Glaucoma is a progressive optic neuropathy associated with damage to retinal ganglion cells (RGCs) and disrupted circadian rhythms. Melatonin is a promising substance to ameliorate glaucoma‐associated compromised circadian rhythms, sleep, mood, and retinal cells function. However, studies estimating melatonin effects in glaucoma are currently lacking. Therefore, In this study, we investigated the effect of long‐term (daily at 10:30 pm for 90 days) oral melatonin administration on systemic (Tb) and local to the organ of vision (IOP) circadian rhythms, pattern electroretinogram (PERG), sleep, and mood, depending on glaucoma stage in patients diagnosed with stable or advanced primary open‐angle glaucoma. In a laboratory study in 15 of them, 24‐hour records of salivary melatonin were obtained and MTNR1B receptor gene polymorphism was assessed. Melatonin increased the stability of the Tb circadian rhythm by improving its phase alignment and alignment with IOP. Melatonin time‐dependently decreased IOP and IOP standard deviation (SD). IOP 24‐hour mean and IOP SD decreases were more pronounced in individuals with the higher initial 24‐hour IOP mean. Melatonin improved RGCs function in advanced glaucoma; N95 amplitude increase correlated positively with RGCs loss. The beneficial effects of melatonin on sleep and mood were greater in advanced glaucoma. Finally, delayed salivary melatonin and Tb phases were observed in MTNR1B G‐allele carriers with advanced glaucoma. Combined, these results provide evidence for melatonin efficiency in restoring disrupted circadian rhythms in glaucoma with different effects of melatonin on systemic vs. local circadian rhythms, indicating that a personalized strategy of melatonin administration may further refine its treatment benefits.

Vinblastine and paclitaxel (Taxol) are widely used chemotherapeutic drugs that inhibit the normal function of microtubules causing mitotic arrest and cell death. Despite these similarities, the signaling pathways that mediate and regulate cell death induced by these agents remain incompletely understood. The purpose of this study was to directly compare the two drugs in terms of their ability to activate components of the c‐Jun N‐terminal protein kinase (JNK) pathway, and to establish the importance of these signaling events in apoptosis induced by these agents. We show that both drugs induce mitotic arrest and subsequent apoptotic cell death with highly similar kinetics and that both activate JNK and induce c‐Jun protein and c‐jun mRNA expression. Surprisingly, vinblastine induced c‐Jun phosphorylation and c‐jun transcriptional activation, although Taxol failed to do so. However, inhibition of JNK or an absence of JNK protected against both vinblastine‐ and Taxol‐induced cell death. These results suggest that although JNK activation plays an important role in cell death induced by both agents, vinblastine and Taxol differ markedly with respect to signaling downstream of JNK, with AP‐1‐dependent and ‐independent mechanisms, respectively. In addition, these results show, contrary to popular belief, that JNK activation is not necessarily accompanied by c‐Jun activation, and thus c‐Jun is not an obligate substrate of JNK.

The purpose of this work was to examine the relationships between geographical coordinates and the prevalence of winter depression (SADW ), and to compare the sleep characteristics and chronotype of youths with and without SADW . We conducted a cross-sectional study of self-reported sleep characteristics, chronotype and winter depression in northern European Russia. Two questionnaires, the Munich Chronotype Questionnaire (MCTQ) and the Seasonal Pattern Assessment Questionnaire (SPAQ), were administered to a total of 3435 adolescents aged 10-20 years (1517 males and 1918 females). The prevalence of SADW in the study population was 8.4% and sub-SADW 11.8%. Four variables predicted the likelihood of SADW in youths: sex [higher in females: odds ratio (OR): 1.87, P < 0.0001], age (increases with age: OR: 1.09, P < 0.001), latitude (higher in the North: OR: 1.49, P < 0.029) and position in the time zone (higher in the West: OR: 1.61, P < 0.001). Later sleeping and waking, longer sleep latencies, more severe sleep inertia, shorter total sleep times and lower sleep efficiencies were observed in both males and females with SADW . The influence of SADW on sleep characteristics was more pronounced on school days. Significant phase delays of the sleep-wake rhythm and severe social jetlag (the difference between the mid-point of sleep phase at weekends and on workdays) were observed in females with SADW , but not in males. There are significant differences in sleep characteristics and chronotype between people with SADW and no-SAD. We demonstrate that both latitude of residence and location within the time zone are significant predictors of SADW in young inhabitants of the North.

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