Dynamic links between mechanical forces and metabolism shape the tumor milieu.

Cell function relies on the spatiotemporal dynamics of metabolic reactions. In all physiopathological processes of tissues, mechanical forces impact the structure and function of membranes, enzymes, organelles and regulators of metabolic gene programs, thus regulating cell metabolism. In turn, metabolic pathways feedback impacts the physical properties of cell and tissues.

Benefits and Harms of 'Smart Drugs' (Nootropics) in Healthy Individuals.

'Smart drugs' (also known as 'nootropics' and 'cognitive enhancers' [CEs]) are being used by healthy subjects (i.e. students and workers) typically to improve memory, attention, learning, executive functions and vigilance, hence the reference to a 'pharmaceutical cognitive doping behaviour'.

Establishing a business case for setting up early detection services for preventing psychosis.

Under standard care, psychotic disorders can have limited response to treatments, high rates of chronicity and disability, negative impacts on families, and wider social and economic costs. In an effort to improve early detection and care of individuals developing a psychotic illness, early intervention in psychosis services and early detection services have been set up in various countries since the 1980s. In April 2016, NHS England implemented a new 'access and waiting times' standard for early intervention in psychosis to extend the prevention of psychosis across England.

The prolyl-isomerase PIN1 is essential for nuclear Lamin-B structure and function and protects heterochromatin under mechanical stress.

Chromatin organization plays a crucial role in tissue homeostasis. Heterochromatin relaxation and consequent unscheduled mobilization of transposable elements (TEs) are emerging as key contributors of aging and aging-related pathologies, including Alzheimer's disease (AD) and cancer. However, the mechanisms governing heterochromatin maintenance or its relaxation in pathological conditions remain poorly understood.

Case Report: Treatment of Kratom Use Disorder With a Classical Tricyclic Antidepressant.

Kratom or (Korth.) is an evergreen tree of the coffee family native to South-East Asia and Australasia. It is used by locals recreationally to induce stimulant and sedative effects and medically to soothe pain and opiate withdrawal.

Psychonauts' psychedelics: A systematic, multilingual, web-crawling exercise.

Psychedelics alter the perception of reality through agonist or partial agonist interaction with the 2A serotoninergic receptor. They are classified as phenethylamines, tryptamines and lysergamides. These classes, according to the United Nations Office on Drugs and Crime (UNODC) and European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), account for an important percentage of the new psychoactive substances (NPS) current scenario.

New psychoactive substances (NPS) and serotonin syndrome onset: A systematic review.

The use of several new psychoactive substances (NPS) has become very popular and is posing global health risks. Chemically and pharmacologically diverse molecules are constantly emerging and are presenting with a wide range of clinical implications. Serotonin toxicity, and specifically Serotonin Syndrome (SS), might develop as a result of an over-activation of the serotoninergic system caused by several mechanisms resulting in a classic triad of altered mental status, neuromuscular effects, and autonomic hyperactivity.

The Psychonauts' World of Cognitive Enhancers.

Background: There is growing availability of novel psychoactive substances (NPS), including cognitive enhancers (CEs) which can be used in the treatment of certain mental health disorders. While treating cognitive deficit symptoms in neuropsychiatric or neurodegenerative disorders using CEs might have significant benefits for patients, the increasing recreational use of these substances by healthy individuals raises many clinical, medico-legal, and ethical issues. Moreover, it has become very challenging for clinicians to keep up-to-date with CEs currently available as comprehensive official lists do not exist.

Novel Opioids: Systematic Web Crawling Within the e-Psychonauts' Scenario.

Background: A wide range of novel psychoactive substances (NPSs) are regularly searched and discussed online by e-psychonauts. Among NPSs, the range of prescription/non-prescription opioids (fentanyl and non-fentanyl analogs) and herbal derivatives currently represents a challenge for governments and clinicians.

Methods: Using a web crawler (i.

The e-Psychonauts' 'Spiced' World; Assessment of the Synthetic Cannabinoids' Information Available Online.

Background: A wide range of novel psychoactive substances (NPS) is regularly searched and discussed online by web-based drug enthusiasts (i.e. the e-psychonauts).

The clinical challenges of synthetic cathinones.

Aims: Within the new psychoactive substances (NPS) scenario, several hundred different molecules, mostly including synthetic cannabinoids and cathinones, have been identified so far. The aims of the paper were to: (i) identify the number of synthetic cathinones mentioned in a range of psychonaut, NPS-related, online sources; and (ii) describe the associated acute/long term clinical scenario and the related treatment/management plan.

Methods: After about 18 months of operation and exclusion of false positives/duplicates, some 4204 unique NPS molecules were included in the NPSfinder® crawling/navigating software database.

New/emerging psychoactive substances and associated psychopathological consequences.

Background: The present paper provides an updated review of both the large number of new/novel/emerging psychoactive substances (NPS) and their associated psychopathological consequences. Focus was here given on identification of those NPS being commented in specialised online sources and the related short-/long-term psychopathological and medical ill-health effects.

Methods: NPS have been identified through an innovative crawling/navigating software, called the 'NPS.

Sterol regulatory element binding protein 1 couples mechanical cues and lipid metabolism.

Sterol regulatory element binding proteins (SREBPs) are a family of transcription factors that regulate lipid biosynthesis and adipogenesis by controlling the expression of several enzymes required for cholesterol, fatty acid, triacylglycerol and phospholipid synthesis. In vertebrates, SREBP activation is mainly controlled by a complex and well-characterized feedback mechanism mediated by cholesterol, a crucial bio-product of the SREBP-activated mevalonate pathway. In this work, we identified acto-myosin contractility and mechanical forces imposed by the extracellular matrix (ECM) as SREBP1 regulators.

Intersections between Regulated Cell Death and Autophagy.

In multicellular organisms, cell death is an essential aspect of life. Over the past decade, the spectrum of different forms of regulated cell death (RCD) has expanded dramatically with relevance in several pathologies such as inflammatory and neurodegenerative diseases. This has been paralleled by the growing awareness of the central importance of autophagy as a stress response that influences decisions of cell life and cell death.

Drosophila p53 integrates the antagonism between autophagy and apoptosis in response to stress.

The tumor suppressor TP53/p53 is a known regulator of apoptosis and macroautophagy/autophagy. However, the molecular mechanism by which TP53 regulates 2 apparently incompatible processes remains unknown. We found that Drosophila lacking p53 displayed impaired autophagic flux, higher caspase activation and mortality in response to oxidative stress compared with wild-type flies.

p53-dependent programmed necrosis controls germ cell homeostasis during spermatogenesis.

The importance of regulated necrosis in pathologies such as cerebral stroke and myocardial infarction is now fully recognized. However, the physiological relevance of regulated necrosis remains unclear. Here, we report a conserved role for p53 in regulating necrosis in Drosophila and mammalian spermatogenesis.

Neurobiological Evidence for the Primacy of Mania Hypothesis.

Background: Athanasios Koukopoulos proposed the primacy of mania hypothesis (PoM) in a 2006 book chapter and later, in two peer-reviewed papers with Nassir Ghaemi and other collaborators. This hypothesis supports that in bipolar disorder, mania leads to depression, while depression does not lead to mania.

Objective: To identify evidence in literature that supports or falsifies this hypothesis.

Xanthurenic Acid Activates mGlu2/3 Metabotropic Glutamate Receptors and is a Potential Trait Marker for Schizophrenia.

The kynurenine pathway of tryptophan metabolism has been implicated in the pathophysiology of psychiatric disorders, including schizophrenia. We report here that the kynurenine metabolite, xanturenic acid (XA), interacts with, and activates mGlu2 and mGlu3 metabotropic glutamate receptors in heterologous expression systems. However, the molecular nature of this interaction is unknown, and our data cannot exclude that XA acts primarily on other targets, such as the vesicular glutamate transporter, in the CNS.

Electroconvulsive therapy improves clinical manifestations of treatment-resistant depression without changing serum BDNF levels.

Electroconvulsive therapy (ECT) is effective in treatment-resistant depression (TRD). It may act through intracellular process modulation, but its exact mechanism is still unknown. Animal research supports a neurotrophic effect for ECT.

Features preceding diagnosis of bipolar versus major depressive disorders.

Background: Better and earlier predictive differentiation of bipolar (BD) vs. unipolar major depressive disorder (UD) diagnoses should improve long-term clinical planning.

Methods: We reviewed randomly selected clinical records of 334 adults diagnosed with DSM-IV-TR BD-I (n=109), BD-II (n=106), and UD (n=119) and compared features preceding major affective episodes or diagnoses, using bivariate, multivariate, and Bayesian methods.