Methiothepin downregulates SNAP-23 and inhibits degranulation of rat basophilic leukemia cells and mouse bone marrow-derived mast cells.

In the present study, we found that methiothepin (a nonselective 5-hydroxytryptamine [5-HT] receptor antagonist) inhibited antigen-induced degranulation in rat basophilic leukemia cells and mouse bone marrow-derived mast cells. Although antigen stimulation induces release of histamine and serotonin (5-HT) by exocytosis and mast cells express several types of 5-HT receptor, the detailed role of these receptors remains unclear. Here, pretreatment of cells with methiothepin attenuated increased intracellular Ca2+ concentration, phosphorylated critical upstream signaling components (Src family tyrosine kinases, Syk, and PLCγ1), and suppressed TNF-α secretion via inhibition of Akt (a Ser/Thr kinase activated by PI3K)and ERK phosphorylation. Furthermore, it inhibited PMA/ionomycin-induced degranulation; this finding suggested that methiothepin affected downstream signaling. IκB kinase ß phosphorylates synaptosomal associated protein 23, which regulates the fusion events of the secretory granule/plasma membrane after mast cell activation, resulting in degranulation. We showed that methiothepin blocked PMA/ionomycin-induced phosphorylation of synaptosomal associated protein 23 by inhibiting its interaction with IκB kinase ß. Together with the results of selective 5-HT antagonists, it is suggested that methiothepin inhibits mast cell degranulation by downregulating upstream signaling pathways and exocytotic fusion machinery through mainly 5-HT1A receptor. Our findings provide that 5-HT antagonists may be used to relieve allergic reactions.

[Environmental risks to housing and living arrangements among older survivors of the Great East Japan Earthquake and their relationships with housing type: The RIAS Study].

Objective　Over the course of their lives, people spend most of their time in the home environment. The Community-based Integrated Care System 2018 by the Ministry of Health, Labour and Welfare in Japan declared the importance of "housing" and "living arrangements" as essential elements to enable older adults to live independently and to protect their privacy and dignity in their communities. The present study aims to clarify the relationship between current housing type and "housing" and "living arrangements" among older survivors of the Great East Japan Earthquake (GEJE).Methods　We used data obtained from 3,856 participants, aged 65 years or older, in the Research project for prospective Investigation of health problems Among Survivors of the GEJE (RIAS). Housing types were categorized as follows: "same housing," "temporary housing," "disaster public housing," "new housing" (in a different area), and "others." Healthy housing scores were calculated using a housing health checklist from the Nationwide Smart Wellness Housing Survey in Japan. "Living arrangements" were assessed based on residential status, social network, and social capital. To determine the risks associated with each "housing" and "living arrangement" category, we used multivariate logistic and linear regression models.Results　The number of participants in each housing type was as follows: 2,531 in "same housing," 146 in "temporary housing," 234 in "disaster public housing," 844 in "new housing," and 101 in "others." Compared with those living in "same housing," those living in "disaster public housing," "new housing," and "others" had a significantly higher healthy housing score, whereas those living in "temporary housing" had a lower score. However, with regards to "living arrangements," the number of residents who were living alone was significantly higher among those in "disaster public housing," and those living in "disaster public housing" as well as "new housing" had low social capital compared with those living in "same housing." The likelihood of having a poor social network was substantially higher for those living in "disaster public housing." Sub-scale analyses indicated that "disaster public housing" was associated with less family support, whereas "new housing" was associated with less support from friends.Conclusion　The present results indicate that older survivors-regardless of whether they live in the existing community-find it challenging to establish new social capital and social networks in a new location without the presence of "someone" they knew before the disaster.

Psychological Distress in Responders and Nonresponders in a 5-year Follow-up Health Survey: The RIAS Study.

BACKGROUND: People with poor health or mental conditions are generally unwilling to participate in the health examinations, and no studies have directly examined the relationship of psychological distress among disaster survivors with participation status to date. The present study thus examined psychosocial differences according to the respondent status in a 5-year follow-up survey among participants in the prospective health surveys on survivors of the Great East Japan Earthquake and Tsunami Disaster study in Iwate Prefecture, Japan. METHODS: We analyzed data from 10,203 Japanese survivors aged ≥18 years (mean age, 65.6 years; 38.0% men) and who underwent health examinations at baseline in 2011. Participants were classified into responders and nonresponders according to their 2015 health examination participation status. Psychological distress was evaluated using the Kessler 6 scale and categorized as none, mild, and severe. Multinominal logistic regression was used to examine the risk of psychological distress in relation to participation status. RESULTS: In the 2015 survey, 6,334 of 6,492 responders and 1,686 of 3,356 nonresponders were analyzed. The most common reasons for nonparticipation in the survey were participated in other health examinations, examined at a hospital, and did not have time to participate. Nonresponse in males was associated only with mild psychological stress, whereas nonresponse in females was associated with mild and severe psychological distress. CONCLUSION: Nonresponders in the follow-up survey had a higher risk of psychological distress than responders. Continuous monitoring of the health of nonresponders and responders may help to prevent future health deterioration.

Receptor dynamics regulates actin polymerization state through phosphorylation of cofilin in mast cells.

Aggregation of IgE bound to the high-affinity IgE receptor (FcεRI) by a multivalent antigen induces mast cell activation, while disaggregation of aggregated FcεRI by monomer hapten immediately terminates degranulation mediated by dephosphorylation of Syk and mediates a decrease in intracellular Ca2+ concentration ([Ca2+]i). The actin polymerization state is intimately involved in mast cell activation mediated by FcεRI aggregation. However, the relation between aggregation-disaggregation of FcεRI and actin rearrangement in mast cells is not well understood. The addition of a multivalent antigen rapidly depolymerized actin filaments, while the subsequent addition of monomer hapten rapidly recovered actin polymerization. Whereas cofilin, an actin-severing protein, was temporally dephosphorylated several minutes after a multivalent antigen stimulation and the addition of monomer hapten rapidly increased cofilin phosphorylation level within 30 s. The removal of extracellular Ca2+ instead of monomer hapten addition did not restore cofilin phosphorylation, suggesting that the significant decrease in [Ca2+]i by monovalent hapten was not a critical reason for the actin rearrangement. Additionally, monovalent hapten did not completely reduce [Ca2+]i in mast cells pretreated with jasplakinolide, an inhibitor of actin depolymerization. These results suggest that the multivalent antigen-induced actin depolymerization mediated by cofilin dephosphorylation, and the subsequent addition of monovalent hapten in the F-actin severing state efficiently elicited actin re-polymerization by cofilin phosphorylation.

A decrease in plasma glucose levels is required for increased endogenous glucose production with a single administration of a sodium-glucose co-transporter-2 inhibitor tofogliflozin.

AIM: To investigate whether changes in endogenous glucose production (EGP) and insulin and glucagon levels are elicited by the decrease in plasma glucose (PG) levels induced by the sodium-glucose co-transporter-2 (SGLT2) inhibitor tofogliflozin. MATERIALS AND METHODS: We evaluated EGP in 12 Japanese patients with type 2 diabetes under the conditions of no drugs administered (CON), single administration of the SGLT2 inhibitor tofogliflozin (TOF), and single administration of TOF with adjustment of PG levels with exogenous glucose infusion to mimic changes in PG levels observed with CON (TOF + G). We evaluated changes in EGP and levels of C-peptide and glucagon from baseline to 180 minutes after drug administration. RESULTS: Endogenous glucose production decreased in the CON (-0.22 ± 0.11 mg/kg·min) and TOF + G experiments (-0.31 ± 0.24 mg/kg·min), but not in the TOF experiment (+0.08 ± 0.19 mg/kg·min). The decrease in C-peptide was significantly greater in the TOF experiment (-0.11 ± 0.06 nmol/L) than in the CON (-0.03 ± 0.06 nmol/L) and the TOF + G experiments (-0.01 ± 0.11 nmol/L), while the increase in glucagon was significantly greater in the TOF experiment (+11.1 ± 6.3 pmol/L), but not in the TOF + G experiment (+8.6 ± 7.6 pmol/L) compared to the CON experiment (+5.1 ± 4.3 pmol/L). CONCLUSIONS: These results indicate that the decrease in PG levels induced by SGLT2 inhibitor administration is required for the increase in EGP and decrease in insulin secretion.

Monomer hapten and hapten-specific IgG inhibit mast cell activation evoked by multivalent hapten with different mechanisms.

Aggregation of IgE bound to high affinity IgE receptor (FcεRI) by multivalent antigen induces mast cell activation. Reportedly, disaggregation of aggregated FcεRI immediately terminated degranulation, and formation of co-ligated FcεRI and low affinity IgG receptor FcγRIIB blocked degranulation by inhibitory signal via SH2-containing inositol 5'-phosphatase 1 (SHIP1) phosphorylation. However, their molecular mechanisms to inhibit mast cell activation have been unclear in detail. Herein, we found that addition of excess monomeric hapten (TNP-alanine) to multivalent antigen (TNP-OVA)-activated rat basophilic leukemia cells and mouse bone marrow-derived mast cells induced immediate and transient Syk dephosphorylation, which was previously phosphorylated by TNP-OVA addition. Syk dephosphorylation correlated to rapidly decreased intracellular Ca2+ concentrations ([Ca2+ ]i ), terminated degranulation, and suppressed cytokine production through inhibition of Akt and ERK phosphorylation. Addition of hapten-specific IgG monoclonal antibody (anti-TNP IgG1) to activated mast cells induced translocation of SHIP1 to the plasma membrane and its phosphorylation, indicating that co-ligation of FcεRI and FcγRIIB after FcεRI aggregation can lead to SHIP1 activation. SHIP1 phosphorylation led to gradually decreased [Ca2+ ]i , weak inhibition of degranulation, and strong inhibition of cytokine production. Our findings clearly show the inhibitory mechanism of cell function in activated mast cells by operating Fc receptor crosslinking.

Onset and remission of common mental disorders among adults living in temporary housing for three years after the triple disaster in Northeast Japan: comparisons with the general population.

BACKGROUND: People living in temporary housing for long periods after a disaster are at risk of poor mental health. This study investigated the post-disaster incidence and remission of common mental disorders among adults living in temporary housing for the 3 years following the 2011 Great East Japan Earthquake. METHODS: Three years after the disaster, face-to-face interviews were conducted with 1089 adult residents living in temporary housing in the disaster area, i.e., the shelter group, and a random sample of 852 community residents from non-disaster areas of East Japan. The World Health Organization Composite International Diagnostic Interview was used to diagnose DSM-IV mood, anxiety, and alcohol use disorders. Information on demographic variables and disaster experiences was also collected. RESULTS: Response rates were 49 and 46% for the shelter group and the community residents, respectively. The incidence of mood/anxiety disorder in the shelter group was elevated only in the first year post-disaster compared to that of the general population. The rate of remission for mood and anxiety disorders was significantly lower in the shelter group than in the community residents. The proportion seeking medical treatment was higher in the shelter group. CONCLUSIONS: The onset of common mental disorders increased in the first year, but then levelled off in the following years among residents in temporary housing after the disaster. Remission from incident post-disaster mental disorders was slower in the shelter group than in the general population. Post-disaster mental health service could consider the greater incidence in the first year and prolonged remission of mental disorders among survivors with a long-term stay in temporary housing after a disaster.

Functional subdivisions of the hypothalamus using areal parcellation and their signal changes related to glucose metabolism.

The hypothalamus consists of numerous nuclei, and is regarded as the highest center for various autonomic functions. Although each hypothalamic nucleus implements a distinct function, it remains difficult to investigate the human hypothalamus at the nucleus level. In the present high-resolution functional MRI study, we utilized areal parcellation to discriminate individual nuclei in the human hypothalamus based on areal profiles of resting-state functional connectivity. The areal parcellation detected ten foci that were expected to represent hypothalamic nuclei, and the locations of the foci were consistent with those of the hypothalamic nuclei identified in previous histological studies. Regions of interest (ROI) analyses revealed contrasting brain activity changes following glucose ingestion: decrease in the ventromedial hypothalamic nucleus and increase in the lateral hypothalamic area in parallel with blood glucose increase. Moreover, decreased brain activity in the arcuate nucleus predicted future elevation of blood insulin during the first 10 min after glucose ingestion. These results suggest that the hypothalamic nuclei can putatively be determined using areal parcellation, and that the ROI analysis of the human hypothalamic nuclei is useful for future scientific and clinical investigations into the autonomic functions.

RELATIONSHIP BETWEEN THE EFFECTIVENESS OF INORGANIC IODINE AND THE SEVERITY OF GRAVES THYROTOXICOSIS: A RETROSPECTIVE STUDY.

OBJECTIVE: Inorganic iodine is often used to treat patients with Graves thyrotoxicosis who do not tolerate thionamides due to adverse effects. However, predictors of continued inorganic iodine efficacy have not been fully elucidated. This study aimed to investigate the factors affecting the continued efficacy of potassium iodide (KI) in patients with Graves thyrotoxicosis. METHODS: In this study, among 1,197 patients with Graves disease who were initially treated with thionamides, we retrospectively studied 24 consecutive Japanese patients whose treatment was changed to KI alone due to the adverse effects of thionamides. We divided these patients into 2 groups: patients who had maintained euthyroid function for at least 180 days (nonrecurrence group, n = 11), and patients who had not maintained euthyroid function for 180 days (recurrence group, n = 13). RESULTS: Free triiodothyronine (FT3) and free thyroxine (FT4) levels on the day of changing from thionamides to KI were statistically higher in the recurrence group than in the nonrecurrence group (FT3, 9.3 [range, 5.2-11.6] vs. 3.7 [3.3-4.8] pg/mL, P = .02 and FT4, 3.6 [1.8-4.5] vs. 1.4 [1.2-1.9] ng/dL, P = .02). FT4 levels on the day of drug change were significantly higher in the recurrence group, even after adjusting for thionamide or KI dose. In the recurrence group, the duration of KI effect was inversed correlated with FT3 and FT4 levels on the day of drug change. CONCLUSION: Continued efficacy of KI after thionamides might be inversely correlated with thyrotoxicosis severity on the day of drug change. ABBREVIATIONS: ANOVA = analysis of variance eTV = estimated thyroid volume FT3 = free triiodothyronine FT4 = free thyroxine IQR = interquartile range KI = potassium iodide MMI = thiamazole PTU = propylthiouracil RAIT = radioactive iodine therapy TRAb = TSH receptor antibody TSH = thyroid stimulating hormone.

[Aging and homeostasis. Aging of skeletal muscle.]

With aging, insulin resistance and sarcopenia in skeletal muscle are induced, resulting in skeletal muscle aging. It is suggested that the former is one of the reasons that mitochondrial function decreases with aging, and the latter is due to endocrinologic dysfunction, neurological mechanism, nutritional deficiency and inactivity such as waste are complicatedly involved. Also, as sarcopenia progresses, the amount of physical activity further decreases, and it is also assumed that insulin resistance and sarcopenia progress synergistically. It is suggested that exercise enhances the activity and amount of mitochondria and works preventively against insulin resistance in skeletal muscle accompanying aging and it also works for prevention and amelioration of sarcopenia. On the other hand, as for nutritional supplementation, it has been reported that it works for improving sarcopenia by amino acid ingestion.

Cutoff value of thyroid uptake of (99m)Tc-pertechnetate to discriminate between Graves' disease and painless thyroiditis: a single center retrospective study.

Thyroid uptake of (99m)Tc-pertechnetate is a useful way to determine the cause of thyrotoxicosis. In daily clinical practice, (99m)Tc-pertechnetate uptake is used to discriminate between Graves' disease and painless thyroiditis when clinical information is not enough to make the distinction. However, since the optimal cutoff value of (99m)Tc-pertechnetate uptake has not yet been elucidated, our aim was to determine this value. We recruited patients with thyrotoxicosis in whom (99m)Tc-pertechnetate uptake was measured in clinical settings between 2009 and 2013. Three experienced endocrinologists (who were blinded to the value of (99m)Tc-pertechnetate uptake and initial treatment) diagnosed the cause of thyrotoxicosis based on thyrotropin, free triiodothyronine, free thyroxine, and thyrotropin receptor antibody levels, and by ultrasound findings and using images of thyroid uptake of (99m)Tc-pertechnetate without the actual values. Ninety-four patients diagnosed as having Graves' disease or painless thyroiditis were finally included. According to the diagnosis, the optimal cutoff value of (99m)Tc-pertechnetate uptake was determined by receiver operating characteristics analysis. A cutoff value of 1.0% provided optimal sensitivity and specificity of 96.6% and 97.1%, respectively. Then, its validity was confirmed in 78 patients with confirmed Graves' disease or painless thyroiditis diagnosed at another institute. Applying this cutoff value to the patients with thyrotoxicosis revealed positive and negative predictive values for Graves' disease of 100% and 88.9%, respectively. In conclusion, a cutoff value for (99m)Tc-pertechnetate uptake of 1.0% was useful to discriminate between Graves' disease and painless thyroiditis.

The characteristics of osteoporotic patients in Graves' disease patients newly diagnosed after menopause: a prospective observational study.

Overt hyperthyroidism is associated with reduced bone density. The extent of restoration of reduced bone density caused by hyperthyroidism in postmenopausal Graves' disease (GD) patients has not fully been investigated. We examined 85 newly diagnosed postmenopausal GD patients, and we measured their serum thyroid hormone levels as well as their bone turnover marker levels and the bone mineral density (BMD) of their lumbar spine (LS), both femoral necks (FN), and left distal radius (DR). We prospectively observed the patients for changes in BMD and bone turnover marker levels during a 24-month period after euthyroidism had been established by ATD treatment. The median age of the subjects was 57 years old (range: 50 to 79). 46 (54.1%) patients had osteoporosis. 42 of the 46 osteoporosis patients had low BMD in the DR. The patients with osteoporosis were significantly older, had a significantly lower BMI, and had significantly higher bone turnover marker levels compared to the normal BMD patients. The best predictor of the BMD in the DR was BMD in the FN (ß = 0.40, p < 0.0001). A total of 42 patients were followed up for 24 months after attainment of euthyroidism, and 19 of them were osteoporosis at the first visit. The BMD of the 19 osteoporotic patients had increased by 4.9% in the LS, 11.9% in the FN, and 9.3% in the DR at 24 months. After maintaining a euthyroid state for 24 months by means of ATD treatment, 26% of the osteoporotic patients had recovered from osteoporosis.

Evanescent Hyperechoic Changes After Fine-Needle Aspiration Biopsy of the Thyroid in a Series With a Low Overall Prevalence of Complications.

OBJECTIVES: The purpose of this study was to assess the frequency of and risk factors for fine-needle aspiration biopsy (FNAB)-related complications in Japanese patients with thyroid nodules evaluated by standard FNAB techniques. METHODS: Six hundred fifty-three consecutive Japanese patients with 742 nodules who had undergone FNAB were enrolled. Nodule characteristics were evaluated, and thyroid volumes were measured. Fine-needle aspiration biopsy-related complications were identified on the basis of sonographic findings and patients' conditions after undergoing FNAB. Comparisons of patients' backgrounds and nodule characteristics were made between those with and without complications. RESULTS: The prevalence rates for FNAB-related complications, including acute transient thyroid swelling after FNAB and appearance of anechoic lesions, were 0.13% and 0.94%. In this study, we could not identify risk factors for FNAB-related complications. The sudden appearance of bright hyperechoic foci within the thyroid immediately after biopsy was reported as an FNAB-related unfamiliar appearance in 5 cases. Experimental FNA using resected porcine thyroid tissue suggested that the etiology of the hyperechoic appearance may be artificial air bubbles or reversed flow of aspirated fluid. CONCLUSIONS: Fine-needle aspiration biopsy-related complications are rare if preventive measures are performed and are not specific to Japanese patients with thyroid nodules. The sudden appearance of bright hyperechoic foci may be cause by contamination from air or fluid.

Oral health-related quality of life and related factors among residents in a disaster area of the Great East Japan Earthquake and giant tsunami.

BACKGROUND: Oral health is one of the most important issues for disaster survivors. The aim of this study was to determine post-disaster distribution of oral health-related quality of life (OHRQoL) and related factors in survivors of the Great East Japan Earthquake and Tsunami. METHODS: Questionnaires to assess OHRQoL, psychological distress, disaster-related experiences, and current systemic-health and economic conditions were sent to survivors over 18 years of age living in Otsuchi, one of the most severely damaged municipalities. OHRQoL and psychological distress were assessed using the General Oral Health Assessment Index (GOHAI) and the Kessler Psychological Distress Scale (K6), Japanese version, respectively. Among 11,411 residents, 1,987 returned the questionnaire (response rate, 17.4%) and received an oral examination to determine number of present teeth, dental caries status, and tooth-mobility grade, and to assess periodontal health using the Community Periodontal Index. Relationships between GOHAI and related factors were examined by nonparametric bivariate and multinomial logistic regression analyses using GOHAI cutoff points at the 25(th) and 50(th) national standard percentiles. RESULTS: GOHAI scores were significantly lower in the 50-69-age group compared with other age groups in this study and compared with the national standard score. In bivariate analyses, all factors assessed in this study (i.e., sex, age, evacuation from home, interruption of dental treatment, lost or fractured dentures, self-rated systemic health, serious psychological distress (SPD), economic status, number of teeth, having decayed teeth, CPI code, and tooth mobility) were significantly associated with OHRQoL. Subsequent multinomial logistic regression analyses revealed that participants of upper-middle age, who had received dental treatment before the disaster, who had lost or fractured dentures, and who had clinical oral health problems were likely to show low levels of OHRQoL. In addition, perceived systemic health and SPD were also related with OHRQoL. CONCLUSIONS: OHRQoL of disaster survivors was associated with oral problems stemming from the disaster in addition to factors related to OHRQoL in ordinary times such as clinical oral status and perceived systemic health. Furthermore, SPD was also associated with OHRQoL, which suggests the disaster's great negative impact on both oral and mental health conditions.

Identifying Residents' Health Issues Six Weeks after the Great East Japan Earthquake.

OBJECTIVE: The aim of this study was to identify the characteristics and health issues of residents in need of assistance in a town affected by the Great East Japan Earthquake, six weeks after the disaster, through an outreach initiative. DESIGN AND SAMPLE: A cross-sectional qualitative design was used. Public health nurses conducted comprehensive semi-structured interviews during home visits with residents. A total of 5,082 residents from the affected town. MEASURES: These included demographic information, public records of the extent of the damages, and qualitative interview data to determine the urgency of the necessary interventions. RESULTS: A total of 281 residents needed some kind of assistance and were identified as "requiring early intervention (within two weeks)" or "requiring assistance (within 12 weeks)." The most common health issue requiring early intervention was "interruption of treatment" (25.0%), followed by "need for mental care." The most frequent health issue requiring assistance within 12 weeks was the "need for mental health care" (39.7%), followed by "interruption of treatment," and "need for nursing care." CONCLUSIONS: During a disaster, it is imperative to identify cases requiring early intervention. Home-visit interviews were necessary to identify existing health concerns to prevent the development of more serious health problems.

The tsunami's impact on mortality in a town severely damaged by the 2011 Great East Japan Earthquake.

This study identifies the relationship between tsunami damage and mortality through a demographic pyramid of a town severely damaged by the tsunami following the Great East Japan Earthquake of 11 March 2011. It uses cross-sectional data collection. Volunteers visited all households, including shelters, and asked residents about the whereabouts of family members and neighbours. The information was collated with lists of evacuees and the dead to confirm the whereabouts of all residents about 50 days after the disaster. Demographic pyramids for the whole population based on pre- and post-disaster data were drawn. In all, 1,412 (8.8 per cent) were dead or missing, 60.2 per cent of whom were aged 65 and over and 37.5 per cent aged 75 and over, suggesting that the very old should be located beyond the reach of tsunamis. The mortality rate of children was lower than that in other studies, which may indicate the efficacy of disaster evacuation drills.

Usefulness of a handheld nebulizer in cough test to screen for silent aspiration.

Cough test to screen for silent aspiration (SA) was reported, and the effectiveness was excellent. However, the device was rather large so that the portability was poor. So, the purpose of this study is to investigate the usefulness of a handheld nebulizer for the test and verify the reproducibility of the method. The subjects were 160 patients who were suspected of having dysphagia and underwent videofluorography (VF) or videoendoscopy (VE). They inhaled 1.0 % citric acid-physiologic saline orally for 1 min using a handheld nebulizer, and the examiner observed the number of coughs: more than five coughs was considered as negative (normal), while less than four coughs was regarded as positive. Among the subjects, 70 patients administered the cough test and VF or VE twice or more at some intervals. The k coefficient was calculated in reproducibility. Using the results of the VF or VE examination as the standards, for SA detection, the sensitivity was 0.86, specificity was 0.71, positive predictive value was 0.53, and negative predictive value was 0.93. The k coefficient was 0.79. In conclusion, the handheld nebulizer was useful in the cough test to screen for SA. Furthermore, satisfactory reproducibility was shown.

Changes in physical activity during the year after the Great East Japan Earthquake and future frailty in older survivors.

AIM: This study examines whether changes in physical activity (PA) during the first year after the Great East Japan Earthquake and Tsunami (2011-2012) contributed to preventing the onset of future frailty among older survivors of the disaster. METHODS: This study tracked 2561 physically active Japanese survivors aged ≥ 65 years (43.6% men; mean age 72.9 years) who had completed self-administered questionnaires in 2011 and 2012. PA levels for participants were classified into four categories based on ≥23 and <23 metabolic equivalent hours/week in 2011 and 2012: "consistently low," "decreasing," "increasing," and "consistently high." Frailty was defined as a Kihon Checklist score ≥ 5, which is used in the long-term care insurance system in Japan. Hazard ratios were calculated for the onset of frailty using a Cox proportional hazards model that fitted the proportional sub-distribution hazards regression model with weights for competing risks of death. RESULTS: From 2012 to 2018, 283 men and 490 women developed frailty. Men with consistently high or increasing PA during the first year after the disaster had a lower risk of frailty. Furthermore, even increasing PA by walking for just 30 min/day prevented future frailty in men; however, this association between a change in PA and the decreased risk of frailty was not observed in women. CONCLUSIONS: Older men who remained physically active or resumed PA at an early stage and at a low intensity, even after being physically inactive owing to the disaster, were able to prevent future frailty. Geriatr Gerontol Int 2024; 24: 563-570.

A Short-Term High-Fat Diet Worsens Insulin Sensitivity with Changes in Metabolic Parameters in Non-Obese Japanese Men.

A short-term high-calorie high-fat diet (HCHFD) impairs insulin sensitivity in non-obese South Asian but not Caucasian men; however, the effect of short-term HCHFD on insulin sensitivity in East Asians is unknown. We recruited 21 healthy non-obese Japanese men to evaluate metabolic parameters and gut microbiota before and after 6-day HCHFD consisting of a regular diet plus a 45% energy excess with dairy fat supplementation. We evaluated tissue-specific insulin sensitivity and metabolic clearance rate of insulin (MCRI) using a two-step hyperinsulinemic euglycemic clamp, glucose tolerance using the glucose tolerance test, and measured ectopic fat in muscle and the liver using ¹H-magnetic resonance spectroscopy. The primary outcome of this study was insulin sensitivity measured by the clamp study. The secondary/exploratory outcomes were other metabolic changes. After HCHFD, levels of circulating lipopolysaccharide binding protein (LBP), a marker of endotoxemia, increased by 14%. In addition, intramyocellular lipid levels in the tibialis anterior and soleus and intrahepatic lipid levels increased by 47%, 31%, and 200%, respectively. Insulin sensitivity decreased by 4% in muscle and 8% in liver. However, even with reduced insulin sensitivity, glucose metabolism was maintained by increased serum insulin concentrations due to lower MCRI and higher endogenous insulin secretion during the clamp. Glucose levels during the meal tolerance test were comparable before and after HCHFD. In conclusion, short-term HCHFD impaired insulin sensitivity in the muscle and livers of non-obese Japanese men with increased LBP and ectopic fat accumulation. Elevated insulin levels from modulated insulin secretion and clearance might contribute to the maintenance of normal glucose metabolism during the clamp and meal tolerance test.

Sarcopenic obesity is associated with cognitive impairment in community-dwelling older adults: The Bunkyo Health Study.

BACKGROUND & AIMS: Coexistence of obesity and decreased muscle strength, defined as sarcopenic obesity, is often observed in the older adults. The present study investigated whether sarcopenic obesity, defined as reduced handgrip strength and increased body mass index (BMI), is associated with cognitive impairment. METHODS: Study participants include 1615 older adults aged 65-84 years who lived in an urban area of Tokyo, Japan and participated in the Bunkyo Health Study. Mild cognitive impairment (MCI) and dementia were defined based on ≤22 points of Montreal Cognitive Assessment and ≤23 points of the Mine-Mental State Examination, respectively. Handgrip strength was measured using a dynamometer in a standing position. We divided participants into four groups according to their sarcopenia (probable) (handgrip strength <28 kg in men and <18 kg in women) and obesity status (BMI ≥25 kg/m2) as control, obesity, sarcopenia and sarcopenic obesity, and investigated the association between cognitive function, sarcopenia, and obesity status. RESULTS: Mean age was 73.1 ± 5.4 years, and 57.6% of study participants were female. The prevalence of control, obesity, sarcopenia, and sarcopenic obesity was 59.4%, 21.2%, 14.6%, and 4.7%, respectively. The prevalence of MCI and dementia, respectively, was highest in participants with sarcopenic obesity, followed by those with sarcopenia, obesity, and control. After multivariate adjustment, sarcopenic obesity was independently associated with increased odds of MCI and dementia compared with the control (MCI: 2.11 [95% confidence interval, 1.12-3.62]; dementia: 6.17 [2.50-15.27]). CONCLUSIONS: Sarcopenic obesity was independently associated with MCI and dementia among Japanese older adults. Future studies are necessary to clarify the causal relationship.