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Hereditary spastic paraplegias (HSPs) are a heterogeneous group of neurodegenerative disorders characterized by progressive spasticity and weakness in the lower extremities. To date, a total of 88 types of SPG are known. To diagnose HSP, multiple technologies, including microarray, direct sequencing, multiplex ligation-dependent probe amplification, and short-read next-generation sequencing, are often chosen based on the frequency of HSP subtypes. Exome sequencing (ES) is commonly used. We used ES to analyze ten cases of HSP from eight families. We identified pathogenic variants in three cases (from three different families); however, we were unable to determine the cause of the other seven cases using ES. We therefore applied long-read sequencing to the seven undetermined HSP cases (from five families). We detected intragenic deletions within the SPAST gene in four families, and a deletion within PSEN1 in the remaining family. The size of the deletion ranged from 4.7 to 12.5 kb and involved 1-7 exons. All deletions were entirely included in one long read. We retrospectively performed an ES-based copy number variation analysis focusing on pathogenic deletions, but were not able to accurately detect these deletions. This study demonstrated the efficiency of long-read sequencing in detecting intragenic pathogenic deletions in ES-negative HSP patients., (© 2023. The Japan Society of Human Genetics.)

Aims: To evaluate the Clinical Frailty Scale (CFS) and a Frailty Index based on laboratory tests (FI-lab) in terms of what each assesses about frailty and to determine the appropriateness of combined use of these two frailty scales., Methods: This was a prospective observational cohort study in an acute geriatric ward of a university hospital. The FI-lab is the proportion of laboratory parameters that yield abnormal results from a total of 23. The FI-lab and CFS were assessed at admission. Data on activities of daily living (ADL), cognition, geriatric syndromes, and comorbidities were also collected. Main outcomes were in-hospital mortality and 90-day mortality after admission., Results: In total, 378 inpatients (mean age 85.2 ± 5.8 years, 59.3% female) were enrolled. ADL and cognition correlated strongly with the CFS (Spearman's |r|> 0.60) but weakly with the FI-lab (|r|< 0.30). Both the CFS and FI-lab correlated weakly with geriatric syndromes and comorbidities (|r|< 0.40). The correlation between the CFS and FI-lab was also weak (r = 0.28). The CFS and FI-lab were independently associated with in-hospital mortality and 90-day mortality after admission. The Akaike information criterion was lower for models using both the CFS and FI-lab than for models using either tool alone., Conclusions: The CFS and FI-lab each reflected only some of the aspects of frailty in acutely hospitalized older patients. The model fit was better when the two frailty scales were used together to assess the mortality risk than when either was used alone., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objectives: We aimed to examine the association between intrinsic capacity (IC) and adverse outcomes of hospitalization., Design: A prospective observational cohort study., Setting and Participants: We recruited patients aged 65 years or older who were admitted to the geriatric ward of an acute hospital between Oct 2019 and Sep 2022., Measurements: Each of the five IC domains (locomotion, cognition, vitality, sensory, and psychological capacity) was graded into three levels, and the composite IC score was calculated (0, lowest; 10, highest). Hospital-related outcomes were defined as in-hospital death, hospital-associated complications (HACs), length of hospital stay, and frequency of discharge to home., Results: In total, 296 individuals (mean age 84.7 ± 5.4 years, 42.7 % males) were analyzed. Mean composite IC score was 6.5 ± 1.8, and 95.6 % of participants had impairment in at least one IC domain. A higher composite IC score was independently associated with lower frequency of in-hospital death (odds ratio [OR] 0.59) and HACs (OR 0.71), higher frequency of discharge to home (OR 1.50), and shorter length of hospital stay (β = -0.24, p < 0.01). The locomotion, cognition, and psychological domains were independently associated with the occurrence of HACs, discharge destination, and length of hospital stay., Conclusion: Evaluating IC was feasible in the hospital setting and was associated with outcomes of hospitalization. For older inpatients with decreased IC, integrated management may be required to achieve functional independence., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

This study aimed to examine the effectiveness of early rehabilitation in patients with femoral neck fractures admitted to acute care settings in Japan using the data registered with the Japan Association of Rehabilitation Databases (JARD). We included data for 401 patients (out of 3088 patients) aged ≥ 65 years (85 males, 316 females) from nine hospitals who sustained a femoral neck fracture between July 2005 and September 2015. Using the number of days until surgery or the number of days until the start of rehabilitation or both as the explanatory variables, and the indoor mobility at discharge as the outcome variable, we calculated the adjusted rate ratio (ARR) and 95% confidence interval (CI) using Poisson regression analysis (age, sex, cognitive impairment, concurrent symptoms, and previous history of fracture adjusted as covariates). The ARR for independent walking at the discharge of the early-rehabilitation group (starting rehabilitation within two days after the injury) was significantly higher (ARR: 2.01, 95% CI: 1.34-3.02) than that of the non-early rehabilitation group. These results suggest that early acute-phase rehabilitation after a femoral neck fracture in older patients allows for better ambulatory ability at discharge, regardless of the time to surgery., Competing Interests: We declare no conflict of interest related to this study.

Purpose: Dehydration is highly prevalent in hospitalized older adults and has been linked to poor outcomes. It is considered a modifiable factor, so early identification and intervention may avoid adverse events and improve quality of life after discharge. Hospital-associated disability (HAD) is known to be a poor prognostic factor and can be categorized into mobility impairment and self-care impairment in setting goals for management. Few studies have directly examined the association between dehydration and HAD and therefore here we examined whether dehydration is a predictor of HAD categorized into mobility and self-care impairment among acute hospitalized older adults., Methods: Patients aged 65 years or older who were admitted to the geriatric ward of an acute hospital were recruited for this prospective cohort study. Estimated serum osmolarity > 300 mOsm/kg was defined as current dehydration. HAD was assessed between baseline and discharge and at 3 months after discharge, and was evaluated separately for mobility and self-care impairments., Results: In total, 192 patients (mean age, 84.7 years; male, 41.1%; dehydration, 31.3%) were analyzed. The occurrence of HAD was significantly higher in the dehydrated group than in the non-dehydrated group (42.4% vs 26.5%) from baseline to 3 months after discharge. In multiple logistic regression analysis, dehydration was significantly associated with HAD in self-care from baseline to 3 months after discharge (odds ratio, 2.25; 95% confidence interval, 1.03-4.94)., Conclusions: Dehydration could predict the occurrence of HAD in acute hospitalized older adults. A multifaceted approach may be necessary to improve the management of dehydration in these patients., (© 2022. The Author(s), under exclusive licence to European Geriatric Medicine Society.)

Background: Geriatric conditions (GCs) are common in the elderly population, but their clinical significance in acute care is not well understood. In this study, we first investigated the cross-sectional associations of GCs with frailty and polypharmacy at the time of admission to an acute care geriatric ward. Then, to clarify the clinical significance of GCs in acute care, we prospectively examined the association of GCs with the incidence of hospital-acquired complications and consequences after discharge., Methods: Participants were 184 patients (40.2% men: mean age 85.0 ± 6.0 years) hospitalized in an acute care geriatric ward at a university hospital. We examined the cross-sectional associations of GCs with frailty and polypharmacy by multiple regression analysis, and then the associations of GCs with the incidence of hospital-acquired complications, falls and death within 3 months of discharge by multiple logistic regression analysis., Results: GCs were associated with frailty and use of polypharmacy, independent of multiple morbidity. GCs were also associated with readmission within 3 months of discharge; however, there was no significant association with the incidence of hospital-acquired complications, falls, or mortality after discharge., Conclusions: These findings suggest that GCs are clinically significant in the hospitalized elderly and further research on GCs is warranted. Geriatr Gerontol Int 2023; 23: 50-53., (© 2022 Japan Geriatrics Society.)

Background: Few studies have examined the relationship between non-cognitive factors and activities of daily living (ADL) according to Alzheimer's disease (AD) stage., Objective: We aimed to identify the differences in non-cognitive factors according to AD stages and their involvement in basic and instrumental ADL performance by using intrinsic capacity (IC) in groups with cognition ranging from normal to moderate or severe AD., Methods: We enrolled 6397 patients aged≥65 years who visited our memory clinic. Non-cognitive IC was assessed using the locomotion, sensory, vitality, and psychological domains. Multiple logistic regression was performed to identify how non-cognitive IC declines over the AD course and examine the correlation between non-cognitive IC and basic and instrumental ADL performance., Results: Non-cognitive IC declined from the initial AD stage and was significantly correlated with both basic and instrumental ADL performance from the aMCI stage through all AD stages. In particular, the relationship between IC and basic ADL was stronger in mild and moderate to severe AD than in the aMCI stage. On the other hand, the relationship between IC and instrumental ADL was stronger in aMCI than in later AD stages., Conclusions: The results show non-cognitive factors, which decline from the aMCI stage, are correlated with ADL performance from the aMCI stage to almost all AD stages. Considering that the relationship strength varied by ADL type and AD stage, an approach tailored to ADL type and AD stage targeting multiple risk factors is likely needed for effectively preventing ADL performance declines.

Progress has been made in the elucidation of sleep and wakefulness regulation at the neurocircuit level 1,2 . However, the intracellular signalling pathways that regulate sleep and the neuron groups in which these intracellular mechanisms work remain largely unknown. Here, using a forward genetics approach in mice, we identify histone deacetylase 4 (HDAC4) as a sleep-regulating molecule. Haploinsufficiency of Hdac4, a substrate of salt-inducible kinase 3 (SIK3) 3 , increased sleep. By contrast, mice that lacked SIK3 or its upstream kinase LKB1 in neurons or with a Hdac4 S245A mutation that confers resistance to phosphorylation by SIK3 showed decreased sleep. These findings indicate that LKB1-SIK3-HDAC4 constitute a signalling cascade that regulates sleep and wakefulness. We also performed targeted manipulation of SIK3 and HDAC4 in specific neurons and brain regions. This showed that SIK3 signalling in excitatory neurons located in the cerebral cortex and the hypothalamus positively regulates EEG delta power during non-rapid eye movement sleep (NREMS) and NREMS amount, respectively. A subset of transcripts biased towards synaptic functions was commonly regulated in cortical glutamatergic neurons through the expression of a gain-of-function allele of Sik3 and through sleep deprivation. These findings suggest that NREMS quantity and depth are regulated by distinct groups of excitatory neurons through common intracellular signals. This study provides a basis for linking intracellular events and circuit-level mechanisms that control NREMS., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Frailty is a dynamic status that can worsen or improve. However, changes in their frailty status that occur during hospitalization and their significance have not been comprehensively investigated. In this study, we explored the association between such changes and mortality 3 months after discharge in older adults hospitalized for acute care. In total, 257 participants (mean age 84.95 ± 5.88, 41.6% male) completed comprehensive geriatric assessments, including the Clinical Frailty Scale (CFS) at admission and discharge. Mean CFS score was 5.14 ± 1.35 at admission. CFS scores increased, indicating deteriorating frailty, in 29.2% of the participants (75/257) during hospitalization. Multiple logistic regression analysis demonstrated a positive association between increased CFS score during hospitalization and mortality (odds ratio, 2.987) independent of potential co-founding factors. This deterioration in frailty during hospitalization may be modifiable risk factor of poor prognosis in older adults who need acute care hospitalization., (© 2022. The Author(s), under exclusive licence to European Geriatric Medicine Society.)

Siponimod, which is approved to treat active secondary progressive multiple sclerosis, acts as a functional antagonist of sphingosine-1-phosphate (S1P) receptor 1 (S1P 1 ) and an agonist of S1P 5 . S1P 1 antagonization, which inhibits lymphocyte egress from lymphoid tissues and subsequent infiltration into the central nervous system (CNS), is considered the main therapeutic mechanism of siponimod. In addition, siponimod's direct effects on CNS glial cells are another potential neuroprotective mechanism because siponimod can penetrate the blood-brain barrier and CNS glial cells express S1P receptors. However, it remains uncertain whether siponimod directly affects CNS glial cells. In this study, we investigated siponimod's effects on astrocytes using mouse primary cultures. Siponimod suppressed nuclear factor kappa B activation and pro-inflammatory cytokine production. Using antagonists for S1P 1 and S1P 5 , we found that siponimod partially exerts its anti-inflammatory effects via S1P 1 , but not via S1P 5 . Moreover, siponimod also inhibited histone deacetylase, suggesting that siponimod exerts broad anti-inflammatory effects via S1P 1 antagonization and histone deacetylase inhibition. Siponimod might suppress disease progression in multiple sclerosis in part via direct inhibition of astroglial CNS neuroinflammation., Competing Interests: Declaration of interest Hideyuki Takeuchi is a Section Editor of Neuroscience Research., (Copyright © 2022 Japan Neuroscience Society and Elsevier Ltd. All rights reserved.)

Objectives: The purpose of this study was to examine the relationship of the serum creatinine/cystatin C ratio (CCR) with hand grip strength (HGS), total body muscle mass, trunk muscle mass, and skeletal muscle mass index (SMI) in patients attending a memory clinic., Design: This cross-sectional study enrolled outpatients of a memory clinic in Japan from October 2010 to July 2017., Setting and Participants: We enrolled 1945 participants aged 60 years or older with measured skeletal muscle mass, HGS, and serum creatinine and serum cystatin C levels., Measures: Linear multiple regression analysis was performed for men and women using total body muscle mass, trunk muscle mass, and SMI as objective variables. The exposure variables were selected from previous reports if they were strongly linked to muscle mass. Total body muscle mass and trunk muscle mass were corrected by dividing by body weight. Multiple regression analysis was also conducted for men and women using HGS as an objective variable. Because cognitive function and HGS are strongly related, we also conducted sensitivity analysis by excluding participants with a Mini-Mental State Examination score < 24 to alleviate any concern that we did not fully adjust for the effect of cognitive dysfunction., Results: In men, CCR was significantly associated with total body muscle mass, trunk muscle mass, and SMI (P = 0.013, P = 0.008, and P < 0.001, respectively). In women, CCR was significantly associated with total body muscle mass and trunk muscle mass (P = 0.013 and P < 0.001, respectively), but not with SMI (P = 0.932). On the other hand, CCR was significantly associated with grip strength in both men and women (P < 0.001 and P < 0.001, respectively)., Conclusions: CCR was associated with both muscle mass and muscle strength. This study suggests that CCR is a useful marker not only for muscle mass but also for muscle strength., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Direct seawater electrolysis potentially simplifies the electrolysis process and leads to a decrease in the cost of green hydrogen production. However, impurities present in the seawater, especially chloride ions (Cl - ), cause corrosion of the electrode material, and its oxidation competes with the anodic oxygen evolution reaction (OER). By carefully tuning electrode substrate and electrolyte solutions, the CoFeO x H y /Ti electrode with high double-layer capacitance actively and stably electro-catalyzed the OER in potassium borate solutions at pH 9.2 in the presence of 0.5 mol kg -1 Cl - . The electrode possesses an active site motif composed of either a Co- or Fe-domain and benefits from an enlarged surface area. Selective OER was demonstrated in Cl - -containing electrolyte solutions at an elevated reaction temperature, stably achieving 500 mA cm -2 at a mere potential of 1.67 V vs. reversible hydrogen electrode (RHE) at 353 K for multiple on-off and long-term testing processes with a faradaic efficiency of unity toward the OER., (© 2022 The Authors. ChemSusChem published by Wiley-VCH GmbH.)

Objectives: Muscle ultrasound is a non-invasive technique that enables identification of the quantity and quality of muscle tissue. It has been used not only for diagnosis of sarcopenia but also for prediction of outcomes in clinical practice. There is now increasing awareness that muscle changes detected during acute hospitalization indicate acute sarcopenia leading to worse outcomes. However, to our knowledge, few studies have investigated this in hospitalized older adults. The aim of this study was to determine whether muscle changes on muscle ultrasound can predict poor outcomes in acute hospitalized older adults., Methods: This prospective, observational cohort study involved 145 acute hospitalized older adults. Bilateral anterior thigh thickness (BATT), echo intensity (EI), and corrected EI of the quadriceps were assessed on admission and 7 d later. The primary outcome was mortality, and the secondary outcomes were hospital-associated complications and decline in activities of daily living (ADLs) at 3 mo after discharge., Results: Changes in BATT, EI, and corrected EI at 7 d after admission were found in 0.2%, 0.0%, and 0.2% of cases, respectively. The respective rates for mortality, hospital-associated complications, and ADL decline were 8.7%, 52.8%, and 43%, respectively. Multivariable logistic regression analysis showed that the BATT value at admission tended to be associated with mortality. Changes in BATT, EI, and collected EI were not associated with adverse outcomes., Conclusions: Acute muscle changes on muscle ultrasound were not associated with mortality, ADL decline, or hospital-associated complications in acute hospitalized older adults. More research in various settings is needed to clarify the value of muscle ultrasound in clinical practice., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: To elucidate recent prescription trends for older adults and the background underlying changes over time with a particular focus on the prevalence of polypharmacy and potentially inappropriate medications (PIMs)., Methods: We cross-sectionally collected prescription data of patients aged ≧65 years who visited chain pharmacies dispensing prescribed drugs from all types of outpatient settings for one month in two sampling periods (October, 2014 and December, 2019), and the data were analysed. Prevalence of polypharmacy and factors associated with PIMs between the two periods were investigated., Results: The average number of drugs prescribed decreased over time (4.05 ± 3.24 in 2014 vs. 3.98 ± 3.16 in 2019, p < 0.001), as did the prevalence of polypharmacy (50.1% in 2014 vs. 48.2% in 2019, p < 0.001). Meanwhile, the prevalence of PIMs exhibited a marked increase (overall: 26.8% in 2014 vs. 43.7% in 2019, aged 65-74: 25.6% in 2014 vs. 40.3% in 2019, aged 75-84: 27.4% in 2014 vs. 43.9% in 2019), which was the most pronounced in patients aged over 85 (29.4% in 2014 vs. 53.0% in 2019). The number of classes of drugs positively associated with PIMs in 2019 increased from that in 2014. The increasing trend was most prominently observed in the oldest age category (over 85 years, 2 in 2014 vs. 6 in 2019)., Conclusions: The comparison of monthly prescribing data with an interval of 5 years suggested an increasing trend in the prevalence of PIMs, contrary to the declining prevalence of polypharmacy., (Copyright © 2022. Published by Elsevier B.V.)

Individuals with mild cognitive impairment (MCI) often make qualitative errors on the Clock Drawing Test (CDT), and these errors are reported to be associated with lower scores on neuropsychological assessments. Gait speed is also closely associated with cognitive dysfunction. However, the association between CDT errors and gait speed has not been investigated in individuals with MCI. Therefore, in this study, we explored the association between gait speed and qualitative errors on the CDT. Participants were 196 outpatients at a memory clinic with a clinical dementia rating of 0.5. The CDT was evaluated using the method of Cahn et al. The participants were divided into tertiles of normal and maximum gait speeds. The CDT error types of stimulus-bound response, conceptual deficit (CD), and planning deficit were found in 24.5%, 29.6%, and 30.1% of the participants, respectively. CD was found in 43.6% of the slowest tertile of maximum gait and in 22.2% of the fastest tertile. Multiple linear regression analysis gait speeds as objective continuous variables revealed that CD was significantly negatively associated with maximum gait, but not with normal gait. No other error types were associated with gait speeds. Only CD type error on the CDT was negatively associated with maximum gait speed, but not normal gait speed in the current study. The association between the qualitative error on the CDT and gait speed provides further basis of the clinical importance of qualitative assessments of CDT., (© 2022. The Author(s).)

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and fatal neurodegenerative disorder that affects upper and lower motor neurons; however, its pathomechanism has not been fully elucidated. Using a comprehensive phosphoproteomic approach, we have identified elevated phosphorylation of Collapsin response mediator protein 1 (Crmp1) at serine 522 in the lumbar spinal cord of ALS model mice overexpressing a human superoxide dismutase mutant (SOD1 G93A ). We investigated the effects of Crmp1 phosphorylation and depletion in SOD1 G93A mice using Crmp1 S522A (Ser522→Ala) knock-in ( Crmp1 k i /ki ) mice in which the S522 phosphorylation site was abolished and Crmp1 knock-out ( Crmp1 -/- ) mice, respectively. Crmp1 ki / ki / SOD1 G93A mice showed longer latency to fall in a rotarod test while Crmp1 -/- / SOD1 G93A mice showed shorter latency compared with SOD1 G93A mice. Survival was prolonged in Crmp1 ki / ki / SOD1 G93A mice but not in Crmp1 -/- / SOD1 G93A mice. In agreement with these phenotypic findings, residual motor neurons and innervated neuromuscular junctions (NMJs) were comparatively well-preserved in Crmp1 ki / ki / SOD1 G93A mice without affecting microglial and astroglial pathology. Pathway analysis of proteome alterations showed that the sirtuin signaling pathway had opposite effects in Crmp1 ki / ki / SOD1 G93A and Crmp1 -/- / SOD1 G93A mice. Our study indicates that modifying CRMP1 phosphorylation is a potential therapeutic strategy for ALS., (Copyright © 2022 Asano et al.)

Kallmann syndrome, a congenital disorder of idiopathic hypogonadotropic hypogonadism associated with anosmia, results in infertility because of anovulation. Assisted reproductive technology (ART) is considered when optimal ovulation induction therapy is difficult or when several cycles of ovulation induction therapy do not result in pregnancy. However, evidence is lacking regarding the optimal ART treatment for Kallmann syndrome. We report the case of a 33-year-old woman who successfully achieved pregnancy and delivery after ART treatment. At 29 years old, she was diagnosed with Kallmann syndrome due to hypothalamic amenorrhea and anosmia. At 33 years old, she revisited the hospital, desiring a child after one year of infertility. Due to anovulation, she was treated with gonadotropin therapy, but controlling follicular development was difficult, and thus ART treatment was initiated. The controlled ovarian stimulation (COS) protocol for ART treatment employed gonadotropins, recombinant follicular stimulating hormone/human menopausal gonadotropin plus human chorionic gonadotropin, to promote follicular growth. Four oocytes were retrieved, and two cleaved embryos were vitrified and cryopreserved. After vitrified-warmed embryo transfer of a morula stage embryo in a hormone replacement cycle, pregnancy was achieved but resulted in a miscarriage. A second oocyte retrieval was performed under the same COS; four oocytes were retrieved, and two cleaved embryos were vitrified and cryopreserved. Further, a pregnancy was achieved through the vitrified warmed embryo transfer. At 40 weeks and 6 days of gestation, a baby boy weighing 3,344 g with an Apgar score of 7/8 was delivered vaginally. The mother's postpartum course and neonate were free from adverse events. For women with Kallmann syndrome, ART treatment and selective embryo cryopreservation may be a reasonable and safe option.

This prospective, cross-sectional, cohort observational study was conducted to evaluate the associations between sedentary behavior and arteriosclerosis-related vascular issues in community-dwelling frail older adults. We included 116 Japanese community-dwelling older adults (92 females and 24 males) who availed daycare at two long-term care insurance facilities in the cities of Yokkaichi and Handa between 2017 and 2019. An unpaired t -test and the chi-square test were used for intergroup comparisons. Logistic regression analysis was conducted with cardio-ankle vascular index as the dependent variable, sedentary behavior as the explanatory variable, and the other evaluated factors as covariates. Long-time sedentary behavior (based on the median value for all participants) was associated with high cardio-ankle vascular index after adjusting for age, sex, body mass index, ankle-brachial index, and walking MET-minutes in 1 week (odds ratio 3.086, 95% confidence interval 1.275-7.467, p =0.012). After adjusting for other variables (care needs certificate, skeletal muscle mass index, body fat percentage, grip strength, 4-m walking duration, etc), there was a significant association between long-time sedentary behavior and high cardio-ankle vascular index values (odds ratio 4.977, 95% confidence interval 1.497-16.554, p =0.009). The results study confirmed an association between long-time sedentary behavior in frail older adults and the degree of arterial stiffness assessed by the cardio-ankle vascular index. Interventions in older adults that focus on daily sedentary time to prevent the onset and exacerbation of geriatric syndromes secondary to the progression of arteriosclerosis warrant further investigation., Competing Interests: The authors report no conflicts of interest.

A 93-year-old woman was diagnosed with Lysinibacillus fusiformis bacteremia complicated with coma blisters. Initial gram staining for L. fusiformis indicated the presence of gram-negative rods; however, subsequent staining of colonies from Mueller-Hinton agar revealed the presence of gram-positive and gram-negative rods with spherical endospores, and Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (VITEK ® MS and microflex® LT/SH) definitively identified the organism as L. fusiformis. The two-week administration of piperacillin/tazobactam and ampicillin resulted in an improvement of the patient's general condition, and the skin lesions gradually improved., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

With the aim of monitoring the mental and physical health of mothers and children following the Fukushima nuclear accident and providing them with necessary care, we have been conducting an annual survey of expectant and nursing mothers since 2011. The Pregnancy and Birth Survey is a mail-in survey of about 15,000 individuals, with a response rate of approximately 50.0% each year. In addition, because respondents to a survey conducted in the immediate aftermath of the disaster showed a particularly high rate of depression, follow-up surveys have been conducted at 4 years after childbirth. Reviewing the results of surveys from FY 2011 through FY 2018, we found that the prevalence of depressive symptoms among mothers was highest in the survey after childbirth and decreased over time. Data of follow-up surveys showed that the prevalence of depression was lower than immediately after childbirth and then decreased over time. The proportion of mothers with radiation anxiety was higher among respondents in the FY 2011 follow-up than in the FY 2014 follow-up, indicating the prolonged impact of the nuclear accident, especially among those who gave birth immediately after the disaster. Characteristics of mothers who received telephone parenting counseling included first delivery, caesarean section, living in evacuation zones, not being able to receive medical examinations as scheduled, and having radiation anxiety. Continuous care should be provided to mothers who gave birth immediately after the nuclear accident, including routine perinatal care and parenting support, provision of information on radiation, and long-term monitoring of their wellbeing.

In 2021, the National Institute of Infectious Diseases, Japan, undertook enhanced event-based surveillance (EBS) for infectious diseases occurring overseas that have potential for importation (excluding coronavirus disease 2019 [COVID-19]) for the Tokyo 2020 Olympic and Paralympic Summer Games (the Games). The pre-existing EBS system was enhanced using the World Health Organization Epidemic Intelligence from Open Sources system and the BlueDot Epidemic Intelligence platform. The enhanced EBS before and during the Games did not detect any major public health event that would warrant action for the Games. However, information from multiple sources helped us identify events, characterize risk and improve confidence in risk assessment. The collaboration also reduced the surveillance workload of the host country, while ensuring the quality of surveillance, even during the COVID-19 pandemic., ((c) 2021 The authors; licensee World Health Organization.)

Oxytocin (Oxt) is known to regulate social communication, stress and body weight. The activation of Oxt receptors (OTR) has clinical potential to abate stress disorders and metabolic syndrome. Kamikihito (KKT) is a traditional Japanese medicine used to treat psychological stress-related disorders. We investigated the effects of KKT, its ingredients and chemical components on Oxt neurons and OTR. C-Fos expression was examined after oral and peripheral administration of KKT in rats. Electrophysiological change of Oxt neurons and Oxt release upon application of KKT were measured in rat brain slice. The direct effect of KKT, its ingredients and its chemical components were examined by cytosolic Ca 2+ ([Ca 2+ ] i ) measurement in Oxt neurons and OTR-expressing HEK293 cells. Both intraperitoneal and oral administration of KKT in rats induced c-Fos expression in neurons of the paraventricular nucleus (PVN) including Oxt neurons. Application of KKT induced activation of Oxt neurons and Oxt release. KKT increased [Ca 2+ ] i in OTR-expressing HEK293 cells, and failed to activate with OTR antagonist. KKT-induced PVN Oxt neuron activation was also attenuated by OTR antagonist. Seven chemical components (rutin, ursolic acid, (Z )-butylidenephtalide, p-cymene, senkunolide, [6]-shogaol, [8]-shogaol) of three ingredients (Zizyphi Fructus, Angelicae Acutilobae Radix, Zingiberis Rhizoma) from KKT had potential to activate OTR. KKT can directly activate PVN Oxt neurons by interacting with OTR. The interaction of seven chemical components from KKT may contribute to activate OTR. Effect of KKT on Oxt neurons and OTR may contribute to the treatment of Oxt related disorders.

Competing Interests: The authors report no disclosures relevant to the manuscript.

Aim: Cerebral small vessel disease and lower urinary tract symptoms are common in older people. However, the association between white matter hyperintensity (WMH) and overactive bladder (OAB) is not fully understood. We aimed to identify the relationship between WMH and OAB., Methods: We carried out neuropsychological testing and head magnetic resonance imaging (T2-weighted and fluid-attenuated inversion recovery) of 72 outpatients at a memory clinic and evaluated their Overactive Bladder Symptom Score. WMH was assessed using the Fazekas scale, and WMH volumes were determined using Software for Neuro-Image Processing in Experimental Research. OAB was diagnosed based on a urinary urgency score (the third question of the Overactive Bladder Symptom Score) of two or higher and a total Overactive Bladder Symptom Score of three or higher. Multivariate logistic analysis was carried out, with the presence/absence of overactive bladder as the outcome variable, and age, sex, body mass index and diabetes mellitus as covariates., Results: Of the 72 participants, 17 (24%) were diagnosed with OAB. WMH assessed by the visual rating scale was not associated with OAB. However, participants with OAB showed significantly higher WMH volume than those without OAB. Regionally, participants with OAB showed high WMH volume in the frontal, occipital and parietal lobes. Multiple logistic regression analysis showed that WMH was significantly associated with OAB (OR 1.82, 95% CI 1.11-2.98), after adjustment for clinically important confounders., Conclusions: Cerebral WMH volume is associated with OAB, independent of age, sex, body mass index and diabetes mellitus. Geriatr Gerontol Int 2021; 21: 996-1002., (© 2021 Japan Geriatrics Society.)

Introduction: The Australian "empathy session," which is a parenting program aimed at alleviating postpartum depression by increasing empathy among expecting couples, was adapted to a life-planning education program for Japanese high school students. In this present study, we aimed to assess changes in high school students' empathy levels., Methods: A nonrandomized, controlled, waitlist intervention was performed in 210 first-year students. They were divided into intervention and waitlist control groups. The life-planning lecture consisted of two parts: (1) reproductive health and (2) empathy and communication skills. The main outcome indicator was the Perspective-Taking subscale of an empathy index. Logistic regression was used to examine the association between the intervention and change in the Perspective-Taking scale score controlling for background factors., Results: As per our findings, a significant difference was noted in the scale scores of Perspective-Taking before and after the program within the intervention group (3.76 ± 0.61 before the lecture and 3.86 ± 0.64 after the lecture; P = 0.01). In the between-group analysis, the likelihood of an increase in the scale score of Perspective-Taking was significantly higher in the intervention group (OR = 2.29, 95 % confidence interval = 1.23-4.26)., Conclusions: Japanese high school students' Perspective-Taking improved through learning reproductive life-planning and communication skills., Competing Interests: None, (Copyright © Japan Medical Association.)

Background: Hospital-associated complications are associated with adverse outcomes after discharge, and a method to help predict the occurrence of these complications needs to be established. Sarcopenia is thought to be one of the factors associated with hospital-associated complication, but sarcopenia assessment in hospitalized patients is often difficult. Focus has recently been placed on morphological and qualitative evaluation of muscle by ultrasound as an index of sarcopenia. Therefore, in this study, we sought to clarify the association of hospital-associated complication with muscle thickness or echo intensity measured by ultrasound and with commonly used sarcopenia-related parameters., Methods: This is a prospective observational cohort study with 156 hospitalized older patients recruited over a year. Bilateral thigh muscle thickness of rectus femoris and vastus intermedius, echo intensity and corrected echo intensity of rectus femoris were measured by ultrasound. Also measured were the sarcopenia-related parameters of handgrip strength, skeletal muscle index, and maximum calf circumference. Hospital-associated complication was defined as the occurrence of any of the following complications: delirium, functional decline, incontinence, falls, pressure injuries, and nosocomial infections., Results: Of 156 patients enrolled at admission, hospital-associated complication was observed in 70 (54.3%). With-hospital-associated complication group had a higher prevalence of emergency admission and a higher corrected echo intensity than without-hospital-associated complication group. Multivariate logistic regression analysis showed that only higher corrected echo intensity was associated with hospital-associated complication (odds ratio 1.036; 95% confidence interval, 1.001-1.072), while handgrip strength, bilateral thigh muscle thickness, skeletal muscle index, and maximum calf circumference were not., Conclusions: Corrected echo intensity might be a useful parameter to help predict hospital-associated complication in acute hospitalized older patients and might contribute to establishing a strategy to prevent hospital-associated complication., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Polycystic ovary syndrome (PCOS) causes anovulation and is associated with a reduced clinical pregnancy rate. Metformin, which is widely used for treating PCOS, can lead to successful pregnancy by restoring the ovulation cycle and possibly improving endometrial abnormality during the implantation period. However, the mechanism by which metformin improves endometrial abnormality remains unknown. Women with PCOS have an aberrant expression of steroid hormone receptors and homeobox A10 (HOXA10), which is essential for embryo implantation in the endometrium., Methods: In this study, we examined whether metformin affects androgen receptor (AR) and HOXA10 expression in PCOS endometrium in vivo and in human endometrial cell lines in vitro. Expression of AR and HOXA10 was evaluated by immunohistochemistry, fluorescent immunocytochemistry, and western blot analysis., Results: AR expression was localized in both epithelial and stromal cells; however, HOXA10 expression was limited to only stromal cells in this study. In women with PCOS, 3 months after metformin treatment, the expression of AR was reduced in epithelial and stromal cells in comparison to their levels before treatment. In contrast, HOXA10 expression in the stromal cells with metformin treatment increased in comparison to its level before treatment. Further, we showed that metformin counteracted the testosterone-induced AR expression in both Ishikawa cells and human endometrial stromal cells (HESCs); whereas, metformin partly restored the testosterone-reduced HOXA10 expression in HESCs in vitro., Conclusions: Our results suggest that metformin may have a direct effect on the abnormal endometrial environment of androgen excess in women with PCOS., Trial Registration: The study was approved by the Ethical Committee of Fukushima Medical University (approval no. 504, approval date. July 6, 2006), and written informed consent was obtained from all patients. https://www.fmu.ac.jp/univ/sangaku/rinri.html.

Neuroinflammation by activated microglia and astrocytes plays a critical role in progression of amyotrophic lateral sclerosis (ALS). Interleukin-19 (IL-19) is a negative-feedback regulator that limits pro-inflammatory responses of microglia in an autocrine and paracrine manner, but it remains unclear how IL-19 contributes to ALS pathogenesis. We investigated the role of IL-19 in ALS using transgenic mice carrying human superoxide dismutase 1 with the G93A mutation (SOD1 G93A Tg mice). We generated IL-19-deficient SOD1 G93A Tg (IL-19 -/- /SOD1 G93A Tg) mice by crossing SOD1 G93A Tg mice with IL-19 -/- mice, and then evaluated disease progression, motor function, survival rate, and pathological and biochemical alternations in the resultant mice. In addition, we assessed the effect of IL-19 on glial cells using primary microglia and astrocyte cultures from the embryonic brains of SOD1 G93A Tg mice and IL-19 -/- /SOD1 G93A Tg mice. Expression of IL-19 in primary microglia and lumbar spinal cord was higher in SOD1 G93A Tg mice than in wild-type mice. Unexpectedly, IL-19 -/- /SOD1 G93A Tg mice exhibited significant improvement of motor function. Ablation of IL-19 in SOD1 G93A Tg mice increased expression of both neurotoxic and neuroprotective factors, including tumor necrosis factor-α (TNF-α), IL-1β, glial cell line-derived neurotrophic factor (GDNF), and transforming growth factor β1, in lumbar spinal cord. Primary microglia and astrocytes from IL-19 -/- /SOD1 G93A Tg mice expressed higher levels of TNF-α, resulting in release of GDNF from astrocytes. Inhibition of IL-19 signaling may alleviate ALS symptoms.

Intracellular aggregates are a common pathological hallmark of neurodegenerative diseases such as polyglutamine (polyQ) diseases, amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and multiple system atrophy (MSA). Aggregates are mainly formed by aberrant disease-specific proteins and are accompanied by accumulation of other aggregate-interacting proteins. Although aggregate-interacting proteins have been considered to modulate the formation of aggregates and to be involved in molecular mechanisms of disease progression, the components of aggregate-interacting proteins remain unknown. In this study, we showed that small glutamine-rich tetratricopeptide repeat-containing protein alfa (SGTA) is an aggregate-interacting protein in neurodegenerative diseases. Immunohistochemistry showed that SGTA interacted with intracellular aggregates in Huntington disease (HD) cell models and neurons of HD model mice. We also revealed that SGTA colocalized with intracellular aggregates in postmortem brains of patients with polyQ diseases including spinocerebellar ataxia (SCA)1, SCA2, SCA3, and dentatorubral-pallidoluysian atrophy. In addition, SGTA colocalized with glial cytoplasmic inclusions in the brains of MSA patients, whereas no accumulation of SGTA was observed in neurons of PD and ALS patients. In vitro study showed that SGTA bound to polyQ aggregates through its C-terminal domain and SGTA overexpression reduced intracellular aggregates. These results suggest that SGTA may play a role in the formation of aggregates and may act as potential modifier of molecular pathological mechanisms of polyQ diseases and MSA.

Interleukin-19 (IL-19) acts as a negative-feedback regulator to limit proinflammatory response of macrophages and microglia in autocrine/paracrine manners in various inflammatory diseases. Multiple sclerosis (MS) is a major neuroinflammatory disease in the central nervous system (CNS), but it remains uncertain how IL-19 contributes to MS pathogenesis. Here, we demonstrate that IL-19 deficiency aggravates experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, by promoting IL-17-producing helper T cell (Th17 cell) infiltration into the CNS. In addition, IL-19-deficient splenic macrophages expressed elevated levels of major histocompatibility complex (MHC) class II, co-stimulatory molecules, and Th17 cell differentiation-associated cytokines such as IL-1β, IL-6, IL-23, TGF-β1, and TNF-α. These observations indicated that IL-19 plays a critical role in suppression of MS pathogenesis by inhibiting macrophage antigen presentation, Th17 cell expansion, and subsequent inflammatory responses. Furthermore, treatment with IL-19 significantly abrogated EAE. Our data suggest that IL-19 could provide significant therapeutic benefits in patients with MS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Horiuchi, Parajuli, Komiya, Ogawa, Jin, Takahashi, Azuma, Tanaka, Suzumura and Takeuchi.)

Background: Polypharmacy, usually defined as the use of 5 or more drugs, is associated with reduced quality of life, adverse events, and frailty. Slow gait speed is a component of physical frailty, and some studies have suggested an association between polypharmacy and slow gait speed., Objective: We aimed to determine the effects of polypharmacy on the gait difference according to stages of cognitive decline in a cross-sectional study of memory clinic patients., Methods: Participants were 431 outpatients aged 65 year or older who were cognitively normal (CN) or had mild cognitive impairment (MCI) or dementia due to Alzheimer's disease. Participants were divided into a polypharmacy group and a non-polypharmacy group in each group. Multiple regression analysis and logistic analysis were used for data analysis., Results: There were 182 patients in the polypharmacy group and 249 patients in the non-polypharmacy group. Multiple regression analysis revealed that gait speed had significant negative associations with number of medications and polypharmacy status in the CN group (β: -0.026 [-0.041 to -0.0018] and -0.128 [-0.022 to -0.0033], respectively) and MCI group (-0.018 [-0.028 to -0.0009] and -0.100 [-0.166 to -0.0034]). Logistic regression analysis also showed that number of medications was associated with slow gait status (< 1 m/s) in the CN group (OR: 1.336 [1.115 to 1.601]) and MCI group (1.128 [1.022 to 1.244])., Conclusion: CN and MCI patients with polypharmacy have slower gait speed. Attention should be paid to decreased gait speed in older adults with polypharmacy even when their cognitive function is relatively preserved.

Background: Few studies have investigated associations between types of clock drawing test (CDT) errors and cognitive impairment., Objective: To explore associations of qualitative errors in the CDT with comprehensive neurocognitive assessment scores and clinical diagnosis., Methods: Outpatients at a memory clinic were enrolled. Frequencies of errors determined by Cahn's method were explored according to cognitive status (cognitively normal [CN] (n = 279), mild cognitive impairment [MCI] (n = 321), and Alzheimer's disease [AD]) (n = 575). Neuropsychological assessment scores were compared between participants with and without errors., Results: Stimulus-bound response (SB) was relatively rare (6.8%) in the CN group but was markedly more common in the MCI (23.4%) and AD (33.2%) groups. Conceptual deficit (CD) was found in more than 20%of CN individuals, as well as about 50%of AD patients. Planning deficit (PD) frequencies were relatively similar among the groups. SB in both of CN and MCI individuals, and CD in both of CN and MCI individuals were associated with lower scores in several neuropsychological assessments. Meanwhile, PD was not associated with lower assessment scores in any of CN, MCI, or AD individuals., Conclusion: The frequencies of SB and CD increased from CN, MCI, to AD but showed somewhat different patterns. Both SB and CD were associated with lower cognition in all three cognitive stages.

Background: Homocysteine is a common risk factor for cognitive impairment and sarcopenia. However, very few studies have shown an association between sarcopenia and serum homocysteine levels after adjustment for cognitive function., Objective: The purpose of this study was to investigate the relationship between homocysteine and sarcopenia in memory clinic patients., Methods: This cross-sectional study investigated outpatients in a memory clinic. We enrolled 1,774 participants (≥65 years old) with measured skeletal muscle mass index (SMI), hand grip strength (HGS), and homocysteine. All participants had undergone cognitive assessments and were diagnosed with dementia, mild cognitive impairment, or normal cognition. Patient characteristics were compared according to sarcopenia presence, SMI level, or HGS. Multivariate logistic regression analysis was performed to determine the association of homocysteine with sarcopenia, low SMI, or low HGS. Next, linear regression analysis was performed using HGS as a continuous variable., Results: Logistic regression analysis showed that low HGS was significantly associated with homocysteine levels (p = 0.002), but sarcopenia and low SMI were not. In linear regression analysis, HGS was negatively associated with homocysteine levels after adjustment for Mini-Mental State Examination score (β= -2.790, p < 0.001) or clinical diagnosis of dementia (β= -3.145, p < 0.001). These results were similar for men and women., Conclusion: Our results showed a negative association between homocysteine and HGS after adjustment for cognitive function. Our findings strengthen the assumed association between homocysteine and HGS. Further research is needed to determine whether lower homocysteine levels lead to prevent muscle weakness.

Oligomeric-brush chains of helical lanthanide (Ln) complexes retain their structural and luminescent behavior after coating onto magnetic nanoparticles (MNPs) consisting of Fe 3 O 4 covered with silicate. It is one of the type of bifunctional NPs exhibiting luminescence of Ln and superparamagnetism of Fe 3 O 4 . In comparison to a simple monolayer of complexes adsorbed on a modified surface, a layer made of luminescent chains allowed us to obtain a more intensive red/green luminescence originating from Eu 3+ /Tb 3+ ions, and at the same time, no visible increase in particle size (compared to Fe 3 O 4 @silica particles) was observed. The luminescent properties of the Tb 3+ complex were altered by MNPs; the decrease of the luminescence was not as large as expected, the excitation spectrum changed significantly, and the average luminescence lifetime was much longer at room temperature. Surprisingly, this phenomenon was not observed at 77 K and also did not occur for the Eu 3+ complexes. The possibility to stack building blocks in a chain using complexes of different lanthanide ions can be used to design novel multifunctional nanosystems., Competing Interests: The authors declare no competing financial interest., (© 2020 American Chemical Society.)

Chronic dehydration mainly occurs due to insufficient fluid intake over a lengthy period of time, and nursing home residents are thought to be at high risk for chronic dehydration. However, few studies have investigated chronic dehydration, and new diagnostic methods are needed. Therefore, in this study, we aimed to identify risk factors for chronic dehydration by measuring serum osmolality in nursing home residents and also to evaluate whether examining the inferior vena cava (IVC) and determining the IVC collapsibility index (IVC-CI) by ultrasound can be helpful in the diagnosis of chronic dehydration. A total of 108 Japanese nursing home residents aged ≥65 years were recruited. IVC measurement was performed using a portable handheld ultrasound device. Fifteen residents (16.9%) were classified as having chronic dehydration (serum osmolality ≥295 mOsm/kg). Multivariate logistic regression analysis showed that chronic dehydration was associated with dementia (odds ratio (OR), 6.290; 95% confidential interval (CI), 1.270-31.154) and higher BMI (OR, 1.471; 95% CI, 1.105-1.958) but not with IVC or IVC-CI. Cognitive function and body weight of residents should be considered when establishing a strategy for preventing chronic dehydration in nursing homes.

To evaluate the predictability of progression of cognitive impairment to dementia using qualitative clock drawing test (CDT) scores, we administered both the CDT using Cahn et al.'s qualitative scoring system and the Mini-Mental State Examination (MMSE) to assess cognitive function in non-demented older individuals attending a memory clinic at a university hospital. Patients visiting the clinic for assessment of cognitive function between January 2015 and December 2019 were enrolled, and only those who were diagnosed as not having dementia at the time of initial assessment completed a follow-up assessment at 1 y ( n = 163). To examine any association of qualitative CDT score with progression to dementia, multiple logistic regression analysis was conducted with the change in diagnosis from non-dementia to dementia at 1 y as the dependent variable. A total of 26 participants (16.0%) were diagnosed as having converted to dementia. Multiple logistic regression analysis revealed that both the qualitative CDT score using Cahn et al.'s scoring system and the existence of conceptual deficits were significantly associated with progression to dementia at 1 y after initial assessment of cognitive function, irrespective of the MMSE score, among non-demented older individuals. The CDT may be a useful predictor of progression to dementia in primary care settings.

It remains controversial whether circulating monocytes expressing CCR2 infiltrate the central nervous system (CNS) and contribute to pathogenicity of amyotrophic lateral sclerosis (ALS). A previous report used conventional immunohistochemistry to show that CCR2 is exclusively expressed by astrocytes, but not infiltrating monocytes/microglia or neurons, in the spinal cords of ALS model mice. In this study, we assessed the cellular distribution of CCR2 in the CNS of ALS mice using CCR2-reporter mice (Ccr2 rfp/+ -Cx3cr1 gfp/+ -SOD1 G93A Tg mice), a more sophisticated method for directly detecting the distribution of CCR2 protein. We found that infiltration of CCR2 + monocytes in the lumbar spinal cord increased over the course of disease progression. Moreover, from the middle stage of disease, CCR2 was partially distributed in microglia and neurons, but not astrocytes, in striking contrast to the previous findings. These novel observations suggested that CCR2 + monocyte infiltration leads to CNS environmental deterioration due to toxic conversion of microglia and neurons, creating a vicious cycle of neuroinflammation and leading to acceleration of ALS pathology. Our findings also show that this reporter mouse is a useful and powerful tool for obtaining new insights into the pathomechanisms of ALS.

Objectives: To clarify (1) the prevalence and associating factors of work-life conflict (WLC);(2) the details of gender-based discrimination;and (3) the association between WLC and gender-based discrimination among various professionals in a medical university organization., Methods: This cross-sectional study, conducted in 2017, included all employees working at a public medical university and two affiliated hospitals that lie in provincial cities in Japan. The outcome of interest was time-based WLC in the work-to-family or family-to-work direction, measured with a shortened version of an existing scale. Gender-based discrimination was measured according to a three-point scale., Results: Among the 3,347 employees, complete data sets were available for 2,285 (complete response rate, 68.3%). Of these, approximately 30% of respondents had perceived WLC. Multivariable logistic regression analysis showed that faculty members, nurses, and employees between 30 and 39 years old had a greater risk of WLC regardless of gender. Men were more likely to perceive gender-based discrimination in the contents of their work and the number of incidental tasks, while women were more likely to perceive discrimination with promotions and evaluation of academic achievements. Both men and women respondents who perceived gender-based discrimination had an increased risk of WLC., Conclusions: When promoting organizational well-being in a medical university, increased attention should be paid to faculty members, nurses and employees between 30 and 39 years old, as they have a greater risk of WLC. Our results also suggest that promoting gender equality is important to help achieve appropriate work-life balance.

Postpartum depression is a serious problem not only for mothers, but also for their children and families. Evidence is scarce on the effectiveness of couple-targeted antenatal interventions aimed at preventing postpartum depression in Asia. Therefore, we implemented an antenatal parenting support program from Australia ("empathy program") at three sites in Japan, and assessed the characteristics of participating couples and changes in their mental health indicators before and after the program (during pregnancy and 6 weeks postpartum, respectively). In this program, participant couples discussed concerns during pregnancy and a "difficult day" scenario with other same-gender participants and then with their own partners. In total, 100 couples attended the program. Among 60 participating mothers, 20% screened positive for maternal depression symptoms (defined as an Edinburgh Postnatal Depression Scale greater than 9). Changes in paternal empathy and maternal antenatal Edinburgh Postnatal Depression Scale score were significantly associated with maternal postpartum Edinburgh Postnatal Depression Scale score in multivariable analyses. Our results indicate that a key in preventing postpartum depression is paternal involvement and long-term support from antenatal phase.

Aims: As the number of older people with dementia increases, safe pharmacotherapy in this population has attracted attention in recent years. The aims of this study were to clarify the prescribing patterns in older patients who were prescribed anti-dementia drugs and to investigate the association of potentially inappropriate medications (PIMs) with the use of anti-dementia drugs., Methods: Adults aged ≥65 years, who were prescribed anti-dementia drugs at 585 pharmacies across Japan (N = 7,953), were surveyed. The percentage of prescriptions of anti-dementia drugs and the effect of those prescriptions on PIMs were investigated., Results: Prescriptions of anti-dementia drugs were found in 4.4% of the entire study population. A multiple logistic regression analysis revealed that the use of anti-dementia drugs reduced the risk of prescribing psychotropic drugs, which represented PIMs, and that a combination of anti-dementia drugs (e.g., cholineesterase inhibitor with memantine) may reduce the risk of prescribing PIMs compared with monotherapy., Conclusion: The use of anti-dementia drugs was associated with fewer prescriptions of drugs considered as PIMs., (The Author(s). Published by S. Karger AG, Basel.)

Background: Cognitive impairment is linked to decreased quality of life (QOL), but few studies have investigated the impact of comorbid sarcopenia., Objective: The aim of this study was to elucidate the association of sarcopenia with QOL in patients with early dementia and mild cognitive impairment., Methods: Individuals with a Clinical Dementia Rating of 0.5 or 1 and a Mini-Mental State Examination score of 20-30 underwent a battery of neuropsychological assessments administered by a group of well-trained clinical psychologists. The EQ-5D was completed by both the patients and their main caregivers. EQ-5D utility and visual analog scale scores were measured. Sarcopenia was defined according to the criteria published in the 2019 consensus update by the Asian Working Group for Sarcopenia., Results: Patients with sarcopenia had significantly lower scores on the Digit Symbol Substitution Test and Trail Making Test Part A. There was a significant negative association between sarcopenia and both self- and proxy-rated EQ-5D utility scores independent of potential confounding factors. However, there was no association between QOL visual analog scale scores and sarcopenia., Conclusion: Given that sarcopenia is often found in individuals with cognitive impairment, early detection by timely screening and effective intervention may help to maintain or improve QOL in this population. However, this study could not determine whether reduced QOL is a direct consequence of sarcopenia.