Obsessive-compulsive disorder induced by donepezil in a patient with Alzheimer's disease.

Background: Donepezil, an acetylcholinesterase inhibitor commonly used to treat Alzheimer's disease (AD), is generally well tolerated. There have been no previous reports on donepezil-induced obsessive-compulsive disorder (OCD). Case Presentation: The patient, a retired man in his 70s diagnosed with AD, displayed OCD symptoms following donepezil initiation, exacerbating post-stroke-specifically, a cerebral infarction in the right posterior limb of the internal capsule. Remarkably, the symptoms abated upon discontinuation of donepezil. Conclusion: Caution should be exercised when using donepezil in patients with a history of stroke.

Rapid and Highly Sensitive Detection of Leishmania by Combining Recombinase Polymerase Amplification and Solution-Processed Oxide Thin-Film Transistor Technology.

Nucleic acid detection is widely used to identify infectious diseases and ensure food safety. However, conventional PCR-based techniques are time consuming. Thus, this study aims to combine recombinase polymerase amplification (RPA), which enables the rapid amplification of even trace amounts of nucleic acid fragments within 10-40 min at 37-42 °C, and solution-processed oxide thin-film transistor (TFT) technology, which exhibits high detection sensitivity, to detect Leishmania. A single-stranded anti-probe was incorporated into the RPA primer to facilitate effective hybridization between the RPA product and the immobilized probe on the solution-processed oxide TFT. The RPA-amplified product carrying an anti-probe enabled specific binding to the chip surface. Changes in current were monitored before and after sample incubation to identify the target nucleic acids in the samples accurately. The proposed method achieved a remarkable limit of detection of 101 copies/µL of the Leishmania HSP70 fragment within 30 min. The design of the probes on the solution-processed oxide TFT surface and the anti-probe simplified the detection of other target nucleic acids, eliminating the need to denature DNA double-strands for specific binding during nucleic acid detection. Thus, the novel method offers the advantage of requiring minimal reagent resources and eliminates the need for complex procedures.

Helicity induction and memory of a lipophilic Brønsted acid-type poly(phenylacetylene) in non-polar solvents.

A novel lipophilic Brønsted acid-type PPA (poly-1-H) bearing a sulfonylphosphoramidic acid moiety, covered with a dynamically axially chiral biphenyl pendant, was synthesized and found to form a preferred-handed helical conformation in non-polar solvents upon complexation with non-racemic amines. This induced helicity was maintained after replacement with achiral amines ("dynamic helicity memory"). In addition, poly-1-H exhibited "static helicity memory" in which the induced helical conformation was maintained in non-polar solvents, even after acidification with a stronger acid without replacement with achiral amines.

Aryloxy Ionic Liquid-Catalyzed Homogenous Esterification of Cellulose with Low-Reactive Acyl Donors.

Ionic liquids (ILs) are recyclable, non-volatile, and can dissolve cellulose, a natural polymer that is insoluble in versatile solvents. Therefore, ILs have been used to modify cellulose. However, 1-ethyl-3-methylimidazolium acetate (EmimOAc), a commercially available IL often used to dissolve and modify cellulose to prepare cellulose-based materials, causes the undesired introduction of an acetyl group derived from the acetate anion of EmimOAc onto the hydroxy group of cellulose during esterification. In this study, for cellulose esterification, we prepared aryloxy ILs as non-carboxylate-type and basic ILs, which can theoretically prevent the undesired introduction of an acyl group from the IL onto the hydroxy group of cellulose. The optimized 1-ethyl-3-methylimidazolium 2-pyridinolate (Emim2OPy) and mixed solvent system achieved rapid cellulose esterification (within 30 min) with an excellent degree of substitution (DS) value (up to >2.9) derived from the employed low-reactive vinyl esters and bio-based unsaturated aldehydes, without any undesired substituent introduction from side reactions.

Ultra-fast One-Handed Helix Induction and Its Static Helicity Memory in a Poly(biphenylylacetylene) with a Catalytic Amount of Chiral Ammonium Salts.

We report an ultra-fast helix induction and subsequent static helicity memory in poly(biphenylylacetylene) (PBPA-A) assisted by a catalytic amount of nonracemic ammonium salts comprised of non-coordinating tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (BArF- ) as a counter anion. The remarkable acceleration of the helix-induction rate in PBPA-A accompanied by the significant amplification of the asymmetry relies on the two methoxymethoxy groups of the biphenyl pendants, which can gain access to enfold the chiral ammoniums in a crown-ether manner in specific aromatic solvents, leading to ultra-fast helicity induction, which is completed within 30 s. In aromatic solvents, helicity memory is lost rapidly, but is quite stable in long-chain hydrocarbons. The best use of specific solvents for helicity induction and static helicity memory, respectively, provides a highly sensitive chirality sensing system toward a small amount of chiral amines and amino acids when complexed with BArF- .

Fabrication and Characterizations of Axial View Liquid Electrode Plasma Atomic Emission Spectrometry for the Sensitive Determination of Trace Zinc, Cadmium, and Lead.

Axial view liquid electrode plasma-atomic emission spectrometry (axial view LEP-AES) was proposed and fabricated successfully in this work. The emission spectra from Zn, Cd, Pb, Ca, and K were applied for characterization and optimization. Comparing with conventional radial view LEP-AES devices, the newly designed axial view-LEP provided better sensing ability toward trace heavy metals. Moreover, pulsed voltage discharge was found to be advantageous over continuous discharge under the same discharge time for detection. The optimized parameters facilitate the limit of detection to achieve 0.24, 0.051, and 0.85 µg L-1 for Zn, Cd, and Pb, respectively. Furthermore, the axial view LEP-AES possessed excellent reproducibility and good durability. The real sample tests using two different certified reference water samples revealed the great potential of the axial view LEP-AES as a novel practical elemental analysis tool.

Enantioseparation on helical poly(diphenylacetylene)s bearing optically-active pendants: Effects of differences in higher-order structures of kinetically-trapped and thermodynamically-stable states on chiral recognition ability.

An optically-active poly(diphenylacetylene) (PDPA) bearing carboxy pendant groups with left-handed helicity memory (M-h-poly-1), synthesized using the noncovalent helicity-induction-and-memory strategy, was converted into a PDPA bearing optically-active pendant groups through an amide bonding (M-hKT-poly-2S), while maintaining the left-handed helicity memory, by reaction with (S)-1-phenylethylamine ((S)-2) using a condensing reagent at room temperature. Its chiral recognition ability was investigated as a chiral stationary phase (CSP) for high-performance liquid chromatography (HPLC). M-hKT-poly-2S exhibited significantly different chiral recognition ability towards racemates compared to the previously reported corresponding helical PDPA bearing the same optically-active pendant groups (M-hTS-poly-2S) (prepared by the reaction of an optically-inactive PDPA bearing carboxy pendants with (S)-2, followed by thermal annealing, to induce a left-handed helical structure in the polymer main chain). Although the main chains of both M-hKT-poly-2S and M-hTS-poly-2S formed almost completely left-handed helical structures, their higher-order structures varied slightly, as confirmed by various spectroscopic methods (UV-Vis, circular dichroism (CD), IR, and vibrational CD). M-hKT-TS-poly-2S, the PDPA formed on the thermal annealing of M-hKT-poly-2S, exhibited the same higher-order structure and chiral discrimination ability as M-hTS-poly-2S. Therefore, slight differences in the higher-order structures of the kinetically-trapped metastable state (M-hKT-poly-2S) and the thermodynamically-stable state (M-hTS-poly-2S), due to differences in synthetic procedures, significantly impact their chiral recognition abilities as CSPs, even with identical primary structures and helix-sense of the polymer main chain.

Automated Paper-Based Femtogram Sensing Device for Competitive Enzyme-Linked Immunosorbent Assay of Aflatoxin B1 Using Submicroliter Samples.

Microfluidic paper-based analytical devices (µPADs) are promising biosensors that may be used in a variety of bioanalytical applications. A µPAD for automating the competitive enzyme-linked immunosorbent assay (ELISA) of small-sized target detection at the femtogram level using submicroliter samples is reported in this study. The proposed µPAD was integrated with a sucrose valve to automate the sequential delivery of reagents, providing simple control of reagent delivery time and simple operation. The use of a sample solution dropping location at the zones on the device that had been prepared with an antibody-conjugated enzyme before immersion in a running buffer allowed minimization of sample volume to 0.6 µL, while eliminating the possible loss of a target molecule by adsorption on the membrane, thus improving detection sensitivity. Furthermore, the proposed device was successfully applied to the automation of competitive ELISA for the detection of aflatoxin B1 (AFB1), a potent carcinogen that causes substantial health risks to humans worldwide, with a detection limit of 60 femtograms or 0.1 ng/mL. The method developed in this study provides high sensitivity, small sample volume, on-site and equipment-free measurements, low-cost operation, and user-friendliness. This approach could be used to analyze small-sized molecules in the fields of food safety and quality control, environmental monitoring, and clinical diagnostics.

Solvent-dependent helix inversion in optically active poly(diphenylacetylene)s and their chiral recognition abilities as chiral stationary phases for high-performance liquid chromatography.

We report the first example of solvent-dependent helix inversion in poly(diphenylacetylene) (PDPA) derivatives. Asymmetrically substituted PDPAs bearing optically active substituents linked through amide bonds formed preferred-handed helical conformations because of the optically active substituents in the pendants, whose helix-senses were inverted upon thermal annealing in polar solvents such as N,N-dimethylformamide and dimethylsulfoxide and in nonpolar solvents such as tetrachloroethane. Unlike the solvent-dependent helix inversion reported for other dynamic helical polymers, the macromolecular helicity induced in the polymer backbone of these PDPAs upon thermal annealing was stably maintained at room temperature, independent of the solvent polarity. These diastereomeric PDPAs with opposite helix-senses generated almost mirror-imaged left- and right-handed circularly polarized light in the same solvent at room temperature. Taking advantage of this unique solvent-dependent helix inversion property, the diastereomeric PDPAs with opposite helix-senses were coated on macroporous silica gel and applied to chiral stationary phases for high-performance liquid chromatography. Despite having the same optically active substituents on the pendant phenyl rings, they showed completely different chiral recognition abilities toward many racemates depending on the helix-sense of the polymer backbone, and the elution order of the enantiomers was reversed for some racemates. The combination of the helix-sense of the polymer backbone and the chirality of the pendants, which afforded a higher chiral recognition ability, differed depending on the racemates.

Visualisation of helical structures of poly(diphenylacetylene)s bearing chiral amide pendants by atomic force microscopy.

The helical structures of poly(diphenylacetylene)s bearing optically active substituents linked through amide bonds and with a helicity memory have been visualised using atomic force microscopy. The polymers self-assembled into an ordered 2D monolayer on highly oriented pyrolytic graphite upon exposure to solvent vapour, whose helical pitch and handedness (right- and left-handed) were for the first time directly revealed at molecular resolution.

Helical springs as a color indicator for determining chirality and enantiomeric excess.

Chirality plays a key role in the physiological system, because molecular functionalities may drastically alter due to a change in chirality. We report herein a unique color indicator with a static helicity memory, which exhibits visible color changes in response to the chirality of chiral amines. A difference of less than 2% in the enantiomeric excess (ee) values causes a change in the absorption that is visible to the naked eyes. This was further quantified by digital photography by converting to RGB values. This system relies on the change in the tunable helical pitch of the π-conjugated polymer backbone in specific solvents and allows rapid on-site monitoring of chirality of nonracemic amines, including drugs, and the simultaneous quantitative determination of their ee values.

Differentiating Mild Cognitive Impairment, Alzheimer's Disease, and Dementia With Lewy Bodies Using Cingulate Island Sign on Perfusion IMP-SPECT.

The cingulate island sign (CIS) on fludeoxyglucose (FDG)-positron emission tomography (PET) is a supporting biomarker of dementia with Lewy bodies (DLB). Its diagnostic accuracy has only been investigated in FDG-PET, however. The present prospective study compared the CIS on I-iodoamphetamine-single photon emission computed tomography (SPECT) among patients with mild cognitive impairment (MCI), AD, or DLB. Fifty-eight patients with MCI, 42 with probable AD, and 58 with probable DLB were enrolled. The "CIScore" used to evaluate the CIS was defined as the ratio of volume of interest (VOI)-1 (indicating posterior cingulate gyrus [PCG]) to VOI-2 (area of significantly reduced regional cerebral blood perfusion [rCBF] in DLB patients compared with in healthy controls). It was calculated using eZIS software. The CIScore for MCI, DLB, and AD was 0.22, 0.23, and 0.28, respectively. The CIScore in the AD group was significantly higher than that in the DLB or MCI groups (AD vs. DLB: p < 0.001, AD vs. MCI: p < 0.005). This suggests that the CIScore can discriminate DLB from AD, if the decrease in rCBF in the PCG is similar between them. We believe that it is difficult to identify MCI based on the CIScore, as the decrease in rCBF in the PCG is not severe. The diagnostic accuracy of the CIScore may be low as it often shows an increase in elderly DLB patients, in whom the pathologically common form is most prevalent (1). Further study should include assessment of multiple components such as symptom classification and age.

Mussel-Inspired Design of a Carbon Fiber-Cellulosic Polymer Interface toward Engineered Biobased Carbon Fiber-Reinforced Composites.

Tuning interactions at the interfaces in carbon fiber (CF)-reinforced polymer composites necessitates the implementation of CF surface modification strategies that often require destructive environmentally unfriendly chemistries. In this study, interfacial interactions in cellulose-based composites are tailored by means of a mussel-inspired adhesive polydopamine (PDA) coating, being inherently benign for the environment and for the structure of CFs. The step-by-step growth of PDA was followed by increasing treatment time leading to a hydrophilic PDA-coated surface, presumably via surface-based polymerization mechanisms attributed to strong π-π stacking interactions. Although PDA deposition led to an initial increase in the interfacial shear strength (IFSS) (5 h), it decreased at a longer reaction time (24 h), the formation of weakly attached PDA particles on the coated surface can possibly lie behind the latter phenomenon. Nevertheless, the mechanical properties of the prepared short CF-reinforced composite were improved (tensile strength increased ∼12% compared to the unmodified surface) with decreasing IFSS owing to the particular morphological design, resulting in longer fiber segments. Our study underlines the importance of the morphological design at the interface and considers PDA as a promising bioinspired material to tailor interfacial interactions.

Awareness of the COVID-19 Outbreak and Resultant Depressive Tendencies in Patients with Severe Alzheimer's Disease.

The ongoing coronavirus disease 2019 (COVID-19) pandemic has substantially affected patients with dementia and their caregivers. However, we found not all Alzheimer's disease (AD) patients were afraid of COVID-19 infection. Therefore, we investigated the association between rate of awareness of COVID-19 and depressive tendency in AD. 126 consecutive outpatients with AD were enrolled in this study from May 25, on the day when the declaration of emergency was lifted in Japan, through June 30, 2020. In addition to routine psychological tests, the participants were asked the following two questions: "Do you know COVID-19?" and "Why are you wearing a face mask?". Moderate to severe AD patients were found to have a low COVID-19 recognition rate and did not fully understand why they were wearing face masks. In addition, because they did not understand the seriousness of the COVID-19 outbreak, their Geriatric Depression Scale scores were also substantially lower. These results may appear to simply indicate that people with severe dementia are unaware of current events. However, these results provide insights into how to care for patients with dementia and how to allocate the time and support of our limited staff during the COVID-19 outbreak.

Synthesis of a poly(diphenylacetylene) bearing optically active anilide pendants and its application to a chiral stationary phase for high-performance liquid chromatography.

Poly(diphenylacetylene) having optically active anilide pendants (poly-1) were synthesized by the condensation reaction of an optically active carboxylic acid with a key precursor polymer containing amino (-NH2) groups, which was prepared by the polymerization of a phthalimide-protected diphenylacetylene monomer using WCl6-Ph4Sn as a catalyst, followed by phthalimide deprotection in the resulting polymer using hydrazine monohydrate. Poly-1 formed a preferred-handed helical conformation (h-poly-1) upon thermal annealing in DMF because of chirality of the pendant group. Poly-1 and h-poly-1 showed different chiral recognition abilities from the analogous poly(diphenylacetylene)s, having the corresponding optically active amide pendants, as chiral stationary phases (CSPs) for high-performance liquid chromatography. The resolution results with the h-poly-1-based CSP were much better than those with the poly-1-based CSP owing to the preferred-handed macromolecular helicity. Among the tested racemates, the h-poly-1-based CSP exhibited superior chiral recognition ability, especially toward binaphthyl compounds and chiral metal complexes.

Helix-Sense-Selective Synthesis of Right- and Left-Handed Helical Luminescent Poly(diphenylacetylene)s with Memory of the Macromolecular Helicity and Their Helical Structures.

Symmetrically substituted poly(diphenylacetylene) (PDPA) bearing carboxy pendants was found to fold into a one-handed helix upon thermal annealing with nonracemic amines in water accompanied by chiral amplification of the helicity. The induced right- or left-handed helical PDPA was retained (memorized) after complete removal of the chiral amines, thus producing a one-handed helical circularly polarized luminescent PDPA in a helix-sense-selective manner. The helical PDPA with static helicity memory is tolerant toward modification of carboxy pendants, providing functional PDPAs with an optical activity solely due to macromolecular helicity. The PDPA and its derivatives before and after the one-handed helicity induction and its subsequent memory of the helicity exhibited well-resolved very simple 1H and 13C NMR and Raman spectra whose spectral patterns are virtually identical independent of the helical sense bias. On the basis of the 1H and 13C NMR, IR, Raman, and vibrational and electronic circular dichroism spectral measurement results combined with theoretical calculations, the key structural features (cis or trans and cisoid or transoid) of the PDPA as well as its helix inversion barrier and absolute handedness (right- or left-handed helix) and helix-sense excess of the one-handed helical PDPA and its derivatives with static helicity memory were determined. As a result, almost complete right- and left-handed helical cis-transoidal PDPAs with 98% helix-sense excess were successfully obtained using noncovalent helicity induction and memory strategy.

Effects of 12-month exercise intervention on physical and cognitive functions of nursing home residents requiring long-term care: a non-randomised pilot study.

AIMS: We performed a 12-month exercise intervention for 'nursing home for the elderly' residents requiring long-term care. We evaluated changes in their muscular strength, muscle mass, and cognitive function. METHODS: Thirty-seven nursing home residents (Mini-Mental State Examination (MMSE): 14.7 ± 7.0, Barthel Index: 44.2 ± 18.9) were enrolled. We divided the participants into the exercise intervention group (n = 19) and non-intervention group (n = 18) ensuring no significant difference in the participants' characteristics at baseline. For the exercise intervention group, exercise was performed for about 40 min twice a week for 12 months. Skeletal Mass Index and grip force were determined to evaluate muscle mass and muscle strength, respectively. MMSE, Trail Making Test (TMT) part A, and Geriatric Depression Scale 15 (GDS15) were used for cognitive function evaluation, with their changes investigated. RESULTS: After 12 months, the MMSE scores were significantly improved in the exercise intervention group compared with the non-intervention group (change from baseline to 12 months: Non-intervention: -1.0 ± 2.8, Intervention: 1.2 ± 3.0; P = 0.04). Moreover, the grip force of the dominant arm was significantly improved in the exercise intervention group compared with the non-intervention group (change from baseline to 12 months: Non-intervention: -1.3 ± 2.8 kg, Intervention: 1.4 ± 4.6 kg; P = 0.007). The prevalence of sarcopenia was significantly increased after 12 months compared with baseline in the non-intervention group (Non-intervention: 61.1% → 75.0%, Intervention: 77.8% → 71.4%; P < 0.02). There were no significant changes in GDS15, Barthel Index and TMT after 12 months in intervention and non-intervention groups. CONCLUSION: Exercise intervention may be effectively used for improving the physical and cognitive functions of nursing home residents requiring long-term care.