Distinct genomic landscapes of gastroesophageal adenocarcinoma depending on PD-L1 expression identify mutations in RAS-MAPK pathway and TP53 as potential predictors of immunotherapy efficacy.

BACKGROUND: The impact of molecular alterations on programmed death-ligand 1 (PD-L1) combined positive score (CPS) is not well studied in gastroesophageal adenocarcinomas (GEAs). We aimed to characterize genomic features of tumors with different CPSs in GEAs. PATIENTS AND METHODS: Genomic alterations of 2518 GEAs were compared in three groups (PD-L1 CPS ≥ 10, high; CPS = 1-9, intermediate; CPS < 1, low) using next-generation sequencing. We assessed the impact of gene mutations on the efficacy of immune checkpoint inhibitors (ICIs) and tumor immune environment based on the Memorial Sloan Kettering Cancer Center and The Cancer Genome Atlas databases. RESULTS: High, intermediate, and low CPSs were seen in 18%, 54% and 28% of GEAs, respectively. PD-L1 positivity was less prevalent in women and in tissues derived from metastatic sites. PD-L1 CPS was positively associated with mismatch repair deficiency/microsatellite instability-high, but independent of tumor mutation burden distribution. Tumors with mutations in KRAS, TP53, and RAS-mitogen-activated protein kinase (MAPK) pathway were associated with higher PD-L1 CPSs in the mismatch repair proficiency and microsatellite stability (pMMR&MSS) subgroup. Patients with RAS-MAPK pathway alterations had longer overall survival (OS) from ICIs compared to wildtype (WT) patients [27 versus 13 months, hazard ratio (HR) = 0.36, 95% confidence interval (CI): 0.19-0.7, P = 0.016] and a similar trend was observed in the MSS subgroup (P = 0.11). In contrast, patients with TP53 mutations had worse OS from ICIs compared to TP53-WT patients in the MSS subgroup (5 versus 21 months, HR = 2.39, 95% CI: 1.24-4.61, P = 0.016). CONCLUSIONS: This is the largest study to investigate the distinct genomic landscapes of GEAs with different PD-L1 CPSs. Our data may provide novel insights for patient selection using mutations in TP53 and RAS-MAPK pathway and for the development of rational combination immunotherapies in GEAs.

Protein tyrosine phosphatase receptor type Q in cerebrospinal fluid reflects ependymal cell dysfunction and is a potential biomarker for adult chronic hydrocephalus.

BACKGROUND AND PURPOSE: Protein tyrosine phosphatase receptor type Q (PTPRQ) was extracted from the cerebrospinal fluid (CSF) of patients with probable idiopathic normal-pressure hydrocephalus (iNPH) by proteome analysis. We aimed to assess the feasibility of using CSF PTPRQ concentrations for the additional diagnostic criterion of iNPH in Japanese and Finnish populations. METHODS: We compared PTPRQ concentrations among patients with probable iNPH and neurologically healthy individuals (normal control [NC] group), patients with normal-pressure hydrocephalus (NPH) of acquired and congenital/developmental aetiologies, patients with Alzheimer's disease and patients with Parkinson's disease in a Japanese analysis cohort. A corresponding iNPH group and NC group in a Finnish cohort was used for validation. Patients in the Finnish cohort who underwent biopsy were classified into two groups based on amyloid and/or tau deposition. We measured PTPRQ expression levels in autopsied brain specimens of iNPH patients and the NC group. RESULTS: Cerebrospinal fluid PTPRQ concentrations in the patients with NPH of idiopathic, acquired and congenital/developmental aetiologies were significantly higher than those in the NC group and those with Parkinson's disease, but iNPH showed no significant differences when compared with those in the Alzheimer's disease group. For the patients with iNPH, the area under the receiver-operating characteristic curve was 0.860 in the Japanese iNPH and 0.849 in the Finnish iNPH cohorts. Immunostaining and in situ hybridization revealed PTPRQ expression in the ependymal cells and choroid plexus. It is highly possible that the elevated PTPRQ levels in the CSF are related to ependymal dysfunction from ventricular expansion. CONCLUSIONS: Cerebrospinal fluid PTPRQ levels indicated the validity of this assay for auxiliary diagnosis of adult chronic hydrocephalus.

Psoriasis associated with ACE inhibitors: an analysis of the FAERS database.

Many case reports have been published concerning the development or exacerbation of psoriasis after administration of angiotensin-converting enzyme (ACE) inhibitors. The aim of the present study was to investigate the association between psoriasis and ACE inhibitors using the US Food and Drug Administration Adverse Event Reporting System (FAERS) data. After excluding patients with psoriasis-related primary diseases, the association of psoriasis with 14 ACE inhibitors was examined using disproportional analyses reporting odds ratio (ROR) and information component (IC). Signals were detected for all 14 ACE inhibitors combined (ROR: 1.25, 95% confidence interval [CI]: 1.14-1.37; IC: 0.31, 95% CI: 0.17-0.44) and individually for lisinopril (ROR: 1.20, 95% CI: 1.05-1.37; IC: 0.25, 95% CI: 0.06-0.45), perindopril (ROR: 1.86, 95% CI: 1.38-2.52; IC: 0.86, 95% CI: 0.43-1.30), and ramipril (ROR: 1.63, 95% CI: 1.36-1.96; IC: 0.69, 95% CI: 0.42-0.96). ACE inhibitors are widely used in patients with hypertension, heart failure, and diabetes mellitus, which are considered comorbidities of psoriasis. Our results suggest that the involvement of ACE inhibitors should be considered in patients on ACE inhibitor therapy who have developed (or show exacerbated) psoriasis.

A genome-wide association study identifies two novel susceptibility loci and trans population polygenicity associated with bipolar disorder.

Genome-wide association studies (GWASs) have identified several susceptibility loci for bipolar disorder (BD) and shown that the genetic architecture of BD can be explained by polygenicity, with numerous variants contributing to BD. In the present GWAS (Phase I/II), which included 2964 BD and 61 887 control subjects from the Japanese population, we detected a novel susceptibility locus at 11q12.2 (rs28456, P=6.4 × 10-9), a region known to contain regulatory genes for plasma lipid levels (FADS1/2/3). A subsequent meta-analysis of Phase I/II and the Psychiatric GWAS Consortium for BD (PGC-BD) identified another novel BD gene, NFIX (Pbest=5.8 × 10-10), and supported three regions previously implicated in BD susceptibility: MAD1L1 (Pbest=1.9 × 10-9), TRANK1 (Pbest=2.1 × 10-9) and ODZ4 (Pbest=3.3 × 10-9). Polygenicity of BD within Japanese and trans-European-Japanese populations was assessed with risk profile score analysis. We detected higher scores in BD cases both within (Phase I/II) and across populations (Phase I/II and PGC-BD). These were defined by (1) Phase II as discovery and Phase I as target, or vice versa (for 'within Japanese comparisons', Pbest~10-29, R2~2%), and (2) European PGC-BD as discovery and Japanese BD (Phase I/II) as target (for 'trans-European-Japanese comparison,' Pbest~10-13, R2~0.27%). This 'trans population' effect was supported by estimation of the genetic correlation using the effect size based on each population (liability estimates~0.7). These results indicate that (1) two novel and three previously implicated loci are significantly associated with BD and that (2) BD 'risk' effect are shared between Japanese and European populations.

Longitudinal changes in 18 F-THK5351 positron emission tomography in corticobasal syndrome.

BACKGROUND AND PURPOSE: Corticobasal syndrome (CBS) is pathologically characterized by tau deposits in neuronal and glial cells and by reactive astrogliosis. In several neurodegenerative disorders, 18 F-THK5351 has been observed to bind to reactive astrocytes expressing monoamine oxidase B. In this study, the aim was to investigate the progression of disease-related pathology in the brains of patients with CBS using positron emission tomography with 18 F-THK5351. METHODS: Baseline and 1-year follow-up imaging were acquired using magnetic resonance imaging and positron emission tomography with 18 F-THK5351 in 10 subjects: five patients with CBS and five age-matched normal controls (NCs). RESULTS: The 1-year follow-up scan images revealed that 18 F-THK5351 retention had significantly increased in the superior parietal gyrus of the patients with CBS compared with the NCs. The median increases in 18 F-THK5351 accumulation in the patients with CBS were 6.53% in the superior parietal gyrus, 4.34% in the precentral gyrus and 4.33% in the postcentral gyrus. In contrast, there was no significant increase in the regional 18 F-THK5351 retention in the NCs. CONCLUSIONS: Longitudinal increases in 18 F-THK5351 binding can be detected over a short interval in the cortical sites of patients with CBS. A monoamine oxidase B binding radiotracer could be useful in monitoring the progression of astrogliosis in CBS.

Tau imaging with [18 F]THK-5351 in progressive supranuclear palsy.

BACKGROUND AND PURPOSE: Visualization of pathogenic protein aggregates is crucial to elucidate pathomechanisms and to make an accurate diagnosis in many neurodegenerative conditions. Aggregates of the microtubule-binding protein, tau, are one of the most important pathogenic molecules in neurodegenerative disorders. Progressive supranuclear palsy (PSP) is characterized by the deposition of tau proteins in some specific area such as the basal ganglia and brainstem. We tried to detect tau lesions in the brains of living patients with PSP with a novel positron emission tomography (PET) tracer, [18 F]THK-5351, which we have recently developed. METHODS: Paraffin-embedded brain sections of the patients with PSP were used for autoradiography with [3 H]THK-5351 and immunohistochemistry. Nine healthy controls, 13 patients with Alzheimer's disease and three patients with PSP participated in this PET study with [18 F]THK-5351. To detect amyloid-ß deposition, PET imaging with Pittsburgh compound B was also performed. RESULTS: Autoradiography in the brain sections of patients with PSP demonstrated [3 H]THK-5351 binding to tau deposits with a high selectivity. Although patients with PSP exhibited no remarkable [18 F]THK-5351 retention in the temporal cortex, significantly higher tracer retention was observed in the globus pallidus and midbrain. In contrast, amyloid imaging with Pittsburgh compound B showed no remarkable accumulation in the cerebral cortex of PSP. CONCLUSIONS: We conclude that [18 F]THK-5351 PET can potentially be used to detect the regional brain distribution of tau lesions in PSP, thereby facilitating the differential diagnosis of neurodegenerative disorders associated with tau protein.

Resonant inelastic x-ray scattering and photoemission measurement of O2: Direct evidence for dependence of Rydberg-valence mixing on vibrational states in O 1s → Rydberg states.

High-resolution resonant inelastic x-ray scattering (RIXS) and low-energy photoemission spectra of oxygen molecules have been measured for investigating the electronic structure of Rydberg states in the O 1s → σ* energy region. The electronic characteristics of each Rydberg state have been successfully observed, and new assignments are made for several states. The RIXS spectra clearly show that vibrational excitation is very sensitive to the electronic characteristics because of Rydberg-valence mixing and vibronic coupling in O2. This observation constitutes direct experimental evidence that the Rydberg-valence mixing characteristic depends on the vibrational excitation near the avoided crossing of potential surfaces. We also measured the photoemission spectra of metastable oxygen atoms (O*) from O2 excited to 1s → Rydberg states. The broadening of the 4p Rydberg states of O* has been found with isotropic behavior, implying that excited oxygen molecules undergo dissociation with a lifetime of the order of 10 fs in 1s → Rydberg states.

De novo EEF1A2 mutations in patients with characteristic facial features, intellectual disability, autistic behaviors and epilepsy.

Eukaryotic elongation factor 1, alpha-2 (eEF1A2) protein is involved in protein synthesis, suppression of apoptosis, and regulation of actin function and cytoskeletal structure. EEF1A2 gene is highly expressed in the central nervous system and Eef1a2 knockout mice show the neuronal degeneration. Until now, only one missense mutation (c.208G > A, p.Gly70Ser) in EEF1A2 has been reported in two independent patients with neurological disease. In this report, we described two patients with de novo mutations (c.754G > C, p.Asp252His and c.364G > A, p.Glu122Lys) in EEF1A2 found by whole-exome sequencing. Common clinical features are shared by all four individuals: severe intellectual disability, autistic behavior, absent speech, neonatal hypotonia, epilepsy and progressive microcephaly. Furthermore, the two patients share the similar characteristic facial features including a depressed nasal bridge, tented upper lip, everted lower lip and downturned corners of the mouth. These data strongly indicate that a new recognizable disorder is caused by EEF1A2 mutations.

RISING beamline (BL28XU) for rechargeable battery analysis.

The newly installed BL28XU beamline at SPring-8 is dedicated to in situ structural and electronic analysis of rechargeable batteries. It supports the time range (1 ms to 100 s) and spatial range (1 µm to 1 mm) needed for battery analysis. Electrochemical apparatus for battery charging and discharging are available in experimental hutches and in a preparation room. Battery analysis can be carried out efficiently and effectively using X-ray diffraction, X-ray absorption fine-structure analysis and hard X-ray photoelectron spectroscopy. Here, the design and performance of the beamline are described, and preliminary results are presented.

Soluble amyloid precursor protein α in the cerebrospinal fluid as a diagnostic and prognostic biomarker for idiopathic normal pressure hydrocephalus.

BACKGROUND: Cognitive impairment is difficult to improve after shunt operation in patients with idiopathic normal pressure hydrocephalus (iNPH). This study aims to identify cerebrospinal fluid (CSF) biomarkers predictive of improvement in cognitive function. METHODS: This study was conducted between January 2008 and December 2010 on consecutive, unselected admissions to our program for the treatment of patients with clinically suspected iNPH. Lumbar CSF concentrations of total tau (Tau), tau phosphorylated at threonine 181 (p-tau), soluble amyloid precursor protein (sAPP), sAPPα, sAPPß, and ß-amyloid(1-42) (Aß42) were analyzed by ELISA. RESULTS: Concentrations of p-tau, sAPP, sAPPα, and sAPPß were strong diagnostic biomarkers for distinguishing between iNPH and Alzheimer's disease (AD). sAPPα exhibited the highest accuracy in differentiating iNPH from patients with AD and normal controls, with an area under the curve value of 0.994. We examined the prognostic value of p-tau and sAPPα for cognition function after surgery. With a cutoff value of 198 ng/ml or less for sAPPα, sensitivity and specificity are 66.7% and 82.9%, respectively, whilst the Mini-Mental State Examination score at 6 months after surgery is expected to be 25 or more. CONCLUSION: Our results show that sAPPα is a suitable biomarker for the diagnosis and prognosis of iNPH.

Ataxia with isolated vitamin E deficiency is caused by mutations in the alpha-tocopherol transfer protein.

Ataxia with isolated vitamin E deficiency (AVED) is an autosomal recessive neurodegenerative disease which maps to chromosome 8q13. AVED patients have an impaired ability to incorporate alpha-tocopherol into lipoproteins secreted by the liver, a function putatively attributable to the alpha-tocopherol transfer protein (alpha-TTP). Here we report the identification of three frame-shift mutations in the alpha TTP gene. A 744delA mutation accounts for 68% of the mutant alleles in the 17 families analysed and appears to have spread in North Africa and Italy. This mutation correlates with a severe phenotype but alters only the C-terminal tenth of the protein. Two other mutations were found in single families. The finding of alpha TTP gene mutations in AVED patients substantiates the therapeutic role of vitamin E as a protective agent against neurological damage in this disease.

Relationships among Grip Strength Measurement, Response Time, and Frailty Criteria.

BACKGROUND: Muscle response in older adults is believed to decrease with maximal muscle strength, although it has not been adequately assessed; further, the relationship between frailty and muscle response remains unexamined. OBJECTIVES: This study aimed to develop a practical method for measuring muscle response using grip strength in older adults and to clarify the relationship between frailty and grip strength response. DESIGN, SETTING, AND PARTICIPANTS: We performed a cross-sectional, clinical, observational study. A total of 248 patients (94 men and 154 women, mean age: 78.2 years) who visited the outpatient unit in the Integrated Healthy Aging Clinic of our Hospital for the first time were enrolled. MEASUREMENTS: Using a grip strength measuring device originally developed by us, we measured grip strength response indices, such as reaction time, time constant, rate of force development (response speed), and maximum grip strength. Grip strength response indices were compared among three groups (robust, pre-frail, and frail) according to the Fried and Kihon checklist assessments for frailty. RESULTS: Based on Fried's assessment, marked differences were found between groups not only in maximal grip strength but also in response time and response speed. Based on the Kihon checklist assessment, there was no significant difference in response time; however, a considerable difference in response speed for the left hand was observed. Moreover, according to the Kihon checklist assessment, some cases showed differences in muscle response although not in maximal muscle strength. CONCLUSIONS: The response speed of grip strength was suggested to decrease with frailty. The results suggest that measurement of grip strength response in both hands is useful to examine the relationship between frailty and grip strength response.

Predictive Validity of Different Walking Measures to Identify the Incident Long-Term Care Needs in Older Adults.

OBJECTIVES: A comfortable walking speed is a suitable measurement of functional status in older adults. In addition to assessing their comfortable walking speed, two complex walking tests were administered to a cohort of older people, assuming that these tests would be a more sensitive predictor of the incident long-term care needs than comfortable walking speed. DESIGN: A prospective observational study was conducted to collect data. SETTING AND PARTICIPANTS: Among the initial 5,563 community-dwelling independent older adults (aged ≥ 65 years), 935 were excluded and the data of 4,628 (mean age, 73.9 ± 5.5 years, 65-94 years; 2,052 men, 2,576 women) older adults were finally analyzed. METHODS: Three walking tasks were administered: comfortable, complicated balance, and Go-stop walking. Complicated balance walking was measured under comfortable walking conditions, with participants having to walk with their hands crossed at the shoulder joint at 90°. For the Go-stop walking test, the time taken to walk 2 meters was measured using a stopwatch. For two years following baseline assessments, participants received monthly follow-ups for incident certification of the need for care under the long-term care insurance (LTCI) system. RESULTS: Low performance in comfortable, complicated balance, and Go-stop walking were 29.8%, 37.7%, and 35.1%, respectively. During the 24-month follow-up period, 246 participants (5.3%) required LTCI certification. The Youden Index was used to determine the cut-points of the incident long-term care needs in the comfortable, complicated balance, and Go-stop walking conditions, which were 1.055 m/s, 0.936 m/s, and 3.205 seconds, respectively. Participants classified as exhibiting low performance included 1,381 (29.8%) under comfortable walking, 1,746 (37.7%) under complicated balance walking, and 1,623 (35.1%) under the Go-stop walking tests. The C-indices of the comfortable, complicated balance, and Go-stop walking tests were 0.72 (95% confidence interval (CI) 0.69-0.76), 0.71 (95% CI 0.67-0.74), and 0.65 (95% CI 0.61-0.69), respectively. Cox proportional hazards regression model revealed significant relationships between the incident long-term care needs and the comfortable (hazard ratio (HR) 2.14, 95% CI 1.62-2.84), complicated balance (1.81, 1.36-2.41), and Go-stop (1.46, 1.12-1.91) walking conditions. CONCLUSIONS AND IMPLICATIONS: The findings suggest that slow walking speed has a considerably greater impact on the incident long-term care needs in older adults. However, the complex walking task did not improve the predictive performance. Comfortable walking speed tests, which can easily be measured to predict the future incident long-term care needs, are effective tools in community health promotion and primary care.

Prediction of Nursing Home Admission Using the FRAIL-NH Scale Among Older Adults in Post-Acute Care Settings.

OBJECTIVES: The FRAIL-NH scale was developed to identify frailty status in nursing home residents. The purpose of this study was to examine the utility of the FRAIL-NH scale for predicting nursing home admission among patients in post-acute care settings. Design/ Setting/ Participants: This single-center, prospective, observational cohort study included participants aged 65 years or older who were admitted to a community-based integrated care ward (CICW) between July 2015 and November 2020. MEASUREMENTS: Using the CICW database, we retrospectively classified participants as robust, prefrail, or frail based on the FRAIL-NH scale the score by identifying variables from our database that were most representative of each component. The following data were collected: examination findings, CICW admission and discharge information, length of CICW stay, and nursing home admission. The participants were divided into two groups based on whether or not they were admitted to a nursing home after CICW discharge. The hazard ratios (HRs) and 95% confidence intervals (CIs) for nursing home admission were calculated according to the FRAIL-NH categories using the Cox proportional hazards models with reference to the robust group. In the multivariate adjusted model, we adjusted for age, sex, nutritional status, cognitive function, living status, and economic status. RESULTS: Data of 550 older adults were analyzed, of which 118 were admitted and 432 were not admitted to a nursing home. The frail group had a higher risk of nursing home admission (HR, 2.22; 95% CI 1.32-3.76) than the robust group. CONCLUSIONS: This study showed that the FRAIL-NH scale was beneficial for predicting nursing home admission among older adults in the post-acute care setting. Thus, assessment using the FRAIL-NH scale may help to consider preparation and support for life after discharge.

Comparative Analysis of Intrinsic Capacity Impairments, Determinants, and Clinical Consequences in Older Community-Dwellers in Japan and Taiwan: Longitudinal Studies Showing Shared Traits and Distinct Presentations.

OBJECTIVES: Despite the recognized impact of intrinsic capacity (IC) impairment on healthy aging, international comparisons in different sociocultural contexts are scarce. This study aimed to compare IC impairment among community-dwelling older adults in Japan and Taiwan to explore the context of healthy aging in different countries. DESIGN: Comparative observational study. SETTING: National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA) in Japan and Longitudinal Aging Study of Taipei (LAST) in Taiwan. PARTICIPANTS: 794 individuals (age range, 60.0-86.5 years) from NILS-LSA and 1,358 (60.0-96.7 years) from LAST. MEASUREMENTS: IC impairment was evaluated across the domains of locomotion, cognition, vitality, sensory capacity, and psychological well-being. Participants were categorized as having impaired IC or healthy. We investigated associations between IC impairment, falls, and all-cause mortality. RESULTS: IC impairment was present in 54.9% and 37.3% of participants in the NILS-LSA and LAST cohorts, respectively. Male NILS-LSA participants with impaired IC (odds ratio [OR]:1.50, 95% confidence interval [CI]:1.03-2.20), with hearing loss (OR:1.98, 95% CI:1.00-3.90) were more likely to fall. In LAST, impaired locomotion (OR:2.14, 95% CI:1.46-3.14) increased the risk of falls. Men with impaired IC (hazard ratio [HR]; 2.14, 95% CI:1.10-4.15) and visual impairment (HR:2.21, 95% CI:1.15-4.25) and women with impaired psychological well-being (HR:4.94, 95% CI:1.28-18.97) in the NILS-LSA cohort had greater risk for all-cause mortality; however, this was not shown for LAST participants. CONCLUSION: The prevalence and distribution of IC impairment and associated biomarkers differed significantly between participants in Japan and Taiwan. However, the associations with adverse outcomes remained similar, emphasizing the need for tailored interventions for healthy aging.

Brain localization of leucine-rich α2-glycoprotein and its role.

OBJECTIVES: We have previously reported that the level of leucine-rich alpha-2-glycoprotein (LRG) expression is specifically increased in cerebrospinal fluid (CSF) of idiopathic normal pressure hydrocephalus (INPH). The objective of this study is to examine the localization of LRG - the cerebral areas where it is expressed. METHOD: The histological sections of autopsied brain specimens from ten subjects, five adult cases (mean age 43.6 years; range 34-50 years) and five senile cases (mean age 76.0 years; range 67-88 years) were prepared, multistained with antibodies against human LRG, glial fibrillary acidic protein (GFAP), CD31, and aquaporin-4 (AQP4), and reviewed for the expression sites of LRG. RESULTS: Immunostains of GFAP and LRG were compared in standard brain specimens from elderly patients. The results indicated that LRG is distributed throughout the entire brain, with especially high expression in the deep cerebral cortex. In addition, the cells that express LRG showed similar morphology to astrocytes. Double staining of CD31 and LRG revealed a significant expression of LRG in the pericapillary regions. The expression was observed in resident astrocytes, as well as in the capillary vessel to which astrocytic processes grow and adhere. When age-related comparisons were made between senile and adult specimens, LRG expression increased with age. CONCLUSION: LRG expression in resident astrocytes increased with age.

Effective multidisciplinary treatment for ovarian granulosa cell tumor with multiple metastases--a case report.

Ovarian granulosa cell tumor (GCT) is among the ovarian sex-cord stromal tumors that are classified as borderline malignancies. We report a case of GCT with multiple metastases for which multidisciplinary treatment including surgery, chemotherapy and radiotherapy was effective. A 41-year-old woman underwent left salpingo-oophorectomy because of an ovarian tumor in 2004. Final pathology confirmed a granulosa cell tumor adult type, FIGO Stage IC. In 2008, tumorectomy of the lower abdominal wall metastases was also performed. After three cycles of BEP chemotherapy for metastases of the right lung, liver, paraaortic lymph node and rectus, surgical resection was performed in 2009. In 2010, local radiation was performed for the first lumbar vertebral metastasis. Ovarian GCTs exhibit slow growth but if the surgical stage is IC or higher, there is the possibility of recurrence. It is important to treat recurrent tumors with the combination of surgery, chemotherapy, and radiation therapy.

[Aortic valve surgery for autoimmune disease].

Aortic valve disease of autoimmune disease is complicated in pre-, peri- and post-operative care. Recommended care in aortitis, ankylosing spondylitis, systemic lupus erythematosus and rheumatoid arthritis were described. Surgical strategy should be determined depending on basic disease, degree of inflammation and region of disease. Because of the fragile tissue of autoimmune disease patient, modified Bentall procedure is recommended to prevent a prosthetic valve dropping off for aortitis. Perioperatively, it is important to control the inflammation of basic disease, thus a steroid cover is necessary perioperatively. Some complications such as infection, out-of-control of anti-coaguration or gastro-intestinal bleeding should be avoided. Post operation, a strict follow up of prosthetic valve and aorta around suture line and control of autoimmune disease should be achieved.

Impact of Frailty on Dietary Habits among Community-Dwelling Older Persons during the COVID-19 Pandemic in Japan.

BACKGROUND: The coronavirus disease (COVID-19) pandemic has resulted in reduced physical activity and social interaction. These restrictions may have affected the food intake habits of frail older people more than non-frail older people. OBJECTIVES: To investigate the association between frailty and change in dietary habit during the pandemic. DESIGN: Cross-sectional mail survey. SETTING: Community-based. PARTICIPANTS: The study questionnaire was mailed to 4,436 older residents of Higashiura, Aich Japan, who were aged ≥75 years and who did not need care as of April 1, 2020. Of these, 2,738 participants provided complete answers to the questionnaires (75-96 years old, 49.3% males). MEASUREMENTS: The participants' frailty status and changes in food consumption during social isolation were assessed. Frailty status was assessed using the five-item frailty screening index (i.e., weight loss, low physical function, low physical activity, cognition, and exhaustion). Any participant who reported an increase or a decrease in ≥1 of the 12 food categories was defined as having change in dietary habit. Using multivariate logistic regression analysis, the odds ratios (ORs) and 95% confidence intervals (CIs) of frailty for changes in diet were estimated by adjusting for age, sex, BMI, and living alone. In each of the 12 food categories, the proportion of participants with increased and decreased food intake was compared between the groups. RESULTS: Among the participants, 470 (17.2%) were frail, and 1,097 (40.1%) experienced a change in dietary habit under social restriction. The adjusted OR (95% CI) of the frail group for a change in dietary habit was 2.01 (1.63-2.47, p<0.001). Participants with decreased consumption of meat, fish, seaweed and mushroom, and fruits and those with increased consumption of eggs, bread, and noodles tended to be frail. CONCLUSION: The nutritional intervention for frail older people should be strengthened during the pandemic.

Study Protocol of a Comprehensive Activity Promotion Program for the Prevention of Dementia: A Randomized Controlled Trial Protocol.

BACKGROUND: Several technical devices are available to monitor and promote changes in behavior toward higher activity. In particular, smartphones are becoming the primary platform for recognizing human activity. However, the effects of behavior change techniques that promote physical, cognitive, and social activities on incident dementia in older adults remain unknown. OBJECTIVES: This randomized controlled trial aims to examine the effects of behavior change techniques on the prevention of dementia among community-dwelling older adults using a smartphone as a behavior change tool. DESIGN: A randomized controlled trial. SETTING: Community in Japan. PARTICIPANTS: The study cohort comprises 3,498 individuals, aged ≥60 years, randomized into two groups: the smartphone group (n = 1,749) and the control group (n = 1,749). INTERVENTION: The smartphone group will be asked to use smartphone applications for at least 30 minutes daily to self-manage and improve their physical, cognitive, and social activities. The smartphone group will perform 60-minute group walking sessions using application-linked Nordic walking poles with cognitive stimulation twice a week during the intervention period. The walking poles are a dual-task exercise tool that works with a smartphone to perform cognitive tasks while walking, and the poles are equipped with switches to answer questions for simple calculation and memory tasks. The smartphone and control groups will receive lectures about general health that will be provided during the baseline and follow-up assessments. MEASUREMENTS: Incident dementia will be detected using cognitive tests (at baseline, after 15 months, and after 30 months) and by preparing diagnostic monthly reports based on data from the Japanese Health Insurance System. Participants without dementia at baseline who will be diagnosed with dementia over the 30-month follow-up period will be considered to have incident dementia. CONCLUSIONS: This study has the potential to provide the first evidence of the effectiveness of information communication technology and Internet of Things in incident dementia. If our trial results show a delayed dementia onset for self-determination interventions, the study protocol will provide a cost-effective and safe method for maintaining healthy cognitive aging.