Purpose: Lifestyle and work habits have been drastically altered by restrictions due to the COVID-19 pandemic. Whether the associated changes in sleep timing modulate the risk of suffering from symptoms of insomnia, the most prevalent sleep disorder, is however incompletely understood. Here, we evaluate the association between the early pandemic-associated change in 1) the magnitude of social jetlag (SJL) – ie, the difference between sleep timing on working vs free days – and 2) symptoms of insomnia. Patients and Methods: A total of 14,968 anonymous participants (mean age: 40 years; 64% females) responded to a standardized internet-based survey distributed across 14 countries. Using logistic multivariate regression, we examined the association between the degree of social jetlag and symptoms of insomnia, controlling for important confounders like social restriction extension, country specific COVID-19 severity and psychological distress, for example. Results: In response to the pandemic, participants reported later sleep timing, especially during workdays. Most participants (46%) exhibited a reduction in their SJL, whereas 20% increased it; and 34% reported no change in SJL. Notably, we found that both increased and decreased SJL, as a result of the COVID-19 pandemic, were associated with later sleep midpoint (indicating a later chronotype) as well as more recurrent and moderate-to-severe symptoms of insomnia (about 23– 54% higher odds ratio than subjects with unchanged SJL). Primarily those with reduced SJL shifted their bedtimes to a later timepoint, compared with those without changes in SJL. Conclusion: Our findings offer important insights into how self-reported changes to the stability of sleep/wake timing, as reflected by changes in SJL, can be a critical marker of the risk of experiencing insomnia-related symptoms – even when individuals manage to reduce their social jetlag. These findings emphasize the clinical importance of analyzing sleep-wake regularity.

Passiflora cincinnataMasters is a Brazilian native species of passionflower. This genus is known in the American continent folk medicine for its diuretic and analgesic properties. Nevertheless, few studies investigated possible biological effects ofP. cincinnataextracts. Further, evidence of antioxidant actions encourages the investigation of possible neuroprotective effects in animal models of neurodegenerative diseases. This study investigates the effect of theP. cincinnataethanolic extract (PAS) on mice submitted to a progressive model of Parkinson’s disease (PD) induced by reserpine. Male (6‐month‐old) mice received reserpine (0.1 mg/kg, s.c.), every other day, for 40 days, with or without a concomitant treatment with daily injections of PAS (25 mg/kg, i.p.). Catalepsy, open field, oral movements, and plus‐maze discriminative avoidance evaluations were performed across treatment, and immunohistochemistry for tyrosine hydroxylase was conducted at the end. The results showed that PAS treatment delayed the onset of motor impairments and prevented the occurrence of increased catalepsy behavior in the premotor phase. However, PAS administration did not modify reserpine‐induced cognitive impairments. Moreover, PAS prevented the decrease in tyrosine hydroxylase immunostaining in thesubstantia nigra pars compacta(SNpc) induced by reserpine. Taken together, our results suggested that PAS exerted a neuroprotective effect in a progressive model of PD.

The COVID-19 pandemic and related restrictions, such as stay-at-home-orders, have significantly altered daily routines and lifestyles. Given their importance for metabolic health, we herein compared sleep and meal timing parameters during vs. before the COVID-19 pandemic based on subjective recall, in an anonymous Swedish survey. Among 191 adults (mean age: 47 years; 77.5% females), we show that social jetlag, i.e., the mismatch in sleep midpoint between work and free days, was reduced by about 17 min during the pandemic compared with the pre-pandemic state (p < 0.001). Concomitantly, respondents’ sleep midpoint was shifted toward morning hours during workdays (p < 0.001). A later daily eating midpoint accompanied the shift in sleep timing (p = 0.001). This effect was mainly driven by a later scheduled first meal (p < 0.001). No difference in the timing of the day’s last meal was found (p = 0.814). Although our survey was limited in terms of sample size and by being cross-sectional, our results suggest that the delay in sleep timing due to the COVID-19 pandemic was accompanied by a corresponding shift in the timing of early but not late meals.

Summary: Weighted blankets have emerged as a potential non‐pharmacological intervention to ease conditions such as insomnia and anxiety. Despite a lack of experimental evidence, these alleged effects are frequently attributed to a reduced activity of the endogenous stress systems and an increased release of hormones such as oxytocin and melatonin. Thus, the aim of the present in‐laboratory crossover study (26 young and healthy participants, including 15 men and 11 women) was to investigate if using a weighted blanket (~12% of body weight) at bedtime resulted in higher salivary concentrations of melatonin and oxytocin compared with a light blanket (~2.4% of body weight). We also examined possible differences in salivary concentrations of the stress hormone cortisol, salivary alpha‐amylase activity (as an indicative metric of sympathetic nervous system activity), subjective sleepiness, and sleep duration. When using a weighted blanket, the 1 hour increase of salivary melatonin from baseline (i.e., 22:00) to lights off (i.e., 23:00) was about 32% higher (p = 0.011). No other significant differences were found between the blanket conditions, including subjective sleepiness and total sleep duration. Our study is the first to suggest that using a weighted blanket may result in a more significant release of melatonin at bedtime. Future studies should investigate whether the stimulatory effect on melatonin secretion is observed on a nightly basis when frequently using a weighted blanket over weeks to months. It remains to be determined whether the observed increase in melatonin may be therapeutically relevant for the previously described effects of the weighted blanket on insomnia and anxiety.

Natural products, sources of new pharmacological substances, have large chemical diversity and architectural complexity. In this context, some toxins obtained from invertebrate venoms have anticonvulsant effects. Epilepsy is a neurological disorder that affects about 65 million people worldwide, and approximately 30% of cases are resistant to pharmacological treatment. Previous studies from our group show that the denatured venom of the ant Dinoponera quadriceps (Kempt) protects mice against bicuculline (BIC)-induced seizures and death. The aim of this study was to investigate the anticonvulsant activity of compounds isolated from D. quadriceps venom against seizures induced by BIC in mice. Crude venom was fractionated by high-performance liquid chromatography (HPLC) resulting in six fractions referred to as DqTx1–DqTx6. A liquid chromatography-mass spectrometry (LC/MS) analysis revealed a major 431 Da compound in fractions DqTx1 and DqTx2. Fractions DqTx3 and DqTx4 showed a compound of 2451 Da and DqTx5 revealed a 2436 Da compound. Furthermore, the DqTx6 fraction exhibited a major component with a molecular weight of 13,196 Da. Each fraction (1 mg/mL) was microinjected into the lateral ventricle of mice, and the animals were observed in an open field. We did not observe behavioral alterations when the fractions were given alone. Conversely, when the fractions were microinjected 20 min prior to the administration of BIC (21.6 nM), DqTx1, DqTx4, and DqTx6 fractions increased the latency for onset of tonic-clonic seizures. Moreover, all fractions, except DqTx5, increased latency to death. The more relevant result was obtained with the DqTx6 fraction, which protected 62.5% of the animals against tonic-clonic seizures. Furthermore, this fraction protected 100% of the animals from seizure episodes followed by death. Taken together, these findings indicate that compounds from ant venom might be a potential source of new anticonvulsants molecules.

Summary: The hormone fibroblast growth factor 21 (FGF21) modulates tissue metabolism and circulates at higher levels in metabolic conditions associated with chronic sleep–wake disruption, such as type 2 diabetes and obesity. In the present study, we investigated whether acute sleep loss impacts circulating levels of FGF21 and tissue‐specific production, and response pathways linked to FGF21. A total of 15 healthy normal‐weight young men participated in a randomised crossover study with two conditions, sleep loss versus an 8.5‐hr sleep window. The evening before each intervention, fasting blood was collected. Fasting, post‐intervention morning skeletal muscle and adipose tissue samples underwent quantitative polymerase chain reaction and DNA methylation analyses, and serum FGF21 levels were measured before and after an oral glucose tolerance test. Serum levels of FGF21 were higher after sleep loss compared with sleep, both under fasting conditions and following glucose intake (~27%–30%, p = 0.023). Fasting circulating levels of fibroblast activation protein, a protein which can degrade circulating FGF21, were not altered by sleep loss, whereas DNA methylation in the FGF21 promoter region increased only in adipose tissue. However, even though specifically the muscle exhibited transcriptional changes indicating adverse alterations to redox and metabolic homeostasis, no tissue‐based changes were observed in expression of FGF21, its receptors, or selected signalling targets, in response to sleep loss. In summary, we found that acute sleep loss resulted in increased circulating levels of FGF21 in healthy young men, which may occur independent of a tissue‐based stress response in metabolic peripheral tissues. Further studies may decipher whether changes in FGF21 signalling after sleep loss modulate metabolic outcomes associated with sleep or circadian disruption.