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Vaccines against coronavirus disease 2019 (COVID-19) have been distributed in most countries for the prevention of onset and aggravation of COVID-19. Recently, there have been increasing numbers of reports on new-onset autoimmune and autoinflammatory diseases following COVID-19 vaccination, however, only little information is available on the long-term safety of these vaccines. Here, we experienced three cases of new-onset rheumatic diseases following COVID-19 vaccination, one case each of rheumatoid arthritis (RA), anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and systemic lupus erythematosus (SLE). The symptom onset ranged from one day to a few days following vaccination. The patients of AAV and SLE were treated successfully with glucocorticoid therapy, and the patient of RA died due to COVID-19. In the literature review of new-onset rheumatic diseases following COVID-19 vaccination, which including seven cases of RA, 37 cases of AAV and 18 cases of SLE, the mean time from vaccination to onset was approximately 11 to 12 days. Most cases improved with glucocorticoid, immunosuppressive drugs and biologic agents. Although such adverse effects are rare, and vaccines are useful in prevent onset and severity of infections, continued accumulation of similar cases is important in terms of examining the long-term safety and understanding pathogenic mechanism of rheumatic diseases.

Abstract LiCoO2 is a historic lithium-ion battery cathode that continues to be used today because of its high energy density. However, the practical capacity of LiCoO2 is limited owing to the harmful phase transition at high voltages, which prevents the realization of its theoretical capacity. Here, we treat LiCoO2 particles with a molten salt of MgF2–LiF as a reaction accelerator to facilitate the diffusion and doping of magnesium into bulk LiCoO2 and to form a stable coating layer on the particle surface. Ex situ X-ray diffraction analysis confirms the inhibition of the harmful phase transition and the emergence of a different phase as the modified LiCoO2 was charged up to 4.7 V. The modified LiCoO2 shows high electrochemical performance during high-voltage operation. This technology provides a guideline for the suppressing fundamental degradation associated with phase transition and achieving ultra-high energy density LiCoO2 cathodes.

Abstract Human instructors fluidly communicate with hand gestures, head and body movements, and facial expressions, but robots rarely leverage these complementary cues. A minimally supervised social robot with such skills could help people exercise and learn new activities. Thus, we investigated how nonverbal feedback from a humanoid robot affects human behavior. Inspired by the education literature, we evaluated formative feedback (real-time corrections) and summative feedback (post-task scores) for three distinct tasks: positioning in the room, mimicking the robot’s arm pose, and contacting the robot’s hands. Twenty-eight adults completed seventy-five 30-s-long trials with no explicit instructions or experimenter help. Motion-capture data analysis shows that both formative and summative feedback from the robot significantly aided user performance. Additionally, formative feedback improved task understanding. These results show the power of nonverbal cues based on human movement and the utility of viewing feedback through formative and summative lenses.

Abstract Background Interprofessional education (IPE) is essential for healthcare students to collaborate effectively in multidisciplinary teams. This study aimed to identify the effect of IPE programmes in nursing care and oral healthcare on dental and nursing students’ perceptions of interprofessional collaboration. Methods The study included 101 third-year dental and 98 fourth-year nursing students. The participants were divided into mixed-professional groups of four (2 dental and 2 nursing students). They participated in nursing care and oral healthcare training programmes that included student-on-student training and discussion groups. Questionnaires regarding perceptions of interprofessional collaboration were distributed to the participants before and after the programmes to compare the programmes before and after and between the dental and nursing students. The Wilcoxon signed-rank test and chi-square test were used to compare the data. Results Data from 79 dental students (42 males and 37 females) and 89 nursing students (4 males and 85 females) who completed both questionnaires were used for the comparisons. Perceptions of the differences between the approaches of different health professionals to nursing care, the roles of other professionals, and the need for multiprofessional collaboration improved significantly among both dental and nursing students after the programmes. Although the perception of their ability to communicate with unfamiliar or new people improved significantly only among the nursing students, other perceptions of their ability to communicate did not improve for either group. More dental students than nursing students chose nursing trainings as good programmes to participate in with other professional students, while more nursing students than dental students chose oral care trainings as good programmes. Many students commented that they learned about nursing and oral healthcare skills as well as the importance of teamwork and communication with other professionals. Seven students commented that they were more motivated to become dentists and nurses. Conclusions This study showed that IPE programmes for nursing care and oral healthcare might be effective at helping students understand other professionals and promoting multiprofessional collaboration. However, further studies are needed to develop IPE programmes to improve attitudes and abilities related to interprofessional communication skills.

Background: Maintaining good asthma control minimizes the risk of exacerbations and lung function decline and is a primary goal of asthma management. The Japanese Pediatric Asthma Guidelines (JPGL) employs different classification criteria for control status from other guidelines, stressing a higher level of control. Based on JPGL, we previously developed a caregiver-completed questionnaire for assessing and achieving best asthma control in preschoolers. In this study, we aimed to develop a questionnaire for school-age children and adolescents. Methods: A working questionnaire comprising 14 items for patients and 34 items for caregivers was administered to 362 asthma patients aged 6–15 years and their caregivers. Separately, physicians filled out a questionnaire to determine JPGL-defined control. Logistic regression analysis was performed to construct a model to predict control levels using data from a randomly selected set of completed questionnaires from two-thirds of the subjects. Validation was performed using the remaining questionnaires. Results: A set of 7 questions, encompassing self-assessed control status at the time of the visit and in the past month, and nocturnal/early morning asthma symptoms for patients and frequency of asthma symptoms, dyspnea, rescue beta-agonist use, and asthma hospitalization for caregivers, were selected and the 7-item model showed a good statistical fit with AIC of 110.5. The model has been named the Best Asthma Control Test for School Children and Adolescents (Best ACT-S). Best ACT-S scores differed significantly in the hypothetical direction among the groups of different JPGL-defined control levels, step-up/down treatment decisions, and presence/non-presence of exacerbations in the previous year. Conclusions: The Best ACT-S is a valid questionnaire for children/adolescents aiming for best asthma control.

BackgroundLarge language models have propelled recent advances in artificial intelligence technology, facilitating the extraction of medical information from unstructured data such as medical records. Although named entity recognition (NER) is used to extract data from physicians’ records, it has yet to be widely applied to pharmaceutical care records. ObjectiveIn this study, we aimed to investigate the feasibility of automatic extraction of the information regarding patients’ diseases and symptoms from pharmaceutical care records. The verification was performed using Medical Named Entity Recognition-Japanese (MedNER-J), a Japanese disease-extraction system designed for physicians’ records. MethodsMedNER-J was applied to subjective, objective, assessment, and plan data from the care records of 49 patients who received cefazolin sodium injection at Keio University Hospital between April 2018 and March 2019. The performance of MedNER-J was evaluated in terms of precision, recall, and F1-score. ResultsThe F1-scores of NER for subjective, objective, assessment, and plan data were 0.46, 0.70, 0.76, and 0.35, respectively. In NER and positive-negative classification, the F1-scores were 0.28, 0.39, 0.64, and 0.077, respectively. The F1-scores of NER for objective (0.70) and assessment data (0.76) were higher than those for subjective and plan data, which supported the superiority of NER performance for objective and assessment data. This might be because objective and assessment data contained many technical terms, similar to the training data for MedNER-J. Meanwhile, the F1-score of NER and positive-negative classification was high for assessment data alone (F1-score=0.64), which was attributed to the similarity of its description format and contents to those of the training data. ConclusionsMedNER-J successfully read pharmaceutical care records and showed the best performance for assessment data. However, challenges remain in analyzing records other than assessment data. Therefore, it will be necessary to reinforce the training data for subjective data in order to apply the system to pharmaceutical care records.

Abstract Background Although more than half of the habitual smokers recognize that they want to quit smoking cigarettes, approximately half have failed to quit and experienced distress relapse; therefore, there is an urgent need to focus on these populations. When chronic behavior occurs, it is necessary to view the behavior in the context of the entire life of the person involved, considering the history of the person. In this study, we aimed to describe experiences with smoking from the onset to the present and the need for smoking cessation among habitual smokers in Japan and to explore efforts to address them. Methods Semi-structured interviews that lasted for 55–90 min were conducted with the cooperation of 16 habitual smokers who smoked cigarettes daily. The content of the interviews included demographic characteristics, experiences with smoking from the onset to the present, whether they have attempted to quit and related experiences, and their thoughts on smoking. Interviews were transcribed verbatim and analyzed qualitatively. The Medical Research Ethics Review Committee of Jikei University approved this study (approval number: 33–384(11008)). Results The participants were aged 26–59 years (mean ± SD: 40.8 ± 8.9 years) and included 10 men and 6 women. The participants started smoking between age 13 and 24 years. The highest number of cigarettes smoked in the participants’ lives ranged from 10 to 80 daily, and 12 participants had attempted to quit smoking so far without success. Regarding experiences with smoking from the onset to the present, four themes of “expand one’s world,” “unconscious attachment,” “attempts and failures,” and “losing oneself” were extracted. Regarding the need for smoking cessation, four themes of “empowerment from experts,” “peer interaction,” “social commitment,” and “recovery of confidence” were extracted. Conclusion To support smoking cessation from the perspective of habitual smokers, in addition to improvements through the existing approaches, it is important to recover their confidence using ongoing activities in peer groups according to the target background and support from experts incorporating visual assessments of lung function, along with multiple short-term goals. It is also necessary to raise awareness in communities through activities.

Background/Aims Understanding of non-alcoholic fatty liver disease (NAFLD) continues to expand, but the relationship between race and ethnicity and NAFLD outside the use of cross-sectional data is lacking. Using longitudinal data, we investigated the role of race and ethnicity in adverse outcomes in NAFLD patients. Methods Patients with NAFLD confirmed by imaging via manual chart review from any clinics at Stanford University Medical Center (1995–2021) were included. Primary study outcomes were incidence of liver events and mortality (overall and non-liver related). Results The study included 9,340 NAFLD patients: White (44.1%), Black (2.29%), Hispanic (27.9%), and Asian (25.7%) patients. For liver events, the cumulative 5-year incidence was highest among White (19.1%) patients, lowest among Black (7.9%) patients, and similar among Asian and Hispanic patients (~15%). The 5-year and 10-year cumulative overall mortality was highest for Black patients (9.2% and 15.0%, respectively, vs. 2.5–3.5% and 4.3–7.3% in other groups) as well as for non-liver mortality. On multivariable regression analysis, compared to White patients, only Asian group was associated with lower liver-related outcomes (aHR: 0.83, P=0.027), while Black patients were at more than two times higher risk of both non-liver related (aHR: 2.35, P=0.010) and overall mortality (aHR: 2.13, P=0.022) as well as Hispanic patients (overall mortality: aHR: 1.44, P=0.022). Conclusions Compared to White patients, Black patients with NAFLD were at the highest risk for overall and non-liver-related mortality, followed by Hispanic patients with Asian patients at the lowest risk for all adverse outcomes. Culturally sensitive and appropriate programs may be needed for more successful interventions.

Abstract Background Globally, the prevalence of childhood obesity has increased considerably, including in Indonesia. Obesity results from multifactorial interactions at the personal, familial, and environmental levels. However, little is known about the factors associated with overweight/obesity among children in Indonesia. This study is intended to identify personal, familial, and environmental factors associated with overweight/obesity in children aged 6–12 years in Indonesia. Methods Study design was a secondary data analysis using the Indonesia Family Life Survey in 2014/2015, focusing on 6,090 children aged 6–12 years. The questions covered the child’s body mass index and potential personal, familial, and environmental factors. Logistic regression analysis was performed to identify the personal, familial, and environmental factors. Results The mean age of participants was 8.9 years (SD = 2.0); 51.0% were boys; 9.4% were overweight; and 8.1% were obese. Overweight and obesity were associated with age [AOR 1.09 (95% CI 1.04–1.14)], having an overweight [AOR 1.93 (95% CI 1.58–2.36)] or obese [AOR 3.36 (95% CI 2.43–4.61)] father compared with a normal father, being of Chinese [AOR 9.51 (95% CI 1.43–79.43)] or Javanese [AOR 1.60 (95% CI 1.16–2.24)] ethnicity compared with Sundanese ethnicity, and residing in an urban area [AOR 1.36 (95% CI 1.10–1.70)]. A lower risk of child overweight/obesity was associated with the father’s perception [AOR 0.56 (95% CI 0.38–0.80)] and mother’s perception [AOR 0.66 (95% CI 0.43–0.98)] of the child’s food consumption as being less than adequate compared with adequate. Conclusions Risk factors in children for overweight/obesity were older age, having an overweight/obese father, membership of certain ethnic groups, and urban residence. The main protective factor was parents’ perception that a child’s food consumption was less than adequate. Health promotion programs focused on these factors could help control or prevent childhood obesity in Indonesia.

The biaxial flexural strength of universal shade and conventional dental resin-based composites before and after alkaline degradation was investigated. Disk samples were prepared from these resin-based composites, and some of the specimens were immersed in 0.1 M NaOH solution to create deteriorated samples. The biaxial flexural strength of the samples before and after the alkaline degradation test was measured and statistically tested. The fracture surfaces after the biaxial flexural test were observed using a scanning electron microscope. The results showed that the biaxial flexural strength of the paste-type universal shade resin-based composite before alkaline degradation was significantly (19%) higher than that of the conventional type, but no difference was observed between the materials after alkaline degradation. On the other hand, the biaxial flexural strength of the flowable universal shade resin-based composites was significantly (around 35%) lower than that of the conventional composite, with or without degradation. Although, for paste-type materials, the biaxial flexural strength of universal shade resin-based composites was higher than that of conventional resin-based composites before alkaline degradation, after degradation the two materials showed similar values. For flowable materials, the biaxial flexural strength of universal shade resin-based composites was lower than that of conventional resin-based composites regardless of the presence or absence of degradation processes. These results suggest that some caution should be used when deciding whether to use flowable universal shade resin-based composite to fill a cavity.

Abstract We aimed to compare longitudinal brain atrophy in patients with neuromyelitis optica spectrum disorder (NMOSD) with healthy controls (HCs). The atrophy rate in patients with anti-aquaporin-4 antibody-positive NMOSD (AQP4 + NMOSD) was compared with age-sex-matched HCs recruited from the Japanese Alzheimer’s Disease Neuroimaging Initiative study and another study performed at Chiba University. Twenty-nine patients with AQP4 + NMOSD and 29 HCs were enrolled in the study. The time between magnetic resonance imaging (MRI) scans was longer in the AQP4 + NMOSD group compared with the HCs (median; 3.2 vs. 2.9 years, P = 0.009). The annualized normalized white matter volume (NWV) atrophy rate was higher in the AQP4 + NMOSD group compared with the HCs (median; 0.37 vs. − 0.14, P = 0.018). The maximum spinal cord lesion length negatively correlated with NWV at baseline MRI in patients with AQP4 + NMOSD (Spearman’s rho = − 0.41, P = 0.027). The annualized NWV atrophy rate negatively correlated with the time between initiation of persistent prednisolone usage and baseline MRI in patients with AQP4 + NMOSD (Spearman’s rho = − 0.43, P = 0.019). Patients with AQP4 + NMOSD had a greater annualized NWV atrophy rate than HCs. Suppressing disease activity may prevent brain atrophy in patients with AQP4 + NMOSD.

Abstract Background Asynchronous e-learning has become the mainstream choice since the transformation of learning formats by the coronavirus disease-19 pandemic. This scoping review aimed to examine the technologies used in asynchronous e-learning for the continuing education of clinical nurses and their modes of delivery and effectiveness. Methods This scoping review covered the period between 2011 and 2023. Six databases were searched for relevant studies following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews (PRISMA-ScR) protocol. Results Sixty articles met the inclusion criteria. There was a noticeable trend toward using diverse technology-enabled and enhanced training (TEET) options after 2017. The enabling technological approaches, such as interactive online modules (25 articles) and video modules (25 articles), are described in the articles. The most commonly used enhancing technologies were scenario-based learning (nine articles), resource access (eight articles), computer simulation or virtual reality (three articles), and gamification (three articles). Among the outcomes, knowledge acquisition was the most commonly examined outcome (41 articles). Conclusions Notably, many interactive TEET modules were used in asynchronous e-learning. There were few studies on gamification, computer simulation or virtual reality, and scenario-based learning (techniques to enhance intrinsic motivation further). However, the adoption of asynchronous e-learning with advanced TEET options is anticipated to increase in the future. Therefore, objective outcome measures are required to determine the effects of such learning methods on knowledge acquisition and behavioral changes.

Abstract Arabitol is gaining attention in the food industry as an alternative sweetener owing to its low-caloric and non-cariogenic characteristics. The yeast strain kiy1 was newly isolated from unpasteurized honey for arabitol production. Based on internal transcribed spacer sequence analysis, the isolated strain was identified as Zygosaccharomyces siamensis. In this study, the effects of different substrates and sugar concentrations on arabitol production were investigated. When three types of carbon sources (glycerol, fructose, and glucose) were used, glucose was the most suitable substrate for arabitol production (68.7 g/L). Maximum arabitol production (101.4 g/L) was observed at a glucose concentration of 30%, and the highest arabitol production yield was 0.34 g/g of initial glucose. In the time-course production of sugar alcohols by strain kiy1, glucose was completely consumed for 8 days. The concentration of arabitol exceeded that of glycerol after 3 days, and the final arabitol concentration reached 83.6 g/L after 10 days. The maximum production rate was 16.7 g/L/day. The yeast produced glycerol as an intracellular sugar alcohol in the early stage of culture and switched its metabolism to arabitol production after the middle stage. Z. siamensis kiy1 possessed an NADP+-dependent arabitol dehydrogenase, which indicated that it probably produces arabitol via ribulose from glucose. These results suggest that the novel yeast strain, Z. siamensis kiy1, is promising for arabitol production. The proposed arabitol production approach can contribute toward its production at the industrial scale. Graphical Abstract

Introduction: The modern worldwide trend toward sedentary behavior comes with significant health risks. An accompanying wave of health technologies has tried to encourage physical activity, but these approaches often yield limited use and retention. Due to their unique ability to serve as both a health-promoting technology and a social peer, we propose robots as a game-changing solution for encouraging physical activity.Methods: This article analyzes the eight exergames we previously created for the Rethink Baxter Research Robot in terms of four key components that are grounded in the video-game literature: repetition, pattern matching, music, and social design. We use these four game facets to assess gameplay data from 40 adult users who each experienced the games in balanced random order.Results: In agreement with prior research, our results show that relevant musical cultural references, recognizable social analogues, and gameplay clarity are good strategies for taking an otherwise highly repetitive physical activity and making it engaging and popular among users.Discussion: Others who study socially assistive robots and rehabilitation robotics can benefit from this work by considering the presented design attributes to generate future hypotheses and by using our eight open-source games to pursue follow-up work on social-physical exercise with robots.

Rehabilitation robots have shown promise in improving the gait of children with childhood-onset motor disabilities. This study aimed to investigate the long-term benefits of training using a wearable Hybrid Assistive Limb (HAL) in these patients. Training using a HAL was performed for 20 min a day, two to four times a week, over four weeks (12 sessions in total). The Gross Motor Function Measure (GMFM) was the primary outcome measure, and the secondary outcome measures were gait speed, step length, cadence, 6-min walking distance (6MD), Pediatric Evaluation of Disability Inventory, and Canadian Occupational Performance Measure (COPM). Patients underwent assessments before the intervention, immediately after the intervention, and at 1-, 2-, 3-month and 1-year follow-ups. Nine participants (five males, four females; mean age: 18.9 years) with cerebral palsy (n = 7), critical illness polyneuropathy (n = 1), and encephalitis (n = 1) were enrolled. After training using HAL, GMFM, gait speed, cadence, 6MD, and COPM significantly improved (all p < 0.05). Improvements in GMFM were maintained one year after the intervention (p < 0.001) and in self-selected gait speed and 6MD three months after the intervention (p < 0.05). Training using HAL may be safe and feasible for childhood-onset motor disabilities and may maintain long-term improvements in motor function and walking ability.

Abstract Lymphatic drainage in the central nervous system is regulated by meningeal lymphatic vasculature, and recurrent neuroinflammation alters lymphatic vessel remodeling. Patients with aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4 + NMOSD) were reported to demonstrate worse outcomes compared with patients with anti-myelin oligodendrocyte glycoprotein-associated disorders (MOGAD). This study aimed to investigate the serum cytokines relevant to vascular remodeling after attacks and their prognostic role in patients with AQP4 + NMOSD. This study measured the serum levels of 12 cytokines relevant to vascular remodeling, including bone morphogenetic protein-9 (BMP-9) and leptin, in 20 patients with AQP4 + NMOSD and 17 healthy controls (HCs). Disease controls included 18 patients with MOGAD. Serum and cerebrospinal fluid interleukin-6 levels were also measured. Clinical severity was evaluated with Kurtzke’s Expanded Disability Status Scale (EDSS). Compared with HCs, patients with AQP4 + NMOSD showed higher BMP-9 (median; 127 vs. 80.7 pg/mL; P = 0.0499) and leptin levels (median; 16,081 vs. 6770 pg/mL; P = 0.0224), but not those with MOGAD. Better improvement in EDSS at 6 months was associated with baseline BMP-9 levels in patients with AQP4 + NMOSD (Spearman’s rho = − 0.47; P = 0.037). Serum BMP-9 is upregulated at relapse and may contribute to vascular remodeling in AQP4 + NMOSD. Serum BMP-9 levels could predict clinical recovery 6 months after the attack.

IntroductionThe wearable cyborg Hybrid Assistive Limb (HAL) is the world’s first cyborg-type wearable robotic device, and it assists the user’s voluntary movements and facilitates muscle activities. However, since the minimum height required for using the HAL is 150 cm, a smaller HAL (2S size) has been newly developed for pediatric use. This study aimed to (1) examine the feasibility and safety of a protocol for treatments with HAL (2S size) in pediatric patients and (2) explore the optimal method for assessing the efficacy of HAL.MethodsThis clinical study included seven pediatric patients with postural and motor function disorders, who received 8–12 sessions of smaller HAL (2S size) treatment. The primary outcome was the Gross Motor Function Measure-88 (GMFM-88). The secondary outcomes were GMFM-66, 10-m walk test, 2- and 6-min walking distances, Canadian Occupational Performance Measure (COPM), a post-treatment questionnaire, adverse events, and device failures. Statistical analyses were performed using the paired samples t-test or Wilcoxon signed-rank test.ResultsAll participants completed the study protocol with no serious adverse events. GMFM-88 improved from 65.51 ± 21.97 to 66.72 ± 22.28 (p = 0.07). The improvements in the secondary outcomes were as follows: GMFM-66, 53.63 ± 11.94 to 54.96 ± 12.31, p = 0.04; step length, 0.32 ± 0.16 to 0.34 ± 0.16, p = 0.25; 2-MWD, 59.1 ± 57.0 to 62.8 ± 63.3, p = 0.54; COPM performance score, 3.7 ± 2.0 to 5.3 ± 1.9, p = 0.06; COPM satisfaction score, 3.3 ± 2.1 to 5.1 ± 2.1, p = 0.04.DiscussionIn this exploratory study, we applied a new size of wearable cyborg HAL (2S size), to children with central nervous system disorders. We evaluated its safety, feasibility, and identified an optimal assessment method for multiple treatments. All participants completed the protocol with no serious adverse events. This study suggested that the GMFM would be an optimal assessment tool for validation trials of HAL (2S size) treatment in pediatric patients with posture and motor function disorders.

The lack of truly robust analgesics for chronic pain is owed, in part, to the lack of an animal model that reflects the clinical pain state and of a mechanism-based, objective neurological indicator of pain. The present study examined stimulus-evoked brain activation with functional magnetic resonance imaging in male and female cynomolgus macaques following unilateral L7 spinal nerve ligation and the effects of clinical analgesics pregabalin, duloxetine, and morphine on brain activation in these macaques. A modified straight leg raise test was used to assess pain severity in awake animals and to evoke regional brain activation in anesthetized animals. The potential effects of clinical analgesics on both awake pain behavior and regional brain activation were examined. Following spinal nerve ligation, both male and female macaques showed significantly decreased ipsilateral straight leg raise thresholds, suggesting the presence of radicular-like pain. Morphine treatment increased straight leg raise thresholds in both males and females whereas duloxetine and pregabalin did not. In male macaques, the ipsilateral straight leg raise activated contralateral insular and somatosensory cortex (Ins/SII), and thalamus. In female macaques, the ipsilateral leg raise activated cingulate cortex and contralateral insular and somatosensory cortex. Straight leg raises of the contralateral, unligated leg did not evoke brain activation. Morphine reduced activation in all brain regions in both male and female macaques. In males, neither pregabalin nor duloxetine decreased brain activation compared with vehicle treatment. In females, however, pregabalin and duloxetine decreased the activation of cingulate cortex compared with vehicle treatment. The current findings suggest a differential activation of brain areas depending on sex following a peripheral nerve injury. Differential brain activation observed in this study could underlie qualitative sexual dimorphism in clinical chronic pain perception and responses to analgesics. Future pain management approaches for neuropathic pain will need to consider potential sex differences in pain mechanism and treatment efficacy.

In this study, we aimed to evaluate the short-term outcomes of a rehabilitation program with the Hybrid Assistive Limb® after soft tissue lengthening in young patients with cerebral palsy. We assessed six patients with cerebral palsy who underwent soft tissue surgery followed by gait training using the Hybrid Assistive Limb®. Clinical assessments were conducted preoperatively, before, immediately after, and at 1, 2, and 3 months after gait training. Gross Motor Function Measure was improved 5.93 ± 6.11% (mean ± standard deviation, p < 0.05), Canadian Occupational Performance Measure performance was improved 3.12 ± 1.53 points, and satisfaction was improved 3.80 ± 2.14 points (p < 0.05). The knee extension strength on the operated side was changed 7.75 ± 4.97 Nm after the intervention (p = 0.07). In ambulatory patients, gait speed was changed 8.37 ± 1.72 m/min, stride length was changed 10 ± 6.16 cm, and 6 min walking distance was changed 52 ± 16 m after the intervention. Training with the Hybrid Assistive Limb® may improve walking ability and clinical outcomes in young patients with cerebral palsy after soft tissue lengthening.

Abstract Background Zalaria sp. Him3 was reported as a novel fructooligosaccharides (FOS) producing yeast. However, Zalaria spp. have not been widely known and have been erroneously classified as a different black yeast, Aureobasidium pullulans. In this study, de novo genome assembly and analysis of Zalaria sp. Him3 was demonstrated to confirm the existence of a potential enzyme that facilitates FOS production and to compare with the genome of A. pullulans. Results The genome of Zalaria sp. Him3 was analyzed; the total read bases and total number of reads were 6.38 Gbp and 42,452,134 reads, respectively. The assembled genome sequence was calculated to be 22.38 Mbp, with 207 contigs, N50 of 885,387, L50 of 10, GC content of 53.8%, and 7,496 genes. g2419, g3120, and g3700 among the predicted genes were annotated as cellulase, xylanase, and β-fructofuranosidase (FFase), respectively. When the read sequences were mapped to A. pullulans EXF-150 genome as a reference, a small amount of reads (3.89%) corresponded to the reference genome. Phylogenetic tree analysis, which was based on the conserved sequence set consisting of 2,362 orthologs in the genome, indicated genetic differences between Zalaria sp. Him3 and Aureobasidium spp. Conclusion The differences between Zalaria and Aureobasidium spp. were evident at the genome level. g3700 identified in the Zalaria sp. Him3 likely does not encode a highly transfructosyl FFase because the motif sequences were unlike those in other FFases involved in FOS production. Therefore, strain Him3 may produce another FFase. Furthermore, several genes with promising functions were identified and might elicit further interest in Zalaria yeast.

Abstract Greater understanding of the mechanism that mediates visceral pain and hypersensitivity associated with irritable bowel syndrome (IBS) would facilitate the development of effective therapeutics to manage these symptoms. An objective marker associated with the underlying mechanisms of visceral pain and hypersensitivity could be used to guide therapeutic development. The current study examined brain activation evoked by rectal distention with functional magnetic resonance imaging (fMRI) in a cynomolgus macaque model of visceral hypersensitivity. Male, cynomolgus macaques underwent five four‐week treatments of dextran sodium sulfate (DSS)‐distilled water (DW), which induced mild–moderate colitis with remission during each treatment cycle. Balloon rectal distention (RD) was performed under anesthesia 14 weeks after the final DSS‐DW treatment. Colonoscopy confirmed the absence of colitis prior to the start of RD. In naïve, untreated macaques, 10, 20 and 30 ml RD did not evoke brain activation. However, insular cortex/somatosensory II cortex and cerebellum were significantly activated in DSS‐treated macaques at 20 and 30 ml rectal distention. Intra‐rectal pressure after DSS treatment was not significantly different from that of naïve, untreated macaques, indicating lack of alteration of rectal functioning following DSS‐treatment. Treatment with 5‐HT3 receptor antagonist alosetron (p.o.) reduced distension‐evoked brain activation and decreased intra‐rectal pressure. The current findings demonstrated activation of brain regions to RD following DSS treatments which was not present in naïve macaques, suggesting visceral hypersensitivity. Brain activation in turn was reduced by alosetron, which could underlie the analgesic effect alosetron in IBS patients.

Leishmaniasis is one of the neglected tropical diseases. Studies show that the poor knowledge about epidemiological aspects of leishmaniasis within communities causes the collapse of existing disease control programs. Therefore, the present study focuses on a detailed survey of the existing awareness among the threatened population in the Medawachchiya Public Health Inspector’s (PHI) Area in the Anuradhapura District, Sri Lanka, aiming to assist the health staff to organize community-based vector control programs effectively in the future. Assessment of the awareness of residents of two hundred and seventy households (n = 270) from 10 Grama Niladhari Divisions (GNDs) was carried out by using a structured questionnaire. Among 143 females and 134 males, only 75.1% had knowledge about the disease, 5.8% (n = 16) of the participants knew only about the vector, and 28.9% (n = 80) knew about control methods. The study showed a considerable lack of awareness about the disease among the studied population. The study found that age and education levels had significant impacts on knowledge, attitudes, and practices. However, factors like gender, marital status, occupation, income, and expenses did not show significant correlations. The present study suggests huge scope for greater achievements in community-related vector control methods by implementing a continuous educational program.

In eutherians, the placenta plays a critical role in the uptake, storage, and metabolism of lipids. These processes govern the availability of fatty acids to the developing fetus, where inadequate supply has been associated with substandard fetal growth. Whereas lipid droplets are essential for the storage of neutral lipids in the placenta and many other tissues, the processes that regulate placental lipid droplet lipolysis remain largely unknown. To assess the role of triglyceride lipases and their cofactors in determining placental lipid droplet and lipid accumulation, we assessed the role of patatin like phospholipase domain containing 2 (PNPLA2) and comparative gene identification-58 (CGI58) in lipid droplet dynamics in the human and mouse placenta. While both proteins are expressed in the placenta, the absence of CGI58, not PNPLA2, markedly increased placental lipid and lipid droplet accumulation. These changes were reversed upon restoration of CGI58 levels selectively in the CGI58-deficient mouse placenta. Using co-immunoprecipitation, we found that, in addition to PNPLA2, PNPLA9 interacts with CGI58. PNPLA9 was dispensable for lipolysis in the mouse placenta yet contributed to lipolysis in human placental trophoblasts. Our findings establish a crucial role for CGI58 in placental lipid droplet dynamics and, by extension, in nutrient supply to the developing fetus.

Objectives To examine the national, 6-year trends in in-hospital clinical outcomes of patients with subarachnoid haemorrhage (SAH) who underwent clipping or coiling and the prognostic influence of temporal trends in the Comprehensive Stroke Center (CSC) capabilities on patient outcomes in Japan.Design Retrospective study.Setting Six hundred and thirty-one primary care institutions in Japan.Participants Forty-five thousand and eleven patients with SAH who were urgently hospitalised, identified using the J-ASPECT Diagnosis Procedure Combination database.Primary and secondary outcome measures Annual number of patients with SAH who remained untreated, or who received clipping or coiling, in-hospital mortality and poor functional outcomes (modified Rankin Scale: 3–6) at discharge. Each CSC was assessed using a validated scoring system (CSC score: 1–25 points).Results In the overall cohort, in-hospital mortality decreased (year for trend, OR (95% CI): 0.97 (0.96 to 0.99)), while the proportion of poor functional outcomes remained unchanged (1.00 (0.98 to 1.02)). The proportion of patients who underwent clipping gradually decreased from 46.6% to 38.5%, while that of those who received coiling and those left untreated gradually increased from 16.9% to 22.6% and 35.4% to 38%, respectively. In-hospital mortality of coiled (0.94 (0.89 to 0.98)) and untreated (0.93 (0.90 to 0.96)) patients decreased, whereas that of clipped patients remained stable. CSC score improvement was associated with increased use of coiling (per 1-point increase, 1.14 (1.08 to 1.20)) but not with short-term patient outcomes regardless of treatment modality.Conclusions The 6-year trends indicated lower in-hospital mortality for patients with SAH (attributable to better outcomes), increased use of coiling and multidisciplinary care for untreated patients. Further increasing CSC capabilities may improve overall outcomes, mainly by increasing the use of coiling. Additional studies are necessary to determine the effect of confounders such as aneurysm complexity on outcomes of clipped patients in the modern endovascular era.

Background: Skin rash often occurs upon oral administration of amoxicillin in children, due to non-immediate hypersensitivity. However, information on delayed hypersensitivity to amoxicillin is scarce. Moreover, the appropriate diagnostic method and actual diagnostic rate of delayed hypersensitivity to amoxicillin among Japanese children are unclear. We conducted intradermal tests (IDTs) and drug provocation tests (DPTs) and retrospectively investigated the proportion of children with a definitive diagnosis of non-immediate hypersensitivity to amoxicillin. We then evaluated the characteristics of patients with a positive allergic workup. Methods: We enrolled children referred for suspected findings of mild or moderate non-immediate hypersensitivity to amoxicillin between August 2018 and March 2020. If the IDT in the delayed phase was negative, DPT with amoxicillin (60–90 mg/kg/day) was performed for 7 days. Non-immediate hypersensitivity to amoxicillin was defined when IDT or DPT was positive. We evaluated the potential of the drug-induced lymphocyte stimulation test (DLST) to reveal hypersensitivity to amoxicillin. Results: This study enrolled 27 children. Fourteen children (52%) had hypersensitivity to amoxicillin, of whom 12 had positive IDTs and two had positive DPTs. No differences in age, sex, history of allergic disease, days from oral use to symptom onset, type of rash at symptom onset, generalized rash, and DLST results were observed between the hypersensitivity and non-hypersensitivity groups. Conclusions: Examination should be performed for children with mild or moderate reactions because positive cases have no significant features and half of the suspected cases are negative.

Becoming homebound can be devastating for older adults in rural communities. This study aimed to identify protective or high-risk social activities associated with homebound status among the rural young old (ages 65–74) and the oldest old (ages ≥ 75). We used data from a survey of older adults in a rural community of Japan in 2014. Questions covered sociodemographic characteristics, homebound status (i.e., going out less than once a week), physical and psychological status, and social activities. Using survey data, we conducted logistic regression analysis to identify protective and high-risk social activities associated with homebound status. Of the 1,564 participants, 51.0 % were the oldest old, and the mean age was 75.2 (±7.0) years. The prevalence of homebound status was 10.5 % total: 5.2 % among the young old and 15.7 % among the oldest old and highest among the female oldest old (19.4 %). The main protective social activity for the young and the oldest old was visiting friends’ houses (adjusted odds ratio [AOR] 5.38, 95 % confidence interval [CI] 1.64–17.64 and AOR 3.49, 95 % CI 1.07–11.42, respectively). For the young old, specific high-risk social activities were advising family and friends (AOR 0.07, 95 % CI 0.01–0.62) and activities to support older adults (AOR 0.17, 95 % CI 0.03–0.84). For the oldest old, a protective social activity was participating in long-term care prevention programs (AOR 28.94, 95 % CI 1.90–441.63). To prevent rural older adults from becoming homebound, support should be provided according to protective and high-risk social activities for age groups, with particular attention to safe socialization amid the threat of COVID-19.