PTIP Associated protein 1, PA1, Is an Independent Prognostic Factor for Lymphnode Negative Breast Cancer

Pax transactivation domain interacting protein (PTIP) associated protein 1, PA1, was a newly found protein participating in the modulation of transactivity of nuclear receptor super family members such as estrogen receptor (ER), androgen receptor (AR) and glucocorticoid receptor (GR). Breast cancer is one of the most life threatening diseases for women and has tight association with estrogen and ER. This study was performed to understand the function of PA1 in breast cancer. The expression of PA1 had been evaluated in a total of 344 primary invasive breast cancer samples and examined the relationship with clinical output, relapse free survival (RFS), breast cancer-specific survival (BCSS). PA1 expression was observed in both nucleus and cytoplasm, however, appeared mainly in nuclear. PA1 nuclear expression was correlated with postmenopausal (P = 0.0097), smaller tumor size (P = 0.0025), negative Ki67 (P = 0.02), positive AR (P = 0.049) and positive ERβ (P = 0.0020). Kaplan–Meier analysis demonstrated PA1 nuclear positive cases seemed to have a longer survival than negative ones for RFS (P = 0.023) but not for BCSS (P = 0.23). In the Cox hazards model, PA1 nuclear protein expression proved to be a significant prognostic univariate parameter for RFS (P = 0.03), but not for BCSS (P = 0.20). In addition, for those patients without lymphnode metastasis PA1 was found to be an independent prognostic factor for RFS (P = 0.025), which was verified by univariate and multivariate analyses. These investigations suggested PA1 expression could be a potential prognostic indicator for RFS in breast cancer.     

The Neural Correlates of Mindful Awareness: A Possible Buffering Effect on Anxiety-Related Reduction in Subgenual Anterior Cingulate Cortex Activity

Background

Human personality consists of two fundamental elements character and temperament. Character allays automatic and preconceptual emotional responses determined by temperament. However, the neurobiological basis of character and its interplay with temperament remain elusive. Here, we examined character-temperament interplay and explored the neural basis of character, with a particular focus on the subgenual anterior cingulate cortex extending to a ventromedial portion of the prefrontal cortex (sgACC/vmPFC).

Methods

Resting brain glucose metabolism (GM) was measured using [¹⁸F] fluorodeoxyglucose positron emission tomography in 140 healthy adults. Personality traits were assessed using the Temperament and Character Inventory. Regions of interest (ROI) analysis and whole-brain analysis were performed to examine a combination effect of temperament and character on the sgACC/vmPFC and to explore the neural correlates of character, respectively.

Results

Harm avoidance (HA), a temperament trait (i.e., depressive, anxious, vulnerable), showed a significant negative impact on the sgACC/vmPFC GM, whereas self-transcendence (ST), a character trait (i.e., intuitive, judicious, spiritual), exhibited a significant positive effect on GM in the same region (HA β = −0.248, p = 0.003; ST: β = 0.250, p = 0.003). In addition, when coupled with strong ST, individuals with strong HA maintained the sgACC/vmPFC GM level comparable to the level of those with low scores on both HA and ST. Furthermore, exploratory whole-brain analysis revealed a significant positive relationship between ST and sgACC/vmPFC GM (peak voxel at x = −8, y = 32, z = −8, k = 423, Z = 4.41, corrected p ^FDR = 0.030).

Conclusion

The current findings indicate that the sgACC/vmPFC might play a critical role in mindful awareness to something beyond as well as in emotional regulation. Developing a sense of mindfulness may temper exaggerated emotional responses in individuals with a risk for or having anxiety and depressive disorders.     

Association between Sleep Duration and Urinary Albumin Excretion in Patients with Type 2 Diabetes: The Fukuoka Diabetes Registry

Objective

Few studies have so far investigated the impact of sleep duration on chronic kidney disease in diabetic patients. The objective of the present study was to examine the relationship between sleep duration and albuminuria in type 2 diabetic patients.

Research Design and Methods

A total of 4,870 Japanese type 2 diabetic patients ≥20 years of age were divided into six groups according to self-reported sleep duration: less than 4.5 hours, 4.5–5.4 hours, 5.5–6.4 hours, 6.5–7.4 hours, 7.5–8.4 hours and more than 8.5 hours. The association between sleep duration and urinary albumin-creatinine ratio (UACR) was examined cross-sectionally.

Results

Both short and long sleep durations were significantly associated with higher UACR levels and higher proportions of patients with albuminuria (≥30 mg/g) and macroalbuminuria (≥300 mg/g) compared with a sleep duration of 6.5–7.4 hours (P for quadratic trend <0.001). A U-shaped association between sleep duration and UACR remained significant even after adjustment for potential confounders, including age, sex, duration of diabetes, current smoking habits, former smoking habits, current drinking habits, regular exercise habits, total energy intake, total protein intake, hypnotic use and estimated glomerular filtration rate. Furthermore, the association remained substantially unchanged after additional adjustment for body mass index, hemoglobin A_1c, systolic blood pressure, renin-angiotensin system inhibitor use and depressive symptoms.

Conclusions

Our findings suggest that sleep duration has a U-shaped association with the UACR levels in type 2 diabetic patients, independent of potential confounders.     

Type D Personality Is Associated with Psychological Distress and Poor Self-Rated Health among the Elderly: A Population-Based Study in Japan

We investigated the association between Type D personality, psychological distress, and self-ratings of poor health in elderly Japanese people. In August 2010, questionnaires were sent to all residents aged ≥65 in three municipalities (n = 21232) in Okayama Prefecture, Japan, and. 13929 questionnaires were returned (response rate: 65.6%). To assess mental and physical health outcomes, we used the Kessler Psychological Distress Scale and a single item question regarding perceived general health. We analyzed 9759 questionnaires to determine odds ratios (ORs) and 95% confidence intervals (CIs) for several health outcomes, adjusting for sex, age, smoking status, frequency of alcohol consumption, overweight status, educational attainment, socioeconomic status, and number of cohabiters. The multiple imputation method was employed for missing data regarding Type D personality. The prevalence of Type D personality in our sample was 46.2%. After adjusting for covariates, we found that participants with Type D personality were at 4–5 times the risk of psychological distress, and twice the risk of poor self-rated health. This association was stronger in participants aged 65–74 years (psychological distress; OR: 5.80, 95% CI: 4.96–6.78, poor self-rated health; OR: 2.84, 95% CI: 2.38–3.38) than in those aged over 75 years (psychological distress; OR: 4.54, 95% CI: 3.96–5.19, poor self-rated health; OR: 2.05, 95% CI: 1.79–2.34). Type D personality is associated with adverse health status among Japanese elderly people in terms of mental and physical risk; therefore, further research into the implications of this personality type is warranted.     

Synthesis and structure–activity relationships of phenyl-substituted coumarins with anti-tubercular activity that target FadD32

In an effort to develop new and potent agents for therapy against tuberculosis, a high-throughput screen was performed against Mycobacterium tuberculosis strain H37Rv. Two 6-aryl-5,7-dimethyl-4-phenylcoumarin compounds 1a and 1b were found with modest activity. A series of coumarin derivatives were synthesized to improve potency and to investigate the structure–activity relationship of the series. Among them, compounds 1o and 2d showed improved activity with IC₉₀ of 2 μM and 0.5 μM, respectively. Further optimization provided compound 3b with better physiochemical properties with IC₉₀ 0.4 μM which had activity in a mouse model of infection. The role of the conformation of the 4- and 6-aryl substituents is also described.     

Constituents of bile, bilirubin and TUDCA, protect against oxidative stress-induced retinal degeneration

Two constituents of bile, bilirubin and tauroursodeoxycholic acid (TUDCA), have antioxidant activity. However, bilirubin can also cause damage to some neurons and glial cells, particularly immature neurons. In this study, we tested the effects of bilirubin and TUDCA in two models in which oxidative stress contributes to photoreceptor cell death, prolonged light exposure and rd10+/+ mice. In albino BALB/c mice, intraperitoneal injection of 5 mg/kg of bilirubin or 500 mg/kg of TUDCA prior to exposure to 5000 lux of white light for 8 h significantly reduced loss of rod and cone function assessed by electroretinograms. Both treatments also reduced light-induced accumulation of superoxide radicals in the outer retina, rod cell death assessed by outer nuclear layer thickness, and disruption of cone inner and outer segments. In rd10+/+ mice, intraperitoneal injections of 5 or 50 mg/kg of bilirubin or 500 mg/kg of TUDCA every 3 days starting at postnatal day (P) 6, caused significant preservation of cone cell number and cone function at P50. Rods were not protected at P50, but both bilirubin and TUDCA provided modest preservation of outer nuclear layer thickness and rod function at P30. These data suggest that correlation of serum bilirubin levels with rate of vision loss in patients with retinitis pigmentosa could provide a useful strategy to test the hypothesis that cones die from oxidative damage in patients with retinitis pigmentosa. If proof-of-concept is established, manipulation of bilirubin levels and administration of TUDCA could be tested in interventional trials.     

Palau’s coral reefs show differential habitat recovery following the 1998-bleaching event

Documenting successional dynamics of coral communities following large-scale bleaching events is necessary to predict coral population responses to global climate change. In 1998, high sea surface temperatures and low cloud cover in the western Pacific Ocean caused high coral mortality on the outer exposed reefs of Palau (Micronesia), while coral mortality in sheltered bays was low. Recovery was examined from 2001 to 2005 at 13 sites stratified by habitat (outer reefs, patch reefs and bays) and depth (3 and 10 m). Two hypotheses were tested: (1) rates of change of coral cover vary in accordance with habitat, and (2) recovery rates depend on recruitment. Coral cover increased most in the sheltered bays, despite a low recruitment rate, suggesting that recovery in bays was primarily a consequence of remnant regrowth. Recruitment densities were consistently high on the wave-exposed reefs, particularly the western slopes, where recovery was attributed to both recruitment and regrowth of remnants. Recovery was initially more rapid at 10 m than 3 m on outer reefs, but in 2004, recovery rates were similar at both depths. Rapid recovery was possible because Palau’s coral reefs were buffered by remnant survival and recruitment from the less impacted habitats.     

Correction: Anthocyanin synthesis potential in betalain-producing Caryophyllales plants

Journal of Plant Research -     

A comparison of head-out mist bathing,with or without facial fanning,with head-out half-body low-water level bathing in humans—a pilot study

To reduce the risks of Japanese-style bathing, half-body bathing (HBLB) has been recommended in Japan, but discomfort due to the cold environment in winter prevents its widespread adoption. The development of the mist sauna, which causes a gradual core temperature rise with sufficient thermal comfort, has reduced the demerits of HBLB. We examined head-out 42 °C mist bathing with 38 °C HBLB up to the navel to see if it could improve thermal comfort without detracting from the merits of HBLB, with and without the effects of facial fanning (FF). The subjects were seven healthy males aged 22–25 years. The following bathing styles were provided: (1) HBLB—head-out half-body low bathing of 38 °C up to the navel (20 min); (2) HOMB—head-out mist bathing of 42 °C and HBLB of 38 °C (20 min); and (3) HOMBFF—HOMB with FF (20 min). HOMB raised the core temperature gradually. HOMBFF suppressed the core temperature rise in a similar fashion to HOMB. Increases in blood pressure and heart rate usually observed in Japanese traditional-style bathing were less marked in HOMBs with no significant difference with and without FF. The greatest body weight loss was observed after Japanese traditional-style bathing, with only one-third of this amount lost after mist bathing, and one-sixth after HBLB. HOMB increased thermal sensation, and FF also enhanced post-bathing invigoration. We conclude that HOMB reduces the risks of Japanese traditional style bathing by mitigating marked changes in the core temperature and hemodynamics, and FF provides thermal comfort and invigoration.     

Effects of isotonic and isometric exercises with mist sauna bathing on cardiovascular,thermoregulatory, and metabolic functions

To clarify the effects of isometric and isotonic exercise during mist sauna bathing on the cardiovascular function, thermoregulatory function, and metabolism, six healthy young men (22?±?1 years old, height 173?±?4 cm, weight 65.0?±?5.0 kg) were exposed to a mist sauna for 10 min at a temperature of 40 °C, and relative humidity of 100 % while performing or not performing ～30 W of isometric or isotonic exercise. The effect of the exercise was assessed by measuring tympanic temperature, heart rate, systolic and diastolic blood pressure, chest sweat rate, chest skin blood flow, and plasma catecholamine and cortisol, glucose, lactate, and free fatty acid levels. Repeated measures ANOVA showed no significant differences in blood pressure, skin blood flow, sweat rate, and total amount of sweating. Tympanic temperature increased more during isotonic exercise, and heart rate increase was more marked during isotonic exercise. The changes in lactate indicated that fatigue was not very great during isometric exercise. The glucose level indicated greater energy expenditure during isometric exercise. The free fatty acid and catecholamine levels indicated that isometric exercise did not result in very great energy expenditure and stress, respectively. The results for isotonic exercise of a decrease in lactate level and an increase in plasma free fatty acid level indicated that fatigue and energy expenditure were rather large while the perceived stress was comparatively low. We concluded that isotonic exercise may be a more desirable form of exercise during mist sauna bathing given the changes in glucose and free fatty acid levels.