Carbonylation of skin collagen induced by reaction with methylglyoxal.

Our previous studies have shown that glycerin, which is present at high concentrations in moisturizers and skin lotions, gradually oxidizes to produce methylglyoxal (MGO). In this study, we observed that MGO-treated porcine dermis type-I collagen was carbonylated in an MGO concentration- and time-dependent manner. Furthermore, we examined the structure of advanced glycation end products (AGEs) induced by MGO reacting with type-I collagen. Our findings demonstrate that the α chains of collagen reacted with MGO and easily transformed into a modified protein containing a methylglyoxal-derived hydroimidazolone (MG-H1) moiety in a concentration- and time-dependent manner. Moreover, porcine skin proteins underwent carbonylation when the skin section was treated with MGO for four weeks. Analysis of the structure of AGEs on the carbonylated proteins extracted from MGO-treated skin sections revealed that skin collagen had been converted to MG-H1-modified protein. These novel findings suggest that continuous application of MGO to the skin leads to carbonylation of proteins, which may cause prompt accumulation of MG-H1-modified dermis collagen, thereby resulting in morphological and functional changes of collagen in the skin.

Association of sleep duration on workdays or free days and social jetlag with job stress.

AIM: The aim of this study was to investigate the impact of sleep problems on job stress in office workers. METHODS: This study included 4645 office workers from 29 companies who completed the study questionnaires between April 2017 and April 2019 in Japan. Sleep duration was assessed based on the participants' subjective sleep schedule on workdays and free days. The midpoint of sleep on free days (sleep-corrected) and social jetlag were calculated in accordance with the Munich Chronotype Questionnaire. To assess job stress, we used the 57-item Brief Job Stress Questionnaire. RESULTS: Multivariate logistic regression analysis revealed that the following factors were significantly associated with high job stress in office workers: a sleep duration <6 h on workdays (OR = 1.77, 95% CI = 1.46-2.15, P < 0.001), a sleep duration <6 h on free days (OR = 1.40, 95% CI = 1.05-1.87, P = 0.022), a sleep duration of at least 8 h on free days (OR = 1.31, 95% CI = 1.06-1.60, P = 0.011), and more than 2 h of social jetlag (OR = 1.33, 95% CI = 1.04-1.70, P = 0.022). CONCLUSION: This study suggests that insufficient sleep, long sleep durations on free days, and social jetlag may be associated with high job stress in office workers.

Oxidative Formation of Methylglyoxal in Glycerol Preparations during Storage.

Methylglyoxal (MGO) is a reactive α-dicarbonyl compound that causes carbonylation of protein and DNA through the pathways of the Maillard reaction. It is known that MGO is physiologically involved in renal dysfunction, vascular disorders, and the acceleration of aging. In this study, we showed for the first time, that a trace amount of MGO was present as an impurity in glycerol preparations used as external medicines and intravenous infusions, when kept unused. The concentration of MGO in the glycerol solutions, diluted to a concentration of 20%, significantly increased after storage for one month when compared to the MGO concentration immediately after opening. Following storage for 6 months at 25°C, MGO concentration increased by about 300 times (approx. 170 µM), and at 40°C, it increased by about 600 times (approx. 350 µM). In the case of intravenous infusion preparations containing 10% glycerol, the MGO concentration increased by 4-15 times (approx. 70 µM) after 2 months of storage at 40°C, and reached over 200 µM after 6 months. Results from the present study showed that glycerol in pharmaceutical preparations is gradually oxidized to form MGO via autoxidation, depending on the temperature and dissolved oxygen content. Thus, we suggest that precautions should be taken when storing glycerol preparations in bottles or plastic containers, with respect to the storage temperature and sealability to prevent MGO formation due to oxidation of glycerol.

Factors associated with hypnotics polypharmacy in the Japanese population.

OBJECTIVE: Insomnia disorder is a global public health issue, commonly treated with hypnotics. However, long-term use of benzodiazepine derivatives (BZDs), especially polypharmacy with this kind of drug, carries risks for dependence and abuse. This study using large-scale medical insurance records investigated the causes of polypharmacy through the treatment of insomnia disorder. METHODS: A cross-sectional study analyzed anonymized medical record data from July 2014 to March 2018 provided by a nationwide Japanese health insurance association covering 405,952 individuals. Outpatients prescribed at least one sleep medication were included. Demographic data, pharmacological classification of the drugs, and comorbidities were assessed using hierarchical logistic regression analysis to explore their associations with polypharmacy. RESULTS: Of the 33,212 outpatients who were prescribed sleep medications, 32.5 % were prescribed multiple types. After adjusting for demographics and type of sleep medications as covariates, hypnotic polypharmacy was significantly associated with younger age, the presence of certain kinds of comorbidities, and using BZD anxiolytics before bedtime with the highest adjusted odds ratios (8.01-9.39) when referenced with BZD hypnotics. On the other hand, usage of orexin receptor antagonists, melatonin receptor agonists, and Z-drugs indicated lower odds ratios (0.74-0.87). CONCLUSIONS: Hypnotic polypharmacy is relatively common in the Japanese general population. With the introduction of non-pharmacological therapy in mind, assessing patients' comorbidities and avoiding the use of benzodiazepines, especially BZD anxiolytics, before bedtime would be recommended to prevent polypharmacy.

On workdays, earlier sleep for morningness and later wakeup for eveningness are associated with better work productivity.

INTRODUCTION: Misalignment of chronotype and social schedules result in sleep and health impairments. Presenteeism, the work productivity loss caused by health problems, has much more social costs than absenteeism and is associated with sleep disturbance. However, little is known about the link between chronotype and presenteeism. In this study, the associations between chronotype, sleep schedules, presenteeism, and the mediating role of sleep disturbance were examined. METHODS: A cross-sectional survey was conducted on 8155 office workers from 42 companies in Japan, from 2017 to 2019. The participants answered self-administered questionnaires asking about presenteeism (Work Limitations Questionnaire [WLQ]), sleep disturbance (Pittsburgh Sleep Quality Index [PSQI]), and habitual sleep schedules which enable to calculate the midpoint of sleep on free days, sleep corrected (MSFsc). The mediating effect was examined by using structural equation modeling (SEM). RESULTS: The participants comprised 4462 males and 3677 females (mean age: 36.7 years), and their mean productivity loss was 5.97%. A later sleep onset (+0.29%/h), early wakeup (+0.14%/h), and eveningness (+0.27%/h, MSFsc) were associated with presenteeism in all participants; however, the effect size and significance differed depending on their chronotype. SEM demonstrated a complete mediation model between chronotype and presenteeism, mediated by sleep disturbance and adjusted by age. CONCLUSIONS: Chronotype did not directly, but indirectly affected presenteeism through sleep disturbance. Eveningness leads to sleep disturbance, which then causes presenteeism. On workdays, early sleep times for morningness people, and late wakeup times for eveningness people may improve their work productivity.

Which sleep hygiene factors are important? comprehensive assessment of lifestyle habits and job environment on sleep among office workers.

BACKGROUND: Although several lifestyle habits are associated with sleep, it is unclear which factors are important. Among office workers, the effect of job environment should also be considered. The multivariate analyses on the effects of lifestyle habits and job environment on sleep among office workers was conducted. METHODS: A cross-sectional survey of 6,342 employees from 29 companies was conducted in 2017-2019. Complete responses and informed consent were provided by 5,640 participants. The survey examined demographic variables, sleep schedules, Pittsburgh Sleep Quality Index (PSQI), Brief Job Stress Questionnaire (BJSQ), and lifestyle habits. RESULTS: Mean values were as follows: age, 36.9 years (±10.2); PSQI, 6.52 (±2.83); and total sleep time, 6h06m (±1h40m) on work days and 7h39m (±1h58m) on free days. After adjusting for job environment and demographic variables, irregular meal time (1.45-2.86), not eating vegetables every day (1.35), nightcap (2.74-3.55), weight gain (1.20-1.42), lack of sunlight in the morning in the bedroom (1.48-1.60), waking up before dawn (2.18), electronic display use in bed (1.50), and daily caffeine intake (1.27) were significantly associated with sleep disturbance. Irregular meal time (1.51-2.37), lack of morning breakfast (1.74-2.95), having dinner within 2 hours before bed time (0.49-0.64), not eating vegetables every day (1.52), lack of sunlight exposure in the morning (1.43-2.01), and caffeine use every day (1.42) were also associated with eveningness (p<.01). CONCLUSION: Each sleep hygiene factor had a different effect size. Sleep hygiene interventions to promote worker sleep health should prioritize factors in accordance with effect size.