in patients aged ≥ 70 years. In contrast, there was no significant medication-related risk in younger patients, suggesting different pathomechanisms between young and old patients.

Gold nanoparticle-induced formation of artificial protein capsids.

Gold nanoparticles are generally considered to be biologically inactive. However, in this study we show that the addition of 1.4 nm diameter gold nanoparticle induces the remodeling of the ring-shaped protein TRAP into a hollow, capsid-like configuration. This structural remodeling is dependent upon the presence of cysteine residues on the TRAP surface as well as the specific type of gold nanoparticle. The results reveal an apparent novel catalytic role of gold nanoparticles.

Chiral meta-molecules consisting of gold nanoparticles and genetically engineered tobacco mosaic virus.

We demonstrate a chiral meta-molecule in the ultraviolet (UV) and visible (VIS) regions using a complex of Au nanoparticles (NPs) and rod-shaped tobacco mosaic virus (TMV). Au NPs five nm in diameter are uniformly formed on peptide-modified TMV. The peptide-modified TMV with uniform-sized Au NPs has improved dispersion in solution. A negative circular dichroism (CD) peak is produced around 540 nm, at plasmonic resonance wavelength of Au NPs. Additionally, modification of a CD peak in the UV region is observed. Attaching NPs to a virus causes the enhancement and modification of CD peaks in both the UV and VIS regions. Our results open a new avenue for the preparation of three dimensional chiral metamaterials at optical frequencies.

Early-start vs delayed-start donepezil against cognitive decline in Parkinson disease: a randomized clinical trial.

BACKGROUND: Cholinergic neurotransmission regulates neuroinflammation in Parkinson disease (PD). RESEARCH DESIGN AND METHODS: The authors conducted a delayed-start study of donepezil for cognitive decline in non-demented PD patients. The study consisted of a 96-week randomized placebo-controlled double-blind phase 1, followed by a 24-week donepezil extension phase 2. The primary outcome measure was a change in the Mini-Mental State Examination (MMSE) at week 120. RESULTS: A total of 98 patients were randomly allocated to the early-start (donepezil-to-donepezil) and delayed-start (placebo-to-donepezil) groups. Mean (SD) of the baseline MMSE was 27.6 (2.0) and 28.0 (2.1), respectively. MMSE change at week 120 was better in the early-start group than in the delayed-start group, but the difference was not significant. The MMSE declined in apolipoprotein ε4 carriers, but not in non-carriers, and the factor interaction (intervention × Îµ4 genotype) was highly significant (P < 0.001). Analyzed with the interaction, the difference was significant (group difference 1.95 [0.33 to 3.57], P = 0.018). The MMSE decline slope in phase 1 was significantly better in the early-start group than in the delayed-start group (P = 0.048). CONCLUSIONS: Cognitive function deteriorated in ε4 carriers, but not in non-carriers, and early-start donepezil may postpone cognitive decline in the former.

Resonant photon tunneling via surface plasmon polaritons through one-dimensional metal-dielectric metamaterials.

We report resonant photon tunneling (RPT) through one-dimensional metamaterials consisting of alternating layers of metal and dielectric. RPT via a surface plasmon polariton state permits evanescent light waves with large wavenumbers to be conveyed through the metamaterial. This is the mechanism for sub-wavelength imaging recently demonstrated with a super-lens. Furthermore, we find that the RPT peak is shifted from the reflectance dip with increasing the number of Al layers, indicating that the shift is caused by the losses in the RPT.

Sensory ganglionopathy associated with drug-induced hypersensitivity syndrome caused by mexiletine.

Although various causes are reported for sensory ganglionopathy, drug-induced hypersensitivity syndrome (DIHS) has not been considered a possibility. We describe a 70-year-old woman, previously administered mexiletine hydrochloride for 4 weeks, who presented with systemic oedematous erythema and subacute progressive gait disturbance. Evaluation revealed lymphadenopathy with atypical lymphocytosis and eosinophilia, and human herpesvirus 6 (HHV-6) reactivation. Neurological examination indicated the almost complete loss of joint positional sense in her extremities; her tendon reflex was lost and there was marked pseudoathetosis and Romberg's sign. Skin biopsy revealed spongiosis with lymphocyte infiltration. Based on these findings, we diagnosed acute sensory ganglionopathy secondary to DIHS. Although her DIHS-induced symptoms subsided after methylprednisolone treatment, partial remission of sensory ganglionopathy occurred, even after subsequent intravenous immunoglobulin therapy. This case suggests the possibility that reactivation of HHV-6 may be involved in the pathomechanism of sensory ganglionopathy.

Low body mass index and life prognosis in Parkinson's disease.

INTRODUCTION: Patients with Parkinson's disease (PD) frequently lose weight, even in the early stages of the disease. Our objective was to clarify the association between low body mass index (BMI) and life prognosis in PD. METHODS: We conducted a retrospective cohort study of 651 PD patients (380 females), with a primary endpoint of survival. Because of sex differences in BMI, male and female data were separated. We compared survival times between underweight (BMI < 18.5) and non-underweight (BMI ≥ 18.5) patients and calculated hazard ratios (HRs) adjusted for other relevant factors. To investigate the semi-quantitative relationship between relative risk of death and BMI, we divided patients into lower, middle, and upper thirds of BMI and calculated the HRs of the lower and upper thirds, with reference to the middle third. RESULTS: Seventy-nine patients (41 females) died over a mean (standard deviation) observation period of 39 (26) months. Underweight patients had poorer life prognosis than non-underweight patients and the difference was larger in males than in females (adjusted HR 3.8 (95% confidence interval 1.9-7.9) in males and 1.8 (0.9-3.5) in females). In males, the relationship between survival and BMI was much poorer in the bottom third and slightly poorer in the top third compared with the middle third. In females, the higher the BMI, the better the survival prognosis; however, the difference was not statistically significant. CONCLUSION: Low BMI had a significant impact on the life prognosis of PD patients, especially males.

Pharmacological interventions for anxiety in Parkinson's disease sufferers.

INTRODUCTION: Anxiety disorders are a common non-motor symptom of Parkinson's disease (PD) with a reported prevalence ranging from 20% to 50%. Although anxiety is associated with Parkinson's disease, anxiety disorders can begin before the onset of motor symptoms, and have been linked to a possible abnormality of dopaminergic, serotonergic, and adrenergic neurons that precedes motor disturbance. AREAS COVERED: Several studies have reported the pharmacological treatment of depression in PD, but none have been randomized clinical trials with a primary outcome measure of anxiety. Two trials showed that pharmacological intervention with tricyclic antidepressants or selective serotonin reuptake inhibitors proved beneficial in treating anxiety in PD. However, the effect size was modest. Anxiety is associated with off-periods and improved by L-Dopa, especially in patients with high levels of anxiety. EXPERT OPINION: Decreasing off-periods is important for managing anxiety in patients with motor fluctuations. Minor suggestive data indicate that tricyclic antidepressants and selective serotonin reuptake inhibitors can be helpful with modest effect sizes, but the former can cause additional side effects. Only one study has examined the use of benzodiazepines to treat anxiety in PD, and benzodiazepines cannot be recommended because they increase the risk of falling. Further clinical studies for pharmacological intervention against anxiety are required.

Video-fluoroscopic swallowing study scale for predicting aspiration pneumonia in Parkinson's disease.

INTRODUCTION: A number of video-fluoroscopic swallowing study (VFSS) abnormalities have been reported in patients with Parkinson's disease (PD). However, the most crucial finding of subsequent aspiration pneumonia has not been validated fully. We conducted a retrospective and case-control study to determine the clinically significant VFSS findings in this population, and to propose a practical scale for predicting aspiration pneumonia in patients with PD. METHODS: We enrolled 184 PD patients who underwent VFSS because of suspected dysphagia. The patients who developed aspiration pneumonia within six months of the VFSS were assigned as cases and the patients without aspiration pneumonia at six months were designated as controls. Logistic regression analysis was performed to determine the prognostic VFSS features based on the data of swallowing 3 mL of jelly, which were used to make a PD VFSS scale (PDVFS). The validity of the new PDVFS was evaluated by ROC analysis. Additionally, we used the survival time analysis to compare time to death between groups, stratified by the PDVFS score. RESULTS: Twenty-five patients developed aspiration pneumonia. Among the previously-proposed VFSS features, mastication, lingual motility prior to transfer, aspiration, and total swallow time were identified as significant prognostic factors. We combined these factors to form the PDVFS. The PDVFS score ranges from 0 to 12, with 12 being the worst. ROC analysis revealed 92% sensitivity and 82% specificity at a cutoff point of 3. The higher PDVFS group showed shorter time-to-death than the lower PDVFS group (log rank P = 0.001). CONCLUSION: Our newly developed VFSS severity scale (based on jelly swallowing) for patients with PD was easy to rate and could predict subsequent aspiration pneumonia and poor prognosis in patients with PD.

Magnetic Properties of Fibonacci-Modulated Fe-Au Multilayer Metamaterials.

Herein we experimentally study magnetic multilayer metamaterials with broken translational symmetry. Epitaxially-grown iron-gold (Fe-Au) multilayers modulated using Fibonacci sequence-referred to as magnetic inverse Fibonacci-modulated multilayers (IFMs)-are prepared using ultra-high-vacuum vapor deposition. Experimental results of in-situ reflection high-energy electron diffraction, magnetization curves, and ferromagnetic resonance demonstrate that the epitaxially-grown Fe-Au IFMs have quasi-isotropic magnetization, in contrast to the in-plane magnetization easy axis in the periodic multilayers.

Effects of cigarettes and alcohol consumption in benign paroxysmal positioning vertigo.

CONCLUSION: Smoking was associated with a lower incidence of benign paroxysmal positioning vertigo (BPPV). A larger study is required to establish the role of smoking in BPPV. OBJECTIVE: To evaluate the effect of cigarette and alcohol consumption on BPPV. PATIENTS AND METHODS: One hundred and fifty-six patients with BPPV and 155 age- and sex-matched normal subjects were compared according to their cigarette and alcohol consumption. Patients with BPPV who had had a recurrence of the disease and those who had not were also compared as to their cigarette and alcohol consumption. The question of whether the length of time until recovery was influenced by cigarette or alcohol consumption was also investigated. RESULTS: Control subjects smoked significantly more often than BPPV patients, and patients without recurrence more frequently than patients with recurrence. Alcohol consumption was also more common in control subjects than in BPPV patients, but there was no difference between patients with recurrence and without recurrence. There was a tendency for smoking patients to recover sooner than non-smoking patients. Alcohol consumption did not affect the length of time until recovery.

Baseline C-Reactive Protein Levels and Life Prognosis in Parkinson Disease.

BACKGROUND: C-reactive protein (CRP) is a biomarker of inflammation, and high levels of CRP correlate with vascular death. Chronic inflammation is considered to be involved in neurodegeneration, although there is no evidence linking it with the process of neurodegenerative diseases. OBJECTIVE: To determine the role of baseline CRP levels in the prognosis of patients with Parkinson disease (PD). METHODS: A cohort of 313 patients with a mean age of 69.1 and mean PD duration of 7.9 years was retrospectively followed for a mean observation time of 1,753 days. CRP was measured when patients were not diagnosed with any infections, and levels were repetitively measured to investigate a tendency of "regression to mean." The primary outcome measure was a survival time from study enrollment to death. RESULTS: During the observation period 56 patients died. Baseline CRP was log-linearly associated with a risk of death in PD. Mean survival time was 3,149 (95% confidence interval; 3,009-3,289) days in patients with CRP ≤ 0.8mg/L (lower two thirds) and 2,620 (2,343-2,897) days in those with CRP > 0.8 mg/L (top third, p < 0.001, log-rank test). The adjusted hazard ratio (HR) per two-fold higher CRP concentration for all deaths was 1.29 (1.10-1.52), and after excluding PD-unrelated deaths, such as cancer or stroke, HR was 1.23 (1.01-1.49) (adjusted for age, sex, PD duration, modified Hohen-Yahr stages, MMSE scores, and serum albumin). CONCLUSIONS: Baseline CRP concentrations were associated with the risk of death and predicted life prognosis of patients with PD. The associations were independent from PD duration, PD severity, cognitive function, ages, and nutritional conditions, suggesting the possibility that subclinical chronic inflammation is associated with a neurodegenerative process in PD.

Baseline Plasma C-Reactive Protein Concentrations and Motor Prognosis in Parkinson Disease.

BACKGROUND: C-reactive protein (CRP), a blood inflammatory biomarker, is associated with the development of Alzheimer disease. In animal models of Parkinson disease (PD), systemic inflammatory stimuli can promote neuroinflammation and accelerate dopaminergic neurodegeneration. However, the association between long-term systemic inflammations and neurodegeneration has not been assessed in PD patients. OBJECTIVE: To investigate the longitudinal effects of baseline CRP concentrations on motor prognosis in PD. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of 375 patients (mean age, 69.3 years; mean PD duration, 6.6 years). Plasma concentrations of high-sensitivity CRP were measured in the absence of infections, and the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) scores were measured at five follow-up intervals (Days 1-90, 91-270, 271-450, 451-630, and 631-900). MAIN OUTCOME MEASURE: Change of UPDRS-III scores from baseline to each of the five follow-up periods. RESULTS: Change in UPDRS-III scores was significantly greater in PD patients with CRP concentrations ≥0.7 mg/L than in those with CRP concentrations <0.7 mg/L, as determined by a generalized estimation equation model (P = 0.021) for the entire follow-up period and by a generalized regression model (P = 0.030) for the last follow-up interval (Days 631-900). The regression coefficients of baseline CRP for the two periods were 1.41 (95% confidence interval [CI] 0.21-2.61) and 2.62 (95% CI 0.25-4.98), respectively, after adjusting for sex, age, baseline UPDRS-III score, dementia, and incremental L-dopa equivalent dose. CONCLUSION: Baseline plasma CRP levels were associated with motor deterioration and predicted motor prognosis in patients with PD. These associations were independent of sex, age, PD severity, dementia, and anti-Parkinsonian agents, suggesting that subclinical systemic inflammations could accelerate neurodegeneration in PD.

Impact of Aspiration Pneumonia on the Clinical Course of Progressive Supranuclear Palsy: A Retrospective Cohort Study.

INTRODUCTION: Although aspiration pneumonia is the most common complication of progressive supranuclear palsy (PSP), the clinical impact of aspiration pneumonia on disease course and survival has not been fully estimated. Thus, we retrospectively analyzed the prognostic factors and clinical consequences of pneumonia in PSP. METHODS: The clinical course of patients with aspiration pneumonia was surveyed. The association between baseline clinical features (2 years from disease onset) and latency to the initial development of pneumonia was investigated using survival time and Cox regression analyses. RESULTS: Ninety patients with a clinical diagnosis of PSP were observed for 5.1±3.8 years (mean±SD), and 22 had aspiration pneumonia. Subsequently, 20 patients (91%) had to discontinue oral feeding entirely and 13 (59%) died, whereas, of 68 patients without pneumonia, only three patients (4%) died. Time to initial development of pneumonia was strongly correlated with survival time (Spearman R = 0.92, P<0.001), with a mean latency of 2.3 years to death. Among baseline clinical features, early fall episodes and cognitive decline were significant predictors of pneumonia (P = 0.001 and P<0.001, respectively, log rank test). Cox regression analysis demonstrated that early fall episodes (adjusted hazard ratio: 3.9, 95% confidence interval: 1.2-12.5, P = 0.03) and cognitive decline (adjusted hazard ratio: 5.2, 95% confidence interval: 1.4-19.3, P = 0.02) independently predicted pneumonia. By contrast, dysphagia was not associated with pneumonia (P = 0.2, log rank test). CONCLUSION: Initial development of pneumonia indicates an unfavorable clinical course and predicts survival time (mean survival time 2.3 years). Patients with early falls and cognitive decline were at high risk of early development of pneumonia.

Impact of glucocerebrosidase mutations on motor and nonmotor complications in Parkinson's disease.

Homozygous mutations of the glucocerebrosidase gene (GBA) cause Gaucher disease (GD), and heterozygous mutations of GBA are a major risk factor for Parkinson's disease (PD). This study examined the impact of GBA mutations on the longitudinal clinical course of PD patients by retrospective cohort design. GBA-coding regions were fully sequenced in 215 PD patients and GD-associated GBA mutations were identified in 19 (8.8%) PD patients. In a retrospective cohort study, time to develop dementia, psychosis, wearing-off, and dyskinesia were examined. Survival time analysis followed a maximum 12-year observation (median 6.0 years), revealing that PD patients with GD-associated mutations developed dementia and psychosis significantly earlier than those without mutations (p < 0.001 and p = 0.017, respectively). Adjusted hazard ratios of GBA mutations were 8.3 for dementia (p < 0.001) and 3.1 for psychosis (p = 0.002). No statistically significant differences were observed for wearing-off and dyskinesia between the groups. N-isopropyl-p[(123)I] iodoamphetamine single-photon emission tomography pixel-by-pixel analysis revealed that regional cerebral blood flow was reduced in the bilateral parietal cortex, including the precuneus of GD-associated mutant PD patients, compared with matched PD controls without mutations.

Delirium and high fever are associated with subacute motor deterioration in Parkinson disease: a nested case-control study.

BACKGROUND: In Parkinson disease (PD), systemic inflammation caused by respiratory infections such as pneumonia frequently occurs, often resulting in delirium in the advanced stages of this disease. Delirium can lead to cognitive and functional decline, institutionalization, and mortality, especially in the elderly. Inflammation causes rapid worsening of PD motor symptoms and signs, sometimes irreversibly in some, but not all, patients. PURPOSE: To identify factors associated with subacute motor deterioration in PD patients with systemic inflammation. METHODS: The association of clinical factors with subacute motor deterioration was analyzed by a case-control study. Subacute motor deterioration was defined as sustained worsening by one or more modified Hoehn and Yahr (H-Y) stages. Using multivariable logistic regression incorporating baseline characteristics (age, sex, PD duration, modified H-Y stage, dementia, and psychosis history) and statistically selected possible predictors (peak body temperature, duration of leukocytosis, and presence of delirium), the odds ratios for these factors were estimated as relative risks. RESULTS: Of 80 PD patients with systemic inflammation, 26 with associated subacute motor deterioration were designated as cases and the remainder as controls. In the 26 cases, 6 months after its onset the motor deterioration had persisted in 19 patients and resolved in four (three were lost for follow-up). Multivariable logistic regression analysis showed that delirium and body temperature are significantly associated with motor deterioration after systemic inflammation (P = 0.001 for delirium and P = 0.026 for body temperature), the adjusted odds ratios being 15.89 (95% confidence interval [CI]: 3.23-78.14) and 2.78 (95% CI: 1.13-6.83), respectively. CONCLUSIONS: In patients with PD and systemic inflammation, delirium and high body temperature are strong risk factors for subsequent subacute motor deterioration and such deterioration can persist for over 6 months.