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Brain amyloid-β protein (Aβ) deposition is a key pathology of Alzheimer's disease (AD). Cholinergic degeneration, including reductions in α7 nicotinic acetylcholine receptors (α7-nAChR), is also known as a pathophysiology of AD. Recent imaging studies have shown cognitively normal subjects with Aβ depositions, indicating a missing link between Aβ deposition and cognitive decline.
To clarify relationships among the Aβ burden, α7-nAChR availability, and cognitive declines in AD.
To measure brain Aβ deposition and α7-nAChR availability in the same patients with AD using positron emission tomography (PET).
Twenty AD patients and age-matched 20 healthy adults were studied. The α7-nAChR availability and Aβ deposition were evaluated using PET with [11C]MeQAA and [11C]PIB, respectively. Levels of specific binding were estimated by a simplified reference tissue method (BPND) for [11C]MeQAA and a tissue ratio method (SUVR) for using [11C]PIB. The values were compared with clinical measures of various cognitive functions using regions of interest (ROIs)-based and statistical parametric mapping (SPM) analyses.
[11C]MeQAA BPND levels were extensively lower in the cholinergic projection regions of AD. There was a significant negative correlation between [11C]PIB SUVR and [11C]MeQAA BPND in the nucleus basalis of Mynert (NBM). The NBM [11C]PIB SUVR was negatively correlated with the [11C]MeQAA BPND level in the anterior and posterior cingulate cortices, whereas the relation within the same region showed weak correlation. Also we found significant correlation between cognitive decline and [11C]MeQAA BPND levels in the NBM.
Aβ deposition-linked α7-nAChR dysfunction may account for cognitive decline in AD.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
It has been said that nearly 30% of the patients with Alzheimer’ disease (AD) manifest loss of appetite, which might increase cognitive impairments and the incidence of neuropsychiatric symptoms, and malnutrition. As a result, a vicious cycle decreases functionality and quality of life in patients with AD. Cholinesterase inhibitors (ChEIs) is the first-line drugs in the treatment of AD. On the one hand, appetite or weight loss can be seen due to gastrointestinal side effects in the treatment of ChEIs. On the other hand, there are some reports in clinical-settings that patients with AD treated with rivastigmine transdermal patch showed the improvement of appetite loss.
To evaluate the efficacy of rivastigmine transdermal patch in AD patients with poor appetite.
In this 16-weeks, multicenter prospective study, patients with mild to moderate AD, who manifest loss of appetite and began to receive rivastigmine transdermal patch therapy, were enrolled. The amount of food, total time-eating, body weight, Mini Mental State Examination (MMSE) and Neuropsychiatric Inventory (NPI) were evaluated.
The amount of food eaten by treated patients significantly increased 10.5% at 8 weeks after the initiation of rivastigmine transdermal patch therapy.
This preliminary results might show favourable effects of rivastigmine transdermal patch therapy on AD patients with loss of appetite.
The Taylor–Melcher (TM) model is the standard model for describing the dynamics of poorly conducting leaky dielectric fluids under an electric field. The TM model treats the fluids as ohmic conductors, without modelling the underlying ion dynamics. On the other hand, electrodiffusion models, which have been successful in describing electrokinetic phenomena, incorporate ionic concentration dynamics. Mathematical reconciliation of the electrodiffusion picture and the TM model has been a major issue for electrohydrodynamic theory. Here, we derive the TM model from an electrodiffusion model in which we explicitly model the electrochemistry of ion dissociation. We introduce salt dissociation reaction terms in the bulk electrodiffusion equations and take the limit in which the salt dissociation is weak; the assumption of weak dissociation corresponds to the fact that the TM model describes poor conductors. Together with the assumption that the Debye length is small, we derive the TM model with or without the surface charge convection term depending upon the scaling of relevant dimensionless parameters. An important quantity that emerges is the Galvani potential (GP), the jump in voltage across the liquid–liquid interface between the two leaky dielectric media; the GP arises as a natural consequence of the interfacial boundary conditions for the ionic concentrations, and is absent under certain parametric conditions. When the GP is absent, we recover the TM model. Our analysis also reveals the structure of the Debye layer at the liquid–liquid interface, which suggests how interfacial singularities may arise under strong imposed electric fields. In the presence of a non-zero GP, our model predicts that the liquid droplet will drift under an imposed electric field, the velocity of which is computed explicitly to leading order.
Few studies have examined the impact of cigarette smoking on the risk for herpes zoster. The Shozu Herpes Zoster (SHEZ) Study is a community-based prospective cohort study over 3 years in Japan aiming to clarify the incidence and predictive and immunological factors for herpes zoster. We investigated the associations of smoking status with past history and incidence of herpes zoster. A total of 12 351 participants provided valid information on smoking status and past history of herpes zoster at baseline survey. Smoking status was classified into three categories (current, former, never smoker), and if currently smoking, the number of cigarettes consumed per day was recorded. The participants were under the active surveillance for first-ever incident herpes zoster for 3 years. We used a logistic regression model for the cross-sectional study on the association between smoking status and past history of herpes zoster, and a Cox proportional hazards regression model for the cohort study on the association with risk of incidence. The multivariable adjusted odd ratios (95% CI) of past history of herpes zoster for current vs. never smokers were 0·67 (0·54–0·80) for total subjects, 0·72 (0·56–0·93) for men and 0·65 (0·44–0·96) for women. The multivariable adjusted hazard ratios (95% CI) of incident herpes zoster for current vs. never smokers were 0·52 (0·33–0·81) for total subjects, 0·49 (0·29–0·83) for men and 0·52 (0·19–1·39) for women. Smoking status was inversely associated with the prevalence and incidence of herpes zoster in the general population of men and women aged ⩾50 years.
It has been demonstrated that negatively distorted self-referential processing, in which individuals evaluate one's own self, is a pathogenic mechanism in subthreshold depression that has a considerable impact on the quality of life and carries an elevated risk of developing major depression. Behavioural activation (BA) is an effective intervention for depression, including subthreshold depression. However, brain mechanisms underlying BA are not fully understood. We sought to examine the effect of BA on neural activation during other perspective self-referential processing in subthreshold depression.
A total of 56 subjects underwent functional magnetic resonance imaging scans during a self-referential task with two viewpoints (self/other) and two emotional valences (positive/negative) on two occasions. Between scans, while the intervention group (n = 27) received BA therapy, the control group (n = 29) did not.
The intervention group showed improvement in depressive symptoms, increased activation in the dorsal medial prefrontal cortex (dmPFC), and increased reaction times during other perspective self-referential processing for positive words after the intervention. Also, there was a positive correlation between increased activation in the dmPFC and improvement of depressive symptoms. Additionally, there was a positive correlation between improvement of depressive symptoms and increased reaction times.
BA increased dmPFC activation during other perspective self-referential processing with improvement of depressive symptoms and increased reaction times which were associated with improvement of self-monitoring function. Our results suggest that BA improved depressive symptoms and objective monitoring function for subthreshold depression.
Enhancement of the quality of laser wake-field accelerated (LWFA) electron beams implies the improvement and controllability of the properties of the wake waves generated by ultra-short pulse lasers in underdense plasmas. In this work we present a compendium of useful formulas giving relations between the laser and plasma target parameters allowing one to obtain basic dependences, e.g. the energy scaling of the electrons accelerated by the wake field excited in inhomogeneous media including multi-stage LWFA accelerators. Consideration of the effects of using the chirped laser pulse driver allows us to find the regimes where the chirp enhances the wake field amplitude. We present an analysis of the three-dimensional effects on the electron beam loading and on the unlimited LWFA acceleration in inhomogeneous plasmas. Using the conditions of electron trapping to the wake-field acceleration phase we analyse the multi-equal stage and multiuneven stage LWFA configurations. In the first configuration the energy of fast electrons is a linear function of the number of stages, and in the second case, the accelerated electron energy grows exponentially with the number of stages. The results of the two-dimensional particle-in-cell simulations presented here show the high quality electron acceleration in the triple stage injection–acceleration configuration.
The existence of Pt7Cu ordering phase (intermetallic compound) was investigated by ab initio calculations and high voltage electron microscopy (HVEM) focusing on irradiation-induced ordering. The Pt7Cu ordering phase (cF32, prototype Ca7Ge) was predicted at 0 K through density functional theory (DFT), and using cluster expansion (CE) method and grand canonical Monte Carlo (GCMC) simulation, the ordering temperature of fcc-based Pt7Cu ordering phase was estimated to be above room temperature. The formation of Pt7Cu ordering phase was confirmed by a short-time irradiation for 3.6×103 s at 600 K. MeV electron irradiation can reduce drastically the annealing time for the ordering in the Pt-Cu alloy system, indicating that the combination of the prediction by ab initio calculations and HVEM can offer the unique opportunity to investigate the existence of ordering phase in alloys.
Preparation of a sigma-CrFe single-phase specimen was achieved by arc melting of pure Fe and Cr, cold rolling, and subsequent annealing at 973 K or 1073 K in vacuum. Cold rolling before annealing is effective for the annealing-induced formation of sigma-CrFe from the bcc solid-solution phase. The phase stability and the structural change from sigma-CrFe to a bcc solid-solution phase under fast electron irradiation were investigated by in situ transmission electron microscope (TEM) observation in the temperature range between 22 K and 473 K by using an ultra-high voltage electron microscope (UHVEM). The phase transition of sigma-CrFe by fast electron irradiation was found to occur at a particular temperature.
Evidence suggests that breastfeeding during infancy lowers the risk of metabolic syndrome (MS) and its attendant risk factors in adult life. To investigate the influence of feeding type on the risk factors of MS, we assessed insulin sensitivity and lipid and apolipoprotein metabolism in preterm infants. Blood samples were collected from preterm infants at the time of discharge. Infants were separated into two groups: a breast milk (BM) group receiving ⩾90% of their intake from BM, and a mixed-fed (MF) group receiving ⩾50% of their intake from formula. The following indices were then compared between the two groups. Blood glucose and serum insulin levels were used to calculate the quantitative insulin sensitivity check index (QUICKI). We also measured serum total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc), apolipoprotein-A1 (apoA1) and apolipoprotein-B (apoB) levels, and the ratios of TC/HDLc, LDLc/HDLc and apoB/apoA1. The mean gestational age was 32.9 weeks at birth, and blood samples were collected at a mean corrected age of 37.4 weeks. There were 22 infants in the BM group and 19 in the MF group. QUICKI was significantly higher in the BM group. TC, HDLc and apoA1 were not significantly different between the groups, but LDLc and apoB levels were significantly higher in the BM group. The TC/HDLc, LDLc/HDLc and apoB/apoA1 ratios were significantly higher in the BM group. In preterm infants, the type of feeding exposure in the early postnatal period may influence glucose, lipid and apolipoprotein metabolism, and affect markers of MS.
The prevalence and epidemiological traits of human immunodeficiency virus (HIV)/hepatitis B virus (HBV) infections in high-risk populations (HRPs) remained unclarified in Japan. We determined the prevalence of HIV, HBV and Treponema pallidum (TP) and the viral genotypes in HRPs who attended primary sexually transmitted infection (STI) clinics in Osaka province during 2006–2011. Of 7898 specimens, 133 (1·7%) were HIV positive, which was significantly higher than the figures reported by Japanese Red Cross (0·0019%) and public health centres (0·27%) in Japan. The frequency of HIV-1 subtype B was 88·7%, followed by CRF01_AE (2·3%) and C (0·8%), which were almost identical to the national trend. HBV seroprevalence was surprisingly high in the HIV-positive group (63·2%), which was significantly higher than that in the HIV-negative group (25·6%). By contrast, there was no statistical correlation between HIV and TP infection. Interestingly, the distinct HBV genotypes Ae and G were prevalent in the HIV-positive population (60·0% and 20·0%, respectively), although both were rarely detected during nationwide surveillance. The transmission of HIV and HBV appeared to occur largely within a closed community early in life. Of note, about one-quarter of HIV-positive cases would have remained untested if health professionals had not motivated individuals to undergo HIV testing. This is the first evidence-based assessment of HIV positivity and HIV/HBV co-infection in HRPs at primary STIs in Japan and the effect of the involvement of health professionals in the diagnosis of HIV infections in asymptomatic carriers. The genotyping of HBV provided valuable information for understanding HIV epidemical traits.
Latest nanotechnology concepts applied in thermoelectric (TE) research have opened many new avenues to improve the ZT value. Low dimensional structures can improve the ZT value as compared to bulk materials by substantial reduction in the lattice thermal conductivity, κL. However, the materials were not feasible for the industrial scale production of macroscopic devices because of complicated and costly manufacturing processes involved. Bulk nanostructured (NS) TEs are normally fabricated using a bulk process rather than a nano-fabrication process, which has the important advantage of producing in large quantities and in a form that is compatible with commercially available TE devices.
We developed fabrication strategies for bulk nanostructured skutterudite materials based on FexCo1-xSb3. The process is based on precipitation of a precursor material with the desired metal atom composition, which is then exposed to thermochemical processing of calcination followed by reduction. The resultant material thus formed maintains nanostructured particles which are then compacted using Spark Plasma Sintering (SPS) by utilizing previously optimized process parameters. Microstructure, crystallinity, phase composition, thermal stability and temperature dependent transport property evaluation has been performed for compacted NS FexCo1-xSb3. Evaluation results are presented in detail, suggesting the feasibility of devised strategy for bulk quantities of doped TE nanopowder fabrication.
The crystallinity of a GaN epitaxial layer on a sapphire substrate after the mechanical ding process was estimated by transmission electron microscopy (TEM) and Raman spectroscopic analysis. TEM observation results showed that, the screw dislocations as a threading dislocation were induced by the mechanical dicing process in the limited area up to approximately 1.2 μm from the dicing-line. On the other hand, the crystal strains were up to approximately 7 μm from the dicing-line edge measured by the Raman spectroscopic analysis. The distance difference between the area of the screw dislocations and of the residual strain is caused by the stress relaxation.
We explore a model of heat transport between two heat reservoirs mediated by a quantum particle. The reservoirs are modeled as ensembles of harmonic modes linearly coupled to the mediator. The steady state heat current, as well as the thermal conductance are obtained for arbitrary coupling strength and will be analyzed for the cases of weak and strong coupling regimes. It is shown that the violation of the virial theorem – the imbalance between the average potential and kinetic energy of the mediator – can be considered as a measure of the coupling strength that takes into account all the relevant factors. The dependence of the thermal conductance on the coupling strength is non-monotonic and displays a maximum. Temperature dependence of the heat conductance may reach a plateau at intermediate temperatures, similar to the classical plateau at high temperatures. We will discuss the origin of Fourier’s law in a chain of macroscopically large, but finite subsystems coupled by the quantum mediators. We will also address the origin of the anomalously large heat current between the scanning tunneling microscope tip and the substrate in deep vacuum which was found in recent experiments.
The Shozu Herpes Zoster (SHEZ) Study was designed to clarify the incidence of and predictive and immunological factors for herpes zoster in a defined community-based Japanese population. As part of this series, a total of 5683 residents aged ⩾50 years received a varicella-zoster virus (VZV) skin test with VZV antigen, and 48 h later, the erythema and oedema were assessed by measuring the longest diameter. The diameters of both the erythema and oedema decreased with the increasing age of the subject. Sixty-three subjects contracted herpes zoster within a year after receiving the VZV skin test. Analysis of the herpes zoster incidence rate vs. the skin test reaction revealed that the shorter the diameter of erythema or oedema, the greater the likelihood of herpes zoster. These results demonstrated that the VZV skin test is an excellent surrogate marker for predicting the risk of herpes zoster.
The near-infrared (NIR) spectral range (2–5 μm) contains a number of interesting features for the study of the interstellar medium. In particular, the aromatic and aliphatic components in carbonaceous dust can be investigated most efficiently with the NIR spectroscopy. We analyze NIR spectra of the diffuse Galactic emission taken with the Infrared Camera onboard AKARI and find that the aliphatic to aromatic emission band ratio decreases toward the ionized gas, which suggests processing of the band carriers in the ionized region.
Strontium-rich epidote, including epidote-(Sr) and epidote with major amounts of Sr (i.e. epidote containing up to 17.3 wt.% SrO), was found in pumpellyite schist and epidote blueschist in a tectonic block in the serpentinite mélange of the Kurosegawa Zone, central Kyushu, Japan. The tectonic block is 20 m wide and made primarily of lawsonite blueschist, with subordinate amounts of pumpellyite schist and epidote blueschist. The pumpellyite schist typically occurs at the edge of the block and is composed mainly of pumpellyite with subordinate amounts of strontium-poor epidote, albite and chlorite, and thin veins of fine-grained calcite and clinopyroxene. Epidote-(Sr) forms rims around strontium-poor epidote, fills fractures in strontium-poor epidote and also occurs interstitially between pumpellyite aggregates and along the boundaries between pumpellyite and calcite-clinopyroxene veins. The epidote blueschist is found between the pumpellyite schist and lawsonite blueschist, and consists mainly of sodic amphibole, epidote and titanite, with albite veining. Strontium-rich epidote occurs as rims, replacing Sr-poor epidote near the albite vein. The bulk strontium contents of the rocks are as follows: lawsonite blueschist (200 ppm), epidote blueschist (2800 ppm) and pumpellyite schist (~10,700 ppm). The chemical and petrological characteristics of the Sr-rich epidote-bearing metabasites suggest that the infiltration of a metamorphic fluid promoted extensive Sr metasomatism during the later stages of high-pressure metamorphism.