Positive Emotional Responses to Socially Assistive Robots in People With Dementia: Pilot Study.

Background: Interventions and care that can evoke positive emotions and reduce apathy or agitation are important for people with dementia. In recent years, socially assistive robots used for better dementia care have been found to be feasible. However, the immediate responses of people with dementia when they are given multiple sensory modalities from socially assistive robots have not yet been sufficiently elucidated. Objective: This study aimed to quantitatively examine the immediate emotional responses of people with dementia to stimuli presented by socially assistive robots using facial expression analysis in order to determine whether they elicited positive emotions. Methods: This pilot study adopted a single-arm interventional design. Socially assistive robots were presented to nursing home residents in a three-step procedure: (1) the robot was placed in front of participants (visual stimulus), (2) the robot was manipulated to produce sound (visual and auditory stimuli), and (3) participants held the robot in their hands (visual, auditory, and tactile stimuli). Expression intensity values for "happy," "sad," "angry," "surprised," "scared," and "disgusted" were calculated continuously using facial expression analysis with FaceReader. Additionally, self-reported feelings were assessed using a 5-point Likert scale. In addition to the comparison between the subjective and objective emotional assessments, expression intensity values were compared across the aforementioned 3 stimuli patterns within each session. Finally, the expression intensity value for "happy" was compared between the different types of robots. Results: A total of 29 participants (mean age 88.7, SD 6.2 years; n=27 female; Japanese version of Mini-Mental State Examination mean score 18.2, SD 5.1) were recruited. The expression intensity value for "happy" was the largest in both the subjective and objective assessments and increased significantly when all sensory modalities (visual, auditory, and tactile) were presented (median expression intensity 0.21, IQR 0.09-0.35) compared to the other 2 patterns (visual alone: median expression intensity 0.10, IQR 0.03-0.22; P<.001; visual and auditory: median expression intensity 0.10, IQR 0.04-0.23; P<.001). The comparison of different types of robots revealed a significant increase when all stimuli were presented by doll-type and animal-type robots, but not humanoid-type robots. Conclusions: By quantifying the emotional responses of people with dementia, this study highlighted that socially assistive robots may be more effective in eliciting positive emotions when multiple sensory stimuli, including tactile stimuli, are involved. More studies, including randomized controlled trials, are required to further explore the effectiveness of using socially assistive robots in dementia care.

Dyadic Art Appreciation and Self-Expression Program (NCGG-ART) for People with Dementia or Mild Cognitive Impairment and Their Family Caregivers: A Feasibility Study.

BACKGROUND: Non-pharmacological interventions effective for depressive mood and bilateral relationships among persons with cognitive impairment (PwCI) and their family caregivers (FCGs) have not been established. OBJECTIVE: To examine the feasibility of a newly developed group-based art appreciation and self-expression program (NCGG-ART) for dyads of PwCI and their FCGs. METHODS: This pilot randomized control trial included 34 dyads of PwCI diagnosed with mild to moderate Alzheimer's disease or mild cognitive impairment, and their FCGs, from an outpatient rehabilitation service (Holistic Physio-Cognitive Rehabilitation [HPCR]). Participants were randomly divided equally into the HPCR (control group) or NCGG-ART and HPCR (intervention group) groups. Both included 1-hour weekly, 6-week programs. The primary outcome was depressive symptoms among FCGs assessed using the Patient Health Questionnaire-9 (PHQ-9). Feasibility outcomes included participant satisfaction and motivation. FCGs were interviewed about their experiences and feelings regarding the program, which were analyzed using content analysis. RESULTS: Thirty-two dyads (intervention group:16; control group:16) completed the study period. High participation rates, satisfaction, and motivation were demonstrated throughout the intervention. Scores in the PHQ-9 among FCGs did not show positive effects: mean changes in the score were 1.3 for the intervention group and -0.8 for the control group (Cohen d:0.56). However, the qualitative analysis revealed favorable experiences and feelings of the FCGs, such as positive emotions, social interactions, and person-centered attitudes to and positive relationships with PwCI. CONCLUSIONS: This program demonstrated high feasibility with FCGs' favorable responses to emotions and relationships with PwCI, ensuring future investigations with a confirmatory study design.

Ultrasonography for Eating and Swallowing Assessment: A Narrative Review of Integrated Insights for Noninvasive Clinical Practice.

Dysphagia is a syndrome of abnormal eating function resulting from a variety of causative diseases, and is associated with malnutrition. To date, the swallowing function has been difficult to examine without the use of invasive and expensive methods, such as the videofluorographic swallowing study or fiberoptic endoscopic evaluation of swallowing. In recent years, progress has been made in the clinical application of ultrasound equipment for the evaluation of body compositions near the body surface, including the assessment of nutritional status. Ultrasound examination is a noninvasive procedure and relatively inexpensive, and the equipment required is highly portable thanks to innovations such as wireless probes and tablet monitoring devices. The process of using ultrasound to visualize the geniohyoid muscle, digastric muscle, mylohyoid muscle, hyoid bone, tongue, masseter muscle, genioglossus muscle, orbicularis oris muscle, temporalis muscle, pharynx, esophagus, and larynx, and the methods used for evaluating these structures, are provided in this study in detail. This study also aims to propose a protocol for the assessment of swallowing-related muscles that can be applied in real-world clinical practice for the diagnosis of sarcopenic dysphagia, which can occur in elderly patients with sarcopenia, and has received much attention in recent years.

The royal food of termites shows king and queen specificity.

Society in eusocial insects is based on the reproductive division of labor, with a small number of reproductive individuals supported by a large number of nonreproductive individuals. Because inclusive fitness of all colony members depends on the survival and fertility of reproductive members, sterile members provide royals with special treatment. Here, we show that termite kings and queens each receive special food of a different composition from workers. Sequential analysis of feeding processes demonstrated that workers exhibit discriminative trophallaxis, indicating their decision-making capacity in allocating food to the kings and queens. Liquid chromatography tandem-mass spectrometry analyses of the stomodeal food and midgut contents revealed king- and queen-specific compounds, including diacylglycerols and short-chain peptides. Desorption electrospray ionization mass spectrometry imaging analyses of 13C-labeled termites identified phosphatidylinositol and acetyl-l-carnitine in the royal food. Comparison of the digestive tract structure showed remarkable differences in the volume ratio of the midgut-to-hindgut among castes, indicating that digestive division of labor underlies reproductive division of labor. Our demonstration of king- and queen-specific foods in termites provides insight into the nutritional system that underpins the extraordinary reproduction and longevity of royals in eusocial insects.

Plastic brain structure changes associated with the division of labor and aging in termites.

Division of labor is a prominent feature of social insect societies, where different castes engage in different specialized tasks. As brain differences are associated with behavioral differences, brain anatomy may be linked to caste polymorphism. Here, we show that termite brain morphology changes markedly with caste differentiation and age in the termite, Reticulitermes speratus. Brain morphology was shown to be associated with reproductive division of labor, with reproductive individuals (alates and neotenic reproductives) having larger brains than nonreproductives (workers and soldiers). Micro-computed tomography (CT) imaging and dissection observations showed that the king's brain morphology changed markedly with shrinkage of the optic lobes during their long life in the dark. Behavioral experiments showed that mature primary kings lose visual function as a result of optic lobe shrinkage. These results suggested that termites restructure their nervous systems to perform necessary tasks as they undergo caste differentiation, and that they also show flexible changes in brain morphology even after the final molt. This study showed that brain morphology in social insects is linked to caste and aging, and that the evolution of the division of labor is underpinned by the development of diverse neural systems for specialized tasks.

The current state of family caregiver burden and support of toilet problems for elderly with mild cognitive impairment and Alzheimer's disease.

OBJECTIVE: To conduct an exploratory examination of caregiver burden involving toilet problems in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) and related characteristics. METHODS: We included 50 outpatients with amnestic MCI and AD and their caregivers. Patients were subclassified into three groups: MCI, mild AD, and moderate/severe AD. We used the Japanese version of the Zarit Burden Interview (J-ZBI) to evaluate caregiver burden and conducted a questionnaire on the frequency of lower urinary tract symptoms and related caregiver burden. We compared the frequency of questionnaire items with the level of burden in each group and subsequently determined the J-ZBI correlation coefficient. RESULTS: Among the questionnaire items, the caregiver's burden of "increased daytime urinary frequency," "nocturia," "urinary incontinence," and "they cannot clean the toilet" statistically significantly correlated with J-ZBI scores (ρ = 0.52, 0.65, 0.79, and 0.83, respectively). Items including "they cannot clean the toilet," "the smell of excrement is bothersome," "assistance for transfer is necessary," "they soil the clothes and bed," and "they cannot clean the genital region" were significantly more common in the patient group with moderate/severe AD. CONCLUSIONS: Lower urinary tract symptoms and toilet problems were significantly correlated with caregiver burden. Toilet problems differ depending on the severity of dementia. Therefore, a support system based on dementia severity is required to address toilet problems.

Functional impact of subunit composition and compensation on Drosophila melanogaster nicotinic receptors-targets of neonicotinoids.

Neonicotinoid insecticides target insect nicotinic acetylcholine receptors (nAChRs) and their adverse effects on non-target insects are of serious concern. We recently found that cofactor TMX3 enables robust functional expression of insect nAChRs in Xenopus laevis oocytes and showed that neonicotinoids (imidacloprid, thiacloprid, and clothianidin) exhibited agonist actions on some nAChRs of the fruit fly (Drosophila melanogaster), honeybee (Apis mellifera) and bumblebee (Bombus terrestris) with more potent actions on the pollinator nAChRs. However, other subunits from the nAChR family remain to be explored. We show that the Dα3 subunit co-exists with Dα1, Dα2, Dß1, and Dß2 subunits in the same neurons of adult D. melanogaster, thereby expanding the possible nAChR subtypes in these cells alone from 4 to 12. The presence of Dα1 and Dα2 subunits reduced the affinity of imidacloprid, thiacloprid, and clothianidin for nAChRs expressed in Xenopus laevis oocytes, whereas the Dα3 subunit enhanced it. RNAi targeting Dα1, Dα2 or Dα3 in adults reduced expression of targeted subunits but commonly enhanced Dß3 expression. Also, Dα1 RNAi enhanced Dα7 expression, Dα2 RNAi reduced Dα1, Dα6, and Dα7 expression and Dα3 RNAi reduced Dα1 expression while enhancing Dα2 expression, respectively. In most cases, RNAi treatment of either Dα1 or Dα2 reduced neonicotinoid toxicity in larvae, but Dα2 RNAi enhanced neonicotinoid sensitivity in adults reflecting the affinity-reducing effect of Dα2. Substituting each of Dα1, Dα2, and Dα3 subunits by Dα4 or Dß3 subunit mostly increased neonicotinoid affinity and reduced efficacy. These results are important because they indicate that neonicotinoid actions involve the integrated activity of multiple nAChR subunit combinations and counsel caution in interpreting neonicotinoid actions simply in terms of toxicity.

Olfactory identification ability in patients with mild cognitive impairment and Alzheimer's disease.

[Purpose] To examine the olfactory identification abilities and specify the difficult-to-identify odors in community-dwelling individuals with mild cognitive impairment (MCI) and Alzheimer's disease (AD). [Participants and Methods] We included, 12 and 17 patients with MCI (MCI group) and AD (AD group), respectively, and 30 community-dwelling older adults with no history of MCI or a dementia diagnosis (control group). Scores on the Japanese odor stick identification test (OSIT-J), an olfactory identification ability test, were compared among the three groups with intergroup differences examined accordingly. Next, we performed intergroup comparisons of the ratios of correct responses for each odor, and the difficult-to-identify odors were examined. [Results] OSIT-J scores of the MCI and AD groups were significantly lower than those of the control group. There were no intergroup differences in the correct identification of pungent odors. No patients in the AD group could identify the odor of cooking gas. The ability to identify food-related odors was reduced in the MCI and AD groups. [Conclusion] Patients with MCI and AD had reduced olfactory identification abilities in comparison to community-dwelling older adults without cognitive decline. These findings suggest the importance of olfactory evaluation before providing patients with dementia with therapeutic interventions associated with olfactory stimuli.

Differences in instrumental activities of daily living between mild cognitive impairment and Alzheimer's disease: A study using a detailed executive function assessment.

AIM: Executive dysfunction is pathognomonic for dementia and impedes the activities of daily living (ADL). This study aimed to examine the relationship of dementia severity with executive dysfunction and ADL in mild cognitive impairment and dementia. METHODS: This single-center study enrolled 86 patients (men, 40; women, 46; mean age, 76.1 ± 7.5 years) referred for cognitive and physical rehabilitation between October 2015 and September 2020. The Clinical Dementia Rating (CDR) was 0.5, 1, and ≥2 in 45, 30, and 11 patients, respectively. The presence and severity of executive dysfunction were assessed using the Behavioral Assessment of the Dysexecutive Syndrome-Japanese version (BADS). The ADL and instrumental ADL (IADL) were assessed using the Barthel Index and Frenchay Activities Index (FAI), respectively. We examined the relationship between CDR severity and overall BADS profile score and its sub-items, and that between the overall BADS profile score and IADL. RESULTS: The cognitive and executive functional assessment scores differed significantly depending on the CDR severity. The CDR severity and overall BADS profile score exhibited significant correlations. The BADS found cognitive impairment in 31%, 70%, and 100% of patients with CDR0.5, CDR1, and CDR≥2, respectively. The FAI score differed according to the CDR severity in women but not in men. The overall profile and age-adjusted BADS scores were strongly correlated with the IADL in women but not in men. CONCLUSIONS: The greater the severity of executive dysfunction, the greater the difficulty in performing ADL. This effect was more pronounced in women and may predict dementia progression. Geriatr Gerontol Int 2021; 21: 1111-1117.

Evaluation of magnetic resonance angiography as a possible alternative to rotational angiography or computed tomography angiography for assessing cerebrovascular computational fluid dynamics.

The aim of this study was to conduct a flow experiment using a cerebrovascular phantom and investigate whether magnetic resonance angiography (MRA) could replace three-dimensional rotational angiography (RA) and computed tomography angiography (CTA) to construct vascular models for computational fluid dynamics (CFD). We performed MRA and 3D cine phase-contrast (PC) MR imaging with a silicone cerebrovascular phantom of an internal carotid artery-posterior communicating artery aneurysm with blood-mimicking fluid, and controlled flow with a flowmeter. We also obtained RA and CTA data for the phantom. Four analysts constructed vascular models based on the three different modalities. These 12 constructed models used flow information based on 3D cine PC MR imaging for CFD. We compared RA-, CTA-, MRA-based CFD results using the micro-CT-based CFD result as the criterion standard to investigate whether MRA-based CFD was not inferior to RA- or CTA-based CFD. We also analyzed the inter-analyst variability. Wall shear stress (WSS) distributions and streamlines of RA- or MRA-based CFD and those of micro-CT-based CFD were similar, but the vascular models and WSS values were different. Accuracy in measurements of blood vessel diameter, cross-sectional maximum velocity, and spatially averaged WSS was the highest for RA-based CFD, followed by MRA-based and CTA-based CFD using micro-CT-based CFD result as the reference. Except maximum velocity from CTA, all other parameters had good inter-analyst agreement using different modalities. The results demonstrated that non-invasive MRA can be used for cerebrovascular CFD models with good inter-analyst agreements.

Cofactor-enabled functional expression of fruit fly, honeybee, and bumblebee nicotinic receptors reveals picomolar neonicotinoid actions.

The difficulty of achieving robust functional expression of insect nicotinic acetylcholine receptors (nAChRs) has hampered our understanding of these important molecular targets of globally deployed neonicotinoid insecticides at a time when concerns have grown regarding the toxicity of this chemotype to insect pollinators. We show that thioredoxin-related transmembrane protein 3 (TMX3) is essential to enable robust expression in Xenopus laevis oocytes of honeybee (Apis mellifera) and bumblebee (Bombus terrestris) as well as fruit fly (Drosophila melanogaster) nAChR heteromers targeted by neonicotinoids and not hitherto robustly expressed. This has enabled the characterization of picomolar target site actions of neonicotinoids, findings important in understanding their toxicity.

Poly(L-glutamic acid)-co-poly(ethylene glycol) block copolymers for protein conjugation.

Poly(L-glutamic acid)-co-poly(ethylene glycol) block copolymers (PLE-PEG) are here investigated as polymers for conjugation to therapeutic proteins such as granulocyte colony stimulating factor (G-CSF) and human growth hormone (hGH). PLE-PEG block copolymers are able to stabilize and protect proteins from degradation and to prolong their residence time in the blood stream, features that are made possible thanks to PEG's intrinsic properties and the simultaneous presence of the biodegradable anionic PLE moiety. When PLE-PEG copolymers are selectively tethered to the N-terminus of G-CSF and hGH, they yield homogeneous monoconjugates that preserve the protein's secondary structure. During the current study the pharmacokinetics of PLE10-PEG20k-G-CSF and PLE20-PEG20k-G-CSF derivatives and their ability to induce granulopoiesis were, respectively, assessed in Sprague-Dawley rats and in C57BL6 mice. Our results show that the bioavailability and bioactivity of the derivatives are comparable to or better than those of PEG20k-Nter-G-CSF (commercially known as Pegfilgrastim). The therapeutic effects of PLE10-PEG20k-hGH and PLE20-PEG20k-hGH derivatives tested in hypophysectomized rats demonstrate that the presence of a negatively charged PLE block enhances the biological properties of the conjugates additionally with respect to PEG20k-Nter-hGH.

The mechanism of loop C-neonicotinoid interactions at insect nicotinic acetylcholine receptor α1 subunit predicts resistance emergence in pests.

Neonicotinoids selectively modulate insect nicotinic acetylcholine receptors (insect nAChRs). Studies have shown that serine with ability to form a hydrogen bond in loop C of some insect nAChR α subunits and glutamate with a negative charge at the corresponding position in vertebrate nAChRs may contribute to enhancing and reducing the neonicotinoid actions, respectively. However, there is no clear evidence what loop C properties underpin the target site actions of neonicotinoids. Thus, we have investigated the effects of S221A and S221Q mutations in loop C of the Drosophila melanogaster Dα1 subunit on the agonist activity of imidacloprid and thiacloprid for Dα1/chicken ß2 nAChRs expressed in Xenopus laevis oocytes. The S221A mutation hardly affected either the affinity or efficacy for ACh and imidacloprid, whereas it only slightly reduced the efficacy for thiacloprid on the nAChRs with a higher composition ratio of ß2 to Dα1 subunits. The S221Q mutation markedly reduced the efficacy of the neonicotinoids for the nAChRs with a higher composition of the ß2 subunit lacking basic residues critical for binding neonicotinoids. Hence, we predict the possibility of enhanced neonicotinoid resistance in pest insect species by a mutation of the serine when it occurs in the R81T resistant populations lacking the basic residue in loop D of the ß1 subunit.

[Examination about the Direction for Uses of the Radiation Exposure Reduction Mechanism (Organ Effective Modulation) in Consideration of Organ Sensitivity].

Automatic exposure control technology can reduce the radiation dose during CT. The purpose of this study is to reveal the important points regarding the usage of organ effective modulation (OEM), by evaluating the characteristics of OEM, an automatic exposure control technology. An analysis of the dosage profiles revealed that OEM may not work with the first rotation of the X-ray tube in the helical method and wide volume method. This phenomenon can be avoided by using the orbital synchronism helical method. This was also demonstrated upon measurement of the integrated absorption dose at the imaging start position. An analysis of standard deviation measurement revealed that with the combined use of OEM and x-y modulation, the reduction in dose may significantly vary depending on the presence or absence of the gantry tilt. Based on the above results, when using OEM to reduce the dose at the imaging start position, the combined use of x-y modulation should be avoided and the orbital synchronism helical method should be used.

Factors associated with cognitive function that cause a decline in the level of activities of daily living in Alzheimer's disease.

AIM: The principal aim of the present study was to clarify what type of cognitive decline results in a decrease in the ability to carry out activities of daily living (ADL) in patients with Alzheimer's disease (AD). METHODS: The participants comprised 1384 outpatients with mild AD. We used the Mini-Mental State Examination (MMSE) and Barthel Index (BI) as indicators of basic ADL, and the Lawton Index (LI) as an indicator of instrumental ADL (IADL). We then analyzed the relationships between MMSE and BI, as well as between MMSE and LI. We also carried out a logistic regression analysis with BI and LI subitems as dependent variables, and MMSE subitems as independent variables. RESULTS: For almost all BI and LI subitems, significantly high odds ratios (OR) were noted in MMSE "Copy the design shown" (e.g. dressing OR 3.66, toilet use OR 3.60 and transfers OR 2.80) and "Write a sentence" (e.g. ability to use telephone OR 5.24, laundry OR 2.60, grooming OR 2.50; P < 0.05). CONCLUSIONS: Visuospatial cognition had an important effect on the decrease in basic ADL and IADL. Furthermore, the subitems with minimal effect on the decrease of basic ADL and IADL differed. Therefore, it appears that specific activities have little effect on the maintenance of ADL and IADL, and that determining residual cognitive function and utilizing this as a means of compensating for decreased ADL is a useful strategy. Geriatr Gerontol Int 2018; 18: 50-56.

Factors associated with increased caregivers' burden in several cognitive stages of Alzheimer's disease.

AIM: To investigate factors associated with caregiver burden (CB) in persons caring for older adults with various cognitive stages of Alzheimer's disease (AD). METHODS: Participants were 1127 outpatients and their caregivers. Participants comprised 120 older adults with normal cognition (NC), 126 with amnestic mild cognitive impairment (aMCI) and 881 with AD. AD patients were subclassified into four groups by Mini-Mental State Examination (MMSE) score: AD29-24 (n = 117), AD23-18 (n = 423), AD17-12 (n = 254) and AD11-0 (n = 87). Participants and their caregivers underwent comprehensive geriatric assessment batteries including Zarit Burden Interview (ZBI) Barthel Index, Lawton Index, Dementia Behavior Disturbance Scale (DBD) to evaluate CB, Instrumental and Basic Activity of Daily Living (IADL/BADL), and Behavioral and Psychological Symptoms of Dementia (BPSD). The comorbidity of geriatric syndrome and the living situation of the patient/caregiver were also assessed. RESULTS: ZBI score was higher in patients with lower MMSE score. Multivariate regression analysis identified that DBD was consistently associated with CB in all patients; symptoms related to memory deficit were related to CB in aMCI; differential IADL, such as inability to use a telephone, use transportation, manage finances, shop, cook and take responsibility for own medication, were related to CB in AD29-24, AD23-18 and AD17-12, and geriatric syndrome including falls and motor disturbance, sleep problems, urinary incontinence, and fatigue was related to CB in AD23-18 and AD17-12. CONCLUSIONS: Multiple factors including BPSD, impaired life function and geriatric syndrome were cognitive stage-dependently associated with CB. Preventive treatment of BPSD and comorbidity, and effective assistance for IADL deficits could contribute to alleviation of CB.