Age and parous-experience dependent changes in emotional contagion for positive infant sounds.

Introduction: Emotional contagion is achieved by inferring and emotionally resonating with other persons' feelings. It is unclear whether age-related changes in emotional contagion for infant sounds are modulated by the experience of childbirth or childcare. This study aims to evaluate changes in inference and emotional resonance for positive and negative infant sounds (laughter and crying) among women, based on age and parous experience. Methods: A total of 241 women (60 young nulliparous, 60 young parous, 60 old nulliparous, and 61 old parous) completed a web-based questionnaire. After listening to three types of infant sounds (laughter, cooing, and crying), participants responded with their valence for hearing infant sounds and estimated infant valence on an 11-point Likert scale. Results: The analysis for emotional resonance revealed that the correlation coefficient between self and estimated infant valences was greater in young parous and old nulliparous women than in young nulliparous women, in laughter and cooing sounds. However, correlation coefficients for crying did not differ among any of the four groups. Conclusion: The degree of emotional resonance for infant valence increased depending on age and parous-experience for positive infant sounds.

Robotic Care Equipment Improves Communication between Care Recipient and Caregiver in a Nursing Home as Revealed by Gaze Analysis: A Case Study.

The use of robotic nursing care equipment is an important option for solving the shortage of nursing care personnel, but the effects of its introduction have not been fully quantified. Hence, we aimed to verify that face-to-face care is still provided by caregivers in transfer situations when using robotic nursing care equipment. This study was conducted at a nursing home where the bed-release assist robot "Resyone Plus" is installed on a long-term basis. Caregiver gaze was analyzed quantitatively for one user of the equipment during transfer situations, and communication time, which involved looking at the face of the care recipient, as well as face-to-face vocalization, was measured. The caregiver spent 7.9 times longer looking at the face of and talking to the care recipient when using Resyone than when performing a manual transfer. In addition, the recipient was observed to smile during Resyone separation, which takes about 30 s. The results indicate a possible improvement in the QOL of care recipients through the use of robotic nursing care equipment as a personal care intervention. The ongoing development of robot technology is thus expected to continue to reduce the burden of caregiving as well as to improve the QOL of care recipients.

Reduction of multiple-caregiver assistance through the long-term use of a transfer support robot in a nursing facility.

The long-term use of transfer support robots in nursing facilities is an important option for improving the efficiency of care work. The "Resyone" transfer support robot is a combination of an electric care bed and a wheelchair, and the wheelchair half of the bed can be detached at the touch of a button. The purpose of this study was to investigate how the long-term use of Resyone would improve the performance of transfer assists, such as reducing the need for multiple caregivers. One Resyone was installed in a nursing facility in Japan and 17 caregivers used it for more than 11 months. The time and number of caregivers required for each transfer assist were surveyed for three 1-week periods: 1 week before (Phase 1) and at 3 weeks (Phase 2) and 11 months (Phase 3) after the introduction of Resyone. In Phase 1, approximately 60% of all transfer assists were performed by two caregivers, but in Phase 2, this was reduced to approximately 20%, and finally, in Phase 3, all transfer assists were performed by a single caregiver. These results suggested that the long-term use of Resyone was associated with improved work efficiency in transfer assistance in a nursing facility.

A rise-assisting robot extends life space and improves facial expressions of nursing home residents.

BACKGROUND: The introduction of nursing care-support devices using robotic technology is expected to reduce the task burden in long-term care facilities. OBJECTIVE: To investigate the use of the rise-assisting robot, Resyone, in extending and improving the life space of nursing home residents with severe care needs. METHODS: We performed a feasibility study in which Resyone was used to facilitate visits to additional sites in and around the nursing home as part of the care package of three residents. Two weeks before and four weeks after implementation of the new arrangements, the 30 caregivers involved were asked to record transfer times and destinations, while also checking the residents' facial expressions. RESULTS: Before implementation, participants had limited life spaces, but afterwards they regularly visited additional destinations including the garden, home entrance and corridors, which previously they had not visited frequently. The residents' facial expressions became more positive and less negative. This study demonstrates that Resyone can enrich care activities in severely disabled individuals. CONCLUSION: These findings suggest that the sustainable use of Resyone would improve the quality of care at care facilities. Moreover, the extension of otherwise limited life space has the potential to improve care receivers' quality of life. TRIAL REGISTRATION: UMIN Clinical Trials Registry No. UMIN000039204 (20/01/2020); retrospectively registered; interventional study; parallel, non-randomized, single blinded. URL of trial registry records: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000044709 .

Investigating proficiency using a lift-type transfer support device for effective care: comparison of skilled and unskilled nursing homes.

PURPOSE: The purpose of the study was to investigate whether the sustained use of the "Hug," a "hugging" type robotic transfer support device, could increase the level of quality of care. METHODS: The effect of proficiency on using the device was examined in terms of time spent for transfer, ratio of transfers using the device, and range of targets. The results were compared between skilled care facilities that had used the device for >24 months and unskilled facilities. RESULTS: The time spent for transfer at the unskilled facility was 4.6 min (2nd week after introduction), was reduced to 3.0 min (5th week), and 1.5 min at the skilled facility. The usage ratio at the unskilled facility was 13% and 30% (2nd and 5th week, respectively), while it was 97% in the skilled facility. Further, we identified wider in the range of target care recipients in the skilled facility. CONCLUSION: It takes time to master the use of Hug; however, its use was associated with many positive aspects, especially from the perspective of care recipients, e.g., better care, use of their own legs, and reduced time for transfers. These findings suggest that the widespread use of Hug would improve the quality of care.IMPLICATIONS FOR REHABILITATIONLess physically burdened on the caregivers using Hug, they can afford to talk to the care recipients.Using recipient's own legs during transfers, it prevents leg muscle disuse.As reduced time for transfers, recipients will have more opportunities to get out of bed.

Identification of care tasks for the use of wearable transfer support robots - an observational study at nursing facilities using robots on a daily basis.

BACKGROUND: To reduce the physical burden of caregivers, wearable transfer support robots are highly desirable. Although these robots are reportedly effective for specific tasks in experimental environments, there is little information about their effectiveness at nursing care facilities. The aim of this study was to identify care tasks and operations suitable for the use of these robots among caregivers in nursing facilities where these robots have been in use on a daily basis. METHODS: A 1-min observational time-motion analysis was conducted to examine care tasks and operations in two nursing facilities where wearable transfer support robots, namely Muscle Suit or HAL® Lumbar Type for Care Support, have been used routinely on a daily basis for more than 24 months. RESULTS: Analysis of the care tasks and their time ratio while wearing the equipment revealed that both robots were used conspicuously for direct care in over 70% of transits, especially during transfer assistance and toileting care. Furthermore, these robots were used intensively in the morning along with wake-up calls to care recipients, where pre-assigned wearers used them as part of their "routine work." CONCLUSIONS: We found that these wearable transfer support robots enabled effective performance of care tasks and operations in nursing facilities where these robots have been used on a daily basis for an extended period of time. These results may lead to the effective implementation and sustained operation of other types of care robots in the future. TRIAL REGISTRATION: UMIN Clinical Trials Registry no. UMIN000039204 . Trial registration date: January 21, 2020. Interventional study. Parallel, non-randomized, single blinded.

Partial Identification of Amyloid-ß Degrading Activity in Human Serum.

The major hallmarks of Alzheimer's disease (AD) are the extracellular accumulation of pathological amyloid beta (Aß) in the brain parenchyma and Aß deposition in cerebral blood walls (cerebral amyloid angiopathy; CAA). Although CAA occurs in more than 80% of AD patients, the mechanisms of Aß deposition and clearance around the vessel walls are unknown. We found Aß-degrading activity in human serum during analysis of the regulatory mechanism of Aß production in human endothelial cells. To elucidate the metabolic dynamics of Aß surrounding the brain microvessels, we identified Aß-degrading activity in human serum (blood Aß-degrading activity: BADA) by column chromatography and LC/MS. BADA exhibited characteristics of an acidic protein, pI 4.3, which had two different protein surface charges (low and high affinity cations). Both BADA fractions had a relative molecular mass of greater than 400 kDa. Furthermore, BADA in the low affinity cation fraction was inhibited by the serine protease inhibitor 4-(2-Aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF). We clarified alpha-2-macroglobulin (a2M) and several serine proteases from this BADA by LC-MS. Moreover, we demonstrated that BADA is increased by approximately 5000-fold in human serum by column chromatography. Therefore, BADA may play an important role in the circulation and metabolism of Aß in human brain microvessels.

Expression-level dependent perturbation of cell proteostasis and nuclear morphology by aggregation-prone polyglutamine proteins.

We describe a gene expression system for use in mammalian cells that yields reproducible, inducible gene expression that can be modulated within the physiological range. A synthetic promoter library was generated from which representatives were selected that gave weak, intermediate-strength or strong promoter activity. Each promoter resulted in a tight expression range when used to drive single-copy reporter genes integrated at the same genome location in stable cell lines, in contrast to the broad range of expression typical of transiently transfected cells. To test this new expression system in neurodegenerative disease models, we used each promoter type to generate cell lines carrying single-copy genes encoding polyglutamine-containing proteins. Expression over a period of up to three months resulted in a proportion of cells developing juxtanuclear aggresomes whose rate of formation, penetrance, and morphology were expression-level dependent. At the highest expression levels, fibrillar aggregates deposit close to the nuclear envelope, indicating that cell proteostasis is overwhelmed by misfolded protein species. We also observed expression-level dependent, abnormal nuclear morphology in cells containing aggresomes, with up to ∼80% of cells affected. This system constitutes a valuable tool in gene regulation at different levels and allows the quantitative assessment of gene expression effects when developing disease models or investigating cell function through the introduction of gene constructs.

Critique of the use of fluorescence-based reporters in Escherichia coli as a screening tool for the identification of peptide inhibitors of Aß42 aggregation.

High-throughput screens that dispense with the need for expensive synthetic Aß peptide would be invaluable for identifying novel anti-aggregants as potential treatments for Alzheimer's disease. A biosynthetic in vivo approach, using a recombinant fluorescent green fluorescent protein (GFP) reporter for the aggregation state of Aß in Escherichia coli, has been reported by other workers. Here, inducible Aß-GFP expression in E. coli was coupled to the concurrent constitutive production of a quasi-random peptide library to screen for anti-aggregant activity. To attempt to introduce greater robustness, mCherry was also co-expressed as an internal fluorescence standard to allow ratiometric comparison between samples. However, fluctuations in mCherry expression levels, as well as a low dynamic range of GFP output between positive and negative anti-aggregant peptides, highlighted limitations with the approach. Despite this, two novel peptides were identified that showed an equivalent in vitro anti-aggregant activity to that of epigallocatechin-3-gallate. Thus, although biosynthetic in vivo strategies show promise as screens for novel activities, unforeseen problems can arise because of the variability inherent in any biological system.

Recombinant production of cathelicidin-derived antimicrobial peptides in Escherichia coli using an inducible autocleaving enzyme tag.

Antimicrobial peptides (AMPs), such as the linear amphipathic cathelicidins, are produced widely in the natural world and are active against a broad range of pathogenic microorganisms. Their potential as a new range of antibiotics has prompted numerous studies of AMP structure and function. Most such studies are performed with chemically synthesised peptides, but a simple and rapid biosynthetic route would offer a more cost-effective alternative for the production of AMPs and analysis of their structure/function relationships. The cysteine protease domain (CPD) from Vibrio cholerae MARTX toxin possesses an autocleaving ability that is inducible by inositol hexakisphosphate (IP(6)). When coupled with a hexa-histidine tag and fused to the C-terminus of an AMP, this AMP-CPD fusion may be expressed in Escherichia coli and purified using immobilized metal affinity chromatography. A brief on-column induction of cleavage liberates the AMP, and subsequent polishing using hydrophobic interaction resin allows for purification of the peptide within a day. We used this system to express and purify several 18-residue cathelicidin variants and tested their activity on E. coli, Pseudomonas putida, Bacillus subtilis and Candida albicans. This approach to linear AMP production may aid rapid construction and purification of structural variants for subsequent functional analysis.

Suppression of embryonic lung branching morphogenesis by antisense oligonucleotides against HOM/C homeobox factors.

The role of HOM/C homeobox genes on rat embryonic lung branching morphogenesis was investigated using the lung bud explant culture system in an air/liquid interface. Knock down of homeobox b3 and b4 expression by antisense oligonucleotide treatment repressed airway branch formation, while antisense oligonucleotide against homeobox a3 showed no effect. Addition of antisense Hoxb3 oligonucleotide resulted in upregulation of collagen type III mRNA and fibroblast growth factor 10 mRNA, while that of the T-box regulatory factor-4 was decreased. Consequently, expression of Clara cell-specific secretory protein was decreased. These results suggest a critical role for homeobox b3 and b4 genes in lung airway branching morphogenesis.

Induction profile of HSP70-cognate genes by environmental pollutants in Chironomidae.

Several species of invertebrates have been studied to examine the toxicological effects of chemicals that include insecticides and heavy metals. We characterized heat-shock protein (hsp) genes from the ubiquitous midge, Chironomidae. More than 70 fold induction of hsp70 expression was detected by quantitative PCR after 37°C treatment in the midge. Expression of hsp70 was induced not only by heat but also by exposure to insecticides and heavy metals such as cadmium and copper. Expression time courses for hsp70 were highly specific to each chemical. When midges were exposed to sub-lethal level of a pyrethroid insecticide, ethofenprox, hsp70 expression was increased over 20 fold with a transient peak at 1.5h. Heavy metal exposure led to delayed hsp70 up regulation of 7 fold at 6-7h. Expression of another hsp70-cognate gene (hsc70) was also characterized. Using these genes we propose a novel system for biomonitoring of heavy metals and other pollutants.

Homeobox B3, FoxA1 and FoxA2 interactions in epithelial lung cell differentiation of the multipotent M3E3/C3 cell line.

HOM/C homeobox (Hox) and forkhead box (Fox) factors are reported to be expressed in the foregut endoderm and are subsequently detected in a spatio-temporal pattern during lung development. Some of these factors were reported to influence the expression of lung marker proteins or to modulate lung development. To clarify the molecular mechanisms for generating functional lung cells from progenitor cell populations, we introduced the forkhead box factors, FoxA1 and FoxA2, and the homeobox factor, HoxB3, into the differentiation process in a multipotent hamster lung epithelial M3E3/C3 cell line. Ectopic expression of FoxA2 promoted differentiation to Clara-like cells with up-regulation of the expression of the lung marker proteins, Clara cell-specific 10-kDa protein and surfactant protein-B. In contrast, FoxA1 repressed the differentiation. HoxB3 transfection induced FoxA2 expression transiently at the pre-differentiation stage. The endogenous HoxB3 expression level decreased at later stages of Clara-like cell differentiation, and the attenuation was enhanced by FoxA2 transfection. HoxB3 is a putative upstream regulator that enhances FoxA2 expression at the pre-differentiation stage. In addition, we found that the expression of HoxA4, HoxA5, and HoxC9 increased differentially during Clara-like cell differentiation. These results suggest that HoxB3 may be a putative positive regulator of FoxA2 expression at the pre-differentiation stage, and those interactions of Fox factors and Hox factors could participate in Clara cell differentiation.

Increased gene expression of lung marker proteins in the homeobox B3-overexpressed fetal lung cell line M3E3/C3.

Homeobox (Hox)-containing factors have been shown to play regulatory roles on lung development. Although HoxB3 gene expression is detected in the prenatal lung during development, its function has not been clarified precisely. We constructed an expression vector of a hamster HoxB3 coding region, which was cloned from hamster fetal lung cell line M3E3/C3. Sixteen-base deletion was found in the hamster HoxB3 coding sequence when compared with the mouse sequence. Under conditions of differentiation, cells transfected transiently with HoxB3 augmented the retinol-induced gene expression of Clara cell-specific secretory protein, whereas the cells showed reduced expression of surfactant-associated protein C. These alterations were attenuated by the transfection with HoxB3 antisense nucleotide. The results show that the cells with overexpressed HoxB3 were reinforced to have characteristics of Clara cells but did not have the characteristics of alveolar type II cells, and that HoxB3 played a stimulatory role on Clara cell differentiation in M3E3/C3 cells. In addition, the expression of Clara cell-specific secretory protein and surfactant-associated protein C genes was enhanced upon transfer of cells to collagen substrate, suggesting that collagen substrate has some regulatory functions on lung cell differentiation through cell adhesion.

Activation of a stress-induced gene by insecticides in the midge, Chironomus yoshimatsui.

Stress proteins (heat shock proteins, HSPs) have been proposed as general biomarkers for environmental monitoring. In the present study, we evaluated the environmental stress-burden on the aquatic midge Chironomus yoshimatsui using hsp70 expression. Larvae collected from streams receiving polluted runoff (field strain) were resistant to the organophosphorus insecticide, fenitrothion (F), and the synthetic pyrethroid, ethofenprox (E), whereas a strain originally collected from an unpolluted area (susceptible strain) showed low resistance to insecticide exposure. To examine the expression of an HSP70 gene in C. yoshimatsui, an hsp70 cDNA probe was prepared using RNA obtained from the field strain larvae and used for Northern blot analyses. The expression of this HSP70 gene in larvae collected from two field sites in May about 1 week after insecticide spraying in the fields was 2.3 (p = 0.018) to 3.3 fold higher than that in the susceptible strain and was also 4.6 and 1.4 (p = 0.033) fold higher than those collected in November 3 months after the cessation of insecticide spraying. In order to identify potential inducers of the HSP70 gene of the field strain, larvae of the susceptible strain were exposed to F or E for 24 h and hsp70 mRNA levels determined. Exposures to F at 0.4 microg/L and E at 1.1 microg/L increased hsp70 mRNA levels 2.7 (p = 0.049) and 4.4 (p = 0.043) fold over controls, respectively. These results suggest that larvae collected from polluted areas are burdened by environmental stressors and the tested insecticides are potential inducers of HSP70. The results also support the suggestion that HSP70 gene expression is a sensitive indicator of low level (nonlethal) exposures to certain insecticides.