Risk prediction of inappropriate implantable cardioverter-defibrillator therapy using machine learning.

We aimed to develop machine learning-based predictive models for identifying inappropriate implantable cardioverter-defibrillator (ICD) therapy. Our study included 182 consecutive cases (average age 62.2 ± 4.5 years, 169 men) and employed 14 non-deep learning models for prediction (hold-out method). These models utilized selected electrocardiogram parameters and clinical features collected after ICD implantation. From the feature importance analysis of the best ML model, we established easily calculable scores. Among the patients, 25 (13.7%) experienced inappropriate therapy, and we identified 16 significant predictors. Using recursive feature elimination with cross-validation, we reduced the features to six with high feature importance: history of atrial arrhythmia (Atr-arrhythm), ischemic cardiomyopathy (ICM), absence of diabetes mellitus (DM), lack of cardiac resynchronization therapy (CRT), V3 ST level at J point (V3 STJ), and V5 R-wave amplitudes (V5R amp). The extra-trees classifier yielded the highest area under receiver operating characteristics curve (AUROC; 0.869 on test data). Thus, the Cardi35 score was defined as [+ 5.5*Atr-arrhythm - 1.5*CRT + 1.0*V3STJ + 1.0*V5R - 1.0*ICM - 0.5*DM], which demonstrated a hazard ratio of 1.62 (P < 0.001). A cut-off value of the score + 5.5 showed high AUROC (0.826). The ML approach can yield a robust prediction model, and the Cardi35 score was a convenient predictor for inappropriate therapy.

The Pressor Response to the Drinking of Cold Water and Cold Carbonated Water in Healthy Younger and Older Adults.

Purpose: Water drinking has been proposed for the treatment of orthostatic hypotension because it can increase blood pressure in patients. This study aimed to investigate whether drinking water with a cold or carbonation stimulus would cause a more effective pressor response, and whether it would be greater in older than in younger adults. Methods: We assessed blood pressure and heart rate from non-invasive arterial pressure (a volume-clamp method) and type II electrocardiography in 13 healthy young adults (6 females, 7 males; mean age, 19.9 ± 1.1 years) and nine healthy older adults (all females; mean age, 71.4 ± 4.2 years) who drank 200 mL of cold, cold carbonated, and room temperature water. Results: The pressor response to the drinking of cold and cold carbonated water was greater than that to room temperature water in both younger and older participants (p < 0.05; changes in systolic blood pressure of room temperature water, cold water and cold carbonated water in young: 15.31 ± 9.66, 22.56 ± 11.51 and 32.6 ± 17.98 mmHg, respectively; changes in systolic blood pressure of room temperature water, cold water and cold carbonated water in elderly: 21.84 ± 14.31, 41.53 ± 19.82 and 48.16 ± 16.77 mmHg, respectively). In addition, the pressor response to cold and cold carbonated water was persistent during the recovery period by about 5-10 mmHg (p < 0.05). Furthermore, the pressor response during the drinking and recovery periods was greater in the older than in the younger participants (p < 0.05). Conclusion: Our data suggest that even smaller amounts of water are able to elicit a sustained pressor response, in particular if the water is cold and carbonated. We speculate that the pressor effect may render cold and carbonated water an appropriate first aid method against certain forms of acute hypotension.

Possible association of papillary muscle hypertrophy with the genesis of J-waves.

BACKGROUND: Although J-waves have been known to be associated with vulnerability to ventricular fibrillation, their electrophysiologic mechanism remains to be elucidated. The papillary muscles (PMs) of the left ventricle (LV) have been recognized as the target site of radiofrequency ablation for ventricular arrhythmias. However, the relationship between PM hypertrophy and J-waves has not been investigated. OBJECTIVE: To investigate the electrocardiographic characteristics, including the J-waves, in patients with solitary PM hypertrophy. METHODS: We studied 101 patients with PM hypertrophy without LV hypertrophy (PMH group) and 159 age- and sex-matched control subjects (control group). The parameters of the 12-lead electrocardiogram and the echocardiogram were compared between the two groups. RESULTS: Compared with the control group, the PMH group had significantly higher incidence (15% vs. 33%, p=0.001) and amplitude (0.17±0.06mV vs. 0.28±0.17mV, p<0.01) of J-waves; significantly longer QRS, QTc, and JTc intervals (p=0.0001, p<0.0001, and p<0.05, respectively); significantly greater Sokolow-Lyon index (p<0.001); and significantly greater LV wall thickness and LV mass index (p<0.0001 for each). Multivariate logistic regression analysis showed that only the PM hypertrophy was an independent predictor of the presence of J-waves. CONCLUSION: PM hypertrophy was related to the genesis of J-waves.

Common variants of HNF1A gene are associated with diabetic retinopathy and poor glycemic control in normal-weight Japanese subjects with type 2 diabetes mellitus.

AIM: This study investigated the associations between the common hepatocyte nuclear factor-1A (HNF1A) variants and the risk of diabetic retinopathy (DR) in relation to the glycemic control and weight status. METHODS: A retrospective longitudinal analysis was conducted among 354 Japanese patients with type 2 diabetes mellitus (T2DM) (mean follow-up duration: 5.8±2.5 years). The multivariable-adjusted hazard ratio (HR) for the cumulative incidence of DR was calculated using a Cox proportional hazard model. During the observation period, the longitudinal associations of the HNF1A diplotypes with the risk of DR and the clinical parameters were also analyzed using the generalized estimating equations approach. RESULTS: The combination of risk variants, i.e., rs1169288-C, rs1183910-A and rs2464196-A, was defined as the H1 haplotype. The incidence of DR was higher in the H1/H1 diplotype cases than in the others (HR 2.75 vs. non-H1/non-H1; p=0.02). Only in normal-weight subjects, the risks of DR and poor glycemic control were higher in the H1/H1 diplotype cases than in the others [odds ratio 4.08 vs. non-H1/non-H1, p=0.02; odds ratio 3.03, p=0.01; respectively]. CONCLUSIONS: This study demonstrated that the common HNF1A diplotype of three risk variants may be an independent risk factor for the development of DR resulting from poor glycemic control in normal-weight patients with T2DM. These results need to be replicated in larger and more varied study populations.

Sex Differences in the Renal Function Decline of Patients with Type 2 Diabetes.

Aims. We aimed to investigate the sex differences in the renal function decline among patients with type 2 diabetic mellitus (T2DM), focusing on the differences in the risk factors at early stage of renal dysfunction. Methods. A clinic-based retrospective longitudinal study (follow-up duration: 8.1 ± 1.4 years) was conducted to assess the sex differences in the annual estimated glomerular filtration rate (eGFR) change in 344 (247 male and 97 female) Japanese T2DM patients. The sex differences in the risk factors of annual eGFR decline were subjected to linear regression analyses. Results. The mean annual eGFR change was -3.5 ± 2.7%/year in females and -2.0 ± 2.2%/year in males (P < 0.001). Baseline retinopathy and proteinuria were significantly associated with a larger eGFR decline, irrespective of sex, while HbA1c and LDL-cholesterol levels were significantly associated with an eGFR decline in females only. Interactive effects were observed between sex and the HbA1c, LDL-cholesterol, retinopathy, or proteinuria levels on the annual eGFR decline. Conclusions. The increased susceptibility to poor metabolic control seemed to contribute to a higher risk of renal dysfunction in females with T2DM. Our study highlights the importance of aggressive therapeutic intervention to improve metabolic profiles at early stage, especially in females.

Combined effects of current-smoking and the aldehyde dehydrogenase 2*2 allele on the risk of myocardial infarction in Japanese patients.

Aldehyde dehydrogenase 2 (ALDH2) detoxifies toxic aldehydes, e.g. acetaldehyde in cigarette smoke; however, the interactive effects between smoking status and the ALDH2 genotype on coronary artery disease (CAD) have not been reported. We investigated the effects of smoking status and the ALDH2 genotype, and assessed their interactive and combined effects on the risk of myocardial infarction (MI) or stable angina (SA), including 221 MI and 175 SA subjects and 473 age- and sex-matched controls without CAD. Current-smoking and the ALDH2*2 allele additively increased the risk of MI (adjusted odds ratio 4.54, 95% confidence interval 2.25-9.15), although this combination was not associated with the risk of SA. This combination also increased the peak creatine kinase (CK) level synergistically in the acute MI (AMI) subjects. Moreover, current-smoking was found to be a significant risk factor for an increased peak CK level in the ALDH2*2 allele carriers (B 2220.2IU/L, p=0.008), but not the non-carriers. Additionally, a synergistic effect of this combination on the triglycerides levels was also found in the AMI subjects. These preliminary findings suggest that the combination of current-smoking and the inactive ALDH2*2 allele may increase the risk of MI additively and the infarct size synergistically.

Chronic kidney disease status modifies the association of CYP2C19 polymorphism in predicting clinical outcomes following coronary stent implantation.

INTRODUCTION: There is some controversy regarding the effect of CYP2C19 polymorphism on clinical outcome in patients with dual antiplatelet therapy. Chronic kidney disease (CKD) is associated with increased risk of cardiovascular event, but the association between the possession of CYP2C19 loss-of-function (LOF) alleles and clinical outcome according to the presence of CKD is poorly understood. The aim of this study was to investigate whether CKD status modifies the association of CYP2C19 polymorphism in predicting outcomes in a prospective cohort study. MATERIAL AND METHODS: We enrolled 331 patients following coronary stent implantation. Patients were divided into two groups: CKD (n=154) and non-CKD (n=177). Platelet reactivity and CYP2C19 polymorphism were examined. The subjects were further divided into two groups according to the possession of CYP2C19 LOF alleles: carriers and non-carriers. Patients were followed up and clinical events were evaluated according to CKD and carrier status. RESULTS: The proportion of high platelet reactivity was significantly higher in carriers than in non-carriers in both CKD (42.4% versus 21.7%; P=0.016) and non-CKD groups (34.3% versus 3.7%; P<0.001). In the non-CKD group alone, the incidence of cardiovascular events was significantly higher in carriers than in non-carriers (13.7% versus 1.7%; P=0.013). Kaplan-Meier analysis demonstrated a significantly higher probability of cardiovascular events in carriers than in non-carriers in the non-CKD group (log-rank test: P=0.013) and there was no significant difference in the CKD group (log-rank test: P=0.591). Multivariate analysis identified carriers as an independent predictor of cardiovascular events only in the non-CKD group alone (hazard ratio: 8.048; 95% confidence interval: 1.066 to 60.757; P=0.043). CONCLUSIONS: CYP2C19 polymorphism significantly correlates with clinical outcome in non-CKD patients, and CKD status modifies the association of CYP2C19 polymorphism in predicting clinical outcomes following coronary stent implantation.

Impact of CYP2C19 polymorphism on clinical outcome following coronary stenting is more important in non-diabetic than diabetic patients.

OBJECTIVE: The aim of this study was to examine the impact of CYP2C19 genotype on clinical outcome in coronary artery disease (CAD) patients with or without diabetes mellitus (DM). METHODS: CYP2C19 polymorphism and DM are associated with increased risk of cardiovascular events during antiplatelet therapy following stent implantation. Platelet reactivity during clopidogrel therapy and CYP2C19 polymorphism were measured in 519 CAD patients (males 70%, age 69 years) treated with stent placement. Patients were divided into two groups; DM (n=249), and non-DM (n=270), and clinical events were evaluated according to the carrier state, which included at least one CYP2C19 loss-of-function allele. RESULTS: The level of platelet reactivity and incidence of cardiovascular events were significantly different between Carriers and non-Carriers of the non-DM (platelet reactivity: 4501+/-1668 versus 3691+/-1714AU min, P<0.01; events, 32/178 versus 2/92, P<0.01, respectively), however, there was no difference in clinical outcome in the DM group (events, 34/168 versus 14/81, respectively, P=0.57). Multivariate analysis identified CYP2C19 loss-of-function allele carriage as an independent predictor of cardiovascular events in non-DM, but not in DM (non-DM, HR 7.180, 95% CI, 1.701 to 30.298, P=0.007; DM, HR 1.374, 95% CI, 0.394 to 4.792, P=0.618). CONCLUSION: The impact of CYP2C19 polymorphism on clinical outcome seems to be more significant in non-DM compared with DM in patients with coronary stents.

Impact of CYP3A5 polymorphism on platelet reactivity at percutaneous coronary intervention and after 9 months of aspirin and clopidogrel therapy in Japanese patients with coronary artery disease.

BACKGROUND: High residual platelet reactivity in patients receiving clopidogrel is associated with an increased risk of a cardiovascular event after coronary stenting. The aim of our study was to evaluate the impact of the cytochrome P450 (CYP) 3A5 and CYP2C19 polymorphisms on platelet reactivity during dual antiplatelet therapy. METHODS: We determined the CYP2C19 and CYP3A5 genotypes of 101 angina patients (65 male patients, mean age 64 years) receiving dual antiplatelet therapy with aspirin and clopidogrel and evaluated the effect of these polymorphism on platelet reactivity at the early and late phases of treatment using a conventional light transmission aggregometry. Early and late phases were defined as 24 h after the loading dose and after 9 months on a maintenance dose of 75 mg daily, respectively. RESULTS: The distribution of the CYP2C19 genotype was 30 % in extensive metabolizers (EM; CYP2C19*1/*1), 46 % in intermediate metabolizers (IM; *1/*2, *1/*3), and 25 % in poor metabolizers (PM; *2/*2, *2/*3, *3/*3). Platelet reactivity levels in during the early and late phases were 3,793 ± 1,476 and 2,960 ± 1,410, respectively, in EM, 4,706 ± 1,417 and 3,239 ± 1,479, respectively, in IM, and 5,402 ± 776 and 4,736 ± 1,356 aggregation units (AU)•min, respectively in EM. The distribution of the CYP3A5 genotype was 33 % in patients carrying the wild-type or one loss-of-function allele (Expressor phenotype; *1/*1 and *1/*3, respectively) and 67 % in those carrying two loss-of-function alleles (Non-expressor; *3/*3). In total, eight patients were EM+Expressor, 22 were EM+Non-expressor, 18 were IM+Expressor, 28 were IM+Non-expressor, eight were PM+Expressor, and 17 were PM+Non-expressor. In the late phase of PM with the CYP2C19 polymorphism, the levels of platelet reactivity according to CYP3A5 genotype were 3,963 ± 1,436 and 5,100 ± 1,190 AU•min in Expressor and Non-expressor, respectively (P < 0.05), however, there was no difference in platelet reactivity between Expressor and Non-expressor in EM and IM. CONCLUSIONS: Our results suggest that antiplatelet response to clopidogrel in the late phase depends on the CYP3A5 polymorphism in PM with CYP2C19.

[Successful treatment of dysphagia due to Wallenberg syndrome using intermittent air stretching method with balloon catheter: a case report].

A 69-year-old woman presented with dysphagia due to Wallenberg syndrome. Videofluorography revealed unilateral dysfunction of the cricopharyngeal muscle, which caused stenosis of the esophageal entrance on the affected side. Pharyngeal fiberscopy indicated that glottal function and the cough reflex were preserved and that the pharyngeal reflex was lost. The stenosis of the esophageal entrance due to dysfunction of the cricopharyngeal muscle on the affected side and the loss of the pharyngeal reflex were considered to cause the patient's dysphagia. Based on above mentioned findings, the intermittent air stretching method with balloon catheter(IASM)was performed. As a result, dysphagia showed rapid improvement without any complications such as aspiration or bleeding. Thus, the IASM may be effective in some cases of dysphagia due to Wallenberg syndrome.

False tendons may be associated with the genesis of J-waves: prospective study in young healthy male.

BACKGROUND: Recent studies showed that J-waves are associated with vulnerability to ventricular fibrillation. Recently we reported the association between false tendons (FTs) and J-waves in a retrospective study. METHODS AND RESULTS: We prospectively studied 50 young healthy men (mean age 24.6±2.7 years). FTs were detected echocardiographically and classified based on their points of attachment as type 1 (longitudinal type), type 2 (diagonal type), and type 3 (transverse type). J-waves were defined as terminal QRS notching or slurring with ≥0.1 mV. The filtered QRS duration (fQRSd), RMS40, and LAS40 were measured on signal-averaged ECGs. FTs were detected in 37 of the 50 subjects (74%). The incidence of J-waves was significantly higher in subjects with type 1 or type 2 FTs than those with no- or type 3 FTs (61% vs. 26%, p<0.05). The leads with J-waves were closely associated with the location of the FT. While no late potential was recorded in any study subjects, fQRSd and LAS40 were significantly longer in subjects with type 1 or type 2 FTs (p<0.05). Univariate and multivariate logistic regression analysis revealed that only the existence of FTs (type 1 or 2) was an independent predictor of the presence of J-waves. CONCLUSIONS: Our results suggest that FTs were related to the genesis of J-waves with conduction delay.

Effect of ECG filter settings on J-waves.

BACKGROUND: While J-waves were observed in healthy populations, variations in their reported incidence may be partly explicable by the ECG filter setting. METHODS: We obtained resting 12-lead ECG recordings in 665 consecutive patients and enrolled 112 (56 men, 56 women, mean age 59.3±16.1years) who manifested J-waves on ECGs acquired with a 150-Hz low-pass filter. We then studied the J-waves on individual ECGs to look for morphological changes when 25-, 35-, 75-, 100-, and 150Hz filters were used. RESULTS: The notching observed with the 150-Hz filter changed to slurring (42%) or was eliminated (28%) with the 25-Hz filter. Similarly, the slurring seen with the 150-Hz filter was eliminated on 71% of ECGs recorded with the 25-Hz filter. The amplitude of J-waves was significantly lower with 25- and 35-Hz than 75-, 100-, and 150-Hz filters (p<0.0001). CONCLUSIONS: The ECG filter setting significantly affects the J-wave morphology.

Comparison of autonomic J-wave modulation in patients with idiopathic ventricular fibrillation and control subjects.

BACKGROUND: Although J-waves are seen in both patients with idiopathic ventricular fibrillation (IVF) and the general population, their genesis remains unclear. To assess the relationship between J-waves and autonomic tone we investigated the circadian variation of J-waves in individuals with and without IVF. METHODS AND RESULTS: In study 1, we obtained resting 12-lead ECG and Holter ECG recordings in 258 individuals undergoing screening for heart disease. In 60 of these subjects (23.3%), we detected J-waves on Holter ECGs; 40 of them (66.7%) had shown no J-waves on 12-lead ECGs. In study 2, we measured the J-wave amplitude, heart rate (HR), and HR variability [high frequency (HF) and the ratio of low- to high-frequency (LF/HF)] on Holter ECGs recorded in 5 patients with IVF and 20 control subjects who had manifested J-waves. The J-wave amplitude increased at night and decreased during the day in both groups; it was significantly higher in the IVF patients (P<0.0001). In both groups, the J-wave amplitude showed a significant negative correlation with HR and LF/HF and a significant positive correlation with HF. The slope of the J/HR and J/(LF/HF) relationship was significantly steeper in the IVF patients. CONCLUSIONS: The J-wave amplitude was more significantly influenced by the autonomic balance in IVF patients than in the controls. Autonomic J-wave modulation may yield important information on the genesis of J-waves.

Electrocardiographic characteristics of patients with false tendon: possible association of false tendon with J waves.

BACKGROUND: The false tendons (FTs) are fibromuscular bands that transverse the left ventricular cavity and often contain conduction tissue, suggesting that FTs may contribute to the occurrence of ventricular arrhythmias. The presence of J waves is associated with vulnerability to ventricular arrhythmias; however, the mechanisms underlying the manifestation of J waves remain to be elucidated. OBJECTIVE: To investigate the electrocardiographic characteristics, including the presence of J waves, in patients with FTs. METHODS: We studied 44 patients with distinct FTs detected by echocardiography (FT group) and 88 age- and sex-matched healthy subjects without FTs (control group). The PQ, QRS, JT, QT, corrected JT, and corrected QT intervals were automatically measured on surface 12-lead electrocardiograms, and the presence or absence of J waves was also determined. J waves were defined as terminal QRS notching or slurring. FTs were classified according to their points of attachment as type 1 (longitudinal, 52%), type 2 (diagonal, 25%), type 3 (transverse, 16%), and type 4 (weblike, 7%). RESULTS: QRS and corrected QT intervals were significantly longer in the FT group than in the control group (P <.005 and P <.05, respectively). The incidence of J waves was significantly higher in the FT group (64%) than in the control group (19%) (P <.0001). J waves were more prevalent in type 1 (78%) and type 2 (73%) than in type 3 (14%) and 4 FTs (33%) (P <0.05) and in patients with thick FTs (≥ 2 mm) than with thinner FTs (<2 mm) (71% vs 33%; P <.05). The J-wave location differed according to the FT type. CONCLUSIONS: Our results suggest that FTs may carry a certain role to the genesis of J waves.

Cardioprotective effects of pravastatin against lethal ventricular arrhythmias induced by reperfusion in the rat heart.

BACKGROUND: Statins are reported to reduce mortality in patients with coronary artery disease and that mortality benefit might be related to the drugs' antiarrhythmic properties. METHODS AND RESULTS: Male rats were fed with or without pravastatin (0.1 mg·kg⁻¹·day⁻¹) for 7 days, and thereafter subjected to 10 min of ischemia by coronary artery ligation followed by 20 min reperfusion. Treatment with pravastatin reduced the frequency and duration of ventricular tachycardia and fibrillation (VT/VF) and improved the arrhythmia score after reperfusion. To investigate the rapid effects of pravastatin, isolated perfused rat hearts were subjected to 20 min of global ischemia followed by 30 or 60 min of reperfusion. Treatment with pravastatin (10 nmol/L) from 10 min before ischemia shortened the total duration of reperfusion-induced VT/VF. Interestingly, pravastatin administered from the beginning of reperfusion also exerted antiarrhythmic effects. These results indicate that pravastatin exerts antiarrhythmic effects not only with daily oral intake but also when administered just before ischemia or even after ischemia. Intracellular calcium ([Ca²âº](i)) overload and collapse of mitochondrial inner membrane potential (Δψ(m)) are associated with the arrhythmogenesis during ischemia-reperfusion. In cultured cardiomyocytes, pretreatment with pravastatin (10 nmol/L) suppressed [Ca²âº](i) overload and prevented Δψ(m) loss induced by H2O2. CONCLUSIONS: Pravastatin attenuated reperfusion-induced lethal ventricular arrhythmias. Inhibition of [Ca²âº](i) overload and preserving Δψ(m) may be the mechanisms of the observed antiarrhythmic effects of pravastatin.

High-glucose condition reduces cardioprotective effects of insulin against mechanical stress-induced cell injury.

AIMS: Mechanical stress induces cardiomyocyte injury and contributes to the progression of heart failure in patients with hypertension. In this study, we investigated whether insulin exerts cardioprotective effects against mechanical stretching-induced cell injury, and whether the protective effect is influenced by high-glucose condition. MAIN METHODS: Cultured neonatal rat cardiomyocytes were plated on silicone chambers, and the cells were mechanically stretched by 15% to induce cell injury. KEY FINDINGS: Mechanical stretching increased reactive oxygen species (ROS) and decreased mitochondrial inner membrane potential (DeltaPsi(m)), eventually leading to cell death by apoptosis and necrosis. Insulin activated the phosphoinositide 3 (PI3) kinase/Akt pathway and reduced apoptosis and necrosis by suppressing ROS increase and preserving DeltaPsi(m). However, high-glucose condition attenuated the insulin-induced Akt phosphorylation and cardioprotection. To investigate the mechanisms that attenuated the effects of insulin in high-glucose condition, we examined the expression of tensin homologue deleted on chromosome 10 (PTEN), which is a negative regulator of the PI3 kinase/Akt pathway. The expressions of PTEN and phosphorylated PTEN were significantly decreased by insulin, and those effects were attenuated in high-glucose condition. SIGNIFICANCE: The present results suggest that insulin prevents mechanical stress-induced cell injury which otherwise lead to heart failure. Furthermore, we found that high-glucose condition prevented the decrease in PTEN expression and the cardioprotective effects induced by insulin.

Surface-displayed antibodies as a tool for simultaneously controlling the arrangement and morphology of multiple cell types with microscale precision.

Cell-cell interactions are considered to play critical roles in the development and physiology of most tissues. However, it is not straightforward to analyze cell-cell interactions with conventional cell culture in which cells are randomly distributed. To overcome this limitation, we employed here an antibody display to sort different cell types onto separate regions on a single substrate with microscale precision, taking advantage of the specific recognition of cell surface markers by surface-displayed antibodies. The results obtained with two sets of cell combinations, T cell/myelomonocytoid cell and neuron/astrocyte, demonstrate that antibody displays are feasible to establish a site-addressable coculture.

A collagen-binding mimetic of neural cell adhesion molecule.

A chimeric protein consisting of a cell-adhesive peptide derived from a neural cell adhesion molecule and a collagen-binding domain was synthesized using recombinant DNA technology. Here, we demonstrate that the chimeric protein binds to type I collagen and promotes the adhesion and neurite extension of hippocampus neurons. These results suggest that the chimeric protein has potential to provide microenvironments for neurons to adhere and survive in collagen-based matrices for use in cell-based therapies for central nervous disorders.

Perceived health as related to income, socio-economic status, lifestyle, and social support factors in a middle-aged Japanese.

BACKGROUND: Few studies have examined the association of perceived health with socio-economic status, especially income, and social isolation and support in Japan. The purpose of this study is to clarify the associations among perceived health, lifestyle, and socio-economic status, as well as social isolation and support factors, in middle-aged and elderly Japanese. METHODS: Subjects were 9,650 participants aged 47-77 years who completed a self-administered questionnaire in 2000 in the second survey of a population-based cohort (the Komo-Ise study). The questionnaire included items on sociodemographic and socio-economic factors, social isolation and support, lifestyle, past history of chronic disease and perceived health. Perceived health was dichotomized into excellent or good health and fair or poor health. A logistic regression analysis was used to determine the odds ratios of socio-economic status, social characteristics and lifestyle in relation to self-reported fair or poor health. RESULTS: We found that household income, physical activity, sleeping, smoking habit, and BMI had a strong association with self-reported fair or poor health in middle-aged and elderly Japanese men and women. Male subjects tended to report fair or poor health as household income decreased. The results for women differed in that social isolation and low social support had a stronger association for self-reported fair or poor health than low household income. CONCLUSIONS: The results indicated that perceived health was associated with socio-economic and social characteristics among middle-aged and elderly residents in Japan.

Body mass index and mortality in a middle-aged Japanese cohort.

BACKGROUND: The relative risk of mortality in low and high body mass index (BMI) categories in various ethnic groups remains a controversial subject. METHODS: To examine the relationship between BMI and mortality, a population-based prospective cohort study was conducted in two areas of Gunma Prefecture, Japan, in 1993. A total of 5,554 men and 5,827 women aged 40-69 years completed a self-administered questionnaire and were followed up until the year 2000. The hazard ratios (HRs) were estimated by the Cox proportional hazards model for different BMI classes. RESULTS: During the seven year follow-up period, 329 men and 147 women died. As compared with those in the reference BMI category (22.0-24.9 kg/m(2)), men and women in the lowest BMI category (<18.5 kg/m(2)) had a HR (95% confidence interval [CI]) of death from all-causes of 2.66 (1.59-4.46) and 3.14 (1.38-7.13), respectively, and women in the highest BMI category (28.0+ kg/m(2)) had a HR of death of 3.25 (1.48-7.15), after adjusting for all possible confounding factors including smoking and after excluding deaths occurring during the first three years of follow-up. CONCLUSION: In this prospective study of a Japanese cohort consisting of subjects ranging in age from 40 to 69 years, the curve depicting the relationship between BMI and all-cause mortality was L-shaped in men and U-shaped in women.