The connection of polymorphism and diurnal changes of the biological clock gene expression with the risk of progression of primary open-angle glaucoma

The purpose of this work is to study the connection betweengenetic factors (polymorphism and expression of key genes of the biological clock (KGBC), key genes controlled by KGBC, melatonin receptors) and the diurnal oscillation of melatonin in patients with stable and progressing primary open-angle glaucoma. Materials and methods. The study involved 115 patients aged 53–86 (averagely, 68.8 ± 7.9 years) with stable and progressive glaucoma. All patients underwent primary ophthalmological examination, tested for diurnal body temperature profile, intraocular pressure (IOP), melatonin (by the DLMO protocol) and were typed for key genes of the biological clock using the real-time polymerase chain reaction. We studied the sleep phase shift to later hours in carriers of the G-allele of the melatonin receptor gene during the progression of glaucoma. Results. The study of the clinical and genotypic features of the POAG course revealed phasal shifts of the circadian rhythms of body temperature, IOP, salivary melatonin levels and sleep phases which contributed to the progression of glaucomatous optic neuropathy. Certain polymorphic variants of genes contribute to individual frequent manifestations of desynchronosis. The clock rs1801260 and MTNR1B rs10830963 gene polymorphism was found to be related to disturbances in melatonin production and sleep phase. Conclusion. Complex manifestations of circadian desynchronization accompanying the progressive course of glaucoma are the late phase of rhythms and a decrease in sleep duration, body temperature, salivary melatonin and IOP, internal desynchronization between IOP and body temperature, IOP and sleep, evening dyslipidemia. The revealed patterns open up prospects for future studies of the relationship between polymorphism and daily changes of the expression of key genes in the biological clock with the risk of progression of primary open angle glaucoma.

O031 Nocturnal melatonin secretion in post-treatment breast cancer patients: a preliminary study

Purpose Breast-cancer patients frequently report of poor sleep-quality. Although the pathophysiology is unclear, circadian-sleep misalignment is a plausible mechanism. We compared nocturnal melatonin-secretion, a circadian rhythm marker, in post-menopausal, post-treatment (≥12-months) female breast-cancer patients (BCG), with post-menopausal female controls with no history of cancer (CG) Methods We recruited 6 BCG and 10 CG from Westmead Hospital breast-cancer outpatient clinic or hospital-staff community, respectively. Participants completed the Pittsburgh Sleep Quality Index (PSQI; >5 PSQI-score=poor sleep-quality) and ~7 days of home-actigraphy (Philips Actiwatch-2, Philips Respironics, USA) to ascertain habitual bed-time (HBT). Later, participants completed an overnight, in-laboratory study, with saliva sampled (n=13) at regular intervals under strict dim-light conditions (<1 lux). Salivary-melatonin concentrations were quantified via radioimmunoassay (University of Adelaide). We measured 1) clock-time when salivary-melatonin concentrations reached 4pg/mL (melatonin onset-[DLMO-4pg/ml]) and 2) time-interval between HBT and DLMO-4pg/ml (indicates circadian-sleep misalignment-[PAR-DLMO]). Data were expressed as median [interquartile range], and compared using 2-sided Mann Whitney U-tests. p<0.05 was considered significant. Results BCG and CG had similar ages (62.5 [59.5–67.3] vs. 58.5 [54.0–66.3] yrs, respectively; p=0.23). Compared with CG, BCG had higher PSQI-scores (8.50 [5.25–10.75] vs. 4.00 [3.75–5.50] a.u.; p=0.07), but similar HBT (22:49 [21:46-23:38] vs. 22:17 [21:59-22:21] h:min; p=0.26). BCG had later DLMO-4pg/ml (20:46 [20:01-22:03] vs. 18:23 [17:55-20:07] h:min; p=0.03) and shorter PAR-DLMO (1.43 [0.96–2.38] vs. 3.63 [2.18–3.90] hrs; p=0.09), than CG. Conclusion Preliminary data indicate BCG had poorer sleep-quality, delayed melatonin onset, and altered circadian-sleep alignment; compared with CG. We speculate disrupted nocturnal melatonin-secretion potentially influences poor sleep-quality reported by breast-cancer patients.

Possible role of melatonin in precocious and accelerated puberty in females during the COVID-19 pandemic

BackgroundPubertal development is a complex process influenced by a multitude of factors; among these, the role of melatonin has only been partially investigated. During the COVID-19 pandemic an unexpected increase in cases of precocious and fast puberty was observed.AimsTo evaluate the possible role of salivary melatonin in precocious and accelerated puberty during the COVID-19 lockdown.Patients and MethodsFifty-four females were evaluated from October 2020 to March 2021; of these, 39 children were diagnosed with central precocious puberty (CPP) and 15 with isolated premature thelarche (IPT). Thirty-three healthy children acted as controls. The enrolled patients were asked to take measures the day before the visit to avoid influencing readings of melatonin secretion. Salivary melatonin levels were analyzed using commercially available ELISA kit.ResultsThere was no difference in the time from B2 to diagnosis (months) between IPT and CPP patients. However, the anamnestic and clinical data of our CPP patients confirmed an acceleration in the stages of pubertal development. As expected, subjects with CPP showed a significantly greater stature SDS and height velocity SDS. There were no differences in BMI SDS and Delta BMI SDS. Interestingly, we discovered a significant difference regarding the use of electronic devices between children with CPP, IPT and controls (p < 0.05). Children with CPP showed significantly lower values of salivary melatonin than patients with TPT and controls (p < 0.0001).DiscussionOur results showed a marked reduction in salivary melatonin in children with CPP diagnosed during and after lockdown for COVID-19. Larger studies are needed to confirm and investigate these findings.

Changes in Salivary Melatonin Levels by Scaling and Root Planning in Patients with Chronic Periodontitis

Background: Periodontitis is a chronic inflammatory disease that causes tissue destruction due to the imbalance in the oxidant-antioxidant system. Melatonin has anti-inflammatory, antioxidant, and immune-modulatory properties and is considered to be a biomarker and diagnostic/therapeutic agent in the pathogenesis of periodontitis. Objectives: The present study aimed to evaluate the salivary melatonin level and its changes following non-surgical periodontal therapy in patients with periodontitis. Methods: In total, 90 salivary samples were collected from 60 patients, including 30 from patients with moderate chronic periodontitis (before periodontal treatment), and 30 from the same patients one month after the non-surgical periodontal therapy, and 30 from periodontally healthy subjects (control). Salivary melatonin levels were measured using the competitive immunoassay of the human melatonin ELISA kit. Results: The highest melatonin concentration was observed in the control group (79.55 ± 59.22; P < 0.05), while the lowest concentration was observed in the pre-treatment group (P < 0.05). In addition, salivary melatonin concentration in the post-treatment group (56.58 ± 46.48) was significantly higher compared to the pre-treatment group (17.25 ± 5.79; P < 0.05). Conclusions: According to the results, salivary melatonin levels improved after non-surgical periodontal therapy, which suggests the involvement of melatonin in the pathogenesis of periodontitis. However, the exact role of melatonin requires further investigation.

Salivary melatonin in oral squamous cell carcinoma patients

Melatonin’s role in circadian rhythm is well documented, as are its’ anti-oxidant, oncostatic and anti-inflammatory properties. Poor sleep quality has been associated as a potential risk factor for several malignancies, including head and neck cancers. The purpose of this study is to determine salivary melatonin (MLT) levels in oral squamous cell carcinoma (OSCC) patients, compare the salivary MLT levels with those in healthy individuals and compare the salivary and serum levels in OSCC patients. Furthermore, the aim is to investigate the potential relationship between sleep quality and salivary MLT levels in OSCC patients. Unstimulated (UWS) and stimulated (SWS) whole saliva was sampled from patients with T1N0M0 and T2N0M0 OSCC (N = 34) and 33 sex and age matched healthy subjects. Serum samples were taken from 11 OSCC patients. Sleep quality was measured using Pittsburgh Sleep Quality Index (PSQI) questionnaire. Melatonin levels in UWS and SWS were significantly higher in the OSCC group. Sleep quality was significantly lower in patients with OSCC (P = 0.0001). ROC analysis was found to be significant (P < 0.001) in evaluating MLT concentration limit in diagnosing OSCC. The expected relationship between sleep quality and salivary MLT levels in OSCC patients was not observed. Our results suggest salivary MLT as a potential biomarker that might facilitate non-invasive detection of early stage OSCC.

Assessing Sleep Architecture With Polysomnography During Posttraumatic Amnesia After Traumatic Brain Injury: A Pilot Study

Background Early-onset sleep disturbance is common following moderate to severe traumatic brain injury (TBI) and often emerges while patients are in posttraumatic amnesia (PTA). However, sleep disruptions during this subacute recovery phase are not well-defined, and research often utilizes indirect measures (actigraphy) that quantify sleep based on activity. This study aims to examine sleep macro-architecture and sleep quality directly with ambulatory polysomnography (PSG) and measure endogenous salivary melatonin levels for patients experiencing PTA following moderate to severe TBI. Method Participants were recruited from an inpatient TBI rehabilitation unit. Nighttime PSG was administered at the patient’s bedside. Two saliva specimens were collected for melatonin testing on a separate evening (24:00 and 06:00 hours) using melatonin hormone profile test kits. Results Of 27 patients in whom PSG was recorded, the minimum required monitoring time occurred in n =17 (adherence: 63%) at a median of 37.0 days (quartile 1 [Q1] to quartile 3 [Q3]: 21.5-50.5) postinjury. Median non–rapid eye movement (NREM) and REM sleep proportions were similar to normal estimates. Slow-wave sleep was reduced and absent in 35.3% of patients. Sleep periods appeared fragmented, and median sleep efficiency was reduced (63.4%; Q1-Q3: 55.1-69.2). Median melatonin levels at both timepoints were outside the normal range of values specified for this test (from Australian Clinical Labs). Conclusion This study reports that ambulatory PSG and salivary melatonin assessment are feasible for patients experiencing PTA and offers new insight into the extent of sleep disturbance. Further research is necessary to understand associations between PTA and sleep disturbance.

098 Effects of Metameric Display-Light on Alertness, Vigilance and Melatonin

Introduction Light emitted from visual displays can acutely increase alertness, improve cognitive performance and suppress melatonin in the evening. Here we tested the influence of different melanopic irradiance levels emitted by a metameric display setting on alertness, vigilance and salivary melatonin levels. Methods In an ongoing study, 37 healthy, male participants have so far completed a 2-week study protocol. Volunteers were assigned to one of four luminance groups which differed in brightness levels (27 cd/m2 - 280 cd/m2). Illuminance ranged between 7 and 85 lx. Within the four groups each volunteer was exposed to a low melanopic (LM) and a high melanopic condition (HM). The LM and HM differed in melanopic irradiance (ca. 3-fold change), but matched in terms of cone excitation (metamers). Before, during and after the light exposure, volunteers performed a psychomotor vigilance task (PVT). Subjective alertness and melatonin levels were continuously measured in half-hourly intervals throughout scheduled wakefulness in the 17-h in lab study. Results Preliminary analysis yielded an overall alerting response in the HM vs. the LM condition (p&lt;0.05) concomitant with a trend of reduced melatonin levels in HM vs. LM (p=0.08). So far, we could not observe a difference in PVT performance for HM and LM (Reaction time responses between 100 and 500 ms). Since we are still lacking statistical power in the ongoing study, we cannot yet satisfactorily interpret interaction effects between melanopic condition and brightness. Conclusion Our data indicate that rather low brightness levels of high melanopic display light impacts alertness and melatonin levels in the evening. Thus, metameric low melanopic display light may be a promising method to attenuate activating properties of evening light on circadian physiology without affecting visual appearance. Support (if any) This project is funded by the Swiss National Science Foundation (SNSF).