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1.
Am J Geriatr Psychiatry ; 32(6): 724-735, 2024 Jun.
Article En | MEDLINE | ID: mdl-38216354

OBJECTIVE: To clarify the relationship between life satisfaction and the psychological characteristics of the oldest-old, and explore the factors for achieving mental health and longevity. DESIGN: This cross-sectional study conducted questionnaire surveys and face-to-face interviews as part of a larger prospective cohort study. SETTING: Arakawa Ward, a district in Tokyo, Japan. PARTICIPANTS: A total of 247 oldest-old individuals from two age groups, 85+ (aged 85-87 years) and 95+ (aged 95 years or older). MEASUREMENTS: Life satisfaction was assessed using the Satisfaction with Life Scale (SWLS), developmental stages of the elderly (Erikson's 8th and 9th stages, i.e., ego integrity, and gerotranscendence), and the Big Five personality traits (extraversion, agreeableness, openness, conscientiousness, and neuroticism) using the NEO-Five Factor Inventory. Multiple regression analyses were performed to examine the relationship between the SWLS scores and each assessment, controlling for age, sex, education, activities of daily living, depressive symptoms, and cognitive function. RESULTS: The SWLS scores of 85+ were positively correlated with scores of ego integrity, extraversion, and conscientiousness. Contrastingly, the SWLS scores of 95+ were positively correlated with gerotranscendence scores. CONCLUSIONS: Psychological characteristics associated with the level of life satisfaction among community-dwelling oldest-old individuals were identified, but a causal relationship between these factors and life satisfaction was not established. Ego integrity, extraversion, conscientiousness, and gerotranscendence may be associated with enhanced life satisfaction and mental health in the oldest-old. Further, the factors associated with life satisfaction in the 85+ and 95+ age groups varied, suggesting that life satisfaction among the oldest-old has different foundations in different age groups.


Personal Satisfaction , Personality , Humans , Aged, 80 and over , Female , Male , Cross-Sectional Studies , Personality/physiology , Aging/psychology , Surveys and Questionnaires , Independent Living , Prospective Studies
2.
Br J Psychiatry ; 223(3): 407-414, 2023 09.
Article En | MEDLINE | ID: mdl-37655816

BACKGROUND: The COVID-19 pandemic has transformed healthcare significantly and telepsychiatry is now the primary means of treatment in some countries. AIMS: To compare the efficacy of telepsychiatry and face-to-face treatment. METHOD: A comprehensive meta-analysis comparing telepsychiatry with face-to-face treatment for psychiatric disorders. The primary outcome was the mean change in the standard symptom scale scores used for each psychiatric disorder. Secondary outcomes included all meta-analysable outcomes, such as all-cause discontinuation and safety/tolerability. RESULTS: We identified 32 studies (n = 3592 participants) across 11 mental illnesses. Disease-specific analyses showed that telepsychiatry was superior to face-to-face treatment regarding symptom improvement for depressive disorders (k = 6 studies, n = 561; standardised mean difference s.m.d. = -0.325, 95% CI -0.640 to -0.011, P = 0.043), whereas face-to-face treatment was superior to telepsychiatry for eating disorder (k = 1, n = 128; s.m.d. = 0.368, 95% CI 0.018-0.717, P = 0.039). No significant difference was seen between telepsychiatry and face-to-face treatment when all the studies/diagnoses were combined (k = 26, n = 2290; P = 0.248). Telepsychiatry had significantly fewer all-cause discontinuations than face-to-face treatment for mild cognitive impairment (k = 1, n = 61; risk ratio RR = 0.552, 95% CI 0.312-0.975, P = 0.040), whereas the opposite was seen for substance misuse (k = 1, n = 85; RR = 37.41, 95% CI 2.356-594.1, P = 0.010). No significant difference regarding all-cause discontinuation was seen between telepsychiatry and face-to-face treatment when all the studies/diagnoses were combined (k = 27, n = 3341; P = 0.564). CONCLUSIONS: Telepsychiatry achieved a symptom improvement effect for various psychiatric disorders similar to that of face-to-face treatment. However, some superiorities/inferiorities were seen across a few specific psychiatric disorders, suggesting that its efficacy may vary according to disease type.


COVID-19 , Cognitive Dysfunction , Psychiatry , Telemedicine , Humans , Pandemics , Randomized Controlled Trials as Topic
3.
Psychiatry Clin Neurosci ; 77(5): 273-281, 2023 May.
Article En | MEDLINE | ID: mdl-36579663

AIM: The authors applied natural language processing and machine learning to explore the disease-related language patterns that warrant objective measures for assessing language ability in Japanese patients with Alzheimer disease (AD), while most previous studies have used large publicly available data sets in Euro-American languages. METHODS: The authors obtained 276 speech samples from 42 patients with AD and 52 healthy controls, aged 50 years or older. A natural language processing library for Python was used, spaCy, with an add-on library, GiNZA, which is a Japanese parser based on Universal Dependencies designed to facilitate multilingual parser development. The authors used eXtreme Gradient Boosting for our classification algorithm. Each unit of part-of-speech and dependency was tagged and counted to create features such as tag-frequency and tag-to-tag transition-frequency. Each feature's importance was computed during the 100-fold repeated random subsampling validation and averaged. RESULTS: The model resulted in an accuracy of 0.84 (SD = 0.06), and an area under the curve of 0.90 (SD = 0.03). Among the features that were important for such predictions, seven of the top 10 features were related to part-of-speech, while the remaining three were related to dependency. A box plot analysis demonstrated that the appearance rates of content words-related features were lower among the patients, whereas those with stagnation-related features were higher. CONCLUSION: The current study demonstrated a promising level of accuracy for predicting AD and found the language patterns corresponding to the type of lexical-semantic decline known as 'empty speech', which is regarded as a characteristic of AD.


Alzheimer Disease , Language Disorders , Humans , East Asian People , Language , Language Disorders/etiology , Machine Learning , Speech , Middle Aged
4.
Front Psychiatry ; 13: 954703, 2022.
Article En | MEDLINE | ID: mdl-36532181

Introduction: Psychiatric disorders are diagnosed through observations of psychiatrists according to diagnostic criteria such as the DSM-5. Such observations, however, are mainly based on each psychiatrist's level of experience and often lack objectivity, potentially leading to disagreements among psychiatrists. In contrast, specific linguistic features can be observed in some psychiatric disorders, such as a loosening of associations in schizophrenia. Some studies explored biomarkers, but biomarkers have yet to be used in clinical practice. Aim: The purposes of this study are to create a large dataset of Japanese speech data labeled with detailed information on psychiatric disorders and neurocognitive disorders to quantify the linguistic features of those disorders using natural language processing and, finally, to develop objective and easy-to-use biomarkers for diagnosing and assessing the severity of them. Methods: This study will have a multi-center prospective design. The DSM-5 or ICD-11 criteria for major depressive disorder, bipolar disorder, schizophrenia, and anxiety disorder and for major and minor neurocognitive disorders will be regarded as the inclusion criteria for the psychiatric disorder samples. For the healthy subjects, the absence of a history of psychiatric disorders will be confirmed using the Mini-International Neuropsychiatric Interview (M.I.N.I.). The absence of current cognitive decline will be confirmed using the Mini-Mental State Examination (MMSE). A psychiatrist or psychologist will conduct 30-to-60-min interviews with each participant; these interviews will include free conversation, picture-description task, and story-telling task, all of which will be recorded using a microphone headset. In addition, the severity of disorders will be assessed using clinical rating scales. Data will be collected from each participant at least twice during the study period and up to a maximum of five times at an interval of at least one month. Discussion: This study is unique in its large sample size and the novelty of its method, and has potential for applications in many fields. We have some challenges regarding inter-rater reliability and the linguistic peculiarities of Japanese. As of September 2022, we have collected a total of >1000 records from >400 participants. To the best of our knowledge, this data sample is one of the largest in this field. Clinical Trial Registration: Identifier: UMIN000032141.

5.
Biomolecules ; 12(9)2022 09 18.
Article En | MEDLINE | ID: mdl-36139160

Two-component signal transduction systems (TCSs) are widespread types of protein machinery, typically consisting of a histidine kinase membrane sensor and a cytoplasmic transcriptional regulator that can sense and respond to environmental signals. TCSs are responsible for modulating genes involved in a multitude of bacterial functions, including cell division, motility, differentiation, biofilm formation, antibiotic resistance, and virulence. Pathogenic bacteria exploit the capabilities of TCSs to reprogram gene expression according to the different niches they encounter during host infection. This review focuses on the role of TCSs in regulating the virulence phenotype of Shigella, an intracellular pathogen responsible for severe human enteric syndrome. The pathogenicity of Shigella is the result of the complex action of a wide number of virulence determinants located on the chromosome and on a large virulence plasmid. In particular, we will discuss how five TCSs, EnvZ/OmpR, CpxA/CpxR, ArcB/ArcA, PhoQ/PhoP, and EvgS/EvgA, contribute to linking environmental stimuli to the expression of genes related to virulence and fitness within the host. Considering the relevance of TCSs in the expression of virulence in pathogenic bacteria, the identification of drugs that inhibit TCS function may represent a promising approach to combat bacterial infections.


Gene Expression Regulation, Bacterial , Shigella , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Escherichia coli/metabolism , Histidine Kinase/genetics , Humans , Shigella/metabolism , Signal Transduction/physiology , Virulence/genetics
6.
Sci Rep ; 12(1): 12461, 2022 08 03.
Article En | MEDLINE | ID: mdl-35922457

In recent years, studies on the use of natural language processing (NLP) approaches to identify dementia have been reported. Most of these studies used picture description tasks or other similar tasks to encourage spontaneous speech, but the use of free conversation without requiring a task might be easier to perform in a clinical setting. Moreover, free conversation is unlikely to induce a learning effect. Therefore, the purpose of this study was to develop a machine learning model to discriminate subjects with and without dementia by extracting features from unstructured free conversation data using NLP. We recruited patients who visited a specialized outpatient clinic for dementia and healthy volunteers. Participants' conversation was transcribed and the text data was decomposed from natural sentences into morphemes by performing a morphological analysis using NLP, and then converted into real-valued vectors that were used as features for machine learning. A total of 432 datasets were used, and the resulting machine learning model classified the data for dementia and non-dementia subjects with an accuracy of 0.900, sensitivity of 0.881, and a specificity of 0.916. Using sentence vector information, it was possible to develop a machine-learning algorithm capable of discriminating dementia from non-dementia subjects with a high accuracy based on free conversation.


Machine Learning , Natural Language Processing , Algorithms , Humans , Language , Neurocognitive Disorders
7.
Biomolecules ; 11(10)2021 10 15.
Article En | MEDLINE | ID: mdl-34680156

Two-component signal transduction systems (TCSs) are widely conserved in bacteria to respond to and adapt to the changing environment. Since TCSs are also involved in controlling the expression of virulence, biofilm formation, quorum sensing, and antimicrobial resistance in pathogens, they serve as candidates for novel drug targets. TCSs consist of a sensor histidine kinase (HK) and its cognate response regulator (RR). Upon perception of a signal, HKs autophosphorylate their conserved histidine residues, followed by phosphotransfer to their partner RRs. The phosphorylated RRs mostly function as transcriptional regulators and control the expression of genes necessary for stress response. HKs sense their specific signals not only in their extracytoplasmic sensor domain but also in their cytoplasmic and transmembrane domains. The signals are sensed either directly or indirectly via cofactors and accessory proteins. Accumulating evidence shows that a single HK can sense and respond to multiple signals in different domains. The underlying molecular mechanisms of how HK activity is controlled by these signals have been extensively studied both biochemically and structurally. In this article, we introduce the wide diversity of signal perception in different domains of HKs, together with their recently clarified structures and molecular mechanisms.


Cytoplasm/genetics , Histidine Kinase/genetics , Histidine/chemistry , Virulence/genetics , Bacteria/genetics , Biofilms , Cytoplasm/chemistry , Histidine/genetics , Histidine Kinase/chemistry , Phosphorylation , Protein Domains/genetics , Protein Processing, Post-Translational/genetics , Quorum Sensing , Signal Transduction/genetics
8.
Front Mol Biosci ; 8: 723274, 2021.
Article En | MEDLINE | ID: mdl-34381818

Bacterial pathogens are able to survive within diverse habitats. The dynamic adaptation to the surroundings depends on their ability to sense environmental variations and to respond in an appropriate manner. This involves, among others, the activation of various cell-to-cell communication strategies. The capability of the bacterial cells to rapidly and co-ordinately set up an interplay with the host cells and/or with other bacteria facilitates their survival in the new niche. Efflux pumps are ubiquitous transmembrane transporters, able to extrude a large set of different molecules. They are strongly implicated in antibiotic resistance since they are able to efficiently expel most of the clinically relevant antibiotics from the bacterial cytoplasm. Besides antibiotic resistance, multidrug efflux pumps take part in several important processes of bacterial cell physiology, including cell to cell communication, and contribute to increase the virulence potential of several bacterial pathogens. Here, we focus on the structural and functional role of multidrug efflux pumps belonging to the Major Facilitator Superfamily (MFS), the largest family of transporters, highlighting their involvement in the colonization of host cells, in virulence and in biofilm formation. We will offer an overview on how MFS multidrug transporters contribute to bacterial survival, adaptation and pathogenicity through the export of diverse molecules. This will be done by presenting the functions of several relevant MFS multidrug efflux pumps in human life-threatening bacterial pathogens as Staphylococcus aureus, Listeria monocytogenes, Klebsiella pneumoniae, Shigella/E. coli, Acinetobacter baumannii.

9.
Front Psychol ; 12: 685430, 2021.
Article En | MEDLINE | ID: mdl-34194376

This study aimed to clarify how behavioral and psychological symptoms of dementia (BPSD) and cognitive function affect the decision-making capacity of persons with Alzheimer's disease (AD) in a real informed consent situation about anti-dementia drug prescriptions. The participants were 76 patients with AD. We used the MacArthur Competence Assessment Tool to assess the capacity for consent to treatment (MacCAT-T). We simultaneously used the Mini-Mental State Examination, Executive Interview, Executive Clock Drawing Task, Logical Memory I of the Wechsler Memory Scale-Revised (LM I), LM II, and Neuropsychiatric Inventory (NPI) to assess cognitive function and psychiatric symptoms. We calculated the correlations between the MacCAT-T scores and the demographic, neuropsychological, and psychiatric variables. Once the univariable correlations were determined, we performed simple linear regression analyses to examine if the regression equations were significant. In the final analyses, we incorporated significant variables into stepwise multiple linear regression analyses to determine the most significant predictors of mental capacity. Age (ß = -0.34), anxiety (ß = -0.27), and LM I (ß = 0.26) were significant predictors of "understanding" (adjusted R 2 = 0.29). LM II (ß = 0.39), anxiety (ß = -0.29), and education (ß = 0.21) were significant predictors of "understanding of alternative treatments" (adjusted R 2 = 0.30). Anxiety (ß = -0.36) and age (ß = -0.22) were significant predictors of "appreciation" (adjusted R 2 = 0.18). Age (ß = -0.31) and anxiety (ß = -0.28) were significant predictors of explained variance in "reasoning" (adjusted R 2 = 0.17). Patients with anxiety had lower scores on all five MacCAT-T subscales: "understanding," without 3.8 [SD = 1.2] vs. with 2.6 [SD = 1.1]; "understanding of alternative treatments," without 2.9 [SD = 2.2] vs. with 1.3 [SD = 1.8]; "appreciation," without 2.9 [SD = 1.1] vs. with 1.9 [SD = 1.2]; "reasoning," without 4.0 [SD = 2.0] vs. with 2.7 [SD = 1.7]; and "expressing a choice," without 1.9 [SD = 0.4] vs. with 1.5 [SD = 0.6]. Considering the effects of BPSD, cognitive function, and age/education when assessing consent capacity in persons with AD is important. Reducing anxiety may contribute to improved capacity in persons with AD.

10.
Front Microbiol ; 12: 652546, 2021.
Article En | MEDLINE | ID: mdl-34093469

The EvgS/EvgA two-component signal transduction system in Escherichia coli is activated under mildly acidic pH conditions. Upon activation, this system induces the expression of a number of genes that confer acid resistance. The EvgS histidine kinase sensor has a large periplasmic domain that is required for perceiving acidic signals. In addition, we have previously proposed that the cytoplasmic linker region of EvgS is also involved in the activation of this sensor. The cytoplasmic linker region resembles a Per-ARNT-Sim (PAS) domain, which is known to act as a molecular sensor that is responsive to chemical and physical stimuli and regulates the activity of diverse effector domains. Our EvgS/EvgA reporter assays revealed that under EvgS-activating mildly acidic pH conditions, EvgS was activated only during aerobic growth conditions, and not during anaerobic growth. Studies using EvgS mutants revealed that C671A and C683A mutations in the cytoplasmic PAS domain activated EvgS even under anaerobic conditions. Furthermore, among the electron carriers of the electron transport chain, ubiquinone was required for EvgS activation. The present study proposes a model of EvgS activation by oxidation and suggests that the cytoplasmic PAS domain serves as an intermediate redox switch for this sensor.

11.
Front Psychiatry ; 12: 685451, 2021.
Article En | MEDLINE | ID: mdl-34987422

Research on elderly financial exploitation has mostly focused on financial abuse that occurs in families and other types of trusted relationships. As such, little is known about financial frauds and scams perpetrated by strangers. Financial fraud and scam prevention activities for older adults must be promoted, for which the correlation between the psychological, social, and cognitive characteristics of their vulnerability needs to be determined. The present study aimed to determine whether cognitive decline is a risk factor for scam vulnerability in older adults. Thus, we created a scam vulnerability scale for older adults with cognitive decline and analyzed the data to reveal the correlation between them, including inhibition and executive function. We conducted an interview survey with 50 older adults with cognitive decline (average age: 79.42 years, SD: 5.44) and 51 older adults without cognitive decline (average age: 76.12 years, SD: 5.82). The interview survey included the scam vulnerability scale, psychosocial questionnaires, and neuropsychological tests. The scale included six items with a four-point Likert scale based on a previous study. Hierarchical multiple regression analysis revealed that lower scores on the Japanese version of the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Jcog; indicating higher general cognitive function) correlated with higher scam vulnerability in the cognitive decline group (ß = -0.46, p < 0.001). In addition, men were found to be more vulnerable in both groups (cognitive decline group: ß = -0.29, p = 0.015, cognitive non-decline group; ß = -0.32, p = 0.018). Inhibition and executive function were found not to correlate significantly with scam vulnerability. These results suggest that mild cognitive decline correlates with higher scam vulnerability, whereas moderate to severe cognitive decline correlates with lower vulnerability, possibly because it makes understanding the scam attempt itself difficult. Older adults with mild cognitive decline and their families, particularly those visiting elderly care or outpatient facilities, should be notified of the scam vulnerability of older clients using the ADAS-Jcog score as an index to help them avoid victimization.

12.
Contemp Clin Trials Commun ; 19: 100649, 2020 Sep.
Article En | MEDLINE | ID: mdl-32913919

INTRODUCTION: Depressive and neurocognitive disorders are debilitating conditions that account for the leading causes of years lived with disability worldwide. However, there are no biomarkers that are objective or easy-to-obtain in daily clinical practice, which leads to difficulties in assessing treatment response and developing new drugs. New technology allows quantification of features that clinicians perceive as reflective of disorder severity, such as facial expressions, phonic/speech information, body motion, daily activity, and sleep. METHODS: Major depressive disorder, bipolar disorder, and major and minor neurocognitive disorders as well as healthy controls are recruited for the study. A psychiatrist/psychologist conducts conversational 10-min interviews with participants ≤10 times within up to five years of follow-up. Interviews are recorded using RGB and infrared cameras, and an array microphone. As an option, participants are asked to wear wrist-band type devices during the observational period. Various software is used to process the raw video, voice, infrared, and wearable device data. A machine learning approach is used to predict the presence of symptoms, severity, and the improvement/deterioration of symptoms. DISCUSSION: The overall goal of this proposed study, the Project for Objective Measures Using Computational Psychiatry Technology (PROMPT), is to develop objective, noninvasive, and easy-to-use biomarkers for assessing the severity of depressive and neurocognitive disorders in the hopes of guiding decision-making in clinical settings as well as reducing the risk of clinical trial failure. Challenges may include the large variability of samples, which makes it difficult to extract the features that commonly reflect disorder severity. TRIAL REGISTRATION: UMIN000021396, University Hospital Medical Information Network (UMIN).

13.
Geriatr Gerontol Int ; 20(8): 773-778, 2020 Aug.
Article En | MEDLINE | ID: mdl-32573085

AIM: To investigate the influence of replacing sedentary time with physical activity on cognitive function using an isotemporal substitution model in a population of community-dwelling oldest old. METHODS: This cross-sectional study included residents of the Arakawa ward, Tokyo, who were part of a prospective cohort from the Arakawa 85+ study. We measured physical activity in 136 participants using a triaxial actigraph. Cognitive function was measured using the Addenbrooke's Cognitive Examination-III and participants were divided into a "cognitive decline group" (Addenbrooke's Cognitive Examination-III ≤88) and "cognitive maintain group" (Addenbrooke's Cognitive Examination-III ≥89). Physical activity was divided into three categories: sedentary behavior (≤1.5 metabolic equivalents), light physical activity (>1.5 to <3.0 metabolic equivalents), and moderate-to-vigorous physical activity (≥3 metabolic equivalents). Using an isotemporal substitution approach, we applied multiple logistic regression analysis to demonstrate the association between cognitive function and replacing 30 min/day of sedentary behavior with an equal period of light physical activity. Covariates included age, education and the Center for Epidemiologic Studies Depression Scale. RESULTS: Our findings showed that in men, replacing 30 min of sedentary behavior per day with light physical activity was associated with a 1.47-fold increase in the odds of maintaining cognitive function. An association between physical activity and cognitive function was not observed in female participants. CONCLUSIONS: Our results indicate that substituting sedentary behavior with light physical activity could be helpful in maintaining cognitive function in community-dwelling oldest old men. These results highlight the importance of behavioral changes to promote cognition. Geriatr Gerontol Int 2020; 20: 773-778.


Cognition/physiology , Cognitive Dysfunction/epidemiology , Exercise/physiology , Sedentary Behavior , Actigraphy , Aged, 80 and over , Cohort Studies , Cross-Sectional Studies , Female , Humans , Independent Living , Male , Prospective Studies , Tokyo/epidemiology
14.
PLoS One ; 15(5): e0233225, 2020.
Article En | MEDLINE | ID: mdl-32407392

OBJECTIVES: As the population of patients with cognitive decline grows, physicians and caregivers need brief screening tools. Comprehensive neurocognitive batteries require special training and time for evaluation. We focused on accessibility and compared the diagnostic power of several easy questions. DESIGN: "Attended With" (AW) and "Head-Turning Sign" (HTS) factors and participants' replies to following questions were recorded: "Do you feel that you have more difficulties in your daily life than you used to?", [no consciousness (C-) or consciousness+ (C+)], "Could you tell me about your daily pleasures or pastimes?" [no pleasure (P-) or pleasure + (P+)], "What are notable current/recent news/topics?" [no news (N-) or news+ (N+)]. SETTING: This took place in our Memory Clinic between May 2016 and July 2019. PARTICIPANTS: We enrolled 162 consecutive cases (44 cognitive normal (CN), 55 amnestic mild cognitive impairment (aMCI), and 48 Alzheimer's disease (AD)). MEASUREMENTS: The sensitivity and specificity of each battery were calculated, and on account of those numbers, the population attributable risk percent % (PAR%) of (AW and HTS+), (C- and P-), (C- and N-), (P- and N-) as analysis of combination of questions, respectively, were calculated. RESULTS: AW had high sensitivity, 87.4, 95.8% (CN vs aMCI + AD, CN + aMCI vs AD) but the sensitivity of HTS was only 46.4, 57.7%, and HTS showed high specificity, 100.0, 71.8%. C- had high sensitivity, 80.6, 87.5%, whereas P- and N- had high specificity, both 83.9% in CN vs aMCI + AD, 88.1% and 75.9% in CN + aMCI vs AD, respectively. In combination analysis, the PAR% of (C- and N-) were as high as (AW and HTS+). CONCLUSIONS: The combination of (C- and N-) is as powerful as (AW and HTS+) in screening AD. Our findings provide novel insights for screening utility of brief questions "Consciousness of Impairment" and "Recent News."


Cognitive Dysfunction/diagnosis , Activities of Daily Living , Aged , Aged, 80 and over , Alzheimer Disease/diagnosis , Communication , Female , Humans , Male , Mental Status and Dementia Tests , Middle Aged , Retrospective Studies , Sensitivity and Specificity , Speech
15.
Front Microbiol ; 11: 474, 2020.
Article En | MEDLINE | ID: mdl-32351457

Induction of the AR2 acid response system of Escherichia coli occurs at a moderately low pH (pH 5.5) and leads to high levels of resistance to pH levels below 2.5 in the presence of glutamate. Induction is mediated in part by the EvgAS two component system. Here, we show that the bacterial signaling molecule indole inhibits the induction of key promoters in the AR2 system and blocks the development of glutamate-dependent acid resistance. The addition of tryptophan, the precursor for indole biosynthesis, had the same effects, and this block was relieved in a tnaA mutant, which is unable to synthesize indole. Expression of a constitutively active EvgS protein was able to relieve the inhibition caused by indole, consistent with EvgS being inhibited directly or indirectly by indole. Indole had no effect on autophosphorylation of the isolated cytoplasmic domain of EvgS. This is consistent with a model where indole directly or indirectly affects the ability of EvgS to detect its inducing signal or to transduce this information across the cytoplasmic membrane. The inhibitory activity of indole on the AR2 system is not related to its ability to act as an ionophore, and, conversely, the ionophore CCCP had no effect on acid-induced AR2 promoter activity, showing that the proton motive force is unlikely to be a signal for induction of the AR2 system.

16.
Anal Biochem ; 600: 113765, 2020 07 01.
Article En | MEDLINE | ID: mdl-32360198

Two-component signal transduction systems (TCSs), consisting of a histidine kinase (HK) and its cognate response regulator, are ubiquitous among bacteria and are associated with the virulence of pathogens. TCSs are potential targets for alternative antibiotics and antivirulence agents. It is, thus, very important to determine HK activity in bacterial TCSs. Here, we describe an immuno-dot blot assay for the inhibition profiling of HKs using the anti-N3-phosphohistidine antibody. This simple method promises reliable detection of HK activity, and it is likely applicable in high-throughput screening of HK inhibitors.


Histidine Kinase/antagonists & inhibitors , Protein Kinase Inhibitors/pharmacology , Quinones/pharmacology , Dose-Response Relationship, Drug , High-Throughput Screening Assays , Histidine Kinase/metabolism , Signal Transduction/drug effects , Structure-Activity Relationship
17.
Psychogeriatrics ; 20(1): 50-58, 2020 Jan.
Article En | MEDLINE | ID: mdl-31083794

AIM: The aim of this study was to examine sociopsychological characteristics of the oldest old in Japan. We conducted a baseline survey of a community-based cohort of persons aged 95 or older. METHODS: Participants were aged 95+ years and resided in Arakawa Ward in Tokyo on 1 January 2016. We mailed a questionnaire to these individuals to assess their physical, mental, and social status. Subsequently, if respondents agreed, we conducted in-home interviews and examined their physical and cognitive function. Also, we mailed non-respondents a simplified version of full questionnaire. Additionally, we examined the basic registered data of the study population and the status of their Long-term Care Insurance. Data at baseline and 1-year follow-up were compared. RESULTS: With regard to Long-term Care Insurance, 423 residents aged 95+ years (78.0%) were on long-term care level, 35 (6.5%) were on support level, and 84 (15.5%) did not require support. At the 1-year follow-up, 275 (50.7%) had the same care level, 107 (19.7%) required a greater level of care, and 131 had died (annual death rate: 24.2%). Compared to the simplified questionnaire group (n = 128) and the full questionnaire-only group (n = 14), a higher proportion of respondents who had completed the full questionnaire and had in-home interviews (n = 26) were men, lived only with a spouse, had higher activities of daily living, and reported more positive feelings and well-being. CONCLUSIONS: In the late nonagenarian population, the annual death rate was high, and care needs increased rapidly. However, some persons maintained the same care level or even showed improvement and successful ageing.


Activities of Daily Living , Aged, 80 and over , Cognition , Insurance, Long-Term Care/statistics & numerical data , Cohort Studies , Female , Humans , Japan , Male , Prospective Studies , Social Environment , Surveys and Questionnaires
18.
J Telemed Telecare ; 26(7-8): 482-487, 2020.
Article En | MEDLINE | ID: mdl-31068063

INTRODUCTION: Studies have demonstrated the high agreement of several remote neuropsychological tests using video teleconferencing (VTC) with face-to-face (FTF) tests. However, the reliability of the remotely administered Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog), one of the most commonly used neuropsychological tests to detect cognitive decline, has not been substantially elucidated, particularly in Japanese populations. Therefore, this study aimed to evaluate the reliability of the remotely administered ADAS-cog compared with FTF-administered ADAS-cog among elderly Japanese participants. METHODS: Participants aged ≥60 years with and without cognitive impairment, i.e. those with mild cognitive impairment (MCI), those with dementia and healthy controls (HCs), were assessed with the ADAS-cog using VTC and FTF testing at an interval of >2 weeks and <3 months. The assessment order (VTC or FTF) was randomized by participants. Participants' scores were compared among the entire sample, as well as subgroups, using intra-class correlation coefficients (ICCs) in a mixed-effects model. RESULTS: A total of 73 participants were included in the study (36 men; age, 76.3 ± 7.6 years). The ICC for the ADAS-cog total score was high in the entire sample (0.86), whereas ICCs were moderate to high for the subgroups (MCI: 0.63, dementia: 0.80 and HC: 0.74). DISCUSSION: The results indicate that a VTC-administered ADAS-cog could be an alternative for an FTF-administered ADAS-cog, although further replication studies with larger sample sizes and a wider range of cognitive functionalities are warranted.


Alzheimer Disease/diagnosis , Geriatric Assessment/methods , Mental Status and Dementia Tests/standards , Telemedicine/methods , Aged , Aged, 80 and over , Cognition , Cognitive Dysfunction/diagnosis , Female , Humans , Japan , Male , Middle Aged , Psychometrics , Reproducibility of Results
19.
Telemed J E Health ; 26(7): 920-928, 2020 07.
Article En | MEDLINE | ID: mdl-31746697

Background: In an aging society, neuropsychological testing using video teleconferencing (VTC) is increasingly important. Despite the potential benefit of a VTC-administered Montreal Cognitive Assessment Tool (MoCA) to detect cognitive decline, only a limited number of studies have investigated this tool's reliability. Therefore, we aimed to evaluate the reliability of VTC-administered MoCA compared with face-to-face (FTF)-administered MoCA among elderly Japanese participants. Moreover, we examined participants' satisfaction with VTC-administered MoCA. Methods: Participants ≥60 years of age with and without cognitive impairment (i.e., those with mild cognitive impairment [MCI], those with dementia, and healthy controls [HC]) were assessed with VTC- and FTF-administered MoCA at an interval of >2 weeks and <3 months. The order effect (VTC first vs. FTF first) and time effect (first vs. second testing session), as well as several covariates such as age and years of education were controlled. Intraclass correlation coefficients (ICCs) were calculated using a mixed-effects model to assess the agreement between the two (VTC- vs. FTF-administered) groups. Participants' satisfaction with VTC-administered MoCA was examined using a Likert scale asking seven questions. Results: We included 73 participants in the study (36 men; age, 76.3 ± 7.5 years). The ICC for the MoCA total score was high in the entire sample (0.85), whereas ICCs were moderate to high for the subgroups (MCI: 0.82, dementia: 0.82, and HC: 0.53). Furthermore, we found good overall participant satisfaction with VTC-administered MoCA. Discussion: VTC-administered MoCA appears viable as an alternative to FTF-administered MoCA, although further replication studies with larger sample sizes are needed.


Cognitive Dysfunction , Aged , Aged, 80 and over , Cognitive Dysfunction/diagnosis , Humans , Infant, Newborn , Japan , Male , Mental Status and Dementia Tests , Neuropsychological Tests , Reproducibility of Results
20.
Electrophoresis ; 40(22): 3005-3013, 2019 11.
Article En | MEDLINE | ID: mdl-31495938

In the bacterial signaling mechanisms known as two-component systems (TCSs), signals are generally conveyed by means of a His-Asp phosphorelay. Each system consists of a histidine kinase (HK) and its cognate response regulator. Because of the labile nature of phosphorylated His and Asp residues, few approaches are available that permit a quantitative analysis of their phosphorylation status. Here, we show that the Phos-tag dye technology is suitable for the fluorescent detection of His- and Asp-phosphorylated proteins separated by SDS-PAGE. The dynamics of the His-Asp phosphorelay of recombinant EnvZ-OmpR, a TCS derived from Escherichia coli, were examined by SDS-PAGE followed by simple rapid staining with Phos-tag Magenta fluorescent dye. The technique permitted not only the quantitative monitoring of the autophosphorylation reactions of EnvZ and OmpR in the presence of adenosine triphosphate (ATP) or acetyl phosphate, respectively, but also that of the phosphotransfer reaction from EnvZ to OmpR, which occurs within 1 min in the presence of ATP. Furthermore, we demonstrate profiling of waldiomycin, an HK inhibitor, by using the Phos-tag Cyan gel staining. We believe that the Phos-tag dye technology provides a simple and convenient fluorometric approach for screening of HK inhibitors that have potential as new antimicrobial agents.


Aspartic Acid/analysis , Bacterial Outer Membrane Proteins/metabolism , Escherichia coli Proteins/metabolism , Fluorescent Dyes/analysis , Histidine/analysis , Multienzyme Complexes/metabolism , Signal Transduction/physiology , Aspartic Acid/metabolism , Bacterial Proteins/metabolism , Fluorescent Dyes/metabolism , Histidine/metabolism , Phosphoproteins/metabolism , Phosphorylation/physiology , Trans-Activators/metabolism
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