Influence of mild-to-moderate alcohol consumption on cardiovascular diseases in men from the general population

Background and methodsThere is controversy about the association between mild-to-moderate alcohol consumption and a reduced risk of cardiovascular diseases. The relationships between daily alcohol consumption and the incidence of acute myocardial infarction (MI) or ischemic stroke (IS) were examined in men in a community-based, prospective cohort study (n = 8014, age 40–80 years, mean age = 64.1 years). Alcohol consumption was categorized into 3 groups (A1, none or occasional; A2, ≤25 g/day; A3, >25 g/day as ethanol) at baseline.ResultsDuring the mean follow-up of 5.5 years, 53 MIs and 186 ISs occurred. On Cox regression analysis adjusted for age, hypertension, diabetes, dyslipidemia, smoking index, and body mass index (BMI), the hazard ratio (HR) for incident MI was significantly lower in the A2 group than in the A1 group (HR = 0.49, p = 0.043). The HR for incident MI in the A3 group tended to be lower than in the A1 group (HR = 0.53, p = 0.10). In obese subjects, while a significantly lower HR for incident MI in the A2 group was retained (HR = 0.29, p = 0.049), no significant difference in the HR of the A3 group compared with the A1 group was found. No significant differences were found in the IS-free curve among the 3 groups of alcohol consumption.ConclusionsAlcohol consumption may have a protective effect on the onset of MI but not on IS in the general population. A U-shaped relation between alcohol consumption and incident MI was found in obese subjects. An appropriate limit for daily alcohol consumption, depending on the risk of ischemic heart disease, may need to be established.     

The proteasomal subunit Rpn6 is a molecular clamp holding the core and regulatory subcomplexes together

Proteasomes execute the degradation of most cellular proteins. Although the 20S core particle (CP) has been studied in great detail, the structure of the 19S regulatory particle (RP), which prepares ubiquitylated substrates for degradation, has remained elusive. Here, we report the crystal structure of one of the RP subunits, Rpn6, and we describe its integration into the cryo-EM density map of the 26S holocomplex at 9.1?? resolution. Rpn6 consists of an α-solenoid-like fold and a proteasome COP9/signalosome eIF3 (PCI) module in a right-handed suprahelical configuration. Highly conserved surface areas of Rpn6 interact with the conserved surfaces of the Pre8 (alpha2) and Rpt6 subunits from the alpha and ATPase rings, respectively. The structure suggests that Rpn6 has a pivotal role in stabilizing the otherwise weak interaction between the CP and the RP.     

A Paced Auditory Serial Addition Task evokes stress and differential effects on masseter-muscle activity and haemodynamics

This study aimed to determine autonomic and jaw-muscle activities, and haemodynamic responses, to acute experimental mental stress in humans. Eleven healthy men (25.2 ± 3.0 years of age) and five healthy women (23.0 ± 3.7 years of age) performed a standardized mental stress task, the Paced Auditory Serial Addition Task (PASAT). Autonomic function, such as heart rate variability (HRV), and haemodynamic changes were recorded simultaneously. The success rate of the PASAT decreased with increased pace and duration. Low-frequency (5.8 ± 1.1 ms(2)) and high-frequency (5.3 ± 0.6 ms(2)) components of HRV decreased during the PASAT (to 5.0 ± 0.9 ms(2) and 4.6 ± 1.1 ms(2), respectively) as an indication of acute stress. Oxygenated haemoglobin in the masseter muscle (14.6 ± 2.2 10(4) units mm(-3)) remained at an elevated level during the PASAT (15.5 ± 2.5 10(4) units mm(-3)), whereas deoxygenated haemoglobin (7.8 ± 2.3 10(4) units mm(-3)) showed a consistent decrease (to 6.8 ± 2.1 10(4) units mm(-3)). Total haemoglobin and jaw-muscle electromyographic (EMG) activity did not change during the PASAT. Thus, PASAT-induced mental stress changed the parasympathetic/sympathetic balance of the heart and had an acute influence on jaw-muscle haemodynamics, but not on jaw-muscle EMG activity. This non-invasive experimental set-up can be applied to study the effects of repeated or longer-lasting mental stress in order to further the understanding of pathophysiological mechanisms in craniofacial pain conditions.     

Multistage bone-charged distraction osteogenesis for aesthetic reconstruction of an extensive bone deficiency in the mandible

Alveolar and mandibular bone defects impair occlusion and affect the aesthetics of facial contouring, making it difficult to obtain a satisfactory outcome. Treatment with distraction osteogenesis (DO) is particularly difficult in cases in which the defective region extends to close to the inferior margin of the mandible. To overcome the limits of current DO, we developed a method as follows. In the first stage, a submucosal space necessary for bone grafting was prepared by soft tissue expansion through DO. In the second stage, an iliac corticocancellous bone was transplanted with its cancellous side in close contact with the new bone in the space formed on the labial side into this new space. In the third stage, the grafted bone was distracted. This technique requires time, but each surgery is of minimum invasiveness and does not leave a visible scar; use of this technique may expand the limited indication of current DO and dental implants.