Alfredo Copertaro

Rotating-shift nurses after a day off: peripheral clock gene expression, urinary melatonin, and serum 17-β-estradiol levels.

OBJECTIVE Impairment of clock gene expression and changes in melatonin and 17-β-estradiol levels may constitute biological alterations underlying the increased risk of breast cancer among shift workers. The aim of this study was to compare levels of selected core clock gene expression, 6-sulfatoxymelatonin (aMT6s), and 17-β-estradiol between rotational shift work (SW) and daytime (DT) workers after a day off. METHODS The cross-sectional study comprised 60 nurses with ≥2 years of SW and 56 permanent DT nurses. Transcript levels of circadian genes BMAL1, CLOCK, NPAS2, CRY1, CRY2, PER1, PER2, PER3, and REVERBα were determined by quantitative real-time polymerase chain reaction (PCR) in lymphocytes. All participants were tested in the early follicular phase of the menstrual cycle. Samples were collected at the beginning of the morning-shift after a regular nights sleep on a day off. Chronotype and sociodemographic characteristics were also evaluated. RESULTS We found a significantly higher expression of BMAL1, CLOCK, NPAS2, PER1, PER2, and REVERBα and a lower expression of PER3, CRY1 and CRY2 among SW compared to DT nurses. SW participants did not demonstrate a significant difference in aMT6s levels, but they did show significantly higher 17-β-estradiol levels compared to DT nurses. Multiple linear regression analysis confirmed the role of SW on expression of BMAL1 (β 0.21, P=0.040), CLOCK (β 0.35, P=0.008), NPAS2 (β 0.30, P=0.012), PER1 (β 0.33, P=0.008), PER2 (β 0.19, P=0.047), PER3 (β -0.27, P=0.012), CRY1 (β -0.33, P=0.002), CRY2 (β -0.31, P=0.005), REVERBα (β 0.19, P=0.045), and on 17-β-estradiol levels (β 0.32, P=0.003). The analysis also confirmed the role of chronotype as an independent factor for PER1 (β 0.48, P=0.001) and PER2 (β -0.22, P=0.022) expression, and 17-β-estradiol levels (β 0.26, P=0.011). CONCLUSIONS Rotating SW nurses show alterations in peripheral clock gene expression and 17-β-estradiol levels at the beginning of the morning shift after a day off.

Relationship of job satisfaction, psychological distress and stress-related biological parameters among healthy nurses: a longitudinal study.

Relationship of Job Satisfaction, Psychological Distress and Stress‐Related Biological Parameters among Healthy Nurses: A Longitudinal Study: Monica Amati, et al. Department of Molecular Pathology and Innovative Therapies, Clinic of Occupational Medicine, Polytechnic University of Marche, Italy

Attachment security and immunity in healthy women.

Background: Attachment security is associated with health and possibly autonomic and endocrine reactivity to stress, however the relationship between attachment style and immune function has not yet been investigated. Methods: A random sample of 61 female nurses provided a blood sample and completed the Perceived Stress Scale, the Multidimensional Scale of Perceived Social Support, the 20-item Toronto Alexithymia Scale, and the Experiences in Close Relationships questionnaire. Immune measures included immunophenotypic analysis, lymphocyte proliferative response to Phytohemagglutinin, and NK cell cytotoxicity (NKCC). Statistical analysis focused on the relationship between attachment-related anxiety or avoidance and immune measures. Multiple regression was used to control for perceived stress and support, alexithymia, health-related behaviors possibly influencing immunity, and use of anti-inflammatory drugs, tobacco or alcohol. Results: Attachment-related anxiety was not associated with any immune parameter. Attachment-related avoidance was associated with lower NKCC. This association was independent from the number of circulating NK cells, which suggests a change in cell functionality. Perceived stress was also associated with lower NKCC. Conclusions: This study suggests a link between attachment security and immunity. While our findings should be interpreted with great caution and need replication, they are consistent with previous work suggesting that insecure attachment may be a risk factor for health and may relate to biological processes relevant to health. PSS = Perceived Stress Scale; MSPSS = Multidimensional Scale of Perceived Social Support; TAS-20 = 20-item Toronto Alexithymia Scale; ECR = Experiences in Close Relationships questionnaire; PHA = Phytohemagglutinin; NKCC = Natural Killer Cell Cytotoxicity; BMI = body mass index.

Circadian Modulation of 8-Oxoguanine DNA Damage Repair

The DNA base excision repair pathway is the main system involved in the removal of oxidative damage to DNA such as 8-Oxoguanine (8-oxoG) primarily via the 8-Oxoguanine DNA glycosylase (OGG1). Our goal was to investigate whether the repair of 8-oxoG DNA damage follow a circadian rhythm. In a group of 15 healthy volunteers, we found a daily variation of Ogg1 expression and activity with higher levels in the morning compared to the evening hours. Consistent with this, we also found lower levels of 8-oxoG in morning hours compared to those in the evening hours. Lymphocytes exposed to oxidative damage to DNA at 8:00 AM display lower accumulation of 8-oxoG than lymphocytes exposed at 8:00 PM. Furthermore, altered levels of Ogg1 expression were also observed in a group of shift workers experiencing a deregulation of circadian clock genes compared to a control group. Moreover, BMAL1 knockdown fibroblasts with a deregulated molecular clock showed an abolishment of circadian variation of Ogg1 expression and an increase of OGG1 activity. Our results suggest that the circadian modulation of 8-oxoG DNA damage repair, according to a variation of Ogg1 expression, could render humans less susceptible to accumulate 8-oxoG DNA damage in the morning hours.

Attachment style and immunity: A 1-year longitudinal study

Previous cross-sectional studies suggested an association between attachment-related avoidance and altered immune function. We aimed at testing this hypothesis with longitudinal data. A random sample of 65 female nurses provided a blood sample and completed measures of perceived stress, social support, alexithymia, and attachment style. Immune assays included lymphocyte proliferative response (LPR) to Phytohemagglutinin and NK cell cytotoxicity (NKCC). State measures (perceived stress and support) and immune measures were collected again after 4, 8, and 12 months. Linear mixed effects models were used to examine the relationship between attachment and immunity. While low to moderate levels of attachment-related avoidance were not associated with NKCC, there was a significant negative association (beta -.35; p=.005) between high levels of avoidance and NKCC. No association was observed between NKCC and attachment-related anxiety, and between LPR and both attachment dimensions. While our findings should be interpreted with caution due to study limitations such as the relatively small sample size and the inclusion of only female participants, they corroborate the notion that attachment is linked to physiology and health.

Peripheral Skin Temperature and Circadian Biological Clock in Shift Nurses after a Day off

The circadian biological clock is essentially based on the light/dark cycle. Some people working with shift schedules cannot adjust their sleep/wake cycle to the light/dark cycle, and this may result in alterations of the circadian biological clock. This study explored the circadian biological clock of shift and daytime nurses using non-invasive methods. Peripheral skin temperature, cortisol and melatonin levels in saliva, and Per2 expression in pubic hair follicle cells were investigated for 24 h after a day off. Significant differences were observed in peripheral skin temperature and cortisol levels between shift and daytime nurses. No differences in melatonin levels were obtained. Per2 maximum values were significantly different between the two groups. Shift nurses exhibited lower circadian variations compared to daytime nurses, and this may indicate an adjustment of the circadian biological clock to continuous shift schedules. Non-invasive procedures, such as peripheral skin temperature measurement, determination of cortisol and melatonin in saliva, and analysis of clock genes in hair follicle cells, may be effective approaches to extensively study the circadian clock in shift workers.

Circadian gene expression and extremely low-frequency magnetic fields: an in vitro study.

It is well known that circadian clocks are mainly regulated by light targeting signaling pathways in the hypothalamic suprachiasmatic nucleus. However, an entrainment mediated by non-photic sensory stimuli was also suggested for peripheral clocks. Exposure to extremely low frequency (ELF) electromagnetic fields might affect circadian rhythmicity. The goal of this research was to investigate effects of ELF magnetic fields (ELF-MF) on circadian clock genes in a human fibroblast cell line. We found that an ELF-MF (0.1 mT, 50 Hz) exposure was capable of entraining expression of clock genes BMAL1, PER2, PER3, CRY1, and CRY2. Moreover, ELF-MF treatment induced an alteration in circadian clock gene expression previously entrained by serum shock stimulation. These results support the hypothesis that ELF-MF may be able to drive circadian physiologic processes by modulating peripheral clock gene expression.

Low perceived social support is associated with CD8+CD57+ lymphocyte expansion and increased TNF-α levels.

Social support has been supposed to have a positive impact on the function of the immune system. However, the relationship between perceived social support and immune function has not yet been fully investigated. In this cross-sectional study, we investigated the link between perceived social support and lymphocyte subpopulations and cytokines. 232 healthy subjects provided a blood sample and completed the Multidimensional Scale of Perceived Social Support (MSPSS) questionnaire. Lymphocyte immunophenotypes and cytokines were determined. Significantly increased CD8+CD57+ lymphocytes and TNF-α levels were found in group with low perceived social support. Multivariate linear regression corrected for possible confounders confirmed a significant role of perceived social support in predicting the number of CD8+CD57+ lymphocyte and TNF-α levels. This study supports the association between perceived social support and immune function. In particular, poor social support may be related to a state of chronic inflammation sustained by CD8+CD57+ lymphocyte expansion and increased TNF-α levels.

Styrene altered clock gene expression in serum-shocked cultured human fibroblasts.

The circadian clock can regulate the metabolic process of xenobiotics, but little is known as to circadian rhythms can be perturbed by xenobiotics. Styrene is a organic chemical widely used in occupational settings. The effects of styrene on the circadian genes of HuDE cells were evaluated after serum-shocking synchronization. A subtoxic dose of 100 µM of styrene altered the expression of clock genes BMAL1, PER2, PER3, CRY1, CRY2, and REV-ERB-α.