Eating during the biological night is associated with nausea.

OBJECTIVES: This study assessed whether there was a time-of-day effect on nausea reports in participants during studies employing circadian protocols. METHODS: Visual-analog-scales of nausea ratings were recorded from 34 participants (18-70years; 18 women) during forced desynchrony studies, where meals were scheduled at different circadian phases. Subjective nausea reports from a further 81 participants (18-35years; 36 women) were recorded during constant routine studies, where they ate identical isocaloric hourly snacks for 36-40 hours. RESULTS: Feelings of nausea varied by circadian phase in the forced desynchrony studies, peaking during the biological night. Nausea during the constant routine was reported by 27% of participants, commencing 2.9 ± 5.2 hours after the midpoint of usual sleep timing, but was never reported to start in the evening (4-9 PM). CONCLUSIONS: Nausea occurred more often during the biological night and early morning hours. This timing is relevant to overnight and early morning shift workers and suggests that a strategy to counteract that is to pay careful attention to meal timing.

Impact of Common Diabetes Risk Variant in MTNR1B on Sleep, Circadian, and Melatonin Physiology.

The risk of type 2 diabetes (T2D) is increased by abnormalities in sleep quantity and quality, circadian alignment, and melatonin regulation. A common genetic variant in a receptor for the circadian-regulated hormone melatonin (MTNR1B) is associated with increased fasting blood glucose and risk of T2D, but whether sleep or circadian disruption mediates this risk is unknown. We aimed to test if MTNR1B diabetes risk variant rs10830963 associates with measures of sleep or circadian physiology in intensive in-laboratory protocols (n = 58-96) or cross-sectional studies with sleep quantity and quality and timing measures from self-report (n = 4,307-10,332), actigraphy (n = 1,513), or polysomnography (n = 3,021). In the in-laboratory studies, we found a significant association with a substantially longer duration of elevated melatonin levels (41 min) and delayed circadian phase of dim-light melatonin offset (1.37 h), partially mediated through delayed offset of melatonin synthesis. Furthermore, increased T2D risk in MTNR1B risk allele carriers was more pronounced in early risers versus late risers as determined by 7 days of actigraphy. Our results provide the surprising insight that the MTNR1B risk allele influences dynamics of melatonin secretion, generating a novel hypothesis that the MTNR1B risk allele may extend the duration of endogenous melatonin production later into the morning and that early waking may magnify the diabetes risk conferred by the risk allele.

Chromosomal region 15q21.1 is a frequent target of allelic imbalance in advanced breast carcinomas.

Allelic imbalance constitutes a major mechanism of genetic aberrations in breast cancer and strongly indicates the involvement of tumor associated genes in the affected chromosomal regions. Preliminary results from our study indicated the existence of a tumor suppressor gene located on chromosomal arm 15q which may be involved in breast cancer progression.1 In the present study, 210 primary breast carcinomas, 30 metastases and 26 local recurrences from primary breast carcinomas have been analyzed with a panel of 18 highly polymorphic microsatellite markers spanning the chromosomal region 15q11-21.3. Allelic imbalance at 15q with at least 1 marker was seen in 36 of 56 (64.3%) metastases and recurrences, but only in 58 of 210 (27.6%) primary tumors (p<0.0001). We identified a subregion defined by microsatellite marker CYP19 (15q21.1) that showed significantly higher frequencies of allelic imbalance in metastases and recurrences (57.6%) when compared to primary carcinomas (8.9%; p<0.0001). Allelic imbalance at 15q was correlated with histopathologic parameters of the patients with primary breast carcinomas. We detected a significant association with established predictors of poor prognosis, i.e., negative estrogen receptor status (p=0.003), negative progesterone receptor status (p=0.028), high grade (p=0.014) and positive axillary lymph nodes (p=0.013). In summary, our data provide further evidence for a novel prognostic marker in breast carcinomas located in the chromosomal region 15q21.