International Expert Opinions and Recommendations on the Use of Melatonin in the Treatment of Insomnia and Circadian Sleep Disturbances in Adult Neuropsychiatric Disorders

Introduction: Insomnia and circadian rhythm disorders, such as the delayed sleep phase syndrome, are frequent in psychiatric disorders and their evaluation and management in early stages should be a priority. The aim of this paper was to express recommendations on the use of exogenous melatonin, which exhibits both chronobiotic and sleep-promoting actions, for the treatment of these sleep disturbances in psychiatric disorders.Methods: To this aim, we conducted a systematic review according to PRISMA on the use of melatonin for the treatment of insomnia and circadian sleep disorders in neuropsychiatry. We expressed recommendations for the use of melatonin in psychiatric clinical practice for each disorder using the RAND/UCLA appropriateness method.Results: We selected 41 studies, which included mood disorders, schizophrenia, substance use disorders, attention deficit hyperactivity disorders, autism spectrum disorders, neurocognitive disorders, and delirium; no studies were found for both anxiety and eating disorders.Conclusion: The administration of prolonged release melatonin at 2–10 mg, 1–2 h before bedtime, might be used in the treatment of insomnia symptoms or comorbid insomnia in mood disorders, schizophrenia, in adults with autism spectrum disorders, neurocognitive disorders and during sedative-hypnotics discontinuation. Immediate release melatonin at <1 mg might be useful in the treatment of circadian sleep disturbances of neuropsychiatric disorders

Recent stressful life events in euthymic MDD patients: sociodemographic and clinical characteristics

Background: Stressful life events (SLE) may influence the illness course and outcome. This study aimed to characterize socio-demographic and clinical features of euthymic major depressive disorder (MDD) outpatients with SLE compared with those without. Methods: The present sample included 628 (mean age=55.1 ± 16.1) currently euthymic MDD outpatients of whom 250 (39.8%) reported SLE and 378 (60.2%) did not. Results: After univariate analyses, outpatients with SLE were most frequently widowed and lived predominantly with friends/others. Moreover, relative to outpatients without SLE, those with SLE were more likely to have a family history of suicidal behavior, manifested melancholic features, report a higher Coping Orientation to the Problems Experienced (COPE) positive reinterpretation/growth and less likely to have a comorbid panic disorder, residual interepisodic symptoms, use previous psychiatric medications, and currently use of antidepressants. Having a family history of suicide (OR=9.697; p=≤.05), history of psychotropic medications use (OR=2.888; p=≤.05), and reduced use of antidepressants (OR=.321; p=.001) were significantly associated with SLE after regression analyses. Mediation analyses showed that the association between current use of antidepressants and SLE was mediated by previous psychiatric medications. Conclusion: Having a family history of suicide, history of psychotropic medications use, and reduced use of antidepressants is linked to a specific “at risk” profile characterized by the enhanced vulnerability to experience SLE

Hepatoprotective activity of aqueous extract of Balanites aegyptiaca L. Delile (Balanitaceae) roots bark

Balanites aegyptiaca (L.) Del (Balanitaceae) is traditionally used for the treatment of various ailments such as syphilis, jaundice and liver disorders, epilepsy, ... This study was designed to evaluate acute toxicity and hepatoprotective effect of aqueous extract of Balanites aegyptiaca on CCl4 induced hepatotoxicity in rats.Methods: Acute toxicity was assessed with the extract at a dose of 2000 mg / kg bw. The extract at doses of 25, 50 and 100 mg / kg b.w. was orally administered respectively to CC14-induced hepatotoxicity (0.5 ml / kg) animals. Silymarin (100 mg / kg) was given as a reference. Biochemical parameters such as ALT, AST, PT, ALB and ALP were assayed as well as enzymatic antioxidant activities SOD, CAT and MDA. Nitrogen monoxide (NO) involved in inflammation was also measured.Results: Activities of liver marker enzymes, ALT, AST and ALP, total protein, albumin and showed a significant hepatoprotective effect. Regarding antioxidant enzymatic activities in vivo (SOD, CAT and MDA) of aqueous extract exhibited a significant effect showing increasing levels of SOD, CAT and reducing malondialdehyde (MDA) levels. The production of NO is significantly reduced compared to the batch intoxicated by CCl4.Conclusion: Balanites aegyptiaca is endowed with hepatoprotective properties that can be attributed to antioxidant potential which could justify its use in traditional medicine in liver disorders

Early anthropogenic impact on Western Central African rainforests 2,600 y ago

A potential human footprint on Western Central African rainforests before the Common Era has become the focus of an ongoing controversy. Between 3,000 y ago and 2,000 y ago, regional pollen sequences indicate a replacement of mature rainforests by a forest–savannah mosaic including pioneer trees. Although some studies suggested an anthropogenic influence on this forest fragmentation, current interpretations based on pollen data attribute the ‘‘rainforest crisis’’ to climate change toward a drier, more seasonal climate. A rigorous test of this hypothesis, however, requires climate proxies independent of vegetation changes. Here we resolve this controversy through a continuous 10,500-y record of both vegetation and hydrological changes from Lake Barombi in Southwest Cameroon based on changes in carbon and hydrogen isotope compositions of plant waxes. δ¹³C-inferred vegetation changes confirm a prominent and abrupt appearance of C4 plants in the Lake Barombi catchment, at 2,600 calendar years before AD 1950 (cal y BP), followed by an equally sudden return to rainforest vegetation at 2,020 cal y BP. δD values from the same plant wax compounds, however, show no simultaneous hydrological change. Based on the combination of these data with a comprehensive regional archaeological database we provide evidence that humans triggered the rainforest fragmentation 2,600 y ago. Our findings suggest that technological developments, including agricultural practices and iron metallurgy, possibly related to the large-scale Bantu expansion, significantly impacted the ecosystems before the Common Era

OPTIMADE, an API for exchanging materials data

: The Open Databases Integration for Materials Design (OPTIMADE) consortium has designed a universal application programming interface (API) to make materials databases accessible and interoperable. We outline the first stable release of the specification, v1.0, which is already supported by many leading databases and several software packages. We illustrate the advantages of the OPTIMADE API through worked examples on each of the public materials databases that support the full API specification

OPTIMADE, an API for exchanging materials data.

The Open Databases Integration for Materials Design (OPTIMADE) consortium has designed a universal application programming interface (API) to make materials databases accessible and interoperable. We outline the first stable release of the specification, v1.0, which is already supported by many leading databases and several software packages. We illustrate the advantages of the OPTIMADE API through worked examples on each of the public materials databases that support the full API specification

Cushing's Syndrome and Fetal Features Resurgence in Adrenal Cortex–Specific Prkar1a Knockout Mice

Carney complex (CNC) is an inherited neoplasia syndrome with endocrine overactivity. Its most frequent endocrine manifestation is primary pigmented nodular adrenocortical disease (PPNAD), a bilateral adrenocortical hyperplasia causing pituitary-independent Cushing's syndrome. Inactivating mutations in PRKAR1A, a gene encoding the type 1 α-regulatory subunit (R1α) of the cAMP–dependent protein kinase (PKA) have been found in 80% of CNC patients with Cushing's syndrome. To demonstrate the implication of R1α loss in the initiation and development of PPNAD, we generated mice lacking Prkar1a specifically in the adrenal cortex (AdKO). AdKO mice develop pituitary-independent Cushing's syndrome with increased PKA activity. This leads to autonomous steroidogenic genes expression and deregulated adreno-cortical cells differentiation, increased proliferation and resistance to apoptosis. Unexpectedly, R1α loss results in improper maintenance and centrifugal expansion of cortisol-producing fetal adrenocortical cells with concomitant regression of adult cortex. Our data provide the first in vivo evidence that loss of R1α is sufficient to induce autonomous adrenal hyper-activity and bilateral hyperplasia, both observed in human PPNAD. Furthermore, this model demonstrates that deregulated PKA activity favors the emergence of a new cell population potentially arising from the fetal adrenal, giving new insight into the mechanisms leading to PPNAD