The Effect of Melatonin on Increasing the Health Related Quality of Life in Non-Metastatic Breast Cancer Patients: Three-Year Follow up a Clinical Trial.

INTRODUCTION: Although breast cancer is common worldwide, if diagnosed early and treated on time, the probability of recovery is high and patients often experience a long life. Reducing the quality of life is a common side effect in patients. Melatonin may have an important role in fatigue, sleep disorders and, as a result, the health-related quality of life (HRQoL) in people. About 184 patients with breast cancer were enrolled in 2 groups: intervention with daily melatonin intake of 18 mg for 3 years (93 patients) and the control group with placebo intake (91 patients). Health-related quality of life and the effect of melatonin on increasing that were evaluated with the EORTC QLQ-C30 questionnaire, third edition at the beginning, 2 months later and 3 years after the beginning of the study. RESULTS: The general score of the HRQoL was significantly different both in the passage of time and in the comparative study of the 2 groups, and it was better in the melatonin group (P < .05). CONCLUSION: Long-term use of 18 mg of melatonin for 3 years in patients with non-metastatic breast cancer can lead to an increase in the patients' quality of life.

The Potential of Integrative Cancer Treatment Using Melatonin and the Challenge of Heterogeneity in Population-Based Studies: A Case Report of Colon Cancer and a Literature Review.

Melatonin is a multifunctional hormone regulator that maintains homeostasis through circadian rhythms, and desynchronization of these rhythms can lead to gastrointestinal disorders and increase the risk of cancer. Preliminary clinical studies have shown that exogenous melatonin alleviates the harmful effects of anticancer therapy and improves quality of life, but the results are still inconclusive due to the heterogeneity of the studies. A personalized approach to testing clinical parameters and response to integrative treatment with nontoxic and bioavailable melatonin in patient-centered N-of-1 studies deserves greater attention. This clinical case of colon cancer analyzes and discusses the tumor pathology, the adverse effects of chemotherapy, and the dynamics of markers of inflammation (NLR, LMR, and PLR ratios), tumors (CEA, CA 19-9, and PSA), and hemostasis (D-dimer and activated partial thromboplastin time). The patient took melatonin during and after chemotherapy, nutrients (zinc, selenium, vitamin D, green tea, and taxifolin), and aspirin after chemotherapy. The patient's PSA levels decreased during CT combined with melatonin (19 mg/day), and melatonin normalized inflammatory markers and alleviated symptoms of polyneuropathy but did not help with thrombocytopenia. The results are analyzed and discussed in the context of the literature on oncostatic and systemic effects, alleviating therapy-mediated adverse effects, association with survival, and N-of-1 studies.

Efficacy of optimal nutraceutical combination in treating PCOS characteristics: an in-silico assessment.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a serious health condition affecting women of reproductive age. High prevalence of PCOS and associated metabolic complications needs effective treatment and management. This study evaluated the efficacy of optimal nutraceutical combinations in improving PCOS characteristics using system biology-based mathematical modelling and simulation. METHODS: A shortlisting of eight potent nutraceuticals was carried out with literature search. Menstrual cycle model was used to perform simulations on an in-silico population of 2000 individuals to test individual and combined effects of shortlisted nutraceuticals on five PCOS characteristics [oligomenorrhea, anovulation, hirsutism, infertility, and polycystic ovarian morphology (PCOM)] for a duration of 6 months. Efficacy was tested across lean and obese phenotypes and age groups. RESULTS: Individual assessment of nutraceuticals revealed seven most potent compounds. Myo-inositol among them was observed to be the most effective in alleviating the PCOS characteristics. The in-silico population analysis showed that the combination of melatonin and ALA along with myo-inositol was efficacious in restoring the hormonal balance across age-groups and Body Mass Index (BMI) categories. CONCLUSION: Supplementation with the combination of myo-inositol, melatonin, and ALA demonstrated potential in managing PCOS symptoms in our in-silico analysis of a heterogeneous population, including lean and obese phenotypes across various severities and age groups, over a 6-month period. Future clinical studies are recommended to validate these findings.

Meta-analysis and machine learning reveal the antiobesity effects of melatonin on obese rodents.

Melatonin appears to be a promising supplement for obesity treatment. The antiobesity effects of melatonin on obese rodents are influenced by various factors, including the species, sex, the dosage of melatonin, treatment duration, administration via, daily treatment time, and initial body weight (IBW). Therefore, we conducted a meta-analysis and machine learning study to evaluate the antiobesity effect of melatonin on obese mice or rats from 31 publications. The results showed that melatonin significantly reduced body weight, serum glucose (GLU), triglycerides (TGs), low-density lipoprotein (LDL), and cholesterol (TC) levels in obese mice or rats but increased high-density lipoprotein (HDL) levels. Melatonin showed a slight positive effect on clock-related genes, although the number of studies was limited. Meta-regression analysis and machine learning indicated that the dosage of melatonin was the primary factor influencing body weight, with higher melatonin dosages leading to a stronger weight reduction effect. Together, male obese C57BL/6 mice and Sprague-Dawley rats with an IBW of 100-200 g showed better body weight reduction when supplemented with a dose of 10-30 mg/kg melatonin administered at night via injection for 5-8 weeks.

Protective Effect of the Novel Melatonin Analogue Containing Donepezil Fragment on Memory Impairment via MT/ERK/CREB Signaling in the Hippocampus in a Rat Model of Pinealectomy and Subsequent Aß1-42 Infusion.

A reduction in melatonin function contributes to the acceleration of Alzheimer's disease (AD), and understanding the molecular processes of melatonin-related signaling is critical for intervention in AD progression. Recently, we synthesized a series of melatonin analogues with donepezil fragments and tested them in silico and in vitro. In this study, one of the most potent compounds, 3c, was evaluated in a rat model of pinealectomy (pin) followed by icvAß1-42 infusion. Melatonin was used as the reference drug. Treatment with melatonin and 3c (10 mg/kg, i.p. for 14 days) had a beneficial effect on memory decline and the concomitant increase in hippocampal Aß1-42 and pTAU in the pin+icvAß1-42 rats. Melatonin supplementation facilitated non-amyloidogenic signaling via non-receptor (histone deacetylase sirtuin 1, SIRT1) and receptor-related signaling (MT/ERK/CREB). The hybrid 3c analogue up-regulated the MT1A and MT2B receptors, pERK and pCREB. Our results strongly support the hypothesis that melatonin-related analogues may become a promising drug candidate for Alzheimer's disease therapy.

Just Let Me Sleep in: Identifying and Treating Delayed Sleep Phase Disorder in Adolescents.

Individuals with delayed sleep phase disorder (DSPD) are unable to naturally fall asleep and awake at conventional times; for this reason, DSPD is often mistaken for insomnia. However, unlike many patients with insomnia, those with DSPD struggle to get up at appropriate times. DSPD is associated with school refusal, academic difficulties, and lower employment rate. DSPD in youth has prevalence as high as 16%, and is often comorbid with other psychiatric disorders. Treatments include appropriate light exposure during the day, melatonin use, developing an evening routine that minimizes arousal-increasing activities, and gradually shifting sleep-wake times toward more functional ones.

Nutritional supplements and IVF: an evidence-based approach.

Many women undergoing IVF take supplements during treatment. The purpose of this review was to systematically review these nutritional supplements. The therapies studied are dehydroepiandrosterone (DHEA), melatonin, co-enzyme Q10 (CoQ1O), carnitine, selenium, vitamin D, myo-inositol, omega-3, Chinese herbs and dietary interventions. A literature search up to May 2023 was undertaken. The data suggest that a simple nutritional approach would be to adopt a Mediterranean diet. With regards to supplements to treat a potential poor ovarian response to ovarian stimulation, starting DHEA and COQ-10 before cycle commencement is better than control therapies. Furthermore, medication with CoQ10 may have some merit, although it is unclear whether its place is for older women, for those with a poor response to ovarian stimulation or for poor embryonic development. There appears a benefit for some IVF outcomes for the use of melatonin, although it is unclear what group of patients would derive the benefit and the appropriate dosing regimen. For women with polycystic ovary syndrome, there may be a benefit to the use of myo-inositol, although again the dosing regimen is unclear. Furthermore, the place of vitamin D supplementation has yet to be clarified, and supplementation with omega-3 free fatty acids may lead to improvements in clinical and embryological IVF outcomes.

Unraveling the impact of melatonin treatment: Oxidative stress, metabolic responses, and morphological changes in HuH7.5 hepatocellular carcinoma cells.

In addition to its highly aggressive nature and late diagnosis, hepatocellular carcinoma (HCC) does not respond effectively to available chemotherapeutic agents. The search is on for an ideal and effective compound with low cost and minimal side effects that can be used as an adjunct to chemotherapeutic regimens. One of the mechanisms involved in the pathology of HCC is the oxidative stress, which plays a critical role in tumor survival and dissemination. Our group has already demonstrated the antitumor potential of melatonin against HuH 7.5 cells. In the present study, we focused on the effects of melatonin on oxidative stress parameters and their consequences on cell metabolism. HuH 7.5 cells were treated with 2 and 4 mM of melatonin for 24 and 48 h. Oxidative stress biomarkers, antioxidant enzyme, mitochondrial membrane potential, formation of lipid bodies and autophagic vacuoles, cell cycle progression, cell death rate and ultrastructural cell alterations were evaluated. The treatment with melatonin increased oxidative stress biomarkers and reduced antioxidant enzyme activities of HuH 7.5 cells. Additionally, melatonin treatment damaged the mitochondrial membrane and increased lipid bodies and autophagic vacuole formation. Melatonin triggered cell cycle arrest and induced cell death by apoptosis. Our results indicate that the treatment of HuH 7.5 cells with melatonin impaired antioxidant defense systems, inhibited cell cycle progression, and caused metabolic stress, culminating in tumor cell death.

Melatonin in cancer biology: pathways, derivatives, and the promise of targeted delivery.

Melatonin, historically recognized for its primary role in regulating circadian rhythms, has expanded its influence particularly due to its wide range of biological activities. It has firmly established itself in cancer research. To highlight its versatility, we delved into how melatonin interacts with key signaling pathways, such as the Wnt/ß-Catenin, PI3K, and NF-κB pathways, which play foundational roles in tumor development and progression. Notably, melatonin can intricately modulate these pathways, potentially affecting various cellular functions such as apoptosis, metastasis, and immunity. Additionally, a comprehensive review of current clinical studies provides a dual perspective. These studies confirm melatonin's potential in cancer management but also underscore its inherent limitations, particularly its limited bioavailability, which often relegates it to a supplementary role in treatments. Despite this limitation, there is an ongoing quest for innovative solutions and current advancements include the development of melatonin derivatives and cutting-edge delivery systems. By synthesizing the past, present, and future, this review provides a detailed overview of melatonin's evolving role in oncology, positioning it as a potential cornerstone in future cancer therapeutics.

Melatonin regulates autophagy in granulosa cells from patients with premature ovarian insufficiency via activating Foxo3a.

Premature ovarian insufficiency (POI) is a diverse form of female infertility characterized by a decline in ovarian function before the age of 40. Melatonin (MT) is a potential clinical treatment for restoring or safeguarding ovarian function in POI. However, the specific therapeutic mechanism underlying this effect remains unclear. To address this, we conducted experiments using human granulosa cells (GCs) from both POI and normal patients. We examined the expression levels of autophagy-related genes and proteins in GCs through qRT-PCR and western blot analysis. Autophagy flux was monitored in GCs infected with GFP-LC3-adenovirus, and the regulatory function of MT in autophagy was investigated. Additionally, we employed pharmacological intervention of autophagy using 3-Methyladenine (3-MA) and RNA interference of Forkhead box O-3A (FOXO3A) to elucidate the mechanism of MT in the autophagy process. Compared to GCs from normal patients, GCs from POI patients exhibited irregular morphology, decreased proliferation, increased apoptosis, and elevated ROS levels. The expression of autophagy-related genes was downregulated in POI GCs, resulting in reduced autophagic activity. Furthermore, MT levels were decreased in POI GCs, but exogenous MT effectively activated autophagy. Mechanistically, melatonin treatment downregulated FOXO3A expression and induced phosphorylation in POI GCs. Importantly, silencing FOXO3A abolished the protective effect of melatonin on GCs. These findings indicate that autophagy is downregulated in POI GCs, accompanied by a deficiency in MT. Moreover, we demonstrated that supplementing MT can rescue autophagy levels and enhance GC viability through the activation of FOXO3A signaling. Thus, MT-FOXO3A may serve as a potential therapeutic target for POI treatment.

Sleep, Dietary Melatonin Supplementation, and COVID-19.

BACKGROUND: During the COVID-19 pandemic, people suffered from major mental health problems. These include stress, anxiety, and confusion about the existing situation of home confinement. Melatonin is a popular anti-inflammatory and antioxidant molecule sold as an over-the-counter dietary supplement. OBJECTIVE: This review discusses the indications for using melatonin in the context of the COVID-19 pandemic, including treatment. METHODS: A comprehensive search of publications was conducted in electronic databases focusing on the administration of melatonin in COVID-19. RESULTS: Stress has a huge negative impact on sleep routines and the quality of life of individuals. Sleep is considered an important modulator of the immune response. Thus, a lack of sleep can weaken immunity, increasing organism susceptibility to infection. For instance, shorter sleep durations are associated with a rise in suffering from the common cold. The administration of melatonin protects against viral and other pathogens and speeds clinical recovery. CONCLUSION: In patients admitted to intensive care units, melatonin decreases the risks of severe complications, such as thrombosis and sepsis, and mortality rates. In addition, it is efficacious in lowering vessel permeability, depression, and sedation, and improving the quality of sleep, which could also help COVID-19 patients achieve better clinical outcomes.

Effects of melatonin intake on depression and anxiety in postmenopausal women: a systematic review and meta-analysis of randomised controlled trials.

We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) evaluating the effects of melatonin intake on depression and anxiety in postmenopausal women. To identify RCTs examining the effect of melatonin supplementation on depression and anxiety scores in postmenopausal women, a comprehensive electronic search was conducted via the Cochrane Central Register of Controlled Trials, Science direct, Google Scholar, PubMed, Medline, Scopus and Web of Science databases using the keywords ("melatonin" OR "N-acetyl serotonin") AND ("menopause" OR "climacteric") AND ("depression" OR "anxiety"). The search strategy was applied to articles published between January 2000 and April 2023. The Cochrane tool was used to evaluate the bias risk in RCTs. For the meta-analysis, fixed effect models and random effect models were employed based on heterogeneity. Preferred Reporting Items for Systematic Reviews and Meta-Analysis in Our Study guidelines were followed. Five RCTs were included in the study, with a total sample size of 441 (experimental: 227 and control: 214). When the effect of melatonin use on depression in menopausal women was analysed, it was found that melatonin significantly reduced menopausal depression (SMD - 0.166, CI = - 0.288/ - 0.045, p < 0.05). When the effect of melatonin use on anxiety in postmenopausal women was analysed, it was found that melatonin significantly improved menopausal anxiety (SMD - 0.806, CI = 1.491/ - 0.120, p < 0.05). Melatonin is promising as a potential treatment to help depression and anxiety in the postmenopausal period. More high-quality studies are needed to determine their safety.

Involvement of Plasma Melatonin in Medication-Overuse Headache: A Cross-Sectional Study.

OBJECTIVES: Patients with medication-overuse headache (MOH) are often complicated with anxiety, depression, and sleep disorders and are associated with dependence behavior and substance abuse. Melatonin has physiological properties including analgesia, regulation of circadian rhythms, soporific, and antidepressant and affects drug preference and addiction. This study aimed to investigate the role of melatonin in MOH compared with episodic migraine (EM) and healthy controls and to verify the relationship between plasma melatonin levels and psychiatric symptoms. METHODS: Thirty patients affected by MOH, 30 patients with EM, and 30 matched healthy controls were enrolled. All subjects completed a detailed headache questionnaire and scales including the Hospital Anxiety and Depression Scale (HADS), the Pittsburgh Sleep Quality Index, the Leeds Dependence Questionnaire. Melatonin levels in plasma samples were measured by enzyme immunoassay method. RESULTS: The levels of plasma melatonin were significantly different among 3 groups of subjects (MOH, 7.74 [5.40-9.89]; EM, 9.79 [8.23-10.62]; Control, 10.16 [8.60-17.57]; H = 13.433; P = 0.001). Significantly lower levels of melatonin were found in MOH patients compared with healthy controls ( P = 0.001). The level of plasma melatonin inversely correlated with the scores of HADS-Anxiety ( r = -0.318, P = 0.002), HADS-Depression ( r = -0.368, P < 0.001), Pittsburgh Sleep Quality Index ( r = -0.303, P = 0.004), and Leeds Dependence Questionnaire ( r = -0.312, P = 0.003). CONCLUSIONS: This study innovatively detects the plasma melatonin levels in MOH patients and explores the association between melatonin levels and psychiatric symptoms. Melatonin may be potential complementary therapy in the treatment of MOH considering its comprehensive role in multiple aspects of MOH.

Melatonin, vitamins and minerals supplements for the treatment of Covid-19 and Covid-like illness: A prospective, randomized, double-blind multicenter study.

BACKGROUND: Melatonin, zinc, and multivitamins are among most recommended supplements in the fight against coronavirus disease 2019 (COVID-19). We aimed to examine the efficacy and safety of this association in the treatment of COVID-19 and COVID-like illnesses. METHODS: We conducted a multicenter prospective, randomized, double-blind, controlled trial. Patients with no medical history consulting the emergency department for covid and covid-like illness and who were not hospitalized were included. Patients were assigned in a 1:1 ratio to the treatment or the placebo group. The primary outcome was studying the effectiveness of zinc multivitamin supplement and melatonin in the treatment of COVID and -like illnesses symptoms' according to the time from randomization to clinical improvement. The pre-specified secondary outcomes were date of disappearance of symptoms present on admission, appearance of an adverse effect due to the administration of the treatment, number of patients developing complications, requiring hospitalization, requiring respiratory support. RESULTS: One hundred sixty four patients were eligible for the study and were randomized to either the treatment group or the placebo group. Overall, 128 of the 164 patients had a PCR for SARS-CoV-2, yielding a positive PCR result in 49.1% of them. Regarding the disappearance of all initial presenting symptoms: on the 5th day of the follow-up, there was a significant difference between the two groups with a p value 0.04;On the 10th day, there was a significant difference too with p value of 0.038. There were no significant differences between the two groups in recovery during the 15th day of follow-up p>0.5. Finally, 100% of patients fully recovered in the treatment group vs 98.8% in the placebo group. No severe adverse events were reported throughout the trial. CONCLUSIONS: Our results showed that daily doses of Melatonin, zinc and vitamins did significantly reduce the duration of symptoms accelerating its disappearance among patients consulting with COVID-19 or COVID-19 like illness.

The Role of Dietary Ingredients in Mental Energy - A Scoping Review of Randomized Controlled Trials.

Low mental energy can contribute to decreased productivity, altered life balance, decreased physical performance, and ultimately affect quality of life. As such, there is a great demand for food and beverage products that positively impact mental energy. Numerous products claim to alter mental energy making continued review of the scientific evidence critical. The objective of this study was to conduct a scoping review of randomized controlled trials to evaluate the effect of 18 dietary ingredients on mental energy outcomes in adults without severe disease. Methods: A literature search, completed using PubMed, resulted in the identification of 2261 articles, 190 of which met eligibility from initial abstract review. Full-text review was completed on the 190 studies which resulted in 101 articles that fully met eligibility for inclusion in this study. The search strategy for two ingredients did not yield any eligible studies, leaving studies for 16 ingredients that were extracted and summarized by reported significantly improved outcomes for cognition, mood and perceived feelings, and sleep assessments. The preliminary results for several dietary ingredients directionally suggested a mental energy benefit (≥20% of outcomes), including ashwagandha, chamomile, dark chocolate, ginseng, green tea, lavender, lion's mane mushroom, maca, tart cherries, turmeric, and valerian root. The results of this scoping review suggest that of the 16 dietary ingredients reviewed, 11 may be promising for further exploration on their potential benefits in supporting mental energy. Given consumer demand and market growth for food and beverage products that positively impact mental energy; continued efforts in assessment method alignment and additional evaluation in well-designed trials is warranted.KEY TEACHING POINTSOf the 16 dietary ingredients reviewed, 11 (ashwagandha, chamomile, dark chocolate, ginseng, green tea, lavender, lion's mane mushroom, maca, melatonin foods, turmeric, and valerian root) may be promising for further exploration on their potential mental energy benefits.Dark chocolate, ginseng, ashwagandha, and lion's mane mushroom were the most promising ingredients for further evaluation in the cognition domain of the ingredients evaluated.Turmeric, maca, lavendar, and ashwagandha were the most promising ingredients for further evaluation in the mood and perceived feelings domain of the ingredients evaluated.Ashwagandha, chamomile, green tea, melatonin foods, valerian root were the most promising ingredients for further evaluation in the sleep domain of the ingredients evaluated.Additional, well-designed, consistent, clinical trials and systematic reviews are warranted as the challenge of heterogeneity in mental energy study design remains.

Safety and efficacy of melatonin supplementation as an add-on treatment for infantile epileptic spasms syndrome: A randomized, placebo-controlled, double-blind trial.

This was a prospective, randomized, double-blind, single-center placebo-controlled trial to assess the efficacy and safety of melatonin as an add-on treatment for infantile epileptic spasms syndrome (IESS). Participants aged 3 months to 2 years with a primary diagnosis of IESS were recruited and assigned to two groups in a 1:1 ratio. Both treatment groups received a combination of adrenocorticotrophic hormone (ACTH) and magnesium sulfate (MgSO4 ) for 2 weeks, and the treatment group also received melatonin (3 mg) between 20:00 and 21:00 daily, 0.5-1 h before bedtime. The study's primary endpoint was the average reduction rate in spasm frequency assessed by seizure diaries. Secondary endpoints included assessment of the response rate, EEG hypsarrhythmia (Kramer score), and psychomotor development (Denver Developmental Screening Test, DDST). Sleep quality was assessed by using the Brief Infant Sleep Questionnaire (BISQ), the Infant Sleep Assessment Scale (ISAS), and actigraphy. Safety parameters were also evaluated. Statistical analyses were conducted on intention-to-treat and per-protocol populations. The trial is registered at Clinicaltrials.gov (ChiCTR2000036208). Out of 119 screened patients, 70 were randomized and 66 completed treatments. In the intention-to-treat population, there were no significant differences in the average percentage reduction of spasm frequency (median [interquartile range, IQR: Q3-Q1], 100% [46.7%] vs. 66.7% [55.3%], p = .288), the 3-day response rate (51.4% vs. 37.1%, p = .229), the 28-day response rate (42.9% vs. 28.6%, p = .212), EEG Kramer scores (2 [3.5] vs. 2 [3], p = .853), or DDST comprehensive months (5 [2.5] vs. 6 [6], p = .239) between the melatonin (n = 35) and placebo (n = 35) groups. However, caregivers reported improved sleep quality after melatonin treatment, with 85.7% reporting regular sleep compared to 42.9% with placebo (42.9%, p < .001). The melatonin group had lower ISAS scores in 4-11-month-old patients compared to the placebo (mean ± SD, 29.3 ± 4.4 vs. 35.2 ± 5.9, p < .001). Moreover, the median (IQR) value of sleep-onset latency was shortened by 6.0 (24.5) min after melatonin treatment, while that in the placebo group was extended by 3.0 (22.0) min (p = .030). The serum melatonin (6:00 h) level (pg/mL) of the children in the melatonin group after treatment was significantly higher than in the placebo group (median [IQR], 84.8 [142] vs. 17.5 [37.6], p < .001). No adverse effects related to melatonin were observed in the study, and there were no significant differences in adverse effects between the melatonin and placebo groups. Although not statistically significant, the results of this randomized clinical trial proved that melatonin supplementation, as an add-on treatment, can improve spasm control rate in the treatment of IESS. For IESS children treated with ACTH, the addition of melatonin was found to improve sleep quality, shorten sleep onset latency, and increase blood melatonin levels. Moreover, it was observed to be a safe treatment option.

Delayed sleep wake phase disorder in adolescents: an updated review.

PURPOSE OF REVIEW: This review examines the most common circadian rhythm disorder in adolescents, delayed sleep phase disorder. It explores the etiology, prevalence, clinical features, diagnostic tools and criteria, and treatment options to identify sleep disorders early in the course. This is important to help improve youths in terms of education and quality of life. RECENT FINDINGS: Recent studies indicate that delayed sleep wake phase disorder has a range of prevalence between 1% and 16%. It is often associated with neurodevelopmental disorders (i.e. attention deficit hyperactivity disorder and autism spectrum disorder) as well as psychopathology (i.e. substance use, anxiety, and depression). It can present with a myriad of symptoms, such as insomnia, restless sleep, and poor daytime cognitive function, often seen in pediatric practice. Important diagnostic measures incorporate history-taking, sleep logs, actigraphy (i.e. Apple watches) and measurement of dim light melatonin onset. Treatments include improved sleep hygiene, chronotherapy, exogenous melatonin administration, and bright light therapy. SUMMARY: There are many environmental and genetic factors that can predispose an individual to circadian rhythm disorders. Delayed sleep phase disorder has detrimental effects on overall health, cognition, and behavior. It is important to screen for this disorder in routine pediatric clinic visits. The goal of early intervention is to prevent health and behavioral complications and treat adolescents using a multimodal approach, especially those with affective/neurodevelopmental conditions, who are prone to having delayed sleep wake phase disorder.

A case of prazosin in treatment of rapid eye movement sleep behavior disorder.

Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by dream-enactment behaviors that emerge during a loss of REM sleep atonia. Untreated RBD carries risks for physical injury from falls or other traumatic events during dream enactment as well as risk of injury to the bed partner. Currently, melatonin and clonazepam are the mainstay pharmacological therapies for RBD. However, therapeutic response to these medications is variable. While older adults are most vulnerable to RBD, they are also particularly vulnerable to the adverse effects of benzodiazepines, including increased risk of falls, cognitive impairment, and increased risk of Alzheimer disease. Prazosin is a centrally active alpha-1 adrenergic receptor antagonist often prescribed for trauma nightmares characterized by REM sleep without atonia in patients with posttraumatic stress disorder. We report a case of successful RBD management with prazosin in a patient in whom high-dose melatonin was ineffective. Although there was no observable reduction in dream-enactment behaviors with high-dose melatonin, the possibility of a synergistic effect of prazosin combined with melatonin cannot be ruled out. This case report supports further evaluation of prazosin as a potential therapeutic for RBD. CITATION: Cho Y, Iliff JJ, Lim MM, Raskind M, Peskind E. A case of prazosin in treatment of rapid eye movement sleep behavior disorder. J Clin Sleep Med. 2024;20(2):319-321.

Modification in ICU Design May Affect Delirium and Circadian Melatonin: A Proof of Concept Pilot Study.

OBJECTIVES: Nonpharmacologic delirium management is recommended by current guidelines, but studies on the impact of ICU design are still limited. The study's primary purpose was to determine if a multicomponent change in room design prevents ICU delirium. Second, the influence of lighting conditions on serum melatonin was assessed. DESIGN: Prospective observational cohort pilot study. SETTING: The new design concept was established in two two-bed ICU rooms of a university hospital. Besides modifications aimed at stress relief, it includes a new dynamic lighting system. PATIENTS: Seventy-four adult critically ill patients on mechanical ventilation with an expected ICU length of stay of at least 48 hours, treated in modified or standard rooms. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The clinical examination included a prospective assessment for depth of sedation, delirium, and pain every 8 hours using validated scores. Blood samples for serum melatonin profiles were collected every 4 hours for a maximum of three 24-hour periods. Seventy-four patients were included in the analysis. Seventy-six percent ( n = 28) of patients in the standard rooms developed delirium compared with 46% of patients ( n = 17) in the modified rooms ( p = 0.017). Patients in standard rooms (vs. modified rooms) had a 2.3-fold higher delirium severity (odds ratio = 2.292; 95% CI, 1.582-3.321; p < 0.0001). Light intensity, calculated using the measure of circadian effective irradiance, significantly influenced the course of serum melatonin ( p < 0.0001). Significant interactions ( p < 0.001) revealed that differences in serum melatonin between patients in standard and modified rooms were not the same over time but varied in specific periods of time. CONCLUSIONS: Modifications in ICU room design may influence the incidence and severity of delirium. Dedicated light therapy could potentially influence delirium outcomes by modulating circadian melatonin levels.

The effects of pinealectomy and melatonin treatment in acrylamide-induced nephrotoxicity in rats: Antioxidant and anti-inflammatory mechanisms.

OBJECTIVE: Acrylamide (AA) is toxic and forms in food that undergoes high-temperature processing. This study aimed to investigate the effects of AA-induced toxicity on renal tissue in pinealectomized rats and the possible protective effect of exogenous Melatonin (ML) administration. MATERIALS AND METHODS: Sixty rats were randomized into 6 groups (n = 10): Sham, Sham+AA, Sham+AA+ML, PX, PX+AA, and PX+AA+ML. Sham and pinealectomized rats received AA (25 mg/kg/day orally) and ML (0.5 ml volume at 10 mg/kg/day, intraperitoneal) for 21 days. RESULTS: The results showed that malondialdehyde (MDA), total oxidant status (TOS), oxidative stress index (OSI), tumor necrosis factor-α (TNF-α), and interleukin 1ß (IL-1ß) levels of the kidney and urea and creatinine levels of serum in the PX (pinealectomy)+AA group were more increased than in the Sham+AA group. In addition, glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and total antioxidant status (TAS) levels decreased more in the PX+AA group than in the Sham+AA group. Also, we observed more histopathologic damage in the PX+AA group. On the other hand, up-regulation of kidney tissue antioxidants, down-regulation of tissue oxidants, and improvement in kidney function were achieved with ML treatment. Also, histopathological findings such as inflammatory cell infiltration, shrinkage of glomeruli, and dilatation of tubules caused by AA toxicity improved with ML treatment. CONCLUSION: ML supplementation exhibited adequate nephroprotective effects against the nephrotoxicity of AA on pinealectomized rat kidney tissue function by balancing the oxidant/antioxidant status and suppressing the release of proinflammatory cytokines.