Assessment of skeletal muscle using deep learning on low-dose CT images.

The visceral fat area obtained by computed tomography (CT) at the navel level is clinically used as an indicator of visceral fat obesity in Japan. Analysis of skeletal muscle mass using CT images at the navel level may potentially support concurrent assessment of sarcopenia and sarcopenic obesity. The purpose of this study was to assess the performance of deep learning models (DLMs) for skeletal muscle mass measurement using low-dose abdominal CT. The primary dataset used in this study included 11,494 low-dose abdominal CT images at navel level acquired in 7,370 subjects for metabolic syndrome screening. The publicly available Cancer Imaging Archive (TCIA) dataset, including 5,801 abdominal CT images, was used as a complementary dataset. For abdominal CT image segmentation, we used the SegU-net DLM with different filter size and hierarchical depth. The segmentation accuracy was assessed by measuring the dice similarity coefficient (DSC), cross-sectional area (CSA) error, and Bland-Altman plots. The proposed DLM achieved a DSC of 0.992 ± 0.012, a CSA error of 0.41 ± 1.89%, and a Bland-Altman percent difference of -0.1 ± 3.8%. The proposed DLM was able to automatically segment skeletal muscle mass measurements from low-dose abdominal CT with high accuracy.

We Should Pay More Attention to Sex Differences to Predict the Risk of Severe COVID-19: Men Have the Same Risk of Worse Prognosis as Women More Than 10 Years Older.

BACKGROUND: Prioritization for novel coronavirus disease 2019 (COVID-19)-related health policies usually considers age and certain other characteristics, but sex is rarely included, despite the higher risk of severe disease in men. The aim of this study was to compare the impact of sex and age on the severity of COVID-19 by estimating the age difference in years for which the risk for men versus women is the same. METHODS: We analyzed 23,414 Japanese COVID-19 inpatients aged 20-89 years (13,360 men and 10,054 women). We graded the severity of COVID-19 (0 to 5) according to the most intensive treatment required during hospitalization. The risk of grade 2/3/4/5 (non-invasive positive pressure ventilation/invasive mechanical ventilation/extracorporeal membrane oxygenation/death), grade 3/4/5, and separately grade 5 was analyzed using a multiple logistic regression model. RESULTS: The odds ratio (OR) of grades 2/3/4/5, 3/4/5 (primary outcome), and 5 for men relative to women was 2.76 (95% CI, 2.44-3.12), 2.78 (95% CI, 2.42-3.19), and 2.60 (95% CI, 2.23-3.03), respectively, after adjustment for age and date of admission. These risks for men were equivalent to those for women 14.1 (95% CI, 12.3-15.8), 11.2 (95% CI, 9.7-12.8), and 7.5 (95% CI, 6.3-8.7) years older, respectively. CONCLUSION: The risks of worse COVID-19 prognosis (grades 3/4/5) in men were equivalent to those of women 11.2 years older. Reanalyzing data extracted from four previous studies also revealed a large impact of sex difference on the severity of COVID-19. We should pay more attention to sex differences to predict the risk of COVID-19 severity and to formulate public health policy accordingly.

Cross-sectional associations between the types/amounts of beverages consumed and the glycemia status: The Japan Public Health Center-based Prospective Diabetes study.

Background: The associations between the types/amounts of beverages consumed in daily life and measures of the glycemia status were investigated in a Japanese population-based cohort. Methods: Data from the baseline survey of the Japan Public Health Center-based Prospective Diabetes cohort were used. A cross-sectional analysis was performed in 3852 men and 6003 women who were evaluated under the fasting condition. The daily consumptions of coffee, green tea, oolong tea, black tea, soft drinks, fruit juices, or plain water were assessed using a self-reported questionnaire. Multivariable-adjusted linear regression analyses were performed using measures of the glycemia status (fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c) ) as dependent variables and the types/amounts of beverages consumed as the independent variables, to calculate the differences according to the types/amounts of beverages consumed. Results: In the multivariable-adjusted models, coffee consumption of ≥240 mL/day was significantly associated with a change of the FPG level by -1.9 mg/dL in men (p = 0.013) and -1.4 mg/dL in women (p = 0.015), as compared to coffee consumption of 0 mL/day. No significant association of the FPG level was observed with any of the other types/amounts of beverages consumed. On the other hand, significant associations were found between the HbA1c levels and consumption of several types of beverages. Conclusions: High coffee consumption was associated with lower FPG levels in this Japanese population. Some unexpected associations of the HbA1c levels with the consumption of some types of beverages were observed, which need to be further investigated.

Association of a SNP in the IAPP gene and hyperglycemia on ß-cell dysfunction in type 2 diabetes: the Toon Genome Study.

OBJECTIVE: In type 2 diabetes, the significant pathological change in pancreatic islets is amyloid deposits. Its major component is islet amyloid polypeptide (IAPP). The objective of this study was to evaluate the possibility that the effect of the IAPP genotype on ß-cell dysfunction in type 2 diabetes is modified by variations in plasma glucose levels. METHODS: Participants from the Toon Genome Study underwent a 75 g OGTT for the diagnosis of glucose tolerance and the evaluation of insulin secretion. We examined the effect of a SNP, rs77397980, on ß-cell function by analyzing an interaction (statistics) between the IAPP genotype and AUC glucose. RESULTS: The ratio of the C-allele carriers was essentially the same among subjects with normal glucose tolerance, impaired glucose tolerance and diabetes. In subjects with diabetes, along with an increase in AUC glucose, fasting insulin remained constant in the T/T homozygotes and appeared to decrease in the C-allele carriers. A homeostasis model assessment (HOMA)-IR appeared to be increased in the former and decreased in the latter. In subjects with diabetes stratified into cases with higher AUC glucose than the median, fasting insulin and HOMA-IR were lower in the C-allele carriers than in the T/T homozygotes. An interaction between the IAPP genotype and AUC glucose was indicated in the effect on HOMA-IR. CONCLUSIONS: The possibility that the association between IAPP genotype and basal insulin level is modified by variation in plasma glucose, resulting in a decreased basal insulin in type 2 diabetes, cannot be excluded. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13340-021-00523-4.

Smoking and severe illness in hospitalized COVID-19 patients in Japan.

BACKGROUND: The aim of this study was to identify associations between smoking status and the severity of COVID-19, using a large-scale data registry of hospitalized COVID-19 patients in Japan (COVIREGI-JP), and to explore the reasons for the inconsistent results previously reported on this subject. METHODS: The analysis included 17 666 COVID-19 inpatients aged 20-89 years (10 250 men and 7416 women). We graded the severity of COVID-19 (grades 0 to 5) according to the most intensive treatment required during hospitalization. The smoking status of severe grades 3/4/5 (invasive mechanical ventilation/extracorporeal membrane oxygenation/death) and separately of grade 5 (death) were compared with that of grade 0 (no oxygen, reference group) using multiple logistic regression. Results were expressed as odds ratios (OR) and 95% confidence intervals (CI) adjusted for age and other factors considering the potential intermediate effects of comorbidities. RESULTS: Among men, former smoking significantly increased the risk of grade 3/4/5 and grade 5, using grade 0 as a reference group, with age- and admission-date-adjusted ORs (95% CI) of 1.51 (1.18-1.93) and 1.65 (1.22-2.24), respectively. An additional adjustment for comorbidities weakened the ORs. Similar results were seen for women. Current smoking did not significantly increase the risk of grade 3/4/5 and grade 5 in either sex. CONCLUSIONS: The severity of COVID-19 was not associated with current or former smoking per se but with the comorbidities caused by smoking. Thus, smoking cessation is likely to be a key factor for preventing smoking-related disease and hence for reducing the risk of severe COVID-19.

A fundamental study assessing the generalized fitting method in conjunction with every possible coalition of N-combinations (G-EPOC) using the appendicitis detection task of computed tomography.

PURPOSE: Increased use of deep learning (DL) in medical imaging diagnoses has led to more frequent use of 10-fold cross-validation (10-CV) for the evaluation of the performance of DL. To eliminate some of the (10-fold) repetitive processing in 10-CV, we proposed a "generalized fitting method in conjunction with every possible coalition of N-combinations (G-EPOC)", to estimate the range of the mean accuracy of 10-CV using less than 10 results of 10-CV. MATERIAL AND METHODS: G-EPOC was executed as follows. We first provided (2N-1) coalition subsets using a specified N, which was 9 or less, out of 10 result datasets of 10-CV. We then obtained the estimation range of the accuracy by applying those subsets to the distribution fitting twice using a combination of normal, binominal, or Poisson distributions. Using datasets of 10-CVs acquired from the practical detection task of the appendicitis on CT by DL, we scored the estimation success rates if the range provided by G-EPOC included the true accuracy. RESULTS: G-EPOC successfully estimated the range of the mean accuracy by 10-CV at over 95% rates for datasets with N assigned as 2 to 9. CONCLUSIONS: G-EPOC will help lessen the consumption of time and computer resources in the development of computerbased diagnoses in medical imaging and could become an option for the selection of a reasonable K value in K-CV.

Inhibition of transient receptor potential vanilloid type 1 through α2 adrenergic receptors at peripheral nerve terminals relieves pain.

The activation of α2 adrenergic receptors contributes to analgesia not only in the central nervous system but also in the peripheral nervous system. We reported that noradrenaline inhibits the activity of transient receptor potential vanilloid 1 (TRPV1) evoked by capsaicin through α2 receptors in cultured rat dorsal root ganglion (DRG) neurons. However, it is unclear whether activation of TRPV1 expressed in peripheral nerve terminals is inhibited by α2 receptors and whether this phenomenon contributes to analgesia. Therefore, we examined effects of clonidine, an α2 receptor agonist, on several types of nociceptive behaviors, which may be caused by TRPV1 activity, and subtypes of α2 receptors expressed with TRPV1 in primary sensory neurons in rats. Capsaicin injected into hind paws evoked nociceptive behaviors and clonidine preinjected into the same site inhibited capsaicin-evoked responses. This inhibition was not observed when clonidine was injected into the contralateral hind paws. Preinjection of clonidine into the plantar surface of ipsilateral, but not contralateral, hind paws reduced the sensitivity to heat stimuli. Clonidine partially reduced formalin-evoked responses when it was preinjected into ipsilateral hind paws. The expression level of α2C receptor mRNA quantified by real-time PCR was highest followed by those of α2A and α2B receptors in DRGs. α2A and α2C receptor-like immunoreactivities were detected with TRPV1-like immunoreactivities in the same neurons. These results suggest that TRPV1 and α2 receptors are coexpressed in peripheral nerve terminals and that the functional association between these two molecules causes analgesia.

Validation of improved 24-hour dietary recall using a portable camera among the Japanese population.

BACKGROUND: The collection of weighed food records (WFR) is a gold standard for dietary assessment. We propose using the 24-h recall method combined with a portable camera and a food atlas (24hR-camera). This combination overcomes the disadvantages of the 24-h dietary recall method. Our study examined the validity of the 24hR-camera method against WFR by comparing the results. METHODS: Study subjects were 30 Japanese males, aged 31-58 years, who rarely cook and reside in the Tokyo metropolitan area. For validation, we compared the estimated food intake (24hR-camera method) and weighed food intake (WFR method). The 24hR-camera method uses digital photographs of all food consumed during a day, taken by the subjects, and a 24-h recall questionnaire conducted by a registered dietitian, who estimates food intake by comparing the participant's photographs with food atlas photographs. The WFR method involves a registered dietitian weighing each food item prepared for the subject to consume and any leftovers. Food intake was calculated for each food group and nutrient using the 24hR-camera vs. weighed methods. RESULTS: Correlation coefficients between the estimated vs. weighed food intake were 0.7 or higher in most food groups but were low in food groups, such as oils, fats, condiments, and spices. The estimated intake of vegetables was significantly lower for the 24hR-camera method compared to the WFR method. For other food groups, the percentages of the mean difference between estimated vs. weighed food intake were -22.1% to 5.5%, with no significant differences between the methods (except for algae, which had a very low estimated intake). The correlation coefficients between the two methods were 0.774 for energy, and 0.855, 0.769, and 0.763 for the macronutrients, proteins, lipids, and carbohydrates, respectively, demonstrating high correlation coefficients: greater than 0.75. The correlation coefficients between the estimated vs. weighed for salt equivalents and potassium intake were 0.583 and 0.560, respectively, but no significant differences in intake were observed. CONCLUSIONS: The 24hR-camera method satisfactorily estimated the intake of energy and macronutrients (except salt equivalents and potassium) in Japanese males and was confirmed as a useful method for dietary assessment.

A comparison in the ability to detect diabetic retinopathy between fasting plasma glucose and HbA1c levels in a longitudinal study.

Aims: The relationship between HbA1c and diabetic retinopathy is expected to differ between different races. In this study, we verified which of HbA1c and fasting plasma glucose (FPG) is more effective for detecting the diabetic retinopathy longitudinally in a Japanese population. Materials and Methods: The study subjects underwent health examinations twice (including eye test and questionnaire of lifestyle and health) in 2008-2009 (baseline) and in 2012-2013 (4-year follow-up). Both non-DM and DM patients at baseline were included as the participants. Of these participants, who had not been diagnosed with retinopathy at the baseline survey (n = 2427; 2150 men and 277 women) had eye fundus photographs taken four years later (follow-up survey). The odds ratios of incidence of retinopathy according to the eight groups of FPG and HbA1c were estimated using multiple logistic regression analysis adjusted for sex and age. Receiver operator characteristic analysis was used to evaluate each value associated with the presence or absence of retinopathy. Results: The odds ratios (95% confidence intervals) of incidence of retinopathy by HbA1c level categories, in ascending order, were 1.0 (ref.), 5.66 (1.14-28.26), 1.69 (0.24-12.04), 3.03 (0.50-18.28), 1.04 (0.09-11.59), 4.73 (0.78-28.69), 4.12 (0.74-22.85) and 24.47 (5.61-106.75). For both FPG and HbA1c levels, the odds ratio for the development of retinopathy increased linearly with the increases in the levels FPG and HbA1c, and no clear threshold was observed. The AUC values (SE) for FPG and HbA1c were almost the same, at 0.750 (0.046) and 0.732 (0.048). Conclusions: It was clarified that the higher the level of FPG and HbA1c was, the higher the incidence of retinopathy after 4 years was. There was no clear threshold. The detection ability of the incidence of retinopathy was almost the same between FPG and HbA1c, suggesting it is possible to detect the risk of retinopathy by HbA1c only.

A Comparison of the Association of Fasting Plasma Glucose and HbA1c Levels with Diabetic Retinopathy in Japanese Men.

INTRODUCTION: The relationship between HbA1c and diabetic retinopathy is expected to differ between different races. This study was designed to verify whether HbA1c or fasting plasma glucose (FPG) is more effective in detecting diabetic retinopathy in a Japanese population. MATERIALS AND METHODS: The study subjects underwent health examinations between 2008 and 2009 with fasting. Of these participants, we analyzed the data for 2,921 Japanese men who had undergone an ophthalmologic examination. Retinopathy was classified into 7 categories according to a simplified diabetic retinopathy scale. The odds ratios of retinopathy according to the eight groups of FPG and HbA1c were estimated using multiple logistic regression analysis adjusted for age. Receiver operator characteristic analysis was used to evaluate each value associated with the presence or absence of retinopathy. Results and Discussion. The odds ratios (95% CI) of retinopathy for HbA1c level categories, in ascending order, were 1.0 (ref.), 0.88 (0.28-2.75), 1.27 (0.44-3.69), 1.52 (0.48-4.79), 1.89 (0.52-6.85), 2.70 (0.66-11.10), 4.10 (0.80-21.00), and 6.34 (2.37-16.97) where the odds ratios significantly increased with HbA1c ≥ 6.8%. The area under the curve (SE) for FPG and HbA1c was almost the same, at 0.668 (0.043) and 0.680 (0.043), respectively. CONCLUSIONS: It was clarified that the higher the level of HbA1c, the higher the prevalence of retinopathy, and there was no clear threshold. The detection ability of retinopathy was almost the same, suggesting that it is possible to detect the risk of retinopathy by HbA1c only.

Serum 25-hydroxyvitamin D3 and risk of type 2 diabetes among Japanese adults: the Hitachi Health Study.

BACKGROUND & AIMS: Increasing evidence has suggested a protective role of vitamin D on diabetes, but epidemiologic evidence is scarce among Asian populations. Here we prospectively examined the association between serum 25-hydroxyvitamin D3 (25[OH]D3) and type 2 diabetes (T2D) risk in Japanese individuals. METHODS: A nested case-control study was conducted in a biomarker cohort of 4754 employees (baseline age 34-69 years) who had attended in a comprehensive health checkup and donated a blood sample. Diabetes diagnosis was based on plasma glucose, glycated hemoglobin, and self-reporting during the 5-year follow-up. Using density sampling, two controls were randomly matched to each case by sex, age, and date of checkup; 336 cases and 668 controls had serum 25(OH)D3 data. Association between serum 25[OH]D3 and the risk of T2D was assessed using conditional logistic regression analysis. RESULTS: Serum 25(OH)D3 was significantly and inversely associated with T2D risk after adjustment for known risk factors other than BMI (OR [highest vs. lowest serum 25(OH)D3 quartile] = 0.58, 95% CI = 0.36-0.92; P for trend = 0.03). This association was somewhat attenuated after additional adjustment for BMI (OR = 0.65, 95% CI = 0.40-1.08; P for trend = 0.08). The inverse association was more evident among individuals whose blood samples were taken during the darker season (OR = 0.45; P for trend = 0.01). In the highest quartile of 25(OH)D3, progression from prediabetes to T2D was about 37% lower than in the lowest quartile. CONCLUSIONS: Higher circulating 25(OH)D3 was associated with a lower risk of T2D, and this association was stronger among individuals whose blood was taken during the darker season and among those with prediabetes.

Prevalence and associated factors of overweight and obesity among schoolchildren in Hanoi, Vietnam.

BACKGROUND: The prevalence of overweight and obesity (OW/OB) has increased rapidly in Vietnam. This study aimed to elucidate the factors influencing OW/OB among secondary schoolchildren. METHOD: A survey was conducted in January 2014 in four randomly selected state schools in two Hanoi urban districts, and 821 students in grade six (11-12 years old) participated. Definitions of OW/OB followed the World Health Organization standard cut-offs. RESULTS: Overall, 4.1% of children were underweight, 59.7% were normal weight, 17.1% were overweight, and 19.1% were obese. The odds of OW/OB were lowest among children whose parents had college/university degrees [father (aOR =0.65, 95% CI: 0.42-1.00); mother (aOR =0.63, 95% CI: 0.41-0.97)] compared with those whose parents had only a primary education. Children with an OW/OB family history had an increased risk of OW/OB. Other associated factors include parental OW/OB and birth weight (BW). The odds of OW/OB were highest among children with parents with OW/OB [father (aOR =2.022, 95% CI: 1.34-3.04); mother (aOR =2.83, 95% CI: 1.51-5.30)] compared with those with normal-weight parents. Children with both parents having OW/OB [both parents (aOR =6.59, 95% CI: 1.28-33.87) had the highest risk, followed by one parent (aOR =2.22, 95% CI: 1.50-3.27)] and then neither parent having OW/OB. Moreover, high-birth-weight children [BW ≥ 3500 g (aOR =1.52, 95% CI: 1.07-2.15)] had greater odds than did normal-birth-weight children. Children who slept 11 h per day [8-11 h (aOR =0.57, 95% CI: 0.40-0.81) or more (aOR =0.44, 95% CI: 0.22-0.87)] had lower OW/OB odds than those who slept 8 h or less. Children with specific positive lifestyle behaviours had lower risk of OW/OB than those who did not engage in positive lifestyle behaviours. The odds were lower among children who exercised for weight reduction (OR = 0.16, 95% CI: 0.11-0.23), lowered food intake (aOR = 0.12, 95% CI: 0.09-0.17), and added vegetables to their diet (aOR = 0.26, 95% CI: 0.19-0.35). CONCLUSION: The results suggest that parents and children with OW/OB parents or a high BW should be educated to prevent OW/OB at an early stage. Positive lifestyle behaviours should be adopted by the students.

Transmitral inflow wave and progression from paroxysmal to permanent atrial fibrillation in Asian people.

OBJECTIVE: Paroxysmal atrial fibrillation could progress to permanent atrial fibrillation. Whether the transmitral inflow waves could be used to predict progression from paroxysmal atrial fibrillation to permanent atrial fibrillation is unknown. Therefore, we investigated the association between the transmitral inflow waves and progression of paroxysmal atrial fibrillation. METHOD: We performed a retrospective study by analysing clinical and echocardiographic data from 88 patients with paroxysmal atrial fibrillation. We excluded patients who had structural heart disease, significant valvular disease, cardiomyopathy, cardiac device implantation or a left ventricular ejection fraction <50%. RESULT: The patients with progression to permanent atrial fibrillation were more likely to be male and had lower peak A velocity than those without progression. After adjusting for covariates, lower peak A velocity remained the independent predictor of progression to permanent atrial fibrillation (p=0.025). CONCLUSION: The A velocity could be useful for predicting progression to permanent atrial fibrillation in Asian people.

Serum amino acid profiles and risk of type 2 diabetes among Japanese adults in the Hitachi Health Study.

Amino acids have emerged as novel biomarkers for predicting type 2 diabetes (T2D), but the epidemiologic data linking circulating amino acid profiles with T2D are sparse in Asian populations. We conducted a nested case-control study within a cohort of 4,754 nondiabetic Japanese employees who attended a comprehensive health checkup in 2008-2009 and agreed to provide blood samples. During a 5-year follow-up, incident T2D cases were ascertained based on plasma glucose, glycated hemoglobin, and self-report. Two controls matched to each case on sex, age, and the date of serum sampling were randomly selected by using density sampling, resulting in 284 cases and 560 controls with amino acid measures. High concentrations of valine, leucine, isoleucine, phenylalanine, tyrosine, alanine, glutamate, ornithine, and lysine were associated with an increased risk of incident T2D, in a linear manner. High glutamine concentrations were associated with a decreased risk of incident T2D. Further adjustment for the homeostasis model assessment of insulin resistance attenuated these associations. Overall, these amino acids may be novel useful biomarkers in the identification of people at risk of T2D before overt symptoms. Insulin resistance may account for or mediate the relationship between these amino acids and risk of incident T2D.

The fluctuation in sympathetic nerve activity around wake-up time was positively associated with not only morning but also daily glycemic variability in subjects with type 2 diabetes.

AIMS: It is known that autonomic nerve activity (ANA) affects glucose metabolism by regulating the secretion of insulin and glucagon. Sympathetic nerve stimulation results in increased blood glucose levels. ANA also showed a circadian variation, and sympathetic nerve activity was minimal at night and began to rise at arousal. Therefore, a drastic alteration in ANA around wake-up would be associated with glycemic variability (GV) known risk factor for cardiovascular disease. We investigated the relation between ANA around wake-up and either morning or daily GV. METHODS: We simultaneously performed Holter ECG and continuous glucose monitoring system in 41 patients with type 2 diabetes (T2D). ANA was assessed by heart rate variability (HRV) analysis. Delta (Δ) wake-up was defined as the difference between the maximum and minimum value during 1 h before and after wake-up time, before breakfast. RESULTS: Δ of low frequency/high frequency (LF/HF) around wake-up time (Δ LF/HF wake-up) was positively associated with Δ glucose wake-up, standard deviation (SD) glucose wake-up, the mean amplitude of glucose excursions (MAGE24h), and SD glucose24h after adjustment for age, sex, BMI, the duration of diabetes, and the prevalence of diabetic polyneuropathy (ß = 0.47, p = 0.011, ß = 0.48, p = 0.009, ß = 0.54, p = 0.002 and ß = 0.41, p = 0.0025, respectively). No association was found between Δ LF/HFwake-up and either mean blood glucose for 24 h, or HbA1c as parameters of chronic hyperglycemia. CONCLUSIONS: In T2D, the fluctuation in fasting sympathetic nerve activity around wake-up was positively associated with not only morning but also daily GV.

Increased risk of non-AIDS-defining cancers in Asian HIV-infected patients: a long-term cohort study.

BACKGROUND: Data on the long-term risks of non-AIDS defining cancers (NADCs) are limited, especially in Asians. The incidence of NADCs may correlate with the epidemiological trend of cancers or oncogenic infection in each country, and thus the target cancers would be different between Western and Asian countries. We aimed to elucidate the incidence of NADCs and its predictive factors in Asian HIV-infected patients. METHODS: Subjects were HIV-infected patients (n = 1001) periodically followed-up for 9 years on average. NADCs were diagnosed by histopathology and/ or imaging findings. Standardized incidence ratios (SIR) were calculated as the ratio of the observed to expected number of NADCs for comparison with an age-and sex-matched general population. Cox's proportional hazards model was used to estimate hazard ratios (HR). RESULTS: During the median follow-up of 9 years, the 10-year cumulative incidence of NADCs was 6.4%.At NADC diagnosis, half of patients presented at age 40-59 years and with advanced tumor stage. Compared with the age-and sex-matched general population, HIV-infected patients are at increased risk for liver cancer (SIR, 4.7), colon cancer (SIR, 2.1), and stomach cancer (SIR, 1.8). In multivariate analysis, a predictive model for NADCs was developed that included age group (40-49, 50-59, 60-69, and ≥ 70 years), smoker, HIV infection through blood transmission, and injection drug use (IDU), and HBV co-infection. The c-statistic for the NADCs predictive model was 0.8 (95%CI, 0.8-0.9, P < 0.001). The higher 10-year incidence rate of NADCs was associated with increasing prediction score. CONCLUSIONS: Liver and colon cancer risk was elevated in Asian HIV-infected individuals, similar to in Western populations, whereas stomach cancer risk was characteristically elevated in Asian populations. Half of Asian NADC patients were aged 40-59 years and had advanced-stage disease at diagnosis. Periodic cancer screening may be warranted for high-risk subpopulations with smoking habit, HIV infection through blood transmission or IDU, and HBV co-infection, and screening should be started over 40 years of age.

Constitutive activity of transient receptor potential vanilloid type 1 triggers spontaneous firing in nerve growth factor-treated dorsal root ganglion neurons of rats.

Dorsal root ganglion (DRG) neurons cultured in the presence of nerve growth factor (NGF, 100 ng/ml) often show a spontaneous action potential. Underlying mechanisms of this spontaneous firing were examined using the patch clamp technique. The spontaneous firing in the on-cell configuration was abolished by a decrease in the Na+ concentration and by the TRPV1 antagonists capsazepine (10 µM) and BCTC (1 µM). These responses were accompanied by hyperpolarization of the resting potential. The holding current observed in neurons voltage clamped at -60 mV in the whole-cell configuration was significantly larger in the neurons that fired spontaneously, indicating that these neurons had an additional cation conductance that caused depolarization and triggered action potentials. The holding current in the firing neurons was decreased by extracellular Na+ reduction, capsazepine and BCTC. The amplitudes of the capsazepine- or BCTC-sensitive component of the holding current in the spontaneously firing neurons were ten times as large as those recorded in the other neurons showing no spontaneous firing. However, the amplitudes of the current responses to capsaicin (1 µM) were not different regardless of the presence of spontaneous firing or treatment with NGF. These results indicate that chronic NGF treatment of cultured DRG neurons in rats induces a constitutively active cation conductance through TRPV1, which depolarizes the neurons and triggers spontaneous action potentials in the absence of any stimuli. Since NGF in the DRG is reported to increase after nerve injury, this NGF-mediated regulation of TRPV1 may be a cause of the pathogenesis of neuropathic pain.

Neuron-like cells in the chick spinal accessory lobe express neuronal-type voltage-gated sodium channels.

Ten pairs of protrusions, called accessory lobes (ALs), exist at the lateral sides of the avian lumbosacral spinal cord. Histological evidence indicates that neuron-like cells gather in the ALs, and behavioral evidence suggests that the ALs act as a sensory organ of equilibrium during bipedal walking. Recently, using an electrophysiological method, we reported that cells showing Na+ currents and action potentials exist among cells that were dissociated from the ALs. However, it was unclear which isoforms of the voltage-gated sodium channel (VGSC) are expressed in the ALs and whether cells having neuronal morphology in the ALs express VGSCs. To elucidate these points, RT-PCR and immunohistochemical experiments were performed. In RT-PCR analysis, PCR products for Nav 1.1-1.7 were detected in the ALs. The signal intensities of the Nav 1.1 and 1.6 isoforms were stronger than those of the other isoforms. We confirmed that an antibody raised against an epitope peptide of the rat VGSC had cross-reactivity to chick tissues by Western blotting, and we performed immunofluorescence staining using the antibody. The AL contained cells having neuron-like morphology and VGSC-like immunoreactivity at their cytoplasm and/or cell membranes. Filament-like structures showing GFAP-like immunoreactivity infilled intercellular spaces. The VGSC- and GFAP-like immunoreactivities did not overlap. These results indicate that the neuronal isoforms of the VGSC are mainly expressed in the AL and that the neuron-like cells in the ALs express VGSCs. Our findings indicate that AL neurons generate action potentials and send sensory information to the motor systems on the contralateral side of the spinal segment.

Adrenergic receptors inhibit TRPV1 activity in the dorsal root ganglion neurons of rats.

Transient receptor potential vanilloid type 1 (TRPV1) is a polymodal receptor channel that responds to multiple types of stimuli, such as heat, acid, mechanical pressure and some vanilloids. Capsaicin is the most commonly used vanilloid to stimulate TRPV1. TRPV1 channels are expressed in dorsal root ganglion neurons that extend to Aδ- and C-fibers and have a role in the transduction of noxious inputs to the skin into the electrical signals of the sensory nerve. Although noradrenergic nervous systems, including the descending antinociceptive system and the sympathetic nervous system, are known to modulate pain sensation, the functional association between TRPV1 and noradrenaline in primary sensory neurons has rarely been examined. In the present study, we examined the effects of noradrenaline on capsaicin-evoked currents in cultured dorsal root ganglion neurons of the rat by the whole-cell voltage clamp method. Noradrenaline at concentrations higher than 0.1 pM significantly reduced the amplitudes of the inward capsaicin currents recorded at -60 mV holding potential. This inhibitory action was reversed by either yohimbine (an α2 antagonist, 10 nM) or propranolol (a ß antagonist, 10 nM). The α2 agonists, clonidine (1 pM) and dexmedetomidine (1 pM) inhibited capsaicin currents, and yohimbine (1 nM) reversed the effects of clonidine. The inhibitory action of noradrenaline was not seen in the neurons pretreated with pertussis toxin (100 µg/ml for 24 h) and the neurons dialyzed intracellularly with guanosine 5'- [ß-thio] diphosphate (GDPßS, 200 µM), the catalytic subunit of protein kinase A (250 U/ml) or okadaic acid (1 µM). These results suggest that noradrenaline directly acts on dorsal root ganglion neurons to inhibit the activity of TRPV1 depending on the activation of α2-adrenoceptors followed by the inhibition of the adenylate cyclase/cAMP/protein kinase A pathway.

High Serum Phospholipid Dihomo-γ-Linoleic Acid Concentration and Low Δ5-Desaturase Activity Are Associated with Increased Risk of Type 2 Diabetes among Japanese Adults in the Hitachi Health Study.

Background: The association between the circulating fatty acid (FA) composition and type 2 diabetes (T2D) has been reported in Western populations, but evidence is scarce among Asian populations, including Japanese, who consume large amounts of fish.Objective: The objective of the present study was to prospectively examine the association between circulating concentrations of individual FAs and T2D incidence among Japanese adults.Methods: We conducted a nested case-control study in a cohort of 4754 employees, aged 34-69 y, who attended a comprehensive health checkup in 2008-2009 and donated blood samples for the Hitachi Health Study. During 5 y of follow-up, diabetes was identified on the basis of plasma glucose, glycated hemoglobin, and self-report. Two controls matched to each case by sex, age, and date of checkup were randomly chosen by using density sampling, resulting in 336 cases and 678 controls with FA measurements. GC was used to measure the FA composition in serum phospholipids. Cox proportional hazards regression was used to estimate the HRs and 95% CIs after adjusting for potential confounders. We examined the association of T2D risk with 25 different individual and combinations of FAs.Results: T2D risk was positively associated with serum dihomo-γ-linoleic acid concentration (highest compared with the lowest quartile-HR: 1.49; 95% CI: 1.04, 2.11; P-trend = 0.02) and inversely associated with Δ5-desaturase activity (highest compared with the lowest quartile-HR: 0.72; 95% CI: 0.52, 0.99; P-trend = 0.02), independent of body mass index (BMI). There were also inverse associations between T2D risk with serum total n-6 (ω-6) polyunsaturated fatty acids (PUFAs), linoleic acid, and cis-vaccenic acid, but these were attenuated and became nonsignificant after adjustment for BMI. Serum n-3 (ω-3) PUFAs and saturated fatty acids (SFAs) were not associated with T2D risk.Conclusions: T2D risk was associated with circulating concentrations of the n-6 PUFA dihomo-γ-linoleic acid and Δ5-desaturase activity but not with n-3 PUFA or SFA concentrations in Japanese adults.