Relationship between office blood pressure and actual antihypertensive drug use in patients with hypertension following the promulgation of the guidelines for hypertension (JSH2019).

To achieve appropriate blood pressure control in the treatment of hypertension in Japan, this study examined the relationship between office blood pressure and actual antihypertensive drug use in general hospitals following the promulgation of the guidelines for hypertension (JSH2019). This study focused on blood pressure levels and drug use in outpatients on antihypertensive treatment from June to July 2020. The subjects were 2,537 patients classified into four groups based on their medical history, patients with: hypertension only; hypertension and cardiovascular disease; hypertension and dyslipidaemia; and hypertension and diabetes mellitus. The results showed a significant difference in systolic blood pressure (SBP) between patients with hypertension only and those with hypertension and cardiovascular disease (138.3±17.9 mmHg vs 135.6±19.9 mmHg, p<0.05). Regarding actual drug use, it was found that diuretics were prescribed more frequently in patients with hypertension and cardiovascular disease than in those with hypertension alone (15.5% vs 37.9%, p<0.05), even though the number of drugs for hypertension did not differ significantly. In addition, the dose of diuretics was greater only in patients with cardiovascular disease. These results show the actual drug use and blood pressure for each comorbidity. Furthermore, they suggest that the results of antihypertensive treatment may differ by changing the combination and dosage of antihypertensive drugs without changing the number of antihypertensive drugs used. The study also shows the problem of using less diuretics depending on the risk the patient has, and solving the problem may lead to achieving further antihypertensive goals.

Safety of tapering tacrolimus dose in patients with well-controlled anti-acetylcholine receptor antibody-positive myasthenia gravis.

BACKGROUND AND PURPOSE: Tapering immunosuppressants is desirable in patients with well-controlled myasthenia gravis (MG). However, the association between tapering of calcineurin inhibitor dosage and reduction-associated exacerbation is not known. The aim of this study was to clarify the frequency of reduction-associated exacerbation when tacrolimus is tapered in stable patients with anti-acetylcholine receptor antibody-positive MG, and to determine the factors that predict exacerbations. METHODS: We retrospectively analyzed 115 patients in whom tacrolimus dosage was tapered. The reduction-associated exacerbation was defined as the appearance or worsening of one or more MG symptoms <3 months after the reduction. RESULTS: Tacrolimus dosage was successfully tapered in 110 patients (96%) without any exacerbation. Five patients (4%) experienced an exacerbation, but symptoms were reversed in all patients when the tacrolimus dose was increased to the previous maintenance level. No patient developed an MG crisis. The age at onset was significantly earlier (30 vs. 56 years, P = 0.025) and the reduction in dosage was significantly larger (2.0 vs. 1.0 mg/day, P = 0.002) in patients with reduction-associated exacerbation than in those without exacerbation. The cut-off values determined in a receiver-operating characteristic curve analysis were 52 years (sensitivity, 57%; specificity, 100%) for the age at onset and 1.5 mg (sensitivity, 80%; specificity, 100%) for the dose reduction. CONCLUSION: Tapering of tacrolimus was possible in most patients with well-controlled anti-acetylcholine receptor antibody-positive MG. Early age at onset and a large reduction from maintenance dosage were associated with exacerbation. Reductions ≤1.5 mg/day from the maintenance dosage should be considered for patients with late-onset disease.

Differences in pain thresholds elicited by intraoral electrical stimuli between individuals with and without diabetes mellitus.

There is little evidence of sensation in individuals with diabetes mellitus (DM) in the dental research field. We investigated whether pain thresholds (PTs) differ between individuals with and without DM (non-DM; NDM). To this end, we assessed whether PTs obtained from the oral cavity, hands, and feet differed from each other and across groups, and whether PTs differed for the three current frequencies used for testing (2000 Hz, 250 Hz, and 5 Hz). Pain threshold measurements were obtained from the oral mucosa and the tips of the fingers and toes of 56 volunteers, including 21 individuals with DM (12 men and 9 women, average age: 72.1 ± 4.7 years) and 35 NDM individuals (17 males and 18 females, average age: 51.2 ± 23.9 years) using the Neurometer CPT/C® device to deliver electrical stimulation. A single operator obtained PT measurements from around the left greater palatine foramen and from the tip of the left first finger and of the left great toe. Individuals with DM had significantly lower PT values than those without DM. The PT values for the oral cavity, hands, and feet differed significantly from each other (foot > hand, foot > oral cavity, hand > oral cavity). Moreover, there was a significant difference in the PT values for 5 Hz and 2000 Hz, as well as for 250 Hz and 2000 Hz. This study concluded that PT values derived from DM participants are lower than those from NDM participants, although PT measurements varied across regions and with current frequency.

CXCL4 is a novel nickel-binding protein and augments nickel allergy.

BACKGROUND: Nickel (Ni) is the most frequent metal allergen and induces a TH1 -dependent type-IV allergy. Although Ni2+ is considered to bind to endogenous proteins, it currently remains unclear whether these Ni-binding proteins are involved in Ni allergy in vivo. We previously reported the adjuvant effects of lipopolysaccharide (LPS) in a Ni allergy mouse model. As LPS induces a number of inflammatory mediators, we hypothesized that Ni-binding protein(s) are also induced by LPS. OBJECTIVE: The objective of this study was to purify and identify Ni-binding protein(s) from serum taken from LPS-injected mice (referred as LPS serum) and examined the augmenting effects of these Ni-binding protein(s) on Ni allergy in an in vivo model. METHODS: BALB/cA mice were sensitized with an i.p. injection of NiCl2 and LPS. Ten days after sensitization, mice were challenged with NiCl2 by an i.d. injection into ear pinnae. Ni-binding protein(s) were purified by Ni-affinity column chromatography and gel filtration. RESULTS: Lipopolysaccharide serum, but not serum taken from saline-injected mice, augmented ear swelling induced by Ni-allergic inflammation. Ni-binding, but not non-binding fraction, purified from LPS serum augmented Ni-allergic inflammation. Mass spectrometry and Western blotting detected CXCL4 in the active fraction. A batch analysis with Ni-sepharose and a surface plasmon resonance analysis revealed direct binding between CXCL4 and Ni2+ . Recombinant CXCL4 augmented Ni-allergic inflammation and exerted adjuvant effects at the sensitization phase. CONCLUSIONS: These results indicate that CXCL4 is a novel Ni-binding protein that augments Ni allergy at the elicitation and sensitization phases. This is the first study to demonstrate that the Ni-binding protein augments Ni allergy in vivo.

Efficacy and safety of rebamipide liquid for chemoradiotherapy-induced oral mucositis in patients with head and neck cancer: a multicenter, randomized, double-blind, placebo-controlled, parallel-group phase II study.

BACKGROUND: Recent preclinical and phase I studies have reported that rebamipide decreased the severity of chemoradiotherapy-induced oral mucositis in patients with oral cancer. This placebo-controlled randomized phase II study assessed the clinical benefit of rebamipide in reducing the incidence of severe chemoradiotherapy-induced oral mucositis in patients with head and neck cancer (HNC). METHODS: Patients aged 20-75 years with HNC who were scheduled to receive chemoradiotherapy were enrolled. Patients were randomized to receive rebamipide 2% liquid, rebamipide 4% liquid, or placebo. The primary endpoint was the incidence of grade ≥ 3 oral mucositis determined by clinical examination and assessed by central review according to the Common Terminology Criteria of Adverse Events version 3.0. Secondary endpoints were the time to onset of grade ≥ 3 oral mucositis and the incidence of functional impairment (grade ≥ 3) based on the evaluation by the Oral Mucositis Evaluation Committee. RESULTS: From April 2014 to August 2015, 97 patients with HNC were enrolled, of whom 94 received treatment. The incidence of grade ≥ 3 oral mucositis was 29% and 25% in the rebamipide 2% and 4% groups, respectively, compared with 39% in the placebo group. The proportion of patients who did not develop grade ≥ 3 oral mucositis by day 50 of treatment was 57.9% in the placebo group, whereas the proportion was 68.0% in the rebamipide 2% group and 71.3% in the rebamipide 4% group. The incidences of adverse events potentially related to the study drug were 16%, 26%, and 13% in the placebo, rebamipide 2%, and rebamipide 4% groups, respectively. There was no significant difference in treatment compliance among the groups. CONCLUSIONS: The present phase II study suggests that mouth washing with rebamipide may be effective and safe for patients with HNC receiving chemoradiotherapy, and 4% liquid is the optimal dose of rebamipide. TRIAL REGISTRATION: ClinicalTrials.gov under the identifier NCT02085460 (the date of trial registration: March 11, 2014).

Intravenous immunoglobulin contributes to the control of antimelanoma differentiation-associated protein 5 antibody-associated dermatomyositis with palmar violaceous macules/papules.

Autoantibodies to melanoma differentiation-associated protein 5 (MDA5) are associated with a subset of patients with dermatomyositis (DM) who have rapidly progressive interstitial lung disease (RP-ILD) with poor prognosis. Intensive immunosuppressive therapy is initiated before irreversible lung damage can occur; however, there are few lines of evidence for the treatment of RP-ILD. Here, we report three cases of anti-MDA5 antibody-associated DM with RP-ILD in which the patients were treated with combined-modality therapy, including high-dose prednisolone, tacrolimus, intravenous cyclophosphamide and intravenous immunoglobulin (IVIG). In all three cases, serum ferritin levels, which are known to represent the disease activity of RP-ILD, were decreased after IVIG administration. IVIG might contribute to the control of the disease activity of anti-MDA5 antibody-positive DM. Moreover, palmar violaceous macules/papules around the interphalangeal joints, which was observed in all three cases in the incipient stage, might be a useful sign in suggesting a diagnosis of anti-MDA5 antibody-associated DM.

Taste-related sensations in old age.

The sense of taste is important as it allows for assessment of nutritional value, safety and quality of foods as well as for food enjoyment and quality of life. Several factors are suggested to be associated with taste sensitivity, and higher prevalence of taste disorder has been reported among older adults. This review focused on the reported causes and correlates of taste decline in older adults, with the aim to consolidating existing evidence and identifying gaps and limitations. Using a scoping review methodology, we sought relevant literature from the last 20 years. Search terms included taste, gustatory sense, older adults and geriatric. Considered research was limited to reports that involved research participants over 60 years old, papers written in English, and manuscripts published after 1995. We have consolidated available evidences on the influences on taste-related sensations among international cohorts of older adults. Influences can be reflected under the topics of physiological changes in the sensory organs, physiological and behavioural variables related to taste sensation. This review identified three areas of historic and current research endeavour related to studies of taste sensation in older subjects: physiological changes in the sensory organs, factors related to the ageing of the individual and behavioural variables affecting taste-related sensation. Key limitations and gaps in the current literature include notable lack of consideration of potential confounding, mediating and moderating effects, while future research is indicated in the areas of measuring the quality of health and life. As global population ageing accelerates in the coming decades, maintaining taste sensations and sensitivity in older adults will be a key measure to ensuring quality of health and life.

Longitudinal study of factors affecting taste sense decline in old-old individuals.

The sense of taste plays a pivotal role for personal assessment of the nutritional value, safety and quality of foods. Although it is commonly recognised that taste sensitivity decreases with age, alterations in that sensitivity over time in an old-old population have not been previously reported. Furthermore, no known studies utilised comprehensive variables regarding taste changes and related factors for assessments. Here, we report novel findings from a 3-year longitudinal study model aimed to elucidate taste sensitivity decline and its related factors in old-old individuals. We utilised 621 subjects aged 79-81 years who participated in the Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians Study for baseline assessments performed in 2011 and 2012, and then conducted follow-up assessments 3 years later in 328 of those. Assessment of general health, an oral examination and determination of taste sensitivity were performed for each. We also evaluated cognitive function using Montreal Cognitive Assessment findings, then excluded from analysis those with a score lower than 20 in order to secure the validity and reliability of the subjects' answers. Contributing variables were selected using univariate analysis, then analysed with multivariate logistic regression analysis. We found that males showed significantly greater declines in taste sensitivity for sweet and sour tastes than females. Additionally, subjects with lower cognitive scores showed a significantly greater taste decrease for salty in multivariate analysis. In conclusion, our longitudinal study revealed that gender and cognitive status are major factors affecting taste sensitivity in geriatric individuals.

Study of factors related to the reflection abilities of dental trainees.

INTRODUCTION: This study analysed the internal and external factors related to the reflection abilities of dental trainees. PARTICIPANTS AND METHODS: We created transcripts from oral presentations by the dental trainees of Hiroshima University Hospital (n = 35, 2012-2013) at a significant event analysis conference. The reflection depths were compared between the trainees of the university hospital and external clinical combination groups. We determined and statistically analysed the reflection depths. RESULTS: At the end of training, a Mann-Whitney U-test revealed a significant difference in the median reflection depths of the groups (U = 66, W = 342 and P = 0.007). The results of multiple regression analysis indicated a significant relation between the reflection depth and external training completion (P = 0.024). There were no relations with other factors, including gender and academic background. CONCLUSION: Experiences in external clinics create a close connection between the staff and trainees because communities of practice can cause deeper reflections. We need to create small groups in large-scale organisations such as university hospitals. This construct can be adapted not only for Japanese dental trainees but also for global dental and other medical trainees.

Diabatic Mechanisms of Higher-Order Harmonic Generation in Solid-State Materials under High-Intensity Electric Fields.

We theoretically investigate mechanisms of higher-order harmonic generation in solid-state materials under a high-intensity ac electric field. A new theoretical framework presented in this Letter holds the legitimacy of Bloch's theorem even under the influence of the high-intensity electric field and provides an exact treatment of the diabatic processes of Bloch electrons. Utilizing this framework, we first discovered that the diabatic processes, namely, ac Zener tunneling and semimetallization of semiconductors, are key factors for nonperturbative mechanisms of HHG. These mechanisms are classified by the field intensity and could be understood by an extended simple man model based on an analogy between tunnel ionization in gaseous media and Zener tunneling in semiconductors. These conclusions would stimulate the universal understanding of HHG mechanisms in both atomic and solid cases.

Assessment of the calcification of the nuchal ligament and osteophytes of the cervical spine in obstructive sleep apnoea subjects and snorers.

The previous reports suggest that obstructive sleep apnoea (OSA) is related to metabolic syndrome, mineral metabolism disorders and cardiovascular disease. In addition, a possible relationship between obesity and the calcification of ligaments has been implied. However, the potential link between OSA and the calcification of ligaments has not been directly studied. In this present study, to investigate the potential link between OSA and the calcification of ligaments, we examined the prevalence of the calcification of ligaments in OSA patients and the relationship between these findings and OSA severity. Eighty consecutive patients (60 males, 20 females) diagnosed as OSA or a heavy snorer based on full-night polyso-mnography were retrospectively recruited from May 2006 to July 2008. Each patient underwent cephalometric imaging examination before the arrangement of an oral appliance. One calibrated observer (YS) reviewed the cephalometric images for the presence of calcification of the nuchal ligament and osteophytes of the cervical spine. The prevalence of calcification of the nuchal ligament in OSA patients and snorers was 46.3% (males: 52%, females: 30%) There was a significant positive correlation between the severity of OSA (AHI) and the calcification of the nuchal ligament before and after adjusting for BMI. The prevalence of the calcification of the nuchal ligament in OSA subjects and snorers was higher than in previous studies with non-OSA subjects. In addition, it is suggested that the severity of OSA correlates with the presence of calcification of the nuchal ligament.

Factors related to taste sensitivity in elderly: cross-sectional findings from SONIC study.

The sense of taste is important, as it allows for assessment of nutritional value, as well as safety and quality of foods, with several factors suggested to be associated with taste sensitivity. However, comprehensive variables regarding taste and related factors have not been utilised in previous studies for assessments of sensitivity. In the present study, we performed cross-sectional analyses of taste sensitivity and related factors in geriatric individuals who participated in the SONIC Study. We analysed 2 groups divided by age, 69-71 years (young-old, n = 687) and 79-81 years (old-old, n = 621), and performed a general health assessment, an oral examination and determination of taste sensitivity. Contributing variables were selected by univariate analysis and then subjected to multivariate logistic regression analysis. In both groups, females showed significantly better sensitivity for bitter and sour tastes. Additionally, higher cognitive scores for subjects with a fine taste for salty were commonly seen in both groups, while smoking, drinking, hypertension, number of teeth, stimulated salivary flow salt intake and years of education were also shown to be associated with taste sensitivity. We found gender and cognitive status to be major factors affecting taste sensitivity in geriatric individuals.

Taste detection ability of elderly nursing home residents.

Due to the rapid rise of aged populations throughout the world, it is essential to elucidate the cause of taste dysfunction, because it may reduce appetite, leading to inadequate dietary intake. We aimed to compare taste detection ability between dependently and independently living geriatric individuals of nearly the same age with oral status. Forty-three elderly individuals considered to be cognitively eligible and residing in nursing homes in Japan were enrolled (n = 43, 82·3 ± 8·5 years) and were compared with an independently living elderly group (n = 949, 79·9 ± 0·8 years), aiming to compare taste detection ability between dependently and independently living elders of nearly the same age. Information regarding comorbidity and medication was obtained as general health status, and oral status including number of present teeth, denture usage and maximal occlusal force was also noted. In the dependently living group, 69·4%, 14·3%, 16·3% and 8·2% of participants could detect sweet, sour, salty and bitter tastes, respectively, which was significantly lower than the independently living group for each taste (97·9%, 70·8%, 89·6% and 43·8% for sweet, sour, salty and bitter tastes, respectively). The multivariate logistic regression analysis revealed that residing in nursing homes was associated with reduced sensitivity for four different tastes. The diseases and the situation of dependent elders were more likely the cause of the decreased taste sensitivity.

Identification of chemoresistant factors by protein expression analysis with iTRAQ for head and neck carcinoma.

BACKGROUND: Cisplatin and other anticancer drugs are important in the treatment of head and neck squamous cell carcinoma; however, some tumours develop drug resistance. If chemoresistance could be determined before treatment, unnecessary drug administration would be avoided. Here, we investigated chemoresistance factors by comprehensive analyses at the protein level. METHODS: Four human carcinoma cell lines were used: cisplatin-sensitive UM-SCC-23, UM-SCC-23-CDDPR with acquired cisplatin resistance, naturally cisplatin-resistant UM-SCC-81B, and UM-SCC-23/WR with acquired 5-fluorouracil resistance. Extracted proteins were labelled with iTRAQ and analysed by tandem mass spectrometry to identify resistance. Protein expression was confirmed by western blotting and functional analysis was carried out using siRNA. RESULTS: Thirteen multiple-drug resistance proteins were identified, as well as seven proteins with specific resistance to cisplatin, including α-enolase. Differential expression of these proteins in cisplatin-resistant and -sensitive cell lines was confirmed by western blotting. Functional analysis for α-enolase by siRNA showed that cisplatin sensitivity significantly was increased in UM-SCC-81B and slightly in UM-SCC-23-CDDPR but not in UM-SCC-23/WR cells. CONCLUSIONS: We identified proteins thought to mediate anticancer drug resistance using recent proteome technology and identified α-enolase as a true cisplatin chemoresistance factor. Such proteins could be used as biomarkers for anticancer agent resistance and as targets of cancer therapy.

Elevation of interleukin-6 and attenuation of tumor necrosis factor-α during wheelchair half marathon in athletes with cervical spinal cord injuries.

STUDY DESIGN: Nonrandomized study. OBJECTIVES: The purpose of this study was to determine the effects of long and intensive exercise on interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in athletes with cervical spinal cord injuries (CSCI). SETTING: The 30th Oita International Wheelchair Marathon Race. METHODS: Blood samples from six athletes with CSCI and eight athletes with thoracic and lumber spinal cord injuries (SCI) participating in wheelchair half marathon race were collected before the race, immediately after the race and 2 h after the race. IL-6, TNF-α, adrenaline and blood cell counts were measured. RESULTS: Monocyte count remained stable throughout the study in the CSCI group but was significantly high at 2 h after the race in the SCI group. Plasma IL-6 concentrations were significantly elevated immediately after the race in both groups, although the levels in CSCI were significantly lower than in the SCI group. Plasma adrenaline was significantly elevated immediately after the race in the SCI group but recovered at 2 h after the race. In contrast, plasma adrenaline did not change in the CSCI group throughout the study and was significantly lower than in the SCI group. Plasma TNF-α did not change throughout the study in the SCI group compared with a significant decrease at 2 h after the race in the CSCI group. CONCLUSION: Long and intensive exercise increased IL-6 in the CSCI group despite the small muscle mass and lack of sympathetic nervous system. The post-race fall in plasma TNF-α in the CSCI group could be related to the inhibitory effect of rising IL-6 in the presence of normal monocyte count and stable adrenaline level.

Cervical curvature variations in patients with infraocclusion.

The purpose of this study was to observe the variations of cervical curvature in patients with infraocclusion, and to compare this with the controls. In this study, the infraocclusion criteria were defined with the Pr-id as <17 mm on the cephalometric image. The subjects were 32 patients with infraocclusion, and 28 controls which matched the distribution for gender and age. The six points of inquiry were as follows: (i) cervical vertebra height, (ii) neck alignment, (iii) ratio of lower facial height, (iv) vertical dimension of occlusion, (v) cervical angle and (vi) occlusal angle. In over 90% of the patients with infraocclusion, the cervical curvature was classified as straight or kyphosis. Conversely, in 36% of the control subjects, the cervical curvature was classified as lordosis. There was a weak positive correlation between the vertical dimension of occlusion and the cervical curvature in all subjects. In the control group, there was a significant and strong positive correlation between the age and cervical curvature, and a strong negative correlation between age and cervical angle and occlusal angle. Conversely, in the patients with infraocclusion, age was only correlated with the ratio of lower facial height. The prevalence of non-lordosis in the patients with infraocclusion was higher in comparison with the control group in our study, and the previous large-scale study of Japanese. However, there was merely a weak positive correlation between the cervical curvature and the vertical dimension of occlusion.

Effectiveness of a simulated patient training programme based on trainee response accuracy and appropriateness of feedback.

INTRODUCTION: Simulated patients (SPs) need education and training in required skills to be effective resources in education. This study was conducted to examine the effectiveness of an SP training programme based on the accuracy of trainee responses and the appropriateness of their feedback. METHODS: Thirty-two applicants to the training programme and 35 experienced SPs were included in this study. The experienced SPs served as a reference group. The rate of accurate responses and the rate of appropriate feedback were assessed with pre- and post-training tests, and these two outcome measures were compared with those of the experienced SPs. RESULTS: No significant differences were found in trainee response accuracy or appropriateness of feedback between pre- and post-training tests. The response accuracy rate of the trainees on the pre-training test was significantly lower than that of SPs with 1-2 years of experience, whilst there was no significant difference between these SPs and the trainees on the post-training test. CONCLUSIONS: Although our study suggests that more training is needed to improve the skills of SPs, the training programme may contribute to helping trainees reach a novice level in the skill of providing accurate responses. SP training should be encouraged to contribute to the effectiveness of such teaching and to establish the validity of the assessment.

Impact of UCP1 and ß3AR gene polymorphisms on age-related changes in brown adipose tissue and adiposity in humans.

BACKGROUND: Brown adipose tissue (BAT) is involved in the regulation of whole-body energy expenditure and adiposity. The activity and prevalence of BAT decrease with age in humans. OBJECTIVE: To examine the effects of single nucleotide polymorphisms of the genes for uncoupling protein 1 (UCP1) and ß3-adrenergic receptor (ß3AR), key molecules of BAT thermogenesis, on age-related decline of BAT activity and accumulation of body fat in humans. METHODS: One hundred ninety-nine healthy volunteers (20-72 years old (y.o.)) underwent fluorodeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT) after 2-h cold exposure to assess BAT activity. The visceral and subcutaneous fat areas at the abdominal level were estimated from the CT images. They were genotyped for -3826 A/G polymorphism of the UCP1 gene and 64 Trp/Arg mutation of the ß3AR gene. RESULTS: BAT was detected in 88 subjects out of 199 (44%), more in younger (30 y.o., 55%) than older subjects (>40 y.o., 15%). BAT prevalence of older subjects tended to be lower in the UCP1 G/G group than the A allele group (A/A and A/G), and also in the ß3AR Arg allele group (Trp/Arg and Arg/Arg) than the Trp/Trp group. When compared subjects who had two or more base substitutions on the two genes (the 2-4 allele group) with those who had less than two base substitutions (the 0-1 allele group), BAT prevalence was comparable in younger subjects (62% vs 50%) but lower in older subjects (0% vs 24%, P<0.05). Visceral fat area of the 2-4 allele group was higher than that of the 0-1 allele group (P<0.05) in older subjects, but not in younger subjects. CONCLUSION: UCP1 -3826 A/G and ß3AR 64 Trp/Arg substitutions accelerate age-related decrease in BAT activity, and thereby may associate with visceral fat accumulation with age.