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Major depressive disorder (MDD) is a complex mood disorder. While much progress has been made in understanding the pathophysiology of MDD, no single mechanism can explain all facets of this disorder. Several studies show that disturbances in biological rhythms can lead to the development of MDD. Indeed, insomnia or hypersomnia are symptoms included in the MDD diagnostic criteria. Clinical studies and meta-analyses showed a strong relationship between MDD and sleep disorders. Sleep disorder and MDD are associated with activation in the hypothalamicpituitary- adrenal (HPA) axis and inflammation. The increase in inflammatory response can activate the kynurenine pathway, decrease serotonin synthesis, and affect other factors involved in the pathophysiology of neuropsychiatric conditions. Moreover, sleep disorders and MDD can change the gut microbiota and alter the microbiota-gut-brain axis. Thus, this review discusses the relationship between MDD, circadian rhythms, and sleep disorders, describing the potential pathophysiological mechanism shared in these conditions. In addition, therapeutic opportunities based on antiinflammatory, antioxidant, HPA axis regulatory, and synapse-modulating actions are raised. For the article search, we used the PubMed database. Both sleep disorders and changes in biological rhythms have a bidirectional relationship with MDD. Although some pathophysiological mechanisms, including inflammation, changes in the gut microbiota, and decreased neuroplasticity, may be involved in the relationship between sleep, circadian rhythms, and MDD, other mechanisms are not yet well understood. Therapeutic opportunities based on anti-inflammatory, antioxidant, HPA regulatory axis, and synapse modulating actions appear to be promising targets in preventing MDD, circadian rhythm disturbances, and sleep disorders., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The part played by oxytocin and oxytocin neurons in the regulation of food intake is controversial. There is much pharmacological data to support a role for oxytocin notably in regulating sugar consumption, however, several recent experiments have questioned the importance of oxytocin neurons themselves. Methods: Here we use a combination of histological and chemogenetic techniques to investigate the selective activation or inhibition of oxytocin neurons in the hypothalamic paraventricular nucleus (OxtPVH). We then identify a pathway from OxtPVH neurons to the bed nucleus of the stria terminalis using the cell-selective expression of channel rhodopsin. Results: OxtPVH neurons increase their expression of cFos after both physiological (fast-induced re-feeding or oral lipid) and pharmacological (systemic administration of cholecystokinin or lithium chloride) anorectic signals. Chemogenetic activation of OxtPVH neurons is sufficient to decrease free-feeding in OxtCre:hM3Dq mice, while inhibition in OxtCre:hM4Di mice attenuates the response to administration of cholecystokinin. Activation of OxtPVH neurons also increases energy expenditure and core-body temperature, without a significant effect on locomotor activity. Finally, the selective, optogenetic stimulation of a pathway from OxtPVH neurons to the bed nucleus of the stria terminalis reduces the consumption of sucrose. Conclusion: Our results support a role for oxytocin neurons in the regulation of whole-body metabolism, including a modulatory action on food intake and energy expenditure. Furthermore, we demonstrate that the pathway from OxtPVH neurons to the bed nucleus of the stria terminalis can regulate sugar consumption. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is associated with inflammation and a high level of comorbidities. Atypical depression (AD) is a MDD subtype based on DSM criteria, that could have specific underlying biological mechanisms. AD is associated with elevated cardiovascular (CVD) comorbidities, higher risk of suicide attempts, hypersomnia, and anxiety disorder. In this study, we aim to investigate if AD and polysomnographic parameters could be associated with low-grade inflammation (LGI). LGI is defined by a range from 3 to 10 mg/L of C-reactive protein levels. We carried out a retrospective cohort study in which 765 individuals with MDD were split into two groups: with and without LGI. Our results exhibit differences between the groups for the polysomnographic parameters, with the LGI group showing parameters already associated with inflammation such as reduced rapid eye movement sleep and elevated hypoxemia markers (identified as CVD risk factor). We found that AD is associated with LGI (OR 1.48; p = 0.047) after adjustment. Likewise, we found an LGI prevalence in AD higher (34.8%) than in MDD without atypical features (26.8%). Overall, these results confirm the low-grade inflammation feature of AD and highlight polysomnographic parameters associated with LGI that could also act as risk factors in this context. [ABSTRACT FROM AUTHOR]

Background: Discovering biological markers is essential for understanding and treating mental disorders. Despite the limitations of current non-invasive methods, neural progenitor cells from the olfactory epithelium (hNPCs-OE) have been emphasized as potential biomarker sources. This study measured soluble factors in these cells in Major Depressive Disorder (MDD), Borderline Personality Disorder (BPD), and healthy controls (HC). Methods: We assessed thirty-five participants divided into MDD (n=14), BPD (n=14), and HC (n=7). MDD was assessed using the Hamilton Depression Rating Scale. BPD was evaluated using the DSM-5 criteria and the Structured Clinical Interview for Personality Disorders. We isolated hNPCs-OE, collected intracellular proteins and conditioned medium, and quantified markers and soluble factors, including Interleukin-6, interleukin-8, and others. Analysis was conducted using one-way ANOVA or Kruskal-Wallis test and linear regression. Results: We found that hNPCs-OE of MDD and BPD decreased Sox2 and laminin receptor-67 kDa levels. MASH-1 decreased in BPD, while tubulin beta-III decreased in MDD compared to controls and BPD. Also, we found significant differences in IL-6, IL-8, MCP-1, and thrombospondin-1 levels between controls and MDD, or BPD, but not between MDD and BPD. Conclusions: Altered protein markers are evident in the nhNPCs-OE in MDD and BPD patients. These cells also secrete higher concentrations of inflammatory cytokines than HC cells. The results suggest the potential utility of hNPCs-OE as an in vitro model for researching biological protein markers in psychiatric disorders. However, more extensive validation studies are needed to confirm their effectiveness and specificity in neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVDs) pose a significant global health threat due to their complex pathogenesis and high incidence, imposing a substantial burden on global healthcare systems. Integrins, a group of heterodimers consisting of α and β subunits that are located on the cell membrane, have emerged as key players in mediating the occurrence and progression of CVDs by regulating the physiological activities of endothelial cells, vascular smooth muscle cells, platelets, fibroblasts, cardiomyocytes, and various immune cells. The crucial role of integrins in the progression of CVDs has valuable implications for targeted therapies. In this context, the development and application of various integrin antibodies and antagonists have been explored for antiplatelet therapy and anti-inflammatory-mediated tissue damage. Additionally, the rise of nanomedicine has enhanced the specificity and bioavailability of precision therapy targeting integrins. Nevertheless, the complexity of the pathogenesis of CVDs presents tremendous challenges for monoclonal targeted treatment. This paper reviews the mechanisms of integrins in the development of atherosclerosis, cardiac fibrosis, hypertension, and arrhythmias, which may pave the way for future innovations in the diagnosis and treatment of CVDs. [ABSTRACT FROM AUTHOR]

Obesity is a consequence of multiple factors, including genetics, lifestyle and nutritional choices, physical activity, sleep duration, screen time, and mood disorders. These behavioral elements can impair the regulation of energy balance and obesity management that link obesity to a constellation of chronic conditions that lead to a high prevalence of cardiometabolic risk factors, metabolic syndrome, and nonalcoholic fatty liver disease. Multidisciplinary therapy is defined as an approach delivered by a multidisciplinary-trained health team covering at least two components of behavior, physical activity/exercise, dietary habits, and/or psychological counseling associated with clinical interventions. This narrative review summarizes the effects of multidisciplinary therapy on neuroendocrine regulation of energy balance, inflammatory biomarkers, cardiometabolic risk factors, metabolic syndrome, nonalcoholic fatty liver diseases, behavior, and quality of life. We found that multidisciplinary therapy, including medical, nutritional, exercise, and behavioral counseling, and/or education, was useful for addressing outcomes such as visceral adiposity, neuroendocrine regulation of energy balance, inflammatory biomarkers, cardiometabolic risk factors, nonalcoholic fatty liver disease, and metabolic syndrome. The effects were mediated by improvements in neuroendocrine regulation of energy balance, downregulation of the pro-inflammatory states, and a reduction in comorbidities. Multidisciplinary therapy also improved mood disorders and quality of life., (© 2024 The Author(s). Annals of the New York Academy of Sciences published by Wiley Periodicals LLC on behalf of The New York Academy of Sciences.)

Background: The risk of workplace violence and job burnout among Chinese correctional officers is high. Stress and insomnia may influence the relationship between workplace violence and job burnout; however, this influence has been rarely studied. This study aimed to explore the effect of workplace violence on job burnout among Chinese correctional officers and to assess the contribution of stress and insomnia to this effect. Methods: In this study, the workplace violence scale, the Assens insomnia scale, the 21-item Depression Anxiety Stress Scale, and the Maslach Burnout Inventory-General Survey scale were used to assess the workplace violence, insomnia, stress, and job burnout experienced by the 472 correctional officers, respectively. Results: The results showed that (1) workplace violence was significantly and positively predictive of job burnout, (2) workplace violence affected job burnout through the mediation of stress, (3) workplace violence affected job burnout through the mediation of insomnia, and (4) stress and insomnia played fully interlocking mediating roles in the effect of workplace violence on job burnout. Conclusion: Stress and insomnia may play a full mediating role in the relationship between workplace violence and job burnout. This suggested that correctional officers may take measures to reduce stress and improve insomnia, thereby reducing their job burnout. Further research may focus on the development of effective interventions to reduce stress and improve insomnia among correctional officers. [ABSTRACT FROM AUTHOR]

Integrin receptors are heterodimeric surface receptors that play multiple roles regarding cell–cell communication, signaling, and migration. The four members of the β2 integrin subfamily are composed of an alternative α (CD11a–d) subunit, which determines the specific receptor properties, and a constant β (CD18) subunit. This review aims to present insight into the multiple immunological roles of integrin receptors, with a focus on β2 integrins that are specifically expressed by leukocytes. The pathophysiological role of β2 integrins is confirmed by the drastic phenotype of patients suffering from leukocyte adhesion deficiencies, most often resulting in severe recurrent infections and, at the same time, a predisposition for autoimmune diseases. So far, studies on the role of β2 integrins in vivo employed mice with a constitutive knockout of all β2 integrins or either family member, respectively, which complicated the differentiation between the direct and indirect effects of β2 integrin deficiency for distinct cell types. The recent generation and characterization of transgenic mice with a cell-type-specific knockdown of β2 integrins by our group has enabled the dissection of cell-specific roles of β2 integrins. Further, integrin receptors have been recognized as target receptors for the treatment of inflammatory diseases as well as tumor therapy. However, whereas both agonistic and antagonistic agents yielded beneficial effects in animal models, the success of clinical trials was limited in most cases and was associated with unwanted side effects. This unfavorable outcome is most probably related to the systemic effects of the used compounds on all leukocytes, thereby emphasizing the need to develop formulations that target distinct types of leukocytes to modulate β2 integrin activity for therapeutic applications. [ABSTRACT FROM AUTHOR]

Introduction and purpose: The main aim of our study is to summarise existing knowledge and draw conclusions about the impact of magnesium deficiency on the occurrence of anxiety. Methodology: The literature available in the National Library of Medicine database at https://pubmed.ncbi.nlm.nih.gov and Google Scholar was reviewed. Articles were searched by using keywords: magnesium, deficiency, supplementation, anxiety disorders. Forty-seven research papers and meta-analyses were analysed. Description of the state of knowledge: Magnesium is an extremely important mineral in the human body involved in many physiological processes. A deficiency of this element affects the whole body and can cause mental disorders - including anxiety disorders. There are many theories showing a link between magnesium and anxiety disorders in both humans and animals. Magnesium has been shown to influence the function of neurotransmitters affecting the experience of anxiety. Supplementation in people with hypomagnesaemia has been proven to improve their health and well-being. However, it should be noted that supplements on the market vary in the bioavailability of the mineral, and the frequency of intake and dosage also affect the bioavailability of magnesium. Conclusions: It is important to ensure adequate levels of magnesium in the diet, given its impact on the proper functioning of the human body (including the nervous system) and the fact that most people consume insufficient amounts of this macronutrient. Evidence of a link between magnesium levels and anxiety has led to increased interest in the potential efficacy of magnesium supplementation to alleviate anxiety symptoms. [ABSTRACT FROM AUTHOR]

Dissociative identity disorder (DID) is life-long, childhood-onset, posttraumatic developmental disorder where chronic early-life maltreatment and attachment disturbances prevents the child's development of a continuous sense of self across emotional states, relationships, and social contexts. As development proceeds, these self-states acquire a sense of themselves, a capacity for information processing, memory, emotion, and behavior. Conceptualizing DID involves paradoxes and apparent contradictions. DID has been categorized as a severe mental illness with major psychiatric comorbidities. Studies show that DID individuals have a unique personality organization with repeated, often covert posttraumatic reactivity, especially in relationships (e.g., therapy). Paradoxically, research shows that, during development, DID individuals preserve psychological resiliencies consistent with responsivity to long-term, psychodynamically informed treatment. These include, when not stressed, capacities for therapeutic alliance, reality testing, and observing ego. [ABSTRACT FROM AUTHOR]

We investigated the mechanisms underlying the effects of the antidepressant fluoxetine on behavior and adult hippocampal neurogenesis (AHN). After confirming our earlier report that the signaling molecule β‐arrestin‐2 (β‐Arr2) is required for the antidepressant‐like effects of fluoxetine, we found that the effects of fluoxetine on proliferation of neural progenitors and survival of adult‐born granule cells are absent in the β‐Arr2 knockout (KO) mice. To our surprise, fluoxetine induced a dramatic upregulation of the number of doublecortin (DCX)‐expressing cells in the β‐Arr2 KO mice, indicating that this marker can be increased even though AHN is not. We discovered two other conditions where a complex relationship occurs between the number of DCX‐expressing cells compared to levels of AHN: a chronic antidepressant model where DCX is upregulated and an inflammation model where DCX is downregulated. We concluded that assessing the number of DCX‐expressing cells alone to quantify levels of AHN can be complex and that caution should be applied when label retention techniques are unavailable. [ABSTRACT FROM AUTHOR]

Background The clinical heterogeneity in major depressive disorder (MDD), variable treatment response, and conflicting findings limit the ability of genomics toward the discovery of evidence-based diagnosis and treatment regimen. This study attempts to curate all genetic association findings to evaluate potential variants for clinical translation. Methods We systematically reviewed all candidates and genome-wide association studies for both MDD susceptibility and antidepressant response, independently, using MEDLINE, particularly to identify replicated findings. These variants were evaluated for functional consequences using different in silico tools and further estimated their diagnostic predictability by calculating positive predictive values. Results A total of 217 significantly associated studies comprising 1200 variants across 545 genes and 128 studies including 921 variants across 412 genes were included with MDD susceptibility and antidepressant response, respectively. Although the majority of associations were confirmed by a single study, we identified 31 and 18 replicated variants (in at least 2 studies) for MDD and antidepressant response. Functional annotation of these 31 variants predicted 20% coding variants as deleterious/damaging and 80.6% variants with regulatory effect. Similarly, the response-related 18 variants revealed 25% coding variant as damaging and 88.2% with substantial regulatory potential. Finally, we could calculate the diagnostic predictability of 19 and 5 variants whose positive predictive values ranges from 0.49 to 0.66 for MDD and 0.36 to 0.66 for response. Conclusions The replicated variants presented in our data are promising for disease diagnosis and improved response outcomes. Although these quantitative assessment measures are solely directive of available observational evidence, robust homogenous validation studies are required to strengthen these variants for molecular diagnostic application. [ABSTRACT FROM AUTHOR]

Depression is a highly prevalent and disabling psychiatric disorder. The hippocampus, which plays a central role in mood regulation and memory, has received considerable attention in depression research. Electroconvulsive therapy (ECT) is the most effective treatment for severe pharmacotherapy-resistant depression. Although the working mechanism of ECT remains unclear, recent magnetic resonance imaging (MRI) studies have consistently reported increased hippocampal volumes following ECT. The clinical implications of these volumetric increases and the specific cellular and molecular significance are not yet fully understood. This narrative review brings together evidence from animal models and human studies to provide a detailed examination of hippocampal volumetric increases following ECT. In particular, our preclinical MRI research using a mouse model is consistent with human findings, demonstrating a marked increase in hippocampal volume following ECT. Notable changes were observed in the ventral hippocampal CA1 region, including dendritic growth and increased synaptic density at excitatory synapses. Interestingly, inhibition of neurogenesis did not affect the ECT-related hippocampal volumetric increases detected on MRI. However, it remains unclear whether these histological and volumetric changes would be correlated with the clinical effect of ECT. Hence, future research on the relationships between cellular changes, ECT-related brain volumetric changes, and antidepressant effect could benefit from a bidirectional translational approach that integrates human and animal models. Such translational research may provide important insights into the mechanisms and potential biomarkers associated with ECT-induced hippocampal volumetric changes, thereby advancing our understanding of ECT for the treatment of depression., (© 2024 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.)

Sleep is one of the complex and important processes during which the direction of brain did many functions. Sleep disorders can be the cause of many diseases like hypertension, diabetes, obesity, depression, heart attack, and stroke. Without good and deep sleep, a defect will occur in many mental skills, such as attention, speed of response, focusing, and even a defect in memory.Rejuvenating of tissue, protein production and release of growth hormones It gets done during sleep. The nervous system and hormonescontrol the biological clock which controls many vital processes in the body like sleep time .In this review we will focus on medicinal plants' role in getting rid of sleep disorders. [ABSTRACT FROM AUTHOR]

Concurrent with recent insights into the neuroprogressive nature of depression, ketamine shows promise in interfering with several neuroprogressive factors, and has been suggested to reverse neuropathological patterns seen in depression. These insights come at a time of great need for novel approaches, as prevalence is rising and current treatment options remain inadequate for a large number of people. The rapidly growing literature on ketamine's antidepressant potential has yielded multiple proposed mechanisms of action, many of which have implications for recently elucidated aspects of depressive pathology. This review aims to provide the reader with an understanding of neuroprogressive aspects of depressive pathology and how ketamine is suggested to act on it. Literature was identified through PubMed and Google Scholar, and the reference lists of retrieved articles. When reviewing the evidence of depressive pathology, a picture emerges of four elements interacting with each other to facilitate progressive worsening, namely stress, inflammation, neurotoxicity and neurodegeneration. Ketamine acts on all of these levels of pathology, with rapid and potent reductions of depressive symptoms. Converging evidence suggests that ketamine works to increase stress resilience and reverse stress-induced dysfunction, modulate systemic inflammation and neuroinflammation, attenuate neurotoxic processes and glial dysfunction, and facilitate synaptogenesis rather than neurodegeneration. Still, much remains to be revealed about ketamine's antidepressant mechanisms of action, and research is lacking on the durability of effect. The findings discussed herein calls for more longitudinal approaches when determining efficacy and its relation to neuroprogressive factors, and could provide relevant considerations for clinical implementation. [ABSTRACT FROM AUTHOR]

Migraine is a common condition with disabling attacks that burdens people in the prime of their working lives. Despite years of research into migraine pathophysiology and therapeutics, much remains to be learned about the mechanisms at play in this complex neurovascular condition. Additionally, there remains a relative paucity of specific and targeted therapies available. Many sufferers remain underserved by currently available broad action preventive strategies, which are also complicated by poor tolerance and adverse effects. The development of preclinical migraine models in the laboratory, and the advances in human experimental migraine provocation, have led to the identification of key molecules likely involved in the molecular circuity of migraine, and have provided novel therapeutic targets. Importantly, the identification that vasoconstriction is neither necessary nor required for headache abortion has changed the landscape of migraine treatment and has broadened the therapy targets for patients with vascular risk factors or vascular disease. These targets include nitric oxide synthase (NOS) and several neuropeptides that are involved in migraine. The ability of NO donors and infusion of some of these peptides into humans to trigger typical migraine-like attacks has supported the development of targeted therapies against these molecules. Some of these, such as those targeting calcitonin gene-related peptide (CGRP), have already reached clinical practice and are displaying a positive outcome in migraineurs for the better by offering targeted efficacy without significant adverse effects. Others, such as those targeting pituitary adenylate cyclase activating polypeptide (PACAP), are showing promise and are likely to enter phase 3 clinical trials in the near future. Understanding these nitrergic and peptidergic mechanisms in migraine and their interactions is likely to lead to further therapeutic strategies for migraine in the future. [ABSTRACT FROM AUTHOR]

The postpartum period is a demanding time during which mothers experience numerous physiological adaptations that enable them to care for their offspring while maintaining their wellbeing. Hypocretins, also known as orexins, are neuropeptides synthesized by hypothalamic neurons that play a fundamental role in several functions, including the promotion of wakefulness and motivated behaviors, such as maternal care. In this regard, several findings suggest that the activity of the hypocretinergic system increases in the early postpartum period and begins to decline as weaning approaches. In particular, hypocretins within the medial preoptic area, a crucial region during this period, modulate both maternal behavior and sleep. Although further studies are necessary to obtain a comprehensive understanding of the role of hypocretins in lactating females, current research suggests that this system participates in promoting active components of maternal behavior and regulating wakefulness and sleep adjustments during the postpartum period, potentially leading to increased wakefulness during this stage. These adaptive adjustments enable the mother to cope with the continuously changing demands of the pups. [ABSTRACT FROM AUTHOR]

Oxytocin is synthesized by hypothalamic supraoptic nucleus (SON) and paraventricular nucleus (PVN) neurons and is released from the posterior pituitary gland to trigger uterine contractions during parturition. In rats, oxytocin neuron innervation by periventricular nucleus (PeN) kisspeptin neurons increases over pregnancy and intra-SON kisspeptin administration excites oxytocin neurons only in late pregnancy. To test the hypothesis that kisspeptin neurons excite oxytocin neurons to trigger uterine contractions during birth in C57/B6J mice, double-label immunohistochemistry for kisspeptin and oxytocin first confirmed that kisspeptin neurons project to the SON and PVN. Furthermore, kisspeptin fibers expressed synaptophysin and formed close appositions with oxytocin neurons in the mouse SON and PVN before and during pregnancy. Stereotaxic viral delivery of caspase-3 into the AVPV/PeN of Kiss-Cre mice before mating reduced kisspeptin expression in the AVPV, PeN, SON and PVN by > 90% but did not affect the duration of pregnancy or the timing of delivery of each pup during parturition. Therefore, it appears that AVPV/PeN kisspeptin neuron projections to oxytocin neurons are not necessary for parturition in the mouse. [ABSTRACT FROM AUTHOR]

Introduction: Sleep disturbances are highly prevalent across most major psychiatric disorders. Alterations in the hypothalamic-pituitary-adrenal axis, neuroimmune mechanisms, and circadian rhythm disturbances partially explain this connection. The gut microbiome is also suspected to play a role in sleep regulation, and recent studies suggest that certain probiotics, prebiotics, synbiotics, and fecal microbiome transplantation can improve sleep quality. Methods: We aimed to assess the relationship between gut-microbiota composition, psychiatric disorders, and sleep quality in this cross-sectional, cross-disorder study. We recruited 103 participants, 63 patients with psychiatric disorders (major depressive disorder [n = 31], bipolar disorder [n = 13], psychotic disorder [n = 19]) along with 40 healthy controls. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). The fecal microbiome was analyzed using 16S rRNA sequencing, and groups were compared based on alpha and beta diversity metrics, as well as differentially abundant species and genera. Results: A transdiagnostic decrease in alpha diversity and differences in beta diversity indices were observed in psychiatric patients, compared to controls. Correlation analysis of diversity metrics and PSQI score showed no significance in the patient and control groups. However, three species, Ellagibacter isourolithinifaciens, Senegalimassilia faecalis, and uncultured Blautia sp., and two genera, Senegalimassilia and uncultured Muribaculaceae genus, were differentially abundant in psychiatric patients with good sleep quality (PSQI >8), compared to poor-sleep quality patients (PSQI ≤8). Conclusion: In conclusion, this study raises important questions about the interconnection of the gut microbiome and sleep disturbances. [ABSTRACT FROM AUTHOR]

Objective: Depression represents one of the most severe psychiatric disorders, characterized by low mood episodes, as well as loss of interest. Major Depressive Episodes (MDE) treatment relies primarily on monoaminergic prescriptions. However, although the presence of many antidepressant medications, their efficacy is still partial. A promising intervention to improve antidepressant treatment may be the use of adjunctive nutraceuticals. Aim of the present study was to assess the efficacy of a N-Acetyl-cysteine, S-Adenosyl-L-Methionine and Folic acid's combination for the treatment of depressive symptoms in a sample of MDE patients. Method: Fifty outpatients with a MDE diagnosis in the context of different psychiatric disorders such as Major Depression, Bipolar Disorder, Anxiety disorders, and Personality disorders were recruited. The sample was divided into different groups based on the nutraceutical administration: a) concurrently with an AD (starter group); b) add-on to an already prescribed treatment; c) single treatment. Results: A significant reduction of CGI-Severity and Improvement scores from baseline to the end of treatment was found. Moreover, the starter group showed a significantly greater CGI-Improvement score compared to the other groups. Ninetyfour percent of patients did not show any side effects. Conclusions: The present study showed promising results for the use of nutraceuticals in the add-on treatment of MDE. Those compounds may be considered a versatile, tolerable, and effective add-on treatment for the reduction of depressive symptoms impact and for improving the functioning of patients affected by MDE. [ABSTRACT FROM AUTHOR]

In the present experiments, we tested the conclusion from previous electrophysiological experiments that gavage of sweet food and systemically applied insulin both stimulate oxytocin secretion. To do so, we measured oxytocin secretion from urethane‐anaesthetised male rats, and demonstrated a significant increase in secretion in response to gavage of sweetened condensed milk but not isocaloric cream, and a significant increase in response to intravenous injection of insulin. We compared the measurements made in response to sweetened condensed milk with the predictions from a computational model, which we used to predict plasma concentrations of oxytocin from the published electrophysiological responses of oxytocin cells. The prediction from the computational model was very closely aligned to the levels of oxytocin measured in rats in response to gavage. [ABSTRACT FROM AUTHOR]

Neuron generation persists throughout life in the hippocampus but is altered in animal models of neurological and neuropsychiatric diseases, suggesting that disease‐associated decline in cognitive and emotional hippocampal‐dependent behaviours might be functionally linked with dysregulation of postnatal neurogenesis. Depletion of the adult neural stem/progenitor cell (NSPCs) pool and neurogenic decline have been recently described in mice expressing synaptic susceptibility genes associated with autism spectrum disorder (ASDs). To gain further insight into mechanisms regulating neurogenesis in mice carrying mutations in synaptic genes related to monogenic ASDs, we used the R451C Neuroligin3 knock‐in (Nlgn3 KI) mouse, which is characterized by structural brain abnormalities, deficits in synaptic functions and reduced sociability. We show that the number of adult‐born neurons, but not the size of the NSPC pool, was reduced in the ventral dentate gyrus in knock‐in mice. Notably, this neurogenic decline was rescued by daily injecting mice with 10 mg/Kg of the antidepressant fluoxetine for 20 consecutive days. Sustained treatment also improved KI mice's sociability and increased the number of c‐Fos active adult‐born neurons, compared with vehicle‐injected KI mice. Our study uncovers neurogenesis‐mediated alterations in the brain of R451C KI mouse, showing that the R451C Nlgn3 mutation leads to lasting, albeit pharmacologically reversible, changes in the brain, affecting neuron formation in the adult hippocampus. Our results suggest that fluoxetine can ameliorate social behaviour in KI mice, at least in part, by rescuing adult hippocampal neurogenesis, which may be relevant for the pharmacological treatment of ASDs. [ABSTRACT FROM AUTHOR]

Background and Purpose: Kaempferol-3-O-sophoroside (PCS-1) is the main component in Crocus sativus (Saffron), a herb with mood-enhancing properties. AMP-activated protein kinase (AMPK) is a potential therapeutic target for depression. This study explores the antidepressive-like properties of PCS-1 and its AMPK activation to confirm AMPK as a target for antidepression., Experimental Approach: Corticosterone (CORT)-induced PC12 cell injury served as an in vitro model to evaluate the neuroprotective effect of PCS-1. Neuro-2a cells and primary neurons were utilized to evaluate the synaptogenesis role of PCS-1. CORT-induced mouse depression model and chronic unpredictable mild stress (CUMS) model were used to assess the antidepressive-like properties of PCS-1 through behavioural tests, magnetic resonance imaging, and biochemical index measurements. Western blot and immunofluorescence assays were used to study the mechanisms of PCS-1. Cellular thermal shift assay was used to confirm the binding target., Key Results: PCS-1 (12.5-50 μM) ameliorated CORT-induced PC12 cell damage, oxidative stress and inflammation. PCS-1 alone promoted an increase in synapses in Neuro-2a cells and primary neurons. Oral administration of PCS-1 (10 and 20 mg·kg -1 ) ameliorated weight loss, dyskinesia, and hippocampal volume reduction induced by CORT and CUMS. PCS-1 bound to AMPK to improve the expression of brain-derived neurotrophic factor (BDNF) and induce autophagy., Conclusion and Implications: PCS-1 binds to AMPK to promote BDNF production and autophagy enhancement, ultimately achieving antidepressant effects. This study provides support for the clinical application of saffron petals and provides further evidence for AMPK as a potential target for antidepression., (© 2023 British Pharmacological Society.)

Objectives: Long-term immunomodulatory therapy of pediatric onset-multiple sclerosis (POMS) is based mainly on published case series and internationally agreed guidelines. Relevant studies in the Greek population are absent from the literature. The purpose of this study is to present data on the efficacy and safety of the 1st line immunomodulatory drugs in the treatment of POMS patients. Materials and methods: The present study included 27 patients meeting the IPMSSG criteria for POMS and who are monitored at the outpatient clinic of the Multiple Sclerosis and Demyelinating Diseases Unit (MSDDU), of the 1st Neurological Department, University Hospital of Aeginition. All patients received 1st line immunomodulatory drugs as initial therapy. Clinical, laboratory, and imaging parameters of the disease were recorded before and after treatment. Results: Post-treatment, a significant reduction of the relapse number (mean ± SD: 2.0 ± 1.0 vs 1.2 ± 1.6, p = 0.002), EDSS progression (mean ± SD: 1.5 ± 0.8 vs 0.9 ± 0.7, p = 0.005) and ARR (mean ± SD: 1.5 ± 0.7 vs 0.4 ± 0.5, p = 0.0001) was observed, while no changes were observed in the EDSS score, (mean ± SD: 1.8 ± 0.6 vs 1.9. 0.6, p = 0.60). Advanced age at treatment initiation increased the risk for drug discontinuation before 24 months of therapy (HR = 0.6, 95% CI (0.35–0.99), p = 0.04). Conclusions: Most pediatric patients are forced to switch to either more efficacious 1st line or 2nd line drugs. Additionally, our study suggests that older age at the time of the 1st line treatment initiation, contributes to earlier drug discontinuation. [ABSTRACT FROM AUTHOR]

Objective: A better understanding of the genetic, molecular and cellular mechanisms of brain-derived neurotrophic factor (BDNF) and its association with neuroplasticity could play a pivotal role in finding future therapeutic targets for novel drugs in major depressive disorder (MDD). Because there are conflicting results regarding the exact role of BDNF polymorphisms in MDD still, we set out to systematically review the current evidence regarding BDNF-related mutations in MDD. Methods: We conducted a keyword-guided search of the PubMed and Embase databases, using 'BDNF' or 'brain-derived neurotrophic factor' and 'major depressive disorder' and 'single-nucleotide polymorphism'. We included all publications in line with our exclusion and inclusion criteria that focused on BDNF-related mutations in the context of MDD. Results: Our search yielded 427 records in total. After screening and application of our eligibility criteria, 71 studies were included in final analysis. According to present overall scientific data, there is a possibly major pathophysiological role for BDNF neurotrophic systems to play in MDD. However, on the one hand, the synthesis of evidence makes clear that likely no overall association of BDNF-related mutations with MDD exists. On the other hand, it can be appreciated that solidifying evidence emerged on specific significant sub-conditions and stratifications based on various demographic, clinico-phenotypical and neuromorphological variables. Conclusions: Further research should elucidate specific BDNF-MDD associations based on demographic, clinico-phenotypical and neuromorphological variables. Furthermore, biomarker approaches, specifically combinatory ones, involving BDNF should be further investigated. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) induces electric fields that depolarise or hyperpolarise neurons. Intermittent theta burst stimulation (iTBS), a patterned form of TMS that is delivered at the theta frequency (~5 Hz), induces neuroplasticity in the hippocampus, a brain region that is implicated in memory and learning. One form of plasticity that is unique to the hippocampus is adult neurogenesis; however, little is known about whether TMS or iTBS in particular affects newborn neurons. Here, we therefore applied repeated sessions of iTBS to male and female mice and measured the extent of adult neurogenesis and the morphological features of immature neurons. We found that repeated sessions of iTBS did not significantly increase the amount of neurogenesis or affect the gross dendritic morphology of new neurons, and there were no sex differences in neurogenesis rates or aspects of afferent morphology. In contrast, efferent properties of newborn neurons varied as a function of sex and stimulation. Chronic iTBS increased the size of mossy fibre terminals, which synapse onto Cornu Ammonis 3 (CA3) pyramidal neurons, but only in males. iTBS also increased the number of terminal‐associated filopodia, putative synapses onto inhibitory interneurons but only in male mice. This efferent plasticity could result from a general trophic effect, or it could reflect accelerated maturation of immature neurons. Given the important role of mossy fibre synapses in hippocampal learning, our results identify a neurobiological effect of iTBS that might be associated with sex‐specific changes in cognition. [ABSTRACT FROM AUTHOR]

The pathogenesis of depression involves cAMP-response element binding protein1 (CREB1) and metabotropic glutamate receptor 7 (GRM7), and their genetic polymorphisms may affect susceptibility to depression. The purpose of this study was to investigate whether the CREB1 polymorphisms rs2253206 and rs10932201 and the GRM7 polymorphism rs162209 are associated with the risk of depression. Using polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing, we analyzed the rs2253206, rs10932201, and rs162209 frequencies in 479 patients with depression and 329 normal controls. The results showed that the rs2253206 and rs10932201 polymorphisms were significantly associated with an increased risk of depression. However, no association was found between rs162209 and depression risk. When the data were stratified for several disease-related variables, none of the three polymorphisms were found to be correlated to onset, disease severity, family history, or suicidal tendency. Thus, the present findings indicate that the CREB1 polymorphisms rs2253206 and rs10932201 may be related to the occurrence of depression. [ABSTRACT FROM AUTHOR]

To date, no study has critically reviewed the current literature on the association between magnesium (Mg) and sleep health. Therefore, we carried out a systematic review to assess the association between Mg and sleep patterns in adults' population through observational and interventional studies. We searched for relevant studies through PubMed (http://www.ncbi.nlm.nih.gov/pubmed), Scopus (http://www.scopus.com), and ISI Web of Science (http://www.webofscience.com) from the earliest available date until November 2021. Eligibility criteria for study selection were guided by the following components identified using the PI(E)CO (Population, Intervention (Exposure), Comparison, Outcome) framework: P (adult population), I(E) (high dietary intake or supplementation of Mg), C (low dietary intake of Mg or placebo group), and O (sleep pattern including sleep duration, sleep-onset latency, night awakenings, sleep stages, and sleep phases). The present study involved 7,582 subjects from 9 published cross-sectional, cohort, and RCT systematically reviewed the possible links between Mg and sleep quality (daytime falling asleep, sleepiness, snoring, and sleep duration) in an adult population. Observational studies suggested an association between Mg statuses and sleep quality, while the RCTs reported contradictory findings. This systematic review revealed an association between magnesium status and sleep quality (daytime falling asleep, sleepiness, snoring, and sleep duration) according to the observational studies, while the randomized clinical trials showed an uncertain association between magnesium supplementation and sleep disorders. The association between dietary magnesium and sleep patterns needs well-designed randomized clinical trials with a larger sample size and longer follow-up time (more than 12 weeks) to further clarify the relationship. [ABSTRACT FROM AUTHOR]

Machine learning as a subset of artificial intelligence presents a promising set of algorithms for tackling increasingly complex challenges. A notable ability of this subgroup of algorithms to tackle tasks without explicit programming coupled with the expanding availability of computational resources and information transparency has made it possible to utilize algorithms to forecast prices. In recent years, cryptocurrency has increased in popularity and has seen wider adoption as a payment method. Cryptocurrency trading and mining have become a potentially very lucrative venture. However, due to the instability of cryptocurrency prices, casting accurate predictions can be quite challenging. A novel way of approaching this challenge is by tackling it through time-series forecasting. A particularly promising method for tackling this type of problem is through the utilization of long-short-term memory artificial neural networks to attain accurate prediction results. However, the forecasting accuracy of machine learning models is highly dependent on adequate hyperparameter settings. Thus, this work presents an improved variation of the arithmetic optimization algorithm, tasked with selecting the best values of a long-short term neural network casting price predictions. The presented approach has been evaluated on publicly available real-world Ethereum trading price data. The attained results of a comparative analysis against several popular metaheuristics indicate that the presented method achieved excellent results, and outperformed aforementioned algorithms in one and four-step ahead predictions. [ABSTRACT FROM AUTHOR]

A fundamental trait of depression is low motivation. Hippocampal neurogenesis has been associated with motivational deficits but detailed evidence on how it regulates human‐relevant behavioral traits is still missing. We used the hGFAP‐TK rat model to deplete actively dividing neural stem cells in the rat hippocampus. Use of the effort‐discounting operant task allowed us to identify specific and detailed deficits in motivation behavior. In this task, rats are given a choice between small and large food rewards, where 2–20 lever presses are required to obtain the large reward (four sugar pellets) versus one press to receive the smaller reward (two sugar pellets). We found that depleting adult neurogenesis did not affect effort‐based choice or general motivation to complete the task. However, lack of adult neurogenesis reduced the pressing rate and thus increased time to complete the required presses to obtain a reward. In summary, the present study finds that adult hippocampal neurogenesis specifically reduces response vigor to obtain rewards and thus deepens our understanding in how neurogenesis shapes depression. [ABSTRACT FROM AUTHOR]

The cortisol awakening response (CAR) is a non-invasive biomarker for hypothalamic-pituitary-adrenal axis (HPA) dysregulation, reflecting accumulated stress over time. In a previous study we reported that a blunted CAR before an inpatient treatment predicted self-reported depressive symptoms six weeks and six months after discharge [Eikeseth, F. F., Denninghaus, S., Cropley, M., Witthöft, M., Pawelzik, M., & Sütterlin, S. (2019). The cortisol awakening response at admission to hospital predicts depression severity after discharge in major depressive disorder (MDD) patients. Journal of Psychiatric Research, 111, 44-50)]. This replication study adopted an improved overall methodology with more stringent assessment protocols and monitoring. The longitudinal design included 122 inpatients from a psychosomatic hospital with a diagnosis of MDD displaying symptoms of moderate to severe major depression (n = 80 females). The CAR was measured at intake. Depression severity was assessed as Beck Depression Inventory II scores at intake, discharge, 6 weeks and 6 months following discharge. Results from the original study were replicated in terms of effect size but did not reach statistical significance (correlation between BDI-II 6 months after discharge and AUCg: r = -0.213; p = 0.054). The replication study yielded nearly identical correlation coefficients as in the original study (BDI-II 6 months and CAR, r = -0.223, p < 0.05). The replication of previously reported effect sizes with a concurrent lack of statistical significance in the more restrictive, larger and better controlled replication study may well inform research on psycho-endocrinological predictors for treatment success, but suggests a rather limited practical relevance for cortisol awakening response measures in this clinical context. [ABSTRACT FROM AUTHOR]

Aim: To review variables and management techniques that may affect anaesthesia failure during root canal treatment and methods of overcoming anaesthesia failure. Methodology: The PubMed and Cochran databases were searched for evidence‐based investigations regarding pain during needle insertion, pain on injection, efficacy of the anaesthetic solutions and anaesthesia techniques, and premedication. Results: Variables such as pain on injection, premedication with various types of drugs, volume of anaesthetic solutions, supplemental anaesthetic techniques, and additives to the anaesthetic solutions may influence pain perception during root canal treatment. Differences between teeth with healthy pulps versus those with irreversible pulpitis should be considered when the effects of variables are interpreted. However, there are several concerns regarding the methodology of investigations that have evaluated anaesthesia success rates. Conclusion: Several variables may influence anaesthesia success rates. There are conditions that may help to predict a patient's pain during endodontic procedures. These conditions could be overcome either by employing methods such as premedication with a non‐steroidal anti‐inflammatory drug prior to the treatment visit or by using supplementary techniques before or during the treatment. However, investigators need to be more careful when reporting details of their studies to reduce concerns regarding their study bias. [ABSTRACT FROM AUTHOR]

Depression is among the main causes of disability, and its protracted manifestations could make it even harder to treat metabolic diseases. Obesity is linked to episodes of depression, which is closely correlated to abdominal adiposity and impaired food quality. The present review is aimed at studying possible links between obesity and depression along with targets to disrupt it. Research output in Pubmed and Scopus were referred for writing this manuscript. Obesity and depression are related, with the greater propensity of depressed people to gain weight, resulting in poor dietary decisions and a sedentary lifestyle. Adipokines, which include adiponectin, resistin, and leptin are secretory products of the adipose tissue. These adipokines are now being studied to learn more about the connection underlying obesity and depression. Ghrelin, a gut hormone, controls both obesity and depression. Additionally, elevated ghrelin levels result in anxiolytic and antidepressant-like effects. The gut microbiota influences the metabolic functionalities of a person, like caloric processing from indigestible nutritional compounds and storage in fatty tissue, that exposes an individual to obesity, and gut microorganisms might connect to the CNS through interconnecting pathways, including neurological, endocrine, and immunological signalling systems. The alteration of brain activity caused by gut bacteria has been related to depressive episodes. Monoamines, including dopamine, serotonin, and norepinephrine, have been widely believed to have a function in emotions and appetite control. Emotional signals stimulate arcuate neurons in the hypothalamus that are directly implicated in mood regulation and eating. The peptide hormone GLP-1(glucagon-like peptide- 1) seems to have a beneficial role as a medical regulator of defective neuroinflammation, neurogenesis, synaptic dysfunction, and neurotransmitter secretion discrepancy in the depressive brain. The gut microbiota might have its action in mood and cognition regulation, in addition to its traditional involvement in GI function regulation. This review addressed the concept that obesity-related low-grade mild inflammation in the brain contributes to chronic depression and cognitive impairments., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The neuropeptide oxytocin (OT) has emerged as an important anorexigen in the regulation of food intake and energy balance. It has been shown that the release of OT and activation of hypothalamic OT neurons coincide with food ingestion. Its effects on feeding have largely been attributed to limiting meal size through interactions in key regulatory brain regions governing the homeostatic control of food intake such as the hypothalamus and hindbrain in addition to key feeding reward areas such as the nucleus accumbens and ventral tegmental area. Furthermore, the magnitude of an anorexigenic response to OT and feeding‐related activation of the brain OT circuit are modified by the composition and flavor of a diet, as well as by a social context in which a meal is consumed. OT is particularly effective in reducing consumption of carbohydrates and sweet tastants. Pharmacologic, genetic, and pair‐feeding studies indicate that OT‐elicited weight loss cannot be fully explained by reductions of food intake and that the overall impact of OT on energy balance is also partly a result of OT‐elicited changes in lipolysis, energy expenditure, and glucose regulation. Peripheral administration of OT mimics many of its effects when it is given into the central nervous system, raising the questions of whether and to what extent circulating OT acts through peripheral OT receptors to regulate energy balance. Although OT has been found to elicit weight loss in female mice, recent studies have indicated that sex and estrous cycle may impact oxytocinergic modulation of food intake. Despite the overall promising basic research data, attempts to use OT in the clinical setting to combat obesity and overeating have generated somewhat mixed results. The focus of this mini‐review is to briefly summarize the role of OT in feeding and metabolism, address gaps and inconsistencies in our knowledge, and discuss some of the limitations to the potential use of chronic OT that should help guide future research on OT as a tailor‐made anti‐obesity therapeutic. The focus of our mini‐review is to briefly summarize the role of oxytocin (OT) in feeding and metabolism, address gaps and inconsistencies in our knowledge, and discuss some of the limitations to the potential use of chronic OT that should help guide future research on OT as a tailor‐made anti‐obesity therapeutic. [ABSTRACT FROM AUTHOR]

Background: Insomnia is considered one of the manifestations of sleep disorders, and its intensity is linked to the treatment effect or suicidal thoughts. Major depressive disorder (MDD) is classified into various subtypes due to heterogeneous symptoms. Melancholic MDD has been considered one of the most common subtypes with special sleep features. However, the brain functional mechanisms in melancholic MDD with insomnia remain unclear. Materials and methods: Melancholic MDD and healthy controls (HCs, n = 46) were recruited for the study. Patients were divided into patients with melancholic MDD with low insomnia (mMDD-LI, n = 23) and patients with melancholic MDD with high insomnia (mMDD-HI, n = 30), according to the sleep disturbance subscale of the 17-item Hamilton Depression Rating Scale. The dynamic amplitude of low-frequency fluctuation was employed to investigate the alterations of brain activity among the three groups. Then, the correlations between abnormal dALFF values of brain regions and the severity of symptoms were investigated. Results: Lower dALFF values were found in the mMDD-HI group in the right middle temporal gyrus (MTG)/superior temporal gyrus (STG) than in the mMDD-LI (p = 0.014) and HC groups (p < 0.001). Melancholic MDD groups showed decreased dALFF values than HC in the right middle occipital gyri (MOG)/superior occipital gyri (SOG), the right cuneus, the bilateral lingual gyrus, and the bilateral calcarine (p < 0.05). Lower dALFF values than HC in the left MOG/SOG and the left cuneus in melancholic MDD groups were found, but no significant difference was found between the mMDD-LI group and HC group (p = 0.079). Positive correlations between the dALFF values in the right MTG/STG and HAMD-SD scores (the sleep disturbance subscale of the HAMD-17) in the mMDD-HI group (r = 0.41, p = 0.042) were found. In the pooled melancholic MDD, the dALFF values in the right MOG/SOG and the right cuneus (r = 0.338, p = 0.019), the left MOG/SOG and the left cuneus (r = 0.299, p = 0.039), and the bilateral lingual gyrus and the bilateral calcarine (r = 0.288, p = 0.047) were positively correlated with adjusted HAMD scores. Conclusion: The occipital cortex may be related to depressive symptoms in melancholic MDD. Importantly, the right MTG/STG may play a critical role in patients with melancholic MDD with more severe insomnia. [ABSTRACT FROM AUTHOR]

n this paper, we investigated the sedative-hypnotic effect of Cinnamomum camphora chvar. Borneol essential oil (BEO, 16.4% borneol), a by-product of steam distillation of Cinnamomum camphora chvar. Borneol, from which natural crystalline borneol (NCB, 98.4% borneol) is obtained. Using locomotor activity tests and pentobarbital sodium-induced sleep test, it was found that BEO significantly reduced locomotor activity (p < 0.05), shortened sleep latency (p < 0.0001), prolonged sleep duration (p < 0.05), and had a sedative-hypnotic effect. We constructed the “components-targets-signaling pathways” and “protein– protein interaction” (PPI) network of BEO using network pharmacology. The results show that the 24 active components of BEO acted on 17 targets, mainly through response to alkaloid and catecholamine transport, and neuroactive ligand-receptor interaction. The PPI network identified 12 key proteins, mainly dopamine receptor (DR)D2, opioid receptor mu 1 (OPRM1), and opioid receptor kappa 1 (OPRK1), and we further analyzed the active components and targets of BEO through molecular docking. The results showed that the active components and targets obtained by network pharmacology analyses had good binding activity, which reflected their multi-component, multi-target, multi-pathway action characteristics. This paper provides a theoretical basis for further study of the mechanism of action of BEO in the treatment of insomnia. [ABSTRACT FROM AUTHOR]

Summary: Most cases of fetal and neonatal thrombocytopenia (FNAIT) are caused by maternal anti‐human platelet antigen‐1a antibodies (anti‐HPA‐1a). Anti‐HPA‐5b antibodies are the second most common antibodies in suspected FNAIT cases. Given the high prevalence of anti‐HPA‐5b antibodies in pregnant women delivering healthy newborns, the association with FNAIT may be coincidental. This review of the literature related to FNAIT using the MEDLINE database was conducted according to PRISMA guidelines. A retrospective analysis of a single‐centre cohort of 817 suspected FNAIT cases was conducted. The pooled prevalence of anti‐HPA‐5b antibodies in unselected pregnant women of European descent was 1.96% (n = 3113), compared with 3.4% (n = 5003) in women with suspected FNAIT. We found weak evidence that a small proportion of pregnant women presenting with anti‐HPA‐5b antibodies will give birth to a newborn with mild thrombocytopenia. The neonatal platelet counts were not different between suspected FNAIT cases (n = 817) with and without maternal anti‐HPA‐5b antibodies. The prevalence of maternal anti‐HPA‐5b antibodies was not different between neonates with intracranial haemorrhage and healthy controls. The current experimental and epidemiological evidence does not support the hypothesis that anti‐HPA‐5b antibodies cause severe thrombocytopenia or bleeding complications in the fetus or newborn. [ABSTRACT FROM AUTHOR]

Background: Incorporating an additive into lidocaine is a method to enhance the efficacy of the inferior alveolar nerve block (IANB) in mandibular posterior teeth. Objectives: To assess the efficacy of incorporating additives into lidocaine in the success rate of IANB for teeth with the diagnosis of normal pulp (NP) or symptomatic irreversible pulpitis (SIP). Methods: Randomized controlled trials (RCTs) assessing the incorporation of additives into lidocaine on the pulpal anaesthesia success rate of mandibular posterior teeth were searched in PubMed, Scopus, Web of Science, Ovid, EBSCO, Embase, and Cochrane databases up to 1 December 2021. The risk of bias (RoB) was assessed by the Cochrane Risk of Bias Tool. A random‐effects model was employed to calculate the pooled risk ratio (RR) with a 95% confidence interval (CI), using STATA 16. The trial sequential analysis (TSA) was applied to calculate the required information size (RIS). The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach was used to assess the certainty of the evidence. Results: Of 6966 records retrieved initially, 14 trials (8 for NP and 6 for SIP groups) were included in qualitative and quantitative syntheses. All trials were categorized as low and unclear RoB for NP and SIP groups, respectively. In the NP group, with 307 participants, no significant effect was observed for additives incorporated into lidocaine (RR: 0.84; 95% CI: 0.53‒1.32; I2 = 98%). Subgroup analysis revealed that adding mannitol led to a higher success rate (RR = 1.24; 95% CI: 1.15–1.34; I2 = 7.16%). In the SIP group, with 434 participants, no significant effect was shown when the additives were incorporated (RR = 1.22; 95% CI: 0.98–1.52; I2 = 0%). Likewise, in subgroup analysis, incorporating mannitol or sodium bicarbonate demonstrated no significant effect (RR = 1.76; 95% CI: 0.93–3.32; I2 = 18.41% and RR = 1.06; 95% CI: 0.65–1.72; I2 = 53.5%, respectively). Discussion: TSA revealed that the outcome was "inconclusive" for each group. The certainty of the evidence was graded as "very low" and "low" for NP and SIP groups, respectively. Conclusions: The very low to low certainty of evidence indicated that incorporating additives into lidocaine did not increase the efficacy of IANB and supplemental injections are still necessary to help practitioners achieve painless dentistry. Registration: PROSPERO database (CRD42020132585). [ABSTRACT FROM AUTHOR]

Dissociative disorders are a common and frequently undiagnosed group of psychiatric disorders, characterized by disruptions in the normal integration of awareness, personality, emotion and behavior. The available evidence suggests that these disorders arise from an interaction between genetic vulnerability and stress, particularly traumatic stress, but the attention paid to the underlying genetic diatheses has been sparse. In this paper, the existing literature on the molecular genetics of dissociative disorders, as well as of clinically significant dissociative symptoms not reaching the threshold of a disorder, is reviewed comprehensively across clinical and non-clinical samples. Association studies suggest a link between dissociative symptoms and genes related to serotonergic, dopaminergic and peptidergic transmission, neural plasticity and cortisol receptor sensitivity, particularly following exposure to childhood trauma. Genome-wide association studies have identified loci of interest related to second messenger signaling and synaptic integration. Though these findings are inconsistent, they suggest biologically plausible mechanisms through which traumatic stress can lead to pathological dissociation. However, methodological concerns related to phenotype definition, study power, and correction for the confounding factors limit the value of these findings, and they require replication and extension in studies with better design. [ABSTRACT FROM AUTHOR]

The hormone, oxytocin, is synthesised by magnocellular neurones of the supraoptic and paraventricular nuclei and is released from the posterior pituitary gland into the circulation to trigger uterine contractions during parturition. Kisspeptin fibre density increases around the supraoptic nucleus over pregnancy and intracerebroventricular kisspeptin excites oxytocin neurones only in late pregnancy. However, the mechanism of this excitation is unknown. Here, we found that microdialysis administration of kisspeptin into the supraoptic nucleus consistently increased the action potential (spike) firing rate of oxytocin neurones in urethane‐anaesthetised late‐pregnant rats (gestation day 18–21) but not in non‐pregnant rats. Hazard analysis of action potential firing showed that kisspeptin specifically increased the probability of another action potential firing immediately after each action potential (post‐spike excitability) in late‐pregnant rats. Patch‐clamp electrophysiology in hypothalamic slices showed that bath application of kisspeptin did not affect action potential frequency or baseline membrane potential in supraoptic nucleus neurones. Moreover, kisspeptin superfusion did not affect the frequency or amplitude of excitatory postsynaptic currents or inhibitory postsynaptic currents in supraoptic nucleus neurones. Taken together, these studies suggest that kisspeptin directly activates oxytocin neurones in late pregnancy, at least in part, via increased post‐spike excitability. Key points: Oxytocin secretion is triggered by action potential firing in magnocellular neurones of the hypothalamic supraoptic and paraventricular nuclei to induce uterine contractions during birth.In late pregnancy, kisspeptin expression increases in rat periventricular nucleus neurones that project to the oxytocin system.Here, we show that intra‐supraoptic nucleus administration of kisspeptin increases the action potential firing rate of oxytocin neurones in anaesthetised late‐pregnant rats, and that the increased firing rate is associated with increased oxytocin neurone excitability immediately after each action potential.By contrast, kisspeptin superfusion of hypothalamic slices did not affect the activity of supraoptic nucleus neurones or the strength of local synaptic inputs to supraoptic nucleus neurones.Hence, kisspeptin might activate oxytocin neurons in late pregnancy by transiently increasing oxytocin neuron excitability after each action potential. [ABSTRACT FROM AUTHOR]

Adult newborn neurons are involved in memory encoding and extinction, but the neural mechanism is unclear. We found the adult newborn neurons at 4 weeks are recruited by learning and subjected to epigenetic regulations, consequently reducing their ability to be re‐recruited later. After removal of the epigenetic blockage, Suv39h1 KO mice showed an increased recruiting number of aged newborn neurons and enhanced flexibility in learning tasks. Besides NRXN1, we found SHANK1, the synaptic scaffold protein, is one of the major targets of Suv39h1, regulating memory stability. Expression of Shank1 is transiently engaged to enhance synaptogenesis during learning and is strongly suppressed by Suv39h1 from 5 h after learning. Exogenously overexpression of Shank1 in dentate gyrus increased the density of mushroom spines and decreased the persistency of old memories. Our study indicated the activity‐regulated epigenetic modification in newly matured newborn neurons in hippocampus insulates temporally distinct experiences and stabilizes old memories. [ABSTRACT FROM AUTHOR]

One of the traditional endocrine views of parturition is the "progesterone withdrawal" theory which states that a fall of progesterone levels and a subsequence estradiol rise lead to the initiation of parturition ([26]). Aiming to identify the potential mechanism of brain signaling in regulating ovoviviparous teleost parturition, the black rockfish ( I Sebastes schlegelii i ) was employed as a research model in the present study. Keywords: transcriptomic data; brain; parturition; ovoviviparous; black rockfish EN transcriptomic data brain parturition ovoviviparous black rockfish 1 6 6 02/08/22 20220204 NES 220204 Introduction Parturition is the physiologic process by which a fetus is expelled from the mother to the extrauterine environment. Principal component analysis (PCA) (A) and heatmap (B) of different expression gene (DEG) function clustering of black rockfish brain before parturition (B I), during parturition (B II), and 24 h after parturition (B III). [Extracted from the article]

Magnesium status and vitamin B6 intake have been linked to mental health and/or quality of life (QoL). In an 8‐week Phase IV randomised controlled study in individuals with low magnesemia and severe/extremely severe stress but who were otherwise healthy, greater stress reduction was achieved with magnesium combined with vitamin B6 than with magnesium alone. We present a previously unreported secondary analysis of the effect of magnesium, with and without vitamin B6, on depression, anxiety, and QoL. Adults with Depression Anxiety Stress Scales (DASS‐42) stress subscale score >18 were randomised 1:1 to magnesium + vitamin B6 combination (Magne B6®; daily dose 300 and 30 mg, respectively) or magnesium alone (Magnespasmyl®; daily dose 300 mg). Outcomes included changes from baseline in DASS‐42 depression and anxiety scores, and QoL (Short Form‐36 Health Survey). DASS‐42 anxiety and depression scores significantly improved from baseline to week 8 with both treatments, particularly during the first 4 weeks. Improvement in QoL continued over 8 weeks. Participants' perceived capacity for physical activity in daily life showed greater improvement with magnesium + vitamin B6 than magnesium alone (Week 4). In conclusion, magnesium supplementation, with or without vitamin B6, could provide a meaningful clinical benefit in daily life for individuals with stress and low magnesemia. [ABSTRACT FROM AUTHOR]

One of the reasons that most multicellular animals survive and thrive is because of the adaptable and plastic nature of their nervous systems. For an organism to survive, it is essential for the animal to respond and adapt to environmental changes. This is achieved by sensing external cues and translating them into behaviors through changes in synaptic activity. The nervous system plays a crucial role in constantly evaluating environmental cues and allowing for behavioral plasticity in the organism. Multiple neurotransmitters and neuropeptides have been implicated as key players for integrating sensory information to produce the desired output. Because of its simple nervous system and well-established neuronal connectome, C. elegans acts as an excellent model to understand the mechanisms underlying behavioral plasticity. Here, we critically review how neuropeptides modulate a wide range of behaviors by allowing for changes in neuronal and synaptic signaling. This review will have a specific focus on feeding, mating, sleep, addiction, learning and locomotory behaviors in C. elegans. With a view to understand evolutionary relationships, we explore the functions and associated pathophysiology of C. elegans neuropeptides that are conserved across different phyla. Further, we discuss the mechanisms of neuropeptidergic signaling and how these signals are regulated in different behaviors. Finally, we attempt to provide insight into developing potential therapeutics for neuropeptide-related disorders. [ABSTRACT FROM AUTHOR]

The third edition of Flow Cytometry Guidelines provides the key aspects to consider when performing flow cytometry experiments and includes comprehensive sections describing phenotypes and functional assays of all major human and murine immune cell subsets. Notably, the Guidelines contain helpful tables highlighting phenotypes and key differences between human and murine cells. Another useful feature of this edition is the flow cytometry analysis of clinical samples with examples of flow cytometry applications in the context of autoimmune diseases, cancers as well as acute and chronic infectious diseases. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid. All sections are written and peer‐reviewed by leading flow cytometry experts and immunologists, making this edition an essential and state‐of‐the‐art handbook for basic and clinical researchers. [ABSTRACT FROM AUTHOR]