Endoplasmic reticulum stress attenuation promotes bovine oocyte maturation in vitro.

We have previously reported that regulation of endoplasmic reticulum (ER) stress during in vitro culture acutely increases bovine embryo developmental rate and cryotolerance; these data indicate that ER stress is a critical factor reducing the quality of in vitro-produced embryos. In the current follow-up study, we examined whether ER stress attenuation during in vitro maturation influences meiotic maturation, oocyte quality, and subsequent embryonic development. Bovine cumulus oocyte complexes (COCs) derived from slaughterhouse ovaries were matured with or without tauroursodeoxycholic acid (TUDCA), a selective inhibitor of ER stress (0, 50, 100, and 200 µM) for 22 h followed by in vitro fertilization, and zygotes were cultured for 8 days. Of the different doses of TUDCA, 100 µM TUDCA significantly increased the maturation rate, and decreased reactive oxygen species in denuded oocytes, and appeared lower number of apoptotic cells in matured COCs. Subsequently, treatment of TUDCA (100 µM) decreased the localization and amount of GRP78/BIP protein level as well as ER stress (GRP78/BIP, PERK, IER1, ATF4, and XBP1) and apoptosis (CHOP and BAX)-related gene expression, while it increased the anti-apoptotic gene BCL2 level in matured COCs. Moreover, addition of TUDCA (100 µM) during IVM significantly improved the blastocyst formation rate (43.6 ± 1.8% vs 49.7 ± 1.3%) and decreased the number of apoptotic cells (7.7 ± 1.1% vs 5.03 ± 0.6%) in blastocysts. These findings suggest that the presence of ER stress during maturation impairs the developmental competence of bovine COCs and that this process can be reversed by TUDCA.

Efficient in vitro embryo production using in vivo-matured oocytes from superstimulated Japanese Black cows.

We examined whether the use of in vivo-matured oocytes, collected by ovum pick-up (OPU) from superstimulated Japanese Black cows, can improve the productivity and quality of in vitro produced embryos. The cows were superstimulated by treatment with progesterone, GnRH, FSH and prostaglandin F2α according to a standardized protocol. The resulting in vivo-matured oocytes were collected by OPU and used subsequently for the other experiments. The immature oocytes from cows in the non-stimulated group were collected by OPU and then subjected to maturation in vitro. We found that the rate of normally distributed cortical granules of the matured oocyte cytoplasm in the superstimulated group was significantly higher than that in the non-stimulated group. The normal cleavage rate (i.e., production of embryos with two equal blastomeres without fragmentation) and freezable blastocyst rate were significantly higher in the superstimulated group than in the non-stimulated group. Among the transferable blastocysts, the ratio of embryos from normal cleavage was also significantly higher in the superstimulated group than in the non-stimulated group. For in vivo-matured oocytes, it was observed that the pregnancy rates were significantly higher when normally cleaved embryos were used for transfer. Taken together, these results suggest that high-quality embryos with respect to developmental kinetics can be efficiently produced with the use of in vivo-matured oocytes collected by OPU from superstimulated Japanese Black cows.

Sericin enhances the developmental competence of heat-stressed bovine embryos.

We investigated the effects of sericin on the developmental competence of bovine embryos exposed to heat stress (HS). Putative zygotes were cultured with sericin and subjected to HS (40.5°C for 6 hr) on Day 2 or 7 followed by continuous culture at 38.5°C until Day 8. Day 2 HS significantly decreased blastocyst development on Day 8 as well as mitochondrial activity, and significantly increased the amount of intracellular reactive oxygen species and terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL)-positive cells, whereas Day 7 HS only significantly decreased mitochondrial activity and increased the number of TUNEL-positive cells in Day 8 blastocysts. These detrimental effects were neutralized by sericin supplementation. Next, to investigate the potential production of blastocysts with high viability in terms of thermotolerance, embryos were cultured with sericin until Day 7, and then exposed to HS in the sericin-free medium. TUNEL-positive cell numbers were significantly lower in blastocysts produced by sericin culture than in control blastocysts. Transcript abundance for HSPA1A and BAX was significantly decreased but IFNT2 levels were increased in blastocysts produced by sericin culture. In conclusion, these findings demonstrate the anti-oxidative and anti-apoptotic activities of sericin, and the potential use of sericin to produce embryos with high viability in vitro.

Television viewing time and mortality from stroke and coronary artery disease among Japanese men and women -- the Japan Collaborative Cohort Study.

BACKGROUND: No study has examined the association between television (TV) viewing time and mortality from stroke and coronary artery disease (CAD) in Japanese. METHODS AND RESULTS: A total of 35,959 men and 49,940 women aged 40-79 years without a history of cardiovascular disease (CVD) and cancer were followed from 1988-1990 until 2009. During 19.2 median years of follow-up, there were 2,553 deaths from stroke, 1,206 from CAD and 5,835 from total CVD. Compared with viewing TV for <2 h/day, mortality from stroke, CAD and total CVD were higher for ≥6 h/day of TV viewing. The multivariable hazard ratios (HRs) for ≥6 h/day of TV viewing were 1.15 (95% confidence interval: 0.96-1.37) for stroke, 1.33 (1.03-1.72) for CAD and 1.19 (1.06-1.34) for total CVD. The corresponding HRs for each 1-h/day increment in TV viewing time were 1.01 (0.99-1.04), 1.04 (1.01-1.08) and 1.02 (1.01-1.04), respectively. The excess risk of mortality from CAD and total CVD was somewhat attenuated after further adjustment for potential mediators such as history of hypertension and diabetes: the multivariable HRs for ≥6 h/day of TV viewing were 1.24 (0.96-1.61) and 1.14 (1.02-1.28). The corresponding HRs for each 1-h/day increment in TV viewing time were 1.03 (1.00-1.07) and 1.01 (1.00-1.03). CONCLUSIONS: Prolonged TV viewing was associated with a small but significant increase in mortality from CAD and total CVD in Japanese.

Transcriptional wiring for establishing cell lineage specification at the blastocyst stage in cattle.

Mice and cattle use distinct pathways for the first cell segregation into inner cell mass (ICM) and trophectoderm (TE) lineages at the blastocyst stage. However, limited knowledge is available regarding the reliable transcriptional networks that orchestrate the complex developmental processes at this stage in nonrodent species. In order to elucidate the site-dominant transcriptomic properties of bovine blastocysts, we separated cell samples into the ICM and TE using both mechanical and chemical methods and performed in silico prescreening for candidate genes that were site-dominantly expressed in bovine blastocysts. We further performed quantitative real-time PCR and in situ hybridization using the site-specific cell samples. As a result, we identified seven ICM-dominant genes and five TE-dominant genes not found in earlier studies. Our findings provide novel insights into the mechanism of cell-fate specification in the pre-implantation bovine embryo.

Body mass index and weight change during adulthood are associated with increased mortality from liver cancer: the JACC Study.

BACKGROUND: We investigated the association of baseline body mass index (BMI) and weight change since age 20 years with liver cancer mortality among Japanese. METHODS: The data were obtained from the Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study). A total of 31 018 Japanese men and 41 455 Japanese women aged 40 to 79 years who had no history of cancer were followed from 1988 through 2009. RESULTS: During a median 19-year follow-up, 527 deaths from liver cancer (338 men, 189 women) were documented. There was no association between baseline BMI and liver cancer mortality among men or men with history of liver disease. Men without history of liver disease had multivariable hazard ratios (HR) of 1.95 (95%CI, 1.07-3.54) for BMI less than 18.5 kg/m(2) and 1.65 (1.05-2.60) for BMI of 25 kg/m(2) or higher, as compared with a BMI of 21.0 to 22.9 kg/m(2). BMI was positively associated with liver cancer mortality among women and women with history of liver disease. Weight change since age 20 years was positively associated with liver cancer mortality among women regardless of history of liver disease. Women with history of liver disease had a multivariable HRs of 1.96 (1.05-3.66) for weight gain of 5.0 to 9.9 kg and 2.31 (1.18-4.49) for weight gain of 10 kg or more, as compared with weight change of -4.9 to 4.9 kg. CONCLUSIONS: Both underweight (BMI <18.5 kg/m(2)) and overweight (BMI ≥25 kg/m(2)) among men without history of liver disease, and weight gain after age 20 (weight change ≥5 kg) among women with history of liver disease, were associated with increased mortality from liver cancer.

Cohort profile of the Japan Collaborative Cohort Study at final follow-up.

The Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study) was established in the late 1980s to evaluate the risk impact of lifestyle factors and levels of serum components on human health. During the 20-year follow-up period, the results of the study have been published in almost 200 original articles in peer-reviewed English-language journals. However, continued follow-up of the study subjects became difficult because of the retirements of principal researchers, city mergers throughout Japan in the year 2000, and reduced funding. Thus, we decided to terminate the JACC Study follow-up at the end of 2009. As a final point of interest, we reviewed the population registry information of survivors. A total of 207 (0.19%) subjects were ineligible, leaving 110 585 eligible participants (46 395 men and 64 190 women). Moreover, errors in coding date of birth and sex were found in 356 (0.32%) and 59 (0.05%) cases, respectively, during routine follow-up and final review. Although such errors were unexpected, their impact is believed to be negligible because of the small numbers relative to the large total study population. Here, we describe the final cohort profile at the end of the JACC Study along with selected characteristics of the participants and their status at the final follow-up. Although follow-up of the JACC Study participants is finished, we will continue to analyze and publish study results.

Healthy lifestyle behaviours and cardiovascular mortality among Japanese men and women: the Japan collaborative cohort study.

AIMS: To examine the combined impacts of healthy lifestyle behaviours on cardiovascular disease (CVD) in Asians. METHODS AND RESULTS: A total of 18 747 men and 24 263 women aged 40-79 without a history of stroke or coronary heart disease (CHD) at baseline in 1988-90 were followed up until 2006. Participants scored one point for each following lifestyle behaviour: consumption of fruits ≥1 intake per day, fish ≥1 intake per day, milk almost every day, exercise ≥5 h per week and/or walking ≥1 h per day, body mass index (BMI) of 21-25 kg/m(2), alcohol intake <46.0 g per day, non-smoking, and sleep duration of 5.5-7.5 h per day. During 16.5 years of follow-up, there were 1907 deaths from total CVDs including 849 strokes and 402 CHDs. For both genders, persons with the highest scores had the lowest CVD mortality. The multivariable hazard ratios (95% confidence interval, population-attributable fraction) for the highest (7-8) vs. lowest (0-2) score categories were 0.35 (0.25-0.49, 52.3%) in men, and 0.24 (0.16-0.36, 44.6%) in women. Similar associations were found for stroke: 0.36 (0.22-0.58, 45.0%) in men and 0.28 (0.15-0.53, 43.4%) in women, and for CHD: 0.19 (0.08-0.50, 76.2%) and 0.20 (0.09-0.47, 34.5%), respectively. CONCLUSION: Mortality from stroke, CHD, and CVD in the highest healthy lifestyle score category was one-third in men and one-fourth in women of those in the lowest scores, suggesting that a large fraction of CVD could be prevented through lifestyle modification.

Altered functions of alveolar macrophages and NK cells involved in asbestos-related diseases.

Asbestos exposure causes asbestosis and malignant mesothelioma, disorders which remain difficult to cure. We focused on alveolar macrophages (AM) and natural killer (NK) cells in asbestosis and mesothelioma, respectively, and examined their functions upon exposure to asbestos or in patients with mesothelioma. Exposure to asbestos caused rat AM to exhibit high production of transforming growth factor-beta (TGF-ß) with prolonged survival in the absence of other cells, not simultaneously with the apoptosis caused by asbestos. The NK cell line showed impaired cytotoxicity with altered expression of activating receptors upon exposure to asbestos, and primary NK cells in culture with asbestos and peripheral blood NK cells in mesothelioma shared a decrease in expression of NKp46, a representative activating receptor. The AM finding indicates that AM contribute to asbestosis by playing a direct role in the fibrogenic response, as well as the inflammatory response. The response of NK cells indicates that exposure to asbestos has an immune-suppressive effect, as well as a tumorigenic effect. Our studies therefore reveal novel effects of asbestos exposure on AM and tumor immunity, which may represent valuable information for construction of a strategy for prevention and cure of asbestosis and malignant mesothelioma.

Parental history and lifestyle behaviors in relation to mortality from stroke among Japanese men and women: the Japan Collaborative Cohort Study.

BACKGROUND: We assessed the impact of parental history of stroke on stroke mortality, as well as the effect modification between lifestyle and stroke mortality, among Japanese. METHODS: In this community-based, prospective cohort study, 22,763 men and 30,928 women aged 40 to 79 years with no history of cardiovascular disease or cancer at baseline (1988-1990) were followed through 2008. We examined the association between parental history of stroke and stroke mortality and estimated the impact of the combination of lifestyle and parental history on stroke mortality in offspring. RESULTS: During a mean follow-up period of 15.9 years, there were 1502 stroke deaths. In both sexes, participants with a parental history of stroke had a higher risk of stroke mortality as compared with those without such a history. The respective multivariable hazard ratio (95% CI) and population attributable fraction were 1.28 (1.10-1.49) and 5.4% in men, 1.22 (1.04-1.43) and 4.3% in women, and 1.25 (1.12-1.40) and 4.8% in all participants, for offspring with a maternal and/or paternal history of stroke. There was an inverse association between healthy-lifestyle score and stroke mortality, irrespective of parental history of stroke. The overall multivariable hazard ratio for the highest (6-8) versus the lowest (0-3) score categories was 0.56 (95% CI, 0.43-0.72) for participants with a maternal and/or paternal history of stroke and 0.44 (0.36-0.53) for those without such a history. CONCLUSIONS: Parental history of stroke was associated with stroke mortality in offspring. The inverse association between healthy lifestyle behaviors and stroke mortality, regardless of parental history, suggests that lifestyle modification is beneficial, even among individuals with a parental history of stroke.

Preliminary assessment of ecological exposure of adult residents in Fukushima Prefecture to radioactive cesium through ingestion and inhalation.

OBJECTIVE: This study aims to estimate the ecological exposure of adult residents of Fukushima Prefecture to ¹³4cesium (Cs) and ¹³7Cs through ingestion and inhalation between July 2 and July 8, 2011. METHODS: Fifty-five sets of meals with tap water, each representing one person's daily intake, were purchased in local towns in Fukushima Prefecture. Locally produced cow's milk (21 samples) and vegetables (43 samples) were also purchased. In parallel, air sampling was conducted at 12 different sites using a high-volume sampler. Nineteen sets of control meals were collected in Kyoto in July 2011. ¹³4Cs and ¹³7Cs levels in the samples were measured using a germanium detector. RESULTS: Radioactivity was detected in 36 of the 55 sample meals from Fukushima, compared with one of 19 controls from Kyoto. The median estimated dose level (µSv/year) was 3.0, ranging from not detectable to 83.1. None of the cow's milk (21) or vegetable (49) samples showed levels of contamination above the current recommended limits (Bq/kg) of 200 for milk and 500 for vegetables. The total effective dose levels by inhalation were estimated to be <3 µSv/year at nine locations, but samples at three other locations close to the edge of the 20-km radius from the crippled nuclear power plant showed higher levels of contamination (µSv/year): 14.7 at Iitate, 76.9 at Namie, and 27.7 at Katsurao. CONCLUSIONS: Levels of exposure to ¹³4Cs and ¹³7Cs in Fukushima by ingestion and inhalation are discernible, but generally within recommended limits.

Impact of Body Mass Index on Obesity-Related Cancer and Cardiovascular Disease Mortality; The Japan Collaborative Cohort Study.

AIM: We aimed to examine the association of obesity-related cancer and cardiovascular disease (CVD) with body mass index (BMI) and the estimated population attributable fraction in lean Asians. METHODS: We studied 102,535 participants aged 40-79 years without histories of cancer or CVD at baseline between 1988 and 2009. The cause-specific hazard ratios (csHRs) of BMI categories (＜18.5, 18.5-20.9, 21.0-22.9 [reference], 23.0-24.9, 25.0-27.4, and ≥ 27.5 kg/m2) were estimated for each endpoint. The events considered were mortalities from obesity-related cancer (esophageal, colorectal, liver, pancreatic, kidney, female breast, and endometrial cancer) and those from CVD (coronary heart disease and stroke). Population attributable fractions (PAFs) were calculated for these endpoints. RESULTS: During a 19.2-year median follow-up, 2906 died from obesity-related cancer and 4532 died from CVD. The multivariable-adjusted csHRs (95% confidence interval) of higher BMI categories (25-27.4 and ≥ 27.5 kg/m2) for obesity-related cancer mortality were 0.93 (0.78, 1.10) and 1.18 (0.92, 1.50) in men and 1.25 (1.04, 1.50) and 1.48 (1.19, 1.84) in women, respectively. The corresponding csHRs for CVD mortality were 1.27 (1.10, 1.46) and 1.59 (1.30, 1.95) in men and 1.10 (0.95, 1.28) and 1.44 (1.21, 1.72) in women, respectively. The PAF of a BMI ≥ 25 kg/m2 for obesity-related cancer was -0.2% in men and 6.7% in women and that for CVD was 5.0% in men and 4.5% in women. CONCLUSION: A BMI ≥ 25 kg/m2 is associated with an increased risk of obesity-related cancer in women and CVD in both sexes.

Dietary intakes of antioxidant vitamins and mortality from cardiovascular disease: the Japan Collaborative Cohort Study (JACC) study.

BACKGROUND AND PURPOSE: Only a few reports have dealt with the association of antioxidant vitamin intakes with mortality or morbidity from cardiovascular disease in Asia. We investigated the relation of dietary vitamins A, E, and C intake with mortality from cardiovascular disease for Japanese men and women. METHODS: The subjects were 23,119 men and 35 611 women aged 40 to 79 years without a history of cardiovascular disease or cancer who responded to the food frequency questionnaire as part of the Japan Collaborative Cohort Study for Cancer Risk (JACC) Study. They were followed up for a median period of 16.5 years. Hazard ratios were calculated per quintile of dietary vitamins A, E, and C intake by using Cox proportional hazard model. RESULTS: During the 859,962 person-year follow-up, there were 2690 deaths (1343 men and 1347 women) from cardiovascular disease, comprising 1227 (607 men and 620 women) from stroke and 557 (311 men and 246 women) from coronary heart disease. The multivariable hazard ratios (95% CI) associated with the highest versus lowest quintiles of vitamin C intake were 0.70 (0.54 to 0.92) for total stroke, 0.63 (0.41 to 0.97) for coronary heart disease, and 0.79 (0.66 to 0.94) for total cardiovascular disease for women, but the inverse associations observed were weak and did not reach statistical significance for men. No significant association was observed between vitamins A or E intake and risk of mortality for either men or women. CONCLUSIONS: Vitamin C intake is inversely associated with mortality from cardiovascular disease for Japanese women.

Rice intake is associated with reduced risk of mortality from cardiovascular disease in Japanese men but not women.

Rice is a staple food in Japan and provides 43% of carbohydrate and 29% of energy intake in the Japanese population. In a prospective study encompassing 83,752 Japanese men and women aged 40-79 y, rice intake was determined by self-administered FFQ. Median follow-up time was 14.1 y from 1988-1990 to the end of 2003, and HR and 95% CI of mortality were calculated according to quintiles of energy-adjusted rice intake. A total of 3514 cardiovascular deaths [1640 strokes, 707 coronary heart disease (CHD), and 560 heart failure] were documented. There was a gender difference on the effect of rice intake on the risk of cardiovascular disease (CVD). Overall, rice intake was inversely associated with CHD, heart failure, and total CVD in men but not in women. Rice intake was not associated with risk of stroke in either gender. The multivariable HR (95% CI) for the extreme quintiles of rice intake in men were 0.70 [(0.49-0.99); P-trend = 0.02] for CHD, 0.70 [(0.46-1.05); P-trend = 0.05] for heart failure, and 0.82 [(0.70-0.97); P-trend = 0.006] for total CVD. For women, rice was not associated with reduced risk of mortality from CVD after adjusting for lifestyle and dietary variables. In conclusion, the consumption of steamed rice was associated with reduced risk of mortality from CVD in Japanese men but not women. This finding necessitates further investigations on the mechanisms leading to this gender difference.

Phylogenetic analysis of Myanmar indigenous chickens using mitochondrial D-loop sequence reveals their characteristics as a genetic resource.

Myanmar indigenous chickens play important roles in food, entertainment, and farm business for the people of Myanmar. In this study, complete mitochondrial D-loop sequences (1232 bp) were analyzed using 176 chickens, including three indigenous breeds, two fighting cock populations, and three indigenous populations to elucidate genetic diversity and accomplish a phylogenetic analysis of Myanmar indigenous chickens. The average haplotype and nucleotide diversities were 0.948 ± 0.009 and 0.00814 ± 0.00024, respectively, exhibiting high genetic diversity of Myanmar indigenous chickens. Sixty-four haplotypes were classified as seven haplogroups, with the majority being haplogroup F. The breeds and populations except Inbinwa had multiple maternal haplogroups, suggesting that they experienced no recent purifying selection and bottleneck events. All breeds and populations examined shared haplogroup F. When 232 sequences belonging to haplogroup F (79 from Myanmar and 153 deposited sequences from other Asian countries/region) were analyzed together, the highest genetic diversity was observed in Myanmar indigenous chickens. Furthermore, Myanmar indigenous chickens and red junglefowls were observed in the center of the star-like median-joining network of 37 F-haplotypes, suggesting that Myanmar is one of the origins of haplogroup F. These findings revealed the unique genetic characteristic of Myanmar indigenous chickens as important genetic resources.

Dietary fiber intake is associated with reduced risk of mortality from cardiovascular disease among Japanese men and women.

Dietary fiber protects against coronary heart disease (CHD), but evidence in Asia is limited. We examined the association between dietary fiber intake and mortality from cardiovascular disease (CVD) in a Japanese population in a prospective study of 58,730 Japanese men and women aged 40-79 y in which dietary fiber intake was determined by a self-administered FFQ. The participants were followed up from 1988-1990 to the end of 2003. Hazard ratios (HR) and 95% CI of mortality were calculated per quintile of fiber intake. During the 14-y follow-up, a total of 2080 CVD deaths (983 strokes, 422 CHD, and 675 other CVD) were documented. Total, insoluble, and soluble dietary fiber intakes were inversely associated with risk of mortality from CHD and total CVD for both men and women. For men, the multivariable HR (95% CI) for CHD in the highest vs. the lowest quintiles were 0.81 [(95% CI, 0.61-1.09); P-trend = 0.02], 0.48 [(95% CI, 0.27-0.84); P-trend < 0.001], and 0.71 [(95% CI, 0.41-0.97); P-trend = 0.04] for total, insoluble, and soluble fiber, respectively. The respective HR (95% CI) for women were 0.80 [(95% CI, 0.57-0.97); P-trend = 0.01], 0.49 [(95% CI, 0.27-0.86); P-trend = 0.004], and 0.72 [(95% CI, 0.34-0.99); P-trend = 0.03], respectively. For fiber sources, intakes of fruit and cereal fibers but not vegetable fiber were inversely associated with risk of mortality from CHD. In conclusion, dietary intakes of fiber, both insoluble and soluble fibers, and especially fruit and cereal fibers, may reduce risk of mortality from CHD.

Cloning, expression, and polymorphisms of natural killer cell receptor NCR1 in pigs.

NCR1 (NKp46) is expressed on the surfaces of natural killer cells and recognizes hemagglutinin on the influenza virus. We cloned the NCR1 gene in pigs and found that porcine NCR1 was minimally expressed in the thymus, suggesting that NCR1 could be a useful marker of natural killer cells in pigs. We observed three nonsynonymous single nucleotide polymorphisms and one deletion of three nucleotides in the coding sequence of porcine NCR1; these may affect the function of NCR1. The polymorphisms detected here may be useful markers for breeding for influenza resistance in pigs.

History of blood transfusion before 1990 is associated with increased risk for cancer mortality independently of liver disease: a prospective long-term follow-up study.

OBJECTIVES: The aim of this work is to investigate the association between transfusion history and cancer mortality in a prospective follow-up study. METHODS: We conducted a prospective cohort study in four areas of Akita Prefecture, Japan, in 10,451 individuals (4,401 men and 6,050 women, aged 40-79 years) without history of cancer. The subjects were followed until 31 December 2003 and the number of deaths from cancer was recorded. RESULTS: After mean follow-up of 12.76 years (140,259 person-years), 520 individuals (333 men and 187 women) died of cancer. History of blood transfusion before 1990 was mildly but significantly associated with overall cancer mortality (hazard ratio = 1.75, 95% confidence interval: 1.32-2.18) and nonliver cancer mortality (HR = 1.68, 95% CI: 1.25-2.26). This significant association remained unchanged after excluding deaths that occurred within 5 years of baseline for overall cancer mortality (HR = 1.47, 95% CI: 1.04-2.09) and for nonliver cancer mortality (HR = 1.43, 95% CI: 1.00-2.04). The significant association for nonliver cancer mortality was confirmed in subjects with no smoking history and/or alcohol consumption (HR = 2.01, 95% CI: 1.35-3.00). Site-specific analysis showed a possible association between transfusion history and death from pancreatic cancer. CONCLUSIONS: History of blood transfusion before 1990 was found to be associated with increased risk for cancer mortality and was independent of liver diseases. The mechanism of the association between blood transfusion and cancer mortality warrants further research.

Role of endoplasmic reticulum stress on developmental competency and cryo-tolerance in bovine embryos.

Endoplasmic reticulum (ER) stress, a dysfunction in protein folding capacity of the ER, is involved in many physiological responses including mammalian reproductive systems. Studies have shown that ER stress interferes with the developmental process of in vitro oocyte maturation and embryo development; however, little is known about its effects on bovine preimplantation embryonic development. In this study, we examined the effects of ER stress during IVC on developmental competency and cryo-tolerance in bovine embryos. IVF-derived zygotes were cultured in CR1aa medium supplemented with tauroursodeoxycholic acid (TUDCA) and/or tunicamycin (TM), which are ER stress-inhibitory and stress-inducing agents, respectively, for 8 days. TM treatment decreased the blastocyst developmental rate and increased the percentage of apoptotic cells compared to that in the control group (10.2 ±â€¯2.3% vs. 39.75 ±â€¯1.3% and 17.8 ±â€¯1.2% vs. 3.6 ±â€¯1.1%, respectively; P < 0.01). However, the blastocyst developmental rate was increased and the percentage of apoptotic cells was decreased by addition of TUDCA in IVC medium compared to that in the control group (50.9 ±â€¯0.9% vs. 39.75 ±â€¯1.3% and 1.13 ±â€¯1.0% vs. 3.6 ±â€¯1.1%, respectively; P < 0.01). Importantly, in the group treated with TM plus TUDCA, the developmental rate and the percentage of apoptotic cells in blastocysts were similar to that in the control group, indicating that TUDCA ameliorates the adverse effects of TM alone on embryo development. In addition, TUDCA treatment significantly reduced the reactive oxygen species, expression of ER stress (GRP78, ATF4, ATF6, IER1, and sXBP1) and pro-apoptotic (CHOP and BAX) genes, while it increased anti-apoptotic BCL2 gene expression and glutathione levels. Moreover, TUDCA improved blastocyst cryo-tolerance as marked by a significantly increased hatching rate and decreased the number of apoptotic cells recorded at 48 h after a post-warming. Therefore, in concordance with a previous report in mice or pig, we showed that TUDCA supplementation during IVC increases the developmental competency of bovine in vitro-derived embryos. Additionally, we found that the presence of TUDCA in IVC medium improves the cryo-tolerance of bovine embryos. These results suggest that modulation of ER stress during IVC contributes to the production of high-quality bovine embryos in terms of cryo-tolerance.

Association of sleep duration with mortality from cardiovascular disease and other causes for Japanese men and women: the JACC study.

STUDY OBJECTIVES: To examine sex-specific associations between sleep duration and mortality from cardiovascular disease and other causes. DESIGN: Cohort study. SETTING: Community-based study. PARTICIPANTS: A total of 98,634 subjects (41,489 men and 57,145 women) aged 40 to 79 years from 1988 to 1990 and were followed until 2003. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: During a median follow-up of 14.3 years, there were 1964 deaths (men and women: 1038 and 926) from stroke, 881 (508 and 373) from coronary heart disease, 4287 (2297 and 1990) from cardiovascular disease, 5465 (3432 and 2033) from cancer, and 14,540 (8548 and 5992) from all causes. Compared with a sleep duration of 7 hours, sleep duration of 4 hours or less was associated with increased mortality from coronary heart disease for women and noncardiovascular disease/noncancer and all causes in both sexes. The respective multivariable hazard ratios were 2.32 (1.19-4.50) for coronary heart disease in women, 1.49 (1.02-2.18) and 1.47 (1.01-2.15) for noncardiovascular disease/noncancer, and 1.29 (1.02-1.64) and 1.28 (1.03-1.60) for all causes in men and women, respectively. Long sleep duration of 10 hours or longer was associated with 1.5- to 2-fold increased mortality from total and ischemic stroke, total cardiovascular disease, noncardiovascular disease/noncancer, and all causes for men and women, compared with 7 hours of sleep in both sexes. There was no association between sleep duration and cancer mortality in either sex. CONCLUSIONS: Both short and long sleep duration were associated with increased mortality from cardiovascular disease, noncardiovascular disease/noncancer, and all causes for both sexes, yielding a U-shaped relationship with total mortality with a nadir at 7 hours of sleep.