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- .

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.

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.

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.

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.

Three-State Switchable Chiral Stationary Phase Based on Helicity Control of an Optically Active Poly(phenylacetylene) Derivative by Using Metal Cations in the Solid State.

An unprecedented three-state switchable chiral stationary phase (CSP) for high-performance liquid chromatography (HPLC) was developed using a helical poly(phenylacetylene) bearing a chiral ( R)-α-methoxyphenylacetic acid residue as the pendant (poly-1). The left- and right-handed helical conformations were induced in poly-1-based CSP upon coordination with a catalytic amount of soluble sodium and cesium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate salts (MBArF), respectively, which are soluble in the HPLC conditions [hexane-2-propanol (95:5, v/v)]. The switch between the two different helical states of poly-1 can be easily achieved by rinsing the poly-1-based CSP with MeOH and the subsequent addition of the proper MBArF salt. Using this dynamic helical CSP, we demonstrate how changes on the orientation of the secondary structure of a chiral polymer (right-handed, left-handed, and racemic helices) can alter and even invert the elution order of the enantiomers. This study was done without adding chiral additives or changing the mobile phase, which could produce changes on the retention times and make it more difficult to determine the role of the secondary structure during the chiral recognition process.

Influence of albumin leakage on glycated albumin in patients with type 2 diabetes undergoing hemodialysis.

Glycated albumin (GA) is recommended as a better glycemic indicator than HbA1c in patients undergoing hemodialysis, because the red blood cell lifespan is generally faster than that in normal subjects. However, GA can be also affected by protein loss in urine and hemodialysis fluid. Therefore, in this study, we investigated the effect of albumin leakage induced by hemodialysis on GA. Nine patients undergoing hemodialysis with a large or small amount of albumin leakage were observed for 9 months in a crossover manner. As a result, it was shown that albumin leakage could affect GA, but the effect was practically small considering the prescription of diabetic drugs. The correlations between HbA1c and blood glucose levels and between GA and blood glucose levels were similar in our study. In conclusion, GA was a reliable indicator, even with the change of hemodialysis modality. The influence of albumin leakage induced by hemodialysis on GA was negligible practically. We should recognize that the preferable glycemic indicator in patients undergoing hemodialysis depends on the hemoglobin and albumin metabolism of each patient.

[A suspicious case of coagulation disorder caused by vitamin K deficiency associated with fasting and antibiotics].

Coagulation disorders due to some antibiotics containing N-methyl-thiotetrazole group and vitamin K (VK) deficiency by microbial substitution in the intestinal flora can occur. We report a case of coagulation disorder under fasting with conventional antibiotics which are not containing N-methyl-thiotetrazole. A 91-year-old man was hospitalized for diagnosis of acute exacerbation of chronic heart failure because of bronchitis. He received treatment of fasting, fluid replacement, antibiotics, and a diuretic. On the 3rd day, left frontal lobe bleeding occurred. We performed conservative treatment with central venous nutrition not containing VK. Administration of antibiotics was completed after 14 days. On the 28th day, catheter-related bloodstream infection developed. Vancomycin and cefazolin were administered. The prothrombin time-international standard ratio (PT-INR) on the 1st day of administration was 1.2; however, it gradually increased to 7.4 on the 7th day of administration. Menatetrenone and fresh frozen plasma were administered as symptomatic treatment. Vancomycin was discontinued because a blood culture was positive for methicillin- susceptible coagulase negative Staphylococcus (CNS). After the 8th day of administration, the PT-INR improved to 1.1, but it increased to 1.9 on the 14th day. VK deficiency due to the antimicrobial drug was predicted. Therefore, VK and fresh frozen plasma were re-administered to improve the PT-INR. The PT-INR returned to normal after administration of cefazolin was terminated. Antimicrobial administration in the long term under the fasting condition can suppress endogenous production of VK by changing intestinal bacteria. And it has been reported that cefazolin which containing Methyl-thiadiazole thiol inhibits VK metabolic cycle and causes coagulation disorder. These reasons seems to a coagulation disorder. Therefore, physicians should monitor the coagulation system in this situation.

Direct Detection of Hardly Detectable Hidden Chirality of Hydrocarbons and Deuterated Isotopomers by a Helical Polyacetylene through Chiral Amplification and Memory.

We report the first direct chirality sensing of a series of chiral hydrocarbons and isotopically chiral compounds (deuterated isotopomers), which are almost impossible to detect by conventional optical spectroscopic methods, by a stereoregular polyacetylene bearing 2,2'-biphenol-derived pendants. The polyacetylene showed a circular dichroism due to a preferred-handed helix formation in response to the hardly detectable hidden chirality of saturated tertiary or chiroptical quaternary hydrocarbons, and deuterated isotopomers. In sharp contrast to the previously reported sensory systems, the chirality detection by the polyacetylene relies on an excess one-handed helix formation induced by the chiral hydrocarbons and deuterated isotopomers via significant amplification of the chirality followed by its static memory, through which chiral information on the minute and hidden chirality can be stored as an excess of a single-handed helix memory for a long time.

Systematic Evaluation of 2-Arylazocarboxylates and 2-Arylazocarboxamides as Mitsunobu Reagents.

2-Arylazocarboxylate and 2-arylazocarboxamide derivatives can serve as replacements of typical Mitsunobu reagents such as diethyl azodicarboxylate. A systematic investigation of the reactivity and physical properties of those azo compounds has revealed that they have an excellent ability as Mitsunobu reagents. These reagents show similar or superior reactivity as compared to the known azo reagents and are applicable to the broad scope of substrates. p Ka and steric effects of substrates have been investigated, and the limitation of the Mitsunobu reaction can be overcome by choosing suitable reagents from the library of 2-arylazocarboxylate and 2-aryl azocarboxamide derivatives. Convenient recovery of azo reagents is available by one-pot iron-catalyzed aerobic oxidation, for example. SC-DSC analysis of representative 2-arylazocarboxylate and 2-arylazocarboxamide derivatives has shown high thermal stability, indicating that these azo reagents possess lower chemical hazard compared with typical azo reagents.

Borylative Radical Cyclizations of Benzo[3,4]cyclodec-3-ene-1,5-diynes and N-Heterocyclic Carbene-Boranes.

Borylative radical cyclization of benzo[3,4]cyclodec-3-ene-1,5-diynes to provide 5-borylated 6,7,8,9-tetrahydrobenzo[a]azulenes has been developed. The experimental results suggest that the reaction proceeds by a radical chain mechanism, in which di-tert-butyl hyponitrite (TBHN) works as a good radical initiator to form boryl radicals from N-heterocyclic carbene-boranes (NHC-boranes). The present reaction is a rare model that illustrates addition of boryl radicals to alkynes.

Utility of the combination of DAT SPECT and MIBG myocardial scintigraphy in differentiating dementia with Lewy bodies from Alzheimer's disease.

PURPOSE: (123)I-2ß-Carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortropane ((123)I-FP-CIT) dopamine transporter single photon emission computed tomography (DAT SPECT) and (123)I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy can be used to assist in the diagnosis of patients with dementia with Lewy bodies (DLB). We compared the diagnostic value of these two methods in differentiating DLB from Alzheimer's disease (AD). Furthermore, we evaluated whether a combination of DAT SPECT and MIBG myocardial scintigraphy would provide a more useful means of differentiating between DLB and AD. METHODS: Patients with AD (n = 57) and patients with DLB (n = 76) who underwent both DAT SPECT and MIBG myocardial scintigraphy were enrolled. The sensitivity, specificity, and accuracy of both methods as well as their combination for differentiating DLB from AD were calculated. Moreover, we examined whether symptoms of the patients with DLB were associated with the patterns of the abnormalities displayed on DAT SPECT and MIBG myocardial scintigraphy. RESULTS: The sensitivity and specificity of differentiating DLB from AD were 72.4 and 94.4 % by the heart to mediastinum ratio of MIBG uptake, 88.2 and 88.9 % by the specific binding ratio on DAT SPECT, and 96.1 and 90.7 % by their combination, respectively. The combined use of DAT SPECT and MIBG myocardial scintigraphy enabled more accurate differentiation between DLB and AD compared with either DAT SPECT or MIBG myocardial scintigraphy alone. There was a significantly higher frequency of parkinsonism in the abnormal DAT SPECT group than the normal DAT SPECT group. On the other hand, there was a higher frequency of the appearance of rapid eye movement (REM) sleep behavior disorder in the abnormal MIBG uptake group than the normal MIBG uptake group. CONCLUSION: These results suggested that using a combination of these scintigraphic methods is a useful and practical approach to differentiate DLB from AD.

The effect of albumin leakage in hemodialysis patients on redox status of serum albumin.

Human mercaptoalbumin (HMA) is a reduced form of albumin that is associated with cardiovascular disease in dialysis patients. Albumin-leaky hemodialysis (HD) is increasingly recognized as a gold standard therapy because it is correlated with better prognosis compared to conventional HD. However, albumin-leaky HD induces low serum albumin concentration because of albumin leakage, which is a classical risk factor for mortality. The aim of this study was to explain the preferable prognosis in patients undergoing albumin-leaky HD with low serum albumin concentration. Ten HD patients were enrolled. They were preconditioned with albumin-non-leaky HD (mean albumin leakage: 1.0 g) for 2 months. Subsequently, albumin-leaky HD (9.1 g) was performed for 6 months, followed by relatively non-leaky HD (within 3.0 g). The ratio and level of HMA were evaluated. The amount of albumin leakage was related to the ratio of HMA, and inversely correlated with serum albumin concentration. The level of HMA was maintained regardless of albumin leakage. Regarding HMA level, a moderate amount of albumin leakage was acceptable. A stably maintained HMA level in albumin-leaky HD patients can contribute to preferable prognosis even if they have low serum albumin concentration.

Direct synthesis of 1,4-diols from alkenes by iron-catalyzed aerobic hydration and C-H hydroxylation.

Various 1,4-diols are easily accessible from alkenes through iron-catalyzed aerobic hydration. The reaction system consists of a user-friendly iron phthalocyanine complex, sodium borohydride, and molecular oxygen. Furthermore, the effect of additional ligands on the iron complex was examined for a model reaction. The second hydroxy group is installed by direct C(sp(3))-H oxygenation, which is based on a [1,5] hydrogen shift process of a transient alkoxy radical that is formed by formal hydration of the olefin.

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.