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Osteoporosis and its related fractures are important public health issues. This study examined the association between the Kessler Psychological Distress Scale (K6) and low bone mass in middle-aged community-dwelling men and women. A crosssectional study was nested in a prospective observational study of 1,101 participants (median age: 57 [49-62] years in men and 58 [50-62] years in women) residing in a rural city in western Japan. Participants were recruited during medical check-ups in 2016 and 2017 from the community-dwelling population. The bone mass of the calcaneus was evaluated using quantitative ultrasound. Of the participants, 56 men (14.9%) and 144 women (19.9%) had a bone mass of less than 70% of the mean of young adults. Univariate analysis revealed that there was a trend toward lower body mass index (BMI) and higher prevalence of low bone mass with an increase in K6 scores in men but not in women. Logistic regression analysis, adjusting for possible confounders (age, BMI, smoking, drinking habits, exercise habits, diabetes, hyperlipidemia, and hypertension), showed significant associations between the K6 scores and low bone mass (odds ratio (OR) = 2.66 for the men with 5 to 12 points of K6, OR = 7.51 for men with ≥ 13 of K6, not for women). We showed an association between psychological distress and low bone mass independent of cofounders among community-dwelling middle-aged men but not women. This suggests that healthy mental health in middle-aged men may be a possible target for the prevention of consequent osteoporosis or fragile bone fractures., Acta medica Nagasakiensia, 66(2), pp.81-86; 2023

Biomedicines, 11(6), art. no. 1572; 2023

Osteoporosis and its related fractures are important public health issues. This study examined the association between the Kessler Psychological Distress Scale (K6) and low bone mass in middle-aged community-dwelling men and women. A crosssectional study was nested in a prospective observational study of 1,101 participants (median age: 57 [49-62] years in men and 58 [50-62] years in women) residing in a rural city in western Japan. Participants were recruited during medical check-ups in 2016 and 2017 from the community-dwelling population. The bone mass of the calcaneus was evaluated using quantitative ultrasound. Of the participants, 56 men (14.9%) and 144 women (19.9%) had a bone mass of less than 70% of the mean of young adults. Univariate analysis revealed that there was a trend toward lower body mass index (BMI) and higher prevalence of low bone mass with an increase in K6 scores in men but not in women. Logistic regression analysis, adjusting for possible confounders (age, BMI, smoking, drinking habits, exercise habits, diabetes, hyperlipidemia, and hypertension), showed significant associations between the K6 scores and low bone mass (odds ratio (OR) = 2.66 for the men with 5 to 12 points of K6, OR = 7.51 for men with ≥ 13 of K6, not for women). We showed an association between psychological distress and low bone mass independent of cofounders among community-dwelling middle-aged men but not women. This suggests that healthy mental health in middle-aged men may be a possible target for the prevention of consequent osteoporosis or fragile bone fractures., Acta medica Nagasakiensia, 66(2), pp.81-86; 2023

Biomedicines, 11(6), art. no. 1572; 2023

To maintain normal level of thyroid hormone, especially for free thyroxine (FT4), individuals with latent thyroid gland damage might have required higher thyroid stimulating hormone (TSH) than those without latent thyroid gland damage. Anti-thyroid peroxidase antibody (TPO-Ab) is a main cause of auto-immune thyroiditis, and therefore euthyroid individuals positive for TPO-Ab might have latent damage to the thyroid gland. Therefore, the association between TSH values and TPO-Ab positivity may be useful to determine the influence of latent thyroid gland damage on requirement of TSH. Furthermore, because latent damage of thyroid might elevate TSH level but not FT4 level, those associations should be observed independent from FT4. This cross-sectional study analyzed 1431 Japanese with normal ranges of free triiodothyronine (FT3) and FT4. Since TPO-Ab is associated with atherosclerosis in euthyroid individuals, cardiovascular risk factors might underlie the association between TPO-Ab and TSH values. After adjusting for FT4 and known cardiovascular risk factors, the adjusted odds ratio (95% confidence interval) of TPO-Ab positivity for logarithmic value of TSH was 1.53 (1.20, 1.95). Essentially the same association was observed when the analysis was restricted to individuals without subclinical hypothyroidism (1.54 [1.15, 2.13]). Euthyroid individuals with latent thyroid gland damage might have increased the requirement of TSH ., Scientific Reports, 13(1), art. no. 14358; 2023

Among euthyroid individuals, having an anti-thyroid peroxidase antibody (TPO-Ab) titer in the normal range (negative) is positively associated with atherosclerosis as evaluated based on carotid intima-media thickness (CIMT). Atherosclerosis is an established risk factor for cardiovascular disease, but no significant association between yearly progression in CIMT and cardiovascular disease has been reported. Therefore, clarifying the association between having a TPO-Ab titer in the normal range and yearly progression in CIMT (i.e., active arterial wall thickening) among euthyroid individuals could help inform strategies for preventing cardiovascular disease. We conducted a prospective study of 1069 Japanese subjects with free triiodothyronine and free thyroxine levels within the normal range. Having a TPO-Ab titer in the normal range was significantly positively associated with baseline atherosclerosis and significantly inversely associated with active arterial wall thickening. After adjusting for known confounding factors, the adjusted odds ratio (OR) and 95% confidence interval (CI) of log (TPO-Ab titer) for baseline atherosclerosis and active arterial wall thickening was 2.16 (1.07, 4.35) and 0.59 (0.37, 0.93), respectively. Since progression in CIMT is a process of aggressive endothelial repair, deficient endothelial repair inhibits active arterial wall thickening. Therefore, high–normal TPO-Ab titers might induce a deficiency in endothelial repair., Journal of Clinical Medicine, 11(3), art. no. 521; 2022

Subclinical hypothyroidism is a condition characterized by a normal range of thyroid hormone [triiodothyronine (T 3) and thyroxine (T 4)] but with an elevated level of thyroid stimulating hormone (TSH) . It is also reported to be associated with hypertension. Since thyroid cysts could have a beneficial effect on the activation of thyroid hormone as reported in our previous study, their presence could influence the association between subclinical hypothyroidism and hypertension. To clarify those associations, a cross-sectional study of 1,724 Japanese within normal range of thyroid hormone (i.e., normal range of free T 3 and free T 4), aged 40-74 years, who participated in an annual health checkup in 2014 was conducted. Among the study population, 98 were diagnosed as having sublicnical hypothyroidism. For participants without a thyroid cyst, hypertension had a significant positive association with subclinical hypothyroidism, while for participants with a thyroid cyst, even though the power could not reach a significant value, an inverse tendency between hypertension and subclinical hypothyroidism was observed. The adjusted odd ratios (ORs) and 95% confidence intervals (CIs) were 1.91 (1.08, 3.37) for participants without thyroid cysts and 0.63 (0.26, 1.55) for participants with thyroid cysts, respectively. The status of thyroid cysts could act as a determining factor in the association between subclinical hypothyroidism and hypertension among participants within normal range of thyroid hormone., Acta medica Nagasakiensia, 65(2), pp.57−62; 2022

The ratio of free triiodothyronine (FT3) to free thyroxine (FT4) (FT3/FT4), a maker of peripheral thyroxin deiodination, could indicate activity of thyroid hormone. Since positive association between subclinical hypothyroidism (SCH) and chronic kidney disease (CKD) was reported, clarifying the association among FT3/FT4, SCH, and CKD could be an efficient tool to make a strategy for preventing CKD. A cross-sectional study with 1724 Japanese with normal thyroid hormone was conducted. Significant positive association between SCH and CKD was observed; the adjusted odds ratio (OR) and 95% confidence interval (95% CI) was 2.23 (1.38, 3.59). Even though, FT3/FT4 was found to be inversely associated with CKD whereas positively associated with SCH; the adjusted ORs and 95% CIs for 1 standard deviation (SD) increment of FT3/FT4 were 0.51 (0.35, 0.74) for CKD and 2.40 (1.34, 4.29) for SCH, respectively. FT3/FT4 was also found to be positively associated with SCH without CKD but not those with CKD; 1 SD increment of FT3/FT4 were 3.44 (1.72, 6.91) for SCH without CKD and 1.11 (0.40, 3.06) for SCH with CKD, respectively. Although further investigation is necessary, present study indicates that higher activity of peripheral thyroxin deiodination might have beneficial association on absence of CKD even among SCH which is positively associated with CKD., Journal of Clinical Medicine, 11(5), art. no. 1269; 2022

Bone mass is tuned by various factors, including aging, menopause, low body weight, and genetic variations. Here, we showed an independent association between a genotype on the fat mass- and obesity-associated FTO gene (#610966 on OMIM) and bone loss after adjusting for age and body mass index (BMI). A cross-sectional study was nested in a prospective observational study of 1,828 participants (median age: 69 [62-76] years in men and 68 [61-75] years in women) residing in a rural city in western Japan (Goto Island study). Participants were recruited during medical checkups in 2014 and 2016 from the community-dwelling population. The bone mass of the calcaneus was evaluated using quantitative ultrasound. The single nucleotide polymorphism (SNP) rs1421085 was genotyped using a hydrolysis probe. The chi-squared test was used to determine whether the variants were in equilibrium in this population. There were differences in medians of BMI among the genotypes (24.3 in CC, 23.0 in CT, and 22.6 in TT, P = 0.01), but not in those of bone mass. There was a significant association between the minor allele (C) and being overweight in a gene dosage-dependent manner (BMI > 25, OR per allele =1.52, 95% CI = 1.07-2.14, P = 0.02 in men, OR = 1.48, 95% CI = 1.16-1.95, P = 0.01 in women). Logistic regression analysis showed a significant protective association in male carriers of the minor allele against low bone mass (QUS T-score less than -2.0) after adjusting for age and BMI in men aged 65-75 years (OR = 0.50, 95% CI = 0.27-0.96, P = 0.036), with no significant association in women.Our study indicated an association between the genetic polymorphism of FTO and bone mass among community-dwelling men aged 65-75 years. The polymorphism may play a role in bone health with higher BMI and other beneficial functions., Acta medica Nagasakiensia, 65(3), pp.77-87; 2022

Height loss starting in middle age is reportedly signifcantly associated with death due to cardiovascular disease. Impaired blood fow is the main pathology in cardiovascular disease. Hematopoietic stem cells such as CD34-positive cells play an important role in maintaining the microcirculation and preventing impaired blood fow by activating endothelial repair and angiogenesis. Therefore, circulating CD34-positive cell count could be associated with height loss. To clarify the association between circulating CD34-positive cell count and height loss, we conducted a follow-up study of 363 Japanese men aged 60–69 years over 2 years. Height loss was defned as being in the highest quartile of height decrease per year. Independent of known cardiovascular risk factors, circulating CD34-positive cell count was signifcantly inversely associated with height loss. The fully adjusted odds ratio (OR) and 95% confdence interval (CI) of height loss for circulating CD34-positive cell count (logarithmic values) was 0.49 (0.32, 0.74). This study suggests that a lower capacity to maintain the microcirculation due to a fewer CD34-positive cells might afect height loss., Scientific Reports, 12(1), art. no. 7175; 2022

Structural arterial stiffness can be evaluated with carotid intima-media thickness (CIMT). Functional arterial stiffness can be evaluated with cardio-ankle vascular index (CAVI). A positive association between CIMT and tooth loss has been reported, but no studies have evaluated the association between CIMT and tooth loss in relation to functional arterial stiffness (functional atherosclerosis). A cross-sectional study of 1235 Japanese individuals aged 40–89 years was conducted. Tooth loss was defined as being in the lowest tertile for the number of remaining teeth (≤20 in men and ≤19 in women). Functional atherosclerosis was defined as CAVI ≥ 9.0. Independent of known confounding factors, CIMT was positively associated with tooth loss only in participants without functional atherosclerosis. Adjusted odds ratios for tooth loss and a 1 standard deviation increment in CIMT were 1.27 (1.04–1.55) for participants without functional atherosclerosis and 0.99 (0.77–1.26) for participants with functional atherosclerosis. CIMT and functional atherosclerosis had a significant effect on tooth loss; the fully adjusted p-value for the interaction on tooth loss was 0.019. Independent of known confounding factors, CIMT is positively associated with tooth loss only in participants without functional atherosclerosis. This finding helps clarify the influence of the progression of arterial stiffness on tooth loss because the progression of structural atherosclerosis might have a beneficial influence on the maintenance of the microcirculation., Journal of Clinical Medicine, 11 (14), art. no. 3993; 2022

Previous studies have reported a close correlation between vascular endothelial growth factor (VEGF), which plays an important role in angiogenesis, and human T-cell leukemia virus 1 (HTLV-1). However, an association between genetic characteristics related to VEGF and HTLV-1 infection has not yet been reported. Because the VEGF polymorphism rs3025039 is inversely associated with serum concentrations of VEGF, we focus on rs3025039 in the present study. To clarify the association between the VEGF polymorphism rs3025039 and HTLV-1 infection, a cross-sectional study of 1924 Japanese individuals aged 60–79 years who participated in general health check-ups was conducted. Using logistic regression, odds ratios (ORs) and 95% confidence intervals (CIs) for HTLV-1 infection in relation to rs3025039 genotype were calculated with adjustment for known confounders. Compared with rs3025039 CC-homozygotes, (T) allele carriers had a significantly lower OR for HTLV-1 infection. The adjusted OR and 95% CI for HTLV-1 infection was 0.70 (0.54–0.91) (p = 0.009). Genetic characteristics related to lower angiogenesis activity might be associated with a lower chance of establishing HTLV-1 infection. Although further investigation is necessary, angiogenesis might play a crucial role in the establishment of HTLV-1 infection., Bioengineering, 9(10), art. no. 527; 2022

Aggressive endothelial repair results in the progression of both structural and functional atherosclerosis, while insufficient endothelial repair worsens functional but not structural atherosclerosis. Aging increases the risk of inadequate endothelial repair. Since low-density lipoprotein cholesterol (LDLc) activates endothelial repair, LDLc may be positively associated with structural atherosclerosis but inversely associated with functional atherosclerosis in older individuals. This cross-sectional study analyzed 1458 participants aged 60 to 79 years. We defined structural atherosclerosis as a carotid intima-media thickness (CIMT) of at least 1.1 mm and functional atherosclerosis as a cardio-ankle vascular index (CAVI) of at least 9.0. LDLc was significantly positively associated with structural atherosclerosis and significantly inversely associated with functional atherosclerosis, independently of known cardiovascular risk factors. For 1 standard increment of LDLc (28 mg/dL for men and 29 mg/dL for women), the odds ratios and 95% confidence intervals after adjustment for known cardiovascular risk factors were 1.28 (1.10, 1.50) for structural atherosclerosis and 0.85 (0.75, 0.96) for functional atherosclerosis. LDLc activates endothelial repair, which results in the development of structural atherosclerosis but maintains endothelial function in older individuals. To evaluate atherosclerosis in clinical practice, the combination of structural and functional assessment of atherosclerosis could be informative., Nutrients, 15(1), art. no. 183; 2022

Height is inversely associated with inflammation that stimulates endothelial repair. In our previous study involving elderly men aged 60–69 years, we found that active arterial wall thickening, which is known as the process of endothelial repair, requires CD34-positive cells. As thyroid hormone regulates CD34-positive cell production and as the absence of thyroid cysts might indicate latent damage in the thyroid, the status of thyroid cysts possibly influences the association between height and active arterial wall thickening. We conducted a 2-year follow-up study of Japanese aged 60–69 years. For participants with thyroid cysts, height was significantly inversely associated with active arterial wall thickening (thyroid function and baseline CIMT adjusted odds ratio of active arterial wall thickening for one increment of standard deviation of height (5.7 cm for men and 4.8 cm for women), 0.66 [0.49, 0.89]), while for those without thyroid cysts, a positive tendency between the two parameters was observed (1.19 [0.96, 1.50]). An inverse association between height and active arterial wall thickening was observed only for elderly participants with thyroid cysts possibly because of a supportive role of thyroid hormone, as the absence of thyroid cysts might indicate latent damage in the thyroid., Biology, 11(12), art. no. 1756; 2022

Structural arterial stiffness can be evaluated with carotid intima-media thickness (CIMT). Functional arterial stiffness can be evaluated with cardio-ankle vascular index (CAVI). A positive association between CIMT and tooth loss has been reported, but no studies have evaluated the association between CIMT and tooth loss in relation to functional arterial stiffness (functional atherosclerosis). A cross-sectional study of 1235 Japanese individuals aged 40–89 years was conducted. Tooth loss was defined as being in the lowest tertile for the number of remaining teeth (≤20 in men and ≤19 in women). Functional atherosclerosis was defined as CAVI ≥ 9.0. Independent of known confounding factors, CIMT was positively associated with tooth loss only in participants without functional atherosclerosis. Adjusted odds ratios for tooth loss and a 1 standard deviation increment in CIMT were 1.27 (1.04–1.55) for participants without functional atherosclerosis and 0.99 (0.77–1.26) for participants with functional atherosclerosis. CIMT and functional atherosclerosis had a significant effect on tooth loss; the fully adjusted p-value for the interaction on tooth loss was 0.019. Independent of known confounding factors, CIMT is positively associated with tooth loss only in participants without functional atherosclerosis. This finding helps clarify the influence of the progression of arterial stiffness on tooth loss because the progression of structural atherosclerosis might have a beneficial influence on the maintenance of the microcirculation., Journal of Clinical Medicine, 11 (14), art. no. 3993; 2022

Previous studies have reported a close correlation between vascular endothelial growth factor (VEGF), which plays an important role in angiogenesis, and human T-cell leukemia virus 1 (HTLV-1). However, an association between genetic characteristics related to VEGF and HTLV-1 infection has not yet been reported. Because the VEGF polymorphism rs3025039 is inversely associated with serum concentrations of VEGF, we focus on rs3025039 in the present study. To clarify the association between the VEGF polymorphism rs3025039 and HTLV-1 infection, a cross-sectional study of 1924 Japanese individuals aged 60–79 years who participated in general health check-ups was conducted. Using logistic regression, odds ratios (ORs) and 95% confidence intervals (CIs) for HTLV-1 infection in relation to rs3025039 genotype were calculated with adjustment for known confounders. Compared with rs3025039 CC-homozygotes, (T) allele carriers had a significantly lower OR for HTLV-1 infection. The adjusted OR and 95% CI for HTLV-1 infection was 0.70 (0.54–0.91) (p = 0.009). Genetic characteristics related to lower angiogenesis activity might be associated with a lower chance of establishing HTLV-1 infection. Although further investigation is necessary, angiogenesis might play a crucial role in the establishment of HTLV-1 infection., Bioengineering, 9(10), art. no. 527; 2022

Height is inversely associated with inflammation that stimulates endothelial repair. In our previous study involving elderly men aged 60–69 years, we found that active arterial wall thickening, which is known as the process of endothelial repair, requires CD34-positive cells. As thyroid hormone regulates CD34-positive cell production and as the absence of thyroid cysts might indicate latent damage in the thyroid, the status of thyroid cysts possibly influences the association between height and active arterial wall thickening. We conducted a 2-year follow-up study of Japanese aged 60–69 years. For participants with thyroid cysts, height was significantly inversely associated with active arterial wall thickening (thyroid function and baseline CIMT adjusted odds ratio of active arterial wall thickening for one increment of standard deviation of height (5.7 cm for men and 4.8 cm for women), 0.66 [0.49, 0.89]), while for those without thyroid cysts, a positive tendency between the two parameters was observed (1.19 [0.96, 1.50]). An inverse association between height and active arterial wall thickening was observed only for elderly participants with thyroid cysts possibly because of a supportive role of thyroid hormone, as the absence of thyroid cysts might indicate latent damage in the thyroid., Biology, 11(12), art. no. 1756; 2022

Aggressive endothelial repair results in the progression of both structural and functional atherosclerosis, while insufficient endothelial repair worsens functional but not structural atherosclerosis. Aging increases the risk of inadequate endothelial repair. Since low-density lipoprotein cholesterol (LDLc) activates endothelial repair, LDLc may be positively associated with structural atherosclerosis but inversely associated with functional atherosclerosis in older individuals. This cross-sectional study analyzed 1458 participants aged 60 to 79 years. We defined structural atherosclerosis as a carotid intima-media thickness (CIMT) of at least 1.1 mm and functional atherosclerosis as a cardio-ankle vascular index (CAVI) of at least 9.0. LDLc was significantly positively associated with structural atherosclerosis and significantly inversely associated with functional atherosclerosis, independently of known cardiovascular risk factors. For 1 standard increment of LDLc (28 mg/dL for men and 29 mg/dL for women), the odds ratios and 95% confidence intervals after adjustment for known cardiovascular risk factors were 1.28 (1.10, 1.50) for structural atherosclerosis and 0.85 (0.75, 0.96) for functional atherosclerosis. LDLc activates endothelial repair, which results in the development of structural atherosclerosis but maintains endothelial function in older individuals. To evaluate atherosclerosis in clinical practice, the combination of structural and functional assessment of atherosclerosis could be informative., Nutrients, 15(1), art. no. 183; 2022

Anti-thyroid peroxidase antibody (TPO-Ab) is revealed to be inversely associated with thyroid cysts among euthyroid population. TPO-Ab causes autoimmune thyroiditis by bolstering thyroid inflammation. Therefore, at least partly, absence of thyroid cysts could indicate latent thyroid damage. Since participants with subclinical hypothyroidism are reported to have higher HbA1c than normal healthy controls, HbA1c could be inversely associated with thyroid cysts through a mechanism reflecting latent thyroid damage. To investigate the association between HbA1c and thyroid cysts among a euthyroid population, a cross-sectional study was conducted on 1,724 Japanese individuals who were within the normal range of thyroid function [i.e., normal range of free triiodothyronine (T3) and free thyroxine (T4)] and aged 40–74 years. Among this study population, 564 were diagnosed with thyroid cysts. Independently of thyroid related hormones [thyroid stimulating hormone (TSH), free T3, and free T4] and known cardiovascular risk factors, HbA1c was found to be significantly inversely associated with the presence of thyroid cysts. This association remained significant even after this analysis was limited to participants within a normal range of TSH. The fully adjusted odds ratios (ORs) of thyroid cysts for 1 standard deviation (SD) increment of HbA1c were 0.84 (0.74, 0.95) for total participants and 0.80 (0.70, 0.92) for participants within a normal range of TSH. Among participants with normal thyroid function, HbA1c was inversely associated with the presence of thyroid cysts. The absence of thyroid cysts and higher levels of HbA1c could indicate the latent functional damage of the thyroid., PLoS ONE, 16(6), art. no. e0253841; 2021

Our recent studies indicate that thyroid cysts have clinical implications. Thyroid cysts could have a positive effect on the supply of thyroid hormones. Both hyperthyroidism and hypothyroidism cause hypertension. Hypothyroidism, but not hyperthyroidism, is a risk factor for atherosclerosis. Therefore, thyroid cysts could be associated with hypertension, and atherosclerosis might influence the association between thyroid cysts and hypertension. To evaluate the clinical significance of thyroid cysts, a cross-sectional study was conducted with 1801 Japanese aged 40–74 years. Thyroid cysts were significantly positively associated with hypertension in participants without atherosclerosis. However, there was a significant inverse association in those with atherosclerosis. The potential confounding factor adjusted odd ratios and 95% confidence intervals (95% CIs) were 1.49 (95% CI 1.17–1.90) for participants without atherosclerosis and 0.49 (95% CI 0.24–0.98) for those with atherosclerosis. The present study demonstrates that thyroid cysts have clinical implications because thyroid cysts support thyroid hormone activity. Our findings provide sufficient evidence to develop a risk assessment for hypertension for the general population, even though further research is required., Scientific reports, 11, art. no. 13922; 2021

Background: High normal levels of thyroid-stimulating hormone (TSH) have been reported to be associated with chronic kidney disease (CKD) among euthyroid individuals. However, there has been only limited research on the association between TSH and proteinuria, a major risk factor for the progression of renal disease. Methods: A cross-sectional study of 1595 euthyroid individuals was conducted. All participants were within the normal range for free triiodothyronine (T3), free thyroxine (T4), and TSH. Analyses were stratified by thyroid cyst status to test the hypothesis that the absence of thyroid cysts, an indicator of latent thyroid damage, is associated with declining ability to synthesis thyroid hormone. Results: For participants with thyroid cysts, a significant inverse association between TSH and proteinuria was observed (adjusted odds ratio (95% confidence intervals) of log-transformed TSH for proteinuria 0.40 (0.18, 0.89)). In participants without thyroid cysts, a significant positive association between those two factors was observed (2.06 (1.09, 3.90)). Conclusions: Among euthyroid individuals in the general population, being in the normal range of TSH was found to have an ambivalent association with proteinuria. Thyroid cyst status could be an effect modifier for those associations., Journal of Physiological Anthropology, 40, art. no. 15; 2021

identifier:Multidisciplinary Respiratory Medicine, 7(1), 48; 2012

Sarcopenia is characterized by a progressive skeletal muscle disorder that involves the loss of muscle mass and low muscle strength, which contributes to increased adverse outcomes. Few studies have investigated the association between chronic infection and sarcopenia. This study aimed to examine the association between human T-cell lymphotropic virus type-1 (HTLV-1) and sarcopenia. We conducted a cross-sectional study and enrolled 2,811 participants aged ? 40 years from a prospective cohort study in Japanese community dwellers during 2017-2019. Sarcopenia was defined as low appendicular skeletal muscle mass and low handgrip strength. The association between HTLV-1 seropositivity and sarcopenia was assessed using multivariable logistic regression. Odds ratio (OR) and 95% confidence interval (CI) of sarcopenia were analysed using HTLV-1 seropositivity.We adjusted for age, sex, body mass index, physical activity, systolic blood pressure, glycated haemoglobin, low-density lipoprotein cholesterol, and smoking and drinking status. Of 2,811 participants, 484 (17.2%) HTLV-1 infected participants were detected. HTLV-1 infection was significantly associated with sarcopenia (adjusted OR 1.46, 95% CI 1.03-2.07, P = 0.034). HTLV-1 was associated with sarcopenia among community-dwelling adults.Active surveillance and early detection of asymptomatic HTLV-1 infection might be beneficial to reinforce countermeasures to inhibit the progress of HTLV infection-associated sarcopenia., Aging, 12(15), pp.15504-15513; 2020

Background: The absence of thyroid cysts may indicate latent thyroid damage, as demonstrated in our previous study. However, the association between the absence of thyroid cysts and latent functional damage of the thyroid is unknown. At low thyroid hormone productivity, which may be associated with latent functional damage of the thyroid, the association between thyroid-stimulating hormone(TSH) and hypertension might be enhanced. Therefore, we evaluated the association between TSH level and hypertension stratified by thyroid cyst status. Methods: We conducted a cross-sectional study of 1724 euthyroid Japanese individuals aged 40?74 years who participated in an annual health checkup in 2014. Results: In the study population, 564 and 686 participants had thyroid cysts and hypertension, respectively. A significant positive association was observed between TSH and hypertension in subjects without a thyroid cyst but not in subjects with thyroid cysts. There was a significant positive association between hypertension and TSH in subjects without a thyroid cyst (odds ratio [OR] 1.27; 95% confidence intervals [CI] 1.01, 1.61) but not in subjects with thyroid cysts (OR 0.79; CI 0.57, 1.09) in the model fully adjusted for known confounding factors. The correlation between the TSH and free triiodothyronine (fee T3) levels (simple correlation coefficient [r] = ? 0.13, p < 0.01) was stronger in the subjects without thyroid cysts than in those with thyroid cysts (r = ? 0.03, p = 0.525). Conclusions: TSH is positively associated with hypertension only in individuals without thyroid cysts. The correlation between the TSH and free T3 levels was stronger in the subjects without thyroid cysts than in those with thyroid cysts. Therefore, the absence of thyroid cysts could be related to the association between TSH level and hypertension, possibly by indicating that the subjects without thyroid cysts had limited thyroid hormone reserves. Therefore, the absence of thyroid cysts could indic, Environmental Health and Preventive Medicine, 25(1), art.no.69; 2020

Anti-thyroid peroxidase antibody (TPO-Ab), which is the known cause of autoimmune thyroid disease, enhances proinflammatory cytokine responses. Since low-grade inflammation is a known risk factor for atherosclerosis, a normal range of TPO-Ab (TPO-Ab negative) could be positively associated with atherosclerosis among participants with normal thyroid function. However, no study reported the association between normal range of TPO-Ab and atherosclerosis among eu-thyroid participants. A cross-sectional study was conducted with 1165 Japanese individuals with normal thyroid function (ie, normal range of free triiodothyronine [free T3] and free thyroxine [free T4]), aged 40 to 74 years, who participated in an annual health checkup in 2014. Among the study population, 115 were diagnosed as having atherosclerosis. A normal range value of TPO-Ab titer is revealed to be positively associated with atherosclerosis; sex, age, thyroid function (free T3 and thyroid-stimulating hormone), and known cardiovascular risk factor adjusted odds ratio and 95% confidence interval of atherosclerosis for logarithmic values of TPO-Ab was 2.23 (1.11, 4.47). When we limited the analysis to participants with normal levels of thyroid-stimulating hormone, this association became slightly stronger (2.65 [1.27,5.51]). Among the eu-thyroid general population, a normal range of TPO-Ab titer is revealed to be positively associated with atherosclerosis. Even though a TPO-Ab titer is not clinically relevant and is not associated with autoimmune thyroid disease, it could influence endothelial remodeling including atherosclerosis., Medicine, 99(38), e22214; 2020

BACKGROUND: Multimorbidity is the presence of two or more chronic diseases and is associated with increased adverse outcomes, including hospitalization, mortality and frequency of use of medical institutions. OBJECTIVE: This study aimed to describe multimorbidity patterns,determine whether multimorbidity was associated with high medical expenditure, and determine whether mental diseases had an interaction effect on this association.METHODS: We conducted a claims data-based observational study. Data were obtained for 7526 individuals aged 0-75 years from a medical claims data set for Goto, Japan, over a 12-month period (2016-17). Annual medical expenditure was divided into quintiles; the fifth quintile represented high medical expenditure. Multimorbidity status was defined as the occurrence of two or more health conditions from 17 specified conditions. Odds ratios (OR) and 95% confidence intervals (CI) for high medical expenditure were calculated by number of comorbidities. RESULTS: In total, 5423 (72.1%) participants had multimorbidity. Multimorbidity was significantly associated with high medical expenditure, even after adjustment for age, sex and income category (OR: 10.36, 95% CI: 7.57-14.19; P < 0.001). Mental diseases had a significant interaction effect on the association between multimorbidity and high medical expenditure (P = 0.001). CONCLUSIONS: Multimorbidity is associated with high medical expenditure in Japan. Mental diseases may contribute to increased medical costs., Family Practice, 37(4), pp.453-458; 2020

Age-related physical changes, such as low-grade inflammation and increased oxidative stress, induce endothelial repair and cause active arterial wall thickening by stimulating the production of CD34+ cells (the principal mediators of atherosclerosis). Despite this, aggressive endothelial repair (progressing atherosclerosis) might cause a wasting reduction in CD34+ cells, which could result in a lower capacity of endothelial repair and hypertension. As yet, no prospective study has clarified the association of circulating CD34+ cells with active arterial wall thickening. We conducted a prospective study of 363 men aged 60?69 years who participated in a general health check-up at least twice from 2014?2017. The circulating CD34+ cell count was significantly positively associated with active arterial wall thickening among subjects without hypertension (n = 236), but not among subjects with hypertension (n = 127). The fully adjusted odds ratios (ORs) of active arterial wall thickening for the logarithmic circulating CD34+ cell count were 1.83 (1.19, 2.84) and 0.69 (0.36, 1.32) for subjects without and with hypertension, respectively. Circulating CD34+ cells are positively associated with active arterial wall thickening in subjects without hypertension. This study demonstrates a means to clarify the mechanisms of endothelial repair in elderly subjects., Scientific Reports, 10(1), art.no.4656; 2020

BACKGROUND: Anti-thyroid peroxidase antibody (TPO-Ab) has been shown to cause autoimmune thyroiditis by inducing a deleterious influence on thyroid hormone synthesis. Further, thyroglobulin, which has an important role in thyroid hormone synthesis, is reported to be high in the fluid from thyroid cysts. Therefore, TPO-Ab could be associated with the presence of thyroid cyst, partly by affecting the activity of thyroid hormone synthesis. METHODS: To investigate the association between TPO-Ab and thyroid cysts, we conducted a cross-sectional study of 1432 Japanese with normal thyroid function [i.e., normal range of free triiodothyronine (free T3) and free thyroxine (free T4)] between the ages of 40 and 74?years, who participated in an annual health check-up. RESULTS: In men, the statistical power did not reach a statistical significance value. Additionally, subjects with TPO-Ab showed lower odds ratios (ORs) of thyroid cysts than those without TPO-Ab. In women, subjects with TPO-Ab showed significantly lower ORs of thyroid cysts than those without TPO-Ab. The fully adjusted ORs were 0.68 (0.40, 1.18) for men and 0.40 (0.27, 0.60) for women. When evaluating the association between logarithmic values of TPO-Ab titer and thyroid cysts in both men and women, a notable inverse correlation was observed. The fully adjusted ORs were 0.68 (0.50, 0.92) for men and 0.68 (0.57, 0.81) for women. CONCLUSION: TPO-Ab titer revealed to be inversely associated with thyroid cysts among Japanese with normal thyroid function. The presence of a thyroid cyst could indicate a lower risk of having TPO-Ab among the general population with normal thyroid function., Environmental health and preventive medicine, 25(1), art.no.7; 2020

Hypertension frequently occurs in subclinical hypothyroidism(SCH).By bolstering thyroid inflammation, anti-peroxidase antibody(TPO-Ab) causes autoimmune thyroiditis, which is one of the most common causes of SCH. Since the absence of thyroid cysts is associated with TPO-Ab (+) based on the indication of latent thyroid damage, we explored the potential mechanism underlying the association among TPO-Ab, SCH, hypertension, and thyroid cysts. A cross-sectional study of 1,483 Japanese aged 40-74 years was conducted. Thyroid cysts were defined as those having a maximum diameter of ? 2.0 mm, containing no solid component. TPO-Ab (+) was positively associated with SCH with hypertension (adjusted odds ratio [OR] and 95% confidence interval [CI], 2.62 [1.40, 4.89]) but not with SCH without hypertension (0.84 [0.37, 1.89]), respectively. Moreover, among participants without thyroid cysts, SCH was positively associated with hypertension (2.15 [1.23, 3.76]) but not among participants with thyroid cysts (0.58 [0.16, 2.16]), respectively. TPO-Ab was positively associated with SCH with hypertension, but not with SCH without hypertension. In addition, status of thyroid cysts might act as a determinant factor on the association between SCH and hypertension. These findings are efficient tools to clarify the background mechanism that underlies SCH., PLoS ONE, 15(10), art.no.e0240198; 2020

Background: Osteoporosis and related fractures, a worldwide public health issue of growing concern, is characterized by compromised bone strength and an increased risk of fracture. Here we show an association between self-reported walking speed and bone mass among community-dwelling postmenopausal Japanese women aged 50 years and older. Design; cross-sectional study: Setting and Participants; The survey population included 1008 postmenopausal women 50?92 years of age residing in rural communities. Methods: Self-reported walking speed was ascertained by asking the participants: “Is your walking speed faster than others of the same age and sex?” to which participants responded “yes (faster)” or “no (moderate/slower).” Calcaneal stiffness index was measured. Results: Women with a faster self-reported walking speed were younger and had a lower BMI, higher stiffness index, and higher grip strength than women with a slower walking speed. Multiple linear regression analysis adjusted for age, BMI, grip strength, comorbidity, current smoking, and alcohol drinking status showed a significant association between faster self-reported walking speed and higher calcaneal stiffness index (p < 0.001). Conclusions: Our findings suggest that questionnaires of walking speed may be useful for predicting bone mass and that a fast self-reported walking may benefit bone health in postmenopausal women., BMC Geriatrics, 20(1), art.no.466; 2020

Objectives: The purpose of this study is to investigate the relationship between medical student readiness for interprofessional learning and interest in community medicine prior to incorporating community-oriented interprofessional education into the curriculum. Methods: A questionnaire was administered to students at Nagasaki University School of Medicine in Japan during each of three consecutive years (N=2244). The Readiness for Interprofessional Learning Scale (RIPLS) was administered in addition to a questionnaire to evaluate interest in community medicine. The Kruskal-Wallis and Steel-Dwass tests were used to determine differences between school years. Correlation between the RIPLS score and interest in community medicine was evaluated with Spearman's rank correlation coefficient. Relationships between RIPLS score and demographic parameters, and interest in community medicine were evaluated with multiple linear regression analysis. Results: Eighty-four percent (1891/2244) of students responded. The RIPLS score was highest in school year 1, followed by year 6, year 5,year 3, and years 4 and 2. Interest in community medicine correlated with the RIPLS score (rs = 0.332, p < 0.001),but less in year 1 (rs = 0.125, p = 0.002) than in other years. RIPLS score was significantly associated with gender, age, school year, interest in community medicine, but not the year that the survey was conducted. Conclusions: Community-oriented interprofessional education has the potential to improve attitudes towards interprofessional learning. When introducing this promising education into the curriculum from year 1, attracting students' interest in community medicine should be considered., International journal of medical education, 11, pp.240-244; 2020

Aims: We previously reported an inverse association between adult height and dyslipidemia in subjects with low, but not high, body mass index (BMI) by elucidating genetic influences. However, the genetic factors that are associated with short stature and dyslipidemia in subjects with a low BMI are unknown. Methods: We conducted a cross-sectional study of 877 elderly Japanese subjects aged ?60 years who underwent a national health check-up in 2014 and 2015. We focused on single nucleotide polymorphism (SNP) rs3782886, since this variant was reported to be associated with metabolic syndrome. Short stature was defined as the lowest 20% of the height distribution (<157.8cm for men and <145.0cm for women), and dyslipidemia was defined by the Japan Atherosclerosis Society (JAS) guidelines as follows: triglycerides (TG) ?150mg/dL and/or low density lipoprotein-cholesterol (LDL) ?140mg/dL, and/or high density lipoproteincholesterol (HDL) <40mg/dL, and/or lipid lowering medication use. Results: Of the study population, 62.3% were major homo, 33.0% were hetero and 4.8% minor homo. With non-minor homo (major homo and hetero) as reference groups, minor homo was significantly positively associated with short stature independent of known cardiovascular risk factors. The multivariable odds ratio (OR) and 95% confidence interval (CI) of short stature for minor homo was 2.23 (1.07, 4.67). Minor homo also showed a significant positive association with dyslipidemia in subjects with a BMI<23kg/m2, 3.20 (1.08, 9.51), but not in those with a BMI?23kg/m2 ,0.77 (0.32, 1.89). Conclusion: SNP rs3782886 is associated with short stature and dyslipidemia in elderly Japanese subjects with a BMI<23kg/m2., Acta medica Nagasakiensia, 62(1), pp.7-14; 2018

Background: Regardless of developments in thoracoscopic esophagectomy (TE), postoperative complications relative to gastric conduit reconstruction are common after esophagectomy. The aim of the present study was to evaluate the predictive factors of major complications related to gastric conduit after TE. Methods: From 2006 to 2015, 75 patients with esophageal cancer who underwent TE were evaluated to explore the predictive factors of major postoperative complications related to gastric conduit. Results: Patients with major complications related to gastric conduit had a significantly longer postoperative hospital stay than patients without these complications (P < 0.01). Multivariate analysis demonstrated that three-field lymph node dissection (3FLND) and high serum levels of creatine phosphokinase (CPK) and C-reactive protein (CRP) at 1 postoperative day (1POD) after TE were significant predictive factors of major complications related to gastric conduit [odds ratio (OR) 5.37, 95% confidence interval (CI) 1.41-24.33, P = 0.02; OR 5.40, 95% CI 1.60-20.20, P < 0.01; OR 5.07, 95% CI 1.47-20.25, P = 0.01, respectively]. The incidence rates of major complications related to gastric conduit for 0, 1, 2, and 3 predictive factors were 5.3%, 18.8%, 58.8%, and 85.7%, respectively (P < 0.01). Conclusions: Two or more factors in 3FLND and the high levels of CPK and CRP at 1POD after TE were identified as the risk model for major complications related to gastric conduit after TE. Trial registration: UMIN Clinical Trials Registry, ID: UMIN000024436, Registered date: Oct/17/2016., BMC Surgery, 18(1), 15; 2018

Background: Asian-specific single nucleotide polymorphism (SNPs) (rs3782886) is reported to be associated with myocardial infarction; sarcopenia is reported to be associated with coronary subclinical atherosclerosis. On the other hand, short stature has been revealed as an independent risk factor for cardiovascular disease. However, no studies have reported on the association between sarcopenia and short stature nor on the impact of rs3782886 on this association. Methods: Since reduced maximum voluntary tongue pressure against the palate (MTP) reflects one aspect of sarcopenia, we conducted a cross-sectional study of 537 community-dwelling elderly Japanese participants aged 60?89 years who had participated in a general health checkup in 2015. Short stature was defined as values at or under the 25th percentile, and reduced MTP was defined as the lowest tertile of the study population (<158.0 cm and <26.5 kPa for men, <145.0 cm and <24.1 kPa for women). Results: Independent of classical cardiovascular risk factors, short stature was revealed to be positively associated with reduced MTP. The adjusted-odds ratio (OR) and 95% confidence interval (CI) of reduced MTP for short stature was 1.87 (1.19, 2.94). We also found that independent of known cardiovascular risk factors, with the non-minor homo of rs3782886 taken as the reference group, the adjusted OR and 95% CI for short stature and reduced MTP of the minor homo allele were 3.06 (1.23, 7.63) and 3.26 (1.33, 8.03), respectively. Conclusion: Short stature is independently associated with reduced MTP, with Asian-specific SNPs possibly playing an important role in this association., Environmental Health and Preventive Medicine, 22, 62; 2017

Age-related disruption of microvascular endothelium exacerbates hypertension and sarcopenia; and atherosclerosis is a well-known biological response to vascular endothelial injury. Therefore, prevalence of atherosclerosis among hypertensive elderly subjects may partly indicate the presence of an appropriate response to endothelial injury. We conducted a cross-sectional study of 795 elderly hypertensive Japanese subjects aged 60-89 years. Since platelet level is an indicator of vascular repair activity, subjects were stratified by platelet counts. No significant association between handgrip strength and subclinical carotid atherosclerosis (carotid intima-media thickness (CIMT) ?1.1mm) was observed for subjects with lower platelet counts, while a significant positive association was observed for subjects with higher platelets. Adjusted odds and 95% confidence intervals of subclinical carotid atherosclerosis for 1 standard deviation increments in handgrip strength were 0.86 (0.61, 1.22) for subjects with lower platelets and 1.82 (1.26, 2.64) for subjects with higher platelets. A positive association between handgrip strength and subclinical carotid atherosclerosis exists in hypertensive elderly subjects with higher, but not lower, platelet counts. These results lead us to speculate that subjects with a beneficial influence on prevention of sarcopenia (maintenance of handgrip strength) may possess the capacity of active endothelial repair that causes atherosclerosis., Oncotarget, 8(41), pp.69362-69369; 2017

CD8+ cytotoxic T lymphocytes (CTLs), which play a major role in the immunological defense against cancer, recognize endogenously produced peptides in the context of MHC class I molecules. We investigated how to induce CD8+ CTL responses against the HER2/neu/c-erbB2 (HER2) oncoprotein often overexpressed in a wide range of human adenocarcinomas. The immunization of BALB/c mice with a syngeneic cell line transduced with HER2 cDNA led to a successful induction of CD8+ CTLs which specifically destroyed HER2-expressing tumor cells. The CTLs recognized the HER2-derived peptide 1 (TYLPTNASL, pos. 63rd-71st amino acid) in the context of MHC class I Kd. The immunization of mice with a truncated HER2 oncoprotein containing 144 amino acids of HER2 (N terminus to 144th amino acid) failed to elicit measurable CTL activity for HER2-expressing target cells. We reconstituted the truncated HER2 protein into a mannan-coated liposome, and complexed the protein with a cholesterol-bearing mannan polysaccharide respectively. Both of these complexes were capable of inducing killer cells specific for HER2-expressing cells in murine model after immunization. These killer cells are Kd restricted CD8+ CTLs which recognize peptide 1. The cholesterol-bearing mannan polysaccharide facilitated the induction of specific CD8+ CTLs by an exogenous HER2 oncoprotein, and may therefore be useful in the development of cancer vaccines., Acta medica Nagasakiensia. 1997, 42(1-2), p.19-24