Soymilk-fermented with Lactobacillus delbrueckii subsp. delbrueckii TUA4408L improves immune-health in pigs.

Lactobacillus delbrueckii subsp. delbrueckii TUA4408L has the ability to grow and ferment soymilk and is able to modulate the innate immune response of intestinal epithelial cells in vitro. These two properties prompt us to evaluate whether the soymilk fermented with the TUA4408L strain can induce beneficial immunomodulatory effects in vivo. For this purpose, pigs were selected as a preclinical model. The studies performed here demonstrated that the L. delbrueckii subsp. delbrueckii TUA4408L-fermented soymilk (TUA4408L FSM) reduced blood markers of inflammation and differentially regulated the expression of inflammatory and regulatory cytokines in the intestinal mucosa. These immunological changes induced by the TUA4408L FSM were associated to an enhanced resistance to pathogenic Escherichia coli and an improved grow performance and meat quality of pigs. The experiments and analysis in our study indicate that the immunobiotic TUA4408L FSM could be an interesting non-dairy functional food to beneficially modulate the intestinal immune system, improve protection against pathogens and reduce inflammatory damage. The preclinical study carried out here in pigs could have a better correlation in humans, compared to a rodent model. However, the clinical relevance of these findings still needs to be confirmed by further research, for example, in controlled human challenge studies.

Cigarette smoking and cervical cancer risk: an evaluation based on a systematic review and meta-analysis among Japanese women.

BACKGROUND: There is a body of evidence to suggest that cigarette smoking increases the risk of cervical cancer in women, but no study has examined the magnitude of the association in Japanese women. Here, we evaluated the association between cigarette smoking and the risk of cervical cancer in Japanese women based on a systematic review of epidemiological evidence. METHODS: Original data were obtained from a MEDLINE search using PubMed or from a search of the 'Ichushi' database, as well as by a manual search. Evaluation of associations was based on the strength of evidence and the magnitude of association, together with biological plausibility as evaluated previously by the International Agency for Research on Cancer. Meta-analysis of associations was also conducted to obtain a summarized overview of the data. RESULTS: We identified two cohort studies and three case-control studies. All five studies had indicated strong positive associations between cigarette smoking and the risk of cervical cancer. Our summary estimate indicated that the relative risk (RR) for individuals who had ever-smoked relative to never-smokers was 2.03 (95% confidence interval: 1.49-2.57). Four studies had also demonstrated dose-response relationships between cigarette smoking and the risk of cervical cancer. CONCLUSION: We conclude that there is convincing evidence that cigarette smoking increases the risk of cervical cancer among Japanese women.

Evidence-based cancer prevention recommendations for Japanese.

A comprehensive evidence-based cancer prevention recommendation for Japanese was developed. We evaluated the magnitude of the associations of lifestyle factors and infection with cancer through a systematic review of the literature, meta-analysis of published data, and pooled analysis of cohort studies in Japan. Then, we judged the strength of evidence based on the consistency of the associations between exposure and cancer and biological plausibility. Important factors were extracted and summarized as an evidence-based, current cancer prevention recommendation: 'Cancer Prevention Recommendation for Japanese'. The recommendation addresses six important domains related to exposure and cancer, including smoking, alcohol drinking, diet, physical activity, body weight and infection. The next step should focus on the development of effective behavior modification programs and their implementation and dissemination.

Validity of self-reported tooth counts and masticatory status study of a Japanese adult population.

Self-reported measures of oral health are often used to assess oral health in populations or groups, but their validity or reliability needs repeated confirmation. The objective of this cross-sectional study was to evaluate the validity of self-reported tooth counts and masticatory status, using data obtained from a sample of Japanese adults. A total of 2356 adults aged 40 to 75 years participated in a questionnaire survey and a clinical oral examination from 2013 through 2016. Self-reported measures were compared with clinically measured values. For tooth counts, mean clinical and self-reported tooth counts in all participants were 23.68 and 23.78 teeth, and no significant difference was detected. Spearman's, Pearson's and intra-class correlation coefficients between clinical and self-reported tooth counts were 0.771, 0.845 and 0.843, respectively. According to the Bland-Altman analysis, the mean difference between clinical and self-reported tooth counts was -0.098 (95% CI: -0.242, 0.047). The upper limit of agreement was 6.919 (95% CI: 6.669, 7.169), and the lower limit of agreement was -7.115 (95% CI: -7.365, -6.865). No significant fixed or proportional bias was observed. For masticatory status, the crude or age- and gender-adjusted mean numbers of total teeth, posterior teeth and 3 kinds of functional tooth units significantly decreased with the deterioration of masticatory status. This study indicated that self-reports were within an acceptable range of clinical measures. Therefore, self-reports were considered valid alternatives to clinical measures to estimate tooth counts and masticatory status in a current Japanese adult population.

Plasma 25-hydroxy vitamin D and subsequent prostate cancer risk in a nested Case-Control study in Japan: The JPHC study.

BACKGROUND/OBJECTIVES: Although vitamin D has been experimentally reported to inhibit tumorigenesis, cell growth and prostate cancer invasion, epidemiologic data regarding prostate cancer risk are inconsistent, and some studies have suggested positive but nonsignificant associations. Further, the impact of vitamin D on prostate cancer between Western and Japanese populations may differ due to different plasma vitamin D levels. SUBJECTS/METHODS: We performed a nested case-control study within the Japan Public Health Center-based Prospective (JPHC) Study in 14,203 men (40-69 years) who answered a self-administered questionnaire at baseline (1990-1994) and gave blood samples, and were followed until 2005. We identified 201 prostate cancers which are newly diagnosed during follow-up (mean 12.8 years). We selected two matched controls for each case from the cohort. We used a conditional logistic regression model to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for prostate cancer with respect to levels of 25-hydroxy vitamin D (25(OH)D) in plasma. RESULTS: We did not observe statistically significant association between 25(OH)D level and total prostate cancer (multivariate OR=1.13 (95%CI=0.66-1.94, Ptrend=0.94) for the highest versus lowest tertile) However, 25(OH) levels were slightly positively associated with advanced cancer. The results remained substantially unchanged after stratification by intake of fish or calcium intake. CONCLUSIONS: 25(OH)D level showed no association with overall prostate cancer among Japanese men in this large cohort.

Coping strategies and risk of cardiovascular disease incidence and mortality: the Japan Public Health Center-based prospective Study.

AIMS: Coping strategies may be significantly associated with health outcomes. This is the first study to investigate the association between baseline coping strategies and cardiovascular disease (CVD) incidence and mortality in a general population cohort. METHODS AND RESULTS: The Japan Public Health Center-based prospective Study asked questions on coping in its third follow-up survey (2000-04). Analyses on CVD incidence and mortality included 57 017 subjects aged 50-79 without a history of CVD and who provided complete answers on approach- and avoidance-oriented coping behaviours and strategies. Cox regression models, adjusted for confounders, were used to determine hazard ratios (HRs) according to coping style. Mean follow-up time was 7.9 years for incidence and 8.0 years for mortality.The premorbid use of an approach-oriented coping strategy was inversely associated with incidence of stroke (HR = 0.85; 95% CI, 0.73-1.00) and CVD mortality (HR = 0.74; 95% CI, 0.55-0.99). Stroke subtype analyses revealed an inverse association between the approach-oriented coping strategy and incidence of ischaemic stroke (HR = 0.79; 95% CI, 0.64-0.98) and a positive association between the combined coping strategy and incidence of intra-parenchymal haemorrhage (HR = 2.03; 95% CI, 1.01-4.10). Utilizing an avoidance coping strategy was associated with increased mortality from ischaemic heart disease (IHD) only in hypertensive individuals (HR = 3.46; 95% CI, 1.07-11.18). The coping behaviours fantasizing and positive reappraisal were associated with increased risk of CVD incidence (HR = 1.24; 95% CI, 1.03-1.50) and reduced risk of IHD mortality (HR = 0.63; 95% CI, 0.40-0.99), respectively. CONCLUSION: An approach-oriented coping strategy, i.e. proactively dealing with sources of stress, may be associated with significantly reduced stroke incidence and CVD mortality in a Japanese population-based cohort.

Recombinant human soluble thrombomodulin in severe sepsis: a systematic review and meta-analysis.

BACKGROUND: Although recombinant human soluble thrombomodulin (rhTM) is a widely used novel anticoagulant agent for disseminated intravascular coagulation (DIC) in Japan, its clinical efficacy in sepsis-induced DIC has not been demonstrated convincingly. OBJECTIVE: To assess the benefits and harms of rhTM in sepsis-induced DIC patients. METHODS: We conducted a systematic review and meta-analysis of rhTM therapy for sepsis-induced DIC for both randomized controlled trials (RCTs) and observational studies (retrospective case-control studies and/or prospective cohort studies) separately. All-cause mortality (28-30 days) as efficacy and serious bleeding complications as adverse effect were measured as primary outcomes. We assessed body of evidence quality at the outcome level by using the Grading of Evidence, Assessment, Development and Evaluation (GRADE) approach. RESULTS: We analyzed 12 studies (838 patients/3 RCTs; 571 patients/9 observational studies). Pooled relative risk was 0.81 (95% CI, 0.62-1.06) in the RCTs, indicating non-significant reduction in mortality, and 0.59 (95% CI, 0.45-0.77) in the observational studies. Meta-regression analysis revealed a significant negative slope between effect size of rhTM therapy and baseline mortality rate in individual studies (P = 0.012), suggesting that probability of a beneficial effect with rhTM therapy increases with increasing baseline risk. Risk of serious bleeding complications was not significantly different between rhTM and control groups. We judged the quality of evidence as moderate for mortality and serious bleeding. CONCLUSIONS: The rhTM was associated with a trend in reduction of mortality at 28-30 days in sepsis-induced DIC patients. Further large rigorous trials are needed to confirm or refute these findings before implications for practice are clear.

Soy food and isoflavone intake and endometrial cancer risk: the Japan Public Health Center-based prospective study.

OBJECTIVE: Compared with western populations, the consumption of soy foods among Japanese is very high and the incidence of endometrial cancer very low. We evaluated the association of soy food and isoflavone intake with endometrial cancer risk in Japanese women. DESIGN: Prospective cohort study. SETTING: Ten public health centre areas in Japan. POPULATION: Forty nine thousand one hundred and twenty-one women of age 45-74 years who responded to a 5-year follow-up survey questionnaire. METHODS: Intakes of soy foods as well as other covariates were assessed in 1995-1998 by a self-administered food frequency questionnaire. Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). MAIN OUTCOME MEASURE: Incidence of endometrial cancer. RESULTS: During an average of 12.1 years of follow up, 112 newly diagnosed endometrial cancer cases were identified. Energy-adjusted intakes of soy food and isoflavone were not associated with the risk of endometrial cancer. The multivariate-adjusted HR per 25 g/day increase in the intake of soy food was 1.02 (95% CI 0.94-1.10), and the corresponding value for isoflavone intake per 15 mg/day was 1.01 (95% CI 0.84-1.22). CONCLUSION: In this population-based prospective cohort study of Japanese women, we observed no evidence of a protective association between soy food or isoflavone intake and endometrial cancer risk.

Association of vegetable and fruit intake with gastric cancer risk among Japanese: a pooled analysis of four cohort studies.

BACKGROUND: Prospective evidence is inconsistent regarding the association between vegetable/fruit intake and the risk of gastric cancer. METHODS: In an analysis of original data from four population-based prospective cohort studies encompassing 191 232 participants, we used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of gastric cancer incidence according to vegetable and fruit intake and conducted a meta-analysis of HRs derived from each study. RESULTS: During 2 094 428 person-years of follow-up, 2995 gastric cancer cases were identified. After adjustment for potential confounders, we found a marginally significant decrease in gastric cancer risk in relation to total vegetable intake but not total fruit intake: the multivariate-adjusted HR (95% CI; P for trend) for the highest versus the lowest quintile of total vegetable intake was 0.89 (0.77-1.03; P for trend = 0.13) among men and 0.83 (0.67-1.03; P for trend = 0.40) among women. For distal gastric cancer, the multivariate HR for the highest quintile of total vegetable intake was 0.78 (0.63-0.97; P for trend = 0.02) among men. CONCLUSIONS: This pooled analysis of data from large prospective studies in Japan suggests that vegetable intake reduces gastric cancer risk, especially the risk of distal gastric cancer among men.

Rice, bread, noodle and cereal intake and colorectal cancer in Japanese men and women: the Japan Public Health Center-based prospective Study (JPHC Study).

BACKGROUND: Colorectal cancer (CRC) incidence rate increased rapidly in Japan between the 1950s and 1990s. We examined the association between rice intake and CRC risk in comparison with bread, noodles and cereal among Japanese adults enrolled in the Japan Public Health Center-based prospective Study. METHODS: A total of 73,501 Japanese men and women were followed-up from 1995 to 1999 until the end of 2008 for an average of 11 years. During 801,937 person-years of follow-up, we identified 1276 incident cases of CRC. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) of CRC for rice, noodle, bread and cereal intake were calculated by Cox proportional hazards model. RESULTS: Overall, no significant association was observed for the highest quartile of rice intake compared with the lowest and the risk of CRC and its subsites in men (HR, 0.77; 95% CI, 0.56-1.07) and women (HR, 1.10; 95% CI, 0.71-1.68). However, a non-significant inverse trend was observed between rice intake and rectal cancer in men. No clear patterns of association were observed in bread, noodle and cereal intake. CONCLUSION: Our findings suggest that the consumption of rice does not have a substantial impact on the risk of CRC in the Japanese population.

Growth stimulation in inflorescences of an Arabidopsis tubulin mutant under microgravity conditions in space.

Cortical microtubules are involved in plant resistance to hypergravity, but their roles in resistance to 1 g gravity are still uncertain. To clarify this point, we cultivated an Arabidopsis α-tubulin 6 mutant (tua6) in the Cell Biology Experiment Facility on the Kibo Module of the International Space Station, and analyzed growth and cell wall mechanical properties of inflorescences. Growth of inflorescence stems was stimulated under microgravity conditions, as compared with ground and on-orbit 1 g conditions. The stems were 10-45% longer and their growth rate 15-55% higher under microgravity conditions than those under both 1 g conditions. The degree of growth stimulation tended to be higher in the tua6 mutant than the wild-type Columbia. Under microgravity conditions, the cell wall extensibility in elongating regions of inflorescences was significantly higher than the controls, suggesting that growth stimulation was caused by cell wall modifications. No clear differences were detected in any growth or cell wall property between ground and on-orbit 1 g controls. These results support the hypothesis that cortical microtubules generally play an important role in plant resistance to the gravitational force.

Communicating by electrolarynx with a blind tetraplegic spinal cord injury patient on mechanical ventilation in the ICU.

STUDY DESIGN: Single-subject case. OBJECTIVES: To describe the atypical presentation of communication with a blind tetraplegic spinal cord injury patient on a respirator using an electrolarynx. SETTING: Critical care center in Osaka, Japan. METHODS: A 53-year-old blind man with tetraplegic spinal cord injury was admitted to our center. It was difficult for him to express his desires and to communicate with others about his severe condition and other details of his care. We began to use an electrolarynx to communicate with this patient because he could move his mouth. RESULTS: With use of the electrolarynx, the patient gradually became better able to speak fluently by electrolarynx on the first day of use. The electrolarynx allowed us and his family to communicate with him. He was pleased with the improvement in communication. CONCLUSION: An electrolarynx is a useful method for communicating with blind tetraplegic spinal cord injury patients on mechanical ventilation.

Dietary patterns and type 2 diabetes in Japanese men and women: the Japan Public Health Center-based Prospective Study.

BACKGROUND/OBJECTIVE: Dietary patterns in Western populations have been linked to type 2 diabetes, but the association of distinctive dietary patterns of Japanese population remains unclear. We prospectively investigated the association between dietary patterns and risk of developing type 2 diabetes among Japanese adults. SUBJECTS/METHODS: Participants were 27, 816 men and 36,889 women aged 45-74 years who participated in the second survey of the Japan Public Health Center-based prospective study and had no history of diabetes. Dietary patterns were derived by using principal component analysis of the consumption of 134 food and beverage items ascertained by a food frequency questionnaire. Odds ratios of self-reported physician-diagnosed type 2 diabetes over 5 year were estimated using logistic regression analysis. RESULTS: A total of 1194 new cases (692 men and 502 women) of type 2 diabetes were self-reported. We identified three dietary patterns: prudent, westernized and traditional Japanese patterns. Any dietary pattern was not significantly associated with type 2 diabetes risk after adjustment for covariates in both men and women. The multivariate-adjusted odds ratios (95% confidence interval) for type 2 diabetes for the highest versus lowest quartile of each dietary pattern score in men and women, respectively, were 0.93 (0.74-1.16) and 0.90 (0.69-1.16) for the prudent pattern, 1.15 (0.90-1.46) and 0.81 (0.61-1.08) for the westernized pattern, and 0.97 (0.74-1.27) and 0.87 (0.66-1.15) for the traditional pattern. CONCLUSIONS: Although a small protective effect of the prudent dietary pattern cannot be excluded, dietary patterns may not be appreciably associated with type 2 diabetes risk in Japanese.

Attributable causes of cancer in Japan in 2005--systematic assessment to estimate current burden of cancer attributable to known preventable risk factors in Japan.

BACKGROUND: To contribute to evidence-based policy decision making for national cancer control, we conducted a systematic assessment to estimate the current burden of cancer attributable to known preventable risk factors in Japan in 2005. METHODS: We first estimated the population attributable fractions (PAFs) of each cancer attributable to known risk factors from relative risks derived primarily from Japanese pooled analyses and large-scale cohort studies and the prevalence of exposure in the period around 1990. Using nationwide vital statistics records and incidence estimates, we then estimated the attributable cancer incidence and mortality in 2005. RESULTS: In 2005, ≈ 55% of cancer among men was attributable to preventable risk factors in Japan. The corresponding figure was lower among women, but preventable risk factors still accounted for nearly 30% of cancer. In men, tobacco smoking had the highest PAF (30% for incidence and 35% for mortality, respectively) followed by infectious agents (23% and 23%). In women, in contrast, infectious agents had the highest PAF (18% and 19% for incidence and mortality, respectively) followed by tobacco smoking (6% and 8%). CONCLUSIONS: In Japan, tobacco smoking and infections are major causes of cancer. Further control of these factors will contribute to substantial reductions in cancer incidence and mortality in Japan.

SIRT3 regulates mitochondrial protein acetylation and intermediary metabolism.

The sirtuins are a family of nicotinamide adenine dinucleotide (NAD(+))-dependent protein deacetylases that regulate cell survival, metabolism, and longevity. Humans have seven sirtuins (SIRT1-SIRT7) with distinct subcellular locations and functions. SIRT3 is localized to the mitochondrial matrix and its expression is selectively activated during fasting and calorie restriction. Activated SIRT3 deacetylates several key metabolic enzymes-acetyl-coenzyme A synthetase, long-chain acyl-coenzyme A (acyl-CoA) dehydrogenase (LCAD), and 3-hydroxy-3-methylglutaryl CoA synthase 2-and enhances their enzymatic activity. Disruption of SIRT3 activity in mice, either by genetic ablation or during high-fat feeding, is associated with accelerated development of metabolic abnormalities similar to the metabolic syndrome in humans. SIRT3 is therefore emerging as a metabolic sensor that responds to change in the energy status of the cell and modulates the activity of key metabolic enzymes via protein deacetylation.

Interleukin-1ß causes long-term potentiation deficiency in a mouse model of septic encephalopathy.

Sepsis induces multiple organ dysfunction syndrome including septic encephalopathy (SE), which results in cognitive impairment. However, an effective treatment for SE remains unknown. We determined the role of interleukin-1ß (IL-1ß) in long-term potentiation (LTP) deficiency after SE. At first, endotoxin level in the blood was increased at 24 h after cecum ligation and puncture (CLP) (i.e. SE model). Second, the expression of IL-1ß and its receptor in the hippocampus was determined by immunohistochemistry and immunoblotting. The number of Iba1-positive cells and their expression of IL-1ß were enhanced by CLP with disruption of the blood brain barrier. Also, Iba1, IL-1ß, and occludin protein expressions were consistent with immunohistochemical results. Third, we used an electrophysiological technique and observed the LTP deficiency, a hallmark of learning and memory, in the slices of hippocampus after CLP. Since type 1 interleukin-1 receptors (IL-1R1s) on neuronal cells were increased in the hippocampus, we utilized IL-1R1 antagonist. Pre-incubation with IL-1R1 antagonist for 30 min before recording of field excitatory post-synaptic potentials (fEPSPs) in the hippocampus canceled LTP deficiency after CLP. These results suggest the novel importance of IL-1ß in synaptic plasticity deficiency associated with sepsis-induced brain inflammation. In a mouse model of SE, IL-1R1 inhibition is important in protecting synaptic function of the hippocampus after induction of SE.

Comparison of neurological outcomes following witnessed out-of-hospital ventricular fibrillation defibrillated with either biphasic or monophasic automated external defibrillators.

BACKGROUND: Biphasic waveform defibrillation results in higher rates of termination of fibrillation than monophasic waveform defibrillation but has not been shown to improve survival outcomes. OBJECTIVE: To compare the effectiveness of a biphasic automated external defibrillator (AED) with a monophasic AED for witnessed out-of-hospital cardiac arrest (OHCA) due to ventricular fibrillation (VF). METHODS: In a prospective population-based cohort study, adults with witnessed VF OHCA were treated with either monophasic or biphasic waveform AED shocks. The primary outcome measure was neurologically favourable 1-month survival, defined as a Cerebral Performance Categories score of 1 or 2. RESULTS: Of 366 adults with witnessed OHCA of presumed cardiac aetiology, 74 (20%) had VF. Termination of VF with the first shock tended to occur more frequently after biphasic AED shocks (36/44 (82%) vs 20/30 (67%), p = 0.14). Return of spontaneous circulation (ROSC) occurred more frequently after biphasic AED shocks (29/44 (66%) vs 8/30 (27%), p = 0.001). Neurologically favourable 1-month survival was also more frequent in the biphasic group (10/44 (23%) vs 1/30 (3%), p = 0.04). The median time interval from the first shock to the second shock was 67 s in the monophasic group and 24 s in the biphasic group (p = 0.001). CONCLUSIONS: Treatment with biphasic AED shocks improved the likelihood of ROSC and neurologically favourable 1-month survival after witnessed VF compared with monophasic AED shocks. In addition to waveform differences, a shorter time interval from the first shock to the second shock could account for the better outcomes with biphasic AED.

Green tea consumption and gastric cancer in Japanese: a pooled analysis of six cohort studies.

BACKGROUND: Previous experimental studies have suggested many possible anti-cancer mechanisms for green tea, but epidemiological evidence for the effect of green tea consumption on gastric cancer risk is conflicting. OBJECTIVE: To examine the association between green tea consumption and gastric cancer. METHODS: We analysed original data from six cohort studies that measured green tea consumption using validated questionnaires at baseline. Hazard ratios (HRs) in the individual studies were calculated, with adjustment for a common set of variables, and combined using a random-effects model. RESULTS: During 2 285 968 person-years of follow-up for a total of 219 080 subjects, 3577 cases of gastric cancer were identified. Compared with those drinking <1 cup/day, no significant risk reduction for gastric cancer was observed with increased green tea consumption in men, even in stratified analyses by smoking status and subsite. In women, however, a significantly decreased risk was observed for those with consumption of > or =5 cups/day (multivariate-adjusted pooled HR = 0.79, 95% confidence interval (CI) = 0.65 to 0.96). This decrease was also significant for the distal subsite (HR = 0.70, 95% CI = 0.50 to 0.96). In contrast, a lack of association for proximal gastric cancer was consistently seen in both men and women. CONCLUSIONS: Green tea may decrease the risk of distal gastric cancer in women.

Increase in body mass index category since age 20 years and all-cause mortality: a prospective cohort study (the Ohsaki Study).

BACKGROUND: It is still unclear whether weight gain from early to late adulthood affects longevity. Furthermore, no study has addressed its association with all-cause and cause-specific mortality in an Asian population. METHODS: We prospectively assessed the association between an increase in body mass index (BMI) category since age 20 years and risk of all-cause, cardiovascular disease (CVD) and cancer mortality. Self-reported information pertaining to BMI was collected from 38 080 Japanese men and women aged 40-79 years at study entry in 1994 after exclusion of participants with a BMI of <18.5 kg/m(2) at age 20 years or at study entry. We defined six patterns of increase in BMI category at age 20 years and study entry: stable normal, overweight and obese, normal to overweight or obese, and overweight to obese. RESULTS: During 7 years of follow-up, 2617 participants died. After adjustment for potential confounders, we observed a significantly increased risk of all-cause mortality for the pattern of normal weight at age 20 years and obese at study entry and of stable obese compared with stable normal in BMI category, the multivariate HRs (95% confidence interval (CI)) being 1.42 (1.08-1.88) and 2.26 (1.45-3.51), respectively. For the pattern of overweight at age 20 years and obese at study entry, the multivariate hazard ratio (95% CI) was 1.35 (0.92-1.98). In contrast, we did not observe an increased risk of all-cause mortality for normal weight at age 20 years and overweight at study entry, and stable overweight. For CVD and cancer mortality, these results were consistently observed. CONCLUSION: We observed an increased risk of all-cause mortality both among participants who had been persistently obese since early adulthood and participants who showed an increase in BMI category from normal to obese, compared with participants with a stable normal BMI category.