Mental and Physical Self-Awareness of Alzheimer Patients: Decreased Awareness of Amnesia and Increased Fear of Falling Compared to Views of Families: The Tajiri and Wakuya Projects.

INTRODUCTION: The purpose of this study is to examine self-awareness of patients with Alzheimer disease (AD) regarding forgetfulness and physical status, with the goal of further psychological understanding of these patients. METHODS: The 255 subjects included 33 healthy volunteers and 48 patients with mild cognitive impairment who were elderly community residents selected from the 2017 Wakuya Project and 174 consecutive outpatients with AD at the Tajiri Clinic. Test data were selected from a pooled database. Results from the Mini-Mental State Examination, Clinical Dementia Rating (CDR), Short Falls Efficacy Scale International (FES), and Everyday Memory Checklist (EMC) were used in the study. FES and EMC data were also obtained from family members for comparison. RESULTS: EMC scores in the AD groups (mild to moderate and moderate to severe) were significantly higher (more complaining memory impairment) than those in the CDR 0 (healthy) group and significantly lower (less self-awareness for memory impairment) than the corresponding EMC scores of families of the subjects. In contrast, FES scores of the AD groups did not differ significantly from those of the CDR 0 group, and these scores were higher (more fear of falling) than those of family members. Additionally, family-FES scores of the AD groups were higher than those of the CDR 0 and 0.5 groups. CONCLUSION: The results showed an evidence of the heterogeneity of awareness, an emotional response (concern or fear, FES), and a cognitive appraisal of function (EMC). These may be explained whereby awareness of/fear of falling increases with AD due to a preserved emotional awareness, whereas awareness of cognitive impairment is impaired due to memory deficits.

The putative ceramide-conjugation protein Cwh43 regulates G0 quiescence, nutrient metabolism and lipid homeostasis in fission yeast.

Cellular nutrient states control whether cells proliferate, or whether they enter or exit quiescence. Here, we report characterizations of fission yeast temperature-sensitive (ts) mutants of the evolutionarily conserved transmembrane protein Cwh43, and explore its relevance to utilization of glucose, nitrogen source and lipids. GFP-tagged Cwh43 localizes at ER associated with the nuclear envelope and the plasma membrane, as in budding yeast. We found that cwh43 mutants failed to divide in low glucose and lost viability during quiescence under nitrogen starvation. In cwh43 mutants, comprehensive metabolome analysis demonstrated dramatic changes in marker metabolites that altered under low glucose and/or nitrogen starvation, although cwh43 cells apparently consumed glucose in the culture medium. Furthermore, we found that cwh43 mutant cells had elevated levels of triacylglycerols (TGs) and coenzyme A, and that they accumulated lipid droplets. Notably, TG biosynthesis was required to maintain cell division in the cwh43 mutant. Thus, Cwh43 affects utilization of glucose and nitrogen sources, as well as storage lipid metabolism. These results may fit a notion developed in budding yeast stating that Cwh43 conjugates ceramide to glycosylphosphatidylinositol (GPI)-anchored proteins and maintains integrity of membrane organization.

Individual variability in human blood metabolites identifies age-related differences.

Metabolites present in human blood document individual physiological states influenced by genetic, epigenetic, and lifestyle factors. Using high-resolution liquid chromatography-mass spectrometry (LC-MS), we performed nontargeted, quantitative metabolomics analysis in blood of 15 young (29 ± 4 y of age) and 15 elderly (81 ± 7 y of age) individuals. Coefficients of variation (CV = SD/mean) were obtained for 126 blood metabolites of all 30 donors. Fifty-five RBC-enriched metabolites, for which metabolomics studies have been scarce, are highlighted here. We found 14 blood compounds that show remarkable age-related increases or decreases; they include 1,5-anhydroglucitol, dimethyl-guanosine, acetyl-carnosine, carnosine, ophthalmic acid, UDP-acetyl-glucosamine,N-acetyl-arginine,N6-acetyl-lysine, pantothenate, citrulline, leucine, isoleucine, NAD(+), and NADP(+) Six of them are RBC-enriched, suggesting that RBC metabolomics is highly valuable for human aging research. Age differences are partly explained by a decrease in antioxidant production or increasing inefficiency of urea metabolism among the elderly. Pearson's coefficients demonstrated that some age-related compounds are correlated, suggesting that aging affects them concomitantly. Although our CV values are mostly consistent with those CVs previously published, we here report previously unidentified CVs of 51 blood compounds. Compounds having moderate to high CV values (0.4-2.5) are often modified. Compounds having low CV values, such as ATP and glutathione, may be related to various diseases because their concentrations are strictly controlled, and changes in them would compromise health. Thus, human blood is a rich source of information about individual metabolic differences.

Can dementia patients live in a community? A case of a patient in trouble with the law.

We experienced a case involving a 67-year-old man with Alzheimer's disease who exhibited criminal behaviour. Although his behaviour improved after admission to a long-term care facility, he was not able to return to his home because he was suspected of theft. At 62 years of age, he developed slowly progressive memory loss and had difficulty managing money. He was diagnosed with Alzheimer's disease and began taking galantamine. He was placed in police custody after he had tried to take another person's fuel tank early one morning. However, he was not charged with theft because he did not remember his actions. Because it was difficult for his sister to constantly monitor him, he was admitted to a long-term care facility. He displayed high emotional insecurity and continually asked when he could return home. His physical function was good, enabling him to perform various activities alone, but he experienced the delusion of theft during these activities. He appealed the decision prohibiting him from going home. However, the staff suggested that he would exhibit problematic behaviours at home, and it was decided that he should not live at home. After living at the long-term care facility for 3 years, he died of acute cardiac infarction. When a person goes to jail for committing a crime, that person can return to society after completing a jail term. That was not the case with this man with Alzheimer's disease. As such, guidelines and standards to evaluate the criminal responsibility of dementia patients need to be established.

A Novel Chemoenzymatic Synthesis of Sulfated Type†2 Tumor-Associated Carbohydrate Antigens by Transglycosylation of Sulfated Lewis X Oxazoline Catalyzed by Keratanase†II.

Sulfated type 2 carbohydrate chains are known tumor-associated carbohydrate antigens (TACAs). Many reports on cancer vaccines employing TACAs as specific antigens have been published, but structurally specified sulfated TACAs have not been used because of the low natural abundance and difficulties in chemical synthesis. We demonstrate for the first time the synthesis of the sulfated type 2 TACAs with an l-fucose branch by keratanase-II-catalyzed transglycosylation of the sulfated Lewis X (Galß(1→4)[Fucα(1→3)]GlcNAc(6-OSO3- ); su-Lex ) oxazoline derivative. Two keratanase IIs (from Bacillus sp. Ks36 and Bacillus circulans KsT202) efficiently catalyzed the transglycosylation reaction of the su-Lex oxazoline derivative, thereby giving the su-Lex dimer as the main product in good yields. Structural analysis of the oligomers confirmed exclusive formation of the ß(1→3) glycosidic bond.

Life concerns of elderly people living at home determined as by Community General Support Center staff: implications for organizing a more effective integrated community care system. The Kurihara Project.

BACKGROUND: In Japan, the integrated community care system aims to enable people to continue to live in their homes. Based on the concept, one of the activities of a Community General Support Center (CGSC) is to provide preventive intervention based on a Community Support Program. Currently, a Basic Checklist (BC) is sent to elderly people to identify persons appropriate for a Secondary Prevention Program. METHODS: To find people who had not responded to the BC, CGSC staff evaluated the files of 592 subjects who had participated in the Kurihara Project to identify activities they cannot do that they did in the past, decreased activity levels at home, loss of interaction with people other than their family, and the need for medical interventions. This information was classified, when applicable, into the following categories: (A) 'no life concerns'; (B) 'undecided'; and (C) 'life concerns'. The relationships between these classifications and clinical information, certified need for long-term care, and items on the BC were examined. RESULTS: The numbers of subjects in categories A, B, and C were 291, 42, and 186, respectively. Life concerns were related to scores on the Clinical Dementia Rating, global cognitive function, depressive state, and apathy. Most items on the BC were not associated with classification into category C, but ≥25% of the subjects had life concerns related to these items. DISCUSSION: Assessment of life concerns by the CGSC staff has clinical validity. The results suggest that there are people who do not respond to the checklist or apply for Long-Term Care Insurance, meaning that they 'hide' in the community, probably due to apathy or depressive state. To organize a more effective integrated community care system, the CGSC staff should focus mainly on preventive care.

Self-Reported Cognitive Decline Based on the Ascertain Dementia 8 Questionnaire May Be Effective for Detecting Mild Cognitive Impairment and Dementia in the Community: The Wakuya Project.

INTRODUCTION: To assess cognitive impairment, self-awareness is an important issue. The Ascertain Dementia 8 questionnaire (AD8) is a brief observation checklist for detecting mild cognitive impairment (MCI) and dementia. After analyzing the reliability and validity of a self-reported Japanese version of the AD8 (AD8-J), we compared self- and informant-reported versions of the AD8-J. METHODS: A total of 93 community residents aged 75 years or older living in Wakuya, Northern Japan, agreed to participate in this study; 35 were rated as Clinical Dementia Rating (CDR) 0 (healthy), 46 as CDR 0.5 (defined herein as MCI), and 12 as CDR 1 or above (dementia, confirmed by the DSM-IV). We examined the reliability and validity using a receiver operating characteristic (ROC) curve. We analyzed the differences between self-reported and informant-reported AD8-J using a repeated measures ANOVA. RESULTS: The self-reported AD8-J showed a satisfactory reliability (i.e., Cronbach coefficient, α = 0.71; Guttman split half method coefficient = 0.60). For CDR 0 vs. CDR 0.5 or above, the area under the ROC curve was 0.74 and the cutoff score was 1/2, with a sensitivity of 70.7% and a specificity of 65.7%. Analysis of the subscores of AD8 suggested that, from the early stage of dementia, the subjects showed a subjective decline in memory and interest in hobbies/activities, as well as problems with judgment. CONCLUSION: It is suggested that the self-reported AD8-J was effective in detecting MCI and dementia. We could use it for detecting MCI and dementia, including in those living alone, in the primary health checkup.

Decreased Time on the Nondominant One-Leg Standing Test Associated with Repeated Falls in Older Residents with Healthy Aging, Mild Cognitive Impairment, and Dementia: The Wakuya Project.

INTRODUCTION: The aim of this study is to clarify the association between repeated falls and the dominant/nondominant side in the open-eyed one-leg standing (OLS) test among people who are healthy or have mild cognitive impairment (MCI) or dementia in a community setting. We recruited 180 participants from 39 areas in the town of Wakuya. METHODS: This is a cross-sectional study. Participants were classified into 3 Clinical Dementia Rating (CDR) groups, i.e., CDR 0 (healthy, n = 71), CDR 0.5 (MCI, n = 85), and CDR 1+ (n = 23), and they were investigated for motor function (grip strength, 6-m normal gait speed, timed up and go test, and OLS test) and falls during the past year. RESULTS: Subjects with a CDR of 0.5 had higher rates of single and repeated falls (13.0 and 23.4%, respectively) than the CDR 0 group (12.1 and 4.5%, respectively), as did those in CDR 1+ group (15.0 and 30.0%). For the CDR 0.5 group, the frequency of falls was negatively (biologically meaningful direction) correlated with the left OLS time. No significant correlations with falls were found for other motor function tests. Another analysis separating the CDR 0.5 group into 2 subgroups (repeated falls vs. no or a single fall) also showed that the left OLS time was lower in subjects with repeated falls. CONCLUSION: People with MCI who had fallen repeatedly in the year before the assessment had a significantly lower left OLS time compared to those who had not fallen or had had 1 fall with MCI. None of the other physical measures were associated with past repeat falls including OLS on the dominant right side. No such findings were noted in the CDR 0 and CDR 0+ groups.

Diverse metabolic reactions activated during 58-hr fasting are revealed by non-targeted metabolomic analysis of human blood.

During human fasting, metabolic markers, including butyrates, carnitines, and branched-chain amino acids, are upregulated for energy substitution through gluconeogenesis and use of stored lipids. We performed non-targeted, accurate semiquantitative metabolomic analysis of human whole blood, plasma, and red blood cells during 34-58 hr fasting of four volunteers. During this period, 44 of ~130 metabolites increased 1.5~60-fold. Consistently fourteen were previously reported. However, we identified another 30 elevated metabolites, implicating hitherto unrecognized metabolic mechanisms induced by fasting. Metabolites in pentose phosphate pathway are abundant, probably due to demand for antioxidants, NADPH, gluconeogenesis and anabolic metabolism. Global increases of TCA cycle-related compounds reflect enhanced mitochondrial activity in tissues during fasting. Enhanced purine/pyrimidine metabolites support RNA/protein synthesis and transcriptional reprogramming, which is promoted also by some fasting-related metabolites, possibly via epigenetic modulations. Thus diverse, pronounced metabolite increases result from greatly activated catabolism and anabolism stimulated by fasting. Anti-oxidation may be a principal response to fasting.

Enantioselective synthesis of silanol.

An enantioselective nucleophilic substitution reaction of achiral dialkoxysilane has been developed. The reaction proceeds with efficient stereocontrol on the silicon chirality center to give the enantioenriched silyl ether, which can be converted to the silanol without loss of enantiopurity. We have analyzed the steric course of the reaction by using DFT calculations and propose a transition state model to explain the observed enantioselectivity.

Clinical management of pressure control ventilation: An algorithmic method of patient ventilatory management to address "forgotten but important variables".

Pressure controlled ventilation is a common mode of ventilation used to manage both adult and pediatric populations. However, there is very little evidence that distinguishes the efficacy of pressure controlled ventilation over that of volume controlled ventilation in the adult population. This gap in the literature may be due to the absence of a consistent and systematic algorithm for managing pressure controlled ventilation. This article provides a brief overview of the applications of both pressure controlled ventilation and volume controlled ventilation and proposes an algorithmic approach to the management of patients receiving pressure controlled ventilation. This algorithmic approach highlights the need for clinicians to have a comprehensive conceptual understanding of mechanical ventilation, pulmonary physiology, and interpretation of ventilator graphics in order to best care for patients receiving pressure controlled ventilation. The objective of identifying a systematic approach to managing pressure controlled ventilation is to provide a more generalizable and equitable approach to management of the ICU patient. Ideally, a consistent approach to managing pressure controlled ventilation in the adult population will glean more reliable information regarding actual patient outcomes, as well as the efficacy of pressure controlled ventilation when compared to volume controlled ventilation.

Monitoring of drug treatment and psychosocial intervention with SPECT in Alzheimer patients Implications for neurologically appropriate psychosocial interventions. An observational study. The Osaki-Tajiri Project.

We previously examined cerebral blood flow (CBF) with single-photon emission computed tomography (SPECT) in Alzheimer's disease (AD) with reference to drug treatment (donepezil) and psychosocial intervention. OBJECTIVE: The aim is to provide "brain-based" evidence for psychosocial interventions using SPECT. METHODS: The participants were 27 consecutive outpatients with AD who received the drug and psychosocial intervention, and SPECT three times (baseline, pre-/post-intervention) at 6 month-intervals. The significance level of changes in CBF (Z score) and the extent of significantly changed areas, calculated with the eZIS system, were used as monitoring parameters. The participants were classified into three groups: improve (post-intervention CBF increased), worsening (progressive decline), and no change. RESULTS: Six, 8, and 13 patients were classified as improve, worsening, and no change, respectively. All subjects in the improve group showed improvement in cognitive test scores for the MMSE and/or the CGI scores associated with the brain area with a CBF increase (right parietal lobe), suggesting appropriate psychosocial intervention (visuospatial intervention). CONCLUSION: These results suggest that monitoring of CBF with the eZIS system may be clinically applicable for monitoring of drug treatment and psychosocial intervention in AD patients.

Nós examinamos previamente o fluxo sanguíneo cerebral (FSC) com tomografia computadorizada de emissão de fóton único (SPECT) na doença de Alzheimer (DA) com referência ao tratamento medicamentoso (donepezila) e intervenção psicossocial. OBJETIVO: Fornecer evidências "baseadas no cérebro" para intervenções psicossociais usando o SPECT. MÉTODOS: Os participantes foram 27 pacientes ambulatoriais consecutivos com DA que receberam a droga e intervenção psicossocial, e SPECT por três vezes (basal, pré/pós-intervenção) em intervalos de seis meses. O nível de significância das mudanças no FSC (escore Z) e a extensão das áreas significativamente alteradas calculadas com o sistema eZIS foram utilizados como parâmetros de monitoramento. Os participantes foram classificados em três grupos: melhora (FSC pós-intervenção aumentada), piora (declínio progressivo) e nenhuma mudança. RESULTADOS: Seis, oito e 13 pacientes foram classificados como melhora, piora e sem alteração, respectivamente. Todos no grupo melhora mostraram aumento dos escores no MEEM e/ou nos escores do CGI associados à área do cérebro com aumento do FSC (lobo parietal direito), sugerindo intervenção psicossocial apropriada (intervenção visoespacial). CONCLUSÃO: Estes resultados sugerem que o monitoramento do FSC com o sistema eZIS pode ser clinicamente aplicável para o monitoramento do tratamento medicamentoso e intervenção psicossocial em pacientes com DA.

Impact of physician education and availability of parameters regarding esophageal pressure and transpulmonary pressure on clinical decisions involving ventilator management.

PURPOSE: This study investigated the effects of physician education and the availability of Peso and PL data on physicians' decisions regarding ventilator management during specific simulated clinical conditions. MATERIALS AND METHODS: The study was a prospective, before-after study using a case scenario-based questionnaire and a case simulator device comprising an Avea ventilator and an artificial lung and esophagus, which was connected to a Series 1101 Electronic Breathing Simulator. The 99 physicians participating in the study were provided with five simulated cases with on-time ventilator graphics without Peso and PL and completed a questionnaire on decisions they would make regarding ventilator management of the cases. Then, after receiving instruction on Peso and PL, they were given the same cases along with ventilator graphics that included Peso and PL. RESULTS: After receiving instruction and data on Peso and PL, statistically significant numbers of physicians changed their answers regarding ventilator management decisions in all five cases. CONCLUSIONS: Providing education and data for Peso and PL had a significant effect on physician decisions regarding ventilator management in simulated cases. The use of case scenario-based education with simulator devices for physicians may hasten worldwide understanding and clinical application of Peso and PL.

Synthesis of type 2 Lewis antigens via novel regioselective glycosylation of an orthogonally protected lactosamine diol derivative.

The novel and efficient synthesis of type 2 Lewis antigens is reported in this study. The rationally designed lactosamine-3,2'-diol derivative with an orthogonal set of protecting groups is efficiently glycosylated with a benzyl protected 1-thio-l-fucoside donor in a unique regioselective manner to produce Lewis x (Le(x)) and Lewis y (Le(y)) derivatives in good yields. These derivatives can be prepared not only exclusively but also synchronously by choosing the appropriate reaction temperature and donor-acceptor molar ratio. The Le(x) derivatives are easily converted into sulfated or non-sulfated Le(x) bearing a terminal azido functionalized oligo-(ethyleneoxide) linker; the Le(y) derivative having the same linker can also be prepared, all of which can be further used for the chemical modification of other compounds and materials.

Monitoring of drug treatment and psychosocial intervention with SPECT in Alzheimer patients: implications for neurologically appropriate psychosocial interventions. An observational study. The Osaki-Tajiri Project / Monitoramento do tratamento medicamentoso e intervenção psicossocial com SPECT em pacientes com Alzheimer: implicações para intervenções psicossociais neurologicamente apropriadas. um estudo observacional. o Projeto Osaki-Tajiri

ABSTRACT We previously examined cerebral blood flow (CBF) with single-photon emission computed tomography (SPECT) in Alzheimer's disease (AD) with reference to drug treatment (donepezil) and psychosocial intervention. Objective: The aim is to provide "brain-based" evidence for psychosocial interventions using SPECT. Methods: The participants were 27 consecutive outpatients with AD who received the drug and psychosocial intervention, and SPECT three times (baseline, pre-/post-intervention) at 6 month-intervals. The significance level of changes in CBF (Z score) and the extent of significantly changed areas, calculated with the eZIS system, were used as monitoring parameters. The participants were classified into three groups: improve (post-intervention CBF increased), worsening (progressive decline), and no change. Results: Six, 8, and 13 patients were classified as improve, worsening, and no change, respectively. All subjects in the improve group showed improvement in cognitive test scores for the MMSE and/or the CGI scores associated with the brain area with a CBF increase (right parietal lobe), suggesting appropriate psychosocial intervention (visuospatial intervention). Conclusion: These results suggest that monitoring of CBF with the eZIS system may be clinically applicable for monitoring of drug treatment and psychosocial intervention in AD patients.

RESUMO Nós examinamos previamente o fluxo sanguíneo cerebral (FSC) com tomografia computadorizada de emissão de fóton único (SPECT) na doença de Alzheimer (DA) com referência ao tratamento medicamentoso (donepezila) e intervenção psicossocial. Objetivo: Fornecer evidências "baseadas no cérebro" para intervenções psicossociais usando o SPECT. Métodos: Os participantes foram 27 pacientes ambulatoriais consecutivos com DA que receberam a droga e intervenção psicossocial, e SPECT por três vezes (basal, pré/pós-intervenção) em intervalos de seis meses. O nível de significância das mudanças no FSC (escore Z) e a extensão das áreas significativamente alteradas calculadas com o sistema eZIS foram utilizados como parâmetros de monitoramento. Os participantes foram classificados em três grupos: melhora (FSC pós-intervenção aumentada), piora (declínio progressivo) e nenhuma mudança. Resultados: Seis, oito e 13 pacientes foram classificados como melhora, piora e sem alteração, respectivamente. Todos no grupo melhora mostraram aumento dos escores no MEEM e/ou nos escores do CGI associados à área do cérebro com aumento do FSC (lobo parietal direito), sugerindo intervenção psicossocial apropriada (intervenção visoespacial). Conclusão: Estes resultados sugerem que o monitoramento do FSC com o sistema eZIS pode ser clinicamente aplicável para o monitoramento do tratamento medicamentoso e intervenção psicossocial em pacientes com DA.